Piribedil: its synergistic effect in multidrug regimens for parkinsonism.

Piribedil, a dopamine agonist, was administered to 13 patients with long-standing Parkinson's disease whose major symptoms were not well controlled on levodopa, anticholinergics, alpha-methyldopa, amantadine, or a combination of these agents. Twelve of the 13 clearly benefited from the addition of Piribedil although side effects precluded long term use in two cases. Beneficial results were obtained by using a combination of Piribedil, levodopa, and anticholinergic drugs. Side effects (hallucinations, confusion, dyskinesias) were frequent, but were usually reversible by lowering the dosage of levodopa or the accompanying anticholinergic medication. The synergistic effect of Piribedil and other antiparkinsonian drugs emphasizes the need for careful titration of all available medications in difficult cases and demonstrates the usefulness of dopamine receptor stimulators when drugs acting presynaptically have failed.

Mental symptoms in Parkinson's disease during chronic treatment with levodopa.

Mental symptoms increased in frequency among 100 patients with parkinsonism treated with levodopa. Dementia was found in about one-third of patients throughout the 6-year treatment period. Thirteen patients became demented during the study, and dementia worsened severely in seven others. Agitated confusion became increasingly frequent and was observed in 60 percent of patients taking levodopa for 6 years. Withdrawal from levodopa decreased agitation, but not dementia. Ten patients received L-tryptophan along with levodopa, but no change in mentation was observed. In view of previous studies of mentation in Parkinson's disease and reports of widespread neuronal changes in the brain of autopsied patients with parkinsonism, our results suggest that the high incidence of dementia in patients with Parkinson's disease who take levodopa reflects prolongation of the course of the illness rather than a direct effect of the medication.

Five years' treatment of Parkinson's disease with levodopa. Therapeutic results and survival of 100 patients.

One hundred patients with Parkinson's disease, who started taking levodopa before the end of 1968, have been assessed after 5 years. Forty-seven patients are still being followed on levodopa, and half of them are at least 25% better than at their pretreatment evaluation. However, the average functional rating is returning toward baseline from its remarkable improvement at 1/2 to 2 years. Abnormal involuntary movements, rapid oscillations in motor performance, postural instability, and dementia have become the major adverse effects. Thirty-two of the 100 patients have died. Life-table analysis shows an excess mortality of 1.9 compared with the U.S. population, a figure that is lower than the 2.9 reported before levodopa's use. Despite its inability to cure Parkinson's disease, levodopa provides symptomatic relief for a prolonged time and it remains the single most effective medication for the illness.

Treatment of "on-off effect" with a dopa decarboxylase inhibitor.

Irregularities in motor response after continuing levodopa therapy of Parkinson disease (the "on-off effect") were assessed with the addition of L-alpha-methyldopa hydrazine (carbidopa) in a double-blind study. Thirteen of 20 patients improved while receiving carbidopa and levodopa while only four of 17 patients improved while receiving placebo and levodopa. Twenty-three of 37 patients improved in a subsequent non-blind trial of carbidopa plus levodopa. Improvement was not dependent on an increase in dose or frequency of levodopa administration. Adverse effects included dyskinesia, imbalance, and confusion; nausea was eliminated. On patient died of glomerulonephritis that predated the drug trial, but worsened progressively during and after it. Carbidopa's suppression of the "on-off effect" suggests that extracerbral factors may be important in this phenomenon.

Neurological features of Gilles de la Tourette's syndrome.

Clinical neurological examinations of 22 patients with Gilles de la Tourette's syndrome and written reports of examinations of seven other patients are reported. Half the personally examined patients had minor motor asymmetries in addition to the typical motor and vocal tics found in all the patients. Thirty-six per cent of patients were left handed or ambidextrous. Electroencephalograms performed on 17 of the 22 patients showed non-specific abnormalities in 12 of them. These findings suggest that a neurological disorder underlies Tourette's syndrome, but they do not clarify its nature.