Epidemiology, aetiology, and clinical management of epilepsy in Asia: a systematic review

Review

Epidemiology, aetiology, and clinical management of epilepsy in Asia: a systematic review Tu Luong Mac, Duc-Si Tran, Fabrice Quet, Peter Odermatt, Pierre-Marie Preux, Chong Tin Tan

Epilepsy is a significant, but often underappreciated, health problem in Asia. Here, we systematically review the literature on epidemiology, aetiology, and management of epilepsy in 23 Asian countries. Prevalence estimates are available for only 11 countries from door-to-door surveys and are generally low. Figures for annual incidence in China and India are similar to those in the USA and Europe but lower than those reported from Africa and Latin America. There is a peak in incidence and prevalence in childhood, but a second peak in elderly people, as seen in developed countries, has not been documented. The main causes are head injuries, cerebrovascular disease, CNS infections, and birth trauma. Availability of epilepsy care depends largely on economic factors. Imaging and neurophysiological facilities are available in most countries, but often only in urban centres. Costly drugs, a large treatment gap, limited epilepsy surgery, and negative public attitude to epilepsy are other notable features of management in Asia. An understanding of the psychosocial, cultural, economic, organisational, and political factors influencing epilepsy causation, management, and outcome should be of high priority for future investigations.

Introduction Epilepsy is a disorder of the brain that is characterised by an enduring predisposition to generate seizures and by its neurobiological, cognitive, psychological, and social consequences.1 WHO estimates that eight people per 1000 worldwide have this disease.2 The prevalence of epilepsy in developing countries is usually higher than in developed countries.3–5 Although substantial economic development and improvement of health services have occurred, Asia is a heterogeneous and resource-constrained continent. Over half of the 50 million people with epilepsy worldwide are estimated to live in Asia. Although much research is done in Asia, information about the recognition of the burden created by the disease is scarce. In 1997, Jallon6 reviewed studies from Asia, mostly done in the 1980s, and showed a prevalence varying from 1·5 per 1000 in Japan to 10·0 per 1000 in Pakistan. Here, we provide an update on prevalence, incidence, demographic data, types of epilepsy, aetiology, treatment, and prognosis in recent years to give a comprehensive view of epilepsy in this region.

Methods Search strategy and selection criteria We searched the PubMed database by using the keyword “epilepsy”, combined with each of the following: “epidemiology”, “prevalence”, “incidence”, “aetiology”, and “treatment” for each Asian country. Other words were also used in association with the keywords. These were “malaria”, “neurocysticercosis”, “cysticercosis”, “encephalitis”, “classification”, “mortality”, “therapy”, “antiepileptic”, “AEDs”, “surgery”, “chirurgical”, “recurrence”, “prognosis”, “stigma”, “stigmatization”, “knowledge”, and “awareness”. Asian countries (n=23) were defined as the countries of the WHO Western Pacific region and WHO Southeast Asian region:7 Bangladesh, Bhutan, Brunei, Cambodia, China, North Korea, India, Indonesia, Japan, Laos, Malaysia, Maldives, http://neurology.thelancet.com Vol 6 June 2007

Mongolia, Burma, Nepal, Pakistan, the Philippines, South Korea, Singapore, Sri Lanka, Thailand, East Timor, and Vietnam. All issues of Neurology Asia and of the national medical journals of Korea (Journal of Korean Medical Science), Singapore (Singapore Medical Journal) and India (Neurology India) were hand-searched with the same criteria. Articles were included if they had at least an abstract in English or French. We included only studies reaching the recommendations of the International League Against Epilepsy (ILAE) 1993 Commission.8 Background references were identified through these searches and through searches of the authors’ own files.

Lancet Neurol 2007; 6: 533–43 Institute of Neurological Epidemiology and Tropical Neurology, Limoges, France (T L Mac, F Quet, P-M Preux); French-Speaking Institute for Tropical Medicine, Vientiane, Laos (D-S Tran); Department of Public Health and Epidemiology, Swiss Tropical Institute, Basel, Switzerland (P Odermatt); and Division of Neurology, University of Malaya, Kuala Lumpur, Malaysia (C T Tan) Correspondence to: Pierre-Marie Preux, Institut d’Epidémiologie Neurologique et de Neurologie Tropicale, (EA3174), Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex, France [email protected]

Data collection and analysis A total of 1348 articles from 20 countries were found using PubMed. No publications were found from Bhutan, Brunei, or North Korea. Most articles originated from Japan (460 articles), India (343 articles), and China (165 articles). Articles were assessed by the first two authors searching in each survey for methods and results on prevalence, incidence, demography, classification, causes, treatment, and knowledge, attitudes, and practice. Data from 119 articles were collected for this Review (see figure for more detail on the selection process).

Results Prevalence The lifetime prevalence of epilepsy varied among countries from 1·5 to 14·0 per 1000 (table 1).9–30 This wide variation could partly result from the use of different methods and different types of questionnaire. Screening questionnaires were mainly derived from WHO questionnaires, but two studies used Limoges’ questionnaire.19,28 The median lifetime prevalence is estimated at 6 per 1000, which is lower than in developing countries in other areas of the world (15 per 1000 in subSaharan Africa and 18 per 1000 in Latin America).4,5 An understanding of these differences could generate 533

Review

hypotheses for studies aimed at identifying ways to prevent this disease: for example, is there a protective factor in Asia or specific risk factors in Africa or Latin America?

Initial PubMed search

1348 articles

Incidence 1039 articles excluded: 228 not written in French or English 143 no abstract 308 non-epilepsy studies* 360 non-epidemiological studies† 309 articles that may contain relevant data

Full-text collection via: Hinari, Science Direct, Epilepsia, The New England Journal of Medicine, Medscape Infectious Diseases 190 articles excluded because the full text was not available or because they did not contain information relevant to this systematic review

Data collection from 119 references

Demographic indicators Age

Figure: Study selection for the systematic review *Articles that were not specifically on epilepsy in Asia, except analytical studies on epilepsy risk factors. †Articles that were not within the framework of this review.

Reference Year

N

Prevalence/1000 Method

China (five provinces)

9,10

2002 and 2003

55 000

China (Shanghai)

11

2002

China (six cities)

12

1985

India (West Godavari)

15

India (Kerala state)

Incidence rates were available from only two countries, China and India; of the five estimates, three were based on retrospective analyses of collections of prevalence data (table 2).9,12,17,18,31 The epilepsy incidence rates reported from China were low—from 28·8 per 100 000 person-years9 to 35·0 per 100 000 person-years in the general population.12 The results from India were higher, and reached 60·0 per 100 000 person-years.31 Overall, the results were not different from those in developed countries where the age-adjusted incidence of epilepsy is 24–53 per 100 000 person-years.32 Some authors report an incidence rate in developing countries that is as high as 190 per 100 000 person-years.33,34 Confirmation of low incidence rates in Asia would be very important, and rigorous populationbased prospective studies are needed.

The publications included in this Review show one peak age for incidence in children19,26 and one peak age for prevalence in young adults.12–13,16,19,35–38 However, one study, done in Shanghai, showed two prevalence age peaks: one between 10 and 30 years old and one in people over 60 years old.11 These figures are summarised in table 3.11,13,16,19,26,35–38 In developed countries, the incidence and prevalence of epilepsy both follow a bimodal distribution with a first peak in childhood and another in old age.32,39,40 The most probable reason for the missing peak in the older age groups in many Asian countries is the relatively young population compared with that in more developed regions.

