Anne Weissbach1, Tobias Bäumer2, Peter P Pramstaller3, Norbert Brüggemann1, Vera Tadic1, Robert Chen4, Christine Klein2, Alexander Münchau5. 1. Institute of Neurogenetics, University of Luebeck, Germany; Department of Neurology, University of Luebeck, Germany. 2. Institute of Neurogenetics, University of Luebeck, Germany. 3. Center for Biomedicine, European Academy of Bolzano, Bolzano, Italy. 4. Division of Neurology, Krembil Neuroscience Centre and Toronto Western Research Institute, University Health Network, Toronto, Canada. 5. Institute of Neurogenetics, University of Luebeck, Germany. Electronic address: alexander.muenchau@neuro.uni-luebeck.de.
Abstract
OBJECTIVES: Mutations in the Parkin and PINK1 gene account for the majority of autosomal recessive early-onset Parkinson cases. There is increasing evidence that clinically asymptomatic subjects with single heterozygous mutations have a latent nigrostriatal dopaminergic deficit and could be taken as in vivo model of pre-symptomatic phase of Parkinsonism. METHODS: We charted premotor-motor excitability changes as compensatory mechanisms for subcortical dopamine depletions using transcranial magnetic stimulation by applying magnetic resonance-navigated premotor-motor cortex conditioning in 15 asymptomatic, heterozygous Parkin and PINK1 mutation carriers (2 female; mean age 53±8years) and 16 age- and sex-matched controls (5 female; mean age 57±9years). Participants were examined at baseline and after acute l-dopa challenge. RESULTS: There were l-dopa and group specific effects during premotor-motor conditioning at an interstimulus interval of 6ms indicating a normalisation of premotor-motor interactions in heterozygous Parkin and PINK1 mutation carriers after l-dopa intake. Non-physiologically high conditioned MEP amplitudes at this interval in mutation carriers decreased after l-dopa intake but increased in controls. CONCLUSION: Premotor-motor excitability changes are part of the cortical reorganization in asymptomatic heterozygous Parkin- and PINK1 mutation carriers. SIGNIFICANCE: These subjects offer opportunities to delineate motor network adaptation in pre-symptomatic Parkinsonism.
OBJECTIVES: Mutations in the Parkin and PINK1 gene account for the majority of autosomal recessive early-onset Parkinson cases. There is increasing evidence that clinically asymptomatic subjects with single heterozygous mutations have a latent nigrostriatal dopaminergic deficit and could be taken as in vivo model of pre-symptomatic phase of Parkinsonism. METHODS: We charted premotor-motor excitability changes as compensatory mechanisms for subcortical dopamine depletions using transcranial magnetic stimulation by applying magnetic resonance-navigated premotor-motor cortex conditioning in 15 asymptomatic, heterozygous Parkin and PINK1 mutation carriers (2 female; mean age 53±8years) and 16 age- and sex-matched controls (5 female; mean age 57±9years). Participants were examined at baseline and after acute l-dopa challenge. RESULTS: There were l-dopa and group specific effects during premotor-motor conditioning at an interstimulus interval of 6ms indicating a normalisation of premotor-motor interactions in heterozygous Parkin and PINK1 mutation carriers after l-dopa intake. Non-physiologically high conditioned MEP amplitudes at this interval in mutation carriers decreased after l-dopa intake but increased in controls. CONCLUSION: Premotor-motor excitability changes are part of the cortical reorganization in asymptomatic heterozygous Parkin- and PINK1 mutation carriers. SIGNIFICANCE: These subjects offer opportunities to delineate motor network adaptation in pre-symptomatic Parkinsonism.
Authors: Lynne Krohn; Francis P Grenn; Mary B Makarious; Jonggeol Jeffrey Kim; Sara Bandres-Ciga; Dorien A Roosen; Ziv Gan-Or; Mike A Nalls; Andrew B Singleton; Cornelis Blauwendraat Journal: Neurobiol Aging Date: 2020-03-10 Impact factor: 4.673
Authors: Rebecca Herzog; Till M Berger; Martje G Pauly; Honghu Xue; Elmar Rueckert; Alexander Münchau; Tobias Bäumer; Anne Weissbach Journal: Front Neurosci Date: 2022-09-15 Impact factor: 5.152