Head Tremor Treatment: How Effective Are Botulinum Toxin Injections?

Injections of botulinum toxin in the splenius capitis muscles are more effective than placebo for the treatment of isolated and essential head tremor, according to study findings published in The New England Journal of Medicine.

Previous findings from meta-analyses suggest that botulinum toxin may treat essential tremor, which is the most common movement disorder among adults.

To test the efficacy and safety of botulinum toxin for head tremor, researchers conducted a multicenter, double-blind, randomized trial, Evaluation of Botulinum Toxin Injection Efficacy in the Treatment of Head Essential Tremor (Btx-HT; ClinicalTrials.gov Identifier: NCT02555982), between 2016 and 2021 at 17 hospitals in the French NS-Park-F-CRIN Network.

Patients (N=115) with essential or isolated head tremor with or without associated limb tremor were randomly assigned in a 1:1 ratio to receive botulinum toxin type A (n=62; mean age, 64.7; 82% women; 89% White) or placebo (n=55; mean age, 66.0%; 78% women; 98% White) injections on day 0 and during week 12. Among the botulinum toxin and placebo groups, 81% and 76% participants had associated limb tremor, and 60% and 55% had moderate severity disease, respectively. Injections were administered in each splenius capitis muscle with electromyographic guidance.

The primary outcome was ³2-point improvement in Clinical Global Impression of Change (CGI) score from baseline to week 18. CGI scale scores range from 3 (“very much improved”) to -3 (“very much worse”).

All trial injections were received by 81% of the botulinum toxin cohort and 96% of the placebo group. Among participants who received botulinum toxin, 27 received 2 doses of 75 IU whereas 23 received a 100 IU dose at the second injection.

The primary efficacy outcome was achieved by 31% of participants who received botulinum toxin compared with 9% of those in the control group (relative risk [RR], 3.37; 95% CI, 1.35-8.42; P =.009).

At week 18, botulinum toxin was favored over placebo for outcomes in:

• Quality of life in Essential Tremor Questionnaire (QUEST; mean difference [MD], -0.31; 95% CI, -0.62 to -0.01),
• essential tremor assessment (ETEA) part A (MD, -0.43; 95% CI, -0.76 to -0.10),
• ETEA part B (MD, -0.48; 95% CI, -0.80 to -0.16),
• median Fahn–Tolosa–Marin Tremor Rating Scale (TRS) part A (MD, -0.15; 95% CI, -0.30 to -0.01), and
• TRS part B (MD, -0.38; 95% CI, -0.72 to -0.05) scores.

Although significant improvements were observed at week 18, by week 24, compared with placebo, botulinum toxin was not associated with the primary outcome (RR, 1.77; 95% CI, 0.77-4.07).

The rates of adverse events (AEs) were 47% among the botulinum toxin group compared with 16% among the placebo cohort (P <.001). The AEs reported by the botulinum toxin group included:

• headache or neck pain (34%),
• dysphagia (16%),
• posterior cervical weakness (15%),
• cervical stiffness (10%), and
• injection site pain (8%).

The major limitation of this study was the proportion of patients lost to follow-up in the botulinum toxin cohort.

“In patients with isolated or essential head tremor, electromyographically guided injection of botulinum toxin into each splenius capitis muscle at day 0 and during week 12 led to greater clinical improvement than placebo at 18 weeks but not at 24 weeks and was associated with adverse events.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.