Review Article

Epidemiology of neurological disorders in India: Review of background, prevalence and incidence of epilepsy, stroke, Parkinson’s disease and tremors M. Gourie-Devi Department of Neurology, Institute of Human Behaviour and Allied Sciences and Senior Consultant in Neurology, Sir Ganga Ram Hospital, New Delhi, India

Abstract

Address for correspondence: Dr. M.Gourie-Devi, Emeritus Professor of Neurology, Institute of Human Behaviour and Allied Sciences (IHBAS), New Delhi - 110 096, India. E-mail: [email protected] Received : 16-10-2014 Review completed : 29-12-2014 Accepted : 05-12-2014

Growth and development of neuroepidemiology in India during the last four decades has been documented highlighting the historical milestones. The prevalence rates of the spectrum of neurological disorders from different regions of the country ranged from 967–4,070 with a mean of 2394 per 100000 population, providing a rough estimate of over 30 million people with neurological disorders (excluding neuroinfections and traumatic injuries). Prevalence and incidence rates of common disorders including epilepsy, stroke, Parkinson’s disease and tremors determined through population‑based surveys show considerable variation across different regions of the country. The need for a standardized screening questionnaire, uniform methodology for case ascertainment and diagnosis is an essential requiste for generating robust national data on neurological disorders. Higher rates of prevalence of neurological disorders in rural areas, 6–8 million people with epilepsy and high case fatality rates of stroke (27–42%) call for urgent strategies to establish outreach neurology services to cater to remote and rural areas, develop National Epilepsy Control Program and establish stroke units at different levels of health care pyramid. Key words: Epilepsy, incidence, India, neuroepidemiology, Parkinson’s disease,

prevalence, screening questionnaire, stroke, tremors

Introduction Developing countries, including India are passing through a phase of epidemiological transition with increasing burden of non‑communicable diseases (NCD) consequent to transformation of scenario with Access this article online Quick Response Code:

Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.149365

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improvement of health care services in preventive and promotive domains. Among the NCDs, neurological disorders form a significant proportion of global burden of disease.[1,2] Two important documents published by World Health Organization (WHO) and World Federation of Neurology bring to forefront the public health challenges posed in dealing with neurological disorders particularly in the developing countries with limited resources.[3,4] In this scenario, it is crucial to determine through neuroepidemiological approach the magnitude and pattern of neurological disorders in India to facilitate planning and prioritising health needs at the local, regional and national levels of health care delivery system with necessary human resources, development of infrastructure, to provide accessible and Neurology India | Nov-Dec 2014 | Vol 62 | Issue 6

Gourie-Devi: Epidemiology of Neurological disorders in India

affordable medical care with allocation of requisite funds to fulfill these objectives. The data from epidemiological surveys in developed countries cannot be extrapolated to India in view of social, cultural and ethnic variations. Hospital‑based data although critical for management, does not adequately reflect the burden of the disease in the community or the complex issues influencing the natural history. In India, as in other developing countries, there is a paucity of trained neurologists necessitating ground plans and policies appropriate to the socioeconomic and cultural background for conducting neuroepidemiological studies. This review focuses on the growth and development of the discipline of neuroepidemiology in India, methodological issues encountered and the strategies developed to address them, analysis of data on prevalence and pattern of neurological disorders and epidemiology of selected disorders including epilepsy, stroke, Parkinson’s disease and tremors. Only the publications on population based studies have been included in this review. Earlier reviews by the author had addressed some of the issues.[5‑7]

Neuroepidemiology in India Background and methodological issues In 1960s neuroepidemiological studies in India were restricted to single disorders such as epilepsy [8] and stroke[9] and it was only two decades later that community‑based studies for a spectrum of neurological disorders were initiated in Bangalore, Bombay, Delhi and Kashmir which provided the foundation and frame work for the emergence of the discipline of neuroepidemiology in India. [10‑14] To overcome the major constraint of few neurologists in developing countries and also to optimize the time spent by the neurologist, Schoenberg recommended strategy of two‑stage methodology; the first stage comprised of administration of questionnaire of symptoms and simple clinical examination by health care personnel and second stage examination by neurologist of individuals identified as having neurological disorder. [15] The Neuroscience program of World Health Organization (WHO) developed the screening questionnaire “WHO protocol” to detect individuals with epilepsy, cerebrovascular disorders, peripheral neuropathy, extrapyramidal disorders (including Parkinson’s disease) migraine and intracranial neoplasms and was pilot tested in Nigeria.[16,17] Gourie‑Devi et al., observed that in the Indian context clinical examination by non‑medical professionals was not acceptable to the people, hence only the questionnaire was administered by trained field workers and neurological examination of ‘screened positive’ subjects was done by neurologist.[11] They further modified and expanded the WHO screening questionnaire to include a wider Neurology India | Nov-Dec 2014 | Vol 62 | Issue 6

