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Table of Contents    
Year : 2017  |  Volume : 65  |  Issue : 7  |  Page : 18-24

Comorbidities of epilepsy

1 Department of Neurology, Agadi Hospital and Sagar Hospital, Bengaluru, Karnataka, India
2 Department of Neurology, K.E.M Hospital, Parel, Mumbai, Maharashtra, India

Date of Web Publication8-Mar-2017

Correspondence Address:
H V Srinivas
Consultant Neurologist, Agadi Hospital and Sagar Hospital, Bengaluru, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/neuroindia.NI_922_16

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 » Abstract 

In epilepsy management, control of seizures is the prime objective. However, the quality of life is affected by comorbid conditions that include the neurological, neuropsychiatric, and neurobehavioural disorders. These are not only reactive processes to a chronic condition but also have a bidirectional relationship, sharing common underlying pathogenesis. This article besides addressing these issues also explores the therapeutic management. A systematic search of PubMed from Jan 2006 to August 2016 was undertaken using the terms “comorbidities” and “epilepsy.” In addition, articles specifically from India and other original papers were selected based on relevance. In this review, the neuropsychiatric, neurobehavioral (mood disorders, behaviour issues, attention deficits, psychosis), and neurologic [cognitive impairment, migraine, SUDEP-Sudden unexpected death in epilepsy (SUDEP)] comorbidities are covered in relation to epilepsy and its treatment. The incidental disorders such as hypertension, diabetes, and cancer that are mentioned in some reports have not been addressed here. Comorbidities in epilepsy are common but poorly understood and often remain unaddressed. The prevalence of comorbid conditions is considerably higher in epilepsy than seen in the general population and other chronic conditions. There is a wide spectrum of secondary disorders that have a marked impact and significantly increase the burden of the primary epilepsy condition. There is a need to acknowledge, screen, and intervene early in newly diagnosed cases for the optimal management of epilepsy.

Keywords: Cognitive, comorbidities, epilepsy, neurobehavioral, neuropsychiatric, SUDEP
Key Messages: Comorbidities are frequent and share common underlying mechanisms with epilepsy. They need to be addressed early in the course of the illness as they have a profound impact on the quality of life and complicate the therapeutic management of epilepsy.

How to cite this article:
Srinivas H V, Shah U. Comorbidities of epilepsy. Neurol India 2017;65, Suppl S1:18-24

How to cite this URL:
Srinivas H V, Shah U. Comorbidities of epilepsy. Neurol India [serial online] 2017 [cited 2021 Jan 19];65, Suppl S1:18-24. Available from:

Epilepsy is a common neurological disorder affecting nearly 70 million people worldwide, with 90% residing in developing regions. In India, the prevalence rate varies from 1.2 to 11.9/1000 population among adults.[1]

The unpredictable nature of recurrent seizures and the unconscious state during the attack is extremely frightening for both, the person with epilepsy (PWE) and the caregivers. There is also an additional burden of stigma and skewed societal attitudes that results in anxiety and depression. In addition, independent of these challenges, literature is replete with information regarding several serious comorbid conditions that occur in PWE.


Comorbidity in epilepsy is a condition that occurs in association with epilepsy, and may be a cause of epilepsy or a consequence, and may precede, co-occur, or follow the diagnosis of epilepsy.[2]

 » Materials and Methods Top

A systematic search of PubMed from January 2006 to August 2016 was undertaken using the terms “Comorbidities” and “Epilepsy,” and out of the total 1407 articles, 472 relevant articles were selected. Further, articles from India and other key original papers were also selected at the authors' discretion. In this review, the neuropsychiatric, neurobehavioral (mood disorders, behavior issues, attention deficits, psychosis), and neurologic [cognitive impairment, migraine, sudden unexpected death in epilepsy (SUDEP)] comorbidities are covered in relation to epilepsy and its treatment. The incidental disorders, such as hypertension, diabetes, and cancer, which are mentioned in some reports have not been addressed here.

 » Neuropsychiatric Comorbidity Top


Prevalence rates of psychiatric comorbidity in adults with epilepsy have varied across studies, ranging from 5.9% to 55%.[3],[4] The variability in the prevalence rates is caused by the different diagnostic methods, ranging from the Structured International Classification of Diseases (SICD) or Diagnostic Statistical Manual (DSM) criteria-based interviews to the unstructured, subjective questionnaire or scale-based surveys that tend to overrate the problems. Furthermore, the type of sample also matters, with a majority of the studies being clinic/institution-based, wherein there is a strong patient selection bias and a more pronounced and higher prevalence of psychopathology reported. In one study, a prevalence rate of as high as 80% was reported in a selected subgroup of patients with temporal lobe refractory epilepsy.[5] Community or population-based studies are more representative as well as less biased and have typically reported relatively lesser numbers.

