Abstracts of the 2nd Congress of the European ...

EUROPEAN JOURNAL OF NEUROLOGY Volume 23, Supplement 1, May 2016

Abstracts of the 2nd Congress of the European Academy of Neurology

Copenhagen, Denmark

Disclaimer: This abstract volume has been produced using author-supplied copy. Editing has been restricted to some corrections of spelling and style where appropriate. No responsibility is assumed for any claims, instructions, methods or drug dosages contained in the abstracts: it is recommended that these are verified independently.

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ISSN 1351-5101(201405)21:5+1

Editor-in-Chief Paul Boon, Belgium

Editorial Board Sharon Abrahams, United Kingdom Alberto Albanese, Italy Yuri Alekseenko, Belarus Maria Pia Amato, Italy Angelo Antonini, Italy Anita Arsovska, FYRO Macedonia Eduard Auff, Austria Anish Bahra, United Kingdom Ronny Beer, Austria Kailash Bhatia, United Kingdom Laurence Bisdorff, Luxembourg Natan Bornstein, Israel Michael Brainin, Austria Adolfo M. Bronstein, United Kingdom Martin Brown, United Kingdom Valmantas Budrys, Lithuania Pasquale Calabrese, Switzerland Stefano F. Cappa, Italy Evelien Carrette, Beglium Mamede Carvalho, Portugal Valeria Caso, Italy Raffaella Chieffo, Italy Giovanni Cirillo, Italy Hannah Cock, United Kingdom Carlo Colosimo, Italy Giancarlo Comi, Italy Charlotte Cordonnier, France Laszlo Csiba, Hungary Maxwell Damian, United Kingdom Marianne de Visser, Netherlands Günther Deuschl, Germany Marianne Dieterich, Germany Volker Dietz, Switzerland Marija Djukic, Germany Mark Edwards, United Kingdom Mikael Elam, Sweden Kirsten Elwischger, Austria Christian Enzinger, Austria Cristian Falup-Pecurariu, United Kingdom Antonio Federico, Italy Daniela Ferrari, Italy José Manuel Morao Cabral Ferro, Portugal Massimo Filippi, Italy Katharina Fink, Sweden Sten Fredrikson, Sweden Franz Gerstenbrand, Austria Nils Erik Gilhus, Norway Colette Griffin, United Kingdom Wolfgang Grisold, Austria Michael Guger, Austria Orsi Györfi, Hungary Ellen Merete Hagen, Norway Hans-Peter Hartung, Germany

Mirjam Heldner, Switzerland David Henshall, Ireland Max Hilz, Germany Rigmor Hoejland Jensen, Denmark Martin Holtkamp, Germany Alex Iranzo, Spain Poul Jennum, Denmark L.J. Kappelle, Netherlands Alexander Karameshev, Bulgaria Viktoria Kdziezyc, Poland Samson Khachatryan, Armenia Thomas Klopstock, Germany Wolfgang Köhler, Germany Daniel Kondziella, Denmark Janika Kõrv, Estonia Jera Kruja, Albania Jan Kuks, Netherlands Theodor Landis, Switzerland Nicola Latronico, Italy Jean Marc Léger, France Maurizio Leone, Italy Vitalie Lisnic, Moldova Antonella Macerollo, Italy Björn Machner, Germany Monica Margoni, Italy Davide Martino, United Kingdom Christopher Mathias, United Kingdom Edgar Meinl, Germany Ioannis Milonas, Greece Antonija Mišmaš, Croatia Monica Moarcas, United Kingdom Xavier Montalban, Spain Lucia Muntean, Germany Bo Norrving, Sweden Jes Olesen, Denmark Józef Opara, Poland Celia Oreja-Guevara, Spain Cristina Panea, Romania Eleftherios Papathanasiou, Cyprus Fabienne Perren, Switzerland Daniela Pohl, Canada Dorota Religa, Sweden Martin Rossor, United Kingdom Roberta Rudà, Italy Evzen Ruzicka, Czech Republic Ettore Salsano, Italy Anna Sauerbier, United Kingdom Reinhold Schmidt, Austria Erich Schmutzhard, Austria Benedikt Schoser, Germany Johann Sellner, Austria Vincenzo Silani, Italy Riccardo Soffietti, Italy

Claudia Sommer, Germany Till Sprenger, Switzerland Israel Steiner, Israel Guido Stoll, Germany Walter Struhal, Austria Pille Taba, Estonia Marc Tardieu, France Klaus V. Toyka, Germany Maria Troiano, Italy Alexander Tsiskaridze, Georgia Josep Valls-Solé, Spain Edina Varga, Hungary Timo Vesikari, Finland Marie Vidailhet, France Angela Vincent, United Kingdom David Vodušek, Slovenia Kristl Vonck, Belgium Nataliya Yavorska, Ukraine

European Journal of Neurology Volume 23, Supplement 1, May 2016 Abstracts of the 2nd Congress of the European Academy of Neurology, Copenhagen, Denmark, May 2016

Contents 1 1

SYMPOSIA Saturday, 28 May 1 3 4 6

8

111 POSTER 111 Saturday, 28 May

Plenary Symposium: Neuroimaging of dementia New perspectives in the treatment of neuromuscular diseases: therapies on the horizon ESO/EAN: Acute stroke: new opportunities and challenges for neurologists EHF/EAN Topical Symposium: CGRP antibodies: a new class of migraine-specific preventive medication

Tuesday, 31 May 16 17 19 ??

21

Understanding functional connectivity using MRI New diagnostic developments in epilepsy Untangling inflammatory and degenerative aspects of multiple sclerosis Plenary Symposium: Highlight and late breaking news

ORAL SESSIONS Saturday, 28 May 21

Autonomic nervous system disorders and Clinical neurophysiology 25 Epilepsy 1 28 Movement disorders 1 30 MS and related disorders 1 34 Neuroepidemiology 37 Neurogenetics 40 Cerebrovascular diseases 1 44 Motor neurone disease 48 Sleep disorders 52 Epilepsy 2 56 MS and related disorders 2 60 Neuro-oncology

63

Cerebrovascular diseases 2 Cognitive neurology/neuropsychology 2 Headache and pain 2 Movement disorders 3 Muscle and neuromuscular junction disease

Monday, 30 May

14

21

Monday, 30 May 93 97 100 104 107

8 10 12

16

MDS-ES/EAN: Update in movement disorders Neurostimulation, what can be achieved in… The changing landscape of coma treatment Evolving concepts in the management of gliomas

93

Sunday, 29 May 63 Child neurology 66 Cognitive neurology/neuropsychology 1 69 MS and related disorders 3 73 Neurorehabilitation 77 Ageing and dementia 80 Headache and pain 1 83 Neuroimaging and Neuroimmunology 87 Critical care 90 Movement disorders 2

111 117 121 130 137 145 152 159 166 171 177 184 190 197 202 209 217 223 230 236 243 250 257 265 270 277 285 291 300 307 314 320 327 334 340 347 353

Ageing and dementia 1 Autonomic nervous system 1 Cerebrovascular diseases 1 Cerebrovascular diseases 2 Cerebrovascular diseases 3 Child neurology/developmental neurology Clinical neurophysiology 1 Cognitive neurology/neuropsychology 1 Critical care Epilepsy 1 Epilepsy 2 Headache and pain 1 Movement disorders 1 MS and related disorders 1 MS and related disorders 2 MS and related disorders 3 Muscle and neuromuscular junction disease 1 Neuro-oncology 1 Neurorehabilitation 1 Peripheral nerve disorders 1 Sleep disorders 1 Spinal cord and root disorders Ageing and dementia 2 Autonomic nervous system 2 Cerebrovascular diseases 4 Cerebrovascular diseases 5 Clinical neurophysiology 2 Epilepsy 3 Headache and pain 2 Movement disorders 2 Movement disorders 3 MS and related disorders 4 MS and related disorders 5 Muscle and neuromuscular junction disease 2 Neuroimaging 1 Neurological manifestations of systemic diseases 1 Peripheral nerve disorders 2

Contents

359 Sunday, 29 May 359 366 373 381 388 394 402 410 417 424 431 438 444 448 455 463 470 476 483 490 497 504 510 517 520 532 540 547 554 564 571 577 581 589 598 606 611 618

625 Monday, 30 May

Ageing and dementia 3 Cerebrovascular diseases 6 Cerebrovascular diseases 7 Cognitive neurology/neuropsychology 2 Epilepsy 4 Headache and pain 3 Motor neurone diseases 1 Movement disorders 4 MS and related disorders 6 MS and related disorders 7 MS and related disorders 8 Muscle and neuromuscular junction disease 3 Neuroepidemiology 1 Neurogenetics 1 Neuroimmunology 1 Neuro-oncology 2 Neuro-ophthalmology/ neuro-otology 1 Neurorehabilitation 2 Neurotoxicology/occupational neurology Peripheral nerve disorders 3 Sleep disorders 2 Ageing and dementia 4 Cerebrovascular diseases 8 Cerebrovascular diseases 9 Epilepsy 5 Headache and pain 4 Motor neurone diseases 2 Movement disorders 5 MS and related disorders 9 MS and related disorders 10 Muscle and neuromuscular junction disease 4 Neuroepidemiology 2 Neurogenetics 2 Neuroimaging 2 Neuroimmunology 2 Neurological manifestations of systemic diseases 2 Neuro-ophthalmology/ neuro-otology 2 Peripheral nerve disorders 4

625 Ageing and dementia 5 631 Cerebrovascular diseases 10 639 Cerebrovascular diseases 11 647 Cognitive neurology/neuropsychology 3 654 Epilepsy 6 662 Headache and pain 5 668 Infection and AIDS 1 675 Motor neurone diseases 3 681 Movement disorders 6 688 Movement disorders 7 694 MS and related disorders 11 703 MS and related disorders 12 711 MS and related disorders 13 718 Muscle and neuromuscular junction disease 5 724 Neurogenetics 3 737 Neuroimmunology 3 739 Neuro-oncology 3 747 Neuro-ophthalmology/ neuro-otology 3 754 Neurorehabilitation 3 760 Neurotraumatology 768 Peripheral nerve disorders 5 774 Sleep disorders 3 781 Ageing and dementia 6 787 Cerebrovascular diseases 12 793 Cerebrovascular diseases 13 800 Epilepsy 7 807 Headache and pain 6 814 Headache and pain 7 822 Infection and AIDS 2 829 Motor neurone diseases 4 834 Movement disorders 8 840 Movement disorders 9 845 MS and related disorders 14 852 MS and related disorders 15 860 Muscle and neuromuscular junction disease 6 867 Neurogenetics 4 874 Neuroimaging 3 882 Neuroimmunology 4 889 Neurological manifestations of systemic diseases 3 894 Neurology and arts; History of neurology; Ethics in neurology; Education in neurology

902 Neuro-ophthalmology/ neuro-otology 4 908 Peripheral nerve disorders 6

© 2016 EAN European Journal of Neurology 22 (Suppl. 1)

Contents

913 FOKUSED WORKSHOPS

947 TOURNAMENTS

913 Saturday, 28 May

947 Sunday, 29 May

913 Advanced imaging methods for the assessment of 914 915 917 918 919

MS pathogenesis and treatment Genetic approaches in neuropathies Addressing quality of care for neurological patients Frontier applications in neurosonology Abnormal movements in sleep New concepts about language processing in the brain

947 Tournament 1 – basic neurology

951 Monday, 30 June 951 Tournament 2 – clinical neurology

956 AUTHOR AND POSTER INDEX

920 Sunday, 29 May 920 Stem cell therapies for the treatment of neurological diseases

921 MDS-ES/EAN: Tics and Tourette syndrome – consensus and controversies

922 Focal dementias 923 MDS-ES/EAN: Biomarkers for Parkinson’s disease 925 Impaired hand function after stroke and peripheral nerve injury: consequences for treatment

926 Monday, 30 May 926 Sleep and cognition 927 Gut microbiota, immunology and neurological diseases 928 Exome sequencing goes bedside: new genes in neurological disorders

930 Syndromes of central visual and vestibular disorders 931 ALS and FTD: two converging diseases?

933 SPECIAL SESSIONS 933 Saturday, 28 May 933 MDS-ES European Basal Ganglia Club 933 Music and neurology - neurological disorders of famous composers

935 Sunday, 29 May 935 New European neurological guidelines 936 EFNA Open Dialogue: Let’s Talk about sex, sleep and stress – Patients’ Choice

938 Monday, 30 May 938 PAUNS/EAN Neuromediterranean Session: Infectious diseases 939 ILAE-CES/EAN: Hot topics in epilepsy

941 Tuesday, 30 May 941 European reference network 942 Shared decision making in neurology 944 RRFS Session-Prospects for neurologists in training in three corners of Europe 945 History of Neurology

© 2016 EAN European Journal of Neurology 22 (Suppl. 1)

© 2016 European Journal of Neurology, 23 (Suppl. 1), 1–20

Symposia Saturday, 28 May Symposium 1 MDS-ES/EAN: Update in movement disorders SYMP01-1 Essential tremor G. Deuschl

Kiel, Germany

Backround and purpose: Essential tremor is so far only clinically defined and the separation from dystonic tremor, some cerebellar tremors and psychogenic tremor may be difficult. Consented differential diagnostic criteria are lacking. Therefore, a classification on the basis of surrogate data would be helpful. Despite significant efforts attempts to classify the patients on the basis of clinical description, pathology, biochemistry, neurophysiology or genetics did unfortunately not lead to a generally accepted consensus. This is in particular surprising as twin studies are suggesting a strong hereditary component for ET. There is still a controversy if ET represents a neurodegenerative entity or only a slowly progressive functional disturbance. Certainly a proof for neurodegeneration needs convincing signs for earlier death or at least a progressive clinical decline apart from the motor disturbance. There are data suggesting that ET can be subdivided on the basis of the age at onset, as the vast majority develops after the age of 50 years. Indeed the early and the late onset cases differ in the amount of patients with alcohol-sensitivity and a positive family history for tremor. Only the late onset cases seem to have a shorter life expectancy and evidence for a more rapid cognitive decline. This needs to be confirmed in prospective studies. The currently reached consensus is that the new definition should include very careful phenotyping of each patient clinically and if possibly with additional methods. Disclosure: Nothing to disclose.

SYMP01-2 Non-motor symptoms in Parkinson's disease K.R. Chaudhuri

whole journey of a person with Parkinson’s. The burden of NMS as a whole is recognised as one of the defining constituent of health related quality of life of people with Parkinson’s. NMS also substantially increases the cost of care of PD and leads to increased hospitalisation, and treatment of NMS poses one of the biggest challenges to health care professionals dealing with PD. However, in the clinic and in clinical practice NMS continues to be regarded as a peripheral issue compared to motor symptoms management of PD. NMS are now the key component of “pre motor “ PD and new evidence suggest evidence of discrete non motor subtypes in PD. This could led to “subtype specific” treatment packages. Evidence also suggest that conventional non oral dopaminergic therapies may help motor and non motor aspects of PD while NMS also may form of the spectrum of acute medical presentations in PD. In part this has led the international Parkinson and Movement Disorder Society (IPMDS) task force to attempt a re-definition of PD incorporating NMS and not base the diagnosis solely on motor symptoms. While motor subtypes within PD have been recognized and researched, recent, clinical and neurobiological research suggests the existence of discrete non-motor subtypes in PD, particularly in untreated (drug naïve) and early PD patients. Several independent observers have reported specific “clusters of NMS dominant PD” using a data driven approach in early and untreated PD patients while others have reported on the burden of NMS in untreated PD and specific NMS dominant phenotypes in untreated or treated PD using observational case series based data. We have reported specific NMS dominant phenotypes of PD as described in the literature using clinical observational studies and address pathophysiological concepts. This is the basis of for several NMS subtypes combining clinical reports with, where possible, evidence base supporting probable biomarkers. References: Chaudhuri KR, Schapira AHV. The non motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 2009; 8: 464-474. Todorova A, Jenner P, Ray Chaudhuri K. Nonmotor Parkinson’s: integral to motor parkinson’s, yet often neglected. Practical Neurology.2014 doi:10.1136/ practneurol-2013-000741 A Sauerbier, P Jenner, A Todorova, K Ray Chaudhuri. Non motor subtypes and Parkinson's disease. Parkinsonism and Related Disorders 22 (2016) S41eS46 Disclosure: Nothing to disclose.

London, United Kingdom

Backround and purpose: Non-motor symptoms (NMS) have emerged as a key component of Parkinson’s disease (PD) from a possible role as clinical biomarker in the premotor phase to a range of symptoms that complicate the

© 2016 EAN

1

2

Symposia

SYMP01-3 Dystonia E. Dietrichs

Oslo, Norway

Backround and purpose: According to the proposed new classification we distinguish isolated (previously called primary) and combined (secondary) dystonias. The causes of most dystonias have remained enigmatic, but novel genetic findings as well as new insights concerning plasticity in basal ganglia and other neural networks may give clues to dystonia pathophysiology. Botulinum toxin represents a good option for symptomatic treatment in many patients, especially for those with focal or segmental dystonia. Deep brain stimulation is also well documented, with good results also for long-term treatment. Disclosure: Nothing to disclose.

SYMP01-4 PSP/MSA M. Stamelou

Athens, Greece

Backround and purpose: Update in Movement Disorders: PSP/MSA Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are atypical parkinsonian syndromes with largely unknown etiology, and no available effective treatments. However, the recent years a plethora of new evidence both in terms of etiology/pathophysiology and treatment options as well as clinical trials have become available. A genome-wide association study in PSP has provided risk-loci, which have been shown to have a direct association to tau pathology in vitro. The first gene (CoQ2) possibly associated with autosomal dominant MSA has been described. In terms of diagnosis, new clinical criteria are under development for PSP, while tau-PET imaging is intensevely being studied. In terms of treatment, the largest double-blind placebo controlled trials have been pulbished in both disorders providing important information for further clinical trials. Currently, a plethora of neuroprotective agents are being tested in double-blind, placebo-controlled trials for both disorders. Disclosure: Nothing to disclose


Symposia

3

Symposium 2 Neurostimulation, what can be achieved in...

SYMP02-3

SYMP02-1

Backround and purpose: Deep Brain Stimulation (DBS) is an invasive neurosurgical intervention established in movement disorders, reported also to improve symptoms of depression, Obsessive Compulsive Disorder, epilepsy, obesity and pain. Over time, several brain structures have been targeted to relieve pain, including the periventricular/ periaqueductal gray area (PAG) and the ventral posterior medial and lateral nuclei of the sensory thalamus (VPL). In our long-term case series, DBS has been used with varying degrees of success for facial pain, post-stroke pain, brachial plexus injury, and phantom limb pain 1. Pain is a multifaceted phenomenon, and some patients, with widespread pain, may benefit from targeting regions involved in its affective dimension, such as the anterior cingulate cortex (ACC). We recently demonstrated that DBS of the ACC can significantly alleviate the suffering of patients with treatment resistant chronic pain 2. This provides a promising avenue for patients for whom other treatments including PAG and VPL DBS are ineffective. Disclosure: Nothing to disclose.

...movement disorders M.J.D. Vidailhet Paris, France

Backround and purpose: Deep brain stimulation has been an major breakthrough in the treatment of movement disorders including dystonia, tremor and severe Tourette syndrome. Indication, efficacy and long term follow-up results will be reviewed from the literature and illustrated by videos and clinical observations. Targets will be discussed (thalamus, pallidum, STN). A few examples of Parkinson’s disease treated by subthalamus nucleus deep brain stimulation will be provided, including positive effects and adverse effects (freezing of gait, eyelid apraxia). Disclosure: Nothing to disclose.

SYMP02-2 ...epilepsy

...chronic pain S. Boccard

Oxford, United Kingdom

K. Vonck

Ghent, Belgium

Backround and purpose: Neurostimulation is an emerging treatment for neuropsychiatric disorders. Excitabilityreducing neurostimulation is pursued as an alternative therapeutic strategy for refractory epilepsy when drugs and surgery fail or are not indicated. For intracranial neurostimulation, stimulation electrodes are inserted into intracerebral targets in ‘deep brain stimulation’ (DBS) or placed over the cortical convexity for ‘cortical stimulation’ (CS) to administer electrical pulses to central nervous system structures. These modalities of neurostimulation are not entirely new for neurological indications. Some have been extensively applied in movement disorders and pain. Several new indications such as obsessive compulsive behaviour and cluster headache are being investigated with promising results. In the past DBS and CS of different brain structures such as the cerebellum, the locus coeruleus and the thalamus were performed mainly in patients with spasticity or psychiatric disorders who had epilepsy as a comorbidity. The vast progress in biotechnology along with the experience in other neurological diseases in the past ten years has led to a renewed interest in intracerebral stimulation for epilepsy. Several epilepsy centers around the world have recently conducted trials with DBS in different intracerebral structures such as the thalamus, the subthalamic nucleus, the caudate nucleus and medial temporal lobe structures. Also CS has been investigated in a multicenter trial in a socalled closed-loop system. Especially CS of eloquent cortex may be developed into a valuable alternative for resective surgery to treat refractory partial focal seizures arising from eloquent cortex. Disclosure: Nothing to disclose.


4

Symposia

Symposium 3 The changing landscape of coma treatment

SYMP03-2

SYMP03-1

Clermont-Ferrand, France

Amantadine, benefit-risk balance in severe brain injury J.T. Giacino

Charlestown, USA

Backround and purpose: This presentation will describe the results of a 12-site randomized, double-blinded, placebo-controlled trial of amantadine hydrochloride (AH) completed in 184 patients with prolonged post-traumatic disorders of consciousness. Patients were in a vegetative or minimally conscious state, between 4 and 16 weeks postinjury and were undergoing inpatient rehabilitation. Following baseline examination, patients were randomized to 4 weeks of amantadine or placebo and followed for 2 additional weeks after drug discontinuation. Rate of functional recovery was monitored on the Disability Rating Scale (DRS) and the Coma Recovery Scale- Revised (CRSR) during the treatment window, and over a two-week washout period. Mixed-effect regression models were used to analyze the results. During the four week treatment period, the amantadine group recovered significantly faster on the DRS compared with the placebo group (0.24 points/ week faster; p=0.007). In a pre-specified subgroup analysis, the treatment effect was similar for patients in both the vegetative and minimally conscious states. The rate of improvement in the amantadine group slowed after treatment discontinuation, so that improvement in the amantadine group was slower than in the placebo group for study weeks 5-6 (.30 DRS points/week slower; p = .02). Degree of improvement in DRS scores between baseline and week 6 (2 week post treatment discontinuation) was similar in the placebo and amantadine groups. There were no significant differences in the incidence of serious adverse events. In conclusion, amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. Disclosure: The National Institute on Disability and Rehabilitation Research (NIDRR Award # H133A031713) provided all support for this study, including funds to purchase amantadine hydrochloride.

Deep brain stimulation in the minimally conscious state: which targets? J.-J. Lemaire

Backround and purpose: The modulation of consciousness processes with deep brain stimulation (DBS) in minimally consciousness state is challenging. Indeed the clinical knowledge is still limited relying on 7 studies published between 1968 and 2016 reporting effects in 58 vegetative or minimally conscious patients. Although very inhomogeneous they harvested clues that electric stimulation of deep gray structures, particularly of the thalamus, can provoke overt conscious behaviors. The role of thalamus in consciousness processes is well documented, notably of intralaminar nuclei as relay-control between the upper brainstem (tegmentum) and the cortex. Nowadays there is a growing body of evidences that consciousness, close to cognition as far as they are different, brings into operation different elements of the overall brain circuitry, such as input relay-controllers within the brainstem and cortices, thalamic nuclei, basal ganglia and the executivebehavioral system. Within such an extended network DBS could potentially modulate deeply located nodes, as it does in movement and neuropsychiatric disorders, which could be relevant for future clinical applications; this therapeuticdriven application could also help to decipher the altered dynamics of neural correlates of disorder of consciousness. Disclosure: Nothing to disclose.

SYMP03-3 Modulating the anterior forebrain mesocircuit in disorders of consciousness N.D. Schiff

New York, USA

Backround and purpose: This presentation will discuss the “mesocircuit hypothesis” for the key role of the human anterior forebrain mesocircuit in recovery from disorders of consciousness following multi-focal brain injuries. The mesocircuit model makes several specific predictions for the co-variation of measures reflecting progressive restoration of cellular and circuit-level functional integrity following severe deafferentation produced by brain injuries. The talk will focus primarily on . modulation of the mesocircuit in studies of human subjects and experimental animal. Testing of model predictions using quantitative measurements of local and global dynamics of the human electroencephalogram (EEG), and measurements from neuroimaging studies of patients with disorders of consciousness will be highlighted. Validation of the predictions derived from this large-scale brain network model may provide a set of measures useful to track recovery and predict the impact of different therapeutic inventions in the injured brain on an individual basis. Disclosure: Nothing to disclose.


Symposia

SYMP03-4

Transcranial direct current stimulation: a promising new avenue S. Laureys

Liege, Belgium

Backround and purpose: The past 15 years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage. Highlighted among these discoveries are unique demonstrations that patients with little or no behavioral evidence of conscious awareness may retain critical cognitive capacities and the first scientific demonstrations that some patients, with severely injured brains and very longstanding conditions of limited behavioral responsiveness, may nonetheless harbor latent capacities for recovery (Laureys & Schiff, NeuroImage 2012; Giacino et al Nature Reviews Neurology 2014). We will here discuss the potential therapeutic efficacy of transcranial direct current stimulation (tDCS) in disorders of consciousness. tDCS was recently shown to improve the level of consciousness in patients in a minimally conscious state (MCS) (Thibaut et al, Neurology 2014). tDCS delivers a weak (usually 1–2 mA) electrical current through the brain using two electrodes, an anode (target electrode) and a cathode (reference electrode) placed on the scalp. It is presumed that anodal tDCS strengthens synaptic connections through a mechanism similar to long-term potentiation and an increase in NMDA receptor excitability, which could improve and strengthen cortical excitability within the stimulated area. We recently identified that responders to tDCS (stimulation over the left prefrontal cortex) showed more grey matter preservation and residual metabolic activity, as compared to non-responders, in the stimulated area (i.e., left prefrontal cortex), in the precuneus, and in the thalamus, all areas known to be involved conscious processes (Thibaut et al, Brain Stimulation 2015). Disclosure: Nothing to disclose.


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6

Symposia

Symposium 4 Evolving concepts in the management of gliomas

SYMP04-2

SYMP04-1

Zurich, Switzerland

How to integrate molecular markers of prognostic significance in the new WHO classification? J. Kros

Rotterdam, The Netherlands

Backround and purpose: Over the past decade a flood of genetic data on primary brain tumors became known. Part of the various genetic aberrations was tested in retrospective and prospective settings for either diagnostic, prognostic or predictive significance. Particularly, codeletion of the chromosome arms 1p and 19q and mutation of IDH1 appeared to have significant impacts on prognosis. The codeletion 1p/19q is diagnostic for oligodendroglioma and were found mutually exclusive with mutations of ATRX, which are associated with astrocytic lineage of tumor cells. Importantly, the codeletion predicts better responsiveness to alkylating chemotherapy. Mutations of IDH are present in 70% of all diffusely infiltrating gliomas and are found in both oligodendrogliomas and astrocytomas. The prognostic impact of IDH mutation reportedly overrides grading of these tumors. The majority of non-IDH mutated gliomas overlap with primary glioblastomas, which usually have a set of additional aberrations like amplification of EGFR. Further, particular astrocytoma subtypes do not have IDH mutations but carry other genetic characteristics: the pilocytic astrocytomas usually come with the KIAA1549BRAF fusion gene while the relative infrequent midline gliomas show mutations in histone H3-K27M. Also for ependymomas and medulloblastomas genetic characteristics have become definers for behavior and therapy responsiveness. In the 2007 edition of the WHO classification of CNS tumors for only few tumors genetic hallmarks were mentioned in the definitions, a big leap forward is made in the 2016 revision where the above mentioned genotypes have been incorporated into the definitions of the tumors. Diagnoses therefore should provide layers of classic histology and molecular data. To accommodate centers without access to molecular diagnostics the term NOS should indicate that only a histopathological diagnosis was provided. Disclosure: Nothing to disclose.

Will new forms of immunotherapy improve the outcome of glioblastomas? M. Weller

Backround and purpose: The current standard of care for glioblastoma of resection followed by involved-field radiotherapy and concomitant and maintenance temozolomide chemotherapy (TMZ/RT->TMZ) prolongs survival to a median of 16 months in clinical trial populations, but survival with glioblastoma is still below 12 months on a population level. Immune inhibition is one of the biological hallmarks of glioblastoma, prompting the clinical development of various immunotherapeutic strategies that are at present explored in phase I-III clinical trials. Efforts focusing on the antagonism of gliomaassociated immunosuppression alone, e.g., blocking the transforming growth factor (TGF)-ß pathway, have not been successful. However, abrogating inhibitory signalling to T cells via cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed death (PD)-1 using various neutralizing antibodies has generated new hope not only for several solid cancers outside the brain, but also for glioblastoma. A phase III trial comparing the PD-1 antibody nivolumab with bevacizumab in glioblastoma at first relapse has completed accrual. Various vaccination approaches are also being tested, including dendritic cell-based vaccines, using either crude tumor lysates (DCVax) or tailored mRNA or peptide stimulation (ICT-107). The most advanced approach explored in phase III (ACT IV) is based on the vaccination against a mutant variant of the epidermal growth factor receptor (EGFR), EGFRvIII, which is expressed in approximately 20-30% of all primary glioblastomas. This mutation results in inability to bind ligand and constitutive signalling activity. Moreover, EGFRvIII represents a unique tumor antigen exhibiting a novel peptide sequence and may thus represent one of the most specific tumor antigens in glioblastoma. Disclosure: Nothing to disclose.


Symposia

SYMP04-3 From chemotherapy to targeted therapy in low grade gliomas R. Soffietti Turin, Italy

Backround and purpose: Several issues regarding the optimization of chemotherapy in newly diagnosed low grade gliomas (grade II WHO) are still debated : association with radiotherapy or initial treatment alone; best regimen and duration; role of molecular factors to predict response and outcome; role of neuroimaging to predict response and outcome. RTOG 9802 has recently reported a significant advantage in terms of PFS and OS for the addition of PCV chemotherapy to radiotherapy in the postsurgical treatment of high risk grade II gliomas. Phase II trials on chemotherapy (temozolomide) alone as initial treatment, delaying RT as salvage, have reported a response rate of about 40-60% with significant seizure reduction. 1p/19q codeletion is so far the unique molecular marker with a predictive value. Commonly used to evaluate the response are the RANO criteria, but a more precise qualification of tumor volume on MRI and/or metabolic evaluation by PET with aminoacids are increasingly adopted. Ongoing studies are evaluating the role of an adjuvant RT+TMZ or of preoperative chemotherapy with TMZ. Targeted agents to inhibit specific molecular changes (m-TOR pathway, IDH1/2 mutations, etc) are entering the area of clinical trials. Disclosure: Nothing to disclose

SYMP04-4 New developments in neuroimaging to monitor response and toxicity following antiangiogenic agents W. Wick

Heidelberg, Germany

Backround and purpose: Disease status evaluation in brain tumors is complicated by treatment-induced changes, which may be desired (as with immunotherapies) or potentially not desired (as with radiotherapy). Similarly, discordance between enhancing and non-enhancing tumor may complicate the assessment of objective responses. Measures to assess pseudoprogression or pseudoresponse have been developed with algorithms reducing imaging bias of calling progression too early. In addition, advanced magnetic resonance imaging (MRI) with T1 subtraction, susceptibility-weighted, dynamic perfusion and diffusion images have been used to reduce the level of uncertainty in the early treatment phase after chemoradiotherapy, but also to substantiate responses in cases, in which contrastenhancement alone is not sufficient to assess the tumor growth or regression. Data on progression patterns, progression types, the value of new MRI techniques and an outlook on metabolic imaging is presented. Disclosure: Nothing to disclose.


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Symposia

Monday, 30 May

PLEN02-2 Imaging of Alzheimer's disease

Plenary Symposium 2 Neuroimaging of dementia PLEN02-1 Imaging of cerebral small vessel disease R. Schmidt

Graz, Austria

Backround and purpose: Cerebral small vessel pathology is heterogeneous and results in lacunar strokes, microinfarcts, white matter lesions, microbleeds , and microstructural abnormalities detectable by advanced MRI techniques. Acute small subcortical infarcts only partly become lacunes. The factors that influence cavitation are widely unknown. Incident lacunes localize preferentially at the edge of white matter abnormalities. It has been suggested that the „white matter hyperintensity penumbra“- the area of microstructurally altered surrounding tissue plays a role in the occurrence of lacunes closely related white matter abnormalities. White matter abnormalities represent a plethora of changes with varying clinical significance. Nonetheless, the magnitude of the diffuse microstructural damage of the white matter rather determines cognitive impairment than the extent of visible white matter foci per se. Another important determinant of cognitive impairment is atrophy. There is increasing evidence that cortical atrophy may have a pure vascular basis. The change of small vessel disease-related lesions might serve as secondary outcome measures in clinical trials in patients with vascular cognitive impairment. Yet, the validation status of lesion change as a surrogate endpoint is incomplete. It is best established for confluent white matter lesions. However, if the expected change in cognitive performance resulting from treatment effects on lesion progression is used as an outcome, the sample size needed to show treatment effects becomes very large. Validation of surrogate endpoints for trials in subcortical vascular cognitive impairment has high priority to foster establishment of treatment options in this heavily understudied endemic of the aging brain. Disclosure: Nothing to disclose

P. Scheltens

Amsterdam, The Netherlands

Backround and purpose: In this overview I will detail how imaging has changed the landscape of diagnosis of dementia. Starting with MRI and followed by PET imaging of glucose consumption and amyloid and tau has made possible to diagnose the underlying disease even before dementia is present. The presence of imaging biomarkers has enabled new criteria to appear and be implemented in clinical trials. Thus, by using imaging as biomarker for diagnosis and staging of disease, clinical trials are now being carried out, creating hope for the patients of the future Disclosure: Nothing to disclose

PLEN02-3 Imaging of frontotemporal dementia M. Filippi

Milan, Italy

Backround and purpose: Frontotemporal dementia (FTD) is a genetically and clinically heterogeneous syndrome that is characterized by overlapping clinical symptoms involving behaviour, personality, language and/or motor functions and degeneration of the frontal and temporal lobes. The term frontotemporal lobar degeneration (FTLD) is used to describe the proteinopathies associated with clinical FTD. An improved reliability in distinguishing FTD syndromes using neuroimaging techniques may become important in the near future, as etiology-specific modifying treatments are likely to be developed and thus enter the clinical arena. Emerging evidence from network-based neuroimaging studies, such as resting state functional MRI and diffusion tensor MRI studies, have implicated specific large-scale brain networks in the pathogenesis of FTD syndromes, suggesting a new paradigm for explaining the distributed and heterogeneous spreading patterns of pathological proteins in FTLD. Furthermore, measurement of white matter tract involvement seems to be a valid biomarker to provide further in vivo insight into disease progression. Preliminary studies in genetically proven cases suggest that key MRI signatures occur in relation to the different FTDrelated genes. However, open questions remain with regard to how and where pathological protein propagation is initiated and the characterization of the major factors playing a role in the modulation of pathology spreading in these conditions. Future longitudinal studies of multimodal imaging datasets, involving subjects in the preclinical phase of the disease, will help understanding the apparent selective network vulnerability of brain regions in various FTD syndromes and predicting disease spread. Disclosure: Nothing to disclose


Symposia

PLEN02-4 Monitoring treatment response in dementia trials N.C. Fox


Backround and purpose: Trials in dementia are changing and so are the roles of imaging in those trials. Historically most trials were in mild-to-moderate Alzheimer’s disease and imaging was only used for inclusion/exclusion. Subsequently imaging has been adopted to assess effects of therapy as a safety read and importantly as an outcome measure. The aims of including imaging as an outcome were to show evidence of disease modification and/or to provide an alternative, more powerful, means of assessing efficacy than clinical scales. Natural history studies estimated that fewer subjects were needed to show a given effect on imaging measures such as rates of brain/hippocampal atrophy. The anti-amyloid immunotherapy trials challenged assumptions about the effects on therapies on brain volume with studies showing that therapies could increase volume losses without cognitive worsening. At the same time amyloid imaging using novel PET ligands started to be included in trials providing the opportunity to “see” the effects of therapy on the molecular pathology. The move to trials aimed at pre-manifest disease (especially AD but also FTD or HD) raises new challenges for monitoring treatment effects. Imaging and other biomarkers become more important in “preclinical” trials as clinical outcomes may take years to detect. The range of imaging modalities available to address these challenges is growing. Novel MR methods are being validated, amyloid PET quantification improved, and now tau-PET offers new possibilities for monitoring treatment response in AD and other tauopathies. These new methods and trials will help provide new insights – and hopefully new therapies. Disclosure: UCL has received payment for image analyses or consultancy from Biogen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, Roche and Sanofi. NF receives no personal compensation for this. NF gratefully acknowledges support from the NIHR, the Queen Square BRU in dementia, the Leonard Wolfson Experimental Neurology Centre, the MRC, the Alzheimer’s Society and Alzheimer’s Research UK


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Symposia

Symposium 5 New perspectives in the treatment of neuromuscular diseases: therapies on the horizon

SYMP05-2

SYMP05-1

SYMP05-3

Amyotrophic lateral sclerosis: still far from an effective therapy? V. Silani

Myasthenia gravis: new therapies for new antibodies? TBA

Immune mediated neuropathies: monoclonal antibodies and what else? E. Nobile-Orazio Milan, Italy

Milan, Italy

Backround and purpose: ALS is a neurodegenerative disease characterized by progressive deterioration mainly involving both the corticospinal tract and the anterior horn cells of the brainstem and spinal cord. Patients develop focal and then generalized weakness leading to paralysis. As recently stated (Mitsumoto et al., 2014), there is no disease-modifying therapy for ALS, though riluzole slows the rate of progression and prolongs survival by 2 or 3 months. It also quite evident that ALS is a complex, multifactorial disease with variations in individual susceptibility and phenotype: the clinical and biological complexities of ALS have probably hindered development of effective therapeutic drugs. Precision medicine may be an innovative approach that applies recently developed biomedical technologies to optimize and individualize treatment to the molecular drivers of an individual’s disease. It involves not creation of treatments that are unique to a patient, but rather classification of individuals into subpopulations that differ in their susceptibility, in the biology and/or prognosis of ALS or in their response to a specific treatment. This approach of using tailored, mechanism-based therapies has been applied to cancer care and gained progressively greater impact, but it is only beginning to be considered in ALS. The key elements of phenotypic classification, comprehensive risk assessment, detecting a presymptomatic period, studying potential molecular pathways, developing disease models, discovering biomarkers, and tailoring interventions to molecular specifics probably embody the most modern therapeutical approach to ALS. Disclosure: Nothing to disclose.

Backround and purpose: Chronic immune-mediated neuropathies, including chronic inflammatory demyelinating neuropathy (CIDP), multifocal motor neuropathy (MMN), neuropathies associated with monoclonal gammopathy, are a group of disorders deemed to be caused by an immune response against peripheral nerve. Several immune therapies are effective in these neuropathies including steroids, plasma exchange and highdose intravenous immunoglobulins (IVIg) in CIDP, IVIg in MMN and plasma exchange in neuropathy associated with IgM monoclonal gammopathy but not all patients respond to or tolerate these therapies. A number of immunosuppressive agents have been used in these neuropathies but their efficacy was not confirmed in randomized trials. More recently, new biological agents such as Rituximab have proved to be effective in patients with neuropathy associated with IgM monoclonal gammopathy. This therapy is currently under consideration in other immune neuropathies even if the preliminary results on their efficacy in CIDP and MMN are less promising than expected. Another monoclonal antibodies, Eculizumab, that inhibits terminal complement activation, has been used in MMN showing a minimal effect in some patients. Other therapies currently used in multiple sclerosis has been recently tested in CIDP. Natalizumab was initially found ineffective in a patient with CIDP even it had some effect on three other patients. The positive response to fingolimod in a patient with demyelinating neuropathy awaits confirmation from an ongoing controlled trial in CIDP. Despite the frequent beneficial effect of currently used immune therapies, new therapies are on the horizon for these neuropathies even if their efficacy needs to be proved in controlled studies. Disclosure: Nothing to disclose


Symposia

SYMP05-4 Genetic treatment in muscular dystrophies: hope or reality? F. Muntoni


Backround and purpose: The improved understanding of the genetic basis and molecular events leading to muscle degeneration in muscular dystrophies, coupled with advances in small molecules aimed at interfering with gene transcription and translation, has very rapidly moved in the last decade from proof of concept studies to phase I; II; and III clinical trials in Duchenne muscular dystrophy (DMD). These approaches take advantages of antisense oligonucleotides to target pre-mRNA and induce redirection of splicing in DMD patients with out of frame deletions; and of small molecules to induce read through of nonsense mutations. Clinical trials in myotonic dystrophy have also rapidly advanced, aimed at using antisense oligonucleotides to target the mutant DMPK allele which characterize this condition. The pace of the development of these novel genetic approaches to treat muscular dystrophies is exciting and one of the fastest in recent drug development program. Nevertheless the outcome of recently completed clinical trials in DMD has been variable, with clear signal of clinical efficacy, especially in specific ranges of age and functional abilities, but also failures to meet endpoints in several phase III trials. The field has learned several lessons, especially on optimal disease cohorts to demonstrate clinical efficacy, importance of harmonization of standards of care and strength and weaknesses of different outcome measures used. The indispensable interface with regulatory authorities in USA and Europe for these rare diseases has also demonstrated that more mutual education is necessary. In my presentation I will summarise the status of the art of these developments Disclosure: Francesco Muntoni has served on scientific advisory boards for AcceleronPharma, Genzyme, Sarepta, Debiopharma Group, GlaxoSmithKline, Prosensa, Servier, Italfarmaco, Summit and Santhera Pharmaceutical, received research support from GlaxoSmithKline and Summit, and has received funding for trials from PTC, Biomarin, Sarepta, Pfizer. He also serves in the Pfizer Rare Disease SAB.


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12

Symposia

Symposium 6 ESO/EAN: Acute stroke: new opportunities and challenges for neurologists

Disclosure: Nothing to disclose.

SYMP06-2 Anterior and posterior circulation: mind the differences D. Strbian

SYMP06-1

Espoo, Finland

Intracranial large vessel occlusions: how to recognize them as fast as possible P. Michel

Lausanne, Switzerland

Backround and purpose: First, stroke has to be recognized or at least suspected, both by patients, bystanders and paramedics. This is probably best achieved by using simple preshospital scales such as the FAST or Cinncinati Prehospital Scale, and will decrease the rate of stroke mimics (false positives) and stroke chameleons (false negatives). Patients with suspected stroke and preshospital thrombolysis criteria should be transferred directly to a thrombolysis-capable hospital (usually stroke units) where imaging can also rapidly determine LVO: Onset of symptoms < 4h Potentially disabling deficit Patient relatively independent No rapid resolution of symptoms. Preimaging prediction of LVO can be done with scores quantifying stroke severity, and other items may be added. Such scores may determine which patients are sent directly to an endovascular hospital (usually stroke centers): Motor symptoms alone (Los Angeles Motor Scale) à cut-off ≥4 points Motor and other symptoms o Cincinnati Prehospital Stroke Severity Scale à cut-off ≥2 points o Rapid Arterial oCclusion Evaluation (RACE) à cut-off ≥5 points NIHSS o < 6h: cut-off ~10 points o > 6h: cut-off =7 points NIHSS plus other items (ASTRAL-Occlusion score), i.e. o Female o No prestroke handicap o Atrial fibrillation o Hemineglect à cut-off ≥16 points Such prediction models can also be used upon hospital arrival or with telemedicine. Given their limited reliability, rapid non-invasive imaging should always be sought, preferably CT-angiography (CTA) or MR-angiography (MRA). Combined with clinical information, CTA and MRA are highly accurate. Images may be transferred by teleradiology to an endovascular center before or during patient transfer. CTA can also be performed in an ambulance (“mobile thrombolysis unit”). Once LVO is documented or highly suspected, the patient should be treated immediately by an experienced endovascular team given the low rate (~10%) of rapid recanalisation with thrombolysis alone.

Backround and purpose: Posterior circulation strokes account for approximately 1/5 to ¼ of all strokes, which affect cerebellum, brainstem, mesencephalon, thalamus, and occipital cortex. Vascular supply of these anatomical structures is covered by the vertebrobasilar system (in comparison of carotid system and anterior circulation). Most acute stroke trials include majority of anterior stroke patients, which is not only given by higher aforementioned natural proportion of these stroke types. Another reason for this selection bias arises from recognition of posterior circulation strokes. Corroborating this, clinical signs of the posterior circulation strokes are underrepresented in the classic and widely-used tool for evaluation of an acute stroke patient – the NIHSS score. The problem of posterior stroke recognition does concern both in-hospital setting as well as emergency medical services, including paramedics. The recognition tools used for prehospital recognition (e.g., FAST) are more sensitive for anterior than posterior circulation. These factors usually translate into longer treatment delay for patients suffering from posterior circulation strokes as compared to anterior circulation strokes. This presentation will cover some facts about preand in-hospital recognition, clinical features, imaging, and treatment of anterior vs. posterior circulation strokes. Disclosure: Nothing to disclose.

SYMP06-3 Pathway of acute stroke: how to reduce the ‘pit-stops’ of acute stroke D. Toni

Rome, Italy

Backround and purpose: The time between stroke onset and revascularization treatments, either i.v. thrombolysis or/ and endovascular procedures, influences the probability of reaching functional independence, the risk of dying and the risk of symptomatic bleeding complications. The interval time between arrival at hospital and start of treatment (door to needle and door to groin puncture) is the only component we can directly control. Several factors are important for the rapid initiation of treatment: - Education of dispatchers and EMS personnel: give to stroke a high priority dispatch - Emergency personnel is prepared via pre-notification from the ambulance, and is ready on arrival; radiology department, laboratory nurse, and stroke unit are alerted - Blood pressure, pulse, body temperature, blood sugar and oxygen saturation are already checked by the ambulance personnel on the way to hospital, as is information about onset. A large-bore iv catheter is inserted on the way to hospital.


Symposia

- Preliminary data on level of consciousness (GCS), neurological symptoms, other illnesses and medications as well as personal identity are transmitted to the ER by the ambulance personnel on the way to hospital - Patient electronic charts are reviewed, eye-witness interview before/during transportation - In the emergency room, preliminary data are confirmed, decision taken that the patient is a candidate for thrombolysis/thrombectomy; transfer to CT scanner without delay, blood tests taken (lab technician waiting for the patient, point-of-care INR) - Thrombolysis infusion prepared in the CT room - Stroke physician interprets the CT/AngioCT scan - etc. Disclosure: Nothing to disclose.

SYMP06-4 Who should treat acute large vessel occlusions: neurologists, radiologists or neuro-interventionalists C. Kremer

Malmö, Sweden

Backround and purpose: Recent stroke trials showed that endovascular treatment is superior to iv. thrombolysis in stroke patiens with large vessel occlusions. In the future there will be an increasing demand of specialists who can perform interventional procedures on stroke patients. The question of training interested colleagues among different medical specializations will become a major one. Up to date there are at least five different specializations involved in the endovascular treatment of stroke patients. The majority of interventions is performed by experienced neurointerventionalists. An overview over the possible advantages and eventual disadvantages regarding the treatment of large vessel occlusions by neurologists, radiologists, and neurointerventionalists will be given. eg. Radiolologists are formally certified but often less involved in the treatment of stroke patients and therefore also less sub-specialized in the treatment of occlusions of the intracranial vessels. Neurointerventionalists are more specialized in in vascular interventions but less involved in the acute care of stroke patients. Vascular neurologists/ strokologists are experienced in acute stroke care and welltrained in meeting the diagnostic and therapeutical challenges in the context of acute stroke treatment. But long-term practical training in performing interventions is lacking. Up to date there are just a few experienced vascular neurologists who can perform endovascular treatments. The presentation will also take into account future perspectives regarding the training of vascular neurologists in performing interventions as a part of their specialization. Disclosure: Nothing to disclose


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14

Symposia

Topical Symposium EHF/EAN Topical Symposium: CGRP antibodies: a new class of migrainespecific preventive medication

SYMPTOP-2

SYMPTOP-1

Backround and purpose: Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide identified in the early 1980s that belongs to a structurally conserved family of peptides that includes calcitonin, adrenomedullin and amylin. CGRP is broadly distributed in the nervous system and in the trigeminal pain pathway. The blood vessels of the meninges are richly innervated by CGRP-containing fibers originating in the trigeminal ganglion0, and CGRP is a potent vasodilator both in cranial arteries. Animal models of headache reported release of CGRP from perivascular trigeminal nerve terminals and modulatory role of CGRP in nociceptive transmission. Human studies demonstrated that intravenous infusion of CGRP induces migraine and CGRP antagonism aborts and prevents migraine attacks. The exact pathways involved in CGRP-induced migraine attacks and mechanisms of action of CGRP antagonists/antibodies are not fully clarified but may involve both peripheral and central site of action. Disclosure: Nothing to disclose.

Current treatment for migraine: efficacy and safety outcomes J. Pascual

Santander, Spain

Backround and purpose: Pharmacological treatment of migraine includes acute medications for the attacks, which all migraine patients need, and preventatives, which are indicated for those patients experiencing ≥3 attacks per month. Nonsteroidals and triptans are the drugs of choice for the acute treatment of migraine attacks. Without objective biomarkers, recommended outcomes for evaluating efficacy of these drugs include pain free at 2 h and sustained pain free over the period of 2-24 h. However, it is possible that these outcome measures do not sufficiently reflect the wishes of patients, who want medications working faster and making them able to function properly. We should not forget that people with migraine have a whole range of potentially disabling associated symptoms, such as nausea/vomiting or photo/phonophobia, which would require outcomes measuring global functional disability. Antihypertensives (beta-blockers and candesartan), antiepiepileptics (topiramate and valproate), flunarizine and amitriptyline are the drugs indicated for migraine prevention. Recommended efficacy outcomes for preventatives include, in this order, number of migraine days or attacks, 50% improvement in migraine frequency or consumption of symptomatic acute treatment. Adverse events tend to precede efficacy and, in clinical practice, represent a significant problem leading to treatment discontinuation. Globally, no more than 50-60% of migraine patients show a significant improvement in migraine frequency and around 50% of our migraine patients experience at least tolerability problems with these medications. In conclusion, we need new options, having more efficacy and better tolerability and safety, both for the acute and preventive treatment of migraine. Disclosure: Nothing to disclose

The role of CGRP in migraine: from molecule to man M. Ashina

Frederiksberg, Denmark

SYMPTOP-3 CGRP antibodies in treatment of migraine: efficacy and mechanism of action P.J. Goadsby


Backround and purpose: Calcitonin gene-related peptide (CGRP) plays a pivotal role in the expression of migraine. Blockade of CGRP mechanisms using monoclonal antibodies provides a way to access this mechanism with high specificity and no off target side effects. I will discuss the antibodies in clinical trials in alphabetical order, using the 50% responder rates as the common endpoint for the top dose tested. All outcomes presented were different from placebo, and each medicine test in episodic (EM) or chronic (CM) migraine. ALD403 is an IgG1 humanised CGRP peptide antibody that was tested in an EM study. A single intravenous dose of 1000mg had a 61% responder rate compared to 33% for placebo. AMG334 is an IgG2 human CLR/RAMP1- CGRP receptor- antibody that was tested in an EM study. Given sc monthly at 70mg the responder rate was 47% compared to placebo at 30%. LY2951742 is a humanised CGRP peptide antibody that was tested in an EM study. Given sc bi-weekly at 150mg the responder rate was 70% with a placebo rate of 45%. TEV-48125 is a humanised CGRP antibody that was tested in an EM study. Given sc monthly 675mg had a response rate of 59% with a placebo of 28%. In a CM study given sc monthly at 900mg the response rate was 55% with a placebo of 31%. As a group, these medicines are well tolerated with the most common issue being relatively minor injection site reactions. None have produced liver enzyme changes or substantial cardiovascular changes. Disclosure: Nothing to disclose.


Symposia

SYMPTOP-4 Can acute and preventive migraine medication pass the blood-brain barrier? G.M. Knudsen

Copenhagen, Denmark

Backround and purpose: It is still debatable to what extent anti-migraine drugs act on receptors located in the brain parenchyma, on the intravascularly located cerebral blood vessels, or affects the nociceptive input from the trigeminal nerves. Whereas the first would require a decent degree of blood-brain barrier (BBB) penetrance and brain retention (at least for acute interventions), the latter two may not. It is important to emphasize that the BBB is not a stable construct; it can be modified in various ways and indeed, some data suggest that the BBB is more leaky under an acute migraine attack. Also, there is accumulating preclinical evidence that inflammatory pain states may be associated with a disrupted BBB function (DosSantos et al, 2014). Even under baseline conditions, however, the BBB is never completely impermeable and the drug concentration that eventually reaches the intraparenchymal receptors, although perhaps in small concentrations, may still be pharmacologically active. That is, arguments for or against central versus peripheral mode of action cannot be based on considerations about concentrations and hardly even on measures of central receptor occupancies as measured with, e.g., positron emission tomography (PET), as long as there is no etablished dose-occupancy-efficacy relationship. Although the dosing scheme used in the study was less optimal, the so far single PET-studies that investigated the effect of triptans on 5-HT1B receptor binding did not show any significant occupancy of the receptor (Varnäs et al, 2013). Disclosure: Nothing to disclose.


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Symposia

Tuesday, 31 May Symposium 7 Understanding functional connectivity using MRI SYMP07-1 Brain functional connectivity assessed using MRI: the basis B.B. Biswal

Newark, USA

Backround and purpose: Although long a condition of interest spanning the gamut of neuroimaging modalities, study of the “null”, “fixation” or “resting” state has recently flourished. The fMRI community, in particular, has zealously embraced resting state approaches to mapping brain organization and function. Now, having demonstrated its utility for charting the large-scale functional architecture of the brain, and potential for the identification of biomarkers for clinical conditions, the field is returning to fundamental questions regarding the significance and validity of resting state (intrinsic brain) phenomena. Here, we discuss these challenges, and outline current developments. Disclosure: Nothing to disclose.

SYMP07-2 Clinical applications in MS M.A. Rocca

disease. However, fMRI still require a careful standardization of acquisition and analysis protocols, a careful assessment of scanner stability over time, and normative values as a reference. Disclosure: Nothing to disclose

SYMP07-3 Implications for clinical trial design and monitoring of drug efficacy T. Sprenger

Wiesbaden, Germany

Backround and purpose: Functional connectivity Implications for clinical trial design and monitoring of drug efficacy In the past decade, a high number of studies on human brain connectivity have been published. These studies have helped to shed light on the network architecture of the human brain and also helped to improve our understanding of brain plasticity. The according non-invasive techniques also hold some promise for implementations in the setting of clinical trials. In this talk, the potential of connectivity studies, especially resting state studies, for use in clinical trials, i.e. to identify patient populations or for use as outcome measures, is discussed together in the context of potential pitfalls. Disclosure: The current and/or previous employers of TS received compensation for speaking/advisory board participation from Actelion, ATI, Biogen, ElectroCore, Genzyme, Teva, Novartis, and Mitsubishi Pharma; TS received research grants from EFIC-Grünenthal, Novartis Pharmaceuticals Switzerland, Swiss MS Society, and the Swiss National Science Foundatio´n.

