BACKGROUND AND PURPOSE
An epileptic area with high endemicity has been described in Bilomo (15, 29), a small village situated some 120 Km north of Yaounde, where several parasitic diseases are endemic: loiasis (40), onchocerciasis (40, 5, 4, 30), schistosomiasis (24), trypanosomiasis (23), and paragonimiasis (32). The relationship between onchocerciasis and epilepsy has been postulated although this remains yet to be confirmed. A case-control study to determine the role of cysticercosis in the aetiology of epilepsy in this area did not find a significant relationship (12). A programme of studies to determine the epidemiological, clinical and etiological features of epilepsy in this area, was thus set up in order to obtain baseline data for the development of a national epilepsy control programme. This study aimed to determine some of the risk and precipitating factors associated with epilepsy in Bilomo village.
PATIENTS AND METHODS
This was a cross-sectional door-to-door community-based survey carried out between August and October 1998. Study site: Bilomo is a small village situated 120 Km north of Yaounde, on the west bank of the Mbam river in the Mbam et Kim Division (headquarters in Bafia), in the Centre Province of Cameroon. It has a population of 1898 subjects (study census) made of the Sanaga people, a sub ethnic group of the Bantous. The geographical features of this region with savanna vegetation in close proximity with the dense and humid equatorial forest; temperatures varying between 22 and 25°C and annual rainfall between 1500 and 2000 mm (26), have rendered it an endemic focus for many parasitic diseases. The inhabitants of the village are mostly peasant farmers practicing mixed farming. The village has 2 health centres (one public and the other catholic) and belongs to Mbangassina health area which is one of the 14 health areas of the Ntui health district. The health district is run by a district health officer (general practitioner). Neither of the centres offered services for the analysis of basic blood biochemistry at the time of the study.
Study instrument: The questionnaire used for the study was that which was developed through collaborative work involving the Institute of Neurological Epidemiology and Tropical Neurology of Limoges (France), the Pan-African Association of Neurological Sciences and the International League Against Epilepsy (Commission on Tropical Diseases, 1993-1997) (31). The purpose of this questionnaire was to standardize information on studies conducted on the epilepsy. This questionnaire is now widely used in various tropical and subtropical regions. It has a modular structure and comprises nine sections: demographic data, screening, confirmation of diagnosis, natural history of the seizure disorder, past medical history, clinical examination, paraclinical examinations (as are available), aetiology and treatment. This modular nature makes it flexible and adaptable in different socio-economic contexts without sacrificing the need for comparability of results. The questionnaire investigates 4 different objectives: screening, clinical forms of epilepsy, aetiology and treatment. Section III - 5 - deals with the past medical history. The questions concern the family history of epilepsy, and the personal history with an emphasis on the pregnancy history of the subject’s mother, birth and psychomotor development, infant diseases and neurological sequaelae due to these diseases and the period before the appearance of this sequaelae. Encephalitis is diagnosed if there is impairment of consciousness, presence of local neurological signs and fever. Encephalopathy presents with alterations of consciousness and neurological abnormalities. Meningitis is characterized by meningeal syndrome associated with fever. Coma beyond 24 hours is considered prolonged.
Inclusion criteria: Indigenous residents of Bilomo village who have presented with at least 2 unprovoked epileptic seizures.
Exclusion criteria: Individuals with febrile convulsions and individuals not resident in Bilomo at the time of study.
Data collection: Survey interviews were conducted by a team of trained personnel. Suspected cases of epilepsy were reviewed by 2 consultant neurologists from the Faculty of Medicine and Biomedical Sciences. The medical case histories, general examination and thorough neurological assessment were done by the consultant neurologists. For confirmed epileptic patients, blood samples were collected and stored in ice-containers for subsequent analysis. Blood samples were examined for full blood count and differential, haemoglobin electrophoresis and blood parasites, - such as Plasmodium species and microfilaria after classic staining methods thick smear stain and May-Grunwald-Giemsa stain. Stool samples were examined in the catholic centre using an optic microscope. Stool parasite studies included cysts, eggs, protozoan and amoebae. Other risk and precipitating factors for epilepsy were recorded as per research instrument. No EEGs were done for technical reasons.
