Changes in Cortical Excitability and Parkinson Tremor After Botulinum Toxin Therapy

Olivia Samotus; Robert Chen; Mandar Jog

doi:10.1212/WNL.0000000000012662

Changes in Cortical Excitability and Parkinson Tremor After Botulinum Toxin Therapy

Neurology. 2021 Oct 4;97(14):e1413-e1424. doi: 10.1212/WNL.0000000000012662.

Authors

Olivia Samotus¹, Robert Chen¹, Mandar Jog²

Affiliations

¹ From the Department of Clinical Neurological Sciences (O.S., M.J.), Lawson Health Research Institute, London Health Sciences Centre; Schulich School of Medicine and Dentistry (O.S., M.J.), University of Western Ontario, London; Krembil Research Institute (R.C.), University Health Network; and Division of Neurology, Department of Medicine (R.C.), University of Toronto, Canada.
² From the Department of Clinical Neurological Sciences (O.S., M.J.), Lawson Health Research Institute, London Health Sciences Centre; Schulich School of Medicine and Dentistry (O.S., M.J.), University of Western Ontario, London; Krembil Research Institute (R.C.), University Health Network; and Division of Neurology, Department of Medicine (R.C.), University of Toronto, Canada. mandar.jog@lhsc.on.ca.

PMID: 34497068
DOI: 10.1212/WNL.0000000000012662

Abstract

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.