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15 pages, 1016 KB  
Review
The Utility of the Electromyography and Ultrasound Guidance Combination for Botulinum Neurotoxin Injection: Focus on the Added Value of Electromyography
by Domenico Antonio Restivo, Mario Stampanoni Bassi, Rosario Marchese-Ragona, Giovanni Castelnovo, Angelo Alito, Demetrio Milardi, Stefano Masiero and Daniele Coraci
Toxins 2026, 18(6), 238; https://doi.org/10.3390/toxins18060238 - 22 May 2026
Abstract
The efficacy of botulinum neurotoxin (BoNT) is strongly dependent on its accurate delivery to hyperactive muscles and, ideally, to motor endplate regions. Although guidance techniques such as electromyography (EMG) and ultrasound (US) improve injection precision, each technique provides only partial information—either functional or [...] Read more.
The efficacy of botulinum neurotoxin (BoNT) is strongly dependent on its accurate delivery to hyperactive muscles and, ideally, to motor endplate regions. Although guidance techniques such as electromyography (EMG) and ultrasound (US) improve injection precision, each technique provides only partial information—either functional or anatomical. Integrating these techniques could enhance targeting accuracy, optimize dose distribution, and reduce off-target effects. A structured PubMed search was performed using terms related to BoNT, spasticity/dystonia, EMG, and US. Filters included clinical trials, randomized controlled trials, meta-analyses and reviews published within the last decade. Fifty-nine studies met the inclusion criteria. The publications were predominantly in neuroscience and rehabilitation journals. Only 17 studies reported combined EMG–US guidance. These focused mainly on stroke and cervical dystonia. While EMG-US integration is a promising strategy, we emphasize the added value of EMG guidance for US approaches, which is particularly important when treating complex neurological conditions involving complex, overlapping muscle activation patterns, or when targeting structures that are inaccessible to conventional imaging techniques. The EMG-US integrated approach is a promising strategy for optimizing BoNT therapy by combining structural visualization with real-time functional assessment. Despite its promising advantages in terms of accuracy and dose optimization, its clinical adoption is limited by a lack of high-quality evidence. Full article
(This article belongs to the Section Bacterial Toxins)
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23 pages, 802 KB  
Article
Influence of Immobilization, Stretching, and Activity on Isometric Muscle Strength and Gait in Young People with Spastic Cerebral Palsy
by Martin Svehlik, Andreas Habersack, Bernhard Guggenberger, Nina Mosser, Markus Tilp, Tanja Kraus and Annika Kruse
J. Clin. Med. 2026, 15(10), 3869; https://doi.org/10.3390/jcm15103869 - 18 May 2026
Viewed by 179
Abstract
Background/Objectives: Neurological impairments in children with Cerebral Palsy (CP) often lead to altered muscle architecture and function, resulting in calf muscle contractures. Orthotic immobilization aims to promote muscle–tendon unit lengthening through sustained stretch but may also induce disuse atrophy. This study investigated [...] Read more.
Background/Objectives: Neurological impairments in children with Cerebral Palsy (CP) often lead to altered muscle architecture and function, resulting in calf muscle contractures. Orthotic immobilization aims to promote muscle–tendon unit lengthening through sustained stretch but may also induce disuse atrophy. This study investigated whether combining immobilization with daily activity yields different effects on muscle strength and gait function compared with immobilization alone. Methods: Fourteen ambulant children with spastic CP and equinus deformity (8 unilateral, 6 bilateral; mean age 9.93 ± 3.0 years; GMFCS I: 10, GMFCS II: 4) participated in a 12-week randomized controlled trial. Participants were assigned to either continuous immobilization (23 h/day) using a dynamic ankle–foot orthosis or a combined protocol consisting of 14 h/day immobilization and 10 h/day of activity involving ankle mobility and calf muscle activation. Outcomes included isometric muscle strength, joint range of motion, gait parameters, and functional measures (Gait Outcomes Assessment List (GOAL) and the Paediatric Outcome Data Collection Instrument (PODCI)). Data were analyzed using linear mixed models with Bonferroni correction. Results: Significant time effects were observed for the knee angle at initial contact (IC), the ankle angle at IC, maximum dorsiflexion, and maximum dorsiflexion during swing. A significant group × time interaction was found only for hindfoot-tibia angle at IC. Within-group improvements were noted in activities of daily living, body image and self-esteem, and basic mobility. No significant changes were found for muscle strength or for most questionnaire subscales. Conclusions: The findings indicate time-related improvements in gait, with no consistent advantage of the combined intervention. Further studies with larger samples are needed to evaluate potential long-term effects. Full article
(This article belongs to the Special Issue Cerebral Palsy: Recent Advances in Clinical Management)
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15 pages, 1822 KB  
Article
Spasticity in Prolonged Disorders of Consciousness: A Prospective Cohort Study
by Nathalie Draulans, Cecile Utens, Danielle Driessen, Willemijn van Erp, Gerard Ribbers, Jörg Wissel and Aurore Thibaut
Brain Sci. 2026, 16(5), 524; https://doi.org/10.3390/brainsci16050524 - 14 May 2026
Viewed by 182
Abstract
Background: Spasticity is a frequent and disabling complication in patients with prolonged disorders of consciousness (PDOC), yet its prevalence, distribution, evolution, and relationship with recovery of consciousness remain poorly characterized. The aim was to investigate the prevalence, severity, distribution, and evolution of spasticity [...] Read more.