spectrum of neurological disorders and using this instrument NEPSIG (Neuro Epidemiological Study In Gowribidanur) through a two‑stage method of survey, the feasibility and logistics in identifying neurological disorders in a population of 57660 comprising of urban and rural population of Gowribidanur town and the surrounding villages, was demonstrated.[10,11] Arguably all these pioneering efforts galvanized and sensitized the neurologists in the country to the discipline of neuroepidemiology and Indian Council of Medical Research  (ICMR) identified neuroepidemiology as a thrust area of research and has been providing grants in a task force mode of support. Certain important concerns were the problems in comparing the data emanating from different regions of the country and the pitfalls identified were small sample size not representative of the population, lack of uniformity in case finding, case ascertainment, training of field workers, standardized screening questionnaires and definitions of diseases. These methodological issues have been dealt with at length through a format of questions and answers for conducting neuroepidemiological surveys in a developing country.[18] To overcome these lacunae a comprehensive Manual was developed at the National Institute of Mental Health and Neurosciences (NIMHANS) with support from ICMR, with focus on logistics and operational aspects of conducting neuroepidemiological survey in a developing country including selection of study population, structured training program of field workers, screening questionnaires for adults and children and definition of diseases.[19,20] These questionnaires were validated in a pilot study by Gourie‑Devi et al., and later used in the major Bangalore Urban‑Rural Neuroepidemiological  (BURN) survey. [21,22] These standardized questionnaires developed by NIMHANS, with minor modifications, based on requirements of the survey and local situation, have been used in neuroepidemiological studies in different regions of the country.[23‑25] It is heartening that the concerns articulated by the author in late 1980s “Can India afford neuroepidemiology” have been firmly dispelled.[26] Prevalence and pattern of neurological disorders Prevalence of neurological disorders was determined through house to house surveys in six studies from different regions of the country comprising of rural population in all studies and urban population in two of them. The crude prevalence rate varied from 967–4,070 per 100000 population with an average of 2394 per 100000 population [Table 1]. [10,13,14,22,27,28] Based on this data it is estimated that for the current population of 1.27 billion, approximately 30 million people suffer from neurological disorders in India. This is an underestimate of the burden since neuroinfections, traumatic injuries and neoplasms and metabolic disorders have not been included in the 589

Gourie-Devi: Epidemiology of Neurological disorders in India

Table 1: Prevalence of neurological disorders (per 100,000 population)

Author

Region

Place

Type of population

Gourie‑Devi[10]

Year of survey 1982-1983

South

Gouribidanur

Kapoor[13] Razdan[14] Das[27] Saha[28] Gourie‑Devi[22]

1986 1986 1989-1990 1992-1993 1994-1995

North North East East South

Delhi Kashmir Malda South 24 parganas Bangalore

Total Urban Rural Rural Rural Rural Rural Total Urban Rural

surveys. The low prevalence rate reported in Kashmir study may be due to non inclusion of headache which is the most common disorder in the community. The variation in prevalence rates across regions can be attributed to differences in case identification, definition of the diseases, non inclusion of some neurological disorders and also due to certain locally prevalent disorders. Neurological disorders affect all age-groups, and age‑specific prevalence rates show increasing prevalence till fourth decade followed by decline to seventh decade. In Bangalore, however, increasing rates to seventh decade were observed indicating that the geriatric population suffers from considerable burden of neurological disorders (age specific prevalence rates per 100000; for age 60 years: 5012).[22] The neurological disorders were more common in rural compared to the urban population with a ratio of 1.9:1 and the prevalence rate was higher in females than males in Bangalore and Malda.[22,27] The prevalence rates in India are comparable to those in Nigeria,[29] and Ethopia,[30] but lower than in Sicily[31] and Tunisia.[32] A wide spectrum of neurological disorders were detected in these surveys including common disorders such as epilepsy, febrile convulsions, headache, cerebrovascular disorders, tremors and mental retardation and others with lower prevalence comprising of Parkinson’s disease and peripheral neuropathy [Table 2].[10,13,14,22,27,28] Most of the disorders had higher prevalence in rural population compared to urban population. Since there were only two studies of urban population in South India, more surveys of urban population from other regions of the country are necessary to confirm the observation. Poliomyelitis with residual deficit were detected in all the surveys reflecting that there is a considerable pool of survivors with poliomyelitis with public health concerns and need for physiotherapy and rehabilitation services. Major outbreaks of Japanese encephalitis in state of Karnataka accounted for the prevalence of postencephalitic sequelae in Gowribidanur and Bangalore, demonstrating the regional health problems.[10,22] It is noteworthy that epilepsy, headache, febrile convulsions and cerebrovascular 590

