Dataset Information

Personalized Bilateral Upper Limb Essential Tremor Therapy with Botulinum Toxin Using Kinematics.

ABSTRACT: Variability of multi-joint essential tremor (ET) between patients and within the two upper limbs makes a visual assessment for the determination of botulinum toxin type A (BoNT-A) injections challenging. Kinematic tremor analysis guidance has succeeded in overcoming this challenge by making effective long-term unilateral BoNT-A injections for disabling ET. In this open-label study, 31 ET participants received three bilateral arm BoNT-A injection cycles over 30 weeks with follow-ups six-weeks post-treatment. Whole-arm kinematic assessment of tremor using a customized, automated algorithm provided muscle selection and dosing per muscle without clinician's assessment. Efficacy endpoints included Fahn-Tolosa-Marin tremor scale, quality of life (QoL) questionnaire, and maximum grip strength. BoNT-A reduced tremor amplitude by 47.7% in both the arms at week-6 (p < 0.005) that persisted from weeks 18?30. QoL was improved by 26.5% (p < 0.005) over the treatment period. Functional interference due to tremor was reduced by 30% (p < 0.005) from weeks 6?30. Maximum grip strength was reduced at week 6 (p = 0.001) but was not functionally impaired for the participants. Effective bilateral ET therapy by personalized BoNT-A injections could be achieved using computer-assisted tremor analysis. By removing variability inherent within the clinical assessments, this standardized tremor analysis method enabled patients to have improved bimanual upper limb functionality after the first treatment.

SUBMITTER: Samotus O

PROVIDER: S-EPMC6409675 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Personalized Bilateral Upper Limb Essential Tremor Therapy with Botulinum Toxin Using Kinematics.

Samotus Olivia O Lee Jack J Jog Mandar M

Toxins 20190219 2

Variability of multi-joint essential tremor (ET) between patients and within the two upper limbs makes a visual assessment for the determination of botulinum toxin type A (BoNT-A) injections challenging. Kinematic tremor analysis guidance has succeeded in overcoming this challenge by making effective long-term unilateral BoNT-A injections for disabling ET. In this open-label study, 31 ET participants received three bilateral arm BoNT-A injection cycles over 30 weeks with follow-ups six-weeks pos ...[more]

PMID: 30791440

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Project description:Botulinum toxin type A (BoNT-A) injection patterns customized to each patient's unique tremor characteristics produce better efficacy and lower adverse effects compared to the fixed-muscle-fixed-dose approach for Essential Tremor (ET) and Parkinson's disease (PD) tremor therapy. This article outlined how a kinematic-based dosing method to standardize and customize BoNT-A injections for tremors was developed. Seven ET and eight PD participants with significant tremor reduction and minimal perceived weakness using optimized BoNT-A injections determined by clinical and kinematic guidance were retrospectively selected to develop the kinematic-based dosing method. BoNT-A dosages allocated per joint were paired to baseline tremor amplitudes per joint. The final kinematic-based dosing method was prospectively utilized to validate BoNT-A injection pattern selection without clinical/visual assessments in 31 ET and 47 PD participants with debilitating arm tremors (totaling 122 unique tremor patterns). Whole-arm kinematic tremor analysis was performed at baseline and 6-weeks post-injection. Correlation and linear regression analyses between baseline tremor amplitudes and the change in tremor amplitude 6-weeks post-injection, with BoNT-A dosages per joint, were performed. Injection patterns determined using clinical assessment and interpretation of kinematics produced significant associations between baseline tremor amplitudes and optimized BoNT-A dosages in all joints. The change in elbow tremor was only significantly associated with the elbow total dose as the change in the wrist and shoulder tremor amplitudes were not significantly associated with the wrist and shoulder dosages from the selected 15 ET and PD participants. Using the kinematic-based dosing method, significant associations between baseline tremor amplitudes and the change (6-weeks post-first treatment) in tremor at each joint with BoNT-A dosages for all joints was observed in all 78 ET and PD participants. The kinematic-based dosing method provided consistency in dose selection and subsequent tremor reduction and can be used to standardize tremor assessments for whole-arm tremor treatment planning.

