Brian G R Neville

University College London, Londinium, England, United Kingdom

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Publications (164)920.27 Total impact

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    ABSTRACT: 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 are currently 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 them 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. Copyright © 2014. Published by Elsevier Inc.
    Epilepsy & Behavior 12/2014; 42C:86-92. · 2.06 Impact Factor
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    ABSTRACT: 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. 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 Pearson's correlation. The screening properties of the SDQ were explored. Regression using generalized estimating equations was used to identify predictors of responses on the SDQ. 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. 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. Copyright © 2014 Elsevier B.V. All rights reserved.
    Epilepsy Research 12/2014; 108(10):1917-26. · 2.19 Impact Factor
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    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. · 3.40 Impact Factor
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    ABSTRACT: Provide data on the distribution of parent- and teacher-reported symptoms of ADHD in childhood epilepsy and describe coexisting cognitive and behavioral disorders in children with both epilepsy and ADHD. Eighty-five (74% of those eligible) children (5-15 years) in a population-based sample with active epilepsy underwent psychological assessment. The ADHD Rating Scale-IV (ADHD-RS-IV) scale was completed by parents (n = 69) and teachers (n = 67) of participating children with an IQ > 34. ADHD was diagnosed with respect to Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.). Parents reported significantly more symptoms of ADHD than teachers (p < .001). Symptoms of inattention were more commonly reported than symptoms of hyperactivity-impulsivity (p < .001). Neurobehavioral comorbidity was similar in those with ADHD and non-ADHD with the exception of oppositional defiant disorder (ODD) and developmental coordination disorder (DCD), which were more common in those with both epilepsy and ADHD. Symptoms of ADHD are very common in childhood epilepsy but prevalence is influenced by informant. © 2014 SAGE Publications.
    Journal of Attention Disorders 11/2014; · 2.40 Impact Factor
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    ABSTRACT: Objectives: This study investigates auditory processing in infants with West syndrome (WS) using event-related potentials (ERPs).Methods: ERPs were measured in 25 infants with mainly symptomatic WS (age range 3–14 months) and 26 healthy term infants (age range 3–14 months) using an auditory novelty oddball paradigm. The ERP recordings were made during wakefulness and repeated in stage II sleep.Results: The obligatory components (P150, N250, and 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 x group interaction F = 22.3, p < 0.0001]. These ERP latency alterations were not affected by pharmacological treatment for WS.Conclusions: This study demonstrated a persistently altered ERP signature in patients with a recent history of infantile spasms. The prolongation of auditory obligatory and novelty ERP in WS patients indicates a severe failure of temporal lobe maturation during infancy. It remains to be investigated if this predicts long-term cognitive impairments characteristic for this epileptic encephalopathy. ANN NEUROL 2014. © 2014 American Neurological Association
    Annals of Neurology 11/2014; · 11.91 Impact Factor
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    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.
    Epilepsia 10/2014; · 4.58 Impact Factor
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    ABSTRACT: 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.
    Pediatrics 05/2014; · 5.30 Impact Factor
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    ABSTRACT: Genetic research has shown that mutations that modify the protein-coding sequence of ATP1A3, the gene encoding the α3 subunit of Na(+)/K(+)-ATPase, cause both rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood. These discoveries link two clinically distinct neurological diseases to the same gene, however, ATP1A3 mutations are, with one exception, disease-specific. Although the exact mechanism of how these mutations lead to disease is still unknown, much knowledge has been gained about functional consequences of ATP1A3 mutations using a range of in-vitro and animal model systems, and the role of Na(+)/K(+)-ATPases in the brain. Researchers and clinicians are attempting to further characterise neurological manifestations associated with mutations in ATP1A3, and to build on the existing molecular knowledge to understand how specific mutations can lead to different diseases.
