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Controversies in Neurology
January 2007

Both Postsynaptic and Presynaptic Dysfunction Contribute to Parkinson Disease: Any Mechanism Will Not Do

Arch Neurol. 2007;64(1):143. doi:10.1001/archneur.64.1.143

Neurologists have argued in this column for years about the optimal treatment of Parkinson disease (PD). Twenty years ago the debate was whether to initiate levodopa at the time of diagnosis or to defer treatment until the symptoms became more severe.1,2 Proponents of delayed therapy perceived that levodopa was only useful for a limited time and should be saved until the symptoms became disabling.1 Others argued that the treatment response lessens because PD is progressive, not because the drug effect wanes.2 More recently, the debate has centered around the notion that prolonged use of levodopa is somehow toxic to dopaminergic neurons while dopamine agonists are nontoxic and perhaps even protective.3-5

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