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Keywords = upper limb spasticity

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10 pages, 251 KB  
Article
Early Use of Botulinum Toxin in Post-Stroke Spasticity Has the Potential to Prevent Post-Stroke Upper Limb Pain—A Secondary Analysis of the EUBoSS Randomised Controlled Trial
by Cameron Lindsay, Fraser Philp and Anand D. Pandyan
Toxins 2026, 18(3), 147; https://doi.org/10.3390/toxins18030147 - 18 Mar 2026
Viewed by 505
Abstract
Post-stroke upper limb pain is prevalent and challenging to manage once established. Early use of botulinum toxin can reduce spasticity and contracture development and has potential to prevent or reduce pain. A secondary analysis of the EUBoSS study was undertaken to report pain [...] Read more.
Post-stroke upper limb pain is prevalent and challenging to manage once established. Early use of botulinum toxin can reduce spasticity and contracture development and has potential to prevent or reduce pain. A secondary analysis of the EUBoSS study was undertaken to report pain prevalence in people post-stroke with severe upper limb impairment and spasticity in a hyper/acute setting, identify if botulinum toxin Type-A (BoNTA) could prevent pain developing and reduce pain if already present and evaluate differences in analgesic use between BoNTA and placebo groups. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ninety-three participants (48F:45M) were randomised at a median of 11 days post-stroke (IQR 8–19) and included in the intention-to-treat analysis. Pain prevalence increased from 29.0% (95% CI [20.1–37.9%]) to 63.4% (95% CI [54.0–72.9%]) at six months. BoNTA treatment may prevent the development of pain at six months (OR = 0.42, 95% CI [0.18 to 1.01]) but not at three months (OR = 0.57, 95% CI [0.25 to 1.32]). The odds ratio for being on at least one analgesic at six months in the BoNTA group was 0.35 ([95% 0.14 to 0.87]). This secondary analysis suggests that early treatment of spasticity with BoNTA may potentially help prevent post-stroke upper limb pain and reduce analgesic use but appears less effective once pain is established. Further prospective studies are required to verify the hypotheses generated from this secondary analysis. Full article
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 352
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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15 pages, 719 KB  
Article
A Retrospective Clinical Analysis of Pain and Spasticity Outcomes Following Gravity-Support Exoskeleton Therapy in Chronic Stroke
by Mirjam Bonanno, Desiree Latella, Paolo De Pasquale, Mauro Botindari, Antonino Lombardo Facciale, Angelo Quartarone, Rosaria De Luca, Giovanni Morone and Rocco Salvatore Calabrò
J. Clin. Med. 2026, 15(6), 2099; https://doi.org/10.3390/jcm15062099 - 10 Mar 2026
Viewed by 255
Abstract
Background: Post-stroke pain (PSP), particularly shoulder pain, is frequent and often underdiagnosed, limiting rehabilitation adherence and functional recovery. Current pharmacological and physical treatments offer only partial relief. Robotic-assisted therapy (RAT), such as the gravity-supporting Armeo® Spring exoskeleton, delivers intensive, task-specific training with [...] Read more.
