Clinical aspects, neuroimaging, and

Epilepsy & Behavior 80 (2018) 184–190

Contents lists available at ScienceDirect

Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh

Clinical aspects, neuroimaging, and electroencephalography of 35 cases of hemiconvulsion-hemiplegia syndrome Mohamed Albakaye a,d,⁎, Halima Belaïdi a, Fatiha Lahjouji a, Leila Errguig a, Callixte Kuate b, Youssoufa Maiga c, Seybou Hassane Diallo c, Najib Kissani d, Reda Ouazzani a a

Clinical Neurophysiology Department, Specialty Hospital, Rabat, Morocco Neurology Department, Hospital Laquintinie, Douala, Cameroon Neurology Department, Gabriel Touré, Hospital, PO Box 267, Bamako, Mali d Neurology Department, CHU Mohammed VI, Marrakesh 40000, Morocco b c

a r t i c l e

i n f o

Article history: Received 29 July 2017 Revised 17 December 2017 Accepted 18 December 2017 Available online xxxx Keywords: Hemiconvulsion-hemiplegia Epilepsy syndrome Febrile

a b s t r a c t Introduction: The hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare consequence of febrile seizures during childhood. It is characterized by the presence of prolonged unilateral clonic seizures occurring during febrile illness in a child less than 4 years of age. Then, a flaccid unilateral hemiplegia with variable duration occurs. Objectives: The objective of the study was to describe the clinical, electroencephalogram (EEG), and neuroimaging treatment and outcome of series of cases of HHE syndrome followed for 10 years in our clinical neurophysiology department of the specialty hospital of Rabat. Patients and methods: We report a retrospective study of 35 patients followed up for HHE syndrome from January 2005 to December 2015. All patients included in the study met the definition criteria for HHE syndrome. Results: The age of onset ranged from 1 to 10 years. Hemiplegia or spastic hemiparesis of the ipsilateral side to the convulsion was present in all patients. Abnormal brain magnetic resonance imaging (MRI) was found in all patients. All patients developed drug-resistant focal epilepsy during the course of the disease. Conclusions: The management of HHE syndrome constitutes a real public health problem in developing countries like Morocco. The neurological morbidity and the severe sequels are of high impact in these young kids. On the one hand, authors highlight the need for improving emergency care of status epilepticus. On the other hand, in our context, the prophylaxis of febrile seizures seems to be the corner stone of the prevention of HHE Syndrome. © 2018 Elsevier Inc. All rights reserved.

1. Introduction The hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare consequence of febrile seizures during childhood. It was first described by Gastaut et al. [1,2]. It is characterized by the presence of prolonged unilateral clonic seizures occurring during febrile illness in a child under 4 years old. Then, a flaccid unilateral hemiplegia with variable duration occurs. Other deficits can be associated such as aphasia or visual deficits. After a free interval of variable duration, 85% of the patients develop focal onset seizures with or without impairment of consciousness, with temporal location during the 3 years following the first seizure [1]. Neuroradiological studies during the acute phase of epilepsy have shown the presence of cytotoxic edema in the affected cerebral hemisphere [9]. A few weeks later, this edema will be followed by a cerebral hemiatrophy of the same hemisphere without following any vascular territory [9,10]. The link between the HHE syndrome and ⁎ Corresponding author at: Clinical Neurophysiology Department, Specialty Hospital, Rabat, Morocco. E-mail address: [email protected] (M. Albakaye).

https://doi.org/10.1016/j.yebeh.2017.12.018 1525-5050/© 2018 Elsevier Inc. All rights reserved.

