Developing a Consistent, Reproducible Botulinum Toxin Type A Dosing Method for Upper Limb Tremor by Kinematic Analysis

Abstract

Botulinum toxin type A (BoNT-A) injection patterns customized to each patient’s unique tremor characteristics produce better efficacy and lower adverse effects compared to the fixed-muscle-fixed-dose approach for Essential Tremor (ET) and Parkinson’s disease (PD) tremor therapy. This article outlined how a kinematic-based dosing method to standardize and customize BoNT-A injections for tremors was developed. Seven ET and eight PD participants with significant tremor reduction and minimal perceived weakness using optimized BoNT-A injections determined by clinical and kinematic guidance were retrospectively selected to develop the kinematic-based dosing method. BoNT-A dosages allocated per joint were paired to baseline tremor amplitudes per joint. The final kinematic-based dosing method was prospectively utilized to validate BoNT-A injection pattern selection without clinical/visual assessments in 31 ET and 47 PD participants with debilitating arm tremors (totaling 122 unique tremor patterns). Whole-arm kinematic tremor analysis was performed at baseline and 6-weeks post-injection. Correlation and linear regression analyses between baseline tremor amplitudes and the change in tremor amplitude 6-weeks post-injection, with BoNT-A dosages per joint, were performed. Injection patterns determined using clinical assessment and interpretation of kinematics produced significant associations between baseline tremor amplitudes and optimized BoNT-A dosages in all joints. The change in elbow tremor was only significantly associated with the elbow total dose as the change in the wrist and shoulder tremor amplitudes were not significantly associated with the wrist and shoulder dosages from the selected 15 ET and PD participants. Using the kinematic-based dosing method, significant associations between baseline tremor amplitudes and the change (6-weeks post-first treatment) in tremor at each joint with BoNT-A dosages for all joints was observed in all 78 ET and PD participants. The kinematic-based dosing method provided consistency in dose selection and subsequent tremor reduction and can be used to standardize tremor assessments for whole-arm tremor treatment planning.