Background: Post-stroke pain (PSP), particularly shoulder pain, is frequent and often underdiagnosed, limiting rehabilitation adherence and functional recovery. Current pharmacological and physical treatments offer only partial relief. Robotic-assisted therapy (RAT), such as the gravity-supporting Armeo® Spring exoskeleton, delivers intensive, task-specific training with visual 2D feedback that may also alleviate PSP while enhancing motor outcomes. This study investigates whether RAT performed with the Armeo® Spring reduces upper-limb PSP in chronic stroke patients versus conventional therapy and evaluates its effects on motor function and functional independence. Methods: In this retrospective parallel group study, 32 chronic post-stroke patients (8 females and 24 males with a mean age of 57 ± 11.74) were allocated to two groups: 16 received upper-limb RAT with the Armeo® Spring, a gravity-supporting exoskeleton, (RAT group) and 16 underwent conventional rehabilitation (CR). The RAT group completed one-hour sessions 6 days/week for 8 weeks, performing 2D/3D gamified tasks targeting shoulder, elbow and forearm movements. The CR group received an equivalent amount of standard therapy, including passive/active-assisted mobilization, Bobath-based neuromuscular facilitation and reaching exercises. Results: Both the Armeo® Spring and conventional therapy groups showed significant reductions in post-stroke pain (RAT p < 0.001 and conventional rehabilitation p = 0.004) and improvements in upper-limb motor function and functional independence (both p ≤ 0.002). Spasticity in the impaired limb decreased modestly in the RAT group (p = 0.031), with no significant between-group differences in pain or spasticity change (p = 0.437; p > 0.05, respectively). Conclusions: Gravity-support exoskeleton training reduced upper-limb spasticity, and no statistically significant between-group differences were observed compared with conventional physiotherapy for pain, mobility, and functional independence. Although clinical outcomes improved, health-related quality-of-life domains showed heterogeneous trajectories, underscoring the complexity of perceived health changes during chronic stroke rehabilitation. Larger randomized controlled trials incorporating neurophysiological and kinematic endpoints and longer follow-up are warranted to confirm effectiveness, particularly in chronic stroke and durability. Full article
(This article belongs to the Section Clinical Neurology)
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13 pages, 294 KB  
Article
Neurological Signs and Symptoms in Human T-Lymphotropic Viruses 1 and 2 Infected Patients Living in the Amazon Region, Northern Brazil
by Giovani Camelo do Nascimento, Lucas Thiago Ferreira Monteiro, Hemengella Karyne Alves Oliveira, Márcio Yutaka Tsukimata, Bianca Lumi Inomata da Silva, Aline Cecy Rocha Lima, Rodrigo Borges de Oliveira, Gabriel dos Santos Pereira Neto, Eduardo Leitão Maia, Ricardo Ishak, Antonio Carlos Rosário Vallinoto and Izaura Maria Vieira Cayres Vallinoto
Viruses 2026, 18(3), 340; https://doi.org/10.3390/v18030340 - 10 Mar 2026
Viewed by 480
Abstract
HTLV-1 and HTLV-2 infections are associated with various neurological manifestations, particularly HTLV-1-associated myelopathy (HAM). This descriptive, cross-sectional observational study aimed to investigate and analyze the neurological manifestations in patients treated at the Service for the Care of People Living with HTLV (Serviço de [...] Read more.
HTLV-1 and HTLV-2 infections are associated with various neurological manifestations, particularly HTLV-1-associated myelopathy (HAM). This descriptive, cross-sectional observational study aimed to investigate and analyze the neurological manifestations in patients treated at the Service for the Care of People Living with HTLV (Serviço de Atendimento à Pessoa Vivendo com HTLV-SAPEVH) at the Federal University of Pará. A cohort of 957 individuals underwent screening for HTLV-1/2 infection using enzyme-linked immunosorbent assay (ELISA), with seropositive samples subsequently confirmed via Western blotting or quantitative polymerase chain reaction (qPCR). HTLV-1/2 infection was confirmed in 69 individuals. Of these, fifteen individuals—diagnosed with HTLV-1 (n = 11) or HTLV-2 (n = 4) infection—who presented with neurological complaints at the first nursing consultation, were referred to a neurologist for clinical evaluation of neurological signs and symptoms. Most of the patients were female (13), ranging from 33 to 80 years of age. Neurological symptoms were present in 86.7%, and included spasticity, paraparesis, chronic pain, both motor and sensory deficits, as well as urinary disorders, predominantly affecting the thoracic spinal cord and lower limbs. Urinary symptoms were observed in 77% of symptomatic patients, often preceding other neurological signs that suggest a role as “sentinel symptoms” in the clinical screening of HTLV carriers. The results demonstrated the presence of neurological impairment in patients infected with both HTLV-1 and HTLV-2, with motor symptoms ranging from moderate to advanced. In addition, cases of cranial nerve and upper limb involvement were reported, a finding that is rarely described in the literature. The study highlights the importance of neurological assessment as early as possible in patients infected with either HTLV-1 or HTLV-2 and suggests that sphincter dysfunctions can serve as early clinical markers of future neurological impairment. Full article
(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections (2nd Edition))
20 pages, 2004 KB  
Article
Modern Upper-Limb Rehabilitation Interventions in Stroke Patients with Spasticity
by Ana Maria Bumbea, Rodica Trăistaru, Elena-Anca Târtea, Alexandra Oltea Dan, Adina Turcu-Stiolica, Daniela Matei, Simona Pătru, Bogdan Stefan Bumbea and Cristiana Octaviana Daia
J. Clin. Med. 2026, 15(4), 1560; https://doi.org/10.3390/jcm15041560 - 16 Feb 2026
Viewed by 629
Abstract
Background: Upper-limb rehabilitation is a decisive factor in improving the quality of life for patients who have experienced a stroke. Modern rehabilitation techniques promote the recovery of upper-limb functionality and prehension, contributing to a reduction in disability. Materials and Methods: This retrospective observational [...] Read more.