7·0 4·6*

Door-to-door survey

48 628

3·6*

Door-to-door survey

63 195

4·4

Door-to-door survey

2004

74 086

6·2

Door-to-door survey

16

2000

238 102

4·7†

Door-to-door survey

India

18

1998

64 963

3·9†

Door-to-door survey

India

29

2006

50 617

3·8†

Door-to-door survey

Laos

19

2006

4310

7·7†

Door-to-door survey

Turkey

26

1997

11 497

7·0†

Door-to-door survey

Sex

Pakistan

21

1994

24 130

10·0†

Door-to-door survey

Vietnam

28

2005

6617

10·7†

Door-to-door survey

Nepal

20

2003

4636

7·3

Epilepsy is slightly more common in men than in women but the sex-specific prevalence is not, in general, significantly different (table 4).11,13,18–20,23,26,35,38

Taiwan

24

1997

10 058

2·4

Community based

Taiwan

30

2001

13 663

2·8†

Community based

Location

Thailand

25

2002

2069

7·2

Community based

Singapore

22

1997

20 542

5·0

Men at 18 years old

Singapore

23

1997

96 047

3·5

Review <9 years

Hong Kong

13

2003

NA

1·5

Estimation in adult patients (≥15 years)

Vietnam

27

2003

NA

14·0

India

14

2003

NA

5·6

Review

India

17

2002

NA

5·0

Review

Two studies (in Pakistan and in India) indicated that the prevalence was higher in rural areas than in urban areas.26,29 Although not significant, a meta-analysis of published and non-published community-based studies in India showed a higher prevalence of 5·5 per 1000 (95% CI 4·0–6·9) in rural areas than that of 5·1 per 1000 (3·5–6·7) in urban areas.35 Indeed, a higher prevalence in rural areas is a common tendency in developing countries.6

Community based

Estimation

N=sample size. NA=not available. *Active epilepsy (seizures within the previous year). †Active epilepsy (seizures within the previous 5 years). Otherwise, details of disease duration were not available.

Table 1: Prevalence of epilepsy in Asia

534

Mortality Data on mortality rate in Asian people with epilepsy are scarce, and those that are available indicate high rates in http://neurology.thelancet.com Vol 6 June 2007

Review

Reference Year

China (five provinces)

N

Incidence/ Method 100 000 person-years

9

2002

55 616

28·8

Door-to-door survey

China

12

1985

63 195

35·0

Door-to-door survey

India

18

1998

64 963

49·3

Door-to-door survey

India

31

1999

NA

60·0

Estimation

India

17

2002

NA

38·0–49·3

Review

N=sample size. NA=not available.

Table 2: Incidence of epilepsy in Asia

developing countries in this region. In one study in Laos, there was a very high case-fatality rate of 90·9 per 1000 person-years.19 This study was in a mountainous region, in which very few people had access to antiepileptic drugs. These data came from a management project after door-todoor screening. The number of patients followed-up was small, but the results might not be too far from the real mortality rate, because almost all patients in Laos were not

adequately treated and Laos is one of the least developed countries in this region. A recent study found a standardised mortality ratio of 3·9 among 2455 people with epilepsy who participated in an assessment of epilepsy management at the primary health-care level in rural China.41 Mortality is also usually high in developing countries in other regions of the world: 28·9 per 1000 person-years in a rural area of Cameroon42 and 31·6 per 1000 person-years in rural central Ethiopia.43 Other studies should be done to confirm this higher mortality rate in Asia, which might partly explain the low prevalence rate. By contrast, mortality in the most developed countries in Asia is low. A study of childhood epilepsy in a Japanese general population showed a mortality of 45·0 per 1000 people accumulated over a long follow-up period (mean: 18·9 years).44 Another study in adult Taiwanese patients showed a mortality of 9 per 1000 person-years.45 Patients with epilepsy in Taiwan had a nearly 3·5 times higher risk of death than the general population (standardised mortality ratio 3·47, 95% CI 2·46–4·91).46 Other researchers examined the outcome in convulsive disorders in a more indirect way: an analysis of 37 125 death certificates in Sri Lanka since 1967 found death by

Reference

Year

Age peak (years) Mean age of onset (years)

% children (<18 years)

N

Method

China (Shanghai)

11

2002

10–30, >60

NA

NA

151

Door-to-door survey

India

16

2000

10–19

NA

NA

1175

Door-to-door survey

Laos

19

2006

11–20

NA

NA

33

Door-to-door survey

Pakistan

26

1997

NA

13·3

74·3

241

Door-to-door survey Door-to-door survey

Turkey

26

1997

NA

12·9

72·0

81

Hong Kong

13

2003

25–30

19·9

NA

736

Adult patients in hospital

India

37

1999

NA

14·3

NA

972

Hospital-registered patients

India

35

1999

10–19

NA

NA

525

Review

Bangladesh

36

2004

16–31

NA

NA

NA

Review

Hong Kong

38

1997

NA

18·8

NA

2952

Review of outpatient records

N=number of patients with epilepsy. NA=not available.

Table 3: Age distribution of patients with epilepsy in Asia

Reference

Year

Male (%)

Female (%)

Male prevalence (‰)

Female prevalence (‰)

N

Method

China (Shanghai)

11

2002

NA

NA

3·6

2·5

151

Turkey

26

1997

54·3

45·7

8·7

6·3

81

Door-to-door survey

India

18

1998

NA

NA

4·4

3·4

254

Door-to-door survey

Laos

19

2006

60·6

39·4

NA

NA

33

Door-to-door survey

Pakistan

26

1997

49·8

50·2

9·2

10·9

241

Door-to-door survey

Nepal

20

2003

NA

NA

6·8

7·9

34

Hong Kong

13

2003

57·1

42·9

NA

NA

736

Hong Kong

38

2001

54·3

45·7

NA

NA

2952

Singapore

23

1997

50·1

49·9

3·5

3·5

336

India

35

1999

NA

NA

5·9

5·5

3207

Door-to-door survey

Community based Adult patients in hospital Review of outpatient records Review <9 years Meta-analysis

N=number of patients with epilepsy. NA=not available.

Table 4: Gender proportions and gender-adjusted prevalence in patients with epilepsy in Asia

http://neurology.thelancet.com Vol 6 June 2007

535

Review

convulsions in 23·7 per 1000.47 The most common cause, febrile convulsions, was documented in 396 (44·9%) deaths. Neonatal and infantile convulsions accounted for 186 (21·1%) deaths. Other causes of death associated with seizures included chest complications (60; 6·8%), drowning (28; 3·2%), asphyxia (20; 2·3%), status epilepticus (19; 2·2%), burns (7; 0·8%), and poisoning (2; 0·2%).47 In this study, deaths due to convulsive disorders showed a decrease from 37·3 per 1000 people in 1967 to 9·5 per 1000 people in 1987.47 Mortality from status epilepticus in patients in a large community hospital in Hong Kong from 1996 to 2001 was 16·0%. Predictors of mortality were older age (OR 1·04, 95% CI 1·01–1·07), a delay in starting treatment (3·52, 1·01–12·18), status epilepticus due to cerebrovascular disease (9·73, 1·58–59·96), and CNS infection (30·27, 3·14–292·19).48 Complications related to steroid treatment in West syndrome were also an important cause of death as seen in Hong Kong.49 Specific mortality rates for the main causes of death must be estimated in Asia to enable better prevention.

epilepsy (relative risk 2·86, 95% CI 2·35–3·48) and a higher number of seizures before seizure control (1·50, 1·30–1·73) increased the risk of recurrence. Seizure-free duration before beginning drug withdrawal (2 years vs 4 years) did not significantly influence this risk.54 Surgery for intractable temporal-lobe epilepsy led to good results in a study in Indonesia.55 Of 56 patients who had anterior temporal lobectomy with amygdalohippocampectomy, 46 patients (82·0%) were seizure-free (Engel I). Six patients (11%) had fewer than two seizures per year (Engel II), and seizures decreased by more than 75% (Engel III) in four patients (7%). Complications included extradural empyema in five patients (9%), depression in two patients (4%), and transient hemiparesis in one patient (2%). 31 patients were able to stop taking antiepileptic drugs. The follow-up varied between 12 and 76 months. This is the only description found in Asia on epilepsy surgery, an efficient solution for intractable epilepsy. Few patients in Asia can benefit from this therapy even if it is available in several countries (see Surgery section).

