Journal of neurology
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Journal of neurology · Oct 2005
ReviewDoes levodopa slow or hasten the rate of progression of Parkinson's disease?
Levodopa therapy, as originally established by George Cotzias [2, 3], is the most powerful treatment for Parkinson's disease (PD). Levodopa's toxicity to neurons in vitro has raised concerns if it might hasten the progression of PD, although in vivo animal studies suggest it may be neuroprotective. ⋯ The clinical outcomes not only indicate that levodopa is effective in a dose-dependent manner in overcoming the signs and symptoms of PD, they also support the concept that the drug does not hasten the disease progression, but rather may slow down the rate of the disease. The clinical study failed to demonstrate any evidence of levodopa worsening early PD. However, the beta-CIT SPECT substudy indicates the opposite effect, namely that levodopa causes a more rapid decline in the integrity of the dopamine transporter located in the nigrostriatal nerve terminals in the striatum. These contradictory findings warrant further investigation into the effect of levodopa on PD. OTHER OBSERVATIONS: The ELLDOPA study was the first levodopa dose-response study ever conducted. It showed that dose is a factor in the cause of producing motor complications of dyskinesias and wearing-off, and that these can develop as early as 5 to 6 months. On the other hand, freezing of gait could be delayed or its occurrence reduced by high dosage levodopa, compared to placebo or low-dose levodopa. Withdrawal of levodopa over a 3-day step-down can be safely carried out without inducing the neuroleptic-like syndrome. The UPDRS was shown to be a reliable linear marker for disease progression. The ELLDOPA study also called into question the interpretation of beta-CIT SPECT in the presence of dopaminergic agents. Neuroimaging in ELLDOPA also showed that some people diagnosed with early PD do not have a dopaminergic deficit, calling into question how difficult the correct diagnosis may be in people with early symptoms of PD.