The prevalence of epilepsy and other seizure disorders in an Arab population: a community-based study

Seizure 2001; 10: 410 414 doi:10.1053/seiz.2001.0602, available online at http://www.idealibrary.com on The prevalence of epilepsy and other seizure disorders in an Arab population: a community-based study S. AL RAJEH, A. AWADA, O. BADEMOSI & A. OGUNNIYI Division of Neurology, King Saud University; King Fahad National Guard Hospital; Riyadh and Department of Neurology, King Faisal University, Dammam, Saudi Arabia Correspondence to: Professor Saad Al Rajeh, Division of Neurology, Department of Medicine, King Saud University, P. O. Box 85064, Riyadh 11691, Saudi Arabia Purpose: To determine the prevalence of epilepsy and other convulsive disorders and the causes of symptomatic epilepsies in a Saudi Arabian population. Methods: Door to door survey of a restricted area inhabited by 23 700 Saudi nationals. The World Health Organization (WHO) protocol designed to detect neurological disorders was used as screening instrument. All patients with probable seizures were examined by a neurologist and 92% of positive cases were investigated by brain computed tomography (CT) and electroencephalogram (EEG). Results: Prevalence rate (PR) for active epilepsy was 6.54/1000 population (95% confidence interval 5.48 7.60). Twenty-eight percent of the patients had partial seizures, 21% generalized seizures and in 51%, it was not possible to determine if the generalized seizures had focal onset or not. The epilepsy was symptomatic in 32% of the cases: pre or perinatal encephalopathy 23%, head injury 4%, childhood neurological infection 4% and stroke 1%. Febrile convulsions PR was 3.55/1000 children under the age of 6 years and isolated seizures were documented in only 0.18/1000 population. Conclusions: The PR of epilepsy in Saudi Arabs is within the range of the values reported in most communities. The causes of symptomatic epilepsies revealed a predominance of perinatal and inherited factors. Isolated and non-convulsive seizures were probably under-recognized due to various social and cultural factors as well as to lack of sensitivity of the questionnaire for non-convulsive seizures. c 2001 BEA Trading Ltd Key words: epilepsy; seizure; epidemiology; prevalence; Saudi Arabia; cerebral palsy. INTRODUCTION Epidemiologic studies on epilepsy show wide variations in prevalence rates (PRs) from 0.9 to 57 per 1000 population 1 3. The marked differences in the reported PRs may be due to many factors such as accuracy of diagnosis, extent of case ascertainment, sampling criteria, instrument used, and population selection. The introduction of the World Health Organization (WHO) research protocol for neurological disorders in developing countries 4 has been a major breakthrough in the standardization of epidemiological research on epilepsy. Until recently, all the information on seizure disorders in the Arabian peninsula was derived from hospital-based populations which may not be totally representative of the burden in the community 5 7. This study was therefore undertaken to determine the prevalence of epilepsy, the type of seizures and their causes in a defined community in the eastern province of Saudi Arabia. MATERIALS AND METHODS The study was carried out in the town of Thugbah with an estimated population of 28 000 of whom 23 700 are Saudi citizens. The entire community was surveyed in two phases. The initial screening phase of Saudi nationals living in Thugbah was performed using an Arabic translation of the WHO protocol designed to detect neurologyogical disorders 4. All those identified as having potential neurological disorders were then evaluated by a neurologist using defined guidelines and specified criteria to diagnose epilepsy. Many of the 1059 1311/01/060410 + 05 $35.00/0 c 2001 BEA Trading Ltd

