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Table of Contents    
ORIGINAL ARTICLE
Year : 2020  |  Volume : 68  |  Issue : 6  |  Page : 1389-1393

Incidence Study of Epilepsy using the ILAE 2017 Classification of Epilepsies in a Cohort of School Children Accessing Education in Government Primary Schools in South India


Department of Neurology, The Institute of Neurological Sciences, *CARE Hospital and NICE Hospital and NICE Foundation, Hyderabad, Telangana, India

Date of Web Publication19-Dec-2020

Correspondence Address:
Dr. Jagarlapudi M. K Murthy
Chief of Neurology, The Institute of Neurological Sciences, CARE Hospitals, Care Outpatient Center, Road No: 10, Banjara Hills, Hyderabad–500 034, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.304099

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 » Abstract 


Background: Recently, the International League Against Epilepsy (ILAE) has proposed new classification schemes for seizures and epilepsy. The applicability of these classification schemes has not been studied in resource-poor countries.
Aim: To determine the incidences of epilepsies in a cohort of school children using the ILAE 2017 classification of epilepsies.
Materials and Methods: The study cohort included 7,408 school going children [age range 5–15 years]. They were followed for new-onset unprovoked seizure and seizure recurrence through first grade to fifth grade. The data collected during the first visit included clinical details including details of seizure semiology. All children had EEG and contrast CT scan. All these data were used to classify seizure type and epilepsy using ILAE classification schemes. The ILAE 2014 epilepsy definition was used to diagnose epilepsy. The average annual incidence rates (AAIR) and 95% confidence intervals (CI) were calculated for epilepsies by onset and by etiology.
Results: The AAIR of epilepsy was 57.85 (95% CI 39.0–82.6) per 100,000 population. The AAIRs per 100,000 for different epilepsies by mode of onset were focal epilepsies 25.07 (95% CI 13.35–42.87); generalized epilepsies 13.5 (95% CI 5.43–27.8); and unknown onset epilepsies 19.28 (95% CI 9.25–35.46). The AAIRs per 100,000 of epilepsies by etiology were focal genetic epilepsies 7.71 (95% CI 2.1–19.75); genetic generalized epilepsies 13.5 (95% CI 5.43–27.8); and epilepsies due to structural cause 17.36 (95% CI 9.25–35.46). The lesional epilepsies seen in this cohort were geographically specific to resource-poor countries. The AAIR of epilepsy due to calcific neurocysticercosis (cNCC) was 9.64 (95% CI 3.1–22.5) per 100,000.
Conclusions: This study demonstrates that the ILAE 2017 classification of epilepsies can be applied in resource-poor countries with limited workup. Lesional epilepsies seen in this study is geographically specific to resource-poor countries.


Keywords: Classification, focal onset epilepsies, generalized onset epilepsies, genetic cause, incidence, International League Against Epilepsy, structural cause, unknown onset epilepsies, unprovoked seizures
Key Messages: Familial amyloidotic polyneuropathy in our country is probably underdiagnosed. Knowledge regarding full clinical spectrum of the disease, high index of suspicion by clinician, and diligent search for pathology may direct genetic testing to establish early diagnosis. This is essential to provide symptomatic treatment, genetic counseling, and offer emerging targeted therapies.


How to cite this article:
Murthy JM, Jaiswal SK, Reddy MP, Srikrishna S. Incidence Study of Epilepsy using the ILAE 2017 Classification of Epilepsies in a Cohort of School Children Accessing Education in Government Primary Schools in South India. Neurol India 2020;68:1389-93

How to cite this URL:
Murthy JM, Jaiswal SK, Reddy MP, Srikrishna S. Incidence Study of Epilepsy using the ILAE 2017 Classification of Epilepsies in a Cohort of School Children Accessing Education in Government Primary Schools in South India. Neurol India [serial online] 2020 [cited 2021 Jan 18];68:1389-93. Available from: https://www.neurologyindia.com/text.asp?2020/68/6/1389/304099




Epilepsy is a common chronic neurological disorder worldwide and affects approximately 0.5 to 1% of children through the age of 16 years.[1] Children in their first year of life are at the highest risk of developing epilepsy. The median age of onset of epilepsy is between 5 and 6 years and plateaus between age 11 and 15 years.[1],[2] The incidence of epilepsy in children ranges from 41 to 187 per 100,000 and the reported incidence is high from developing countries.[2]

