[Show abstract][Hide abstract] ABSTRACT: Methods:
Children (5-15years) with active epilepsy were screened using the parent-report (n=69) and self-report (n=48) versions of the Spence Children's Anxiety Scale (SCAS) and the self-report version of the Children's Depression Inventory (CDI) (n=48) in a population-based sample.
A total of 32.2% of children (self-report) and 15.2% of children (parent-report) scored ≥1 SD above the mean on the SCAS total score. The subscales where most difficulty were reported on parent-report were Physical Injury and Separation Anxiety. There was less variation on self-report. On the CDI, 20.9% of young people scored ≥1 SD above the mean. Children reported significantly more symptoms of anxiety on the SCAS total score and three of the subscales (p<.05). There was a significant effect on the SCAS total score of respondents by seizure type interaction, suggesting higher scores on SCAS for children with generalized seizures on self- but not parent-report. Higher CDI scores were significantly associated with generalized seizures (p>.05).
Symptoms of anxiety were more common based on self-report compared with parent-report. Children with generalized seizures reported more symptoms of depression and anxiety.
[Show abstract][Hide abstract] ABSTRACT: Objective
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.Methods
The Children with Epilepsy in Sussex Schools (CHESS) study is a population-based study involving school-aged children (5–15 years) with active epilepsy (taking one or more antiepileptic drug and/or had a seizure in the last year) in a defined geographical area in England. Clinical data were collected on 85 children (74% of eligible population) who underwent comprehensive psychological assessment. Health, education, and social care resource use was collected retrospectively over an 18-month period. Regression analysis was used to identify variables associated these with costs.ResultsThe mean (standard deviation) 18-month cost of health care for a child with active epilepsy was £3,635 (£5,339), with mean education and social care cost of £11,552 (£8,937) and £1,742 (£8,158), respectively, resulting in total mean costs per participant of £16,931 (£14,764). Health care costs were significantly associated with seizure frequency and etiology (all p-values < 0.05). Combined health care, social care, and education costs were significantly related to cognitive impairment (intelligence quotient [IQ] <85) and seizure frequency (p < 0.05). The mean cost of health care, social care, and education over 18 months for participants with cognitive impairment was £23,579 (95% confidence interval [CI] £16,489–£30,670) compared to £7,785 (95% CI £4,943–£10,627) for those without impairment.SignificanceActive childhood epilepsy has significant health, social care, and education costs. This is the first study to comprehensively document the economic impact on these sectors as well as factors associated with these costs. When caring for children with epilepsy in England, costs incurred by education and social care sectors are approximately four times the costs incurred by the health care sector. Increased costs were associated with cognitive impairment (IQ <85) and weekly or greater seizure frequency.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Journal of Clinical and Experimental Neuropsychology 04/2015; 37(4):1-10. DOI:10.1080/13803395.2015.1024103 · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberous sclerosis complex (TSC) is associated with intellectual disability, but the risk pathways are poorly understood.
The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of the natural history of TSC. One hundred and twenty-five UK children age 0-16 years with TSC and born between January 2001 and December 2006 were studied. Intelligence was assessed using standardized measures at ≥2 years of age. The age of onset of epilepsy, the type of seizure disorder, the frequency and duration of seizures, as well as the response to treatment was assessed at interview and by review of medical records. The severity of epilepsy in the early years was estimated using the E-Chess score. Genetic studies identified the mutations and the number of cortical tubers was determined from brain scans.
TSC2 mutations were associated with significantly higher cortical tuber count than TSC1 mutations. The extent of brain involvement, as indexed by cortical tuber count, was associated with an earlier age of onset and severity of epilepsy. In turn, the severity of epilepsy was strongly associated with the degree of intellectual impairment. Structural equation modelling supported a causal pathway from genetic abnormality to cortical tuber count to epilepsy severity to intellectual outcome. Infantile spasms and status epilepticus were important contributors to seizure severity.
