Abnormal motor cortex plasticity in premanifest and very early manifest Huntington disease.
BACKGROUND
Cognition is affected early in Huntington disease (HD), and in HD animal models there is evidence that this reflects abnormal synaptic plasticity. The authors investigated whether there is any 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 (seven premanifest, eight 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 200 ms). The size of the motor-evoked potential was measured at regular intervals until 21 min after cTBS.


RESULTS
HD gene carriers and controls responded differently to theta burst stimulation (F(4.9,131.9)=1.37, p=0.048) with controls having more inhibition than HD gene carriers (F(1,27)=13.3, p=0.001). Across all time points, mean inhibition differed between the groups (F(2,26)=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 (Unified Huntington Disease Rating Scale 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.
Orth
Michael
M
Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, UK. michael.orth@uni-ulm.de
Schippling
Sven
S
Schneider
Susanne A
SA
Bhatia
Kailash P
KP
Talelli
Penelope
P
Tabrizi
Sarah J
SJ
Rothwell
John C
JC
D000328:Adult; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D042241:Early Diagnosis; D004558:Electric Stimulation; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D013223:Statistics as Topic; D013826:Theta Rhythm