Amre Shahwan

Publications of Amre Shahwan

• The prevalence of seizures in comatose children in the pediatric intensive care unit: a prospective video-EEG study.

  Authors: Amre Shahwan, Catherine Bailey, Lara Shekerdemian, A Simon Harvey

  Epilepsia. 02/2010; 51(7):1198-204.

  Studies in adult and neonatal intensive care units (ICUs) report a high prevalence of epileptic seizures in comatose patients. The prevalence of seizures in pediatric ICUs is variably reported in aStudies in adult and neonatal intensive care units (ICUs) report a high prevalence of epileptic seizures in comatose patients. The prevalence of seizures in pediatric ICUs is variably reported in a few retrospective studies using different electroencephalography (EEG) methods. We aimed to determine prospectively the prevalence of epileptic seizures (clinical and subclinical) in comatose children in the pediatric ICU using continuous video-EEG (v-EEG) monitoring. We performed v-EEG in consecutive children aged 2 months to 17 years admitted to the pediatric ICU with sustained depressed consciousness over a period of 15 months. We monitored 100 comatose children, 69% within 24 h of ICU admission. Median length of ICU stay was 5 days. Median duration of v-EEG was 20 h. Epileptic seizures were identified in only seven patients, of whom six had a history of epilepsy with witnessed seizures immediately prior to v-EEG. All epileptic seizures were recorded in the first 3 h of v-EEG. Seizures were suspected by ICU staff in 18 monitored patients, only four of whom had confirmed epileptic seizures. The lower prevalence of epileptic seizures and the shorter length of ICU stay in children compared to adults and neonates suggest a different spectrum of disease and neurologic response. Short-duration v-EEG in patients with a history of prior seizures, epilepsy, or clinical events suspected to be seizures seems more appropriate than routine v-EEG in all comatose children in the pediatric ICU.

• Vagus nerve stimulation for refractory epilepsy in children: More to VNS than seizure frequency reduction.

  Authors: Amre Shahwan, Catherine Bailey, Wirginia Maxiner, A Simon Harvey

  Epilepsia. 12/2008;

  Summary Purpose: Vagus nerve stimulation (VNS) is used increasingly as adjunctive therapy for refractory epilepsy. Studies of VNS in children report mainly seizure frequency reduction as a measure ofSummary Purpose: Vagus nerve stimulation (VNS) is used increasingly as adjunctive therapy for refractory epilepsy. Studies of VNS in children report mainly seizure frequency reduction as a measure of efficacy and clinical details are often scanty. We report our experience with VNS in children with refractory epilepsy and emphasize the positive effects of VNS in terms of seizure severity. Methods: We reviewed 26 consecutive children who had VNS with a minimum follow-up period of 18 months. We examined their clinical characteristics, seizure types, seizure frequency, epilepsy syndrome diagnosis, and response to VNS in terms of seizure frequency and seizure severity. Results: Fifty-four percent of patients responded to VNS with >/=50% seizure frequency reduction. Patients with Lennox-Gastaut syndrome (LGS) and tonic seizures had a higher responder rate; 78% (seven of nine patients) (p < 0.01). Status epilepticus (SE) episodes were reduced or ceased in the four patients with recurrent SE. Seizure severity, duration, and recovery time decreased in all responders. Increased alertness was reported in all responders and three nonresponders. Conclusion: Decreased seizure severity, recovery time, abolition of daytime drop attacks, and reduced hospitalization due to SE improved patients' lives over and above the benefit from seizure frequency reduction.

• The controversial association of ABCB1 polymorphisms in refractory epilepsy: an analysis of multiple SNPs in an Irish population.

  Authors: Amre Shahwan, Kevin Murphy, Colin Doherty, Gianpiero L Cavalleri, Clare Muckian, Pat Dicker, Mary McCarthy, Peter Kinirons, David Goldstein, Norman Delanty

  Epilepsy research. 03/2007; 73(2):192-8.