    The Lancet Neurology 05/2014; 13(5):503-514. · 21.82 Impact Factor
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    ABSTRACT: We estimated premature mortality and identified causes of death and associated factors in people with active convulsive epilepsy (ACE) in rural Kenya. In this prospective population-based study, people with ACE were identified in a cross-sectional survey and followed up regularly for 3 years, during which information on deaths and associated factors was collected. We used a validated verbal autopsy tool to establish putative causes of death. Age-specific rate ratios and standardized mortality ratios were estimated. Poisson regression was used to identify mortality risk factors. There were 61 deaths among 754 people with ACE, yielding a rate of 33.3/1,000 persons/year. Overall standardized mortality ratio was 6.5. Mortality was higher across all ACE age groups. Nonadherence to antiepileptic drugs (adjusted rate ratio [aRR] 3.37), cognitive impairment (aRR 4.55), and age (50+ years) (rate ratio 4.56) were risk factors for premature mortality. Most deaths (56%) were directly related to epilepsy, with prolonged seizures/possible status epilepticus (38%) most frequently associated with death; some of these may have been due to sudden unexpected death in epilepsy (SUDEP). Possible SUDEP was the likely cause in another 7%. Mortality in people with ACE was more than 6-fold greater than expected. This may be reduced by improving treatment adherence and prompt management of prolonged seizures and supporting those with cognitive impairment.
    Neurology 01/2014; · 8.30 Impact Factor
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    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.
    Epilepsia 01/2014; 55(1):108-16. · 4.58 Impact Factor
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    ABSTRACT: To establish the efficacy and safety of methylphenidate (MPH) treatment for attention deficit hyperactivity disorder (ADHD) in a group of children and young people with learning disability and severe epilepsy. This retrospective study systematically reviewed the case notes of all patients treated with methylphenidate (MPH) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD at a specialist epilepsy center between 1998 and 2005. Treatment efficacy was ascertained using clinical global impressions (CGI) scores, and safety was indexed by instances of >25% increase in monthly seizure count within 3 months of starting MPH. Eighteen (18) patients were identified with refractory epilepsies (14 generalized, 4 focal), IQ <70, and ADHD. Male patients predominated (13:5) and ADHD was diagnosed at a median age of 11.5 years (range 6-18 years). With use of a combination of a behavioral management program and MPH 0.3-1 mg/kg/day, ADHD symptoms improved in 61% of patients (11/18; type A intraclass correlation coefficient of CGI 0.85, 95% confidence interval [CI] 0.69-0.94). Daily MPH dose, epilepsy variables, and psychiatric comorbidity did not relate to treatment response across the sample. MPH adverse effects led to treatment cessation in three patients (dysphoria in two, anxiety in one). There was no statistical evidence for a deterioration of seizure control in this group with the use of MPH. Methylphenidate with behavioral management was associated with benefit in the management of ADHD in more than half of a group of children with severe epilepsy and additional cognitive impairments. Eighteen percent had significant side effects but no attributable increase in seizures. Methylphenidate is useful in this group and is likely to be under employed.
    Epilepsia 10/2013; · 4.58 Impact Factor
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    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.
    Epilepsia 10/2013; · 4.58 Impact Factor
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    ABSTRACT: Purpose: Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based; few studies have compared different ecological sites in SSA. We characterized active convulsive epilepsy (ACE) identified in cross-sectional community surveys in SSA, to understand the clinical features and consequences. Method: A detailed clinical and neurophysiological description of ACE in 2,170 people identified from a community survey of 586,584 people across five sites in Africa: South Africa; Tanzania; Uganda; Kenya and Ghana are provided. Results: Over half (51%) of ACE occurred in children. Focal features (EEG, seizure types and neurological deficits) were present in 60% of ACE cases. A third of primarily generalised seizures had focal features on EEG. Status epilepticus occurred in 377/1,633 (23%) of people with ACE. Only 786/2,091 (38%) individuals were on antiepileptic drugs. Important comorbidities of ACE were malnutrition (320/2,115 [15%]), cognitive impairment (494/2,131 [23%]) and neurological deficits (319/ 2,130 [15%]). The consequences of ACE were burns (347/2,125 [16%]), head injuries (post seizures) (25/1,905 [1%]), no education (938/2,135 [44%]) and, in adults, being unmarried (695/1,030 [68%]) or unemployed (646/1,098 (58%); all were more common than in controls. There were significant differences in the comorbidities across the sites. Conclusion: Focal features are common in ACE suggesting identifiable and preventable causes. Malnutrition, cognitive and neurological disorders are common in ACE and should be included in the management. There are significant consequences of epilepsy such as burns, lack of education and marriage prospects, which need to be addressed.
