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Epilepsy in India I: Epidemiology and public health

Identifieur interne : 000256 ( Pmc/Corpus ); précédent : 000255; suivant : 000257

Epilepsy in India I: Epidemiology and public health

Auteurs : Senthil Amudhan ; Gopalkrishna Gururaj ; Parthasarathy Satishchandra

Source :

RBID : PMC:4564458

Abstract

Of the 70 million persons with epilepsy (PWE) worldwide, nearly 12 million PWE are expected to reside in India; which contributes to nearly one-sixth of the global burden. This paper (first of the two part series) provides an in-depth understanding of the epidemiological aspects of epilepsy in India for developing effective public health prevention and control programs. The overall prevalence (3.0-11.9 per 1,000 population) and incidence (0.2-0.6 per 1,000 population per year) data from recent studies in India on general population are comparable to the rates of high-income countries (HICs) despite marked variations in population characteristics and study methodologies. There is a differential distribution of epilepsy among various sociodemographic and economic groups with higher rates reported for the male gender, rural population, and low socioeconomic status. A changing pattern in the age-specific occurrence of epilepsy with preponderance towards the older age group is noticed due to sociodemographic and epidemiological transition. Neuroinfections, neurocysticercosis (NCC), and neurotrauma along with birth injuries have emerged as major risk factors for secondary epilepsy. Despite its varied etiology (unknown and known), majority of the epilepsy are manageable in nature. This paper emphasizes the need for focused and targeted programs based on a life-course perspective and calls for a stronger public health approach based on equity for prevention, control, and management of epilepsy in India.


Url:
DOI: 10.4103/0972-2327.160093
PubMed: 26425001
PubMed Central: 4564458

Links to Exploration step

PMC:4564458

Le document en format XML

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<name sortKey="Mathew, T" uniqKey="Mathew T">T Mathew</name>
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<name sortKey="Udani, Vp" uniqKey="Udani V">VP Udani</name>
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<name sortKey="Dharnidharka, V" uniqKey="Dharnidharka V">V Dharnidharka</name>
</author>
<author>
<name sortKey="Nair, A" uniqKey="Nair A">A Nair</name>
</author>
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<name sortKey="Joshua, Sp" uniqKey="Joshua S">SP Joshua</name>
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<name sortKey="Mahapatra, Ak" uniqKey="Mahapatra A">AK Mahapatra</name>
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</author>
<author>
<name sortKey="Sinha, S" uniqKey="Sinha S">S Sinha</name>
</author>
<author>
<name sortKey="Satishchandra, P" uniqKey="Satishchandra P">P Satishchandra</name>
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</TEI>
<pmc article-type="review-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Ann Indian Acad Neurol</journal-id>
<journal-id journal-id-type="iso-abbrev">Ann Indian Acad Neurol</journal-id>
<journal-id journal-id-type="publisher-id">AIAN</journal-id>
<journal-title-group>
<journal-title>Annals of Indian Academy of Neurology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0972-2327</issn>
<issn pub-type="epub">1998-3549</issn>
<publisher>
<publisher-name>Medknow Publications & Media Pvt Ltd</publisher-name>
<publisher-loc>India</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26425001</article-id>
<article-id pub-id-type="pmc">4564458</article-id>
<article-id pub-id-type="publisher-id">AIAN-18-263</article-id>
<article-id pub-id-type="doi">10.4103/0972-2327.160093</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Epilepsy in India I: Epidemiology and public health</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Amudhan</surname>
<given-names>Senthil</given-names>
</name>
<xref ref-type="aff" rid="aff1"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gururaj</surname>
<given-names>Gopalkrishna</given-names>
</name>
<xref ref-type="aff" rid="aff1"></xref>
<xref ref-type="corresp" rid="cor1"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Satishchandra</surname>
<given-names>Parthasarathy</given-names>
</name>
<xref ref-type="aff" rid="aff2">1</xref>
</contrib>
</contrib-group>
<aff id="aff1">Department of Epidemiology, Centre for Public Health, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India</aff>
<aff id="aff2">
<label>1</label>
Director/Vice-chancellor and Professor of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India</aff>
<author-notes>
<corresp id="cor1">
<bold>For correspondence: Dr. Gopalkrishna Gururaj,</bold>
Department of Epidemiology, Centre for Public Health, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore - 560 029, Karnataka, India. E-mail:
<email xlink:href="epiguru@yahoo.com">epiguru@yahoo.com</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub">
<season>Jul-Sep</season>
<year>2015</year>
</pub-date>
<volume>18</volume>
<issue>3</issue>
<fpage>263</fpage>
<lpage>277</lpage>
<history>
<date date-type="received">
<day>19</day>
<month>12</month>
<year>2014</year>
</date>
<date date-type="rev-recd">
<day>26</day>
<month>1</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>04</day>
<month>4</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright: © Annals of Indian Academy of Neurology</copyright-statement>
<copyright-year>2015</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract>
<p>Of the 70 million persons with epilepsy (PWE) worldwide, nearly 12 million PWE are expected to reside in India; which contributes to nearly one-sixth of the global burden. This paper (first of the two part series) provides an in-depth understanding of the epidemiological aspects of epilepsy in India for developing effective public health prevention and control programs. The overall prevalence (3.0-11.9 per 1,000 population) and incidence (0.2-0.6 per 1,000 population per year) data from recent studies in India on general population are comparable to the rates of high-income countries (HICs) despite marked variations in population characteristics and study methodologies. There is a differential distribution of epilepsy among various sociodemographic and economic groups with higher rates reported for the male gender, rural population, and low socioeconomic status. A changing pattern in the age-specific occurrence of epilepsy with preponderance towards the older age group is noticed due to sociodemographic and epidemiological transition. Neuroinfections, neurocysticercosis (NCC), and neurotrauma along with birth injuries have emerged as major risk factors for secondary epilepsy. Despite its varied etiology (unknown and known), majority of the epilepsy are manageable in nature. This paper emphasizes the need for focused and targeted programs based on a life-course perspective and calls for a stronger public health approach based on equity for prevention, control, and management of epilepsy in India.</p>
</abstract>
<kwd-group>
<kwd>Aetiology</kwd>
<kwd>control</kwd>
<kwd>epilepsy</kwd>
<kwd>epidemiology</kwd>
<kwd>etiology</kwd>
<kwd>gender</kwd>
<kwd>incidence</kwd>
<kwd>prevalence prevention</kwd>