prolonged febrile seizure has been established, but the main mechanism remains unknown. The HHE syndrome has become very rare in developed countries probably due to the use of benzodiazepines during prolonged febrile seizures [3,4,7]. In Africa, this disease still remains unrecognized and under diagnosed due to the high frequency of febrile seizure and the low use of benzodiazepines in children during prolonged febrile seizures. In our context, fewer studies have been done concerning the illness. The objective of our study was to describe the clinical, neuroradiological, and therapeutic characteristics and outcome of case series of HHE syndrome followed-up for 10 years at the Clinical Neurophysiology Department of the specialty Hospital in Rabat, Morocco. 2. Patients and methods This was a retrospective study including 35 patients, recruited in the Clinical Neurophysiology Department of the Specialty Hospital of Rabat, Morocco during 10 years, from January 2005 to December 2015. The patients included in the study met the following criteria: medical history of febrile seizures during childhood; occurrence of hemiplegia

M. Albakaye et al. / Epilepsy & Behavior 80 (2018) 184–190

during a febrile seizure; absence of acute pathology of vascular, infectious, metabolic, or traumatic origin which could explain the seizures; and the presence of cerebral hemiatrophy contralateral to the hemiplegia on the brain MRI. For each patient, a medical information sheet was

185

made including the following clinical information: gender, past medical history, age at onset of the first febrile seizure, duration of the hemiplegia and type of seizures; antiepileptic drug taken during the seizures; type and location of electroencephalogram (EEG) abnormalities; MRI

Table 1 The clinical and neuroradiological findings of patients recruited for the study. Patients Age of the first Time to Medical febrile seizure hemiplegia History

Sex Duration Type of seizures of epilepsy

EEG abnormalities

Locations of EEG abnormalities

MRI abnormalities

1

1 year

4 months

FS NDD

F

1 year

Slow spike–waves

Right temporal

2

7 years

4 months

FS

F

2 years

Slow spike–waves

Right frontotemporal

Right cerebral hemiatrophy with hippocampal sclerosis Right cerebral hemiatrophy

3

4 months

4 months

FS

F

3 years

Slow spike–waves


4

6 years

12 months

FS

M

2 years

Slow spike–waves

Left frontotemporal

5

12 years

4 months

FS, NDD

F

3 years

Slow spike–waves

Left temporal

6

6 months

4 months

FS

M

2 years

Slow spike–waves

Right temporal

Left cerebral hemiatrophy with hippocampal sclerosis Right cerebral hemiatrophy

7

7 years

4 months

FS

M

2 years

Slow spike–waves


Right cerebral hemiatrophy

8

4 years

12 months

FS

M

2 years

Slow spike–waves

Right temporal

9

4 years

12 months

FS NDD

F

1 year

Focal onset seizures with impairment of consciousness Focal onset seizures with impairment of consciousness Focal onset seizures with impairment of consciousness Focal onset seizures without impairment of consciousness Focal onset seizures with impairment of consciousness Focal onset seizures without impairment of consciousness Focal onset seizures without impairment of consciousness Focal onset seizures without impairment of consciousness Generalized tonic–clonic seizures

Slow spike–waves

Left temporal

10

2 years

4 months

FS

M

2 years

Generalized tonic–clonic seizures Slow waves

Left frontotemporal

11

3 years

12 months

FS; NDD F

3 years

Slow spike–waves

Left parietooccipital

12

6 years

Unknown

FS

F

2 years

Slow waves

Left temporal

13

3 years

4 months

FS

F

3 years

Slow waves

Left temporoparietal

14

2 years

12 months

FS

M

2 years

Focal onset seizures with impairment of consciousness Focal onset seizures without impairment of consciousness Focal onset seizures with impairment of consciousness Generalized tonic–clonic seizures

Right cerebral hemiatrophy, Gliosis Left cerebral hemiatrophy with ventricular Dilatation Left cerebral hemiatrophy with ventricular attraction Left cerebral hemiatrophy with ventricular Dilatation Left cerebral atrophy with ventricular dilatation Left cerebral hemiatrophy

