Abnormal motor cortex plasticity in premanifest and very early manifest Huntington’s disease
- Michael Orth1,*,
- Sven Schippling2,
- Susanne A Schneider3,
- Kailash Bhatia4,
- Penelope Talelli5,
- Sarah J Tabrizi6,
- John Rothwell5
- 1 Department of Neurology, University of Ulm, Germany;
- 2 Department of Neurology, University Hospital Medical Center, Hamburg-Eppendorf, Germany;
- 3 Neurogenetics Unit, University Hospital Luebeck, Germany;
- 4 Institute of Neurology, Queen Square, London, United Kingdom;
- 5 Institute of Neurology, United Kingdom;
- 6 Department of Neurodegenerative Diseases, Institute of Neurology, Queen Square, London WC1N 3BG, Uni, United Kingdom
- Correspondence to: , ; michael.orth{at}uni-ulm.de
- Received 6 January 2009
- Accepted 27 August 2009
- Published Online First 13 October 2009
Abstract
Background: Cognition is affected early in Huntington’s disease, and in HD animal models there is evidence that this reflects abnormal synaptic plasticity. We investigated whether there is evidence for abnormal synaptic plasticity using the human motor cortex-rTMS model, and if so, if there is any difference between premanifest HD gene carriers and very early manifest HD patients or any relationship with ratings of the severity of motor signs.
Methods: Fifteen HD gene carriers (7 premanifest, 8 very early manifest) and 14 control participants were given a continuous train of 100 bursts of theta burst stimulation (cTBS: three pulses at 50 Hz and 80% AMT repeated every 200ms). The size of the motor evoked potential was measured at regular intervals until 21 minutes after cTBS.
Results: HD gene carriers and controls responded differently to theta burst stimulation (F4.9,131.9=1.37, p=0.048) with controls having more inhibition than HD gene carriers (F1,27=13.3, p=0.001). Across all time points mean inhibition differed between the groups (F2,26=6.32, p=0.006); controls had more inhibition than either HD gene carrier subgroup (p=0.006 for premanifest and p=0.009 for early symptomatic) whereas there was no difference between premanifest and early symptomatic HD gene carriers. The measure of cortical plasticity was not associated with any clinical ratings (UHDRS motor score, estimate of age at onset).
Conclusions: Motor cortex plasticity is abnormal in HD gene carriers but is not closely linked to the development of motor signs of HD.
