Freezing of gait (FOG) in Parkinson disease (PD) is common and disabling. It has 3 phenotypes,1 the least common one being akinetic freezing (a lack of discernible leg movements despite an intention to walk). The other phenotypes can be characterized as freezing with attempted but ineffective stepping: one involves alternating-leg trembling with a frequency of 3 to 8 Hz, the other by small, shuffling steps. The underlying pathophysiological substrate remains insufficiently understood. In this Viewpoint, we address this fascinating but hitherto largely neglected paradox: levodopa generally reduces the severity of FOG, but 2 recent observations showed that in patients with parkinsonism who were untreated—even those with severe disease—the ineffective stepping phenotype of freezing is absent.2,3 Such observations suggest that long-term pulsatile levodopa treatment may contribute to FOG development. Initially, it is difficult to reconcile levodopa’s beneficial symptomatic outcomes with this negative development. We provide a new framework to explain this paradox as a basis for research and treatment.
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Nonnekes J, Bereau M, Bloem BR. Freezing of Gait and its Levodopa Paradox. JAMA Neurol. Published online December 16, 2019. doi:10.1001/jamaneurol.2019.4006
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