Epilepsy and other seizure disorders in an Arab population 411 cases were already being followed-up and investigated in the King Fahd University Hospital, Al Khobar. The others were investigated by electroencephalography (EEG) and brain computed tomography (CT) when possible, to determine the seizure types and putative causes. Magnetic resonance imaging was not available at that time. Details of the survey have been described elsewhere 8. Subjects resident in Thugbah on the study reference date (August 2, 1989) constituted the study population which was used to calculate the respective point prevalence rates. The following definitions were used for the study. Seizures: A clinical condition resulting from an abnormal and excessive discharge of cerebral neurons. The clinical manifestations could consist of sudden and transitory impairment of consciousness with or without convulsions, or other motor, sensory, somatosensory, autonomic and psychic features perceived by the patient or the relations. Seizure-type description followed the criteria of the International League Against Epilepsy 9 which included both clinical and EEG findings. Epilepsy: Two or more afebrile seizures which were not associated with acute CNS insult and not occurring within a 24 hour period. Active epilepsy: Epileptic patient whose seizures occurred not more than 6 months before the study reference date. Individuals who were seizure-free but on specific antiepileptic drug therapy were included in this group. Febrile convulsions (FC): Seizures in children less than 6 years old occurring during a febrile illness without other presumed CNS causes, irrespective of their nature and duration. Isolated seizures: Only one or more epileptic attack occurring within a period of 24 hours. The point PRs were expressed as the number of cases existing on the study reference date per 1000 population. The age- and sex-specific rates were calculated using the total number of subjects for the age and sex-specific group as the denominator. Statistical method for calculating the 95% confidence intervals was based on the test of proportions. RESULTS A total 23 227 Saudi nationals (98% of the eligible subjects) were screened, and 22 630 of them formed the study population (i.e. those residents in Thugbah on the study reference date). One hundred and fortyeight (95 males, 53 females) had active epilepsy and febrile convulsions were present in 19 (15 males, four females). The overall point prevalence rate for active epilepsy was 6.54/1000 (95% CI: 5.48 7.6/1000) with the sex-specific rates for males and females of 8.34 and 4.75 per 1000 population respectively. The age and sex specific prevalence rates are shown in Table 1. Table 1: Age and sex specific prevalence rates of epilepsy in Thugbah (per 1000 population). Age group Males a Females a Total a in years <9 8.66 4.28 6.48 (37/4273) (18/4207) (55/8480) 10 19 13.92 7.17 10.51 (38/2729) (20/2788) (58/5517) 20 29 6.79 3.49 4.99 (13/1914) (8/2290) (21/4204) 30 39 2.84 2.87 2.86 (3/1054) (3/1045) (6/2099) 40 49 3.57 3.48 3.52 (2/561) (2/574) (4/1135) 50 59 0.0 3.55 1.53 (0/373) (1/282) (1/655) >60 2.84 10.6 5.56 (1/352) (2/188) (3/540) TOTAL 8.35 4.75 6.54 (94/11 256) (54/11 374) (148/22 630) a Number of cases/screened population in each group in parentheses. Based on clinical, EEG and CT data, the types of seizures and their putative causes were determined in 136 cases (92%). Thirty-eight patients (28%) had partial seizures, with secondary generalization in 29 of them. These were simple partial in 21 cases and complex partial in 17. Twenty-eight patients (21%) had primary generalized seizures including four children with absence. In the remaining 70 cases (51%) the seizures were unclassifiable either because the patients were unable to give clear ictal details or the EEG failed to show focal or generalized epileptiform pattern. Of the 136 patients, 92 (68%) had idiopathic or cryptogenic epilepsy. The epilepsy was symptomatic in the remaining 44 cases. It was associated with infantile hemiplegia in nine (7%) cases with or without mental retardation, and other types of cerebral palsy in 17 cases (12%). Five other patients (4%) had microcephaly. The epilepsy followed head injury in five cases (4%), childhood infection (probably meningo-encephalitis) in six cases (4%) and stroke in two cases. There was a positive family history of epilepsy in 32 cases (24%), 23 of whom had idiopathic or cryptogenic epilepsy and nine had associated cerebral palsy or microcephaly.