Among these population studies, the method of ascertainment influences the prevalence rates. The Health Styles Survey [6] examined self-reported epilepsy, depression, and anxiety in 4345 respondents through a mail survey in the US, and found that people with self-reported epilepsy were twice as likely to report depression and anxiety compared to people who did not report epilepsy.

Using a similar methodology of self-reporting in an epilepsy-specific, 11-item survey of 3488 respondents in the US, the EPIC (Epilepsy Comorbidities) study reported that people with epilepsy are more likely to report neuropsychiatric disorders compared to those without epilepsy (major depression and anxiety in 32.5% and 22.4% people with epilepsy versus 25.6% and 13.9% in people without epilepsy, respectively). This study also found significantly high prevalence of bipolar disorders and attention deficit hyperactivity disorders (ADHD) in people with epilepsy.[7]

On the other hand, in the Canadian Community Health Survey (CCHS) that studied the mental health status of 36984 people using the WHO Composite International Diagnostic Interview (CIDI), the prevalence of major depressive disorders was 17.4% in PWE.[8]

In India, there few adult, population-based epidemiological studies reporting on comorbidities associated with epilepsy; however, in two clinic-based studies from South India, prevalence of psychiatric morbidity was studied in PWE and compared to that in patients with chronic asthma and healthy controls. In both studies, standardized interview protocols, i.e. the Mini International Neuropsychiatric Interview (MINI) and the SCID DSM IV, were used to ascertain psychopathology. Both studies showed significantly increased psychiatric comorbidity associated with epilepsy compared to patients with asthma and normal controls, as well as increased lifetime prevalence rates of psychiatric conditions comparable to the CCHS.[9],[10]

Overall, across studies, irrespective of the methodology used or the type of sample, there is a clear consensus that the prevalence of psychiatric comorbidity is significantly higher in people with epilepsy compared to other chronic conditions and the general population.[11],[12],[13]

Risk factors and mechanisms

Psychiatric comorbidity in epilepsy cannot be regarded as a mere reactive process to a chronic condition. The risk factors identified are biological, pharmacological, and psychosocial.[14] Psychosocial factors include a restricted lifestyle, stigma, and social rejection.[15] In two Indian studies, poor compliance to antiepileptic drugs (AEDs) and AED polytherapy were identified as additional risk factors.[9],[10]

In terms of the biological mechanisms, it is now increasingly being recognized that epilepsy is a spectrum disorder and that there are complex relationships between epilepsy, neurological and psychiatric disorders, with all sharing common underlying pathologies.[16] There is a bidirectional relationship between epilepsy and psychiatric disorders, implying that either of them can antedate or follow the other, and the modification of one increases the risk for the development of the other.[17] This bidirectional relationship has been reported in a study that showed the risk of unprovoked seizure increase during the two years before and after hospitalization for depression or psychosis.[18]

The most widely studied and reported psychopathology is depression and its bidirectional relationship with epilepsy. Depressive symptoms develop not only after the onset of epilepsy but may also precede the onset of seizures. In a community-based sample of 976 adults with active epilepsy who answered a questionnaire, the depression scores predicted seizure frequency and vice versa.[19]

The mechanism of the bidirectional relationship has been studied in both animal models and human studies. Several animal studies such as the GAERS (Genetic Absence Epilepsy Rats Study) showed that depression and anxiety preceded epilepsy and that there were possible inborn defects that led to a disrupted synaptic transmission of 5 hydroxytryptamine (HT), serotonin and norepinephrine (NE).[20]

Human studies have focused on the relationship between temporal lobe epilepsy (TLE) and major depressive disorders in imaging and genetic studies. The medial temporal lobe and its association with the limbic system, the emotional regulator in the brain, is the target in the positron emission tomography (PET) imaging study, wherein deficit 5-HT1A receptor binding is seen in medial temporal regions in depressive disorders; similar deficits are also seen in patients with TLE.[21],[22]

In the vulnerable, elderly, and pediatric populations, the presence of comorbidities result in far greater management challenges. In the elderly patients with epilepsy, an increase in the prevalence of psychiatric comorbidities (i.e., depression and anxiety disorders),[23],[24] and in children, an increase in behavioral problems, have been reported.

