[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.
Full-text · Article · Nov 2015 · Epilepsy & Behavior
[Show abstract][Hide abstract]ABSTRACT: Background:
Mutations in the gene ATP1A3 have recently been identified to be prevalent in patients with alternating hemiplegia of childhood (AHC2). Based on a large series of patients with AHC, we set out to identify the spectrum of different mutations within the ATP1A3 gene and further establish any correlation with phenotype.
Clinical data from an international cohort of 155 AHC patients (84 females, 71 males; between 3 months and 52 years) were gathered using a specifically formulated questionnaire and analysed relative to the mutational ATP1A3 gene data for each patient.
In total, 34 different ATP1A3 mutations were detected in 85 % (132/155) patients, seven of which were novel. In general, mutations were found to cluster into five different regions. The most frequent mutations included: p.Asp801Asn (43 %; 57/132), p.Glu815Lys (16 %; 22/132), and p.Gly947Arg (11 %; 15/132). Of these, p.Glu815Lys was associated with a severe phenotype, with more severe intellectual and motor disability. p.Asp801Asn appeared to confer a milder phenotypic expression, and p.Gly947Arg appeared to correlate with the most favourable prognosis, compared to the other two frequent mutations. Overall, the comparison of the clinical profiles suggested a gradient of severity between the three major mutations with differences in intellectual (p = 0.029) and motor (p = 0.039) disabilities being statistically significant. For patients with epilepsy, age at onset of seizures was earlier for patients with either p.Glu815Lys or p.Gly947Arg mutation, compared to those with p.Asp801Asn mutation (p < 0.001). With regards to the five mutation clusters, some clusters appeared to correlate with certain clinical phenotypes. No statistically significant clinical correlations were found between patients with and without ATP1A3 mutations.
Our results, demonstrate a highly variable clinical phenotype in patients with AHC2 that correlates with certain mutations and possibly clusters within the ATP1A3 gene. Our description of the clinical profile of patients with the most frequent mutations and the clinical picture of those with less common mutations confirms the results from previous studies, and further expands the spectrum of genotype-phenotype correlations. Our results may be useful to confirm diagnosis and may influence decisions to ensure appropriate early medical intervention in patients with AHC. They provide a stronger basis for the constitution of more homogeneous groups to be included in clinical trials.
[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.
Full-text · Article · Apr 2015 · Journal of Clinical and Experimental Neuropsychology
[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.
Full-text · Article · Apr 2015 · Psychological Medicine
[Show abstract][Hide abstract]ABSTRACT: Objective: To explore the structure-function relation of the temporal lobe in newly diagnosed West syndrome of unknown cause (uWS). / Methods: Quantitative magnetic resonance imaging (3D structural MRI and diffusion tensor imaging, DTI) was analysed by voxel-based morphometry (VBM) and tractbased spatial statistics (TBSS) in 22 patients and healthy age-matched controls. The electrophysiological responsiveness of the temporal lobe was measured using the N100 auditory event-related potential (ERP) to a repeated 1000Hz tone. Neurocognitive function was assessed using the Bayley scales of infant development II (BSID-II). Tests followed first-line treatment with Vigabatrin (17) or high dose oral prednisolone (5). / Results: Total temporal lobe volume was similar in patients and controls. Patients had a smaller temporal stem (TS) [p < 0.0001] and planum temporale (PT) [p = 0.029] bilaterally. TS width asymmetry with a larger right-sided width in controls, was absent in patients [p = 0.033]. PT asymmetry was present in both groups, being larger on the right [p = 0.048]. VBM grey matter volume was increased at the left temporal lobe (superior and middle temporal gyri, the perirhinal cortex and medial temporal lobe) [p<0.005, family wise error-corrected]. VBM grey matter volume correlated with the duration of infantile spasms. [Pearson’s R = - 0.630, p = 0.009] DTI metrics did not differ between patients and controls on TBSS. Patients’ mean BSID-II scores were lower [p<0.001] and their auditory N100 ERP attenuated less than controls’ [p = 0.002]. / Significance: The functional networking and white matter development of the temporal lobe are impaired following infantile spasms. Treatment may promote structural plasticity within the temporal lobe following infantile spasms, manifest as increased grey matter volume on VBM. It remains to be investigated further whether this predicts patients’ longterm cognitive difficulties.