Milan, Italy

Backround and purpose: In MS, physical and cognitive deficits not only reflect structural damage, but also functional imbalance in and between brain networks. Taskrelated and resting-state (RS) functional MRI (fMRI) allows to investigate brain activity across the whole brain and to measure the degree of functional correlation between different cortical regions. Functional connectivity (FC) abnormalities have been shown in patients with MS, from the earliest stages of the disease, in patients with clinically isolated syndromes (CIS) suggestive of MS. A comparison between CIS and relapsing-remitting (RR) MS patients has suggested that cortical reorganization might be an early but finite compensatory phenomenon in this condition. FC abnormalities affect also inter-network connectivity and are related to the extent of T2 lesions and the severity of disability. FC abnormalities of cognitive-related networks have been shown to contribute to the presence and severity of cognitive deficits in patients at different stages of the disease. The potential role of fMRI in the monitoring of cognitive rehabilitation treatment in patients affected by MS has been been demonstrated. Overall, fMRI offers a promising venue to investigate the functional impact of MS pathology, complementing structural conventional and quantitative MRI techniques, to understand better MS pathophysiology from the earliest clinical stages of the


Symposia

Symposium 8 New diagnostic developments in epilepsy SYMP08-1 Definition and classification of seizures J. Peltola

Tampere, Finland

Backround and purpose: The International League Against Epilepsy (ILAE) has recently presented new important contributions, which have been prepared by international task forces as draft manuscripts and then presented to all for comment. “A practical clinical definition of epilepsy” was published 2014. The comments made by the epilepsy community have had a major impact on the final version. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked seizures occurring >24 h apart; (2) one unprovoked seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. In April 2016 a draft version of “Operational Classification of Seizure Types” was posted on the ILAE web site to recognize that some seizure types can have either a focal or generalized onset, to allow classification when the onset is unobserved, to include some missing seizure types and to adopt more transparent names. Changes include: (1) “partial” becomes “focal”; (2) seizures of unknown onset can still be classified; (3) awareness is used as a classifier of focal seizures; (4) the terms dyscognitive, simple partial, complex partial, psychic, secondarily generalized are eliminated; (4) bilateral tonicclonic seizure replaces secondarily generalized seizure. The new classification does not represent a fundamental change, but allows greater flexibility and transparency in naming seizure types. Comments are still open until 4 June 2016. Disclosure: Nothing to disclose.

SYMP08-2 Neurophysiological assessment of epilepsies P.A. Boon

Ghent, Belgium

Backround and purpose: Electroencephaolography (EEG) has an undebated role in confirming the clinical diagnosis of epilepsy in patients with seizures. It is a highly standardized, widely available, uninvasive, reliable and cheap method to record field potentials from brain cortex. Interictal epileptiform discharges (IEDs) are the signature of epilepsy, providing information on which part(s) of the brain are involved in the epileptic process. Interpreting EEG signals involves both sound knowledge of recognizable patterns and insight in electro-clinical correlations. The relationship between the occurrence of IEDs and the type and severity of seizures is complex. In some types of

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epilepsy, EEG allows predicting the natural course or the response to therapy, but this is not the case in many other types of epilepsy. A normal interictal EEG does not exclude epilepsy. EEG recording during photic stimulation or hyperventilation and after sleep deprivation may enhance the sensitivity of EEG in some epileptic conditions. VideoEEG monitoring is a cornerstone diagnostic procedure in patients with medically refractory epilepsy who need a presurgical workup. Diagnostic video-EEG may be necessary to rule out (psychogenic) non-epileptic seizures in some patients. A small number of patients, in whom non-invasive EEG does not provide adequate localizing information needs invasive EEG recording. This EEG modality requires EEG electrodes in the subdural space or in the brain parenchyma, using open and/or stereotactic procedures. Magnetoencephalography (MEG) is a non-invasive tool for neurophysiological diagnosis that when compared to EEG, has a higher spatial resolution and does not require contact electrodes. Whether and in which way MEG may be useful for presurgical localization of the epileptogenic zone in refractory epilepsy patients remains a matter of debate. MEG has a clear potential in determining a presurgcial strategy for invasive EEG-electrodes in highly selected patients. Moreover, MEG is feasible and useful for functional mapping of eloquent cortical areas. Disclosure: Nothing to disclose.

SYMP08-3 3D multimodal imaging for epilepsy surgery J.S. Duncan


Backround and purpose: Brain imaging is critical for successful epilepsy surgery and includes high-resolution structural imaging to revel underlying lesions, and the relationships of lesions to normal anatomy, tractography to delineate critical pathways, such as corticospinal tract and optic radiation, functional MRI to infer the location of eloquent cortex, and arteriography and venography to indicate the anatomy of vessels that must not be compromised. Further, functional imaging of regional cerebral glucose uptake (PET), ictal blood flow (SPECT), electrical and magnetic source imaging and EEG-fMRI can infer the lateralization and localization of epileptic foci and networks. Viewing all these data simultaneously in a common3D anatomical reference enhances decision making regarding the strategy of intracranial EEG recording and the precise placement of individual electrodes, and the planning of surgical resections. Software is now being created to semi-automate the placement of electrodes, with template libraries and with programmes for determining electrode trajectories according to preset rules, such as minimum distance from blood vessels, avoiding sulcal pial boundaries, traversing the skull orthogonally and maximising grey matter contact. Resection planning will integrate these data with the output of intracranial EEG, resulting in a 3D resection target that may then be displayed in the eyepiece of the opera ting microscope, to enable an optimal resection.


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Symposia

Disclosure: Research grant support from UK Department of Health and Wellcome Trust, collaboration with Medtronic.

SYMP08-4 Genetic screening J.M. Serratosa Madrid, Spain

Backround and purpose: More than 80 genes have been found to be responsible for either one specific or several epilepsy phenotypes. Genetic testing in the epilepsies is now widely available in most European countries and is helping clinicians reach a precise diagnosis (offering prognostic and genetic counseling information) and select the most adequate treatment. Genetic testing may reduce diagnostic work-up costs and relieve anxiety to families. Most epilepsies in which a gene has been identified are rare. Among these, the epileptic encephalopathies (EEs) of childhood, the progressive myoclonic epilepsies and some familial epilepsies are the most representative groups. In the EEs it is important to test the parents as most mutations occur de novo and this reinforces the role of a variation in the disease. Different genetic screening techniques are now available including classic Sanger sequencing, next generation sequencing (using gene panels or whole exome or genome sequencing), MLPA and CGH karyotyping. The most appropriate test to be performed highly depends on the phenotype of the patient and on local resources and insurance coverage. Selecting the most cost-effective test for each patient and interpreting the results requires expertise in the field of genetic of the epilepsies. Each genetic finding must be correlated with the clinical picture. The presence of a variation in other affected or non-affected family members or parents, the communication of previously similar phenotypes with the same mutation or mutations in the same gene, and the predicted or reported functional effect must all be considered in order to assign causing pathogenicity. Disclosure: Nothing to disclose.


Symposia

Symposium 9 Untangling inflammatory and degenerative aspects of multiple sclerosis SYMP09-1 Insights from MS pathology W. Brück

University Medical Center Göttingen, Neuropathology, Göttingen, Germany

Backround and purpose: There is increasing evidence from morphological studies that inflammatory and neurodegenerative mechanisms are involved in multiple sclerosis. Besides characteristic lesions in the white matter, there is increasing evidence that inflammatory and degenerative events occur also in the grey matter lesions as well as in the normal appearing white and grey matter. Inflammation and degeneration occurs from the start of the disease and strongly depend on each other. The present lecture aims at demonstrating the quantity and quality of inflammation as well as the nature and extent of neurodegeneration in multiple sclerosis from relapsingremitting to progressive MS as well as within white and grey matter lesions and the normal appearing grey and white matter. The contribution of adaptive and innate immunity as well as the role of peripheral and resident immune cells in mediating neuroaxonal damage in different disease stages will be discussed. Disclosure: Wolfgang Brück is supported by the Deutsche Forschungsgemeinschaft, SFB Transregio 43, The brain as a target of inflammatory processes, project B9, the German Ministry for Education and Research (BMBF), ‘‘German Competence Network Multiple Sclerosis’’ (KKNMS), Pattern MS/NMO and German MS Brain Bank), and by the Klaus Tschira Foundation

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SYMP09-2 Insights from experimental models M. Kerschensteiner

Ludwig-Maximilians-University Munich, Department of Clinical Neuroimmunology, Munich, Germany

Backround and purpose: Here, I want to discuss how insights from the in vivo analysis of experimental models can improve our understanding of the relation of inflammation and neurodegeneration in MS. To illustrate this I will use our recent insights into the in vivo pathogenesis of immune mediated axon damage as an example. Such immune-mediated damage to axons plays a crucial role in multiple sclerosis (MS), however we still understand very little about how immune cells can initiate axon damage. In vivo visualization of fluorescently labeled macrophages/microglia and axons recently allowed us to observe the spatially restricted degeneration of axons in mouse models of MS. This “focal axonal degeneration” appears to be a novel type of axonal degeneration that is characterized by intermediated stages that can persist for several days and progress either to the degeneration or full recovery of the affected axons. Refined subcellular and molecular in vivo imaging approaches now further allow us to investigate the molecular mediators that drive axonal degeneration and to better understand the relation between structural and functional axon damage in neuroinflammatory lesions. Finally we can use cortical imaging approaches in models of gray matter pathology to follow up on recent histopathological findings that indicate the presence of widespread synaptic deficits in advanced stages of MS. Using these examples, I hope to illustrate how recent advances in light microscopy can help us to reveal and mechanistically dissect the interactions of activated immune cells and CNS target cells as they happen in the living CNS. Disclosure: The work presented has been supported by research grants from the European Research Council, the German Federal Ministry for Research and Education and the the German National Science Foundation.


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Symposia

SYMP09-3 Insights from clinical imaging P. Matthews

Department of Neurosciences, Oxford, United Kingdom

Backround and purpose: Acute relapses in MS are associated with new, worsening focal inflammation. Clinical symptoms and signs of relapses are frequently associated with appropriately localised Gd-enhancement and new T2-hyperintense MRI lesions. Their frequency is a strong predictor of short-term disability progression and beneficial effects of current anti-inflammatory medicines to slow relapse rate. More recent evidence suggests that measures of cortical lesion evolution also contribute. Nonetheless, the volume or number of T2 lesions, which are related heterogeneously to inflammatory infiltrates and oedema, demyelination and any subsequent glial scar, do not explain disability well in populations sampled crosssectionally. By contrast, brain volume differences, which have been related largely to loss or atrophy of neurons and their processes, explain a substantial proportion of the variability in disability in the population. Anti-inflammatory treatments for MS slow rates of brain atrophy in patients with relapsing remitting MS, consistent with their impact on relapses and relative rates of relapse related disability progression. However, with one possible exception, these medicines do not slow brain atrophy or disability progression in primary or secondary progressive MS. Recent work using PET with radioligands binding to the 18 kD mitochondrial translocator protein (TSPO) have provided increasingly compelling evidence that chronic, innate immune injury mediated by microglia or astrocyte activation not addressed by most medicines well may be an important factor responsible. Disclosure: Nothing to disclose.

SYMP09-4 Insights from therapeutic trials X. Montalban

Barcelona, Spain



Oral Session Saturday, 28 May Autonomic nervous system disorders and Clinical neurophysiology O1101 Intravascular electroencephalography: a pilot study in patients undergoing neurointerventional surgery V. Keereman1, P. van Mierlo2, L. Defreyne3, P.A. Boon1

LCEN3, Department of Neurology, Ghent University Hospital, 2MEDISIP, Department of Electronics and Information Systems, Ghent University, 3Vascular and Interventional Radiology, Ghent University Hospital, Ghent, Belgium 1

Background and aims: Invasive electroencephalography (EEG) is used in the presurgical evaluation of patients with refractory epilepsy. Although it yields high quality recordings, electrode implantation is associated with a risk of complications. Therefore, a less invasive alternative would be of interest. In this study we demonstrate the feasibility of recording intravascular EEG from an electrode inside the cerebral vasculature. Methods: Intra-arterial EEG was recorded in 5 patients undergoing a neuro-interventional procedure. Before the start of the procedure, 9 EEG recording electrodes were attached using the standard 10-20 system (Fp1-Fp2-C3-C4T3-T4-O1-O2-Cz). A microcatheter was placed over a 0.010” guidewire in the M2 segment of the medial cerebral artery. The micro-catheter was withdrawn so that the distal end of the guidewire was 5mm outside the catheter. The proximal end of the guidewire was connected to the EEG recording amplifier. EEG was recorded for 15 minutes. Results: There were no artefacts that significantly affected signal quality on the intra-arterial EEG channel. Fig. 1 shows an EEG epoch, recorded in a patient in whom the guidewire was placed in the right M2 segment. A highfrequency discharge is detected on the intra-arterial channel which was also detected on the nearest scalp electrode (T4). Fig. 2 depicts the standard deviation on each channel, demonstrating that the amplitude of the intra-arterial channel is approximately 3 times higher than the scalp channels.

Epoch demonstrating the EEG signal recorded on the intravascular (IV) and scalp channels. The intravascular electrode was placed in the M2 segment of the right medial cerebral artery. A high-frequency discharge is observed on the intravascular channel as well as on the nearest scalp electrode (T4).

Signal standard deviation on all channels, demonstrating the higher amplitude of the intravascular channel compared to the scalp EEG channels.

Conclusion: We have demonstrated the feasibility of recording intra-arterial EEG using a guidewire and microcatheter. Our results indicate that intra-arterial EEG could be a less invasive alternative to invasive EEG. Disclosure: Nothing to disclose

© 2016 EAN

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Oral Sessions

O1102 Fatigue of forearm extensor muscles induced by repetitive peripheral magnetic stimulation in healthy subjects C. Cabib1, M. Garcia-Magaña2, M. Morales1, L. Izquierdo-Robert1, P. Pereira3, P. Arias4, J. Valls-Sole5

1Neurology, EMG Unit, Hospital Clinic of Barcelona, Barcelona, Spain, 2Unidad Medicina Familiar, Física y Rehabilitación, Instituto Mexicano del Seguro Social Jalisco, Guadalajara, Mexico, 3Neurology, Hospital Garcia de Orta, Lisbon, Portugal, 4Universidade da Coruña, Coruña, Spain, 5Neurology, Hospital Clinic Barcelona- EMG Unit, Barcelona, Spain

Background and aims: Fatigue is a common symptom associated to several neuromuscular disorders. Electromyostimulation (EMS) is a tool commonly used in neurorehabilitation and in the study of muscle fatigue. However, long-duration electrical stimulation may be painful and this may limit its applicability. Magnetic stimulation of axon terminals and muscle causes considerably less discomfort than EMS. We investigated whether painless repetitive peripheral magnetic stimulation (rPMS) was adequate to induce fatigue, and its profile compared to the fatigue induced by voluntary contraction and EMS in 8 healthy volunteers. Methods: Main outcome measure was force caused by maximal isometric voluntary contraction (MVC) of forearm wrist-extensors, which was performed before (T0) and immediately after (T1) 7seconds of one of three interventions: submaximal voluntary contraction (SVC), EMS (100Hz) and rPMS (30Hz, 55%stimulator-output). Induced torque was similar for all three procedures (~25% maximal voluntary force-MVF). Related outcome measures were relaxation time after MVC and muscle twitch to electrical stimulation, as peripheral-fatigue indices, and motor evoked-potentials to transcranial magnetic stimulation, as central-fatigue index. Results: A significant 10%-decline on MVF was induced by rPMS and EMS, but not by SVC. Relaxation phase was significantly lengthened after both EMS and rPMS (Fig.1). As a difference with EMS, rPMS frequently induced potentiation of muscle twitch (Fig.2). No signs of central fatigue were found after any intervention.

Conclusion: rPMS proved to be successful in revealing peripheral muscle fatigue in this experimental setup, similar to that of EMS with similar torques. Our findings support the possible role of rPMS in further research with patients experiencing fatigue. Disclosure: Nothing to disclose

O1103 De-synchronization does not contribute to intra-cortical inhibition and facilitation: a paired-pulse paradigm combined with triple stimulation study L. Caranzano1, M.A. Stephan2, F. Herrmann3, D. Benninger1

Lausanne, Switzerland, 2Clinical Neurosciences, CHUV, Lausanne, Switzerland, 3Département de médecine interne, de réhabilitation et de gériatrie, HUG, Lausanne, Switzerland 1

Background and aims: The paired-pulse transcranial magnetic stimulation (TMS) paradigms allow the exploration of motor cortex physiology. The Triple Stimulation Technique (TST) improves conventional TMS in more precise quantifying cortico-spinal conduction by reducing effects of de-synchronization of motor neuron discharges and, thereby, also the variability of MEPs. The objective of our study was to explore paired-pulse (PP) TMS paradigms of inhibition and facilitation with the TST in order to study whether the de-synchronization contributes to these phenomena and whether the combined TMS-TST protocol could improve consistency of responses, which could allow their implementation for diagnostic purposes in various clinical conditions with altered intra-cortical inhibition or facilitation. Methods: We investigated the PP paradigms of short intracortical inhibition (SICI) with 2 ms inter-stimulus intervals (ISI) and of intra-cortical facilitation (ICF) with 10 ms ISI in 22 healthy subjects applying either conventional TMS alone or combined with the TST protocol in a randomized order. Results: The results of the PP paradigms of short intracortical inhibition and facilitation with conventional TMS and combined with the TST do not differ. There is an interindividual variability in those measures, which can be reduced by combining the PP paradigm with the TST. Conclusion: These results do not suggest a contribution of the de-synchronization of motor neuron discharges to the paired-pulse paradigms of short intra-cortical inhibition and


Oral Sessions

facilitation. Combining these PP TMS paradigm with the TST may improve the accuracy which could be useful for clinical practice. Disclosure: Nothing to disclose

O1104 Autonomic dysfunction in Wilson's disease: a comprehensive evaluation K. Li1, C. Lindauer1, R. Haase1, H. Reichmann2, U. Reuner2, T. Ziemssen2

1Center of Clinical Neuroscience, 2Department of Neurology, University Hospital Carl Gustav Carus, Dresden, Germany

Background and aims: Wilson’s disease is reported to have autonomic dysfunction, but comprehensive autonomic function evaluation, especially with Baroreflex sensitivity (BRS) and spectral analyses is lacking. We aimed to comprehensively assess autonomic function in Wilson’s disease. Methods: 26 patients with Wilson’s disease and 26 healthy controls were recruited. 20 patients in the Wilson’s disease group were examined again in a three-year follow-up. All the participants were evaluated by a questionnaire on dysautonomia symptoms, sympathetic skin response, pupillography with pupil diameter in darkness (PDD) and pupil light reflex, 24 hour blood pressure monitoring, and cardiovascular autonomic function examination in various conditions including at rest, deep breathing, Valsalva manoeuvre, isometric handgrip and passive tilting. BRS and spectral analyses were performed via trigonometric regressive spectral analysis. Results: Patients with Wilson’s disease showed autonomic dysfunction mainly in the following aspects: 1. the heart rate was higher than the control group, both at rest and during 24h monitoring. 2. The BRS was lower in all the cardiovascular autonomic function examinations. When tested three years later, BRS did not decrease further under different tests except BRS at rest. 3. The pupillography demonstrated that patients with Wilson’s disease had a smaller PDD and larger relative reflex amplitude at threeyear follow-up compared with the control group. There was a significant correlation between PDD and clinical severity, disability and cirrhosis. Conclusion: The present study suggests that patients with Wilson’s disease have autonomic dysfunction in heart rate, BRS, PDD, and pupil light reflex. Furthermore, some of the impairments progress with disease duration. Disclosure: Nothing to disclose

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Background and aims: Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, progressive, adultonset, hereditary disorder. Its neurological hallmark is an axonal sensory-motor and autonomic neuropathy. Reliable quantification of sudomotor function could prove essential in the diagnosis and management of the disease. Sudoscan is a fairly recent technique that provides a quick, noninvasive and quantitative assessment of the sudomotor function. Our aim was to assess the diagnostic value of Sudoscan for the detection of symptoms, particularly dysautonomia, in TTR-FAP. Methods: 133 TTR-FAP Val30Met carriers, divided in asymptomatic and symptomatic in stage 1 of the disease, were compared with thirty-seven healthy controls. We analysed the right sural sensory nerve action potential (SNAP), the feet sympathetic skin response (SSR) and the electrochemical skin conductance (ESC) for both hands and feet measured by Sudoscan. Results: All neurophysiological measures were significantly worse (all p 0.88). Exploratory factor analysis individualized 8 homogeneous axes. Internal consistency was acceptable (a=0.65-0.91), except for “personality” domain (alpha=0.58). Divergent validity was good. SS-QOL scores were significantly different between groups opposed by their modified Rankin score at baseline (0-1 versus>1) or their overall quality of life compared to the pre-stroke status (non-aggravated versus aggravated). Domains of the SS-QOL were moderately (r>0.35) to strongly (r>0.5) correlated with reference scales. Only “Personality” and “Memory” domains were, respectively, not correlated to the Hospital Anxiety and Depression scale and the Mini-Mental State Evaluation. Conclusion: Thanks to encouraging and acceptable psychometric properties, the French version of the SS-QOL scale appears to be a valid, reliable and responsive instrument to assess quality of life after stroke. Disclosure: Nothing to disclose


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Poster Sessions

P21038

P21039

Cerebral venous thrombosis: retrospective analysis of cases from tertiary hospitals in Hong Kong

Different strokes in younger folks: defining the causes of stroke in people under 45 years

T.C. Li, Y.F. Cheung, W.C. Fong

A. Lockhart, R. O'connor, I. Noone, N. Tubridy, S. O'riordan, C. Mc Guigan

MED, Queen Elizabeth Hospital, HKSAR, China

Background and aims: Cerebral venous thrombosis (CVT) is an important cause of stroke. The majority of case series are from Caucasian countries, while data from Asia is comparatively scarce. It is essential to obtain distinctive local data on CVT in Hong Kong, with an aim to identify their prognostic indicators. Methods: Subjects were recruited from three tertiary hospitals in the period from 2003 to 2014. Relevant results and functional outcomes at 1, 6 and 12 months were recorded. Unfavourable outcome was defined as mRS>2. Primary outcome was defined as unfavourable outcome at one month. Results: 98 patients were included. Common predisposing conditions included the use of oral contraceptive pills (14.3%), malignancy (14.3%) and infections (10.2%). At one month, 35 (35.7%) patients had unfavourable outcomes, while 21 (21.4%) and 16 (16.3%) patients had unfavourable outcomes at 6 and 12 months respectively. Using a logistic regression model, predictors of death and dependence at one month were age>65 (odds ratio [OR]=8.27), hemiparesis (OR=4.06), non-central nervous system tumour (OR=44.52), intracerebral haemorrhage (OR=11.48) and mass effect on imaging (OR=19.68). Over a median followup duration of 51 months, 16 patients died. Kaplan-Meier survival analyses were performed. Conclusion: Older patients, having hemiparesis on presentation, intracerebral haemorrhage or mass on imaging, or those with an underlying non-central nervous system tumour were at risk of unfavourable outcomes. Future research is necessary to clarify whether more intensive treatment and rehabilitation may benefit these patients. Disclosure: Nothing to disclose

Department of neurology, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland, Dublin, Ireland

Background and aims: 5-10% of strokes occur in patients under 45 years of age. This population requires more extensive investigation as the aetiology of stroke is more heterogenous compared with older populations. Methods: A retrospective audit was performed on all patients under the age of 45 years who presented to a university hospital between 1st January 2010 to 30th September 2015. Clinical presentation, duration of symptoms and clinical outcomes were recorded in addition to investigation results including CT and MRI brain, CT angiography, US carotids, echocardiograms, 24hr Holter, vasculitic screen and thrombophilia screen. Stroke aetiology was assigned according to the internationally recognised TOAST criteria. Results: 66 patients were identified. Age ranged from 20-45 years. 53% male, 47% female. Only 5 (7.57%) were thrombolysed and one had thrombectomy. 2 (3%) had large vessel atherosclerosis, 12 (18.18%) cardioembolic, 7 (10.6%) due to small vessel disease, 18 (27.27%) due to another identified cause, of which 12 (66.7%) were due to vertebral or carotid dissection, 12 (18.18%) were cryptogenic/uncertain, 15 (22.72%) were haemorrhagic. Conclusion: This study highlights the heterogenous aetiology of stroke in patients under 45 years. In this group, large vessel atherosclerosis is uncommon and more unusual aetiologies must be sought, requiring more extensive investigations (e.g. haematological and cardiac). Fewer patients in this cohort were thrombolysed compared to older cohorts. Delay in patient presentation and initial misdiagnosis of stroke as migraine, inner ear disorders etc. could account for missed opportunities for thrombolysis. Disclosure: Nothing to disclose


Poster Sessions

P21040

P21041

Determinants of adherence to oral anticoagulants in patients with atrial fibrillation and stroke

Intracerebral haemorrhage in an adult with Down syndrome and Moya Moya disease

A. Polymeris, C. Traenka, L. Hert, D.J. Seiffge, N. Peters, G.M. de Marchis, L. Bonati, P.A. Lyrer, S.T. Engelter

J.P. Marto, C. Borbinha, S. Calado, M. Viana-Baptista

Stroke Center and Neurology, University Hospital Basel, Basel, Switzerland

Background and aims: Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are of proven benefit in patients with stroke attributable to atrial fibrillation (AF). However, little is known about adherence to NOACs and its determinants. Methods: Novel-Oral-Anticoagulants-in-Stroke-Patients (NOACISP) is a prospective monocentric registry aiming at retrieving real-world data in patients with stroke associated with AF. This is a nested analysis focused on adherence to treatment. Adherence was assessed using a structured interview including the self-reported number of missed doses and expressed as the percentage of prescribed doses actually taken. Patients reporting at least one missed dose were classified as non-adherent. To establish determinants of adherence we compared demographic variables, medication details, stroke characteristics and occurrence of adverse and outcome events between adherent and nonadherent patients using univariate analyses. Results: We included 225 patients (52% female, mean age 77.9 ± 9.2 years). Fifty patients had VKAs and 175 NOACs. Mean follow-up was 11.6 (range 3–24) months. Mean adherence was 98.8%. Adherent were 178 patients (79%) and non-adherent 47 (21%). Adherence did not differ between VKA- and NOAC-treated patients. Adherence was positively associated with (a) higher total daily pill burden, (b) caregiver administering doses, (c) modified Rankin Scale of ≥3 and (d) previous antithrombotic treatment. Forgetfulness was the most common reason for nonadherence. Conclusion: In our cohort adherence was remarkably high. Determinants of adherence were -counterintuitively- a high number of daily taken medications and -expectedly- a caregiver involved in daily intake, as well as the previous intake of antithrombotic agents. Disclosure: Our research has been granted support from the Swiss Heart Foundation.

379

Neurology, Hospital Egas Moniz-Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal

Background and aims: Moya Moya disease is defined by a progressive stenosis of intracranial internal carotid arteries and their proximal branches, predisposing to cerebrovascular events. Down syndrome is associated with Moya Moya disease, and usually presents with paediatric ischemic stroke. Clinical case: A 26-year-old woman with Down syndrome and corrected congenital heart disease, without history of cerebrovascular disease, admitted to the emergency department with intense bilateral headache and recurrent vomiting. After discharge with the diagnosis of gastroenteritis, without resolution of the headache, a CT scan showed a right thalamic hematoma with ventricular extension. Three months after the event the mRS was 1. On follow-up a magnetic resonance angiography revealed an absence of flow in the intracranial right internal carotid artery and multiple threadlike vessels. To clarify these findings a digital subtraction angiography demonstrated the same vessel occlusion besides a left internal carotid artery stenosis and occlusion of the ipsilateral anterior cerebral artery, development of exuberant collateral vasculature at the base of the brain, collateral flow to the cerebral anterior circulation from branches of the external carotid arteries and development of pial arteries. With evidence of characteristic angiographic findings, with a Suzuki grade of V and IV, right and left, respectively, the diagnosis of Moya Moya syndrome was admitted due to the association of typical angiographic features with Down syndrome. Conclusion: Moya Moya Syndrome is a diagnosis to have in mind in patients with Down syndrome and cerebrovascular events. This case illustrates this association, and stresses that it can present with a haemorrhagic event in the adult. Disclosure: Nothing to disclose


380

Poster Sessions

P21042 Auditory evoked potentials in patients with posterior circulation stroke and vertebral artery hypoplasia B. Zivadinovic1, J. Stamenovic2, B. Bisevac2

1Neurology, Clinical Center Nis, Nis, Serbia, 2Neurology, Clinical centre Nis, Nis, Serbia

Background and aims: Auditory evoked potentials (AEPs) represent an electrophysiological method used in the diagnostics of pathological changes of the brain stem. Brief click stimulates the auditory nerve and responses generated along the auditory pathway are registered, perceiving both its peripheral and central part. All the waves are generated in the structures of the brain stem that are vascularised by the posterior circulation arteries. Chronic insufficient vascularisation in that region leads to changes in morphology and latency of the waves. The aim of the paper was to show an increased number of AEP pathologic findings in the group of patients suffering from posterior circulation stroke (vertebrobasilar circulation) PCS with vertebral artery hypoplasia (VAH). Methods: Our study enrolled 50 patients with diagnosed PCS, 19 of them (38%) had confirmed VAH. The presence of VAH was determined by performing Echo-ColourDoppler method of blood vessels of the neck and proved by computed tomography angiography (CTA), where the values of vessel diameter ≤ 2mm were used as a criterion for hypoplasia. Results: A statistically significant number of pathological AEP findings is noted in the group with VAH (p= 0.0435). Patients with a more severe form of stroke have statistically significantly higher number of pathological findings (p=0,049). In the group of patients with lethal outcome, pathological AEP are registered in 100% of patients. Conclusion: Based on the results from our research we have proved that the number of AEP pathologic findings is increased in the group of patients suffering from PCS with VAH. Disclosure: Nothing to disclose


Poster Sessions

381

P21044

Cognitive neurology/ neuropsychology 2

Could ambulatory blood pressure monitoring be a routine investigation for patients with mild cognitive impairment?

P21043 Long lasting neuropsychological deficits in patients with Transient Global Amnesia (TGA) S. Fragkiadaki1, D. Kontaxopoulou1, I. Beratis1, S. Triantafyllou1, M. Ioakeimidis2, G. Papadimitropoulos1, A. Bonakis1, K. Voumvourakis1, L. Stefanis1, G. Tsivgoulis1, S.G. Papageorgiou1 Athens, Greece, 22nd Department of Neurology, Athens University, Attikon University Hospital, Athens, Greece

1

Background and aims: Previous findings indicate that patients with TGA present with severe episodic memory deficit lasting 75%) has switched from injectables. 15% of patients were treated with second line and they switched only to DMF. 67% of the patients treated with teriflunomide have switched because of phobia/no tolerability; 16% AE, 10% IN and 7% others. 44% of the patients treated with DMF have switched because of phobia/no tolerability; 23% AE, 23% IN 5 % safety and 5% others. Conclusion: The most frequent cause to switch to new oral treatments was no tolerability to injections. Patients, who switched to DMF, have more severe and active disease than to teriflunomide. Disclosure: Nothing to disclose


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Poster Sessions

P22117 Atypical presentation of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report with spinal cord involvement M. Padroni1, C. Calanca2, V. Rispoli1, V. Tugnoli3, E. Baldi3, E. Fainardi4, E. Granieri1, M. Pugliatti1, L. Caniatti3

1Department of Biomedical and Surgical Sciences Section of Neurological, Psychiatric and Psychological Sciences, University of Ferrara, Ferrara, Italy, 2Neuropsychology Unit, Azienda Ospedaliero-Universitaria Sant'Anna, Ferrara, Italy, 3Neurology Unit, Azienda OspedalieroUniversitaria Sant'Anna, Ferrara, Italy, 4Neuroradiology Unit, Azienda Ospedaliero-Universitaria Sant'Anna, Ferrara, Italy

Background and aims: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder of uncertain aetiology, involving the central nervous system (CNS) with distinct clinical and radiological features. Subacute gait ataxia, diplopia and cerebellar dysarthria are the cardinal clinical features. Typical brain MRI shows punctuate and curvilinear gadolinium enhancement (“saltand-pepper-like”) of the brachium pontis with possible extension of the lesions into the cerebellar hemispheres white matter. We aim to describe an atypical case with spinal cord involvement. Methods: We report the case of a 49-year-old immunocompetent man presenting with subacute gait ataxia, diplopia, cerebellar dysarthria and spastic paraparesis, associated with attention/executive functions impairment. Brain MRI showed hyperintense lesions on T2 and FLAIR images with punctate contrast enhancement, involving the brainstem, the cerebellum and subcortex. Spinal MRI revealed a bulky spinal cord with a longitudinally extensive lesion with same MRI characteristics as in the brain. Possible differential diagnoses such as CNS lymphoma, vasculitides, infectious and others autoimmune diseases were ruled out. Clinical and radiological features were consistent with CLIPPERS and the patient was treated with intravenous methylprednisolone for five days, followed by tapering dose of oral steroids and long-term immunosuppression. Results: The patient’s outcome was an abrupt clinical and radiological improvement, with an almost clear disappearance of enhancing lesions in both brain and spinal MRI, supporting the diagnostic hypothesis of CLIPPERS.

Coronal and axial FLAIR and post-contrast T1-weighted MRI images showing FLAIR hyperintense lesions with punctuate contrast enhancement predominantly in the pons (A). After steroids therapy no one of the lesions showed contrast enhancement and there was a reduction in the extent of FLAIR hyperintensity (B),

Sagittal T2 and post-contrast T1-weighted MRI images showing FLAIR cervical spinal cord lesion with punctuate enhancement (A) that almost disappeared after steroids therapy (B)

Conclusion: CLIPPERS may present with spinal cord involvement, in the form of longitudinally extensive lesions with punctuate contrast enhancement with prompt response to intravenous steroids. Disclosure: Nothing to disclose

P22118 Prevalence of depression and fatigue in the 11-year follow-up from the BENEFIT study I.-K. Penner1, F. Foley2, G. Edan3, M. Freedman4, X. Montalban5, H.-P. Hartung6, E.J. Fox7, B. Hemmer8, F. Barkhof9, S. Schippling10, R. Koelbach11, D. Pleimes12, G. Suarez13, E.-M. Wicklein14, L. Kappos15

1COGITO Center for Applied Neurocognition and Neuropsychological Research, Düsseldorf, Germany, 2School of Psychology, Yeshiva University, New York, USA, 3CHU Hopital Pontchaillou, Rennes, France, 4University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Canada, 5Department of Neurology-Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain, 6Neurology, HeinrichHeine Universität, Düsseldorf, Germany, 7Central Texas Neurology Consultants, Round Rock, USA, 8Technische Universität München Cluster for Systems Neurology (SyNergy), Munich, Germany, 9VU University Medical Center, Amsterdam, Netherlands, 10University Hospital Zurich, Switzerland, 11PAREXEL International, Berlin, Germany, 12Myelo Therapeutics GmbH, Berlin, Germany, 13Bayer HealthCare Pharmaceuticals, Whippany, USA,


Poster Sessions 14Bayer Pharma AG, Berlin, Germany, 15Neurology, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Basel, Switzerland

Background and aims: Fatigue/depression impact working and social lives for patients with MS. Here we analyse the prevalence of these outcomes in the 11-year follow-up of the BENEFIT trial. Methods: Patients with CIS who had ≥2 clinically-silent brain lesions were randomized to interferon beta-1b (early treatment) or placebo (delayed treatment) for 2 years or until CDMS. At 11 years, all patients were approached for follow-up, including Fatigue Scale for Motor and Cognitive Functions (FSMC) and Center for Epidemiological Studies Depression scale (CES-D), both assessed for the first time in BENEFIT. Results: Of the 468 original patients, 278 (59.4%) participated in BENEFIT 11 (early: 167, delayed: 111). There were no clinically-significant differences in FSMC or CES-D scores between the two groups. In 68.7% of the overall population, no depressive symptoms were reported on the CES-D (missing, 1.1%). 46.0% reported no fatigue, while 11.9%, 10.8%, and 28.8% of patients reported mild, moderate, and severe fatigue (missing, 2.5%). 49.3% reported no cognitive fatigue while mild, moderate, or severe cognitive fatigue was seen in 14.0%, 12.2%, and 21.9% (missing, 2.5%). 45.0% reported no motor fatigue while mild, moderate, or severe motor fatigue was seen in 10.8%, 9.4%, and 32.4% (missing, 0.7%). No relationship between CES-D/FSMC and MRI was seen. Conclusion: Depression prevalence in the BENEFIT 11 cohort, where all patients received interferon beta-1b relatively early, was lower than reported in natural history or clinical studies. Moderate/severe motor fatigue appeared to be more frequent than cognitive fatigue, with an overall fatigue prevalence below previously-reported MS cohorts. Disclosure: This research was supported by Bayer HealthCare Pharmaceuticals, Inc.

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P22119 Incorporating the TEMSO SIENA analysis improves correlation of brain atrophy and disability progression M. Pia Sormani1, E.-W. Radue2, T. Sprenger3, L. Gaetano2, N. Mueller-Lenke2, J. Wuerfel2, K. Thangavelu4, S. Cavalier4, L. Kappos5

1University of Genoa, Genoa, Italy, 2Medical Image Analysis Center (MIAC AG), c/o University Hospital Basel, Basel, Switzerland, 3DKD Helios Klinik, Wiesbaden, Germany, 4Sanofi Genzyme, Cambridge, USA, 5University Hospital Basel, Basel, Switzerland

Background and aims: In patients with relapsing-remitting MS, treatment effect on brain atrophy has been proven to correlate with effect on disability progression over 2 years. Brain volume loss (BVL) in the TEMSO (NCT00134563) study population has been evaluated using a blinded structural image evaluation using normalization of atrophy (SIENA) method. The data from this analysis were assessed for further investigation of the correlation between treatment effect on brain atrophy and effect on disability progression. Methods: A meta-analysis published by Sormani et al. (Ann Neurol. 2014;75:43) was repeated, replacing the original TEMSO analysis with results from the SIENA analysis. The relationship of BVL with disability progression within the TEMSO SIENA dataset was analysed using a Cox model of disability progression (adjusted for covariates). Results: The coefficients of determination (R2) for the relationship of treatment effect on brain atrophy, and on combined MRI markers with treatment effect on disability progression, improved from 0.46 to 0.61, and from 0.75 to 0.79, respectively, when using the SIENA assessment of BVL compared with the original meta-analysis. In the Cox model, BVL over 2 years had a significant impact on disability progression, with a risk reduction of 11% for every 1% change in brain volume (P=0.0203). Conclusion: Incorporating the results of the TEMSO SIENA MRI analysis into the meta-analysis improved the correlation between treatment effect on brain volume and disability progression. Patient-level data showed significant correlation between BVL and disability progression over 2 years, strengthening the validity of these observations and the rationale for analysing TEMSO MRI data using SIENA. Disclosure: Study supported by Sanofi Genzyme.


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Poster Sessions

P22120

P22121

Functional and structural MRI predictors of disability worsening in multiple sclerosis: a 4-year follow-up study

Multimodal evoked potentials predict NEDA evolution in patients starting first-line treatment for multiple sclerosis

F. Pirro1, M.A. Rocca1, P. Valsasina1, E. Pagani1, A. Meani1, M. Copetti2, F.G. Martinelli Boneschi3, M. Rodegher3, G. Comi3, A. Falini4, M. Filippi1

M. Pisa1, M. Bianco2, S. Guerrieri1, G. Di Maggio1, M. Romeo1, L. Moiola1, V. Martinelli1, G. Comi1, L. Leocani1

1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 2Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, 3Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 4Neuroradiology, Università Vita-Salute San Raffaele, Milan, Italy

Background and aims: We assessed the value of conventional, diffusion tensor imaging (DTI) and resting state (RS) functional connectivity (FC) MRI measures in predicting clinical deterioration over a four-year period in multiple sclerosis (MS). Methods: Baseline brain MRI brain scans were obtained from 258 MS patients (132 relapsing remitting [RR], 63 secondary progressive [SP], 19 primary progressive [PP] and 44 benign [B] MS), who were followed-up with clinical visits and rating of the Expanded Disability Status Scale (EDSS) score for a median period of 3.8 years. T2 and T1 lesion volumes, normalized white (WM), grey (GM) and deep GM volumes, DTI metrics from the main brain WM tracts and RS FC scores of the sensorimotor and default mode (DMN) networks were obtained. Multivariable analyses, adjusted for baseline EDSS and follow-up duration, were performed to identify the predictors of neurological deterioration at follow-up. Results: At follow-up, 90 MS patients (35%) showed significant worsening of disability. The multivariable model with EDSS score deterioration as dependent variable, identified decreased RS FC of the left postcentral gyrus (p=0.03), average RS FC of the sensorimotor network (p=0.02), baseline GM atrophy (p=0.001), reduced fractional anisotropy of the right cingulum (p=0.003) and decreased RS FC in the right middle temporal gyrus of the DMN (p=0.01) as predictors of disability worsening (C-index=0.78). Conclusion: In addition to the well-known role of structural damage to the WM and GM, RS FC abnormalities in the sensorimotor network and DMN contribute to identify MS patients with a worse clinical outcome over time. Disclosure: This study has been partially supported by a grant from FISM 2014/R/7.

1

Neurology, san Raffaele Hospital, Milan, Italy, 2Milan, Italy

Background and aims: EPs have good predictive value on disability progression but no data are available about predictive value of EPs on NEDA evolution (No Evidence of Disease Activity) which is the goal for MS treatments. Methods: 96 MS patients underwent multimodal EP (VEPBAEP-SEP-MEP) at first-line treatment initiation. All patients received a 2.5±0.8 years clinical and neuroradiological follow-up; 59 of them received a 7±1.4-year follow-up. Each EPs was assessed with an abnormality score (0 to 3); maximum possible multimodal EP score (GEPs) was 36. Patients were defined NEDA if no MRI or clinical activity and no confirmed disability progression occurred during the follow-up. Results: A total of 35 patients (36.5%) reached NEDA criteria after 2 years. Mean GEPs was 4.09 in NEDA patients and 7.44 in patients with active disease (n=61). A logistic regression was performed to ascertain the effects of GEPs, MRI lesion load, EDSS and disease duration on the likelihood that participants have NEDA evolution. The model correctly classified 77.1% of cases (pG and we found four novel mutations including c.(2040+2dup), c.(1650delG), c.(1837T>G) and c.(2596delG). Conclusion: This is the first comprehensive report of lateonset Pompe disease in Iranian patients. Distinct phenotypic and genotypic features of Pompe disease in this population are highlighted. Disclosure: Nothing to disclose

N. Ortiz1, R. Margalef2, M. Sisquella2, M. Bosque2, C. Romeu2, O. Mayoral3, S. Monterde4, M. Priego5, J. Tomas6, M.M. Santafe6

1Reus, Spain, 2Unidad d'Histología i Neurobiología, Facultat de Medicina i Ciencies de la Salut, Universitat Rovira i Virgili, Reus, Spain, 3Unidad de terapia física, Hospital Provincial de Toledo, Toledo, Spain, 4Unidad de Fisioterapia, Universidad Rovira i Virgili, Reus, Spain, 5U, Reus, Spain, 6Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut. Universitat Rovira i Virgili, Reus, Spain

Background and aims: An abnormal release of acetylcholine (ACh) in the synaptic cleft seems responsible for localized increase in diameter of muscle fibres called "contraction knots" located below the synapse and the accumulation of which is considered a myofascial trigger point identifiable by palpation and electromyography in humans. We have studied if the increase of acetylcholine in the synaptic cleft into muscles of mice generates contraction knots comparable to those described in humans. Methods: We use neostigmine to increase ACh in the synaptic cleft. For in vivo experiments, neostigmine is injected subcutaneously in adult male Swiss mice. We made intracellular electrophysiology study in the levator auris longus (LAL) and diaphragm. In addition, the end plate noise is evaluated with an EMG. To evaluate the morphology of synaptic contacts the AChR are stained with α-bungarotoxin rhodaminated in the LAL muscle. The presence of glycosaminoglycans (GAGs) is assessed with the PAS- Alcian technique. Results: When neostigmine is applied subcutaneously (in vivo, in toto) spontaneous ACh release is strongly increased in the LAL muscle but not in the diaphragm. When neostigmine is added in the bath of the recording chamber spontaneous ACh release is increased in LAL and diaphragm. Noise plate is also increased. We observe abundant contracted synaptic contacts and we have obtained images of contraction nodes rich in GAGs. Conclusion: Mice treated with a single subcutaneous injection of neostigmine can be a good model for the study of myofascial trigger points because they showed an increase in spontaneous ACh release, noise plate and contraction knots. Disclosure: This work is funded by a grant from FISS (PI13 / 02084)


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P22126

P22128

Neutral lipid storage with myopathy the role of micro RNA and muscle imaging

Clusters of cognitive impairment among different forms of myotonic dystrophies

V. Pegoraro1, C. Angelini1, E. Pinzan2, E. Tasca2

S.Z. Peric1, G. Mandic-Stojmenovic2, V. Ilic3, M. Kovacevic1, A. Parojcic3, V. Dobricic4, J. Pesovic5, I. Novakovic4, D. Savic-Pavicevic5, V. Rakocevic-Stojanovic4

Venice, Italy, Neuromuscular, IRCCS san Camillo, Venice, Italy 1

2

Background and aims: Neutral Lipid storage with Myopathy (NLSDM) is a rare autosomal recessive disorder of triglyceride metabolism, due to ATGL protein mutations code by PNPLA2 gene, characterized by a storage of lipid droplets (LD) in liver, muscle, leukocytes causing muscle damage, hepatosteatosis, cardiomyopathy, diabetes. ATGL acts hydrolysing the first fatty acid from triacylglycerols. Aim: Since no studies have been reported so far on microRNAs profile in NLSDM patients, we explore the role of microRNA in regulating lipid metabolism and lipolysis in a NLSDM family. Methods: In an NLSDM family the severity of clinical features were highly variable. In two male siblings aged 61-50 there was an asymmetric distal myopathy, while in a 58-year-old woman hepatosteatosis, diabetes were the main signs, they have 2 heterozygous ATGL mutations. 3 family member and 1 carrier were studied: 3 muscle biopsies were done, in 2 male siblings demonstrating progressive lipid storage, mitochondrial complexes investigated. MicroRNAs were investigated in plasma in four family members. Results: In the 61-year-old man there was a progressive decrease of OxPhos complexes in two successive biopsies. Muscle imaging by Whole body CT showed fatty replacement in posterior thigh and paraspinal muscles. In the 50-year-old brother distal leg muscles were asymmetrically involved. MicroRNAs were investigated: MiR-1, MiR 133-a, MiR 133-b, MiR-206 appeared 10-20fold increased in male siblings correlating with muscle atrophy, in women with hepatosteatosis MiR133-b was 10-fold elevated. Conclusion: MicroRNAs showed an impressive dysregulation in plasma of affected patients, suggesting a signalling role of Myo-microRNA in muscle atrophy. Disclosure: Nothing to disclose

P22127 Abstract cancelled

Belgrade, Serbia, 2Neurology Clinic, Clinical Centre of Serbia, Belgrade, Serbia, 3Neurology Clinic, Belgrade, Serbia, 4Neurology Clinic, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia, Belgrade, Serbia, 5Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia, Belgrade, Serbia 1

Background and aims: Neuropsychological examinations in myotonic dystrophy (DM) patients show a great variability of results from a condition of intellectual disability to the subtle impairments. It is unclear if different clusters of neuropsychological deficits appear in different forms of DM, or if there are patients with no cognitive deficit at all. Aim: To assess cognitive impairments among patients with different forms of DM type 1 (DM1) and type 2 (DM2), and to potentially define cognitive clusters in these disorders. Methods: Study comprised 101 DM1 and 46 DM2 adult patients who were genetically confirmed. Patients underwent analysis of five cognitive domains (visuospatial, executive, attention, memory and language). Results: Virtually all DM1 patients had cognitive defect with approximately 2 to 3 cognitive domains affected. On the other hand, one third of DM2 patients had completely normal neuropsychological findings, and in other two thirds approximately 1-2 domains were affected. Cluster analysis showed that in both diseases visuospatial and executive dysfunctions seemed to be the main cognitive defects, while memory and language impairments appeared in more severe phenotypes. Our results showed that a single form of DM1 or DM2 may consist of several cognitive clusters. Conclusion: Understanding of cognitive impairments in DM is very important to follow positive and side effects in ongoing and future clinical trials. Disclosure: This study was supported by the Ministry of Education, Science and Technological Development of Serbia – grant #175083.


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Poster Sessions

P22129 Progressive Merosin deficiency associated with Lama2 new mutation in a patient deviating from the classical clinical and morphological phenotypes L. Peverelli1, I. Colombo1, R. Del Bo2, C. Cinnante3, F. Magri2, F. Fortunato2, R. Tironi1, A.L' Erario1, E. Mauri2, N. Grimoldi4, G.P. Comi2, M.G. Moggio1, M. Sciacco1

1Neuromuscular and Rare Diseases Unit, Department of Neuroscience Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, 2IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy., 3University of Milan, Neuroradiology Unit, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, 4Department of Pathophysiology and Transplantation, University of Milan, Neurosurgery Unit, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

Background and aims: Two main clinical phenotypes are associated with LAMA2 mutations (merosin deficiency): a severe congenital muscular dystrophy and a milder Limb Girdle Muscular Dystrophy. Methods: A 74-year-old male, born of consanguineous parents, began to suffer from severe headache in his fifties. A brain MRI showed diffuse and symmetric white matter lesions (WML). No muscle weakness was detected at disease onset though CK levels were elevated (300-1100 U/L) and EMG was myopathic. Initially, CADASIL (Cerebral Autosomal Dominant Arteriopathy, Subcortical Infarcts, Leukoencephalopathy) was suspected because the patient's mother and her sisters had been diagnosed cognitive impairment, however, full NOTCH3 sequence analysis was negative. Results: At age 67 years he thus underwent left biceps muscle biopsy which showed mild mitochondrial alterations and multiple mtDNA deletions at Southern blot analysis. No mutations were detected in nuclear genes causing multiple mtDNA deletions. Immunohistochemistry for muscular dystrophy-related proteins, including merosin, was normal. Due to neuroradiological worsening and development of fatigability, he underwent another muscle biopsy at age 74 years with evidence of neurogenic alterations with slight dystrophic and mitochondrial abnormalities. Neuropsychological tests are normal. Immunofluorescence showed faint merosin sarcolemmal binding. A gene analysis of LAMA2 showed homozygous IVS 19+2 InsT mutation.

A&B: Brain MRI. Flair transversal (A) and T2 coronal (B) showing diffuse bilateral White Matter Lesions. C&D: Immunofluorescence staining with Merosin antibody on the first muscle biopsy (C) and on the second (D). Original Magnification 40X (Merosin Laminin Alpha2). Normal Merosin binding (C) and scattered mild Merosin reduction of binding (D).