Slow spike–waves

Right temporoparietal

15

3 years

4 months

FS

M

2 years

Slow spike–waves


16

5 years

Unknown

FS NDD

F

3 years

Slow spike–waves

Left temporal

17

4 years

12 months

FS

F

2 years

Slow spike–waves

Right temporoparietal

18

5 years

4 months

FS NDD

F

2 years

19 20

3 years 5 years

12 months Unknown

FS FS

M F

2 years 3 years

21

4 years

4 months

FS, NDS

M

2 years

22

5 years

12 months

FS

F

3 years

23

2 years

12 months

FS

F

2 years

24

1 year

4 months

FS NDD

F

3 years

25

1 years

12 months

FS

M

2 years

26

2 years

4 months

FS NDD

M

3 years

27

6 months

12 months

FS

M

2 years

28

8 years

12 months

FS

M

3 years

29 30 31

2 years 1 year 5 years

4 months Unknown 4 months

FS NDD FS FC

M M M

3 years 2 years 3 years

32

3 years

4 months

FS NDD

F

2 years

33

2 years

12 months

FC, NDD

M

3 years

34

9 years

4 months

FS

F

2 years

35

4 years

12 months

FS

F

2 years

Focal onset seizures without impairment of consciousness Focal onset seizures with impairment of consciousness Focal onset seizures with impairment of consciousness Focal onset seizures with impairment of consciousness Generalized tonic–clonic seizures Focal onset seizures without impairment of consciousness Focal onset seizures without impairment of consciousness Focal onset seizures without impairment of consciousness Focal onset seizures with impairment of consciousness Focal onset seizures without impairment of consciousness Focal onset seizures without impairment of consciousness Focal onset seizures with impairment of consciousness Focal onset seizures with impairment of consciousness Focal onset seizures with impairment of consciousness Generalized tonic–clonic seizures Generalized tonic–clonic seizures Focal onset seizures without impairment of consciousness Generalized tonic–clonic seizures Focal onset seizures with impairment of consciousness Focal onset seizures without impairment of consciousness Focal onset seizures with impairment of consciousness

FS: febrile seizure; NDD: neonatal delivery distress; M: male sex; F: female sex.

Right cerebral hemiatrophy with hippocampal sclerosis Left cerebral hemiatrophy

Right cerebral atrophy with ventricular attraction Right cerebral hemiatrophy with hippocampal sclerosis Left cerebral hemiatrophy

Slow waves

Right temoporooccipital hemiatrophy Secondarily generalized Right cerebral hemiatrophy

Spike–waves Spike–waves

Secondarily generalized Left cerebral hemiatrophy Secondarily generalized Right cerebral hemiatrophy

Slow spike–waves Left temporoparietal Slow spike–waves


Slow waves


Left cerebral hemiatrophy and ventricular dilatation Right cerebral hemiatrophy with ventricular attraction Right cerebral hemiatrophy

Slow waves

Right temporal


Slow spike–waves

Right temporal


Slow spike–waves Slow spike–waves

Secondarily generalized Right cerebral hemiatrophy with ventricular attraction Right temporal Right hemiatrophy

Slow waves

Left temporoparietal

Left cerebral hemiatrophy

Slow spike–waves Slow waves Slow waves

Right frontotemporal Right temporoparietal Left temporal

Right cerebral hemiatrophy Right cerebral hemiatrophy Left cerebral atrophy

Slow spike–waves

Slow spike–waves

Secondarily generalized Right cerebral hemiatrophy with hippocampal sclerosis Left frontotemporal Left cerebral hemiatrophy with hippocampal sclerosis Right frontotemporal Right cerebral hemiatrophy

Slow spike–waves

Left frontotemporal

Spike–waves

Left cerebral hemiatrophy

186


abnormalities; and the outcome of the patients, as well as their social and professional insertion. The statistical analysis was done using the SPSS© software version 11.5. Quantitative variables were presented as mean and standard deviation while qualitative variables were presented as frequency and percentages. A value of p b 0.05 was considered statistically significant. Verbal or written consent from patient's family was provided prior to recruitment. Participants were informed that the information collected was anonymous. The study protocol had obtained clearance from the University Ethics Committee as well as an administrative authorization from the Hospital prior to the recruitment. 3. Results

(14%). See Fig. 1. All the patients who did brain magnetic resonance imaging (MRI) had cerebral hemiatrophy. See Figs. 2(A, B) and 3(A, B). The hemiatrophy was associated with hippocampal sclerosis in six patients. See Fig. 4(A, B). 3.3. Treatment Our patients were initially given a single antiepileptic drug, carbamazepine being the drug of choice associated or not with clobazam as standard treatment. For patients with recurrent seizures, they were associated with sodium valproate and/or phenobarbital. All the patients finally had drug-resistant epilepsy. See Table 2.

