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Journal of Neurological Sciences [Turkish] 28:(1)# 26; 101-108, 2011 http://www.jns.dergisi.org/text.php3?id=419 Case Report Omental Transplantation For Amyotrophic Lateral Sclerosis: Case report Hernando RAFAEL1, Rafaela MEGO1, Juan Pedro AMEZCUA2, Wilfredo GARCIA2 1
Sanatorio San Hipolito, Neurosurgery, Mexico city, Mexico 2Instituto Maxicano del seguro social, General surgery and anesthesiology, Mexico city, Mexico
Summary Objective: Up to date,the cause of amyotrophic lateral sclerosis (ALS ) is not known. Several factors have been etiologically linked with this disease, but none of them with ischemia in the anterior horns of the spinal cord, in the pyramids and in bulbar nuclei of the cranial nerves.The goal of the present study was to place omentum on the medullo-spinal junction to a patient with severe ALS Method: A 60-year-old man with a bulbar form of ALS received an omental transplantation on the anterior and right lateral surface of the medulla oblongata.During surgery we found: 1)vascular anomalies; 2) atherosclerosis in both V4 segments of the vertebral arteries;3) several exsanguinated perforating arteries over the surface of the pyramids,and 4) hypotrophy of the anterior surface of the pyramids. Result: Subjective and objective clinical improvement occurred beginning the first day after surgery.This improvement was better during the first days or weeks after operation than in the following months.At present,fourteen months after surgery,the bulbar symptoms have improved by 90% and he can walk at a slow pace with or without assistance. Conclusions: These observations suggests that the bulbar form of ALS is caused by progressive ischemia in the intraparenchymal territory of the anterior-ventral spinal arteries. Because ,in contrast to this, its revascularization by means of omentum produced neurological improvement. Key words: Amyotrophic lateral sclerosis, Anterior-ventral spinal arteries, Anterior spinal artery, Cerebral atherosclerosis, Pyramids, Vertebral arteries Amiyotrofik Lateral Skleroz İçin Omental Transplantasyon Olgu Sunumu Özet Amaç: Bugün için amiyotrofik lateral sklerozun (ALS) nedeni bilinmemektedir. Etyolojik olarak bir çok faktörle bu hastalık arasında bir bağlantı kurulmuştur ancak kranial sinirlerin piramidte ve bulbar nükleusları seviyesinde ve spinal kordun ön köklerindeki iskemisi ile ilgili bir ilinti belirtilmemiştir. Bu çalışmanın amacı ağır bir ALS olgusunda medüllo-spinal birleşke yerine omentum yerleştirilmesidir. Yöntem: Bulbar tipte ALS tanılı 60 yaşında bir erkek hastanın medulla oblangata anterior ve sağ lateral yüzeyine omental transplantasyon uygulandı. İşlem sırasında: 1) damarsal anomaliler, 2)vertebral arterlerin V4 segmentinde ateroskleroz, 3)piramidin yüzeyinde çok sayıda kansız kalan perforatör arterler ve 4)piramidin anterior yüzeyinde hipotrofi gözlendi. Sonuç: Cerrahi sonrası hemen akabinden başlayan objektif ve subjektif klinik düzelme gözlendi.Bu düzelme ilk günler ve haftalarda daha iyi ancak aylar geçtikçe azaldı. Cerrahiden 14 ay sonra bulbusa ilişkin semptomlarda %90’a varan düzelmeler saptandı ve hasta destekle ve desteksiz yavaş adımlarla yürür haldedir.
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Yargı: Bu gözlemler bulbar tip ALS’de antero-ventral spinal arterlerin bölgesel parankim içersindeki ilerleyici iskemisini düşündürmektedir. Omentum ile revaskülarizasyon, bu olayın tersine, nörolojik düzelmeyi sağladı. Anahtar Kelimeler: Amiyotrofik lateral skleroz, Anterior-ventral spinal arterler, Anterior spinal arter, Serebral ateroskleroz, Piramid, Vertebral arterler and weakness in the right lower limb and six months later,weakness in the upper limb. Besides this, he presented, occasionally, fasciculations in the trunk and thighs. Four years before his hospitalization he began with bulbar symptoms(Figure,1) characterized by progressive difficulty in pronouncing words,swallowing and breathing.Sometimes he presented fits of apnea for a few seconds.Moreover,he began with irritability, anxiety ,isolation, depression and aggressiveness. Finally, in the last 6 months he slept almost seated and with help of oxygen,with sensation of constriction of the thorax.These symptoms improved following hyperbaric oxygen therapy for 1 to 2 minutes. He never presented sensory,bladder or rectal disorders.During these years of disease,the patient was attended in the Instituto Nacional de Neurología y Neurocirugía (México ) and in the Centro Internacional de Restauración Neurológica (Cuba),among other neurological centers .In all of them,he was diagnosed of ALS.