[Show abstract][Hide abstract]ABSTRACT: Objective
To explore the structure–function relation of the temporal lobe in newly diagnosed West syndrome of unknown cause (uWS).Methods
Quantitative magnetic resonance imaging (three-dimensional [3D] structural MRI and diffusion tensor imaging [DTI]) was analyzed using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) in 22 patients and healthy age-matched controls. The electrophysiologic responsiveness of the temporal lobe was measured using the N100 auditory event-related potential (aERP) to a repeated 1,000 Hz tone. Neurocognitive function was assessed using the Bayley Scales of Infant Development, Second Edition (BSID-II). Tests followed first-line treatment with vigabatrin (17 patients) or high-dose oral prednisolone (5 patients).ResultsTotal temporal lobe volume was similar in patients and controls. Patients had a smaller temporal stem (TS) (p < 0.0001) and planum temporale (PT) (p = 0.029) bilaterally. TS width asymmetry with a larger right-sided width in controls was absent in patients (p = 0.033). PT asymmetry was present in both groups, being larger on the right (p = 0.048). VBM gray matter volume was increased at the left temporal lobe (superior and middle temporal gyri, the peri-rhinal cortex, and medial temporal lobe) (p < 0.005, family wise error-corrected). VBM gray matter volume correlated with the duration of infantile spasms (Pearson's r = −0.630, p = 0.009). DTI metrics did not differ between patients and controls on TBSS. Mean BSID-II scores were lower (p < 0.001) and auditory N100 ERP attenuated less in patients than in controls (p = 0.002).SignificanceThe functional networking and white matter development of the temporal lobe are impaired following infantile spasms. Treatment may promote structural plasticity within the temporal lobe following infantile spasms, manifest as increased gray matter volume on VBM. It remains to be investigated further whether this predicts patients' long-term cognitive difficulties.
[Show abstract][Hide abstract]ABSTRACT: Objective
This study investigates auditory processing in infants with West syndrome (WS) using event-related potentials (ERPs).
ERPs were measured in 25 infants with mainly symptomatic WS (age range = 3–10 months) and 26 healthy term infants (age range = 3–9 months) using an auditory novelty oddball paradigm. The ERP recordings were made during wakefulness and repeated in stage II sleep.
The obligatory components (P150, N250, P350) and novelty response components (P300, Nc) were recordable during both sleep and wakefulness in patients and controls. All ERP latencies decreased with age in controls but not in the WS group (age × group interaction, F = 22.3, p < 0.0001). These ERP latency alterations were not affected by pharmacological treatment for WS.
This study demonstrated a persistently altered ERP signature in patients with a recent history of infantile spasms. The prolongation of auditory obligatory and novelty ERPs in WS patients indicates a severe failure of temporal lobe maturation during infancy. It remains to be investigated whether this predicts long-term cognitive impairments characteristic for this epileptic encephalopathy.
Full-text · Article · Jan 2015 · Annals of Neurology
[Show abstract][Hide abstract]ABSTRACT: Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease.
A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II software package.
The crude incidence for convulsive epilepsy was 17.4/100,000 per year (95%CI: 13.1-23.0). Remission was 4.6% and 3.9% per year for males and females, respectively. The standardized mortality ratio was 2.6 (95%CI: 1.7-3.5), with 33.3% of deaths directly related to epilepsy. Mortality was higher in men than women (adjusted rate ratio (aRR) 2.6 (95%CI: 1.2-5.4)), and was significantly associated with older ages (50+ years versus those 0-5 years old (RR 4.8 (95%CI: 0.6-36.4)).
The crude incidence was lower whilst mortality rates were similar to other African studies; however, this study found higher mortality amongst older males. Efforts aimed at further understanding what causes epilepsy in older people and developing interventions to reduce prolonged seizures are likely to reduce the overall burden of ACE in rural South Africa.
[Show abstract][Hide abstract]ABSTRACT: OBJECTIVE: We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa. METHODS: We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors. RESULTS: The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p < 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in ACE were neurologic impairments, acute encephalopathy, previous hospitalization, and presence of antibody titers to falciparum malaria and HIV; these differed across sites. Burns (15%), lack of education (49%), being single (77%), and unemployment (78%) were common in CSE; these differed across the 3 sites. Nine percent with and 10% without CSE died. CONCLUSIONS: CSE is common in people with ACE in Africa; most occurs with febrile illnesses, is untreated, and has focal features suggesting preventable risk factors. Effective prevention and the management of infections and neurologic impairments may reduce the burden of CSE in ACE.