Scalp acupuncture guidance for identifying the optimal site for transcranial electrical stimulation of the hand.

Transcranial electrical stimulation (tES) often targets the EEG-guided C3/C4 area that may not accurately represent M1 for hand muscles. This study aimed to determine if the neuroanatomy-based scalp acupuncture-guided site (AC) was a more effective spot than the C3 site for neuromodulation. Fifteen healthy subjects received one 20-minute session of high-definition transcranial alternating current stimulation (HD-tACS) intervention (20 Hz at 2 mA) at the AC or C3 sites randomly with a 1-week washout period. Subjects performed ball-squeezing exercises with the dominant hand during the HD-tACS intervention. The AC site was indiscernible from the finger flexor hotspot detected by TMS. At the baseline, the MEP amplitude from finger flexors was greater with less variability at the AC site than at the C3 site. HD-tACS intervention at the AC site significantly increased the MEP amplitude. However, no significant changes were observed after tACS was applied to the C3 site. Our results provide evidence that HD-tACS at the AC site produces better neuromodulation effects on the flexor digitorum superficialis (FDS) muscle compared to the C3 site. The AC localization approach can be used for future tES studies.

Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Stroke: 2- and 3-Year Follow-up From the Pilot Study.

OBJECTIVE: To assess whether a long-term home-based intervention using Paired VNS therapy is feasible and whether the benefits of Paired VNS therapy are maintained beyond 1 year. DESIGN: A long-term follow-up study. SETTING: Three centers in the United States and 1 in the United Kingdom. PARTICIPANTS: Adults with chronic ischemic stroke (n=15) with moderate to severe arm and hand impairment. INTERVENTIONS: Participants were implanted with a VNS device followed by 6 weeks of in-clinic therapy with Paired (Active) or control VNS followed by home-based rehabilitation through day 90 (blinded phase). The control VNS group then crossed over to receive 6 weeks of in-clinic Active VNS. Participants in both groups then continued a long-term home exercise program with self-administered Active VNS. MAIN OUTCOME MEASURES: Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT) Functional scores were evaluated at the end of in-clinic therapy and day 90. Since both groups were subsequently receiving home-based rehabilitation with Active VNS during the long term, follow-up outcome assessments were pooled for the analyses at 6, 9, and 12 months, as previously reported. Here, we report pooled analysis of outcomes beyond 1 year. RESULTS: One year after Paired VNS therapy, FMA-UE improved by an average of 9.2±8.2 points, as previously reported. Overall, the 2- and 3-year FMA-UE gain from baseline was 11.4±8.7 (P<.001) and 14.8±10.2 points (P<.001), respectively. At years 2 and 3, FMA-UE improved by an additional 2.9 (P=.03 for change vs year 1, n=14) and 4.7 (P=.02 for change vs year 1, n=14) points, respectively. At year 1, 73% (11/15) of participants were responders (FMA-UE change ≥6) and by year 3, 85.7% (12/14) were responders. At years 2 and 3, the WMFT score improved by an additional 0.21 points (P=.03 for change vs year 1, n=15) and 0.42 points (P=.01 for change vs year 1, n=13), respectively. Responder rate (WMFT change ≥0.4) was 46.6% (7/15), 73.3% (11/15), and 69.2% (9/13) at years 1, 2, and 3, respectively. Long-term significant improvements were also observed for Motor Activity Log (MAL) and Stroke Impact Scale, Hand section (SIS-Hand). There were no serious long-term adverse events from the stimulation. CONCLUSIONS: Significant effects of Paired VNS therapy at 1 year were maintained at years 2 and 3, and further improvements in both impairment and function were observed in years 2 and 3. These changes were associated with improvements in measures of activity and participation.

Design and Validation of a Low-Cost Mobile EEG-Based Brain-Computer Interface.