Background: Upper-limb rehabilitation is a decisive factor in improving the quality of life for patients who have experienced a stroke. Modern rehabilitation techniques promote the recovery of upper-limb functionality and prehension, contributing to a reduction in disability. Materials and Methods: This retrospective observational study aimed to highlight improvements in prehension through the application of current actual and modern rehabilitation techniques targeting key muscle groups involved in upper-limb recovery. Data from a total of 52 patients were identified and categorized into two groups based on the specific rehabilitation protocols they received during their hospitalization: a study group and a control group. Both groups underwent individualized rehabilitation, differing only in the type of electrotherapy applied: the study group received functional electrical stimulation (FES) and shock wave therapy (RSWT), while the control group received conventional electrical stimulation. Results: After adjusting for baseline differences in severity and time since stroke, patients in the study group demonstrated a significantly greater improvement in functional parameters compared to the control group. The results show us a significant improvement of functionality after RSWT and FES in the study group, with values from 0.28 ± 0.28 to 0.99 ± 0.36 (p-value < 0.001) regarding Hand Grip, suggesting that the treatment effect persists even when initial clinical advantages in the control group are accounted for. Muscle force increased from 0.39 ± 0.54 to 7.67 ± 3.89, p-value < 0.001. Conclusions: The combined application of functional electrical stimulation and shock wave therapy, as modern rehabilitation interventions, provided additional benefits in upper-limb and prehension rehabilitation compared to classical electrical stimulation alone. Our findings suggest that the combined application of RSWT and FES is strongly associated with improved upper-limb recovery, even after adjusting for baseline clinical imbalances. While these results support the integration of these modern techniques into stroke protocols, further prospective randomized controlled trials are needed to confirm the definitive treatment advantage over conventional methods. Full article
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17 pages, 934 KB  
Systematic Review
Mirror Therapy Versus Motor Imagery in Stroke Neurorehabilitation: A Systematic Review with Comparative Narrative Synthesis
by Luis Polo-Ferrero, Javier Torres-Alonso, Juan Luis Sánchez-González, Sara Hernández-Rubia, Arturo Dávila-Marcos, María Agudo Juan, Javier Oltra-Cucarella and Rubén Pérez-Elvira
Life 2026, 16(2), 306; https://doi.org/10.3390/life16020306 - 10 Feb 2026
Viewed by 749
Abstract
Background: Motor imagery (MI) and mirror therapy (MT) are widely used neurorehabilitation strategies to enhance motor recovery after stroke and are commonly applied as adjuncts to conventional rehabilitation therapy (CRT). However, direct comparative evidence between these interventions remains limited. This systematic review compared [...] Read more.
