ABSTRACT

Background

This hospital-based study aimed to evaluate the frequency and diagnostic pattern of epilepsy in our locality among population with age range from birth to 18 years.

Methods

127 patients out of a total of 565 regularly attended the out-patient epilepsy clinic, were included in this study over 6 months period.

Results

At the time of interview, 48% had age ranges from 12-18 years, 78% were rural residents and 62.2% were illiterate. About 70% had age at onset of 5.9±3.5 years. Parental consanguinity was reported in 41%. Family history of epilepsy was reported in 17.3%. About 80% reported no etiology for epilepsy (idiopathic/cryptogenic group). CNS infection (68%), perinatal complications (20%) and head trauma (12%) were identified in the symptomatic group. Mental retardation was reported in 66.7%. Febrile convulsion was reported in 10.2%. Normal EEG was reported in 31.5%. About 48% had localization-related epilepsy while 42% and 9.5% had generalized and undetermined epilepsies. Frontal and temporal foci were common sites for producing epileptic discharges (37.7% for each). The generalized tonic-clonic seizures were frequent in generalized epilepsy (72.1%). Rolandic epilepsy was the most frequent type of age specific epileptic syndrome (26.9%).

Conclusion

Our study is considered a preliminary review for population-based epidemiological studies in childhood epilepsy in Upper Egypt. This will be of value in planning early prevention and management with proper revision of AEDs according to the available resources.

Key words: Epilepsy, Epidemiology, Egypt, Hospital-based / Egypte, Epidémiologie, Epilepsie, Hôpital

RESUME

Objectif

Étudier la fréquence et les aspects diagnostiques d’une série hospitalière allant de la naissance à 18 ans, dans notre localité

Méthodes

127 patients sur une population de 565 vus en consultation d’épilepsie en ambulatoire ont été inclus ans cette série

Résultats

48% des patients avaient entre 12-18 ans, 78% étaient issues d’une population rurale et 62% étaient illettrés. Environ 70% estimaient le début de leur maladie à 5,9+3,5 ans. Une consanguinité était retrouvée dans 41% des cas.Des antécédents familiaux d’épilepsie étaient retrouvés dans 41% des cas. Aucune étiologie était objectivée dans 80% des cas. Une infection du système nerveux central (68%), des complications périnatales (20%), et un traumatisme crânien (12%) étaient identifiés dans le groupe symptomatique. Un retard mental était observé dans 66,7% des cas et les convulsions fébriles, 10,2%. La normalité de l’EEG constituait 31,5% des patiens. 48% avaient une focalisation de l’épilepsie tandis que 42% et 9,5% étaient respectivement généralisés et indéterminés. La topographie frontale et temporale étaient les zones présentant le plus de décharges paroxystiques (37.7%). Les crises tonico-cloniques répondaient fréquentes et répondaient à une épilepsie généralisée. L’épilepsie rolandiqe était le type le plus fréquent de l’épilepsie – syndrome.

Conclusion

Notre étude est considérée comme étant préliminaire et portait sur une population d’enfants épileptiques résidant en Haute Egypte. Ces données devraient permettre la mise en place d’une prévention et d’un traitement par les antiépileptiques en tenant compte des ressources disponibles.

Mots clés : Egypte, Epidémiologie, Epilepsie, Hôpital

INTRODUCTION

Epilepsy is a common medical illness worldwide. It is estimated that 0.5-1% of all children have epilepsy, with the majority presenting during infancy or early childhood (33). The prevalence of epilepsy in general population is ~8.2 per 1,000. It is higher in developing countries (as in Colombia, Ecuador, India, Liberia, Nigeria, Panama, United Republic of Tanzania and Venezuela) in which a prevalence of >10 per 1,000 were reported (26, 32). In Upper Egypt, Assiut Governorate, the prevalence rate was 12.9 per 1,000 (38). The prevalence of epilepsy in the pediatric population is 4-6 per 1,000 children (18). When categorized by age, the overall average annual incidence of epilepsy is 73-150 per 100,000 in children <1year of age, with this value decreasing by 50% in children 1-4 years, 72-86 per 100,000 in children <9 years and 40 per 100,000 in patients 10-14 years of age. Studies in developed countries suggest an annual incidence of epilepsy is approximately 50 per 100,000 of the general population. One of the main reasons for the higher incidence of epilepsy in developing countries is exposure to higher risks of permanent brain damage like CNS infection, head trauma, perinatal complications and malnutrition (26, 32, 38). New onset epilepsy is common in patients <20 years of age. The incidence is highest from 12 months of life through 2 years of age; these rates are due, in part to epilepsy associated with mental retardation and cerebral palsy (24). Furthermore, mortality is increased in patients with epilepsy. However, in general, childhood epilepsy has an excellent prognosis than epilepsy in adults (38). Aim of the work

Assiut University Hospital is a tertiary referral hospital. As far as our knowledge, this is the first study in our locality aimed to determine the pattern of epilepsy and epileptic syndromes in a pediatric age group of epileptic patients. The patients in this study were the attendees to the out-patient epilepsy clinic of Assiut University hospital throughout a period of 6 months (from May 1st – 31st October 2005).

SUBJECTS AND METHOD

Subjects

This study included all patients with active epilepsy (n=127) within the age range from birth to 18 years, recruited over a period of 6 months (from May 1st – 31st October 2005) from the out-patient epilepsy clinic, Assiut University Hospital, Assiut, Egypt. Active epilepsy is defined as two or more unprovoked epileptic seizures with at least one seizure occurring within previous 5 years, regardless of the AED (16). People with the last seizure more than 5 years ago but still being treated with AEDs was in some studies also included in the group with active epilepsy. This study was carried out with permission of Assiut University hospital ethical committee. Written informed consent was obtained from patients, parents and guardians.