    30th International Epilepsy Congress, Montreal, Canada; 06/2013
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    ABSTRACT: PURPOSE: Convulsive status epilepticus (CSE) is the most common pediatric neurologic emergency and is often associated with unfavorable neurodevelopmental outcomes. The early developmental trajectory of children following CSE has not been previously investigated, leaving a gap in our understanding of how these adverse long-term outcomes emerge. METHODS: We prospectively recruited children aged between 1 and 42 months from a predefined geographic region of North London who had at least one episode of CSE and classified them as prolonged febrile seizures (PFS) or nonfebrile CSE. Neuropsychological and imaging investigations were conducted within 6 weeks of CSE (baseline) and were repeated a year later (follow-up). Neurodevelopment was assessed using the Bayley Scales of Infant Development III and compared to normally developing children. Predictors of neurodevelopmental scores at baseline and follow-up were investigated using regression analyses. KEY FINDINGS: Of the 54 children that underwent investigations a mean of 38 days following CSE, 27 had PFS (mean age 18.4 months) and 27 had nonfebrile CSE (mean age 15.5 months). In addition, 17 healthy controls were assessed (mean age 20.49 months). Children with nonfebrile CSE had a worse developmental outcome than children with PFS (p < 0.002), despite there being no differences in seizure characteristics. In contrast to expectations, the PFS group had a worse developmental outcome than controls (p = 0.002). There were no significant differences in performance from baseline to 1-year follow-up for the 70.4% of children who provided data. Seizure characteristics were not shown to be significant predictors of performance. SIGNIFICANCE: CSE is associated with developmental impairments within 6 weeks of the acute event that continue to be present a year onward. This is also true of PFS cases that under-perform relative to controls despite mean scores within the clinically normal range. The absence of a change in performance from baseline to follow-up as well as the lack of a relationship between seizure characteristics and developmental outcomes supports the notion that premorbid abilities may be overshadowing any direct effects of CSE itself on outcome.
    Epilepsia 04/2013; · 4.58 Impact Factor
  • Brian G R Neville
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    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 01/2013; 111:27-33.
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    ABSTRACT: Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal injury may be evident in human children after prolonged febrile seizures. The current study addressed this question by investigating memory abilities in 26 children soon after a prolonged febrile seizure (median: 37.5 days) and compared their results to those of 37 normally developing children. Fifteen patients were reassessed at a mean of 12.5 months after their first assessment to determine the transiency of any observed effects. We used the visual paired comparison task to test memory abilities in our group, as this task does not depend on verbal abilities and also because successful performance on the task has been proven to depend on the presence of functional hippocampi. Our findings show that patients perform as well as controls in the absence of a delay between the learning phase and the memory test, suggesting that both groups are able to form representations of the presented stimulus. However, after a 5-min delay, patients' recognition memory is not different from chance, and comparison of patients and controls points to an accelerated forgetting rate in the prolonged febrile seizure group. The patients' performance was not related to the time elapsed from the acute event or the duration of the prolonged febrile seizure, suggesting that the observed effect is not a by-product of the seizure itself or a delayed effect of medication administered to terminate the seizure. By contrast, performance was related to hippocampal size; participants with the smallest mean hippocampal volumes revealed the biggest drop in performance from the immediate to the delayed paradigm. At follow-up, children were still showing deficiencies in recognizing a face after a 5-min delay. Similarly, this suggests that the observed memory impairments are not a transient effect of the prolonged febrile seizures. This is the first report of such impairments in humans, and it is clinically significant given the links between mesial temporal sclerosis and prolonged febrile seizures. The persistence of these impairments a year onwards signals the potential benefits of intervention in these children who run the risk of developing episodic memory deficits in later childhood.