Background: Motor imagery (MI) and mirror therapy (MT) are widely used neurorehabilitation strategies to enhance motor recovery after stroke and are commonly applied as adjuncts to conventional rehabilitation therapy (CRT). However, direct comparative evidence between these interventions remains limited. This systematic review compared the effects of MI and MT on motor function, functional performance, spasticity, and gait-related outcomes in adults after stroke. Methods: A systematic comparative review with narrative synthesis was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251274308). PubMed, Cochrane Library, CINAHL, Scopus, Web of Science, and ScienceDirect were searched up to July 2025. Clinical trials directly comparing MI and MT in adults with stroke were included. Methodological quality was assessed using the PEDro scale, and risk of bias was evaluated with the Cochrane RoB 2 tool. Results: Six clinical trials involving 206 participants were included. Both MI and MT were associated with significant pre–post improvements across motor function, functional performance, spasticity, and gait-related outcomes. Between-group comparisons yielded heterogeneous findings, with no consistent evidence supporting the superiority of either intervention. Isolated advantages of MI were reported for specific upper-limb subdomains, but these effects were not consistently replicated. Overall methodological quality ranged from low to moderate, and all included studies were judged to be at high risk of bias according to the RoB 2 tool. Conclusions: MI and MT appear to provide comparable benefits for motor and functional recovery after stroke when used as adjuncts to CRT. Current evidence does not support the preferential use of one intervention, highlighting the need for well-designed trials with improved methodological rigor. Full article
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11 pages, 1998 KB  
Case Report
Transcutaneous Spinal Cord Stimulation Improves Upper and Lower Limbs’ Motor and Sensory Function in a Subject with Central Cord Syndrome: A Case Report
by Fernando Reyes, Camila Parker, Tania Turquie, Aldo Chimal, Lorermy Villalobos, Frida Bailey, Antonio Ibarra, Igor Lavrov and Carlos A. Cuellar
Neurol. Int. 2026, 18(2), 31; https://doi.org/10.3390/neurolint18020031 - 10 Feb 2026
Viewed by 707
Abstract
Background: Central cord syndrome (CCS) is the most common incomplete spinal cord injury, producing more severe motor deficits in the upper than lower extremities and impairing sensory and autonomic function. Although transcutaneous spinal cord stimulation (tSCS) has shown benefits in motor and sensory [...] Read more.
Background: Central cord syndrome (CCS) is the most common incomplete spinal cord injury, producing more severe motor deficits in the upper than lower extremities and impairing sensory and autonomic function. Although transcutaneous spinal cord stimulation (tSCS) has shown benefits in motor and sensory recovery after spinal cord injury, studies have not explicitly documented whether CCS subjects were included. The aim of this study was to assess the effects of tSCS over 12 weeks on motor and sensory outcomes in a subject with CCS. Methods: A 20-year-old male with a C7 injury was evaluated at baseline and after 12 weeks with the American Spinal Cord Injury Impairment scale, Modified Ashworth Scale, Penn and Spasm Frequency Scale, 3-Meter Walk Test and 6-Minute Walk Test, 9-Hole Peg Test, Box and Block Test, hand dynamometry, and lower-limb EMG. tSCS was applied between T9 and L1 at 30 Hz. Results: At 12 weeks, upper-limb motor and sensory scores improved, while spasm frequency and hand spasticity were reduced. Manual dexterity improved bilaterally in the 9-Hole Peg and Box and Block Tests, with a 2 kg gain in right-hand grip strength. In the 6-Minute Walk Test, the distance covered increased from 224.4 m to 295.2 m, and a 1.36 s reduction in 3-Meter walking time was achieved. Conclusions: tSCS improved motor and sensory function and reduced spasticity and spasms. These findings suggest that tSCS may serve as an effective complementary intervention for motor and sensory rehabilitation in individuals with mild cervical injuries, including CCS. Full article
(This article belongs to the Topic Advances in Neurorehabilitation)
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13 pages, 746 KB  
Review
Exploratory Use of Proximal Cryoneurolysis and Distal Botulinum Toxin Type A for Upper-Limb Spasticity: A Case Report with Scoping Review
by Di Lorenzo Luigi, De Meo Bruno, Forte Alfonso Maria, Forte Francesco, Palmieri Vincenzo, Pirraglia Nicola and D’Avanzo Carmine
Toxins 2026, 18(2), 66; https://doi.org/10.3390/toxins18020066 - 27 Jan 2026
Viewed by 792
Abstract
Background: Upper-limb spasticity involving the shoulder girdle and elbow flexors often impairs functional hand use, and although Botulinum toxin type A (BoNT-A) is a first-line therapy, severe proximal synergies may persist while higher doses risk distal weakness. Methods: We report a case of [...] Read more.