Population size

Crude rate

57660 17734 39926 48798 63645 37286 20842 102557 51502 51055

1382 1252 1425 3487 967 2856 2907 3126 2190 4070

disorder together constituted 80% of all neurological disorders in the community. This data obviously has implication in developing strategy for health services with focus on neurology services for these disorders at the primary and secondary level of health care.

Epidemiology of Individual Neurologic Disorders Epidemiology of epilepsy Prevalence of epilepsy The global burden of disease study of 2000 provides an estimate of 50 million people with epilepsy and more than 80% of them in developing countries.[33] In India Epilepsy was included in mental morbidity surveys during 1960s and 1970s which were conducted by psychiatrists in different regions of the country with research grant from ICMR [Table 3].[34‑37] The crude prevalence rate varied from 2.2–10.4 per 1000 population. The concerns were the small sample size in all, except one, of these studies and the definition of epilepsy was not included. It is also not clear if only ‘active epilepsy’ was included and whether the questionnaire was formulated to detect generalized, focal and complex partial seizures. In this context it is pertinent to acknowledge the commendable contribution of psychiatrists for including epilepsy to provide primary care under the National Mental Health Program (NMHP) initiated in 1982 and now further expanded to include more than 200 districts by Government of India.[38,39] A significant mile stone was the multicentre “Collaborative epidemiological study of epilepsy in India”, PL 480 funded project of ICMR, which was initiated in 1969 and included, Bangalore, Bombay, Calcutta, New Delhi and Madras. Although this was hospital based, the study provides valuable data on clinical parameters, electroencephalographic, and psychosocial aspects and follows up over 4 years.[40] From 1968–2008, fourteen surveys have been done in different regions of the country to determine the prevalence of epilepsy [Table 4]; four of them comprising both urban and rural population,[8,10,22,46] seven only rural population[13,25,27,28,42‑44] and three only urban population [23,41,45] were included. Most of the studies are from North, South and East India, one Neurology India | Nov-Dec 2014 | Vol 62 | Issue 6

Gourie-Devi: Epidemiology of Neurological disorders in India

Table 2: Prevalence rates and pattern of major neurological disorders (per 100000 population)*

Place Author

Gowribidanur Gourie‑Devi[10]

Population All disorders Epilepsy Febrile convulsions Headache Stroke Mental retardation Parkinson’s disease Tremors Poliomyelitis Peripheral nerve disorders Postencephalitic sequelae

Total 57660 1382 463 64 173 52 111 7 23 99 52 23

Urban 17734 1252 248 79 394 45 101 6 17 96 68 ‑

Delhi Kapoor,[13]

Kuthar valley Razdan[14]

Malda Das[27]

Saha[28]

Rural 48798 3487 402 NA 1695 88 109 NA NA 496 NA NA

Rural 63645 967 247 NA NA 43 209 14 17 218 29 NA

Rural 37286 2856 306 54 1858 126 43 16 8 56 75 NA

Rural 20842 2907 360 NA 873 168 206 53 96 NA 80 NA

Rural 39926 1425 558 57 75 55 115 8 25 100 45 33

Bangalore Gourie‑Devi[22] Urban 51502 2190 577 198 981 136 107 14 56 52 50 21

Rural 51055 4070 1193 462 1259 165 178 41 378 168 84 26

Total 102557 3126 883 330 1119 150 142 33 215 110 67 36

*Crude prevalence rates; NA ‑ Not available

Table 3: Prevalence rates of epilepsy based on mental morbidity surveys from 1962 to 1976 (per 1000 population)

Author

Year of Region survey

Surya[34] Dube[35] Sethi[36] Nandi[37]

1962 1962 1962 1975

South india North india North india East india

Place

Type of population

Population Crude Comment size rate

Pondicherry Agra Lucknow West Bengal

Urban Urban and rural Rural Rural

2730 29468 2691 3718

2.2 2.24 2.2 4.6

Mental morbidity survey; house to house; questionnaire Mental morbidity survey; house to house; questionnaire Mental morbidity survey; questionnaire Mental morbidity survey; questionnaire