<kwd>risk factors</kwd>
<kwd>urban-rural differentials</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec1-1">
<title>Introduction</title>
<p>Epilepsy is the second most common and frequently encountered neurological condition that imposes heavy burden on individuals, families, and also on healthcare systems. As per a recent study, 70 million people have epilepsy worldwide and nearly 90% of them are found in developing regions.[
<xref rid="ref1" ref-type="bibr">1</xref>
] The study also estimated a median prevalence of 1.54% (0.48-4.96%) for rural and 1.03% (0.28-3.8%) for urban studies in developing countries. With a conservative estimate of 1% as prevalence of epilepsy, there are more than 12 million persons with epilepsy (PWE) in India, which contributes to nearly one-sixth of the global burden. Though existing for centuries and well-known for more than 2,000 years (as described by Hippocrates), it is only in recent years that epilepsy has attracted the attention of the medical community. Consequently, efforts are being made for better understanding of the disease and also to organize comprehensive services. In order to organize preventive, promotive, curative, and rehabilitative services for PWE (the public health approach); understanding the burden, distribution, risk factors, and determinants of epilepsy through epidemiological approaches becomes crucial.</p>
<p>The purpose of the present review is to bring together available information on the distribution and determinants of epilepsy through comprehensive review of published research from India. The review undertaken in two parts provides a complete understanding of epilepsy with part 1 focusing on disease, risk factors, and causes; while part 2 focuses on impact, burden, and program-related aspects.</p>
<sec id="sec2-1">
<title>Data sources and searches</title>
<p>A systematic literature search was performed for English language literature with a combination of electronic and manual methods. Databases searched included PubMed, Medline, Ebscohost, and Google Scholar. The keywords and Medical Subject Headings (MeSH) used for electronic search were “epilepsy” combined with each of the following:“epidemiology”, “prevalence”, “incidence”, “mortality”, “morbidity”, “aetiology”, “risk factors”, “ infections”, “neurocysticercosis”, “traumatic brain injuries”, and “febrile seizures”. The above search words were combined with other search words “India”, “South Asia”, “developing countries”, “tropical countries”, “West Asia” using Boolean operator “AND” for retrieving studies related to India. Manual search was done from National Institute of Mental Health and Neurosciences (NIMHANS) library for those articles whose full text was not available electronically. Publications not available in the public domain were obtained by contacting the authors directly. Reference lists of the identified articles were snowballed and the relevant articles, abstracts, and book chapters were reviewed further.</p>
<p>In this review, all epidemiological studies on epilepsy (from 1950 to July, 2014) from India have been included. Studies included are predominantly population based, published in peer-reviewed journals, that used valid study instruments, standard definitions, and methodology with adequate information on sample size, age and gender distribution, classification if any, along with diagnostic information were preferred for inclusion. Some studies from outside India, school based, and those from medical care settings that are relevant to the current scenario were also included. Case reports, clinical trial studies, animal studies, articles that focused exclusively on specific forms of epilepsy (e.g., electroclinical syndrome), specific etiologic categories of epilepsy (genetic/structural/provoked), and seizures were excluded. The initial search retrieved 1,059 records. After exclusion, 147 full text records and references from six reviews were reviewed for relevance [
<xref ref-type="fig" rid="F1">Figure 1</xref>
]. Studies were classified and stored in the respective databases based on the subthemes, which were then abstracted into respective tables that included information on author, year of publication, place of study, study setting, study sample, diagnostic tool, prevalence, incidence, and other remarks. Recent estimates on disability-adjusted life years (DALYS) were arrived by analyzing the data of Global Burden of Disease (GBD) 2010 from the Institute of Health Metrics and Evaluation.[
<xref rid="ref2" ref-type="bibr">2</xref>
]</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption>
<p>Flowchart of study selection</p>
</caption>
<graphic xlink:href="AIAN-18-263-g001"></graphic>
</fig>
</sec>
</sec>
<sec id="sec1-2">
<title>Methodological Issues</title>
<p>Most recently, the International League against Epilepsy (ILAE) has revised its conceptual definition of epilepsy to an operational definition to bring the term in concordance with common usage. Accordingly, epilepsy is defined as a disease of the brain with any of the following conditions: i. At least two unprovoked (or reflex) seizures occurring >24 h apart; ii. one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; and iii. diagnosis of an epilepsy syndrome.[
<xref rid="ref3" ref-type="bibr">3</xref>
]</p>
<p>From a classification perspective, ILAE has moved from validation of history; neurological or clinical evaluation; to the proposed multiaxial classification using five level or axes namely ictal semiology, seizure type, epilepsy syndrome, epilepsy etiology, and impairment.[
<xref rid="ref4" ref-type="bibr">4</xref>
] Even though the proponents and opponents of this classification method debate fiercely on its broad applications, the problems of definition exist in this classification and many strongly believe that it is still not best suited for population-based epidemiological studies; thus reemphasizing the need for case definition, which is the central pillar of epidemiological research.[
<xref rid="ref5" ref-type="bibr">5</xref>
] Despite these merits and demerits, epilepsy epidemiology has been making significant strides to refine methodological issues in India over the year.</p>
<p>From a methodological perspective, differences exist across the studies due to varying sample sizes, data collection personnel, nature of the population (urban or rural), duration of study, data collection tools (questionnaires and interviews), and other factors.[
<xref rid="ref6" ref-type="bibr">6</xref>
] From a diagnostic perspective, a good history by an observant witness remains the hallmark in the diagnosis of epilepsy. Earlier, the diagnosis of epilepsy was established by non-neurologists (medical or trained non-medical staff) or through a two-step process of screening and diagnostic evaluation, which at times has given rise to fallacious results due to false positives and false negatives. Even though some investigative procedures have been used in a few studies, significant limitations exist in India as such facilities are not available in rural areas and are also not reliable in the absence of specific history.</p>