  Controversy has surrounded the reported association of the single nucleotide polymorphism (SNP) C3435T of the ATP-binding cassette subfamily B member 1 (ABCB1, MDR1) gene, with refractory epilepsy.Controversy has surrounded the reported association of the single nucleotide polymorphism (SNP) C3435T of the ATP-binding cassette subfamily B member 1 (ABCB1, MDR1) gene, with refractory epilepsy. Here we examine this question by: (1) attempting to replicate the original association, (2) assessing the association of other variants in high linkage disequilibrium (LD) with C3435T, and (3) evaluating and comparing our findings with other published studies. We defined drug-responsiveness as seizure freedom or a 50% or more reduction in seizure frequency in the preceding year. Drug resistance was defined as a less than 50% reduction in seizure frequency in the preceding year. We used a combination of map-based (tagging SNPs) and direct sequence-based methods allowing a comprehensive assessment of variation across the associated interval. Genotypic data on 8 SNPs was collected on 440 patients, of whom 242 were drug-responsive and 198 were drug-resistant. We were unable to observe the original association of drug-resistant epilepsy with C3435T, nor any association with other functional variants at SNP or haplotype level in the ABCB1 gene. Evaluation of other attempted replication studies suggest that if the original C3435T association is indeed real, it would appear highly sensitive to the phenotype used. Alternatively, the discrepant results of this and other association attempts may be indicative of the original report of the CC genotype at C3435T in ABCB1 being a false positive finding. Variability in phenotypic descriptions in genetic association studies may partly explain the inconsistency of attempted replications.

• Examining the role of common genetic variation in the gamma2 subunit of the GABA(A) receptor in epilepsy using tagging SNPs.

  Authors: Peter Kinirons, Gianpiero L Cavalleri, Amre Shahwan, Nicholas W Wood, David B Goldstein, Sanjay M Sisodiya, Norman Delanty, Colin P Doherty

  Epilepsy research. 09/2006; 70(2-3):229-38.

  INTRODUCTION: Mutations in the gamma2 subunit gene of the GABA(A) receptor, GABRG2, have been shown to cause generalised epilepsy syndromes in rare familial cases. Here we set out to examine whetherINTRODUCTION: Mutations in the gamma2 subunit gene of the GABA(A) receptor, GABRG2, have been shown to cause generalised epilepsy syndromes in rare familial cases. Here we set out to examine whether common variation in GABRG2 predisposes to the development of common, complex forms of epilepsy in two large independent cohorts. METHODS: We have applied a tagging single nucleotide polymorphism (tSNP) technique allowing us to satisfactorily represent common variation in the gene. However, to ensure maximal representation of functional variation and in particular in cases of low minor allele frequency (MAF), we have identified and forced known functional variation as tagging SNPs. We examined the association between tagging SNPs and subtypes of epilepsy in two independent cohorts; the first consisted of 677 cases and 384 healthy controls, the second of 684 cases and 277 healthy controls. RESULTS: We failed to detect any variation that conferred an increased risk of disease development in both cohorts. DISCUSSION: Our results suggest that common variants of strong effect in GABRG2 do not appear to play a role in the development of common, complex forms of epilepsy. This report illustrates a number of important features of study design in genetic association studies, including the simultaneous use of map and sequence-based techniques and the necessity of replication before robust conclusions can be drawn from results.

• A pharmacogenetic exploration of vigabatrin-induced visual field constriction.

  Authors: Peter Kinirons, Gianpiero L Cavalleri, Rinki Singh, Amre Shahwan, James F Acheson, Nicholas W Wood, David B Goldstein, Sanjay M Sisodiya, Colin P Doherty, Norman Delanty

  Epilepsy research. 09/2006; 70(2-3):144-52.

