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Epidemiology of epilepsy in New Valley Governorate, Al Kharga District, Egypt
Epilepsy Research (2013) 104, 167—174
journal homepage: www.elsevier.com/locate/epilepsyres
Epidemiology of epilepsy in New Valley Governorate, Al Kharga District, Egypt Hamdy N. El-Tallawy a, Wafaa M.A. Farghaly a,∗, Ghaydaa A. Shehata a, Nabil M. Abdel-Hakeem b, Tarek A. Rageh a, Noha A. Abo-Elftoh a, Ahmed Hegazy b, Reda Badry a a b
Department of Neurology, Faculty of Medicine, Assiut University, Egypt Department of Neurology, Faculty of Medicine, Al-Azhar University (Assiut Branch), Egypt
Received 16 May 2012; received in revised form 20 August 2012; accepted 26 August 2012 Available online 13 September 2012
KEYWORDS Epidemiology; Epilepsy; Active epilepsy; Egypt; New Valley
Summary Epilepsy is one of the serious neurological disorders which results in profound morbidity and mortality. Although epilepsy has no geographical boundaries, understanding cultural, social, and economic backgrounds is a very important step for interpretation of its epidemiological characteristics. This work aims to study the epidemiological profile of epilepsy in New Valley Governorate and to estimate its magnitude of treatment gap. It was conducted in a door to door survey, including all inhabitants (62,583 subjects), by 3 neurologists to detect any suspected case of focal or generalized epilepsy. All suspected cases were subjected to detailed history, clinical examination, EEG, neuroimaging studies, and estimation of serum drug level if needed. The study revealed that life time prevalence of epilepsy in Al Kharga district is 6.76/1000, with highest peak during early child hood, while that of active epilepsy is 4.99/1000 population. The annual incidence rate is 43.14/100,000, and age specific incidence rate has a U-shaped pattern with two peaks of incidence at early infancy and elderly. Localization-related epilepsy is the most frequently encountered type (53.7%). However the treatment gap of epilepsy in New Valley is similar to that in developing countries (61.5%). Conclusion: Prevalence and Incidence Rate of epilepsy in New Valley are similar to that in industrialized countries. © 2012 Elsevier B.V. All rights reserved.
Introduction
∗ Corresponding author at: Neurology and Psychiatry Department, Assiut University Hospitals, PO Box 71516, Assiut, Egypt. Tel.: +20 02 088 2350833; fax: +20 02 088 2351838. E-mail addresses: [email protected], [email protected] (W.M.A. Farghaly).
Epilepsy is the most common serious neurological disorder (Sander, 2003). It knows no geographical, racial, or social boundaries. The etiology of seizures is multi factorial in any given individual, and is best thought of, as an interaction between genetically determined seizure threshold, underlying predisposing pathologies or metabolic derangements, and acute precipitating factors (Guberman and Bruni, 1999).
0920-1211/$ — see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eplepsyres.2012.08.010
168 WHO estimates that 8 people per 1000 worldwide have epilepsy. The prevalence of epilepsy in developing countries is usually higher than in developed countries (Perucca et al., 2001; Preux and Druet-Cabanac, 2005). Worldwide, about 65 million people are estimated to be living with epilepsy (Ngugi et al., 2010). Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy (ILAE, 2011). In well developed countries, with universal health care systems, and routine medical registration, researchers usually rely on available medical records, and health care data bases to estimate prevalence of epilepsy. On the other hand, in developing countries where such universal health care systems are absent, and sources of information are lacking, population-based studies with direct personal interviews through door-to-door survey, especially when conducted by neurologists, remains the main tool for data collection necessary for epidemiological studies.
Aim of the work To study the epidemiology of epilepsy in New Valley Governorate-Al Kharga District, and to estimate the magnitude of treatment gap among those epileptic patients far away from advanced health services.
Ethics The study was approved by the ministry of health and by the ethical committee of Assiut University Hospitals. A written informed consent was also obtained from each patient and/or the responsible member of each family in case of children and elderly personnel to participate in this study according to the ethical committee of Assiut University Hospitals.
H.N. El-Tallawy et al. dementia, CVS, extra pyramidal syndromes, ataxia, muscle diseases, cerebral palsy, together with, Bell’s palsy, and nocturnal enuresis). The project was carried out through 3 stages, from June 1st 2005 to May 31st 2008, and included all households in a door to door survey, reaching homes of all inhabitants, to capture both health-seeking and non health seeking subjects to minimize non participation as possible as we can.
Instruments An Arabic screening questionnaire was designed specifically for this project, by a group of professors of neurology, based on their knowledge and review of existing screening tools. The screening questionnaire was designed to pick up any case of major neurological disorders (epilepsy, dementia, CVS, extra pyramidal syndromes, ataxia, muscle diseases, cerebral palsy, together with, Bell’s palsy, and nocturnal enuresis). The questionnaire was reviewed by 11 professors of neurology as referees, from 5 Local Egyptian Universities, and accordingly, it was reconstructed. Then it was validated by application on 100 inpatients of neurology department, and another 100 patients from the outpatients’ neurology clinic of Assiut University Hospitals (El Tallawy et al., 2010).
Stage I: screening and demographic data collection Screening of all households of Al-Kharga District, by 3 neurologists with special experience in epilepsy, was carried out by direct interview with every member in the families and/or the responsible person of each family, using the standardized Arabic screening questionnaire to pick up any suspected case of epilepsy (sensitivity 93.2% and specificity 96%) (El Tallawy et al., 2010). Collection of demographic data was recorded by 15 female social workers who accompanied the specialists during house visits.
Stage II: case ascertainment
New Valley Governorate (consists of 3 districts; Al Kharga, the largest one, Al Dakhla, and Al Farafra) was chosen for this study because although it comprises 44% of Egypt’s area, it has poor health services (no neurologists, no EEG equipments, no CT scanners). It is also far away from well developed health centers (230 km to the west south of Assiut; the nearest well developed health center).