<p>It is important to differentiate acute symptomatic seizures from unprovoked seizures (epilepsy) in order to systematically classify cases and determine prognosis. Acute symptomatic seizures are events, occurring in close temporal relationship with an acute nervous system insult, which may be metabolic, toxic, structural, infectious, or due to inflammation. Acute symptomatic seizures differ from epilepsy in several important aspects. Unlike epilepsy, the proximate cause, temporal sequence, biological plausibility, and dose effect of acute symptomatic seizures are clearly identifiable to ascertain the cause. Acute symptomatic seizures are not necessarily characterized by a tendency for recurrence and have better prognosis, thus exempting them from the criteria of enduring predisposition to seize for epilepsy.[
<xref rid="ref7" ref-type="bibr">7</xref>
] As sophisticated skills and techniques are required to distinguish acute symptomatic seizures from unprovoked seizures, most of the epidemiologic studies relying on field surveys have included such seizures as “epilepsy”, or failed to distinguish these from unprovoked seizures.[
<xref rid="ref8" ref-type="bibr">8</xref>
<xref rid="ref9" ref-type="bibr">9</xref>
] If all people with acute symptomatic seizures are categorized as having epilepsy, it would add to the burden and stigma, and hence this distinction is important. Thus, the results of such epidemiological studies on epilepsy need to be appraised and interpreted with caution.</p>
<p>Despite all these limitations, epidemiological research on epilepsy in India has progressed significantly in terms of methodology, data analysis, and management along with interpretations of data.</p>
</sec>
<sec id="sec1-3">
<title>Epilepsy: Global Scenario</title>
<p>At the global level, it is estimated that nearly 70 million people suffer from epilepsy and the prevalence of epilepsy across the globe is estimated to be 5-9 per 1,000 population.[
<xref rid="ref1" ref-type="bibr">1</xref>
<xref rid="ref10" ref-type="bibr">10</xref>
] As per the GBD analysis for 2010, epilepsy accounted for 0.7% of the global burden or more than 17 million DALYs and nearly 90% of these were reported from low and middle-income countries (LMICs). DALYs across the globe has varied from 6.2 million in Africa to as low as 1.6 million in the European region with southeast Asia contributing for 3.2 million DALYs; an increase from 0.3 to 0.5% during 1990-2010 [
<xref ref-type="fig" rid="F2">Figure 2</xref>
]. Within the southeast Asia region, the prevalence of epilepsy varied from 2 to 10 per 1,000 population and more than half of the total DALYs due to epilepsy (as estimated from GBD 2010) were accounted from India [
<xref ref-type="fig" rid="F3">Figure 3</xref>
].[
<xref rid="ref2" ref-type="bibr">2</xref>
] This huge burden from India can probably be attributed to large population, lower income and education, sociocultural prejudices, inadequate resources, competing infectious and noncommunicable diseases, and the low importance given for public health aspects of epilepsy.</p>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption>
<p>Disability-adjusted life years (DALYs) due to epilepsy among six WHO regions (GBD 2010). WHO = World Health Organization, GBD = Global Burden of Disease</p>
</caption>
<graphic xlink:href="AIAN-18-263-g002"></graphic>
</fig>
<fig id="F3" position="float">
<label>Figure 3</label>
<caption>
<p>DALYs due to epilepsy in Southeast Asia (GBD 2010). SEARO = South-East Asia Regional Office</p>
</caption>
<graphic xlink:href="AIAN-18-263-g003"></graphic>
</fig>
</sec>
<sec id="sec1-4">
<title>Epilepsy in High-Income Countries (HICs)</title>
<p>The existence of well-established health information and medical record systems along with countrywide census allow for accurate estimates of epilepsy burden in the HICs. The prevalence of epilepsy in HICs has varied from 4 to 7 per 1,000 population.[
<xref rid="ref11" ref-type="bibr">11</xref>
] Many countries have reduced the burden due to earlier and prompt response with significant emphasis on prevention of conditions that lead to epilepsy, besides the socioeconomic progress.</p>
</sec>
<sec id="sec1-5">
<title>Epilepsy in India</title>
<sec id="sec2-2">
<title>Prevalence</title>
<p>The prevalence of epilepsy is a strong indicator reflecting the presence of epilepsy (in the past or at a given point of time) indicating the number of people requiring services. Earlier, epilepsy was considered a mental and behavioral problem, and hence the initial studies on epilepsy were carried out by psychiatrists as a part of psychiatric morbidity survey using locally developed study instruments.[
<xref rid="ref12" ref-type="bibr">12</xref>
<xref rid="ref13" ref-type="bibr">13</xref>
<xref rid="ref14" ref-type="bibr">14</xref>
<xref rid="ref15" ref-type="bibr">15</xref>
<xref rid="ref16" ref-type="bibr">16</xref>
<xref rid="ref17" ref-type="bibr">17</xref>
<xref rid="ref18" ref-type="bibr">18</xref>
<xref rid="ref19" ref-type="bibr">19</xref>
<xref rid="ref20" ref-type="bibr">20</xref>
<xref rid="ref21" ref-type="bibr">21</xref>
] Methodological issues mentioned earlier prevailed in all these studies. With advances in diagnosis and management in the neurological sciences, there was a transitional shift with studies on epilepsy carried out as a part of neuroepidemiological surveys on large population by a two-stage process. This involved an initial screening by trained non-professionals followed by diagnostic confirmation by professionals using the standardized protocol and study instruments. Over time, there has been a notable shift in the areas of study instruments, case ascertainment, and case definition. Case definitions of International Classification of Diseases (ICD), World Health Organization (WHO),[
<xref rid="ref18" ref-type="bibr">18</xref>
<xref rid="ref22" ref-type="bibr">22</xref>
] and others (Hauser and Kurland[
<xref rid="ref23" ref-type="bibr">23</xref>
]) that were used initially are being replaced with the adoption of ILAE definition.[
<xref rid="ref24" ref-type="bibr">24</xref>
] In recent times, there have been studies focusing exclusively on epilepsy and even epilepsy registries have been established in India.[
<xref rid="ref25" ref-type="bibr">25</xref>
] These developments have helped in better understanding of the epidemiology of epilepsy in the development of programs and services. Recently, a three-stage survey methodology was used for detecting active convulsive epilepsy in population-based studies in health and demographic surveillance systems. Even though, this was found to be cheaper than a two-stage survey, it has low sensitivity and cannot be replicated in many places.[
<xref rid="ref26" ref-type="bibr">26</xref>
]</p>
<p>In countries with better access to healthcare and good recording system, various newer methods, data sources, and techniques have been used to understand the epidemiology of epilepsy. Besides two-stage methods and surveillance, three-stage method (field screening by neurologist, neurological evaluation at hospital, and EEG confirmation at hospital) and audit of epilepsy services were used.[
<xref rid="ref27" ref-type="bibr">27</xref>
<xref rid="ref28" ref-type="bibr">28</xref>
<xref rid="ref29" ref-type="bibr">29</xref>
] Various sources of data like coded medical records,[
<xref rid="ref30" ref-type="bibr">30</xref>
] national or regional registers,[
<xref rid="ref31" ref-type="bibr">31</xref>
] general practice record,[
