Patients on levodopa who develop motor fluctuations:
More frequent, small doses of levodopa or liquid Sinemet
Selegiline agonists (or COMI inhibitors)
Consider neurotransplantation or pallidal surgery
Patients with unremitting tremor:
Thalamic surgery (ablative or deep brain stimulation)
Patients with hallucinations:
Reduce medications. Stop all drugs except Sinemet
Consider Clozapine or other neuroleptic with few extrapyramidal side effects
Modified from Hughes AJ, Calasimo C, Kleedorfer B, et al: Ihe dopaminergic response in multiple system atrophy. J Neurol Neurosurg Psychiatry 1992;55:1009-1013.
symptoms need urgent treatment to protect the patient's safety or job security, levodopa is introduced because it is the most effective drug with the most rapid onset of action. If symptoms can be treated more slowly, the use of anticholinergic drugs in young patients with tremor-predominant PD is often helpful, and amantadine or dopamine agonists can be used as dopamine drugs that may delay the need to start levodopa in other patients. In patients who are just starting Sinemet, the controlled-release form is often selected to minimize the number of doses needed each day. As the disease progresses, combinations of drugs are usually needed, and most patients will require both an agonist and Sinemet within the first 7 years of therapy. In elderly patients, especially those with hallucinations or dementia, however, Sinemet alone, usually in the regular formulation, is often the most practical regimen because of its relative simplicity. In terms of referral to a movement disorder specialist, if the patient develops complicated dyskinesia, a prominent behavioral problem, or additional neurological signs that suggest the presence of another parkinsonian disorder (Parkinson-plus syndromes), he or she should be evaluated in a center that has expertise in these unusual problems and has access to experimental drugs and surgical protocols.
One particularly difficult problem in managing PD patients is hallucinosis. Patients who are treated chronically with dopaminergic drugs develop visual hallucinations that can become frightening and severely disabling to the patient and caregiver. In this situation, the drug dosage
should be reduced, and most patients are best managed on Sinemet alone. In some instances, novel neuroleptics with few extrapyramidal side effects can be used.
Clozapine has been successful in abating hallucinations and psychotic behavior in PD patients, but it is an expensive drug and is associated with the potentially lethal side effect of agranulocytosis.'^ Other antipsychotic drugs and alternate therapies are currently being evaluated for this area of serious disability.
Prognosis and Future Perspectives. Survival of patients with PD has greatly improved since the development of levodopa. Prior to the advent of levodopa, mortality among PD patients was three times the normally expected mortality. However, with the advent of levodopa and other medications, the life span of PD patients is almost the same as that of an age-matched control population without the disease. y Some studies have suggested that PD patients are more likely to die from infection than from cancer compared to an age-matched group of controls. Early, even presymptomatic, detection of disease is paramount to early intervention, and major efforts are currently aimed at identifying biological markers for both the presence of disease (trait marker) and disease activity (state marker).
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