  INTRODUCTION: Use of the antiepileptic drug (AED) vigabatrin is severely limited by irreversible visual field constriction, an adverse reaction to the drug reported in approximately 40% of patients.INTRODUCTION: Use of the antiepileptic drug (AED) vigabatrin is severely limited by irreversible visual field constriction, an adverse reaction to the drug reported in approximately 40% of patients. Given the evidence suggesting an idiosyncratic drug response, we set out to detect genetic variation of strong, clinically relevant effect that might guide clinicians in the safe, controlled prescribing of this otherwise usefuldrug. METHODS: Patients with a history of at least 1-year exposure to vigabatrin were enrolled at two independent referral centers. Using Goldmann perimetry, visual fields and the extent of constriction were calculated for each patient. We examined the correlation between the extent of vigabatrin induced visual field constriction and genetic variation across six candidate genes (SLC6A1, SLC6A13, SCL6A11, ABAT, GABRR1 and GABRR2). We availed of HapMap data and used a tagging SNP technique in an effort to efficiently capture all common variation within these genes. We attempted to replicate any positive associations before drawing conclusions from our results. RESULTS: The degree of visual field constriction correlated with three SNPs and one haplotype in a cohort of 73 patients. However we were unable to replicate these findings in a second independent cohort consisting of 58 patients, suggesting the initial results were possibly false positives, or variants of weak effect. CONCLUSION: Common variants of strong, clinically relevant effect do not appear to reside in the candidate genes studied here. This does not rule out the presence of genetic variants of weak effect in these genes, nor of variants of strong effect in other genes.

• Atypical presentation of ataxia-oculomotor apraxia type 1.

  Authors: Amre Shahwan, Philip J Byrd, A Malcolm R Taylor, Therese Nestor, Stephanie Ryan, Mary D King

  Developmental medicine and child neurology. 07/2006; 48(6):529-32.

  A subgroup of autosomal recessive cerebellar ataxias (ARCAs) associated with oculomotor apraxia (OMA) and other variable features has been reported. Ataxia-oculomotor apraxia types 1 and 2 (AOA1 andA subgroup of autosomal recessive cerebellar ataxias (ARCAs) associated with oculomotor apraxia (OMA) and other variable features has been reported. Ataxia-oculomotor apraxia types 1 and 2 (AOA1 and AOA2) belong to this subgroup and have been described in adults with early onset cerebellar ataxia. AOA1 is associated with oculomotor apraxia, severe sensorimotor neuropathy, choreiform movements, cognitive impairment, and cerebellar atrophy at an early age. We describe a male child with AOA1 who is homozygous for the G837A (W279X) mutation in the APTX gene. He presented at the age of 3 years 6 months with some atypical features including absence of OMA, chorea, and cerebellar atrophy. These manifestations, in addition to peripheral neuropathy, appeared at 8 years of age. We highlight the importance of considering the diagnosis of AOA1 in children with early-onset cerebellar ataxia, once other well-known disorders such as Friedreich's ataxia and ataxia-telangiectasia have been excluded.

• Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects.

  Authors: Amre Shahwan, Michael Farrell, Norman Delanty

  Lancet neurology. 05/2005; 4(4):239-48.

  The progressive myoclonic epilepsies (PMEs) are a group of symptomatic generalised epilepsies caused by rare disorders, most of which have a genetic component, a debilitating course, and a poorThe progressive myoclonic epilepsies (PMEs) are a group of symptomatic generalised epilepsies caused by rare disorders, most of which have a genetic component, a debilitating course, and a poor outcome. Challenges with PME arise from difficulty with diagnosis, especially in the early stages of the illness, and further problems of management and drug treatment. Recent advances in molecular genetics have helped achieve better understanding of the different disorders that cause PME. We review the PMEs with emphasis on updated genetics, diagnosis, and therapeutic options.

• Malignant refractory epilepsy in identical twins mosaic for a supernumerary ring chromosome 19.

  Authors: Amre Shahwan, Andrew J Green, Aiveen Carey, Raymond L Stallings, Odette C O'Flaherty, Mary D King

  Epilepsia. 09/2004; 45(8):997-1000.

  We report identical twins with supernumerary ring chromosome 19 mosaicism, who had severe refractory epilepsy at an early age. The epilepsy was dominated largely by severe life-threatening tonicWe report identical twins with supernumerary ring chromosome 19 mosaicism, who had severe refractory epilepsy at an early age. The epilepsy was dominated largely by severe life-threatening tonic seizures. Both twins died, likely as a consequence of their severe epilepsy. They displayed no dysmorphic features. Eight cases of ring chromosome 19 have been reported in the literature, all to our knowledge without epilepsy. The clinical picture of these twins emphasizes the importance of carrying out a karyotype study on patients with early-onset epilepsy even in the absence of dysmorphic features.