Background: The combined use of Robot-assisted UL training and Botulinum toxin (BoNT) appear to be a promising therapeutic synergism to improve UL function in chronic stroke patients. Objective: To evaluate the effects of Robot-assisted UL training on UL spasticity, function, muscle strength and the electromyographic UL muscles activity in chronic stroke patients treated with Botulinum toxin. Methods: This single-blind, randomized, controlled trial involved 32 chronic stroke outpatients with UL spastic hemiparesis. The experimental group (n = 16) received robot-assisted UL training and BoNT treatment. The control group (n = 16) received conventional treatment combined with BoNT treatment. Training protocols lasted for 5 weeks (45 min/session, two sessions/week). Before and after rehabilitation, a blinded rater evaluated patients. The primary outcome was the Modified Ashworth Scale (MAS). Secondary outcomes were the Fugl-Meyer Assessment Scale (FMA) and the Medical Research Council Scale (MRC). The electromyographic activity of 5 UL muscles during the "hand-to-mouth" task was explored only in the experimental group and 14 healthy age-matched controls using a surface Electromyography (EMGs). Results: No significant between-group differences on the MAS and FMA were measured. The experimental group reported significantly greater improvements on UL muscle strength (p = 0.004; Cohen's d = 0.49), shoulder abduction (p = 0.039; Cohen's d = 0.42), external rotation (p = 0.019; Cohen's d = 0.72), and elbow flexion (p = 0.043; Cohen's d = 1.15) than the control group. Preliminary observation of muscular activity showed a different enhancement of the biceps brachii activation after the robot-assisted training. Conclusions: Robot-assisted training is as effective as conventional training on muscle tone reduction when combined with Botulinum toxin in chronic stroke patients with UL spasticity. However, only the robot-assisted UL training contributed to improving muscle strength. The single-group analysis and the qualitative inspection of sEMG data performed in the experimental group showed improvement in the agonist muscles activity during the hand-to-mouth task. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03590314.

We investigated the muscle alterations related to spasticity in stroke quantitatively using a portable manual spasticity evaluator. Methods: Quantitative neuro-mechanical evaluations under controlled passive elbow stretches in stroke survivors and healthy controls were performed in a research laboratory of a rehabilitation hospital. Twelve stroke survivors and nine healthy controls participated in the study. Spasticity and catch angle were evaluated at 90°/s and 270°/s with the velocities controlled through real-time audiovisual feedback. The elbow range of motion (ROM), stiffness, and energy loss were determined at a slow velocity of 30°/s. Four-dimensional measures including joint position, torque, velocity and torque change rate were analyzed jointly to determine the catch angle. Results: The catch angle was dependent on the stretch velocity and occurred significantly later with increasing velocity (p < 0.001), indicating position dependence of spasticity. The higher resistance felt by the examiner at the higher velocity was also due to more extreme joint position (joint angle) since the spastic joint was moved significantly further to a stiffer elbow position with the higher velocity. Stroke survivors showed smaller ROM (p < 0.001), higher stiffness (p < 0.001), and larger energy loss (p = 0.005). Compared to the controls, stroke survivors showed increased reflex excitability with higher reflex-mediated torque (p < 0.001) and at higher velocities (p = 0.02). Conclusion: Velocity dependence of spasticity is partially due to joint angle position dependence with the joint moved further (to a stiffer position where higher resistance was felt) at a higher velocity. The "4-dimensional characterization" including the joint angle, velocity, torque, and torque change rate provides a systematic tool to characterize catch angle and spasticity quantitatively.