INTRODUCTION Up to date, Amyotrophic lateral sclerosis (ALS) is considered a fatal neurological disease that attacks the nerve cells responsible for controlling voluntary muscles.The specific cause of this disease is not known, but about 90 to 95% of all ALS cases are sporadic. Based on anatomical(1,9,21,24,25) and pathological(2) findings, as well as in previous neurosurgical experiences(15,17,18) with omental transplantation on the upper cervical cord and medulla oblongata, we decided to place omentum on the pyramidal decussation to a patient with severe ALS. CASE PRESENTATION A 60-year-old man was admitted to a local hospital in Mexico city,because of difficulty in walking and bulbar symptoms. In 1999, he began with progressive weakness in the left foot, ascending after 8 months to the leg and thigh, and later on, cramps and weakness in the left upper limb. Two years later,he presented cramps
Figure 1: Preoperative course (years)
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V block. Preoperative computarized tomography (CT) and magnetic resonance imaging (MRI) scans showed : 1) moderate cortical atrophy in frontal lobes; 2) moderate dilatation of the frontal horns of the ventricular system;3) atherosclerosis at the supraclinoid carotids, basilar artery and V4 segments of the vertebral arteries (VAs ),and 4) doubtful zones of microinfarcts in the cervical cord and medulla oblongata (Figure,2 ).Two electrodiagnostic tests revealed denervation, fasciculations and poor motor neuroconduction in several peripheral nerves.Neurological data suggestive that the primary cause of these pyramidal and bulbar syndromes are of ischemic origin initiated in the anterior surface of the pyramidal decussation (right pyramid and later on, in the left pyramid) ( Figure,3). That is, a bulbar form of ALS. In August 2009,an omental transplantation was proposed to the patient and his family.Before surgery,the patient´s status was recorded on videotape.
Past and family history. The patient had been a chauffeur and cigarette smoking since 20 to 50 years (about 1/2 packet per day).Likewise between 40 to 50 years of age, he was a car mechanic and was exposed to organic solvents. In July 2005, he was diagnosed of essential arterial hypertension (EAH), and his blood pressure varied between 135/85 and 150/100 mmHg, which was treated with enalapril and occasionally,sublingual nifedipine. In June 2008,he was diagnosed of type 2 diabetes mellitus (DM) and received 1/2 tablet of bieuglucon M per day and a food regime.His glycemias varied between 115 and 240 mg per cent (Figure, 1). There was no family history of neurodegenerative diseases. Examination. The patient appeared older than his age and was lucid. He came to the hospital walking at a slow pace and with help of a walker. His arterial pressure was 140/90 mm Hg, heart rate 82 /min and respiratory rate 24 min. The respiration was superficial and of the abdominal type. Hemoglobin 16.3 gr %,glucose 122 mg %,total cholesterol 204 mg %, triglycerides 104 mg %,urea 31 mg% and creatinin 0.90 mg %. He presented slight bilateral peripheral facial paresis, severe dysarthria ,severe weak voice(he be heard to 35 cm), hypotonic uvula and soft palate,moderate impairment of the nausea reflex,fasciculations and moderate paresis of the tongue.Third-degree spastic tetraparesis of the upper limbs and seconddegree of the lower. Paresis in the fingers and toes.He showed hyperreflexia in the upper and lower extremities,and bilateral Hoffmann and Babinski signs. Slight muscular atrophy in the lower limbs,and in contrast,absence of atrophy in the small hand muscles. The superficial and deep sensory signs were normal.
Operation. With the diagnosis of progressive ischemia in the pyramidal decussation,an omental transplantation was performed on 29 th August 2009,without complications.The upper cervical cord and medulla oblongata were located through a laminectomy at the C1-C2 level. During surgery we made 5 important observations: 1) moderate hypoplasia in the V4 segment of the right VA; 2) absence of the right anterior-ventral spinal artery (AVSA) ;3) moderate atherosclerosis in both V4 segments of the VAs ;4) several exsanguinated circumferential and perforating arteries over the surface of the pyramids, and 5) hypotrophy of the anterior surface of the pyramids. The neurosurgical procedures for omental transplantation (free omental graft ) was carried out according to a technique described in earlier reports(15,17,18).Briefly, an end-to-end anastomoses by invagination between right occipital vessels and the gastroepiploic vessels were performed.Afterwards, a small segment of
A chest X-ray showed aortic and cardiac hypertrophy (degree I ) as well as diffuse interstitial pulmonary fibrosis. The electrocardiogram revealed first-degree A-
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of the accesory nerve by below(19), and placed on the anterior,right lateral and posterior surface of the medulla oblongata.
omentum was passed between the right cranial root of the eleventh nerve by above, and the posterior root of C1 and spinal root
Figure 2: Preoperative MRI scan without contrast,showing the presence of doubtful zones of microinfarcts in the cervical cord and medulla oblongata.