Background: Spasticity is a frequent and disabling complication in patients with prolonged disorders of consciousness (PDOC), yet its prevalence, distribution, evolution, and relationship with recovery of consciousness remain poorly characterized. The aim was to investigate the prevalence, severity, distribution, and evolution of spasticity in PDOC patients undergoing early intensive neurorehabilitation (EIN), and to explore clinical factors associated with spasticity and its relationship with level of consciousness (LOC). Methods: This study was embedded in the nationwide prospective DOCTOR cohort and included 126 PDOC patients admitted for EIN in the Netherlands between 2019 and 2023. Spasticity was assessed at admission and discharge using the Ashworth Scale (AS) across seven bilateral muscle groups. Associations between spasticity, demographic and clinical variables, medication use, nociception, and recovery of consciousness were analyzed. Results: Spasticity was highly prevalent at EIN admission (88%) and discharge (90%), with mostly bilateral and widespread involvement. Elbow flexors, wrist flexors, hip adductors, and knee flexors were most frequently affected. Severe spasticity was present in 19% at admission and 30% at discharge. Spasticity severity correlated positively with pain scores and use of spasmolytics, but not with LOC. No association was found between spasticity at admission and recovery of consciousness. Conclusions: Spasticity is nearly ubiquitous and often progressive in PDOC, even during specialized neurorehabilitation. Its evolution appears independent of recovery of consciousness, underscoring the need to assess and manage spasticity as a distinct clinical entity. Prospective interventional studies are warranted to optimize spasticity treatment in this population. Full article
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13 pages, 639 KB  
Article
Early Intervention of Hemiplegic Shoulder Pain in the Context of Post-Stroke Shoulder Spasticity: A Canadian Cross-Sectional Survey
by Farris Kassam, Fraser MacRae, Linden Lechner, Heather Dow, Ève Boissonnault, Fiona Huang and Paul Winston
Toxins 2026, 18(5), 228; https://doi.org/10.3390/toxins18050228 - 12 May 2026
Viewed by 313
Abstract
Objectives: To investigate current Canadian physicians’ practice patterns of treating upper limb post-stroke spasticity (PSS) and hemiplegic shoulder pain (HSP) acutely after a stroke. In addition, by examining Canadian physicians’ diagnostic capabilities, time till treatment, minimum criteria to begin treatment, mechanisms of treatment, [...] Read more.
Objectives: To investigate current Canadian physicians’ practice patterns of treating upper limb post-stroke spasticity (PSS) and hemiplegic shoulder pain (HSP) acutely after a stroke. In addition, by examining Canadian physicians’ diagnostic capabilities, time till treatment, minimum criteria to begin treatment, mechanisms of treatment, targeting of muscles, and benefits and adverse effects of treatment, we aim to learn about areas of improvement to optimize PSS management for Canadians. Design: The present study was a cross-sectional survey, polling practicing Canadian physicians. Results: A total of 17 physicians completed the survey, all PM&R specialists, save one neurologist. Four provinces were represented in the responses. Participants had, on average, over ten years of experience managing post-stroke spasticity in outpatient and inpatient clinics. All 17 perform botulinum neurotoxin A (BoNT-A) injections for HSP associated with PSS. Most participants reported that they will begin BoNT-A treatments 2–3 weeks post-stroke, most commonly targeting the pectoralis major, subscapularis, and latissimus dorsi. Participants reported the mean median dosage they use as onabotulinum toxin A (169.12 units, SD = 73.70), incobotulinum toxin A (178.13 units, SD = 65.75), and abobotulinum toxin A (470.83 units, SD = 171.17). For injection guidance, participants responded that they use ultrasound for the largest percentage of their caseload, followed by electromyography, then electrical stimulation, then palpation. Very seldom did participants use palpation alone. Conclusions: From the limited sample included in analyses, the Canadian physicians respondents seem to be treating HSP and associated PSS with variable strategies. Further research is required to align dosages, targets, and guidance strategies as they vary considerably. Full article
(This article belongs to the Special Issue Botulinum Toxin: Advancing Treatments for Spasticity)
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18 pages, 1507 KB  
Article
Telerehabilitation and Face-to-Face Exergame Delivery Modalities to Improve Postural Control in Children with Cerebral Palsy: A Randomised Controlled Trial
by Valeska Gatica-Rojas and L. Eduardo Cofré Lizama
Med. Sci. 2026, 14(2), 246; https://doi.org/10.3390/medsci14020246 - 8 May 2026
Viewed by 273
Abstract
Background: Low-cost virtual reality exergames may help maintain and improve postural control in children with spastic hemiplegia cerebral palsy (CP). This study aimed to evaluate the comparative effectiveness of the same six-week, low-cost exergame programme delivered via telerehabilitation (TR) and face-to-face (FF) in [...] Read more.