    Brain 09/2012; 135(Pt 10):3153-64. · 10.23 Impact Factor
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    ABSTRACT: Aim  To identify predictors of seizure control in newly presenting children with epilepsy in countries with limited resources. Method  Three hundred and ninety children (273 males, 117 females) aged 2 months to 15 years with newly diagnosed epilepsy were enrolled prospectively at first visit to the multidisciplinary clinic at the children's hospital in Dhaka, Bangladesh. Data about seizures, motor disability, psychomotor development, and electroencephalography were obtained. Regular monitoring of antiepileptic drug treatment was continued at least for one year. Associations between seizure control and potential predictors were determined by multivariate analysis. Results  Three hundred and ninety children were enrolled in 6 months, of whom over 60% were from low-income families, 60% had onset at under 1 year, 74% had more than one seizure per week, 69% a single-seizure type, and 38% a history of delayed onset of breathing at birth. Cognitive deficits (IQ<70; 58%) and/or motor (significant limitation of daily living activities; 47%) deficits were common. After 1 year of regular treatment, seizure control was good (seizure freedom) in 53%, and poor (at least one seizure in the last 3mo of follow-up) in 47%. The predictors of poor seizure control were an IQ<70, associated motor disability, multiple seizure types, and a history of cognitive regression (1.9 times more likely to have poor seizure control). Interpretation  Seizure control can be predicted using three clinical factors (motor disability, cognitive impairment, and multiple seizure types) at the first clinic visit. Such predictors assist the development of referral plans and management guidelines for childhood epilepsies in resource-poor countries.
    Developmental Medicine & Child Neurology 06/2012; 54(10):918-24. · 2.68 Impact Factor
  • Archives of Disease in Childhood 05/2012; 97(Suppl 1):A135-A136. · 2.91 Impact Factor
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    ABSTRACT: Seizures are common in comatose children, but may be clinically subtle or only manifest on continuous electroencephalographic monitoring (cEEG); any association with outcome remains uncertain. cEEG (one to three channels) was performed for a median 42 h (range 2-630 h) in 204 unventilated and ventilated children aged ≤15 years (18 neonates, 61 infants) in coma with different aetiologies. Outcome at 1 month was independently determined and dichotomized for survivors into favourable (normal or moderate neurological handicap) and unfavourable (severe handicap or vegetative state). Of the 204 patients, 110 had clinical seizures (CS) before cEEG commenced. During cEEG, 74 patients (36%, 95% confidence interval, 95% CI, 32-41%) had electroencephalographic seizures (ES), the majority without clinical accompaniment (non-convulsive seizures, NCS). CS occurred before NCS in 69 of the 204 patients; 5 ventilated with NCS had no CS observed. Death (93/204; 46%) was independently predicted by admission Paediatric Index of Mortality (PIM; adjusted odds ratio, aOR, 1.027, 95% CI 1.012-1.042; p < 0.0005), Adelaide coma score (aOR 0.813, 95% CI 0.700-0.943; p = 0.006), and EEG grade on admission (excess slow with >3% fast, aOR 5.43, 95% CI 1.90-15.6; excess slow with <3% fast, aOR 8.71, 95% CI 2.58-29.4; low amplitude, 10th centile <9 µV, aOR 3.78, 95% CI 1.23-11.7; and burst suppression, aOR 10.68, 95% CI 2.31-49.4) compared with normal cEEG, as well as absence of CS at any time (aOR 2.38, 95% CI 1.18-4.81). Unfavourable outcome (29/111 survivors; 26%) was independently predicted by the presence of ES (aOR 15.4, 95% CI 4.7-49.7) and PIM (aOR 1.036, 95% CI 1.013-1.059). Seizures are common in comatose children, and are associated with an unfavourable outcome in survivors. cEEG allows the detection of subtle CS and NCS and is a prognostic tool.