 » Neurobehavioral Comorbidity in Children With Epilepsy Top

Magnitude, spectrum, and risk factors

A large number of studies over a decade have unequivocally demonstrated that children with epilepsy (CWE) have significantly higher neurobehavioral comorbidities compared to the general population and children with other chronic conditions.[25],[26]

In India, in the only pediatric population-based epidemiological study, screening questionnaires and interviews with caregivers and teachers revealed significant issues impacting the psychological well being of the children and caregivers.[27]

In another Indian study, from a tertiary referral center in Vellore, children with intellectual disability were excluded and yet significant psychopathology in 53% of the CWE was found. In addition, the authors reported an unusual finding of more problems in the high-income groups unlike in the western studies, wherein the low-income groups appeared to have more issues. It was postulated that social support is an important protective factor, and in developing countries, there was greater social support in the low-income groups compared to the nuclear families of the high-income groups.[28]

In a recent study from Mumbai, 222 CWE were compared to a control group of 226 matched children without epilepsy. The Strengths and Difficulties Questionnaire was administered and academic records were examined. The authors found that 39.1% of CWE had behavioral problems as compared to 7.9% children without epilepsy.[29]

The spectrum of behavioral disorders has been studied in several population-based studies. In one of the most comprehensive US national studies, the authors reported significantly increased depression, anxiety, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), developmental delays, and conduct disorders in CWE compared to the general population.[30]

In a recent, prospective, community “Children with Epilepsy in Sussex Schools” (CESS) study in the UK, school children with active epilepsy were evaluated with valid, disorder-specific instruments and DSM IV text revision (TR) criteria and 80% had behavioural, and/or cognitive problems with 40% suffering from intellectual disability (ID) 33% from attention disorders (ADHD), and 21% from autism (ASD).[31]

The significantly higher prevalence of attention disorders reported consistently across studies are of concern because they impact academic learning and school performance.[32],[33],[34],[35] ADHD is characterized by hyperactivity, impulsivity, and inattention, and in CWE, it is the inattention type of disorder that has been frequently observed.[32]

The risk factors for behavioral issues are wide ranging and include the presence of early abnormal developmental trajectories,[36] catastrophic childhood epilepsy syndromes,[37] anti-epileptic drug (AED) polypharmacy,[38] abnormalities in the brain morphology,[39] and early age of seizure onset.[40]

 » Neurological Comorbidities Top

Migraine and epilepsy

Migraine and epilepsy are reported to occur together independent of the seizure type, age of onset, and etiology,[41] and may have a common genetic susceptibility.[42] In a review of 13 studies, the prevalence of epilepsy in patient with migraine ranged from 1–17% with a median of 5.9%,[43] while in another study from India, migraine was observed in 26% among PWE as against 15% in the control group.[44]


Premature mortality in people with epilepsy is well recognized. This could be due to epilepsy causative factors (tumors, cerebrovascular disease) or may be related to the seizures (accidental drowning or road traffic accidents), status epilepticus, or due to comorbid depression leading to suicide. In addition, a small but significant number of people with epilepsy have sudden unexpected death in epilepsy (SUDEP). The incidence of SUDEP varies from 0.1 for 1000 person years in population-based cohorts of newly diagnosed patients, 2–5 per 1000 person years in chronic cases, and up to 9 per 1000 among candidates for epilepsy surgery.[45]

As the term implies, death is unexpected and sudden without any obvious cause. However, it occurs more commonly in young adults with refractory epilepsy having tonic–clonic seizures, on AED polytherapy, and during sleep. It is presumed that a seizure induced cardiorespiratory event is responsible,[46] and in one study, a long-term electrocardiogram monitoring, over several months, detected ictal asystole in 3 out of 20 (15%) patients.[47] It is critical to recognize the existence of SUDEP and to prevent it by managing refractory epilepsy more aggressively.

In addition to SUDEP, there is a growing concern regarding the incidence of suicidality associated with epilepsy.[48] A bidirectional relationship has been suggested wherein there is not only a higher risk of suicide among people with epilepsy but also a five-fold higher risk for developing epilepsy among individuals who exhibited suicidality prior to the onset of epilepsy.[17] The risk of suicide is 2.4 times higher in PWE, 11–12 times higher in those with epilepsy and anxiety or psychosis, and 32 times higher in those with epilepsy and depression.[49] The risk is significantly higher in PWE with TLE [50] especially in conjuction with exposure to certain AEDs.[51]

Cognitive impairment

Cognitive impairment, although frequent, is often underreported and unaddressed despite its significant impact on the quality of life.[52],[53] Multifactorial causes [54] include (1) underlying structural brain damage and MRI volumetric anomalies,[55],[56] (2) seizure duration [57] and its increased frequency,[58] and (3) effects of AEDs.[59] Certain AEDs also affect the developing fetus of mothers with epilepsy, with the offspring having a lower intelligence quotient (IQ) score.[60],[61]

In newly diagnosed CWE, impairments may antedate epilepsy, with the early cognitive compromise being further magnified by the onset of epileptogenesis, and later on, by the chronicity of seizures.[62],[63],[64]

A pattern of generalized, diffuse cognitive impairment and low intelligence is reported for both idiopathic localization related and primary generalized epilepsies.[62] Domain-specific memory impairment in TLE has been the focus of most studies. However, in TLE, extra-temporal deficits have been found suggesting a more widespread network dysfunction [65],[66] and the presence of different cognitive phenotypes even in localization-related TLE.[67]

