Botulinum Neurotoxin Reduces Hand Tremor in Upper-Extremity Dystonic Tremor

January 5, 2021
Marco Meglio
Marco Meglio

Marco Meglio, Associate Editor for NeurologyLive, has been with the team since October 2019. Follow him on Twitter @marcomeglio1 or email him at mmeglio@neurologylive.com

Objective reduction in tremor was accompanied by improvement in specific motor tasks and a larger proportion of patients in the botulinum neurotoxin group reporting a global subjective improvement in symptoms.

Newly published data in JAMA Neurology from a randomized, placebo-controlled clinical trial demonstrated that botulinum neurotoxin (BoNT) injections are superior to placebo in reducing tremor severity in upper-extremity dystonic tremor (DT).

The primary outcome, total score on the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS), proved to be significantly lower in the BoNT group at 6 weeks (adjusted mean difference, –10.9; 95% CI, –15.4 to –6.5; P <.001) and 12 weeks (adjusted mean difference, –5.7; 95% CI, –11.0 to –0.5; P = .03) when compared to placebo.

Because 2 patients in the placebo group had a generalized distribution of dystonia, a post hoc sensitivity analysis was performed excluding these 2 patients. The primary outcome remained statistically significant at 6 weeks (adjusted mean difference, –10.2; 95% CI, –14.9 to –5.6; P < .001).

Lead author Roopa Rajan, MD, DM, department of neurology, All India Institute of Medical Sciences, and colleagues collected data on 30 adult patients with upper-extremity DT treated at a movement disorder clinic who were randomized 1:1 to BoNT or saline injection, 0.9%, using a computer-generated randomization sequence.

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In addition to changes on FTM-TRS, there was a greater number of participants in the BoNT group who reported improvement on the Global Impression of Change (PGIC) assessment (PGIC 1, 2, and 3: BoNT: 4 [26.7%], 6 [40.0%], and 5 [33.3%]; placebo: 5 [33.3%], 10 [66.7%], and 0, respectively; P = .047).

"This placebo-controlled, parallel-group randomized clinical trial provides level 1 evidence to support the use of BoNT injections for reducing tremor severity in patients with upper extremity DT,” Rajan et al concluded.

There were no demonstratable differences in FTM-TRS part C, the Writing Movement Score (WMS), and the Writing Speed Score (WSS) and accelerometric measures. Grip strength by dynamometer was similar in both groups at (adjusted mean difference, –0.2 log10 [kgf/m2] 2/Hz-Hz; 95% CI, –0.9 to 0.4 log10 [kgf/m2] 2/Hz-Hz; P = .45) and 12 weeks (adjusted mean difference, –0.09 log10 [kgf/m2] 2/Hz-Hz; 95% CI, –0.4 to 0.6 log10 [kgf/m2] 2/Hz-Hz; P = .72).

Eight patients (53.3%) in the BoNT group and 6 (42.8%) in the placebo group (P = .57) reported at least 1 adverse effect (AE). Hand weakness was the most frequent, occurring in 6 participants in the BoNT group (40%) and 4 on placebo (28.6%; P = .52).

Pain was the second most frequent AE (BoNT: 5 [33.3%]; placebo: 5 [35.7%]; P = .47) and only 1 patient in the BoNT group had severe hand weakness that affected functionality.

Injections were guided to the tremulous muscles of the upper extremity, while injection patterns and doses were individualized according to tremor phenomenologic findings. After the 12-week study period, all patients were offered open-label BoNT injections, with a reassessment period 6 weeks later. In total, 24 participants received the open-label injection, with a median number of 6 muscles (range, 2–9) injected per participant and a mean total dose of 69.2 (standard deviation [SD], 32.2).

Rajan and colleagues found that the mean FTM-TRS total score was significantly lower at 6 weeks after injection (before BoNT, 34.0 [SD, 2.9]; after BoNT, 26.7 [SD, 2.8]; P <.001). Additionally, there was reported benefit by 12 (70.6%) of the participants on the PGIC.

"Future studies are needed to assess the long-term stability of effects of treatment with BoNT during repeated injection sessions and to identify subgroups who are most likely to benefit from this treatment,” the study authors concluded.

REFERENCES
Rajan R, Srivastava AK, Anandapadmanabhan R, et al. Assessment of botulinum neurotoxin injection for dystonic hand tremor. JAMA Neurol. Published December 21, 2020. doi: 10.1001/jamaneurol.2020.4766