The classification of epileptic seizures and epilepsies has recently been revised by the International League Against Epilepsy (ILAE) and new classification schemes for both seizures[3] and epilepsies[4] have been proposed. The ILAE has also proposed a new operational definition of epilepsy.[5] In the new ILAE 2017 classification of epilepsies, there is a greater emphasis on putative etiologies at each classification step.[4] However, available diagnostic aids may differ substantially between upper-middle/high-income countries and resource-poor countries. We studied the incidence of epilepsies using the new ILAE 2017 classification of epilepsies with limited resources in a cohort of school children accessing education in government primary schools in south India.[4]


 » Material and Methods Top


This is a longitudinal follow-up study of epilepsy in a cohort of school children accessing education in government primary schools in south India. The study has the approval of the institute ethics committee (CARE-CF/DNB/AUG/2023/17 dated 12.8.2013). Of the 250 government primary schools adopted by NICE Foundation, Hyderabad, under its School Health Program, 18 schools were randomly selected from five Mandals in Hyderabad district, Telangana state, a province in south India. The study cohort included 7,408 school children aged between 5 and 15 years, registered on rolls as on the study date, January 1, 2006. Students admitted in the subsequent years were not included in the study. The study period was between January 1, 2006 and December 31, 2012. This cohort was followed for the incidence of new-onset seizures through first grade to fifth grade.

Under the School Health Program, NICE Foundation runs school outpatient clinics for the health needs of children studying in the schools adopted by the foundation. Children with specialty-related problems are referred to the specialists working in the hospitals recognized by the foundation. Children with neurological diseases are referred to as the neurology department, CARE Hospitals, Hyderabad for further evaluation. Children with new-onset seizures were further studied in detail. The help of the school teacher and/or coordinator was taken to recruit all possible cases of new-onset seizures. Seizures were classified as unprovoked seizures using the criteria proposed by ILAE.[6] For this study, children with new-onset unprovoked seizures were considered.

At the first visit to the neurology outpatient clinic, CARE Hospitals, the following data were collected: demographic data, age of onset, date of seizure, history of febrile seizures and other antecedents, family history of epilepsy, detailed eye witness account of seizure semiology, and neurological findings. While taking a history, the emphasis was laid on features for focal onset. All patients had 40-min awake and sleep EEG and plain and contrast CT. None of the children had magnetic resonance imaging and also genetic and metabolic workup. The foundation paid for all the investigations and drugs from the fund is raised from the philanthropists and others. There was no conflict of interest. Children were prescribed the appropriate antiepileptic drugs (AEDs) when it was indicated, mostly monotherapy. NICE Foundation provided AEDs to the children free of cost. Children were followed at an interval of 3 months or whenever required. Children were followed for any recurrence of seizures. In children with recurrence of seizures, a detailed eye witness account of the event was taken with emphasis on features for focal onset.

The data collected at the first visit and also the details of second seizure were used to apply the new ILAE 2017 classification of epilepsies.[4] The diagnosis of epilepsy was done by using the new ILAE 2014 definition.[5] The seizure type was done using the new ILAE 2017 seizure classification.[3] Seizure classification was based on the mode of seizure onset into focal, generalized, and unknown onset. In children with genetic focal epilepsies, EEG findings were considered when the seizure onset was uncertain.

The first step in the classification of epilepsies was defining the seizure type into focal onset, generalized onset, and unknown onset. The next step was categorizing epilepsies into focal, generalized, combined focal and generalized, or unclassifiable. This was followed by the etiological classification of epilepsies. The etiological classification was as proposed by ILAE.[4],[7] Genetic epilepsies and probable genetic epilepsies were considered together for calculating the incidence rates.

Diagnostic clinic-radiological criteria for neurocysticercosis (NCC) proposed by Brutto et al. were used for radiologic diagnosis of NCC and small calcific lesion measuring less than 20 mm on plain CT was diagnosed as the calcific stage of neurocysticercosis (cNCC).[8] Children with a single unprovoked seizure due to cNCC were considered to have epilepsy as this lesion was shown to have an enduring predisposition for seizure recurrence.[9]

Classification of seizure and epilepsies was done by the first two authors (JMKM, SKS), neurologists with a special interest in epilepsy. In the event of disagreement, the final results of classification were based on discussion and the evidence from investigations, mainly EEG and contrast CT.

Statistical methods

AIR indicates the rate of occurrence of new cases of epilepsy per 100,000 population per year. It included all the new cases between January 2006 and December 2012. The average annual incidence rate (AAIR) was calculated for seven consecutive years. The 95% confidence intervals (CI) of the incidence were calculated assuming a Poisson distribution for the observed cases.