As shown in (Fig. 1), all subjects suspected of having epilepsy during screening (responded positive to any screening question), were invited to attend Al-Kharga General Hospital where they were re-evaluated for confirmation of the diagnosis, and to collect additional detailed information about prodroma and aura symptoms, detailed description of seizure semiology by any witness, as well as post-ictal symptoms. Then they were subjected to full neurological and physical examination in a specifically prepared clinical sheet for epilepsy.
Sample size
Stage III: investigations
All inhabitants of El-Kharga district (62,583 subjects), with 51.4% males and 48.6% females, are included.
Afterwards, patients were invited to attend Assiut University hospital to perform conventional EEG, psychometric assessment of IQ using Stanford Bennit test (version IV), video EEG monitoring (64 cases who have their most recent seizures within the previous 6 months despite proper use of antiepileptic drugs), neuro-imaging (CT and/or MRI) were done for suspected symptomatic cases, and estimation of serum level of AEDs (134 cases having their most recent
Study area
Methods In absence of adequate cover by health insurance system, we conducted a project in Al Kharga district aiming to study the epidemiology of major neurological disorders (epilepsy,
Epidemiology of epilepsy in Egypt
Figure 1
169
An algorithm showing cascade of events from screening to case ascertainment and investigations.
seizures within the previous 6 months, to ascertain proper use of AEDs). Capture of new incident cases was facilitated through: (1) regular advertisement and periodic interviews in the local mass media for all inhabitants to attend Al Khargha general hospital in case of any neurological events where they will be investigated freely and prescribed the proper treatment. (2) Cooperation and continuous communication with the general practitioners in Al Khargha General Hospital, rural and urban health units. (3) If subjects were not at their homes at the first visit, they were revisited for three times late to insure their participation.
treated expressed as percentage of the total number of people with active epilepsy (Kale, 2002). Seizure types were then clinically ascertained and classified according to the classification of the ILAE, 1981 (commission on classification and terminology of the international League Against Epilepsy, 1981), and etiologic categories included idiopathic (presumably genetic), symptomatic, and cryptogenic (of unknown cause) according to (ILAE, 1993).
Case definitions used
Table 1 illustrates age-specific life time Prevalence and Incidence Rate of epilepsy in Al Kharga District (New Valley) at different age groups. Along 1 year from the 1st of June 2007 to the end of May 2008, 27 new cases of epilepsy with onset during that year have been recorded yielding a total incidence rate of 43.14/100,000 population/year.
According to the guidelines for epidemiology studies on epilepsy proposed by the Commission on Epidemiology and prognosis of the International League Against Epilepsy (ILAE, 1993). Epilepsy was defined as a condition characterized by two or more un-provoked seizures occurring at least 24 h apart. Active epilepsy: Due to problems in recall of date of last seizure, and lack of use of calendars, a patient is termed to have active epilepsy when the most recent seizure has occurred within 1-year prior to interview, regardless of antiepileptic drug treatment (Birbeck and Kalichi, 2004; Edwards et al., 2008; Longe and Osuntokun, 1989). Treatment gap is defined as the number of people with active epilepsy not on treatment or not appropriately
Results
Variation with demographic factors Sex The life time prevalence of epilepsy was slightly higher among total females (7.3/1000) than males (6.7/1000), but the difference was statistically significant (p < 0.05) only during late adulthood (40—<60) (6.1/1000 versus 3.4/1000).
170 Table 1
H.N. El-Tallawy et al. Age-specific life time Prevalence and Incidence Rate of epilepsy in Al Kharga District (New Valley).
Age group
Total POP
Life-time prevalence
Incidence
Total cases
Cases/1 year
Birth to <2
1744
14
2 to <6
6026
53
6 to <12
8715
88
12 to <18
7617
70
18 to <40
22,999
127
40 to <60
11,545
52
3937
19
62,583
423
>60 Total
Prev/100095%CI 8.0 (6.9—9.5) 8.8 (8.1—9.5) 10.1 (9.5—10.8) 9.2 (8.6—9.9) 5.5 (5.2—5.8) 4.5 (4.1—4.9) 4.8 (4.2—5.5) 6.76 (6.6—7.0)
Residence The total life time prevalence of epilepsy was slightly higher in rural (7.2/1000) than urban communities (6.9/1000), but the difference was statistically significant (p < 0.05) only during late childhood (6—12 years) (14.2/1000 versus 8.5/1000). Active epilepsy During the period of the study, 312 patients reported to have active epilepsy, yielding a prevalence of 4.99/1000 population. Only 4.5% of total patients with epilepsy (n = 19/423) reported remission of their seizures according to the international standards (>5 years). Moreover 12.5% (n = 53/423) reported seizure remission according to our community standards (>2 years and <5 years). An extra 9.2% (39/423) had seizure remission >1 year and <2 years. Seizure type Depending on electro-clinical and neuro-imaging studies, 51.0% (n = 216) of total patients with epilepsy were found to have localization related epilepsy. On the other hand
Table 2
Incidence/100,00095% CI
3
172.0 (22.7—366.51) 99.6 (19.94—179.2) 45.9 (0.93—90.87) 39.4 (0.18—83. 95) 13 (1.72—27. 80) 34.6 (0.69—68. 59) 101.6 (2.08—201. 12) 43.14 (26.87—59. 41)
6 4 3 3 4 4 27
etiological classification revealed that 35% of cases had symptomatic epilepsy, Table 2. Table 3 shows the proportion of different seizure types among total epileptic patients and during different age groups.
Specific epileptic syndromes Twenty cases had been diagnosed to have specific epileptic syndromes, out of whom, 12 had childhood Absence Epilepsy, 4 had Progressive Myoclonic Epilepsy, 3 had Lennox-Gastaut Syndrome, and one had Juvenile Myoclonic Epilepsy.
Family history Positive consanguineous marriage between parents was recorded among 43.0% (n = 182) of patients with epilepsy. Furthermore, an extra 139 patients (32.9%) reported positive grandparents’ consanguinity. However, 19.1% (n = 81) of our patients had positive family history of epilepsy. Table 4 shows the rate of active epilepsy and the magnitude of treatment gap.