Prognosis In general, a third to two-thirds of patients will have recurrent seizures within 5 years of the first unprovoked seizure.50,51 Similar recurrence rates are seen in Asia. A study in Thai children showed a cumulative risk of recurrence of 25% at 14 days, 50% at 4 months, 51% at 6 months, and 66% at 12 months.52 In children treated for epilepsy, follow-up after withdrawal of antiepileptic drugs (average duration 43·5 months) showed a cumulative risk of recurrence of 10% at 12 months and 12% at 36 months.53 The need for two AEDs to control seizures was a risk factor for recurrence (incidence 0·025 vs 0·002, p=0·001).53 Another study in India noted seizure recurrence in 31% of patients (of all ages) during a followup period of 18 months. Longer duration of active Reference

Year

Clinical classification Numerous clinical studies have been published but few have described the distribution of seizure types in community-based studies. In addition, comparison of the results from different studies is difficult because classifications used are not homogeneous. Here, we present only the results based on the 1981 ILAE classification (table 5).13,16,19,22,38,49,56–59 The range of patients with generalised seizures was 50–69%, and 31–50% had partial seizures.16,19,22,56 The prevalence rates of symptomatic, idiopathic, and cryptogenic epilepsy were 22–53%, 4–42%, and 13–60%, respectively.13,19,38,49,56,59 The predominance of generalised epilepsy and wider range of cryptogenic epilepsy may be

Seizure type classification

Aetiological classification

GS

US

IE

CE

SE

FS

N

Method

India

16

2000

58·8

30·6

NA

NA

NA

NA

Laos

19

2006

63·6

27·3

9·1

27·3

48·5

24·2

1175 33

Door-to-door survey

Hong Kong

13

2003

NA

NA

NA

38·7

13·6

38·7

736

Hong Kong

49

2001

NA

NA

NA

18·0

22·0

53·3

105

Children with West syndrome

Hong Kong

38

2001

NA

NA

NA

3·9

59·9

35·1

2952

Review of outpatient records

Hong Kong

56

2001

49·5

48·2

2·3

42·4

16·8

40·8

309

Child patients

India

57

2005

42·0

58·0

NA

NA

NA

NA

112

PWE with follow-up >12 months at tertiary care epilepsy centre and aged >16 years

Malaysia

58

1993

86·0

14·0

NA

NA

NA

NA

593

Adult patients with EEG

Malaysia

58

1993

92·0

8·0

NA

NA

NA

NA

593

Child patients with EEG

Malaysia

59

1999

NA

NA

NA

78·0*

22·0

165

Newly diagnosed epilepsy

Singapore

22

1997

69·0

31·0

NA

NA

NA

NA

106

All epilepsy

Singapore

22

1997

29·0

64·0

7·0

NA

NA

NA

14

Door-to-door survey Adult patients in hospital

Refractory seizures

GS=generalised seizures. FS=focal seizures. US=unclassified seizures or multiple seizure types. IE=idiopathic epilepsy. CE=cryptogenic epilepsy. SE=symptomatic epilepsy. N=number of patients with epilepsy. NA=not available. PWE= people with epilepsy. EEG=electroencephalogram. *This figure applies to IE and CE combined.

Table 5: Clinical classification of patients in studies on epilepsy in Asia

536

http://neurology.thelancet.com Vol 6 June 2007

Review

due to differences in the extent of imaging studies and the lack of standardised classification and terminology in epilepsy research in Asia. Electroencephalographic data were often not available, which could also have influenced the proportions of idiopathic epilepsy reported in several studies. Population-based studies with electroencephalographic recording are required to enable accurate clinical classification of epilepsy in Asia.

Causes There are very few studies on the causes of epilepsy in Asian populations, and there are particularly few case– control studies or cohort studies. From the available literature, causes seem to be dominated by head injury, birth trauma, and intracranial infections, such as neurocysticercosis or meningoencephalitis. Where socioeconomic development is better, head trauma and stroke are the leading causes of epilepsy. In China in the 1980s, brain injury, intracranial infection, and cerebrovascular disease, in that order, were the leading putative causes of epilepsy.12 Cases reported from China during 1994–2003 allowed the estimation of an average incidence of 8·7% for epilepsy with cerebrovascular disease and of 8% with posttraumatic epilepsy.60 In patients in Hong Kong, the commonest causes were cerebrovascular disease (26·2%), a history of CNS infection (26·0%), head trauma (11·4%), perinatal insult (9·7%), congenital brain malformation (7·4%), hippocampal sclerosis (5·9%), and intracranial neoplasm (5·6%).61 By contrast, in 300 incident cases of epilepsy in Nepal 47% were caused by neurocysticercosis, 9% by tumour, 4% by vascular disease, and 2% by head injury.20 In this section, we elaborate on these causes of epilepsy in Asia.

Head injury In Asia, post-traumatic epilepsy is one of the most common complications of head injury. One study claimed that post-traumatic epilepsy accounted for 5% of total epilepsy and 20% of symptomatic epilepsy.60 A history of major brain trauma (20·9%) was also the leading cause of epilepsy in surgically treated patients in China.62

CNS infections In developing countries in other regions of the world, such as sub-Saharan Africa or Latin America, CNS infections seem to explain the high prevalence of epilepsy. The Commission on Tropical Disease of the International League Against Epilepsy listed several diseases as causes of epilepsy, including malaria, tuberculosis, schistosomiasis, AIDS, and cysticercosis—among these, the latter seems to be the most common cause of epilepsy.3 In Asia, there is a lack of rigorous analytical studies to assess the effect of these infections in epilepsy. An association between neurocysticercosis and epilepsy was found in numerous studies in Africa5 and Latin America.63,64 Neurocysticercosis was the cause of epilepsy in about 50% of patients in some studies,42,65 and seizures http://neurology.thelancet.com Vol 6 June 2007

occur in 50–80% of patients with parenchymal cysticercosis.65 In Asia, many studies report the presence of cysticercosis (taeniasis).65–76 However, there are few studies on the relation between neurocysticercosis and epilepsy in Asia, and their results vary widely. Neurocysticercosis is probably an important cause of seizures and epilepsy in regions with a high prevalence of Taenia solium infection in human beings. In Asia, this includes India, Nepal, Bali, Papua and Sulawesi in Indonesia, and parts of Vietnam and China. Cysticercosis is only rarely detected in the most economically advanced countries of Asia, such as South Korea,74 but the prevalence might also be low in poor regions.15,19,71 In a meta-analysis, seizures were the most common symptom (56·2%) of cysticercosis in China.69 Another study noted that between 8·7% and 50·0% of cysticercosis-infected patients had recent seizures.66 Single CT enhancing lesions and neurocysticercosis together accounted for 67% of the provoking factors of acute symptomatic seizures.77 Conversely, in some studies, the cysticercosis seropositivity was not higher in patients with epilepsy in regions with either a low prevalence (eg, Laos19) or a high prevalence (eg, Indonesia73). Paragonimiasis is endemic in several Asian countries: China, South Korea, the Philippines, Japan, and Vietnam.78,79 During migration, the causal lung fluke may reach the brain and may cause seizures, epilepsy, and other neurological syndromes.80–82 However, no study has quantified the importance of Paragonimus infection in epilepsy. Malaria is still widely endemic in Asia, with more than 3 million cases per year. India, Burma, Indonesia, Pakistan, Cambodia, Papua New Guinea, and Bangladesh each have more than 50 000 cases per year.83 Malaria causes various symptoms, such as fever and convulsions. 7·7% of patients with childhood malaria (with or without the presence of cerebral malaria) in a retrospective survey in Thailand had convulsions.84 In cerebral malaria, convulsions present in 60% of cases.85 However, we did not find any analytical study reporting the relation between malaria and epilepsy in Asia. Nevertheless, the link between epilepsy and malaria was recently supported by a case–control study in Gabon and a cohort study in Mali in Africa.86,87 Japanese encephalitis is one of the most common encephalitic disorders worldwide. Most of China, southeast Asia, and the Indian subcontinent are affected.88 65% of patients with Japanese encephalitis have acute symptomatic seizures and 13% have chronic epilepsy.89 In a study in India, 30 of 65 patients with Japanese encephalitis had seizures in the first weeks of illness; 19 of them had two or more seizures.90

Genetic factors Two studies in India found no relation between being a twin and epilepsy, and twins of people with epilepsy did not have a high risk of epilepsy.91,92 Case–control studies in 537

Review

China have found no relation between epilepsy and susceptibility genes, such as GABABR1,93,94 KHDRBS3 (T-STAR),95 and CACNA1G (calcium channel, voltage dependent, T-type, alpha 1G subunit).96 However, numerous studies have confirmed familial history of epilepsy and parental consanguinity as risk factors. In Kerala, south India, a family history of epilepsy was three times more common in patients with epilepsy than in controls (OR 3·2, 95% CI 2·1–4·7)97 and two times higher in another study in north India (2·1, 1·1–4·3).31 Family history was also a risk factor for epilepsy in studies in Laos19 and China.98 This level of risk is similar to that in studies from Africa.5 In Asia, consanguineous marriage is common in certain cultures, in particular among Indian and Muslim populations. Consanguinity of parents was significantly more common among patients than among controls (13·1% vs 6·6%).97 The odds ratio for parental consanguinity was higher in patients with generalised epilepsy than for controls (2·6; 95% CI 1·5–4·4).97 Another study of 316 patients with epilepsy of Indian origin in Malaysia showed that 29·5% of them had a parental consanguineous marriage, and that there was a significant association with parental consanguinity in idiopathic and cryptogenic epilepsies.99 Consanguinity could be a target for a campaign to prevent epilepsy.