Method

Clear history was obtained from both patients and witnesses. We used the international classification of epileptic seizures, epilepsies, epileptic syndromes of League Against epilepsy (ILAE) and guidelines for epidemiological studies of The Commission on Epidemiology and Prognosis, ILAE (1993) for determination of seizure types, epilepsy disorders and age-specific epileptic syndromes, epidemiology and prognosis (10). Seizures was typed as generalized, focal localization-related and undetermined. Based on the etiology, epilepsy is categorized into idiopathic, cryotogenic and remote symptomatic. Idiopathic epilepsy has a presumed genetic origin as benign rolandic epilepsy, childhood absence epilepsy and others. Cryptogenic epilepsy has no discernible cause; however, it is believed to have an underlying pathologic cause for which improvements in diagnostic techniques may eventually provide an explanation. Remote symptomatic epilepsy shows no immediate cause for the seizure, but there is a prior brain injury (e.g., major head trauma, meningitis and stroke) that is an established risk factor for seizures. All patients were subjected to: A) detailed history taking including age of at onset, developmental history, presence of prenatal, perinatal and postnatal insults, history of fever before the attacks or other situation related to epilepsies, History of acute CNS insults before the onset of the seizures as severe head trauma, meningoencephalities among others, progressive brain disease, or other chronic medical illnesses. Family history included, consanguineous marriage, history of epilepsy of the same type or other types in the family, as well as other related conditions as febrile convulsions. Detailed description of the seizures included data of the first fit including the age of onset [neonatal (from birth – <2months), infancy (>2-12 months), early or late childhood (>1-12 years) and juvenile (>12-18 years)], events that occurred before during and after the attack, prodroma, aura, ictus and post ictal status, the duration of onset and that of recovery, time of the attacks (nocturnal, diurnal and both), seizure frequency before starting AEDs, history of occurrence of status epilepticus or serial fits, history of multiple types of seizures, the type of AEDs (monotherapy versus polytherapy), compliance to AEDs and the degree of control on treatment. According to the degree of control on AED(s), seizures are divided into controlled if there is no seizures for ≥1year and uncontrolled if there is decrease in the frequency or change in the character of seizure from wild picture to mild presentation, 2) Full neurological examination to determine associated neuroimpairments, 3) Conventional EEG in which awake and sleep records was obtained for all patients. Conventional EEG was done using 8 channels (although the yield of 8 channels is very low but it one available in our locality according to our resources). Nihon Kohden machine, employing scalp electrodes placed according to the international 10-20 system with bipolar and referential montages), and 4) Neuroimaging CT- or MRI-brain) were done to all patients.

Statistical analysis

Data were analyzed using SPSS (version, 11) computer program. Data were presented as mean + SD. Chi-square test was used for comparison between numerical data. Student’s t-test was used for comparison. P-value <0.05 was significant. RESULTS

A total of 127 patients with age range from birth to 18 years old (64 males and 63 females) out of a total of 565 epileptic patients that attended our out-patient epilepsy clinic were recruited. This represents 22.5 % frequency rate for epilepsy among children and adolescence in this clinic.