Background: Upper-limb spasticity involving the shoulder girdle and elbow flexors often impairs functional hand use, and although Botulinum toxin type A (BoNT-A) is a first-line therapy, severe proximal synergies may persist while higher doses risk distal weakness. Methods: We report a case of a 47-year-old woman with neurodegenerative tetraparesis and marked shoulder and elbow flexor spasticity treated with bilateral percutaneous cryoneurolysis of the lateral pectoral, thoracodorsal, and musculocutaneous nerves, followed by distal BoNT-A injections, and we conducted a scoping review following Arksey and O’Malley, Levac, and PRISMA-ScR methods to contextualize the current evidence. Results: At one-month follow-up, the patient showed a reduction in MAS from 4 to 1–2, complete resolution of pain, improved passive shoulder abduction and elevation, preserved distal dexterity, and high satisfaction with no adverse events. The scoping review identified consistent MAS and range-of-motion improvements across multiple case reports and small series involving similar proximal nerve targets. Conclusions: The combined proximal cryoneurolysis–distal BoNT-A approach appears to be a feasible dual-modulation strategy for complex upper-limb spasticity when the preservation of hand function is essential, and the emerging literature supports its further investigation. Full article
(This article belongs to the Section Bacterial Toxins)
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18 pages, 1940 KB  
Article
Longitudinal, Multi-Cycle Evaluation of Passive Function Improvement in People with Arm Spasticity Treated with Botulinum Toxin A
by Stephen A. Ashford, Khan Buchwald, Klemens Fheodoroff, Jorge Jacinto, Ajit Narayanan, Richard J. Siegert, Christian Hannes and Lynne Turner-Stokes
Toxins 2026, 18(1), 51; https://doi.org/10.3390/toxins18010051 - 19 Jan 2026
Viewed by 725
Abstract
Improvement in passive function (i.e., ease of caring for a limb) is a common goal for treatment of spasticity in the arm with botulinum toxin. A large international, observational, 2-year longitudinal study (ULIS-III, N = 953) was conducted in real-life practice. This original [...] Read more.
Improvement in passive function (i.e., ease of caring for a limb) is a common goal for treatment of spasticity in the arm with botulinum toxin. A large international, observational, 2-year longitudinal study (ULIS-III, N = 953) was conducted in real-life practice. This original secondary analysis examines whether improvement in passive function goals were met over repeated injection cycles. We report changes by cycle measured by the Passive Function sub-scale of the Arm Activity measure (ArmA-PF) and examine predictors of improvement and injection occurrence. Inclusion in this analysis was based on passive function being selected as a primary or secondary goal for one or more cycle of treatment (n = 542/953). Goals were assessed at the start and end of each cycle using the Goal Attainment Test score and the ArmA-PF. Over all cycles of treatment, goals were set for 1641/2187 injections (75.0%) and achieved in 1250 (76.2%). Significant improvements in ArmA-PF score were identified for at least six cycles (p < 0.001) with evidence of cumulative benefit over successive cycles. This occurred regardless of patient-related baseline characteristics, with the possible exception of some relationship with injection localization techniques. In conclusion, repeated botulinum toxin injections provide significant improvement in passive function, which was sustained over repeated cycles of treatment. Full article
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21 pages, 1566 KB  
Article
Robot-Assisted Mirror Therapy for Upper Limb and Hand Recovery After Stroke: Clinical Efficacy and Insights into Neural Mechanisms
by Shixin Li, Jiayi Zhang, Yang Xu and Yonghong Yang
J. Clin. Med. 2026, 15(1), 350; https://doi.org/10.3390/jcm15010350 - 2 Jan 2026
Viewed by 1037
Abstract
Objective: This study investigated the efficacy and neural mechanisms of robot-assisted mirror therapy (RMT) for post-stroke upper limb rehabilitation. RMT integrates the multimodal feedback of mirror therapy with robotic precision and repetition to enhance cortical activation and neuroplasticity. Methods: Seventy-eight stroke patients were [...] Read more.
