Clinical aspects of motor fluctuations in Parkinson's disease.

Fluctuations in motor response eventually affect most patients with Parkinson's disease who have been exposed to chronic, intermittent levodopa administration for longer than 5 years. Response oscillations are often related to the timing of levodopa doses (predictable "wearing-off"), but random "on-off" effects also occur in one subgroup of patients. The underlying pathophysiology of each type of effect may be different. Treatment also differs: Patients with complex refractory oscillations may benefit from continuous dopaminergic stimulation with enteral infusions of levodopa or subcutaneous infusions of apomorphine. Three major types of abnormal drug-induced involuntary movements (interdose and biphasic dyskinesias and "off-period" dystonia) accompany these response oscillations in most patients, making fluctuating Parkinson's disease symptoms the most challenging problem in antiparkinsonian therapy. The underlying mechanisms for motor fluctuations have only been partially explained, and preventive treatment strategies have yet to be defined in properly designed prospective long-term studies.