El Diario de Pontevedra : periódico liberal: Ano XXVI Número 7664 - 1909 novembro 26

<p>Optimization of BoNT-A parameters over the study treatment course for ET participants.</p

Long-term tremor therapy for Parkinson and essential tremor with sensor-guided botulinum toxin type A injections

<div><p>Objective</p><p>Current 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.</p><p>Methods</p><p>A 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.</p><p>Results</p><p>Following 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.</p><p>Conclusions</p><p>Kinematics 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.</p></div

Study design, follow-up and analysis of participant datasets in the form of a CONSORT flow diagram.

<p>Study design, follow-up and analysis of participant datasets in the form of a CONSORT flow diagram.</p

Significant effect of serial kinematically-based BoNT-A treatments on reducing tremor severity and functional disability caused by tremor and QoL improvements by validated clinical scales and kinematic tremor analysis along the whole-arm.

<p>(a-b) Mean UPDRS item 20 and 21 in the treated and untreated limbs in PD and ET participants; (c) Mean FTM part A-C scores in PD participants; (d) Mean FTM part A-C scores in ET participants; Mean angular RMS tremor amplitudes at the wrist in (e) PD participants and in (f) ET participants; (g) Mean QUEST score in ET participants; (h) mean Likert scale scores in PD and ET participants; (i) Percentage of participants who scored ≤3 on the MMT scale for finger flexion and extension, and (j) Mean maximal grip strength scores in the treated limb in both participant groups. Asterisks indicate statistical significance in means compared to week 0 and the asterisk colours are coordinated with each line plot (*). Injections were administered every 16 weeks starting at week 0.</p

Functional Ability Improved in Essential Tremor by IncobotulinumtoxinA Injections Using Kinematically Determined Biomechanical Patterns – A New Future

<div><p>Objective</p><p>Effective treatment for functional disability caused by essential tremor is a significant unmet need faced by many clinicians today. Current literature regarding focal therapy by botulinum toxin type A (BoNT-A) injections uses fixed dosing regimens, which cannot be individualized, provides only limited functional benefit and unacceptable muscle weakness commonly occurs. This 38-week open label study, the longest to-date, demonstrates how kinematic technology addressed all these issues by guiding muscle selection.</p><p>Method</p><p>Participants (n = 24) were assessed at weeks 0, 6, 16, 22, 32, and 38 and injected with incobotulinumtoxinA at weeks 0, 16, and 32. Clinical assessments including UPDRS tremor items, Fahn-Tolosa-Marin (FTM) tremor rating scale assessing tremor severity, writing and functional ability, quality of life questionnaire (QUEST) and objective kinematic assessments were completed at every visit. Participants performed two postural and two weight-bearing scripted tasks with motion sensors placed over the wrist, elbow and shoulder joints. These sensors captured angular tremor amplitude (RMS units) and acceleration joint motion that was segmented into directional components: flexion-extension (F/E), pronation-supination and radial-ulnar at the wrist, F/E at the elbow, and F/E and adduction-abduction at the shoulder. Injection parameters were determined using kinematics, followed by the clinician’s determination of which muscles would contribute to the specific upper limb tremor biomechanics and dosing per participant.</p><p>Results</p><p>Multi-joint biomechanical recordings allowed individualized muscle selection and showed significant improvement in whole-arm function, FTM parts A-C scores, at week 6 which continued throughout the study. By week 38, the total FTM score statistically significantly reduced from 16.2±4.6 at week 0 to 9.5±6.3 (p<0.0005). UPDRS item 21 score rating action tremor was significantly reduced from 2.6±0.5 at week 0 to 1.6±1.1 (p = 0.01) at week 32. Quality of life (QUEST) significantly improved from 40.3±15.8 at week 0 to 31.1±15.3 (p = 0.035) at week 32 and to 27.8±15.3 (p = 0.028) at week 38. Kinematics provided an objective, secondary outcome measure, which showed a significant decrease in tremor amplitude in the wrist and shoulder joints (p<0.05). Eight participants (40%) self-reported mild weakness in injected muscles but had no interference in arm function.</p><p>Conclusion</p><p>Kinematic tremor assessments provide the injector unique insight to objectively individualize and personalize injection parameters demonstrating BoNT-A effectively alleviates functional disability caused by essential tremor. Kinematic technology is a promising method for standardizing assessments and for focal upper limb tremor treatment.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02427646?term=NCT02427646&rank=1" target="_blank">NCT02427646</a></p></div

ET participant demographics and baseline UPDRS, QUEST and FTM parts A to C scores.