Proportion of different types of epilepsy.
Type
Etiology Idiopathic
Symptomatic
Cryptogenic
Total
N
%
N
%
N
%
N
Generalized Localization related
131 106
31 25
46 102
10.9 24.1
19 19
4.5 4.5
196 227
Total
237
56
148
35
38
9
423
% 46.3 53.7 100
NB: 11 cases, had mixed types of seizures, but commonly localization related type. Another 12 cases had mixed types of seizures, but most commonly generalized type.
Epidemiology of epilepsy in Egypt
171
51 8 15.1 27.9 5.4 216 34 64 118 23
184 126 33 3 5 5 12
Total N = 423
43.5 29.8 7.8 0.7 1.2 1.2 2.8
Table 4
Treatment gap.
Epileptic patients
N
%
Patients with active epilepsy Patients with active epilepsy never received AEDs Patients with active epilepsy and inappropriately treated Treatment gap
312/423 122
73.7 39.1
70
22.4
192/312
61.5
73.7% 26.3% — 47.4% — 14 5 — 9 — 69.2% 21.2% 11.5% 36.5% 3.8% 36 11 6 19 2 49.6% 3.9% 16.5% 29.1% 6.3% 63 5 21 37 8 103 13 37 53 13 Localization related Simple C.P. SSG Mixed
45.8% 5.8% 16.4% 23.5% 5.8%
5 4 — — — — 1 26.9% 23% 3.9% — — — — 14 12 2 — — — — 44.1% 34.6% 4.7% — 1.6% 2.4% 0.8% 56 44 6 — 2 3 1 48.4% 29.3% 11.1% 1.3% 1.3% 0.9% 4.5% 109 66 25 3 3 2 10 Generalized GTC Tonic Clonic Atonic Myoclonic Absence
Late 40 to <60 years N = 52 Early 18 to <40 years N = 127
Adulthood Childhood Birth to <18 years N = 225 Seizure type
Table 3
Proportion of different seizure types among total patients with epilepsy and during different age groups.
Elderly >60 years N = 19
26.3% 21.1% — — — — 5.2%
Discussion The majority of people with epilepsy have a good prognosis if they received appropriate treatment (Sander, 2003). In an attempt to bring epilepsy out of the shadow, and to improve the treatment of patients with epilepsy, a door to door survey was conducted, as a first step, in such far district in Egypt, which is far away from well equipped health centers. The first step was to throw some light on epidemiological characteristics of epilepsy in New Valley, to estimate the prevalence of active epilepsy, and the magnitude of treatment gap. The recorded life time prevalence of epilepsy (6.76/1000) in Al-Kharga district is less than that estimated by WHO of 8/1000 population worldwide (WHO, 2001). It is nearly similar to that recorded in China (7/1000) (Wang et al., 2002) and in New York (5.2/1000) (Kelvin et al., 2007). On the other hand, it is far less than that recorded in Sub-Saharan Africa where a median rate of 15/1000 people has been reported (Preux and Druet-Cabanac, 2005). Moreover a much higher prevalence (134.5/1000) has been reported in Cameroon (Prischich et al., 2008). This low prevalence of epilepsy in New Valley, even lower than that recorded in cities lying on Nile Valley, in Egypt, could be a reflection of a protective factor or factors in that open area, with little inhabitants, closed community, far away from pollution. The age-specific prevalence increases steadily from infancy (8/1000) to reach a peak of 10.1/1000 during late childhood, and then declines steadily to its least value at late adulthood (4.5/1000) and elderly (4.8/1000). This pattern of age specific prevalence is nearly similar to that reported in developing countries, where it peaks in adolescence and early adulthood (Banerjee et al., 2009). The incidence rate (43.14/100,000 people a year) recorded in this study is far lower than that recorded in Sub-Saharan Africa where high incidence rates ranging from 63 to 158/100,000 inhabitants have been recorded (Preux and Druet-Cabanac, 2005). Moreover, this incidence rate in New Valley, lies within the lower range (40—70/100,000 inhabitants) of that recorded in industrialized most developed countries in non tropical areas (Sander and Shorvon, 1996), where the incidence rate is generally accepted as being around 50/100,000 people a year (Sander, 2003). This lower incidence rate in New Valley could perhaps be due to a lower rate of symptomatic epilepsy, especially lower rate of CNS infection (e.g., neurocystisercosis) than in South Africa, and tropical areas. The U-shaped age specific incidence rate recorded in our study is similar to that recorded in developed countries where the incidence rate of epilepsy, follows
172 a bimodal distribution with a first peak in childhood and another in old age (Jallon, 2002), a finding which may reflect multiple etiologies among persons at the two extremes of life. Moreover, Banerjee et al. (2009) in a descriptive review of epidemiology of epilepsy found that in developed countries the incidence of epilepsy tends to be high in the first year of life and early child hood, lowest in adult years through the fifth decade of life, and then increased in the oldest age group. Taking in consideration that the life time prevalence equals new incident cases plus survived epileptic cases; the high incidence rate accompanied by low prevalence at the two extremes of life in New Valley, could be attributed to high mortality rate at these two age groups.
Age and residence specific prevalence rate The higher prevalence of epilepsy among rural than urban inhabitants in New Valley, was previously reported by Sander and Shorvon (1996) as a consistent finding, for unclear reasons, that the prevalence rates of epilepsy are higher in rural than urban areas. However, we suggest that this could be explained by the higher rate of consanguinity in rural than urban communities and thus higher rate of idiopathic epilepsy. On the other hand the significantly higher prevalence during early childhood, could be due to the fact that this is an age at which children go outdoors, become more liable to head injury and CNS infections, and thus remote symptomatic epilepsy could be a contributing factor to the higher prevalence during this age period. The recorded prevalence of active epilepsy (4.99/1000) lies within the range reported in epidemiological studies in most countries worldwide where it was found to be ranged from 4 to 10/1000 people (Sander, 2003; Sander and Shorvon, 1996). Moreover, a nearly similar rate (5.4/1000) was recorded in France by Picot et al. (2008). However the adopted definitions of active epilepsy were different in the two studies. In our study, active epilepsy is considered when the most recent seizure has occurred within 1-year period from the date of interview, but within the previous 5 years in Picot’s study (Picot et al., 2008). On the other hand, higher prevalence of active epilepsy ranging from 14 to 57/1000 have been reported from some African, and south American countries (Hauser et al., 1991). Moreover, age-adjusted prevalence of active epilepsy in Cameroon has been estimated to be 134.5/1000 population (n = 19/181) (Prischich et al., 2008). Our estimated lower prevalence of active epilepsy could be explained firstly by the lower total life time prevalence of epilepsy, and secondly by inclusion of different definitions of active epilepsy in different studies.