Conclusion: We report the case of a patient carrying one new homozygous LAMA2 mutation associated with severe and progressive brain neuroradiological lesions and poor skeletal muscle involvement, the latter possibly due to preservation of relatively high levels of residual merosin in muscle tissue. This case contributes to expand the spectrum of both genotypes and clinical phenotypes in merosinassociated disorders. Disclosure: Nothing to disclose

P22130 Evolution of inflammatory and degenerative pathological profiles in inclusion body myositis M. Pinto1, R. Taipa2, M. Pires2

1Neurology Department, Centro Hospitalar de Lisboa Ocidental-Hospital Egas Moniz, Lisbon, Portugal, 2Neurology Department and Neuropathology Unit, Centro Hospitalar do Porto-Hospital de Santo António, Porto, Portugal

Background and aims: Sporadic inclusion body myositis is an inflammatory myopathy. The pathological diagnosis relies on the presence of rimmed vacuoles, typical cytoplasmic filaments and non-necrotic muscle fibre invasion by inflammatory cells. Evidence suggests that an interaction between both inflammatory and degenerative components may be in its origin, but the timing on which they contribute to muscle insult is still controversial. We aim to correlate the severity of inflammatory and degenerative elements in muscle samples from sIBM patients, with the evolution of disease and patients’ age at the time of muscle biopsy. Methods: Muscle biopsy specimens that fulfilled criteria for pathologically possible or definite sIBM were considered. Inflammatory and degenerative features were assessed through semi-quantitative scales for inflammatory cell infiltration and rimmed vacuoles. These variables were compared with chronologic clinical data using statistic tools. Results: No statistically relevant correlation was found between age or time from onset, and the presence of rimmed


Poster Sessions

vacuoles or inflammatory infiltration severity. Nevertheless, a significant relation between the number of vacuoles and the severity of inflammatory infiltration was found. There was also a tendency for milder profiles in muscle samples obtained from the deltoids versus those from lower limbs. Conclusion: We did not find a predominant profile according to the age or time from disease onset. The relation between the expression of rimmed vacuoles and the severity of inflammation suggests that these could be a mutual, rather than a sequential, phenomena. Muscle selection for biopsy could be an important issue regarding an accurate pathologic diagnosis of sIBM. Disclosure: Nothing to disclose

P22131 Necrotizing myopathies: a single-centre experience V. Ponzalino, S. Bortolani, L. Vercelli, S. Boschi, E. Vittonatto, L. Chiado Piat, N. Ragusa, L. Pinessi, T. Mongini Department of Neurosciences “Rita Levi Montalcini”, University of Torino, Italy, Turin, Italy

Background and aims: Necrotizing myopathies (NM) are a heterogeneous group of pathologies characterized by necrosis of muscle fibres without or with scarce inflammatory infiltrates in muscle biopsy. They usually present with subacute onset of proximal limb weakness, often complicated by dysphagia and respiratory difficulties, and high levels of serum CK; the disease may be severely invalidating and life-threatening. The most frequent cause is an autoimmune activation (NAM); alternatively, paraneoplastic or toxic etiopatogenesis must be considered. Differential diagnosis is important to establish the correct therapy. Methods: We reviewed clinical aspects, diagnostic processes and therapy outcomes in a cohort of fifteen patients referred to our Neuromuscular Unit, affected by a necrotizing myopathy. Results: 2 patients had an anti-SRP positive NAM; 2 a paraneoplastic NM; 5 an overlap NM, 1 patient a statinrelated-NM and 2 a post-vaccinic NM. In three “idiopathic” cases, no specific cause was identified. In all cases, the most relevant diagnostic clues were the clinical history, muscle biopsy features, search for specific autoantibodies (mainly anti-SRP), EMG (“irritative” pattern), and muscle MRI (STIR-positive alterations). Conclusion: The therapeutical response correlated with the diagnostic delay; in fact, as previously reported, NAMs are often steroid-resistant and require a combination of immunosuppressive approaches. In most cases IVIg produced a clinical stabilization; the most striking results were observed in anti SRP-positive NMAs after rituximab therapy. Disclosure: Nothing to disclose

575

P22132 Anti-3-hydroxy-3-methylglutarylcoenzyme A reductase-associated autoimmune myopathy: case series and magnetic resonance imaging findings A. Shah, J. Hersheson, M. Novak, A. Davis, M. Stevens, M. Espasandin, S. Vaidya, S. Marino, A. Radunovic Barts Health NHS Trust, London, United Kingdom

Background and aims: Autoantibodies to 3-hydroxy-3methylglutaryl-coenzyme reductase (HMGCR) have recently been described in patients with necrotizing autoimmune myopathy. Emerging evidence suggests this is a distinct disease entity that can occur regardless of prior statin use. While most cases reported have had necrotizing myopathy, the spectrum of histopathological features in anti-HMGCR positive patients is also widening. We are not aware of a series in the literature describing the magnetic resonance imaging (MRI) features seen in this condition. Methods: We present a series of 9 patients with myopathy associated with anti-HMGCR autoantibodies. The clinical, pathological and MRI muscle findings are described. Results: We describe 9 patients, ranging from 34 to 70 years of age at onset (mean age 56), with a female preponderance (67%). Peak serum creatine kinase ranged from 3,408 to 26,506 u/l (normal range 25-200). 7 patients reported prior statin use. All patients had a muscle biopsy, most showing a typical necrotizing myopathy. However, we found that necrosis was not always prominent. All patients were treated with steroids or intravenous immunoglobulin, or both. In addition, steroid-sparing agents (methotrexate or azathioprine) were initiated when appropriate. Immunomodulatory therapy resulted in clinical and biochemical improvement in all cases. Muscle MRI findings were variable between cases. Some patients had normal MRI muscles prior to treatment, while others had radiological features of muscle inflammation; in some cases, this subsided with treatment. Conclusion: Anti-HMGCR antibody-associated myopathy can occur with or without prior statin use, and the histopathological features are variable. We show that muscle MRI abnormalities, when found, can improve after treatment. Disclosure: Nothing to disclose


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Poster Sessions

P22133

P22134

Anti-musk antibody negative myasthenic crisis patients managed with rituximab: report of two cases

Myasthenia gravis associated with scleroderma: the first case in Greece and systematic review of the literature

P. Ranganathan

P. Zis1, P. Kokotis1, P. Sfikakis2

Chennai, India

Neurology, University of Athens, Athens, Greece, 2First Department of Propaedeutic Medicine, University of Athens, Athens, Greece

1

Background and aims: The main therapy for myasthenic crisis is intravenous immunoglobulin or plasma exchange. Sometime in spite of above therapy patient may not respond. 2 patients with myasthenic crisis managed with Rituximab is discussed in this report. Methods: 2 patients with myasthenic crisis who are acetylcholine receptor antibody positive, anti-musk antibody negative not responded to IVIG therapy were managed with rituximab. Results: Case 1: A 45-year-old male, myasthenic patient on pyridostigmine and azathioprine undergone thymectomy for thymoma. In the post-operative period he developed myasthenic crisis. He had five-day course of IVIG, but no response. As immediate plasma exchange is a problem, it was decided to use rituximab. He had 500mgm of rituximab at standard rate of infusion in ICU. He recovered in three days and was extubated. Case 2: A 40-year-old male, myasthenic patient on irregular follow up but taking T.Pyridostigmine and azathioprine presented with dropped neck and breathing difficulty. He was immediately admitted in the ICU. He had thymectomy in the past with residual thymus lesion. For IVIG no response. He had 500mgm of rituximab in the ICU, due to partial response he had another same dose in fifteen days. He recovered well, extubated and got discharged. Case 1 & 2 serum acetylcholine receptor antibody positive and anti-musk antibody negative. Conclusion: Rituximab can be useful in acetylcholine receptor antibody positive, anti-musk antibody negative myasthenic crisis patients who not responded to standard therapy like IVIG. Disclosure: Nothing to disclose

Background and aims: Myasthenia gravis (MG) occurring in patients with scleroderma has been described on few cases and has been associated with treatment with d-penicillamine. We report the first Greek case of a patient with scleroderma who developed MG without prior exposure to d-penicillamine and we systematically review the literature regarding this rare combination of diseases. Methods: Case report and a systematic review of the literature. Results: A 66-year-old Caucasian woman with a diagnosis of scleroderma came to our attention because of unilateral ptosis. According to the patient, the weakness did show a diurnal variation and was accompanied by generalized fatigue. Neurophysiological testing showed positive rapid decremental responses of muscle action potentials to repetitive nerve stimulation on both the right orbicularis oculi and the right trapezius muscles. Immunological screening revealed an elevated acetylcholine receptor (AChR) antibody count. A chest axial computed tomography did not reveal the presence of a thymoma or a thymus gland enlargement. A diagnosis of myasthenia gravis was set and initiation of helped significantly with the myasthenic symptoms. Conclusion: Comorbidity of MG not induced by d-penicillamine and scleroderma is rare but may exist. In total 8 more cases with scleroderma that developed MG without prior exposure to d-penicillamine were found. All cases were women (ages range 24-72 years). In 5 cases MG preceded the diagnosis of scleroderma. Although he possibility of this being a coincidence cannot be excluded we believe that this case will increase clinician's awareness about this combination of autoimmune diseases. Disclosure: Nothing to disclose


Poster Sessions

Neuroepidemiology 2 P22135 Association between ambient temperature and stroke hospitalisations in Minsk, Belarus O. Mukalova1, A. Mukalau2, A. Pyko2

Minsk, Belarus, 2Belarussian State Medical University, Minsk, Belarus

1

Background and aims: Temperature might be an important environmental risk factor for stroke. The objective of this study was to investigate the association between daily ambient temperature and stroke hospitalisations using a case-crossover design in Minsk. Methods: From emergency healthcare registry of Minsk we obtained records 01 Jan 2013 - 31 Dec 2014 with non-missing doctor-validated ICD10 codes to determine stroke cases. Using official temperature data and time of the admission records we determined 24h average temperature prior to the stroke cases and control periods. The time-stratified casecrossover design was applied to investigate the association between temperature and stroke hospitalisations. Daily temperature during stroke cases were matched with 4 controls lag periods [lag (0) as day of the case, lag (-14), lag (-7), lag (+7) and lag (+14), divisible by 7 days to avoid week cycles]. We applied conditional logistic regression analysis to assess the association; To investigate potential departures from linearity for the temperature, restricted cubic splines (three splines corresponding to four knots at fixed percentiles 5, 35, 65, and 95 of the distribution) were used. Results: During the period, we observed 14,052 stroke cases (42% males, mean age 72.1 [Std.Dev 14.1] years), temperature varied from -4.1° to 34.8°C (mean+15.2[Std. Dev 7.1]°) in April-September period and from -22.6° to 18.5° (mean+0.1[Std.Dev 6.9]°) in October-March period. Preliminary analysis suggests non-linear U-shape relationship between stroke and temperature (pic1) with the lowest risk at 4.7°C. Low temperature (T1wGdTD that was >T1wGdSD, showing similar bell shape profiles. The FLAIR outcome was always20.0%) of the left and right BCA was found in 6 cases (10.3%). Tortuosity of the left VA was detected in 11 cases (18.9 %), of the right VA in 5 (8.6%). Conclusion: According to the results of DS BCA, VD caused by NVC in many cases is combined with extravasal compression of VA on the same side and VA tortuosity. The aspect ratio of NVC and signs of VA tortuosity established that in 30% of cases VA deformation was detected on the side of NVC. Disclosure: Nothing to disclose


Poster Sessions

617

P22208 Gradenigo's syndrome caused by odontogenic infection: an unusual aetiology M. Machio Castello1, M. Oses1, L. Olivie García1, R. Rigual Bobillo1, M. Ruggiero García1, M.T. Montojo Villasanta1, J. Villacampa Aubá2, M.A. Garcia Torres1, I. Zamarbide Capdepón1

Neurology, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain, 2Department of Ear, Nose and Throat Medicine., Hospital Fundación Jiménez Díaz, Madrid, Spain 1

Background and aims: Gradenigo’s syndrome is characterized by unilateral facial pain at the trigeminal nerve region, ipsilateral abducens nerve paresis and deafness. All these symptoms are usually caused by petrositis as a complication of acute suppurative otitis media. Methods: Clinical case report. Results: A 70-year-old patient with an odontogenic infection developed left sided retro-orbital pain, ipsilateral sixth cranial nerve palsy and V2-V3 division affectation (paraesthesias, numbness and dysesthesias), being diagnosed with Gradenigo’s syndrome. High-resolution brain MRI showed a hypointense lesion in the left cavum trigeminale in T2 weighted images, with significant enhancement after gadolinium administration, spreading towards the sphenopalatine fossa via the V2 and V3 division. The patient received antibiotic treatment with a complete clinical and radiological recovery.

Figure 3: complete radiological resolution after antibiotic treatment (MRI 3T, axial high resolution T2).

Conclusion: We found no recent case reports in the literature of an odontogenic infection producing Gradenigo’s syndrome. Perineural inflammatory dissemination via V2-V3 could explain the pathogenical mechanism of our patient’s case. Disclosure: Nothing to disclose

Figure 1: left V2 division enhancement (MRI 3T, axial T1-SPIR). Left cavum trigeminale occupation (MRI 3T, axial high resolution T2).

Figure 2: 27th left tooth extraction and left buccinator muscle thickening at CT scan. Enhancement at left buccinator, foramen rotundum and left cavum trigeminale at MRI 3T axial T1-SPIR.


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Poster Sessions

Peripheral nerve disorders 4

P22210

P22209

Sjögren’s syndrome presenting as subacute sensory ataxic neuronopathy and sensorineural hearing loss

Utility of sensory nerve conduction and summed Z-scores in polyneuropathy T. Sand1, K.B. Nilsen2, M. Engstrom1, R. Michler3, T. Wader3, K. Todnem3

1Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway, 2Oslo, Norway, 3Department of Neurology and Clinical Neurophysiology, Trondheim, Norway

Background and aims: The purpose of our study was 1) to estimate the sensitivity of sensory nerve conduction (NC) compared motor nerve conduction parameters in polyneuropathy (PNP) and 2) to estimate the sensitivity of summed Z-score nerve conduction variables in polyneuropathy. Methods: Consecutive patients (n=92) with clinically confirmed PNP of various aetiologies (21 had diabetes, 21 had cancer) were included (64% men, age mean 65 years, age range 30-85). Motor studies included median, ulnar, tibial and peroneal nerves with F-responses. Sensory studies included median, ulnar, radial, sural, peroneal and plantar medial nerves. Age and height adjusted reference values were calculated from 509 subjects (using 2SD cut-offs). Results: Motor leg nerve sensitivities were similar for conduction velocity (CV) (42-48%) and amplitude (4157%) while F-abnormality occurred in 25-32%. Sensory nerve sensitivities were lower for leg conduction velocities (31-40%) compared to leg sensory amplitudes (41-73%) while median and ulnar NC-variables were about equally sensitive for CV and amplitude (21-33%). Radial nerve sensory CV and amplitude were somewhat more sensitive (39-49%). Summed Z-scores for 13 sensory nerve variables were more sensitive (79%) than 18 motor nerve variables (65%). The highest sensitivity (84%) was achieved for a combination of six leg and one arm sensory variables and seven leg motor NC variables. Conclusion: Several sensory nerves of the leg and the radial nerve should be included in NC-studies of PNP patients. Summed Z-scores should be used more often since this method is very sensitive and largely eliminates problems with “false positives” in multiparameter test protocols. Disclosure: Nothing to disclose.

M. Santos1, R. Martins1, R. Paquete Oliveira2, A. Furtado2, A.P.S.P. Lobo1, R. Manso3, B. Grima2, L. Santos4, M.C.M. Costa1

1Neurology, Hospital Prof. Dr. Fernando Fonseca, EPE, Amadora/Lisbon, Portugal, 2Department of Internal Medicine-Systemic Immune-mediated Diseases Unit, Hospital Prof. Dr. Fernando Fonseca, EPE, Amadora, Portugal, 3Anatomical Pathology, Hospital Prof. Dr. Fernando Fonseca, EPE, Amadora/Lisbon, Portugal, 4Neurophysiology Laboratory, Hospital Prof. Dr. Fernando Fonseca, EPE, Amadora/Lisbon, Portugal

Background and aims: Differential diagnosis of ganglioneuropathy includes paraneoplastic, inflammatory, infection and metabolic diseases and iatrogenic causes. Neurological symptoms occur in 20% of Sjögren’s syndrome cases and may sometimes precede the sicca syndrome. Methods: Case report Results: A 51-year-old woman was admitted because of a three month-long history of gait imbalance, distal paraesthesia of upper limbs, loss of proprioception in the extremities, inability to perform fine hand movements and bilateral hearing loss, with a progressive course. Neurological examination showed generalized hyporeflexia, severe loss of vibration sensation, pseudoathetotic hand postures and sensory (limb and gait) ataxia. ENT examination disclosed bilateral sensorineural hearing loss. Neuroaxis MRI showed ischemic microangiopathic leukoencephalopathy and a continuous T2 hyperintensity of the spinal dorsal columns. Electromyography revealed a polyganglionopathy. Body CT and FDG-PET were negative for neoplasia, but the latter showed increased uptake in the salivary glands. Analytics showed positive ANA (1/640), anti-SSB antibody and lupus anticoagulant. CSF studies were unremarkable. Analytic screening for infectious, metabolic, endocrinological and paraneoplastic causes and anti-inner ear antibodies were negative. Schirmer test and salivary scintigraphy were normal. Salivary gland biopsy showed mild inflammatory changes (Chisholm-Mason grade 1). A diagnosis of Sjögren’s syndrome was established and the patient begun immunosuppressive therapy with cyclophosphamide and corticotherapy along with physiotherapy, with minor improvement in fine motor skills and gait.


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619

P22211 Sensory ganglionopathy associated with gluten sensitivity: a case report J. Sequeira, S. Dias, J. Morgado, C.M.C. Capela, A. Calado, R.M.G. Pedrosa

Neurology, Centro Hospitalar Lisboa Central, Lisbon, Portugal

Spine MRI showing a continuous T2 hyperintensity of the spinal dorsal columns (arrow)

Brain MRI disclosed ischemic microangiopathic leukoencephalopathy

Conclusion: The authors present a case of Sjögren’s syndrome presenting as a sensory ataxic neuronopathy with prominent sensorineural hearing loss, in the absence of a sicca syndrome or other systemic features, which made diagnosis particularly challenging. Disclosure: Nothing to disclose

Background and aims: Sensory ganglionopathies are a rare type of peripheral neuropathy characterised by damage to the dorsal root ganglia and are frequently associated with systemic immune-mediated disorders or paraneoplastic syndromes. The authors present a case of sensory ganglionopathy due to gluten sensitivity (GS). Methods: Case report. Results: A 63-year-old previously healthy Caucasian female presented with a 1-year history of gait impairment associated with right hemibody paraesthesias. Examination demonstrated a wide-based gait with a positive Romberg test, right hemiataxia and ipsilateral hypoesthesia. Electromyography showed widespread loss of right sensory-nerve action potentials, compatible with a sensory ganglionopathy. Brain and cervical spine magnetic resonance imaging were normal. Cerebrospinal fluid analysis was unremarkable. Exhaustive laboratory workup for infectious, paraneoplastic or autoimmune diseases was negative. The patient was treated with 5-day course of intravenous immunoglobulin (IVIG) 30g/d followed by methylprednisolone 1g daily for 5 days with significant clinical improvement. She was readmitted one and a half years later due to progressive neurological worsening and was treated again with IGIV with similar results. Repetition of the laboratorial workup revealed high levels of antigliadin IgG antibodies and a diagnosis of GS was assumed. The patient began a gluten-free diet with a dramatic neurological response and resolution of unspecific gastrointestinal symptoms. Duodenal biopsy performed five months later was normal. Conclusion: GS is an autoimmune disease with systemic manifestations triggered by the ingestion of gluten. Neurologic dysfunction can be the presenting feature even in the absence of gastrointestinal symptoms. Precocious detection is essential to allow timely therapeutic intervention and ensure clinical stabilization and improvement. Disclosure: Nothing to disclose


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P22212

P22213

Rituximab in the treatment of anti-myelinassociated glycoprotein (anti-MAG) neuropathy resistant to conventional immune therapies: a 15-year experience

Interest of anti-ganglioside antibodies for the diagnosis of neuropathies of unknown aetiology: a series of 47 patients

S. Simonetti

Neurology and Neurophysiology, Clinica Villa Montallegro, Genoa, Italy

Background and aims: Rituximab, a monoclonal antibody directed against the B-cell surface membrane CD20, has been shown to be effective in neuropathies with IgM antimyelin-associated glycoprotein (MAG) antibodies in small series and a small placebo-controlled trial. However, a larger randomized controlled trial recently failed to show significant clinical improvement, and, until now, the exact effective dose and the long-term effects are not known. Methods: We report the clinical, electrophysiological and immunological findings of eight cases with chronic progressive sensorimotor neuropathies associated with antiMAG antibodies and IgMK or IgMλ monoclonal gammopathy of undetermined significance (MGUS) treated with cycles of four weekly infusions of rituximab (375/m2), during a 15 years follow-up. All the eight patients had previous ineffective treatment with various combination of intravenous immunoglobulins, plasma exchange, prednisone, pulse intravenous cyclophosphamide, chlorambucil and cyclosporine. Quantitative assessment included modified Rankin disability score, MRC strength score, four limb sensory score, electrodiagnostic studies, autoantibodies serum concentration, and B-cell count. Results: All the eight patients noted a subjective amelioration within 3 months, while an initial objective improvement was observed within 6 months after treatment. In five of the seven patients with IgMK MGUS, the clinical and neurophysiological improvement persisted until two or three years, while, in the remaining two, there was a hitherto stable remission after one or two cycles. In the patient with IgMλ MGUS, the modest improvement lasted about one year. No significant side effects were reported. Conclusion: Our results seem to indicate that Rituximab may be a safe, effective, long lasting and, occasionally, resolutive treatment in IgM anti-MAG neuropathies. Disclosure: Nothing to disclose

M. Stéphant1, P. Chretien2, C. Cauquil1, G. Beaudonnet3, A. Not1, S. Hacein-Bey2, D. Adams1, C. Labeyrie1

1Neurologie Adulte-NNERF (French Reference Center for FAP and other Rare Peripheral Neuropathies), CHU Bicêtre, Le Kremlin-Bicêtre, France, 2Laboratoire d’immunologie, CHU Bicêtre, Le Kremlin-Bicêtre, France, 3Laboratoire d’Electrophysiologie, CHU Bicêtre, Le Kremlin-Bicêtre, France

Background and aims: Dysimmune neuropathies, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), represent a heterogeneous group of peripheral nerve disorders. Antiganglioside antibodies (AGA) can be detected, except for some well-defined entities; the interpretation of their positivity remains unclear. Methods: We retrospectively selected AGA positive neuropathies over a 2-year period in a tertiary referral centre for rare neuropathies and specifically studied neuropathies of unknown aetiology, in order to determine their clinical, biological and electrophysiological profile. Results: 165 patients were AGA positive: 64 presented a definite neuropathy, 86% of them dysimmune, and 65 a neuropathy of unknown aetiology among which 47 cases were included in our study. Most patients (68%) presented a sensory neuropathy, often painful but not severe (median ONLS 2). 13 patients (28%) were treated with intravenous immunoglobulins with improvement in 7. 8 patients (17%) fulfilled the criteria for sensory neuronopathies. They were younger (p=0.0013), more severe on the ONLS and INCAT scales (p=0.0432 and p=0.0026) but their AGA profile did not differ from other patients. 26 patients (55%) had at least one AGA anti-disialosyl positive, among which 7 (27%) had a monoclonal protein (MP), 13 (50%) ataxia and 3 (11%) cranial nerve involvement suggesting incomplete CANOMAD syndrome. 5 patients (19%) met the criteria for sensory neuronopathies. 11 patients (24%) had a MP with more AGA polypositivity profiles (p=0.024). Conclusion: Among immune-mediated neuropathies, sensory entities are difficult to classify. In our study there seems to exist a continuum among “sensory neuronopathyCANOMAD-CIDP”, in which AGA could be useful biomarkers. Disclosure: Nothing to disclose


Poster Sessions

621

P22214

P22215

An unusual cause of transient diplopia

Acute polyneuropathy secondary to thiamine deficiency: one year of follow-up

K. Szőke, Z. Aranyi, G. Bozsik, D. Bereczki Budapest, Hungary

Background and aims: We present a case of a 51-year-old male patient. The patient presented at our clinic after the third relapse of transient diplopia. The first episode took place 5 years earlier. In the case of the two previous episodes extensive work-up had been done. The third episode of diplopia lasted several days but at the time of admission it had already been ceased. The patient incidentally complained about the tingling of the fingertips, a feature he hadn't considered significant before. Methods: After admission we started a diagnostic work-up including MRI of the head, electrophysiological and laboratory studies. Results: On examination we found diminished reflexes on the upper extremities, areflexia on the lower extremities but the examination was otherwise normal. A repeat MRI scan was performed, there was no structural alteration of notice. After a normal repeat edrophonium test we performed more extensive electrophysiological testing. In the peripheral nerves of the extremities we found temporal dispersion both in the motor and sensory fibres, lacking F-waves and F-waves with profoundly prolonged latencies. The electromyography showed mild chronic neurogenic changes. The facial nerve was also affected. Conclusion: On the basis of the clinical features and findings we concluded that the transient diplopia was caused by a chronic demyelinating polyneuropathy. Unfortunately, until now the complete work-up is lacking due to the patient refusal of further testing. The case exemplifies that a Miller Fisher Syndrome-like form of a chronic demyelinating polyneuropathy can be a cause of fluctuating diplopia as a presenting complaint. Disclosure: Nothing to disclose

H. Tibar1, W. Regragui2, E. Ait Ben Haddou2, A. Benomar2, M. Yahyaoui2

Rabat, Morocco, 2Department of Neurology B and Neurogénétics, CHU Ibn Sina Rabat, hôpital des spécialités ONO, Rabat, Mohammed V University, Rabat, médecine school of Rabat, Rabat, Morocco

1

Background and aims: Thiamin deficiency can typically take two neurological aspects: Wernicke encephalopathy (EW) and chronic polyneuropathy (PN). We report the case of combination of EW to acute PN and discuss the pathophysiology Methods: The patient was first admitted to the emergency department then hospitalized in the department of neurologyB. The diagnosis of EW associated to acute PN was confirmed based on clinical history, neurological examination, cerebral MRI, EMG study, CSF analysis and the vitamin B1 dosage. We followed the patient for a year Results: L.K. is 55-year-old woman, obese, with history of alternating diarrhoea-constipation. The waning of an episode of acute gastritis, she presented hyperemesis, mental confusion and horizontal diplopia with ascending tetraplegia. Neurological examination found a delirium, bilateral paralysis of the VI nerve and total flaccid quadriplegia. Brain MRI revealed hyperintensity periacqueducal on T2 and flair. The EMG study found an axonal sensorimotor PN with normal CSF; campylobacter-jejuni serology and anti-GQ1b-antibodies were negative. VitaminB1 was very low. The patient began to recover her motor deficit 8 days after we started vitaminB1 substitution and Immunoglobulins, while the delirium disappeared three weeks later. One year later, the patient has completely recovered her motor deficit. Conclusion: Acute PN due to thiamine deficiency is rare, explained by an acute and important vitaminB1 lost. The combination of two acute complications in our patient may be attached to the importance of hyperemesis occurring on a deficiency ground and chronic malabsorption. The vitamin substitution is very efficient and must be started the earliest possible to ensure good recovery. Disclosure: Nothing to disclose


622

Poster Sessions

P22216

P22217

Clinical features in a CIDP (Chronic Inflammatory Demyelinating Polyneuropathy) population from Southern Italy

Lewis-Sumner syndrome (L-SS), a rare variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

A. Topa1, E. Spina1, R. Iodice1, S. Tozza1, L. Ruggiero1, M. Esposito1, L. Santoro1, F. Manganelli2

M.H. Torregrosa Martinez, M. Molina Sánchez, P. Hernández Navarro, L.A. Lozano García-Caro

1Department of Neurosciences and Reproductive and Odontostomatologic Sciences, University Federico II, Naples, Italy, 2Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II of Naples, Italy

Background and aims: To describe clinical features in a cohort of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) from a tertiary care neuromuscular centre in Campania, Southern Italy. Methods: We selected the patients fulfilling definite European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria for CIDP among those affered to our neuromuscular centre at University Federico II of Naples in the last 15 years. Results: We identified 60 patients with a diagnosis of definite CIDP. Male:Female ratio was 2.33:1. Mean age was 55.35 years, mean age of onset was 44.02 years and mean disease duration was 11.05 years. Three patients were dead. 10 patients (16.67%) had acute onset. The course of disease was monophasic in 13.33% of patients, relapsing in 55% and progressive in 31.67%. According to EFNS criteria, 26.67% of patients presented an atypical phenotype: 62.5% had a multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, 31.25% a pure sensory variant and 6.25% a distal acquired demyelinating symmetric (DADS) neuropathy. Regarding clinical disability, mean value of Rankin Modified Scale (RMS) was 2.31 and 15% of patients showed severe disability (RMS ≥4). Lastly, 86.67% of patients were responsive to corticosteroids or intravenous immunoglobulin (IVIG). Notably, 73.08% of patients responded to IVIG and 26.92% responded to corticosteroids. Conclusion: Overall, our data are in line with those previously reported for CIDP, also in other geographic areas. Notably, the majority of patients responded to treatment and only a minority of patients showed severe disability. Disclosure: Nothing to disclose

Neurology, Hospital Universitario Príncipe de Asturias, Madrid, Spain

Background and aims: Multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy or L-SS, is a variant of CIDP defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. Methods: A 38-year-old man suffered progressive and asymmetrical distal limbs weakness and paraesthesia, which started in the left foot, followed by both hands. Initial neurological examination revealed atrophy of the lower left limb and both upper limbs distal muscles, upper limbs hyporeflexia and patellar and Achilles reflexes absence, generalized fasciculations and patched sensory loss in the right hand and feet. Results: Electromyographic studies showed sensory-motor demyelinating multineuropathy. No serum antiganglioside or anti-myelin associated glycoprotein antibodies were detected. Other potential causes of neuropathy were excluded by means of appropriate complementary tests. Mild recovery was observed after initial treatment with intravenous immunoglobulin (IVIg). Later worsening of symptoms required subsequent IVIg cycles. Conclusion: A case of L-SS with typical clinical and electrophysiological outcomes is reported. Remarkable symptoms of this disease are a progressive course with an asymmetric distal pattern of distribution. IVIg continues to be the first-line therapy. We emphasize the importance of recognizing L-SS as an independent entity from CIDP and multifocal motor neuropathy (MMN). It would facilitate early diagnosis and treatment of patients with an asymmetric sensory or sensorimotor demyelinating neuropathy. Disclosure: Nothing to disclose


Poster Sessions

623

P22218

P22219

Motor unit number estimation in acute inflammatory demyelinating polyneuropathy

Can a mobile phone be used to test vibration sensation?

M. Vaeggemose1, A. Fuglsang-Frederiksen2, H. Andersen1, B. Isak2, T. Harbo1, H. Tankisi2

1Medical School, University of Manchester, Manchester, United Kingdom, 2Medical School, University of Edinburgh, Edinburgh, United Kingdom, 3Neurology, Salford Royal Foundation Trust, Manchester, United Kingdom

1Department of Neurology, Aarhus University Hospital, Aarhus, Denmark, 2Clinical Neurophysiology, Aarhus University Hospital, Aarhus C, Denmark

Background and aims: To evaluate motor unit loss using Multiple Point Stimulation (MPS)-Motor Unit Number Estimation (MUNE) and motor unit number index (MUNIX) in patients with Acute Inflammatory Demyelinating Polyneuropathy (AIDP). Methods: MPS-MUNE and MUNIX on abductor pollicis brevis (APB) were done at week 1 and week 4 of symptom onset in 10 AIDP patients (mean age: 50.10) and in 22 healthy controls (mean age: 49.82). Motor unit size was calculated as surface-Motor-Unit-Potential (sMUP) and Motor-unit-size-index (Musix). Electromyography of APB was performed in all patients. Results: In AIDP patients, MPS-MUNE (week 1: 85 (18193), week 4: 87 (18-158)) and MUNIX (week 1: 113 (23256), week 4: 124 (26-187)) differed from control MPSMUNE (141 (66-329) and MUNIX (203 (116-364)) (p65 years) who met the criteria for MCI and evaluated their cognitive performances at baseline and annual for the next three years. The diagnostic of dementia was established using DSM IVTR criteria. Results: From the all patients, 199 patients (54%) had amnestic MCI and 166 patients (46%) non-amnestic MCI. The rate of conversion in the first year was 10.4%, in the second year 17.8% and in the third year 23.3%. The mean rate of conversion during the follow-up period was 18.9% for Alzheimer's disease (AD), 11.8% for vascular sementia (VD) and 13.2% for Alzheimer's disease with cerebrovascular disease (AD with CVD). The rate of conversion for specific MCI subtypes was 17.1%/year for patients with amnestic MCI and 11.5%/year for nonamnestic MCI. During the follow-up period 69 patients converted to AD; 71% were patients with amnestic MCI, 43 of the patients converted to VD; 46.5% were patients with amnestic MCI and 48 patients converted to /ad with CVD; 68.7% were patients with amnestic MCI. The mean age for convertors was 72.8 and for non-convertors 74.2. The AD converters have high serum cholesterol levels, high density lipoprotein and the debut of hypertension before 65. Conclusion: The combination of amnestic MCI subtypes with the clinical risk factors increased the risk of conversion to dementia. Disclosure: Nothing to disclose

D. Religa1, L. Bognandi2, P. Čermáková1, B. Winblad3, M. Seyed-Fereshtehnejad2, S. Garcia-Ptacek2, M.E. Eriksdotter1 1Stockholm, Sweden, 2NVS, Karolinska Institute, Stockholm, Sweden, 3Department of Neurobiology, Care Sciences and Society, Karolinska Institute/European Alzheimer’s Disease Consortium, Karolinska Institute, Stockholm, Sweden

Introduction: Emerging evidence shows an association between atrial fibrillation (AF) and dementia. Treatment for AF in patients with dementia has been suggested to be lower than for patients without dementia due to a higher risk of bleeding. Studies have not included all types of dementia disorders. Aims: This study aimed to find the prevalence of AF in different dementia disorders and to assess prevalence of warfarin use in dementia disorders. Methods: A register-based, cross-sectional study, combining data from several registries. Patients from the Swedish Dementia Registry (n=29,630) within 2007-2012 were included. Results: In the total study cohort, prevalence of AF was 19%. AF was more prevalent in mixed dementia (MD) (OR 1.1; 95% CI 1.0-1.3) and vascular dementia (VD) (OR 1.3; 95% CI 1.1-1.4) and more associated with MD and VD than Alzheimer’s disease (AD) even after adjustment for confounders. 40% of individuals with AF got treated with warfarin. Warfarin use was more associated with MD (OR 1.2; 95% CI 1.0-1.4) and VD (OR 1.3; 95% CI 1.1-1.5) than AD, after controlling for confounders. Conclusion: The burden of AF is high in dementia patients. The burden is highest in patients with MD and VD, disorders possibly partially caused by AF. Warfarin treatment is more often associated with MD and VD than other dementia diagnoses, probably due to a higher risk of stroke. Disclosure: Nothing to disclose

© 2016 EAN

625

626

Poster Sessions

P31003

P31004

Accuracy of clinical diagnosis of dementia with Lewy bodies: a systematic review and meta-analysis

High incidence of sporadic CreutzfeldtJakob disease in Slovenia in 2015

G. Rizzo1, S. Arcuti2, M. Copetti3, M. Alessandria2, R. Savica4, A. Fontana5, R. Liguori1, G. Logroscino6

Bologna, Italy, Department of Clinical Research in Neurology, University of Bari, Tricase, Italy, 3Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, 4Department of Neurology and Health Science Research, Mayo Clinic, Rochester, USA, 5Unit of Biostatistics, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy, 6BARI, Italy 1

2

Background and aims: The diagnosis of dementia with Lewy bodies (DLB) is based on diagnostic criteria, which were updated over the years. Our aim was to perform a systematic review of the studies on diagnostic accuracy in DLB and to meta-analyse sensitivity, specificity and accuracy of the used diagnostic criteria, to evaluate how they changed over time. Methods: We searched on MEDLINE and SCOPUS databases for studies reporting diagnostic parameters regarding the clinical diagnosis of DLB. We performed meta-analysis on those using pathological examination as gold standard. Results: We selected 21 studies on 21 populations and 1520 patients. Pooled sensitivity, specificity and accuracy were respectively 59.9%, 93% and 79.3% for criteria antecedents to McKeith 1996, 56.1%, 86.9% and 75.6% for McKeith criteria 1996 and 84.5%, 59.6% and 75.8% for McKeith criteria 2005. Looking at “possible” or “probable” diagnosis separately, sensitivity, specificity and accuracy were: i) 65.6%, 80.5% and 77.8% for McKeith 1996-possible in early stages, and 66.1%, 71.5% and 68.6% in late stages; ii) 19.4%, 95.1% and 77.6% for McKeith1996-probable in early stages, and 46.7%, 93.2% and 83.7% in late stages; iii) 86%, 36.7% and 69.4% for McKeith 2005-possible in late stages, and 83.8%, 66.9% and 77.6% for McKeith 2005-probable in late stages. No studies evaluated McKeith criteria 2005 in early stages. Conclusion: One out of five patients with DLB has a misdiagnosis. Diagnostic criteria have become more sensitive and less specific over time. Diagnostic accuracy did not substantially change in last years. Further improvement is needed to optimize the clinical diagnosis of DLB, eventually using biomarkers. Disclosure: Nothing to disclose

T. Rus1, N. Čakš Jager2, M. Popović3, M. Blaško Markič2, M. Kramberger Gregoric1 1Neurologic clinic, University medical centre Ljubljana, Ljubljana, Slovenia, 2National Institute of Public Health of Slovenia, Ljubljana, Slovenia, 3Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

Background and aims: Creutzfeldt-Jakob disease (CJD) is a fatal prion disease presenting as rapidly progressive dementia with additional neurological signs. Mortality rate of sporadic CJD (sCJD) in European countries is 0.22–1.72 per million. Mean mortality rate in Slovenia in the period 1993-2014 has been 1.25 per million. Methods: We investigated patients presenting with rapidly progressing dementia admitted to Department of Neurology, University Medical Center Ljubljana. We excluded treatable causes and used diagnostic criteria for CJD. Autopsies were performed on patients that died. We also acquired data of patients diagnosed with suspected CJD reported from other Slovenian hospitals to National Institute of Public Health. Results: There were 6 patients with probable or definite sCJD diagnosed at our clinic and additional 3 in other Slovenian hospitals in 2015. Altogether there were 9 cases, incidence was 4.36 cases per million including definite and probable diagnosis. 7 patients were diagnosed with definite sCJD at autopsy. 2 were diagnosed with probable sCJD, one of which died recently and brain autopsy is pending. There were 6 females and 3 males, mean age was 71.9 years. There was no specific geographic pattern identified. Conclusion: Incidence rate of sCJD in Slovenia in 2015 was high. However, there was fluctuation sCJD cases in Slovenia in the period 1993-2014, mortality rate varied from 0.0 to 3.5 per million. High incidence of sCJD in 2015 probably reflects fluctuation of sporadic cases of rare disease in a relatively small cohort of two million inhabitants of Slovenia. Disclosure: Nothing to disclose


Poster Sessions

627

P31005

P31006

Clinical variability in GerstmannSträussler-Scheinker syndrome: a retrospective case study

Timed Up and Go Dual Task and 11C-PiBPET as prognostic indicators of progression in mild cognitive impairment and mild AD

R. Rusina1, S. Johanidesová2, Z. Rohan3, R. Matěj3 1Neurology, Charles University in Prague, First Faculty of Medicine, General Teaching Hospital, Prague, Czech Republic, 2Neurology, Thomayer Hospital, Prague, Czech Republic, 3Pathology and Molecular Medicine, Thomayer Hospital, Prague, Czech Republic

Background and aims: Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare autosomal dominant disease caused by pathogenic mutations in the prion protein gene (PRNP), usually m anifesting as a progressive ataxia with late cognitive decline. Methods: We present data of 6 patients with neuropathologically and genetically confirmed GSS sharing the same mutation P102L of PRNP. Clinical data and MRI were available in all cases, EEG in five and cerebrospinal fluid analysis in four cases. Results: The age of onset was 37-62 years, with disease duration ranking from 6 to 48 months. Positive family history was found in 4 cases, dementia and behavioural changes were present in all cases; 2 patients showed MRI hyperintensities in the caudate and putamen evoking Creutzfeldt-Jakob disease; periodic triphasic complexes on EEG were observed only in one patient. All analysed cerebrospinal fluid samples revealed a very high level of total tau protein; however, protein 14-3-3 was positive only in 2 cases. Conclusion: Our observation demonstrates a very variable clinical manifestation, disease duration and family history in GSS despite sharing the same PRNP mutation. This highlights the importance of genetic testing and neuropathological confirmation of all suspected CreutzfeldtJakob disease cases and/or atypical neurodegenerations. Disclosure: This study was supported by grant P303/12/1791 of the Grant Agency of the Czech Republic.

M. Schjonning Nielsen1, A. Hviid Simonsen2, I. Law3, V. Siersma4, S.G. Hasselbalch2, P. Høgh1

1Roskilde Regional Dementia Research Centre, Dept of Neurology, University Hospital Copenhagen , Roskilde, Denmark, 2Memory Disorders Research Group, Rigshospitalet, Copenhagen, Denmark, 3Dept. of clinical Physiology, Nuklear Medicin and PET, University of Copenhagen, Rigshospitalet Klinik for Klinisk Fysiologi, Nuklear Medicin og PET, Rigshospitalet, Copenhagen, Denmark, 4Department of Public Health, University of Copenhagen, Research Unit for General Practice and Section of General Practice, Copenhagen, Denmark

Background and aims: With age, motor performance declines and elders become increasingly depended on cognition to perform motor tasks. As cognition worsens in mild cognitive impairment (MCI), impairment in gait and balance increases. Timed Up and Go Dual Task (TUG-DT) is a reliable tool for measuring mobility and the ability to perform tasks simultaneously. We aimed to evaluate how TUG-DT correlates with cortical amyloid uptake with 11C-PiB-PET in MCI and mild AD and to investigate the ability of TUG-DT as a prognostic indicator of progression in MCI compared to 11C-PiB-PET. Methods: We studied patients diagnosed with MCI or mild AD and a healthy control group (HC). TUG-DT and 11C-PiB-PET were performed at baseline. Patients were clinically evaluated, including TUG-DT, yearly. Dual-task cost (DT-cost) was measured as the difference in performance time between TUG and TUG-DT. Results: A total of 57 patients (MCI=18, AD=10, HC=29) were included. A significant lower DT-cost was found in the HC compared to the MCI and AD. No significant difference in DT-cost was found between the progressive and the stable MCI groups nor between the MCI with a positive 11C-PiB-PET and a negative 11C-PiB-PET. A positive significant correlation between DT-cost and a positive 11C-PiB-PET was seen for the entire cohort Conclusion: Our findings indicated that TUG-DT potentially has the ability to differentiate between MCI and HC, but not to predict clinical progression in MCI. A positive correlation between DT-cost and 11C-PiB-PET was found. Disclosure: This study was supported by The Velux Foundations


628

Poster Sessions

P31007

P31008

Quantitative electroencephalography (qEEG) as a prognostic marker of progression in mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD)

Czech Brain Aging Study (CBAS) – National longitudinal cohort study with AD biomarkers. Design and first data about progression rates in 3 year follow-up

M. Schjonning Nielsen1, A. Hviid Simonsen2, S.G. Hasselbalch2, P. Høgh1

K. Sheardova1, M. Vyhnálek2, Z. Nedelska2, J. Laczó2, R. Andel3, R. Marciniak1, D. Hudecek1, B. Dvorakova1, O. Lerch2, J. Hort2

1Regional Dementia Research Centre, Dept. of Neurology, University Hospital Copenhagen, Roskilde, Roskilde, Denmark, 2Memory Disorders Research Group, Rigshospitalet, Copenhagen, Denmark

Background and aims: Biomarkers of dementia, that are inexpensive, widely available, and accessible in a normal clinical settings are currently lacking. qEEG based on the Statistical Pattern Recognition method (qEEG-SPR) is an inexpensive and simple method, which has demonstrated promising results in differentiating AD from both other dementias and healthy controls as well as potentially predicting progression from MCI to AD. We aimed to investigate the potential of qEEG as a prognostic marker of clinical progression in AD, and in MCI regardless of the underlying aetiology. Methods: We studied a cohort of patients clinically diagnosed with either MCI or mild AD. All had a standard EEG performed at baseline, but the EEG was not part of the diagnostic work-up. Patients were subsequently clinically evaluated on a yearly basis to determine clinical progression. The EEG data were recorded in a standardized way and analysed using the SPR method (qEEG), where EEG features from an individual were compared to data from the qEEG database. Results from the qEEG-analysis indicated either a progressive (AD or DLB/PDD-like) or a nonprogressive condition. Results: A total of 64 patients (MCI=38, AD=26) were included. At baseline 39.5% in the MCI group had a qEEG indicating a progressive disorder, compared to 61.5% in the AD group. No significant difference in qEEG results (progressive vs non-progressive) was found between the clinically stable and progressive subgroups within the MCI group. Conclusion: These preliminary analyses indicated that the qEEG-SPR method did not have the ability to predict clinical progression in our group of MCI patients. Disclosure: The study was founded by the Velux Foundation

st Neurology Department, ICRC, St. Anne´s University Hospital, Brno, Czech Republic, Brno, Czech Republic, 2Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic, 3School of Aging Studies, University of South Florida, Tampa, Florida, USA 11

Background and aims: CBAS is a longitudinal study investigating early markers of Alzheimer’s disease (AD) and risk factors of dementia, based on well-defined cohorts of subjects with AD biomarkers. Methods: Prospective data from non-demented subjects 55+older are collected in 2 CBAS memory clinics in Prague and Brno and entered to CBAS database. All underwent biomarker assessment – UDS neuropsychological examination, 3T brain MRI, APOE genotyping and fill in multiple questionnaires about cognitive complaints. In a subset, brain amyloid-beta load is assessed by amyloid-PET and/or CSF. Standard criteria based consensual diagnosis classifies subjects into cohorts; normal controls (NC), subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Possible MCI aetiology is based on biomarkers and 2011 Albert’s NIA-AA guidelines. Subjects are followed annually; additional data are collected from experimental neuropsychology, spatial navigation, life-style questionnaires and from CSF and DNA biomarker analyses. Progression from NC/SCD to MCI or dementia, and from MCI to dementia or back to norm is the main outcome; also longitudinal quantitative measures of cognitive decline are used for evaluation of early markers of AD and risk factors for progression. Results: From 1785 subjects examined in 2011-2015, 752 met CBAS inclusion criteria and were entered into CBAS database. 1/3 finished 3 and more years follow-up. Current data about stratification to NC, SCD, MCI, dementia and progression rates will be presented. Conclusion: CBAS is a unique database of well-defined cohorts at risk of AD in culturally homogenous white Caucasian Czech population allowing analysing possible new biomarkers and risk factors of AD. Disclosure: Nothing to disclose


Poster Sessions

629

P31009

P31010

Combination therapy of cholinesterase inhibitor plus memantine for behavioural and psychological symptoms in Alzheimer's disease patients

miRNA expression profiles in cerebrospinal fluid and blood of patients with Alzheimer’s disease and other types of dementia: an exploratory study

C. Shin

S.S. Sørensen1, A.-B. Nygaard2, T. Christensen1

Neurology, Seo-Gwang general hospital, Gwang-ju, Korea, Republic of

Background and aims: To compare the effectiveness of combination therapy with cholinesterase inhibitors (ChEI) plus memantine in the treatment of delusion, aggression and psychosis with older Alzheimer’s disease (AD) patients (age >75 years). Methods: We was used to compare the clinical effects of combination therapy of cholinesterase inhibitors (ChEI) plus memantine (n=50) in all AD patients with behavioural and psychological symptom of dementia (BPSD) (assessed by NPI baseline score). Primary efficacy measure: Neuropsychiatric Inventory (NPI); secondary efficacy measures: Clinical Global Impression (CGI), CohenMansfield Agitation Inventory (CMAI), Mini-Mental State Examination (MMSE) and instrumental activities of daily living (ADL). Results: The addition of memantine resulted in stabilization of the Mini-Mental State Examination scores for 6 months. NPI scores decreased significantly from baseline to month 6 (P 200 CGG repeats) and grey zone (45-55 CGG repeats). Female premutation carriers may present primary ovarian insufficiency (FXPOI), males may present tremor ataxia syndrome (FXTAS) and neuropsychological developmental problems. The aim of our study was to perform a systematic study on eye movements, tremor, repetitive hand/finger movements and neuropsychological performance of Fragile X (FraX) premutation carriers. Methods: We examined 5 asymptomatic FraX premutation carriers. Tremor (resting, postural, intentional, kinetic) and repetitive hand and finger movements were recorded with accelerometry. Computerized electrooculography system was used for analysis of smooth pursuit eye movement, reflexive saccades, optokinetic nystagmus. Correlation between the alteration of hand and eye movements were statistically analysed. Neuropsychological assessment was performed with a complex battery including Montreal Cognitive Assessment (MOCA-III), Rey auditory verbal learning test (RAVLT) and Rey-complex figure test. Results: Tremor examination showed a tendency towards low frequencies (2-3Hz) in three cases at postural and/or kinetic position. The maximum frequency of repetitive hand/finger movements was decreased in three cases. We have found saccadic SPEM in two cases. Gaze-evoked endpoint nystagmus with low amplitude was present in all cases. Impaired visuospatial processing could be detected in three cases. MOCA-III score in one case, RAVLT score in two cases was lower than normal. Conclusion: This is the first systematic study on the correlation between eye movement disorders and repetitive motor performance in FraX premutation carriers. Relevance of current findings should be elucidated with further investigation. Disclosure: Nothing to disclose

M. Kovács1, G. Deli2, Z. Aschermann2, P. Ács2, E. Bosnyák3, J. Janszky3, A. Makkos1, S. Komoly3, N. Kovacs1

Pécs, Hungary, 2University of Pécs, Pécs, Hungary, Department of Neurology, University of Pécs, Pécs, Hungary 1 3

Background and aims: To assess the frequency and severity of various non-motor symptoms (NMS) in Parkinson’s disease (PD) including the impulse control disorder (ICD) symptoms. Methods: A total of 621 patients with PD treated at University of Pécs was enrolled into this cross-sectional study. The Hungarian validated versions of the following scales were assessed: MDS-UPDRS, ACE, MoCA, ESS, PDSS-2, NMSS, LARS), MIDI and QUIP. Results: Occurrence of various NMS were the following: neurocognitive disorder: 25.2%, hallucinations: 7.4%, depression: 75.0% (clinically pertinent: 38.6%), anxiety: 80.3% (clinically pertinent: 36.3%), apathy 20.1%, dopamine-dysregulations syndrome: 8.9%, sleep problems: 69.2% (clinically pertinent: 47.4%), daytime sleepiness: 53.3% (clinically pertinent: 6.0%), pain: 71.3% (clinically pertinent: 42.3%), urinary problems: 68.4% (clinically pertinent: 40.2%), constipation: 50.5% (clinically pertinent: 23.4%), orthostatic hypotension: 66.5% (clinically pertinent: 9.4%) and fatigue: 87.7% (clinically pertinent: 53.9%). Sexual dysfunctions occurred more often in males (31.6% vs. 18.1%, p5x upper limit of normal (ULN) was higher with daclizumab HYP than intramuscular interferon beta-1a (Table). This analysis further explores liver transaminase elevations in DECIDE. Methods: RRMS patients were randomised to daclizumab HYP 150mg subcutaneous every 4 weeks or interferon beta1a 30mcg intramuscular once weekly for 96−144 weeks. Time to onset and duration (days) and rates of resolution of ALT or AST elevations ≥3x or >5x ULN were evaluated (see Table footnotes for definitions). Results: Incidence of ALT-AST elevations was similar between treatment groups during the first year; subsequently, incidence decreased for interferon beta-1a but remained relatively stable for daclizumab HYP (Figure A-B). Median time to onset of first ALT-AST elevation ≥3x or >5x ULN was longer with daclizumab HYP than interferon beta-1a (Table). Overall, median durations of ALT-AST elevations ≥3x or >5x ULN were similar between treatment groups, although slightly lower with daclizumab HYP (Table). Most patients with elevations ≥3x and >5x ULN had events that resolved during study follow-up (Table). Median durations of elevations were comparable between patients who were/ were not dosed with daclizumab HYP on the first day the ALT-AST elevation was observed, respectively (ALT-AST elevation ≥3x ULN: 87.0 [n=47] vs. 78.0 [n=49] days; ALTAST elevation >5x ULN: 63.0 [n=16] vs. 93.0 [n=43] days).

Conclusion: Time to onset of ALT-AST elevations ≥3x or >5x ULN differed between treatment groups; however, the durations and rates of resolution during follow-up were similar. Disclosure: This study was funded by Biogen and AbbVie Biotherapeutics Inc; medical writing support for the development of this abstract was provided by Excel Scientific Solutions and was funded by Biogen and AbbVie Biotherapeutics Inc.


696

Poster Sessions

P31135

P31136

Assessment of 2015 neuromyelitis optica criteria in Rouen university hospital

Observational, retrospective study to characterise patients with RRMS and long-term treatment with sc interferon (IFN) beta 1-a

L. Fechtenbaum1, R. Marignier2, R. Lefaucheur1, F. Le Goff1, J. Gueudry3, D. Maltete1, B. Bourre1

Neurology, Rouen university hospital, Rouen, France, Neurology, Bron neurological hospital, Lyons, France, 3Ophtalmology, Rouen university hospital, Rouen, France 1 2

Background and aims: To assess impact of the 2015 criteria for neuromyelitis optica spectrum disorder (NMOSD) diagnosis and the delay to obtain it. To evaluate indications and efficiency of serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) assessment. To describe seronegative patients features. Methods: We performed a monocentric retrospective study. We included all patients tested for AQP4-IgG in Rouen university hospital between the 17th January 2011 and the 20th June 2014. All samples were analysed in Lyon Hospital. Clinical, biological, radiological features, final diagnosis and the delay to obtain it, were analysed. Results: 101 patients were included. The new NMOSD criteria facilitated the diagnosis for 8 patients (42%) including 4 seropositive patients with monofocal symptoms (21%). Diagnosis delay from the first examination was significantly shorter with the new criteria (18.7 months) than with the 2006 one's (39.3 months) (p=0.02). In our study, seropositives and seronegatives patients did not differ significantly regarding the clinical, biological and imaging features. Conclusion: The new NMOSD diagnosis criteria facilitate earlier and more accurate diagnosis. The AQP4-IgG allows NMOSD diagnosis whereas the symptoms are monofocal. Disclosure: Nothing to disclose

J.R. Ara1, S. Martínez-Yélamos2, A. Saiz3, A. Escartín4, E. Munteis5, M.Á. Hernández6, L. Midaglia7, M. Arias8, Y. Aladro9, C. de Andrés10, J.A. García Merino11, X. Olascoaga12, B. Casanova13, A. Roque14, L. Brieva15, A. Rodriguez-Antiguedad16, D. Muñoz17, O. Fernandez18 Hospital Miguel Servet, Saragossa, Spain, 2Neurology, Hospital Universitario de Bellvitge, Barcelona, Spain, 3Service of Neurology, Hospital Clinic, Barcelona, Spain, 4Hospital de Santa Creu i Sant Pau, Barcelona, Spain, 5Hospital del Mar, Barcelona, Spain, 6Hospital Nuestra Señora de La Candelaria, Santa Cruz de Tenerife, Spain, 7Hospital Xeral Cies, Vigo, Spain, 8Hospital de Santiago de Compostela, Santiago de Compostela, Spain, 9Hospital de Getafe, Madrid, Spain, 10Hospital Gregorio Marañón, Madrid, Spain, 11Neurologia , H. Universitario Puerta de Hierro , Madrid, Spain, 12Hospital Universitario de Donostia, Gipuzkoa, Spain, 13Hospital La Fé, Valencia, Spain, 14Merck, Madrid, Spain, 15Hospital Arnau de Vilanova, Lérida, Spain, 16Hospital de Basurto, Vizcaya, Spain, 17Neurologia , H. Xeral Cies , Vigo, Spain, 18Fundacion IMABIS, Hospital Universitario Carlos Haya, Malaga, Spain 1

Background and aims: To describe clinical and radiological characteristics at baseline and during the treatment with sc IFN beta 1-a for 10 years or more in patients with RRMS. Methods: Observational, retrospective study of patients with RRMS who were treated for 10 years or more with sc IFN beta-1a. Demographic, clinical, and radiological characteristics of patients were described at baseline and during follow-up to assess relapses and disability progression. Results: 128 patients were included in the study. The mean age was 47.9 years and the mean age at the onset of symptoms was 30.3 years. 19.5% had received previous MS treatments. Mean time of treatment with sc IFN-β1a was 12.6 years. Annualised relapse rates (ARR) at 2, 5 and 10 years of treatment were 0.32, 0.26 and 0.19 respectively. Median time to first relapse was 5.2 years; 50.3% of patients were free of relapses at 5 years and 41.7% at 10 years. 39% of the patients were free of clinical disease activity (exacerbations or progression) at 10 years. The EDSS did not change significantly between 2.0±1.4 at onset of treatment and 2.3±1.7 at end of follow-up; 61.4% of patients were free of disability progression (EDSS). Evolution of MRI lesions also remained constant during the study; 18% of patients discontinued treatment after ≥10 years. Conclusion: IFN-β1a sc was effective controlling clinical activity after 10 years of treatment in a subset of patients with RRMS. Disclosure: This study was sponsored by Merck KGaA (Darmstadt, Germany).


Poster Sessions

697

P31137

P31138

Neural cell adhesion molecules in acute optic neuritis: relation to clinical and paraclinical findings.

Long-term efficacy of teriflunomide in patients recently diagnosed with relapsing forms of MS

J.L. Frederiksen1, K. Farooq2, S. Gnanapavan3

M. Freedman1, G. Comi2, A. Miller3, J. Wolinsky4, J. Oh5, K. Thangavelu6, P. Truffinet7, L. Kappos8

Clinic of Multiple Sclerosis and Optic Neuritis, Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark, 2Department of Neurology, Copenhagen, Denmark, 3Blizzard Institute, London, United Kingdom 1

Background and aims: More than 50% of patients with acute optic neuritis (AON) develop multiple sclerosis (MS). AON patients were chosen to achieve a homogenous patient group in which complete diagnostic work up was performed within one month from onset. The levels of Neural Cell Adhesion Molecules (NCAM) in the CSF was compared with demographic and paraclinical findings suggestive of MS. Methods: NCAM level in the CSF was measured in 50 consecutive patients with AON, median age 32 (18-62) years and healthy controls (HC). Associations between NCAM levels and age, gender, results of brain MRI at 3.0T and routinely measured biomarkers in the CSF in patients with AON were assessed. Results: The median level of NCAM in the CSF was 348 ng/ml in AON, compared to a mean value 412 +/- 109 ng/ ml in HC. There was no age and gender difference. There was neither significant association between NCAM and presence of elevated leucocyte count in the CSF, nor elevated IgG index, nor presence of oligoclonal IgG bands in the CSF. No significant association was found between brain MRI and NCAM level. Patients with a normal NCAM level tended to be more likely to also have a normal brain MRI (p=0.057, Fisher exact test). We observed a nonsignificant trend towards increased NCAM and the presence of Gadolinium enhancing lesions on brain MRI. Conclusion: We observed no significant association between NCAM level and the results of routinely measured biomarkers in the CSF and brain MRI in 50 consecutive patients with AON. Disclosure: Nothing to disclose.

