Effective Management of Upper Limb Parkinsonian Tremor by IncobotulinumtoxinA Injections Using Sensor-based Biomechanical Patterns

BACKGROUND Focal treatment of Parkinson's disease tremor by botulinum toxin type A incobotulinumtoxinA (BoNT-A) injections has been inadequately investigated and at best provides modest relief with significant muscle weakness. Complexity of multi-joint tremulous movements results in non-individualized dosing regimens. This 38-week open-label study used kinematic technology to guide muscle selection and improve efficacy of incobotulinumtoxinA (BoNT-A) injections for Parkinson's disease tremor. METHODS Participants (n=28) attended study visits at weeks 0, 6, 16, 22, 32, and 38, and were injected with BoNT-A at weeks 0, 16, and 32. During each visit, clinical tremor scales, the Unified Parkinson's Disease Rating Scale (UPDRS) and the Fahn-Tolosa-Marin (FTM), and kinematic assessments were conducted. Participants performed rest and postural scripted tasks with motion sensors placed over the wrist, elbow, and shoulder joints where tremor was quantified by angular root mean square (RMS) amplitude in multiple degrees of freedom at each joint. Injection parameters were determined using the clinician's interpretation of which muscles would contribute to the upper limb tremor biomechanics analyzed kinematically. RESULTS Kinematic measures of tremor amplitude allowed detailed segmentation of tremor into directional components at each arm joint permitting a statistically significant decrease in mean UPDRS item 20 (rest tremor) at week 16 (p=0.006) and at week 32 (p=0.014), and in FTM tremor severity scores at week 6 (p=0.024). Ten participants perceived mild muscle weakness following the third treatment, which did not interfere with performing activities of daily living. DISCUSSION Kinematics is a simple method for standardizing assessments and treatment of upper limb Parkinson's disease tremor, thereby personalizing tremor therapy and optimizing the effect of BoNT-A injections for Parkinson's disease tremor.