Objective: This study investigated the efficacy and neural mechanisms of robot-assisted mirror therapy (RMT) for post-stroke upper limb rehabilitation. RMT integrates the multimodal feedback of mirror therapy with robotic precision and repetition to enhance cortical activation and neuroplasticity. Methods: Seventy-eight stroke patients were randomly assigned to control, mirror therapy (MT), or RMT groups. All received conventional rehabilitation; the MT group additionally underwent mirror therapy, and the RMT group received robot-assisted mirror therapy combined with functional electrical stimulation. The primary outcome was the Fugl–Meyer Assessment for Upper Extremity (FMA-UE), with secondary measures including spasticity, dexterity, daily living, and quality of life. Functional near-infrared spectroscopy (fNIRS) was applied to assess cortical activation and connectivity at baseline, post-intervention, and one-month follow-up. Results: All groups showed significant time effects, though between-group differences were limited. Subgroup analysis revealed that patients at Brunnstrom stages I–II in the MT group achieved greater improvements in upper limb function, dexterity, and daily living ability. fNIRS findings showed enhanced activation in the right sensory association cortex and increased prefrontal–sensory connectivity. Conclusions: While all interventions improved motor outcomes, MT yielded slightly superior recovery associated with neuroplastic changes. RMT demonstrated high safety, compliance, and potential benefit for patients with severe motor deficits. Full article
(This article belongs to the Section Brain Injury)
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13 pages, 1185 KB  
Systematic Review
Botulinum Toxin Combined with Robot-Assisted Therapy for Post-Stroke Spasticity: A Systematic Review
by Salvatore Facciorusso, Stefania Spina, Mirko Filippetti, Rajiv Reebye, Gerard E. Francisco and Andrea Santamato
Toxins 2025, 17(12), 569; https://doi.org/10.3390/toxins17120569 - 25 Nov 2025
Cited by 1 | Viewed by 1538
Abstract
(1) Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (2) Methods: We systematically searched major medical [...] Read more.
(1) Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (2) Methods: We systematically searched major medical databases and trial registries up to April 2025 for randomized controlled trials in adults with post-stroke spasticity comparing botulinum toxin type-A injection plus RAT with toxin injection plus conventional therapy, or RAT alone with RAT combined with toxin injection. Risk of bias was assessed using the RoB 2 tool, and findings were synthesized narratively. (3) Results: Seven trials (n = 229) were included. Across all studies, toxin treatment reduced spasticity within groups, whereas additional spasticity reduction with RAT versus conventional rehabilitation was inconsistent. In contrast, several lower-limb trials reported greater improvements in walking capacity and balance when RAT was added, while upper-limb trials showed comparable motor recovery across treatment arms with occasional advantages in strength and movement quality. A pilot four-arm study suggested that starting RAT around four weeks after injection may maximize upper-limb motor gains. (4) Conclusions: The combination of BoNT-A with RAT appears safe and is particularly promising for gait rehabilitation, but further research is needed to define optimal timing and protocols. Full article
(This article belongs to the Section Bacterial Toxins)
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12 pages, 1287 KB  
Article
Efficacy and Safety of IncobotulinumtoxinA in Older Patients with Upper Limb Spasticity: A Pooled Analysis
by Michael C. Munin, Alexandre Camões-Barbosa, Carlos Cordero-García, Alessio Baricich, Stefano Carda, Michael Althaus, Georg Comes, Matteo Vacchelli and Jörg Wissel
Geriatrics 2025, 10(6), 155; https://doi.org/10.3390/geriatrics10060155 - 24 Nov 2025
Cited by 1 | Viewed by 1018
Abstract
Background/Objectives: The aim of this study was to compare the efficacy and safety of a single cycle of incobotulinumtoxinA versus placebo in pooled data from older patients (aged ≥65 years) with upper limb spasticity (ULS). Methods: This study was a post [...] Read more.