Figure 3: Schematic diagram ilustrating the pyramidal decussation and tracts,as well as the bulbar nuclei of the cranial nerves and anterior horns of the cervical spinal cord.A1/C1 and A2/C2 cell groups. A1 and A2 noradrenergic groups. NTS, nucleus tractus solitarii. NA,nucleus ambiguus. DMNV,dorsal motor nuclei of the vagus. DAP,descending autonomic pathways.CRC,cardiovascular reflex center (commissural portion of the NTS ).
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Postoperative course. On the first postoperative day, facial expression, swallowing, voluntary movement of upper limbs and breathing improved by 30% ,and three days later, voluntary movement of upper limbs improved by 60$ and in lower extremities by 30%. Besides this, the intensity of the voice,dysarthria,respiration ,swallowing ,movement of the tongue and voluntary movement of his extremities improved by 70%.This postoperative picture was recorded on videotape. Six weeks after surgery,he could walk at slow pace without assistrance up to several meters. Moreover, the fits of apnea disappeared and his blood pressure was normalized (mean value,115/80 mmHg ). Postoperative CT scans (October 15,2009) showed omentum in the inferior part of the pontine cistern, magna cistern and on the right lateral surface of the medulla oblongata(Figure,4).
Figure 4: Postoperative CT scan without contrast obtained 6 weeks after surgery,showing the presence of omental tissue in the pontine cistern, right lateral surface of the medulla oblongata, magna cistern and behind the occipital bone.Cortical atrophy in the frontal-parietal lobe and ventricular dilation.
At present(October 2010),fourteen months after the operation,his blood pressure is 135/80 mm Hg,heart rate 82/ min, respiratory rate 18 / min and his respiration of the thoracic type.His blood glucose varies between 115 and 216 mg% and he receive antidiabetic treatment. The intensity of voice (to be heard to several meters of distance),dysarthria,swallowing and movement of the tongue have improved by 90 %.The motor evaluation in the upper limbs is of degree 4-5 and in lower limbs of degree 3. Spasticity has diminished. He can walk at a slow pace with or without assistance.He receive aspirin 500 mg per day and 1 mg of clonazepam at night.
DISCUSSION The onset of the symptoms in our patient was insidious,course undulating (periods of clinical improvement alternated with those of worsening) and progressive. The disease began in the anterior surface of the pyramidal decussation,especially in the antero-lateral portion of the right pyramidal tract (Figure, 3) and six years later (Figure, 1),in both nucleus ambiguus, the hypoglossal nuclei,the dorsal motor nuclei of the vagus(DMNV), the facial nuclei, the A1/C1 cell groups, the bulbar
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Thereby,the gait and cognitive impairment in persons with moderate or severe ALS is related with the frontal atrophy and ventricular dilation (Figure.4).
respiratory centers,and the ventrolateral (dorsal respiratory groups) and commissural (cardiovascular reflex center,CRC) portions of the nucleus tractus solitarii (NTS)(19). That is, in the intraparenchymal territory of the short (average diameter of 0.25 mm) and long (average diameter of 0.40 mm ) branches originated from the AVSAs (mean diameter of 0.75 mm),as well as of many minute arteries less than 0.10 mm in diameter perforating the pyramids directly from the AVSAs(1,11,21).Therefore, the symptoms were directly related with the absence of the right AVSA and atherosclerosis in both V4 segments of the VAs.So then, this region of the lower brainstem and upper cervical cord seems that is the most affected part in patients with sporadic ALS(4).