Epilepsy care Typically, there is great variability in the case management of epilepsy among different countries. In southeast Asia, this variability depends on factors such as the economic status, the quality of the health system and peripheral services, rural or urban residence, and the cultural frameworks of societies.33,100

Health-care facilities According to WHO, the median number of hospital beds for epilepsy care per 100 000 population is very low in Asia: 0·05 in southeast Asia and 0·46 in the Western Pacific—fewer than in Africa (0·55) and far fewer than in Europe (1·65).101 Similarly, the number of neurologists is extremely low in most Asian countries. In 2004, in India, Laos, and Bangladesh, WHO estimated that there was fewer than one neurologist per million inhabitants. In Japan, there are between one and 50 neurologists per million people,101,102 and a proportion of these neurologists work in the private sector.100 In 2001, a comparative study of epilepsy reference centres in Europe and Asia showed that medical specialists in Asia examined more patients per day in walk-in clinics than did their European counterparts.103 The development of epilepsy care is commonly driven by epileptologists—neurologists with a special interest in epilepsy. If an epileptologist is defined practically as someone who has had a period of fellowship after training in general neurology, only Japan, South Korea, Singapore, and Taiwan have at least one epileptologist per million people. Paramedical professionals, such as nurses, occupational therapists, 538

and educators rarely participate in the management of epilepsy in Asia—another difference from epilepsy care in Europe.103 Technologies such as electroencephalography, CT, and MRI used in epilepsy diagnosis are widely available in Asian countries, but their accessibility varies in the different geographical regions. In developed economies, such as Japan, South Korea, Singapore, and Taiwan, sophisticated facilities are highly accessible to most of the population, whereas almost no electroencephalography or imaging facilities are available in other countries, such as Cambodia, East Timor, Laos, or Mongolia. In addition, many of these facilities are privately operated and available only in big cities, with MRI being mainly used for assessments for epilepsy surgery.100 However, the development of these facilities is changing rapidly. Currently, there are 15 ILAE chapters in Asia. They are located in Bangladesh, China and Hong Kong, India, Indonesia, Japan, South Korea, Malaysia, Mongolia, Nepal, Pakistan, the Philippines, Taiwan, Thailand, and Singapore. These chapters are absent in the less developed nations.

Antiepileptic drugs Antiepileptic drugs are the simplest and the safest means of controlling epilepsy. Various first-generation antiepileptic drugs—phenytoin, carbamazepine, valproic acid, phenobarbital, clonazepam, primidone, and ethosuximide—are used widely in Asian countries104 (table 6),20,39,61,105–112 and monotherapy is common. The particular drug used depends on the medical culture and practices in each country. Second-generation antiepileptic drugs, such as lamotrigine, gabapentin, tiagabine, felbamate, vigabatrin, or topiramate, are used widely in Malaysia, China, and Singapore and in some of the economically less developed countries, including the Philippines and Vietnam.7,113 Clobazam, oxcarbazepine, and levetiracetam are available in large Asian countries, such as India, but are prohibitively expensive. Access to drugs is probably easier in Asia than in Africa but this varies widely according to the context (degree of development, urbanisation, etc). Although first-generation antiepileptic drugs are predominant, there are availability and accessibility problems in several places. In 2003, a study in Long Xuyen, Vietnam, showed that drugs were available but only for a short period of time. Moreover, these antiepileptic drugs were sold in pharmacies that were located in only a small area in the city centres.114 In most parts of Asia, there are limited amounts of or no subsidised antiepileptic drugs. The patients and families have to pay beyond their means for even the most common first-generation drugs. For example, the yearly cost of 100 mg daily phenobarbital, one of the cheapest drugs, is about US$30 in Laos, which is about the monthly salary of a school teacher; in north India, this cost is US$11. In consequence, almost all patients would not be able to have long-term treatment if it http://neurology.thelancet.com Vol 6 June 2007

Review

Reference First or secondgeneration AEDs

Monotherapy or polytherapy

AEDs used

Comments

Hong Kong

61

First and second

Monotherapy: 57·4%

Phenytoin used in 38·7%

India

39

First

Polytherapy: 57·8% (entry) Carbamazepine used at entry and monotherapy: 76·4% and at follow-up (follow-up)

India (secondary level hospital)

105

NA

Polytherapy: 20·8%

Phenytoin used in 93·0%

India (university medical centres)

106

First and second

Polytherapy: 24·5% and monotherapy 75·5%

Carbamazepine used in 47·4%

Indonesia

107

First and second

NA

NA

Availability of AEDs depending on urban or rural area

Nepal (hospital)

20

First

NA

NA

AEDs used depending on geographical location. Monotherapy: with carbamazepine used at 92·0% in one hospital

Sri Lanka

108

First

Monotherapy: 75·0%

Carbamazepine used in 48·0%

Sri Lanka (hospital)

109

First

Monotherapy: 70·8%

Carbamazepine

Taiwan

110

First and second

Polytherapy: 0·6% and monotherapy: 29·4%

Carbamazepine used in 78·4%

Second-generation AEDs are available in private clinic

Taiwan

111

First

Monotherapy: 61·0%

Carbamazepine used in 56·9%

Thailand

112

NA

Polytherapy: 58·6%

NA

First-generation antiepileptic drugs (AEDs): phenytoin, carbamazepine, valproic acid, phenobarbital, clonazepam, primidone, ethosuximide. Second-generation AEDs: lamotrigine, gabapentin, tiagabine, felbamate, vigabatrin, topiramate. NA=not available.

Table 6: Use of antiepileptic drugs in Asian countries

is not funded. The average annual cost (direct and indirect) of outpatient treatment of epilepsy is US$47 per patient. In general, the cost of phenobarbital in southeast Asia is 2·7 times higher than in Europe,101 and two to six times higher than in sub-Saharan Africa. The annual cost incurred in emergency and inpatient management in India is estimated to be US$810·50 and US$168·30, respectively, for all the patients attending a secondary hospital.105 In general, the cost of treatment is much lower than productivity losses, and it would be cost efficient for governments or societies to invest in epilepsy treatment.105

Epilepsy control assessment Treatment with phenobarbital was assessed in 2455 Chinese patients from rural areas in a community-based intervention trial. In 68% of patients who completed 12 months’ treatment, seizure frequency was decreased by at least 50%, and a third of patients were seizure-free. 72% of patients who completed 24 months’ treatment had at least 50% reduction in seizure frequency and a quarter of patients remained seizure-free. 597 patients discontinued treatment before the end of the study. Many of those withdrew because of a misunderstanding that they were cured on becoming seizure-free (28%); others withdrew because they perceived the treatment to be ineffective (16%). Only 5% discontinued the treatment because of adverse events.115 Another study in India showed that strict drug compliance and early treatment (with phenobarbital or phenytoin or both) were important predictors of a 2 year terminal remission.116

Treatment gap The treatment gap was defined by a workshop of the ILAE as the difference between the number of people http://neurology.thelancet.com Vol 6 June 2007

with active epilepsy (defined in this case as two or more unprovoked seizures on different days in the previous year) and the number whose seizures are being appropriately treated in a given population at a given point in time, expressed as a percentage.33,117 In developing countries in sub-Saharan Africa and Latin America, up to 90% of people with epilepsy receive inadequate treatment or no treatment at all.33,118,119 In Asian countries, the treatment gap was 29–98%, with values for most countries between 50% and 80%. The treatment gap was higher in rural areas than in urban areas (table 7).9,10,16,17,21,26,35,120–126 In rural areas, lack of antiepileptic drugs and knowledge of epilepsy contribute to the treatment gap.