Type of epilepsy Classification of seizure type depends mainly on accuracy of history taking of seizure semiology, besides availability of sophisticated diagnostic tools. So it is expected that localization-related epilepsies to predominate in centers of epilepsy with increased sophisticated diagnostic equipments. In a review of previous studies of descriptive epidemiology of epilepsy, Banerjee et al. (2009), found that a higher proportion of generalized epilepsy was reported in half of the studies. Although this is partially true, our
H.N. El-Tallawy et al. recorded rate of localization-related seizures (55.1%) is nearly similar to that recorded in different areas in Europe [in France 61.1% (Picot et al., 2008), in Spain 63% (Luengo et al., 2001), in Aeolian Islands 62% (Gallitto et al., 2005)], and also in Minnesota 59% (Hauser et al., 1991), in Bolivia and Turkey 53% in each (Nicoletti et al., 1999); and (Karaagac et al., 1999) respectively. The commonest types of seizures were the primary GTC (29.8%) followed by the focal seizures with secondary generalization (27.9%). Similarly in France, Picot et al. (2008) recorded GTC in 30.9%, but a lower rate of focal seizures with secondary generalization (9.2%). Our results are contrary to the reported findings of Banerjee et al. (2009) where they found that the incident studies performed in developing countries, particularly in Africa, reported a greater proportion of individuals with generalized onset seizures than partial seizures. Despite being, community-based study, the accuracy in analysis of detailed seizure semiology, by specialists of neurology who conducted screening of all households, and assessment of suspected patients with epilepsy by another 3 staff members of neurology with special experience in epilepsy, besides the dependence on electro-clinical methods in diagnosis, makes our results comparable with other highly specialized centers. Furthermore the recorded proportion of symptomatic epilepsy (35%) is similar to that of Hauser et al. (1991) (35%), in Rochester Minnesota. Also it lies within the range recorded in most Asian countries where the rate of symptomatic epilepsy ranged from 22 to 53% (Mac et al., 2007). Subsequently, Banerjee et al. (2009), in a review of epidemiological studies of epilepsy, reported that regardless of the time or region of the study there is preponderance of epilepsy to be of unknown etiology, a finding which suggests that the use of sophisticated medical infrastructure such as imaging technology does not always increase the ability to detect a cause of epilepsy. The high rate of parental (36.8%) and grand parents’ consanguinity (28.1%) is consistent with numerous studies which have confirmed familial history of epilepsy, and parental consanguinity as risk factors for epilepsy (Mac et al., 2007; Ramasundrum, 2004). The nature of this closed community with high rate of consanguineous marriage could be a contributing factor to the high rate of idiopathic and other genetically determined epileptic syndromes. More than 1/3 of patients (39.1%) with active epilepsy, in New Valley, did not receive treatment at all. However, this rate is far lower than that recorded in China, in 2002, where more than 60% of patients with active epilepsy, in the largest country in the world, do not receive any treatment (Wang et al., 2002). Taking in consideration patients who are inappropriately treated, the level of treatment gap in New Valley reaches 61.5%. This is consistent with the findings of Mbuba et al. (2008) in meta-analysis of 27 studies from Africa, Asia, and Latin America where they found that the overall estimate of treatment gap is 56%. However, our estimated treatment gap is lower than that reported by ILAE/IBE/WHO in their introduction to the Global Campaign against Epilepsy ‘‘Epilepsy out of the Shadows’’ where they stated that globally 85% of people with epilepsy are either inappropriately treated or not treated at all (Meinardi et al., 2001). In Asian countries, the treatment gap ranged from 29 to 98% with values for most countries between 50% and 80%
Epidemiology of epilepsy in Egypt (Mac et al., 2007). In Sub-Saharan Africa and Latin America, up to 95% of people with epilepsy receive inadequate treatment or no treatment at all (Scott et al., 2001). It is so gloomy that about 60% of patients, or more, with active epilepsy in developing countries, and in the largest district of Egypt (New Valley), do not receive any treatment or are not appropriately treated. Most probably, this is due to the widely prevailing misconception of the nature of epilepsy and cultural beliefs that might affect people’s health-seeking strategies. If epilepsy is stigmatized, people are unlikely to admit that they are diseased and to know that adequate treatment exists, or to maintain compliance. Moreover, the lack of health facilities (no EEG machines, no CT scanners, no MRI machines, no specialists of neurology), besides the far distance from well qualified health care centers and the deficiency of AEDS, due to low socioeconomic standards would contribute to this high treatment gap. This wide treatment gap could be reduced by application of adequate public educational programs to dispel disease stigma, adequate training of health professionals, family doctors, and the supply of appropriate treatment. Door to door survey, to reach both heath seeking and non health seeking inhabitants will help better estimation of prevalence of epilepsy, distribution of knowledge among publics, and in bringing epilepsy out of the shadow, with subsequent reduction of treatment gap.
Conclusions The life time prevalence of epilepsy in Al Kharga District (New Valley) is 6.76/100 population, with peak prevalence during early childhood. The Annual Incidence Rate of Epilepsy is 43.14/100,000 population, with highest peaks during early infancy and elderly, and least value during early adulthood. Three quarters (73.7%) of patients (n = 312) have been reported to have active epilepsy, with a total prevalence of active epilepsy of 4.99/1000 population. The treatment gap in New Valley is 61.5%.
Funding sources None.