Objective: We designed and validated a wireless, low-cost, easy-to-use, mobile, dry-electrode headset for scalp electroencephalography (EEG) recordings for closed-loop brain-computer (BCI) interface and internet-of-things (IoT) applications. Approach: The EEG-based BCI headset was designed from commercial off-the-shelf (COTS) components using a multi-pronged approach that balanced interoperability, cost, portability, usability, form factor, reliability, and closed-loop operation. Main Results: The adjustable headset was designed to accommodate 90% of the population. A patent-pending self-positioning dry electrode bracket allowed for vertical self-positioning while parting the user's hair to ensure contact of the electrode with the scalp. In the current prototype, five EEG electrodes were incorporated in the electrode bracket spanning the sensorimotor cortices bilaterally, and three skin sensors were included to measure eye movement and blinks. An inertial measurement unit (IMU) provides monitoring of head movements. The EEG amplifier operates with 24-bit resolution up to 500 Hz sampling frequency and can communicate with other devices using 802.11 b/g/n WiFi. It has high signal-to-noise ratio (SNR) and common-mode rejection ratio (CMRR) (121 dB and 110 dB, respectively) and low input noise. In closed-loop BCI mode, the system can operate at 40 Hz, including real-time adaptive noise cancellation and 512 MB of processor memory. It supports LabVIEW as a backend coding language and JavaScript (JS), Cascading Style Sheets (CSS), and HyperText Markup Language (HTML) as front-end coding languages and includes training and optimization of support vector machine (SVM) neural classifiers. Extensive bench testing supports the technical specifications and human-subject pilot testing of a closed-loop BCI application to support upper-limb rehabilitation and provides proof-of-concept validation for the device's use at both the clinic and at home. Significance: The usability, interoperability, portability, reliability, and programmability of the proposed wireless closed-loop BCI system provides a low-cost solution for BCI and neurorehabilitation research and IoT applications.

Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.

BACKGROUND: Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke. METHODS: In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group). Randomisation was done by ResearchPoint Global (Austin, TX, USA) using SAS PROC PLAN (SAS Institute Software, Cary, NC, USA), with stratification by region (USA vs UK), age (≤30 years vs >30 years), and baseline Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score (20-35 vs 36-50). Participants, outcomes assessors, and treating therapists were masked to group assignment. All participants were implanted with a vagus nerve stimulation device. The VNS group received 0·8 mA, 100 µs, 30 Hz stimulation pulses, lasting 0·5 s. The control group received 0 mA pulses. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme. The primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy. FMA-UE response rates were also assessed at 90 days after in-clinic therapy (secondary endpoint). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT03131960. FINDINGS: Between Oct 2, 2017, and Sept 12, 2019, 108 participants were randomly assigned to treatment (53 to the VNS group and 55 to the control group). 106 completed the study (one patient for each group did not complete the study). On the first day after completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points (SD 4·4) in the VNS group and by 2·4 points (3·8) in the control group (between group difference 2·6, 95% CI 1·0-4·2, p=0·0014). 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group (between group difference 24%, 6-41; p=0·0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. INTERPRETATION: Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm impairment after ischaemic stroke. FUNDING: MicroTransponder.

Telerehabilitation of acute musculoskeletal multi-disorders: prospective, single-arm, interventional study.

BACKGROUND: Acute musculoskeletal (MSK) pain is very common and associated with impaired productivity and high economic burden. Access to timely and personalized, evidence-based care is key to improve outcomes while reducing healthcare expenditure. Digital interventions can facilitate access and ensure care scalability. OBJECTIVE: Present the feasibility and results of a fully remote digital care program (DCP) for acute MSK conditions affecting several body areas. METHODS: Interventional single-arm study of individuals applying for digital care programs for acute MSK pain. Primary outcome was the mean change between baseline and end-of-program in self-reported Numerical Pain Rating Scale (NPRS) score and secondary outcomes were change in analgesic consumption, intention to undergo surgery, anxiety (GAD-7), depression (PHQ-9), fear-avoidance beliefs (FABQ-PA), work productivity (WPAI-GH) and engagement. RESULTS: Three hundred forty-three patients started the program, of which 300 (87.5%) completed the program. Latent growth curve analysis (LGCA) revealed that changes in NPRS between baseline and end-of-program were both statistically (p < 0.001) and clinically significant: 64.3% reduction (mean - 2.9 points). Marked improvements were also noted in all secondary outcomes: 82% reduction in medication intake, 63% reduction in surgery intent, 40% in fear-avoidance beliefs, 54% in anxiety, 58% in depression and 79% recovery in overall productivity. All outcomes had steeper improvements in the first 4 weeks, which paralleled higher engagement in this period (3.6 vs 3.2 overall weekly sessions, p < 0.001). Mean patient satisfaction score was 8.7/10 (SD 1.26). STRENGTHS AND LIMITATIONS: This is the first longitudinal study demonstrating the feasibility of a DCP for patients with acute MSK conditions involving several body areas. Major strengths of this study are the large sample size, the wide range of MSK conditions studied, the breadth of outcomes measured, and the very high retention rate and adherence level. The major limitation regards to the absence of a control group. CONCLUSIONS: We observed very high completion and engagement rates, as well as clinically relevant changes in all health-related outcomes and productivity recovery. We believe this DCP holds great potential in the delivery of effective and scalable MSK care. TRIAL REGISTRATION: NCT, NCT04092946 . Registered 17/09/2019.