References

Year

Treatment gap (%)

China

9,10

2002 (and 2003)

62·6

India

120

2003

50·0–70·0

India

17

2002

73·0–78·0

India (semi-urban)

16

2000

38·0

India (rural)

35

1999

>70·0

India (rural)

121

1999

54·0

India (rural)

122

1997

78·0

India (semi-urban)

123

1997

57·0

India (rural)

124

1988

74·5

India (urban)

125

1988

29·0 >70·0

Nepal

126

2004

Pakistan (rural)

21,26

1994 (and 1997)

98·0

Pakistan (urban)

21,26

1994 (and 1997)

>72·0

Turkey

26

1997

70·0

Table 7: Treatment gap for epilepsy in Asia

539

Review

Surgery The ILAE reported the presence of epilepsy surgery centres in 26 countries worldwide from 1980 to 1990; at that time, only four Asian countries were on the list: Japan, China, Taiwan, and Vietnam.127 More recent reports revealed some others in Hong Kong, India, Iran, North Korea and South Korea, the Philippines, Singapore, Thailand, and Turkey.128,129 A cohort study of patients with medically refractory temporal-lobe epilepsy in India showed a significantly better outcome of surgery (77·0% seizure-free, 32·7% off medication) compared with medical treatment (11·5% seizure-free, 0·8% off medication). There was no statistically significant difference in mortality between the two groups.130

Concepts of disease and use of traditional, complementary, and alternative medicine There are few dedicated studies on the concepts of disease and use of traditional, complementary, and alternative medicine among patients with epilepsy in Asia, although many clinicians practising in the region have reported widespread use of traditional medicine and spiritual medium, particularly in rural areas.20,100,131 Tan and Lim100 reported prevalence of syncretism (ie, simultaneously holding to concepts from different schools of thought) in concepts and practice among the ethnic Chinese patients with chronic epilepsy in Kuala Lumpur, with some patients attributing the illness to epilepsy as well as to the traditional concepts of “weakness” (xu), “hotness” (re), “wind” (feng), and “supernatural cause” (xie). Rajbhandari20 reported that 69% of the newly diagnosed patients with epilepsy in Kathmandu worshipped family gods, 66% wore mantra butti, jantar, and beets (items believed to protect patients from evil spirits), and 58% made animal sacrifices. Tsai132 Reference

Year

N

reported from Taiwan that 50% of their patients used Chinese traditional medicine, and 47% sought folk healing methods including Qian interpretation, fortune telling, Qigong, geomancy, and shamanism. The use of these traditional treatment modalities is probably related to the large treatment gap in large parts of Asia. Some of the so-called traditional preparations are adulterated with conventional antiepileptic drugs, which complicates the management of these patients.133 This situation is comparable to that in sub-Saharan Africa.5 As long as traditional beliefs exist, patients with epilepsy are not likely to be correctly treated.

Knowledge, attitudes, and practice Numerous studies on knowledge, attitudes, and practice have been done, particularly in Chinese communities within and outside China (table 8).16,134–144 Stigma was least important but evident in some advanced regions, such as Hong Kong or Singapore.131,137,138 In Hong Kong, 94·1% of respondents thought that people with epilepsy could be married, but only 67·8% would allow their child to marry a person with epilepsy;138 from the reports discussed in this Review, it seems that people in Hong Kong have the most open-minded attitudes towards epilepsy. In another study in China, only 13·0% of the respondents would allow their child to marry a person with epilepsy.141 Lack of awareness may be a factor explaining stigma. In almost all studies, a third to a half of responding people thought that a person with epilepsy cannot work like other people, and a quarter thought that epilepsy is a mental illness or a form of insanity. As in other parts of the world, epilepsy is believed to be a contagious disease,123,145 and some people avoid touching patients, especially during seizures, when some simple forms of help may avoid dangerous situations. Health education campaigns are necessary to rehabilitate

Proportion of affirmative answers Q1 (%)

Q2 (%)

Malaysia

134

1999

379

99·0

Malaysia

135

2000

839

91·0

9·0*

Burma

136

2002

296

Hong Kong

137

2004

233

Hong Kong

138

2002

1128

58·2

India

16

2000

1118

Korea

140

2003

820

Taiwan

141

1995

2610

87·0

Vietnam

143

2005

523

68·0

Vietnam

144

2006

1000

54·6

Indonesia

139

2002

84

100·0

57·0

Thailand

142

1999

284

57·8

18·2

Q3 (%)

Population interviewed Q4 (%)

Q5 (%)

13·0

91·0

57·0

Public

24·0

58·0

80·0

52·0

Public

82·0

25·0*

86·0

56·0

29·0

Public

96·0

10·0*

10·0

89·0

56·0

Public

10·4

22·5†

88·8

67·8

Public

98·7

27·3

45·6

89·2

71·3‡

Public

93·0

34·0

52·0

49·0

4·0

Public

31·0

82·0

28·0

Public

25·0

NA

NA

14·0

Public

23·8*

57·9

81·3

44·0

Public

43·0

75·0

44·0

School teacher

NA

94·7

41·2

School teacher

7·0*

Q1=have you ever heard about epilepsy? Q2=do you think that epilepsy is a mental illness? Q3=do you think that people with epilepsy would not be employed like others? Q4=would you allow your child to associate with a child with epilepsy at school or in play? Q5=would you allow your child to marry a person with epilepsy? N=number of respondents. NA=not available. *Epilepsy is a form of insanity. †Employers would terminate the employment contract after an epileptic seizure in an employee with unreported epilepsy. ‡Patient with epilepsy can lead a married life.

Table 8: Awareness, attitudes and understanding towards epilepsy in Asia

540

http://neurology.thelancet.com Vol 6 June 2007

Review

patients with epilepsy in the community and to improve their quality of life.

Conclusion There have been significant advances in the understanding of the epidemiology of epilepsy in Asia over the past 20 years. The median lifetime prevalence rate is estimated to be six per 1000 people, which is lower than in other developing regions. However, the number of affected patients in the region is large and much remains poorly documented or unknown. There are few data on incidence and mortality (in particular in elderly people), the treatment gap, public understanding and attitudes, patients’ concepts of disease, and help-seeking behaviour. What distinguishes epilepsy in Asia from other regions is probably not so much genetics or biological differences of Asians or environmental factors that influence the causes of symptomatic epilepsy, but most likely, the psychosocial, cultural, economic, organisational, and political factors that influence epilepsy causation, management, and outcome. These areas should be the focus of further study, and governments must give a higher priority to the fight against epilepsy in Asia. Some of the countries included in this Review are no longer poor, and could make free or subsidised antiepileptic drugs available to the general public, as the cost of even phenobarbital can be a burden on some of these communities. Nurturing of epileptologists who can spearhead improvements in epilepsy care in the community is also important. Moreover, governments should give high priority to the development of epilepsy surgery to treat drug-resistant epilepsy and should identify centres to be equipped with physical facilities such as video-electroencephalography and MRI. Contributors TLM and DST contributed equally in reviewing all the publications and analysing data, FQ and PO participated in interpretation, and the work was coordinated by PMP and CTT. All authors contributed to the writing of the paper. Conflicts of interest We have no conflicts of interest. Acknowledgments We thank Sandra Gresiak for her help typing the paper and obtaining references. We have received an unrestricted grant from Sanofi Aventis. References 1 Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46: 470–72. 2 World Health Organization: epilepsy: epidemiology, aetiology and prognosis. WHO Factsheet, 2001: number 165. 3 Commission on Tropical Diseases of the International League Against Epilepsy. Relationship between epilepsy and tropical diseases. Epilepsia 1994; 35: 89–93. 4 Burneo JG, Tellez-Zenteno J, Wiebe S. Understanding the burden of epilepsy in Latin America: a systematic review of its prevalence and incidence. Epilepsy Res 2005; 66: 63–74. 5 Preux PM, Druet-Cabanac M: Epidemiology of epilepsy in subSaharan Africa. Lancet Neurol 2005; 4: 21–31. 6 Jallon P. Epilepsy in developing countries. Epilepsia 1997; 38: 1143–51.