Table 4: Prevalence rates of epilepsy based on Neuroepidemiological surveys conducted from 1968 to 2008 (per 1000 population)

Author

Year of Region survey

Place state

Type of population Total Urban Rural Total Semiurban Rural Urban‑Parsis

45778 16135 29643 57660 17734 39926 14010

9.0 7.5 9.8 4.6 2.5 5.6 4.7

Special group‑parsis WHO Questionnaire

Rural

63645

2.5

WHO questionnaire

Rural

48798

4.0

WHO questionnaire

Rural

37286

3.0

WHO questionnaire

Rural

64963

Rural Rural Total Urban Rural Semiurban Urban

20842 8595 102557 51502 51055 238102 52377

7.6 Ep‑4.6; HWE‑3.0 3.6 5.6 8.8 5.8 11.9 4.9 5.6

Total Urban Rural Rural

50617 12512 38105 14086

3.8 6.2 3.0 6.5

Mathai[8]

1968‑1969 South india

Vellore Tamil Nadu

Gourie‑ Devi[10]

1982‑1983 South india

Gowribidanur Karnataka

Bharucha[41]

1985

West india

Koul[42]

1986

North india

Kapoor[13]

1986

North india

Das[27]

1989‑1990 East india

Mani[43]

1990‑1991 South India

Saha[28] Kokkat[44] Gourie‑devi[22]

1992‑1993 East india 1993 North india 1994‑1995 South india

Radhakrishnan[45] 1996‑1997 South india Das[23] 2003‑2004 East india Rajsekhar[46]

2003‑2004 South India

Goel[25]

2007‑2008 North india

Bombay Maharashtra Kuthar valley kashmir Ballabgarh Haryana Malda West Bengal Yelandur Karnataka South 24 parganas Haryana Bangalore Karnataka Kerala Kolkata West bengal Vellore Tamil nadu Dehradun

Population Crude Comment size rate Questionnaire

NEPSIG protocol

ICEBERG screening instrument‑modified

WHO questionnaire Questionnaire NIMHANS questionnaire

WHO questionnaire‑modified NIMHANS questionnaire WHO questionnaire

NIMHANS questionnaire

HWE - Hot water epilepsy, ICEBERG - International community based epilepsy research group, NEPSIG - Neuroepidemiological study in gowribidanur, NIMHANS - National institute of mental health and neurosciences, WHO - World health organization

report from West India but none from vast regions of Central and North‑East regions. In the earlier Neurology India | Nov-Dec 2014 | Vol 62 | Issue 6

studies the WHO questionnaire and in the last decade NIMHANS questionnaire has been used for survey. 591

Gourie-Devi: Epidemiology of Neurological disorders in India

The mean crude prevalence rate was 5.7 per 1000 population (range 2.5–11.9) for the entire surveyed population; 5.3 (2.5–7.5) in urban population and slightly higher rate of 5.8 (2.5–11.9) in rural population. There was no significant difference in rates between men and women. The peak prevalence rates were in the second and third decades and a second peak in the elderly due to occurrence of seizures due to stroke. In a meta‑analysis published 15 years ago, Sridharan and Murthy reported similar overall prevalence of 5.3/1000; in urban areas it was 5.1 and in rural area was 5.5/1000.[47] The slightly higher rates currently observed may be due to the recent surveys reporting higher prevalence in rural area attributed to neurocysticercosis (NCC) contributing to a significant proportion of seizures in the community.[25,46] In population based surveys only two studies focused on NCC contributing to prevalence of epilepsy. In the study from Vellore, South India[46] 34% of patients with active epilepsy were confirmed to have NCC by CT scan and enzyme‑linked immunotransfer blot (EITB) and from Dehradun, North India, 35% had NCC based only on CT scan.[25] It is interesting to note that the overall prevalence rate of epilepsy has almost remained constant over the last two decades. Based on the prevalence data it is estimated that there are 6 to 8 million people with epilepsy in India. The crude prevalence rate of epilepsy in other developing countries has also a wide variation: 4.4 and 4.6 in China,[48,49] 7.0 in Turkey,[50] 9.0 in Srilanka[51] and 9.9 in Pakistan[52] per 1000 population. In both Pakistan and Turkey the prevalence was much higher in rural compared to urban population (Pakistan‑14.8 in rural and 7.4 in urban; Turkey‑8.8 in rural and 4.5 in urban).[50] Similarly in Tanzania the rate was 10.2/1000 in the rural population and an interesting observation was that the rates varied widely over a range of 5.7–37.1 among different villages in the sampled area.[53] Incidence of epilepsy The crude annual incidence rates per 100000, in three studies which determined the incidence of epilepsy through community‑based studies were 49.3 for rural population of South India,[43] 42.1 for rural population of West Bengal [54] and 25.2 for urban population of Kolkata.[55] The rates in India are comparable to developed countries with the reported rates varying from 28.9–53.1[56] and lower than in other developing countries at 69.4 in Benin,[57] 73.0 in Tanzania,[53] 77.0 in Kenya,[58] and 92.0 in Honduras,[59] per 100000 population. These variations across countries and regions may be due to locally prevalent risk factors such as infections (NCC) and the level of primary health care for head injuries, obstetric, perinatal and pediatric services, in preventing birth trauma and prompt management of infections in neonates and infancy. 592