Objective: This longitudinal observational study investigated how neural stretch-resistance in wrist and finger flexors develops after stroke and relates to motor recovery, secondary complications, and lesion location. Methods: Sixty-one patients were assessed at 3 weeks (T1), three (T2), and 6 months (T3) after stroke using the NeuroFlexor method and clinical tests. Magnetic Resonance Imaging was used to calculate weighted corticospinal tract lesion load (wCST-LL) and to perform voxel-based lesion symptom mapping. Results: NeuroFlexor assessment demonstrated spasticity (neural component [NC] >3.4N normative cut-off) in 33% of patients at T1 and in 51% at T3. Four subgroups were identified: early Severe spasticity (n = 10), early Moderate spasticity (n = 10), Late developing spasticity (n = 17) and No spasticity (n = 24). All except the Severe spasticity group improved significantly in Fugl-Meyer Assessment (FMA-HAND) to T3. The Severe and Late spasticity groups did not improve in Box and Blocks Test. The Severe spasticity group showed a 25° reduction in passive range of movement and more frequent arm pain at T3. wCST-LL correlated positively with NC at T1 and T3, even after controlling for FMA-HAND and lesion volume. Voxel-based lesion symptom mapping showed that lesioned white matter below cortical hand knob correlated positively with NC. Conclusion: Severe hand spasticity early after stroke is negatively associated with hand motor recovery and positively associated with the development of secondary complications. Corticospinal tract damage predicts development of spasticity. Early quantitative hand spasticity measurement may have potential to predict motor recovery and could guide targeted rehabilitation interventions after stroke.

Background: The EXOPULSE Mollii method is an innovative full-body suit approach for non-invasive electrical stimulation, primarily designed to reduce disabling spasticity and improve motor function through the mechanism of reciprocal inhibition. This study aimed to evaluate the effectiveness of one session of stimulation with the EXOPULSE Mollii suit at different stimulation frequencies on objective signs of spasticity and clinical measures, and the subjective perceptions of the intervention. Methods: Twenty patients in the chronic phase after stroke were enrolled in a cross-over, double-blind controlled study. Electrical stimulation delivered through EXOPULSE Mollii was applied for 60 min at two active frequencies (20 and 30 Hz) and in OFF-settings (placebo) in a randomized order, every second day. Spasticity was assessed with controlled-velocity passive muscle stretches using the NeuroFlexor hand and foot modules. Surface electromyography (EMG) for characterizing flexor carpi radialis, medial gastrocnemius, and soleus muscles activation, Modified Ashworth Scale and range of motion were used as complementary tests. Finally, a questionnaire was used to assess the participants' perceptions of using the EXOPULSE Mollii suit. Results: At group level, analyses showed no significant effect of stimulation at any frequency on NeuroFlexor neural component (NC) and EMG amplitude in the upper or lower extremities (p > 0.35). Nevertheless, the effect was highly variable at the individual level, with eight patients exhibiting reduced NC (>1 N) in the upper extremity after stimulation at 30 Hz, 5 at 20 Hz and 3 in OFF settings. All these patients presented severe spasticity at baseline, i.e., NC > 8 N. Modified Ashworth ratings of spasticity and range of motion did not change significantly after stimulation at any frequency. Finally, 75% of participants reported an overall feeling of well-being during stimulation, with 25% patients describing a muscle-relaxing effect on the affected hand and/or foot at both 20 and 30 Hz. Conclusions: The 60 min of electrical stimulation with EXOPULSE Mollii suit did not reduce spasticity consistently in the upper and lower extremities in the chronic phase after stroke. Findings suggest a need for further studies in patients with severe spasticity after stroke including repeated stimulation sessions. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04076878, identifier: NCT04076878.

Background: The assessment of muscle properties is an essential prerequisite in the treatment of post-stroke patients with limb spasticity. Most existing spasticity assessment approaches do not consider the muscle activation with voluntary contraction. Including voluntary movements of spastic muscles may provide a new way for the reliable assessment of muscle spasticity. Objective: In this study, we investigated the effectiveness and reliability of maximum isometrics voluntary contraction (MIVC) based method for spasticity assessment in post-stroke hemiplegia. Methods: Fourteen post-stroke hemiplegic patients with arm spasticity were asked to perform two tasks: MIVC and passive isokinetic movements. Three biomechanical signals, torque, position, and time, were recorded from the impaired and non-impaired arms of the patients. Three features, peak torque, keep time of the peak torque, and rise time, were computed from the recorded MIVC signals and used to evaluate the muscle voluntary activation characteristics, respectively. For passive movements, two features, the maximum resistance torque and muscle stiffness, were also obtained to characterize the properties of spastic stretch reflexes. Subsequently, the effectiveness and reliability of the MIVC-based spasticity assessment method were evaluated with spearman correlation analysis and intra class correlation coefficients (ICCs) metrics. Results: The results indicated that the keep time of peak torque and rise time in the impaired arm were higher in comparison to those in the contralateral arm, whereas the peak torque in the impaired side was significantly lower than their contralateral arm. Our results also showed a significant positive correlation (r = 0.503, p = 0.047) between the keep time (tk) and the passive resistant torque. Furthermore, a significantly positive correlation was observed between the keep time (tk) and the muscle stiffness (r = 0.653, p = 0.011). Meanwhile, the ICCs for intra-time measurements of MIVC ranged between 0.815 and 0.988 with one outlier. Conclusion: The findings from this study suggested that the proposed MIVC-based approach would be promising for the reliable and accurate assessment of spasticity in post-stroke patients.