A major concern is whether or not seizures cause progressive cognitive impairment,[68] impacting the life span [69] and leading to adverse cognitive aging in the later years of life.[70] Longitudinal serial magnetic resonance imaging (MRI) has revealed progressively decreasing volumes in patients with unilateral TLE with continuing seizures.[71] However, the results of other longitudinal studies have yielded mixed results with some reporting a decline,[72],[73] and others, a stable, long-term functioning.[74],[75] A follow-up evaluation, after 3–8 years, of newly diagnosed patients of the multicenter, randomized clinical trial, SANAD (Standard and New Antiepileptic Drugs) study revealed that, although several cognitive measures remained stable, there was a significant decline in the psychomotor speed and memory. Mood issues impacted test performance; however, due to the heterogeneity in demographics and seizure variables, all risk factors could not be identified.[76]

Of interest is also whether or not cognitive impairments persist even after seizures are controlled. Problems are known to persist if there is an underlying brain damage or developmental encephalopathy. However, even in other types of epilepsy, despite seizure control, certain subtle residual cognitive difficulties remain.[77],[78]

Epilepsy surgery is regarded as curative, and postoperative seizure freedom and AED stoppage should arrest cognitive decline. However, a systematic review revealed a pooled estimate of 44% risk of verbal memory decline and 34% risk for naming difficulties after left temporal lobe surgery.[79] Factors that predicted memory decline after surgery included dominant temporal lobe resections, preoperative normal memory scores, older age at onset, absence of hippocampal sclerosis, and lack of seizure control after surgery.[80]

The decline in verbal memory after dominant temporal lobe surgery has been consistently reported; however, the percentages vary across studies, and there is limited data regarding long-term outcomes after surgery. In a recent study conducted in India, an improvement as well as decline in a subset of patients after surgery was found, but the decline percentage was less than that reported in western studies.[81],[82] In another study from India, memory improvement was reported after the nondominant lobe resection, in patients who achieved a seizure-free status.[83]

In a longitudinal, prospective, controlled study performed 10 years after temporal lobe surgery, the authors reported an initial verbal memory decline in the first 2 years after dominant lobe surgery; however, subsequently, no further decline was noted in the long term, negating the notion that there may be ongoing progressive decline after surgery.[84]

Multiple psychosocial issues of daily life restrictions, educational, and vocational marginalization, low self-esteem, and stigma are frequently associated with epilepsy,[85] and sometimes persist even after a person becomes seizure free, resulting in what is known as the “burden of normality.”[86]

Overall, cognitive, psychiatric, behavioral, and psychosocial problems occur in all types of epilepsy in varying degrees, in both chronic as well as newly diagnosed patients and are a huge burden for patients and families. Hence, it is now strongly recommended that all newly diagnosed patients be screened and tracked for timely intervention.[87]

 » Management in Epilepsy With Comorbidities Top

A comprehensive epilepsy management must go beyond seizure control and include the addressal of comorbidities to improve the quality of life.[88] It is important to be aware of the different types of comorbidities and the various drugs that can optimize or worsen epilepsy and comorbidity management [Table 1].[89],[90],[91] Future research has to be directed at understanding the common pathogonomic pathways to address epilepsy and the comorbidities with the same therapy.
Table 1: Drugs to be preferred and avoided in epilepsy and comorbidity

Click here to view

 » Conclusions Top

Comorbidities in epilepsy have remained invisible due to poor awareness among patients, families, and treating physicians. The high prevalence of a number of comorbidities in epilepsy complicates the management and significantly increases the burden of epilepsy. The report of the International League Against Epilepsy (ILAE) Commission states that epilepsy should no longer be regarded as benign in view of the large number of comorbidities associated with even relatively uncomplicated epilepsies.[92] The time has come to acknowledge and understand these problems to be able to manage them effectively at the very onset of epilepsy.


We would like to acknowledge the help of Ms Tanvi Dingankar for the PubMed Search.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest

 » References Top

Amudhan S, Gopalkirshna G, Satishchandra P. Epilepsy in India 1: Epidemiology and public health. Ann Indian Acad Neurol 2015;18:263-77.  Back to cited text no. 1
[PUBMED]  [Full text]  
Feinstein AR. The pre-therapeutic classification of comorbidity in chronic disease. J Chronic Dis 1973;23:455-69.  Back to cited text no. 2
Gatatziz A, Trimble MR, Sander JW. Psychiatric comorbidity in epilepsy. Acta Neurol Scand 2004;110:207-20.  Back to cited text no. 3
Gudmundsson G. Epilepsy in Iceland. A clinical and epidemiological investigation. Acta Neurol Scand 1966;43:124.  Back to cited text no. 4
Perini GI, Tosin C, Carraro C, Bernasconi G, Canevini MP, Canger R, et al. Interictal mood and personality disorders in temporal lobe epilepsy and juvenile myoclonic epilepsy. J Neurol Neurosurg Psychiatry 1996;61:601-5.  Back to cited text no. 5
Kobau R, Gilliam F, Thurman DJ. Prevalence of self-reported epilepsy or seizure disorder and its associations with self-reported depression and anxiety: Results from the 2004 Healthstyles Survey. Epilepsia 2006;47:1915-21.  Back to cited text no. 6
Ottman R, Lipton R, Etinger AB, Wan GJ. Comorbidities of epilepsy: Results from the Epilepsy Comorbidities and Health (EPIC) survey Epilepsia 2011;52:308-15.  Back to cited text no. 7
Tellez-Zenteno J, Patten S B, Jette N, Williams J, Wiebe S. Psychiatric comorbidity in epilepsy: A population-based analysis. Epilepsia 2007;48:2336-44.  Back to cited text no. 8
Jacob R, Tharyan P. Psychiatric comorbidity and quality of life in people with epilepsy. German J Psychiatry 2010;13:79-85.  Back to cited text no. 9
Amruth G, Praveen-Kumar S, Nataraju B, Kasturi P. Study of psychiatric comorbidities in epilepsy by using the Mini International Neuropsychiatric Interview. Epilepsy Behav 2014;33:94-100.  Back to cited text no. 10
Brooks-Kayal A, Bath KG, Berg AT, Galanopoulou AS, Holmes GL, Jensen FE, et al. Issues related to symptomatic and disease-modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy. Epilepsia 2013;54(Suppl 4):44-60.  Back to cited text no. 11
Jalava M, Sillanpaa M. Concurrent illnesses in adults with childhood onset epilepsy: A population-based 35-year follow-up study. Epilepsia 1996;37:1155-63.  Back to cited text no. 12
Swinkels WA, Kuyk J, de Graaf EH, van Dyck R, Spinhoven P. Prevalence of psychopathology in Dutch epilepsy inpatients: A comparative study. Epilepsy Behav 2001;2:441-7.  Back to cited text no. 13
Torta R, Keller R. Behavioral, psychotic, and anxiety disorders in epilepsy: Etiology, clinical features, and therapeutic implications. Epilepsia 1999;40:S2-20.  Back to cited text no. 14
De Boer HM, Mula M, Sander JW. The global burden and stigma of epilepsy. Epilepsy Behav 2008;12:540-6.  Back to cited text no. 15
Sensen FE. Epilepsy as a spectrum disorder: Implications from novel clinical and basic neuroscience. Epilepsia 2011;52(Suppl 1):1-6.  Back to cited text no. 16
Hesdorffer DC, Hauser WA, Olafsson E, Ludvigsson P, Kjartansson O. Depression and suicide attempt as risk factors for incident unprovoked seizures. Ann Neurol 2006;59:35- 41.  Back to cited text no. 17
Adelow C, Andersson T, Ahlbom A, Tomson T. Hospitalisation for psychiatric disorders before and after onset of unprovoked seizures/epilepsy Neurology 2012;78:396-401.  Back to cited text no. 18
Thapar A, Roland M, Harold G. Do depression symptoms predict seizure frequency – or vice versa? J Psychosom Res 2005;59:269-74.  Back to cited text no. 19
Jones NC, Salzberg MR, Kumar G, Couper A, Morris MJ, O'Brien TJ. Elevated anxiety and depressive-like behavior in a rat model of genetic generalized epilepsy suggesting common causation. Exp Neurol 2008;209:254-60.  Back to cited text no. 20
Toczek MT, Carson RE, Lang L, Ma Y, Spanaki MV, Der MG, et al. PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy. Neurology 2003;60:749-56.  Back to cited text no. 21
Hasler G, Bonwetsch R, Giovacchini G, Toczek MT, Bagic A, Luckenbaugh DA, et al. 5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression. Biol Psychiatry. 2007; 62:1258–64.  Back to cited text no. 22
Kanner AM, Nieto JC. Depressive disorders in epilepsy. Neurology 1999;53 (5 Suppl 2):S26-32.  Back to cited text no. 23