Demographic data was illustrated in table 1. It demonstrated the age at interview, sex, residential distribution, educational level distributions, age at onset of epilepsy, parental consanguinity and family history of epilepsy. The age range of our sample at the time of interview was 2-18 years with mean of 11.3±4.8 years with equal numbers from both genders (male to female ratio=1.02:1). Half of patients (48%) were interviewed at the age range of >12-18 years. Females had older age at the time of interview in the age range >6-12 years (9.5±1.6 versus. 8.1±1.4 years) than males (p<0.01). 78% of patients were from rural areas. All were from low-income families. Illiteracy rate was high (62.2%) and ~19% of the patients discontinued education because of their illness. It was found that 70% (n=89) of patients developed seizures during childhood period (>1-12 years), with mean age of 5.9±3.5 years. Females had significantly older age at onset than males during the childhood period (p<0.05). Approximately 41% (52/127) of patients had consanguineous marriage among parents. Positive family history of epilepsy was reported in 17.3% (22/127). In table 2, patients were categorized according to the electro-clinical diagnosis into three groups: generalized, localization-related and undetermined (not known whether generalized or localized). The localization-related represented nearly half of the patients (48%), in which, approximately 80.3% (49/61) of them were clinically diagnosed as generalized epilepsy but EEG revealed that seizures originated from a specific focus and spread to other brain lobes (secondary generalization). Partial epilepsy with secondary generalization was the most frequent type of localization-related epilepsy group of patients (62.3 %). Frontal and temporal lobe epilepsies were the most frequent types of localization-related epilepsies (n=23 or 37.7% for each) while parietal and occipital foci were reported in 18% (n=11) and 6.6% (n=4). Epileptic EEG activity was identified in 68.5% (n=87) of patients. Most of the patients with epileptic EEG activity had focal activities (n=53 or 60.9%) in which the focus remained localized to the same site (simple focal) in 28.3% of them (n=15) while the majority (n=38 or 71.7%) had tendency to secondary generalization. Of these with focal EEG activity the highest proportion (37.7% or 20/53) were localized to the temporal lobe, followed by the frontal lobe (34.0 % or 18/53) while activities localized to the parietal and occipital lobes were reported in 18.9% (or 10/53) and 7.6% (or 4/53). The generalized tonic-clonic seizures were the most common type of generalized epilepsies (72.1%). Among the generalized types of epilepsy, myoclonic epilepsy had the earliest age at onset (4.5+2.3), although it is non-statistically significant. Seven age-specific epileptic syndromes were identified (20.5% or 26/127) included: rolandic epilepsy (benign epilepsy with centrotemporal spikes), Lennox-Gastaut syndrome, childhood absence, juvenile absence, juvenile myoclonic epilepsy, benign childhood epilepsy with occipital paroxysms and myoclonic-astatic epilepsy. Rolandic epilepsy was the most frequent type (27% of this group of patients). Within the localization-related epilepsies. Forty patients (31.5%) had normal interictal EEG record (neither background abnormality nor epileptic activity in the EEG). Generalized seizures dominated this group (n=32 or 80%) and most of the patients with generalized epilepsy had generalized tonic-clonic seizures (65% or 26/32). 7.5% (n=3) had complex partial seizures while 12.5% (n=5) had focal seizures. Approximately 41.5% of patients of the idiopathic group had normal EEG while only 20% of the cryptogenic group and 12 % of the symptomatic group had normal EEG. Table (3) demonstrated that most cases (53.7%) (44/82) of the idiopathic group of epilepsies had generalized seizures. On the other hand, most cases of the symptomatic (64%) (16/25) and cryptogenic (50%) (10/20) groups were localization-related epilepsies. Idiopathic/cryptogenic of localization-related group represented 73.8% (45/61) in which the idiopathic group represented 57.4% (35/45) while symptomatic group represented 26.2% (16/61) of the localization-related group of patients. The cryptogenic group of generalized seizures was significantly younger (P<0.001) than those of the idiopathic and symptomatic groups. Patients with idiopathic undetermined epilepsies were younger at age of onset of their epilepsies than both symptomatic and cryptogenic groups of (P<0.001). Symptomatic undetermined group was younger at age of onset of illness than the cryptogenic group (P<0.001). Table 4 showed that the known etiology for epilepsy was identified in 19.7% of patients (remote symptomatic epilepsy) while the etiology remained unknown in the majority of patients (80.3%) (idiopathic/cryptogenic epilepsy) in which most were of idiopathic category (n= 82 or 64.6%). Most of the symptomatic epilepsies were due to non-specific CNS infection (68% or 17/25) while perinatal complications and head trauma were the etiology in 20% (or 5/25) and 12% (or 3/25) of symptomatic patients. The patients with cryptogenic epilepsy recorded the highest rate of positive parental consanguinity (50 % or 10/20) compared to symptomatic (44% or 11/25) and idiopathic (37.8% or 31/82) groups, respectively. Twenty six percent of epileptic patients in this study (n=33) had mental retardation (MR) in addition to seizures, 60.7% (20/33) of them were of cryptogenic type while 39.3% (13/33) were of symptomatic type of epilepsy. In both symptomatic and cryptogenic group of MR, the frequency rate was higher for males (n=21 or 63.6%) compared to females (n=12 or 36.4%) (male to female ratio=1.9/1). The symptomatic group were significantly younger than the cryptogenic group (P<0.001), females were significantly younger than males in both cryptogenic and symptomatic group of patients (P<0.01). DISCUSSION

Seizures are the most frequent reason for visits to the pediatric neurologist office. Approximately 50% of cases of epilepsy begin in childhood or adolescence (20). The small unexpected small number of children attended our clinic although our hospital is a tertiary referral hospital, is attributed to the fact that our clinic serves only patients with no health insurance.

This prospective hospital-based study was carried out over a 6 months period from May 1st to 31st of October 2005). The out-patient epilepsy clinic of Assiut University Hospital manages adult and children with epilepsy who were not covered by insurance service and all families were from low-income. The frequency of patients attending the clinic (adults and children) during the period of study was 565 patients. Out of whom 127 were children and adolescents which represent a relative frequency rate of 22.5%.

In this study, the highest frequency rate (48%) at the time of interview was during childhood with mean; age of 5.9±3.5 years, this is followed by infancy (15.8%) with mean age of 0.72±0.2 years which is consistent with many studies. Cowan et al. (12) reported that seizures began before age of one year in 32% of cases. Krammer et al. (24) in their consecutive study on 440 patients from Isreal found that 18% of the seizures began in infancy (under the age of one year), 64% in childhood period (2-10 years of age), and 18% in adolescents (11-15 years of age). Al-Sulaiman and Ismail (3) in their comparative prospective study carried on 263 children Saudia Arabia, found that the overall mean age of epilepsy was 4.2 years with range of 0.05-13 years and the recorded age of onset was within the first year of life in 48.7% of the patients. In the epidemiological study of Shawki et al. (38), 68.5% of cases of epilepsy developed their first seizures before the age of 12 years. The authors attributed this to the high percentage of brain immaturity with poor ability of the brain to protect itself from abnormal electrical discharges and to the higher incidence of risk factors at that age including perinatal complications, CNS infections, head trauma and metabolic disorders (38).

In this study, most of the patients (78%) were rural residents and illiterate (62.2%). It has been estimated that in developing countries, 60-75% are living in rural areas while in developed countries, 25% of population live in rural areas. Literacy rates differ in rural and urban areas (34). In India 29% of those in villages are literate whilst 57% of those in cities can read and write (38). When these estimates are applied to Egypt as one of the developing countries, still a higher percent of our sample of epileptic patients are illiterate (62.2 %) or at least discontinue education (18.9 %) probably because of the illness. In the epidemiological study carried in Assiut Governorate (1993-1994) by Shawki et al. (38), high incidence of epilepsy with high frequencies of seizures was reported among rural residents. The authors attributed this to the higher incidence of symptomatic cases (traumatic, perinatal complications and CNS infections), beside the higher rates of consanguineous marriage among rural residents.

