Changes in Cortical Excitability and Parkinson Tremor After Botulinum Toxin Therapy.

This study investigated the relationship between botulinum toxin type A (BoNT-A) administration, tremor amplitude, and modulation of intracortical excitability and sensorimotor processing using paired-pulse transcranial magnetic stimulation (pp-TMS) in early, tremor-dominant Parkinson's disease (PD) patients. Twelve "De-novo" (naïve to anti-PD medications) and seven "L-dopa" (optimized on levodopa) PD participants with tremor affecting one arm were recruited. All participants received 4 serial BoNT-A treatments for tremor every 12-weeks and peak effect was assessed 6-weeks post-treatment, totaling 8 visits over 42-weeks. Injection parameters were based on kinematic tremor analysis. Short interval intracortical inhibition (SICI), intracortical facilitation (ICF), long interval intracortical inhibition (LICI), and measures of sensorimotor interaction (short- (SAI) and long- (LAI) latency afferent stimulation) were assessed in both hemispheres using pp-TMS paradigms at each time-point. Linear mixed models analyzed the effect of each pp-TMS measure and tremor severity within each cohort and the association between pp-TMS and tremor severity in the "De-novo" cohort over 42-weeks. T-tests compared pp-TMS measures between hemispheres per time-point. Baseline SICI, LICI, and SAI was reduced (higher MEP ratio) on the tremulous/treated-side compared to the non-tremulous-side in "De-novo" participants. On the treated-side in the "De-novo" cohort, BoNT-A treatment significantly reduced ICF and increased LICI, SAI and LAI (lower MEP ratio) at peak BoNT-A time-points. The change in tremor severity was significantly associated with changes in SICI, LICI and LAI. Our findings suggest that tremor severity in early PD may be related to impaired intracortical inhibition and defective sensorimotor integration.

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© 2021 American Academy of Neurology.