Steffens DC, Skoog I, Norton MC, Hart AD, Tschanz JT, Plassman BL, et al. Prevalence of depression and its treatment in an elderly population: The Cache County study. Arch Gen Psychiatry 2000;57:601-7.  Back to cited text no. 24
McDermott S, Mani S, Krishnaswami S. A population-based analysis of specific behavior problems associated with childhood seizures. J Epilepsy 1995;8:110-8.  Back to cited text no. 25
Davies S, Heyman I, Goodman R. A population survey of mental health problems in children with epilepsy. Dev Med Child Neurol 2003;45:292-5.  Back to cited text no. 26
Hackett R, Hackett L, Bhakta P. Psychiatric disorder and cognitive function in children with epilepsy in Kerala, south India. Seizure 1998;7:321-4.  Back to cited text no. 27
Datta SS, Premkumar TS, Chandy S, Kumar S, Kirubakaran C, Gnanamuthu C, et al. Behaviour problems in children and adolescents with seizure disorder: Associations and risk factors. Seizure 2005;14:190-7.  Back to cited text no. 28
Anita M, Mona PG, Maninde S. Neurobehavioral comorbidities in children with epilepsy. J Neurol Neurophysiol 2016;7:1-6.  Back to cited text no. 29
Russ SA, Larson K, Halfon N. A national profile of childhood epilepsy and seizure disorder. Pediatrics 2012;129:256-64.  Back to cited text no. 30
Reilly C, Atkinson P, Krishna BD, Chin RFMC, Aylett SE, Victoria Burch V, et al. Neurobehavioral comorbidities in children with active epilepsy: A population-based study. Pediatrics 2014;133:1586-93.  Back to cited text no. 31
Dunn DW, Austin JK, Harezlak J, Ambrosius WT. ADHD and epilepsy in childhood. Dev Med Child Neurol 2003;45:50-4.  Back to cited text no. 32
Hermann BP, Jones JE, Sheth R, Koehn M, Becker T, Fine J, et al. Growing up with epilepsy: A two-year investigation of cognitive development in children with new onset epilepsy. Epilepsia 2008;49:1847-58.  Back to cited text no. 33
Thome-Souza S, Kuczynski E, Assumpcao F Jr, Rzezak P, Fuentes D, Fiore L, et al. Which factors may play a pivotal role on determining the type of psychiatric disorder in children and adolescents with epilepsy? Epilepsy Behav 2004;5:988-94.  Back to cited text no. 34
Davis SM, Katusic SK, Barbaresi WJ, Killian J, Weaver AL, Ottman R, et al. Epilepsy in children with attention-deficit/hyperactivity disorder. Pediatr Neurol 2010;42:325-30.  Back to cited text no. 35
Brooks-Kayal A. Molecular mechanisms of cognitive and behavioral comorbidities of epilepsy in children Epilepsia 2011;52:13-20.  Back to cited text no. 36
Raha S, Shah U, Udani V. Neurocognitive and neurobehavioral disabilities in epilepsy with electrical status epilepticus in slow sleep (ESES) and related syndromes. Epilepsy Behav 2012;25:381-5.  Back to cited text no. 37
ChoudharyA, Gulati S, Sagar R, Kabra M, Sapra S. Behavioral comorbidity in children and adolescents with epilepsy. J Clin Neurosci 2014;21:1337-40.  Back to cited text no. 38
Saute R, Dabbs K, Jones JE, Jackson DC, Seidenberg M, Hermann BP. Brain morphology in children with epilepsy and ADHD. PLOS One. 2014;9:e95269.  Back to cited text no. 39
Hoie B, Sommerfelt K, Waaler P, Alsaker FD, Skeldsvoll H, Mykleturn A. Psychosocial problems and seizure related factors in children with epilepsy. Dev Med and Child Neurol 2006;48:213-9.  Back to cited text no. 40
Ottman R, Lipton RB, Comorbidity of migraine and epilepsy. Neurology 1994;44:2105-10.  Back to cited text no. 41
Clarke T, Baskurt Z, Strug LJ, Pal DK. Evidence of shared genetic risk factors for migraine and Rolandic epilepsy. Epilepsia 2009;50:2428-33.  Back to cited text no. 42
Andermann E, Andermann F. Migraine-epilepsy relationships: Epidemiological and genetic aspects. In: Andermann FA, Lugaresi E, editors. Migraine and Epilepsy. Boston: Butterworths; 1978. pp. 281-91.  Back to cited text no. 43
Shyam Babu C, Satishchandra P, Sinha S, Subbakrishna DK. comorbidities in people living with epilepsy. Hospital based case-control study from a resource poor setting Epilepsy Res 2009;80:146-52.  Back to cited text no. 44
Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in epilepsy: Current knowledge and future directions. Lancet Neurol 2008;7:1021-31.  Back to cited text no. 45
So EL. Demystifying sudden unexpected death in epilepsy – Are we close? Epilepsia 2006;47(Suppl 1):87-92.  Back to cited text no. 46