In this study, parental consanguinity was reported in 41% of patients. Similarly Khedr et al. (21) reported 41.7% of consanguinity among parents of epileptic patients. Shawki et al., (38) reported higher percentage of consanguineous marriage among parents of epileptics than non epileptics (64.9% versus 47.5%). In Saudi Arabia, Al Rajeh et al. (2) reported consanguineous marriage in 53% in parents of epileptic children. In this study, highest percentage of positive consanguinity was found among cryptogenic (50%), followed by symptomatic (44%) and least among idiopathic (37.8%) epilepsies. Al-Sulaiman and Ismail (3) reported parental consanguinity in 29.7% of epileptic Saudian children in which 80 % of them were idiopathic/cryptogenic cases, while only 20 % of cases were symptomatic. El-Afify et al., (14) reported family history of epilepsy in 13.8% of patients with primary epilepsy and 5.9% in those with symptomatic epilepsy. Granierri et al. (17) reported family history in 18.3%. Shawki et al., (38) reported epilepsy in 22% of the epileptic relatives, 50% of them were first degree, 30.6% of them were second degree while 19.4% were third degree relatives. Also Beilmann et al. (5) reported family history of epilepsy in 13.9% of their patients. Familial aggregation studies are consistent in showing an increased risk of epilepsy in the relatives of patients with idiopathic/cryptogenic generalized and partial epilepsies that occur in the absence of environmental insults to the CNS (33).

In this study, no etiology (idiopathic/cryptogenic group) was identified for epilepsy in the majority patients (80.3%). This is consistent with many studies. Different studies reported that primary epilepsy represented from 44-76% of all patients with epilepsy (12). Muhammad et al. (29) reported that primary epilepsy was more common than secondary epilepsy among Egyptian school children in the age period from 4-12 years, and all cases below 2 years were categorized as secondary epilepsy. In Shawki et al. (38), no etiology for epilepsy was identified in 58.2% of patients. Endziniene et al. (15), in their hospital-based study carried in the Neurology Clinic of Kaunas Medical Academy Lithuania, no etiology was identified in 60.3% of patients.

In our study, known cause for epilepsy was identified in 19.7% of patients (symptomatic or secondary epilepsy), among which non-specific CNS infection represented 68% of them, followed by perinatal complications (20%) while head trauma was reported in only 12% of children. El-Afify et al. (14) reported that head trauma, CNS infections and birth traumatic events were the most common causes among children while vascular, neoplastic and traumatic convulsions were frequent among adult and elderly onset epilepsy. Shawki et al. (38) reported that 29.7% of their patients developed epilepsy as a result of non-specific CNS infection, followed by prenatal and perinatal causes (23.7%) particularly in patients with epilepsy onset before 12 years age while head trauma represented 8.5% of their cases. Al Rajeh et al. (1) reported that perinatal encephalopathy accounted for 40% of cases of children less than 5 years with lower percentage in their later studies (23.4 %) (2). In the latter study, CNS infection accounted for only 4% of symptomatic group and acute symptomatic convulsions were uncommon (3%). Bielmann et al. (5) in a trial to estimate the prevalence of childhood epilepsy in Estonia, symptomatic epilepsy was recorded among 40.7 % of patients out of which perinatal events were the most frequent etiology. In the temperate region of South Africa, Cape Town, the prevalence of secondary epilepsy was higher than that found in developed countries. Even higher percentage of symptomatic epilepsy was found in some studies due to availability of neuroimaging techniques of investigations. Cowan (13) identified a cause for seizures in 25-45% of their patients. Kwong et al. (25), reported symptomatic epilepsy in 61% of epileptic patients and Perinatal factors were the most frequently found cause of epilepsy, and Perinatal asphyxia represented 46.4% of cases in other studies (4). It is apparent that there are great variations in the etiologic factors of secondary epilepsy. However in the overall developing countries, in Africa and elsewhere, the low socioeconomic state especially in rural areas and poor antenatal and perinatal care are responsible for a high frequency of birth injuries in infants. Also, infectious diseases of the CNS (meningitis, encephalitis and brain abscess) accounts for a high proportion of secondary epilepsy. Leary et al., (26) postulated that the high prevalence symptomatic epilepsy in developing countries raises the concern among the health population for the need for preventive measures within the community aimed to reduce the prevalence of perinatal insult, meningitis, tuberculosis, neurocysticercosis and cerebral trauma.

In this study, mental retardation (MR) represented the most common neuroimpairment among cryptogenic and symptomatic group of patients (60.7% and 39.3%). MR had been considered the most common associated abnormality (26%) with epilepsy of unknown etiology (23). Intellectual deficits play a significant role in the psychosocial comorbidity of children with epilepsy (29). Many studies suggested that risk of epilepsy is highest in children when associated with serious neurologic abnormality, such as MR and cerebral palsy (37). Hence delineation of specific epileptic syndrome has important implications when considering intellectual potentials, as early educational intervention is critical. The recurrence rate is approximately 70% in both children and adults once the patient had two seizures (20).In general the risk for recurrence in epilepsy is high and higher in children with an associated serious neurologic abnormality, such as mental retardation and cerebral palsy (38).

According to the international classification of epilepsies and epileptic syndromes, we distinguished Three main types of patients; generalized epilepsy (42.5%), localization-related epilepsy (48%) and undetermined seizures (9.5%). Endziniene et al. (15) demonstrated that 50% of their pediatric epileptic patients were localization-related epilepsies, while generalized epilepsies were reported only in 29.9% while 15.9% were undetermined whether partial or generalized and 4.2% were unclassifiable. In contrast, Al Rajeh et al. (1) demonstrated that generalized epilepsies were the commonest type of epilepsy between ages of 1-5 years (74%) followed by febrile convulsions (20%) while isolated seizures were reported in 3% of studied patients. In the study of Al Rajeh et al. (2), the authors reported partial seizures in 28%, generalized seizures in 21% and they were unable to determine whether generalized or focal in 51% of their studied patients. In our study, specific age-related epileptic syndromes represented 20.5% (26/127). In contrast, the prospective study carried by Al-Sulaiman et al. and Ismail (3) reported specific age related epileptic syndromes in 11.4% of their studied patients. Regarding different subtypes of generalized epilepsies, we identified four subtypes of generalized epilepsy among which the generalized tonic-clonic seizures were the most frequent (72.1%), followed by absence (14.9%). Granieri et al. (17) reported tonic, clonic and tonic-clonic seizures in 74.9% and childhood absence in 6.6% of epileptics. Haerer et al. (18) reported tonic-clonic attacks in 75% and absence seizures in 0.4%. Shawki et al. (38) demonstrated that generalized tonic-clonic seizures were the most frequent type of seizures (49.5%), followed by atonic seizures (25.3%) then tonic seizures (21.6%), while myoclonic seizures (2.6%) and absence (1.0%) were the least frequent types. It is a common observation that absence epilepsy has low frequency among other types of epilepsy, a finding which could be explained by the fact that absence has mild symptoms and could not be easily recognized (32).