The findings support the proposition that severe, early onset epilepsy may impair intellectual development in TSC and highlight the potential importance of early, prompt and effective treatment or prevention of epilepsy in tuberous sclerosis.
Psychological Medicine 04/2015; 45(11):1-11. DOI:10.1017/S0033291715000264 · 5.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Childhood epilepsy is associated with a range of neurobehavioural comorbidities including Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), motor impairments and emotional problems. These difficulties frequently have a greater impact on quality of life than seizures. Pathological Demand Avoidance (PDA) is a term increasingly in use in the UK and Europe to describe behaviours associated with an extreme resistance to demands and requests and the need to be in control in social interactions. In a population-based group of 85 children with epilepsy, four (5%) were identified as displaying significant symptoms of PDA, were assessed using the Extreme Demand Avoidance Questionnaire (EDA-Q) and are described in detail. As well as significant symptoms of PDA, the four children met criteria for a range of neurobehavioural disorders; all four had cognitive impairment (IQ < 85) and met DSM-IV-TR criteria for ADHD. Three, in addition, met criteria for ASD and Developmental Coordination Disorder (DCD) and two for Oppositional Defiant Disorder (ODD). All four experienced their first seizure before 5 years of age. School and parent reports indicated very significant functional impairment and management concerns, particularly with respect to complying with everyday demands. Symptoms of PDA should be considered when evaluating neurobehavioural comorbidity in childhood epilepsy.
Research in Developmental Disabilities 12/2014; 35(12):3236–3244. DOI:10.1016/j.ridd.2014.08.005 · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
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.Methods
Eighty-five (74%) of 115 children with “active” epilepsy (experienced a seizure in the past year and/or on antiepileptic drugs [AEDs]) underwent psychological assessment including measures of IQ, aspects of working memory and processing speed. Sixty-five of the 85 were able to complete subtests on the Wide Range Achievement Test–Fourth Edition (WRAT-4). Paired sample t-tests were conducted to compare subtest scores. Factors associated with academic performance after controlling for IQ were examined using linear regression.ResultsSeventy-two percent of the children, who could complete subtests on the WRAT-4, displayed “low achievement” (1 standard deviation [SD] below test mean) and 42% displayed “underachievement” (1 SD below assessed IQ) on at least one of the four WRAT-4 subtests. The mean scores on the Math Computation subtest and Sentence Comprehension subtest were significantly lower than scores on the Word Reading (p < 0.05) and Spelling (p < 0.001) subtests. Younger age at seizure onset was associated (p < 0.05) with decreased scores on three of the four WRAT-4 subtests after controlling for IQ. Difficulties with auditory working memory were associated with difficulties on reading comprehension (p < 0.05), and parent-reported difficulties with school attendance were associated with decreased scores on the Spelling and Word Reading subtests after controlling for IQ (p < 0.05).SignificanceDifficulties with academic achievement are common in school-aged children with “active” epilepsy. Much of the difficulties can be attributed to lowered global cognition. However, specific cognitive deficits, younger onset of first seizure, and school attendance difficulties may contribute to difficulties independent of global cognition. There is a need to screen all children with “active” epilepsy for difficulties in school achievement, to identify contributory factors and to identify efficacious interventions for ameliorating such difficulties.
[Show abstract][Hide abstract] ABSTRACT: Most patients with tuberous sclerosis complex (TSC) suffer from epilepsy, and many have cognitive and behavioral problems like severe intellectual disability, autism, and hyperactivity. Only rare patients with TSC and autism have a normal intelligence quotient. We report a 13-year-old girl with definite TSC who had early-onset severe epilepsy, autistic behavior, and moderate developmental delay. By school age, however, she had normal intelligence; her intelligence quotient was at least 70 based on a Stanford-Binet test that she refused to complete. She showed good reading, writing, and language comprehension skills, and the special abilities of hyperlexia, hypermnesia, and hypercalculia. However, she did not speak. Criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and her Childhood Autism Rating Scale score of 36 indicated mild to moderate autism. She had severe electroencephalographic abnormalities: hypsarrhythmia, multifocal or generalized epileptiform discharges, and electrical status epilepticus during sleep, with a continuous left temporal focus. Magnetic resonance imaging showed many cortical tubers in all brain lobes, and subependymal nodules. We discuss possible explanations for her lack of speech. Considered as speech apraxia, her mutism could be either a symptom of her TSC or a component of her autism. Another possibility is that long-lasting electrical status epilepticus during sleep led to her autistic behavior and language arrest. Still another possibility is that a disinhibited mammalian target of rapamycin (mTOR) pathway was at the root of all of her neuropsychiatric symptoms.
