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.
Using transcranial magnetic stimulation (TMS) we examined motor cortex excitability in 8 premanifest HD gene carriers, 8 very early symptomatic HD patients and 22 healthy controls. Electrophysiological measures were correlated with the clinical stage of HD to identify motor cortical dysfunction prior to overt clinical disease onset.
Premanifest and early manifest HD patients had higher resting and active motor cortex thresholds than controls (p=0.024). At rest, recruitment of motor evoked potentials was more gradual in both patient groups than in controls (p=0.001). When active, recruitment and the duration of the cortical silent period were similar in all groups. There was a tendency for short latency intra-cortical inhibition (SICI) 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 controls and premanifest patients (p<0.001) and in contrast to all other measures was inversely associated with predicted years to onset of HD signs (p=0.013, adjusted R2=0.32) and the UHDRS motor score (p=0.001, adjusted R2=0.5). A combination of age, CAG repeat length, and SAI strongly predicted the UHDRS motor score (p=0.001, adjusted R2=0.68).
Since reduced excitatory and inhibitory corticospinal thresholds and MEP recruitment in patients at rest do not correlate with symptom severity, they may be a consequence of carrying the HD mutation. In contrast, SAI correlated with the severity of motor signs and may reflect the disease state.