3.1. The sociodemographic and clinical characteristics of the patients

3.4. Outcome

A total of 35 patients were recruited for the study, including 21 males (60%) and 14 females (40%). See Table 1. Among the 35 patients recruited, 23 had a medical history of febrile seizure during childhood, and 12 had seizures during or immediately after delivery. The age at onset of the first seizure was determined between 1 and 4 years in 57.1% (n = 20) and between 4 and 8 years in 31.4% (n = 11). Hemiplegia or spastic hemiparesis following unilateral seizures was present in all patients. This hemiplegia was associated respectively to ipsilateral spastic hypertonia with limping while walking among 24 patients (68.6%), developmental disabilities in 5 patients (14.3%), speech disorder in 4 patients (11.4%), and swallowing difficulties and strabismus in 2 patients (0.6%). Hemiplegia or hemiparesis was observed at the age of 4 months in 48.6% (n = 17) of the patients, 12 months in 40% (n = 14), and unknown in 11.4% (n = 4). All our patients had focal and drug-resistant epilepsy. First seizures started since the age of 1 to 2 years in 54.3% of patients (n = 19) and 2 to 3 years in 45.7% (n = 16). The mean frequency of the seizures varied from three to four per day, and they were of focal onset without impairment of consciousness in 48%, focal with impaired awareness in 42% and generalized in 20% of the patients.

All our patients failed in their early years at school. Presently, they had difficulties to carry out stable professional activities due to the high frequency of the seizures. One patient disappeared and was not found by his family, while another patient attempted suicide. See Table 2.

3.2. EEG and brain MRI aspects Abnormalities found on EEG were slow spike–wave activity in 60% (n = 21) of cases, slow waves in 28.6% (n = 10), and spike–waves in 11.4% (n = 4). Their locations were mainly frontotemporal (60%), temporoparietal (20%), and generalized

4. Discussion 4.1. Epidemiological aspects The incidence and prevalence of HHE syndrome remain unknown. The pic of incidence occurs in the first two years of life, and the disease is rarely observed after 4 years [8]. In developed countries, the incidence of HHE syndrome has considerably decreased during the past twenty years probably due to early and better management of status epilepticus by the use of intrarectal diazepam [1,7,8]. In Africa, HHE syndrome seems to be less diagnosed giving the high frequency of febrile seizures and the absence of health education concerning the use of intrarectal diazepam in children during prolonged febrile seizures. In our study, we collected 35 cases of HHE syndrome 60% of which are male. The male predominance was found in the series of Toldo et al. [10], while in the series of Mondal et al. there was a female predominance [11]. Nowadays in Morocco, HHE is rarely encountered due to the recent improvement in maternal and neonates' health care management and due to the training of pediatricians on the use of intrarectal diazepam in prolonged febrile seizures.

Fig. 1. EEG: Showing right fronto-temporal epileptic abnormalities, such as spikes and slow spikes.


187

Fig. 2. Brain T2 weighted MRI sequence (A) showing right cerebral hemiatrophy. EEG (B), showing generalized spikes and waves discharges.

