Heidemarie Zach1,2, Michiel F Dirkx1, Dominik Roth3, Jaco W Pasman1, Bastiaan R Bloem1, Rick C Helmich4. 1. Radboud University Medical Centre; Donders Institute for Brain, Cognition and Behaviour; Department of Neurology; Nijmegen, The Netherlands. 2. Department of Neurology, Medical University Vienna, Vienna, Austria. 3. Department of Emergency Medicine, Medical University Vienna, Vienna, Austria. 4. Radboud University Medical Centre; Donders Institute for Brain, Cognition and Behaviour; Department of Neurology; Nijmegen, The Netherlands rick.helmich@radboudumc.nl.
Abstract
OBJECTIVE: We tested the hypothesis that there are two distinct phenotypes of Parkinson's tremor, based on inter-individual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor, by comparing inter-individual differences in the dopamine response of tremor to that of bradykinesia. METHODS: In this exploratory study, we performed a levodopa challenge in 76 tremulous Parkinson patients. Clinical scores (MDS-UPDRS part-III) were collected OFF and ON a standardized dopaminergic challenge (200/50mg dispersible levodopa-benserazide). In both sessions, resting tremor intensity was quantified using accelerometry, both during rest and during cognitive co-activation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for resting tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately six months. RESULTS: The dopamine response of resting tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster-analysis on three clinical and electrophysiological markers of tremor dopamine-responsiveness revealed three clusters: dopamine-responsive, intermediate, and dopamine-resistant tremor. A repeated levodopa challenge after six months confirmed this classification. Patients with dopamine-responsive tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. CONCLUSION: Parkinson's resting tremor can be divided into three partially overlapping phenotypes, based on the dopamine-response. These tremor phenotypes may be associated with different underlying pathophysiological mechanisms, requiring a different therapeutic approach.
OBJECTIVE: We tested the hypothesis that there are two distinct phenotypes of Parkinson's tremor, based on inter-individual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor, by comparing inter-individual differences in the dopamine response of tremor to that of bradykinesia. METHODS: In this exploratory study, we performed a levodopa challenge in 76 tremulous Parkinsonpatients. Clinical scores (MDS-UPDRS part-III) were collected OFF and ON a standardized dopaminergic challenge (200/50mg dispersible levodopa-benserazide). In both sessions, resting tremor intensity was quantified using accelerometry, both during rest and during cognitive co-activation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for resting tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately six months. RESULTS: The dopamine response of resting tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster-analysis on three clinical and electrophysiological markers of tremordopamine-responsiveness revealed three clusters: dopamine-responsive, intermediate, and dopamine-resistant tremor. A repeated levodopa challenge after six months confirmed this classification. Patients with dopamine-responsive tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. CONCLUSION:Parkinson's resting tremor can be divided into three partially overlapping phenotypes, based on the dopamine-response. These tremor phenotypes may be associated with different underlying pathophysiological mechanisms, requiring a different therapeutic approach.
Authors: Daniel Rodríguez-Martín; Joan Cabestany; Carlos Pérez-López; Marti Pie; Joan Calvet; Albert Samà; Chiara Capra; Andreu Català; Alejandro Rodríguez-Molinero Journal: Front Neurol Date: 2022-06-02 Impact factor: 4.086
Authors: Robert Chen; Alfredo Berardelli; Amitabh Bhattacharya; Matteo Bologna; Kai-Hsiang Stanley Chen; Alfonso Fasano; Rick C Helmich; William D Hutchison; Nitish Kamble; Andrea A Kühn; Antonella Macerollo; Wolf-Julian Neumann; Pramod Kumar Pal; Giulia Paparella; Antonio Suppa; Kaviraja Udupa Journal: Clin Neurophysiol Pract Date: 2022-06-30