On the other hand ,in addition to the progressive deterioration in the motor nuclei of the cranial nerves VII, IX,X,XI and XII; the disappearance of the fits of apnea and normalization of EAH since the immediate postoperative, it suggests that both of them symptoms were also caused by progressive ischemia(19,20) in the bulbar respiratory centers, the DMNV (its activation produce bronchial constriction), the ventrolateral portions of the NTS ,and the A1/C1 cells groups and CRC of the NTS related with EAH ,as we schematize in the Figure, 3. The omentum is the best tissue for developing vascular connections with underlying and adjacent zones through(6,16,20):First,anastomoses between the omental blood neovessels with the small leptomeningeal vessels, and second, other omental neovessels which pass through the omental-brain interface and penetrate vertically and deeply in the underlying brain.So that, the pyramids and surrounding areas receives an increase in blood flow,oxygen, neurotransmitters,neurotrophic factors, adipocytokines and omental stem cells(8,16,23). Thus an increase in blood flow and oxygen stimulates the cycle of Krebs in the neuroglia and neurons into affected nervous tissue.Therefore,our neurosurgical technique provide from the first,a revascularization (since the 6 hours after surgery) in the ischemic zone and later on, adult mesenchymal stem cells for differentiating into multiple cell types including neuroglia and neurons.
After surgery,the results were similar to other previous observations in patients with ischemic injury in the encephalon or spinal cord(5,13,15,17,18,20), ie, neurological improvement was better during the first days or weeks after the operation than in the following months. Observation suggestive that the functional recovery is directly related with the quantity of residual nervous tissue in ischemia and ischemic penumbra in the lower brainstem,especially in the pyramids(constituted by pyramidal axons of the upper limbs,trunk, and lower limbs) and bulbar nuclei. Normally each one of the two pyramidal tracts at a level just rostral to the decussation is formed by slightly over one million axons(9). Therefore, the hypotrophy in the pyramids suggest a reduction in the number of pyramidal fibers and thus, to cause Wallerian and retrograde degeneration,as well as transneuronal degeneration(3) in the frontal lobes and motor neurons in the anterior horns of the spinal cord .In other words, the severity of involvement in the frontal, temporal and parietal white matter is correlated with severity in the pyramidal tracts(7,14,22).
For these reasons we believe that an omental transplantation on the medullospinal junction for the treatment of the bulbar form of ALS is better than a single injection of stem cells to the anterior part of the upper cervical cord(4), and still more, that the autologous transplantation of stem 106
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cells in the frontal motor cortex(12) or the intravenous administration of stem cells(10). Because first, the affected zone should be revascularized through the omentum and thus, the intraparenchymal territory of the AVSAs and anterior spinal artery(ASA) with a mean diameter of 0.80 mm( range 0.34 to 1.12 mm)(11,25) receives blood flow,oxygen neurotrophic factors,adipocytokines and omental stem cells.Likewise,the omentum placed on the right lateral and posterior surface of the medulla oblongata can revascularize to the A1 and A2 noradrenergic neurons, the CRC and the right descending autonomic pathway(DAP) related with EAH.
Received by: 15 June 2010 Revised by: 22 October 2010 Accepted: 30 November 2010
The Online Journal of Neurological Sciences (Turkish) 1984-2011 This e-journal is run by Ege University Faculty of Medicine, Dept. of Neurological Surgery, Bornova, Izmir-35100TR as part of the Ege Neurological Surgery World Wide Web service. Comments and feedback: E-mail:
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Likewise the progressive spinal muscular atrophy (PSMA)(2), a spinal form of ALS , especially the Aran-Duchenne syndrome may also be caused, essentially, by a progressive reduction of the blood flow in the anterior radicular arteries (anastomotic branches with the ASA between the C5 to T1 level )(25), which are originated from deep muscular branches of the thyrocervical and costocervical arteries;due to vascular anomalies and/or atherosclerosis in the vertebral-subclavian junction. In such a way that,an omental transplantation on the anterior and lateral surface of the cervical cord (at the C5-6 level) could be the more advised.
REFERENCES 1.
2. 3.
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CONCLUSION The present result indicate that the bulbar form of ALS and possibly the spinal form (Aran-Duchenne syndrome),both of them are caused by progressive ischemia in the intraparenchymal territory of the AVSAs or ASA(at the C5 to T1 level), respectively. Because its revascularization by means of omental tissue produced neurological improvement.However,large trials are needed to confirm these findings.