<xref rid="ref32" ref-type="bibr">32</xref>
] indexed record filing system (medical records linkage system),[
<xref rid="ref33" ref-type="bibr">33</xref>
] hospital records (inpatients, outpatients, and electroencephalography),[
<xref rid="ref34" ref-type="bibr">34</xref>
] and prescription database[
<xref rid="ref35" ref-type="bibr">35</xref>
<xref rid="ref36" ref-type="bibr">36</xref>
] were used to identify the study population. In some studies, community sources like insurance and sickness funds have been used to measure disease prevalence (more often in the occupational groups).[
<xref rid="ref37" ref-type="bibr">37</xref>
<xref rid="ref38" ref-type="bibr">38</xref>
] In some countries with universal healthcare systems, administrative data of an individual healthcare from hospitals, clinics, and physician offices can be linked to study the epidemiology of epilepsy.[
<xref rid="ref39" ref-type="bibr">39</xref>
] Some studies have used multiple sources of information like key informant (teachers, health workers, religious leaders, and traditional healers) to improve the sensitivity of case ascertainment.[
<xref rid="ref40" ref-type="bibr">40</xref>
] Data collection using diagnostic epilepsy interviews fromcomputer-assisted telephonic interview (CATI)/computer-assisted personal interview (CAPI) and data analysis using imputation techniques were also used in some studies.[
<xref rid="ref41" ref-type="bibr">41</xref>
<xref rid="ref42" ref-type="bibr">42</xref>
] In most recent times, capture-recapture methods have been used to estimate the prevalence of epilepsy by cross-referencing information from multiple sources.[
<xref rid="ref43" ref-type="bibr">43</xref>
<xref rid="ref44" ref-type="bibr">44</xref>
] Presently, the limited availability and content of different data sources restrict the application of some of the newer methods in Indian setting.</p>
<p>Several studies in India that have shown varying prevalence rate at different times and places are shown in Tables
<xref ref-type="table" rid="T1">1a</xref>
<xref ref-type="table" rid="T3">c</xref>
. Temporal trends and higher mortality rates have to be considered besides the methodological issues while interpreting the results from earlier studies which invariably reported lower prevalence rates. Excluding the study, which reported a 5-year period prevalence of 22.2 per 1,000 population among children aged 8-12 years[
<xref rid="ref71" ref-type="bibr">71</xref>
], the prevalence rate of epilepsy among adults and elderly varied from 1.2 to 11.9 per 1,000 population. Some studies have reported prevalence of active epilepsy defined as the number of individuals with epilepsy per thousand population at the time of study,[
<xref rid="ref40" ref-type="bibr">40</xref>
<xref rid="ref58" ref-type="bibr">58</xref>
<xref rid="ref60" ref-type="bibr">60</xref>
<xref rid="ref63" ref-type="bibr">63</xref>
] while some reported on lifetime prevalence which includes anyone who developed epilepsy prior to the study.[
<xref rid="ref24" ref-type="bibr">24</xref>
]</p>
<table-wrap id="T1" position="float">
<label>Table 1a</label>
<caption>
<p>Prevalence of epilepsy in rural population of India</p>
</caption>
<graphic xlink:href="AIAN-18-263-g004"></graphic>
</table-wrap>
<table-wrap id="T2" position="float">
<label>Table 1b</label>
<caption>
<p>Prevalence of epilepsy in urban and semiurban populations in India</p>
</caption>
<graphic xlink:href="AIAN-18-263-g005"></graphic>
</table-wrap>
<table-wrap id="T3" position="float">
<label>Table 1c</label>
<caption>
<p>Prevalence of epilepsy from mixed (both urban and rural) population in India</p>
</caption>
<graphic xlink:href="AIAN-18-263-g006"></graphic>
</table-wrap>
<p>Few studies reported the prevalence rate adjusted for standard population, while Mani
<italic>et al</italic>
., and Pal
<italic>et al</italic>
., provided the prevalence rate adjusted for survey sensitivity.[
<xref rid="ref24" ref-type="bibr">24</xref>
<xref rid="ref40" ref-type="bibr">40</xref>
<xref rid="ref60" ref-type="bibr">60</xref>
<xref rid="ref63" ref-type="bibr">63</xref>
] During 1980s, Gourie-Devi
<italic>et al</italic>
., reported a prevalence of 5.6 per 1,000 for rural and 2.5 per 1,000 for urban area (overall - 4.6 per 1,000) from a mixed population of Gowribidanur in Karnataka, while Koul
<italic>et al</italic>
., reported a prevalence of 2.5 from the rural population of Kuthar valley in Kashmir.[
<xref rid="ref72" ref-type="bibr">72</xref>
<xref rid="ref53" ref-type="bibr">53</xref>
] In 1990s, Mani
<italic>et al</italic>
., reported a lifetime prevalence of 5.4 per1,000 among the rural population of Yelandur in Karnataka, while Radhakrishnan
<italic>et al</italic>
., reported a prevalence of 4.9 per 1,000 from the urban population in Kerala.[
<xref rid="ref24" ref-type="bibr">24</xref>
<xref rid="ref60" ref-type="bibr">60</xref>
] During 2000s, the largest Bangalore Urban Rural Neuro-Epidemiological Survey (BURNs)in Karnataka by Gourie-Devi
<italic>et al</italic>
., provided a prevalence rate of 5.8 per 1,000 for urban and 11.9 per 1,000 for rural (overall - 8.82 per 1,000), while Das
<italic>et al</italic>
., reported a prevalence of 5.7 per 1,000 for the urban population of Kolkata.[
<xref rid="ref70" ref-type="bibr">70</xref>
<xref rid="ref59" ref-type="bibr">59</xref>
] Interestingly, the prevalence rate within a defined region (Karnataka) as shown by two studies at an interval of 20 years has shown a rising trend from 5.6 to 11.9 per 1,000 for rural population and 2.5 to 5.7 per 1,000 for urban population (an overall prevalence varying from 4.6 to 8.8 per 1,000).</p>
<p>To develop a better understanding of prevalence issues, meta-analysis approaches are helpful; however, there are very few studies. Reddy and Chandrasekhar analyzed data from 13 psychiatric epidemiological studies (1967-1995) that yielded a prevalence estimate of 4.4 per 1,000 population (3.7-5.1 per 1,000 population).[
<xref rid="ref75" ref-type="bibr">75</xref>
] The estimated rural rate was 4.8 per 1,000 and the urban rate was 2.5 per 1,000, while the prevalence rate estimated for male and female was 4.9 per 1,000 and 3.9 per 1,000, respectively. Sridharan and Murthy included 20 studies (majority being psychiatric epidemiological studies) and using a pooled sample of 598,910, arrived at a prevalence of 5.34 per 1,000 (4.25-6.41 per 1,000), after correcting for interstudy variation.[
<xref rid="ref76" ref-type="bibr">76</xref>
] The estimated rural rate was 5.5 per 1,000 and the urban rate was 5.1 per 1,000; while the prevalence rate estimated for male and female was 5.9 per 1,000 and 5.5 per 1,000, respectively. Though the prevalence estimates from both the meta-analysis have not included larger population-based neuroepidemiological studies, the estimates of prevalence are comparable with the estimates of Mani
<italic>et al</italic>
., BURNs, Radhakrishnan
<italic>et al</italic>
., and Das
<italic>et al</italic>
.[
<xref rid="ref24" ref-type="bibr">24</xref>
<xref rid="ref59" ref-type="bibr">59</xref>
<xref rid="ref60" ref-type="bibr">60</xref>
<xref rid="ref70" ref-type="bibr">70</xref>
]</p>