Guided Self-rehabilitation Contracts Combined With AbobotulinumtoxinA in Adults With Spastic Paresis.

BACKGROUND AND PURPOSE: Guided self-rehabilitation contracts (GSCs) are a diary-based rehabilitation strategy, wherein specific muscles are identified for prescription of high-load, home self-stretching techniques. We assessed the effect of GSCs combined with simultaneous upper limb (UL) and lower limb (LL) abobotulinumtoxinA injections on composite active range of motion (CXA) in adults with chronic spastic paresis. METHODS: This was an international, prospective, single-arm, open-label study (ENGAGE, NCT02969356). Personalized GSCs were monitored by phone every other week, alongside 2 consecutive abobotulinumtoxinA injections (1500 U) across UL and LL, over 6 to 9 months. Primary outcomes were responder rates (CXA improvement ≥35° [UL] or ≥5° [LL]) at week 6 cycle 2. Secondary outcomes were active function (UL: Modified Frenchay Scale [MFS]; LL: 10-m barefoot maximal walking speed [WS]) and quality of life (12-item Short Form Health Survey, SF-12). RESULTS: Of the 153 treated participants, 136 had primary endpoint data; 72.1% (95% confidence interval [CI], 64.0-78.9) were responders. Mean (SD) CXA changes from baseline to last study visit were +49.3° (63.4) for UL and +20.1° (27.6) for LL. Mean (95% CI) changes from baseline to week 12 cycle 2 were +0.55 (0.43-0.66) in MFS, +0.12 m/s (0.09-0.15) for WS, and +4.0 (2.8-5.2) for SF-12 physical scores. In the safety population (n = 157), 49.7% of participants reported treatment-emergent adverse events (AEs); 12.1% reported 25 serious AEs. DISCUSSION AND CONCLUSIONS: GSC combined with simultaneous UL and LL abobotulinumtoxinA injections led to improvements in CXA and function in both limbs, and quality-of-life physical scores. These results suggest the beneficial effect of combined GSC and abobotulinumtoxinA therapy in the management of spastic paresis.Video Abstract available for more insight from the authors (see the Supplementary Video, available at: http://links.lww.com/JNPT/A346).

Real-World Adherence to OnabotulinumtoxinA Treatment for Spasticity: Insights From the ASPIRE Study.

OBJECTIVE: To identify baseline characteristics and treatment-related variables that affect adherence to onabotulinumtoxinA treatment from the Adult Spasticity International Registry (ASPIRE) study. DESIGN: Prospective, observational registry (NCT01930786). SETTING: International clinical sites. PARTICIPANTS: Adults with spasticity (N=730). INTERVENTIONS: OnabotulinumtoxinA at clinician's discretion. MAIN OUTCOME MEASURES: Clinically meaningful thresholds used for treatment adherent (≥3 treatment sessions during 2-year study) and nonadherent (≤2 sessions). Data analyzed using logistic regression and presented as odds ratios (ORs) with 95% confidence intervals (CIs). Treatment-related variables assessed at sessions 1 and 2 only. RESULTS: Of the total population, 523 patients (71.6%) were treatment adherent with 5.3±1.6 sessions and 207 (28.4%) were nonadherent with 1.5±0.5 sessions. In the final model (n=626/730), 522 patients (83.4%) were treatment adherent and 104 (16.6%) were nonadherent. Baseline characteristics associated with adherence: treated in Europe (OR=1.84; CI, 1.06-3.21; P=.030) and use of orthotics (OR=1.88; CI, 1.15-3.08; P=.012). Baseline characteristics associated with nonadherence: history of diplopia (OR=0.28; CI, 0.09-0.89; P=.031) and use of assistive devices (OR=0.51; CI, 0.29-0.90; P=.021). Treatment-related variables associated with nonadherence: treatment interval ≥15 weeks (OR=0.43; CI, 0.26-0.72; P=.001) and clinician dissatisfaction with onabotulinumtoxinA to manage pain (OR=0.18; CI, 0.05-0.69; P=.012). Of the population with stroke (n=411), 288 patients (70.1%) were treatment adherent with 5.3±1.6 sessions and 123 (29.9%) were nonadherent with 1.5±0.5 session. In the final stroke model (n=346/411), 288 patients (83.2%) were treatment adherent and 58 (16.8%) were nonadherent. Baseline characteristics associated with adherence: treated in Europe (OR=2.99; CI, 1.39-6.44; P=.005) and use of orthotics (OR=3.18; CI, 1.57-6.45; P=.001). Treatment-related variables associated with nonadherence: treatment interval ≥15 weeks (OR=0.42; CI, 0.21-0.83; P=.013) and moderate/severe disability on upper limb Disability Assessment Scale pain subscale (OR=0.40; CI, 0.19-0.83; P=.015). CONCLUSIONS: These ASPIRE analyses demonstrate real-world patient and clinical variables that affect adherence to onabotulinumtoxinA and provide insights to help optimize management strategies to improve patient care.