Approximately 10.2% of our patients presented with febrile convulsions. Febrile convulsions represented 24% of our generalized epilepsies. Febrile convulsion is considered a fundamental marker of an individuals’ seizure threshold and risk for development further epilepsy. Many studies demonstrated that febrile seizures most often precede generalized tonic-clonic afebrile seizures (9). Higher percentages (8.9-23%) were reported by Rocca et al. (35). Khedr et al. (22) reported that fever is the most frequent precipitating cause of seizure in 48.6% of their studied epileptic patients. Febrile convulsions are linked to subsequent epileptic seizures through a preexisting liability of the brain to convulse, either genetically determined or induced by a lesion during brain development (35). Many data support the hypothesis of genetic propensity for febrile convulsions (generalized tonic-clonic seizures), which may represent early expression of a low seizure threshold that subsequently develops into epilepsy (21, 29).

Approximately 31.5% of our patients although had clinical seizures reported normal EEG with no background or epileptic activity. Although the percentage is higher than that in other studies but this is not surprising as it is generally known among neurologists that a seizure disorder is a clinical diagnosis. The 8 channels EEG machine used has a low or poor yield compared with machines of higher channels. Although this could be taken as one of the limitations of our study however, many other studies that used high sensitive EEG machines recorded normal results. It could also be due to different sensitivities of different EEG techniques. Waaler et al. (40) recorded absence of epileptogenic activity in 14% of patients. Yoshinaga et al. (41) found epileptic discharges in 75.6% of epileptic patients on initial EEG, which is higher than figures reported previously for adults. The cumulative incidence of epileptic discharges was 92.3% by the third EEG recording. The authors reported 17.1% of patients with non-specific idiopathic generalized epilepsy had no epileptic discharges even after three EEG recordings. This has been attributed to the lower incidence of epileptic discharges in patients with partial seizures than those in patients with generalized seizures (41).

In our study, the most frequently diagnosed childhood epilepsy (electro-clinical) was localization-related epilepsy (48%). This is comparable to adult onset epilepsy in which partial epilepsies were the most frequent types (22). Recent several studies of new onset of seizures showed that the majority of childhood onset epilepsy is localization-related or partial, not generalized, as was not believed in the past. In general, it was postulated that partial epilepsies comprise slightly over 50% of all epilepsies and accounts for about 40-50% of childhood epilepsy and 90% of epilepsy in adults (20). In a study carried in a general children hospital in Southern Stockholm, Sweden, by Braathen and Theorell (7), partial seizures were seen in 52% of the children. In a study of Berg et al. (6) of new onset epilepsy in Connecticut, the distribution of epileptic syndromes in children at the time of diagnosis was 45% to 55% localization-related, 30% generalized and 10-15% undetermined. In this study, partial epilepsy with secondary generalization was the most frequent type of localization-related epilepsy (62.3%) compared to simple partial epilepsy (22.95%). While complex partial seizure was the least frequent (14.8%). In a community-based study in Ulanga, a rural Tanzanian district, focal seizures with secondary generalization was more common than simple focal seizures (37). Symptomatic group represented 26.2% of our localization-related group of patients and this is consistent with many studies. Braathen and Theorell (7) reported that the localization-related epilepsy was symptomatic in 30% and therapy-resistant in 23%. We observed that the frontal and temporal lobe epilepsies represented the most frequent types of localization-related epilepsies (37.7% for each). Al-Sulaiman and Ismail (3) reported that the most reliable EEG abnormalities are the focal spikes or sharp wave discharges over the frontal or temporal lobes. The authors postulated that the frontal and temporal foci are highly epileptogenic in greater than 85% of individuals. Chabolla (10) postulated that the temporal and frontal lobes are the most common sites of producing epileptic discharges.
We identified 7 age specific epileptic syndromes in 20.5% of our patients. It has been suggested that 50% of pediatric epilepsy cases have been found to fit into the category of unique pediatric epilepsy syndromes, or special syndromes (7). In this study, the rolandic epilepsy or benign epilepsy with centrotemporal spikes represented the most frequent type of them (26.92%) and it represented 5.5% of all studied patients. In the study of Braathen and Theorell study (7), benign childhood epilepsy with centrotemporal spikes represented 11% of their patients. Onsurbe Ramirez et al. (31) postulated that benign childhood epilepsy with centrotemporal spikes is the most frequent epileptic syndrome during childhood. Benign childhood syndromes have no impact in child development (34). Benign childhood epilepsy with occipital paroxysms was diagnosed with great probability in only 7.7% of our age-specific epileptic syndromes and only 1.6% of all studied patients. It has been suggested that the EEG of the syndrome of idiopathic partial epilepsy with occipital paroxysms shows a considerable clinical and prognostic heterogeneity. The semiology of seizures varies considerably among patients and the blocking by eye opening which is considered the hallmark of this type of epilepsy is non-specific as it may appear in other idiopathic or symptomatic epilepsies of childhood and even in non epileptic disorders, notably basilar migraine (28). Lennox-Gastaut syndrome (LGS) represented 19.2% of the epileptic syndromes and 3.9% of all studied patients. No patient with LGS has history of infantile spasms (West syndrome) before the onset of developing LGS. This is in contrast to Markand et al. (27) who reported LGS in 25% of their patients with cryptogenic epilepsy and 20% of them had prior infantile spasms with hypsarrythmia. LGS is one of the catastrophic disorders which have a remarkably positive effect on development (34).