<p>ET participant demographics and baseline UPDRS, QUEST and FTM parts A to C scores.</p

CONSORT flow diagram displaying the progress of the study’s design.

<p>CONSORT flow diagram displaying the progress of the study’s design.</p

IncobotulinumtoxinA treatments significantly reduced severity of tremor and provided functional benefit for fine and gross motor tasks with mild muscle weakness in treated muscles.

<p>(A) Tremor severity, FTM part A sub-category score (max: /4 per task), significantly decreased. (B) Handwriting, spiral and line writing tasks showed significant improvement, signified by FTM part B summed score, and functional disability, FTM part C summed score (max: /4 per category, 8 categories in total), was significantly reduced. (C) Quality of life, measured by QUEST tallied 30-items (max: /4 per item), significantly increased. (D) Angular RMS tremor amplitude (primary y-axis) and hand and finger acceleration values (secondary y-axis) at each arm joint was averaged per time-point. Significant reductions in wrist and shoulder tremor amplitudes resembled change in hand and finger acceleration values. (E) Angular wrist tremor RMS amplitude for each scripted-task was significantly reduced. (F) Maximal grip strength (blue) was significantly reduced, but did not impair function, and perceived muscle weakness (red) yielded no significant change at injection visits. All plotted values are means for all participants per each time-point. Asterisks represented statistical significant change (p<0.05) compared to baseline. Error bars represent standard deviation of population.</p

Mean injected dosage per arm muscle treated at each treatment time-point.

<p>Mean injected dosage per arm muscle treated at each treatment time-point.</p

STN-DBS parameter optimization for speech in PD (Knowles et al., 2018)

<div><b>Purpose:</b> The settings of 3 electrical stimulation parameters were adjusted in 12 speakers with Parkinson’s disease (PD) with deep brain stimulation of the subthalamic nucleus (STN-DBS) to examine their effects on vowel acoustics and speech intelligibility.</div><div><b>Method: </b>Participants were tested under permutations of low, mid, and high STN-DBS frequency, voltage, and pulse width settings. At each session, participants recited a sentence. Acoustic characteristics of vowel production were extracted, and naive listeners provided estimates of speech intelligibility.</div><div><b>Results:</b> Overall, lower-frequency STN-DBS stimulation (60 Hz) was found to lead to improvements in intelligibility and acoustic vowel expansion. An interaction between speaker sex and STN-DBS stimulation was found for vowel measures. The combination of low frequency, mid to high voltage, and low to mid pulse width led to optimal speech outcomes; however, these settings did not demonstrate significant speech outcome differences compared with the standard clinical STN-DBS settings, likely due to substantial individual variability.</div><div><b>Conclusions: </b>Although lower-frequency STN-DBS stimulation was found to yield consistent improvements in speech outcomes, it was not found to necessarily lead to the best speech outcomes for all participants. Nevertheless, frequency may serve as a starting point to explore settings that will optimize an individual’s speech outcomes following STN-DBS surgery.</div><div><br></div><div><b>Supplemental Material S1. </b>Estimated pairwise differences for speech intelligibility (%) from the final model.</div><div><b><br></b></div><div><b>Supplemental Material S2. </b>Estimated pairwise differences for four-vowel articulation index (VAI) from the final model.</div><div><br></div><div><b>Supplemental Material S3. </b>Estimated pairwise differences for F2 transition extent (Hz) from the final model.</div><div><br></div><div>Knowles, T., Adams, S., Abeyesekera, A., Mancinelli, C., Gilmore, G., & Jog, M. (2018). Deep brain stimulation of the subthalamic nucleus parameter optimization for vowel acoustics and speech intelligibility in Parkinson’s disease. <i>Journal of Speech, Language, and Hearing Research, 61, </i>510–524<i>.</i> https://doi.org/10.1044/2017_JSLHR-S-17-0157</div