Changes in Cortical Excitability and Parkinson Tremor After Botulinum Toxin Therapy

Background and Objectives To investigate 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 patients with early, tremor-dominant Parkinson disease (PD). Methods Twelve de novo (naive to anti-PD medications) and 7 l-dopa (optimized on levodopa) participants with PD 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 posttreatment, totaling 8 visits over 42 weeks. Injection measures 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-latency afferent [SAI] and long-latency afferent [LAI] 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. Results Baseline SICI, LICI, and SAI was reduced (higher motor evoked potential [MEP] ratio) on the tremulous/treated side compared to the nontremulous 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. Discussion Our findings suggest that tremor severity in early PD may be related to impaired intracortical inhibition and defective sensorimotor integration.