CONCLUSIONS

The results of this study proposed the need for 1) Long-term population epidemiological outcome studies aimed to clarify the prevalence of seizure disorders and to identify and classify epilepsy disorders in children group of population in our locality as this will be of value in early management according to the available resources., 2) Preventive measures by raising the standard of health education system as this will help at reducing the prevalence of CNS infections, perinatal insults and cerebral trauma as these represent the main causes of remote symptomatic epilepsy in our patients. 3) Recognition of the prevalence of comorbid intellectual disability among children with epilepsy is important, as this will be useful in planning further EEG research and performing EEG in different clinical settings. Furthermore, this knowledge will facilitate early educational intervention and multidisciplinary therapeutic and rehabilitation approaches.

Table (1): Demographic data of the studied group of patients

Values are expressed as number (%) and mean±SD. Percentage was calculated from the number in each category. M/F=male to female ratio; yrs=years; 0.00” = 1 week.

Table (2): Clinical characteristics of the studied group of patients

Table (3): Characteristics of the studies group of patients: categorization in relationship with the etiology and type of seizures

Values are expressed as number (%) and mean±SD. Percentage was calculated from the number in each category. 0.00″ = 1 week. *significance if comparison occurred versus idiopathic while †significance if comparison occurred versus symptomatic. Significance is expressed as follow: *†P<0.05, **††P<0.01, ***†††P<0.001 Table (4): Characteristics of mentally retarded group of patients

Values are expressed as number (%) and mean±SD. Percentage was calculated from the number in each category. M/F=male to female ratio, 0.00″ = 1 week. *significance if cryptogenic was compared versus symptomatic while †significance if males were compared versus females. Significance is expressed as follow: *†P<0.05, **††P<0.01, ***†††P<0.001

Yaounde (CAMEROON) on the 3rd and the 4th of October 2007.

International Course of Neurosurgery with the World Federation of Neurosurgical Societies (WFNS)

Yaoundé (CAMEROUN), 03 et 04 Octobre 2007.

Cours International de Neurochirurgie avec la World Federation of Neurosurgical Societies (WFNS)

Contact :

Dr SAMUEL WANDJA (wandjasamuel@yahoo.fr)

RESUME

Nous rapportons le premier cas de sarcoglycanopathie diagnostiqué en Côte d’Ivoire chez un enfant de 8 ans, tunisien, né de parents consanguins. Le tableau clinique réalisait une myopathie de « Duchenne like »Les taux des CPK atteignaient 150 fois la normale. L’EMG a confirmé le syndrome myogène. La biopsie musculaire avec études immunohistochimiques et l’analyse en western blot, réalisées en Europe, ont mis en évidence le déficit en sarcoglycane caractérisé par un immunomarquage totalement négatif pour l’alpha sarcoglycane et un immunomarquage présent mais anormal pour la bêta et la gamma-sarcoglycane. Compte tenu de l’origine tunisienne du patient les recherches génétiques ont été orientées en premier lieu vers la sarcoglycanopathie gamma.
Les complications cardiaques qui dominent classiquement le pronostic des sarcoglycanopathies n’existaient pas chez notre patient qui n’avait que des complications orthopédiques. La corticothérapie a entraîné une stabilisation de l’évolution de la maladie.
Cette observation nous a permis de relever les problèmes de la prise en charge de cette pathologie dans notre contexte de travail où le diagnostic de certitude qui nécessite des techniques spécialisées est impossible.

Mots-clés : Afrique, enfant, myopathie, sarcoglycanopathie

SUMMARY

The authors report the first case of sarcoglycanopathy observed in Côte d’Ivoire. It concern a 8 years old Tunisian child born from consanguineous parents which were germen cousins . The clinical feature was a Duchenne like »myopathy. The CPK rate was very high ( 150x N ) EMG confirmed myopathic syndrome. The muscular biopsy with immunohistochimical studies and the western bloc analyse, were done in Europe. There obvioused the defect of the sarcoglycanes protein with a negative immune marquage for the alpha sarcoglycane and an abnormal immune marquage for the beta and the gamma-sarcoglycanes. Because of the tunisian origin of the child the genetic researches were in first focused on the gamma sarcoglycanopathy.
Cardiac complications, which classically dominate the prognostic of the sarcoglycanopathies, were absent in our case. The corticotherapy has stabilized the course of the disease
This case report relieves the difficulties of the care of the muscular progressive dystrophies in our working area where the certification of the diagnosis is not possible due to the lack of the means of the diagnosis, which are specialized, expensive and so inexistent in most of African countries

Keyswords: Africa, child, myopathy, sarcoglycanopathy

INTRODUCTION

Les progrès de la neurogénétique ont complètement révolutionné la classification des dystrophies musculaires progressives (DMP) en permettent d’individualiser plusieurs types de myopathies en rapport avec une altération des gènes codant pour les différentes protéines de la fibre musculaire. Ainsi les sarcoglycanopathies regroupent l’ensemble des DMP touchant les quatre gènes codant pour les différents types de sarcoglycanes : alpha, bêta, delta et gamma.(1)Plusieurs termes comme LGMD (limb girdle myopathy dystrophy ) 2C, 2D, 2 E et 2F ou SGC (sarcoglycanopathies)A, B,C ou D sont utilisés pour les désigner.