412 S. Al Rajeh et al. Febrile convulsions were documented in 19 out of 5353 cases below the age of 6 years screened. The overall point prevalence rate was 3.55/1000 in the pediatric population. The male sex-specific rate of 5.18/1000 (14/2701) was markedly higher than the figure of 1.88/1000 obtained in females (5/2652). Isolated seizures were documented in three males and one female. The overall crude prevalence rate was 0.18/1000. DISCUSSION This study shows that epilepsy and other seizure disorders are not uncommon in the area surveyed where the demographic characteristics are similar to those from other parts of KSA 10. The overall prevalence rate of 6.54/1000 for active epilepsy is comparable to the results of other studies from both the developed countries and most developing ones. The average prevalence rate in 32 studies from different parts of the world has been estimated at 5.16/1000 1. The PR (per 1000 population) was 9.8 in Pakistan 11, 6.7 8 in different regions of Ecuador 12, 5.7 6.8 in USA 13, 14, 5.3 in Nigeria 15, 4.8 in the Peoples Republic of China 16, 4.8 among the Parsi community in India 17 and 3.6 in Tunisia 18. The sex ratio shows male preponderance. This male excess is presumed to reflect the contribution of etiologic factors such as head trauma known to be more frequent in males 14, 17, 19. This is however difficult to apply to our cases as head injury was responsible for the epilepsy in only five cases. It is possible that epilepsy in women was under-reported in this study due to various social and cultural factors. For instance, women with epilepsy may have difficulties getting married as well as the possible association of epilepsy with evil spirits, etc. Most of our patients had what were described as generalized tonic clonic seizures. However, a detailed history plus EEG findings suggested a focal onset in 28% of them. True primary generalized seizures were observed in only 20% of the cases. In more than half of the cases, it was impossible to know if the generalized seizure had a focal onset. This was mainly for those patient who had a normal or non specific EEG and were unable, because of their age or an associated handicap, to describe a clear focal onset. These frequencies were in accordance with our previous hospital-based study 7 but probably underestimated the frequency of focal seizures. Under-estimation of partial seizures is a common feature of all community-based studies 2. Sander and Shorvon 20 estimated that if all partial seizures in a community could be detected, an overall prevalence of 10 per 1000 for active epilepsy probably would apply to all western populations. Although, in most epidemiologic studies performed in developing countries, the frequency of complex partial seizures did not exceed 6% 11, 16, 17, it reached 9.4% in our study. Absence seizures were observed in 2.7% of our cases which is in the range reported from similar studies 1, 2, 16. However, our questionnaire probably had low specificity for detecting absences in particular and seizures that are not convulsive in general 21. Sixty-eight percent of our cases had no clear etiology. In the absence of magnetic resonance imaging, many symptomatic epilepsies might have been missed and probably classified as either cryptogenic or even idiopathic. Around 70% of epilepsies having no clear etiology has been reported in many similar studies 2, 11, 14, 16, 18. Twenty-five of our 44 cases with known etiology (57%) were due to pre or perinatal fixed encephalopathy. This figure was much higher than the 4.8% reported from Rochester, USA 14 or even the 10% reported from Tunisia 18. Surprisingly, perinatal fixed encephalopathy was not reported as a cause of epilepsy in either China or Pakistan 11, 16. Pediatric intracranial infection was the second most common etiology in our cases with a frequency of 4% similar to the 3 5% reported from other places14, 16, 18 except Pakistan where it constituted almost 10% of the cases 11. However, it is possible that some of the microcephaly cases were due to intrauterine infection. Head injury was also responsible for 4% of epilepsies in our cases, as in Rochester 14 but much less than in China and Pakistan 11, 16. The role of cerebrovascular disease and cerebral tumors in our cases was