Genetic heterogeneity in autosomal dominant essential tremor.

PURPOSE: To perform linkage analysis of candidate loci in a large Midwestern family with autosomal dominant essential tremor. METHODS: Thirty-eight members of a six-generation family were evaluated for essential tremor using consensus criteria. Linkage analysis was performed with microsatellite markers reported for three genetic loci associated with familial essential tremor. RESULTS: Patients exhibited a combination of postural and kinetic tremor involving primarily the arms and hands, with a mean age of onset of 31 years. Genetic studies excluded linkage to ETM1 and ETM2 loci, as well as a candidate locus for parkinsonism and postural tremor on chromosome 4p. CONCLUSION: Familial essential tremor is a common hereditary movement disorder demonstrating phenotypic variability and genetic heterogeneity.

Intravenous loading of valproate for epilepsy.

Valproate is an antiepileptic drug that has broad spectrum activity against several types of seizure. Little information is available about the use of valproate for acute loading of patients when a rapid increase in serum level is needed. We describe the use of intravenous valproate in 20 adults with epilepsy. In each case, a loading dose was calculated by multiplying the patient's body mass, desired change in serum level, and estimated volume of distribution. The mean dose (+/- SD) administered was 1420 +/- 440 mg (19.4 +/- 5.4 mg/kg). In four patients, the dose was infused at 20 mg/min; in all other patients, infusions were performed at 50 mg/min. The infusions were tolerated well and few clinical side effects were observed. Postinfusion levels were drawn and the apparent volume of distribution was calculated to be 0.22 +/- 0.04 L/kg. The results indicate that intravenous valproate may be used to quickly and efficiently increase serum levels in patients with epilepsy.