Data analysis: This was done using EPI Info version 6.04 c.
Using the questionnaire, one hundred and fifteen (115) subjects from the study village population of 1898 subjects were suspected of having epilepsy. After a clinical review (history and clinical examination) by consultant neurologists, 93 cases of epilepsy were confirmed, giving a prevalence rate of epilepsy in Bilomo of 4.9%. A history of central nervous system infections was reported by the patients or relatives in less than 10% of cases. These included meningitis (complicated or uncomplicated), meningo-encephalitis although the specific aetiologic diagnosis could not be determined. The neurological examination was abnormal in 22.58% of the 93 epileptic patients. Mental retardation was found in 17.2%, psychological disorders in 16.1%, a pyramidal syndrome (unilateral or bilateral weakness with spasticity and Babinski sign) in 6.4%, language disorders in 4.3%, and a cerebellar syndrome in 1.1% of the patients. Several patients had a combination of signs. Language disorders consisted mainly of aphasia or dysphasia. The psychological disorders were predominantly behavioural. All these disorders were reported by 12 patients to have existed for at least one year before the examination date. Subcutaneous nodules were observed in 13 patients (13.98%). Pruriginous dermatoses were found in 23 patients (24.73%).
Risk factors for epilepsy were found in 66 patients (70.97%). The most frequent risk factor (63.44%) was a positive family history. The other risk factors were prenatal disease conditions (8.60%) and perinatal pathologies (19.35%), central nervous system infections (9.67%) and head injury (5.37%). The perinatal risk factor most observed in our series was prolonged labour in 7 cases (7.52%). Most of the patients, whose education was limited at the primary level (77.4%) and secondary (7.5%), were school drop outs and the main reasons given were lack of financial resources and seizure severity. Some had never been to school at all (15.5%).
The age at which the first seizure occurred is shown in Table I below.
Table I: Distribution of patients according to age of first seizure.
|Age at onset (years)||Male (n = 51)||Female (n = 42)||Total (n=93)||Percentage (%)|
|0 - 2||1||3||4||4.30|
|3 - 6||5||4||9||9.68|
|7 - 12||19||14||33||35.48|
|13 - 20||21||20||41||44.09|
|21 and more||4||0||4||4.30|
The age of patients at which the first seizures occurred was between 6 months and 35 years. The first seizures occurred before the age of 20 years in 93.55% of patients. Some of the precipitating factors for seizures found are shown in Table II below.
Table II: Distribution of patients according to precipitating factors
|Precipitating Factors||Children (n=27)||Adults (n=66)||Total (n=93)||Percentage (%)|
Sleep and treatment withdrawal were the main seizure precipitating factors. Some patients had an association of several precipitating factors.
Stool examination for parasites was performed in 87 patients and the results are shown in Table III below.
Table III: Stool examination Findings
|Parasite eggs||Children||Adults||Total (%)|
|Ascaris||18 (72%)||28 (45.16%)||46 (52.87)|
|Trichocephale||5 (20%)||14 (22.58%)||19 (21.84)|
|Ankylostoma||1 (4%)||15 (24.19%)||16 (18.39)|
|Oxyura||0 (%)||3 (4.84%)||3 (3.45)|
|Taenia||1 (4%)||1 (1.61%)||2 (2.30)|
|Anguillulos||0 (0%)||1 (1.61%)||1 (1.15)|
Blood examinations were done in 89 patients and the results are shown in Table IV below.