1University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Canada, 2University Vita-Salute San Raffaele, Milan, Italy, 3Icahn School of Medicine at Mount Sinai, New York, USA, 4University of Texas Health Science Center at Houston, Houston, USA, 5St Michael's Hospital, Toronto, Canada, 6Sanofi Genzyme, Cambridge, USA, 7Sanofi Genzyme, Chilly-Mazarin, France, 8University Hospital Basel, Basel, Switzerland

Background and aims: To optimise outcomes in patients with relapsing MS, treatment should begin promptly following diagnosis. We investigated long-term outcomes in a subgroup of recently diagnosed patients receiving teriflunomide in TEMSO (NCT00134563) and TOWER (NCT00751881). Methods: Patients were randomised 1:1:1 to placebo or teriflunomide 7mg or 14mg, for 108 (TEMSO) or ≥48 (TOWER) weeks. Both studies included recently diagnosed patients (≤1 year since diagnosis, previously untreated with disease-modifying therapies). In the extensions (TEMSO extension, NCT00803049), teriflunomide-treated patients continued treatment (early treatment); placebo-treated patients switched to teriflunomide (14mg in TOWER and 7mg or 14mg in TEMSO, delayed treatment). MRI was included in TEMSO only. Annualised relapse rate (ARR) up to 5 years was assessed in pooled TEMSO/TOWER populations. Outcomes are presented by core study treatment. Results: TEMSO/TOWER included 587 recently diagnosed patients (259 in TEMSO) with a median baseline Expanded Disability Status Scale (EDSS) score of 2.0 (range: 0.0, 5.5); 81 patients had EDSS scores >3.5. In TEMSO, the probability of freedom from MRI activity was significantly greater with teriflunomide 14mg vs. placebo (odds ratio 2.46; p=0.0079) over 2 years in the core study. Over 5 years, ARR was lower with early (14mg, 0.215) vs. delayed (placebo, 0.320) treatment (relative risk reduction 32.7%, p=0.0189). Disability data in this population will be presented. Conclusion: These data demonstrate a significant effect of teriflunomide 14mg on MRI activity vs. placebo in recently diagnosed patients. Significant long-term efficacy on ARR was observed in recently diagnosed patients treated with teriflunomide 14mg, demonstrating the benefits of early vs. delayed treatment. Disclosure: Study supported by Sanofi Genzyme.


698

Poster Sessions

P31139 A retrospective analysis of efficacy in McDonald 2010 multiple sclerosis (MS) patients in the ORACLE-MS study M. Freedman1, T. Leist2, G. Comi3, B.A.C. Cree4, P.K. Coyle5, H.-P. Hartung6, P. Vermersch7, D. Damian8, F. Dangond8

1University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Canada, 2Thomas Jefferson University, Philadelphia, USA, 3Università Vita-Salute San Raffaele, Milan, Italy, 4Multiple Sclerosis Center, San Francisco, USA, 5Stony Brook University, Stony Brook, USA, 6Heinrich Heine University, Düsseldorf, Germany, 7Université de Lille, Lille, France, 8EMD Serono, Inc, Billerica, USA

Background and aims: In the ORACLE-MS study, patients with clinically isolated syndrome (CIS) at high risk for MS were randomised to cladribine tablets 3.5 or 5.25 mg/kg bodyweight (cumulative over 2 years) given annually in short-duration courses. Risk of clinically definite MS (CDMS) conversion was significantly reduced by cladribine vs. placebo. Methods: This retrospective analysis assessed the effects of cladribine on time to next relapse/disability progression in ORACLE-MS patients who met the McDonald 2010 MS criteria at baseline, as well as in patients not fulfilling these criteria (i.e., “true” CIS). Results: At baseline, 36.2% of patients (223/616) met the McDonald 2010 diagnostic criteria. In this subgroup (Figure 1), cladribine 3.5mg/kg (n=68) significantly reduced the risk of next relapse/disability worsening versus placebo (n=72, HR 0.26, 95% CI 0.12–0.58; p=0.0009), consistent with a 74% risk reduction. In “true” CIS patients (Figure 2), cladribine 3.5mg/kg (n=138) significantly reduced the risk of next relapse/disability worsening (i.e. CDMS) versus placebo (n=134, HR 0.37, 95% CI 0.22–0.63; p=0.0003), consistent with a 63% risk reduction. In each subgroup, the risk of next relapse/disability worsening was also reduced with cladribine 5.25mg/kg.

Conclusion: Compared with placebo, cladribine 3.5mg/kg significantly reduced the risk of relapse/disability worsening in patients meeting both up to date definitions for MS or CIS. Disclosure: Study supported by Merck, Darmstadt, Germany.


Poster Sessions

699

P31140

P31141

Number needed to treat analysis comparing teriflunomide with injectable and oral disease-modifying therapies in relapsing multiple sclerosis

INSPIRATION-MRI: standardised acquisition and centralised quantitative reading of MRI scans of RRMS patients in German daily clinical practice

M.S. Freedman1, A.E. Miller2, K. Thangavelu3, S. Hass3, T.P. Leist4

A. Gass1, J. Gregori2, S. Hoffmann2, A. Fuchs3, C. Cornelissen3

1University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Canada, 2Icahn School of Medicine at Mount Sinai, New York, USA, 3Sanofi Genzyme, Cambridge, USA, 4Comprehensive Multiple Sclerosis Center, Thomas Jefferson University Hospital, Philadelphia, USA

Background and aims: Recently approved diseasemodifying therapies (DMTs) used in patients with relapsing forms of MS (RMS) include injectable (subcutaneous pegylated interferon-beta-1a [pegIFNB-1a], glatiramer acetate [GA]) and oral (teriflunomide, fingolimod, dimethyl fumarate [DMF]) agents. As no head-to-head trials of these DMTs exist, number needed to treat (NNT) analysis, a scientifically valid methodology, may be used to evaluate comparative efficacy. Methods: NNT values were derived from placebocontrolled 1-year studies with injectable DMTs (pegIFNB1a, ADVANCE, NCT00906399; GA 40mg, GALA, NCT01067521) and 2-year studies with oral DMTs (DMF 240mg, DEFINE, NCT00420212, CONFIRM, NCT00451451; fingolimod 0.5mg, FREEDOMS, NCT00289978, FREEDOMS II, NCT00355134; teriflunomide 14mg, TEMSO, NCT00134563, TOWER, NCT00751881). Pooled data were used for DMF and teriflunomide. NNT to prevent 1 relapse or 1 patient experiencing disability progression (confirmed for ≥12 weeks; DP) are presented. Results: Over durations studied, risk of relapse vs placebo was significantly reduced with all DMTs. NNT to prevent relapse was lower in TEMSO/TOWER (4.7) vs ADVANCE (7.1) and GALA (5.7) (1-year data), and comparable between TEMSO/TOWER (5.6), DEFINE/CONFIRM (5.6), FREEDOMS (4.5), and FREEDOMS II (5.3) (2-year data). Most DMTs significantly reduced risk of DP vs placebo; exceptions were GA (GALA), fingolimod (FREEDOMS II), and DMF (CONFIRM). NNT to prevent DP was lower in TEMSO/TOWER (1 year; 17.2) vs ADVANCE (26.0), and comparable between TEMSO/ TOWER (2 years; 15.3), DEFINE/CONFIRM (15.4), and FREEDOMS (15.3). Conclusion: NNT to prevent relapse and DP for teriflunomide 14mg was lower, or comparable to, other DMTs, supporting the established clinical efficacy of teriflunomide 14mg and suggesting equal efficacy to other DMTs in treating RMS. Disclosure: Study supported by Sanofi Genzyme.

1Neurology, University Hospital Mannheim, Mannheim, Germany, 2mediri GmbH, Heidelberg, Germany, 3Nuremberg, Germany

Background and aims: MRI has become an integral part of RRMS-patient management. However, quantitative analysis of lesion-load has mainly been realized in clinical trials. We investigate whether additional quantitative information and visualisation of lesion-load is regarded useful in the daily management. INSPIRATION-MRI is a non-interventional study to validate the feasibility and potential benefit of standardised MRI-acquisition and MRIreading in clinical practice. Methods: This study included 253 patients in 18 centres. Sites underwent expert training and sequence implementation employing standardized MRI-sequences. In addition, a quantitative MRI analysis was performed (volume of T2-, T1-hypointense and contrast-mediaenhancing lesions, percentage of brain volume change via boundary shift integral). The results were visualised and provided to the physicians. Results: 251 of 253 (99.2%) baseline data sets passed MRIdata quality analysis. 35.1% of the patients were treated with fingolimod upon study inclusion (21.5% interferons, 17.5% dimethylfumarate, 6.8% natalizumab, 6.8% copaxone, 12.3% no/other). The mean number (±SD)/ml volume (±SD) of T2/FLAIR lesions at baseline was 30.1(±2.8)/11033.1(±1578.9), of black holes 4.0(±0.9)/490.3(±135.5) and of CM enhancing lesions 0.4(±0.2)/31.1(±20.3). The lesion-count of T2/FLAIR lesions differed between neurologists (lesion count ≥9: 48.2%), radiologists (64.9%) and central reading (80.9%). Conclusion: Sophisticated quantitative MRI-analysis is provided in a real world situation. A standardised analysis of MRI-data revealed differences between the estimation of lesion-numbers provided by the centres and the quantitative approach of the central reader. A standardised analysis might improve the comparability of individual MRI-scans from different sites. A standardised quantitative analysis of lesion load and volumes, and visualisation of MRIabnormalities may facilitate MRI-data use by the responsible neurologist. Disclosure: This research was supported by the Novartis Pharma GmbH, Nuremberg, Germany


700

Poster Sessions

P31142

P31143

Quality of life in carers of patients with relapsing-remitting multiple sclerosis: a pilot study

Brain health: time matters in multiple sclerosis – developmental process and objectives of international consensus policy recommendations

D. Gigineishvili, M. Kareli, A. Tevzadze, S. Karakov, M. Kiziria, A. Tsiskaridze, R. Shakarishvili Tbilisi State University, Tbilisi, Georgia

Background and aims: To measure the health-related quality of life (QOL) in people caring for patients with relapsing-remitting form of multiple sclerosis (MS) and currently treated with disease-modifying medications. Methods: 25 carers (mean age 40.7; 56% women, 56% partners) were identified by people with MS. Eligible patients were selected via Sarajishvili Institute of Neurology database for MS. QOL measured by 36-item Short Form Health Survey (SF-36), mental status assessed by Beck depression Inventory (BDI). Differences in SF-36 dimension scores between groups were assessed using t-tests. Linear and ordered regression analyses were used to evaluate correlation between clinical, demographic variables and SF-36 dimension scores. Results: Compared to carers, patients were found to have a lower QOL (P18 years old, with documented RRMS and Expanded Disability Status Scale scores ≤5.5; and neurologically stable, relapse-free, and free of corticosteroid treatment for ≥30 days before randomisation. The primary endpoint is patient medication satisfaction measured by the Medication Satisfaction Questionnaire. Secondary endpoints include patient-reported assessment of convenience, symptomatic changes, fatigue, and mental health status. Results: The CONFIDENCE trial started recruitment in Q3 2015. Conclusion: This study will provide additional information on the use of the GA40 compared with the GA20 regimen by assessing patient treatment satisfaction and experiences over a 6-month interval. Disclosure: Sanjay Gandhi, Augusto Grinspan, David Kormann and Antonella Veneziano are employees of Teva Pharmaceutical Industries. Gary Cutter has served on data and safety monitoring boards for Apotek Pharmaceuticals, Biogen-Idec, The Cleveland Clinic, GlaxoSmithKlein Pharmaceuticals, Gilead Pharmaceuticals, Modigenetech/ Prolor, Merck/Ono Pharmaceuticals, Merck, Neuren Pharmaceuticals, Sanofi-Aventis, Teva Pharmaceuticals Industry, Vivus, Washington University, the National Heart, Lung, and Blood Institute (Protocol Review Committee),


Poster Sessions

MS and related disorders 12 P31146 Reversibility of Natalizumab effects on peripheral immune cell dynamics in patients with multiple sclerosis (MS) T. Plavina1, K.K. Muralidharan1, G. Kuesters1, D. Mikol1, K. Evans1, M. Subramanyam1, I. Nestorov1, Y. Chen1, P.-R. Ho1, D. Amarante1, J. de Seze2, R. Fox3, R. Gold4, D. Jeffery5, L. Kappos6, B. Weinstock-Guttman7, H.-P. Hartung8, B. Cree9

Biogen, Cambridge, USA, 2Neurology, University Hospital Strasbourg, Strasbourg, France, 3Cleveland, USA, 4Bochum, Germany, 5Piedmont HealthCare, Mooresville, USA, 6University Hospital Basel, Basel, Switzerland, 7Jacobs MS Center and Pediatric MS Center of Excellence, Jacobs Neurological Institute, Barcelona, Spain, 8Neurology, Heinrich-Heine Universität, Düsseldorf, Germany, 9Department of Neurology, University of California San Francisco, San Francisco, USA 1

Background and aims: Although several MS therapies are available, the duration of their effects on the immune system have not been fully characterised. The effects of natalizumab, an anti-α4-integrin monoclonal antibody, on immune cell composition were described previously. Here, we sought to characterise the reversibility of natalizumabinduced changes in peripheral immune cells of natalizumabtreated MS patients following therapy interruption or discontinuation. Methods: Pharmacokinetic (PK), pharmacodynamic (PD), and peripheral immune cell data were available from 167 patients from RESTORE (treatment-interruption study). PK and total lymphocyte data were available from 573 patients from AFFIRM and SENTINEL (2-year natalizumab phase 3 studies). Serum natalizumab concentrations were measured using ELISA. Expression and saturation of α4-integrin, immune cell subsets, and VCAM-1 binding were measured using flow cytometry of whole blood. PK/ PD marker changes over time were summarized using point estimates. Results: Peripheral composition and immune cell levels from natalizumab-treated MS patients demonstrated reversibility to levels consistent with those of untreated patients by 16-20 weeks following natalizumab discontinuation. Time to PD marker normalisation was consistent with time to reach undetectable serum natalizumab concentration. The ability of lymphocytes to bind VCAM-1 ex vivo progressively increased until weeks 16-20, stabilizing thereafter, suggesting reversibility/ normalization of immune cell functionality to mediate α4-integrin-VCAM-1 adhesion interactions by 16-20 weeks. Conclusion: Natalizumab’s effects on peripheral immune cells and other PD markers were reversible by ~16-20 weeks after the final natalizumab dose. An enhanced understanding of the duration of natalizumab-associated PD effects could serve to guide clinicians in making treatment

703

sequencing decisions, particularly given the increasingly complex MS treatment landscape. Disclosure: Support: Biogen Author disclosures too lengthy to list here. If accepted, author disclosures will be listed in the presentation.

P31147 Working memory and its relationship with the mood level in patients with multiple sclerosis E. Tyburski, A. Potemkowski, A. Sołtys, M. Chęć, A. Samochowiec Department of Clinical Psychology, University of Szczecin, Szczecin, Poland

Background and aims: The presence of different forms of working memory disturbances have been demonstrated in patients with multiple sclerosis (MS). So far only a few studies have analysed the described dysfunctions depending on the type of the course of MS which is significant to understand their character and causes. The aim of this study was to determine the level of working memory and to demonstrate the relationship between working memory and the mood level in patients with a different course of MS. Methods: 25 patients with primary progressive multiple sclerosis (PPMS), 25 patients with secondary progressive multiple sclerosis (SPMS), and 25 healthy controls (HC) were involved in the study. The groups did not differ in terms of age, sex, and years of education. The Digit Span WAIS-R (DS), the Spatial Span WMS-III (SS) and the Beck Depression Inventory (BDI) were used in study. Results: Patients obtained lower scores in both neuropsychological tests in comparison with HC. There were no differences between PPMS and SPMS groups. Only the PPMS group demonstrated a significant negative correlation between both DS coefficients: forward digit span and backward digit span and the total result of BDI. Conclusion: The study demonstrated the presence of verbal and non-verbal dysfunction of working memory in patients with different course of MS. The study provided valuable information on the lack of a visible relationship between working memory and the mood level, which turned out to be in contradiction with the previously published data. Disclosure: E. Tyburski: the research was supported by 5043000240764/2011 (Faculty of Humanities, University of Szczecin), A. Potemkowski: nothing to disclose, A. Sołtys: nothing to disclose, M. Chęć: nothing to disclose, A. Samochowiec: nothing to disclose


704

Poster Sessions

P31148

P31149

Executive dysfunctions differ between secondary progressive and primary progressive MS

Comparison of MRI criteria for the diagnosis of multiple sclerosis: role of cortical lesions

E. Tyburski, A. Potemkowski, A. Sołtys, M. Chęć, A. Samochowiec

P. Preziosa1, M.A. Rocca1, S. Mesaros2, M. Copetti3, A. Rovira4, J. Sastre-Garriga5, J. Drulovic2, A. Droby6, F. Zipp6, M. Calabrese7, M. Filippi1

Department of Clinical Psychology, University of Szczecin, Szczecin, Poland

Background and aims: Despite the fact that executive dysfunctions are observed in MS patients, little is known about differences between groups with different courses of MS. The aim of this study was to characterise executive functions of patients with secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS). Methods: 25 patients with PPMS, 25 patients with SPMS, and 25 healthy controls (HC) were involved in the study. The groups did not differ in terms of age, years of education, and sex. The phonemic version (words beginning with k) of the Verbal Fluency Test (VFT), the Stroop Colour-Word Test (SCWT) as well as the Trail Making Test (TMT) were administered in the study. A repeated measures analysis of variance test was used for inter- and intra-group comparisons. Results: Executive dysfunctions were observed in 21 (84%) patients with PPMS and in 21 (84%) patients with SPMS. Patients obtained lower scores in all neuropsychological tests in comparison with HC. PPMS differed from SPMS only in TMT scores. In both assessed groups the ability of attention switching in the verbal task was weaker than in the non-verbal task and worse than the ability of verbal dominant reaction inhibition. Conclusion: Executive dysfunction was demonstrated in patients with a different course of MS. The analysis of neuropsychological functioning profile revealed a significant heterogeneity of the clinical picture of executive dysfunctions, a selective nature of its symptoms as well as variable intensity of deficit in inter- and intra-individual aspect in both groups of patients. Disclosure: E. Tyburski: the research was supported by 5043000240764/2011 (Faculty of Humanities, University of Szczecin), A. Potemkowski: nothing to disclose, A. Sołtys: nothing to disclose, M. Chęć: nothing to disclose, A. Samochowiec: nothing to disclose

1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy, 2Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, 3Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, 4Department of Radiology, Vall d'Hebron University Hospital, Barcelona, Spain, 5Neurology Unit, Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain, 6Department of Neurology, Johannes Gutenberg University Medical Center Mainz, Mainz, Germany, 7University of Verona, Verona, Italy

Background and aims: Since the publication of the revised McDonald 2010 criteria, new data regarding the application of MRI for the diagnosis of multiple sclerosis (MS) have become available. In a single-centre study, adding the assessment of cortical lesions has been shown to modify the diagnostic algorithm resulting in higher specificity (Filippi 2010). Aim of this study was to test the performance of different sets of imaging criteria, including the assessment of cortical lesions, for the development of MS in a multicentric cohort of clinically isolated syndrome (CIS) patients. Methods: Brain double inversion recovery (DIR) and brain and cord T2-weighted and post-contrast T1-weighted sequences were acquired from 72 CIS patients from five European Centres within 3 months and after 12 months from disease onset. Patients were clinically followed for ≥24 months or until the development of clinically defined MS (median follow-up 24.2 months). Sensitivity, specificity and accuracy of the different DIS MRI criteria for the development of MS were tested. Results: At follow-up, 65 CIS patients (90%) had MS (clinically and/or radiologically). The sensitivity of all criteria was high (McDonald 2005 83%, McDonald 2010 92%, Filippi 2010 80%). Specificity of Filippi 2010 was higher (67%) compared to the others (50% for McDonald 2005 and 2010). The accuracy of all criteria was high (McDonald 2005 81%, McDonald 2010 89%, Filippi 2010 79%). Conclusion: Adding the evaluation of cortical lesions improves specificity of the diagnostic criteria preserving sensitivity and accuracy in a multicentric cohort of CIS patients. Disclosure: Data were collected within the MAGNIMS network.


Poster Sessions

705

P31150

P31151

Anti-myelin antibodies in demyelinating disorders – a search for disease biomarkers.

Gait performance gets closer to normalcy after a 15-day course of fampridine in patients with primary progressive multiple sclerosis.

K. Prus, E. Belniak, K. Mitosek Szewczyk, K. Rejdak Neurology, Medical University of Lublin, Lublin, Poland

Background and aims: Autoimmune demyelinating disorders of the central nervous system (CNS) including Multiple Sclerosis (MS) are believed to be one of the main causes of disability in young adults. The mechanisms underlying the spread of demyelinating lesions are not fully understood yet, so are disease specific autoantigens. Methods: Sera of MS patients (n=23) were collected and tested for Anti-MBP and Anti–MOG antibodies with the use of ELISA assay. The results were compared to characteristic patient features such as EDSS score, time of disease onset and patients age. Results: A tendency towards higher levels of Anti-MBP and Anti-MOG antibodies was found in patients with early disease onset. There was no correlation between the duration of the disease and serum level of antibodies. Higher concentration of Anti-MBP antibodies was found in patients with lower EDSS score. No elevated levels of antimyelin autoantibodies were found in patients with an episode of MS relapse (n=3). Conclusion: Data on the levels of anti-myelin antibodies during course of demyelinating disorders are contradictory. Detection of autoantibody in serum seem to depend not only on a type of the disease, but also its stage, patients age at disease onset and technical issues (type of array or antigen epitopes that are recognized by autoreactive immunoglobulins). Precise knowledge of the mechanisms of the immune response could enable the use of new, more effective, antigen-specified methods of treatment and biomarkers, that could be used in the diagnosis and evaluation of the course of the disease. Disclosure: Nothing to disclose

I. Pulido-Valdeolivas1, I. González-Suárez2, A. Montero Atalaya1, D. Gómez Andrés1, J.A. Martín-Gonzalo3, I. Rodríguez-Andonaegui3, C. Oreja-Guevara2, E. Rausell1

1Anatomy, Histology and Neuroscience, Universidad Autónoma de Madrid, Madrid, Spain, 2Neurology, Hospital Universitario Clínico San Carlos, Madrid, Spain, 3Physiotherapy School. ONCE-UAM, Madrid, Spain

Background and aims: Fampridrine has been recently approved for symptomatic treatment of patients with multiple sclerosis (MS) based on the improvement of walking speed as measured by 25FWT. However, gait abnormalities in MS are much more beyond than lower walking speed. Whether fampridine improved global gait performance or not in MS in general and in primary progressive MS (PPMS) remain unknown. Methods: We assessed gait of 10 patients with PPMS before and after 15 days of treatment with fampridine (10 mg TID) by means of instrumented gait analysis. Multivariate indices of proximity to a control group of 13 healthy subjects were calculated using random forest models with 6 spatiotemporal parameters and 37 kinematic parameters from 4-5 left and 4-5 right gait cycles of each patient before and after the treatment with fampridine. The change after the treatment with fampridine was contrasted by a paired Wilcoxon’s sign test. Results: Random forests were able to distinguished patients from healthy subject (AUC = 0.99) and were used to build a specific index for PPMS. Healthy subjects show a median index of 0.032 (range: 0.006-0.244). Before the treatment, PPMS show a median index of 0.952 (range: 0.844-0.989). After treatment, median index reduced to 0.757 (range: 0.410-0.966) with a median decrease of 0.166 (range: -0.020.575, p-value=0.006). Conclusion: Global gait performance get closer to normalcy after 15-day course of fampridine in primary progressive multiple sclerosis; but a wide range of change occur in our sample of patients. Disclosure: Nothing to disclose


706

Poster Sessions

P31152

P31153

Transcranial sonography of subcortical structures in patients with multiple sclerosis

Characterisation of NMO spectrum disorders in an Italian cohort of patients

P. Puz, A. Lasek-Bal Katowice, Poland

Background and aims: Transcranial sonography may be applied to assess the basal ganglia nuclei and brain atrophy by the measurement of the width of the third ventricle. The aim of this study was to assess usefulness of trans-cranial sonography in patients with multiple sclerosis (MS) by examining the echogenicity of subcortical structures and the width of the third ventricle. Methods: TCS evaluation of substantia nigra, brainstem raphe nuclei, diameter of the third ventricle, width of the anterior horn of the lateral ventricle, thalamus, lenticular nucleus and head of the caudate nucleus in 41 patients with relapsing-remitting (RRMS) and 23 with secondary progressive MS (SPMS) and 20 healthy controls was compared. A potential link between the patients' age, sex, EDSS score, relapse index and ultrasound parameters was assessed. Results: The following were found in patients with MS, as compared to the control group: a greater surface area of the substantia nigra, a longer diameter of the third ventricle and wider frontal horns of the lateral ventricles, hypoechogenicity of the brainstem raphe and hyperechogenicity of the lenticular nucleus. The study group was found to have a significant correlation between the surface area of the substantia nigra and: the age of patients, the duration of the illness, EDSS score, the number of relapses. There was a significant correlation between the diameter of the third ventricle and: the age of patients and EDSS score. Conclusion: Patients with MS reveal ultrasound features of subcortical structure atrophy. Selected TCS findings show a correlation with disease progression and activity. Disclosure: Nothing to disclose

M. Radaelli1, F. Sangalli1, F. Esposito2, L. Moiola1, B. Colombo1, R. Fazio1, V. Martinelli1, M. Comola1, G. Comi1

Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 2Department of Neurology, Scientific Institute San Raffaele, Milan, Italy 1

Background and aims: The discovery of a high specific serum antibody binding Aquaporine-4 (AQP4-IgG) has dramatically changed the traditional concept of Devic disease enlarging the spectrum of Neuromyelitis Optica (NMOSD). Methods: We retrospectively collected clinical, neuroradiological and immunological data of Italian patients with NMOSD. Results: 75 patients satisfy the new criteria for NMOSD. The 88% of patients were female. 30 patients showed a limited form of NMO. 58 patients showed AQP4-IgG. NMOSD course is highly variable however 47% of our patients showed a severe disability. Moreover, the mean time to reach a severe disability was only 4 years. A normal brain MRI was present at disease onset in the majority of our cases, however about the 50% of patients developed brain lesions during the follow-up Conclusion: Our study confirms the usefulness of the new classification in clinical practice given that about 40% of our patients did not satisfy the old 2006 diagnostic criteria even showing the same aetiology and disabling course of NMO. The AQP4-IgG determination is warranted early in the diagnostic work up of CNS diseases to reach as soon as possible the correct diagnosis. Disclosure: Nothing to disclose


Poster Sessions

P31154

P31155

Clinical spectrum of multiple sclerosis and response to treatment in south Indian population

A case of very late onset neuromyelitis optica spectrum disease

B. Rangappan Munirathinam1, J. Marimuthu2, U.M. Elumalai2

CHENNAI, India, Neurology, Tamil Nadu Govt multi super speciality hospital, Chennai, India

1

2

Background and aims: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that exhibit marked clinical heterogeneity. The clinical and epidemiological heterogeneity and the response to treatment were studied in our population Methods: 22 MS patients (9 men and 13 women) who satisfied the diagnostic criteria for definite MS and who had a remitting and a relapsing course were followed prospectively in our tertiary care hospital. All patients underwent neurological examination, 1.5T MRI, electrophysiological studies, CSF analysis, EDSS and MMSE scale for outcome measurement after treatment with interferon beta 1a or monoclonal antibody (natalizumab) as per Canadian MS working group updated recommendations. Results: The age of onset for MS were 20- 29yrs in 77.2% (n=17) and 30-44 yrs. in 22.8% (n=5). The initial clinical manifestations were predominantly visual impairment (63.3%), other cranial nerve dysfunction (9%), impairment of sensory functions (9%) and motor impairment (18.7%). The interval between the first symptom and relapsing symptom ranged from 4- 48 months with a mean of 23.3 months, and the mean number of relapses was 5. Positive rates of CSF oligoclonal bands, IgG index and the number of patients with characteristic brain MRI lesions were low. However, the visual evoked potentials abnormality was relatively high (64.4%). Cognitive and affective disorders were not observed. The existing treatment modalities produced modest improvement of 1 to 2 grades in EDSS scales. Conclusion: Early institution of the disease modifying therapy in MS & remitting relapsing MS can prevent the disabling residual neurological deficits. Disclosure: Nothing to disclose

707

M. Reis Costa, P. Alves, T. Teodoro, P. Antunes, L. Albuquerque

Department of Neurology, Department of Neuroscience, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal, Lisbon, Portugal

Background and aims: Neuromyelitis Optica (NMO) presents usually around 40 years old and is most common in females. Optic neuritis, myelitis and at least 2 of the following define it: longitudinally extensive myelitis (LEM), positive anti-aquaporin4 antibody (anti-AQP4) and MRI not suggestive of multiple sclerosis. NMO spectrum disorders (NMOSD) do not meet all these criteria, have high recurrence rates and need aggressive immunosuppressive therapy. Older age at onset is associated with earlier death due to myelitis and infection. Results: An 86-year-old man admitted with MRC 2 paraparesis, D8 sensory level, severe proprioceptive defect and hypopalesthesia, constipation and urinary retention, for the last 4 days. Spine MRI showed increased T2 signal from D6 to the conus medullaris, head MRI presented leucoaraiosis. CSF analysis revealed 12cells/mm3, hyperproteinorraquia of 132mg/dl, cultural and CRP tests for neurotrophic viruses and Mycoplasma pneumoniae were negative. Serum infectious serologies and autoimmunity were negative and anti-AQP4 antibody was positive. Evoked visual potentials showed bilateral optic tract involvement. Methylprednisolone pulse and plasmapheresis achieved improvement of the motor deficit. Oral corticotherapy and Azathioprine were introduced, however, due to multiple urinary tract infections and toxic hepatitis, the last was switched to Mycophenolate mofetil. Seven months after admission he died of septic shock in the context of pyelonephritis.

Figure 1. Dorso-lumbar spine MRI (sagittal T2) spinal cord hyperintensity


708

Poster Sessions

P31156 Whole brain and grey matter atrophy are correlated to long-term disability progression in multiple sclerosis patients. V. Reyes Garrido1, T. Muñoz Ruiz1, V. Fernandez Sanchez1, J.A. Sánchez García1, P. Urbaneja Romero1, A. Gallardo Tur1, A. Leon Martin1, M. Guerrero Fernandez1, M.J. Postigo1, B. Asenjo Benítez1, Ó. Fernández Fernández2 1Hospital Regional Málaga, Málaga, Spain, 2IBIMA, Málaga, Spain

Figure 2. Dorso-lumbar spine MRI (sagittal STIR) spinal cord hyperintensity

Figure 3. Lumbar spine MRI (axial T2) central spinal cord hyperintensity

Conclusion: NMOSD was established due to the presence of LEM and positive anti-AQP4 antibody. In the face of a clinical-radiological compatible syndrome, the hypothesis of NMO/NMOSD should be investigated even in the elderly. This case supports the growing plurality of NMOSD and its therapeutic challenge in an elder. Disclosure: Nothing to disclose

Background and aims: Recent studies of magnetic resonance imaging (MRI) in multiple sclerosis (MS) have highlighted the potential of measuring brain atrophy as a marker that better correlates with disability than traditional MRI measures. Our goals are to quantify the whole brain and grey matter (GM) volume and estimate the correlation of these variables with the disability measured by Kurtzke's Expanded Disability Status Scale (EDSS) in patients with early diagnosis of clinically isolated syndrome (CIS) or relapsing remitting MS (RRMS). Methods: Untreated CIS (n=6) and RRMS (n=35) patients were selected (34% men, 66% women). (Age (median, range)31.17(18-48) years). We quantified volumes by using SIENAX in their first diagnostic MRI. We correlated them with the disability scores at the moment of diagnosis (EDSS=2.85(1-6.5)), after six months(EDSS=1.47(0-6.5)), one year (EDSS=1.46(0-6.5)) and two years (EDSS=1.5(06.5)). We also quantified conventional measures of lesion load measured in T2 and black holes in T1 weighted images (number and volume). Results: We found a significant negative correlation between measures of whole brain and GM volume and disability measured by EDSS at diagnosis, six months, one year and two years (table 1). The significance for whole brain volume disappeared when using normalized values, but there was a significant correlation of normalized GM volume with EDSS at one year and two years (table 2). We didn’t find a significant correlation between conventional MRI measures and EDSS scores (table 3)

Table 1. Correlations between unnormalized whole brain, grey matter (GM) and white matter (WM) volumes and EDSS scores.


Poster Sessions

Correlations between normalized whole brain, grey matter (GM) and white matter (WM) volumes and EDSS scores.

709

Results: Mean total treatment duration was 11.8 months. The drop-out rate from premature treatment discontinuation was low (4.7%) during the first 12 months. Mean quantitative treatment adherence at Month 12 was 96.4%. Analyses in different subgroups showed similar quantitative adherence according to gender, MS duration, age, and number of relapses (Table). Patients who dropped out had lower adherence (90.0%) than those who did not (97.0%). High numbers of doctor–patient interviews were associated with high adherence (5, n=143: 97.3%; 4, n=44: 94.8%; 3, n=45: 96.0%; 2, n=35: 94.7%). Mean qualitative treatment adherence (% of the weeks’ treatment was injected correctly with evenly distributed time intervals) at month 12 was 84.0%; correlation between quantitative and qualitative treatment adherence was significant (correlation coefficient 0.469; pC mutation in the DCAF13 gene and c.983 T>C mutation in the NOV gene cosegregating in the family. There was no additional crossover in the family to narrow it to one gene. The two DCAF13 and NOV gene mutations are located on 8q23.3 and 8q24.12, which is consistent with the location 8q23.3-q24.13 reported previously for a group of Japanese families. The DCAF13 mutation is located in alterative transcription start site(TSS) and the function of alterative TSS is unknown. The missense NOV mutation is near the C terminus in a site that is highly conserved across species. It was predicted to have deleterious effect on protein function. Conclusion: In this study, we identify two novel mutations in the DCAF13 and NOV genes associated with FCMTE in Asian populations. The interval between two mutations is 15.6Mb, which is very closed each other. Future studies of additional families with this phenotype are warranted to confirm whether it is the bigenic inheritance or to narrow it to one gene. Disclosure: Nothing to disclose

Background and aims: Cerebroretinal microangiopathy with calcification and cysts (CRMCC) is a recently described, very rare multisystem disorder. The clinical phenotype of CRMCC is wide and variable, making the diagnosis of CRMCC more difficulty. The genetic study of CRMCC has been reported recently. The biallelic heterozygous mutations in CTC1 gene, encoding conserved telomere maintenance component 1, were identified in families with CRMCC from different ancestry (European, American, and African). To data, there has not been a report about genetically confirmed family of CRMCC from China Methods: Coding and uncoding regions of the CTC1 gene, covering the promoter, coding exons and exon–intron junctions, were amplified by polymerase chain reaction (PCR) from genomic DNA of three individuals in the family Results: We firstly identify a novel biallelic heterozygous missense variants (c.775G>A p.V259M and c.2066A>G p.Y689C) of CTC1 gene in a Chinese family with CRMCC. The c.2066A>G mutation (p.Y689C) in CTC1 is a novel variant. Such variant was not found in any of the 85 healthy individuals in the same community. Conclusion: This is the first report of a genetically confirmed case of CRMCC from China. Targeted sequencing of CTC1 gene is useful for genetic diagnosis in the family with CRMCC and different diagnosis for other patients with similar disease manifestations. Various mutations in CTC1 gene identified from different ancestry CRMCC patients suggest possible genetic heterogeneity. Disclosure: Nothing to disclose

Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China

Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China


Poster Sessions

729

P31195

P31196

A novel EPM2a mutation affecting only the cytoplasmic isoform of laforin leads to late onset and slow progression of Lafora disease with prominent parkinsonism.

Further evidence that mutations in AARS2 cause an adult onset leukodystrophy

D. Lynch, D. Hughes, A. Pittman, H. Houlden

Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom

Background and aims: Lafora Body Disease (LD) is an autosomal recessive form of Progressive Myoclonic Epilepsy which typically presents in childhood or adolescence. Patients develop seizures, myoclonus, hallucinations and dementia and death occurs in the early 20s. In this report we describe a patient who presented in adulthood with early onset dementia and Parkinsonism, with a history of myoclonus and seizures. Methods: Whole exome sequencing was carried out on the patient's DNA, with familial segregation analysis performed for the putative pathogenic variant identified. Results: Whole exome sequencing identified a novel homozygous c. 962T>G p. F321C mutation in EPM2a, encoding laforin. The mutation was found to segregate with disease in an affected sister. The mutation occurs at a highly conserved residue in EPM2a and is predicted to be pathogenic by all available in silico tools. This mutation only affects the cytoplasmic isoform of laforin, leaving the nuclear isoform unaffected. We hypothesise that this accounts for the late onset and prolonged survival of the patient. Conclusion: This is the first report of a case of LD with prominent Parkinsonism and is one of the oldest cases described to date. This report highlights the utility of whole exome approaches to the diagnosis of parkinsonism and dementia and suggests an interesting genotype-phenotype correlation in the EPM2a gene. Disclosure: Nothing to disclose

D. Lynch1, W.J. Zhang1, R. Lakshmanan2, R. Phadke3, I. Davagnanam2, H.A. Hanağası4, A. Bhattacharjee5, H. Wilson6, N.C. Fox7, H. Houlden1 Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom, 2Dept of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom, 3Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, United Kingdom, 4Istanbul, Turkey, 5London, 6Dept of Neurology, Royal Free Hospital, London, United Kingdom, 7London, United Kingdom 1

Background and aims: Adult onset leukodystrophies are rare, heterogeneous disorders leading to progressive degeneration of the white matter. Recent advances in genetics have led to an explosion in the number of genes now known to cause leukodystrophies. In this study we aimed to detect the underlying genetic defect in a cohort of undiagnosed adult onset leukodystrophy cases using focused exome sequencing. Methods: Focused exome sequencing was carried out using Agilent Technology (6000 disease and uncharacterised genes). Variant prioritization was carried out with reference to known leukodystrophy genes or mimics and predicted damaging variants at conserved residues. Results: We identified homozygous or compound heterozygous mutations in AARS2 in 4 index cases (and 1 sibling). All cases presented with a syndrome characterised by adult onset neuropsychiatric and cognitive changes, extrapyramidal and upper motor neuron signs. All cases had diffuse, symmetric T2 hyperintensities on MRI with white matter rarefaction and restricted diffusion. Conclusion: Mutations in AARS2 have previously been identified to cause ovario-leukodystrophy in 6 cases. In this work, we confirm that mutations in this gene are responsible for a minority of adult onset leukodystrophy cases, describing 5 additional patients. In addition, we present further imaging and the first pathological description of an AARS2 brain, which appeared strikingly similar to the pathology seen in Hereditary Leukoencephalopathy with Axonal Spheroids (HDLS), caused by mutations in the CSF1R gene. Disclosure: Nothing to disclose


730

Poster Sessions

P31197

Neuroimmunology 3

C9ORF72 hexanucleotide repeat expansion in ALS patients from Russia

P31198

E. Lysogorskaia, N. Abramycheva, M. Stepanova, M. Zakharova, S. Illarioshkin

Research Center of Neurology, Moscow, Russian Federation

Background and aims: The frequency of mutations in a particular gene in ALS patients depends, to a considerable degree, on the population studied. We conducted a comprehensive genetic study and report the frequency of C9orf72 mutations in ALS patients from Russia in this poster. Methods: The presence of expanded GGGGCC hexanucleotide repeats in C9ORF72 was detected using amplified fragment length polymorphism (AFLP) analysis and repeat-primed polymerase chain reaction (PCR). Characteristic stutter amplification pattern on the electropherogram was considered as an evidence of a pathogenic repeat expansion. Automated ABI Prism 3130 Genetic Analyzer (ABI) and GeneMapper software (version 4, ABI) for data analysis were used for both applications. Results: Cohorts of amyotrophic lateral sclerosis (ALS) patients and control individuals of Caucasian origin from the Central European Russia (Moscow city and region) were analysed for the presence of hexanucleotide repeat GGGGCC expansion within the first intron of the C9ORF72 gene. A group of 208 Russian patients with ALS was examined. The frequency of C9orf72 mutations in sporadic ALS patients was found to be 2.3%. The mutation was not found in familial ALS cases and control cases. No carriers of an intermediate number of GGGGCC repeats (20–30 copies) were revealed among our patients with ALS. Conclusion: These results suggest that the frequency of C9ORF72 hexanucleotide repeats expansions in the Central European Russian ALS patients is significantly lower than in Western European or Northern American ALS patients of Caucasian origin but higher than in Asian ALS patients. Disclosure: Nothing to disclose

Results of a multicentre, noninterventional study (NIS) on the longterm tolerability of octagam® 5% in neurologic indications in Germany A. Debes, C. Lietz, S. Tascou

Octapharma GmbH, Langenfeld, Germany

Background and aims: Intravenous immunoglobulin (IVIg) is generally used for replacement therapy in primary or secondary immunodeficiencies and for immunomodulation in the treatment of autoimmune diseases. IVIg as immunomodulatory therapy in neurologic indications is recommended especially for immunemediated neuropathies and inflammatory myopathies. A multicentre, non-interventional study (NIS) was performed between 1995 and 2013 to evaluate long-term data on the tolerability of octagam® 5% in the treatment of different antibody deficiencies and autoimmune diseases. Methods: A subgroup analysis of this study evaluating the long-term use of octagam® 5% in patients with inflammatory polyneuropathies, inflammatory myopathies and myasthenia gravis is presented. Results: A total of 10,255 patients were included in this long-term study. The majority of patients (63%) were treated for replacement therapy in primary and secondary immunodeficiencies, 31% for immunomodulatory therapy in autoimmune diseases such as immune thrombocytopenia (ITP) and different neurologic indications. 201 patients with inflammatory neuropathies, inflammatory myopathies and myasthenia gravis were enclosed in the study who received a total of 6,823 infusions with octagam® 5%. The mean observation time ranged from 84 weeks for CIDP (chronic inflammatory demyelinating neuropathy) patients to 142 weeks for MMN (multifocal motor neuropathy) patients. The median dosage per infusion was between 0.2g/kg and 0.4g/kg. ADRs were observed in 7% of the patients and in 16 out of 6,823 infusions (0.23%). The most frequent ADRs were headache, fever and nausea. Conclusion: The results demonstrate the good long-term tolerability of octagam® 5% in the immunomodulatory therapy of neurologic diseases. Disclosure: A. Debes, C. Lietz and S. Tascou are employees of Octapharma GmbH


Poster Sessions

P31199

P31200

First case of anti SOX-1 (AGNA) paraneoplastic antibodies positive, seronegative, neuromyelitis optica in an elderly woman

Faciobrachial dystonic seizures. The importance of thinking about autoimmunity

M. Turk1, M. Klarendic2, T. Rus2, B. Meglic2, U. Rot2 1

Novo mesto, Slovenia, 2Ljubljana, Slovenia

Background and aims: Neuromyelitis optica (NMO) is an immune-mediated demyelisation disorder characterized by optic neuritis and longitudinally extensive transverse myelitis. It can occasionally develop in patients with cancer in relation to aquaporin-4 IgG (AQP4-IgG) or CV2/CRMP3 antibodies. Case of seronegative paraneoplastic NMO associated with SOX1 antibodies was not described yet. Methods: We present a 79-year-old female with diabetes and arterial hypertension, admitted to our department due to acute bilateral vision loss that was diagnosed as optic neuritis. After five days acute paraplegia of lower limbs and transverse hypoesthesia below C5 segment developed. MR scan revealed transverse demyelinisating spinal lesion extending from C2-Th2 segment. Head MR was negative for multiple sclerosis. Diagnose of NMO was made. Her vision recovered gradually after corticosteroids and plasmapheresis treatment in the next 2 weeks, but the paraparesis was only partially improved. Screening for different autoimmune conditions was made. Results: AQP4-IgG and MOG antibodies were negative. Cerebrospinal fluid was normal, except mildly elevated proteins (0.5). Sedimentation rate in serum was elevated (65) but other general blood results were normal. Serum tumour markers were negative except S-Cyfra 21 was slightly elevated (3.5). Rheumatologic tests were negative. Serum paraneoplastic antibody screening showed positive SOX1 and slightly elevated GAD65 antibodies while others (including CV2/CRMP3 antibodies) were negative. Extensive screening did not reveal the primary malignancy. Conclusion: Our case is the first one of seronegative NMO with positive SOX1. Although a cancer was not found, the age of the patient, positive SOX1, GAD65 antibodies and S-Cyfra 21 are strongly suggestive for a paraneoplastic NMO. Disclosure: Nothing to disclose

731

T. Liaño Sanchez, M.E. García, B. Parejo Carbonell, B. Abarrategui, I. Garcia Morales Madrid, Spain

Background and aims: Antibodies against leucine rich glioma inactivated–1 protein (LGI1) are associated with a characteristic type of seizures called faciobrachial dystonic seizures (FBDS), which can precede the development of limbic encephalitis (LE). Typically, they affect males, are daily, brief, refractory to antiepileptic drugs (AEDs) and show good response to immunotherapy. We present a patient with epileptic seizures, recognized as FBDS, which lead to the diagnosis of an underlying autoimmune aetiology.

VGKC complex antibodies

Methods: A 75-year-old male was admitted for stereotyped episodes of faciobrachial contraction and mild hyponatremia. Magnetic resonance imaging (MRI) and routine electroencephalogram (EEG) were normal and the diagnosis of vascular related seizures and syndrome of inappropriate antidiuretic hormone secretion (SIADH) was made. Three AED were needed to achieve adequate seizure control. Two months later, he was re-admitted for an increase in seizure frequency (30-50 daily) with similar characteristics but bilateral localization, accompanied by cognitive impairment and severe hyponatremia.

Clinical evolution


732

Poster Sessions

Results: Gadolinium MRI, lumbar puncture and routine EEG were normal. PET-CT showed enhanced ganglia in supraclavicular and iliac regions. Biopsy of the supraclavicular ganglion was negative for malignancy. Autoimmune aetiology was suspected, and methylprednisolone bolus (1gr/day) with intravenous immunoglobulin (0.4g/kg/day) were administrated for five days. Cognitive improvement, seizure-free status and normal sodium levels were achieved. Onconeuronal and anti-NMDA antibodies were negative, and LGI-1 antibodies were positive in cerebrospinal fluid.

Routine EEG

Conclusion: Identifying seizures as FBDS should lead to a diagnosis of an LGI-1 related autoimmune condition. Immunotherapy is the most effective treatment for seizure control and it avoids the development of LE. Disclosure: Nothing to disclose

P31201 Borreliosis and associated autoimmunity I. Lisá1, J. Ďurovská2, J. Pancák3, G. Timarova4, Ľ. Lisý5 1Bratislava, Slovakia, 21st Department of Neurology, Bratislava, Slovakia, 31st Department of Neurology, Medical Faculty, Bratislava, Slovakia, 42nd Department of Neurology, Medical Faculty, Comenius University, Bratislava, Slovakia, 5Dept Neurology, Slovak Medical University, Bratislava, Slovakia

Background and aims: Mutual relationship of borreliosis and MS attracted attention because of frequent positivity of antiborrelia antibodies in patients with MS-from 1.1% up to 54% according to different authors. Controversial was the opinion about possible causal relationship of borreliosis to MS. Kurtz/ 1986/ suggested that borreliosis could be one of risk factors for MS while other authors refused this association. Methods: We have analysed 22 patients with different autoimmune neurological diseases - MS, CIDP, polymyositis - with previous treated borrelia infection and persistent positivity of antiborrelia specific antibodies. The second group were 22 patients with neuroborreliosis treated lege artis by antibiotics, in whom signs and symptoms of autoimmunity developed. We analysed clinical symptomatology, MRI and cerebrospinal fluid results, other possible infections and immunological status and the presence of system and antineuronal antibodies. Results: Common finding in both groups was frequent presence of autoantibodies 22 /22 in 1st and 15/22 in the 2nd, deficit of cellular immunity 7/22 vs. 15/22. Remarkable was finding of atopic terrain in the first group 18/22. Most successful treatment in the 1st group were intravenous immunoglobulins in all 7 treated patients. Plasma exchange in two did not improve clinical status and corticotherapy was partially successful in 6/10. Azathioprin added did not bring further benefit. Conclusion: Results of our study confirmed that in patients with deficit of cellular immunity borreliosis also after lege artis treatment can induce autoimmune pathomechanisms and that in case of persistent clinical neurological symptomatology adequate immunomodulatory therapy should be considered. Disclosure: Nothing to disclose


Poster Sessions

733

P31202

P31203

Myasthenia gravis: diagnostic and therapeutic aspects in Ukraine

Coexistence of onconeuronal antibodies anti-Hu and anti-Yo in a patient with small-cell lung carcinoma

R. Lomako, V. Pashkovskyi

Neurology Department, Dnepropetrovsk Regional Clinical Hospital n.a. Mechnikov, Dnepropetrovsk, Ukraine

Background and aims: Myasthenia gravis (MG) is an autoimmune disease, characterised by disturbances of neuro-muscular junction and caused by production of autoantibodies to different structures of neuro-muscular synapse with unknown aetiology. The purpose of study was to establish immunological subtypes of MG in Ukrainians and to compare 2 treatment approaches. Methods: 80 patients with MG were examined: 53 women and 27 men aged 18-55 years. Immunological examination and chest CT-scan was performed. Results: 60 patients were AChR-Ab-positive, 5 Musk-Abpositive, others were seronegative (untyped to structures of synapse). From 80 patients 40 had changed in the mediastinum (23 had thymoma, 17 had unreduced thymus). Thymectomy was performed in these 40 patients. After surgery 10 patients had full regress of symptoms within 12 months. Severity of MG correlated with Ab level among AchR-positive patients. Patients with Ab level of 0.5-20nmol\l had minimal symptoms of disease (Class I-II MGFA), 20-100nmol\l had moderate symptoms of disease (Class IIA-III B MGFA), above 100nmol\l had severe symptoms of disease (Class III B-V MGFA). Patients were divided into 2 groups according to their treatment (one group received methylprednisolone at dose 0.5mg\kg per day, another group received IVIg at dose 400mg\kg per day over 5 days every monthly with azathioprine 2mg\kg per day. Patients MGFA class in 1 year was used to assess efficacy of the treatment. Conclusion: Early thymectomy improves course of disease. Severity of myasthenia correlated with Ab level. More effective treatment was IVIg for 5 days monthly with azathioprine 2mg\kg daily. Disclosure: Nothing to disclose

E. Monreal1, L. Crespo-Araico2, P. Agüero-Rabes2, P. Martínez-Ulloa2, F. Acebrón-Sánchez2, R. Toledano2, Á. Carrasco3, J. Buisan4, Í. Corral2

1Madrid, Spain, 2Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain, 3Immunology, Hospital Universitario Ramón y Cajal, Madrid, Spain, 4Neurology, Hospital Universitario Ramon y Cajal, Madrid, Spain

Background and aims: Anti-Yo antibodies have been related with other auto-antibodies, especially those against peripheral antigens (e.g. calcium channel, acetylcholine receptor), but not with other onconeuronal antibodies. We report a patient with a small-cell lung carcinoma (SCLC) with positivity against both anti-Hu and anti-Yo. Methods: A 69-year-old man, heavy ex-smoker, is evaluated due to a subacute slowly progressing constitutional syndrome, diurnal somnolence, memory loss, hyperphagia, photophobia, constipation, instability, abulia, apathy and abandonment of quotidian activities. On the neurological examination, it is demonstrated an impairment of the cortical functions (mainly memory, attention and executive functions), a moderate cerebellar syndrome, bilateral ptosis, supranuclear vertical gaze palsy, anisocoria, asterixis, right hemiparesis and hemihypoesthesia. Results: The CSF analysis only showed a mild isolated hyperproteinorachia, but a limbic, diencephalic and brainstem encephalitis was demonstrated on a MRI (Image 1). A SCLC was detected on a body CT, anatomopathologically confirmed with a fibrobronchoscopy. The serum IFI was normal, but positivity against anti-Hu, anti-SOX1 and anti-Yo was demonstrated on a CSF IFI (Image 2), lately confirmed on the immunoblot analysis (Image 3). The patient mildly improved initially with immunotherapy and chemotherapy. He finally died after severe progression of the cerebellar syndrome due to a resistance against cisplatin.

Image 1. Cerebral MRI showing FLAIR hyperintensities in the medial temporal lobes, bilateral thalami and insula and in the periaqueductal grey matter.


734

Poster Sessions

P31204 Response to therapeutic plasma exchange in central nervous system inflammatory diseases: multiple sclerosis and autoimmune encephalitis T. Moser, G. Harutyunyan, A. Karamyan, F. Otto, C. Bacher, V. Chroust, M. Leitinger, H.F. Novak, E. Trinka, J. Sellner

Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria

Image 2. CSF IFI with positivity against anti-Hu (blue circles), antiSOX1 (yellow circles) and anti-Yo (red circles) antibodies.

Image 3. Immunoblot showing strong positivity against anti-Hu antibodies and mild positivity against anti-SOX1 and anti-Yo antibodies.

Conclusion: Although the anti-Hu antibodies could have caused all the symptoms, a role of the coexisting anti-Yo has to be considered in the progression of the cerebellar syndrome. Therefore, it is important to consider an association of antibodies in a patient with multifocal symptoms in order to search and treat each tumour classically related. Disclosure: Nothing to disclose

Background and aims: Plasma exchange (PLEX) is an effective rescue therapy for acute, steroid-refractory central nervous system inflammatory disorders (CNS-ID). While PLEX is increasingly often used in deteriorating autoimmune encephalitis (AE), there is scarce knowledge about the extent of clinical improvement in these patients. Here, we aimed to characterize the spectrum of CNS-ID treated with PLEX and to compare clinical response across different entities. Methods: We studied the courses of all patients with CNSID undergoing PLEX at our Neurological Intensive Care Unit (NICU) between 2003 and 2015 by retrospective chart review. The response to PLEX within the 3-6-month followup was rated with a scoring system adapted from Magaña et al. (2011). Diagnosis of definite and probable AE was based on the criteria proposed by Mittal and Dalmau (2015/2016, respectively). Results: We identified a total of 40 patients with CNS-ID, 21 patients with multiple sclerosis (MS, 52.5%), 12 with AE (30%) and 7 with other CNS-ID (CNS-SLE, CRION, ADEM and NMOSD, 17.5%). Of those with AE, 8 patients had definite AE (IgG for NMDA-R n=4, LGI1 n=2, MA2 n=1 and AMPA n=1) and 8 received PLEX within the last 3 years. The overall rate of non-responders was 25% (figure 1), whereas a good and mild response was observed in 53% and 23%, respectively.

Figure 1. Subgroup analysis of clinical response to PLEX in CNS-ID

Conclusion: AE constitutes an emerging subgroup of CNSID treated with PLEX. Lack of improvement after PLEX is consistent among different CNS-ID. Studies in larger cohorts are warranted to define predictors of insufficient response and additional rescue concepts within different entities of AE.