Acknowledgment Research team would like to thank Sanofi Pharmaceutical Company because of its helpful role in performing this work.
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journal homepage: www.elsevier.com/locate/epilepsyres
Epidemiology of epilepsy in New Valley Governorate, Al Kharga District, Egypt Hamdy N. El-Tallawy a, Wafaa M.A. Farghaly a,∗, Ghaydaa A. Shehata a, Nabil M. Abdel-Hakeem b, Tarek A. Rageh a, Noha A. Abo-Elftoh a, Ahmed Hegazy b, Reda Badry a a b
Department of Neurology, Faculty of Medicine, Assiut University, Egypt Department of Neurology, Faculty of Medicine, Al-Azhar University (Assiut Branch), Egypt
Received 16 May 2012; received in revised form 20 August 2012; accepted 26 August 2012 Available online 13 September 2012
KEYWORDS Epidemiology; Epilepsy; Active epilepsy; Egypt; New Valley
Summary Epilepsy is one of the serious neurological disorders which results in profound morbidity and mortality. Although epilepsy has no geographical boundaries, understanding cultural, social, and economic backgrounds is a very important step for interpretation of its epidemiological characteristics. This work aims to study the epidemiological profile of epilepsy in New Valley Governorate and to estimate its magnitude of treatment gap. It was conducted in a door to door survey, including all inhabitants (62,583 subjects), by 3 neurologists to detect any suspected case of focal or generalized epilepsy. All suspected cases were subjected to detailed history, clinical examination, EEG, neuroimaging studies, and estimation of serum drug level if needed. The study revealed that life time prevalence of epilepsy in Al Kharga district is 6.76/1000, with highest peak during early child hood, while that of active epilepsy is 4.99/1000 population. The annual incidence rate is 43.14/100,000, and age specific incidence rate has a U-shaped pattern with two peaks of incidence at early infancy and elderly. Localization-related epilepsy is the most frequently encountered type (53.7%). However the treatment gap of epilepsy in New Valley is similar to that in developing countries (61.5%). Conclusion: Prevalence and Incidence Rate of epilepsy in New Valley are similar to that in industrialized countries. © 2012 Elsevier B.V. All rights reserved.
Introduction
∗ Corresponding author at: Neurology and Psychiatry Department, Assiut University Hospitals, PO Box 71516, Assiut, Egypt. Tel.: +20 02 088 2350833; fax: +20 02 088 2351838. E-mail addresses: [email protected], [email protected] (W.M.A. Farghaly).
Epilepsy is the most common serious neurological disorder (Sander, 2003). It knows no geographical, racial, or social boundaries. The etiology of seizures is multi factorial in any given individual, and is best thought of, as an interaction between genetically determined seizure threshold, underlying predisposing pathologies or metabolic derangements, and acute precipitating factors (Guberman and Bruni, 1999).
0920-1211/$ — see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eplepsyres.2012.08.010
168 WHO estimates that 8 people per 1000 worldwide have epilepsy. The prevalence of epilepsy in developing countries is usually higher than in developed countries (Perucca et al., 2001; Preux and Druet-Cabanac, 2005). Worldwide, about 65 million people are estimated to be living with epilepsy (Ngugi et al., 2010). Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy (ILAE, 2011). In well developed countries, with universal health care systems, and routine medical registration, researchers usually rely on available medical records, and health care data bases to estimate prevalence of epilepsy. On the other hand, in developing countries where such universal health care systems are absent, and sources of information are lacking, population-based studies with direct personal interviews through door-to-door survey, especially when conducted by neurologists, remains the main tool for data collection necessary for epidemiological studies.
Aim of the work To study the epidemiology of epilepsy in New Valley Governorate-Al Kharga District, and to estimate the magnitude of treatment gap among those epileptic patients far away from advanced health services.
Ethics The study was approved by the ministry of health and by the ethical committee of Assiut University Hospitals. A written informed consent was also obtained from each patient and/or the responsible member of each family in case of children and elderly personnel to participate in this study according to the ethical committee of Assiut University Hospitals.
H.N. El-Tallawy et al. dementia, CVS, extra pyramidal syndromes, ataxia, muscle diseases, cerebral palsy, together with, Bell’s palsy, and nocturnal enuresis). The project was carried out through 3 stages, from June 1st 2005 to May 31st 2008, and included all households in a door to door survey, reaching homes of all inhabitants, to capture both health-seeking and non health seeking subjects to minimize non participation as possible as we can.
Instruments An Arabic screening questionnaire was designed specifically for this project, by a group of professors of neurology, based on their knowledge and review of existing screening tools. The screening questionnaire was designed to pick up any case of major neurological disorders (epilepsy, dementia, CVS, extra pyramidal syndromes, ataxia, muscle diseases, cerebral palsy, together with, Bell’s palsy, and nocturnal enuresis). The questionnaire was reviewed by 11 professors of neurology as referees, from 5 Local Egyptian Universities, and accordingly, it was reconstructed. Then it was validated by application on 100 inpatients of neurology department, and another 100 patients from the outpatients’ neurology clinic of Assiut University Hospitals (El Tallawy et al., 2010).
Stage I: screening and demographic data collection Screening of all households of Al-Kharga District, by 3 neurologists with special experience in epilepsy, was carried out by direct interview with every member in the families and/or the responsible person of each family, using the standardized Arabic screening questionnaire to pick up any suspected case of epilepsy (sensitivity 93.2% and specificity 96%) (El Tallawy et al., 2010). Collection of demographic data was recorded by 15 female social workers who accompanied the specialists during house visits.
Stage II: case ascertainment
New Valley Governorate (consists of 3 districts; Al Kharga, the largest one, Al Dakhla, and Al Farafra) was chosen for this study because although it comprises 44% of Egypt’s area, it has poor health services (no neurologists, no EEG equipments, no CT scanners). It is also far away from well developed health centers (230 km to the west south of Assiut; the nearest well developed health center).