Background: Low-cost virtual reality exergames may help maintain and improve postural control in children with spastic hemiplegia cerebral palsy (CP). This study aimed to evaluate the comparative effectiveness of the same six-week, low-cost exergame programme delivered via telerehabilitation (TR) and face-to-face (FF) in CP children. Methods: In this randomised controlled trial, 15 CP patients completed 18 sessions over 6 weeks. The TR group received remotely delivered sessions, whereas the FF control group completed in-person sessions with a physiotherapist. Outcomes were assessed at baseline; weeks 2, 4, and 6; and follow-ups at weeks 8 and 10. Postural control (centre-of-pressure sway area; CoPsway) was measured during eyes open (EO), eyes closed (EC), voluntary mediolateral sway to a 30 bpm auditory cue (EO/EC), and during exergames targeting mediolateral (ML-WS) and anteroposterior (AP-WS) weight-shifting. Timed Up and Go (TUG) and Modified Modified Ashworth Scale (MMAS) were also assessed. Results: At week 6, both TR and FF significantly reduced CoPsway (TR: p = 0.001, EC; FF: p = 0.01, EO). TR also improved dynamic postural control (p < 0.05) and TUG scores (p = 0.03), with functional gains sustained until week 10. Between-group comparisons revealed that TR achieved significantly greater reductions in AP weight-shifting (SDML, p = 0.001; VML, p = 0.004) and TUG (p = 0.009) than FF, with these advantages persisting throughout follow-up as revealed by post hoc analysis. Conversely, only FF significantly reduced ankle muscle tone (MMAS, p = 0.05). TR demonstrated broader improvements in secondary CoP metrics and superior long-term retention of functional mobility gains. Conclusions: Both six-week exergame interventions led to improvements in postural control. This trial demonstrated that telerehabilitation is a viable, comparable alternative to face-to-face delivery. Long-term retention suggests both modalities are complementary, offering flexible solutions to enhance routine physiotherapy service pathways. These findings provide a basis for validating these models across larger clinical cohorts. Full article
(This article belongs to the Section Translational Medicine)
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29 pages, 384 KB  
Review
Percutaneous Cryoneurolysis for Upper Limb Spasticity: A Systematic Scoping Review of Current Evidence, Safety Profile, and Implications for Hand and Upper Extremity Practice
by Marco Passiatore, Luciano Maria Bissolotti, Marta Starnoni, Luca Pecori, Anna Paola D’Apolito, Francesco De Santis and Rocco De Vitis
J. Clin. Med. 2026, 15(9), 3541; https://doi.org/10.3390/jcm15093541 - 6 May 2026
Viewed by 514
Abstract
Background/Objectives: Percutaneous cryoneurolysis (CNL) has emerged as a minimally invasive neuromodulatory technique for focal spasticity management, with growing international clinical adoption since 2018. Its application to upper limb motor nerve targets—including branches of the musculocutaneous, radial, median, ulnar, pectoral, and thoracodorsal nerves—is of [...] Read more.
