Action of physostigmine on inherited ataxias.

Physostigmine improved videotape scores of ataxia in patients with various inherited ataxias. This improvement occurred in 12 out of 12 patients when the drug was given as a single dose and in nine of 11 patients when the drug and placebo were given in a long-term, double-blind randomized trial. Patients report various mild to moderate clinical benefits after the sustained use of physostigmine for 6 to 36 months. Videotape scores showed an average of 30% numerical improvement in seven patients after 6 months' sustained treatment. The acute responses are not blocked by methylscopolamine, methylscopolamine did not make ataxia more severe, nor have any patients had fasciculations or changes in strength while on physostigmine. We therefore presume that a central cholinergic mechanism plays some role in the pathophysiology of the inherited ataxias. We do not have direct data on the site or nature of this mechanism. Further studies with other cholinergic agents are now required to investigate the effects and potential clinical efficacy of this class of compounds more completely than has been done up to now.