negligible although they accounted together for more than 9% of the cases in Rochester 14. Some of these apparent peculiarities in the etiology of epilepsy in KSA could be explained by the demographic structure of the Saudi community where 76% of the population are less than 35 years old, and most of the subjects are below the ages when strokes and tumors become important causes of epilepsy. Strokes for example were reported to be the cause of epilepsy in 49% of patients aged more than 60 years in England 22 and 46% in Sweden 23. Another important factor to consider is the high rate of consanguineous marriages in Saudi society with its inevitable consequence of a high frequency of inherited neurologyogical disorders. The consanguinity rate in this community was 56% 8. It is highly probable that some of the socalled cerebral palsies corresponded to inherited fixed encephalopathies of undetermined origin as we have found in a previous study 24. Febrile convulsions were not uncommon from the results of this study and the male excess conforms with the observation of other workers in Saudi Arabia as well as findings from other countries 7, 25, 26. Although the prevalence rate in this study was

Epilepsy and other seizure disorders in an Arab population 413 similar to the figures reported from Guam, Italy and Sweden, it was however markedly lower than the figure of 9.4 136.2/1000 obtained in some other communities 1, 26, 27. The wide variation in the reported prevalence rates for FC probably arose from the differences in the age groups studied and the populations sampled. It is possible to explain our low figures for FC on the basis of the efficient primary health system operative in Saudi Arabia with consequent improved maternal and child care and prompt treatment of childhood febrile episodes before FC developed. However, other factors such as case concealment and recall bias might have contributed to the low prevalence rates of FC. The frequency of isolated seizures was not used in the determination of the overall epilepsy prevalence rate to avoid methodological problems commonly associated with lifetime prevalence studies 28. The rate of recurrence after a first seizure has been reported to vary from 27 to 100% which indicates that isolated seizures are not totally benign 29, 30. It is therefore envisaged that following up these cases as part of assessing a larger population would accurately define their natural history in Saudi nationals. In conclusion, this study showed that the prevalence rate of epilepsy in Saudi Arabia is within the range reported in most other communities. The causes of symptomatic epilepsies revealed however a predominance of perinatal/inherited factors. The attributable risk needs to be studied in depth by subsequent case-control studies. Other issues such as the incidence, risk factors and natural histories of both first unprovoked seizures and febrile convulsions need to be addressed. These unanswered questions suggest that further community studies are required to obtain comprehensive and accurate information on these disorders in our environment so as to plan for effective interventions where indicated. ACKNOWLEDGEMENTS The authors would like to thank Drs F. Farah, H. Ismail and H. Al Freihi for their help and King Abdul Aziz City for Science and Technology for funding the research project (no. AT/10/25). REFERENCES 1. Hauser, W. A. Epidemiology of epilepsy. In: Neurological Epidemiology. Principles and Clinical Applications. Advances in Neurology (Ed. B. S. Schoenberg). 1978: Vol. 19: pp. 313 399. 2. Sander, J. W. A. S and Shorvon, S. D. Epidemiology of the epilepsies. Journal of Neurology Neurosurgery and Psychiatry 1996; 61: 433 443. 3. Schoenberg, B. S. Recent studies of the epidemiology of epilepsy in developing countries. A coordinated program for prevention and control. Epilepsia 1987; 28: 721 722. 4. World Health Organization Protocol: Epidemiologic Studies of Neurologogical Disorders. Geneva, WHO, 1981. 5. Abo Melha, A. M. and Al-Rajeh, S. The pattern and type of seizure disorders among a selected group of Saudi children. Saudi Medical Journal 1987; 8: 583 591. 6. Panayiotopoulos, C. P. and Obeid, T. Juvenile myoclonic epilepsy: an autosomal recessive disease. Annals of Neurology 1989; 25: 440 443. 