Trial of Botulinum Toxin for Isolated or Essential Head Tremor.

Abstract

BACKGROUND:

Local injections of botulinum toxin type A have been used to treat essential head tremor but have not been extensively studied in randomized trials.

METHODS:

In a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo. Botulinum toxin or placebo was injected under electromyographic guidance into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome was improvement by at least 2 points on the Clinical Global Impression of Change (CGI) scale at week 6 after the second injection (week 18 after randomization). The CGI scale was used to record the patient's assessment of the degree of improvement or worsening of head tremor since baseline; scores range from 3 (very much improved) to -3 (very much worse). Secondary outcomes included changes in tremor characteristics from baseline to weeks 6, 12, and 24.

RESULTS:

A total of 120 patients were enrolled; 3 patients were excluded during screening, and 117 patients were randomly assigned to receive botulinum toxin (62 patients) or placebo (55 patients) and were included in the intention-to-treat analysis. Twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections during week 12. The primary outcome - improvement by at least 2 points on the CGI scale at week 18 - was met by 31% of the patients in the botulinum toxin group as compared with 9% of those in the placebo group (relative risk, 3.37; 95% confidence interval, 1.35 to 8.42; P = 0.009). Analyses of secondary outcomes at 6 and 12 weeks but not at 24 weeks were generally supportive of the primary-outcome analysis. Adverse events occurred in approximately half the patients in the botulinum toxin group and included head and neck pain, posterior cervical weakness, and dysphagia.

CONCLUSIONS:

Injection of botulinum toxin into each splenius capitis muscle on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane, and was associated with adverse events. (Funded by the French Ministry of Health; Btx-HT ClinicalTrials.gov number, NCT02555982.).

• Authors: Ana Marques, Bruno Pereira, Marion Simonetta-Moreau, Giovanni Castelnovo, Marie De Verdal, Frédérique Fluchère, Chloé Laurencin, Bertrand Degos, Mélissa Tir, Alexandre Kreisler, Geneviève Blanchet-Fourcade, Dominique Guehl, Olivier Colin, Aurelia Poujois, Sophie Sangla, Laurent Tatu, Philippe Derost, Dominique Gayraud, Christine Tranchant, David Amarantini, David Devos, Olivier Rascol, Jean-Christophe Corvol, Franck Durif, Isabelle Rieu, Btx-HT Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 389 Issue 19 Pg. 1753-1765 (Nov 09 2023) ISSN: 1533-4406 [Electronic] United States
• PMID: 37937777 (Publication Type: Randomized Controlled Trial, Multicenter Study, Journal Article)
• Copyright: Copyright © 2023 Massachusetts Medical Society.

Chemical References

• Botulinum Toxins, Type A
• Neuromuscular Agents

Topics

• Adult
• Humans
• Botulinum Toxins, Type A (administration & dosage, adverse effects, therapeutic use)
• Double-Blind Method
• Essential Tremor (drug therapy)
• Head
• Treatment Outcome
• Tremor (drug therapy)
• Electromyography (methods)
• Injections, Intramuscular (methods)
• Headache (chemically induced)
• Neck Pain (chemically induced)
• Neuromuscular Agents (administration & dosage, adverse effects, therapeutic use)