Ryvlin P, Montavont A, Kahane P. Sudden unexpected death in epilepsy from mechanism to prevention. Curr Opin Neurol 2006;19:194-9.  Back to cited text no. 47
Jones JE, Hermann DD, Barry JJ, Gilliam FG, Kanner AM, Meador KJ. Rates and risk factors for suicide, suicidal ideation and suicide attempts in chronic epilepsy. Epilepsy Behav 2003;4:S31-8.  Back to cited text no. 48
Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and risk of suicide: A population-based case – control study. Lancet Neurol 2007;6:693-8.  Back to cited text no. 49
Robertson MM. Suicide, parasuicide, and epilepsy. In: Engel J, Pedley TA, editors. Epilepsy: A Comprehensive Textbook. Philadelphia: Lippincott–Raven; 1997. pp. 2141-51.  Back to cited text no. 50
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Sciences, Office of Biostatistics (2008). Statistical review and evaluation: Antiepileptic drugs and suicidality. May 21, 2008.  Back to cited text no. 51
Witt JA, Helmstaedter C. Should cognition be screened in new-onset epilepsies? A study in 247 untreated patients. J Neurol 2012;259:1727-31.  Back to cited text no. 52
Witt JA, Helmstaedter C. Cognition in the early stages of adult epilepsy. Seizure 2015;26:65-8.  Back to cited text no. 53
Rudzinski LA, Meador KJ. Epilepsy and neuropsychological comorbidities. Continuum 2013;19:682-96.  Back to cited text no. 54
Baxendale SA, van Paesschen W, Thompson PJ, Connelly A, Duncan JS, Harkness WF, et al. The relationship between quantitative MRI and neuropsychological functioning in temporal lobe epilepsy. Epilepsia 1998;39:158-66.  Back to cited text no. 55
Griffith HR, Pyzalski RW, Seidenberg M, Hermann BP. Memory relationships between MRI volumes and resting PET metabolism of medial temporal lobe structures. Epilepsy Behav 2004;5:669-76.  Back to cited text no. 56
Jokeit H, Ebner A. Long term effects of refractory temporal lobe epilepsy on cognitive abilities: A cross-sectional study. J Neurol Neurosurg Psychiatry 1999;67:44-50.  Back to cited text no. 57
Helmstaedter C, Kurthen M, Lux S, Reuber M, Elger CE. Chronic epilepsy and cognition: A longitudinal study in temporal lobe epilepsy. Ann Neurol 2003;54:425-32.  Back to cited text no. 58
Kwan P, Brodie MJ. Neuropsychological effects of epilepsy and antiepileptic drugs. Lancet 2001;357:216-22.  Back to cited text no. 59
Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med 2009;360:1597-605.  Back to cited text no. 60
Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): A prospective observational study. Lancet Neurol 2013;12:244-52.  Back to cited text no. 61
Hermann B, Jones J, Sheth R, Dow C, Koehn M, Seidenberg M. Children with new-onset epilepsy: Neuropsychological status and brain structure. Brain 2006;129:2609-19.  Back to cited text no. 62
Hermann BP, Jones JE, Jackson DC, Seidenberg M. Starting at the beginning: The neuropsychological status of children with new-onset epilepsies. Epileptic Disord 2012;14:12-21.  Back to cited text no. 63
Oostrom KJ, Smeets-Schouten A, Kruitwagen CL, Peters AC, Jennekens-Schinkel A. Not only a matter of epilepsy: Early problems of cognition and behavior in children with “epilepsy only”— A prospective, longitudinal, controlled study starting at diagnosis. Pediatrics 2003;112:1338-44.  Back to cited text no. 64
Dabbs K, Jones J, Seidenberg M, Hermann B. Neuroanatomical correlates of cognitive phenotypes in temporal lobe epilepsy. Epilepsy Behav 2009;15:445-51.  Back to cited text no. 65
Stretton J, Thompson PJ. Frontal lobe function in temporal lobe epilepsy. Epilepsy Res 2012;98:1-13.  Back to cited text no. 66
Hermann B, Seidenberg M. Epilepsy and cognition. Epilepsy Currents 2007;7:1-6.  Back to cited text no. 67
Seidenberg M, Pulsipher DT, Hermann B. Cognitive progression in epilepsy. Neuropsychol Rev 2007;17:445-54.  Back to cited text no. 68
Whalley LJ, Starr JM, Athawes R, Hunter D, Pattie A, Deary IJ. Childhood mental ability and dementia. Neurology 2000;55:1455-9.  Back to cited text no. 69
Martin RC, Griffith HR, Faught E, Gilliam F, Mackey M, Vogtle L. Cognitive functioning in community dwelling older adults with chronic partial epilepsy. Epilepsia 2005;46:298-303.  Back to cited text no. 70
Fuerst D, Shah J, Shah A, Watson C. Hippocampal sclerosis is a progressive disorder: A longitudinal volumetric MRI study. Ann Neurol 2003;53:413Y416.  Back to cited text no. 71
