Krishna B. Das

Neurobehavioral Comorbidities in Children With Active Epilepsy: A Population-Based Study

BACKGROUND: In addition to recurrent epileptic seizures, children with epilepsy can have coexisting cognitive and behavioral difficulties but the spectrum and prevalence of such difficulties are uncertain. METHODS: The Children with Epilepsy in Sussex Schools study is a prospective, community-based study involving school-aged children (5–15 years) with active epilepsy in a defined geographical area in the United Kingdom. Participants underwent comprehensive psychological assessment, including measures of cognition, behavior, and motor functioning. Consensus neurobehavioral diagnoses were made with respect to Diagnostic and Statistical Manual, Fourth Edition-Text Revision (DSM-IV-TR) criteria. RESULTS: A total of 85 children (74% of eligible population) were enrolled; 80% of children with active epilepsy had a DSM-IV-TR behavioral disorder and/or cognitive impairment (IQ <85). Intellectual disability (ID) (IQ <70) (40%), attention-deficit/hyperactivity disorder (ADHD) (33%), and autism spectrum disorder (ASD) (21%) were the most common neurobehavioral diagnoses. Of those who met criteria for a DSM-IV-TR behavioral disorder, only one-third had previously been diagnosed. Logistic regression revealed that seizures in the first 24 months compared with first seizures at 24 to 60 or 61+ months (odds ratio [OR] 13, 95% confidence interval 2.2–76.9; OR 21.3, 3.2–148.9) and polytherapy (OR 7.7, 1.6–36.3) were independently associated with ID and the presence of ID was associated with a diagnosis of ASD (OR 14.1, 2.3–87.1) after Bonferroni adjustment. Epilepsy-related factors did not independently predict the presence of behavioral disorders. CONCLUSIONS: Screening for neurobehavioral comorbidities should be an integral part of management in children with “active” epilepsy. There is a need for research to identify neurobiological mechanisms underpinning neurobehavioral impairments and studies to evaluate possible treatments.

Psychogenic nonepileptic seizures in children: A review

One of the considerations when a child presents with paroxysmal events is psychogenic nonepileptic seizures (PNES). PNES are discernible changes in behavior or consciousness that resemble epileptic seizures but are not accompanied by electrophysiologic changes. They are usually understood as the manifestation of a conversion disorder that reflects underlying psychological distress. There is a lack of population‐based data on the prevalence or incidence of PNES in pediatric populations. The prevalence of PNES in children would appear to be lower than that in the adult population, but the prevalence of PNES seems to increase with age, and nonepileptic paroxysmal events are more likely to be PNES in adolescence than earlier in childhood. In terms of manifestation, PNES in childhood have been described using various categorizations and terminology, making comparisons across studies difficult. There is some evidence that events are more likely to involve unresponsiveness in younger children and prominent motor symptoms in older children. The most common precipitating factors would appear to be school‐related difficulties and interpersonal conflict within the childs family. In terms of psychopathology, children with PNES are at high risk for symptoms of depression and anxiety. Accurate diagnosis of PNES in children is likely to involve taking a comprehensive description of the episodes, garnering the childs medical/developmental history, video‐electroencephalography (video‐EEG) to rule out epileptic seizures, and an evaluation of family functioning. The importance of effective and sensitive communication of the diagnosis of PNES has been emphasized and management approaches will typically involve multidisciplinary efforts to safely manage the events at home and at school. Interventions to reduce the effect of precipitating psychosocial stressors and the involvement of a mental health professional to treat comorbid psychopathology will also form part of an effective management plan. Outcome at follow‐up is reported to be largely positive, although studies have not been able to follow all children, and few studies have focused on predictors of a good outcome. Future controlled intervention studies using a range of outcome measures are needed to identify efficacious approaches and predictors of best outcome.

Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures.