Treatment gap in epilepsy Proportion of patients with active epilepsy not receiving treatment in the developing countries is very high varying from 80–94%.[60] In India treatment gap (TG) was determined through prevalence studies and the TG was lowest at 29% among Parsis in Bombay,[41] 38% in Kerala,[45] 50% in Bangalore, Karnataka,[61] 65% in West Bengal,[28] 75% in Kashmir,[42] and 78% in Yelandur, Karnataka.[43] The TG was lower in urban population compared to rural areas perhaps due to better awareness about the disorder and availability of health services in closer proximity. In the systematic review of 74 population based studies of prevalence of epilepsy from 38 countries, the treatment gap varied widely among countries; in low‑income countries it was 75–95%, over 50% in lower middle and upper middle‑income countries and less than 10% in high‑income countries.[62] The TG also varied considerably within countries and was higher in rural areas. Epidemiology of cerebrovascular disorders Cerebrovascular disorders (CVD) are increasing in prevalence and incidence in India due to rapid escalation of risk factors including hypertension diabetes mellitus, smoking and obesity affecting considerable proportion of adult population. Global Burden of Disease study shows that of the 9.4 million deaths in India, 619,000 were due to stroke and Disability Adjusted Life Years (DALYs) lost were 28.5 million highlighting the fact that CVD leads to considerable mortality and morbidity.[63] Therefore there is likely to be a major crisis in India unless national measures to prevent/control risk factors of CVD are instituted and adequate services are put in place for the management and rehabilitation of stroke.[64] Another issue of concern is that 20–30% of strokes occur in people younger than 45 years and is more frequently seen in India compared to the west.[64] Prevalence of stroke Although there are numerous hospital based studies of stroke in India only a few population‑based surveys have been done to determine the prevalence of stroke and the very first survey on a large urban and rural population was conducted by Abraham et al., in late 1960’s in Vellore.[9] Since most studies used WHO definition of stroke, only completed stroke were included in the surveys and transient ischemic attacks were excluded underestimating the actual burden of cerebrovascular disorders. During the last four decades community‑based studies in different regions of the country showed crude prevalence rates of completed strokes varying from 52–472 per 100000 persons, with the exception of a very high rate of 842 among Parsis, a distinct ethnic community [Table 5].[9,10,13,14,22,27,65,67,69,70] (The study from Rhotak was a part of WHO Collaborative study of 17 centers in developing and developed countries which Neurology India | Nov-Dec 2014 | Vol 62 | Issue 6

Gourie-Devi: Epidemiology of Neurological disorders in India

was latter extended to include a larger sample).[65,66] The mean CPR in urban population (excluding the prevalence rate in Parsis) was 153/100000 (range 44–472) and in rural region was 93/100000 (range 31–165). Higher prevalence in urban compared to rural regions has been reported in South Asia.[71] To a certain extent this wide variation can be explained by differences in methodology, age structure of population, however there could be genuine regional differences due to the degree and nature of risk factors. It is noteworthy that surveys conducted in two different areas in Kolkata showed a remarkable difference in crude prevalence rate; 147 in Southern part[69] and 487 (per 100000 from Central part[23] re‑emphasizing the need to explore further to identify the risk factors by case control studies. Even allowing for these variations, a matter of concern is that in the last two decades there is a significant increase in prevalence rate of stroke. Meta‑analysis of studies conducted from 1980–2001 gave a weighted average of prevalence rates of 154 per 100000 population.[72] Pooled analysis through forecasting method has shown that the estimated prevalence rates of stroke for the years 2000 and 2015 are 108 and 133 per 100,00 population, respectively, indicating a dramatic rise in prevalence of stroke over a period of 15 years, and by 2015 it is estimated that there will be 1,667,372 cases of stroke in India.[73] The prevalence rates are similar to other developing countries.[74] Age‑specific prevalence rates increased with the maximum prevalence rates in the 6th and 7th decades in most of the surveys.[68] The crude prevalence and age adjusted rates of stroke in rural Kashmir were high, almost double, in males (187 and 334/100000) compared to women (94 and 175/100000);[68] higher rate in men was also reported in Parsis.[67] In rural population of Eastern India the prevalence rate was equal among men and women.[28] In contrast, in Kolkota age-adjusted