4.2. Clinical characteristics The HHE syndrome was described to be linked to multiple etiologies, but in most cases, the cause is not known [1]. Hyperthermia is often present during the acute phase of seizure which seems to indicate that HHE syndrome is a consequence of prolonged febrile seizures [1]. Seizures occur most often before the age of 4 years in a context of fever. More than 65% of our patients were less than 4 years old during their first seizure with a mean age of 2.5 years during diagnosis. In our context, the late diagnosis and the absence of MRI finding during the acute phase of HHE syndrome is explained by the path taken by the patients with epilepsy, who in most cases consult the hospital only after trying all other possible traditional practices. During the HHE syndrome, the seizures are immediately followed up by ipsilateral hemiplegia [9–11]. In our study, hemiplegia was observed in all patients but with longer duration. The duration of hemiplegia in our patients was noted by the family or the doctors who referred the patients. The hemiplegia of HHE syndrome can disappear after some days or leave a discrete spastic hemiparesis, and could also persist definitely [7,10].

It has been established that the constitution of a definite hemiplegia after febrile seizure is partly in relationship with duration of the seizure and the age of onset. The risk is more important when the duration of the seizure is more than 5 h and the age of the patient less than 18 months [7,12]. In our study, the exact duration of the seizures were not known by the patient's family who focus most often on the spectacular manifestation of the seizure. On the other hand, the age at onset of the seizures was between 1 and 4 years for our patients. The younger age of the patients during their first febrile seizure and the frequency of the seizures could be the factors, explaining the hemiplegia in our patients. These factors may explain the late diagnosis encountered in our patients. No patient in our study had family medical history of epilepsy or febrile seizures. No case of meningitis or other previous pathologies were linked to the hemiplegia. However, cases of idiopathic HHE syndrome were observed [9]. In 85% of cases, the HHE syndrome patients developed focal epilepsy in the 3 years that follow the first febrile seizure [9]. According to Chauvel et al. [5], this duration is between 1 month and 9 years. In case series, this duration varies between 12 months and 9 years. The seizure could be generalized or

188


Fig. 3. Brain T2 weighted MRI sequence (A) and FLAIR weighted MRI sequences (B), showing left cerebral hemiatrophy.

focal with or without impairment of consciousness [1,7]. Focal epilepsies were most often of temporal lobe [1,7]. In our series, the seizures were of temporal origin in 16 patients. The HHE Syndrome is usually associated with developmental disabilities and other motor or visual deficits [6]. Behavioral disorders such as aggression, agitation, and anxiety were equally described [7]. In our study, spastic hypertonia of the weak side of the body was observed in 24 patients, followed by mental disabilities in 5 patients. Four patients had speech disorder such as aphasia, and was present especially in patients having right hemiplegia. Three patients presented with visual hallucinations, wandering, anxiety, and sometimes an aggression toward family members. 4.3. EEG results For the diagnosis of HHE syndrome, EEG is not mandatory. However, this electrophysiological exam is important at the acute phase of the disease in order to rule out anticonvulsant status epilepticus [1]. Temporal location of the anomalies on the EEG is an argument for surgery with good prognosis [1]. In the series reported by Auvin et al. [1], the anomalies found were slow waves and sharp waves with temporal location. All

patients in our study did an EEG during their first consultation. The anomalies were essentially slow spike–waves, slow waves, and spike–waves.

4.4. Pathophysiologic aspects The pathophysiologic mechanism of HHE syndrome remains unknown. The proposed pathogenic mechanism is neuronal lesion induced by venous thrombosis and/or by neuronal toxicity [12]. The role of cerebral malformation and/or cortical dysplasia was suggested. On the other hand, thalamic dysfunction induced by cell damage can be responsible for the dysfunction of the thalamocortical circuit and can play a major role in the genesis of epilepsy [12]. Neuropathological studies have shown anomalies of diffusion and diffused cytotoxic edema limited in the epileptic hemisphere, this edema induced neuronal lesions. A reduction in the diffusion coefficient of water has been shown in experiments and in patients with epilepsy with generalized tonic–clonic seizures. Spectroscopic MRI studies done in patients during the acute phase of HHE syndrome have shown a reduction in the pic of N-acetyl-aspartate in the

Fig. 4. FLAIR weighted MRI sequences (A) and T2 weighted MRI sequence (B), showing a cerebral hemiatrophy, associated with left hippocampal scleroatrophy.