The phenomenon of exaggerated motor overflow is well documented in stroke survivors with spasticity. However, the mechanism underlying the abnormal motor overflow remains unclear. In this study, we aimed to investigate the possible mechanisms behind abnormal motor overflow and its possible relations with post-stroke spasticity. 11 stroke patients (63.6 ± 6.4 yrs; 4 women) and 11 healthy subjects (31.18 ± 6.18 yrs; 2 women) were recruited. All of them were asked to perform unilateral isometric elbow flexion at submaximal levels (10, 30, and 60% of maximum voluntary contraction). Electromyogram (EMG) was measured from the contracting biceps (iBiceps) muscle and resting contralateral biceps (cBiceps), ipsilateral flexor digitorum superficialis (iFDS), and contralateral FDS (cFDS) muscles. Motor overflow was quantified as the normalized EMG of the resting muscles. The severity of motor impairment was quantified through reflex torque (spasticity) and weakness. EMG-EMG coherence was calculated between the contracting muscle and each of the resting muscles. During elbow flexion on the impaired side, stroke subjects exhibited significant higher motor overflow to the iFDS muscle compared with healthy subjects (ipsilateral or intralimb motor overflow). Stroke subjects exhibited significantly higher motor overflow to the contralateral spastic muscles (cBiceps and cFDS) during elbow flexion on the non-impaired side (contralateral or interlimb motor overflow), compared with healthy subjects. Moreover, there was significantly high EMG-EMG coherence in the alpha band (6-12 Hz) between the contracting muscle and all other resting muscles during elbow flexion on the non-impaired side. Our results of diffuse ipsilateral and contralateral motor overflow with EMG-EMG coherence in the alpha band suggest subcortical origins of motor overflow. Furthermore, correlation between contralateral motor overflow to contralateral spastic elbow and finger flexors and their spasticity was consistently at moderate to high levels. A high correlation suggests that diffuse motor overflow to the impaired side and spasticity likely share a common pathophysiological process. Possible mechanisms are discussed.

Background: Flexor spasticity of the upper limb is common in poststroke patients and seriously affects the recovery of upper limb function. However, there are no standard management protocols for this condition. Radial extracorporeal shock wave therapy (rESWT) is widely used for various diseases, some studies reported the effects of ESWT on reducing spasticity, but the mechanism of ESWT to reduce spasticity by affecting the excitability of stretch reflex or non-neural rheological components in spastic muscles or both is not yet clear. A large randomized controlled trial with comprehensive evaluation indicators is still needed. The study is to observe the effect of rESWT on flexor spasticity of the upper limb after stroke and explore its mechanism. Methods: A prospective, randomized, double-blind controlled trial is to be performed. One hundred participants will be recruited from the Inpatient Department of Zhujiang Hospital. Eligible patients will be randomly allocated to either receive three sessions of active rESWT (group A) or sham-placebo rESWT (group B) with 3-day intervals between each session. Assessment will be performed at baseline and at 24 h after each rESWT (t1, t2, and t3). The primary assessment outcome will be the Modified Ashworth Scale, and other assessments include surface electromyography, MyotonPRO digital muscle function evaluation, and infrared thermal imaging. All data will be analyzed using intention-to-treat principles. Multiple imputation by chained equations will be used to address missing data caused by loss to follow-up and nonresponses. Per protocol, analyses will also be performed on the participants who complete other assessments. Statistical analysis will be performed using SPSS software (version 20.0) and the significance level set at p < 0.05. Discussion: This trial aims to analyze the application of rESWT for the management of spasticity after stroke via appropriate assessments. We hypothesized that after receiving active rESWT, patients would show greater improvement of upper limb muscles compared with patients within the sham-placebo group. The rESWT would be an alternative to traditional methods, and the results of this study may provide support for the further study of potential mechanisms. Clinical Trial Registration:www.chictr.org.cn, identifier: ChiCTR1800016144.