Project description:ObjectiveCurrent pharmacological agents used to treat Parkinson disease (PD) tremor and essential tremor (ET) provide suboptimal benefit and are commonly associated with significant adverse effects. Botulinum toxin type A (BoNT-A) has been shown to be effective for wrist tremor though functionally bothersome muscle weakness frequently occurs. This is the longest study to date demonstrating that BoNT-A therapy coupled with kinematic guidance can provide efficacious outcomes for upper limb tremor with minimized unwanted weakness.MethodsA total of 28 PD and 24 ET participants with bothersome, disabling tremor, received six serial BoNT-A treatments every 16 weeks starting at week 0 with a follow-up visit 6 weeks following a treatment, totaling 96 weeks. Clinical scales, including Fahn-Tolosa-Marin tremor rating scale (FTM), and sensor-based tremor assessments were conducted at each visit. Kinematics was utilized to identify which arm muscles contributed to the tremulous movements and the experienced injector used clinical expertise in determining BoNT-A dosages.ResultsFollowing BoNT-A treatment, clinical ratings of tremor severity and functional ability (FTM) showed significant improvements following the first treatment which was maintained up to week 96 in PD and ET. Kinematics detected a significant reduction in PD and ET tremor amplitudes by 70% and 76% over the treatment course, respectively. By objectively distinguishing tremulous muscles and tremor severity, adverse effects were limited to mild perceived weakness by participants in injected muscles during follow-ups. Following the fourth treatment, BoNT-A dosages in flexor and extensor wrist muscles and biceps were reduced for those experiencing residual weakness which ultimately did not interfere with tremor relief or arm function.ConclusionsKinematics is an objective method that can aid clinicians in assessing and determining optimal BoNT-A parameters to alleviate both PD and ET tremor. BoNT-A injections are tolerable and effective when focal therapy regimens are determined and optimized kinematically over a long-term.

Project description:Repeated injection cycles with abobotulinumtoxinA, a botulinum toxin type A, are recommended in current clinical guidelines as a treatment option for adults with upper limb spastic paresis. However, the magnitude of the maximal therapeutic effect of repeated abobotulinumtoxinA treatment across different efficacy parameters and the number of injection cycles required to reach maximal effect remain to be elucidated. Here, we present a post hoc exploratory analysis of a randomized, double-blind, placebo-controlled trial (12-24 weeks; NCT01313299) and open-label extension study (up to 12 months; NCT0131331), in patients aged 18-80 years with hemiparesis for ≥6 months after stroke/traumatic brain injury. Two inferential methods were used to assess the changes in efficacy parameters after repeat abobotulinumtoxinA treatment cycles: Mixed Model Repeated Measures analysis and Non-Linear Random Coefficients analysis. Using the latter model, the expected maximal effect size (not placebo-controlled) and the number of treatment cycles to reach 90% of this maximal effect were estimated. Treatment responses in terms of passive and perceived parameters (i.e. modified Ashworth scale in primary target muscle group, disability assessment scale for principal target for treatment or limb position, and angle of catch at fast speed) were estimated to reach near-maximal effect in two to three cycles. Near-maximal treatment effect for active parameters (i.e. active range of motion against the resistance of extrinsic finger flexors and active function, assessed by the Modified Frenchay Scale) was estimated to be reached one to two cycles later. In contrast to most parameters, active function showed greater improvements at Week 12 (estimated maximal change from baseline-modified Frenchay Scale overall score: +0.8 (95% confidence interval, 0.6; 1.0) than at Week 4 (+0.6 [95% confidence interval, 0.4; 0.8]). Overall, the analyses suggest that repeated treatment cycles with abobotulinumtoxinA in patients chronically affected with upper limb spastic paresis allow them to relearn how to use the affected arm with now looser antagonists. Future studies should assess active parameters as primary outcome measures over repeated treatment cycles, and assess efficacy at the 12-week time-point of each cycle, as the benefits of abobotulinumtoxinA may be underestimated in the studies of insufficient duration. Abbreviated summary In this post hoc analysis of repeated abobotulinumtoxinA injection cycles in upper limb spastic paresis, Gracies et al. used statistical modelling to elucidate the maximal therapeutic effect of abobotulinumtoxinA. Notably, the number of injections required to reach this maximal effect was higher for active (e.g. active function) compared with passive (e.g. tone) parameters.

Dataset Information

Personalized Bilateral Upper Limb Essential Tremor Therapy with Botulinum Toxin Using Kinematics.

Publications

Personalized Bilateral Upper Limb Essential Tremor Therapy with Botulinum Toxin Using Kinematics.

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