189

Table 2 Treatment and outcome data. Patients

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

Neurologic sequelae

Left hemiparesia, developmental disabilities, hypertonia Left hemiparesia, spastic hypertonia Left hemiparesia, developmental disabilities, hypertonia Right hemiparesia, Aphasia Right hemiparesia, spastic hypertonia Left hemiparesia, spastic hypertonia Left hemiparesia, spastic hypertonia Left hemiparesia, spastic hypertonia Right hemiparesia, spastic hypertonia Right hemiparesia, Aphasia Right hemiparesia, spastic hypertonia Right hemiparesia, spastic hypertonia Right hemiparesia, mental retardation, hypertonia Left hemiparesia, spastic hypertonia Left hemiparesia, spastic hypertonia Right hemiparesia, spastic hypertonia Left hemiparesia, developmental disabilities Left hemiparesia, spastic hypertonia Right hemiparesia, developmental disabilities Left hemiparesia, developmental disabilities, hypertonia Right hemiparesia, developmental disabilities Left hemiplegia, swallowing disorder Left hemiplegia, developmental disabilities Left hemiparesia, spastic hypertonia Left hemiparesia, spastic hypertonia Left hemiparesia, spastic hypertonia Left hemiparesia, spastic hypertonia Right hemiparesia, Aphasia Left hemiparesia, spastic hypertonia Left hemiplegia, developmental disabilities Right hemiparesia, Aphasia Left hemiplegia, Strabismus Right hemiparesia, spastic hypertonia Left hemiparesia, spastic hypertonia Right hemiparesia, spastic hypertonia

Antiepileptic drugs

Outcome

CLZ, PB, CBZ, VPA CLZ, PB, CBZ, VPA PB, CBZ, VPA CLZ, VPA, CBZ CLZ, VPA, CBZ, LMT VPA, CBZ, LMT, BZP VPA, CBZ, CLZ PB, CBZ, CLZ CBZ, PB, CLZ PB, CBZ, VPA, CLZ PB, CBZ, VPA PB, VPA, CBZ PB, CBZ, PB, PB, CBZ VPA, CBZ, TPM, LEV, BZP VPA, CBZ, LMT, CLZ VPA, CBZ, CLZ CBZ, PB, CLZ CBZ, PB, CLZ PB, CBZ, CLZ CBZ, PB, CLZ CBZ, PB, CLZ PB, CBZ, VPA PB, VPA, CBZ, CLZ VPA, PB CBZ, CLZ PB, CBZ, VPA, CLZ VPA, CBZ, CLZ LEV, VPA, CLZ VPA, CBZ VPA, CBZ, CLZ TPM, OXC, VPA, PB VPA, CBZ, PB PB, VPA, CBZ CBZ, VPA, LEV PB, VPA, CBZ, CLZ

Under treatment

Social or study integration

Convulsions remission Convulsions remission Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant and attempted suicide Drug-resistant Stop of convulsion Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant Drug-resistant

Stop of work Failure in school Failure in school Failure in school Failure in school and Stop of work Failure in school Failure in school and Stop of work Stop of work Restart of work Stop of work Stop of work Stop of work Failure in school and Stop of work Failure in school and Stop of work Failure in school Failure in school and Restart of work Lost from contact with family Failure in school Failure in school and Restart of work Failure in school Failure in school Failure in school Failure in school and Stop of work Failure in school Failure in school Failure in school Failure in school Failure in school Failure in school Failure in school Failure in school Failure in school Failure in school Failure in school Failure in school

CLZ: clobazam; PB: phénobarbital; CBZ: carbamazépine; VPA: sodium valproate; LEV: lévétiracétam; LMT: lamotrigine; TPM: topiramate; OXC: oxcarbazépine.