Background/Objectives: Percutaneous cryoneurolysis (CNL) has emerged as a minimally invasive neuromodulatory technique for focal spasticity management, with growing international clinical adoption since 2018. Its application to upper limb motor nerve targets—including branches of the musculocutaneous, radial, median, ulnar, pectoral, and thoracodorsal nerves—is of direct relevance to clinicians involved in the surgical and non-surgical management of hand and upper extremity spasticity. The existing literature lacks a comprehensive systematic appraisal of its evidence base. This systematic scoping review aimed to map all published evidence on CNL for spasticity across all aetiological groups and anatomical regions, with particular attention to upper limb and hand-relevant targets; appraise methodological quality using design-appropriate tools; characterise the safety profile; apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to key outcome domains; and identify critical evidence gaps. Methods: A systematic scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines (search through February 2026). PubMed/MEDLINE, Embase (via Ovid), Scopus, and the Cochrane Library were searched. Methodological quality was assessed using JBI Critical Appraisal Checklists, Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I), and A MeaSurement Tool to Assess systematic Reviews-2 (AMSTAR-2). Certainty of evidence was evaluated using GRADE. Results: Twenty-five studies met inclusion criteria; no randomised controlled trials (RCTs) were identified. In the largest prospective observational cohort (n = 59, 12-month follow-up), CNL produced statistically significant improvements in passive range of motion (ROM), Modified Ashworth Scale (MAS) scores, and pain in patients with upper limb spasticity refractory to botulinum toxin type A (BoNT-A). A prospective safety study (n = 113 patients; 277 nerves) documented that 96.75% of nerve treatments produced no post-procedural sensory disturbance; the risk was approximately 10-fold higher for mixed sensorimotor than purely motor nerve targets (7.1% vs. 1.1%). Certainty of evidence was Very Low (⊕◯◯◯) for all efficacy outcomes and Low (⊕⊕◯◯) for safety. Conclusions: CNL represents a mechanistically sound second-line or complementary intervention for refractory focal spasticity. In the upper extremity context, it may additionally serve as a reversible functional evaluation tool before irreversible surgical decisions—including selective neurotomy—are made. The evidence base is critically constrained by the absence of RCTs, confirmed cohort overlap between the two largest primary studies, financial conflicts of interest with the primary device manufacturer identified in ≥48% of included studies (≥12/25), and single-institution concentration of primary evidence (≥69% of primary clinical studies from one research group). Multiple ongoing controlled trials are expected to provide higher-quality evidence to inform guideline development. Full article
(This article belongs to the Special Issue Innovation in Hand Surgery)
17 pages, 1064 KB  
Article
Focal Muscular Vibration During Intensive Rehabilitation in the Treatment of Spasticity After a Severe Acquired Brain Injury: A Pilot Randomized Controlled Trial
by Augusto Fusco, Dario Mattia Gatto, Davide Giannuzzi, Letizia Castelli, Gianpaolo Ronconi, Claudia Lombardo, Stefano Bonomi and Cristina Cuccagna
J. Clin. Med. 2026, 15(9), 3363; https://doi.org/10.3390/jcm15093363 - 28 Apr 2026
Viewed by 353
Abstract
Background: Spasticity significantly impairs functional recovery after severe acquired brain injury. Current management methods predominantly rely on pharmacological interventions, which can cause substantial side effects or require invasive medical procedures in refractory cases. Focal muscle vibration, a noninvasive technique that applies mechanical [...] Read more.
Background: Spasticity significantly impairs functional recovery after severe acquired brain injury. Current management methods predominantly rely on pharmacological interventions, which can cause substantial side effects or require invasive medical procedures in refractory cases. Focal muscle vibration, a noninvasive technique that applies mechanical vibrations to muscle–tendon units and alters spinal and cortical excitability via proprioceptive pathways, has been effective in reducing spasticity in subjects with stroke. However, there is limited data to support focal muscle vibration as a viable option for improving functional recovery in patients with severe acquired brain injury. Objectives: To evaluate the clinical effects of adding focal muscle vibration to standard physiotherapy compared with standard physiotherapy alone in patients with severe acquired brain injury and spastic hypertonia. Methods: Twenty-four patients were randomly assigned to receive focal muscle vibration in addition to standard care (n = 12) or standard care alone (n = 12) for 3 weeks. Assessments were conducted at baseline, immediately after physiotherapy, and 3 weeks after physiotherapy. The outcomes assessed included the Modified Ashworth Scale, Disability Rating Scale, Modified Barthel Index, and three pain measures. Results: A significant reduction in spasticity was observed in the focal muscle vibration group, as indicated by the Modified Ashworth Scale scores (p = 0.014). Disability Rating Scale scores demonstrated a statistically significant decrease in disability ratings at the end of treatment (p = 0.002) and during the follow-up phase (p = 0.002). Between-group comparisons of change scores revealed a statistically significant improvement in disability ratings in the focal muscle vibration group during the treatment phase (p = 0.011). Significant functional gains were noted on the Disability Rating Scale, which persisted at the follow-up evaluation. Conclusions: Focal muscle vibration reduces muscle spasticity and improves functional status in patients with severe acquired brain injury during inpatient rehabilitation. Future studies with larger sample sizes, blinded assessments, and stratified randomization are needed to verify these findings and develop standardized treatment protocols for this underserved population. Full article
(This article belongs to the Section Brain Injury)
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20 pages, 10730 KB  
Article
Rapsyn Homolog RPY-1 Modulates Locomotor Responses of Caenorhabditis elegans to Radial Extracorporeal Shock Waves
by Tanja Hochstrasser, Leon Kaub and Christoph Schmitz
Biomedicines 2026, 14(5), 960; https://doi.org/10.3390/biomedicines14050960 (registering DOI) - 22 Apr 2026
Viewed by 386
Abstract
Background/Objectives: Radial extracorporeal shock wave therapy (rESWT) is used to treat neuromuscular disorders such as spasticity, but the mechanisms by which rESWT modulates muscle tone remain incompletely understood. One proposed mechanism involves mechanical perturbation of the neuromuscular junction (NMJ), particularly destabilization of [...] Read more.