The effective relief of muscle spasticity requires prompt solutions in rehabilitation medicine. This study aimed to reveal that the highest region of muscle spindle abundance is the optimal target of botulinum toxin A (BTX-A) injections for relieve muscle spasm.

Hereditary spastic paraplegia (HSP) is a neurological, genetic disorder that predominantly presents with lower limb spasticity and muscle weakness. Pediatric pure HSP types with infancy or childhood symptom onset resemble in clinical presentation to children with bilateral spastic cerebral palsy (SCP). Hence, treatment approaches in these patient groups are analogous. Altered muscle characteristics, including reduced medial gastrocnemius (MG) muscle growth and hyperreflexia have been quantified in children with SCP, using 3D-freehand ultrasound (3DfUS) and instrumented assessments of hyperreflexia, respectively. However, these muscle data have not yet been studied in children with HSP. Therefore, we aimed to explore these MG muscle characteristics in HSP and to test the hypothesis that these data differ from those of children with SCP and typically developing (TD) children. A total of 41 children were retrospectively enrolled including (1) nine children with HSP (ages of 9-17 years with gross motor function levels I and II), (2) 17 age-and severity-matched SCP children, and (3) 15 age-matched typically developing children (TD). Clinically, children with HSP showed significantly increased presence and severity of ankle clonus compared with SCP (p = 0.009). Compared with TD, both HSP and SCP had significantly smaller MG muscle volume normalized to body mass (p ≤ 0.001). Hyperreflexia did not significantly differ between the HSP and SCP group. In addition to the observed pathological muscle activity for both the low-velocity and the change in high-velocity and low-velocity stretches in the two groups, children with HSP tended to present higher muscle activity in response to increased stretch velocity compared with those with SCP. This exploratory study is the first to reveal MG muscle volume deficits in children with HSP. Moreover, high-velocity-dependent hyperreflexia and ankle clonus is observed in children with HSP. Instrumented impairment assessments suggested similar altered MG muscle characteristics in pure HSP type with pediatric onset compared to bilateral SCP. This finding needs to be confirmed in larger sample sizes. Hence, the study results might indicate analogous treatment approaches in these two patient groups.

Hereditary spastic paraplegia (HSP) encompass a variety of neurodegenerative disorders that are characterized by progressive deterioration of walking ability and a high risk for long-term disability. The management of problems associated with HSP, such as stiffness, deformity, muscle contractures, and cramping, requires strict adherence to recommended physiotherapy activity regimes. The aim of this paper is to conduct a critical narrative review of the available evidence focusing exclusively to the therapeutic advantages associated with various forms of physical therapy (PT) in the context of HSP, emphasizing the specific benefit of every distinct approach in relation to muscle relaxation, muscle strength, spasticity reduction, improvement of weakness, enhancement of balance, posture, walking ability, and overall quality of life.

The purpose was to examine the immediate effects of dry needling to spastic finger muscles in chronic stroke. Ten chronic stroke patients with spasticity in finger flexors participated in this experiment. Dry needling to the flexor digitorum superficialis (FDS) muscle was performed under ultrasound guidance for about 30 s (about 100 times). Clinical assessment and intramuscular needle EMG readings were made before and immediately after dry needling. Immediately after needling, the FDS muscle was felt less tight to palpation and the proximal phalangeal joint rested in a less flexed position (p = 0.036). The MAS score decreased for FDS (p = 0.017) and flexor digitorum profundus (FDP) (p = 0.029). Motor unit action potential (MUAP) spikes decreased from 41.6 ± 5.5 to 6.7 ± 2.2 spikes/s (p = 0.002), an 84% reduction after dry needling. However, the pre-needling spike frequency was not correlated to MAS or resting position of the FDS muscles. Dry needling to the spastic finger flexors leads to immediate spasticity reduction, increased active range of motion, and decreased frequency of motor unit spontaneous firing spikes. The results suggest that latent trigger points possibly exist in spastic muscles and they contribute partly to spastic hypertonia of finger flexors in chronic stroke.