damaged cerebral hemisphere as compared to the contralateral hemisphere [12]. 4.5. Neuroradiological aspects In our study, cerebral MRI showed unilateral morphologic anomalies such as cerebral atrophy, cortical sulcus effacement, ipsilateral attraction of the ventricular system, and reactional gliosis in the damaged hemisphere. It was equally described in HHE syndrome a reduction in diffusion in the left frontal region on the diffusion MRI sequences [10,12]. This reduction of diffusion is due to functional connection of the frontal region with other zones of the hemisphere [10,12]. In our study, we observed anomalies respectively in the frontotemporal and temporoparietal regions. Other morphologic abnormality such as lesion of the mesiotemporal region linked to hippocampal sclerosis was found in six patients. This internal hippocampal atrophy is a radiologic argument linked to the presence of a medical history of febrile seizure during childhood before 3 or 4 years [15]. However, it was reported that the hippocampal atrophy is not linked to the number of seizures, neither their frequency, nor the duration of epilepsy [15]. 4.6. Treatment The objective of the antiepileptic drugs is to prevent recurrence after the first seizure. For focal onset epilepsy, carbamazepine is the drug of choice in our context, whether with or without impairment of consciousness or with secondary generalization. In Rabat Department, this choice is based on its low cost and availability in the Moroccan market. In the study by Salih et al., five patients over six were taking only carbamazepine or carbamazepine associated with phenytoine

or sodium valproate [7,9]. The association of carbamazepine and phenobarbital was reported as efficient in the control of seizures [9]. In our context, phenytoine was not available; our patients were given carbamazepine or phenobarbital as a first line treatment with or without association with clobazam as reference treatment. In case of persistent seizures, the patients were associated phenobarbital and/or sodium valproate with the previous medication as second line treatment. The new generation antiepileptic drugs such as levetiracetam, lamotrigine, topiramate, and oxcarbazepine were tried as second line treatment in seven patients. Drug-resistant focal epilepsies were observed in all our patients. See Table 2. Neurosurgical treatment such as hemispherectomy and callosotomy were reported as efficient in the management of HHE syndrome in patients with drug-resistant epilepsy [13,14]. Decompressive hemicraniectomy was reported as equally efficient in the acute phase of HHE syndrome with intracranial hypertension linked to cerebral edema [15]. In HHE syndrome associated with hippocampal sclerosis, anterior temporal lobectomy is particularly efficient [1,16]. According to Chabardès et al., patients who could be concerned by this type of surgery represented 20%, and those who presented with hippocampal sclerosis had better outcomes with absence of seizure in 70 to 80% of cases after epilepsy surgery [16]. This alternative therapy used frequently in developed countries, is being reproduced in developing countries. In Morocco for example, hundreds of patients presented with focal drug-resistant epilepsy have been treated surgically. However, no case of HHE syndrome was treated surgically [17]. 4.7. Outcome The patients with HHE syndrome often maintain motor and cognitive sequela. In 20% of cases, the hemiplegia of HHE syndrome disappears in

190


12 months with the possibility of persistent spastic pyramidal syndrome [7,9] and usually cognitive deterioration [7]. In our study, the clinical outcome was favorable. All our patients developed focal drug-resistant epilepsy with neurological sequelae, such as spastic hypertonia, which alters the quality of life of the patients. These sequelae were associated with developmental disabilities. On the social level, we found academic failure with difficulties on social and professional insertion. We have observed one case of attempted suicide and a disappearance of a patient never found by his family. 4.8. Limitations of the study The main limitation of the study is the retrospective design, its location in only one reference center in Morocco and the few number of patients. 5. Conclusion The management of HHE syndrome constitutes a real public health problem in developing countries like Morocco. The neurological morbidity and the severe sequela are of high impact in these young kids. On the one hand, authors highlight the need for improving emergency care of status epilepticus. On the other hand, in our context, the prophylaxis of febrile seizures seems to be corner stone of the prevention of HHE syndrome. Conflict of interest None. References [1] Auvin S, Bellavoine V, Merdariu D, Elmaleh-Bergés M, Gressens P, Boespflug-Tanguy O. Hemiconvulsion-hemiplegia-epilepsy syndrome: current under standings. European. J Pediatr Neurol 2012;16:413–21.