Table IV: Blood examination parameters.
|Blood Parameter||Mean ± SD|
|Red blood cells (x 106 /mm3)||5.38±1.04|
|Mean RBC Hb concentration (%)||27.7±2.12|
|Mean global Hb level (pg)||24.60±2.57|
|White blood cells (x 103 /mm3)||6.46±2.61|
|Neutrophilic PMN cells||44.61±10.23|
|Eosinophilic PMN cells (%)||14.19±6.49|
|Basophilic PMN cells (%)||0.08±0.27|
|Platelets (x 103 /mm3)||136±204.1|
|Erythrocyte sedimentation rate (mm in first hour)||8.7±20.81|
|Fasting blood sugar (g/L)||0.85±0.30|
Hypereosinophilia (considered as greater than 5% of eosinophilic polymorphonuclear cells) was found in 90.1% of these patients. Haemoglobin electrophoresis was done in 90 patients and 4 males and 10 females (15.6 %) were carriers of the S gene (haemoglobin AS). There was no case of homozygous sickle-cell patient found amongst the epileptic patients.
A summary of risk factors is shown in Table V below. The factors are not mutually exclusive (a single patient could have more than one risk factor).
Table V: Summary of Risk Factors for epilepsy.
We found a risk factor in 66 patients (71.0%). Hypereosinophilia and a positive family history were the most frequent risk factors (90.1% and 63.4% respectively). The other risk factors included prenatal (8.6%) and perinatal (19.4%), central nervous system (CNS) infections (9.7%) and head injury (5.4%). CNS infections included meningitis, meningo-encephalitis and were diagnosed mainly clinically so cases of cerebral malaria and other specific infections could not be determined. According to Jallon (20), a specific aetiology has been found for epilepsy in about 25 to 30% of cases in most studies and the aetiology of epilepsy varies significantly with age. More than a quarter of our cases could not be associated with an aetiologic factor. The percentage generally reported in Africa is variable: 40.8% by Dongmo (14) in Cameroon; 57% by Collomb (7) in Senegal; 64% by Giordano (17) in Côte d’Ivoire; 20.8% by Tchawouo (38) in Cameroon; 17.5% by Sridharan (37) in Lybia. Studies in industrialised countries report higher figures like Jallon et al (21) who found a specific aetiology in 71.0% of cases of first epileptic seizure in the canton of Geneva and Granieri et al. (18) who reported 60.4% in Italy. The determination of specific aetiologies for the epilepsies diagnosed was beyond the scope of the current study.
A positive family history of epilepsy was found in 63.4% of our cases. This figure may be considered unusually high as patients or relatives frequently deny a positive family history because of the stigma associated with epilepsy. However, in this rural area of high endemicity for epilepsy, stigma does not appear to be a major issue. Rather, the patients here tend to consider epilepsy as a serious problem for which they need help. The figures for a positive family history from other studies in Africa and Asia vary considerably: 5.8% by Camara (6) in an urban area in Cameroon, 53% by Collomb (7) in Senegal, 7.7% by Tekle-Haimanot (39) in Ethiopia, 12% by Ruberti in Kenya (33), 38% by Rwiza (34) in Tanzania and 36.6% by Singh (36) in India. The frequency of a positive family history varies depending on the definition of the family and the local marriage customs. We considered the extended family in our survey (including in the family, uncles, aunts, cousins, nephews and nieces). Consanguineous marriages are practised frequently in Bilomo village. In some of the families we studied, up to 6 members of the family were affected while some families had not even a single case of epilepsy. However, it can not yet be determined if these cases of epilepsy in families have a genetic character. Genetic diseases like sickle cell anaemia which can be complicated by stroke and epilepsy, was not found in any of our epileptic patients although the prevalence of the Hb S trait was high. In the last decade, several different chromosomal loci for common generalized epilepsies have been identified (11). These include two separate loci for juvenile myoclonic epilepsy in chromosomes 6p and 15q. The epilepsy locus in chromosome 6p expresses the phenotypes of classic juvenile myoclonic epilepsy, pure generalised tonic clonic seizure on awakening, and possibly juvenile myoclonic epilepsy mixed with absences (11). The familial cases of epilepsy in our study could either represent a familial genetic trait or a familial exposition to an environmental epileptic risk factor. Genetic studies need to be done on the most affected families in order to attempt to unravel the possible genetic predisposition to epilepsy in these families.