The Use of Botulinum Toxin for Treatment of Spasticity.

Spasticity is one component of the upper motor neuron (UMN) syndrome resulting from a multitude of neurologic conditions, such as stroke, brain injury, spinal cord injury, multiple sclerosis, and cerebral palsy. It is clinically recognized as a phenomenon of velocity-dependent increase in resistance, i.e., hypertonia. Recent advances in the pathophysiology of spasticity improve our understanding of mechanisms underlying this complex phenomenon and its relations to other components of UMN syndrome (weakness and disordered motor control), as well as the resultant clinical problems. This theoretical framework provides a foundation to set up treatment goals and to guide goal-oriented clinical assessment and treatment. Among a spectrum of treatment options, botulinum toxin (BoNT) therapy is the preferred treatment for focal spasticity. The evidence is very robust that BoNT therapy effectively reduces spasticity; however, it does not improve voluntary movement. In this chapter, we highlight a few issues on how to achieve the best clinical outcomes of BoNT therapy, such as dosing, dilution, guidance techniques, adjunctive therapies, early treatment, repeated injections, and central effects, as well as the ways to improve motor function in selected subgroups of patients with spasticity. We also discuss the reasons of poor responses to BoNT therapy and when not to use BoNT therapy.

Exoskeleton-assisted Gait Training in Persons With Multiple Sclerosis: A Single-Group Pilot Study.

OBJECTIVE: To investigate the feasibility of conducting exoskeleton-assisted gait training (EGT) and the effects of EGT on gait, metabolic expenditure, and physical function in persons with multiple sclerosis (MS). DESIGN: Single-group pilot study. SETTING: Research laboratory in a rehabilitation hospital. PARTICIPANTS: Individuals with MS (N=10; mean age, 54.3±12.4y) and Expanded Disability Status Scale 6.0-7.5. INTERVENTIONS: All participants completed up to 15 sessions of EGT. MAIN OUTCOME MEASURES: Timed 25-foot walk test at self-selected and fast speed, 6-minute walk test, metabolic expenditure of walking and timed Up and Go test were assessed during walking without the exoskeleton at baseline and immediate post training. RESULTS: All participants tolerated the training intensity and completed training without adverse events. After training, gait speed was improved and metabolic expenditure was reduced significantly during the timed 25-foot walk test at self-selected speed. CONCLUSIONS: EGT is not only feasible but may also improve gait efficiency for persons with MS. Our observed improvement in gait speed was associated with reduced metabolic expenditure, which was likely because of improved neuromotor coordination. Further studies are required to investigate the effectiveness and integration of EGT in the continuum of MS rehabilitation.

The ReWalk ReStore™ soft robotic exosuit: a multi-site clinical trial of the safety, reliability, and feasibility of exosuit-augmented post-stroke gait rehabilitation.