http://neurology.thelancet.com Vol 6 June 2007

7

8

9

10

11

12

13 14 15

16

17 18

19 20 21 22 23 24 25

26

27 28

29

30

31

32

33

WHO-Regional Office for the Western Pacific. Epilepsy in the Western Pacific Region: a call to action: Global Campaign Against Epilepsy. Geneva: WHO, 2004. Commission on epidemiology and prognosis, International League Against Epilepsy. Guidelines for epidemiologic studies on epilepsy. Epilepsia 1993; 34: 592–96. Wang W, Wu J, Wang D, et al. Epidemiological survey on epilepsy among rural populations in five provinces in China. Zhonghua Yi Xue Za Zhi 2002; 82: 449–52. Wang WZ, Wu JZ, Wang DS, et al. The prevalence and treatment gap in epilepsy in China: an ILAE/IBE/WHO study. Neurology 2003; 60: 1544–45. Huang M, Hong Z, Zeng J, et al. The prevalence of epilepsy in rural Jinshan in Shanghai. Zhonghua Liu Xing Bing Xue Za Zhi 2002; 23: 345–46. Li SC, Schoenberg BS, Wang CC, et al. Epidemiology of epilepsy in urban areas of the People’s Republic of China. Epilepsia 1985; 26: 391–94. Fong GCY, Mak W, Cheng TS, et al. A prevalence study of epilepsy in Hong Kong. Hong Kong Med J 2003; 9: 252–57. Bharucha NE. Epidemiology of epilepsy in India. Epilepsia 2003; 44: 9–11. Murthy JMK, Vijay S, Ravi Raju C, et al. Acute symptomatic seizures associated with neurocysticercosis: A community-based prevalence study and comprehensive rural epilepsy study in South India. Neurol Asia 2004; 9: 86. Radhakrishnan K, Pandian JD, Santhoshkuma T, et al. Prevalence, knowledge, attitude and practice of epilepsy in Kerala, South India. Epilepsia 2000; 41: 1027–35. Ray BK, Bhattacharya S, Kundu TN, et al. Epidemiology of epilepsyIndian perspective. J Indian Med Assoc 2002; 100: 322–26. Mani KS, Rangan G, Srinivas HV, et al. The Yelandur study: a community-based approach to epilepsy in rural South India— epidemiological aspects. Seizure 1998; 7: 281–88. Tran DS, Odermatt P, Le TO, et al. Prevalence of epilepsy in a rural district of central Lao PDR. Neuroepidemiology 2006; 26: 199–206. Rajbhandari KC. Epilepsy in Nepal. Neurol J Southeast Asia 2003; 8: 1–4. Aziz H, Ali SM, Frances P, et al. Epilepsy in Pakistan: a community based epidemiologic study. Epilepsia 1994; 35: 950–58. Loh NK, Lee WL, Yew WW, et al. Refractory seizures in a young army cohort. Ann Acad Med Singap 1997; 26: 471–74. Lee WL, Low PS, Murugasu B, et al. Epidemiology of epilepsy in Singapore children. Neurol J Southeast Asia 1997; 2: 31–35. Su CL, Chang SF, Chen ZY, et al. Prevalence of epilepsy in Ilan, Taiwan. Taiwan Epileps Soc Bull 1997; 7: 47. Asawavichienjinda T, Sitthi-Amorn C, Tanyanont W. Prevalence of epilepsy in rural Thailand: a population-based study. J Med Assoc Thai 2002; 85: 1066–73. Aziz H, Guvener A, Akhtar SW, et al. Comparative epidemiology of epilepsy in Pakistan and Turkey: population based studies using identical protocols. Epilepsia 1997; 38: 716–22. Mori P. Combattre l’épilepsie au Vietnam. Pulsations 2003; 4: 10. Cuong LQ, Doanh NV, Jallon P. Prevalence of epilepsy in Thai BaoBac Ninh, a region in Vietnam affected by neurocysticercosis. Epilepsia 2005; 46: 132. Rajshekhar V, Raghava MV, Prabhakaran V, et al. Active epilepsy as an index of burden of neurocysticercosis in Vellore district, India. Neurology 2006; 67: 2135–39. Chen CC, Chen TF, Hwang YC, et al. Population-based survey on prevalence of adult patients with epilepsy in Taiwan (Keelung community-based integrated screening no.12). Epilepsy Res 2006; 72: 67–74. Sawhney IM, Singh A, Kaur P, et al. A case control study and one year follow-up of registered epilepsy cases in a resettlement colony of North India, a developing tropical country. J Neurol Sci 1999; 165: 31–35. Jallon P. Epilepsy and epileptic disorders, an epidemiological marker? Contribution of descriptive epidemiology. Epileptic Disord 2002; 4: 1–13. Scott RA, Lhatoo SD, Sander JWAS. The treatment of epilepsy in developing countries: where do we go from here? Bull World Health Organ 2001; 79: 344–51.

541

Review

34 35 36 37

38

39

40

41

42

43

44

45 46 47

48

49 50

51

52 53

54 55

56

57

58 59 60 61

542

Singhal BS. Neurology in developing countries: a population perspective. Arch Neurol 1998; 55: 1019–21. Sridharan R, Murthy BM. Prevalence and pattern of epilepsy in India. Epilepsia 1999; 40: 631–36. Mannan MA. Epilepsy in Bangladesh. Neurol Asia 2004; 9: 18. Radhakrishnan K, Nayak SD, Kumar SP, et al. Profile of antiepileptic pharmacotherapy in a tertiary referral center in South India: a pharmacoepidemiologic and pharmacoeconomic study. Epilepsia 1999, 40: 179–85. Ng KK, Ng PW, Tsang KL, et al. Clinical characteristics of adult epilepsy patients in the 1997 Hong Kong epilepsy registry. Chin Med J (Engl) 2001; 114: 84–87. Lim SH. Seizures and epilepsy in the elderly: epidemiology and etiology of seizures and epilepsy in the elderly in Asia. Neurol Asia 2004; 9: 31–32. Sander JWAS, Hart YM, Johnson AL, et al. National general practice study of epilepsy: newly diagnosed epileptic seizures in general population. Lancet 1990; 336: 1267–71. Ding D, Wang W, Wu J, et al. Premature mortality in people with epilepsy in rural China: a prospective study. Lancet Neurol 2006; 5: 823–27. Kamgno J, Pion SDS, Boussinesq M. Demographic impact of epilepsy in Africa: result of a 10 year cohort study in a rural area of Cameroon. Epilepsia 2003; 44: 956–63. Tekle-Haimanot R, Forsgren L, Abebe M, et al. Clinical and electroencephalographic characteristics of epilepsy in rural Ethiopia: a community-based study. Epilepsy Res 1990; 7: 230–39. Wakamoto H, Nagao H, Hayashi M, et al. Long-term medical, educational, and social prognoses of childhood-onset epilepsy: a population-based study in a rural district of Japan. Brain Dev 2000; 22: 246–55. Tsai JJ. Mortality of epilepsy from national vital statistics and university epilepsy clinic in Taiwan. Epilepsia 2005; 46: 8–10. Chen RC, Chang YC, Chen TH, et al. Mortality in adult patients with epilepsy in Taiwan. Epileptic Disord 2005; 7: 215–19. Senanayake N, Peiris H. Mortality related to convulsive disorders in a developing country in Asia: trends over 20 years. Seizure 1995; 4: 273–77. Hui AC, Joynt GM, Li H, et al. Status epilepticus in Hong Kong Chinese: aetiology, outcome and predictors of death and morbidity. Seizure 2003; 12: 478–82. Wong V. West syndrome—The University of Hong Kong experience (1970–2000). Brain Dev 2001; 23: 609–15. Hauser WA, Rich SS, Annegers JF, et al. Seizure recurrence after a 1st unprovoked seizure: an extended follow-up. Neurology 1990; 40: 1163–70. Berg AT, Shinnar S. The risk of seizure recurrence following a first unprovoked seizure: a quantitative review. Neurology 1991; 41: 965–72. Boonluksiri P. Risk of recurrence following a first unprovoked seizure in Thai children. Neurol J Southeast Asia 2003; 8: 25–29. Boonluksiri P. Risk of seizure recurrence after antiepileptic drug withdrawal in Thai children with epilepsy. Neurol Asia 2006; 11: 25–29. Verma A, Misra S. Risk of seizure recurrence after antiepileptic drug withdrawal, an Indian study. Neurol Asia 2006; 11: 19–23. Muttaqin Z. Surgery for temporal lobe epilepsy in Semarang, Indonesia: the first 56 patients with follow up longer than 12 months. Neurol Asia 2006; 11: 31–36. Kwong KL, Chak WK, Wong SN, et al. Epidemiology of childhood epilepsy in a cohort of 309 Chinese children. Pediatr Neurol 2001; 24: 276–82. Thomas SV, Koshy S, Nair CR, et al. Frequent seizures and polytherapy can impair quality of life in persons with epilepsy. Neurol India 2005; 53: 46–50. Win MN. The EEG and epilepsy in Kelantan—a hospital/laboratorybased study. Med J Malaysia 1993; 48: 153–59. Manonmani V, Tan CT. A study of newly diagnosed epilepsy in Malaysia. Singapore Med J 1999; 40: 32–35. Li S, Wang X, Wang J, et al. Cerebrovascular disease and posttraumatic epilepsy. Neurol Asia 2004; 9 (suppl): 12–13. Hui AC, Kwan P. Epidemiology and management of epilepsy in Hong Kong: an overview. Seizure 2004; 13: 244–46.