[2] Nabbout R, Vezzani A, Dulac O, Chiron C. Acute encephalopathy with inflammationmediated status epilepticus. Lancet Neurol 2011;10:99–108. [3] Gastaut H, Poirier F, Payan H, Salamon G, Toga M, Vigouroux M. HHE syndrome; hemiconvulsion, hemiplegia, epilepsy. Epilepsia 1960;1:418–44. [4] Freeman JL, Coleman LT, Smith LJ, Shield LK. Hemiconvulsion-hemiplegia-epilepsy syndrome: characteristic early magnetic resonance imaging findings. J Child Neurol 2002 Jan;17:10–6. [5] Chauvel P, Dravet CH. Le syndrome Hemiconvulsion-hémiplégie-épilepsie. Les syndromes épileptiques de l'enfant et l'adolescent. 4eédition. Monte rouge: John Libbey; 2003; 277–94. [6] Mirsattari SM, Wilde NJ, Pigott SE. Long-term cognitive outcome of, hemiconvulsionhemiplegia-epilepsy syndrome affecting the left cerebral hemisphere. Epilepsy Behav 2008;13:678–80. [7] Bourrous M, Lagmiri K, Amine M, Abidi M, Bouskraoui M. Le syndrome hemiconvulsion-hémiplégie-épilepsie de l'enfant. J Pediatr Pueric 2010;23:322–7. [8] Van Toorn R, Janse van Rensburg P, Solomons R, Ndondo AP, Schoeman JF. Hemiconvulsion-hemiplegia-epilepsy syndrome in South African children: insights from a retrospective case series. Eur J Paediatr Neurol 2012;16:142–8. [9] Salih MA, Kabiraj M, Al- Jarallah AS, El Desouki M, Othman S, Palkar VA. Hemiconvulsion-hemiplegia-epilepsy syndrome: clinical, electroencephalographic and neuroradiological study. Childs Nerv Syst 1997;13(5):257–63. [10] Toldo I, Calderone M, Boniver C, Dravet CH, Guerrini R, Laverda AM. Hemiconvulsion-hemiplegia-epilepsy syndrome: early magnetic resonance imaging findings and neuroradiological follow-up. Brain Dev 2007;29(2):109–11. [11] Mondal RK, Chakravarty D, Das S. Hemiconvulsion-hemiplegia epilepsy syndrome and inherited protein S deficiency. Indian J Pediatr 2006;73(2):157–9. [12] Auvin S, Devisme L, Maurage CA, Soto-Ares G, Cuisset JM, Leclerc F, Vallée L. Neuropathological and MRI findings in an acute presentation of hemiconvulsionhemiplegia: a report with pathophysiological implications. Seizure 2007;16:371–6. [13] Devlin AM, Cross JH, Harkness W, Chong WK, Harding B, Vargha-Khadem F. Les résultats cliniques de hémisphérectomie pour l'épilepsie dans l'enfance et l'adolescence. Cerveau 2003;126:556–66. [14] Hollande KD, Buchhalter J. Hemiconvulsion-hemiplegia-epilepsy syndrome: another case for epilepsy surgery. Neurology 2008;70:2097–8. [15] Berhouma M, Chekili R, Brini I, Kchir N, Jemel H, Bousnina S. Decompressive hemicraniectomy in a space-occupying presentation of hemiconvulsionhemiplegia-epilepsy syndrome. Clin Neurol Neurosurg 2007;109:914–7. [16] Barr WB, Ashtari M, Schaul N. Bilateral reductions in hippocampal volume in adults with epilepsy and a history of febrile seizures. J Neurol Neurosurg Psychiatry 1997; 63(4):461–7. [17] Ouazzani R, Lahjouji F, Belaïdi H, Khamlichi A, Jiddane M, Birouk N. La chirurgie de l'épilepsie au Maroc, étude et suivi à long terme de 51 patients. Afr Middle East Epilepsy J 2013;2(2):15–9.