Our study found less than 10% of cases with central nervous system infections. This figure is midway between the higher levels reported in other African countries: Collomb 19.6% in Senegal (7), Debouverie 28.9% in Burkina-Faso (10) and much lower figures: 2.1% by Danesi (9) in Nigeria, 2.5% by Grunitzky in Togo (19), 4% by Mwinzi in Kenya (25) and 1.2% by Billinghurst in Uganda (3). The association of onchocerciasis and epilepsy has been discussed by several authors (4, 16) and that of cysticercosis by Avode et al. (1). In a case-control study on neurocysticercosis and epilepsy, a significant correlation between neuroocysticercosis and epilepsy was not found in this area (12). However, such a relationship has been reported in a study in the western region of Cameroon (27). Hypereosinophilia was found in 90.1% of our patients. Dada reported a much lower figure (35.9%) in Nigeria on a sample of 175 epileptic patients (8) but they considered hypereosinophilia as greater than 8%. Many factors may explain the occurrence of hypereosinophilia in our patients: intestinal parasitoses as shown in Table IV, blood and cutaneous nematodes (filariasis) like onchocerciasis. Subcutaneous nodules, presumed to be onchocerca nodules were observed in 13 patients (13.98%). Stool examinations showed eggs of intestinal parasites (Ascaris sp as leading parasite) in 95% of the epileptic cases in the present study. A recent study conducted in Egypt has shown a relationship between Ascaris infection and epilepsy (41). In this study involving 537 patients with epilepsy, the level of ascaridiasis infection was severe to moderate for 68 % of them, and after anti-helminthic treatment, the authors observed a reduction of the annual average number of partial seizures by 10 % (p<0.001), whereas the mean number of generalised seizures did not vary significantly. Studies employing both neuro-imaging and biological techniques are needed to examine the aetiopathogenic role of neurocysticercosis, onchocerciasis, trypanosomiasis, ascaridiasis and neurological complications of HIV (28) as well as other infections in epilepsy in this area.
The common risk factors for epilepsy in the prenatal period apart from maternal fever were not observed in our study (maternal infections, stroke, drug poisoning and anaemia). The perinatal risk factor most observed in our series was prolonged labour in 7 cases (7.52%). In most studies the incidence of obstetrical trauma is higher (14, 38, 2, 22). In Bilomo, pregnant women are followed-up by well trained personnel in the health centres who do early detection of dystocic cases and quickly transfer to the district hospital for appropriate management. Home deliveries are done for non high risk pregnancies by well trained traditional birth attendants under the supervision of the health centre personnel.
The role of head injury in the development of epilepsy is known and is linked to the presence of open scalp wounds, intracranial haematomas and prolonged loss of consciousness (more than 24 hours) as Salazar et al. reported in Vietnam (35) that 53% of patients with a skull wound developed epilepsy. However in Bilomo all head injury cases were minor, with no apparent impact on epilepsy.
Other rare risk factors like sickle-cell disease may be important in our population. The haemoglobin S trait was present in 15.6% of our patients.
Sleep and treatment withdrawal were the main precipitating factors of epilepsy found in this study. The low level of education and low socio-economic status of most of the patients might explain poor treatment compliance. Alcohol use or abuse was not a major precipitating factor as majority of the patients were young and supposedly not yet engaged in this practice.
A better understanding of the risk factors in this rural area of Cameroon is necessary for the improvement of the management of epilepsy, which we have shown to be possible in spite of several difficulties, with the available treatment regimens (13).
The data from this preliminary study suggests that in Bilomo village, the risk factors associated with epilepsy may include both hereditary (not proven) and acquired factors. We postulate that there may be a complex interplay of both these factors in the aetiopathogenesis of epilepsy in this area. These results call for more studies to determine the aetiologic factors and more importantly, the interplay between these factors that is responsible for rendering epilepsy endemic in this area. Such information is essential for the development of an effective national epilepsy control programme.
|The authors acknowledge the personnel of the Bafia Health District for their contribution to the conduct of this study. Special thanks to Reverend Sister Franca de Simone of the Catholic Health Centre Nyamanga for her assistance.|