Abnormal motor cortex excitability in preclinical and very early Huntington's disease.
BACKGROUND
In Huntington's disease (HD), the cerebral cortex is involved early in the disease process. The study of cortical excitability can therefore contribute to understanding HD pathophysiology.


METHODS
With transcranial magnetic stimulation (TMS) we examined motor cortex excitability in 8 premanifest HD gene carriers, 8 very early symptomatic HD patients, and 22 healthy control subjects. Electrophysiological measures were correlated with the clinical stage of HD to identify motor cortical dysfunction before overt clinical disease onset.


RESULTS
Premanifest and early manifest HD patients had higher resting and active motor cortex thresholds than control subjects (p = .024). At rest, recruitment of motor evoked potentials was more gradual in both patient groups than in control subjects (p = .001). When active, recruitment and the duration of the cortical silent period were similar in all groups. There was a tendency for short interval intra-cortical inhibition to have a higher threshold in all patients taken together but not in each group separately. Short latency afferent inhibition (SAI) was reduced in early manifest patients compared with control subjects and premanifest patients (p < .001) and in contrast to all other measures was inversely associated with estimated time to onset (p = .013, adjusted R(2) = .32) and the Unified Huntington's Disease Rating Scale motor score (p = .001, adjusted R(2) = .5). A combination of age, CAG repeat length, and SAI strongly predicted the Unified Huntington's Disease Rating Scale motor score (p = .001, adjusted R(2) = .68).


CONCLUSIONS
Our findings add to the evidence for early cortical involvement in HD possibly before HD signs appear.
Schippling
Sven
S
Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, United Kingdom.
Schneider
Susanne A
SA
Bhatia
Khailash P
KP
Münchau
Alexander
A
Rothwell
John C
JC
Tabrizi
Sarah J
SJ
Orth
Michael
M
D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D013181:Cortical Spreading Depression / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D004576:Electromyography / Q000379:methods; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009431:Neural Conduction / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D050781:Transcranial Magnetic Stimulation / Q000379:methods