BACKGROUND: Atypical walking in the months and years after stroke constrain community reintegration and reduce mobility, health, and quality of life. The ReWalk ReStore™ is a soft robotic exosuit designed to assist the propulsion and ground clearance subtasks of post-stroke walking by actively assisting paretic ankle plantarflexion and dorsiflexion. Previous proof-of-concept evaluations of the technology demonstrated improved gait mechanics and energetics and faster and farther walking in users with post-stroke hemiparesis. We sought to determine the safety, reliability, and feasibility of using the ReStore™ during post-stroke rehabilitation. METHODS: A multi-site clinical trial (NCT03499210) was conducted in preparation for an application to the United States Food and Drug Administration (FDA). The study included 44 users with post-stroke hemiparesis who completed up to 5 days of training with the ReStore™ on the treadmill and over ground. In addition to primary and secondary endpoints of safety and device reliability across all training activities, an exploratory evaluation of the effect of multiple exposures to using the device on users' maximum walking speeds with and without the device was conducted prior to and following the five training visits. RESULTS: All 44 study participants completed safety and reliability evaluations. Thirty-six study participants completed all five training days. No device-related falls or serious adverse events were reported. A low rate of device malfunctions was reported by clinician-operators. Regardless of their reliance on ancillary assistive devices, after only 5 days of walking practice with the device, study participants increased both their device-assisted (Δ: 0.10 ± 0.03 m/s) and unassisted (Δ: 0.07 ± 0.03 m/s) maximum walking speeds (P's < 0.05). CONCLUSIONS: When used under the direction of a licensed physical therapist, the ReStore™ soft exosuit is safe and reliable for use during post-stroke gait rehabilitation to provide targeted assistance of both paretic ankle plantarflexion and dorsiflexion during treadmill and overground walking. TRIAL REGISTRATION: NCT03499210. Prospectively registered on March 28, 2018.

Effect of Intrathecal Baclofen on Pain and Quality of Life in Poststroke Spasticity.

Background and Purpose- Intrathecal baclofen (ITB) is an effective treatment for managing patients with severe poststroke spasticity, who can experience continued pain and decline in their quality of life (QoL). SISTERS (Spasticity In Stroke-Randomized Study) was a randomized, controlled, open-label, multicenter, phase 4 study to evaluate ITB therapy versus conventional medical management (CMM) with oral antispastic medications for treatment of poststroke spasticity. Methods- Poststroke patients with spasticity in ≥2 extremities and an Ashworth Scale score of ≥3 in ≥2 affected lower extremity muscle groups were randomized (1:1) to ITB (N=31) or CMM (N=29). Both treatment arms received physiotherapy throughout. The primary outcome was the change in average Ashworth Scale score in the lower extremities of the affected side from baseline to month 6. Here, we report results for secondary outcomes: pain via the Numeric Pain Rating Scale, health-related QoL by the EuroQol-5 dimensional 3 level utility score and health status visual analog scale score, stroke-specific QoL, and patient satisfaction. Analyses were performed on an intention-to-treat basis. Results- We observed significant treatment effects in favor of ITB over CMM for changes from baseline to month 6 in Numeric Pain Rating Scale scores for actual pain (ITB versus CMM: mean, -1.17 [SD, 3.17] versus 0.00 [3.29]; median, -1.00 versus 0.00; P=0.0380) and least pain (mean, -1.61 [2.29] versus 0.24 [3.07]; median, -1.00 versus 0.00; P=0.0136), and EuroQol-5 dimensional 3 level utility scores (mean, +0.09 [0.26] versus +0.01 [0.16]; median, +0.07 versus 0.00; P=0.0197). Between-group differences were not statistically significant for EuroQol-5 dimensional 3 level visual analog scale, stroke-specific QoL summary, or Numeric Pain Rating Scale worst pain scores, although ITB patients showed greater numeric improvements from baseline during follow-up. More ITB patients than CMM patients (73% versus 48%) were satisfied with the spasticity reduction at month 6. Conclusions- These data support that ITB therapy is associated with improvements in pain and QoL in poststroke patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01032239.

Randomized Sham-Controlled Trial of Navigated Repetitive Transcranial Magnetic Stimulation for Motor Recovery in Stroke.

