Long-term tremor therapy for Parkinson and essential tremor with sensor-guided botulinum toxin type A injections

Abstract

Objective: Current pharmacological agents used to treat Parkinson disease (PD) tremor and essential tremor (ET) provide suboptimal benefit and are commonly associated with significant adverse effects. Botulinum toxin type A (BoNT-A) has been shown to be effective for wrist tremor though functionally bothersome muscle weakness frequently occurs. This is the longest study to date demonstrating that BoNT-A therapy coupled with kinematic guidance can provide efficacious outcomes for upper limb tremor with minimized unwanted weakness.

Methods: A total of 28 PD and 24 ET participants with bothersome, disabling tremor, received six serial BoNT-A treatments every 16 weeks starting at week 0 with a follow-up visit 6 weeks following a treatment, totaling 96 weeks. Clinical scales, including Fahn-Tolosa-Marin tremor rating scale (FTM), and sensor-based tremor assessments were conducted at each visit. Kinematics was utilized to identify which arm muscles contributed to the tremulous movements and the experienced injector used clinical expertise in determining BoNT-A dosages.

Results: Following BoNT-A treatment, clinical ratings of tremor severity and functional ability (FTM) showed significant improvements following the first treatment which was maintained up to week 96 in PD and ET. Kinematics detected a significant reduction in PD and ET tremor amplitudes by 70% and 76% over the treatment course, respectively. By objectively distinguishing tremulous muscles and tremor severity, adverse effects were limited to mild perceived weakness by participants in injected muscles during follow-ups. Following the fourth treatment, BoNT-A dosages in flexor and extensor wrist muscles and biceps were reduced for those experiencing residual weakness which ultimately did not interfere with tremor relief or arm function.

Conclusions: Kinematics is an objective method that can aid clinicians in assessing and determining optimal BoNT-A parameters to alleviate both PD and ET tremor. BoNT-A injections are tolerable and effective when focal therapy regimens are determined and optimized kinematically over a long-term.

Fig 1. Study design, follow-up and analysis of participant datasets in the form of a CONSORT flow diagram.

Fig 2. Significant effect of serial kinematically-based BoNT-A treatments on reducing tremor severity and functional disability caused by tremor and QoL improvements by validated clinical scales and kinematic tremor analysis along the whole-arm.

(a-b) Mean UPDRS item 20 and 21 in the treated and untreated limbs in PD and ET participants; (c) Mean FTM part A-C scores in PD participants; (d) Mean FTM part A-C scores in ET participants; Mean angular RMS tremor amplitudes at the wrist in (e) PD participants and in (f) ET participants; (g) Mean QUEST score in ET participants; (h) mean Likert scale scores in PD and ET participants; (i) Percentage of participants who scored ≤3 on the MMT scale for finger flexion and extension, and (j) Mean maximal grip strength scores in the treated limb in both participant groups. Asterisks indicate statistical significance in means compared to week 0 and the asterisk colours are coordinated with each line plot (*). Injections were administered every 16 weeks starting at week 0.