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Autosomal recessive parkin (PARK2) gene-related parkinsonism may be phenotypically and pathophysiologically distinct from idiopathic Parkinson's disease (PD). Furthermore, asymptomatic subjects carrying a single parkin mutation ("parkin carriers") may show striatal dopaminergic dysfunction and increased cortical movement-related activation. Here, we used transcranial magnetic stimulation (TMS) to study corticospinal and intracortical excitability in manifesting parkin patients and asymptomatic carriers. We studied resting and active motor thresholds (RMT/AMT), central motor conduction time (CMCT), active recruitment curves, short-interval intracortical inhibition (SICI) and facilitation (ICF), SICI recruitment curve, and cortical silent period (CSP) in 8 patients "off" medication, 7 carriers, and two groups of age-matched controls (n = 21). Patients had longer CMCTs compared to controls with a significant negative correlation between CMCT duration and onset age (r = -0.83, P = 0.04). Carriers had increased RMT/AMT; the time course of SICI/ICF and the duration of CSP were normal in both patients and carriers; however slight abnormalities in the recruitment of SICI were found in the carriers. Prolonged CMCT and normal cortical inhibitory mechanisms in parkin patients may be of value in the differentiation from idiopathic PD. The subclinical electrophysiological abnormalities found in carriers may represent underlying compensatory mechanisms.

Original publication

DOI

10.1002/mds.22025

Type

Journal article

Journal

Mov Disord

Publication Date

15/10/2008

Volume

23

Pages

1812 - 1819

Keywords

Adult, Aged, Analysis of Variance, Case-Control Studies, Electric Stimulation, Electromyography, Evoked Potentials, Motor, Female, Humans, Male, Middle Aged, Motor Cortex, Mutation, Neural Conduction, Parkinson Disease, Pyramidal Tracts, Reaction Time, Recruitment, Neurophysiological, Sensory Thresholds, Transcranial Magnetic Stimulation, Ubiquitin-Protein Ligases