Background: The reliable assessment, attribution, and alleviation of upper-limb joint stiffness are essential clinical objectives in the early rehabilitation from stroke and other neurological disorders, to prevent the progression of neuromuscular pathology and enable proactive physiotherapy toward functional recovery. However, the current clinical evaluation and treatment of this stiffness (and underlying muscle spasticity) are severely limited by their dependence on subjective evaluation and manual limb mobilization, thus rendering the evaluation imprecise and the treatment insufficiently tailored to the specific pathologies and residual capabilities of individual patients. Methods: To address these needs, the proposed clinical trial will employ the NEUROExos Elbow Module (NEEM), an active robotic exoskeleton, for the passive mobilization and active training of elbow flexion and extension in 60 sub-acute and chronic stroke patients with motor impairments (hemiparesis and/or spasticity) of the right arm. The study protocol is a randomized controlled trial consisting of a 4-week functional rehabilitation program, with both clinical and robotically instrumented assessments to be conducted at baseline and post-treatment. The primary outcome measures will be a set of standard clinical scales for upper limb spasticity and motor function assessment, including the Modified Ashworth Scale and Fugl-Meyer Index, to confirm the safety and evaluate the efficacy of robotic rehabilitation in reducing elbow stiffness and improving function. Secondary outcomes will include biomechanical, muscular activity, and motor performance parameters extracted from instrumented assessments using the NEEM along with synchronous EMG recordings. Conclusions: This randomized controlled trial aims to validate an innovative instrumented methodology for clinical spasticity assessment and functional rehabilitation, relying on the precision and accuracy of an elbow exoskeleton combined with EMG recordings and the expertise of a physiotherapist, thus complementing and maximizing the benefits of both practices. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04484571.

Multiple sclerosis (MS) is a progressive disease with a fluctuating and unpredictable course that has no curative treatment at present. One of its main characteristics is the variety of signs and symptoms that produce a high percentage of patients who present alterations in balance and gait during the development of the disease, decreased muscle strength, spasticity, or decreased pimax. Rehabilitative therapy, especially physiotherapy, is the main course of the treatment of these alterations using reflex locomotion and the Bobath concept as a form of kinesitherapy that activates the preorganized circuits of the central nervous system.

Background: Neural impairments that follow hemiparetic stroke may negatively affect passive muscle properties, further limiting recovery. However, factors such as hypertonia, spasticity, and botulinum neurotoxin (BoNT), a common clinical intervention, confound our understanding of muscle properties in chronic stroke. Objective: To determine if muscle passive biomechanical properties are different following prolonged, stroke-induced, altered muscle activation and disuse. Methods: Torques about the metacarpophalangeal and wrist joints were measured in different joint postures in both limbs of participants with hemiparetic stroke. First, we evaluated 27 participants with no history of BoNT; hand impairments ranged from mild to severe. Subsequently, seven participants with a history of BoNT injections were evaluated. To mitigate muscle hypertonia, torques were quantified after an extensive stretching protocol and under conditions that encouraged participants to sleep. EMGs were monitored throughout data collection. Results: Among participants who never received BoNT, no significant differences in passive torques between limbs were observed. Among participants who previously received BoNT injections, passive flexion torques about their paretic wrist and finger joints were larger than their non-paretic limb (average interlimb differences = +42.0 ± 7.6SEM Ncm, +26.9 ± 3.9SEM Ncm, respectively), and the range of motion for passive finger extension was significantly smaller (average interlimb difference = -36.3° ± 4.5°SEM; degrees). Conclusion: Our results suggest that neural impairments that follow chronic, hemiparetic stroke do not lead to passive mechanical changes within the wrist and finger muscles. Rather, consistent with animal studies, the data points to potential adverse effects of BoNT on passive muscle properties post-stroke, which warrant further consideration.