Helmstaedter C, Kurthen M, Lux S, Johanson K, Quiske A, Schramm J, et al. Temporal lobe epilepsy: Longitudinal clinical, neuropsychological and psychosocial follow-up of surgically and conservatively managed patients. Nervenarzt 2000;71:629-42.  Back to cited text no. 72
Hermann BP, Seidenberg M, Dow C, Jones J, Rutecki P, Bhattacharya A, et al. Cognitive prognosis in chronic temporal lobe epilepsy. Ann Neurol 2006;60:80-7.  Back to cited text no. 73
Holmes MD, Dodrill CB, Wilkus RJ, Ojemann LM, Ojemann GA. Is partial epilepsy progressive? Ten-year follow-up of EEG and neuropsychological changes in adults with partial seizures. Epilepsia 1998;39:1189-93.  Back to cited text no. 74
Griffith HR, Martin RC, Bambara JK, Faught E, Vogtle LK, Marson DC. Cognitive functioning over 3 years in community dwelling older adults with chronic partial epilepsy. Epilepsy Res 2007;74:91-6.  Back to cited text no. 75
Taylor J, Baker GA. Newly Diagnosed Epilepsy: Cognitive outcomes at 5 years. Epilepsy Behav 2010;18:397-403.  Back to cited text no. 76
Berg AT, Langfitt JT, Testa FM, Levy SR, DiMario F, Westerveld M, Kulas J. Residual cognitive effects of uncomplicated idiopathic and cryptogenic epilepsy. Epilepsy Behav 2008;13:614-9.  Back to cited text no. 77
Berg AT. Epilepsy, cognition, and behavior: The clinical picture. Epilepsia 2011;52:7-12.  Back to cited text no. 78
Sherman EM1, Wiebe S, Fay-McClymont TB, Tellez-Zenteno J, Metcalfe A, Hernandez-Ronquillo L, et al. Neuropsychological outcomes after epilepsy surgery: Systematic review and pooled estimates: Cognitive change after epilepsy surgery. Epilepsia 2011;52:857-69.  Back to cited text no. 79
Helmstaedter C. Neuropsychological aspects of epilepsy surgery. Epilepsy Behav 2004;5(Suppl 1):S45-55.  Back to cited text no. 80
Shah U, Desai A, Ravat S, Muzumdar D, Godge Y, Sawant N, Jain M, et al. Memory outcomes in mesial temporal lobe epilepsy surgery. Int J Surg 2015.  Back to cited text no. 81
Narenmandula B, Zhou X, Li Y, Tu D, Bao Y, Zheng R, Xu H. Effects of white matter microstructure lesions on language and memory function in magnetic resonance imaging-negative temporal lobe epilepsy determined by diffusion tensor imaging. Neurol India 2016;64:1233-42  Back to cited text no. 82
Sanyal SK1, Chandra PS, Gupta S, Tripathi M, Singh VP, Jain S, et al. Memory and intelligence outcome following surgery for intractable temporal lobe epilepsy: Relationship to seizure outcome and evaluation using a customized neuropsychological battery. Epilepsy Behav 2005;6:147-55.  Back to cited text no. 83
Rosswall LA, Engman E, Samuelson H, Malmgren K. Cognitive outcomes 10 years after temporal lobe epilepsy surgery: A prospective controlled study. Neurology 2010;74:1977.  Back to cited text no. 84
Jacoby A, Baker GA, Steen N, Potts P, Chadwick DW. The clinical course of epilepsy and its psychosocial correlates: Findings from a U.K. Community study. Epilepsia 1996;37:148-61.  Back to cited text no. 85
Wilson S, Baldin P, Saling M. The “burden of normality”: Concepts of adjustment after surgery for seizures. J of Neurol Neurosurg Psychiatry 2001;70:649-56.  Back to cited text no. 86
Witt JA, Helmstaedter C. Cognition in the early stages of adult epilepsy. Seizure 2015;26:65-8.  Back to cited text no. 87
Rakesh PS, Ramesh R, Rachel P, Chanda R, Satish N, Mohan VR. Quality of life among people with epilepsy: A cross sectional study from rural southern India. Natl Med J India 2012;25:261-4.  Back to cited text no. 88
Sirven JI. Management of epilepsy comorbidities. Continuum 2016;22:191-203.  Back to cited text no. 89
Agrawal N and Govender S. Epilepsy and neuropsychiatric comorbidities. Adv Psychiatric Treat 2011;17:44-53.  Back to cited text no. 90
Newale S, Bachani DS. Demographic characteristics of epilepsy patients and antiepileptic drug utilization in adult patients: Results of a cross-sectional survey. Neurol India 2016;64:1180-6.  Back to cited text no. 91
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Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van EMde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010;51:676-85.  Back to cited text no. 92


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