<p>Amidst these different rates, the interpretation and extrapolation of the data to the vast country like India needs to be made with caution in the presence of few well-designed, multicentric, population-based studies conducted using standardized protocols. Among recent studies in the past 20 years, the prevalence estimates were found to range from 3.0 to 11.9 per 1,000 population, when either standard study instrument or ILAE case definition was used among the general population.[
<xref rid="ref23" ref-type="bibr">23</xref>
<xref rid="ref24" ref-type="bibr">24</xref>
<xref rid="ref40" ref-type="bibr">40</xref>
<xref rid="ref45" ref-type="bibr">45</xref>
<xref rid="ref46" ref-type="bibr">46</xref>
<xref rid="ref48" ref-type="bibr">48</xref>
<xref rid="ref54" ref-type="bibr">54</xref>
<xref rid="ref56" ref-type="bibr">56</xref>
<xref rid="ref60" ref-type="bibr">60</xref>
<xref rid="ref61" ref-type="bibr">61</xref>
<xref rid="ref68" ref-type="bibr">68</xref>
<xref rid="ref70" ref-type="bibr">70</xref>
] It is important to recognize that these prevalence estimates of India were comparable with rates of developed countries (2.7-12.4 per 1,000) and the problem is as similar as in HICs of the world.[
<xref rid="ref1" ref-type="bibr">1</xref>
]</p>
</sec>
<sec id="sec2-3">
<title>Incidence</title>
<p>The rate at which the new cases are developing in the community during a defined time point (incidence rate) is helpful for organizing preventive services and estimating the true burden. But there is an inherent complexity and resource intensity involved in conducting such incidence studies. Data from HICs reported the incidence rates varying from 0.4 to 0.7 per 1,000.[
<xref rid="ref10" ref-type="bibr">10</xref>
] In 1993, Hauser
<italic>et al</italic>
., reported an incidence rate of 0.44 per 1,000 per year from Rochester through a 50-year follow-up period.[
<xref rid="ref77" ref-type="bibr">77</xref>
] Among the developing countries, an annual incidence rate of 0.73 per 1,000 population per year was reported from a rural Tanzanian district in Africa, while it varied from 1.2 to 1.9 per 1,000 population per year in the Andean region of Ecuador.[
<xref rid="ref8" ref-type="bibr">8</xref>
<xref rid="ref78" ref-type="bibr">78</xref>
] These differences in incidence rate were largely explained by the inherent regional and socioeconomic differences and the variations in the inclusion of epilepsy subtypes and methodological issues.</p>
<p>Studies from India have reported incidence rates varying from 0.2 to 0.6 per 1,000 population [
<xref ref-type="table" rid="T4">Table 2</xref>
]. The incidence rates reported from India are comparable with developed countries and lower than most of the developing countries which ranged from 1.0 to 1.9 per 1,000 per year.[
<xref rid="ref10" ref-type="bibr">10</xref>
<xref rid="ref81" ref-type="bibr">81</xref>
] Saha
<italic>et al</italic>
., reported an incidence rate of 0.42 per 1,000 per year from a 5-year longitudinal study in rural West Bengal, which was quite similar to the incidence rate of 0.49 per 1,000 per year reported by Mani
<italic>et al</italic>
., from the 1-year Yelandur study in rural area.[
<xref rid="ref24" ref-type="bibr">24</xref>
<xref rid="ref79" ref-type="bibr">79</xref>
] However, the incidence rates reported from urban regions were quite variable with higher rate of 0.60 per 100 per year from an urban resettlement colony compared to 0.27 per 1,000 per year from urban area.[
<xref rid="ref56" ref-type="bibr">56</xref>
<xref rid="ref80" ref-type="bibr">80</xref>
] The heavily concentrated migrant rural population in the urban resettlement colonies and slums in recent years might be one of the possible reasons for high incidence rate reported in urban resettlement colony. Thus, it is evident that there exists a wide rural-urban gap for incidence of epilepsy with likely hot spots in urban regions due to migrant rural population.</p>
<table-wrap id="T4" position="float">
<label>Table 2</label>
<caption>
<p>Incidence of epilepsy in Indian epidemiological studies</p>
</caption>
<graphic xlink:href="AIAN-18-263-g007"></graphic>
</table-wrap>
</sec>
<sec id="sec2-4">
<title>Mortality</title>
<p>Even though mortality from epilepsy is low, various studies from across the world have revealed a higher risk of premature mortality among people with epilepsy.[
<xref rid="ref82" ref-type="bibr">82</xref>
] Given the higher prevalence and incidence along with poor socioeconomic status and higher treatment gap, higher epilepsy related mortality is likely to be more frequent in India. Data is extremely limited on this issue in India due to absence of defined cohort for follow-up studies, poor medical record system, and the weak vital registration system failing to capture precise cause or conditions at the time of death. The commonest causes of death among PWE that are related directly to seizures are injuries, status epilepticus (SE), and sudden unexpected death in epilepsy (SUDEP). The other causes of death among PWE are certain infections like pneumonia, chronic intoxication with drugs, suicides, cerebral vascular lesions, and other medical conditions.</p>
<p>Mortality data is usually represented by four indices namely specific mortality rate (number of deaths from epilepsy per 1,000 population), proportionate mortality rate (number of deaths from epilepsy per 1,000 total deaths), case fatality rate (deaths from epilepsy per 100 cases), and standardized mortality ratio (SMR; ratio of number of deaths in those with epilepsy to the expected deaths in the people with epilepsy, if they experience the death rates of standard population). The mortality rate of epilepsy reported from western literatures has varied from 1 to 2 per 100,000 population and are often influenced by the nature and characteristics of death certificates.[
<xref rid="ref83" ref-type="bibr">83</xref>
] Among the hospital-based studies in India, a case fatality rate of 29% was reported among 117 hospitalized patients with SE, while another study reported a mortality rate of 29.7% among SE patients with central nervous system infection.[
<xref rid="ref84" ref-type="bibr">84</xref>
<xref rid="ref85" ref-type="bibr">85</xref>
] Abnormality on neurological examination, older age group, refractoriness, and male sex were associated with higher mortality besides other factors like socioeconomic status, time since diagnosis, higher seizure frequency, prolonged seizure duration, delay in initiating treatment, poor Glasgow Coma Scale (GCS) score at admission, and poor drug compliance.[
<xref rid="ref86" ref-type="bibr">86</xref>
<xref rid="ref87" ref-type="bibr">87</xref>
] Earlier, only two community-based studies on Parsi population in India reported the epilepsy-related mortality.[
<xref rid="ref88" ref-type="bibr">88</xref>
] The study from Mumbai urban Parsi population reported a SMR of 0.76, while the study from Vasai Parsi rural population reported a SMR of 7.8 for 5-year follow-up and 3.9 for 10-year follow-up. Recently, an annual mortality rate of 7.6 per 100,000 per year and a SMR of 2.58 was reported for epilepsy in a 5-year follow-up among the general population in Kolkata.[
<xref rid="ref56" ref-type="bibr">56</xref>
] Overall, the mortality among the rural population with epilepsy was found to be higher than the urban population which probably is linked to access and availability of services.</p>
</sec>
</sec>
<sec id="sec1-6">
<title>Epidemiological Correlates</title>
<sec id="sec2-5">
<title>Age</title>
