THE EFFECTS OF CLONAZEPAM AND VIGABATRIN IN HYPEREKPLEXIA

Hyperekplexia is an autosomal dominant disorder caused by a point muta tion in the al subunit of the glycine receptor, characterized by exces sive startle responses followed by temporary generalized stiffness. Cl onazepam, effective in open case studies, potentiates, through unknown mechanisms, the neurotransmitter gamma-aminobutyric acid (GABA). Viga batrin increases GABA by inhibition of the GABA catabolic enzyme GABA- transaminase. Effects of clonazepam (1 mg for 1 day) and vigabatrin (1 000 mg per day for 5 days) were investigated in a double-blind placebo -controlled cross-over study in 4 patients with hyperekplexia. The pha rmacodynamic parameters were startle reflexes, studied 3 times during the day. At each time, 2 trains of IO auditive stimuli (113 dB) were g iven at intervals of 10 and 60 s. Startle movements were quantified wi th summed areas of EMG-bursts of the orbicularis oculi, sternocleidoma stoid, biceps and thenar muscles. The degrees of stiffness and drowsin ess were quantified with visual analogue scores (VAS) IO times during the day, by both the patient and the observer. Clonazepam, but not vig abatrin, reduced startle activity significantly in both paradigms. The degree of stiffness and drowsiness was not significantly influenced b y either drug. (C) 1997 Elsevier Sciences B.V.