Elles présentent une grande similitude clinique, et seule l’approche mixte combinant l’immunocytochimie et une analyse mutationnelle permet de les distinguer, d’où l’importance de la biopsie musculaire pour l’analyse des protéines musculaires à l’aide d’anticorps spécifiques.
En rapportant ce cas de myopathie magrébine due à une sarcoglycanopathie notre objectif était de mettre en exergue les difficultés du diagnostic et de la prise en charge de cette pathologie, dans notre contexte de travail en Afrique.

OBSERVATION

A B est un garçon tunisien, né le 22 août 1992, lycéen vivant en Côte d’Ivoire, âgé de 8 ans lorsqu’il est reçu en consultation de neurologie dans une clinique privée d’Abidjan en Janvier 2001. C’est le 2è enfant d’une famille de trois enfants. Ses parents sont consanguins, cousins germains eux même nés de parents consanguins. Il n’y a ni antécédent personnel pathologique, ni antécédent familial de myopathie. La marche a été acquise à l’âge de 13 mois. Dès les premiers pas il a présenté des difficultés motrices notamment lors de la station debout, de la montée des escaliers avec des chutes fréquentes. Il n’a jamais pu courir, n’était pas capable de se doucher car il ne pouvait pas lever le pommeau de douche au- dessus de sa tête. Il présentait une lenteur dans les gestes de la vie
quotidienne.

L’examen clinique a objectivé un syndrome myogène des ceintures. La marche était très peu
dandinante, difficile sur les talons, instable mais possible sur les orteils. A la station debout on notait une instabilité en appui monopodal et une impossibilité de sauter à cloche pied. Le déficit moteur proximal touchait le tronc, la ceinture scapulaire et la ceinture pelvienne. Il y avait un signe de Gowers. L’amyotrophie des cuisses et des épaules était nette.Les réflexes idiomusculaires étaient abolis. Les réflexes ostéotendineux étaient normaux. Il n’y avait pas de troubles sensitifs. Le développement intellectuel était normal et les résultats scolaires étaient excellents. Le déficit musculaire s’accompagnait de déformations marquées du squelette : attitude en hyperlordose du rachis et bascule antérieure du bassin. On notait une rétraction tendineuse tricipitale et achilléenne avec une flexion dorsale à 90°. Il n’y avait pas de pseudohypertrophie des mollets. L’examen des appareils cardiovasculaire et respiratoire était normal.
L’hémogramme était normal. La VS était normale. L’EMG confirmait le syndrome myogène des 4 membres respectant la face. Le dosage des enzymes musculaires montrait des chiffres de CPK très élevés à 6800UI/l.(N=270UI/ L)
Le patient est évacué en France, au CHU à Tours, dans le service spécialisé des consultations pluridisciplinaires neuromusculaires où il bénéficiera d’une série d’investigations complémentaires plus poussées non disponibles à Abidjan. La biopsie musculaire du quadriceps (Service d’anatomie pathologique – Hôpital Bretonneau) ayant confirmé la dystrophie musculaire, l’hypothèse d’une dystrophinopathie ou d’une sarcoglycanopathie est évoquée en raison de l’origine tunisienne des parents. Les immunomarquages sur des coupes de muscle congelé avec un témoin positif ont révélé après un contrôle à 2 reprises un immunomarquage totalement négatif pour l’alpha sarcoglycane, tandis qu’il existait un marquage anormal, mais présent, des myocytes pour la bêta et la gamma-sarcoglycanes. L’analyse en Western blot des protéines du complexe de la dystrophine (Laboratoire de Biochimie et Génétique Moléculaire- Hôpital Cochin )était également en faveur du diagnostic de sarcoglycanopathie.
L’aspect d’ensemble de cette dystrophie musculaire et son profil immunohistochimique étaient donc très en faveur d’une sarcoglycanopathie, en particulier d’un déficit en alpha-sarcoglycane ou adhalinopathie. Mais à ce stade, il n’était pas possible de savoir si l’anomalie primaire concernait l’alpha sarcoglycane ou la gamma-sarcoglycane, car l’anomalie d’une des deux sarcoglycanes retentit très souvent sur l’autre, ce qui explique qu’elles peuvent paraître simultanément diminuées lors de l’étude de la biopsie musculaire. L’étude génétique moléculaire effectuée dans le cadre de l’étiquetage de la myopathie, a permis de confirmer l’origine génétique de la myopathie. L’ECG et l’échographie cardiaque réalisés dans le cadre du bilan évolutif à la recherche des complications cardiaques étaient normaux.

Le traitement a comporté pendant 2 ans une physiothérapie douce secondairement associée à une corticothérapie par voie orale instituée à la dose de 30 mg/j pendant 10 jours avec des interruptions de 10 jours.
L’évolution clinique a été marquée avant l’instauration de la corticothérapie par une aggravation très lente avec une progression distale du déficit moteur,une démarche de plus en plus dandinante, une rétraction tendineuse rotulienne, une abolition des réflexes ostéotendineux, et une lordose plus accentuée. Six mois après l’introduction de la corticothérapie une stabilisation clinique a été constatée avec l’amélioration du déficit moteur distal et la disparition des rétractions tendineuses. Les contrôles de l’ECG et de l’échographie cardiaque restaient normaux après 2 ans dévolution.

COMMENTAIRES

Nous rapportons le premier cas de sarcoglycanopathie diagnostiqué en Côte d’Ivoire où la rareté de l’affection peut s’expliquer par les faibles possibilités d’investigation des maladies neuromusculaires, qui restent limitées aux dosages enzymatiques et à l’ENMG. Or l’ENMG n’est disponible que dans très peu d’hôpitaux publics. Les techniques spécialisées de génétique moléculaire et d’immunomarquage qui permettent de faire le diagnostic des sarcoglycanopathies ne sont pas disponibles. Par ailleurs, le tableau clinique de type Duchenne like réalisé par les sarcoglycanopathies peut égarer le diagnostic et faire retenir celui de Myopathie de Duchenne considérée comme la plus fréquente des myopathies de l’enfant (1) Enfin la pratique peu répandue des mariages consanguins en Côte d’Ivoire où elle ne concerne que quelques groupes ethniques à la différence des pays maghrébins pourrait également expliquer la relative rareté de ces affections dans ce pays.