As shown in (Fig. 1), all subjects suspected of having epilepsy during screening (responded positive to any screening question), were invited to attend Al-Kharga General Hospital where they were re-evaluated for confirmation of the diagnosis, and to collect additional detailed information about prodroma and aura symptoms, detailed description of seizure semiology by any witness, as well as post-ictal symptoms. Then they were subjected to full neurological and physical examination in a specifically prepared clinical sheet for epilepsy.
Sample size
Stage III: investigations
All inhabitants of El-Kharga district (62,583 subjects), with 51.4% males and 48.6% females, are included.
Afterwards, patients were invited to attend Assiut University hospital to perform conventional EEG, psychometric assessment of IQ using Stanford Bennit test (version IV), video EEG monitoring (64 cases who have their most recent seizures within the previous 6 months despite proper use of antiepileptic drugs), neuro-imaging (CT and/or MRI) were done for suspected symptomatic cases, and estimation of serum level of AEDs (134 cases having their most recent
Study area
Methods In absence of adequate cover by health insurance system, we conducted a project in Al Kharga district aiming to study the epidemiology of major neurological disorders (epilepsy,
Epidemiology of epilepsy in Egypt
Figure 1
169
An algorithm showing cascade of events from screening to case ascertainment and investigations.
seizures within the previous 6 months, to ascertain proper use of AEDs). Capture of new incident cases was facilitated through: (1) regular advertisement and periodic interviews in the local mass media for all inhabitants to attend Al Khargha general hospital in case of any neurological events where they will be investigated freely and prescribed the proper treatment. (2) Cooperation and continuous communication with the general practitioners in Al Khargha General Hospital, rural and urban health units. (3) If subjects were not at their homes at the first visit, they were revisited for three times late to insure their participation.
treated expressed as percentage of the total number of people with active epilepsy (Kale, 2002). Seizure types were then clinically ascertained and classified according to the classification of the ILAE, 1981 (commission on classification and terminology of the international League Against Epilepsy, 1981), and etiologic categories included idiopathic (presumably genetic), symptomatic, and cryptogenic (of unknown cause) according to (ILAE, 1993).
Case definitions used
Table 1 illustrates age-specific life time Prevalence and Incidence Rate of epilepsy in Al Kharga District (New Valley) at different age groups. Along 1 year from the 1st of June 2007 to the end of May 2008, 27 new cases of epilepsy with onset during that year have been recorded yielding a total incidence rate of 43.14/100,000 population/year.
According to the guidelines for epidemiology studies on epilepsy proposed by the Commission on Epidemiology and prognosis of the International League Against Epilepsy (ILAE, 1993). Epilepsy was defined as a condition characterized by two or more un-provoked seizures occurring at least 24 h apart. Active epilepsy: Due to problems in recall of date of last seizure, and lack of use of calendars, a patient is termed to have active epilepsy when the most recent seizure has occurred within 1-year prior to interview, regardless of antiepileptic drug treatment (Birbeck and Kalichi, 2004; Edwards et al., 2008; Longe and Osuntokun, 1989). Treatment gap is defined as the number of people with active epilepsy not on treatment or not appropriately
Results
Variation with demographic factors Sex The life time prevalence of epilepsy was slightly higher among total females (7.3/1000) than males (6.7/1000), but the difference was statistically significant (p < 0.05) only during late adulthood (40—<60) (6.1/1000 versus 3.4/1000).
170 Table 1
H.N. El-Tallawy et al. Age-specific life time Prevalence and Incidence Rate of epilepsy in Al Kharga District (New Valley).
Age group
Total POP
Life-time prevalence
Incidence
Total cases
Cases/1 year
Birth to <2
1744
14
2 to <6
6026
53
6 to <12
8715
88
12 to <18
7617
70
18 to <40
22,999
127
40 to <60
11,545
52
3937
19
62,583
423
>60 Total
Prev/100095%CI 8.0 (6.9—9.5) 8.8 (8.1—9.5) 10.1 (9.5—10.8) 9.2 (8.6—9.9) 5.5 (5.2—5.8) 4.5 (4.1—4.9) 4.8 (4.2—5.5) 6.76 (6.6—7.0)
Residence The total life time prevalence of epilepsy was slightly higher in rural (7.2/1000) than urban communities (6.9/1000), but the difference was statistically significant (p < 0.05) only during late childhood (6—12 years) (14.2/1000 versus 8.5/1000). Active epilepsy During the period of the study, 312 patients reported to have active epilepsy, yielding a prevalence of 4.99/1000 population. Only 4.5% of total patients with epilepsy (n = 19/423) reported remission of their seizures according to the international standards (>5 years). Moreover 12.5% (n = 53/423) reported seizure remission according to our community standards (>2 years and <5 years). An extra 9.2% (39/423) had seizure remission >1 year and <2 years. Seizure type Depending on electro-clinical and neuro-imaging studies, 51.0% (n = 216) of total patients with epilepsy were found to have localization related epilepsy. On the other hand
Table 2
Incidence/100,00095% CI
3
172.0 (22.7—366.51) 99.6 (19.94—179.2) 45.9 (0.93—90.87) 39.4 (0.18—83. 95) 13 (1.72—27. 80) 34.6 (0.69—68. 59) 101.6 (2.08—201. 12) 43.14 (26.87—59. 41)
6 4 3 3 4 4 27
etiological classification revealed that 35% of cases had symptomatic epilepsy, Table 2. Table 3 shows the proportion of different seizure types among total epileptic patients and during different age groups.
Specific epileptic syndromes Twenty cases had been diagnosed to have specific epileptic syndromes, out of whom, 12 had childhood Absence Epilepsy, 4 had Progressive Myoclonic Epilepsy, 3 had Lennox-Gastaut Syndrome, and one had Juvenile Myoclonic Epilepsy.
Family history Positive consanguineous marriage between parents was recorded among 43.0% (n = 182) of patients with epilepsy. Furthermore, an extra 139 patients (32.9%) reported positive grandparents’ consanguinity. However, 19.1% (n = 81) of our patients had positive family history of epilepsy. Table 4 shows the rate of active epilepsy and the magnitude of treatment gap.
Proportion of different types of epilepsy.