prevalence rate was three times higher in women compared to men (men‑196 and women 564 per 100000 population which was attributed it to poor control of hypertension in women.[69] Incidence of stroke The overall annual incidence rates are available only from few regions in the country; the rates per 100000 population varied from 13 in Vellore[9] 33 in Rohtak[65] to 36/100000 in Kolkata.[69] The age adjusted rate per 100000 persons was 105 in Kolkata,[69] 135 in Trivandrum (based on Trivandrum stroke registry),[75] and 152 for Mumbai (based on “Mumbai Stroke Registry)[76] which are similar to incidence rates/100000 of China (in three cities 76 to 150/100000),[77] and also as in developed countries including Perth (160), South London (130/100000). [78] In view of the problems of determining the actual burden of strokes in developing countries, particularly in view of rising trend in low‑income and middle‑income countries,[79] stepwise approach has been proposed by WHO to facilitate standardized approach to data collection and surveillance.[80,81] The strategy essentially consists of three steps: Outcome of stroke patients in hospital, fatal events in the community and non‑fatal events in the community and it is envisaged that this approach will provide the framework for creation of registries.[80‑82] A multicentre study “Indian Collaborative Acute Stroke Study (ICASS)” based on step approach was initiated in seven cities and this experience has led to concept of establishing registries.[64,75,83,84] Currently feasibility studies are underway for urban and rural registries under the aegis of ICMR with the goal to develop National stroke registry. Risk factors for stroke In population based case control studies hypertension was observed to be the most important risk factor

Table 5: Prevalence of stroke in india: Rate per 100000 population

Author

Year of survey

Place

Population size

Abraham[9]

1968-1069

Vellore

258576

Bansal[65,66]

1974

Rohtak

130211 79046 51165 57660 17734 39926 14010 48798 63645 37286 102557 51502 51055 50291 52377

Gourie‑ Devi[10]

1982-1983

Gowribidanur Karnataka

Bharucha[67] Kapoor[13] Razdan[68] Das[27] Gourie‑Devi[22]

1985 1986 1986 1989-1990 1994-1995

Bombay Ballabgarh Kuthar valley Malda Bangalore

Banerjee[69] Das[70]

1998-1999 2003-2004

Kolkota Kolkata

Neurology India | Nov-Dec 2014 | Vol 62 | Issue 6

Type of population Total Urban Rural Total Urban Rural Total Urban Rural Urban‑parsis Rural Rural Rural Total Urban Rural Urban Urban

Crude prevalence rate 57 63 31 44 44 45 45 55 52 842 88 143 126 150 136 165 147 472 593

Gourie-Devi: Epidemiology of Neurological disorders in India

in urban population in Kolkata and among Parsis in Mumbai, however diabetes mellitus was also a significant risk factor among Parsis although not significant in Kolkata.[69,85] In another community based survey in rural Kashmir, 58% were detected to have hypertension.[68] Surveys in different regions of India have shown that hypertension is widely prevalent in India affecting 25–40% of adults in urban and 12–17% in rural areas.[86] Mortality in stroke Deaths due to stroke account for a significant proportion of all deaths in the community in India is evident from the elegant study by Joshi et al., who determined mortality due to chronic diseases through verbal autopsy covering a population of 180162 in 45 villages in East and West Godavari in Andhra Pradesh during the period from 2003–2004.[87] Stroke was the cause of death in 13% of the total 1354 deaths and was comparable to ischemic heart disease (14%). The case fatality was 27% in Trivandrum, Kerala,[75] 30%in Mumbai,[76] and 42% in Kolkata[70,88] by 28–30 days, following stroke and a matter of serious concern is early deaths of 20% in Kerala[75] and 33% in Kolkata[88] in the first 7–10 days. The lower case fatality rate in Kerala reflects better health care than in Kolkata. In the recent long term study in Kolkata over 7 years, the case fatality was 59% at 5 years and 61% at 7 years.[88] In view of the increasing burden of cardiovascular diseases and stroke and high prevalence of risk factors of hypertension and diabetes,[89] there is an urgent need to initiate preventive programs.[76,90] It is a good augury that Government of India had launched the pilot phase of “National program for prevention and control of diabetes, cardiovascular diseases and stroke” in 2008[91] in 100 districts and it is planned to expand the program to all districts. With effective implementation of the program it is expected that there would be a tangible reduction in stroke incidence and prevalence. Movement disorders Parkinson’s disease Among the movement disorders, epidemiology of Parkinson’s disease has been better studied than other disorders in India. Population based surveys (excluding Parsis) have shown a crude prevalence rate (CPR) of Parkinson’s disease varying from 6–53/100000 [Table 6].[14,19,22,26‑28,93] In the survey in Bangalore the rate was three times higher in rural compared to urban region (Rural 41 and urban 14/100000.[22] The CPR of 328 and age‑adjusted rate of 192/100000 population in the Parsis is considerably higher than in the developing countries including China, Nigeria and non‑Parsi community of India and is even more than developed countries.[92] Parsis form an ethnic 594