Background/Objectives: Radial extracorporeal shock wave therapy (rESWT) is used to treat neuromuscular disorders such as spasticity, but the mechanisms by which rESWT modulates muscle tone remain incompletely understood. One proposed mechanism involves mechanical perturbation of the neuromuscular junction (NMJ), particularly destabilization of acetylcholine receptor (AChR) clusters in the postsynaptic membrane. Because rapsyn knockout mice are not viable, Caenorhabditis elegans (C. elegans) provides an alternative model for studying neuromuscular signaling, expressing the rapsyn homolog RPY-1, a postsynaptic scaffolding protein involved in AChR organization at the NMJ. This study examined whether loss of RPY-1 alters locomotor responses of C. elegans to radial extracorporeal shock wave (rESW) exposure. Methods: Wild-type worms and rpy-1 knockout worms (rpy-1-KOs) were exposed to defined numbers of rESWs. Locomotor behavior was quantified using automated tracking of parameters describing speed, trajectory and body-wave dynamics. Behavioral responses were analyzed both as absolute values and relative to genotype-specific baseline values. Results: rESW exposure produced pronounced alterations in locomotor behavior across all parameters analyzed. Absolute values revealed baseline differences between genotypes. After normalization to genotype-specific baseline values, wild-type worms and rpy-1-KOs responded similarly to moderate exposure levels. At higher exposure levels, genotype-dependent differences became more apparent. Locomotor impairment was most pronounced immediately after exposure but improved during the subsequent recovery period of three hours. Conclusions: rESWs induced strong but largely reversible locomotor alterations in C. elegans during the first hours after exposure. Loss of the rapsyn homolog RPY-1 modified these responses, particularly at higher exposure levels. These findings indicate that RPY-1 influences behavioral responses to rESW exposure, while direct effects on NMJ structure or AChR organization cannot be determined from the present data. Full article
(This article belongs to the Section Cell Biology and Pathology)
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11 pages, 744 KB  
Review
Muscle-Specific Dosing of OnabotulinumtoxinA in Post-Stroke Upper-Limb Spasticity: A Descriptive Literature Review
by Małgorzata Cisowska-Adamiak, Magdalena Mackiewicz-Milewska and Elżbieta Dorota Miller
Toxins 2026, 18(4), 192; https://doi.org/10.3390/toxins18040192 - 21 Apr 2026
Viewed by 406
Abstract
Background: Botulinum neurotoxin type A is widely used in the management of post-stroke upper-limb spasticity; however, many studies report total injected doses rather than muscle-specific dosing, limiting clinical applicability. This study aimed to evaluate how frequently muscle-level dosing protocols of onabotulinumtoxinA are reported [...] Read more.
Background: Botulinum neurotoxin type A is widely used in the management of post-stroke upper-limb spasticity; however, many studies report total injected doses rather than muscle-specific dosing, limiting clinical applicability. This study aimed to evaluate how frequently muscle-level dosing protocols of onabotulinumtoxinA are reported and to assess consistency of dosing patterns across published studies. Methods: A literature search was conducted in PubMed, Wiley/Cochrane Library, and EBSCO/CINAHL using a structured search strategy informed by PRISMA guidelines. Studies published within the last 10 years reporting on onabotulinumtoxinA treatment in post-stroke upper-limb spasticity with muscle-specific dosing data were included. Studies not providing muscle-level dosing or not allowing extraction of post-stroke upper-limb data were excluded. Data were summarized descriptively and compared across studies. Results: Twenty-seven full-text articles were assessed, and five studies met the inclusion criteria. Muscle-specific dosing was consistently reported for commonly treated muscles such as biceps brachii and wrist and finger flexors, whereas other muscles were less frequently targeted. Variability in dosing between studies was observed, particularly in multicenter real-world datasets. Standardized high-dose protocols contrasted with individualized dosing strategies, which generally showed more moderate dose ranges. Expert recommendations often suggest higher doses than those observed in routine clinical practice. Conclusions: Muscle-specific dosing of onabotulinumtoxinA in post-stroke upper-limb spasticity is reported infrequently, and substantial variability exists between studies and clinical practice. Standardized reporting of muscle-level dosing and its relationship to baseline spasticity severity is needed to improve clinical applicability and reproducibility. Full article
(This article belongs to the Special Issue Botulinum Toxin Application in Post-Stroke Rehabilitation)
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17 pages, 1073 KB  
Review
Cannabinoids in Motor Control: From Receptor Distribution to Motor Disorders
by Dan Faganeli and Metoda Lipnik-Stangelj
Biomedicines 2026, 14(4), 844; https://doi.org/10.3390/biomedicines14040844 - 8 Apr 2026
Viewed by 604
Abstract
Cannabinoid receptors occupy strategic control nodes within motor circuitry, making them potential targets for modulating different motor manifestations. They are positioned both within basal ganglia circuits that regulate movement and within spinal circuits that control skeletal muscle tone. Consequently, cannabinoids have been studied [...] Read more.