Type
Etiology Idiopathic
Symptomatic
Cryptogenic
Total
N
%
N
%
N
%
N
Generalized Localization related
131 106
31 25
46 102
10.9 24.1
19 19
4.5 4.5
196 227
Total
237
56
148
35
38
9
423
% 46.3 53.7 100
NB: 11 cases, had mixed types of seizures, but commonly localization related type. Another 12 cases had mixed types of seizures, but most commonly generalized type.
Epidemiology of epilepsy in Egypt
171
51 8 15.1 27.9 5.4 216 34 64 118 23
184 126 33 3 5 5 12
Total N = 423
43.5 29.8 7.8 0.7 1.2 1.2 2.8
Table 4
Treatment gap.
Epileptic patients
N
%
Patients with active epilepsy Patients with active epilepsy never received AEDs Patients with active epilepsy and inappropriately treated Treatment gap
312/423 122
73.7 39.1
70
22.4
192/312
61.5
73.7% 26.3% — 47.4% — 14 5 — 9 — 69.2% 21.2% 11.5% 36.5% 3.8% 36 11 6 19 2 49.6% 3.9% 16.5% 29.1% 6.3% 63 5 21 37 8 103 13 37 53 13 Localization related Simple C.P. SSG Mixed
45.8% 5.8% 16.4% 23.5% 5.8%
5 4 — — — — 1 26.9% 23% 3.9% — — — — 14 12 2 — — — — 44.1% 34.6% 4.7% — 1.6% 2.4% 0.8% 56 44 6 — 2 3 1 48.4% 29.3% 11.1% 1.3% 1.3% 0.9% 4.5% 109 66 25 3 3 2 10 Generalized GTC Tonic Clonic Atonic Myoclonic Absence
Late 40 to <60 years N = 52 Early 18 to <40 years N = 127
Adulthood Childhood Birth to <18 years N = 225 Seizure type
Table 3
Proportion of different seizure types among total patients with epilepsy and during different age groups.
Elderly >60 years N = 19
26.3% 21.1% — — — — 5.2%
Discussion The majority of people with epilepsy have a good prognosis if they received appropriate treatment (Sander, 2003). In an attempt to bring epilepsy out of the shadow, and to improve the treatment of patients with epilepsy, a door to door survey was conducted, as a first step, in such far district in Egypt, which is far away from well equipped health centers. The first step was to throw some light on epidemiological characteristics of epilepsy in New Valley, to estimate the prevalence of active epilepsy, and the magnitude of treatment gap. The recorded life time prevalence of epilepsy (6.76/1000) in Al-Kharga district is less than that estimated by WHO of 8/1000 population worldwide (WHO, 2001). It is nearly similar to that recorded in China (7/1000) (Wang et al., 2002) and in New York (5.2/1000) (Kelvin et al., 2007). On the other hand, it is far less than that recorded in Sub-Saharan Africa where a median rate of 15/1000 people has been reported (Preux and Druet-Cabanac, 2005). Moreover a much higher prevalence (134.5/1000) has been reported in Cameroon (Prischich et al., 2008). This low prevalence of epilepsy in New Valley, even lower than that recorded in cities lying on Nile Valley, in Egypt, could be a reflection of a protective factor or factors in that open area, with little inhabitants, closed community, far away from pollution. The age-specific prevalence increases steadily from infancy (8/1000) to reach a peak of 10.1/1000 during late childhood, and then declines steadily to its least value at late adulthood (4.5/1000) and elderly (4.8/1000). This pattern of age specific prevalence is nearly similar to that reported in developing countries, where it peaks in adolescence and early adulthood (Banerjee et al., 2009). The incidence rate (43.14/100,000 people a year) recorded in this study is far lower than that recorded in Sub-Saharan Africa where high incidence rates ranging from 63 to 158/100,000 inhabitants have been recorded (Preux and Druet-Cabanac, 2005). Moreover, this incidence rate in New Valley, lies within the lower range (40—70/100,000 inhabitants) of that recorded in industrialized most developed countries in non tropical areas (Sander and Shorvon, 1996), where the incidence rate is generally accepted as being around 50/100,000 people a year (Sander, 2003). This lower incidence rate in New Valley could perhaps be due to a lower rate of symptomatic epilepsy, especially lower rate of CNS infection (e.g., neurocystisercosis) than in South Africa, and tropical areas. The U-shaped age specific incidence rate recorded in our study is similar to that recorded in developed countries where the incidence rate of epilepsy, follows
172 a bimodal distribution with a first peak in childhood and another in old age (Jallon, 2002), a finding which may reflect multiple etiologies among persons at the two extremes of life. Moreover, Banerjee et al. (2009) in a descriptive review of epidemiology of epilepsy found that in developed countries the incidence of epilepsy tends to be high in the first year of life and early child hood, lowest in adult years through the fifth decade of life, and then increased in the oldest age group. Taking in consideration that the life time prevalence equals new incident cases plus survived epileptic cases; the high incidence rate accompanied by low prevalence at the two extremes of life in New Valley, could be attributed to high mortality rate at these two age groups.
Age and residence specific prevalence rate The higher prevalence of epilepsy among rural than urban inhabitants in New Valley, was previously reported by Sander and Shorvon (1996) as a consistent finding, for unclear reasons, that the prevalence rates of epilepsy are higher in rural than urban areas. However, we suggest that this could be explained by the higher rate of consanguinity in rural than urban communities and thus higher rate of idiopathic epilepsy. On the other hand the significantly higher prevalence during early childhood, could be due to the fact that this is an age at which children go outdoors, become more liable to head injury and CNS infections, and thus remote symptomatic epilepsy could be a contributing factor to the higher prevalence during this age period. The recorded prevalence of active epilepsy (4.99/1000) lies within the range reported in epidemiological studies in most countries worldwide where it was found to be ranged from 4 to 10/1000 people (Sander, 2003; Sander and Shorvon, 1996). Moreover, a nearly similar rate (5.4/1000) was recorded in France by Picot et al. (2008). However the adopted definitions of active epilepsy were different in the two studies. In our study, active epilepsy is considered when the most recent seizure has occurred within 1-year period from the date of interview, but within the previous 5 years in Picot’s study (Picot et al., 2008). On the other hand, higher prevalence of active epilepsy ranging from 14 to 57/1000 have been reported from some African, and south American countries (Hauser et al., 1991). Moreover, age-adjusted prevalence of active epilepsy in Cameroon has been estimated to be 134.5/1000 population (n = 19/181) (Prischich et al., 2008). Our estimated lower prevalence of active epilepsy could be explained firstly by the lower total life time prevalence of epilepsy, and secondly by inclusion of different definitions of active epilepsy in different studies.