The potassium-chloride co-transporter KCC2, encoded by SLC12A5, plays a fundamental role in fast synaptic inhibition by maintaining a hyperpolarizing gradient for chloride ions. KCC2 dysfunction has been implicated in human epilepsy, but to date, no monogenic KCC2-related epilepsy disorders have been described. Here we show recessive loss-of-function SLC12A5 mutations in patients with a severe infantile-onset pharmacoresistant epilepsy syndrome, epilepsy of infancy with migrating focal seizures (EIMFS). Decreased KCC2 surface expression, reduced protein glycosylation and impaired chloride extrusion contribute to loss of KCC2 activity, thereby impairing normal synaptic inhibition and promoting neuronal excitability in this early-onset epileptic encephalopathy.

Unusual side effects of lamotrigine therapy.

An 8-year-old boy developed tremor, unsteadiness, chorea, and eye movement abnormalities on starting lamotrigine for myoclonic jerks. Investigations for a neurodegenerative disorder were negative. Symptoms and signs resolved on stopping lamotrigine. He was well and asymptomatic on follow-up after 4 years. Another 7-year-old boy who started on lamotrigine for suspected absence seizures developed abnormalities of eye movement with associated cognitive decline, which also resolved on discontinuing the medication. Eye movement abnormalities, involuntary movements, and behavioral changes appear to be unusual side effects of lamotrigine therapy. (J Child Neurol 2003;18:479—480).

Academic achievement in school‐aged children with active epilepsy: A population‐based study

To provide population‐based data on the performance of school‐aged children with epilepsy on measures of academic achievement and factors associated with this performance after controlling for IQ.

Factors associated with quality of life in active childhood epilepsy: A population-based study

BACKGROUND Improving health-related quality of life (HRQOL), rather than just reducing seizures, should be the principal goal in comprehensive management of childhood epilepsy. There is a lack of population-based data on predictors of HRQOL in childhood epilepsy. METHODS The Children with Epilepsy in Sussex Schools (CHESS) study is a prospective, population-based study involving school-aged children (5-15 years) with active epilepsy (on one or more AED and/or had a seizure in the last year) in a defined geographical area in the UK. Eighty-five of 115 (74% of eligible population) children underwent comprehensive psychological assessment including measures of cognition, behaviour, and motor functioning. Parents of the children completed the Quality of Life in Childhood Epilepsy (QOLCE).Clinical data on eligible children was extracted using a standardised pro forma. Linear regression analysis was undertaken to identify factors significantly associated with total Quality of Life in this population. RESULTS Factors independently significantly associated (p < .05) with total QOLCE scores were seizures before 24 months, cognitive impairment (IQ < 85), anxiety, and parent reported school attendance difficulty. These factors were also significantly associated with total QOLCE when children with IQ < 50 were excluded from analysis. CONCLUSIONS The majority of factors associated with parent reported HRQOL in active childhood epilepsy are related to neurobehavioural and/or psychosocial aspects of the condition.

The health, education, and social care costs of school-aged children with active epilepsy: A population-based study

To provide data on the health, social care, and education costs of active childhood epilepsy and factors associated with these costs over an 18‐month period in a population‐based sample.

Cognition in school-aged children with “active” epilepsy: A population-based study