Cannabinoid receptors occupy strategic control nodes within motor circuitry, making them potential targets for modulating different motor manifestations. They are positioned both within basal ganglia circuits that regulate movement and within spinal circuits that control skeletal muscle tone. Consequently, cannabinoids have been studied across diverse motor disorders, most notably in movement disorders and tone disorders, particularly those resulting in spasticity. Because motor control spans multiple anatomically and functionally distinct levels, relating cannabinoid signaling to effects on motor function is not straightforward. Limited understanding of cannabinoid receptor distribution has led to cannabinoids being tested even in disorders where receptor localization would predict little or no benefit. Mapping receptor distribution within individual motor circuits and integrating them with their pharmacological effects can help anticipate how cannabinoid signaling shapes motor output. Combined with characteristic motor manifestations, one can identify motor disorders in which cannabinoids may have therapeutic value. In this review, we integrate existing evidence to place cannabinoid receptors within key motor pathways, ranging from basal ganglia circuits controlling movement to peripheral mechanisms governing muscle tone. We consider both cannabinoid 1 receptor (CB1R) and cannabinoid 2 receptor (CB2R), with CB2R gaining attention only recently for its potential relevance within the central nervous system. Building on this framework, we infer how cannabinoids acting at these sites may modulate motor control, and consequently, influence motor manifestations across major motor disorders. Finally, we examine how these distribution-based expectations align with available clinical observations. Full article
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18 pages, 1330 KB  
Article
Effects of Robot-Assisted Gait Training on Stage-Based Lower Limb Motor Recovery and Muscle Tone in Subacute Stroke: A Randomized Controlled Trial
by Yoo Kyeong Han, Kyung Han Kim, Jung Eun Son, Arum Jeon, Hyo Been Lee, Miae Lee, Seong Gue Noh, Eo Jin Park, Seung Ah Lee, Sung Joon Chung, Dong Hwan Kim and Seung Don Yoo
J. Clin. Med. 2026, 15(7), 2514; https://doi.org/10.3390/jcm15072514 - 25 Mar 2026
Viewed by 594
Abstract
Background/Objectives: Abnormal muscle tone and impaired motor control commonly limit gait recovery after stroke. Robot-assisted gait training has been introduced to augment conventional rehabilitation; however, its effects on stage-based motor recovery, functional ambulation, and muscle tone during the subacute phase remain unclear. Methods: [...] Read more.
Background/Objectives: Abnormal muscle tone and impaired motor control commonly limit gait recovery after stroke. Robot-assisted gait training has been introduced to augment conventional rehabilitation; however, its effects on stage-based motor recovery, functional ambulation, and muscle tone during the subacute phase remain unclear. Methods: This prospective, single-center, randomized controlled trial enrolled 30 patients with subacute stroke who received robot-assisted gait training plus conventional rehabilitation (R-BoT Plus group, n = 15) or conventional rehabilitation alone (control group, n = 15) over 4 weeks. The primary outcome was the change in Brunnstrom recovery stage of the lower extremities (BRS-LE). Secondary outcomes included Functional Ambulation Category (FAC), Fugl–Meyer Assessment for the Lower Extremity (FMA-LE), clinical spasticity measures (Modified Ashworth Scale and Modified Tardieu Scale), and muscle mechanical properties (MyotonPRO). Exploratory analyses were conducted to examine the associations between changes in stage-based motor recovery (ΔBRS-LE), functional ambulation (ΔFAC), and MyotonPRO parameters. Within-group changes were assessed using the Wilcoxon signed-rank test. Between-group effects were primarily evaluated using baseline-adjusted ANCOVA with HC3 robust standard errors, with Wilcoxon rank-sum tests on change scores as sensitivity analyses. Associations between changes in clinical outcomes and MyotonPRO parameters were evaluated using Spearman’s rank correlation coefficient (ρ). Results: BRS-LE (p = 0.014) and functional ambulation (p = 0.041) were significantly improved in the R-BoT Plus group. Changes in FMA-LE and clinical spasticity measures did not differ significantly between groups. Quantitative myotonometry revealed selective muscle- and parameter-specific changes. No robust correlations were observed between MyotonPRO parameters and changes in BRS-LE. Conclusions: The addition of robot-assisted gait training to conventional rehabilitation was associated with greater improvements in stage-based lower-limb motor recovery and functional ambulation in patients with subacute stroke. In contrast, cumulative impairment scores and conventional clinical spasticity measures demonstrated limited changes between groups. Quantitative muscle mechanical assessment revealed selective muscle-specific adaptations, supporting its role as a complementary tool for mechanistic characterization rather than as a surrogate marker of motor recovery. Future studies incorporating dose-matched designs and longer follow-up periods are warranted to clarify the independent and long-term effects of robot-assisted gait training. Full article
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17 pages, 46945 KB  
Article
High-Sensitivity Bio-Waste-Derived Triboelectric Sensors for Capturing Pathological Motor Features in Hemiplegia Rehabilitation
by Shengkun Li, Huizi Liu, Chunhui Du, Yanxia Che, Chengqun Chu and Xiaoyan Dai
Micromachines 2026, 17(4), 395; https://doi.org/10.3390/mi17040395 - 25 Mar 2026
Viewed by 468
Abstract
Continuous monitoring of pathological motor features is vital for post-stroke rehabilitation but remains challenged by power reliance and low sensitivity of wearable sensors. Here, we develop a high-sensitivity, self-powered breathable nanogenerator (BN-TENG) utilizing fish-scale-derived biological hydroxyapatite/carbon (Bio-HAp/C) fillers within electrospun polyvinylidene fluoride (PVDF) [...] Read more.
