Injection Botulinum Toxin reduces essential or isolated head tremor severity: NEJM

The injection of the botulinum toxin failed to reduce the severity at 24 weeks when the effects of injection might be expected to wane and were associated with adverse events. The study findings were published in The New England Journal of Medicine.

"On the primary outcome, 31% of patients with head tremors in the botulinum toxin group improved by at least 2 points on the Clinical Global Impression of Change (CGI) scale at 18 weeks, versus 9% in the placebo group (relative risk 3.37)," the researchers reported.

Scores on the CGI scale can vary from 3 to -3, with 3 being "very much improved" and -3 being "very much worse." CGI scores at weeks 6 and 12 supported the primary outcome of head tremor improvement, but scores at week 24 did not.

Local injections of botulinum toxin type A have been used for treating essential head tremors but have not been extensively studied in randomized trials. Therefore, Ana Marques, the Hôpital Gabriel Montpied, CHU Clermont-Ferrand, France, and colleagues conducted Btx-HT, a multicenter, double-blind, randomized trial enrolling adult patients with essential or isolated head tremors. Out of 120 patients, 117 were assigned in a ratio of 1:1 to receive botulinum toxin type A (n=62) or placebo (n=55). During week 12, twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections.

Botulinum toxin or placebo was injected into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome of the study was determined as an improvement by at least 2 points on the CGI scale at week 6 after the second injection (week 18 after randomization). Secondary outcomes included changes from baseline in tremor characteristics to weeks 6, 12, and 24.

The study led to the following findings:

• 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).
• 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.

"Our trial had stringent requirements for outcome assessment, enrollment, and injection technique, and about 40% and 30% of the patients in the botulinum toxin group at weeks 6 and 18, respectively, had improvement by at least 2 points on the CGI scale," the researchers wrote.

Reference:

Marques A, Pereira B, Simonetta-Moreau M, Castelnovo G, De Verdal M, Fluchère F, Laurencin C, Degos B, Tir M, Kreisler A, Blanchet-Fourcade G, Guehl D, Colin O, Poujois A, Sangla S, Tatu L, Derost P, Gayraud D, Tranchant C, Amarantini D, Devos D, Rascol O, Corvol JC, Durif F, Rieu I; Btx-HT Study Group. Trial of Botulinum Toxin for Isolated or Essential Head Tremor. N Engl J Med. 2023 Nov 9;389(19):1753-1765. doi: 10.1056/NEJMoa2304192. PMID: 37937777.