William George Ondo

This double-blind, placebo-controlled, phase II trial (NCT04766723) investigated the efficacy and safety of incobotulinumtoxinA (Xeomin^®) in the treatment of essential tremor (ET) of the upper limb (UL). Adults with ET of the UL were randomized 2:1 (n = 78) and treated (n = 77) with intramuscular injections of incobotulinumtoxinA or placebo at semi-flexible doses into their motor-dominant arm. The primary endpoint was the change from baseline to week 6 in maximum tremor amplitude at wrist level. Baseline characteristics of treated patients were well matched across treatment arms. The primary endpoint was not met; maximum tremor amplitude at the wrist decreased from baseline to week 6 in both groups, with changes numerically favoring placebo (least squares mean treatment difference 0.21, p = 0.28). At week 6, compared with the placebo group, the incobotulinumtoxinA group had improvement in The Essential Tremor Rating Assessment Scale (TETRAS) performance dominant UL score (p = 0.006) and Quality of Life in ET (QUEST) total score (p = 0.073). However, these secondary outcomes must be interpreted descriptively as exploratory findings. Although the p-value and the 95% confidence interval including zero did not support statistical significance, the observed numerical treatment difference in change from baseline in QUEST total score suggests that the treatment effect may be consistent with the minimal clinically important difference in favor of incobotulinumtoxinA. Improvement in TETRAS Activities of Daily Living UL score was similar in both groups at week 6 (p = 0.933). IncobotulinumtoxinA was generally well tolerated. Treatment of UL ET with incobotulinumtoxinA did not show superiority over placebo for the primary endpoint. Secondary and other efficacy endpoints should therefore be viewed as exploratory, generating hypotheses suggesting potential improvements in TETRAS UL performance score and quality of life that require confirmation in further research. IncobotulinumtoxinA demonstrated a favorable safety profile without any new or unexpected safety concerns.

Background: Minimum clinically important difference (MCID) helps distinguish clinically meaningful benefit from statistically significant, but clinically trivial, change. Modified versions of the Essential Tremor Rating Assessment Scale (TETRAS), including the modified activities of daily living (mADL) scale and the mADL11 scale, are frequently used as primary outcome measures in essential tremor (ET) clinical trials, but MCIDs for these measures have not been established. Here, we estimated MCIDs for the mADL and mADL11 scales in ET. Methods: Data from the TRANQUIL multicenter, randomized controlled trial of an artificial intelligence–driven transcutaneous peripheral nerve stimulation device for ET were analyzed. Anchor‐based approaches using the Clinical Global Impression of Improvement (CGI‐I) and the Patient Global Impression of Improvement (PGI‐I) were used as primary methods for MCID estimation. Mean changes in mADL and mADL11 were calculated for participants rated as “minimally improved” and “no change.” Associations between anchor measures and score changes were assessed with Spearman's correlation coefficients. Receiver operating characteristic (ROC) analyses were performed to identify cutoff values that best distinguished minimal improvement from no change. Results: The anchor measures demonstrated acceptable correlations with changes in mADL and mADL11 scores. Estimated MCID values for mADL ranged from −3.5 to −6.2, and values for mADL11 ranged from −1.0 to −4.1 ROC‐derived estimates produced the lowest thresholds, whereas PGI‐I–based estimates yielded the highest. Our recommended MCID values, based on patient report, are −6.2 for mADL and −4.1 for mADL11. Conclusions: This study establishes clinically meaningful change thresholds for two commonly used TETRAS‐based outcome measures in ET. These MCIDs may aid interpretation of future clinical ET trials.

Received: 18 October 2025 Accepted after revision: 10 March 2026 Accepted Manuscript online: 17 March 2026 © . Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Background: Transcutaneous afferent patterned stimulation (TAPS) is a non-invasive, wrist-worn neurostimulation therapy that has demonstrated acute and short-term lasting tremor reduction in patients with essential tremor (ET). However, the longer-term improvement in underlying tremor severity from consistent use of TAPS has not been fully explored. Methods: We conducted a retrospective analysis of the multicenter PROSPECT trial, which evaluated twice-daily TAPS use over three months in patients with ET. Underlying tremor improvement was assessed by comparing pre-stimulation tremor severity at baseline with pre-stimulation tremor severity at 1- and 3-month follow-up visits. Tremor severity was measured using the Bain & Findley Activities of Daily Living (BF-ADL) scale and the Tremor Research Group’s Essential Tremor Rating Assessment Scale (TETRAS). Responders were defined as patients demonstrating at least a 1-point improvement on any qualifying task. Results: Among 192 patients with available data, pre-stimulation BF-ADL scores improved significantly by 2.0 points at 1 month and 2.7 points at 3 months compared with baseline (p < 0.001). Pre-stimulation TETRAS scores also showed significant improvements at both time points (p < 0.001). Measurements at 1 and 3 months were made an average of 16.2 hours after the prior stimulation session. Over 80% of patients met responder criteria for underlying tremor improvement on BF-ADL and TETRAS at both follow-up visits. Improvements were observed even among patients using TAPS approximately once daily. Conclusions: Consistent use of TAPS was associated with significant improvement in underlying tremor severity in patients with essential tremor. These findings suggest that regular TAPS use may confer sustained therapeutic benefit.

Background: A number of adaptive devices are marketed and sold to patients with tremor; however, there is essentially no published data on their efficacy. Objective: The aim of the study was to evaluate the objective efficacy and subjective preferences of 6 commercially available adaptive eating devices for patients with tremor. Methods: We compared six devices (Gyenno Spoon, Tremelo, a weighted spoon, S'up Spoon, Steady Spoon, and Eli Spoon) and a regular “control” spoon using an objective eating test. We measured the percentage of successfully transferred couscous to a cup adjacent to the subject's mouth and recorded relative patient preferences. Results: The mean percentages of successful transfer, in descending order of success, were as follows: S'up Spoon (93.6%), Gyenno Spoon (88.9%), weighted spoon (80.7%), Tremelo (78.0%), Steady Spoon (78.9%), control (74.3%), and Eli Spoon (67.6%). Subjective preferences ranked from best to worst based on average ranking were as follows: weighted spoon, S'up Spoon, Gyenno Spoon, Tremelo, control, Steady Spoon, and Eli Spoon. Conclusion: Overall, simple strategies, including a deeper bowl and heavier spoon, outperformed more complicated counterweight/actuator devices.