7. Al Rajeh, S., Abo Melha, A. M., Awada, A., Bademosi, O. and Ismail, H. Epilepsy and other convulsive disorders in Saudi Arabia: a prospective study of 1000 consecutive cases. Acta Neurologica Scandinavica 1990; 82: 341 345. 8. Al Rajeh, S., Bademosi, O., Ismail, H. et al. A community survey of neurological disorders in Saudi Arabia. Neuroepidemiology l993; 12: l64 l78. 9. Commission on classification and terminology of the International League Against Epilepsy. Proposal for revised international classification of epilepsies, epileptic syndromes and related disorders. Epilepsia 1989; 30: 389 399. 10. Shatta, A. A. Studies on Saudi society (Arabic). Dar Alam Al kutub lil Nashr, Riyadh, 1985. 11. Aziz, H., Ali, S. M., Frances, P., Khan, M. I. and Hasan, K. Z. Epilepsy in Pakistan. A population based epidemiologic study. Epilepsia 1994; 35: 950 958. 12. Placencia, M., Shorvon, S. D., Paredes, V., Bimos, C., Sander, J. W. A. S. and Cascante, S. M. Epileptic seizures in an Andean region of Ecuador. Incidence, prevalence and regional variations. Brain 1992; 115: 771 782. 13. Haerer, A. F., Anderson, D. W. and Schoenberg, B. S. Prevalence and clinical features of epilepsy in a biracial United States population. Epilepsia 1986; 27: 66 75. 14. Hauser, W. A. and Kurland, L. T. The epidemiology of epilepsy in Rochester, Minnesota. 1935 through 1967. Epilepsia 1975; 16: 1 66. 15. Osuntokun, B. O., Adeuja, A. O. G., Nottidge, V. A. et al. Prevalence of the epilepsies in Nigerian Africans: a community-based study. Epilepsia 1987; 28: 272 279. 16. Li, S., Schoenberg, B. S., Wang, C., Cheng, X., Zhou, S. and Bolis, C. L. Epidemiology of epilepsy in urban areas of the Peoples Republic of China. Epilepsia 1985; 26: 391 394. 17. Bharucha, N. E., Bharucha, E. P., Bharucha, A. E., Brishe, N. V. and Schoenberg, B. S. Prevalence of epilepsy in the Parsi community of Bombay. Epilepsia 1988; 29: 111 115. 18. Attia-Romdhane, N., Mrabet, A. and Ben Hamida, M. Prevalence of epilepsy in Kelibia, Tunisia. Epilepsia 1993; 34: 1028 1032. 19. Annegers, J. F., Grabow, J. D., Grover, R. V. et al. Seizures after head trauma: a population study. Neurology 1980; 30: 683 689. 20. Sander, J. W. A. S. and Shorvon, S. D. Incidence and prevalence studies in epilepsy and their methodological problems: a review. Journal of Neurology Neurosurgery and Psychiatry 1987; 50: 829 839. 21. Placencia, M., Sander, J. W. A. S., Shorvon, S. D., Ellison, R. H., Suarez, S. and Cascante, S. M. Validation of a screening questionnaire for the detection of epileptic seizures in epidemiological studies. Brain 1992; 115: 783 794. 22. Sander, J. W. A. S., Hart, Y. M., Johnson, A. L. and Shorvon, S. D. The National General Practice Study of Epilepsy: newly diagnosed seizures in a general population. Lancet 1990; 336: 1267 1271. 23. Forsgren, L., Bucht, G., Erickson, S. and Begmark, L. Incidence and clinical characteristics of unprovoked seizures in adults. A prospective population-based study. Epilepsia 1996; 37: 224 229. 24. Al Rajeh, S., Bademosi, O., Awada, A., Ismail, H., Al

414 S. Al Rajeh et al. Shammasi, S. and Dawodu, H. Cerebral palsy in Saudi Arabia: A case-control study of the risk factors. Developmental Medicine in Child Neurology 1991; 33: 1048 1052. 25. Izuora, G. I. and Anis, A. S. Neurological disorders in Saudi children at the Al Majardah General Hospital, Asir Region. Annals of Saudi Medicine 1992; 12: 191 195. 26. Tsuboi, T. Epidemiology of febrile and afebrile convulsions in children in Japan. Neurology 1984; 34: 175 181. 27. Stanhope, J. M., Brody, J. A., Brink, E. and Morris, C. E. Convulsions among the Chamoro people of Guam, Marianas Islands. I: Seizure disorders. American Journal of Epidemiology 1972; 95: 292 304. 28. Hauser, W. A. Methodologic issues on studies of seizure disorders and the epilepsies. In: Clinical relevance in the epidemiology of epilepsies. XIXth International Epilepsy Congress, Rio de Janeiro, 1990, Sanofi Pharma,1990 (Ed. P. Jallon). pp. 4 11. 29. Hauser, W. A., Anderson, V. E., Loewenson, R. D. and McRoberts, S. M. Seizure recurrence after a first unprovoked seizure. Epilepsia 1986; 27: 43 50. 30. Annegers, J. F., Shirts, S. B., Hauser, W. A. and Kurland, L. T. Risk of recurrence after an initial unprovoked seizure. Epilepsia 1986; 27: 43 50.