Poster Sessions

Disclosure: Nothing to disclose

P31206

Aseptic meningitis as a rare manifestation of neuro-Behçet’s disease: long-term follow-up of six patients

Humoral response against myelin associated glycoprotein in Parkinson’s disease reflect oligodendroglial degeneration

P31205

735

A.N. Ozdag Acarli1, T. Gunduz1, S. Ala1, G. Akman Demir2, M. Kürtüncü1

E. Papuc, K. Rejdak

1

Background and aims: Identification of disease-specific diagnostic and prognostic biomarkers which would allow for an early detection and follow up of Parkinson’s disease (PD) patients would be important. Recently, we confirmed the presence of adaptive immune response against different glial derived antigens in PD. The aim of present study was to assess humoral response against myelin associated glycoprotein (MAG) on a larger group of PD patients. Methods: IgM autoantibodies against MAG were measured by ELISA system in 66 PD patients and 66 control subjects. Results: The study confirmed significantly increased production of anti-MAG IgM antibodies in parkinsonian patients (00.05). Conclusion: Results of our study provide evidence for activation of humoral response against this glial derived protein in PD patients, but argue against utility of antiMAG antibodies as biomarkers of disease severity. Our results also indicate the potential protective role of autoimmunity in maintaining the body homeostasis with possibility of clearance of abnormal proteins. Further studies are necessary to confirm the role of anti-MAG antibodies as a biomarker of PD, especially in relation to other neurodegenerative disorders. Disclosure: Nothing to disclose

Istanbul Faculty of Medicine, Istanbul, Turkey, 2Istanbul Florence Nightingale Hospital, Istanbul, Turkey

Background and aims: Aseptic meningitis (AM) is a rare neurological manifestation of Behçet's disease (BD). In this study, we present the clinical and laboratory features of 6 patients with AM related to BD. Methods: Retrospective chart review of patients with Neuro-BD managed in Istanbul Faculty of Medicine between 1985 and 2015, were reviewed for patients with AM without any parenchymal lesion at onset. Results: Among 485 patients with Neuro-BD, 6 patients (3 male, 3 female) with AM were identified. AM was the presenting symptom in 5 cases. The median follow-up of patients was 5 years (min: 3 months, max: 14 years). Four of the patients had lymphocytic and the remaining 2 patients had neutrophilic pleocytosis in the cerebrospinal fluid (CSF) analysis. Four patients had elevated protein levels and 2 had decreased glucose levels in the CSF. Only one of five patients had oligoclonal bands in the CSF. None of the patients had meningeal contrast enhancement in the brain MRI. Four patients were treated successfully either with high or low dose methylprednisolone, whereas 2 patients' symptoms resolved spontaneously without any treatment. All patients showed total or nearly total improvement in about 2 weeks after treatment. Long-term immunosuppression was accomplished by azathioprine in 4 patients. Two patients did not receive any immunosuppressant treatment. One of two untreated patients had two relapses with parenchymal lesions. Conclusion: AM is an extremely rare complication of neuro-BD. It has a favourable response to corticosteroids and azathioprine. However, patients without any immunosuppressant treatment may have relapses. Disclosure: Nothing to disclose

Neurology, Medical University of Lublin, Lublin, Poland


736

Poster Sessions

P31207

P31208

Sjogren Syndrome presenting as autoimmune non-vasculitic meningoencephalitis (NAIM) and sensory ganglionopathy

Oxysterols, memory lymphocytes and multiple sclerosis: a peculiar team

J.P.G.N.T. Peres1, A.H. Valverde2 1

Alcabideche, Portugal, Amadora, Portugal 2

Background and aims: NAIM was the proposed term by Caselli in 1999 to describe 5 patients with corticosteroid responsive encephalopathy, autoimmune features without specific biomarker or evidence of vasculitis. We present the case of a patient with uncommon combination of NAIM and ganglionopathy as presentation of a primary Sjogren syndrome (pSS). Results: Case report: A 68-year-old woman, with relevant personal history of Hashimoto thyroiditis, presents to the emergency department with subacute onset of visual and auditory hallucinations, persecutory delusions and progressive gait incapacity. Neurological examination was remarkable for disorientation, impaired attention, incoherent speech with delusional thoughts of the persecutory type, postural and rest tremor of the limbs, cogwheel rigidity, brisk osteo-tendinous reflexes and astasia-abasia. Later developed xerostomy and unilateral left parotiditis. CSF examination revealed increase protein content (74mg/dl) with predominance of immunoglobulin type G), no cells. EEG revealed generalised slowing. Normal Brain MRI. Electroneuromyography compatible with sensory ganglionopathy. Somatosensitive evoked potentials showed dysfunction of the posterior columns below cervical level. Antibodies anti Ro (SSA) and Anti La (SSB) were negative, but salivary glands scintigraphy (99TcO4-) revealed submaxillary and parotid glands hypocaptation. Schirmner test was positive and a submaxillary gland biopsy revealed T lymphocyte infiltrate, confirming the diagnosis of pSS. After immunosuppression a clinical improvement was observed. Conclusion: This kind of severe and simultaneous affection of Central and Peripheral nervous system caused by pSS has never, to our knowledge, been reported. It’s important to consider systemic autoimmune diseases, namely pSS, in the differential diagnosis of a simultaneous lesion of the central and peripheral nervous system. Disclosure: Nothing to disclose

A. Clottu1, A. Mathias1, J. Seebach2, D.P. Renaud1, C. Pot1

1Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland, 2Department of Medical Specialties, HCUGE, Geneva, Switzerland

Background and aims: Oxysterols, hydroxylated cholesterol metabolites, regulate the immune response and promote inflammation. Among the oxysterols, 7alpha,25hydroxycholesterol (7alpha,25-OHC) is the strongest ligand of the G protein-coupled receptor Epstein-Barr virus induced gene 2 (EBI2). We have previously shown in the murine model experimental autoimmune encephalomyelitis that memory CD4+ T-cells migrate specifically in response to 7alpha,25-OHC via EBI2. However, the role of EBI2 in human lymphocytes during multiple sclerosis (MS) is still unknown. Our aims are to assess EBI2 expression and EBI2 function in lymphocytes from healthy donors (HD) as well as MS patients. Methods: EBI2 expression was measured on human peripheral blood mononuclear cells by flow cytometry, and the function of EBI2 in cell migration was assessed using a transwell assay. Results: Among HD, we observed the highest levels of EBI2 expression on memory B and CD4+ T-cells, while 7alpha,25-OHC induced chemotaxis predominantly in memory CD4+ T-cells. This chemotaxis was specific to EBI2 as both selective EBI2 inhibition and oxysterol gradient disruption abolished the migration. MS patients undergoing treatment targeting cell trafficking (i.e. natalizumab) showed significant changes in EBI2 expression and migration profile compared to before the treatment onset. Conclusion: These data suggest a significant role for EBI2 in human CD4+ T-cell migration, notably in patients with MS. As selective targeting of immune cells trafficking has become an important tool in the clinical setting to dampen autoimmunity, uncovering the role of EBI2 in MS may therefore promote novel therapeutic approaches. Disclosure: Nothing to disclose


Poster Sessions

737

P31209

P31210

Epidemiological features of paraneoplastic polyneuropathies in cancer patients.

CLIPPPERS syndrome - a very rare case of brainstem inflammation

Y. Raduta1, V. Raduta2, V.V. Ponomarev1, V. Sushko3

A. Rojek1, R. Podemski1, M. Waliszewska-Prosół2, A. Pokryszko-Dragan3, J. Bladowska4, K. Obara1

1Neurology, Belorussian medical Academy of Postgraduate Education, Minsk, Belarus, 2Neurology, Brest regional hospital, Brest, Belarus, 3Oncology, Brest regional oncology centre, Brest, Belarus

Neurology, Wrocław Medical University, Wroclaw, Poland, Wroclaw, Poland, 3Department of Neurology, Wroclaw Medical University, Wroclaw, Poland, 4Radiology, Medical University, Wroclaw, Poland

Background and aims: Paraneoplastic polyneuropathies (PPN) can develop on the preclinical stage of tumour. Our purpose was to establish the epidemiological features of PPN in small cell lung cancer (SLC), breast cancer (BC) and non‐Hodgkin lymphoma (NL) patients in Brest region of the Republic of Belarus (a population of about 1.6 million). Methods: We studied 174 patients with morphologically confirmed tumours: 81 patients with SLC, 77 with BC and 13 with NL form in the time period from 2012 till 2015. The study included 81–men and 93 women with average age of 52.8±10.2. PPN diagnoses were assessed according to the neurological examination, EMG and immunological assay using-serum onconeuronal antibodies. Results: We found symmetrical, distal, sensory, axonal‐ demyelinating PPN in 32 patients (18.3%) suffering from various forms of tumors. Particularly affected were patients with SLC: 17 53% and BC: 13 (40%), as well NL: 2 (32%). Anti‐Hu antibodies were detected in patient group with SLC 9 (52.3%), NL 1 (50%) and anti‐Yo in group with BC ‐6 (46%). Conclusion: Our results suggest that development of PPN can be often detected in patients with SLC and BC types of tumours, which prevail in women at the age of 51±8.3 years. This discovery has a potential diagnostic value as it allows to diagnose a tumour before clinical manifestation. Disclosure: Nothing to disclose

Background and aims: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare disease affecting brainstem, characterized by perivascular infiltration with lymphocytes and macrophages in the absence of an infectious pathogen. This autoimmune condition can be a diagnostic challenge and deserves attention because of its very good response to immunosuppressive therapy. Case Presentaion: A 57-year-old man was admitted to the Neurology Department because of a 9-month history of progressive cerebellar-pyramidal syndrome with concomitant headaches. The neurological examination revealed: dysarthria, dysphagia, nystagmus, gait ataxia and paresis of the left limbs with pyramidal signs. Emotional disturbances (uncontrolled crying, periodic anxiety) were also observed. Cognitive impairment and psychiatric disorders were excluded. Demyelinating process, cerebrovascular disease, spinocerebellar ataxia, multiple system atrophy and neuroborreliosis were considered in differential diagnosis. The magnetic resonance imaging (MRI) of the brain and cervical spine showed numerous, hyperintense punctate lesions, scattered within supra- and infratentorial regions and along cervical spine, with the contrast enhancement. CT brain angiography presented a hypoplasia/agenesis of the right posterior cerebral artery (part P1) and narrowing of the right vertebral artery. Laboratory serum tests, autoimmune disease markers and CSF analysis were within normal limits. On treatment with corticosteroids, an improvement in 2 weeks was observed. Conclusion: In the presented case, clinical picture of the disease as well as characteristic pattern of MR findings and exclusion of infectious background, correspond with the rare, nonspecific, autoimmune condition named CLIPPERS and described in the scarce literature. Established diagnosis allowed to achieve good outcome after immunosuppressive therapy. Disclosure: Nothing to disclose

1 2


738

Poster Sessions

P31211 Coexistence of autoimmune diseases and autoantibodies in patients with myasthenia gravis S. Tamer1, H.N. Günes2, E. Gökçal1, T. Yoldas2

1Neurology, Van Regional Training and Research Hospital, Van, Turkey, 2Neurology, Ankara Education and Research Hospital, Ankara, Turkey

Background and aims: In this study, we investigated 75 Turkish myasthenia gravis (MG) patients for coexistent autoimmune diseases (AIDs) and for some autoantibodies characteristic for most relevant AIDs. Methods: Demographic and clinical characteristics of the patients were recorded. In all patients, thyroid function tests, thyroid autoantibodies, and other different autoantibodies were studied. The diagnosis of autoimmune thyroid diseases (AITD) was made with clinical features, physical examination, and laboratory findings. The diagnosis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were made according to the revised criteria of American College of Rheumatology. Other AIDs were recorded whether the patient already had a diagnosis or there have been investigated clinical findings and/or laboratory abnormalities. Results: 39 patients (52%) had autoantibody positivity in their sera. Thyroid autoantibodies and antinuclear antibody positivity were mostly detected. Of these, 21 patients did not have any diagnosis of AIDs. 18 patients (24%) had AIDs. These were AITD (16%), RA (4%), SLE (2.6%), and Lambert–Eaton myasthenic syndrome (1.3%). 10 of these AIDs had the diagnosis before and 8 of patients were newly diagnosed. Conclusion: MG has an increased frequency of coexisting AIDs. Autoantibodies that are characteristic for some AIDs can be found without any clinical findings of AIDs. Clinical attention for AIDs is especially needed during the follow-up of MG patients. Disclosure: Nothing to disclose


Poster Sessions

739

Neuro-oncology 3

P31213

P31212

Bilateral facial nerve palsy secondary to administration of nab-paclitaxe

Skull chloroma in a patient with myeloid leukaemia and pancytopenia

D. Naoumis1, I. Spanou1, M. Antonopoulou1, A. Isaakidou2, N. Kentepozidis2, E. Kouremenos1

A.C. Mergeani, O. Rusu, C. Coclitu, A. Ciobotaru, T. Parvu, O.A. Bajenaru, F. Antochi

2

Neurology, University Emergency Hospital Bucharest, Bucharest, Romania

Background and aims: Chloroma is a rare type of tumour that develops from myeloid cells. The name was given due to the greenish appearance caused by high levels of myeloperoxidase. The term granulocytic sarcoma was applied since about 30% are not green coloured due to the presence of other peroxidase types. Most recently, the term myeloblastoma has been proposed as the most accurate description. The tumour is essentially a localised solid collection of leukemic cells that occurs outside the bone marrow in parts of the body such as the chest, vertebrae, pelvis, skin, lymph nodes and skull. The aim of our study is to present a rare case of a patient with myeloid leukaemia associated with this type of tumour. Methods: We describe the case of a 56-year-old female with medical history of myeloid leukaemia admitted to our hospital for somnolence, diffuse headache and fatigue. The neurologic exam showed no focal neurological signs. The lab exam showed severe pancytopenia, inflammatory syndrome and high levels of LDH. Results: We performed a CT scan that revealed a tisular mass situated predominantly epicranial in the right parietal region with intravenous contrast enhancement, that produced osteolysis of the adjacent bone and endocranial invasion but without involvement of the brain parenchyma. Conclusion: We choose to present this case to underline that consideration and proper diagnosis is important since these sarcomas are very sensitive to focal irradiation or chemotherapy. They generally resolve completely in less than 3 months, although they may recur. Disclosure: Nothing to disclose

1

Neurology, 251 Hellenic Air Force Hospital, Athens, Greece, Oncology, 251 Hellenic Air Force Hospital, Athens, Greece

Background and aims: Bilateral paralysis of the facial nerve is a relatively rare presentation and often indicates a serious underlying medical condition, ranging from neurologic, infectious, neoplastic, traumatic or metabolic disorders. Paclitaxel is a chemotherapeutic agent that causes neurotoxicity as a side effect. It predominantly causes a reversible and symmetric sensory axonal peripheral neuropathy, but rarely also motor and autonomic neuropathy. It has been described as a causative of bilateral facial nerve palsy. Risk factors for neurotoxicity include paclitaxel dose per cycle and cumulative, prior or concurrent therapy with other neurotoxic chemotherapy agents such as cisplatin and underlying medical conditions associated with neuropathy. Methods: We describe a case of a 54-year-old woman with stomach cancer, with bilateral facial nerve palsy after 9 cycles of nab- paclitaxel therapy. Results: Neuroimaging tests, CSF analysis and laboratory tests were all negative. Three months after discharge, the diplegia was completely resolved. Conclusion: We reinforce the importance of considering the range of differential diagnosis in all cases presenting with bilateral facial nerve palsy. All the patients treated with paclitaxel, especially those with high dose, should be carefully monitored for unexpected neurologic toxicity, particularly if they have received prior taxanes or other neurotoxic chemotherapy. More research must be done in order to reduce paclitaxel neurotoxicity. Disclosure: Nothing to disclose


740

Poster Sessions

P31214 Primary dural involvement of multiple myeloma (MM): description of 2 cases A. Olaskoaga1, L. Martinez-Merino1, L. Pulido1, A. Gorosquieta2, M.C. Viguria2, E. Erro1

1Neurology, Complejo Hospitalario Navarra, Pamplona, Spain, 2Hematology, Complejo Hospitalario Navarra, Pamplona, Spain

Background and aims: MM is a neoplastic proliferation of plasma cells. Central nervous system (CNS) involvement results either from direct extra-osseous spread from adjacent skeletal plasmacytomas or from extra-medullary disease via haematogenous dissemination. Dural involvement is the most-common intracranial manifestation of MM and usually occurs due to direct extension of a plasmacytoma of the skull. In contrast, primary dural involvement is rare. Leptomeningeal involvement is usually the result of haematogenous spread. Methods: Description of two patients with primary dural involvement of MM: Case 1: 64-year-old male diagnosed of MM 2 years before. Had received several lines of treatment with partial answer. Affection of bones, skin and testicles. Neurological clinic consisted in multiple cranial affectation. CSF: negative for malignant cells. MRI: dural and leptomeningeal affectation adjacent to cavernous sinus as well as leptomeningeal dissemination signs. Case 2: 66-year-old woman diagnosed of MM 2 years before. In clinical remission after one line of treatment. Bone affection and a pancreas plasmocytoma. Presented complex bilateral ophthalmoparesis. CSF: negative. MRI: bilateral paquimeningeal disease expanding to both cavernous sinus.

MRI case 1

Conclusion: Primary dural involvement of MM may occur at the level of the skull base with extension into the cavernous sinus. Intrathecal chemotherapy associated with systemic chemotherapy may result in good clinical response. Although neurological complications related to MM are not uncommon, direct involvement of the CNS is rare and represents a diagnostic and therapeutic challenge. Disclosure: Nothing to disclose

P31215 Solitary intraventricular metastasis from lung adenocarcinoma mimicking glioblastoma I.A. Orban, L. Dumitrescu, I. Gobej, I. Olaru Popescu, C. Nechifor, B.O. Popescu, R. Tanasescu Neurology, Colentina Clinical Hospital, Bucharest, Bucharest, Romania

Introduction: Solitary intraventricular metastasis is a very rare finding, accounting for 0.14% of intraventricular tumours in autopsy studies. The three most common primary sites for intraventricular metastases are renal cell carcinoma, melanoma and breast carcinoma. Methods: We report the case of a 57-year-old woman, smoker, with chronic hepatitis C, presenting with new onset headache. Brain MRI showed a contrast-enhancing tumour located in the right trigone of the right lateral ventricle with MRI features suggestive of glioblastoma. A second brain MRI three months later showed the irregular and inhomogeneous gadolinium-enhancing mass infiltrating the medial occipital ventricular wall and spreading into the splenium of corpus callosum and septum pellucidum. The tumour was neurosurgically removed. Results: The pathology of the tumour revealed a cerebral metastasis from a lung adenocarcinoma with adenosquamous areas. The subsequent chest CT confirmed a left pulmonary superior lobe mass. The patient died one month later after a right hemispheric tumour spread with oedema and hydrocephalus ensued. Conclusion: This report highlights a rare manifestation of a secondary tumour with radiological features mimicking a primary brain tumour and originating from a less common primary site. Although uncommon, metastasis should be considered in the differential diagnosis of solitary intraventricular tumours.

MRI case 2

Results: Both patients received treatment with VDT-PACE and intrathecal citarabine. Case 2 received also local radiotherapy. Both are having clinical and radiological improvement after 6 months.

MRI of the intraventricular metastasis


Poster Sessions

741

P31217 Intramedullary pleomorphic xanthoastrocytoma with anaplastic features: a triple rare entity C. Rosado Coelho1, J. Pimentel2, P. Pereira2, L. Roque3, J.P. Farias4

1Department of Neurology, Hospital de São Bernardo do Centro Hospitalar de Setúbal, Setúbal, Portugal, 2Laboratory of Neuropathology (department of Neurology), Hospital de Santa Maria do Centro Hospitalar de Lisboa Norte, Lisbon, Portugal, 3Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia, Lisbon, Portugal, 4Department of Neurosurgery, Hospital de Santa Maria do Centro Hospitalar de Lisboa Norte, Lisbon, Portugal

MRI of the intraventricular metastasis


P31216 Posterior reversible encephalopathy syndrome in pediatric oncology: 4 clinical cases J. Passos1, M. Valente1, S. Nunes2, D. Salgado1

Neurology, Instituto Português de Oncologia Francisco Gentil, Lisboa, Lisbon, Portugal, 2Pediatrics, Instituto Português de Oncologia Francisco Gentil, Lisboa, Lisbon, Portugal

1

Background and aims: Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterised by headache, seizures, visual disturbances and typical imaging findings. Several risk factors (arterial hypertension (AH), bone marrow transplantation (BMT), graft versus host disease (GVHD), and systemic inflammatory response syndrome (SIRS)) have been identified, and frequently they co-occur. Methods: Case report. Results: 9-year-old girl with β-thalassemia who underwent BMT, had focal seizures that evolved to generalised tonic clonic-crisis (CTCG). Electroencephalogram (EEG) was compatible with status epilepticus (SE). MRI showed symmetrical, posterior white matter hyperintense lesions on T2. 12 years old boy with acute lymphocytic leukaemia–T underwent intensified chemotherapy. One week after treatment, he presented with multiple GTCS preceded by pressure peaks. EEG was characterized by abundant critical activity and MRI showed cortical-subcortical of frontoparietal-occipital symmetrical topography. 11 years old boy with mediastinal lymphoma T under chemotherapy, had two GTCS. MRI revealed cortical and subcortical bihemispheric T2 hyperintensity that focally enhanced after Gd. EEG showed bilateral irritative signals. A 3-year-old girl with acute lymphocytic leukaemia–B under chemotherapy. After acute renal failure and maintained AH, she presented focal motor seizure with dyscognitive features. MRI revealed hyperintensity on T2 and FLAIR the occipital periventricular white matter. The EEG showed slow and irregular activity. Clinical evolution was favourable in all cases. Conclusion: These case reports are in line with current conceptualization of PRES as a complication of systemic processes. Seizures frequently prompted MRI assessment and syndrome identification. Disclosure: Nothing to disclose

Introduction: Pleomorphic xanthoastrocytoma (PXA) is a rare tumour usually of low-grade anaplasia, accounting for 1% of astrocytic tumours, being most frequently supratentorial. Most PXA do not have anaplastic features and the location in the spinal cord has been rarely reported in the literature. Methods: Case report. Results: We describe a 36-year-old man who presented with a 2-months history of progressive lumbar pain, lower extremity weakness, right lower limb and saddle hypoesthesia. MRI demonstrated a contrast-enhancing intramedullary mass, at the level of T12-L1. The patient was submitted to a partial resection of the mass and the neuropathological examination revealed PXA, with P53 immunopositivity and IDH1 immunonegativity. However, the genetic analysis by PCR revealed a mutation of IDH1 R132C. The patient was started on radiation treatment and chemotherapy with temozolomide. Tumour progression occurred and the patient died 7 months later. Conclusions: 31% of PXA show anaplastic features. Only 6 cases of PXA of the spinal cord have been described in the literature, equally distributed between both genders, ages between 12 and 66 years. Only 1 case was located in the conus medullaris and another one with anaplastic features. Most cases have similar neuroimaging. This is the only case with IDH1 R132C mutation, which is rare in CNS tumours (approximately 4%). This diagnosis should be thought in spite of atypical and rare features of this tumour. Disclosure: Nothing to disclose


742

Poster Sessions

P31218

P31219

Dramatic response and prolonged survival after intensive chemotherapy with autologous stem cell transplantation in a case of lymphomatosis cerebri

Supplementary motor area activation in patients with frontal lobe gliomas in Uzbekistan.

L. Royer-Perron, C. Houillier, K. Mokthari, D. Leclercq, S. Choquet, A. Alentorn, A. Duran-Pena, K. Hoang-Xuan, A. Gonzalez-Aguilar

Traumatology, Orthopedics, Neurosurgery and Field Military Surgery, Tashkent Medical Academy, Tashkent, Uzbekistan

APHP, CHU Pitié-Salpêtrière and LOC network, Paris, France

Background and aims: Lymphomatosis cerebri (LC) is a rare presentation of primary central nervous system lymphoma characterised by diffuse, nonenhancing infiltrative lesions and associated with a poor outcome. The optimal treatment remains unknown. Methods: We reviewed the case of a patient suffering from LC who achieved a dramatic clinical response and prolonged remission after intensive chemotherapy with autologous stem cell transplantation. Results: Our patient presented at age 57 with nonspecific symptoms of loss of motivation and libido, and subsequently developed ataxia, a pyramidal syndrome, walking difficulties, a subcortical dementia, and sphincter dysfunction. Initial MRI showed diffuse, bilateral hemispheric signal abnormalities without contrast enhancement or mass effect ("leukoencephalopathy"). Spectroscopy revealed an elevated choline to N-acetylaspartate ratio and perfusion study was normal. Lumbar puncture showed 8 white cells and a protein level of 1.03g/l. Diagnosis was achieved with cerebral biopsy, which revealed a diffuse large B-cell lymphoma. The patient received a high-dose methotrexate based chemotherapy regimen (rituximab, methotrexate 3g/m2, carmustine, etoposide) followed by high dose aracytine, then intensive chemotherapy (thiotepa, busulfan, cyclophosfamide) with stem cell rescue, as first line consolidative treatment. Symptoms improved dramatically with treatment and the patient is still alive 75 months later, in clinical remission, despite few changes of the initial lesions on MRI. To our knowledge, this is the first report of the use of this treatment regimen, and the longest reported survival, in a LC patient. Conclusion: LC can be highly sensitive to high dose chemotherapy. Conventional neuroimaging is not optimal for the therapeutic evaluation and follow-up of this disease. Disclosure: Nothing to disclose

J. Sabirov, R. Egamberdiev

Background and aims: We tested the hypothesis that in some patients with lesions affecting the SMA, the contralateral SMA exhibits some of the activation normally associated with the ipsilateral SMA. Methods: Functional MR imaging studies in seven healthy volunteers and 19 patients with frontal lobe tumours or arteriovenous malformations were reviewed retrospectively. The hemisphere in which the SMA activation predominated was tabulated for right and left motor tasks. The relative hemispheric dominance in the SMA for the right and left motor tasks was compared in the healthy and patient groups and with the location of the lesion in the patient group. Results: None of the control subjects performing a right hand motor task activated predominantly the right SMA. 50% of the patients with lesions overlapping the left SMA performing the right motor task activated predominantly the right SMA. 57% of control subjects performing the left hand motor task activated the left SMA predominantly. 100% of patients with lesions overlapping the right frontal SMA performing the left motor task activated the left SMA predominantly. Conclusion: The supplementary motor area (SMA) is thought to play a key role in initiation and control of motor and speech functions (1, 2) Injury to the SMA during surgical excision of medial frontal lobe lesions may also result in severe motor or speech deficits (3–5). These deficits are transient and most patients fully recover from SMA injuries. The closer the lesion to the SMA, the greater is the risk of postoperative deficit from surgical resection (6). Disclosure: Nothing to disclose


Poster Sessions

743

P31220 A case report of primary central nervous system lymphoma M. Scarioni, P. Basilico, A.M. Pietroboni, A. Arighi, G.G. Fumagalli, A. Calvi, D. Galimberti, E. Scarpini Neurology, University of Milan, Milan, Italy

Background and aims: We describe a case of Primary Central Nervous System Diffuse Large B-cell Lymphoma (PCNSDLBCL) presenting on brain MRI scans with extensive lesions involving the corpus callosum (CC) and the periventricular and periaqueductal areas. Methods: A 37-year-old man was referred for gradual onset of cognitive-motor slowing, headache and blurred vision. Brain MRI, whole-body PET, lumbar puncture, blood tests and brain biopsy were performed. Results: Brain MRI at onset revealed multiple enhancing and non-enhancing T2 hyperintense white matter lesions; CSF analysis showed the presence of oligoclonal bands (pattern 2) and 10 mononuclear WBC/mmc; blood analysis detected high-titre MOG antibodies. Whole-body PET scan did not show areas of pathological hyperaccumulation; distribution of lymphocyte subsets in peripheral blood was normal. Four months later a severe clinical worsening occurred. MRI showed extensive T2 hyperintense white matter lesions outlining the fourth and third ventricle and the periacqueductal space, in contact with the ependymal surface, involving the corpus callosum in its entirety and extending to the temporal lobes and to the brainstem, with some enhancing nodular areas. The patient underwent stereotactic brain biopsy with histologic diagnosis of PCNSDLBCL (Ki-67 proliferative index:>90%).

FLAIR, coronal section

T2-weighted MRI, sagittal section

Conclusion: The CC and periventricular white matter are frequently affected in multiple sclerosis and neuromyelitis optica. CNS lymphomas may have characteristic imaging findings on MRI (such as their predilection for the periventricular regions, often in contact with ventricular surfaces); nevertheless, such findings cannot unequivocally distinguish CNS lymphoma from other brain lesions. The majority of PCNSDLBCL are histologically diagnosed. Disclosure: Nothing to disclose

FLAIR, axial section


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Poster Sessions

P31221

P31222

Headache in renal cell carcinoma; a possible paraneoplastic symptom?

Germinoma mimicking lesion of inflammatory aetiology on MRI

S. Thissen

T. Urbanic Purkart1, M. Asslaber2, E. Holl3, T. Seifert-Held1, F. Payer1

Heerlen, Netherlands

Background and aims: Paraneoplastic neurological syndromes (PNS) are defined by the presence of cancer and exclusion of other known causes of neurological symptoms. PNS can occur with or without onconeural antibodies and antibodies without PNS. In renal cell carcinoma (RCC) paraneoplastic cerebellar ataxia, motor neuron disease and leucocytosis have been reported. Symptoms often resolved after removal of the tumour. We present a patient with headache that resolved after detecting and resecting RCC. Methods: A 48-year-old man presented with severe throbbing continuous headache since a week, without fever, confusion, seizures, psychiatric symptoms or memory deficits. He had a common cold 2 weeks before. Acetaminophen 1500mg daily brought no relief. Medical history revealed anti-phospholipid syndrome with pulmonary and deep venous thrombosis, necessitating use of oral anticoagulation. His GP prescribed doxycycline because of leucocytosis, suspecting Q-fever. Examination and temperature were normal. CT- and MRI-cerebrum were normal. ESR and CRP were elevated with leucocytosis. CRP normalized quickly, but ESR remained elevated, around 70. The rheumatologist didn’t find underlying inflammatory disorders. Three months later renal cell carcinoma was detected. After removing the tumour surgically, the headache resolved almost directly, as did the elevated ESR. Results: Onconeural antibodies (Hu, Yo, Ri, Tr, amphiphysine, CV2, Ma1/2) negative C. burnetii negative Conclusion: Our patient presented with refractory headache and elevated ESR resolving after treatment of renal cell carcinoma. According to Graus et al, this fits the diagnostic criteria of possible PNS. Of course, a coincidental association is not ruled out. However, diagnosis of PNS should be considered whenever thorough evaluation fails to explain neurologic symptoms. Disclosure: Nothing to disclose

Neurology, Medical University of Graz, Graz, Austria, Neuropathology, Department of Neuropathology, Graz, Austria, 3Neurosurgery, Medical University of Graz, Graz, Austria 1 2

Background and aims: Intracranial midbrain mass lesions with spontaneous radiological improvement present a challenge for the treating physician. Methods: Case report Results: In 2011 an 18-year-old male patient presented to the emergency room with acute hemicranial throbbing headache and vomiting without focal neurological signs and symptoms. On cranial MRI a midbrain mass lesion with homogenous contrast enhancement and signs of ventricle enlargement has been diagnosed. A ventriculostomy and simultaneous ventricular CSF analyses have been performed. Histology of the ventricular CSF revealed glial fragments in a fibrillary matrix without sign of malignant cells. A tentative diagnosis of low grade glioma (LGG) has been stated. In 9/12 external ophthalmoplegia occurred in conjunction with signs of progression on MRI. At this time eye alignment surgery was performed. Without any other treatment this lesion vanished (5/13). In 1/14 progressive neurological deterioration with gait disturbance, dysarthria and dizziness appeared concomitant with progression of the midbrain lesion on MRI. Extensive diagnostic work-up did not show any other abnormalities and biopsy could not be offered. Due to varying appearance on MRI an inflammatory aetiology of the lesion was postulated and corticosteroid therapy with subsequent immunosuppressive therapy has been induced. After short term clinical stabilization and distinct radiological regression of the lesion, however, disease progression with a new thalamic lesion evolved. After biopsy histology verified an intracranial germinoma with extensive granulomatous inflammation. Tumour specific radiation therapy has been initiated with marked improvement. Conclusion: Differential diagnosis of vanishing midbrain lesions on MRI include in rare cases intracranial tumours like germinoma with extensive granulomatous inflammatory component. Disclosure: Nothing to disclose


Poster Sessions

P31223

P31224

Basal ganglia germinoma in adult: a case report

Frontal parafalcine meningioma presenting as parkinsonism

C. Vialatte de Pémille1, K. Mokhtari1, F. Bielle1, C. Alapetite2, A. Idbaih3

S. Vijayarangam Shanmugam1, P. Hart1, S. Stapleton2, S. Omer1

1GHPS, Paris, France, 2Radiotherapy, Institut Curie, Paris, France, 3Paris, France

Background and aims: Germ Cell Tumours (GCT) represent 0.5 to 2% of the Central Nervous System (CNS) tumours. 65% are germinomas. Germinomas affect patients under 20 years old in 90% of cases. Their location is almost exclusively within the midline (i.e. pineal gland and suprasellar region). The prognosis is quite favourable with a 5-year survival rate of 90% after radiotherapy alone. We report an atypical case of ectopic germinoma located in basal ganglia without brain atrophy affecting a North African adult. Methods: A 21-year-old man, with no personal nor familial past medical history, consults for isolated progressive left hemiparesis. The MRI shows multiple right basal ganglia enhanced lesions with peri-tumour oedema. A negative check-up, including whole body CT scan, HIV serology, ophthalmologic exam, and PET scan is performed. Stereotactic biopsy confirms the diagnosis of germinoma. No abnormal cell nor elevated Placental alkaline phosphatase (PALP) level have been found in the CSF. The patient underwent craniospinal radiotherapy alone.

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1Department of Neurology, St Georges University Hospital NHS Foundation Trust, London, United Kingdom, 2Department of Neurosurgery, St Georges University Hospital NHS Foundation Trust, London, United Kingdom

Background and aims: We present 2 patients with Parkinsonism due to large frontal parafalcine meningiomas, who showed remarkable recovery following tumour removal. Methods: Patient 1: A healthy 63-year-old man presented with a left sided akinetic rigid syndrome, without symptoms or signs of raised intracranial pressure. He showed no response to L-dopa therapy. MRI brain scan showed a right sided frontal parafalcine meningioma with mass effect. Following surgical removal of the tumour, the parkinsonian features resolved completely. Patient 2: 60-year-old man presented with tremor, cogwheel rigidity, and gait disturbance. There were no signs of raised intracranial pressure. He did not respond to levodopa. MRI brain scan showed a very large frontal parafalcine meningioma. Following surgical removal of the tumour and intensive rehabilitation, the parkinsonian features completely resolved. Results: MRI Head in patient 1 showed a right sided frontal parafalcine meningioma with mass effect. MRI brain scan patient 2 showed a very large frontal parafalcine meningioma. Conclusion: Unilateral and bilateral parkinsonism is a well-recognised presentation of large meningiomas. Brain imaging should be performed in patients who fail to respond to L-Dopa therapy, particularly in the presence of atypical features. Disclosure: Nothing to disclose

Results: Intracranial germinomas are rare tumours, affecting principally young patients and mostly located in the pineal region. Prevalence is higher in Asia. Atypical locations are even rarer. Basal ganglia germinomas in adults have exceptionally been described, especially out of Asia. Conclusion: Intracranial germinomas are rare tumours, affecting principally young patients and mostly located in the pineal region. Atypical locations in adults are exceptional. They need to be recognized for an appropriate optimal medical management. Disclosure: Nothing to disclose


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Poster Sessions

P31225 Meningioma associated with noninfectious leptomeningitis in a patient with rheumatoid arthritis S.-Y. Yang

Gyeonggi-do, Korea, Republic of

Background and aims: Rheumatoid meningitis is one of rare complications of rheumatoid arthritis (RA). Most patients with rheumatoid meningitis have chronic and severe RA. There are no reliable correlations between meningioma and rheumatoid meningitis. Methods: We report a case of 54-year-old woman who had rheumatoid arthritis, presenting headache with neck stiffness and dysarthria. Results: Brain imaging showed right frontal extra-axial mass with perilesional leptomeningeal enhancement, possibly leptomeningitis. Conclusion: Symptoms were relieved after surgical removal of meningioma followed by no disease-modifying antirheumatic therapy, and her follow-up brain MRI scan showed complete resolution of peritumoral leptomeningitis. Disclosure: Nothing to disclose


Poster Sessions

Neuro-ophthalmology/ neuro-otology 3 P31226 Assessing rotation and acting forces in vestibular patients during walking and balance tasks with combined motion capture and accelerometers J. Decker1, C. Pradhan1, T. Brandt2, K. Jahn3, R. Schniepp1

1Center for Sensorimotor Research, University of Munich, Munich, Germany, 2German Center for Vertigo and Balance Disorders, University of Munich, Munich, Germany, 3Neurology, Schön Klinik Bad Aibling, Bad Aibling, Germany

Background and aims: In this study, we investigated the relationship of position and forces acting on the semicircular canals (Reid’s plane) during gait tasks and its effects on gait trajectory and stability. Furthermore, we attempted to quantify the effects of these forces and positions on the gait cycle. Methods: Three healthy age defined groups each with 10 subjects, and 10 bilateral vestibulopathy patients (BVP) were recruited. Motion capturing was achieved using Qualisys® (Figure 1a.). Synchronised APDM Opal® Acceleration sensors were attached. Subjects were asked to walk along an elongated circle during different tasks and speeds (preferred, slow, maximal).

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Results: Deviations from the optimal path in BVP (slow: 5.23±0.96; preferred: 4.48±0.78; maximal: 3.19±7.36, meters) were larger than for younger healthy subjects (slow: 3.78±0.76; preferred:3.12±0.37; maximal: 2.72±0.38, meters, P=0.037; 0.002;0.267; respectively) and older healthy subjects (slow: 2.95±0.37; preferred: 2.95±0.08; maximal: 2.83±0.36, meters, P=0.006; 0.002; 0.600 respectively) for all gait speeds except maximal. Phase difference between head and trunk angles revealed significant differences between groups during slow(F=5.306, P=0.013) and maximal- (F=3.455, P=0.048) but not preferred speed-gait (F=2.871, P=0.077). Conclusion: This study confirms the speed dependent sensory processing during gait but also demonstrates its relationship to gait trajectory. Deviations are higher during slow and preferred speed gait in BVP compared to maximal speed gait due to the decreased sensory inputs. These results signify the requirement of additional sensory information to maintain stability in BVP and higher Age. Disclosure: Nothing to disclose

Figure 1a-Marker / Sensor Positions-Sample Data Motion Capture


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Poster Sessions

P31227 Ophthalmologic presentation of CADASIL J. Martins1, J. Serino2, V. Carvalho1, C. Cunha1, J. Martins3

Neurology, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal, 2Ophthalmology, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal, 3Neuroradiology, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal 1

Background and aims: CADASIL is a genetic nonamyloid non-atherosclerotic arterial disease, whose cardinal signs are recurrent stroke, subcortical dementia and migraine with aura. Recent studies expand the expression of disease involving the choroid, retina, optic nerve and heart. Methods: Clinical Case: Female, 63-year-old, with hypertension and dyslipidemia, both medicated, otherwise healthy. She had four close family members with history of vascular events, including stroke or myocardial infarction, before the age of 50. She noticed vision problems in her left eye of acute onset. Her visual acuities were 10/10 OD and 1/10 OS with a left relative afferent pupillary defect. Bilateral funduscopic examination showed: narrowing and arteriolar sheathing, arteriovenous nipping, discrete perifoveal pigment changes, left optic disc atrophy. Without other neurological abnormalities. Humphrey perimetry: paracentral scotoma in OD; inferior cecocentral and upper arcuate scotomas in OS. Brain MRI: important periventricular and subcortical ischemic leukoencephalopathy, and multiple ischemic vascular lacunae. Additionally, several enlarged Virchow-Robin spaces were located mostly at external capsules and anterior temporo-polar regions. Results: The molecular study detected the mutation c.1672C>T(p.Arg558Cys) in heterozygosity in NOTCH3 gene.

Retinography

Genealogic tree

Conclusion: CADASIL diagnosis was suspected taking into account family history and atypical imaging findings. Cerebral and retinal vessels share anatomical and physiological properties. The abnormalities of retina and optic nerve may be due to direct microvascular damage or due to trans-synaptic retrograde degeneration after injuries involving optic radiation. Although there are reports describing retinal and optic nerve changes in advanced stages of CADASIL, to our knowledge, this is the first case presenting initially as an ophthalmologic impairment. Disclosure: Nothing to disclose

Left: Humphrey perimetry. Right: Brain MRI


Poster Sessions

749

P31228

P31229

Regional patterns of brain grey and white matter abnormalities in patients with hereditary optic neuropathies: dominant optic atrophy vs. Leber hereditary optic neuropathy

Disconjugate horizontal eye movements in spinocerebellar ataxia type 3 (SCA3)

R. Messina1, M.A. Rocca1, S. Bianchi-Marzoli2, M. Petrolini1, J. Milesi3, F. Darvizeh4, F. Bandello3, G. Comi5, A. Falini6, M. Filippi1

Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 2Department of Ophthalmology, Istituto Auxologico Italiano, Milan, Italy, 3Department of Ophthalmology, San Raffaele Scientific Institute, Milan, Italy, 4Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy, 5Department of Neurology, San Raffaele Scientific Institute, Milan, Italy, 6Neuroradiology, Università Vita-Salute San Raffaele, Milan, Italy 1

Background and aims: Previous studies revealed an involvement of the whole visual pathway in patients with Leber Hereditary Optic Neuropathy (LHON), whereas Dominant Optic Atrophy (DOA) patients had tissue loss of the anterior optic pathway and distributed brain white matter (WM) microstructural abnormalities. Here, we compared the regional patterns of grey matter (GM) and WM abnormalities between DOA and LHON patients. Methods: High-resolution T1-weighted and diffusion tensor images were derived from 16 LHON patients, 19 DOA patients and 20 controls. Voxel-wise methods were used to map the regional distribution of damage in the brain WM and GM. Results: Compared to controls, LHON and DOA patients had reduced WM volume of the optic chiasm and optic tracts. LHON patients had also atrophy of the left optic radiation (OR) compared to controls and DOA patients as well as reduced left primary visual cortex volume compared to controls. Compared to controls, LHON patients had decreased fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) of the OR. Compared to controls and LHON, DOA patients had lower MD, RD and axial diffusivity in the WM of the cerebellum, brainstem, thalamus and fronto-occipital-temporal lobes. Conclusion: Both LHON and DOA patients had an involvement of the anterior visual pathway. In LHON patients, structural damage extends only to the posterior optic pathway, whereas in DOA patients there is a more diffuse WM damage, suggesting that different molecular defects and genetic inheritance might lead to different pattern of structural brain abnormalities in hereditary optic neuropathies. Disclosure: Nothing to disclose

A. Novo1, C. Duque1, J. Ribeiro1, J. Castelhano2, J.M.G. Lemos1, C. Januário1

Neurology, CHUC, Coimbra, Portugal, 2Biomedical Engineering, IBILI, University of Coimbra, Coimbra, Portugal

1

Background: Several oculomotor abnormalities have been described in spinocerebellar ataxia type 3 (SCA3). However, little is known about eye movement static and dynamic conjugacy in this disease. Aim: To perform a quantitative analysis of ocular conjugacy in SCA3 patients. Methods: 22 patients with genetically confirmed SCA3 underwent complete neurological examination. The scale for the assessment and rating of ataxia (SARA), neuroophthalmological examination and binocular videooculography were also performed. Results: 64% of patients were female, patients’ median age was 53.5 years and median disease duration was 8.5 years. Horizontal strabismus was a universal finding. Esotropia at far and near was present in 59% and 29% of patients, respectively. Highly prevalent (95%) pervasive saccadic intrusions (SI, mean 45/min) were frequently disconjugate between eyes (i.e., dynamic overshoots within SI were larger in the adducting eye, giving the appearance of monocular disconjugate adducting intrusions in 4 patients). Horizontal saccades were also markedly disconjugate between eyes, being shorter and slower in the abducting eye (amplitude and velocity disconjugacy ratio, 0.95). Gazeevoked and optokinetic nystagmus were equally disconjugated between the abducting and adducting eye (disconjugacy ratio, 0.87 and 0.90, respectively). While ocular alignment measurements were not associated or correlated with any of the above-mentioned dynamic disconjugacy ratios, ocular alignment at near was strongly correlated with SARA (r=0.612; p=0.049). Conclusion: Static and dynamic ocular disconjugacy are highly prevalent in SCA3 and seem to represent two unrelated pathophysiological processes, both occurring in cerebellum. Ocular alignment at near may be a potential biomarker of SCA3. Disclosure: Nothing to disclose


750

Poster Sessions

P31230

P31231

Improvement of visual field with medicinal herbs in normal tension glaucoma: a small open pilot study

Why and when to refer patients for vestibular evoked myogenic potentials: a critical review

T. Okabe

E. Papathanasiou1, D. Straumann2

Department of Pathology, University of Tokyo, Tokyo, Japan

Background and aims: Glaucoma is a progressive optic neuropathy and a leading cause of blindness. Neural losses from glaucoma are irreversible. At the present time, the aim of glaucoma treatment is to slow progression and minimise the risk of further damage. Functional improvement with treatment is not expected. Over several hundred years, traditional medicinal herbs have been used for treatment of glaucoma in Asian countries. An open trial was carried out to see whether traditional herbal therapy could improve vision in normal tension glaucoma. Methods: The clinical trial was performed to test the therapeutic effect of medicinal herbs for patients with normal pressure glaucoma. Nine patients of 32-65yr. old were diagnosed as normal pressure glaucoma with intraocular pressure of 8-18mmHg. They were treated with mixtures of 23-28 medicinal herbs prescribed according to the differential diagnosis by traditional herbal medicine. Using Humphery Field Analizer, visual field test was used to evaluate the effectiveness of the herbal therapy. Results: Intraocular pressure was not changed with the herbal therapy. However, visual field test demonstrated that mean deviation (MD) was improved after 3-10 months of treatment in all the patients. Visual field index (VFI) was also increased after the therapy. Conclusion: Although the mechanism of improved vision cannot be proven, it is likely that the herbal therapy resulted in some reversal of retinal ganglion cell dysfunction. Disclosure: Nothing to disclose

1Clinical Neurophysiology, Clinic B, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus, 2Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

Background and aims: Vestibular evoked myogenic potentials (VEMPs) are now used by an increasing number of laboratories to evaluate otolith inner ear function and their pathways through the central nervous system. So far, however, it remains unclear whether VEMPs add further information beyond what a good clinical neuro-otological examination and other auxiliary tests (calorics, pure tone audiometry, video head impulse test, subjective visual vertical) can provide. Methods: MEDLINE (accessed by PubMed, September 1964-February 2015) was searched with the following string: (“vestibular evoked myogenic potentials” [all fields]). Only articles published in English were evaluated. One author (ESP) independently screened all titles and abstracts of the articles identified by the searches to assess their eligibility. Results: VEMPs are useful not only for confirming the presence of superior semi-circular canal dehiscence (SSCD), but also for confirming the presence of relevant acoustic neuromas, bilateral vestibulopathies, inferior vestibular neuritis and vestibular dysfunction in inherited neuropathies. They can also confirm the presence of Menière’s disease (MD) versus vestibular migraine and predict later hearing loss in MD. The existence of idiopathic otolithic vertigo has also been proposed on the basis of VEMPs. Sometimes VEMPs are the only way of evaluating the vestibular system, such as in congenital nystagmus. Further work is required, especially with respect to the more recently discovered ocular VEMPs. Conclusion: From this review we can conclude that the usefulness of VEMPs goes beyond the confirmation of SSCDs and can be useful in a multitude of clinical cases. Disclosure: Nothing to disclose


Poster Sessions

P31232

P31233

Isolated opsoclonus: a case series Pappa1,

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Alentorn1,

Ibanez1,

E. A. M.J. A.-I. G. Breton3, B. Gaymard3, D. Psimaras1

Grinea2,

Pitie Salpetriere Hospital, Neuro oncology Mazarin, Paris, France, 2Intensive Care Unit of Neurology, Pitié-Salpêtrière Hospital, Paris, France, 3Pitié-Salpêtrière Hospital, Paris, France 1

Background and aims: Opsoclonus or flutter (O/F), of equal clinical significance, are characterized by chaotic eye movements and are typically associated with myoclonus. In the paediatric population an occult neuroblastoma is found in almost 50% of cases. In adults there is often a correlation between symptoms’ appearance and neoplasia or infection. The pathogenic mechanism of O/F is to be elucidated. We report a series of seven patients presenting to our hospital with isolated O/F (not associated with myoclonic jerks). Methods: All patients underwent complete clinical examination and paraclinical investigations including eye movement recording. Results: Median age of appearance of symptoms was 41 years and sex ratio was 5 women: 2 men. In 43% (3/7) of our cases O/F remains at this day of unknown aetiology. As far as the rest of the patients are concerned, a specific cause was identified (Mycoplasma infection, paraneoplastic syndrome and a cerebellar lesion). Abnormalities were found on only one patient (14%) in brain Magnetic Resonance Imaging. The clinical course was favourable in most cases. Four patients were treated with immunotherapy (intravenous immunoglobulins, cyclophosphamide), associated to tumour treatment in the oncologic patients. Interestingly, in one case O/F spontaneously regressed within 3 months. Conclusion: We present the largest, to the best of our knowledge, series of adult isolated O/F cases, systematically associated to ataxia but not to myoclonus as classically described. We propose that such cases deserve additional evaluation as classical opsoclonus/myoclonus syndrome does, in order to identify underlying pathologies (mainly neoplastic and infectious) and rapidly administer an adequate treatment. Disclosure: Nothing to disclose

Isolated unilateral ptosis due to neurovascular conflict G. Piccirillo1, F. Trojsi2, R. Conforti3, G. Tedeschi2

1Institute of Diagnosis and Care “Hermitage” Capodimonte, Naples, Italy, 2Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences., Second University of Naples., Naples, Italy, 3Neuroradiology Unit, Second University of Naples, Naples, Italy

Background and aims: Isolated ptosis due to partial oculomotor nerve palsy (ONP) is unusual with only few cases reported in the literature to date. In case of unilateral ptosis, systemic diseases, such as myasthenia gravis or other autoimmune diseases, are mainly screened, although other conditions to be considered are vascular lesions and, in particular, neurovascular conflicts. Methods: A 50-year-old woman developed a right ocular ptosis in the last years (Fig.1). She did not notice fluctuations or worsening of this symptom throughout the day. Moreover, electromyographic and serum investigations, performed to exclude a neuromuscular junction disease, were negative. we performed a brain magnetic resonance imaging with angiography (magnetic resonance angiography, MRA) of intracranial vessels.

Right ptosis in position of primary gaze. RE: right eye, LE: left eye.

Results: Specifically, the coronal reconstruction of threedimensional constructive interference in steady-state (3D-CISS) MR sequences showed that the cisternal segment of the right ON was slightly pressed downwardly by the right posterior cerebral artery (PCA) and laterally by the posterior communicating artery (PCoA) (Fig. 2, 3).

The 3D-CISS MR sequences. On the left, coronal reconstructions of cisternal portion of oculomotor nerves. On the right, sagittal reconstruction of the right and left cisternal portion of oculomotor nerve, respectively in the top and bottom


752

Poster Sessions

sensitivity of the digital flicker test in AON. Follow up of the patients may provide evidence of an accurate and easyto-use tool in diagnosing acute ON and signs of demyelinating disease in the visual pathway. Disclosure: The study was supported by the Danish Multiple Sclerosis Society

P31235 No gender difference on optic coherence tomography in acute optic neuritis G. Pihl-Jensen, J.L. Frederiksen MRA TOF 3D sequence shows the anomalous arrangement of the vessels on the right side. The figure pointed out the atypical path of the superior cerebellar artery, the posterior communicating artery and the posterior cerebral artery

Conclusion: We considered that, probably, the selective chronic injury of the right oculomotor fascicles, innervating the right levator palpebrae superioris, could have caused a partial fascicular oculomotor paresis with ipsilateral ptosis. We briefly discussed the potential, although unusual, vascular aetiologies of partial oculomotor nerve palsy. Disclosure: Nothing to disclose

P31234 Sensitive assessment of acute optic neuritis by a new digital flicker test G. Pihl-Jensen1, S. Trauzettel-Klosinski2, J.L. Frederiksen1 1

Glostrup, Denmark, 2Tübingen, Germany

Background and aims: Optic neuritis (ON) is primarily a clinical diagnosis but clinical tests with increased sensitivity, and tests which predict MS risk in the ON patients, are needed. The Aulhorn flicker test was shown in the 1980’s to effectively diagnose acute ON. The aim of this study was to examine the applicability of a new, digitalised version of the analogue test for acute ON (AON). Methods: A psychophysical test where the subjective brightness of a steady field is adjusted to that of a flickering field of randomised varying frequencies 0-60Hz. Recorded luminances are plotted against frequencies. The normal curve shows light-enhancement at medium frequencies whereas the AON curve is hypothesized to show darkness enhancement and cancelled Brücke-Bartley-effect at these frequencies. Visual acuity (VA) and flicker test measurements were obtained in AON patients. 52 consecutively referred, untreated ON patients were included (bilateral in 5/52). Results: Mean logMAR VA was 0.52 (SD:0.58) and mean age 37.1 year (SD:11.2). The flicker test was performed 22 days (SD:15) following ON onset. 49/52 patients showed abnormal response corresponding to 94.23%. 20/52 patients were re-examined 3 months following ON onset where 7/20 showed normal response (1/20 in the acute phase) which may indicate a dynamic response of the flicker test at different time points following ON onset. Conclusion: Preliminary results indicate very good

Glostrup, Denmark

Background and aims: Optic neuritis (ON) and multiple sclerosis (MS) occur more often in women than in men and much attention in MS is currently on gender differences. Studies of optic coherence tomography (OCT) have indicated the value of retinal nerve fibre layer thickness (RNFLT) and macular cube volume (MCV) as prognostic markers in ON and MS. The aim of the study was to examine gender specific differences in retinal nerve RNFLT and MCV in patients with acute optic neuritis. Methods: An ongoing observational study of OCT measurements of RNFLT and MCV in ON patients referred, between July of 2013 and April of 2014 referred, in the acute inflammatory phase. The main outcome was between gender difference in RNFLT and MCV. Results: 65 patients were included (48 females/17 males). Mean age did not differ between genders (male: 33 years, female: 34 years, p= 0.991). No significant difference was shown between female ON and male ON eyes with regards to RNFLT (male: 117.8μm, female: 124.81μm (p=0.741)) or MCV (male: 9.99mm3, female: 10.10mm3 (p=0.432)). Both genders had highly significant intereye asymmetry in RNFLT, i.e. difference between ON affected eye and unaffected eye (p0.050. Onset time of swallowing therapy after stroke was effective on swallowing recovery on the main outcome variables. So that in first group patients, recovery was rather than other groups P1mm). Four presented significant cervical vessels hemodynamic stenosis (1 VA occlusion), three had concomitant intracranial symptomatic stenosis. Classical angiography and thoracic-abdominal-pelvic CT with contrast were performed in all, Aortic involvement was documented in 4, several aortic ramifications were involved in all. Follow-up data from 3 patients (3 years median) showed no changes in 1, 1 partial recanalisation of VA occlusion and 1 evolution into bilateral MCA stenosis. Conclusion: Median age at diagnosis was high, which can be explained by the rareness of the disease. Intima-media thickness was present in all patients. Frequent involvement of intra-cranial vessels is not a prominent feature in other studies and requires angiographic confirmation and, if real, can translate a selection bias. Disclosure: Nothing to disclose

A. Riahi, I. Bedoui, H. Derbali, M. Messelmani, M. Mansour, J. Zaouali, R. Mrissa

Neurology department, Military Hospital of Tunis, Tunis, Tunisia

Background and aims: Cerebral small vessel disease (CSVD) refers to a variety of conditions affecting small arterioles, venules and capillary in the brain. It can be assessed through its consequences on brain imaging: lacunar infarcts and leucoaraiosis. The aim of our study is to evaluate the cognitive impairment associated with CSVD, and to analyse its correlation with MRI findings. Methods: Patients with brain MRI features of CSVD were included. We tested the global cognitive performance, episodic memory, attention, visuospatial functions and executive functions. Subsequently we investigated the correlations with the imaging data (lacunar infarcts number and location and leukoaraiosis). Results: 100 patients (mean age: 68.4 ±10.1 years; sex ratio: 1.43) presented with a total of 516 lacunar infarcts and moderate or severe leucoaraiosis according to Fazekas scale in 40% of cases. Among them, 22% presented with major neurocognitive disorder, and other 22% with minor neurocognitive disorder. Attention impairment, visuospatial and executive functions disorders were observed in 52%, 44% and 35% respectively. Episodic memory disorders were correlated to the severity of leucoaraiosis (p20). Depressive symptoms were not correlated with age, number of lacunes or severity of leukoaraiosis. Among the different white matter and basal ganglia regions, the caudate nuclei infarctions were significantly correlated to depression (p 95% of right internal carotid artery and right subclavian artery, respectively. The patient was treated with re-stenting with conventional balloon for both stenoses, without residual stenosis. In 2013, ultrasound of cervico-cerebral arteries revealed recurrent ISR of right internal carotid artery, with a 50% residual stenosis and we initiated chronic treatment with azathioprine for endothelial proliferation. At 6 months of follow-up, the patient has no complications and no other new ISR documented by ultrasound. Conclusion: We have chosen this case to emphasise the optimal treatment with repeated carotid angioplasty with balloons and stents associated with immunosuppressive therapy for recurrent in-stent restenosis. Disclosure: Nothing to disclose


Poster Sessions

791

P32020

P32023

Cerebral reperfusion syndromecomplication of carotid artery endarterectomy: a case report

Prevalence of post-stroke spasticity in Poland and its impact on activities of daily living and quality of life in one-year follow-up

O. Rusu1, C. Coclitu1, A. Ciobotaru1, T. Parvu1, A.C. Mergeani1, M.T. Vasile1, B. Dorobat2, F. Antochi1

Neurology, University Emergency Hospital Bucharest, Bucharest, Romania, 2Interventional Neuroradiology, University Emergency Hospital Bucharest, Bucharest, Romania 1

Background and aims: Reperfusion (or hyperperfusion) syndrome is a possible complication of a number of revascularisation procedures involving cerebro-vascular circulation, including carotid and vertebral artery endarterectomy or angioplasty, extra-cranial intracranial by-pass, clipping of intracranial artery aneurism. Several interrelated factors have been reported in the pathophysiology of the cerebral hyperperfusion syndrome, such as impaired cerebral autoregulation, critical stenosis, periprocedural hypertension, ischaemia-reperfusion injury, baroreceptor dysfunction, oxygen-derived free radicals. Methods: We report the case of an 80-year-old female, who underwent a right carotid endarterectomy for a symptomatic high-grade carotid stenosis (European Stroke Organisation guidelines) and developed reperfusion syndrome a few days after surgery. The initial symptoms were marked by headache, myoclonic movements of the right leg, motor deficit of the right limbs followed by a prolonged partial with secondary generalised epileptic status and then left hemiplegia. Cerebral CT scan showed a large frontotemporo-parietal hypodense area, with effacement of sulci and ipsilateral lateral ventricle, suggesting the presence of brain oedema. Electroencephalogram recording demonstrated bilateral temporo-parietal spike and wave complexes. Results: Clinical and neuroradiological outcomes were unfavourable, with haemorrhagic transformation and fatal prognosis 19 days later through infectious complications in the context of the severe neurologic condition. Conclusion: When a headache, focal neurological deficit or epileptic seizures follow carotid artery endarterectomy, it is important to consider reperfusion syndrome, a rare, but a serious complication following cerebral revascularisation interventions. Disclosure: Nothing to disclose

M. Schinwelski1, E. Sitek2, J. Sławek2 Neurology, St. Adalbert Hospital, Copernicus, Gdańsk, Poland, 2Neurological-Psychiatric Nursing, Medical University of Gdańsk, Gdansk, Poland 1

Background and aims: The present study aimed to establish the frequency of spasticity in Polish population, its impact on activities of daily living (ADL) and quality of life (HRQoL) as well as its predictors in stroke survivors in oneyear follow-up. Methods: Among 381 patients admitted to the Neurology Department following ischemic and haemorrhagic stroke in one year, 121 paretic patients (aged 73±11 years) fulfilled the inclusion criteria. During three visits: 3, 6 and 12 months after stroke muscle strength was assessed by Medical Research Council (MRC) and muscle tone was rated using Modified Ashworth Scale (MAS). ADL and HRQoL were evaluated with Barthel Index (BI), Modified Rankin Scale (mRS) and SF36, respectively. Results: Spasticity was present in 45% of the patients (55/121) at 3-month follow-up. Severe spasticity (MAS≥3) was observed in 15% of the patients (19/121). After one year 33/94 (35%) patients showed spasticity and 19/94 (20%) had severe spasticity. Prevalence of spasticity in lower limbs during three visits was 32%, 31% and 27% respectively. Spasticity occurred more frequently in upper limbs and in the younger group of patients (5: 2, can't stop: 3. We analysed the second of two trials. Data were recorded from 272 patients of the German Consortium for Frontotemporal Degeneration: 111 behavioural variant frontotemporal dementia (bvFTD), 98 primary progressive aphasia variants (semantic/ non-fluent/ logopenic), 30 PSP, 17 corticobasal syndrome (CBS), 16 amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). Diagnosis was made according to the internationally established clinical criteria. 30 healthy controls (HC) were compared to the patients. Results: The applause sign occurred in all subject groups, one control included (Fig. 1). It was significantly more common in PSP as compared to bvFTD, PPA and HC. Comparison between the other groups failed to show significant differences of clapping performance. The sign was correlated with measures of executive-, visuospatialand language function as well as disease severity.