Introduction: There is a lack of population-based data on specific cognitive profiles in childhood epilepsy. This study sought to determine the frequency of impairments in global cognition and aspects of working memory and processing speed in a population-based sample of children with “active” epilepsy (on antiepileptic Drugs (AEDs), and/or had a seizure in the last year). Factors significantly associated with global and specific difficulties in cognition were also identified. Method: A total of 85 (74% of eligible population) school-aged children (5–15 years) with “active” epilepsy underwent comprehensive psychological assessment including assessment of global cognition, working memory, and processing speed. Scores on cognitive subtests were compared via paired-samples t tests. The factors associated with cognitive difficulties were analyzed via linear regression. Results: A total of 24% of children were functioning below IQ 50, and 40% had IQ scores below 70. Scores on the Processing Speed Index were significantly lower than scores on the Verbal or Performance indexes on Wechsler instruments. The Coding subtest was a significant weakness compared with the other Wechsler subtests. A total of 58% of children displayed “memory underachievement” (memory score 1 SD below assessed IQ) on at least one of the four administered working memory subtests. Factors significantly associated with globally impaired cognition included being on polytherapy (β = –13.0; 95% CI [–19.3, –6.6], p = .000) and having attention-deficit/hyperactivity disorder (ADHD; β = –11.1, 95% CI [–3.0, –19.3], p = .008). Being on polytherapy was also associated with lower scores on the working memory and processing speed composite scores. Having developmental coordination disorder (DCD) was associated with a lower score on the processing speed composite. Conclusions: There is a high rate of global and specific cognitive difficulties in childhood epilepsy. Difficulties are most pronounced in aspects of working memory and processing speed. Predictors of cognitive impairment in childhood epilepsy include epilepsy-related and behavioral factors, which may differ depending on the domain of cognition assessed.

Features of autism spectrum disorder (ASD) in childhood epilepsy: A population-based study

In a defined geographical area in the south of the UK, 115 children with active epilepsy (i.e., children who had seizures in the last year and/or children who were taking antiepileptic drugs (AEDs)) were identified via a computerized database and liaison with local pediatricians. Eighty-five (74%) of the children (5-15years of age) underwent a comprehensive psychological assessment. Twenty-one percent of the children met the DSM-IV-TR criteria for ASD, and 61% of those with ASD had another DSM-IV-TR behavioral or motor disorder. The Autism Spectrum Screening Questionnaire (ASSQ) was completed by parents (n=69) and by teachers (n=67) of children with an IQ>34. Only 9% of children on parent ratings and 15% of children on teacher ratings had no features of ASD. Parents reported significantly (p<.05) more features of ASD on the ASSQ compared with teachers. Factors significantly associated with responses on the ASSQ included respondent (parents reported more features), school placement (more features in specialized settings), and respondent by school placement interaction. Effective screening for ASD in children with epilepsy will need a consideration of the impact of informant and school placement on ratings. In conclusion, features of ASD were common in children with epilepsy regardless of cognitive ability. The ASSQ was a useful screening instrument in this population, and combining parent and teacher forms was optimal in terms of screening properties.

Screening for mental health disorders in active childhood epilepsy: Population-based data

BACKGROUND Children with epilepsy are at increased risk for behavioral and psychiatric disorders and it has been recommended that all children with epilepsy be screened for such conditions. There is thus a need to identify appropriate screening measures in this population. METHODS Children with active epilepsy (on AEDs and/or had a seizure in the last year) with an IQ>34 (n=69) were screened for behavioral/psychiatric disorders using the parent and teacher versions of the Strengths and Difficulties Questionnaire (SDQ) in a population-based sample. Consensus clinical diagnoses were made with respect to DSM-IV-TR data. Parent and teacher responses on the SDQ total and subscales were compared using paired samples t-tests and Pearsons correlation. The screening properties of the SDQ were explored. Regression using generalized estimating equations was used to identify predictors of responses on the SDQ. RESULTS 62% of children received a DSM-IV-TR diagnosis. On the total SDQ score the number of children identified at risk by parents (61%) was higher than the number identified by teachers (43%). Mean parent scores were significantly higher than teacher scores on the SDQ Conduct and Hyperactive subscales and total score after Bonferroni correction (adjusted alpha p<.007). Sensitivity and specificity of the SDQ total score were maximized by combining parent and teacher responses. The positive predictive values (PPVs) were much higher for the total score than the specific subscales suggesting that while the SDQ total score has good predictive ability the specific scales are less useful. Respondent (i.e., parent and teacher) was a significant predictor of scores for some but not all subscales. CONCLUSION The SDQ can be considered a promising tool for screening children with active epilepsy provided the total score is used as a screener for the presence of any DSM-IV-TR disorder and multi-informant data are used.