No abstract

Mutations in ATP1A3 cause Alternating Hemiplegia of Childhood (AHC) by disrupting function of the neuronal Na+/K+ ATPase. Published studies to date indicate 2 recurrent mutations, D801N and E815K, and a more severe phenotype in the E815K cohort. We performed mutation analysis and retrospective genotype-phenotype correlations in all eligible patients with AHC enrolled in the US AHC Foundation registry from 1997-2012. Clinical data were abstracted from standardized caregivers’ questionnaires and medical records and confirmed by expert clinicians. We identified ATP1A3 mutations by Sanger and whole genome sequencing, and compared phenotypes within and between 4 groups of subjects, those with D801N, E815K, other ATP1A3 or no ATP1A3 mutations. We identified heterozygous ATP1A3 mutations in 154 of 187 (82%) AHC patients. Of 34 unique mutations, 31 (91%) are missense, and 16 (47%) had not been previously reported. Concordant with prior studies, more than 2/3 of all mutations are clustered in exons 17 and 18. Of 143 simplex occurrences, 58 had D801N (40%), 38 had E815K (26%) and 11 had G937R (8%) mutations. Patients with an E815K mutation demonstrate an earlier age of onset, more severe motor impairment and a higher prevalence of status epilepticus. This study further expands the number and spectrum of ATP1A3 mutations associated with AHC and confirms a more deleterious effect of the E815K mutation on selected neurologic outcomes. However, the complexity of the disorder and the extensive phenotypic variability among subgroups merits caution and emphasizes the need for further studies.

No abstract

Summary:Purpose: Few reports detailing the electroclinical features of epileptic spasms persisting beyond infancy have been published. We sought to characterize this unique population further.Methods: We retrospectively reviewed the clinical and video-EEG data on 26 patients (4-17 years; mean, 93 months) with a confirmed diagnosis of epileptic spasms and who were evaluated at our tertiary referral center between 1993 and 2000.Results: In half of our cases, epileptic spasms were associated with disorders of neuronal migration, severe perinatal asphyxia, and genetic anomalies. Interictal EEGs showed generalized slowing in the majority of patients, and a slowwave transient followed by an attenuation of the background amplitude was the most common ictal EEG pattern associated with an epileptic spasm (19 cases). Other seizure types (number of cases in parentheses) included tonic seizures with or without a preceding spasm (13), partial seizures (11), myoclonic seizures (11), generalized tonic-clonic seizures (six), atypical absence seizures (two), and atonic seizures (one). Cases with a more organized EEG background (especially with frequencies Ն7 Hz) were more likely to have better cognition. Continued disorganization of the EEG background and persistence of hypsarrhythmia were associated with poor developmental outcome.Conclusions: Patients with epileptic spasms persisting beyond age 2 years constitute a truly refractory population, one that should be better recognized by clinicians. Interestingly, although many therapies resulted in a >50% reduction in seizures, neither neurocognitive function nor quality of life was substantially improved with intervention. The interictal EEG background is the most helpful in predicting neurologic outcome.

ResumoObjetivo: este artigo tem como objetivo discutir um dos principais problemas com os quais um pediatra geral tem que lidar no campo da neurologia infantil, que são os distúrbios paroxísticos não-epilépticos. Estes episódios também são uma causa freqüente de consultas aos neuropediatras e de internação em unidades de monitorização por vídeo-eletrencefalograma.Fontes dos dados: revisão da literatura sobre o assunto na Medline. Vários compêndios de neurologia pediátrica também foram usados, por conterem informações importantes sobre o assunto.Síntese dos dados: muitas das entidades discutidas neste artigo são freqüentes na população pediátrica, como, por exemplo, a síncope, as crises de perda do choro, e os movimentos patológicos associados ao refluxo gastroesofágico. Outras entidades são mais raras, como as distonias paroxísticas e a distonia com flutuação diurna.Conclusões: o conhecimento básico das várias síndromes associadas com distúrbios paroxísticos não-epilépticos é extremamente importante para o pediatra geral, porque pode evitar exames desnecessários e o diagnóstico errôneo de epilepsia, expondo as crianças às medicações que não vão melhorar o quadro clínico, e que podem causar efeitos colaterais.J Pediatr (Rio J) 2002; 78 (Supl.1): S73-S88: epilepsia, convulsão, distúrbios paroxísticos não-epilépticos, síncope, distúrbios do movimento, tetania, hiperecplexia, vertigem. AbstractObjective: this article aims at reviewing one of the most important problems faced by pediatricians in the field of child neurology. The paroxystic non-epileptic events are also a frequent reason for pediatric neurology consultations and admission for diagnostic videoelectroencephalogram monitoring.Sources: literature review on the subject was perform on Medline, data were also collected from the main Pediatric Neurology Textbooks, which were found to be an important and unique source of information on the subject.

The SCN1A gene has been implicated in the etiology of various forms of epilepsy. New research has linked this gene to specific types of epilepsy, all of which present in infancy or early childhood. This study examines the time course and pathology of pediatric patients who have a mutation in the SCN1A gene in order to open a discussion regarding the key trends of this form of epilepsy as well as important clinical considerations in management for patients who present with symptoms relating to the SCN1A mutations. We retrospectively examined 20 patients who presented to the clinic with focal seizures, as well as were positive for an SCN1A genetic mutation. Despite the small sample size, we were able to find important trends in the time course of the disorder as well as important areas of clinical practice that must be taken into consideration for these patients.

No abstract

No abstract