Conclusion: Our study confirms the occurrence of the applause sign in bvFTD, PSP and CBS and adds the occurrence in PPA, ALS/FTD and HC. Although still suggestive of PSP, clinically it must be interpreted with caution. From the correlation found with various cognitive measures we suggest the applause sign to be indicative of disease severity. Disclosure: This research was supported by a Federal ministry of Education and Research (BMBF) by a grant given to the German Consortium for Frontotemporal Degeneration (grant number O1GI1007A).


Poster Sessions

841

P32121

P32123

Abstract cancelled

Differences in MDS-UPDRS scores based on Hoehn and Yahr stage and disease duration: results of a large international multicentre study of 3206 patients (the QUALPD study)

P32122 Demography and clinical profile among Parkinson Disease patients in Egypt: data of 374 cases H. Shehata, N. Shalaby, A. Abdelalim, A. Elmazny Neurology, Cairo University, Cairo, Egypt

Background and aims: Though PD is a common neurodegenerative disorder; yet, there are sparse data about its demography in Egypt. This study was performed to identify the demography and clinical profile of Egyptian patients with PD. Methods: Medical records of 374 idiopathic PD patients attending a tertiary referral centre from 2004 till 2014 in Cairo were reviewed to collect their clinical characteristics. Results: Out of 374 cases, 269 patients were males (71.9%) and 105 patients were females (28.1%). The mean age of the patients was 62.4±8.7 years (34–83 years). The mean age of onset in those patients was 49.8±6.5 years (31–80 years). No significant difference between males and females in age of onset (P>0.05). Family history of PD was positive in 18 patients (4.8 %). The main presenting feature was bradykinesia in 211 patients (56.4%), tremor in 95 patients (25.4%), rigidity in 46 patients (12.3%) and postural instability in 22 patients (5.9%). Unilateral onset was detected in 323 patients (86.4%) The mean UPDRS (motor section) score was 63.9±12.2 during off-state and 19.6±8.5 during on-state The most common non-motor manifestations were depression (n=143), sleep disturbances or EDS (n=87), constipation (n=269), pains and cramps (n= 106), urinary symptoms (n=172) and autonomic symptoms (n=39). 306 patients (81.8%) were on levodopa at mean doses 572.7±112.5; 111 patients (29.7%) were on dopamine agonists, 37.patient (9.9%) were on rasagilin and 209 patients (55.9%) were on amantadine. Conclusion: Basic demographic data among Egyptian PD patients are comparable to other countries. Additional studies are required in this field. Disclosure: Nothing to disclose

M. Škorvánek1, P. Martinez-Martin2, N. Kovacs3, I. Zezula4, M. Rodriguez-Violante5, J.-C. Corvol6, P. Taba7, K. Seppi8, O. Levin9, A. Schrag10, T. Foltynie10, V. Han1, C. Goetz11, G.T. Stebbins11, Qualpd Study Group12

1Department of Neurology, P.J.Safarik University in Kosice, Kosice, Slovakia, 2National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain, 3Department of Neurology, University of Pecs, Pecs, Hungary, 4Institute of Mathematics, P.J.Safarik University in Kosice, Kosice, Slovakia, 5Movement Disorders Unit, Instituto Nacional de Neurologia y Neurocirugia, Mexico DF, Mexico, 6Département des maladies du système nerveux, Sorbonne Universités, UPMC Univ Paris; and INSERM UMRS_1127, CIC_1422; and CNRS UMR_7225; and AP-HP; and ICM, Hôpital Pitié-Salpêtrière, Paris, France, 7Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia, 8Medical University of Innsbruck, Innsbruck, Austria, 9Neurology department, Russian Medical Academy of Postgraduate Education, Moscow, Russian Federation, 10Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, United Kingdom, 11Department of Neurological Sciences, Rush University Medical Center, Chicago, USA, 12Kosice, Slovakia

Background and aims: The MDS-UPDRS is a newly developed comprehensive tool to assess PD. This study aims to analyse the MDS-UPDRS part I-IV scores and their differences based on Hoehn and Yahr stage (HY) and disease duration in a large cohort of Parkinson's disease (PD) patients. Methods: This cross-sectional study collected demographic data and MDS-UPDRS scores including HY. MDS-UPDRS part I-IV subscores were analysed using one-way ANOVA for each HY stage and for 5-year increments in disease duration. Results: Mean participant age of the 3206 patients was 65.8±10.6 years, 53.3% were men, mean disease duration was 11.5±4.6 years and median HY was 2 (range 0-5). Scores of all four MDS-UPDRS parts increased significantly through HY stages 1-5, with an average increase of 3.8; 7.7; 14.6; and 2.0 points consecutively for parts I-IV, respectively. For 5-year increments in disease duration, MDS-UPDRS subscores increased by an average of 1.6; 3.3; 4.2; and 1.4 points consecutively for parts I-IV, respectively. This increase was significant during the first 15 years of disease for all four parts, while parts II, III and IV increased significantly also in the 15-20-year interval and only part II increased significantly in the 25 and more years interval. There was no change observed in the 20-25year interval for any MDS-UPDRS part. Conclusion: MDS-UPDRS scores for all four parts significantly increase with every HY stage and also with


842

Poster Sessions

5-year increments in disease duration in the first 15 years of the disease. Disclosure: The funding for research leading to this study was provided by the Slovak Research and Development Agency under contract no. APVV-14-0415 and by the Slovak Scientific Grant Agency under contract no. VEGA 1/0024/14 ; by the Movement Disorder Society that received partial support from UCB Spain; from the program “Investissements d'Avenir” ANR-10-IAIHU-06; by the Grant PUT1239 of the Estonian Research Council; by the Bolyai Scholarship of the Hungarian Academy of Sciences, OTKA PD103964 and the Hungarian Brain Research Program-Grant No. KTIA_13_NAP-A-II/10 governmentbased funds; and by the Austrian Science Fund (FWF project number: KLI82-B00).

P32124 Multiple system atrophy (MSA) phenotype associated with frontotemporal lobar degeneration (FTLD)–TDP pathology A.L. Sousa1, R. Taipa2, M. Melo Pires2, M. Magalhães1

Neurology, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal, 2Neuropathology Unit, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal 1

Background and aims: Multiple system atrophy is a sporadic alpha-synucleinopathy characterised by progressive autonomic failure, parkinsonism and cerebellar ataxia. FTLD is a heterogeneous group of disorders, which includes tauopathies, associated with progressive behaviour and cognitive dysfunction. Methods: A case report. Results: The present case is a 56-year-old man with an atypical parkinsonian syndrome. Symptoms began at age 50 with erectile dysfunction. Soon followed a poorly L-doparesponsive parkinsonism, a progressive gait disorder with postural instability and falls, bilateral pyramidal signs and autonomic failure. He later developed severe dysarthria, dysphagia requiring a gastrostomy, nocturnal stridor and urinary symptoms with the need for chronic urinary catheterization. He never had cognitive complaints, including language or behavioural dysfunction. He became permanently wheelchair bound at age 56. He died ten years later with the diagnosis of probable MSA-p. The neuropathological examination showed cortical and subcortical cerebral atrophy most striking in the frontal region and in the striatum, with associated TDP-43 pathology. No cerebellar p62 positive/TDP-43 negative inclusions were found. There were no signs of noteworthy alpha-synucleinopathy or tauopathy. Conclusion: There are rare descriptions in the literature of clinically and pathologically proven MSA patients with some clinical features of FTLD; there are also reports of families with both MSA and motor neuron disease related with C9Orf72 repeat expansions. However, to the best of our knowledge, this is the first case of frontotemporal lobar degeneration-TDP pathology presenting with an MSA-p phenotype. The disproportionate involvement of the

striatum, not usually found in FTLD-TDP descriptions, may have contributed to the clinical presentation. Disclosure: Nothing to disclose

P32125 MicroRNA in CSF and plasma as diagnostic biomarkers in Parkinson’s disease and multiple system atrophy C. Starhof1, A.-M. Hejl2, N. Heegaard3, K. Winge1

1Departement of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark, 2Department of Neurology, Rigshospitalet, Copenhagen, Denmark, 3Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark

Background and aims: Differentiation among parkinsonian syndromes is challenging. The diagnosis relies entirely on clinical criteria and reliable biomarkers are much needed. Circulating microRNAs (miRNAs) represent a class of potential biomarker. MiRNA are small, non-coding RNAs involved in post-transcriptional regulation of protein synthesis and evidence suggests that miR-7-5p and -153 regulate the synthesis of alpha-synuclein. In this study, we aimed to 1) perform miRNA profiling in CSF and subsequent 2) validate biomarker potential of differentially expressed miRs in new sets of CSF and EDTA-plasma samples in PD (Parkinson’s disease), MSA and PSP patients compared to control subjects. Materials and methods: All samples, obtained from Bispebjerg Movement Disorders Biobank, was collected in polypropylene-tubes, centrifuged, aliquoted and stored at -80°C. Small RNA was isolated from 250µl CSF and 200µl EDTA-plasma. MiRNA profiling (n=40) was performed using Exiqon® miRCURY PCR-panel І, investigating 372 miRNAs. Validation in CSF and EDTA-plasma (n=115) of 46 selected miRs, from the CSF-profiling and literature review, is ongoing. Results: While miR-7-5p and miR-153 were not detected in CSF a principal components analysis suggested that MSA patients could be differentiated based on miRNA expression values. Thus, 26 miRs were found differentially expressed (p1.5). Among these, the most significant differentially expressed miRs between MSA and PD were miR-99-3p, miR-338-3p, miR-9-3p, miR-142-3p, and miR-106-5p. Conclusion: MiRNA profiling is possible in CSF, despite an overall low miRNA concentration. Several miRNAs were found to be differentially expressed and thus eligible for further validation in independent sample sets. Disclosure: Nothing to disclose


Poster Sessions

843

P32126

P32127

Adherence to pharmacotherapy in Parkinson's disease patients who take 3 and more daily doses of dopaminergic medication

Determinants of disability and quality of life in mild to moderate Parkinson's disease

I. Straka1, M. Škorvánek2, P. Valkovic1 1

Bratislava, Slovakia, 2Kosice, Slovakia

Background and aims: Study was aimed to detect extent of adherence to therapy in patients with Parkinson´s disease (PD) who take 3 and more daily doses of dopaminergic drugs and to identify causes of low level of adherence. Methods: Non-demented patients with idiopathic PD were included. We used validated Slovak versions of questionnaires and scales: MMSE, 8-Item Morisky Medication Adherence Scale for PD and for comorbidities associated with PD, PDQ-8, WOQ-9, GDS, NMSS, and MDS-UPDRS parts III and IV. Results: 81 subjects were studied (52 men and 29 women) with mean age of 66.5 years and median Hoehn & Yahr stage of 2.5 (range 1-4). The average number of daily doses of antiparkinsonian drugs was 5.4. 56 moderate level of adherence). We have found that the rate of non-adherence is associated with frequency and severity of non-motor symptoms (NMS) and with non-compliance with time of medication intake. Analysis of NMS found significant correlations between the level of non-adherence and NMSS domains attention/memory and problems with perception/ hallucinations. Time-adherence correlated with NMSS domains sleep/fatigue and attention/memory. Adherent and non-adherent patients differed in the accuracy of medication intake, the total score of NMSS, and the score of WOQ-9. Conclusion: Non-adherence is associated mainly with the frequency and severity of NMS (especially with forgetfulness and fatigue). Lower time-adherence is linked to increased rates of motor complications and with wearingoff phenomenon. Disclosure: Project was supported by research grant provided by Novartis Slovensko, s.r.o.

N. Subasic, E. Suljic, D. Imamovic, S. Hajric, Z. Ajanovic, A. Mehicevic

Neurology, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina

Background and aims: To identify factors that independently contribute to disability and quality of life (QoL) in patients with mild to moderate Parkinson's disease. Methods: Survey covered 100 patients with established diagnosis of the PD. Hoehn-Yahr scale and Shwab & England scale were used for evaluation of symptoms and signs of the PD. Disease-specific QoL questionnaire (PDQ39) and Beck Scale of Depression were filled by the examined persons after eliminatory Mini Mental State Examination (score >23) by the examiners. Results: Average age of the patients was 68.6+/-8.0 of which 58% were male and 42% were female. Most patients lived in the community, (79%). At the onset of the disease, in 59% of the patients the right side of the body was affected, and in 41% of the patients the left side. The higher stage of the disease (Hoehn and Yahr scale) and higher disability in performing daily activities (Shwaba and England scale) have contributed to the significant increase in quality of life scores (pT in exon 6 of XPA gene, coding for a truncated protein p.Arg228* (the most frequent mutation among XPA in North Africa). These data confirm the diagnosis of Xeroderma Pigmentosum (XP) type A.

Genetic test conclude that the amino acid substitution found in the patient’s CPOX gene is an almost certain pathogenic mutation for hereditary coproporphyria.


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Poster Sessions

P32175 Are mutations in the GJB1 gene risk factor for multiple sclerosis? B. Peterlin1, T. Hojs Fabjan2, M. Menih2, G. Rudolf1, A. Peterlin1, A. Maver1

1Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia, 2Department of Neurology, University Clinical Centre Maribor, Maribor, Slovenia

Conclusion: XP is a rare and heterogeneous recessive autosomal genodermatosis due to DNA nucleotide excision repair defect. Cutaneous involvement is the major sign with photosensitivity and high risk of cutaneous carcinoma. 5 out of 8 groups of XP display neurological symptoms (cognitive disorder, microcephalia, epilepsy, cerebellar syndrome, axonal polyneuropathy, deafness). XPA is characterised by predominant neurological achievement and second-rate cutaneous symptoms with rare carcinomas. Disclosure: Nothing to disclose

Background and aims: Rare associations among common and genetic diseases might reveal genetic risk factors and important pathological mechanisms for common diseases. Although familial contribution to multiple sclerosis (MS) aetiology is well established, monogenic forms or genetic risk factors with moderate effect on MS have not been described to date. Based on the comorbidity of MS and X-linked Charcot-Marie-Tooth disease in a Slovene family, we aimed to analyse the contribution GJB1 pathogenic variants in the aetiology of MS. Methods: We present a first familial case of multiple sclerosis in a family with the X-linked Charcot-Marie-Tooth disease. Furthermore, we analysed GJB1 variants in exomes of 12 familial and 46 sporadic Slovene MS cases by clinical exome sequencing. Results: We identified a novel GJB1 pathogenic sequence variant (c.502T>G, p. Cys168Gly) In a Slovene family with hereditary neuropathy. Among eight family members with clinically, electrophysiologically and/or genetically confirmed neuropathy, two family members developed MS, while five affected family members had normal MRI and had no symptoms or signs of MS. We haven’t found any pathogenic sequence variant in the GJB1 gene in Slovene familial and sporadic MS cases. Conclusion: In addition to three previous reports of association between X-linked Charcot-Marie-Tooth disease and sporadic MS and several reports of transient white matter lesions and neurologic deficits in patients carriers of GJB1 mutations, we describe the first familial case of MS. Analysis of familial and sporadic MS patients imply that pathogenic sequence variants in the GJB1 gene might present rare but important risk factors for MS. Disclosure: Nothing to disclose


Poster Sessions

869

P32176

P32177

Six generations of Frontotemporal Dementia linked to chromosome 3 (FTD3): demographics of the Danish CHMP2B family

The role of ApoE gene polymorphism and vascular risk factors in the susceptibility to early and late Alzheimer's disease in an Iranian population

P. Roos1, P. Johannsen1, J. Stokholm1, G. Waldemar1, A. Isaacs2, J. Brown3, J. Nielsen1

S. Samadzadeh1, R. Abolfazli1, A. Shakoori2, T. Sabokbar3

Background and aims: A truncating mutation in the CHMP2B gene located on chromosome 3 causes an autosomal dominantly inherited behavioural variant Frontotemporal Dementia, FTD-3 (1). The disease was traced to a woman born in 1876 in a large Danish family (2,3). Amongst her descendants we have investigated a large cohort of presymptomatic and clinically affected CHMP2B mutation carriers. Here we present extensive demographic data. Methods: The pedigree of this CHMP2B family was established through family investigations and meetings during more than two decades. Cognitive and behavioural symptoms were described by close relatives, and age of onset (AOO) as assessed by the physician was estimated in all affected family members. AOO and course of disease was analysed by ANOVA using SAS. Results: The first four generations of the Danish CHMP2B family comprise 240 individuals born within the years 1876 to 1993. So far FTD-3 has been clinically diagnosed in 46 family members, 13 of whom are alive. Additionally, 15 presymptomatic mutation carriers have been identified in the fifth generation, whilst sixth generation is too young for genetic counselling. Median and mean AOO was 57 (range 48–70), and expected life span was reduced by 9 years in mutation carriers. AOO was not related to AOO in the affected parent, nor was AOO correlated to gender. There was no anticipation, and the mean AOO seemed to be consistent through the generations. Conclusion: FTD-3 is clinically variable; however, AOO is consistent through the generations, and life expectancy is reduced. Disclosure: Nothing to disclose

Background and aims: The aim of the present study was to determine the association of different alleles of ApoE (E2, E3, and E4) and vascular risk factors in an Iranian sample of early and late AD in Tehran. Methods: We enrolled 70 Iranian patients with confirmed diagnosis of AD based on DSM-IV. All subjects were genotyped for APOE by Apo E Strip Assay kit. Family history of AD and vascular risk factors were gathered from his/her hospital file. Results: The study reveals the E3/E3 has higher frequency in both EOAD and LOAD, and therefore in total population. The E3/E4 genotype is the next frequent genotype with higher frequency in LOAD relative to EOAD and also reveals that the E3/E4 genotype has significant relation with the record of AD in family history of a patient for the subset of EOAD (p=0.013). The vascular risk factors such as CAD and HLP have significant relation with onset of AD (late more than early) with p values of 0.027 and 0.036 respectively. The other factors, namely DMII, HTN and smoking don’t indicate significant relation with onset of AD. Conclusion: The main concluding points of study are firstly, high frequency of E3/E3 and then E3/E4 genotypes among AD in this study, secondly, there is a significant relation between E3/E4 genotype and family history in subset of EOAD patients, and lastly, there are also other significant relations including CAD and HLP with Alzheimer onset, and also, BMI with gender for subset of LOAD. Disclosure: Nothing to disclose

1Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 2Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK, London, United Kingdom, 3Department of Neurology, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK, Cambridge, United Kingdom

1Neurology department, Tehran university of medical sciences, Tehran, Iran, Islamic Republic of, 2Tehran University of Medical Sciences, Department of Medical Genetics, Cancer Institute, Tehran, Iran, Islamic Republic of, 3Neurology & Neurosciences Research Center, Qom University of Medical Sciences, Qom, Iran, Islamic Republic of


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Poster Sessions

P32178

P32179

New mutation in hereditary spastic paraplegia in Murcia

Late-onset Alexander disease: a novel mutation

I. Sanchez Ortuño, A. Sanz Monllor, N. García Lax, J.Á. Motos García, M. Palao Rico, J.A. Iniesta Valera

D. Sangalli1, A. Ciammola1, C. Morelli1, A. Moroni2, I. Ceccherini3, F. Girotti1, V. Silani1

Neurology, Hospital General Universitario Reina Sofía, Murcia, Spain

Background and aims: The hereditary spastic paraplegias (HSPs) comprise a group of genetically heterogeneous neurodegenerative diseases. Our aim was to study the molecular basis of a case with hereditary spastic paraplegia. Methods: Clinical description and evolution of two brothers and their father affected with HSP, and molecular study of SPG4, SPG3A and SPG6 genes, involved in this pathology, sequencing both strands of the exons and adjacent intron of the genes identified in the proband and his brother affected, and then validation of the identified mutation in their parents. Results: Male, 42-year-old with spastic gait a hyperreflexia in lower limbs. His brother (32 years) with mild spasticity and also hyperreflexia in lower limbs and father (74 years), with no defined progressive frame gait disturbance. Cerebral and hole spine MRI, blood test and serology analysis was performed without any notable alteration. The study of genes SPG6 and SPG3A showed no remarkable genetic disturbance, but in the SPG4 gene identified a new point mutation (c.1536 +3A>G) that were heterozygous for the two brothers. The mutation affects the processing donor site of intron 13: IVS13+3A> G. The in silico modelling suggests that this mutation significantly affect the processing of intron 13, and his study in parents confirmed the presence in the father but not the mother. Conclusion: We identified a novel mutation in the SPG4 gene, that affects the intron 13 processing. It`s associated with the development of autosomal dominant inheritance HSP. Other three mutations are described in intron 13 with the same effect. Disclosure: Nothing to disclose

Neurology, IRCCS Istituto Auxologico Italiano, Milan, Italy, Università degli studi di Milano, Milan, Italy, 3Istituto Giannina Gaslini, Genoa, Italy

1 2

Background and aims: Alexander disease (AxD) is a rare neurologic disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). It is an autosomal dominant disease characterised by astrocytic inclusion. 3 clinical subtypes are described, based on age of onset: infantile, juvenile and adult. Here we describe the case of an adult woman, diagnosed with AxD, who showed a novel mutation in GFAP. Methods: A 54-year-old Caucasian woman presented with asymmetric spasticity mostly on the left side, unsteadiness of gait, slurred speech and ataxia for 5 years. She had a history of ovarian cancer, diagnosed and surgically treated when she was 48 years old. She underwent MRI examination of head and spinal cord, which showed atrophy of the medulla and upper cervical cord. Hematologic screening and cerebrospinal fluid examinations were normal. No paraneoplastic antibodies were detected. The data suggested the possibility of AxD. Results: Peripheral blood was obtained and all nine exons and adjacent intronic regions of GFAP were amplified and directly sequenced. A missense heterozygous mutation in exon 1 was highlighted (c.219G>C). It results in an amino acid exchange on position 73 from methionine to isoleucine (p.M73I). This is the first time this mutation has been described in healthy or affected people. It was impossible to obtain consent to contact genetically related relatives for GFAP screening. Conclusion: We detected a new possible pathogenic mutation in an adult patient. Its role is strongly supported by other nucleotide substitutions in the same codon, already described in families affected by AxD. Disclosure: Nothing to disclose


Poster Sessions

871

P32180

P32181

Ataxia-neuropathy with cognitive decline due to a novel mutation in MTCOII, a subunit of mitochondrial complex IV

Diagnostic accuracy of laboratory tests and muscle biopsy in patients with genetically confirmed mitochondrial disease

J. Schäfer1, S. Jackson2 1

Dresden, Germany, 2Dept. of Neurology, Dresden, Germany

Background and aims: The ataxia-neuropathy spectrum covers a large clinical and pathogenic variety of diseases and also includes hereditary disorders of mitochondrial function. These can be caused by genetic defects in mtDNA or in nuclear genes which encode for proteins controlling the maintenance of mtDNA. In mitochondrial disease, the ataxia typically occurs in combination with various central nervous system features, including epilepsy, cognitive decline and white matter lesions on MRI. Although mutations in mitochondrial polymerase-gamma (POLG) have now been recognized as the commonest cause of mitochondrial disease leading to ataxia-neuropathy, a considerable proportion of such patients do not have POLGdeficiency. Methods: A 43-year-old patient with no history of mitochondrial disease developed progressive ataxia, neuropathy, cognitive impairment and deafness. Biochemical measurement of respiratory chain activities and sequencing of POLG and eventually the entire mitochondrial genome was performed in the patient and his parents. Results: Respiratory chain complex-IV activity was reduced by 50% in muscle from the patient, and sequencing of the patient´s mtDNA revealed a novel mutation in MTCOII, a subunit of cytochrome oxidase. Using the accepted canonical criteria for assigning pathogenicity to novel mtDNA mutations, the mutation was regarded pathogenic. Conclusion: We identified a patient with a progressive lateonset ataxia and neuropathy associated with deafness and cognitive decline. A novel causative missense mutation was found in MTCOII, a subunit of cytochrome oxidase. In contrast to the few other patients with MTCOII-mutations described so far, our patient did not manifest a myopathy and presented in adulthood. Disclosure: Nothing to disclose.

S. Schreglmann1, J. Petersen2, L. Hoffelner2, V.M. Mihaylova2, M. Auer2, G. Kägi3, A. Schaller4, H. Jung2

1Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL), Institute of Neurology, London, United Kingdom, 2Department of Neurology, University Hospital Zurich, Zurich, Switzerland, 3Department of Neurology, Kantonsspital St. Gallen, St. Gallen, Switzerland, 4Department of Genetics, Inselspital Bern, Berne, Switzerland

Background and aims: Mitochondrial disease (MD), a disorder of respiratory chain dysfunction, can present with the full gamut of neurological symptoms affecting the central (CNS) and peripheral nervous system (PNS). Diagnosis still often rests on muscle biopsy. Clinical, laboratory and imaging heterogeneity complicate recognition, identification and diagnosis of MC. We assessed the results of diagnostic tests in a cohort of genetically confirmed MD patients and compared their usefulness. Methods: Retrospective case series in a university hospital neurogenetics clinic. Results: Out of 54 patients with genetically (mostly muscle) confirmed MD, 29 (53.7%) showed signs for central (CNS) and 38 (70.4%) for peripheral nervous system (PNS) involvement. Diagnostic tests showed abnormal results in line with the diagnosis in 88% for genetic testing in blood (n=8), 65% for abnormal resting serum CK (m>190 w>170; n=48), 62% of muscle histology (n=52), 62% for raised (>0.4g/l) CSF protein (n=26), 55% for an abnormal rise (>5mM) of lactate in the NIFET (non ischaemic forearm exercise test; n=11), 48% for raised (> 2.1 mmol/l) CSF lactate (n=29), 40% for abnormal rise (>5mM) of lactate in the SATET (sub anaerobic threshold exercise test; n=15), 38% for raised (>2.4mmol/l) resting serum lactate (n=40), 30% for abnormal endocrine (thyroid or glucose) measures (n=46), 27% for abnormal glucose metabolism (HbA1c >6.5%) (n=44) and 11% for abnormal thyroid measures (n=44). Conclusion: The high rate of false negative results in both laboratory and histopathology tests documented in genetically confirmed cases shows the considerable limitations of these tests in the diagnosis of MD. Disclosure: SRS is supported by research grants by the EAN (Department to Department program), the Swiss National Science Foundation and the Swiss Neurological Society.


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P32182

P32183

Phenotypic features of GDAP1 mutations in Tunisian Charcot-Marie-Tooth patients

Expression changes of genes associated with apoptosis and survival processes in Parkinson’s disease

I. Kacem1, A. Gargouri Berrechid1, Y. Sidhom1, A. Nasri1, M. Ben Djebara1, E. Leguern2, R. Gouider1 Department of Neurology/ Research Unit UR12SP21, Razi Hospital, Tunis, Tunis, Tunisia, 2Department of Genetics and Cytogenetics, La Pitié Salpêtrière Hospital, Paris, France 1

Background and aims: Mutations in the gangliosideinduced differentiation associated-protein 1 (GDAP1) gene have been associated with both autosomal recessive (AR) and dominant (AD) Charcot-Marie-Tooth (CMT) axonal neuropathy. It is considered as a rare form of CMT in European countries. Our goal is to report phenotypic features of GDAP1 mutations in a Tunisian CMT series Methods: We performed a prospective study of a cohort of CMT Tunisian patients due to a GDAP1 gene mutation, followed in the neurology department of Razi Hospital, Tunisia from 2002 to December 2015. Clinical and electrophysiological data were analysed. Results: Among 128 patients with CMT, genetic mutation was identified in 41patients belonging to 17 families. The mutations in the GDAP1 gene were found in 4 families (23%). In these cases, consanguinity was found in all cases. Mean age of onset was 1.9 years. Pyramidal signs were found in 1 family with novel mutation. Electrophysiological data showed axonal forms in all cases. Mean Over Neuropathy Limitations Scale (ONLS) was 3.7 with mean Charcot Marie Tooth Neuropathy Score (CMTNS) of 13 Conclusion: GDAP1 gene mutations are characterized by an early onset with a severe phenotype. We suggest GDAP1 as the first gene that should be analysed in Tunisian patients affected by AR CMT Disclosure: Nothing to disclose

E. Tüzün, N. Yalçınkaya, H. Haytural, R. Türkoglu, B. Bilgic, H. A. Hanağası, H. Gürvit Istanbul, Turkey

Background and aims: Parkinson’s disease (PD) is a neurodegenerative disorder characterised by progressive degeneration of the dopaminergic neurons in substantia nigra, presumably due to increased apoptosis and oxidative stress. Our aim was to investigate whether PD-induced survival/apoptosis gene expression changes can serve as prognostic biomarkers of PD. Methods: We measured expression levels of phosphatidylinositol-4.5-bisphosphate 3-kinase (PI3K)/Akt pathway factors and additional apoptotic and anti-apoptotic factors in peripheral blood mononuclear cells (PBMC) of PD patients (n=50) and healthy controls (n=50) by real time PCR. Cerebral expression levels of the same molecules were measured in brain samples of mice with rotenoneinduced parkinsonism by PCR. Results: Expression levels of apoptotic factors phosphatase and tensin homolog (PTEN) and mitochondrial apoptosisinducing factor 1 (AIFM1) were significantly decreased, anti-apoptotic factors DJ-1 and Akt-1 were significantly increased and anti-apoptotic Bcl-2 was significantly decreased in PD patients. Expression levels of AIFM1 were correlated with Hoehn-Yahr scores. PD patients with postural instability showed significantly reduced expression levels of anti-apoptotic DJ-1, Akt-1 and mTOR than PD patients without postural instability. Expression profiles of brain samples of mice with rotenone-induced PD model and PBMC samples of PD patients showed remarkable resemblance. Conclusion: Our results indicate that the anti-apoptotic PI3K/Akt pathway is overactivated in PD, presumably as an effort to compensate for increased neuronal apoptosis and oxidative stress. By contrast, patients with postural instability show reduced anti-apoptotic factor expression suggesting that this compensating mechanism fails in patients with this particular motor symptom. PBMC expression levels of AIFM1 might serve as a biomarker of disability and disease progression in PD. Disclosure: Nothing to disclose


Poster Sessions

P32184 mtDNA alterations and autism associated nuclear gene variants in the background of autism spectrum disorder N.A. Varga1, K. Pentelényi1, P. Balicza1, V. Reményi1, V. Hársfalvi1, R. Bencsik1, A. Illés1, C. Prekop2, M.J. Molnar1

1Neurology, Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary, 2Vadaskert Kórház és Szakambulancia, Budapest, Hungary

Background and aims: Autism spectrum disorder (ASD) is a neurodevelopmental disorder, with unclear etiological background. Mitochondrial dysfunction (MD) is a common metabolic abnormality associated to ASD. Our aim was to estimate in our ASD cohort the prevalence of mtDNA alterations, the mutation frequencies in genes associated with mtDNA maintenance and the alterations of genes associated to ASD. Methods: We screened 60 ASD patients and 98 healthy individuals for most common mtDNA disorders (mtDNA deletions, m.A3243, m.A8344G, m.T8993C/A). Next generation sequencing (NGS) was performed with TrusightAutism RapidCapture Kit (Illumina) to detect 103 ASD associated nuclear gene variations and SureSelectQTX Kit (Agilent) to detect 51 nuclear gene variations responsible for mtDNA maintenance. Results: In 10 cases (16.6%) mtDNA deletion was confirmed (MD-ASD cases). The results showed significant difference between autistic and control cohorts (p=0.016). In MD-ASD cases NGS testing identified pathogenic mutations in genes responsible for mtDNA maintenance in 4 cases, in genes related to ASD in 2 cases. One syndromic autism form was identified. In 50% of cases, beside the ASD associated rare single variants, alterations in genes responsible for mtDNA maintenance were detected. Phenotypically MD specific symptoms were most frequently present in MD-ASD patients than in idiopathic ASD cases. Conclusion: Among patients with ASD the presence of mtDNA alteration is more common than in control persons. The mtDNA deletion is usually not a single genetic alteration in ASD, it coexists both in syndromic and nonsyndromic ASD forms either with other ASD associated genetic risk factors and/ or alterations in genes responsible for intergenomial communication. Disclosure: This project was supported by KTIA_AIK_121-2013-0017, KTIA_13_NAP-A-III/6


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874

Poster Sessions

P32186

Neuroimaging 3

Superficial siderosis: a case report

P32185 A comprehensive assessment of cervical cord lesions in patients with multiple sclerosis on T1-MPRAGE at 3T: relationship with cord atrophy and disability M.A. Rocca1, P. Valsasina2, P. Preziosa2, M. Aboulwafa1, M. Horsfield3, G. Comi4, A. Falini5, M. Filippi1

1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy, 2Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 3University of Leicester, Leicester, United Kingdom, 4Department of Neurology, San Raffaele Scientific Institute, Milan, Italy, 5Neuroradiology, Università Vita-Salute San Raffaele, Milan, Italy

Background and aims: We characterised the spatial distribution of cervical cord T1 lesions in a large cohort of multiple sclerosis (MS) patients; assessed the influence of cord T1 lesions on atrophy quantification and analysed their association with disability. Methods: 3Tesla cervical cord sagittal 3D T1-weighted scans were acquired from 63 relapsing remitting (RR), 30 secondary progressive (SP), 20 primary progressive (PP), 20 benign (B) MS and 47 healthy controls. Cord T1-hypointense lesions were identified and binary lesion masks were produced. The active surface (AS) method was applied to calculate cross-sectional area (CSA). Betweengroup comparisons of T1 lesions and cord atrophy were performed with ANOVA models (age-adjusted). Results: T1 hypointense lesions were detected in 114 MS patients, with a higher frequency in SPMS vs RRMS, and PPMS vs RRMS and SPMS patients. Cord atrophy was found in MS patients vs controls, and in RRMS and PPMS vs controls, RRMS vs BMS and SPMS vs RRMS patients. Whole-cord CSA was not correlated with cord T1 lesion number. The regional distribution of cord atrophy was modestly correlated with T1 lesion number. There was a strong correlation between cord atrophy and T1 lesions and disability, both at a global and regional analysis. Conclusion: T1 hypointense cervical cord lesions were detected in a large proportion (85%) of MS patients. T1 lesions did not influence cord area estimates produced by the AS method. The association between cord T1 lesions and cord atrophy was modest. However, both cord T1 lesions and atrophy contributed, independently, to patient physical disability. Disclosure: This study has been partially supported by a grant from Fondazione Italiana Sclerosi multipla (FISM 2014/PMS/6).

F.D. Örken, E. Timer, S. Mumcu, M. Korkmaz, Z. Tanriverdi, B. Aydin Islamoglu

Neurology, Sisli Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey

Background and aims: Superficial siderosis (SS) is an exceptionally rare condition of the CNS caused by hemosiderin deposition in the subpial layers of brain, spinal cord and cranial nerves. The cardinal features of SS are deafness, ataxia and myelopathy. We present here a case of progressive ataxia with CNS SS. Methods: A 61-year-old male with hypertension and diabetes mellitus and subdural hematoma (SH) evacuation presented with progressive ataxia, right side numbness, tinnitus, and hearing loss. Physical examination was normal. On neurologic examination he has a bilateral sensorineuronal hearing loss, right side pyramidal signs and gait ataxia. Laboratory tests were normal, consisting of routine blood and urine analyses, blood coagulation, liver and kidney functions and blood ion concentrations. Differential diagnose of progressive ataxia was considered and no abnormalities were found. Magnetic resonance imaging revealed a hypodense rim around the cerebellum, brainstem and spinal cord (image 1 and 2). The patient was diagnosed with SS with radiological findings. Cranial MRI, MRA and spinal MRI imaging did not reveal any pathology that could cause SS.

Image-1 (A-C)T2 weighted and SWI axial MRI of the brain shows a rim of hypointensity on the surface of cerebral hemispheres. (D-F) T2 weighted coronal and SWI axial image shows a cerebellar vermis and mesencephalic rim of hypointensities.

Image-2 (A-D) T2 weighted images shows a hypointense rim surrounding the spinal cord


Poster Sessions

875

Results: SS is caused by chronic, slow, or repeated bleeding into the subarachnoid space. The most common aetiologies are trauma, previous surgical procedures, dural tears and tumours of the CNS. We present 61-year-old patient with hearing loss, pyramidal signs, gait ataxia and diagnosed with superficial siderosis. Previous surgery for SH evacuation is a risk factor for later development of the disease. Conclusion: Our case emphasized that SS could mimic degenerative cerebellar disease and could be a late complication of neurointerventional procedures. Disclosure: Nothing to disclose

P32187 A case of spontaneous bilateral dissecting aneurysms of the internal carotid arteries T. Parvu, C.I. Coclitu, O. Rusu, A. Ciobotaru, A.C. Mergeani, O. Bajenaru, F. Antochi

Neurology, University Emergency Hospital Bucharest, Bucharest, Romania

Background and aims: Bilateral dissecting pseudoaneurysms are a rare form of carotid artery dissection of traumatic or spontaneous origin. Recurrence and progression of the lesion are frequent, with stroke being the main neurological feature. Treatment of choice is controversial, while medical treatment being more frequent. Methods: We present the case of a 63-year-old patient who was referred to our clinic with a history of two episodes of transient loss of consciousness for which he underwent CT-angiography of supraaortic trunks showing bilateral dissecting aneurysms of the internal carotid arteries (ICA) and foetal origin of both posterior cerebral arteries. The patient had multiple cardiovascular risk factors: smoking, dyslipidaemia, arterial hypertension, and didn’t report any trauma of the head or cervical region. An initial brain MRI demonstrated multiple acute ischemic lesions in the frontal and parietal subcortical regions. Conventional angiography confirmed the diagnosis and identified a stenosis on the left ICA for which angioplasty and double stenting was performed. Follow-up MRI didn’t show any abnormal diffusion restriction.

CT angiography reconstruction of the supraaortic trunks

Results: The clinical, laboratory and imaging investigations suggested spontaneous bilateral dissecting aneurysms of the internal carotid arteries which determined a hemodynamically significant stenosis of the left ICA and cerebral microinfarctions which were considered to be embolic in nature. Connective tissue disease assessment is necessary for ruling out an underlying cause. Conclusion: Endovascular treatment of the left ICA stenosis, followed by double antiplatelet therapy, successfully controlled the progression of ischemic events. Disclosure: Nothing to disclose

Left: right internal carotid artery aneurysm; right: left internal carotid artery aneurysm


876

Poster Sessions

P32188

P32189

Correlation between brain MRI and anosognosia

Patterns of regional grey matter and white matter atrophy progression contributing to clinical deterioration in MS: a 5-year tensor-based morphometry study

E. Pinzan1, C. Angelini2, F. Bevilacqua3, E. Tasca1, S. Baldanzi4, G. Siciliano4, V. Pegoraro2

Neuromuscular, IRCCS san Camillo, Venice, Italy, 2Venice, Italy, 3Neurology Unit, IRCCS San Camillo, Lido Venice, Italy, 4Pisa, Italy

1

Background and aims: Myotonic dystrophy type 1 is a multi-system disorder. Anosognosia (Gk. “gnosis”, knowledge; “nosos”, disease) has been defined as “apparent unawareness, misinterpretation, or explicit denial of illness” or as well as impaired insight for behavioural and cognitive problems. It is considered as an inability of patient to be aware of their medical condition. The was to correlate neuroradiological changes with neuropsychological and psychological features; to quantify MRI lesions by a quantitative score(ARWMC). Methods: We analysed 27 genetically proven DM1 patients (male/female: 19/8; age: 47.1 ±12.2 years; disease duration: 19.4 ±9.4 years). One patient refused MRI because of claustrophobia. All patients were investigated by neuropsychological assessment, structured psychological interview, brain MRI. We used the age related white matter changes (ARWMC) score to classify white matter lesions as follow: 0 normal, 1 focal lesion below 5 mm diameter, 2 confluent lesions, 3 diffuse involvement. Results: In our study brain involvement in DM1 has been demonstrated using neuroimaging technique. Patients with DM1 have more frequent and characteristic lesions in fronto-temporal regions. Our study revealed the presence of white matters lesion in DM1, mainly localised within anterior temporal lobes and frontal lobes, are more characteristic in the disease. The prevalence of lesions, located in frontal lobe, are frequent, there is an almost absence of lesion in the parietal areas, and there is the presence of more prominent lesions, focal and initially confluent, in the temporal area (in both hemispheres). Conclusion: Anosognosia was present in 72% of patients, seventeen of 27 patients showed anosognosia. In anosognosic patients the distribution of white matter lesions is mainly located in bilateral fronto-temporal regions. Disclosure: Nothing to disclose

P. Preziosa1, M.A. Rocca1, E. Pagani1, S. Mesaros2, J. Drulovic2, M. Filippi1

Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 2Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia 1

Background and aims: To investigate the regional patterns of grey matter (GM) and white matter (WM) atrophy progression over five years in multiple sclerosis (MS) patients and their association with clinical and cognitive deterioration. Methods: Clinical (EDSS and phenotype changes), neuropsychological (Rao’s battery) and brain MRI (dualecho and 3DT1-weighted sequences) assessment were performed at baseline (T0) and after 5 years (Y5) from 66 MS patients with different clinical phenotypes and 7 controls. At T0 and Y5, measures of brain lesion volume and regional atrophy were obtained. Using Tensor-Based Morphometry, longitudinal changes of GM and WM volumes in MS patients at Y5 and according to the presence of neurologic deterioration, phenotype modification and cognitive worsening were assessed. Results: At Y5, 36/66 (55%) MS patients showed disability worsening, 14/66 (21%) evolved to a worse clinical phenotype and 18/63 (29%) presented cognitive deterioration. At T0, compared to controls, MS patients showed a widespread pattern of GM and WM atrophy. At Y5, MS patients developed further GM atrophy of deep GM nuclei, several fronto-temporo-parieto-occipital regions and cerebellum. Atrophy progression of the main WM tracts also occurred. Compared to stable patients, those with clinical and cognitive worsening showed a left-lateralized pattern of GM and WM atrophy, involving deep GM nuclei, several fronto-temporo-parieto-occipital regions, the cerebellum and the majority of WM tracts. Conclusion: GM and WM atrophy of relevant brain regions occurs in MS after 5 years. A different vulnerability of the two brain hemispheres to irreversible structural damage might contribute to clinical and cognitive worsening in MS. Disclosure: Nothing to disclose


Poster Sessions

P32190 Asymmetric reversible restricted diffusion in hyperammonaemic encephalopathy: a case report N. Randhawa1, J. Chew2, J. Shewchuk2, H. Nygaard3

Vancouver, Canada, 2Neuroradiology, University of British Columbia, Vancouver, Canada, 3Adult Neurology, University of British Columbia, Vancouver, Canada

1

Background and aims: Hyperammonemia is a common metabolic derangement that can contribute to encephalopathy in medically-unwell patients. Here we report a case of severe encephalopathy with atypical MRI findings related to hyperammonemia in the critical care setting. Methods: Literature review and illustrative case.

Diffusion weighted B1000 (a, d, g), ADC (b, e, h), and T2 FLAIR images (c, f, i) at 3 days (a, b, c), 16 days (d, e, f) and 43 days (g, h, i) from presentation, demonstrating initial restricted diffusion in the bilateral cingulate gyri and left peri-insular cortex, persisting at 16 days with near recovery by 43 days.

Results: A 51-year-old woman with HCV cirrhosis was transferred to the intensive care unit for sepsis and persistent, severe encephalopathy following elective cholecystectomy. The patient had a GCS of 5T and a nonlocalizing neurologic examination. Work-up for CNS infection was negative and continuous EEG monitoring showed severe encephalopathy without epileptiform activity. MRI showed prominent restricted diffusion in the cortical ribbon of the left insula and bilateral frontal lobesFigure 1 (a, b, c). A serum ammonia was subsequently measured and found to be elevated at 157umol/l. Normalization to 31umol/l was achieved with aggressive medical management (Lactulose, Rifaxamin, Polyethylene Glycol) which coincided with improved neurological status and resolution of MRI abnormalities–Figure 1 (g, h, i). With correction of hyperammonemia, the patient had a nearnormal neurologic examination with only subtle higherorder cognitive difficulties upon discharge to a local rehabilitation hospital approximately six weeks after initial presentation. Conclusion: Our case highlights the MRI findings in acute hyperammonemic encephalopathy with unique, rarely reported features of unilateral insular involvement and

877

reversible restricted diffusion. Recognition and treatment of hyperammonemic encephalopathy is imperative to improving both morbidity and mortality outcomes in these critically-ill patients and hence should not be missed as a potential treatable aetiology for persistent encephalopathy in the medically unwell patient. Disclosure: Nothing to disclose

P32191 Altered corticostriatal connectivity in Parkinson’s disease is related to cognitive impairment I. Rektorova1, L. Anderkova1, M. Barton2

1Applied Neuroscience Research Group, CEITEC Masaryk University, Brno, Czech Republic, 2Multimodal and Functional Imaging Research Group, CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic, Brno, Czech Republic

Background and aims: Parkinson’s disease (PD) is associated with changes in cognitive functions and restingstate functional connectivity (rs-FC). We focused on subcortical-cortical FC differences in patients with mild PD as compared to age-matched healthy controls (HC). Methods: Rs-fMRI data were acquired in 47 HC and 33 PD using 3T MRI. Seed-based FC analysis was used with seeds in dorsal, middle and ventral striatum. Group effects were assessed using one-way ANOVA model, cognitive measures were added as covariates of interest. Data were analysed using SPM12. Results are reported at voxel-level p(uncorr)C) were novel alterations which were predicted by in silico analysis pathogenic. Neither variant was present in 290 healthy individuals. Conclusion: The Cx32 mutations are common causes of hereditary neuropathies among Hungarian patients. However, it is an X-linked inherited gene the females show milder neuropathic symptoms than males. According to the familial segregation analysis, the investigation of control cohort, the taxonomy study and in silico analysis, the novel sequence variants are pathogenic alterations. Disclosure: This study was supported by the Hungarian Brain Research Program (KTIA_13_NAP-A-III/6 to V.AV.)

M. Moldovan1, R. Arnold2, M. Rosberg1, S. Alvarez1, R. Morris2, C. Krarup3

1Neuroscience and Pharmacology, Copenhagen University, Copenhagen, Denmark, 2Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, Australia, 3Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark

Background and aims: In conditions of a neurotoxic insult involving the peripheral nerves, the resulting sensory-motor polyneuropathy is commonly length-dependent. When facing perturbations in membrane potential, the axonal excitability is maintained by an interplay between the nodal K+ slow outward rectifier conductance (GKsN) and the internodal hyperpolarisation-activated cyclic nucleotidegated channels inward rectifier conductance (GH). The aim of this study was to investigate whether these rectifying conductances are distributed uniformly along the length of peripheral motor axons. Methods: Multiple measures of motor nerve excitability by “threshold-tracking” were used to ascertain the voltagedependent and passive cable axonal properties at different sites of stimulation along peripheral nerves in 20 healthy adult volunteers (median nerve at wrist and elbow and peroneal nerve) as well as in 15 adult female Long Evans rats under general anaesthesia (ulnar, tibial and caudal nerve – 2 sites). Interpretation of the excitability measures was carried out by optimising the parameters of the “Bostock” nodal-internodal myelinated motor axon mathematical model. Results: Excitability measures differed considerably both between nerves and along the same nerve, especially in response to prolonged subthreshold depolarising and hyperpolarizing currents. In both human and rat there was an increase in GH, a decrease in GKsN and an increase in axonal cable capacitance CAX with increasing distance of the stimulation site from the spinal cord. Conclusion: Our data suggest that there is a lengthdependent gradient of the distribution of rectifying conductances required for the maintenance of membrane potential of peripheral nerves. This could contribute to length-dependent gradients in susceptibility to neuropathy. Disclosure: Nothing to disclose


912

Poster Sessions

P32258

P32259

Uncommon cluster of Guillain-Barré cases in northern Portugal – an outbreak?

Late onset transthyretin familial amyloid polyneuropathy in Valencia, a nonendemic area

S. Moreira1, C. Santos2, P. Grebe3, J. Roriz3

Santa Maria da Feira, Portugal, 2Neurology, Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal, 3Neurology, CHEDV, Santa Maria da Feira, Portugal 1

Background and aims: Guillain-Barré Syndrome (GBS) and its variants are usually sporadic, with only a few reports on outbreaks. We report a cluster of atypical GBS cases which disclose an uncommonly high incidence of this pathology in a short period of time. Methods: Retrospective analysis of the clinical process of 6 cases identified by clinicians of the neurology department of CHEDV as having GBS, between August and September 2015. Results: The reported 6 cases account for a transient peak in incidence of GBS. All cases presented with acutely progressing flaccid tetraparesis and sensitive deficits evocative of GBS, associating: bilateral facial paresis in 2, hyperreflexia in 1, bulbar signs in 2, respiratory involvement in 3 and progression after 4 weeks in 2. Only 3 patients had clinical evidence of previous infection. All but 1 showed albuminocytologic dissociation in CSF. Electromyography was congruent with an axonal polyneuropathy in 2 cases (motor in 1, sensitivo-motor in another), a demyelinating sensitivo-motor polyneuropathy in 2 cases and a demyelinating motor polyradiculoneuropathy in the remaining 2. They were all treated with IGIV, except for one, who improved while being treated with acyclovir and prednisolone for previous herpes simplex virus II infection. All recovered with minimal signs at discharge. Conclusion: The reported cluster of GBS is remarkable for its clinical heterogeneity, with no seeming common infection in its aetiology. Assuming that this cluster was not a mere coincidence, there may exist environmental factors, other than the underlying microorganism which triggers immune response, that modulate autoimmunity in GBS outbreaks. Disclosure: Nothing to disclose

N. Muelas Gomez1, T. Sevilla1, M. Frasquet Carrera1, R. Sivera2, F. Mayordomo3, M.M. Cano Teuler4, R. Sánchez-Roy5, M.Á. Garcia-Quesada6, M. Garcés-Sánchez1, P. Martí Martínez1, I. Azorin3, C. Gomis3, L. Bataller1, J.F. Vázquez Costa7, M.R. Vilchez8, J.J. Vilchez1

1Neurology, Hospital La Fe, Valencia, Spain, 2Neurology, Hospital San Francesc de Borja. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Gandia, Spain, 3Neuromuscular, IIS la Fe, Valencia, Spain, 4Neurology, Hospital General de Valencia, Valencia, Spain, 5Neurology, Hospital Arnau de Vilanova, Valencia, Spain, 6Neurology, Hospital General Universitario de Elche, Elche, Spain, 7Valencia, Spain, 8Instituto de Investigación Sanitaria La Fe, Valencia, Spain

Background and aims: Diagnosis of TTR-FAP in nonendemic areas is challenging due to variable presentation, late onset and lack of family history. A prompt diagnosis is essential for early treatment. Methods: 21 patients diagnosed with TTR-FAP in a nonendemic Spanish area between 1994 and 2015. Clinical, pathological and genetic features were reviewed Results: All but two patients were male. The mean age at onset was 61 years. All patients had small and large fibre sensory impairment and most presented motor signs. The referral clinical picture included sensory and sensory-motor neuropathy (15 patients); ataxia and neuropathy (2); gastrointestinal and constitutional syndrome (2); entrapment neuropathy (1) and cardiopathy (1). All but one patient developed autonomic manifestations in variable degree. The neuropathy course was rapid and disabling. 16 patients associated cardiac involvement. 11 patients died (average of 5.5 years) due to cardiopathy and malnutrition. 2 patients underwent liver transplantation but TTR-FAP continued to progress. Nerve biopsies showed loss of myelinated and amyelinated nerve fibres. Atypical features were presented in some nerve biopsies. Amyloid deposits were detected in 50%. Paraneoplastic and vasculitic neuropathy and CIDP were misleading diagnosis. Five TTR mutations were identified (Val30Met in 70%). Conclusion: TTR-FAP profile in Valencia is similar to other non-endemic areas: low incidence, late onset, male preponderance, sporadic presentation and rapid and severe course. We report atypical presentations, widening the phenotypic spectrum of TTR-FAP. A high degree of TTRFAP suspicion in idiopathic sensory-motor neuropathies is need, even in absence of amyloid deposits in biopsies. We recommend going straightforward to TTR gene analysis. Disclosure: Nothing to disclose



Focused Workshop Saturday, 28 May

Editor of Neurology; she receives research funding from EPSRC, UKMSS, NMSS, NIHR ULCH BRC and UCL.

