Objective: To perform a detailed longitudinal clinical and neurophysiological investigation in monogenic Dopa-responsive dystonia (DRD) patients with mutations in the guanosine triphosphate cyclohydrolase 1 (GCH1) gene.
Background: The lack of a clear understanding of the pathophysiology of dystonia seems at least partly explained by a paucity of multimodal longitudinal studies on monogenic forms that could lay the ground for genotypic-neurophysiological correlations.
In this respect, DRD due to mutations in the GCH1 gene encoding an essential enzyme for dopamine production, might serve as a monogenic model disease for idiopathic, genetically undefined disease forms.
Method: Twenty GCH1 mutation carriers and 20 healthy controls participated in our detailed, video-guided clinical examination and neuronavigated dual-pulse transcranial magnetic stimulation (TMS) study investigating short-interval intracortical inhibition and premotor-motor interaction, including measurements under dopaminergic treatment (On L-Dopa treatment) and after a 22-hour drug withdrawal (OFF L-Dopa treatment), as well as longitudinal measurements in 2014 and 2019 in a subgroup of patients and controls.
Results: There was no group effect (GCH1 mutation carriers vs. controls) on short-interval intracortical inhibition and premotor-motor interaction, but a clear improvement of clinical symptoms and a shift towards premotor-motor facilitation under dopaminergic treatment (ON L-Dopa vs. OFF L-Dopa treatment). We found no change in motor network excitability and interaction nor a change of the good responsiveness to medication over time in GCH1 mutation carriers re-investigated after five years.
Conclusion: Our data show L-Dopa-sensitive clinical and neurophysiological network responses but no significant differences in neurophysiology, medication effect, and clinical presentation in our longitudinal comparisons after five years. Additional follow-up investigations over a longer time period are planned to complement our present study.
To cite this abstract in AMA style:
A. Steinmeier, MG. Pauly, DM. Al-Shorafat, G. Saranza, AE. Lang, N. Brüggemann, V. Tadic, C. Klein, K. Lohmann, MJN. Brown, C. Beste, A. Münchau, T. Bäumer, A. Weissbach. Multimodal, longitudinal investigation in Dopa-responsive dystonia [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/multimodal-longitudinal-investigation-in-dopa-responsive-dystonia/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/multimodal-longitudinal-investigation-in-dopa-responsive-dystonia/