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Correspondence to: Hernando Rafael E-mail:
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Akar ZC,Dujovny M,Gomez-Tortosa E,Salavin KV,Ausman JI. Microvascular anatomy of the anterior surface of the medulla oblongata. J Neurosurg 1995;82;97-105 Alpers BJ. Clinical neurology. Fifth edition. Chapter 19. Philadelphia,Davis Co 1963,pp 866-907. Blackwood W. Normal structure and general pathology of the nerve cell and neuroglia.In,Blackwood W, Corsellis JAN(eds).Greenfield´s Neuropathology.Third edition.London,Edward Arnold 1975,pp 1-42. Deda H,Inci Mc,Kurekei Ae,Sav A, Kayihan K,Ozgun E,et al. Treatment of amyotrophic lateral sclerosis patients by autologus bone marrowderived hematopoietic stem cell transplantation:a 1year following-up.Cytotherapy 2009;11(1):18-25. Goldsmith HS,Neil-Dwyer G,Barsoum L. Omental transposition to the chronically injured human spinal cord. Paraplegia 1986; 24;173-174 Goldsmith HS.The omentum:present status and future applications.In Goldsmith HS(ed).The omentum:Research and clinical applications.New York,Springer-Verlag 1900,pp131-145. Ishikawa T,Morita M,Nakano I.Constant blood flow reduction in premotor frontal lobe regions in ALS with dementia:A SPECT study with 3D-SSP. Acta Neurol Scand 2007;116(5): 340-344 Kowalczyk P,Olkowski R,Sienkiewicz.Latka E,Lisik W,Sinski M,Kosicradzki M,et al. Human omentum majus as a potential source of osteogenic cells for tissue engineering(preliminary report) Ann Transplant 2004; 9(suppl 11):61-63.
J.Neurol.Sci.[Turk]
9.
10.
11.
12.
13.
14.
15.
16.
Lassek AM, Rassmussen GL.The human pyramidal tract: A fiber and numerical analysis.Arch Neurol Psychiat(Chicago ) 1939;42:872-876. Lunn JS,Hefferan M,Marsala M,Feldman E. Stem cells :Comprehensive treatment for amyotrophic lateral sclerosis in conjunction with growth factor delivery.Growth Factors 2009;27(3):133-140. Marinkovic S,Milisavljevic M,Gibo H,Matikovic A,Djulejie V. Micorsurgical anatomy of the perforating branches of the vertebral artery. Surg Neurol 2004;61(2):190-197. .Martinez H,Gonzales-Garza M,Moreno-Cuevas J,Caro E,Gutierrez-Jimenez E,Segura J. Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients. Cytotherapy 2009;11:26-34. Nagashima Ch,Masumori Y,Hori E,Kubota S, Kawamura S,Shimada Y,et al. Omentum transplantation to the cervical cord with microangioanastomosis.No Shinkei Geka(Jpan) 1991;19:309-318. Palm WM,Saczynski JJ, Van der Grond J,Sigurdsson S,Kjartansson O,Jonsson PV, et al. Ventricular dilation:Association with gait and cognition. Ann Neurol 2009;66(4):485-493. Rafael H. Cervical spondylotic myelopathy:Surgical results and factors affecting outcome with special reference to age differences.Neurosurgery 2003;53(39:787-788. Rafael H. Aplicación clinica del epiplón en el sistema nervioso central. Acta Med Per 2008;25(3):176-180.
17. Rafael H.Brainstem ischemia .J Neurosurg:Spine 2009;11:88-90. 18. Rafael H,Mego R,Amezcua JP,García W. Transplante de epiplón para neurálgia occipital primaria. Acta Med Per 2009;26(2):92-94 19. Rafael H. Nervios Craneanos. Tercera edición. México,DF:Editorial Prado ,2009,pp 147-245. 20. Rafael H,Ayulo V, Mego R. Trasplante de epiplón sobre la bifurcación carotídea en contra de la hipertensión arterial esencial. Rev Mex Cardiol 2010; 21(1):19-24 21. Santos-Franco I, de Oliveira E,Mercado R,OrtizVelazques I,Revuelta-Gutierrez R,Gómez-Llata S. Microsurgical considerations of the anterior spinal and anterior-ventral spinal arteries.Acta Neurochir(Wien) 2006;118(3):329-339. 22. Senda J,Ito M,Watanabe H,Atsuta N,Kawai Y,Katsuno N, et al.Correlation between pyramidal tract degeneration and widespread white matter involvement in amyotrophic lateral slcerosis:A study with tractography and diffusion-tensor imaging. ALS 2009;10(5):288-294. 23. Schipper BM,Marra KG,Zhang W,Donnenberg AD,Rubin JP. Regional anatomic and age effects on cell function of human adipose-derived stem cells. Ann Plast Surg 2008;60(5):538-544. 24. Stopford JSB. The ateries of the pons and medulla oblongata.J Anat 1916;50:255-280 25. Suh T,Alexander L.Vascular system of the human spinal cord. Arch Neurol Psychiat (Chicago) 1939; 41:659-677.
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