Amyotrophic Lateral Sclerosis

Abstract

Cerebrospinal fluid (CSF) levels of homovanillic acid (HVA), a major catabolite of dopamine, were substantially less in 21 patients with amyotrophic lateral sclerosis (ALS) than in 19 controls. There was also a significant reduction in the probenecid-induced accumulation of HVA in the CSF of ALS patients as compared with control subjects. Since probenecid inhibits the efflux of HVA from the central nervous system, the results suggest that central dopamine synthesis may be diminished in ALS. A therapeutic trial of levodopa, the immediate precursor of dopamine, in ten ALS patients failed to improve motor function. Defects in central dopamine metabolism, inferred from these tests applicable to the living patient, evidently may attend neurologic disorders which are unresponsive to precursor loading with levodopa.