Background: Cerebral palsy (CP) is the most common cause of physical disability in childhood. Muscle pathologies occur due to spasticity and contractures; therefore, diagnostic imaging to detect pathologies is often required. Imaging has been used to assess torsion or estimate muscle volume, but additional methods for characterizing muscle composition have not thoroughly been investigated. MRI fat fraction (FF) measurement can quantify muscle fat and is often a part of standard imaging in neuromuscular dystrophies. To date, FF has been used to quantify muscle fat and assess function in CP. In this study, we aimed to utilize a radiomics and FF analysis along with the combination of both methods to differentiate affected muscles from healthy ones. Materials and Methods: A total of 9 patients (age range 8-15 years) with CP and 12 healthy controls (age range 9-16 years) were prospectively enrolled (2018-2020) after ethics committee approval. Multi-echo Dixon acquisition of the calf muscles was used for FF calculation. The images of the second echo (TE = 2.87 ms) were used for feature extraction from the soleus, gastrocnemius medialis, and gastrocnemius lateralis muscles. The least absolute shrinkage and selection operator (LASSO) regression was employed for feature selection. RM, FF model (FFM), and combined model (CM) were built for each calf muscle. The receiver operating characteristic (ROC) curve and their respective area under the curve (AUC) values were used to evaluate model performance. Results: In total, the affected legs of 9 CP patients and the dominant legs of 12 healthy controls were analyzed. The performance of RM for soleus, gastrocnemius medialis, and gastrocnemius lateralis (AUC 0.92, 0.92, 0.82, respectively) was better than the FFM (AUC 0.88, 0.85, 0.69, respectively). The combination of both models always had a better performance than RM or FFM (AUC 0.95, 0.93, 0.83). FF was higher in the patient group (FFS 9.1%, FFGM 8.5%, and FFGL 10.2%) than control group (FFS 3.3%, FFGM 4.1%, FFGL 6.6%). Conclusion: The combination of MRI quantitative fat fraction analysis and texture analysis of muscles is a promising tool to evaluate muscle pathologies due to CP in a non-invasive manner.

The term hereditary spastic paraplegia (HSP) embraces a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. There currently exist no specific therapies for HSP, and treatment is exclusively symptomatic, aimed at reducing muscle spasticity, and improving strength and gait. The authors set out to perform a comprehensive systematic review of the available scientific literature on the treatment of HSP, applying Cochrane Collaboration methods. The Google Scholar, PubMed and Scopus electronic databases were searched to find relevant randomized control trials (RCTs) and open-label interventional studies, prospective, and retrospective observational studies of supplements, medications, and physical therapy, as well as case reports and case series. Two authors independently analyzed 27 articles selected on the basis of a series of inclusion criteria. Applying a best-evidence synthesis approach, they evaluated these articles for methodological quality. A standardized scoring system was used to obtain interrater assessments. Disagreements were resolved by discussion. The 27 articles focused on pharmacological treatment (n = 17 articles), physical therapy (n = 5), surgical treatment (n = 5). The drugs used in the 17 articles on pharmacological therapy were: gabapentin, progabide, dalfampridine, botulinum toxin, L-Dopa, cholesterol-lowering drugs, betaine, and folinic acid. Gabapentin, progabide, dalfampridine, and botulinum toxin were used as antispastic agents; the study evaluating gabapentin efficacy was well-designed, but failed to demonstrate any significant improvement. L-Dopa, cholesterol-lowering drugs, betaine, and folinic acid were only used in specific HSP subtypes. Two of the three studies evaluating cholesterol-lowering drugs (in SPG5 patients) were well-designed and showed a significant reduction of specific serum biomarkers (oxysterols), but clinical outcomes were not evaluated. The articles focusing on physical treatment and surgical therapy were found to be of low/medium quality and, accordingly, failed to clarify the role of these approaches in HSP. Despite recent advances in understanding of the pathogenesis of HSP and the possibility, in several centers, of obtaining more precise and rapid molecular diagnoses, there is still no adequate evidence base for recommending the various published therapies. Well-designed RCTs are needed to evaluate the efficacy of both symptomatic and pathogenetic treatments.