Type of epilepsy Classification of seizure type depends mainly on accuracy of history taking of seizure semiology, besides availability of sophisticated diagnostic tools. So it is expected that localization-related epilepsies to predominate in centers of epilepsy with increased sophisticated diagnostic equipments. In a review of previous studies of descriptive epidemiology of epilepsy, Banerjee et al. (2009), found that a higher proportion of generalized epilepsy was reported in half of the studies. Although this is partially true, our
H.N. El-Tallawy et al. recorded rate of localization-related seizures (55.1%) is nearly similar to that recorded in different areas in Europe [in France 61.1% (Picot et al., 2008), in Spain 63% (Luengo et al., 2001), in Aeolian Islands 62% (Gallitto et al., 2005)], and also in Minnesota 59% (Hauser et al., 1991), in Bolivia and Turkey 53% in each (Nicoletti et al., 1999); and (Karaagac et al., 1999) respectively. The commonest types of seizures were the primary GTC (29.8%) followed by the focal seizures with secondary generalization (27.9%). Similarly in France, Picot et al. (2008) recorded GTC in 30.9%, but a lower rate of focal seizures with secondary generalization (9.2%). Our results are contrary to the reported findings of Banerjee et al. (2009) where they found that the incident studies performed in developing countries, particularly in Africa, reported a greater proportion of individuals with generalized onset seizures than partial seizures. Despite being, community-based study, the accuracy in analysis of detailed seizure semiology, by specialists of neurology who conducted screening of all households, and assessment of suspected patients with epilepsy by another 3 staff members of neurology with special experience in epilepsy, besides the dependence on electro-clinical methods in diagnosis, makes our results comparable with other highly specialized centers. Furthermore the recorded proportion of symptomatic epilepsy (35%) is similar to that of Hauser et al. (1991) (35%), in Rochester Minnesota. Also it lies within the range recorded in most Asian countries where the rate of symptomatic epilepsy ranged from 22 to 53% (Mac et al., 2007). Subsequently, Banerjee et al. (2009), in a review of epidemiological studies of epilepsy, reported that regardless of the time or region of the study there is preponderance of epilepsy to be of unknown etiology, a finding which suggests that the use of sophisticated medical infrastructure such as imaging technology does not always increase the ability to detect a cause of epilepsy. The high rate of parental (36.8%) and grand parents’ consanguinity (28.1%) is consistent with numerous studies which have confirmed familial history of epilepsy, and parental consanguinity as risk factors for epilepsy (Mac et al., 2007; Ramasundrum, 2004). The nature of this closed community with high rate of consanguineous marriage could be a contributing factor to the high rate of idiopathic and other genetically determined epileptic syndromes. More than 1/3 of patients (39.1%) with active epilepsy, in New Valley, did not receive treatment at all. However, this rate is far lower than that recorded in China, in 2002, where more than 60% of patients with active epilepsy, in the largest country in the world, do not receive any treatment (Wang et al., 2002). Taking in consideration patients who are inappropriately treated, the level of treatment gap in New Valley reaches 61.5%. This is consistent with the findings of Mbuba et al. (2008) in meta-analysis of 27 studies from Africa, Asia, and Latin America where they found that the overall estimate of treatment gap is 56%. However, our estimated treatment gap is lower than that reported by ILAE/IBE/WHO in their introduction to the Global Campaign against Epilepsy ‘‘Epilepsy out of the Shadows’’ where they stated that globally 85% of people with epilepsy are either inappropriately treated or not treated at all (Meinardi et al., 2001). In Asian countries, the treatment gap ranged from 29 to 98% with values for most countries between 50% and 80%
Epidemiology of epilepsy in Egypt (Mac et al., 2007). In Sub-Saharan Africa and Latin America, up to 95% of people with epilepsy receive inadequate treatment or no treatment at all (Scott et al., 2001). It is so gloomy that about 60% of patients, or more, with active epilepsy in developing countries, and in the largest district of Egypt (New Valley), do not receive any treatment or are not appropriately treated. Most probably, this is due to the widely prevailing misconception of the nature of epilepsy and cultural beliefs that might affect people’s health-seeking strategies. If epilepsy is stigmatized, people are unlikely to admit that they are diseased and to know that adequate treatment exists, or to maintain compliance. Moreover, the lack of health facilities (no EEG machines, no CT scanners, no MRI machines, no specialists of neurology), besides the far distance from well qualified health care centers and the deficiency of AEDS, due to low socioeconomic standards would contribute to this high treatment gap. This wide treatment gap could be reduced by application of adequate public educational programs to dispel disease stigma, adequate training of health professionals, family doctors, and the supply of appropriate treatment. Door to door survey, to reach both heath seeking and non health seeking inhabitants will help better estimation of prevalence of epilepsy, distribution of knowledge among publics, and in bringing epilepsy out of the shadow, with subsequent reduction of treatment gap.
Conclusions The life time prevalence of epilepsy in Al Kharga District (New Valley) is 6.76/100 population, with peak prevalence during early childhood. The Annual Incidence Rate of Epilepsy is 43.14/100,000 population, with highest peaks during early infancy and elderly, and least value during early adulthood. Three quarters (73.7%) of patients (n = 312) have been reported to have active epilepsy, with a total prevalence of active epilepsy of 4.99/1000 population. The treatment gap in New Valley is 61.5%.
Funding sources None.
Acknowledgment Research team would like to thank Sanofi Pharmaceutical Company because of its helpful role in performing this work.
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