Levetiracetam monotherapy in juvenile myoclonic epilepsy.

PURPOSE: To describe our experience with levetiracetam (LEV) as initial or conversion monotherapy treatment for juvenile myoclonic epilepsy (JME). Valproate, the usual first line agent for JME, has chronic adverse effects, particularly for women of childbearing potential. Since JME requires lifetime treatment, chronic adverse effects of therapy are important consideration. METHODS: We reviewed the medical records of patients with JME treated with LEV in the first 4 years after marketing. We recorded demographic data, results of EEG and imaging studies, antiepileptic drug (AED) history, LEV initial dose and final dose, side effects related to LEV, and therapeutic response to treatment. We classified JME into definite and probable based on clinical and EEG criteria. The minimum duration of follow up was 1 year. RESULTS: LEV was the first therapy in 12 patients and the initial appropriate agent in 16. Fourteen patients had been treated with another appropriate AED. Eighty percent (24/30) of patients became seizure free with LEV monotherapy and two additional patients showed improved seizure control. Final therapeutic doses of LEV ranged from 12 to 50mg/(kgday). Complete seizure control using LEV was not predicted by previous AED use. Treatment failure with valproate also did not predict failure of LEV. Patients with definite JME responded best within the study group (11 of 11 seizure free, p<0.05). CONCLUSIONS: This study supports consideration of LEV for first line treatment of JME and suggests the need for a large prospective trial.

Limb-girdle muscular dystrophy in the United States.

Limb-girdle muscular dystrophy (LGMD) has been linked to 15 chromosomal loci, 7 autosomal-dominant (LGMD1A to E) and 10 autosomal-recessive (LGMD2A to J). To determine the distribution of subtypes among patients in the United States, 6 medical centers evaluated patients with a referral diagnosis of LGMD. Muscle biopsies provided histopathology and immunodiagnostic testing, and their protein abnormalities along with clinical parameters directed mutation screening. The diagnosis in 23 patients was a disorder other than LGMD. Of the remaining 289 unrelated patients, 266 had muscle biopsies sufficient for complete microscopic evaluation; 121 also underwent Western blotting. From this combined evaluation, the distribution of immunophenotypes is 12% calpainopathy, 18% dysferlinopathy, 15% sarcoglycanopathy, 15% dystroglycanopathy, and 1.5% caveolinopathy. Genotypes distributed among 2 dominant and 7 recessive subtypes have been determined for 83 patients. This study of a large racially and ethnically diverse population of patients with LGMD indicates that establishing a putative subtype is possible more than half the time using available diagnostic testing. An efficient approach to genotypic diagnosis is muscle biopsy immunophenotyping followed by directed mutational analysis. The most common LGMDs in the United States are calpainopathies, dysferlinopathies, sarcoglycanopathies, and dystroglycanopathies.

Novel mutation in the SPG3A gene in an African American family with an early onset of hereditary spastic paraplegia.

BACKGROUND: Mutations in a novel GTPase gene SPG3A cause an autosomal dominant hereditary spastic paraplegia linked to chromosome 14q (SPG3), which accounts for approximately 10% to 15% of all autosomal dominant hereditary spastic paraplegia cases. The mutational spectrum of the SPG3A gene and the phenotype/genotype correlations have not yet been established. OBJECTIVE: To describe a kindred with an infantile onset of hereditary spastic paraplegia caused by a novel mutation in the SPG3A gene. PATIENTS: Complete neurological examination and genetic analysis were performed on 6 affected members of a small African American kindred. Linkage analysis to genetic markers near autosomal dominant hereditary spastic paraplegia loci on chromosomes 2p and 14q was performed. The coding sequence of the SPG3A gene was analyzed, and the identified change in the sequence was tested for being a benign polymorphism by sequencing 200 chromosomes from normal controls. RESULTS: Every affected individual had signs of uncomplicated spastic paraparesis without additional neurological abnormalities. None of the affected family members had ever walked normally. The history was consistent with an infantile onset, despite the normal acquisition of motor milestones. Genetic analysis suggested linkage to the SPG3A locus on chromosome 14q. Analysis of the SPG3A gene revealed a missense mutation C635T, predicted to result in a threonine to isoleucine substitution at codon 156. Analysis of 200 normal chromosomes did not identify the same change in healthy subjects. CONCLUSION: We report a novel mutation in the SPG3A gene in an African American family with an infantile onset of autosomal dominant hereditary spastic paraplegia.

Neurocutaneous syndromes.

Neurocutaneous syndromes are congenital or hereditary conditions that have many features in common: hereditary transmission, involvement of organs of ectodermal origin (nervous system, eyeball, retina, and skin), slow evolution of lesions in childhood and adolescence, and disposition to fatal malignant transformation. Except for Sturge- Weber syndrome, these major neurocutaneous syndromes are genetically determined, although sporadic cases can occur. This article reviews the clinical features of the more common neurocutaneous syndromes, including tuberous sclerosis complex, neurofibromatosis, Sturge-Weber syndrome, Ehlers-Danlos syndrome, and von Hippel-Lindau disease.