<p>Similar to Hauser
<italic>et al</italic>
., who reported a bimodal distribution of epilepsy incidence with peaks during the 1
<sup>st</sup>
year of life and in persons aged more than 74 years, Mani
<italic>et al</italic>
., and Banerjee
<italic>et al</italic>
., have reported a bimodal incidence with peaks during early childhood and during 70s and 80s of life.[
<xref rid="ref24" ref-type="bibr">24</xref>
<xref rid="ref56" ref-type="bibr">56</xref>
<xref rid="ref77" ref-type="bibr">77</xref>
] This bimodal distribution with the second peaking of epilepsy in later years, warrants further investigation to explore the possible association with increasing incidence of stroke and injuries (and its complications) in India.[
<xref rid="ref56" ref-type="bibr">56</xref>
]</p>
<p>With respect to prevalence, Nandi
<italic>et al</italic>
., reported a higher prevalence of epilepsy in the 1
<sup>st</sup>
decade of life as early as 1970s.[
<xref rid="ref18" ref-type="bibr">18</xref>
] The prevalence rate for children varied from 2.02 per 1.000to as high as 22.2 per 1,000.[
<xref rid="ref55" ref-type="bibr">55</xref>
<xref rid="ref71" ref-type="bibr">71</xref>
] Perinatal injury, newborn distress, head trauma, neonatal hypoglycemia, malnutrition, and neurocyticersosis were reported as important risk factors of epilepsy in Indian children.[
<xref rid="ref89" ref-type="bibr">89</xref>
<xref rid="ref90" ref-type="bibr">90</xref>
] Later, majority of studies from India reported a higher prevalence during the 2
<sup>nd</sup>
decade, while a recent estimate from Raina
<italic>et al</italic>
., have reported a higher prevalence in the 4
<sup>th</sup>
decade.[
<xref rid="ref24" ref-type="bibr">24</xref>
<xref rid="ref55" ref-type="bibr">55</xref>
<xref rid="ref56" ref-type="bibr">56</xref>
<xref rid="ref59" ref-type="bibr">59</xref>
<xref rid="ref60" ref-type="bibr">60</xref>
] This changing pattern in the age-specific occurrence of epilepsy might be linked to demographic transition, changing living conditions, improved healthcare services, changing dietary habits (related to neurocysticercosis (NCC)), increasing awareness, and better help-seeking behaviors.</p>
</sec>
<sec id="sec2-6">
<title>Gender</title>
<p>Except for the recent study by Pandey
<italic>et al</italic>
., earlier studies from India reported higher prevalence among males as compared to females [
<xref ref-type="table" rid="T5">Table 3</xref>
]. Poor reporting due to cultural factors and differentially higher mortality among female children due to poor care might have contributed to this difference. With the progress of time, this difference appears to have been narrowed. Radhakrishnan
<italic>et al</italic>
., reported a prevalence rate of 5.2 per 1,000 for males and 4.7 per 1,000 for females,[
<xref rid="ref60" ref-type="bibr">60</xref>
] while Gourie-Devi
<italic>et al</italic>
., reported the rates of 6.1 per 1,000 and 5.2 per 1,000 for males and females, respectively (unpublished data). Similarly, Das
<italic>et al</italic>
., reported a prevalence rate of 5.9 per 1,000 for males and 5.2 per 1,000 for females.[
<xref rid="ref59" ref-type="bibr">59</xref>
] This study also reported higher prevalence for men in the younger age group and women in the older age group. Thus, despite the narrowing of gender differentials, the prevalence and incidence of epilepsy in males are still higher than females requiring further exploration. Among females, it is estimated that there are about 2.73 million women with epilepsy (WWE) in India with 52% of them belonging to the reproductive (15-49 years) age group.[
<xref rid="ref93" ref-type="bibr">93</xref>
]</p>
<table-wrap id="T5" position="float">
<label>Table 3</label>
<caption>
<p>Gender-specific prevalence rates for epilepsy in India</p>
</caption>
<graphic xlink:href="AIAN-18-263-g008"></graphic>
</table-wrap>
</sec>
<sec id="sec2-7">
<title>Urban-rural differences</title>
<p>Clearly the rural rates outnumbered the urban rates in almost all of the studies at any point of time in India. This clearly highlights the need to focus and strengthen services in rural areas and to examine the reasons for the differences. The BURNs study from Bangalore and surrounding region reported a nearly two times higher prevalence of epilepsy in rural areas as compared to the urban areas.[
<xref rid="ref70" ref-type="bibr">70</xref>
] Similarly, a striking urban-rural difference with higher rural rates has been reported for incidence of epilepsy also. An annual incidence rate of 0.42 per 1,000 per year was reported for rural population by Mani
<italic>et al</italic>
., as compared to 0.27 per 100,000 per year for urban population by Banerjee
<italic>et al</italic>
.[
<xref rid="ref24" ref-type="bibr">24</xref>
<xref rid="ref56" ref-type="bibr">56</xref>
] Besides social issues, the possible reasons for this observed difference could be attributed to lack of facilities for good antenatal/postnatal care, birth injury, malnutrition, systemic and central nervous system (CNS) infections, high rates of neurotrauma, and also limited services in rural areas. Infections other than NCC and exposure to toxins such as lead and other pollutants could also be contributory in nature.[
<xref rid="ref68" ref-type="bibr">68</xref>
]</p>
</sec>
</sec>
<sec id="sec1-7">
<title>Socioeconomic Correlates (Education, Occupation, and Income)</title>
<p>Detailed data on occurrence of epilepsy as per education, occupation, and income are limited due to difficulties in measuring these variables in field studies. However, socioeconomic factors by its strong association with birth trauma, infections, poor nutrition, poor hygiene, and poor health-seeking behavior influence the risk of epilepsy and its outcome. Even among the few incidence studies, the socioeconomic parameters were rarely assessed for valid association. In an earlier hospital-based study, 71.6% of PWE had education up to middle school; probably linked to differentially higher representation from urban areas.[
<xref rid="ref94" ref-type="bibr">94</xref>
] With regard to education, people who have completed up to high school education in slum area had higher rates for epilepsy.[
<xref rid="ref56" ref-type="bibr">56</xref>
] A recent hospital-based study on 196 cases in Karnataka has showed that more than 80% patients belonged to low socioeconomic status and were unskilled workers.[
<xref rid="ref95" ref-type="bibr">95</xref>
] Findings from these hospital-based studies should be interpreted with caution due to differential health-seeking pattern of poor people in the public sector hospitals. In a recent community based study by Banerjee
<italic>et al</italic>
., higher proportion of epilepsy was reported among manual workers and those who had a monthly income between 2,000 and 5,000 INR both in the slum and non-slum area.[
<xref rid="ref56" ref-type="bibr">56</xref>
] However; across the globe, low socioeconomic status, low income, and less education are regarded as risk factors for epilepsy. These factors have a direct impact on hospitalization, uncontrolled seizures, and drug-related side effects among the PWE.[
<xref rid="ref96" ref-type="bibr">96</xref>
<xref rid="ref97" ref-type="bibr">97</xref>
]</p>
<sec id="sec2-8">
<title>Etiology</title>