Background and Purpose- We aimed to determine whether low-frequency electric field navigated repetitive transcranial magnetic stimulation to noninjured motor cortex versus sham repetitive transcranial magnetic stimulation avoiding motor cortex could improve arm motor function in hemiplegic stroke patients when combined with motor training. Methods- Twelve outpatient US rehabilitation centers enrolled participants between May 2014 and December 2015. We delivered 1 Hz active or sham repetitive transcranial magnetic stimulation to noninjured motor cortex before each of eighteen 60-minute therapy sessions over a 6-week period, with outcomes measured at 1 week and 1, 3, and 6 months after end of treatment. The primary end point was the percentage of participants improving ≥5 points on upper extremity Fugl-Meyer score 6 months after end of treatment. Secondary analyses assessed changes on the upper extremity Fugl-Meyer and Action Research Arm Test and Wolf Motor Function Test and safety. Results- Of 199 participants, 167 completed treatment and follow-up because of early discontinuation of data collection. Upper extremity Fugl-Meyer gains were significant for experimental ( P<0.001) and sham groups ( P<0.001). Sixty-seven percent of the experimental group (95% CI, 58%-75%) and 65% of sham group (95% CI, 52%-76%) improved ≥5 points on 6-month upper extremity Fugl-Meyer ( P=0.76). There was also no difference between experimental and sham groups in the Action Research Arm Test ( P=0.80) or the Wolf Motor Function Test ( P=0.55). A total of 26 serious adverse events occurred in 18 participants, with none related to the study or device, and with no difference between groups. Conclusions- Among patients 3 to 12 months poststroke, goal-oriented motor rehabilitation improved motor function 6 months after end of treatment. There was no difference between the active and sham repetitive transcranial magnetic stimulation trial arms. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02089464.

Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke.

Background and Purpose- We assessed safety, feasibility, and potential effects of vagus nerve stimulation (VNS) paired with rehabilitation for improving arm function after chronic stroke. Methods- We performed a randomized, multisite, double-blinded, sham-controlled pilot study. All participants were implanted with a VNS device and received 6-week in-clinic rehabilitation followed by a home exercise program. Randomization was to active VNS (n=8) or control VNS (n=9) paired with rehabilitation. Outcomes were assessed at days 1, 30, and 90 post-completion of in-clinic therapy. Results- All participants completed the course of therapy. There were 3 serious adverse events related to surgery. Average FMA-UE scores increased 7.6 with active VNS and 5.3 points with control at day 1 post-in-clinic therapy (difference, 2.3 points; CI, -1.8 to 6.4; P=0.20). At day 90, mean scores increased 9.5 points from baseline with active VNS, and the control scores improved by 3.8 (difference, 5.7 points; CI, -1.4 to 11.5; P=0.055). The clinically meaningful response rate of FMA-UE at day 90 was 88% with active VNS and 33% with control VNS ( P<0.05). Conclusions- VNS paired with rehabilitation was acceptably safe and feasible in participants with upper limb motor deficit after chronic ischemic stroke. A pivotal study of this therapy is justified. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02243020.

Intrathecal baclofen therapy versus conventional medical management for severe poststroke spasticity: results from a multicentre, randomised, controlled, open-label trial (SISTERS).

BACKGROUND: Intrathecal baclofen (ITB) is a treatment option for patients with severe poststroke spasticity (PSS) who have not reached their therapy goal with other interventions. METHODS: 'Spasticity In Stroke-Randomised Study' (SISTERS) was a randomised, controlled, open-label, multicentre phase IV study to evaluate the efficacy and safety of ITB therapy versus conventional medical management (CMM) with oral antispastic medications for treatment of PSS. Patients with chronic stroke with spasticity in ≥2 extremities and an Ashworth Scale (AS) score ≥3 in at least two affected muscle groups in the lower extremities (LE) were randomised (1:1) to ITB or CMM. Both treatment arms received physiotherapy throughout. The primary outcome was the change in the average AS score in the LE of the affected body side from baseline to month 6. Analyses were performed for all patients as randomised (primary analysis) and all randomised patients as treated (safety analysis). RESULTS: Of 60 patients randomised to ITB (n=31) or CMM (n=29), 48 patients (24 per arm) completed the study. The primary analysis showed a significant effect of ITB therapy over CMM (mean AS score reduction, -0.99 (ITB) vs -0.43 (CMM); Hodges-Lehmann estimate, -0.667(95.1%CI -1.0000 to -0.1667); P=0.0140). More patients reported adverse events while receiving ITB (24/25 patients, 96%; 149 events) compared with CMM (22/35, 63%; 77 events), although events were generally consistent with the known safety profile of ITB therapy. CONCLUSIONS: These data support the use of ITB therapy as an alternative to CMM for treatment of generalised PSS in adults. TRIAL REGISTRATION NUMBER: NCT01032239; Results.