Continuous monitoring of pathological motor features is vital for post-stroke rehabilitation but remains challenged by power reliance and low sensitivity of wearable sensors. Here, we develop a high-sensitivity, self-powered breathable nanogenerator (BN-TENG) utilizing fish-scale-derived biological hydroxyapatite/carbon (Bio-HAp/C) fillers within electrospun polyvinylidene fluoride (PVDF) nanofibers. The Bio-HAp/C enhances electron-trapping capability, while a high-resilience ethylene-vinyl acetate (EVA) spacer optimizes contact-separation dynamics. The BN-TENG achieves a superior sensitivity of 16.28 V·N−1 and remarkable stability over 10,000 cycles. By implementing a multi-node sensing strategy, the sensor successfully captures complex hemiplegic patterns, including compensatory shoulder hiking, distal muscle spasticity, and postural asymmetry. By resolving subtle micro-vibrations missed by traditional electronics, this work provides a sustainable, autonomous interface for characterizing pathological motor features and assessing rehabilitation progress in hemiplegic patients. Full article
(This article belongs to the Special Issue Flexible Triboelectric Nanogenerators)
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16 pages, 2667 KB  
Article
Influence of Immobilization, Stretching, and Activity on the Morphological Properties of Spastic Gastrocnemius Muscles
by Andreas Habersack, Annika Kruse, Bernhard Guggenberger, Nina Mosser, Markus Tilp and Martin Svehlik
Children 2026, 13(3), 414; https://doi.org/10.3390/children13030414 - 18 Mar 2026
Cited by 1 | Viewed by 449
Abstract
Background/Objectives: Children with cerebral palsy (CP) often develop altered muscle architecture and calf muscle contractures. Orthotic immobilization aims to provide prolonged stretch to lengthen the muscle belly and muscle–tendon unit (MTU), but immobilization may also cause atrophy. This study investigated whether immobilization combined [...] Read more.
Background/Objectives: Children with cerebral palsy (CP) often develop altered muscle architecture and calf muscle contractures. Orthotic immobilization aims to provide prolonged stretch to lengthen the muscle belly and muscle–tendon unit (MTU), but immobilization may also cause atrophy. This study investigated whether immobilization combined with periods of daily muscle activation has a different effect on calf muscle properties than continuous immobilization alone. Methods: Fourteen children with CP and equinus deformity (mean age: 9.9 ± 3.0 years; GMFCS Level I: 10, II: 4) were enrolled in a 12-week randomized controlled trial. Participants were allocated to one of two groups: continuous immobilization (23 h per day) with a dynamic ankle–foot orthosis (AFO), or a combined regimen consisting of immobilization (14 h) and a daily activity phase (10 h). Gastrocnemius medialis (GM) MTU properties, including muscle belly and Achilles tendon (AT) length, fascicle length, and muscle volume, among others, were assessed four times using three-dimensional (3D) freehand ultrasound. Results: Significant within-group increases in MTU and AT lengths were observed over time at both a 90° ankle position (p < 0.01) and a more dorsiflexed ankle position (4 Nm applied torque, p < 0.01). However, no significant group × time interactions were observed for any parameter. Conclusions: Contrary to our hypothesis, combining activity and immobilization did not confer additional benefits. Nevertheless, shorter orthosis-wearing time had the same effect on the MTU and could lead to improved compliance with orthosis treatment in CP. Larger trials are needed to support our findings. Full article
(This article belongs to the Collection Advancements in the Management of Children with Cerebral Palsy)
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19 pages, 3428 KB  
Article
Comparative Analytics and Pharmacodynamics of the Complex Protein-Free Botulinum Toxin Type A Formulations DaxibotulinumtoxinA, IncobotulinumtoxinA and RelabotulinumtoxinA
by Stefanie Honndorf, Katja Kühbach, Karl-Heinz Eisele, Alina Shokurova, Philipp Buch, Claudia Jatzke, Harold Victor Taylor and Klaus Fink
Toxins 2026, 18(3), 142; https://doi.org/10.3390/toxins18030142 - 14 Mar 2026
Viewed by 1207
Abstract
Botulinum neurotoxin type A (BoNT/A) is intramuscularly injected for the treatment of, e.g., spasticity, cervical dystonia or facial lines. Several BoNT/A products with or without complexing proteins, with non-interchangeable dose units and various duration of effect claims, are approved but hard to compare. [...] Read more.
