12 research outputs found

    Exploring the effects of spinal cord stimulation for freezing of gait in parkinsonian patients

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    Dopaminergic replacement therapies (e.g. levodopa) provide limited to no response for axial motor symptoms including gait dysfunction and freezing of gait (FOG) in Parkinson’s disease (PD) and Richardson’s syndrome progressive supranuclear palsy (PSP-RS) patients. Dopaminergic-resistant FOG may be a sensorimotor processing issue that does not involve basal ganglia (nigrostriatal) impairment. Recent studies suggest that spinal cord stimulation (SCS) has positive yet variable effects for dopaminergic-resistant gait and FOG in parkinsonian patients. Further studies investigating the mechanism of SCS, optimal stimulation parameters, and longevity of effects for alleviating FOG are warranted. The hypothesis of the research described in this thesis is that mid-thoracic, dorsal SCS effectively reduces FOG by modulating the sensory processing system in gait and may have a dopaminergic effect in individuals with FOG. The primary objective was to understand the relationship between FOG reduction, improvements in upper limb visual-motor performance, modulation of cortical activity and striatal dopaminergic innervation in 7 PD participants. FOG reduction was associated with changes in upper limb reaction time, speed and accuracy measured using robotic target reaching choice tasks. Modulation of resting-state, sensorimotor cortical activity, recorded using electroencephalography, was significantly associated with FOG reduction while participants were OFF-levodopa. Thus, SCS may alleviate FOG by modulating cortical activity associated with motor planning and sensory perception. Changes to striatal dopaminergic innervation, measured using a dopamine transporter marker, were associated with visual-motor performance improvements. Axial and appendicular motor features may be mediated by non-dopaminergic and dopaminergic pathways, respectively. The secondary objective was to demonstrate the short- and long-term effects of SCS for alleviating dopaminergic-resistant FOG and gait dysfunction in 5 PD and 3 PSP-RS participants without back/leg pain. SCS programming was individualized based on which setting best improved gait and/or FOG responses per participant using objective gait analysis. Significant improvements in stride velocity, step length and reduced FOG frequency were observed in all PD participants with up to 3-years of SCS. Similar gait and FOG improvements were observed in all PSP-RS participants up to 6-months. SCS is a promising therapeutic option for parkinsonian patients with FOG by possibly influencing cortical and subcortical structures involved in locomotion physiology

    Developing a Consistent, Reproducible Botulinum Toxin Type A Dosing Method for Upper Limb Tremor by Kinematic Analysis

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    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

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

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    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

    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.

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    <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
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