Focused Workshop 1 Advanced imaging methods for the assessment of MS pathogenesis and treatment

FW01-2

FW01-1

Backround and purpose: There is a continuous quest to move MR imaging to higher fields strengths as this improves the signal-to-noise ratio (SNR). In terms of clinical applocations, field strength moved from low field (0.5 Tesla) to high field (3T), as reviewed in Neuroradiology (2009;51:279-292). More recently, so-called ultra-high field (7T) scanners have become available for whole body imaging and has been approved by regulators for human applications. MRI at 7T provides challenges in terms of signal homogeneity, artefacts and limitations in terms of RF deposition, which are being overcome slowly. It is an interesting research tool that offers new possibilities for niche applications such as improved detection of cortical lesions (Brain. 2016 Mar 8. pii: aww037. [Epub ahead of print]), which are particularly extensive in progressive MS (Neurology. 2015 Nov 10;85(19):1702-9). The higher SNR can also be used to study small structures such as the hippocampus, hypothalamus. Due to susceptibility artefacts around osseous structures, imaging at 7T in the optic nerve and spinal cord is quite challenging. The enhanced susceptibility effects at 7T within veins and lesions with iron accumulation however is advantageous and helps to differentiate MS from other disorders such as Susac syndrome (Mult Scler. 2012 Nov;18(11):1592-9) and NMO (AJNR Am J Neuroradiol. 2016 Mar 24). Disclosure: Consultancy agreements with Roche, Novartis, Biogen, Genzyme, Synthon, TEVA. Research support to my group from Toshiba, Philips, Novartis, TEVA.

The promise of ultra high field MRI in multiple sclerosis F. Barkhof


Insight into the pathogenesis of multiple sclerosis using metabolic imaging O. Ciccarelli


Backround and purpose: The mechanisms that underlie the pathogenesis of multiple sclerosis (MS) are patially understood, and include inflammatory demyelination, oxidative stress, mitochondrial dysfunction, glutamate excitotoxicity, sodium homeostasis imbalance, neuroaxonal degeneration and gliotic response. These mechanisms lead to pathological abnormalities, which are responsbile for acute and progressive disability. Metabolic imaging comprises techniques that exploit the magnetic resonance properties of atomic nuclei, such as protons or sodium ions. These techniques include 1H-Magnetic Resonance Spectroscopy (MRS) and Sodium Imaging. I will describe the insights into the pathogenesis of MS which have been provided by MRS and Sodium imaging studies. These studies have suggested mitochondrial metabolic dysfunction and neuroaxonal loss at the onset of acute events, in relapsing remitting MS and in the early stages of primary progressive MS, increased mitochondrial activity after acute MS lesions, raised total sodium concentration within and outside lesions (especially in progressive MS), reduced concentration of GABA in the hippocampus and sensorimotor cortex in patients with progressive MS than healthy controls, increased glutamate levels in acute lesions and normal-appearing white matter, abnormalities in the glutamatergic pathways in the cervical cord of early primary progressive MS (in the absence of extensive spinal cord atrophy), and glial activation in T2 lesions and normal-appearing white matter. Clinical translation of metabolic imaging techniques may be useful to answer key questions on the pathogenesis of MS. Further technical developments aim at improving the sensitivity and specificity of these techiques anf at translating them to clinical trials. Disclosure: OC serves as a consultant for Biogen, Genzyme, Roche, GE Healthcare and Novartis (payments are made to the institution); she receives an honorarium as Associate

© 2016 EAN

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Focused Workshop

FW01-3 Assessing tissue damage and repair in multiple sclerosis by positron emission tomography B. Stankoff

Paris, France

Backround and purpose: Positron emission tomography, a quantitative nuclear medicine technology that uses labeled compounds recognizing specific biological targets, offers the unique opportunity to directly assess some key mechanisms involved in MS pathophysiology. Several stilbene and benzothiazole derivatives have been repurposed for the dynamic imaging by PET of myelin loss and repair in the MS brain. Robust non-invasive quantification techniques were validated and recently allowed to perform longitudinal studies in vivo. A great heterogeneity in individual remyelination potential was shown during the relapsing remitting phase of the disease, with a close correlation between remyelinating ability, neurodegeneration and neurological disability. The most popular target for PET microglial imaging is the TSPO macromolecular complex, which is drastically up-regulated in activated microglial cells. PET with the reference compound [11C]-PK11195 identified diffuse microglial activation in the normal appearing white matter and in the cortex of patients with a progressive form of MS. To circumvent some weaknesses of this tracer, a range of improved second-generation TSPO ligands has been developed, and novel fluorinated compounds should now allow to disseminate this imaging technology to many centres. The central benzodiazepine receptor antagonist 11C-Flumazenil (FMZ) is an imaging marker of neuronal integrity, and has been used to quantify and regionally map the neuronal component of grey matter damage in MS, both at the group level and at the individual level. The combination of these imaging probes with MRI sequences will enable to detangle several key pathophysiologic mechanisms that drive disability in MS, and will contribute to the development of new therapies. Disclosure: Nothing to disclose.

Focused Workshop 2 Genetic approaches in neuropathies FW02-1 Genotype-phenotype correlations in hereditary neuropathies M. Auer-Grumbach Graz, Austria

Backround and purpose: Hereditary neuropathies are clinically and genetically very heterogenous with more than 60 genes identified so far. The classical and most common form is Charcot-Marie-Tooth disease (CMT, also known as motor and sensory neuropathy, HMSN), which is characterized by slowly progressive weakness and wasting in the distal parts of upper and lower limbs, symmetric footdeformities and variable sensory disturbances. The underlying pathological event is demyelinating (primarily affecting Schwann cells, CMT1) or axonal (primarily affecting axons, CMT2) nerve damage. Phenotype-genotype correlation studies have shown, that some genetic subtypes are associated with a particular phenotype. Knowledge of additional features such as vocal cord paralysis, scoliosis, optic atrophy, hearing loss, and ulcero-mutilating features amongst others often serves to a definite genetic diagnosis. Mutations in known CMT genes leading to such complicated phenotypes of hereditary neuropathies will be discussed in detail based on case reports. Disclosure: Nothing to disclose.

FW02-2 Whole-exome sequencing in patients with inherited neuropathies: outcome and challenges J. Baets

Antwerp, Belgium

Backround and purpose: The genetic diversity of inherited neuromuscular disorders such as inherited peripheral neuropathies is extensive and recently the more widespread use of next generation sequencing (NGS) technologies and most notably whole-exome sequencing (WES) has accelerated gene discovery and genetic diagnosis. Although traditional genetic strategies were more bound to the lines of previously established knowledge, WES and is powerful enough to be truly “disruptive” by rapidly yielding large quantities of unbiased genetic data. Genetic heterogeneity now turns out to be much more extensive. Expanding disease spectra break up the boundaries between disease entities and pressurize existing genotype-phenotype correlations to the point of making them unintelligible. The unexpected identification of (spurious) variations in known and novel genes is puzzling. A huge task still waits to establish the causal links between this overabundance of genetic variation and disease. Still, the absence of a precise genetic diagnosis in patients precludes genetic counselling, pre-implantation genetic diagnosis and ultimately therapy.


Focused Workshop

At the same time WES is an extremely powerful tool as it holds the promise of fully saturating the causal genetic map of Mendelian disease. Disclosure: Nothing to disclose.

FW02-3 New opportunities of therapy in genetic neuropathies D. Pareyson

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Focused Workshop 3 Addressing quality of care for neurological patients FW03-1 Optimising quality of care in epilepsy E. Ben-Menachem

Gothenburg, Sweden

Milan, Italy

Backround and purpose: There is still no effective drug treatment for Charcot-Marie-Tooth (CMT) and related neuropathies. A Cochrane review of the six randomised controlled trials (RCTs) performed with ascorbic acid confirms that the drug is not effective in adults and children with CMT1A. Promising therapeutic approaches for different CMT types, based on cellular and animal model data, include: progesteron antagonists, high-throughput screening for compounds down-regulating PMP22 expression, regulators of unfolded protein response and endoplasmic reticulum stress, Histon Deacetylase 6 Inhibitors, modulators of neuregulin pathways, of GABA-B receptor and of P2X7 receptor. PXT3003, a fixed combination of low doses of baclofen, naltrexone hydrochloride and sorbitol, has been tested in CMT1A rats and in a phase II RCT in CMT1A patients; a phase III trial in under preparation. It is likely that other RCTs will start soon. L-serine supplementation appears a promising treatment for HSAN 1, associated with mutations in SPTCL1/2. Great advances are being achieved for hereditary amyloidosis associated with transthyretin gene mutations (TTR), for which orthotopic liver transplantation was the only available treatment until recently. TTR stabilizers (Tafamidis meglumine, for adult patients with stage 1 symptomatic polyneuropathy, and diflunisal as an off-label drug) showed encouraging results by significantly slowing disease progression. Oral doxycyclin plus tauroursodeoxycholic acid (TUDCA) is another promising approach aimed at both preventing and removing amyloid deposition. TTR gene silencing by means of either small interfering RNA or antisense oligonucleotides proved safe and effective in lowering TTR levels in phase II trials and phase III RCTs for both treatments are ongoing. Disclosure: Nothing to disclose

Backround and purpose: The key to improving quality care is to improve access to epilepsy centers and the facilities that they offer. It is important that when offering treatment for epilepsy the patient becomes a partner in care with access to as much information as possible about the disease and prognosis and possibilities of treatment. Quality of care means access to: Appropriate diagnostic capabilities delivered in a timely fashion. (1 or more EEG, MRT, possibly CSF when applicable, detailed history, physical exam, in difficult cases genetic testing, autoimmune analysis, if applicable). Lack of availability of video-EEG (vEEG) facilities will decrease the possibility of optimal care as a diagnosis can be difficult unless seizures are evaluated with a combination of vEEG and ECG. Once a patient has been diagnosed, then treatment is offered. This can vary widely. The quality of care is greatly improved if the physician is well versed in the treatment possibilities for all types of epilepsy. It is usual to start with an antiseizure drug before going on to more advanced treatment options. If a patient does not become seizure free after 2-3 appropriate antiseizure drugs, then a new diagnostic evaluation should be done and other options such as epilepsy surgery considered. All along the support of a trained epilepsy nurse improves patient care by creating almost constant access to a professional when encountering social problems involved with epilepsy as well as a person whom to immediately report possible side effects that can be headed off before becoming serious. Access to a neuropsychologist and a social worker are important in epilepsy care enabling an assessment of cognitive deficits and an evaluation and treatment of psychological comorbidities. An interested psychiatrist is very important but many times not available. Together an epilepsy team will work together with the patient to provide the best care that is currently available. In Europe there are many such facilities, but unfortunately they are not evenly distributed so many patents will not have access to high quality care unless referred to centers specializing in epileptology. It should be the duty of all countries in Europe to strive to broaden the access of expert care to all regions in order to reach every patient. The social and economic gains of improve epilepsy care should make this mission of highest priority in every society. Disclosure: Nothing to disclose.


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Focused Workshop

FW03-2

FW03-3

Quality standards of multiple sclerosis service

Health related quality of life in Parkinson's disease

A. Chaudhuri

M. Faber

Backround and purpose: Multiple Sclerosis (MS) is a lifelong neurological disease with a high socio-economic burden. There is significant variability in timely diagnosis, treatment and care plan of MS patients. The key components of the proposed Quality Standards of MS service are: 1: ACCESS TO A DESIGNATED MS SERVICE: Patients must have access to a specialist neurological service, which should consist of, as a minimum, a consultant neurologist and a specialist nurse. 2: EARLY DIAGNOSIS OF MS: Patients are entitled to a timely diagnosis based on contemporary criteria with timely access to investigations (MRI and laboratory tests). 3: MANAGEMENT OF MS: There should be ease of access to multi-disciplinary specialist MS clinics for management of relapses and relapse-related symptoms. In addition to pharmacological therapy, a priority should be to improve symptom control and health related quality of life (HRQoL) using patient reported outcome measures (PROMs). 4: ACCESS TO APPROVED DISEASE MODIFYING THERAPIES: The treatment decision has to be individualised and take into account patient expectations and preferences while balancing potential benefits against risks of treatment appropriate for life-stage. 5: LONG TERM CARE FOR PATIENTS: The comprehensive care plan for MS patients should reach beyond specialist clinics into individual homes, workplaces and social life to deliver the best possible and full quality of life and identify community nursing, rehabilitative, psychological and social resources for continuation of support. 6: RESEARCH AWARENESS: Research should be an expected standard of clinical service and MS patients should be made aware of research projects for volunteerring and participation. Disclosure: Nothing to disclose

Backround and purpose: Quality of life is a complex construct, and it is difficult to measure. Patients have a unique perspective on what good quality of care constitutes. Knowing this perspective not only empowers professionals to tailor their care to their patients’ individual needs, it also strengths the engagement between patients and their healthcare team. To better capture the patients’ perspectives, we developed and validated both a Dutch and a NorthAmerican Patient Centeredness Questionnaire for PD (PCQ-PD). Based on experiences of nearly 2,000 patients with Parkinson’s disease, ‘provision of tailored information’ and ‘emotional support’ could be identified as key elements in the care pathway that needed improvement. This example clearly demonstrates that patient experience scores can serve as a valid and powerful stepping stone for optimization of patient centred care delivery. Another way to encourage patient-centred care is to incorporate patient-reported outcomes (PROMs) into clinical settings. The PDQ-39, i.e. the standardized and disease-specific quality of life measure for Parkinson’s disease, is such a PROM. When incorporated into the health care visit, PROMs could fuel conversations between patients and providers that lead to shared decision making and promote the delivery of individualized care. Interviews with patients, neurologists and physiotherapists revealed that the impact highly depends on the presentation format and benchmarks used. In the Netherlands, a routine collection of the PCQ-PD and the PDQ-39 has recently been implemented. The standardized approach allows us to assess the care performance and its impact. During the workshop we will elaborate on the opportunities and challenges that come with this innovation. Disclosure: Nothing to disclose.

Romford, United Kingdom

Nijmegen, The Netherlands


Focused Workshop

Focused Workshop 4 Frontier applications in neurosonology FW04-1 Magnetic resonance guided focused ultrasound for neurological disorders I. Schlesinger Haifa, Israel

Backround and purpose: Magnetic resonance guided focused ultrasound is a new technology that enables intracranial ablation without incisions. The ultrasound rays warm up the tissue through an intact skull creating the lesion with real-time MRI monitoring for localization and thermography. Intracranial tissue is warmed up gradually in a step wise fashion while the patient is awake. If adverse events occur the target can be repositioned before ablation. This technology is being used to treat patients with disabling tremor due to Essential tremor and Parkinson’s disease. In these patients, lesioning the ventral intermediate nucleus of the thalamus is effective in relieving tremor with infrequent long term adverse events. Ameliorating central neuropathic pain, reducing motor fluctuations in Parkinson's disease and disruption of the blood-brain barrier have anecdotally been reported and offer a glimpse at possible future applications. Disclosure: Nothing to disclose

FW04-2 Ultrasound on the earth and in the orbit Z. Garami

Houston, USA

Backround and purpose: Space adaptation syndrome and visual impairment with increased intracranial pressure (ICP) remain a puzzling problem of astronauts health and missions. These changes define the visual impairment/ intracranial pressure (VIIP) syndrome. There are limited pre- and postflight measures to define the risk and even less inflight data is available. The goal of this study was to use multi-equipment ultrasound protocol simultaneously to measure intracranial and extracranial flow patterns (carotid duplex) before an astronauts mission to established baseline data that could provide important information about flow patterns during ICP with and without gravity. Simultaneous, multi-equipment ultrasound testing could be helpful to study cerebral autoregulation and the connection between extra/intracranial flow, as well as arterial/venous flow patterns with and without gravity in cerebrovascular syndromes. VIIP syndrome remains a puzzling problem of astronauts` health and it prevents the planning of longer missions to explore our boundaries in the universe. These observations are also relevant for medical conditions with ICP on Earth. TCD is already a useful tool in detecting vasospasm and occlusion in our every day practices but there is still room for improvement when dealing with unrecognized and underdetected ischemia and hypoperfusion after stroke, intracerebral or subarachnoid, and cerebellar hemorrhages. The danger of intracranial

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hypertension is frequently underestimated, especially in stroke patients. In many cases, ICP is not monitored, and it may cause severe secondary insults by unrecognized ICP elevation. Therefore, non invasive ICP assessment tools and methods developed for NASA could be a helpful tool for our patients, too. Disclosure: Nothing to disclose.

FW04-3 The unstable carotid artery plaque D. Russell

Oslo, Norway

Backround and purpose: Carotid plaque characteristics can help to identify those patients with a relatively higher risk for stroke and help select patients who may benefit from intervention over medical treatment alone. Echolucent plaques are thought to be more unstable than echo-rich plaques. Shear wave elastography provides information about plaque stiffness and a better correlation to histology compared to GSM assessments. 3D imaging has been used in volumetric measurements and the detection of plaque ulceration. Ultrasound contrast agents are helpful in detecting plaque surface irregularities and plaque neovascularization. Superb microvascular Imaging is a new ultrasound image technique (Toshiba Medical Systems) that allows the visualization of very small low-flow signals from small blood vessels in the plaque without the use of contrast agents. Symptomatic patients with microembolic signals, assessed by TCD, have a higher risk for developing ipsilateral stroke. MRI detects intraplaque hemorrhage, lipid-rich core, calcification, the fibrous cap and ulceration. Dynamic contrast-enhanced MRI allows assessment of plaque neovascularization. Patients with silent cerebral ischaemic events have a higher risk of future stroke. Positron emission tomography (PET) imaging assesses specific metabolic functions with tracers labelled with positron emitting radio-isotopes. PET with 18Fludeoxyglucose can probe plaque inflammation in unstable plaques directly. Biomarkers have been shown to improve prediction independent of conventional risk factors and a recent study suggests that -butyrobetaine (BB) and its precursor trimethyllysine (TML) may predict cardiovascular mortality. Application of plaque imaging in prospective studies will hopefully, in the near future, tell us how we can best guide treatment, especially in asymptomatic patients. Disclosure: Nothing to disclose.


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Focused Workshop

Focused Workshop 5 Abnormal movements in sleep

FW05-2 Simple motor movements A. Iranzo

FW05-1

Barcelona, Spain

Regulation of motor control during sleep P.-H. Luppi

Lyons, France

Backround and purpose: Paradoxical sleep (PS) is characterised by muscle atonia induced by ponto-medullaryspinal pathways. It was first demonstrated that a pontine area recently named sublaterodorsal tegmental nucleus (SLD) contains the neurons inducing the muscle atonia of PS. Besides, it was shown that glycine induces the hyperpolarization of motoneurons during PS. We recently define in detail the network responsible of muscle atonia during PS combining Fos staining, retrograde tracing and immunohistochemistry or “in situ” hybridization of markers of cholinergic, glutamatergic, GABAergic and glycinergic neurons. We showed that glutamatergic neurons localized in the SLD triggered muscle atonia during PS by means of their descending projections to GABA/glycinergic neurons localized in the ventral medullary formation namely the ventral gigantocellular reticular nucleus (GiV). We further showed that these neurons project to the spinal cord and are activated during PS. To directly demonstrate the role of these glutamate and GABA/glycinergic neurons in PS atonia, we inactivated SLD glutamatergic or GiV GABA/ glycinergic transmission using transfection with AAVs of short hairpin RNA specific of the mRNAs of the vesicular glutamate 2 (vGLUT2) or GABA/glycine vesicular (vGAT) transporters. These animals display absence of atonia and large movements during PS confirming the role of the SLD glutamatergic neurons and the GABA/glycinergic neurons in the induction of muscle atonia during PS. In line with these results, we propose that REM sleep behavior disorder (RBD) is due to a specific degeneration of PS-on glutamatergic neurons localized in the SLD or the glycinergic/GABAergic premotoneurons localized in the GiV. Conversely, cataplexy in narcoleptic would be induced by a recruitment of the SLD neurons by a neuronal network regulating emotion. Disclosure: Nothing to disclose.

Backround and purpose: Sleep is a physiological state characterized by reduced bodily movement. However, healthy people, particularly young persons, may display non pathological simple manifestations like facial grimaces, minor jerks, and isolated behaviors such as kicking, slapping and sobbing. These “normal” behaviors may occur during the transition from wakefulness to sleep (e.g., hypnic starts), nonREM sleep (e.g. sleep talking) and REM sleep (e.g., head myoclonus, repetitive movements of the feet and hands). In addition, the following pathological conditions may present with simple motor events. REM sleep behavior disorder. In addition to complex behaviors like punching or jumping out of bed, patients present simple manifestations such as jerks, grimaces, kissing, laughing or waving arms. NONREM sleep parasomnias. In addition to complex behaviors occurring in sleepwalking and night terrors patients may present confusional arousals where they simply open their eyes, look around, mutter and sit up in bed. Nocturnal frontal lobe epilepsy. Besides dystonic postures and wandering patients may display minor events called paroxysmal arousals consisting in body jerks and raising the head and sit on bed. Hypnagogic foot tremor. Series of rhythmic and fast movements of the whole foot during light sleep. Periodic leg movements in sleep. These movements may be minor, asymptomatic, and only involving the foot and ankle. Restless legs syndrome. Patients may show foot taping to alleviate their unpleasant leg sensations during wakefulness. Cataplexy. Some cataleptic events may be minor only involving the head or the knees during few seconds. Disclosure: Nothing to disclose.


Focused Workshop

FW05-3 Complex motor movements R. Khatami

Barmelweid, Switzerland

Backround and purpose: Motor symptoms during sleep comprise a spectrum of paroxysmal phenomena that lead to sleep disruption, sleep fragmentation and eventually contribute to excessive daytime sleepiness. According to the International Classification of Sleep Disorders (ICSD-III) paroxysmal motor phenomena during sleep include parasomnias, sleep-related movement disorders, epilepsies and isolated symptoms. This workshop aims at characterizing the clinical features, etiology, electrophysiological features and treatment of complex motor behavior occurring during NREM-sleep, REM sleep or sleep state transitions. Starting from video presentations the semiology of typical and atypical features will be introduced. Complex motor symptoms may present as repetitive movements or semi-purposeful often stereotyped behavior. Specific forms include violent behaviors leading to self-injuries or harmful behavior directed to others. Clinical and electrophysiological features will be added to further characterize the underlying pathophysiology. The workshop will show that complex motor behaviors are not necessarily a unitary phenomenona, but should rather be considered as the manifestation of a variety of different diseases, as exemplified by cases of arousal disorders, nocturnal frontal lobe epilepsy and psychiatric disorders. Thus, careful examination and extended diagnostic workup is needed for proper diagnosis of underlying disease and adequate treatment. Disclosure: Nothing to disclose.

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Focused Workshop 6 New concepts about language processing in the brain FW06-1 The dual-loop model and aphasia C. Weiller

Freiburg, Germany

Backround and purpose: A dual-loop model for the processing of language in the brain was proposed early in history and has also formed the basis for many neuropsychological models. These models incorporate a (direct) route for sensorimotor mapping and a (indirect) route for “semantic“ processing. Dual-loop models also emerged in the field of visual processing, motor control, or spatial attention. Thus, a general dual-loop system emerges as a framework for the interpretation of cognition in human brains independent of the modality. Modern imaging techniques like Diffusion-Tensor-Imaging (DTI) based fibre tracking identified several long human association tracts for ventral and dorsal pathways. The extreme capsule (EmC)/ IFOF and uncinate fascicle (UF) are part of the ventral system, and the superior longitudinal fasciculi (SLF II, III) and the arcuate fasciculus (AF) are all dorsal pathways. This talk reviews language processing in the brain in the context of a domain general dual-loop system on basis of imaging studies in normal subjects and patients with aphasia. In short: speech production is a dorsal stream task, while comprehension requires the ventral stream. At the acute stage, Wernicke’s aphasia (posterior STG/MTG) and Broca’s aphasia (mainly inferior frontal gyrus (IFG) map to defined brain regions affecting both streams, thus explaining phonological (d) and semantic (v) paraphasias and comprehension problems (v) in Wernicke’s and agrammatism in Broca’s aphasia, as the IFG comprises the necessary interaction node for the two stream to extract structure from a sequence, a prerequisite for syntax processing. Disclosure: Nothing to disclose.

FW06-2 The impact of bilingualism on cognitive functions across the lifespan and in brain diseases T. Bak

Edinburgh, United Kingdom

Backround and purpose: The last decades have witnessed fundamental changes in our understanding of both brain and language. In neurosciences, the static localisationist view of a 1:1 correspondence between circumscribed brain areas and specific cognitive functions gave way to a dynamic interaction of multiple networks, in which the same function can be distributed among many areas and the same area can be part of different networks. In parallel, the concept of language as an autonomous, “informationally encapsulated”


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Focused Workshop

module has been superseded by the notion of widely distributed language-related brain networks, going well beyond the traditional language areas and interacting with other aspects of cognition. These advances in the neuroscience of language have been of particular importance for our understanding of bilingualism. Firstly, we came to realise that different languages of a multilingual person cannot be reduced to static representations in isolated brain areas but are subject to parallel activation, inhibition, switching and monitoring within the same brain networks. Secondly, the tension between this parallel activation and a selective output necessary for successful communication constitutes a permanent training for frontal-executive functions. Accordingly, the cognitive effects of bilingualism transcend language itself, leading to a better performance on many executive tasks, particularly those requiring inhibition and switching. This mechanism offers an explanation for a number of recent empirical findings, in which bilinguals were show to be more resistant to cognitive ageing than monolinguals, develop dementia ca. 4 years later and show a significantly better cognitive recovery after stroke. Disclosure: Nothing to disclose.

FW06-3 The writing brain J.-F. Démonet


Backround and purpose: A vast neural network underpins the functional processing by which the orthographic signal is transformed to motor output; at the neocortical level, these neural territories encompass the upper lateral premotor and parietal cortex. The premotor component, first described by Exner, likely plays a role of buffer interfacing orthographic and allographic components of handwriting. The involvement of the premotor cortex in the nondominant hemisphere and of transcallosal connections has yet to be specified as well as the role of the superior parietal cortex. The neural correlates of central orthographic processes in handwriting involve “Broca’s area and the posterior temporal cortex in which we observed "dual route" effects, referring to dorsal/ventral processing, respectively involved in sublexical and lexical semantic aspects of orthographic coding. For a review: Planton et al. The “handwriting brain”: a meta-analysis of neuroimaging studies of motor versus orthographic processes Cortex 2013 49: 2772-2787 Disclosure: Nothing to disclose

Sunday, 29 May Focused Workshop 7 Stem cell therapies for the treatment of neurological diseases FW07-1 Adult Stem Cells for the treatment of multiple sclerosis A. Uccelli

Genova, Italy

Backround and purpose: Adult stem cell treatments are a promising strategy for curing multiple sclerosis (MS). Results obtained from pioneer clinical studies of transplantation of autologous hematopoietic stem cells (AHSC) have demonstrated that this procedure is highly effective in severe forms of MS based on the abrogation of autoreactive clones and reset of the immune system. However, this procedure associates with consistent risks of severe and rarely lethal adverse events. Neural precursor cells (NPC) exert neuroprotective and immunomodulatory effects fostering tissue repair in mice with experimental autoimmune encephalomyelitis (EAE). Similar encouraging results have been obtained in EAE using induced pluripotent stem cells (iPS). However, safety and feasibility issues concerning their transplantation in MS are yet to be addressed. Mesenchymal stem cells (MSC) isolated from the bone marrow or adipose tissues display a significant therapeutic plasticity as reflected by their ability to enhance tissue repair and influence the immune response leading to significant amelioration of EAE. Thus, small clinical trials in MS subjects have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. A large phase II multicenter clinical trial is on-going with the aim of demonstrating safety and efficacy of MSC. Overall, current experimental evidence suggests that clinical exploitation of adult stem cells for MS may lead to novel strategies aimed at blocking uncontrolled inflammation, protecting neurons and promoting repair, but not at restoring deranged neural network responsible for irreversible disability. Disclosure: Nothing to disclose.


Focused Workshop

FW07-2 Stem Cells in muscle diseases Y. Torrente

Milan, Italy

Backround and purpose: Cell therapy is one promising approach to correct genetic diseases by contributing to tissue regeneration; stem cells can be isolated from a healthy donor or, when possible from the same patient. In the first case cells will be transplanted under a regime of immune suppression while in the second case, cells will have to be genetically corrected before transplantation in the same patient from which they were derived. The overall objective of our work is the validation of a clinical treatment for patients affected by Duchenne muscular dystrophy. The project does the groundwork for a phase I/II clinical trial consisting of an intramuscular transplantation of autologous CD133+ stem cells after their engineering through a lentiviral vector. The trial is oriented to DMD boys as Duchenne muscular dystrophy is a X-linked disorder characterized by a mutation in dystrophin gene. Efficacy and possible adverse effects have to be evaluated to test whether this approach may represent a first step towards an efficacious therapy for muscular dystrophy. Our previous works indicated that CD133+ stem cells, a recently identified population of progenitor cells, produce functional improvement upon intra-arterial injection in a mouse model of muscular dystrophy. It thus could be possible to focus on this type of stem cell for autologous transplantation in DMD animal models. Recently transplantation of engineered dystrophic canine muscle-derived CD133+ cells gave promising results in Golden Retriever dystrophic dogs, the most reliable animal model that shows a form of dystrophy very similar to and even more severe than DMD. Disclosure: Nothing to disclose.

FW07-3 Cell transplantation for stroke S.I. Savitz

Houston, USA

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Focused Workshop 8 MDS-ES/EAN: Tics and Tourette syndrome - consensus and controversies FW08-1 Challenges in diagnosing tics, Tourette's and comorbidities K. von Plessen

Bergen, Norway

Backround and purpose: Diagnostic categories within Tic disorders (inclusive Tourette syndrome) include transient, as well as more chronic conditions. Tic disorders are characterized by the presence of tics, which are involuntary contractions of muscles or vocal expressions, but may also compromise more complex behaviors. Tourette syndrome is a relatively frequent and complex neuropsychiatric disease that requires interdisciplinary collaboration between medical professionals, especially because the presence of comorbid conditions is rather the rule than the exception. Comorbidity with Attention-Deficit/Hyperactivity Disorder and obsessive-compulsive disorder is frequent and may pose several diagnostic challenges in young people. A recent European guideline thus recommends the use of a structured diagnostic instrument to screen for other psychiatric diagnoses and specific instruments allowing a dimensional mapping tics and possible other co-morbid conditions. Besides the most frequent instruments for diagnostic mapping of psychopathology, also current theories and concepts regarding the neurobiological/ neuropsychological basis and subsequent adaptation to tics will be presented. Disclosure: Nothing to disclose.

FW08-2 Tics and Tourette syndrome - Movement disorders or behavioural conditions? A.E. Cavanna

Birmingham, United Kingdom

Backround and purpose: Patients with Tourette syndrome (TS) show a wide range of clinical presentations, characterised by different levels of severity and complexity. The concept of ‘TS spectrum’ encompasses conditions characterised by tics only (‘pure TS’), tics and complex symptoms such as self-injurious behaviours (‘full-blown TS’), tics and co-morbid behavioural problems such as obsessive-compulsive disorder and attention-deficit and hyperactivity disorder (‘TS-plus’). Over the last decade, clinical studies using principal component factor analysis and hierarchical cluster analysis have suggested the existence of discrete phenotypes within the TS spectrum. These findings have important implications for the understanding of genotype-phenotype correlations, as well as impact on patients’ health-related quality of life and choice of treatment interventions.


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Focused Workshop


Focused Workshop 9 Focal dementias

FW08-3 Treatment of tics and Tourette syndrome Cannabis, deep brain stimulation and beyond K. Müller-Vahl

FW09-1 The parietal lobes J.M. Schott


Hanover, Germany

Backround and purpose: Tourette syndrome (TS) is a childhood onset neurodevelopmental disorder characterized by multiple motor and one or more vocal tics. The majority of patients suffers, in addition, from psychiatric comorbidities such as attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), depression, anxiety, and self-injurious behavior. Tics most typically start at age 6-8 years, fluctuate spontaneously in the course of the disease, are influenced by different environmental factors, and improve spontaneously in adolescence and young adulthood in the majority of patients. Treatment of patients with TS depends not only on severity of tics, but also the presence and severity of comorbidities. Since it is well known that TS can cause significant impairment in patient’s quality of life, in addition, overall social impairment has to be taken into consideration. First-line treatment for tics includes either cognitive behavioral treatment (using habit reversal training or exposure and response prevention training) or pharmacotherapy (using dopamine receptor blocking drugs including aripiprazole, tiapride (in children), sulpiride, and risperidone). However, in most European countries only haloperidol is formally approved for the treatment of tics. Since these substances are not effective in all patients and often associated with significant adverse effects, several other treatment alternatives have we suggested. There is increasing evidence that cannabis-based medication might be such an alternative treatment option that improves not only tics, but also psychiatric symptoms such as ADHD and OCD. In adult, severely affected, and otherwise treatment resistant patients surgical treatment with deep brain stimulation should be taken into consideration. Disclosure: Nothing to disclose.

Backround and purpose: Building on the theme of this focussed workshop, this session will present an overview of the cortical dementias that have a particular prediliction for the parietal lobes, using posterior cortical atrophy sometimes termed the visual variant of Alzheimer's disease - and corticobasal syndrome as the exemplar disorders. Starting with an overview of the anatomy and normal cognitive functions subserved by the parietal lobes, aspects of the history, examination and neuropsychology associated with dominant and non-dominant parietal lobe dysfunction will be illlustrated using videos. This will be followed by a discussion of the relevant investigations (imaging and CSF) and the underlying pathology of the neurodegenerative disorders leading to parietal lobe dysfunction. Disclosure: I acknowledge the support of the NIHR Queen Square Dementia BRU, the NIHR UCL/H Biomedical Research Centre, Wolfson Foundation, EPSRC, MRC, ARUK, and EU Horizon 2020. I have received research funding from AVID Radiopharmaceuticals, have consulted for Roche Pharmaceuticals and Eli Lilly, and serve on a Data Safety Monitoring Committee for Axon Neuroscience SE


Focused Workshop

FW09-2

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Focused Workshop 10 MDS-ES/EAN: Biomarkers for Parkinson's disease

The temporal lobes S.F. Cappa

Milan, Italy

Backround and purpose: Focal degeneration of the temporal lobes is the hallmark of the semantic variant of frontotemporal lobar degeneration. This condition, originally described by Arnold Pick, is most often associated with asymmetric involvement, prevalent on the left side, resulting in a clinical picture of progressive semantic dysfunction characterized by a level of selectivity and a severity of progression, which cannot be observed in any other neurological disease. The study of patients affected by this condition, most commonly due to TDP 43 proteinopathy, has provided unique insights into the neurology of meaning representation. The less common presentation with greater right sided involvement is characterized by a different symptom complex, in which disorders of high order visual processing are often associated with prominent behavioural manifestations. The neuropsychological study of the latter cases is providing complementary insights into the neurology of non-verbal semantics and of social cognitive abilities. Atypical presentations of Alzheimer’s disease (AD) can also affect the temporal lobes focally for a prolonged period of time. Also in this case the asymmetry of involvement is a crucial determinant of the neuropsychological features, in term of aphasic (left sided) or visuospatial (right sided) presentations. A selective involvement of the medial temporal lobe is the hallmark of the puzzling condition of hippocampal sclerosis. Often diagnosed as AD in the past, this frequent cause of memory impairment in the elderly population can be associated with a number of degenerative and non degenerative conditions, including TDP 43 pathology. Disclosure: Nothing to disclose

FW09-3

FW10-1 The need for better biological markers for PD W. Poewe

Innsbruck, Austria

Backround and purpose: Slowing of disease progression remains the single most important unmet need in the treatment of Parkinson’s Disease (PD). However, numerous clinical trials over the past 20 years failed or produced inconclusive results. Reasons for such failures include difficulties in choosing clinical endpoints and the lack of reliable biomarkers sensitive to disease progression. In addition, target populations for neuroprotective or diseasemodifying trials have been those with early, clinically established PD. Recent research has provided substantial evidence that the pathology underlying PD likely begins years before the first manifestation of classical motor signs of PD. It is therefore conceivable that disease-modifying or neuroprotective interventions targeting the earliest phases of PD might offer greater potential for disease modification as compared to later stages. Idiopathic REM-sleep behavior disorder, hyposmia, depression, constipation have all been associated with an increased risk to later develop classical motor PD and might represent “pre-motor” stages of the illness. Recently a task force of the International Parkinson’s Disease and Movement Disorder Society (MDS) has proposed operational research criteria for the definition of prodromal PD. Nevertheless validated biomarkers are needed to enhance sensitivity and specificity of such criteria. The same holds true for early diagnosis as well as measuring disease progression. Disclosure: Nothing to disclose

The frontal lobes R. Ossenkoppele


Backround and purpose: The frontal lobes play an important role in modulating human behavior, cognitive processes and motor function. This presentation focuses on how distinct neurodegenerative conditions (e.g. behavioral variant frontotemporal dementia, non-fluent variant primary progressive aphasia and progressive supranuclear palsy) affect the frontal lobes. More specifically, I will address the clinical syndromes, neuroimaging features and neuropathological changes associated with these diseases. Finally, I will present our studies on the behavioral/ dysexecutive variant of Alzheimer’s disease. Disclosure: Nothing to disclose.


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Focused Workshop

FW10-2 Alpha-Synuclein: a new evidence? W. Meissner

Bordeaux, France

Backround and purpose: The discovery of alpha-synuclein as the main constituent of Lewy bodies in surviving dopamine neurons in Parkinson’s disease (PD) has stimulated research to determine the usefulness of this protein as biomarker for the diagnosis and prognosis of PD. In its physiological form, alpha-synuclein forms an unfolded monomer with a role in vesicle trafficking and recycling. The protein can undergo a multitude of posttranslational modifications including truncation and phosphorylation, and forms aggregates under particular conditions. Oligomers are currently believed to be the most toxic aggregates and seem to have a major role in the underlying neurodegenerative process. Several studies have reported decreased levels of total alpha-synuclein and increased concentrations of oligomers in the cerebro-spinal fluid (CSF) of PD patients compared to healthy controls. Total alpha-synuclein CSF levels were also decreased in patients with multiple system atrophy, suggesting that this marker may not be useful for the distinction between synucleinopathies. Preliminary results of prospective studies further suggest that concentrations of total alphasynuclein are not changing over time and are not correlated with disease severity. More recent studies have looked at alpha-synuclein levels in more accessible fluids (e.g. blood and saliva) and tissues (e.g. skin, salivary glands and colon biopsies). In this line, preliminary evidence suggests increased plasma concentrations of exosomal alphasynuclein. These results, together with encouraging findings in tissues, warrant replication and further investigation. The presentation will discuss recent progress and promising future avenues for the development of alpha-synuclein as biomarker in PD and synucleinopathies. Disclosure: Nothing to disclose

FW10-3 Imaging Markers: MRI U. Sabatini Rome, Italy

Backround and purpose: When magnetic resonance imaging (MRI) was initially introduced in clinical practice, conventional neuroimaging techniques had a marginal role in the diagnosis of Parkinson’s disease (PD). The increasing prevalence of PD, partly as a consequence of population ageing, the introduction of experimental therapeutic strategies, and technological advances in MRI have stimulated the development of MRI techniques with a potential for greater sensitivity and specificity for early diagnosis and the quantification of the pathological process. With the introduction of higher field magnets and novel imaging sequences, microstructural, metabolic and functional data is, as never before, contributing to the search for reliable biomarkers of disease progression in PD. Results from existing studies have suggested several MRI-

based measures as potential biomarkers of PD pathology, albeit none of them has yet been identified as a clear winner. These studies converge towards the notion that a single MRI modality cannot be sufficient to characterise the complex pathological mechanisms underlying PD. In fact, multimodal MRI sequences are able to capture tissue characteristics at different scales: macroscopic structure can be assessed through volumetric T1-weighted, microstructural alterations can be detected through diffusion-weighted, iron deposition in specific brain structure can be quantified through R2* imaging. For this reason, the integration of multimodal MRI indexes is crucial, since they probably carry complementary information regarding the biological process of interest. Datasets in a large cohorts of accurately selected patients, acquired at multiple sites, will grant the opportunity of testing multimodal MRI techniques over large amounts of clinical, neuroimaging and genetic data. Disclosure: Nothing to disclose.

FW10-4 Imaging Markers: PET/SPECT P. Remy

Créteil, France

Backround and purpose: The use of dopaminergic presynaptic ligands such as 18F-DOPA (PET) or cocaine analogues (PET/SPECT) has been used for years to measure the progression of neurodegenerative process in Parkinson’s disease (PD). Although several studies have used PET or SPECT to investigate neuroprotective potentiality of several treatments, to date results have been either negative or highly debated. One major issue is to obtain a clinical benefit in patients whose disease has been slowed according to imaging data. Another marker which has been more recently used is the measure of endogenous synaptic dopamine release. Using an 11C-Raclopride displacement method it is possible to demonstrate enhanced dopamine availability in the striatum induced by cell or gene therapy. Eventually, new processes are now investigated to identify alternative markers of PD, such as inflammatory process, using ligand of the TSPO which reveals glial activation. In addition, a ligand of a-synuclein would be considered as a dramatic improvement in our ability to measure PD degenerative process and to evaluate immunotherapy against a-synuclein deposition which is already investigated in patients. Disclosure: Nothing to disclose.


Focused Workshop

Focused Workshop 12 Impaired hand function after stroke and peripheral nerve injury: consequences for treatment FW12-1 Treatment of hand function after peripheral nerve injury

cooperative tasks is followed by EMG responses in muscles of the (contralateral) coupled affected limb, i.e. unaffected motor centres influence synergistically acting movements of the paretic limb. In contrast, following stimulation of the affected limb, no contralateral responses appear due to defective processing of afferent input. As a consequence, it may be therapeutically possible to strengthen the influence of unaffected motor centres on the performance of affected limb movements through training of cooperative limb movements required during activities of daily living.

J. Valls-Solé


Backround and purpose: Nerve growth after injury in peripheral nerves is a physiological process. It occurs naturally after the lesion and, although it can be promoted by some drugs such as growth factors, it will occur even in rather adverse situations if the nerve has not lost its continuity. There are many problems with reinnervation: There is a critical window of time in which regeneration must occur for optimal recovery to be achieved. If distal Schwann cells lack axonal contact for a long time, they degenerate, reduce secretion of growth factors, disappear from the bands of Büngner and stop replication, leading to irreversible changes detrimental for functional recovery. It is nowadays impossible to guide the regenerating axons up to the target that they had before the lesion. If nerve regeneration occurs, reinnervating axons may end up innervating a structure different from the one they were innervating before the injury. There are changes at motoneuronal level that make the motoneurons hyperexcitable and respond to inputs from many sources to which they did not respond before the injury. Finally, axon growing means also axonal branching. This provides electrophysiologic studies but also more possibilities of innervation errors and inefficacy of the reinnervated targets. The recovery of hand function depends on all these factors, which are conditioning the rehabilitation progress. Disclosure: Nothing to disclose.

FW12-3

Barcelona, Spain

FW12-2 Normal and impaired neural coupling of cooperative hand movements V. Dietz

Zurich, Switzerland

Backround and purpose: In recent years it has become evident that, in a number of functional movements, synergistically acting limbs become task-specifically linked by a soft-wired ‘neural coupling’ mechanism (e.g. the legs during balancing, the arms and legs during gait and both arms during cooperative hand movements). Experimentally this mechanism becomes elucidated by reflex responses as a marker for a neural coupling. This reflected by the taskspecific appearance of reflex EMG responses to nonnoxious nerve stimulation, not only in muscles of the stimulated limb, but also, with same long latency, in muscles of meaningful coupled (contralateral) limb(s). After a stroke, nerve stimulation of the unaffected limb during such

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Bilateral hand movement training after stroke: what is the benefit? C. Renner

Leipzig, Germany

Introduction: Different training strategies have been tested in neurorehabilitation of motor function. Examples include constraint-induced movement therapy (CIMT) and bilateral arm training (BAT), They are based on divergent hypotheses of poststroke reorganization. CIMT promotes activation of the ipsilesional hemisphere counteracting contralesional activation, while BAT involves bihemispheric activation. Yet severely impaired stroke patients unable to move their hands are unable to perform CIMT. Methods: 60 patients with a severe arm paresis were recruited for this randomized single-blinded study and stratified according to lesion location. The bilateral arm training entailed a repetitive training on an “arm-cycle” followed by synchronized bilateral repetitive distal hand training. The unilateral arm training was identical but performed by the paretic limb only. Both trainings were administered twice daily over six weeks and incorporated shaping elements. Main outcome measures included the FMA and biomechanical parameters measuring isometric force and rate of force generation. Results: Both trainings lead to a significant improvement of the FMA and all biomechanical parameters. Patients with pure subcortical stroke, but not patients with cortical involvement of stroke, showed a significantly greater improvement following the bilateral training in FMA (p=0.03) and hand extension (p=0.02) compared to unilateral training. Conclusion: Bilateral arm training followed by repetitive bilateral hand training leads to greater improvements in motor control and force of the severely paretic upper limb compared to the unilateral training after pure subcortical stroke lesions. These findings may assist in planning different therapeutic regiments in the context of motor impairment severity and lesion location.


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Focused Workshop

Monday, 30 May Focused Workshop 13 Sleep and cognition FW13-1 Sleep and cognition P. Maquet

Liege, Belgium

Backround and purpose: Human performance results from an interaction between circadian rhythmicity and homeostatic sleep pressure accumulated during wakefulness. Whether and how this interaction is represented at the level of regional brain responses has not been established. We quantified changes in brain responses to 2 cognitive tasks during 13 functional magnetic resonance imaging (fMRI) sessions scheduled across the circadian cycle during 42h of wakefulness in 33 healthy participants. The temporal profile of cortical responses shows a significant circadian rhythmicity, the phase of which varies across brain regions. Cortical responses also significantly decrease with accrued sleep debt. By contrast, subcortical areas exhibit primarily a circadian modulation, which closely follows the melatonin profile. These results demonstrate a local modulation of brain responses by both circadian rhythmicity and sleep pressure. These results have important bearing on our understanding of sleepiness-related traffic and work accidents, insomnia and rehabilitation programs. Disclosure: Nothing to disclose

FW13-2 Sleep and emotion V. Sterpenich Disclosure: Nothing to disclose

Geneva, Switzerland

Backround and purpose: Recent research has demonstrated that freshly encoded memory traces are replayed during sleep. This mechanism allow information to be integrated into an existing network of representations. During wakefulness, the brain is bombarded with large amounts of information. Thus, to better understand how replay during sleep contributes to memory processes, we need to determine what type of information is prioritized for subsequent replay during sleep. We hypothesized that information with an affective value, which might require long-term behavioral changes, would benefit from offline reprocessing during sleep. Thus, memories of emotionally relevant experiences may have a higher probability of being reprocessed during sleep. Using simultaneous EEG-fMRI recordings, we measured brain activity while healthy participants played alternating blocks of two distinct games, one of which they would eventually win. We also measured brain activity during different sleeps stages. Using a neural decoding approach we found that the pattern of brain activity associated with the rewarded game occurs spontaneously during deep sleep and more frequently than the non-rewarded game. In a second experiment, we


Focused Workshop

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artificially reactivated emotional memory traces during sleep using auditory cues in patients with intracranial EEG recordings. We observed that the cues associated with positive events would elicit distinct iEEG responses during sleep in brain regions involved in emotion and memory. Taken together, these findings suggest a general mechanism whereby the brain selectively consolidates memories with a high value for survival. The replay of relevant memories occurs during a physiological state, i.e. sleep, that is highly favorable for neural plasticity. Disclosure: Nothing to disclose

Focused Workshop 14 Gut microbiota, immunology and neurological diseases

FW13-3

Backround and purpose: Modifications in the bacterial composition and diversity of the human gut microbiota (microbial dysbiosis) have been associated with digestive tract dysfunctions such as inflammatory bowel diseases. More strikingly, microbial dysbiosis may be associated with pathologies at distance from the intestine and strong evidence, from both human studies and animal models, links intestinal microbiota dysbiosis with metabolic disorders, such as obesity. More recently, associations between microbial imbalances in the gut and neurologic and behavioural disorders have been described in animal models. While some gut microbes have the capability to produce neuromediators that may exert effects in the brain, only sparse data are available in humans and most of them remain highly descriptive. Yet, the possible involvement of the ‘microbiota-gut-brain’ axis in the development of disorders ranging from autism, multiple sclerosis or depression is currently being investigated. The development of meta-omic technologies that give insight into the functions and potential effect of the non-cultured intestinal bacteria on the host health will surely help understanding how modifications in this finely tuned ecosystem lead to these pathological processes. This may finally lead to the development of new therapeutical approaches to treat and ameliorate these neurological diseases. Disclosure: Nothing to disclose

Sleep and dementia S. Overeem

Heeze, The Netherlands

Backround and purpose: Alzheimer's disease (AD) is the most common form of progressive dementia. It has been known for a long time that AD patients frequently suffer from sleep disturbances as well as circadian rhythm disorders. In recent years however, evidence is accumulating that suggests a bidirectional relationship between AD and sleep, i.e. sleep disturbances may be a risk factor to develop AD. Several epidemiological studies have shown that sleep restriction increases the risk of cognitive impairment. Experiments in mice showed that sleep deprivation leads to a marked increase in amyloid beta accumulation. Most likely, sleep contributes to the clearance of metabolites such as amyloid beta from the brain. More recently, studies have shown comparable mechanisms in humans. For example, sleep deprivation lead to an increase in cerebrospinal fluid amyloid beta levels in healthy subjects. Besides a link between sleep and amyloid dynamics, other factors may be at play. For example, melatonin may have antioxydant, neuroprotective as well as anti-amyloidogenic effects. Disclosure: Nothing to disclose

FW14-1 Microbiota and the gut-brain axis P. Lepage

Micalis Institute, INRA, AgroParisTech, Université ParisSaclay, Jouy-en-Josas, France

FW14-2 Microbiota and CNS autoimmunity (Multiple Sclerosis) G. Krishnamoorthy

Martinsried, Germany

Backround and purpose: Autoimmunity results from a combined influence of genetic and environmental factors. Emerging evidence in the experimental models of autoimmunity suggests an important contribution of gut microbiota in the disease development. In this presentation, i will present evidence for the role of gut microbiota in mouse models of Multiple Sclerosis, an autoimmune disease of the central nervous system with the special emphasis on how to modulate gut microbiota for therapeutic benefit. Disclosure: Nothing to disclose


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Focused Workshop

FW14-3 Gut microbiome: a key regulator of neurodevelopment and behaviour J.F. Cryan

Cork, Ireland

Backround and purpose: The brain-gut-microbiota axis is emerging as a research area of increasing interest for those investigating the biological and physiological basis of neurodevelopmental, age-related and neurodegenerative disorders. The routes of communication between the gut and brain include the vagus nerve, the immune system, tryptophan metabolism, via the enteric nervous system or by way of microbial metabolites such as short chain fatty acids. Studies in animal models have shown that the development of an appropriate stress response is dependent on the microbiota. Developmentally, a variety of factors can impact the microbiota in early life including mode of birth delivery, antibiotic exposure, mode of nutritional provision, infection, stress as well as host genetics. At the other extreme of life, individuals who age with considerable ill health tend to show narrowing in microbial diversity and a proinflammatory phenotype. Stress can significantly impact the microbiota-gut-brain axis at all stages across the lifespan. We have recently shown that fundamental brain processes important for neurological diseases are regulated by the microbiome. These include adult hippocampal neurogenesis and hippocampal expression of BDNF. In the amygdala, germ free animals have increased volume, spine density and morphology, whereas in the prefrontal cortex myelination and myelin-related gene expression is dependent on the microbiome. It has also recently been shown that microglia activation and blood brain barrier integrity are also microbiome-dependent processes. Further studies will focus on understanding the mechanisms underlying such brain effects. Together these data offer the intriguing possibility of therapeutically targeting specific brain processes via the gut microbiome. Disclosure: Nothing to disclose.

Focused Workshop 15 Exome sequencing goes bedside: new genes in neurological disorders FW15-1 Cerebellar ataxias: exome sequencing unravels novel genes, false friends and clinical hints for bedside M. Synofzik1, F. Harmuth2, S. Züchner3, L. Schöls1, P. Bauer1, R. Schüle1

Tübingen, Germany, 2Institute of Medical Genetics and Applied Genomics, Tübingen, Germany, 3Miami, USA 1

Backround and purpose: Cerebellar ataxias present a heterogeneous group of degenerative and metabolic diseases. Based on the advances of next-generation sequencing (NGS) techniques such as panel, whole exome sequencing (WES) and whole genome sequencing (WGS), the number of newly identified genetic causes of ataxias is rapidly increasing, with >120 ataxia-associated genes now being identified. This talk will demonstrate that these genetic advances provide unprecedented options to diagnose previously unsolved ataxia patients, to define the genetic basis of many rare and complex ataxia disorders, and to pave the way towards molecular pathways and treatments. In step one, a state-of-the art overview on NGS findings in ataxias will be provided, including several novel ataxia genes identified by our and other groups. These novel ataxia genes provide insights into underlying pathways, and also putative future biomarkers and treatments. Second, we will show that such NGS results yield not only constructive findings, but also warrant a new level of critical interpretation. NGS and recent related publications deliver a high number of rare variants in known ataxia genes with questionable significance, and flag putatively novel putative ataxia genes which are not yet sufficiently validated. Third, we will show that NGS does not make clinical ataxia expertise dispensable, but, on the contrary, warrants a new level of specific clinical expertise. A high degree of clinical ataxia specialist knowledge is indispensable to reliably interpret the variant lists produced by NGS. Moreover, we will show how clinical hints allow to pinpoint the genetic diagnosis in ataxias even before and without NGS. Disclosure: Matthis Synofzik has received speaker honoraria and research support by Actelion Pharmaceuticals. He was awarded a Else Kröner Memorial Stipend by the Else Kröner-Fresenius Stiftung.


