Mexiletine for the Treatment of Focal Dystonia

Dystonia is a complex neurological disorder with an unknown pathogenesis likely involving the basal ganglia. There is no adequate treatment for dystonia. Recent studies using intramuscular and intravenous lidocaine have shown improvement in dystonic movements. It has been proposed that patients with dystonia have reduced presynaptic inhibition of alpha motoneurons leading to overactivation in response to movement. This may also reflect a hyperexcitability at the cortical level, which can be reduced by altering peripheral input. Mexiletine, an antiarrhythmic similar to lidocaine, but available orally, may benefit patients with dystonia, as has been shown in several recent open-label studies. This trial offers the possibility of treating dystonia as well as further elucidating the level of dysfunction in the nervous system in dystonic patients. We propose a double-blind cross over study comparing mexiletine to placebo in the treatment of patients with idiopathic dystonia. The patients will be evaluated by clinical rating scales as well as neurophysiological studies. In order to study the physiologic effect and attempt to localize the neuroanatomic sight of action of mexiletine, studies of peripheral reflexes, reciprocal inhibition and cortical excitation will be performed. These studies will include blink reflex recovery curves, tonic vibration reflex, H-reflex and transcranial magnetic stimulation.