Evolution of upper limb kinematics four years after subacute robot-assisted rehabilitation in stroke patients.

Purpose: To assess functional status and robot-based kinematic measures four years after subacute robot-assisted rehabilitation in hemiparesis. Materials and methods: Twenty-two patients with stroke-induced hemiparesis underwent a ≥3-month upper limb combined program of robot-assisted and occupational therapy from two months post-stroke, and received community-based therapy after discharge. Four years later, 19 (86%) participated in this follow-up study. Assessments 2, 5 and 54 months post-stroke included Fugl-Meyer (FM), Modified Frenchay Scale (MFS, at Month 54) and robot-based kinematic measures of targeting tasks in three directions, north, paretic and non-paretic: distance covered, velocity, accuracy (root mean square (RMS) error from straight line) and smoothness (number of velocity peaks; upward changes in accuracy and smoothness represent worsening). Analysis was stratified by FM score at two months: ≥17 (Group 1) or <17 (Group 2). Correlation between impairment (FM) and function (MFS) was explored at 54 months. Results: FM scores were stable from 5 to 54 months (+1[-2;4], median [1st; 3rd quartiles], ns). Kinematic changes (three directions pooled) were: distance -1[-17;2]% (ns); velocity, -8[-32;28]% (ns); accuracy, +6[-13;98]% (ns); smoothness, +44[-6;126]% (p < 0.05). Group 2 showed decline vs. Group 1 (p < 0.001) in FM (Group 1, +3[1;5], p < 0.01; Group 2, -7[-11;-1], ns) and accuracy (Group 1, -3[-27;38]%, ns; Group 2, +29[17;140]%, p < 0.001). At 54 months, FM and MFS were highly correlated (Pearson's rho = 0.89; p < 0.001). Conclusions: While impairment appeared stable four years after robot-assisted upper limb training during subacute post-stroke phase, movement kinematics deteriorated despite community-based therapy, especially in more severely impaired patients. Trial registration: EudraCT 2016-005121-36. Registration: 2016-12-20. Date of enrolment of the first participant to the trial: 2009-11-24.

The H2 robotic exoskeleton for gait rehabilitation after stroke: early findings from a clinical study.

BACKGROUND: Stroke significantly affects thousands of individuals annually, leading to considerable physical impairment and functional disability. Gait is one of the most important activities of daily living affected in stroke survivors. Recent technological developments in powered robotics exoskeletons can create powerful adjunctive tools for rehabilitation and potentially accelerate functional recovery. Here, we present the development and evaluation of a novel lower limb robotic exoskeleton, namely H2 (Technaid S.L., Spain), for gait rehabilitation in stroke survivors. METHODS: H2 has six actuated joints and is designed to allow intensive overground gait training. An assistive gait control algorithm was developed to create a force field along a desired trajectory, only applying torque when patients deviate from the prescribed movement pattern. The device was evaluated in 3 hemiparetic stroke patients across 4 weeks of training per individual (approximately 12 sessions). The study was approved by the Institutional Review Board at the University of Houston. The main objective of this initial pre-clinical study was to evaluate the safety and usability of the exoskeleton. A Likert scale was used to measure patient's perception about the easy of use of the device. RESULTS: Three stroke patients completed the study. The training was well tolerated and no adverse events occurred. Early findings demonstrate that H2 appears to be safe and easy to use in the participants of this study. The overground training environment employed as a means to enhance active patient engagement proved to be challenging and exciting for patients. These results are promising and encourage future rehabilitation training with a larger cohort of patients. CONCLUSIONS: The developed exoskeleton enables longitudinal overground training of walking in hemiparetic patients after stroke. The system is robust and safe when applied to assist a stroke patient performing an overground walking task. Such device opens the opportunity to study means to optimize a rehabilitation treatment that can be customized for individuals. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( https://clinicaltrials.gov/show/NCT02114450 ).

Acoustic startle reflex in patients with chronic stroke at different stages of motor recovery: a pilot study.