community, distinct from the rest of population in India, therefore this data cannot be extrapolated to determine the estimates in the general population. Age‑specific prevalence rates for PD increase with advancing age[14,26,28,92] and are as high as 247/100000 above age of 60.[14] In most studies sex‑specific prevalence rates were higher in men than in women with the exception of studies from Eastern India which reported that women were more commonly affected than men and this was attributed to longer life expectancy in women.[23,28] Incidence and mortality rates of PD are available only from one recent community based study; average age‑adjusted incidence rate for the period 2003–2007 was 5.7/100000 per year and the average annual mortality rate during the same period was 2.9/100000 per year.[93] The incidence rates were much higher in developed countries including United  Kingdom [94]  (MacDonald‑2000) Japan[95] (Harada 1983) and Rochester[96]  (Rajput 1984) and lower in China[97,98] (Li 1985B, Wang 1996) compared to India. The overall prevalence and incidence of Parkinson’s disease in India is low. The prevalence studies had used WHO questionnaire with modifications or NIMHANS questionnaire, which were designed to detect a spectrum of neurological disorders. It is possible that screening questionnaire specifically focused to elicit more detailed information of the symptoms of PD would provide more reliable data. Anderson et al.,[99] elaborated on the issues related to case ascertainment in prevalence surveys of Parkinson’s disease in different countries and emphasized the importance of validation and Muthane et al.,[100] reiterating these problems focused on specific concerns in conducting prevalence studies in India. Sarangmath et al.,[101] validated Parkinson’s disease screening questionnaire suited to Indian conditions which could be administered by nonmedical persons and since the sensitivity and specificity were high the authors suggested that it can be effectively used in developing countries for population based surveys. In future using this questionnaire and with uniform methodology if community surveys are conducted in the country, it will be possible to generate comparable data across different regions. In the elderly homes in Bangalore prevalence of PD was three times higher in Indians compared to Anglo‑Indians (mixed Indian and British ancestry) suggesting genetic background to the disorder since both the groups were from shared environment.[102] In contrast although the prevalence of PD in Indians living in India is low, community based survey in Singapore showed interesting observation of age‑adjusted prevalence rates in Indians (0.28%), Malay (0.29%) and Chinese (0.33%), which were comparable to that of Western countries.[103] Similarly Chinese in Taiwan had a higher incidence rate than those in mainland China.[97,98,104] These data Neurology India | Nov-Dec 2014 | Vol 62 | Issue 6

Gourie-Devi: Epidemiology of Neurological disorders in India

Table 6: Prevalence of Parkinson’s disease in India: Rate per 100000 population

Author

Year of survey Place

Gourie‑ Devi[10]

1982-1983

Gowribidanur Karnataka

Bharucha[92] Razdan[14] Das[27] Saha et al.[28]

1985 1986 1989-1990 1992-1993

Gourie‑Devi[22]

1994-1995

Bombay Kuthar valley Malda South 24 parganas Bangalore

Das[26] Das[93]

2003-2004 2003-2007

Kolkata Kolkata

Type of population Population size Crude prevalence rate Age‑adjusted rate Total Semiurban Rural Urban‑parsis Rural Rural Rural