Focused Workshop

FW15-2

FW15-3

Atypical parkinsonian syndromes: rapidly expanding genetic disease spectrum, yet distinct clinical and imaging signatures

Motor neuron disease and spastic paraplegias: large-scale exome sequencing reveals common pathogenetic hubs

H. Houlden


Backround and purpose: Parkinsonism is defined by akinesia associated with rigidity or rest tremor. The akinesia can be bradykinesia, hypokinesia or reduced facial expression. There are a variety of causes of parkinsonism, but Parkinson’s disease (PD) is the most common. The “atypical parkinsonian syndromes” (called in the past “Parkinson’s plus syndromes”) are characterized by a rapidly progressive parkinsonism that has a poor or brief response to dopaminergic therapy and often with one or more atypical features that include; early postural instability/ autonomic failure, supranuclear gaze palsy, pyramidal or cerebellar signs, alien limb and apraxia. In addition to the usually acquired atypical forms there are an expanding group of inherited parkinsonian syndrome such as the recessive PLA2G6, FBX07, SPG11, PANK2 and other very rare syndromes associated with brain iron where many remain genetically undefined. The diagnostic differentiation of the atypical parkinsonsian disorders is essential for both clinical practice and research because the diagnostic tools needed for investigation, prognosis and treatments differ significantly to PD. Atypical parkinsonian disorders have a shorter survival time and more complications. Drug and surgical therapies differ significantly and there are few effective treatments. However, early identification of the different atypical parkinsonian disorders can reduce complications, inform prognosis and allow patients to be enrolled in clinical trials. Genetic testing and imaging signatures are becoming increasingly important tools in which to become adept, and along with clinical skills are essential to the movement disorder specialist in clinical practice and for research. Disclosure: Nothing to disclose

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R. Schüle

Tübingen, Germany

Backround and purpose: Motor neuron disease and hereditary spastic paraplegias (HSP) comprise a heterogeneous group of degenerative diseases affecting the upper and/or lower motor neurons and their axonal projections. The increasing availability and decreasing cost of whole exome sequencing (WES) and whole genome sequencing (WGS) have led to an unprecedented discovery rate of novel genes causing these rare conditions. Despite the genetic heterogeneity, the predilection of motor neurons for the disease pathology and the selective vulnerability of long axonal projections, at least in HSPs, suggest a shared pathophysiology among the genetically defined subtypes of motor neuron disease and HSPs. Discovery of novel disease genes by us and others over the past few years have opened up our view from a gene-centric to a network-centric focus on pathophysiology. In this talk, we will discuss recent advances in genetics of motor neuron disease and HSPs and will highlight how these novel discoveries translate into a better understanding of the cellular mechanisms involved. This mechanistic approach may open up novel therapeutic targets and opportunities. Disclosure: Nothing to disclose.


930

Focused Workshop

Focused Workshop 16 Syndromes of central visual and vestibular disorders

FW16-3

FW16-1

Munich, Germany

Cortical visual disorders and neglect C. Kennard

Oxford, United Kingdom

Backround and purpose: Disorders of the striate and extrastriate cortex lead to a multiplicity of visual disorders which range from a homonymous hemianopia to very specific visual impairments such as prosopagnosia and visuo-spatial neglect. Recent behavioural studies along with functional brain imaging have shed new light on these disorders and in some have offered the prospect for therapeutic interventions. The commonest visual deficit is homonymous hemianopia and several methods have been devised for restoring function either of the visual field itself or by behavioural modification. The current controversy relating to some of these techniques will be discussed. Focal lesions of the extrastriate cortex can lead to specific visual deficits of, for example, colour (achromatopsia), motion (akinetopsia), face (prosopagnosia) and form (visual agnosia) and current views of their functional visual localisation will be described. Visuo-spatial neglect is no longer considered to be a unitary disorder but rather it consists of a number of component deficits, with the precise combination varying from patient to patient, presumably determined by the exact location and extent of brain damage. Mechanisms underlying neglect may not be neglect specific ie they may occur on their own without neglect. Recognition of these component deficits are leading to the introduction of novel therapies such as scanning therapy and hemianopic patching, inducing shifts in spatial representations, prism adaptation and treating non-spatially lateralised deficits pharmacologically. Disclosure: Nothing to disclose.

Central vestibular disorders (from brainstem to cortex) T. Brandt

Backround and purpose: The traditional classification of vestibular disorders is based on the anatomical site of the lesion. While it distinguishes between the peripheral and the central vestibular system, certain weaknesses become apparent when applied clinically. For example, peripheral and central lesions may cause similar symptoms such as skew deviation or tilts of perceived vertical which originate with unilateral lesions of graviceptive pathways from the labyrinth and the vestibular nuclei to the midbrain tegmentum and cerebellum. Further, disorders of “higher vestibular function” are missing. A concept of disorders of higher vestibular function is proposed which involve cognition and more than one sensory modality. Three conditions exemplify such higher disorders: room tilt illusion, spatial hemineglect, and bilateral vestibulopathy all of which present with deficits of orientation and spatial memory. Further elaboration of such disorders of higher multisensory functions with respect to lesion site and symptomatology is desirable. The room tilt illusion and spatial hemineglect involve vestibular and visual function to the extent that both conditions can be classified as either disorders of higher vestibular or of higher visual functions. A possible way of separating these disorders in a first step is to determine whether the causative lesion site affects the vestibular or the visual system. For the vestibular system this lesion site may be peripheral or central. Disclosure: Nothing to disclose.

FW16-2 Peripheral vestibular disorders with essential bedside testing B.M. Seemungal



Focused Workshop

Focused Workshop 17 ALS and FTD: two converging diseases?

FW17-2

FW17-1

Edinburgh, United Kingdom

Neuropathology of FTD and ALS comparing the patterns of propagation J. Brettschneider

Philadelphia, USA

Backround and purpose: Neurodegenerative diseases share a common pathological hallmark – the accumulation of characteristic proteins into insoluble aggregates in or among selectively vulnerable neurons and glial cells. The disease-related proteins are transformed from their normal conformation into fibrillar or multimeric species that function as seeds and templates to drive non-pathological protein counterparts to adopt a similar structural alteration. Neuropathological studies have identified that stereotypical patterns of pathology occur in various neurodegenerative diseases over time, and that progression of these patterns is associated with increasing severity of the clinical phenotype. Disclosure: Nothing to disclose.

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Assessment of neuropsychology in ALS and FTD T. Bak

Backround and purpose: Cognitive assessment in patients presenting with motor symptoms faces particular challenges. Patients’ performance is determined not only by their cognitive functions but also by their motor impairment: bulbar symptoms influence tasks requiring a verbal response (e.g. naming, verbal fluency) while tasks involving writing or drawing can be compromised by a wide range of motor symptoms, from weakness, through tremor, rigidity, akinesia and dystonia to apraxia. However, most currently available neuropsychological tests assume normal motor performance. Hence, they cannot distinguish whether a low score on a particular task is due to motor or cognitive dysfunction, a crucially important question when assessing the cognitive status. In my presentation, I will discuss examples of the interference between motor and cognitive functions on neuropsychological testing. I will then present a new cognitive screening tool, ECAS (Edinburgh Cognitive Screen for ALS), specifically developed to assess cognitive functions in patients with motor impairment. It has been designed to minimize the influence of motor dysfunction through tasks requiring only minimal motor input such as pointing or yes/no answers. The whole test can be completed in a spoken or a written version. As such, the ECAS allows an adequate cognitive assessment in patients of the ALS/ FTD spectrum. I will then present an overview of the neuropsychological studies in ALS/FTD, focusing on the question whether the cognitive picture can be sufficiently explained by a combination of ALS and FTD or whether ALS/FTD patients show a specific pattern of cognitive dysfunction, distinct from that reported in ALS andFTD alone. Disclosure: Nothing to disclose.


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Focused Workshop

FW17-3 ALS and FTD: genetics and phenotypes V. Silani

Milan, Italy

Backround and purpose: ALS and FTD are since 2006 to be considered a single disease: the neuropathology first provided proof and genetics largely confirmed and contributed in defining this convergence. The discovery of TARDBP and FUS supported recognition that ALS and FTD represent overlapping clinical syndromes and this convergence has been further strengthened by the discovery of C9orf72, Ubiquilin 2 (UBQLN2) and other genes. It is now accepted that ALS constitutes a continuum with FTD, with pure ALS and pure FTD at the ends of this spectrum of motor neuron and frontotemporal neuron involvement. Intermediate phenotypes include ALS with cognitive impairment, ALS with behavioural impairment, and ALSFTD. The clinical implications are so relevant both in the subgrouping of the patients and in the design of clinical trials that further investigations are highly needed for the most accurate definition of the cognitive and motor involvement in both the diseases. The overlap between ALS and FTD is indeed quite intricate, requiring to be identified according to the most updated neuropsychological testing (i.e. ECAS) in order to further address the most appropriate therapeutical strategies. C9orf72 mutations have been significantly reported in ALS with cognitive/behavioural changes and antisense oligonucleotide (ASO) therapy is now emerging as a highly promising approach. Of converse, a subgroup of FTD patients (10%) may show some sign of motor neuron degeneration, requiring prompt identification to define strategies to oppose weakness. Disclosure: Nothing to disclose.



Special Session Saturday, 28 May Special Session 1 MDS-ES European Basal Ganglia Club SPS01-1

Special Session 2 Music and neurology - neurological disorders of famous composers SPS02-1 Subarachnoidal haemorrhage as a likely cause of Mendelssohn's death

Consciousness, Emotions and Basal Ganglia

H. Bäzner

Mannheim, Germany

Y. Agid

Paris, France

Backround and purposes: In the human brain, the basal ganglia are considered to play a role in the selection and shaping of sensori-motor programs and the automatic execution of learned motor plans. The anatomo-physiology of the basal ganglia is characterized by four main features: segregation of neuronal circuits; convergence of informations; close interrelationships with the cerebral cortex; complex interactions between the different corticosubcortico-cortical neuronal loops. They are thus composed not only of sensori-motor territories but also associative and limbic territories, considered to play a role in intellectual and emotional functions. It is, therefore, hypothesized that the basal ganglia are also involved in the control of intellectual and psychic functions underlying associativolimbic areas within these structures. There are two ways to study the role of the basal ganglia in the control of intellectual and emotional functions in humans, whether in normal subjects or in patients: one way is to look at the activated or de-activated brain areas using functional neuroimaging in subjects who are confronted with various types of emotions. Another approach is to modify the activity of the basal ganglia neuronal circuits to see if one can reproduce these emotional and intellectual disturbances. Several examples using neuroimaging and deep brain stimulation will be provided to demonstrate that phylogenetically ancient structures such as the basal ganglia are directly involved in the subconscious processing of emotions in normal subjects or emotional disturbances in patients with neuro-psychiatric disorders. But, what do we mean by subconsciousness? Disclosure: Nothing to disclose.

Backround and purposes: Felix Mendelssohn-Bartholdy (3 February 1809 – 4 November 1847) was a German composer, pianist, organist and conductor of the early Romantic period. In the final years of his life Mendelssohn suffered from poor health, which at the time was attributed to “nervous problems” and overwork. The sudden and tragic death of his older sister Fanny (14 November 1805 – 14 May 1847), who herself was an excellent pianist and composer caused him great distress. She reportedly died only hours after a sudden severe headache followed by coma. Less than six months later, on 4 November, Mendelssohn himself died in Leipzig. Early biographies mention a series of strokes as his final disease. The “strokes” were characterised by very severe headache and loss of consciousness. According to various sources, also his grandfather Moses and both his parents had died from similar “strokes”. The courses of the disease of both siblings make a diagnosis of subarachnoid hemorrhage possible. Given the family history also inherited neurovascular diseases affecting cerebral blood vessels have to be discussed. Disclosure: Nothing to disclose

SPS02-2 Mozart's plausible neurological disorders C. Gardner-Thorpe

Exeter, United Kingdom

Backround and purposes: Possible neurological diagnoses of Mozart will be discussed with particular emphasis on plausible hypotheses, bearing in mind the problems of retrospective diagnosis of medical conditions and especially after the passage of sginficant amounts of time. Consideration of literature is the only available method for retrospective diagnosis and therefore the discussion is based upon this material. Re-analysis of historical data is almost always useful, and a proper method of discussion. It is by no means possible to reach a firm conclusion but possibilities will be discussed.

© 2016 EAN

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Special Sessions


SPS02-4

Stroke in famous composers

Wagner's migraine and Gershwin's uncinate seizures

SPS02-3 T. Breitenfeld

V. Vukovic-Cvetkovic

Zagreb, Croatia

Backround and purposes: Creatvity is a highly appreciated, remarkable and uniquely human skill defining the ability to use imagination or original and unusual ideas to create something new or imaginative. The quick advancement of neuroscience has enabled us to observe creativity not only as mystery but also in the context of science. Stroke is one of the most common of all neurological diseases, one of the leading causes of death and leading cause of disability. This was true historically as well as now. The goal of biopathographies is to investigate lives and creativity of famous composers from psychological as well as medical point of view. Last decades gave us a whole new insight into famous composers' creative lives. Looking at musical history, nearly a quarter of those considered “great composers” suffered from vascular disease. The most prominent renaissance composers were stroke victims, like Orlando di Lasso (Orlande de Lassus) and Giovanni Pierluigi da Palestrina as well as German Baroque giants – Heinrich Schutz, Johann Sebastian Bach, Georg Friedrich Handel and Christoph Willibald Gluck. Further on Giuseppe Verdi, Hector Berlioz, Antonin Dvorak, Igor Stravinski, Sergej Prokofiev,Jean Sibelius and Benjamin Britten among others, are also famous composers that suffered or died of stroke. These composers all had wide talent, success, importance, and ultimately, stroke. Cerebrovascular disorders of famous composers will be discussed in this presentation, together with their influence on composers’ creativity. Disclosure: Nothing to disclose.

Copenhagen, Denmark

Backround and purposes: Analysis of Richard Wagner´s (1813-1883) letters and diary entries of his wife Cosima Wagner reveal that the German composer was severely burdened by migraine which he described as “the main plague of his life”. His headache manifestations were characterised by severe headache attacks, lasting one or more days, with marked nausea, photo-, phono- and osmophobia. Physical activity aggravated the pain. R. Wagner also desribed visual aura disturbances in the form of flickering zig-zag patterns and visual field defects. The headache features completely fulfils the criteria of the International Headache Society for migraine with and without aura (ICHD-3 beta). George Gershwin (1898-1937) died due to a brain tumor. Gershwin always complained of a rather odd epigastric sensation, which is classically described in patients suffering from temporal lobe epilepsy due to hippocampal sclerosis. His neurological symptoms first appeared in February 1937 during a presentation making a blunt mistake; he experienced a "mental lapse" lasting a few seconds and at the same time a smell of burnt rubber. Soon after these simple olfactory partial (uncinate) seizures begun, he experienced progressive clinical deterioration, with severe headaches and dizziness,eventually lapsing into a coma. A gliomatosus cyst was diagnosed, which on microscopic examination proved to be a "glioblastoma multiforme". He underwent a surgical intervention, however, Gershwin died soon after the procedure in July 1937, without recovering his consciousness. Disclosure: Nothing to disclose.


Special Sessions

SPS03-2

Sunday, 29 May Special Session 3 New European neurological guidelines SPS03-1 Neurostimulation in neuropathic pain G. Cruccu1, N. Attal2 1

935

Rome, Italy, 2Boulogne-Billancourt, France

Background and purposes: Previous EFNS guidelines on neurostimulation therapy for neuropathic pain date back to 2007. Here we aimed at updating those guidelines, expanding the search to new techniques and long-term pain conditions other than neuropathic pain, and assessing the evidence with the GRADE system. Methods: We conducted a systematic review and metaanalysis of trials published between 2006 and 2014. Pain conditions included neuropathic pain, fibromyalgia, complex regional pain syndrome type I (CRPS) and failed back surgery syndrome (FBSS). We assessed spinal cord stimulation (SCS), deep brain stimulation (DBS), epidural motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation (rTMS) and transcranial direct electrical stimulation (tDCS) of the motor cortex (M1) or dorsolateral prefrontal cortex (DLPCF). We used the GRADE system to assess quality of evidence and propose recommendations. Results: We achieved weak recommendations for SCS added to conventional medical management in diabetic painful neuropathy, FBSS and CRPS, for SCS versus reoperation in FBSS, for MCS in neuropathic pain, for rTMS of M1 in neuropathic pain and fibromyalgia, and for tDCS of M1 in neuropathic pain. We achieved inconclusive recommendations for DBS in neuropathic pain, rTMS and tDCS of the DLPCF, and for motor cortex tDCS in fibromyalgia and spinal cord injury pain. Conclusions: Given the weak evidence available so far, for future trials we encourage large scale multicentre studies of non-invasive and invasive neurostimulation. We also recommend high quality studies of predictive factors of the efficacy of these techniques. Disclosure: Nothing to disclose.

Diagnosis and management of tick borne encephalitis P. Taba

Tartu, Estonia

Background and purposes: The incidence of tick borne encephalitis (TBE) increases in Europe due to an extended season of the infection and the enlargement of endemic areas. To provide recommendations on the diagnosis and management of TBE, based on evidence or consensus decisions. For systematic evaluation, literature was searched from 1970 to 2015, and recommendations were prepared according to the evidence classification, or consensus decisions by the Task Force. There is a strong evidence the the European vaccines against TBE induce a high level of seropositivity. Vaccination is recommended for all age groups in the highly endemic areas, but also for individuals at risk in areas with a lower incidence, and travellers if their visits will include extensive outdoor activities in endemic areas. It is not recommended to use post-exposure prophylaxis after a tick bite. A case of TBE is defined by the presence of clinical signs of meningitis, meningoencephalitis or meningoencephalomyelitis with cerebrospinal fluid pleocytosis and demonstration of recent infection with TBEV by the presence of specific serum IgM and IgG antibodies, CSF IgM antibodies, or TBEV IgG seroconversion. Treatment of TBE is symptomatic. Patients with a potentially life threatening course of meningoencephalitis or meningoencephalomyelitis should be admitted to an intensive care unit. In case of brain edema, analgosedation should be deepened; osmotherapy and corticosteroids are not routinely recommended. If intracranial pressure is increased, therapeutic hypothermia or decompressive craniectomy might be considered. Epileptic seizures should be treated as any other symptomatic seizures. No effective antiviral or immunomodulating therapy is available for TBE. Disclosure: Nothing to disclose.

SPS03-3 Prehospital stroke management A. Kobayashi

Warsaw, Poland

Background and purposes: Reduction of delay between onset and hospital arrival and adequate pre-hospital care of persons with acute stroke are important for improving chances of a favorable outcome. The objective is to recommend evidence-based practices for the management of patients with suspected stroke in the pre-hospital setting. The GRADE methodology was used to define the key clinical questions. An expert panel then reviewed the literature, established the quality of the evidence, and made recommendations. These guidelines inform on the contemporary approach to patients with suspected stroke in the pre-hospital settings. Further studies, preferably randomized controlled trials, are required to examine the impact of particular interventions on quality parameters and


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outcome. Disclosure: Nothing to disclose.

Special Session 4 EFNA Open Dialogue: Let's talk about sex, sleep and stress

SPS03-4 Alcohol-withdrawal seizures G. Brathen1, E. Ben-Menachem2, E. Brodtkorb1, M.E. Hillbom3, S. Jesse4, M. Keindl5, A.C. Ludolph4, R. Tanasescu6, M. Leone7

1Dept of Neurology & Clin. Neurophysiology, Trondheim University Hospital, Trondheim, Norway, 2SU/Sahlgrenska Hospital, Institute of Clinical Neuroscience, Gothenburg, Sweden, 3Oulu University Hospital, Department of Neurology, Oulu, Finland, 4University Ulm, Department of Neurology, Ulm, Germany, 5Danube University, Krems, Austria, 6Colentina Clinical Hospital Bucharest, Neurology, Bucharest, Romania, 7San Giovanni Rotondo, Italy

Introduction: Among the many mechanisms by which alcohol use may lead to seizures, Alcohol withdrawal seizures (AWSz) is probably the best-defined entity, being a symptom of the alcohol withdrawal syndrome (AWS) and occurring in more than 90% of cases within 48h of cessation of sustained drinking. As recurrence is common, acute treatment and prevention is important. Potential complications such as Wernicke encephalopathy need early attention. A major challenge is the lack of clear definitions of the different types of alcohol-related seizures. The objective was to update the EFNS guideline published in 2005, and to set recommendations according to the GRADE system. Methods: The workgroup selected 10 PICO questions for an updated literature search in Pubmed, EMBASE, the Cochrane library, and CINAHL. For drugs for seizure prevention, the search strategy was adopted from recent Cochrane reviews. At a workshop in November, 2015, we reviewed the search results. Grading of outcomes is ongoing. Results: Preliminary results are presented. Although important, the dosing and frequency of Thiamine treatment is virtually undocumented. Benzodiazepines but not other anticonvulsants reduced the seizure risk significantly compared to placebo. In three randomized controlled studies, phenytoin failed to prevent recurrent seizures. No recent evidence supports advice to people with epilepsy regarding safe levels or frequency of alcohol consumption. Conclusion: Despite a considerable body of new literature during the last 10 years, little new evidence has emerged. The GRADE method requires experience and may be perceived as challenging, but is an important step towards a standardized method of evidence assessment. Disclosure: Nothing to disclose

SPS04-1 Sleep: raising awareness of sleep disorders in the neuroscientific and neurological communities W. Oertel

Marburg, Germany

Background and purposes: Sleep disorders are a neglected area in neurology. Little teaching is done on this topic and few Chairs of Neurology at the academic institutions in Europe are occupied by sleep experts. Neurological sleep disorders include insomnia (a complex of several disorders leading to impaired or lack of sleep), restless legs syndrome (the second or third most common neurological disorder – 3% of the European population need respective therapy), sleep apnoea (affecting 2-5% in adult males), the rare disorder narcolepsy or REM-sleep behaviour disorder (characterised by the loss of atonia, i.e. patients act out their dreams. RBD is now accepted as the most specific prodromal stage of the chronic neurodegenerative disorder Parkinson’s disease). In addition, sleep plays a major role in the formation of our memory. Thus, sleep disorders may have a negative impact on cognitive performance and even on the development of dementia in the long term. The presentation will address: -New basic and clinical scientific findings in sleep research in 2015 and 2016? -Sleep disorders as a comorbidity of other neurological disorders. -Teaching, awareness and knowledge on how sleep and sleep disorders can be improved in the neuroscientific and neurological community, as well as in the general public. -Tools and skills in how sleep disorders can be accurately diagnosed as a neurological sleep disorder, per se, or as a symptom of/comorbidity of other neurological disorders. Management and treatment of neurological sleep disorders. Disclosure: Nothing to disclose.


Special Sessions

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SPS04-2

SPS04-3

Stress: addressing mental health in neurological disorders: experiences and findings from clinical practice in neuropsychiatry

Communicating on sexual dysfunction as a symptom of neurological disorders

C. Schmidt-Kraepelin Düsseldorf, Germany

Background and purposes: Symptoms of mental disorders are common aspects in the course of neurological disorders and affect about 30-50% of the patients. However they are frequently underrecognised by clinicians. We addressed this issue within our department for Neuropsychiatry by developing a clinical routine to improve the collaboration between Neurology and Psychiatry. The presentation will cover experiences from clinical practice and findings from self report questionnaires, namely the Beck Depression Inventory (BDI) and the Brief Symptom Inventory (BSI), which allow to asses different domains of the mental burden. Of all respondents (n=157), 51% stated to have suffered from psychological distress within the past seven days, and 43% reported depressive symptoms of clinical relevance (21% mild, 17% moderate, 5% severe). The mean global severity index GSI (M=0.64, SD=0.52) was below a psychiatric inpatient population, but exceeded the 1 SD range of healthy persons, known from the literature. The results reveal a high burdening due to symptoms of mental disorders in patients with neurological disorders and suggest the need for a wider application of psychometric measurements in clinical routines. We shall discuss options from the field of Neuropsychiatry and Psychotherapy to improve collaborative approaches for the treatment of such complex comorbidities. Disclosure: Nothing to disclose

D.B. Vodušek

Ljubljana, Slovenia

Background and purposes: Communication is an important component of patient care, and the single most important aspect of managing sexual dysfunction. Building the patient-doctor relationship with compassion and shared respect is a prerequisite for effective communication. Communication skills and the psychosocial dimensions of patient care should be tought in medical schools and residency programmes. Patient centered care is defined as a consultation focused on the patient in a holistic manner, incorporating patient preferences and social context (rather than limiting focus to a disease or a body part). In the patient centered interview the patient’s concerns (fears, symptoms, perspectives, values …) and information needs are of primary importance. There is increased awarenes among health professionals that sexual issues are dominant issues related to quality of life in chronic disease. Sexual problem identification should be regarded as a necessary aspect of medical care. The extent of the initial sexual inquiry should be individualized, based on the clinical setting, patient characteristics and type of visit. If a good screening sexual history is routinely elicited, the patients may be sensitized to a number of issues which he or she might not have been aware; if concerns about sexual functioning arrive in the future, the patient will feel more comfortable discussing them. The benefits for both patient and clinician exceed the costs in time and effort when a screening sexual history is obtained routinely. Nurses are particularly important in promoting sexual help and assessing and documenting the patient experience of sexuality with chronic (neurologic) disease. Disclosure: Nothing to disclose.


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SPS05-2

Monday, 30 May Special Session 5 PAUNS/EAN Neuromediterranean Session: Infectious diseases SPS05-1 Life-threatening infections of the central nervous system: time matters for optimal antimicrobial and adjunctive therapies E. Schmutzhard

Innsbruck, Austria

Background and purposes: In severe bacterial meningitis, cerebral malaria or viral (e.g. HSV I) encephalitis a delay in initiating the appropriate antimicrobial chemotherapeutic agent for merely 2 hours, let alone for more, increases both morbidity and mortality significantly. This aspect has been known for long and has been confirmed in several prospective studies. Equally, critical care management is essential to improve outcome in patients with acute, lifethreatening infections of the nervous system. In this presentation various the current knowledge on critical care management modalities, e.g. osmo-therapy, ICP monitoring, CPP monitoring, decompressive craniectomy, temperature monitoring and -management in severe CNS infections, leading to qualitative or quantitative impairment of consciousness or refractory status epilepticus, amongst others, will be critically reviewed. Similarly, the choice of the appropriate antimicrobial chemotherapeutic agent has to be as correct as possible, i.e. it depends on the expected pathogenic germ, the expected local/regional resistance pattern and the way of application. In view of the most recent publications on ICP/CPP management, temperature management, decompressive craniectomy etc. it is, by now, widely accepted that every patient with acute, sever and potentially life-threatening infection of the central nervous system needs – beside the quickest possible and best possible empirical antimicrobial chemotherapy – the quickest possible admission to a neurocritical care unit allowing for the earliest possible and best neurocritical care management. Disclosure: Nothing to disclose.

Infectious neuropathies N. Birouk

Rabat, Morocco

Background and purposes: Infectious neuropathies are heterogeneous regarding their multiple causes and numerous clinical presentations. They still represent an important world health issue. The infectious agent can involve the peripheral nerve directly or indirectly by autoimmune and/ or inflammatory process. The HIV related neuropathy became the major complication of HIV infection. The most frequent form is the painful distal and symmetric polyneuropathy; it can be either HIV induced or antiretroviral toxic neuropathy. Inflammatory neuropathies such as acute or chronic polyradiculoneuropathies can be encountered at early stage of disease. Peripheral neuropathy in patients with chronic infection with hepatitis C virus is mainly due to associated cryoglobulinemia and vasculitis that leads to acute or sub acute mononeuritis multiplex. The polyneuropathy in this context can be also induced by direct neurotoxic effect of the treatment. In Lyme disease the involvement of peripheral nerves is part of meningoradiculitis with frequent involvement of cranial nerves. The incidence of leprosy decreased in last years but the disease is still present in some countries. It can be associated with mononeuropathy multiplex involving mostly small nerve fibers. The most frequent infectious neuropathy in the world remains an active infectious ganglioneuritis caused by varicella zoster virus, producing shingles. Infectious diseases are an important part of differential diagnosis of peripheral neuropathies because most of them are potentially treatable. The systematic diagnosis tests for the most frequent ones such as HIV and hepatitis C is highly recommended in a patient with polyneuropathy. Other infections are discussed regarding particular clinical presentations and in some geographic areas. Disclosure: Nothing to disclose

SPS05-3 Early neuropathological changes during septic shock F. Chrétien

Paris, France

Background and purposes: Septic shock is a major cause of mortality in intensive care units (Annane et al., Lancet 2005). We found in 40% of survivors a neurological achievement at the shutdown of sedation under the shape of a confusion entering within the framework of a septic encephalopathy or delirium, the latter being associated with higher mortality (Eidelman et al, JAMA 1996). Similarly, septic shock is an independent risk factor for progression to dementia disorders compared with other pathologies of resuscitation (Hiwashina, Ely et al., JAMA 2010). It was suggested that alterations of the blood-brain barrier (BBB), resulting from microglial and endothelial activation (van Gool WA et al., Lancet 2010), could explain these anomalies


Special Sessions

by increasing the passage of inflammatory mediators and neurotoxic substances into the central nervous system (CNS) (Iacobone et al., Crit Care Med 2009). However, there are currently only limited studies on the pathophysiology of sepsis associated encephalopathy. We decided to set up an animal model and to monitor early neuropathological changes during sepsis. For studying microglial cell morphological changes, we developed, an 3D automated tissue imaging system by confocal microscopy coupled to mathematical modelisation for studying microglial cells. Microglial cell are extremely dynamic and their morphology is representative of their function. Due to a complex « dendritic-like » shape, precise morphological cell parameters are not easy to determine. The knock-in mouse model CX3CR1 GFP/+, is extremely useful to visualise microglial cells within the brain parenchyma showing precisely all cell processes in details. In this model, with our approach, we observed a very rapid activation of microglial cells that pre-exist to BBB dysfunction. Disclosure: Nothing to disclose.

SPS05-4 Post-infectious encephalitis N. Mohsen

Tripoli, Lebanon

Background: Post-infectious Encephalitis is usually represented by the acute disseminated encephalomyelitis, but other forms include acute hemorrhagic encephalitis and Bickerstaff brainstem encephalitis. ADEM is an inflammatory demyelinating disease of the CNS with no specific test or biomarker to recognize. It is difficult to distinguish ADEM from MS or NMO in the acute or early phases. MRI and laboratory tests are crucial for diagnostic. In this presentation we review the clinical and paraclinical profile of ADEM and its variants from recent studies and reports with a look on reports from the Middle East and North Africa. We will also discuss current treatment strategies based on latest studies and reports. Disclosure: Nothing to disclose.

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Special Session 6 ILAE-CEA/EAN: Hot topics in epilepsy SPS06-1 Recent advances in structural brain imaging in epilepsies R.K. Kälviäinen Kuopio, Finland

Background and purposes: Structural MRI is the main neuroimaging technique for identification of an epileptogenic lesion epileptogenic lesion. Analysis of MRI data showing epileptogenic lesions in 2740 surgical patients in Bonn, Germany, led to an idea of a specific epilepsy MRI protocol, which is now widely adapted The scans need to be interpreted by an experienced (neuro)radiologist with relevant information about the clinical phenotype. Still, up to 30% of patients with refractory focal epilepsy do not have distinct lesions on MRI and are called MRI-negative. Advances in MRI acquisition including diffusion-weighted imaging, post-processing techniques, and quantification of imaging data increase the accuracy of lesion detection. Hippocampal sclerosis can be assessed with volumetry and T2 relaxometry. Double-inversion recovery, arterial spin labelling and developments in diffusion imaging methods (etc. diffusional kurtosis imaging) increase sensitivity for the detection of focal cortical dysplasia. New significant epileptogenic lesions like temporal anteroinferior encephaloceles have been recognized with better structural imaging techniques. Stereotactic placement of intracranial EEG electrodes is increasingly used in presurgical evaluation in epilepsy. Recently the development of semiautomated computer-assisted planning software has markedly reduced the planning time of electrode placement by calculating quantitative measures of trajectory suitability. This planning requires the integration of multimodal imaging data from CT to show the skull surface, T1-weighted MRI for the grey matter map, and MRA, CTA or T1-weighted MRI with gadolinium enhancement to show the arteries and veins. Disclosure: Nothing to disclose.

SPS06-2 EEG and MEG monitoring in epilepsy S. Beniczky

Dianalund, Denmark

Backround: Recording electromagnetic signals from the brain is one of the most important methods for diagnostic workup of patients with epilepsy. We will summarise the role of these methods in the diagnosis and classification of patients with epilepsy. We will discuss ways to increase the yield of these methods and we will focus on the advances in the electromagnetic source imaging. We will review the most relevant methods and the evidence for the clinical usefulness of electric and magnetic source imaging. Special


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emphasis will be given to the analysis of ictal signals. Disclosure: Nothing to disclose

SPS06-3 Epilepsy and gender G. Luef

Innsbruck, Austria

SPS06-4 Seizures and epilepsy in the aging population H. Stefan

Erlangen, Germany

Backround: Because of increase of aging population in addition to dementia and diabetes epilepsies in the alderly require special attention. Epidemiological studies in industrial countries indeed indicate a marked increase in incidence of epilepsies with aging population. Data concerning charachteristics of patients with epilepsies in the elderly (1st seizure after 65 years of life) were compared starting earlier in 174 patients. Diagnostic criteria including differential diagnosis of nonepileptic seizures are analyzed, video-EEG documentations presented. Aetiology differs in Youger and older patient groups. Parkinson is only found in 0.32% in association with epilepsy. Eldery suffer more from postictal deficits. For drug treatment lamotrigine was used most often. The findings are discussed with regard to choice of treatment and patient care. Disclosure: Nothing to disclose.


Special Sessions

Tuesday, 31 May

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Special Session 8 European reference network SPS08-1 European Reference Network: an EU law E. Terol

Brussels, Belgium

SPS08-2 E-PILEPSY, a pre-ERN pilot netwok of cooperation in epilepsy surgery P. Ryvlin


Background and purposes: E-PILEPSY is a healthcare project funded in 2013 by the Directorate Generale for health and consumers of the European commission (DG-Sanco) with the view to optimize and harmonize epilepsy surgery throughout Europe. It is one of the only two pilot networks of cooperation funded by DG-Sanco, and the only one in clinical neurosciences. These networks of cooperation are pilot in that they test and anticipate the potential format of future European Reference Networks (ERN). ERN, which legal framework and objectives are detailed in other abstracts from this session, will be deployed in 2017. E-PILEPSY initially includes 28 partners, including 25 epilepsy surgery centers, the European Epilepsy Monitoring Association (EEMA), the International League Against Epilepsy (ILAE) and the WHO. After two years of activity, E-PILEPSY have gained another 27 European epilepsy surgery centers. E-PILEPSY planned to achieve its objectives by developing several web-based tools, inlcuding: 1) a website primarily targeting patients with epilepsy, their family and primary care giver, to provide them with fair information on epilepsy surgery (http://www.e-pilepsy.eu/), including an E-Eligibility tool to self-assess appropriateness for pre-surgical meeting, 2) an IT platform offering neurophysiological and neuroimaging post-processing tool (E-Processing), 3) a E-Neuropsych tool offering web-based neuropsychological assessment, 4) an E-Care visioconference meeting organised monthly to discuss complex epilepy surgery cases, and 5) a E-Database to capture all relevant information regarding patients entering pre-surgical evaluation. The E-PILEPSY network will consolidate a self-sustained activity, offering all above services to European epilepsy surgery centers committing to the network activity. Disclosure: Nothing to disclose

Merging rare and complex diseases in a neurologically driven ERN H. Cross


Background and purposes: Over the past two years a pilot network has been developed for increasing awareness and accessibility to epilepsy surgery for adults and children across Europe (www.e-pilepsy.eu). This has developed e – tools to aid referral and presurgical evaluation of patients (eg e-neuropsych, e-postprocessing, e-ligibility, e-guidelines) as well as platforms for multidisciplinary discussion and patient documentation. As part of the new procedures recently defined by the EU call for European Reference Networks, discussion has been ongoing about the possibility of expanding the network incorporating all health providers in Europe with an internationally recognized expertise in the diagnosis and treatment of rare and complex epilepsies (Epi-CARE). The epilepsies are now known to be a large group of heterogeneous diseases; with an increasing number with specific diagnosis there is the real possibility for individualised treatments of which epilepsy surgery remains just one. Deliverables of the ongoing ‘e-pilepsy’ project are also being be considered and the relationship between this and the ERN on rare and complex epilepsies (Epi-CARE) defined in collaboration with e-pilepsy coordinators. Such a network however has to be reviewed and coordinated in the wider context of the broad theme of rare neurological diseases, for which there are several existing parallel networks, and consideration given as to how different centres will be recognised and contribute. The over-riding objective remains one of furthering our understanding of these rare conditions, and enhancing patient care. Disclosure: Nothing to disclose.


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SPS08-4 ERN and cross-border healthcare in Neurology: the patient's point of view A. Little

Dublin, Ireland

Background: European Reference Networks (ERN) hold great promise for improved treatment and care for patients with rare and complex diseases. This is particularly the case in less densely populated European countries where the provision of highly specialised healthcare that patients require may not be available because of the low prevalence of their particular disease. The European Federation of Neurological Associations (EFNA), as a pan-European group of patient organisations, is well placed to recognise the benefits that could be on offer to patients across a wide spectrum of rare neurological disease areas. We strive to add capacity to our members to allow them to be the most effective advocates possible in their own disease specific areas. We embrace the concept of Partnership for Progress – working at a high level with relevant stakeholders from all relevant fields. As a European network of associations, some representing neurological diseases with high prevalence rates, others representing rare conditions, EFNA offers excellent potential to support patient-centric care and empowerment. We have a wealth of unique expertise and experience that can help maximise the inclusion of patients with rare diseases in the development of ERNs. We recognise that a high level of involvement of patients in the decision and opinion-making processes is essential to ensure the successful development of ERNs. Low prevalence added to complexity of rare diseases, and limited experience and expertise in the field, renders the role of rare disease patients, being experts in their own disease areas, as vital in the development of ERNs. Disclosure: Nothing to disclose

Special Session 9 Shared decision making in neurology SPS09-1 SDM as the concept for medicine of the 21st century - chances and challenges N. Donner-Banzhoff Marburg, Germany

Background: Neurology is perhaps the medical discipline which has changed most dramatically over the last 30 years. Previously a field with a strong diagnostic emphasis, there are now effective pharmacological treatments available for most patients. Treatments are either prescribed for symptomatic relief or for long-term modification of the disease process. While the former can be immediately evaluated by each patient, the effect of the latter is abstract or even negative, such as the prevention of relapse. The lack of immediate effect, often in combination with side-effects, makes patients question the value of their treatment. Many become non-adherent. While clinical guidelines have traditionally been prescriptive, they do not prepare clinicians sufficiently to answer their patients’ questions. Shared decision-making (SDM) requires clinicians to present relevant, mostly quantitative information on benefit and harm in an unbiased and easy to understand way. To fulfil this task, decision aids (DAs) have been developed. They present evidence-based information on prognosis, benefit and harms of treatment. Computerized, interactive devices help present quantitative effects in numerical, verbal and graphical form. Algorithms incorporating risk or prognostic factors help tailor predictions to the individual patient. Lastly, patients and clinicians can be prompted to reflect on values attached to possible outcomes. There is now a reliable evidence base for DAs and communication according to the SDM philosophy. Despite progress being made in this area, implementation of DAs and the related competences and attitudes of clinicians is still far from satisfactory. Disclosure: Nothing to disclose


Special Sessions

SPS09-2

SPS09-3

SDM in multiple sclerosis treatment decision making

SDM in Parkinson treatment choices

C. Heesen

Nijmegen, The Netherlands

Hamburg Germany

Background: MS treatment is one of the most rapid developing therapeutic areas in neurology. However, treatment remain partially effective and risks increase with efficacy. People with MS are confronted with a bunge of uncertainties starting with giving a definite diagnosis, having a prognostic estimate and reasoning about treatment effectiveness in given cases. As well the evidence for treating relapses with steroids is juts shortening time on relapse but not effecting long-term outcome. On the other hand treatment adherence rates are as low as 30-50% for firstline drugs as injectables. Therefore, decisions in MS should be made strongly preference sensitive. A couple of studies since 2004 have shown, that MS patients want to be actively involved in health care decisions, they appreciate extended information, they are able to understand and perform basic statistical calculations as absolute risk reductions. Furthermore, risk attitudes seem to differ compared to their physicians. This has been demonstrated in risk evaluations of JC-virus infections under natalizumab treatment. A multilingual risk knowledge tool has been validated in 7 countries showing substantial knowledge differences between countries. Based on evidence-based patient information modules, randomized trials have shown that the percentage of informed choices can be increased and treatment adherence enhanced as well as steroid usage patterns altered. Current work investigates decision coaching by MS nurses and web-based support modules. A multilingual risk knowledge tool has been validated in 7 countries showing substantial knowledge differences between countries. Disclosure: Nothing to disclose.

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F.A.P. Nijhuis

Background:In every stage of Parkinson’s disease (PD) treatment decisions must be made. Evidence-based medicine integrates best research evidence with clinical expertise and patient values to achieve the best possible patient management. Therefore, to reach an evidence-based treatment choice, shared decision-making (SDM) plays a vital, but too often neglected role. Though SDM is rapidly gaining interest in medical research and clinical practice, in the field of PD, SDM is still in its infancy. Interventions: While SDM interventions are not frequently reported in PD, closely related interventions to empower patients are, for example patient-reported outcome tools, patient experience questionnaires, and Online Health Communities. One of the striking findings from patient experience questionnaires is the quest for more active involvement in decision-making. To address this, we have designed two decision aids (DA) to improve SDM in PD for two important decisions; starting medication after diagnosis and choosing a treatment in the advanced stage. Results: Designing the DAs started with several studies on the role of SDM in current clinical care, from the perspective of neurologists and PD patients. We are now testing the DA for advanced therapies in a feasibility study. Possible barriers and facilitators for the implementation of SDM become apparent, of whom some are specific for PD, such as limited decision-making capacities in PD patients. Conclusions: SDM is vital in evidence-based practice, although in PD it has not given much attention yet. The DAs under construction will stimulate SDM and thereby improve evidence-based practice in PD. Disclosure: Abbott, Apotheekzorg, and Medtronic funded studies but had no influence on study design, data interpretation, or reporting. I have no other conflicts of interest.


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SPS09-4 SDM in stroke acute care and secondary prevention C. McKevitt


Background: Shared decision making represents a bridge between two contemporary impulses: an ethical position which rejects medical paternalism in favour of an ‘empowered’ patient with the right to choose preferred treatment options; and evidence based medicine which, being scientifically grounded, promises care that is both effective and cost-effective. Research into shared decision making practices and outcomes suggests that there are many unanswered questions about methods, benefits, and the wider implications of adopting this approach to clinical care. This paper focuses on shared decision making in relation to stroke across three phases of the patient journey: acute presentation when decisions about thrombolytic therapy arise; sub-acute rehabilitation where shared decision making may assume the particular forms of goal setting and self-management; and on-going clinical management, usually in primary care settings, to reduce the risk of stroke recurrence. The paper draws on theoretical and empirical literature, and studies from the South London Stroke Register. It provides an overview of the current picture of shared decision making in stroke. By considering the clinical and social contexts in which stroke is managed and experienced, the paper highlights factors that may complicate shared decision making for this condition. Disclosure: I acknowledge the support of King's College London and the National Institute of Health Resaerch Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London.

Special Session 10 RRFS Session-Prospects for neurologists in training in three corners of Europe SPS10-1 Prospects for young neurologists in the Nordic countries D. Kondziella

Copenhagen, Denmark

Background: The Nordic countries comprise Iceland, Finland and the 3 Scandinavian monarchies Denmark, Sweden and Norway as well as the autonomous regions Greenland, the Faroe Islands (Denmark) and Åland (Finland). The total population is around 26 million people who enjoy one of the highest living standards world-wide. In line with this, neurology services are well-established although they may be geographically widespread, particularly outside the capital and university cities. This talk will focus on residency programs in Denmark, Sweden and Norway. In general, residency programs are wellorganized and cover 5 years of training, including obligatory rotations in neurosurgery and (except for Norway) psychiatry. Of note, Scandinavian countries have a wellearned reputation for offering family-friendly working conditions and fortunately, this also applies to neurology residencies. Disclosure: Nothing to disclose

SPS10-2 Neurology Education in Western Europe E. Moro

Grenoble, France


Special Sessions

SPS10-3 Neurology Education in Central and Eastern Europe I. Szocs

Budapest, Hungary

Background: Having in view the ever-growing integration of the medical-job market across European countries, the need for standardizing neurological training is ever higher. The length of neurological residency ranges from 3 to 6 years accross Central and Eastern European countries. The extent of neuroimaging or neurosurgery rotation varies considerably. What figures in the curricula of trainees is even more diverse: internal medicine, intensive care, psychiatry wards are visited in most countries. Attending a facility for rehabilitation or infectious diseases is not required in each case. The curriculum is frequently changed resulting in a dissimilar level of competence of neurologists within the same country. The expectations toward a trainee to demonstrate practical skills, neurophysiology or ultrasound techniques during the board examination vary widely. The board examination itself is also considerably different being only written in some countries, requiring assessment of several clinical cases in others. Some countries do not have a board examination at all. Rotation in an outpatient clinic is not requiered in some, while it’s obligatory in other countries. In most, the hospital rotation outweighs by much the stay in the out-patient clinic. What’s even more stunning, some countries do not require obligatory hospital rotation. Training programmes vary widely between and within Central and Eastern European countries. This diversity could explain some of the discontent and frustration of our trainee colleauges met during several surveys. It could also have a negative impact on quality control of neurological education and competence of residents resulting in poorer patient care. Disclosure: Nothing to disclose.

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Special Session 11 History of Neurology SPS11-1 A short introduction to the history of Scandinavian neurology: from the sagas to the Nobel prizes R. Stien

Oslo, Norway

Background: 5000-year-old trepanned skulls and signs of chronic neurological diseases in the skeletons in the Viking graves show that neurological conditions were recognised and treated in ancient times in Scandinavia. Numerous Nordic sagas (chronicles) mention neurological diseases, their treatment and even some first descriptions of conditions much later acknowledged as neurological entities. Later the most prominent researchers were the Danish medical family Bertelsen (Bartholin) and their pupil Niels Stensen (Nicolaus Steno). In the 19th century neurology developed from internal medicine in Sweden, from electrotherapy in Norway, from pathology in Finland and from psychiatry in Denmark. Academic chairs in clinical neurology were established in Sweden in 1887, Norway in 1893, Finland in 1918, Denmark in 1934 and Iceland in 1974. Well-known diseases with well-known eponyms were described in Scandinavia long before the naming publication. Scandinavian eponyms are later linked to a variety of neurological diseases like: Følling, Wohlfart, Kugelberg, Wellander, Refsum and Krabbe. During the last century the Scandinavian contribution to neuro-science has been important. In Denmark main fields have been cerebral circulation and multiple sclerosis, in Finland neuro-genetics and neuropathology, in Iceland neuro-genetics and “slow virus infections”, in Norway neuroanatomy and neurophysiology and in Sweden neuro-pharmacology and movement disorders. The Scandinavian high standard of neuro-science has led to Nobel prizes in physiology and medicine: Ragnar Granit 1967 (Finland/Sweden), Arvid Carlsson 2000 (Sweden) and May-Britt and Edvard Moser 2014 (Norway). Disclosure: Nothing to disclose.


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SPS11-2

SPS11-4

Nicolaus Steno, Discours on the Anatomy of the Brain, Paris 1665, with a new programme for brain research

The regional CBF changes during migraine attacks

T. Kardel

Glostrup, Denmark

Copenhagen, Denmark

Background: Niels Stensen, or Nicolaus Steno, is known for his Discourse on the Anatomy of the Brain[1] delivered in Paris 1665 and published in 1669. The Discourse contains anatomical plates with cross-sections from a human brain and a critique of speculative theories on the brain’s function just published by René Descartes and Thomas Willis.[2] Thus, Descartes held that there is one single centre of cognition seated in the pineal body. Steno provides a new program for research to obtain certain knowledge on brain function from anatomical findings. He stresses the infinity of researches to be undertaken on men and in animals and in foetal states. Special attention, he says, is necessary when working on such delicate pieces to undeceive those who keep to what they find in the books of the Ancients. He concludes that we shall always remain in a miserable ignorance if we content ourselves with the little light the Ancient left us and if the men most prone to make research do not join their works and their industry. Less known is his Letter on a Calf with Hydrocephalus studied in 1669 at Innsbruck. The letter was published in Copenhagen.[3] Its format is strikingly similar to a case report in our time. See poster. The author declares that only by autopsy he could demonstrate that a disease in the foetus itself was the cause of deformities that would otherwise be attributed to the imagination of the mother, in this case a cow. Disclosure: Nothing to disclose.

J. Olesen

Background: 50 years ago nothing was known about regional cerebral blood flow (rCBF) or the diameter of the brain arteries during migraine. But from 1965 onwards the Danish professor Niels Lassen developed ever improving methods for the measurement of rCBF. The first studies using these methods demonstrated reduced rCBF during attacks and seemed to confirm the then generally accepted ischemic hypothesis of migraine but with more spatial resolution it was shown that the reduced flow spread gradually and was more compatible with cortical spreading depression (CSD). Furthermore, headache occurred during low flow and subsequent increased flow often outlasted the headache. Regulatory abnormalities also suggested CSD. The changes were confirmed and expanded using single photon computed tomography (SPECT). All these changes were observed only in patients with neurological symptoms and were partly responsible for the clear separation between migraine with aura and migraine without aura that came later. All the findings have later been confirmed using PET or fMRI. High Ressolution MRA has shown no arterial dilatation of extracerebral arteries but moderate dilatation of intracerebral arteries during migraine attack. Currently studies continue with PET and advanced MR methods. Disclosure: Nothing to disclose.

SPS11-3 Functional mapping of the human brain using regional cerebral blood flow techniques – the early development L. Friberg

Fredriksberg, Denmark



Tournament Session Sunday, May 29 2016 Tournament Basic T101 Cognitive correlates of the brain functional connectome abnormalities in pediatric patients with Multiple Sclerosis E. de Meo1, M.A. Rocca1, L. Moiola2, A. Ghezzi3, P. Veggiotti4, R. Capra5, M.P. Amato6, L. Vacchi1, A. Fiorino7, L. Pippolo8, M.C. Pera4, M. Copetti9, G. Comi7, A. Falini10, M. Filippi1

1Neuroimaging Research Unit, Institute of Experimental Neurology, DIvision of Neuroscience, San Raffaele Scientific Institute, Milan, Italy, 2Department of Neurology, San Raffaele Scientific Institute, Milan, Italy, 3Multiple Sclerosis Study Center, Hospital of Gallarate, Gallarate, Italy, 4Department of Child Neurology and Psychiatry, C. Mondino National Neurological Institute, Pavia, Italy, 5Regional Multiple Sclerosis Center, Presidio di Montichiari, Spedali Civili di Brescia, Brescia, Italy, 6Department of Neurology, University of Florence, Florence, Italy, 7Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 8Centro Studi Sclerosi Multipla, Ospedale di Gallarate, Gallarate, Italy, 9Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, 10Neuroradiology, Università Vita-Salute San Raffaele, Milan, Italy

Background and aims: This study investigated abnormalities of functional organization of large-scale brain networks (connectome) using resting-state (RS) fMRI and graph theory in pediatric multiple sclerosis (MS) patients and their contribution to cognitive impairment. Methods: Fifty-four pediatric MS patients and 27 age- and sex-matched healthy controls (HC) were studied. Patients with abnormal performance in ≥3 tests of a neuropsychological battery for children were classified as cognitively impaired (CI). Functional connectivity between 160 cortical and subcortical brain regions was estimated using a bivariate correlation analysis. Between-group differences of global and local network connectivity metrics were investigated. Results: Global network metrics did not differ between pediatric MS patients and HC and between cognitively preserved (CP) and CI MS patients. Compared to HC, MS patients showed limited differences in hub distribution with the formation of hubs (not present in HC) in the left cerebellar lobule VI and supplementary motor area and the loss of one hub in the left medial frontal gyrus (MFG).

Compared to HC, CP MS patients harboured additional hubs in the left middle temporal gyrus and occipital lobe. Conversely, CI MS patients lost hubs in the right precuneus, right occipital lobe, bilateral thalamus and cerebellum crus I. They also showed additional hubs in the left precuneus and right superior temporal gyrus. Conclusion: The global topology of functional network organization is relatively preserved in pediatric MS patients. Functional abnormalities of local network reorganization play a major role in determining cognitive impairment in these patients. Disclosure: Partially supported by a grant from Italian Ministry of Health (GR-2009-1529671) and Fondazione Italiana Sclerosi Multipla (FISM2011/R/19).

T102 Zinc release and action at excitatory Schaeffer collateral-CA1 pyramidal cell synapses A. Ekmen, A. Vergnano, P. Paoletti

CNRS UMR8197, INSERM U1084, Institut de Biologie de l'Ecole Normale Supérieure, Paris, France

Background and aims: Zinc contained in presynaptic vesicles with glutamate is a neurotransmitter candidate as it has a inhibitory effect on postsynaptic responses. In epilepsy, as in other pathologies linked to glutamatergic transmission dysfunctions, changes in synaptic concentration of zinc has been described. A detailed knowledge of the zinc modulation properties hence presents a potential therapeutic interest. Methods: To investigate synaptic zinc, an electrophysiological approach has been adopted by performing patch-clamp recordings on hippocampal slices. CA1 pyramidal cells have been recorded by stimulating Schaeffer collateral inputs. The exploitation of the knock-in mice (GluN2A-H128S mutant), in which the high affinity zinc inhibitory site of NMDA receptors (NMDAR) has been selectively invalidated, combined with the use of ZnT3 (zinc transporter) knock-out mice and tricine (zinc chelator) allowed to demonstrate that zinc is likely to play an active role as an endogenous modulator of excitatory neurotransmission.

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Tournament Sessions

T103 Modifications of gray matter volume in migraine patients over four years: A tensor-based morphometry study R. Messina1, M.A. Rocca1, B. Colombo2, E. Pagani1, A. Falini3, G. Comi2, M. Filippi1

1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 2Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 3Neuroradiology, Università Vita-Salute San Raffaele, Milan, Italy

Generation and characterisation of the GluN2A-H128S knock-in mice

Results: The research showed that: NMDARs embedded in their native environment are inhibited by low nanomalor zinc concentrations, following short train stimuli, vesicular zinc can be released in the synaptic cleft and sensed by postsynaptic NMDARs and concentrations reached in the cleft following such protocols are in the submicromolar range.

Results-figure2

Background and aims: A previous longitudinal study found grey matter (GM) atrophy of sensory-discriminative brain regions in migraine patients after one year. In this study, we explored longitudinal GM changes over a fouryear follow-up in migraineurs and their association with patients’ clinical characteristics and disease activity. Methods: Using a 3.0 Tesla scanner, brain dual-echo and 3D T1-weighted scans were acquired from 25 migraine patients and 25 healthy controls at baseline and after 4 years. Tensor-based morphometry and SPM12 were used to assess longitudinal changes of GM volumes. Results: 8 patients (32%) reported an increased number of migraine attacks at follow-up. At baseline, compared to controls, migraine patients showed cerebellar GM atrophy and higher volume of regions of the right fronto-temporoparietal lobes. At follow-up, compared to controls, migraine patients had an increased volume of fronto-parietal regions, which was related to a higher number of migraine attacks at baseline (r=0.58, p