62 63

64

65

66

67 68

69

70

71

72

73

74

75

76 77

78 79

80 81 82

83 84 85 86

87

88

Xiao B, Huang ZL, Zhang H, et al. Aetiology of epilepsy in surgically treated patients in China. Seizure 2004; 13: 322–27. Del Brutto OH, Santibanez R, Idrovo L, et al. Epilepsy and Neurocysticercosis in Atahualpa: a door-to-door survey in rural coastal Ecuador. Epilepsia 2005; 46: 583–87. Garcia HH, Del Brutto OH, and the Cysticercosis working group in Peru. Neurocysticercosis: updated concepts about an old disease. Lancet Neurol 2005; 4: 653–61. Rajshekhar V, Joshi DD, NQ Doanh, et al. Taenia solium taeniosis/ cysticercosis in Asia: epidemiology, impact and issues. Acta Trop 2003; 87: 53–60. Rajshekhar V. Epidemiology of Taenia solium taeniasis/cysticercosis in India and Nepal. Southeast Asian J Trop Med Public Health 2004; 35: 247–51. Ito A, Nakao M, Wandra T. Human taeniasis and cysticercosis in Asia. Lancet 2003; 362: 1918–20. Joshi DD, Maharjan M, Johnsen MV, et al. Taeniasis/cysticercosis situation in Nepal. Southeast Asian J Trop Med Public Health 2004; 35: 252–58. Chen YD, Xu LQ, Zhou XN. Distribution and disease burden of cysticercosis in China. Southeast Asian J Trop Med Public Health 2004; 35: 231–39. Willingham AL III, De NV, Doanh NQ, et al. Current status of cysticercosis in Vietnam. Southeast Asian J Trop Med Public Health 2003; 34 (suppl 1): S35–50. Kuruvilla A, Pandian JD, Radhakrishnan VV, et al. Neurocysticercosis: a clinical and radiological appraisal from Kerala State, South India. Singapore Med J 2001; 42: 297–303. Erhart A, Dorny P, Van De N, et al. Taenia solium cysticercosis in a village in northern Viet Nam: seroprevalence study using an ELISA for detecting circulating antigen. Trans R Soc Trop Med Hyg 2002; 96: 270–72. Theis JH, Goldsmith RS, Flisser A, et al. Detection by immunoblot assay of antibodies to Taenia solium cysticerci in sera from residents of rural communities and from epileptic patients in Bali, Indonesia. Southeast Asian J Trop Med Public Health 1994; 25: 464–68. Chung CK, Lee SK, Chi JG. Temporal lobe epilepsy caused by intrahippocampal calcified cysticercus. J Korean Med Sci 1998; 13: 445–48. Dorny P, Somers R, Cam-Thach D, et al. Cysticercosis in Cambodia, Lao PDR and Vietnam. Southeast Asian J Trop Med Public Health 2004; 35: 223–26. Veliath AJ, Ratnakar C, Thakur LC. Cysticercosis in South India. J Trop Med Hyg 1985; 88: 25–29. Murthy JM, Yangala R. Acute symptomatic seizures—incidence and etiological spectrum: a hospital-based study from south India. Seizure 1999; 8: 162–65. Strobel M, Veasna D, Saykham M, et al. Pleuro-pulmonary paragonimiasis. Med Mal Infect 2005; 35: 476–81. Tran DS, Nanthapone S, Odermatt P, et al. A village cluster of paragonimiasis in Vientiane province, Lao PDR. Southeast Asian J Trop Med Public Health 2004; 35: 323–26. Higashi K, Aoki H, Tatebayashi K, et al. Cerebral paragonimiasis. J Neurosurg 1971; 34: 115–27. Kaw GJL, Sitoh YY. Clinic in diagnostic imaging. Singapore Med J 2001; 42: 89–91. Choo JK, Suh BS, Lee HS, et al. Chronic cerebral paragonimiasis combined with aneurismal subarachnoid hemorrhage. Am J Trop Med Hyg 2003; 69: 466–69. WHO, UNICEF. Roll Back Malaria: World Malaria Report. Geneva: WHO, 2005. Wattanagoon Y, Srivilairit S, Looareesuwan S, et al. Convulsions in childhood malaria. Trans R Soc Trop Med Hyg 1994; 88: 426–28. Faiz MA, Rahman MR, Hossain MA, et al. Cerebral malaria—a study of 104 cases. Bangladesh Med Res Counc Bull 1998; 24: 35–42. Ngoungou EB, Dulac O, Poudiougou B, et al. Epilepsy as a consequence of cerebral malaria in area in which malaria is endemic in Mali, West Africa. Epilepsia 2006; 47: 873–79. Ngoungou EB, Koko J, Druet-Cabanac M, et al. Cerebral malaria and sequelar epilepsy: first matched case–control study in Gabon. Epilepsia 2006; 47: 2147–53. Solomon T, Dung NM, Kneen R, et al. Japanese encephalitis. J Neurol Neurosurg Psychiatry 2000; 68: 405–15.

