Clinical correlations of partial deficiency of lipoamide dehydrogenase.

Reduced activities of lipoamide dehydrogenase (LAD) relative to cytochrome oxidase have been found in 12 or 26 patients with inherited ataxias. One of the 12 patients had adult-onset ataxia plus ragged-red muscle fibers. The other 11 had Friedreich syndrome or early-onset variants of this, as did 6 patients with normal enzyme activity. However, the 11 patients with reduced enzyme activity were clinically more homogeneous than the 6 with normal activity.

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.