<p>A complex interaction between genes and environment was found to be involved in the early pathogenesis of epilepsy. The etiology of primary and secondary epilepsy varies significantly with the causes being unclear for primary epilepsy and, many conditions being causative for secondary epilepsy. Among the secondary seizures, conditions like brain injury and hypoxia due to poor medical care at the time of delivery, malnutrition and infection in the mother during pregnancy, traumatic/acquired brain injuries, and certain metabolic conditions play a major role as risk factors. A population-based, case-control study in India reported family history of the epilepsy, antecedent history of febrile seizures, birth by complicated labor, and neonatal seizures as strong independent predictors of epilepsy.[
<xref rid="ref98" ref-type="bibr">98</xref>
] These seizures are of special relevance and importance in India as majority of them are potentially preventable in nature.</p>
<p>The population-based, case-control studies in India found febrile seizures to be a significant risk factor for developing epilepsy.[
<xref rid="ref80" ref-type="bibr">80</xref>
<xref rid="ref99" ref-type="bibr">99</xref>
] A study on febrile seizures in a south Indian district found that 2.7% of children with febrile seizures had developed epilepsy.[
<xref rid="ref100" ref-type="bibr">100</xref>
] The risk of developing epilepsy in a child with febrile seizures was further associated with family history of epilepsy, cerebral palsy, or low Apgar scores. It should be noted that these risk factors are different from the risk factors associated with recurrence of febrile seizures (age <18 months, family history of febrile seizures, and multiple febrile seizures during the first episode). Also, there exists a complexity in the cause-effect relationship between febrile seizures and epilepsy.[
<xref rid="ref101" ref-type="bibr">101</xref>
]</p>
<p>The etiology of epilepsy is directly linked to seizure types and the majority of hospital-based studies have recorded a higher frequency for partial epilepsies: 57 and 80%.[
<xref rid="ref102" ref-type="bibr">102</xref>
<xref rid="ref103" ref-type="bibr">103</xref>
] While the community-based studies recorded a higher frequency for generalized seizures ranging from 79 to 54.5%.[
<xref rid="ref24" ref-type="bibr">24</xref>
<xref rid="ref63" ref-type="bibr">63</xref>
<xref rid="ref53" ref-type="bibr">53</xref>
] Within generalized epilepsy, tonic-clonic was the commonest type. The overlooking of most striking symptom by the respondents and interviewer for the generalized seizures and misclassification of partial seizures with secondary generalization as generalized seizures in community studies could be the possible reason for observed differences between hospital- and community-based studies.</p>
</sec>
<sec id="sec2-9">
<title>Neuroinfections</title>
<p>Despite significant advances in prevention and control of communicable and infectious diseases in India, infections are still a major cause and remain a challenge to policy makers in the country. The most common mechanism causing epilepsy in these conditions is attributed to increased neuronal excitability due to proinflammatory signals induced by nervous system infections. Acute symptomatic seizures are commonly seen as a manifestation of bacterial meningitis (Meningococcus, Pneumococcus, and
<italic>Haemophilus influenzae</italic>
), CNS tuberculosis, viral encephalitis (Japanese encephalitis, herpes simplex type I, dengue, and human immunodeficiency virus (HIV)), malaria, NCC, and other emerging and reemerging infectious diseases. Some parts of India are known epidemic regions of Japanese encephalitis where epilepsy occurs as a result of long-term sequelae. A study on 100 autopsied cases of SE from a tertiary care center in India, identified neuroinfections and stroke as important etiological factors.[
<xref rid="ref87" ref-type="bibr">87</xref>
] However, there is a scarcity of data on epilepsy associated with CNS infections due to lack of advanced investigative facilities in India. A hospital-based study from south India, among 1,117established cases identified cerebrovascular disease as a major cause in 26% of the cases followed by neuroinfections, birth trauma, and cerebral tumors.[
<xref rid="ref104" ref-type="bibr">104</xref>
]</p>
<p>Even though, acute symptomatic seizures (provoked) are the most common manifestation of neuroinfections, NCC, and neurotrauma, the epilepsy (unprovoked seizures) related to these conditions is equally important, especially in a resource-poor setting like India with huge treatment gap. Neuroinfections, NCC, and neurotrauma along with birth injuries are the most frequent causes of secondary epilepsy, especially in developing countries and are potentially preventable with appropriate community interventions.[
<xref rid="ref105" ref-type="bibr">105</xref>
]</p>
</sec>
<sec id="sec2-10">
<title>Neurocysticercosis (NCC)</title>
<p>The rising prevalence of epilepsy in recent years in developing countries has been attributed to NCC, an infection caused by
<italic>Taenia solium</italic>
larvae. NCC, once thought of confined to the defined and focal population has now widespread distribution in the general population due to changing dietary habits and lifestyles. Solitary cystic granuloma (SCG) was the most common presentation accounting for more than 60% of NCC in India with more than 90% of patients with SCG presenting with acute symptomatic seizures.[
<xref rid="ref106" ref-type="bibr">106</xref>
] In a series of 500 children with NCC, 94.8% had seizures at presentation.[
<xref rid="ref107" ref-type="bibr">107</xref>
] The relationship between NCC and epilepsy has been explored for long time and debates are still going on about their relationship. Because of the high prevalence of epilepsy and NCC, there exists a cause and incidental relationship between the two.[
<xref rid="ref108" ref-type="bibr">108</xref>
] The prevalence of active epilepsy related to NCC varied from 1.3 to 4.5 per 1,000 population in Indian studies.[
<xref rid="ref109" ref-type="bibr">109</xref>
<xref rid="ref110" ref-type="bibr">110</xref>
<xref rid="ref111" ref-type="bibr">111</xref>
<xref rid="ref112" ref-type="bibr">112</xref>
] In a farming community, prevalence of 6.6% was reported for epilepsy and 18.6% for
<italic>Taenia solium</italic>
infection.[
<xref rid="ref113" ref-type="bibr">113</xref>
] Even though, NCC was reported in nearly one-third of all cases of acute epilepsy in both the urban and rural areas of Vellore, low seroprevalence of systemic cysticercosis was reported among PWE in Kerala.[
<xref rid="ref68" ref-type="bibr">68</xref>
<xref rid="ref114" ref-type="bibr">114</xref>
] Koul
<italic>et al</italic>
., have attributed relative lack of cysticeral infection in the local community as possible reason for their observed low prevalence of epilepsy.[
<xref rid="ref53" ref-type="bibr">53</xref>
] Altogether, nearly one-third of epilepsy were associated with NCC and the cost estimated for treating all the prevalent cases of SCG was to the tune of INR 1.184 billion in 2007.[
<xref rid="ref115" ref-type="bibr">115</xref>
] Even though more advanced investigative facilities are available to facilitate the proper detection of the cases, the studies on NCC are limited in resource-poor settings due to limited availability of neuroimaging and immunological techniques.</p>