 » Results Top


The number of children registered on rolls as on the date of start of the study (January 1, 2006) was 7,408 including 3297 (44.5%) boys and 4111 (55.5%) girls and age ranged between 5 and 15 years [Table 1]. All children were from low socioeconomic strata, living in the slums surrounding the schools. The environment surrounding the slums was unhygienic with pig population. Of the 65 children referred for possible new-onset seizures, seven (10.7%) children were diagnosed to have psychogenic non-epileptic seizures (PNES), 21 (32.3%) had acute symptomatic seizures, and 37 (57%) had unprovoked seizures.
Table 1: Demographic data of the study cohort

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There were 37 children with a new-onset unprovoked seizure during the study period, an average of 5.28 cases for the year. The AAIR of unprovoked seizure (s) (≥1) was 71.35 (95% CI 50.2–98.35) per 100,000. Of the 37 children with unprovoked seizures, seven (29.4%) children had no seizure recurrence during the study period of 7 years. The remaining 30 (81%) children (mean age 9.47 years, range 5–15 years, M: F = 1:1) fulfilled the criteria of the new ILAE 2017 definition of epilepsy. The AAIR of epilepsy was 57.85 (95% CI 39.0–82.6) per 100,000 [Table 2]. The age-specific AAIR was 45.24 (95% CI 27.24–70.64) per 100.000 in the age group 5–10 years and 111.61 (95% CI 55.71–199.7) in the age group 11–15 years. The gender-specific AAIR was 52.13 (95% CI 29.17–85.97) per 100,000 for girls and 64.99 (95% CI 36.3–107.2) per 100,000 for boys.
Table 2: Unprovoked seizures and Epilepsy: Incidence

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The AAIRs of different epilepsies per 100,000 by mode of seizure onset included focal-onset epilepsies in 25.07 (95% CI 13.35–42.87); generalized onset epilepsies in 13.5 (95% CI 5.43–27.8) and unknown-onset epilepsies in 19.28 (95% CI 9.25–35.46) [Table 3]. The AAIRs per 100,000 of epilepsies by etiology were (i) genetic focal epilepsy syndromes: 7.71 (95% CI 2.1–19.75); (ii) genetic generalized epilepsy syndromes 13.5 (95% CI 5.43–27.8); (iii) epilepsies due to structural cause: 17.36 (95% CI 7.94–32.95); and (iv) epilepsies of unknown cause: 19.28 (95% CI 9.25–35.46). The AAIR of epilepsy due to cNCC was 9.64 (95% CI 3.1–22.5) per 100,000 [Table 4].
Table 3: Epilepsy syndromes and epilepsies: Incidence

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Table 4: Epilepsies and epilepsy syndromes: Etiology

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 » Discussion Top


Our study suggests that the new ILAE 2017 classification of epilepsies can be applied in resource-poor countries with limited diagnostic workup. The epilepsy spectrum seen in this cohort reflects the garden variety of epilepsies seen in this age group. The etiology of lesional epilepsy seen in this cohort is geographically specific to resource-poor countries. This cohort reflects the real-world situation of epilepsy care in resource-poor countries.

In this cohort of school-going children aged 5–15 years, using the ILAE 2014 definition of epilepsy and new ILAE 2017 classification of epilepsies, the AAIR of unprovoked seizures (≥1) was 71.35 per 100,000 and the AAIR of epilepsy was 57.85 per 100,000. The incidence of unprovoked seizures (≥1) observed in our study was comparable to the study from Tunisia, which reported 76.24 per 100,000 per year in children aged 5–15 years.[10] However, the incidence of epilepsy observed in our study was much lower than other cohort-based studies from resource-poor countries. These studies were not exactly comparable as the age group studied was different. In the rural birth cohort study from Kenya, the annual incidence of epilepsy in children aged 6–12 years was 187 per 100,000.[11] In the community-based studies in high-income countries, the reported incidence ranged from 33.3 to 82 per 100,00 persons per year.[2] The community-based incidence study from rural Vietnam reported a crude annual incidence of 96.8 per 100,000 in children aged 1–15 years.[12] The possible reasons for the lower incidence of epilepsy observed in our study include: (i) the study cohort did not include children of all ages and (ii) the epilepsy spectrum seen in this cohort may not reflect the total epilepsy spectrum seen in this age group.

In the present study, the gender-adjusted AAIR for girls was 52.13 and 64.99 per 100,000 in boys. In the Vietnam rural community-based study, it was: 100.7 for girls and 93.2 for boys.[12] The incidence in boys and girls was almost identical in the studies from countries with high income.[2]

Across all incidence studies in high-income countries, focal seizures were more common than generalized seizures, 53–63% vs 23–40%.[2] In the study from Chile, the focal seizure was the seizure type in 54%.[13] In this study, the focal-onset seizure was the seizure type in 43.3%. There was no good explanation for this lower incidence of focal onset seizures. In this study, about a third of children had unknown-onset motor seizures. It is possible that parents/caregivers, in their anxiety might not have observed the focal onset of seizures. Extensive diagnostic evaluation including MRI would have shifted some of these children from unknown onset to focal onset seizures.

