麻豆传媒

Injections of botulinum toxin type A were significantly more effective than placebo at reducing essential or isolated head tremor severity at 18 weeks, the multicenter trial in France found.

On the primary outcome, 31% of head tremor patients in the botulinum toxin group improved by at least 2 points on the Clinical Global Impression of Change (CGI) scale at 18 weeks, compared with 9% in the placebo group (relative risk 3.37, 95% CI 1.35-8.42, P=0.009), reported Ana Marques, MD, PhD, of the Hôpital Gabriel Montpied, CHU Clermont-Ferrand in France, and co-authors.

Scores on the CGI scale can range 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's head tremor improvement, but scores at week 24 did not.

"Our trial had stringent requirements for enrollment, outcome assessment, and injection technique, and approximately 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," Marques and colleagues wrote in the .

"These differences between the trial groups were generally sustained at other time points but not at 24 weeks, a time at which the effect of botulinum toxin injection has typically waned," they added.

About half of the botulinum toxin group experienced adverse events including neck and head pain, posterior cervical weakness, and dysphagia.

Still, Marques said in an email to 麻豆传媒, "Clinicians can now propose botulinum toxin injections more confidently in splenius capitis muscles to their patients with isolated or essential head tremor."

Essential tremor is prevalent of approximately 1% in the general population and in 4 to 5% of people older than 65. Agents that help essential limb tremor, like beta-blockers, are usually less effective in head tremor, Marques and co-authors noted.

Botulinum toxin is widely used for the treatment of head tremor, but randomized trials assessing its effect are limited, they added. An by the Movement Disorder Society concluded there was insufficient evidence to support the use of any agent for head tremor.

In Btx-HT, researchers randomly assigned participants with severe essential or isolated head tremor to botulinum toxin (62 people) or placebo (55 people). People with dystonic head tremor, Parkinson's disease, and tremor as a component of a cerebellar syndrome were excluded.

Patients were an average age of 64.7 and 66 years in the intervention and placebo groups, respectively, and were mainly female (82% and 78%) and white (89% and 98%). Most participants in both groups (60% and 55%) had moderate tremor severity at baseline.

Participants were assessed at day 0, at weeks 6, 12, 18, and 24, and had telephone interviews at intermediate weeks to assess adverse events.

Injections of 75 IU (1.5 ml) doses were administered to the splenius capitis muscle at day 0 and week 12 under electromyographic guidance. Single or multiple injection sites were used based on electromyographic findings and the neurologist's judgement.

The week 12 dose of botulinum toxin either matched the dose injected on day 0 (75 IU) or was increased to 100 IU (2 ml) if the day 0 dose was considered ineffective at the week 6 visit. In the botulinum toxin group, 27 of 50 people received the same dose of botulinum toxin both at baseline and at week 12, while 23 received 100 IU.

Twelve people in the botulinum toxin group discontinued the trial, including seven due to adverse events. In the placebo group, two people discontinued the trial for other reasons.

Secondary outcomes were generally supportive of the primary outcome "with respect to reductions in subjective and objective measures of head tremor severity, functional affects, and social embarrassment," Marques and co-authors noted.

Adverse events occurred in 47% of the botulinum toxin group and 16% of the placebo group. In the botulinum toxin group, headache or neck pain occurred in 34%, posterior cervical weakness in 15%, and dysphagia in 16%.

Two people in the botulinum group experienced severe adverse events resulting in hospitalization: severe dysphagia in one person, and a general feeling of weakness, difficulty finding words, and dizziness in the other.

The researchers acknowledged study limitations including loss of patients to follow-up, external psychological factors that may have increased tremors, and a risk of partial unmasking. In addition, the trial population had limited racial diversity.

Comment