Background/Objectives: The aim of this study was to compare the efficacy and safety of a single cycle of incobotulinumtoxinA versus placebo in pooled data from older patients (aged ≥65 years) with upper limb spasticity (ULS). Methods: This study was a post hoc analysis of pooled data from seven prospective, multicenter, phase II or III trials of incobotulinumtoxinA in adult patients aged ≥65 years from across the world with post-stroke ULS or upper and lower limb spasticity, including a subgroup with moderate-to-severe ULS. Changes from baseline in ULS severity were evaluated using the (modified) Ashworth Scale across different spasticity patterns at 4 and 12 weeks after incobotulinumtoxinA injection. Results: In 267 older patients with ULS, including a subgroup of 207 with moderate-to-severe ULS, all ULS patterns statistically analyzed (elbow flexion, thumb-in-palm, clenched fist, wrist flexion, and pronated forearm) were improved more by incobotulinumtoxinA than placebo at week 4 (p < 0.05). For most of these patterns, the difference remained significant at week 12 (p < 0.05). IncobotulinumtoxinA was generally well tolerated. Conclusions: This study, which analyzed data from the largest cohort of older patients in the literature, provides information regarding the use of incobotulinumtoxinA in ULS, the efficacy and favorable safety profile of incobotulinumtoxinA for the treatment of ULS in older patients, particularly in those with moderate-to-severe spasticity, was confirmed. Full article
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13 pages, 310 KB  
Study Protocol
Myotonometric and Postural Analysis in Patients with Post-Stroke Hemiparesis Included in a Rehabilitation Program: A Study Protocol
by Constantin Ioan Covasala, Elena Constanta Amaricai, Sorana Sacui (Teaha), Anca Valentina Onciulenco, Alexandru Ianculescu, Cosmin Liviu Chifane, Nicoleta Flavia Roman and Catalin Nicolae Hreniuc
Life 2025, 15(12), 1791; https://doi.org/10.3390/life15121791 - 21 Nov 2025
Viewed by 972
Abstract
This observational study aims to assess both the posture and muscle tone characteristics of the upper and lower limbs in patients with hemiparesis following a cerebrovascular accident. Measurements will be taken comparatively between the affected and non-affected sides. The study will include patients [...] Read more.
This observational study aims to assess both the posture and muscle tone characteristics of the upper and lower limbs in patients with hemiparesis following a cerebrovascular accident. Measurements will be taken comparatively between the affected and non-affected sides. The study will include patients with both ischemic and hemorrhagic strokes. Assessments will be conducted at months 1, 3, and 6 after the stroke event. In order to ensure the homogeneity of the study group, all patients will follow a physical exercise program tailored to their clinical stage of recovery. Myotonometric evaluation will be performed using the Myoton PRO Digital Palpation Device, which allows the assessment of muscle tone, elasticity, dynamic stiffness, tension state, relaxation time, and deformation ratio during muscle relaxation. Postural assessment will be conducted using the GaitON device by Auptimo. In addition to these instrumental evaluations, the following clinical scales will be applied: the Modified Ashworth Scale, Barthel Index, Instrumental Activities of Daily Living and the Modified Rankin Scale. Based on the three successive evaluations (at one, three, and six months after stroke event) we expect that with the spasticity decrease and the improvement of the posture of patients participating in the physical exercise program, both the objectively assessed parameters and the scores obtained from clinical scales will evolve in favor of better functioning. Full article
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12 pages, 438 KB  
Article
Early Botulinum Toxin Type A Injection May Improve Motor Recovery in Patients with Post-Stroke Spasticity: A Secondary Analysis from a Longitudinal Cohort Study
by Alessandro Picelli, Andrea Santamato, Michela Cosma, Alessio Baricich, Carmelo Chisari, Marzia Millevolte, Cristina Del Prete, Ilenia Mazzù, Rita Di Censo, Nicola Smania and Mirko Filippetti
Toxins 2025, 17(11), 558; https://doi.org/10.3390/toxins17110558 - 13 Nov 2025
Cited by 1 | Viewed by 1851
Abstract
Spasticity after stroke impairs motor control, delays recovery, and reduces quality of life. Botulinum toxin type A is the first-line treatment, but it is often administered in the chronic phase, potentially limiting its impact on rehabilitation. Emerging evidence suggests that earlier treatment may [...] Read more.
