Assessment of Botulinum Neurotoxin Injection for Dystonic Hand Tremor: A Randomized Clinical Trial.

Importance: There is an unmet need for safe and efficacious treatments for upper-extremity dystonic tremor (DT). To date, only uncontrolled retrospective case series have reported the effect of botulinum neurotoxin (BoNT) injections on upper-extremity DT.

Objective: To assess the effect of BoNT injections on tremor in patients with upper-extremity DT.

Design, Setting, and Participants: In this placebo-controlled, parallel-group randomized clinical trial, 30 adult patients with upper-extremity DT treated at a movement disorder clinic in a tertiary care university hospital were randomized in a 1:1 ratio to BoNT or saline injection, 0.9%, using a computer-generated randomization sequence. Randomization was masked using opaque envelopes. The participant, injector, outcome assessor, and statistician were blinded to the randomization. Participants were recruited between November 20, 2018, and December 12, 2019, and the last follow-up was completed in March 2020.

Interventions: Participants received electromyographically guided intramuscular injections of BoNT or placebo into the tremulous muscles of the upper extremity. Injection patterns and doses were individualized according to tremor phenomenologic findings.

Main Outcomes and Measures: The primary outcome was the total score on the Fahn-Tolosa-Marin Tremor Rating Scale 6 weeks after the intervention. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. All patients were offered open-label BoNT injections after 12 weeks and reassessed 6 weeks later.

Results: A total of 48 adult patients with a diagnosis of brachial dystonia with DT were screened. Fifteen were ineligible and 3 refused consent; therefore, 30 patients (mean [SD] age, 46.0 [18.6] years; 26 [86.7%] male) were recruited, with 15 randomized to receive BoNT and 15 to receive placebo. In the intention-to-treat group, the Fahn-Tolosa-Marin Tremor Rating Scale total score was significantly lower in the BoNT group at 6 weeks (adjusted mean difference, -10.9; 95% CI, -15.4 to -6.5; P < .001) and 12 weeks (adjusted mean difference, -5.7; 95% CI, -11.0 to -0.5; P = .03). More participants in the BoNT group reported global improvement on the Global Impression of Change (PGIC) assessment (PGIC 1, 2, and 3: BoNT: 4 [26.7%], 6 [40.0%], and 5 [33.3%]; placebo: 5 [33.3%], 10 [66.7%], and 0, respectively; P = .047). Subjective hand weakness (BoNT: 6 [40.0%]; placebo: 4 [28.6%], P = .52) and dynamometer-assessed grip strength (mean difference, -0.2 log10[kgf/m2]2/Hz-Hz; 95% CI, -0.9 to 0.4 log10[kgf/m2]2/Hz-Hz; P = .45) were similar in both groups.

Conclusions and Relevance: In this randomized clinical trial, botulinum neurotoxin injections were superior to placebo in reducing tremor severity in upper-extremity DT. An individualized approach to muscle selection and dosing was beneficial without unacceptable adverse effects.

Trial Registration: Clinical Trials Registry of India (https://ctri.nic.in) Identifier: CTRI/2018/02/011721.