<p>Prevalent cases from large community-based studies might have overestimated the NCC-related epilepsy due to contamination by acute symptomatic seizures associated with the transitional phase of NCC.[
<xref rid="ref47" ref-type="bibr">47</xref>
] Prospective cohort studies are needed to clearly examine the association of different evolutive phases of the parasite and the development of seizures in establishing the causal link between epilepsy and NCC.</p>
</sec>
<sec id="sec2-11">
<title>Neurotrauma</title>
<p>With increasing modernization and motorization, there is a rising trend for secondary seizures or post-traumatic seizures (PTSs) resulting from road traffic injuries, falls, violence, and industrial accidents. In a study of acquired brain injuries in Bangalore, it was observed that 9% of individuals with traumatic brain injuries (TBIs) continued to have PTSs at 1 year after discharge.[
<xref rid="ref116" ref-type="bibr">116</xref>
] In another prospective hospital-based study from New Delhi, PTSs was observed in 11.4% of the patients with TBIs during the 2-year follow-up.[
<xref rid="ref117" ref-type="bibr">117</xref>
] Majority of PTSs were reported in age groups of 5-44 years, because of the vulnerability of these age groups to injuries. Early PTSs (seen in 4-25% of patients) are observed more common in children, while late seizures (reported in 9-42% of patients) are observed more common in patients of TBI with early PTSs, brain contusion, and subdural hematoma.[
<xref rid="ref118" ref-type="bibr">118</xref>
]</p>
</sec>
<sec id="sec2-12">
<title>Metabolic conditions</title>
<p>Epilepsy also occurs as a common accompanying condition of certain disorders like brain tumors and other metabolic conditions associated with low calcium, sodium, or blood sugar levels. However, studies on these risk factors of epilepsy in India are very few. Electrolyte and fluid imbalance due to diarrhea and other inborn errors of metabolism such as phenylketonuria or aminoacidurias are the other risk factors for infancy and childhood seizures besides birth injury and brain infections; while in the elderly, stroke is observed as the most common causes of seizures followed by metabolic derangements.[
<xref rid="ref119" ref-type="bibr">119</xref>
] Hypo/hyperglycemia, uremia, hyponatremia, or hypocalcemia, are the common metabolic derangements which provoke seizures among the elderly. It was observed that several risk factors of stroke, such as hypertension were found to be associated with epilepsy independently, without the occurrence of stroke. Dementia particularly Alzheimer, major depression and alcohol abuse were the other risk factors for seizures in elderly.[
<xref rid="ref120" ref-type="bibr">120</xref>
<xref rid="ref121" ref-type="bibr">121</xref>
<xref rid="ref122" ref-type="bibr">122</xref>
<xref rid="ref123" ref-type="bibr">123</xref>
]</p>
</sec>
<sec id="sec2-13">
<title>Natural course and management of epilepsy</title>
<p>The causes and risk factors of epilepsy vary widely, and so the treatment protocol and outcome also. Generally it is known that epilepsy tends to worsen in untreated patients or in whom treatment is initiated late or among those who discontinue. In a series of longitudinal surveys by Nandi
<italic>et al</italic>
., among the rural population of West Bengal, no appreciable change was observed in epilepsy status at the end of 1 year, while 45.6% got cured and 9% died at the end of 10 years.[
<xref rid="ref124" ref-type="bibr">124</xref>
<xref rid="ref125" ref-type="bibr">125</xref>
]</p>
<p>Many studies have demonstrated that patients with fewer seizures before optimal treatment are more likely to achieve complete seizure control.[
<xref rid="ref126" ref-type="bibr">126</xref>
] With regard to outcome, four prognostic groups can be defined; associated with excellent, good, certain, and bad prognosis.[
<xref rid="ref127" ref-type="bibr">127</xref>
] Special therapeutic modalities are required for management of epilepsy among pregnant mothers, and elderly with associated comorbid conditions, SE and refractory epilepsy.[
<xref rid="ref93" ref-type="bibr">93</xref>
<xref rid="ref128" ref-type="bibr">128</xref>
<xref rid="ref129" ref-type="bibr">129</xref>
<xref rid="ref130" ref-type="bibr">130</xref>
] In a study on “difficult-to-control” epilepsy, onset below 2 years of age, male sex, perinatal insults, and certain seizure types emerged as risk factors for refractoriness.[
<xref rid="ref131" ref-type="bibr">131</xref>
] Despite its varied etiology, and majority of them resulting from unknown causes, it has been shown that epilepsy can be managed effectively by single or simple inexpensive medication with 70-80% of persons able to lead a normal life.[
<xref rid="ref132" ref-type="bibr">132</xref>
] Thus, proper understanding of the causes and risk factors of epilepsy are essential for effective management of epilepsy in India where majority of patients are still untreated or inadequately treated.</p>
</sec>
<sec id="sec2-14">
<title>Refractory epilepsy in India</title>
<p>If the seizures are difficult to control with medication; they are referred to as refractory or intractable. The exact magnitude of medically intractable epilepsy in India is unknown.[
<xref rid="ref133" ref-type="bibr">133</xref>
]</p>
<p>A study done in the pediatric population found neuroinfections as a leading cause of intractable epilepsy.[
<xref rid="ref134" ref-type="bibr">134</xref>
] A study done in the North Indian population identified structural cerebral abnormality, non-response to first AED, delayed mile stones, high initial seizure frequency, partial seizure type, febrile seizures, and age of onset before 14 years as significant predictors of refractory epilepsy.[
<xref rid="ref98" ref-type="bibr">98</xref>
] It is essential to identify those patients at risk of developing refractory epilepsy early in their clinical course to evaluate for a possible surgical treatable cause and this would also minimize the toxicity from overdose of antiepileptic drugs and polytherapy.</p>
</sec>
<sec id="sec2-15">
<title>Summary</title>
<p>The present review on the distribution and determinants of epilepsy from an epidemiological and population perspective emphasizes the need for life-course approach in prevention and management and also the need for focused and targeted programs. The increasing burden of epilepsy in India in coming years due to sociodemographic and epidemiological transition warrants public health community to give priority for this eminently preventable and manageable condition in healthcare delivery. However, a proper understanding of the epidemiology of epilepsy is required to discern and delineate factors that are of relevance (that can be modified) in prevention, management, and rehabilitation. Future studies need to move to nationally representative populations using well-defined methodologies for developing a strong public health response for prevention and control of epilepsy in India.</p>
</sec>
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<bold>Source of Support:</bold>
Nil</p>
</fn>
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<bold>Conflicts of Interest:</bold>
None declared.</p>
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