Botulinum neurotoxin type A (BoNT/A) is intramuscularly injected for the treatment of, e.g., spasticity, cervical dystonia or facial lines. Several BoNT/A products with or without complexing proteins, with non-interchangeable dose units and various duration of effect claims, are approved but hard to compare. The goal of this study was to compare the complexing protein-free approved BoNT/A products IncobotulinumtoxinA (INCO), DaxibotulinumtoxinA (DAXI) and RelabotulinumtoxinA (RELA) in vitro and in vivo. BoNT/A protein content per 100 U was lowest in INCO and highest in DAXI (INCO 0.44, RELA 0.46, DAXI 0.58 ng/100 U). Relative bioactivity of INCO, DAXI and RELA was comparable (116, 104 and 117 U/100 labeled units). INCO and DAXI caused a maximum mouse digit abduction score (DAS) 2–3 days after IM injection of 20 or 40 U/kg. The DAS after 20 U/kg INCO was higher and showed a 10 days longer paralysis than DAXI at equivalent dosing. The in vivo spread of DAXI in the mouse gastrocnemius muscle was indistinguishable from that after INCO, and the spread of RELA ex vivo in porcine muscle was larger than INCO but equal to 0.9% NaCl. These results show the differences between 150 kDa botulinum type A toxin products beyond the published claims. Full article
(This article belongs to the Section Bacterial Toxins)
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22 pages, 4382 KB  
Article
EMG-Driven Musculoskeletal Modelling Framework for Virtual Simulation of Upper Limb Activation-Modulated Impairment Scenarios
by Dovydas Cicėnas and Kristina Daunoravičienė
Medicina 2026, 62(3), 530; https://doi.org/10.3390/medicina62030530 - 12 Mar 2026
Viewed by 643
Abstract
Background and Objectives: Surface electromyography (EMG) is widely used to assess muscle activation. However, direct interpretation of its functional biomechanical consequences remains challenging. This study aimed to develop and evaluate an EMG-driven musculoskeletal simulation framework for investigating how controlled modifications of muscle activation [...] Read more.
Background and Objectives: Surface electromyography (EMG) is widely used to assess muscle activation. However, direct interpretation of its functional biomechanical consequences remains challenging. This study aimed to develop and evaluate an EMG-driven musculoskeletal simulation framework for investigating how controlled modifications of muscle activation patterns influence joint-level biomechanics in the upper limb. The objective was not to reproduce specific clinical pathologies but to enable systematic virtual scenario analysis of activation-dependent movement alterations. Materials and Methods: Surface EMG signals were recorded from five healthy adults (3 males, 2 females; age 22 ± 1 years) during cyclic elbow flexion/extension tasks using a wireless system (sampling frequency: 2000 Hz). Processed and normalized EMG envelopes were directly applied as prescribed neural inputs in forward dynamic simulations implemented in OpenSim, without optimization-based muscle recruitment. Controlled virtual scenarios were generated through parametric modification of activation signals to represent reduced activation capacity, increased antagonist co-activation, spasticity-like activation modulation, and tremor-like oscillatory modulation. Joint kinematics, joint moments, and movement stability were evaluated. A Movement Quality Index (MQI) was introduced as a comparative research metric integrating biomechanical performance indicators. Simulations were deterministic and analyzed descriptively. Results: Distinct activation modifications produced characteristic kinematic and kinetic responses. Reduced activation capacity decreased simulated joint moment output, increased co-activation altered joint moment timing and mechanical stability, and tremor-like oscillatory modulation generated periodic fluctuations in joint kinematics and kinetics. The MQI enabled quantitative differentiation between simulated scenarios and severity levels within the controlled modelling framework. Conclusions: The proposed EMG-driven forward dynamic simulation framework provides a methodological platform for controlled virtual scenario analysis of activation-dependent biomechanical changes. The findings highlight the sensitivity of joint-level mechanics to altered muscle activation patterns, within the deterministic modelling environment. The framework is intended for research-oriented biomechanical investigation and hypothesis testing rather than direct clinical diagnosis of neuromuscular disorders. Full article
(This article belongs to the Section Sports Medicine and Sports Traumatology)
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