piperidines and Spinocerebellar-Ataxias

To elucidate characteristic changes of brain acetylcholinesterase (AChE) in cerebellar degenerative disorders. Eight patients with the cerebellar variant of multiple system atrophy (MSA-C), 7 patients with spinocerebellar ataxia type-3 (SCA-3), 3 patients with SCA-6, and 13 healthy age-matched volunteers participated in this study. Brain AChE activity was measured by [(11)C] N-methylpiperidin-4-yl propionate PET in all subjects. Brain AChE activities were significantly decreased in the thalamus (-27%) and the posterior lobe of cerebellar cortex (-36%) in patients with MSA-C and in the thalamus (-23%) in patients with SCA-3 compared with healthy controls (P < 0.01). Thalamic AChE activities of SCA-3 patients were negatively correlated with the unified Parkinson's disease rating scale motor subscore (P < 0.001). AChE activities were not significantly altered in the cerebral cortex in any disease group. Reduction of AChE activities in the thalamus and cerebellum in MSA and in the thalamus in SCA-3 suggest that cholinergic modulating drugs may have a role in the treatment of ataxia and other symptoms in these disorders.

Topics: Acetylcholinesterase; Adult; Aged; Brain; Carbon Radioisotopes; Cerebellar Cortex; Cerebral Cortex; Female; Humans; Image Processing, Computer-Assisted; Machado-Joseph Disease; Magnetic Resonance Imaging; Male; Middle Aged; Multiple System Atrophy; Neurologic Examination; Piperidines; Positron-Emission Tomography; Propionates; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Thalamus