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Cystinosis is a lysosomal storage disorder usually presenting with renal disease in infancy. As soon as the diagnosis is made, cysteamine (a cystine-depleting medication), is started, significantly improving life expectancy. We describe a young woman taking lifelong cysteamine for nephropathic cystinosis, who became acutely encephalopathic with a spastic tetraparesis secondary to cysteamine toxicity, which was potentially worsened by copper deficiency. On replacing copper and reducing the dose of cysteamine, she made a full neurological recovery. We discuss the case, and review cystinosis and what is known about cysteamine toxicity.
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OBJECTIVES: Annual completion of a Valproate Risk Acknowledgement Form (RAF) is mandated in the United Kingdom due to neurodevelopmental risks of in utero valproate exposure. The number of women of childbearing potential taking valproate, the uptake of the RAF within this population and their clinical outcomes is not known or monitored. This study surveyed responses of clinicians administering the RAF to women of childbearing potential taking valproate medications. MATERIALS AND METHODS: Study design-national online survey distributed to clinical specialists throughout the United Kingdom via their national organizations. Participants-clinicians qualified to counsel and administer the valproate RAF (as defined by the Medicines and Healthcare products Regulatory Agency). Main outcome measures-quantitative and qualitative responses regarding identification, uptake, effects and reactions to the RAF. Trial registration-registered at the Clinical Governance and Audit Committee at Royal Free London NHS Foundation Trust Hospital. RESULTS: 215 respondents covering more than 4775 patient encounters were captured. Most patients continued on valproate, 90% with epilepsy as the indication. Respondents reported that seizure control deteriorated when switched to levetiracetam (33%) and lamotrigine (43%), compared to 7% when continuing valproate (P < .001). CONCLUSIONS: 33%-43% of clinicians reported seizure control deterioration in women changed to alternatives to valproate. Informed consent requires women considering a change are given this information. Systematic capture of data automated through online RAFs and linked to patient outcomes is needed. There remains little data on valproate given for indications other than epilepsy.
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Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Médicos/normas , Complicações na Gravidez/tratamento farmacológico , Inquéritos e Questionários , Ácido Valproico/uso terapêutico , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Epilepsia/epidemiologia , Feminino , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Gravidez , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Medição de Risco/legislação & jurisprudência , Medição de Risco/normas , Reino Unido/epidemiologia , Ácido Valproico/efeitos adversosRESUMO
PURPOSE: Partial Epilepsy with Pericentral Spikes (PEPS) is a novel Mendelian idiopathic epilepsy with evidence of linkage to Chromosome 4p15. Our aim was to identify the causative mutation in this epilepsy syndrome. METHODS: We re-annotated all 42 genes in the linked chromosomal region and sequenced all genes within the linked interval. All exons, intron-exon boundaries and untranslated regions were sequenced in the original pedigree, and novel changes segregating correctly were subjected to bioinformatic analysis. Quantitative polymerase chain reaction was performed to examine for potential copy number variation (CNV). RESULTS: 29 previously undescribed variants correctly segregating with the linked haplotype were identified. Bioinformatic analysis demonstrated that six variants were non-synonymous coding sequence polymorphisms, one of which, in Q8IYL2 (Gly400Ala), was found in neither Caucasian (n=243) and ancestry-matched Brazilian (n=180) control samples, nor subjects from the 1000 Genome Project. No gene duplications or deletions were identified in the linked region. DISCUSSION: We postulate that Q8IYL2 is a causative gene for PEPS, after exhaustive resequencing and bioinformatic analysis. The function of this gene is unknown, but it is expressed in brain tissue.
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Variações do Número de Cópias de DNA , Epilepsias Parciais/genética , Saúde da Família , Metiltransferases/genética , Linhagem , Alanina/genética , Brasil , Biologia Computacional/métodos , Feminino , Ligação Genética , Genótipo , Glicina/genética , Humanos , MasculinoRESUMO
The inter-rater reliability, expressed as kappa score, k, of the Engel and International League Against Epilepsy (ILAE) classifications of epilepsy surgery seizure outcome has not previously been evaluated. In a consecutive series of 76 patients (40 male; 25 children), 75 undergoing resective and 1 disconnective surgery at a mean age of 27.5 years (13 months-62 years), one observer classified 88% (n=67) and a second observer classified 87% (n=66) of patients as either Engel I or II (free from or rare disabling seizures) after a median follow up of 36 months (range 12-92 months); comparably, both observers classified 84% (n=64) as ILAE 1-3. Correlation for Engel versus ILAE for observer 1 was 0.933 (p<.0005) and for observer 2 was 0.931 (p<.0005). Both ILAE (k 0.81, 95% confidence intervals 0.69, 0.91) and Engel (k 0.77, 95% CI 0.65, 0.87) classifications have very acceptable inter-rater reliability as well as significant correlation.
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Epilepsia/cirurgia , Resultado do Tratamento , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Variações Dependentes do Observador , Estudos Retrospectivos , Adulto JovemRESUMO
This article summarises the management of different situations in which patients present to the acute medical service with seizures. It covers the management of single attacks of loss of consciousness, multiple seizures and status epilepticus in patients with and without known epilepsy. The importance of a good history and witness account where there is a diagnostic issue is stressed. In the case of multiple seizures and status epilepticus, the investigation of the cause of the attacks as well as their acute management is reviewed.
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The genetic analysis of simple Mendelian epilepsies remains a key strategy in advancing our understanding of epilepsy. In this article, we describe a new family epilepsy syndrome, partial epilepsy with pericentral spikes, which we map to chromosome 4p15. We distinguish it clinically, electrophysiologically, and genetically from previously described Mendelian epilepsies. The family described is a large Brazilian kindred of Portuguese extraction in which affected family members manifest a variety of seizure types, including hemiclonic, hemitonic, generalized tonic-clonic, simple partial (stereotyped episodes of epigastric pain), and complex partial seizures consistent with temporal lobe epilepsy. The syndrome is benign, either requiring no treatment or responding to a single antiepileptic medication. Seizure onset is in the first or second decades of life, with seizures in individuals up to the age of 71 years and documented encephalogram changes up to the age of 30 years. A key feature of partial epilepsy with pericentral spikes is a characteristic encephalogram abnormality of spikes or sharp waves in the pericentral region (centroparietal, centrofrontal, or centrotemporal). This distinctive encephalogram abnormality of pericentral spikes unites these several seizure types into a discrete family epilepsy syndrome. As with other familial epilepsies, the inherited nature of this new syndrome may be overlooked because of the variability in penetrance and seizure types among affected family members.