In our study, the distribution of epilepsies by mode of onset was: (i) focal-onset epilepsies in 13 (43.3%): (ii) generalized onset epilepsies in 7 (23.3%); and (iii) unknown-onset epilepsies in 10 (33.3%). The Norwegian Mother and Child Cohort Study (MoBa) used the new ILAE classification systems in the age group 3–13 years. In this study of children with epilepsy, focal-onset epilepsies accounted for 59% and generalized onset epilepsies for 35% of cases. The distribution of epilepsies by mode of onset was highly dependent on the age of onset. Focal seizures were the most frequent seizure type at all ages and were a dominant seizure type at a later age of onset.[14] In the Connecticut study of childhood-onset seizures, the distribution of epilepsy syndromes using the ILAE 1989 classification of epilepsies and epileptic syndromes included focal (localization-related) epilepsies in 59%, generalized epilepsies in 29%, and undetermined in 12%.[15],[16] The reasons for the low frequency of focal-onset epilepsies in our study were uncertain. Limited diagnostic workup might be one of the possible reasons.

In our study, the distribution of epilepsies by etiology were: (i) focal epilepsies in 13 (43.3%) including focal genetic epilepsies in 4 (13.3%), and focal epilepsies due to structural lesion in 9 (30%); (ii) generalized genetic epilepsies in 7 (23.3%); and (iii) unknown epilepsies due to unknown cause in 10 (33.3%). In the MoBa study in children aged > 5 years, the etiology was genetic and presumed genetic in 28% and structural lesion in 17%.[14] In the population-based study from Rochester (1980–2004), approximately half of children had an unknown etiology for their epilepsy. Of the remainder, 22% were genetic and 28% were structural/metabolic.[17]

The etiological spectrum of lesional epilepsy seen in this cohort was geographically specific to resource-poor countries. The reported etiologies include birth-related trauma, neonatal hypoglycemia-related brain injury, and central nervous system infection, particularly cNCC.[18],[19],[20],[21],[22] In countries endemic to NCC, a calcific lesion on brain CT is a measure of previous brain cysticercal infection (cNCC).[8] A recent large CT-based study showed robust epidemiological evidence favoring the relationship between epilepsy and cNCC (OR = 3.04. 95% CI 1.35–6.81).[23] cNCC lesion as a cause of epilepsy was much less common in children as compared to adults (15% vs 55%).[24] In a hospital-based study of the 558 children with focal seizures, cNCC accounted for 6.2% of etiology.[25] In this study, cNCC accounted for 16.6% of all the causes and 55.5% of lesional epilepsy. The AAIR of epilepsy due to cNCC was 9.64 per 100,000.

This study suggests that the new ILAE 2017 classification of epilepsies can be applied in resource-poor countries with limited diagnostic workup. The epilepsy spectrum seen in this cohort reflects the common forms of epilepsies and epilepsy syndromes seen in this age group. However, in one-third of children, epilepsy was unknown-onset epilepsy due to unknown causes. Probably this group requires a detailed diagnostic evaluation to define epilepsy more precisely. We believe the distribution of epilepsies shown in this study is representative of similar resource-poor countries with limited access to health care. However, the limitations of the study are the highly selective cohort and the small sample size.

The study cohort was highly selective and included those children who were able to attend the schools in the government sector with limited infrastructure in resource-poor countries. The spectrum of epilepsies and epilepsy syndromes seen in this study cohort was the common types of epilepsies/epilepsy syndromes seen in this age group. However, severe epilepsies were not represented in this cohort. It is very obvious that such children will not be sent to these schools. Diagnosis of epilepsy or epilepsy syndromes was established in two-thirds of children from the data available from the seizure semiology, neurologic examination, EEG findings, and contrast CT brain. In the remaining one-third of children, perhaps MR imaging might have shown a structural lesion in a very few. We have not done genetic studies in these 10 children who were otherwise healthy. Most genetic generalized and focal epilepsy syndromes seen in children are mostly polygenic and usually genetic studies are not advised. Genetic testing is often done in children with severe epilepsies like developmental and/or epileptic encephalopathies. MoBa study shows the importance of neuroimaging and genetic investigations in early-onset epilepsies.[14] The study cohort does not belong to this age group.

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Conflicts of interest

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[PUBMED]  [Full text]  
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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