Spasticity after stroke impairs motor control, delays recovery, and reduces quality of life. Botulinum toxin type A is the first-line treatment, but it is often administered in the chronic phase, potentially limiting its impact on rehabilitation. Emerging evidence suggests that earlier treatment may enhance recovery, though functional benefits remain uncertain. We conducted a secondary analysis of a multicenter, open-label, longitudinal cohort study to investigate whether the timing of the first botulinum toxin type A injection influences outcomes in post-stroke patients naïve to this treatment. All participants received botulinum toxin injections combined with conventional rehabilitation. Assessments were performed at baseline and at 4, 12, and 24 weeks post-injection. The primary outcome was muscle tone; secondary outcomes included motor strength, sensorimotor recovery, and global disability. Statistical analyses used mixed-effects models and trend tests. Patients treated within 90 days of stroke onset showed greater reductions in spasticity at 4 and 12 weeks compared with later treatment. Despite having more severe baseline impairments, early treated patients demonstrated faster and more pronounced improvements in upper-limb strength, sensorimotor recovery, and global disability. Early toxin administration is associated with enhanced reduction in spasticity and improved motor recovery, particularly in patients with severe initial deficits. Full article
(This article belongs to the Special Issue Botulinum Toxin: Advancing Treatments for Spasticity)
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Systematic Review
Effects of Combining Transcranial Direct Current Stimulation with Virtual Reality on Upper Limb Function in Patients with Stroke: A Systematic Review and Meta-Analysis
by Auwal Abdullahi, Thomson W. L. Wong and Shamay S. M. Ng
Bioengineering 2025, 12(11), 1205; https://doi.org/10.3390/bioengineering12111205 - 4 Nov 2025
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Abstract
Background: Persistent upper limb hemiparesis in patients with stroke can result in significant long-term disability and reduced quality of life. Transcranial direct current (tDCS) stimulation and virtual reality (VR) as stand alone or in combination are currently used for the rehabilitation of upper [...] Read more.
Background: Persistent upper limb hemiparesis in patients with stroke can result in significant long-term disability and reduced quality of life. Transcranial direct current (tDCS) stimulation and virtual reality (VR) as stand alone or in combination are currently used for the rehabilitation of upper limb function following stroke. Objectives: The aim of this study is to determine the effects of combining tDCS with VR on level of motor impairment, motor function, spasticity, ADL, quality of life, manual dexterity, sensation, muscle strength, handgrip strength, cognitive flexibility and speed of processing, motor performance, cognition, and executive function after stroke. Design: The study is a systematic review and meta-analysis. Data Sources and Methods: PubMED, Embase, Web of Science (WoS), PEDro, and Scopus were searched until June 2023 for randomized controlled trials (RCTs) on the subject matter using the following keywords: stroke, upper extremity, upper limb, virtual reality, virtual rehabilitation, noninvasive brain stimulation, transcranial direct current stimulation, transcortical direct current stimulation, and tDCS. Methodological quality and risks of bias of the included studies were assessed using the PEDro scale and Cochrane risks of bias assessment tool, respectively. Random effect model analysis was used to compute the effect size and standardized mean difference (SMD). Results: The results showed that the included studies reported that combining tDCS with VR may improve level of motor impairment, motor function, spasticity, ADL, quality of life, manual dexterity, sensation, muscle strength, handgrip strength, cognitive flexibility and speed of processing, motor performance, cognition, and executive function. However, the result of the meta-analysis showed that it is only superior to the control at improving motor function (SMD = 0.44, 95% CI = 0.09 to 0.79, p = 0.01). Conclusions: Use of a combination of tDCS with VR may help optimize upper limb function outcomes. However, standardization of the protocol of such an intervention is needed in order to make it applicable in the real world. Registration: The study was registered in PROSPERO (registration number, CRD42023435702). Full article
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