Cognitive and behavioral neurology: official journal of the Society for Behavioral and Cognitive Neurology 06/2014; 27(2):88-95. DOI:10.1097/WNN.0000000000000026 · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: We draw attention to a number of important considerations in the arguments about screening and outcome of intervention in children with autism and other developmental disorders. Autism screening in itself never provides a final clinical diagnosis, but may well identify developmental deviations indicative of autism-or of other developmental disorders-that should lead to referral for further clinical assessment. Decisions regarding population or clinic screening cannot be allowed to be based on the fact that prospective longitudinal RCT designs over decades could never be performed in complex developmental disorders. We propose an alternative approach. Early screening for autism and other developmental disorders is likely to be of high societal importance and should be promoted and rigorously evaluated.
Journal of Autism and Developmental Disorders 02/2014; 44(8). DOI:10.1007/s10803-014-2070-5 · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infantile spasms (IS) have long been suspected to be a risk factor for impairment in intellectual development, but there are no controlled, prospective longitudinal data in well-characterized conditions to confirm this suspicion. We tested the hypothesis in a longitudinal study of children with tuberous sclerosis (TS), who have a high risk of developing IS.
Eleven infants with TS were recruited and studied longitudinally using the Mullen Scales of Early Learning. Seizure histories were assessed using a structured parent interview and by review of medical notes. Intellectual development was examined in relation to the onset and length of exposure to IS and other types of seizures.
Six children developed IS and five children developed other types of seizure disorders. Among those that developed IS, estimated mean IQ dropped significantly (nonparametric test for trend p = 0.002) from 92 (prior to onset of spasms) to 73 (after exposure to IS for a month or less) and 62 (after exposure to IS for more than a month). By contrast, there was no significant drop in estimated IQ among the five infants exposed to other types of seizure disorders (nonparametric test for trend p = 0.9). All six children exposed to infantile spasms developed clinically significant intellectual impairment.
These data provide the first clear evidence of clinically significant, dose dependent, impairment in intellectual development following exposure to infantile spasms. The mechanisms underlying this developmental impairment and methods for preventing it require in depth study.
[Show abstract][Hide abstract] ABSTRACT: Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences.
We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities.
Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy.
There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people with ACE and should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed.
[Show abstract][Hide abstract] ABSTRACT: Pediatric neurology comprises a very large of number of conditions exhibiting symptoms and signs in several functional domains arising from damage and dysfunction to the developing nervous system. The diagnostic process involves ensuring that data from all possible domains are sought including those that are unaffected. The subsequent analysis involves fitting these data into patterns of classical natural history and rigorous investigation of the aspects that do not appear to fit. There may be a pattern of illness that is immediately recognized or something that is a fairly close fit. However, the aim is to develop a pathogenic sequence for the condition particularly so that conditions that have been lumped together for convenience are separated into distinct disease entities. The major presentations of pediatric neurology of fixed central motor impairments (the cerebral palsies), the epilepsies, and the progressive degenerative diseases are in the process of being split into such pathogenic sequences so that definitive treatments and possible primary prevention can be added to aims of simple diagnostic recognition. Much of this is at an early stage and pediatric neurology is still a young and fast developing specialty.
Handbook of Clinical Neurology 04/2013; 111:27-33. DOI:10.1016/B978-0-444-52891-9.00003-8