La fréquence réelle des myopathies est méconnue mais les sarcoglycanopathies représentent 20% des cas de myopathie (13, 18) Ce sont les plus fréquentes des myopathies des ceintures après les calpaïnopathies qui représentent environ 50% de l’ensemble des LGMD (17)Parmi les sarcoglycanopathies, les alpha-SGP sont les plus fréquentes (11,16) Les ,γ et -sarcoglycanopathies s’observent chez l’enfant mais les α-sarcoglycanopathies peuvent s’observer à tout âge (12) .

La classique appartenance à un groupe particulièrement exposé est typiquement illustrée par notre observation qui concerne un enfant maghrébin tunisien, né de parents consanguins, cousins germains, eux-mêmes issus d’une famille endogamique.En effet malgré leur caractère ubiquitaire la plupart des sarcoglycanopathies surviennent dans un groupe de population caractérisée par une forte endogamie. C’est le cas des tunisiens du Maghreb, des communautés de blancs de l’île de la Réunion, des Amishs de l’Indiana ou des Mémonites américains (1) Ainsi la sarcoglycanopathie gamma (LGMD 2C) concerne plus particulièrement deux groupes ethniques : les populations à forte endogamie du pourtour méditerranéen et les Tziganes vivant en Europe. Dans certaines contrées, comme le Maroc ou l’Algérie, elles peuvent même représenter jusqu’à la moitié des cas de dystrophie musculaire autosomique récessive (1) C’est pourquoi devant l’origine tunisienne de notre patient, les recherches génétiques ont été en premier lieu orientées vers une sarcoglycanopathie gamma.
La population à risque de la sarcoglycanopathie bêta (LGMD 2 E) est la communauté d’Amishs de l’Indiana et de Pennsylvanie. Quant à la sarcoglycanopathie delta (LGMD2F) elle concerne à ce jour moins d’une dizaine de familles brésiliennes. Seule la sarcoglycanopathie alpha (LGMD 2D) a une distribution géographique universelle (1)
Le tableau clinique de notre patient réalisait une myopathie des ceintures non spécifique qui a posé des problèmes de diagnostic différentiel difficiles à résoudre sur la base des seuls arguments cliniques. (8,15,17) Il s’agissait d’abord de reconnaître la sarcoglycanopathie devant un phénotype clinique de myopathie des ceintures de type Duchenne ou Becker like semblable à celui des dystrophinopathies (8,17) puis de préciser le type de sarcoglycanopathie. Au sein même des sarcoglycanopathies, il existe des similitudes cliniques difficiles à distinguer et les particularités propres à chacune des sarcoglycanopathies peuvent contribuer au diagnostic (1)
La liste des explorations des sarcoglycanopathies étant longue et sophistiquée, il est nécessaire de recourir à une stratégie raisonnée, de la biopsie musculaire à la découverte de la mutation causale. Il n’y a pas de schéma formellement déterminé et c’est toujours une anamnèse et un examen clinique soigneux qui dicteront le choix de ces examens (9,15) Mais la biopsie musculaire doit précéder chaque fois que possible l’analyse génotypique (4,17) Les examens génétiques restent actuellement le seul moyen de confirmer l’affection avec certitude et permettent d’individualiser les particularités paracliniques propres à chacune des sarcoglycanopathies. (4,11).

Les seules complications observées chez notre patient étaient orthopédiques à type de scoliose, d’hyperlordose et de rétractions tendineuses. Elles aboutissent classiquement à terme à la perte de la marche à un âge relativement jeune (1, 6,10, 17).

A ce stade de l’évolution le pronostic vital de notre patient était préservé en l’absence des complications cardiorespiratoires qui font toute la gravité de la myopathie dont elles déterminent le pronostic vital. Les troubles du rythme et de la conduction, ou la cardiomyopathie dilatée ou non peuvent être à l’origine du décès des patients à un âge relativement jeune (1,5, 7, 14) Il est difficile de prédire avec certitude l’absence de complications cardiaques. Mais les complications cardiaques sont observées surtout chez les patients atteints d’un déficit en α SG, en γ SG mais aussi en  SG (5) alors que les complications respiratoires à type de syndrome restrictif, d’apnée du sommeil, d’insuffisance respiratoire et d’infections pulmonaires surviennent surtout dans les α et γ sarcoglycanopathies (1).

L’évolution est habituellement lente et surtout très variable. Plusieurs études insistent sur la grande variabilité intra et interfamiliale (1,2,3,10) Mais la plupart des patients ayant une mutation des gènes du  et γ sarcoglycane présentent des tableaux cliniques sévères (2,5,17) Néanmoins des variantes moins sévères, paucisymptomatiques ont été décrites au Brésil (1)
Notre patient a d’abord bénéficié uniquement d’une kinésithérapie régulière. Elle permet souvent de retarder la perte de la marche. La corticothérapie a entraîné la stabilisation de la maladie en retardant l’évolution clinique et en corrigeant les faiblesses musculaires (1, 3,7) Devant le vide thérapeutique, son usage est préconisé même s’il ne s’agit pas d’un traitement codifié(1).

CONCLUSION

Cette observation montre qu’en Côte d’Ivoire, l’investigation paraclinique des myopathies est limitée aux examens de routine ce qui pourrait expliquer la relative méconnaissance et la sous estimation probable de cette pathologie dans ce pays.

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