http://neurology.thelancet.com Vol 6 June 2007

Review

89 90 91 92 93

94

95 96

97 98

99 100 101

102

103 104

105

106 107 108 109

110 111

112 113 114

115

116

117

Murthy JMK. Some problems and pitfalls in developing countries. Epilepsia 2003: 44 (suppl 1): 38–42. Misra UK, Kalita J. Seizures in Japanese encephalitis. J Neurol Sci 2001; 190: 57–60. Jain S, Padma MV, Puri A, et al. Twin birth and epilepsy: an expanded India study. Neurol J Southeast Asia 1999; 4: 19–23. Sharma K. Genetic epidemiology of epilepsy: a twin study. Neurol India 2005; 53: 93–98. Lu J, Chen Y, Pan H, et al. The gene encoding GABBR1 is not associated with childhood absence epilepsy in the Chinese Han population. Neurosci Lett 2003; 343: 151–54. Ren L, Jin L, Zhang B, et al. Lack of GABABR1 gene variation (G1465A) in a Chinese population with temporal lobe epilepsy. Seizure 2005; 14: 611–13. Chen YC, Zhang YH, Lu JJ, et al. Association of child absence epilepsy with T-STAR gene. Zhonghua Yi Xue Za Zhi 2003; 83: 1134–37. Chen Y, Lu J, Zhang Y, et al. T-type calcium channel gene alpha (1G) is not associated with childhood absence epilepsy in the Chinese Han population. Neurosci Lett. 2003; 341: 29–32. Nair RR, Thomas SV. Genetic liability to epilepsy in Kerala State, India. Epilepsy Res 2004; 62: 157–64. Zeng J, Hong Z, Huang MS, et al. A case-control study on the risk factors and other socio-psychological factors of epilepsy. Zhonghua Liu Xing Bing Xue Za Zhi 2003; 24: 116–18. Ramasundrum V, Tan CT. Consanguinity and risk of epilepsy. Neurol Asia 2004; 9: 10–11. Tan CT, Lim SH. Epilepsy in Southeast Asia. Neurol J Southeast Asia 1997; 2: 11–15. WHO, International Bureau for Epilepsy, International League Against Epilepsy. Atlas—epilepsy care in the world 2005. Geneva: WHO, 2005. World Health Organization. Neurology Atlas 2004: http://www.who. int/mental_health/neurology/neurogy_atlas_results6-8.pdf (accessed Feb 28, 2007). Seino M. Comprehensive epilepsy care: Contributions from paramedical professionals. Neurol J Southeast Asia 2001; 6: 1–5. Commission on Tropical Diseases of the International League Against Epilepsy. Availability and distribution of antiepileptic drugs in developing countries. Epilepsia 1985; 26: 117–21. Krishnan A, Sahariah SU, Kumar Kapoor S. Cost of epilepsy in patients attending a secondary-level hospital in India. Epilepsia 2004; 45: 289–91. Thomas SV, Sarma PS, Alexander M, et al. Economic burden of epilepsy in India: Epilepsia 2001; 42: 1052–60. Gunawan D. Epilepsy management with limited resources, Indonesian experience. Neurology Asia 2004; 9 (suppl 1): 16–17. Seneviratne U, Rajapakse P, Pathirana R, et al. Knowledge, attitude, and practice of epilepsy in rural Sri Lanka. Seizure 2002; 11: 40–43. Kariyawasam SH, Bandara N, Koralagama A, et al. Challenging epilepsy with antiepileptic pharmacotherapy in a tertiary teaching hospital in Sri Lanka. Neurol India 2004; 52: 233–37. Lillian L, Chun-Hing Y, Der-Jen Y, et al. Medication education for patients with epilepsy in Taiwan. Seizure 2003; 12: 473–77. Chen LC, Chen YF, Yang LL, et al. Drug utilization pattern of antiepileptic drugs and traditional Chinese medicines in a general hospital in Taiwan—a pharmaco-epidemiologic study. J Clin Pharm Ther 2000; 25: 125–29. Silpakit O, Silpakit C. A Thai version of a health-related quality of life instrument for epilepsy. Neurol J Southeast Asia 2003; 8: 103–07. Nassiri R, Stelmasiak Z. Pharmacotherapy of epilepsy. Neurol Neurochir Pol 2000; 34: 47–58. Mac TL, Le VT, Vu AN, et al. AEDs availability and professional practice in delivery outlets in a city centre in southern Vietnam. Epilepsia 2006; 47: 330–34. Wang WZ, Wu JZ, Ma GY, et al. Efficacy assessment of phenobarbital in epilepsy: a large community-based intervention trial in rural China. Lancet Neurol 2006; 5: 46–52. Mani KS, Rangan G, Srinivas HV, et al. Epilepsy control with phenobarbital or phenytoin in rural south India: the Yelandur study. Lancet 2001; 357: 1316–20. Meinardi H, Scott RA, Reis R, et al. ILAE Commission on the Developing World: the treatment gap in epilepsy: the current situation and ways forward. Epilepsia 2001; 42: 136–49.

http://neurology.thelancet.com Vol 6 June 2007

118 Anonymous. In the shadow of epilepsy. Lancet 1997; 349: 1851. 119 Shorvon SD, Farmer PJ. Epilepsy in developing countries: a review of epidemiological, sociocultural and treatment aspects. Epilepsia 1988: 29 (suppl 1): S36–45. 120 Gourie-Devi M, Satishchandra P, Gururaj G. Epilepsy control program in India: a district model. Epilepsia 2003; 44: 58–62. 121 Pal DK. Methodologic issues in assessing risk factors for epilepsy in an epidemiologic study in India. Neurology 1999; 53: 2058–63. 122 Mani KS. Epidemiology of epilepsy in Karnataka, India. Neurosci Today 1997; 1: 167–74. 123 Bharucha NE, Weiss MG, Bharucha EP, et al. Sociocultural aspects of epilepsy in developing countries: presented at the 22nd Epilepsy congress, Dublin, Ireland, July 1997. 124 Koul R, Razdan S, Motta A. Prevalence and pattern of epilepsy (Lath/ Mirgi/Laran) in rural Kashmir, India. Epilepsia 1988; 29: 116–22. 125 Bharucha NE, Bharucha EP, Bharucha AE, et al. Prevalence of epilepsy in the Parsi community of Bombay. Epilepsia 1988; 29: 111–15. 126 Rajbhandari KC: Epilepsy in Nepal. Can J Neurol Sci 2004; 31: 257–60. 127 ILAE commission report. A global survey on epilepsy surgery, 1980–1990. A report by the Commission on Neurosurgery of Epilepsy, International League Against Epilepsy. Epilepsia 1997; 38: 249–55. 128 Wieser HG, Silfvenius H. Overview: epilepsy surgery in developing countries. Epilepsia 2000; 41: 83–89. 129 Lee BI. Current status and future direction of epilepsy surgery in Asia. Neurol Asia 2004; 9: 47–48. 130 Panda S, Radhakrishnan K, Sarma PS. Mortality in surgically versus medically treated patients with medically refractory temporal lobe epilepsy. Neurol Asia 2004; 9: 129. 131 Pan APS, Lim SH. Public awareness, attitudes and understanding toward epilepsy among Singaporean Chinese. Neurol J Southeast Asia 2000; 5: 5–10. 132 Tsai JJ. Help-seeking behavior among patients with epilepsy. Epilepsia 1991; 32: 32. 133 Goh KJ, Ma WT, Ali Mohd M, et al. Case reports of covert use of Phenobarbital in patients taking Diankexing and Diankening, traditional herbal medicine for epilepsy. Neurol Asia 2004; 9: 55–57. 134 Lim KS, Tan LP, Lim KT, et al. Survey of public awareness, understanding and attitudes toward epilepsy among Chinese in Malaysia. Neurol J Southeast Asia 1999; 4: 31–36. 135 Ramasundrum V, Mohd Hussin ZA, Tan CT. Public awareness, attitudes and understanding towards epilepsy in Kelantan, Malaysia. Neurol J Southeast Asia 2000; 5: 55–60. 136 Win NN, Soe C. Public awareness, attitude and understanding toward epilepsy among Myanmar people. Neurol J Southeast Asia 2002; 7: 81–88. 137 Wong V, Chung B, Wong R. Pilot survey of public awareness, attitudes and understanding towards epilepsy in Hong Kong. Neurol Asia 2004; 9: 21–27. 138 Fong CY, Hung A. Public awareness, attitude, and understanding of epilepsy in Hong Kong Special Administrative Region, China. Epilepsia 2002; 43: 311–16. 139 Rambe AS, Sjahrir H. Awareness, attitudes and understanding towards epilepsy among school teachers in Medan, Indonesia. Neurol J Southeast Asia 2002; 7: 77–80. 140 Kim MK, Kim IK, Kim BC, et al. Positive trends of public attitudes toward epilepsy after public education campaign among rural Korean residents. J Korean Med Sci 2003; 18: 248–54. 141 Chung MY, Chang YC, Lai CW. Survey of public awareness, understanding and attitudes towards epilepsy in Taiwan. Epilepsia 1995; 36: 488–93. 142 Kankirawatana P. Epilepsy awareness among schoolteachers in Thailand. Epilepsia 1999; 40: 497–501. 143 Tuan NA, Tomson T, Cuong LQ, et al. Public awareness understanding and attitudes towards epilepsy in Bavi, Vietnam: first Report from the APIBAVI study. Epilepsia 2005; 46: 192. 144 Cuong LQ, Thien DD, Jallon P. Survey of public awareness, attitudes and understanding toward epilepsy in Nhan Chinh, Hanoi, Vietnam, in 2003. Epilepsy Behav 2006; 8: 176–80. 145 Ab Rahman AF. Awareness and knowledge of epilepsy among students in a Malaysian university. Seizure 2005; 14: 593–96.

543