Lamotrigine and catamenial epilepsy

SummaryCatamenial epilepsy (CE) is characterized by epileptic seizures in the female occurring rhythmatically with the menstrual cycle. Hormonal mechanisms have been proposed as a cause of this epileptic form. Few reports about the efficacy of anti-epileptic drugs (AEDs) have been published. We studied prospectively women with CE who were treated with lamotrigine (LTG) for a period of 3 months in order to evaluate its efficacy, measuring the progesterone levels before and after LTG at the same time. LTG seemed to be efficacious in 66% of women, meaning the disappearance of seizures or reduction of 50% or more of the number of seizures. The reported side effects were few and mild, and the drug was well tolerated. Serum progesterone levels were found to rise during LTG treatment

The Proteomic Profile of Hereditary Inclusion Body Myopathy

Hereditary inclusion body myopathy (HIBM) is an adult onset, slowly progressive distal and proximal myopathy. Although the causing gene, GNE, encodes for a key enzyme in the biosynthesis of sialic acid, its primary function in HIBM remains unknown. The goal of this study was to unravel new clues on the biological pathways leading to HIBM by proteomic comparison. Muscle cultures and biopsies were analyzed by two dimensional gel electrophoresis (2-DE) and the same biopsy extracts by isobaric tag for relative and absolute quantitation (iTRAQ). Proteins that were differentially expressed in all HIBM specimens versus all controls in each analysis were identified by mass spectrometry. The muscle cultures 2-DE analysis yielded 41 such proteins, while the biopsies 2-DE analysis showed 26 differentially expressed proteins. Out of the 400 proteins identified in biopsies by iTRAQ, 41 showed altered expression. In spite of the different nature of specimens (muscle primary cultures versus muscle biopsies) and of the different methods applied (2D gels versus iTRAQ) the differentially expressed proteins identified in each of the three analyses where related mainly to the same pathways, ubiquitination, stress response and mitochondrial processes, but the most robust cluster (30%) was assigned to cytoskeleton and sarcomere organization. Taken together, these findings indicate a possible novel function of GNE in the muscle filamentous apparatus that could be involved in the pathogenesis of HIBM

The homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered overall cellular sialylation in hereditary inclusion body myopathy

AbstractHereditary inclusion body myopathy (HIBM) is a neuromuscular disorder, caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, the key enzyme of sialic acid biosynthesis. In Middle Eastern patients a single homozygous mutation occurs, converting methionine-712 to threonine. Recombinant expression of the mutated enzyme revealed slightly reduced N-acetylmannosamine kinase activity, in agreement with the localization of the mutation within the kinase domain. B lymphoblastoid cell lines derived from patients expressing the mutated enzyme also display reduced UDP-N-acetylglucosamine 2-epimerase activity. Nevertheless, no reduced cellular sialylation was found in those cells by colorimetric assays and lectin analysis, indicating that HIBM is not directly caused by an altered overall expression of sialic acids

Auditory Hallucinations in Acute Stroke

Auditory hallucinations are uncommon phenomena which can be directly caused by acute stroke, mostly described after lesions of the brain stem, very rarely reported after cortical strokes. The purpose of this study is to determine the frequency of this phenomenon. In a cross sectional study, 641 stroke patients were followed in the period between 1996–2000. Each patient underwent comprehensive investigation and follow-up. Four patients were found to have post cortical stroke auditory hallucinations. All of them occurred after an ischemic lesion of the right temporal lobe. After no more than four months, all patients were symptom-free and without therapy. The fact the auditory hallucinations may be of cortical origin must be taken into consideration in the treatment of stroke patients. The phenomenon may be completely reversible after a couple of months

Evidence for Genetic Heterogeneity Supports Clinical Differences in Congenital Myasthenic Syndromes

Congenital myasthenic syndromes (CMS) define a diverse group of disorders, all of which compromise neuromuscular transmission. Symptoms can be present at birth or appear during childhood, and can range in severity. Both autosomal dominant and recessive forms exist, and a number of clinical subtypes have been described. The cause of many cases of CMS has been traced to mutations in the genes for the acetylcholine receptor (AChR) subunits, previously mapped to chromosomes 2 and 17. Recently, an additional form of CMS known as familial infantile myasthenia (FIM) was linked to chromosome 17p. The gene for FIM has not yet been identified. We examined the DNA from 5 families of Iranian Jewish origin (6 affected individuals) who have been diagnosed with a phenotypically unique form of CMS. Four of the families are consanguinous, and all families originate from the same geographical region, thus it is highly likely that they would carry the same ancestral CMS mutation. We examined these families for linkage to the regions on chromosomes 2 and 17 containing the AChR subunit genes, and to the region on 17p to which FIM was localized. Our data excludes linkage to these regions, suggesting that the clinical differences seen among patients with CMS correlate with locus heterogeneity, and that a defect in a different gene is responsible for the CMS in these patients