Customized Injections Enhance Botulinum Toxin for Essential Hand Tremor


Customizing injection sites and amounts of botulinum toxin for different presentations of essential hand tremor has been shown to avoid hand weakness.

Dr Shivam Mittal

Shivam Mittal, MD, from the department of neurology at Yale University School of Medicine, in New Haven, Connecticut

Shivam Mittal, MD

Customizing the intramuscular sites and amounts of botulinum toxin injection for different presentations of essential hand tremor was found to reduce tremor without the hand weakness seen in trials with fixed injection methods, which has limited its use in clinical practice.

Results of the new trial were presented at the International Congress of Parkinson’s Disease and Movement Disorders, in Hong Kong, by Shivam Mittal, MD, from the department of neurology at Yale University School of Medicine, in New Haven, Connecticut, who described the rationale for the trial and unique approach to administering the agent, in comments to NeurologyLive.

"We have designed this randomized double-blinded placebo-controlled study using a customized injection approach, with botulinum toxin injections in 8 to 14 upper limb muscles under electromyography [EMG] guidance," Mittal explained.

Mittal clarified that while more than half of patients with essential tremor can improve with oral tablets, many must consider invasive treatment such as deep brain stimulation surgery or thalamotomy.

"Thus, there is an unmet need for patients who are not eligible for surgical treatment." Mittal said. "There have been 2 randomized double-blinded placebo-controlled studies done almost 2 decades ago on botulinum toxin injections for essential hand tremor which showed improvement in tremor, but its clinical use is limited due to profound hand weakness as an adverse effect."

This customized, flexible approach to administering the botulinum toxin injections starts with evaluating the patient's hand tremor and the muscles causing the prominent tremor at various joints, such as the proximal and distal interphalangeal joints in finger tremor or the radial or ulnar flexion and extension in wrist tremor. Tremor activity in these muscles is then confirmed by rhythmic burst potentials on needle EMG.

Mittal and colleagues then selected the dose and injection site based on the activity and size of the muscle. They administered an average of 9 injections per patient, with a range of 8 to 14 injections. The total dose of Incobotulinumtoxin A (IncoA; Xeomin, Merz) ranged from 80 to 120 Units/patient (100 U average).

In the trial, 33 subjects were randomized to either the customized injections of IncoA or saline placebo, and evaluated at week 4, 8 and at week 16, when a second set of injection was administered. Subjects then crossed over to the other treatment condition, and were evaluated at week 20, 24 and 28. Tremor severity was measured with the Fahn Tolosa Marin (FTM) tremor scale, and patients self-estimated improvement with the Patient Global Impression of Change (PGIC).

Mittal reported that there was a statistically significant improvement in clinical rating score of tremor at weeks 4 and 8, following the IncoA injection compared to placebo. In addition, 19 patients provided their perspective of change in the PGIC; with 10 of the 19 (53%) in the IncoA group expressing much improvement and 3 of 19 (15%) in the saline group expressing much improvement.

"There was a significant improvement in the clinical rating score of action and postural tremor at 4 and 8 weeks following the botulinum toxin injections without any significant hand weakness compared to the placebo group," Mittal said. "Customized injection approach to botulinum toxin injections is a potential therapeutic agent for medical refractory essential tremor patients.”


Mittal S, Machado D, Richardson D, Dubey D, Jabbari B. Botulinum toxin in essential hand tremor: a randomized double-blind placebo-controlled study with customized injection approach. Presented at: 2018 International Congress of Parkinson's Disease and Movement Disorders; Hong Kong; October 6, 2018.

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