BACKGROUND: Acoustic startle reflex (ASR) can be used as a tool to examine reticulospinal excitability. The potential role of reticulospinal mechanisms in the development of spasticity has been suggested but not tested. OBJECTIVE: To examine reticulospinal excitability at different stages of motor recovery in patients with chronic stroke using the ASR. METHODS: Sixteen subjects with hemiplegic stroke participated in the study. We examined ASR responses at rest and contralateral motor overflow during voluntary elbow flexion. RESULTS: ASR responses in impaired biceps muscles showed different patterns at different stages. In subjects without spasticity, ASR responses were less frequent (10% on impaired side) and had normal duration (<200 ms). In subjects with spasticity, the responses were more frequent (58.3% on impaired side) and longer lasting (up to 1 minute). However, no correlation between exaggerated reflex responses and Modified Ashworth Scale (MAS) scores was observed. During voluntary elbow flexion on the impaired side, similar positive linear force-electromyogram (EMG) relationships were found in subjects with and without spasticity. Electromyographic activity of the resting nonimpaired limb increased proportionally in subjects with spasticity (r = 0.6313, P = .0004), but no such correlation was found in subjects without spasticity (r = 0.0191, P = .9612). CONCLUSIONS: Preliminary findings of exaggerated ASR responses and associated contralateral overflow only in spastic biceps muscles in patients with chronic stroke suggest the important role of reticulospinal mechanisms in the development of spasticity.

A randomized, double-blind, placebo-controlled trial of DaxibotulinumtoxinA for Injection for the treatment of upper limb spasticity in adults after stroke or traumatic brain injury.

BACKGROUND: Intramuscular injection of botulinum toxin type A is a first-line pharmacotherapy for adults with upper limb spasticity (ULS). However, reemergence of symptoms within 12 weeks of treatment is common and longer-lasting treatments are needed. OBJECTIVE: To evaluate the efficacy and safety of three doses of DaxibotulinumtoxinA for Injection (DAXI) for treatment of ULS in adults with stroke or traumatic brain injury. INTERVENTION: Intramuscular injections of placebo (N = 24), DAXI 250 U (N = 22), DAXI 375 U (N = 19), or DAXI 500 U (N = 18) to the suprahypertonic muscle (SMG) and other muscle groups. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Twenty-six study centers across the United States. PARTICIPANTS: Eighty-three adult patients with ULS were randomly assigned to each treatment group and followed for up to 36 weeks. OUTCOME MEASURES: Co-primary endpoints were the Modified Ashworth Scale (MAS) score change from baseline in the designated SMG and Physician Global Impression of Change (PGIC) at Week 6. RESULTS: The mean changes from baseline in MAS score for the designated SMG for placebo and the DAXI 250 U, 375 U, and 500 U groups were -0.6, -0.9, -0.9, and -1.8, respectively, at Week 4 and -0.8, -0.9, -1.0, and -1.5, respectively, at Week 6. Statistically significant improvement in MAS score compared with placebo was reported only for the 500 U dose (Week 4: p < .001; Week 6: p = .049). Significant improvements in PGIC ratings compared with placebo were reported for DAXI 375 U (p = .015) and DAXI 500 U (p = .009) at Week 4 but not for any DAXI doses at Week 6. All DAXI doses were well tolerated with no trend toward more adverse events with increased dose. CONCLUSION: Results from this Phase 2 study indicate that DAXI 500 U is effective and well tolerated for treatment of adults with ULS.

The Role of Botulinum Toxin Type-A in Spasticity: Research Trends from a Bibliometric Analysis.

Botulinum toxin type-A (BoNT-A) has emerged as a key therapeutic agent for the management of spasticity. This paper presents a comprehensive bibliometric and visual analysis of research concerning BoNT-A treatment of spasticity to elucidate current trends and future directions in this research area. A search was conducted in the Web of Science database for articles focused on the use of BoNT-A in spasticity published between 2000 and 2022. We extracted various metrics, including counts of publications and contributions from different countries, institutions, authors, and journals. Analytical methods in CiteSpace were employed for the examination of co-citations, collaborations, and the co-occurrence of keywords. Our search yielded 1489 publications. Analysis revealed a consistent annual increase in research output. The United States, United Kingdom, and Italy were the leading contributors. The top institution in this research was Assistance Publique Hopitaux, Paris. The journal containing the highest number of relevant publications was Toxins. Key frequently occurring keywords were 'stroke', 'cerebral palsy', 'adult spasticity', and 'upper extremity'. This study identified 12 clusters of keywords and 15 clusters of co-cited references, indicating the main focus areas and emerging themes in this field. This study comprehensively analyzed and summarized trends in BoNT-A research in the field of spasticity over the past 22 years.