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Viewpoint
December 16, 2019

Freezing of Gait and its Levodopa Paradox

Author Affiliations
  • 1Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Rehabilitation, Nijmegen, the Netherlands
  • 2Department of Rehabilitation, Sint Maartenskliniek, Nijmegen, the Netherlands
  • 3Department of Neurology, Besançon University Hospital, Besançon, France
  • 4Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Center of Expertise for Parkinson & Movement Disorders, Department of Neurology, Nijmegen, the Netherlands
JAMA Neurol. Published online December 16, 2019. doi:10.1001/jamaneurol.2019.4006

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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