    European Journal of Intensive Care Medicine 04/2012; 38(5):853-62. · 5.17 Impact Factor
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    ABSTRACT: Pneumococcal meningitis (PM) is a severe and life-threatening disease that is associated with cognitive impairment including learning difficulties, cognitive slowness, short-term memory deficits and poor academic performance. There are limited data on cognitive outcomes following exposure to PM from Africa mainly due to lack of culturally appropriate tools. We report cognitive processes of exposed children as measured by auditory and visual event-related potentials. Sixty-five children (32 male, mean 8.4 years, SD 3.0 years) aged between 4-15 years with a history of PM and an age-matched control group of 93 children (46 male; mean 8.4 years, SD 2.7 years) were recruited from a well-demarcated study area in Kilifi. In the present study, both baseline to peak and peak-to-peak amplitude differences are reported. Children with a history of pneumococcal meningitis had significantly longer auditory P1 and P3a latencies and smaller P1 amplitudes compared to unexposed children. In the visual paradigm, children with PM seemingly lacked a novelty P3a component around 350 ms where control children had a maximum, and showed a lack of stimulus differentiation at Nc. Further, children with exposure to PM had smaller peak to peak amplitude (N2-P1) compared to unexposed children. The results suggest that children with a history of PM process novelty differently than do unexposed children, with slower latencies and reduced or absent components. This pattern suggests poorer auditory attention and/or cognitive slowness and poorer visual attention orienting, possibly due to disruption in the functions of the lateral prefrontal and superior temporal cortices. ERPs may be useful for assessment of the development of perceptual-cognitive functions in post brain-injury in African children by providing an alternate way of assessing cognitive development in patient groups for whom more typical standardized neuropsychological assessments are unavailable.
    BMC Infectious Diseases 03/2012; 12:79. · 2.56 Impact Factor

Publication Stats

4k Citations
920.27 Total Impact Points


  • 1999–2014
    • University College London
      • Institute of Child Health
      Londinium, England, United Kingdom
    • Alder Hey Children's Healthcare Hospital
      Liverpool, England, United Kingdom
  • 2008–2013
    • National Centre for Young People with Epilepsy
      Lingfield, England, United Kingdom
    • London School of Hygiene and Tropical Medicine
      • Department of Infectious Disease Epidemiology
      London, ENG, United Kingdom
  • 2012
    • University of Oxford
      Oxford, England, United Kingdom
    • Dartmouth College
      • Department of Neurology
      Hanover, New Hampshire, United States
  • 2011–2012
    • Kilimanjaro Christian Medical Centre
      Moschi, Kilimanjaro, Tanzania
  • 2008–2012
    • Kenya Medical Research Institute
      • Centre for Clinical Research
      Nairoba, Nairobi Area, Kenya
  • 2003–2012
    • Dhaka Shishu Hospital
      Mujib City, Dhaka, Bangladesh
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdam, North Holland, Netherlands
  • 2002–2012
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • King Abdulaziz University
      • Department of Pediatrics
      Jeddah, Mintaqat Makkah, Saudi Arabia
  • 1996–2011
    • WWF United Kingdom
      Londinium, England, United Kingdom
    • Great Ormond Street Hospital for Children NHS Foundation Trust
      • • Neurosciences Unit
      • • Department of Neurophysiology
      Londinium, England, United Kingdom
  • 2007–2010
    • KEMRI-Wellcome Trust Research Programme
      Kilifi, Kilifi, Kenya
    • Université Libre de Bruxelles
      Bruxelles, Brussels Capital Region, Belgium
  • 1994–2003
    • University of London
      Londinium, England, United Kingdom
  • 1993–1998
    • Institute for Child Health Policy (ICHP)
      • Institute of Child Health
      London, Ohio, United States