57660 17734 39926 14010 63645 37286 20842

7 6 8 328 14 16 53

Total Urban Rural Urban Urban

102557 51502 51055 52377 100802

33 14 41 46 41

suggest that environmental factors may be of greater relevance than genetic factors in the pathogenesis of Parkinson’s disease. With this conflicting evidences it becomes clear that there is a need to carry out in‑depth studies to analyze the relative contribution of environmental and genetic factors to the development of the disorder. Temporal trends in prevalence of PD is best illustrated by low prevalence rate of 57/100000 in China reported in early 1990s[105] and recently with improved methodology and survey of large population showed a prevalence rate of 1.7% in the age‐group of 65 years and above[106] comparable to Rotterdam and seven European studies.[107] Cognizance of temporal trends in China has to be taken since a similar situation may arise in India which would demand detailed assessment of factors such as life expectancy, survival, treatment options and changing environmental factors. The low prevalence of PD in India (with the exception of Parsi population) compared to the Western countries is at variance with the interesting observations made through a meticulous study by Muthane et al.,[108] that normal human brains in India have 40% lower number of melonized neurons in substantia nigra compared to brains in United  Kingdom. However there was no age‑related progressive loss of dopaminergic neurons as is expected.[109] Although there are fewer number of pigmented neurons the dopamine produced was comparable to the levels observed in the West.[108] These observations and possibly some protective factors, account for the low prevalence of PD in India.[108] Undiagnosed PD in the elderly is a problematic issue in many countries and the patients therefore do not have the benefit of treatment and necessary health care services. In old age homes in Bangalore, PD was diagnosed for the first time in17.8% of 612 residents highlighting the fact of poor awareness about the disorder.[110] A population based survey in China showed that 48% of PD cases were undiagnosed and were detected only during the survey.[106] Neurology India | Nov-Dec 2014 | Vol 62 | Issue 6

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Determination of risk factors in Parkinson’s disease is difficult in the absence of a biological marker, its occurrence in the elderly and relative infrequency. Therefore it is not surprising that there are only three studies from India, two were hospital based in Delhi[111] and Eastern India,[112] and one population‑based study in Kolkata.[93] Family history of PD and past history of depression were associated with increased risk in studies at Delhi and Eastern India. The additional risk factors in the Delhi study were male gender and well water drinking while in Eastern India exposure to pesticides, other toxins and rural living. In Kolkata hypertension was a risk factor and interestingly in all the three studies tobacco smoking or chewing had protective effect. Almost similar observations were made in a case‑control study in China with positive family history, living near rubber plants, drinking river‑water being associated with an increased risk and drinking well water, living in small cities and drinking liquor with decreased risk of developing PD.[113] Tremors Essential tremors (ET) were the commonest among all movement disorders with overall prevalence rates varying over a wide range of 8–395/100000 [Table 2, Das et al][10,13,14,24,27,28,114] The rural population of Malda, West Bengal[27] had the lowest prevalence rate while the highest was in urban population of Kolkata and above 40 years it was 910/100000.[114] The crude prevalence rate for the Parsis was exceptionally high at 1663/100000 and age‑specific prevalence rates showed increase with age beyond 40 years at 2763/100000.[115] Methodological issues particularly the questionnaire and definition might have contributed to some extent to the variation, but it would be worth‑while to conduct well planned studies to identify environmental factors and neurobiological and genetic basis of tremors in the context of the local population. In other developing countries the population based prevalence rates are similar to the rates in India: for China‑11,[97] Tanzania‑41,[116] and 237/100000 for Singapore.[117] 595

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Future Prospects This review makes it abundantly clear that there are lacunae in conducting population based surveys in India. Standardized questionnaires, uniform methods of case ascertainment, and diagnostic criteria will facilitate collection of robust national data of prevalence and incidence of neurological disorders. If regional differences were to be observed then search for etiological basis will move forwards the understanding of the disorder. Neuroepidemiological studies have been conducted from Northern, Southern, Eastern and Western regions of the country but there are no reports from Central India and North Eastern regions. Attempts have to be made to generate data in these regions. Focus should be on development of cohorts in the community which will help in planning interventional studies and also facilitate studies on natural history of neurological disorders. The estimated burden of neurological disorders (excluding infections, traumatic injuries) of 30 million demands a public health approach, availability and accessibility of health care services. Paucity of trained neurologists necessitates redefining health services with integration of neurology care in the general health care and optimal utilization of the existing three tier‑system of health services and implement the tested models for delivery of neurology care at primary levels.[118,119] District model for providing services to people with epilepsy has been expanded to the concept of “National epilepsy control program”.[61,120,121] Analysis of temporal trends in Asia including India clearly indicates increase in incidence of stroke with a significant proportion of strokes occurring in the young.[122] To reduce the stroke fatality and disability it has been suggested that stroke units can be established in low and middle income countries in cost effective manner.[123] Through a well planned multipronged targeted approach it is practical and feasible to provide neurology care, even to the remote and rural areas, leading to decrease in mortality, disability and improved quality of life.

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