Improved perseveration with amantadine

We report here 3 patients who showed marked improvement of clonic and intentional perseverations following the administration of amantadine. Patient 1 had a subacute encephalitis of unknown etiology. Magnetic resonance imaging documented lesions predominantly in the bilateral putaminal and frontal subcortical areas, and positron emission tomography revealed frontal glucose hypometabolism. Daily amantadine hydrochloride of 200 mg with or without 10 mg of trihexyphenidyl, reduced his clonic and intentional perseverations. The diagnosis of patients 2 and 3 was vascular dementia with multiple subcortical ischemic lesions, and single photon emission CTs showed reduced cerebral blood flow in the frontal lobes. Their clonic perseveration subsided and intentional perseveration disappeared after the administration of 150 mg of daily amantadine hydrochloride. Associated Parkinsonism and confusional state also improved in patient 1, but not in patients 2 or 3. Amantadine increases the pre-sypaptic synthesis and release of dopamine, and works as a dopamine system activator. Our findings suggest that the disturbance of dopamine system, especially meso-limbofrontal projection, has some contributions to the perseveration of these patients.