NL
DE
Freezing of gait is among the most mysterious and dramatic symptoms in persons with Parkinson’s disease and atypical parkinsonism. During an episode of freezing of gait, patients have the feeling that their feet are suddenly being glued to the floor, despite their intention to walk. Although freezing is both common and disabling, its pathophysiological substrate is poorly understood.
A recent study, with Jamie Jansen and Tamine Capato as shared first-authors, studied the levodopa-paradox surrounding freezing of gait: levodopa is the most effective symptomatic treatment for freezing of gait, but long-term pulsatile levodopa treatment has also been linked to an increase in the occurrence of freezing. Controlled studies could shed further light on this apparent levodopa paradox, but controlled experimentation is difficult as it would be unethical to withhold levodopa from persons with Parkinson’s disease for several years in healthcare settings where levodopa is available.
Therefore, out-of-the-box methods were needed. In several parts of the world, persons with Parkinson underserved: levodopa is not available, too expensive, or treatment is delayed because it is difficult to consult a neurologist. Such underserved populations (in effect creating levodopa-naive cohorts) provide a unique opportunity to study the levodopa paradox. Last-author Jorik Nonnekes obtained a personal ZonMW OffRoad Grant and subsequently led an international team that compared the occurrence of freezing of gait in a levodopa-naive cohort in Brazil to a levodopa-treated cohort (consisting of persons with Parkinson from Brazil and the Netherlands).
An association between long-term pulsatile levodopa treatment and an increased occurrence of freezing of gait was found. Future studies should now further explore the role of non-physiological stimulation of dopamine receptors in generating freezing of gait, as a basis for possible prevention studies.
Read the publication here
Jansen JAF, Capato TTC, Darweesh SKL, Barbosa ER, Donders R, Bloem BR, Nonnekes J. Exploring the levodopa-paradox of freezing of gait in dopaminergic medication-naive Parkinson's disease populations. NPJ Parkinsons Dis 2023;9:130
