Post-stroke Spasticity Research Articles

Estimating the cost consequence of the early use of botulinum toxin in post-stroke spasticity: Secondary analysis of a randomised controlled trial

Objective To estimate the cost-consequence of treating spasticity early with botulinum toxin in the acute stroke unit. Design Secondary cost-consequence analysis, using data from a double-blind randomised-controlled trial. Setting Single-centre specialised stroke unit. Subjects and Interventions Patients with Action Research Arm Test grasp-score of <2 and who developed spasticity within six weeks of a first stroke were randomised to receive injections of: 0.9% sodium-chloride solution (placebo) or onabotulinumtoxin-A (treatment). Main measures Resource use costs were calculated for the study. Mean contracture costs for each group were calculated. The Barthel Index and Action Research Arm Test were used to generate a cost per unit of improvement. Results There were no significant differences associated with early treatment use. The mean contracture cost for the treatment group was £817 and for the control group was £2298 (mean difference = −£1481.1(95% CI −£2893.5, −£68.7) (p = 0.04). The cost per unit of improvement for the Barthel Index was −£1240 indicating that the intervention costs less and is more effective. The cost per unit of improvement for the Action Research Arm Test was −£450 indicating that the intervention costs less and is more effective. Conclusions Treating spasticity early in stroke patients at risk of contractures with botulinum toxin leads to a significant reduction in contracture costs. The cost per improvement of Barthel and Action Research Arm Test indicates that the intervention costs less and is more effective. Trial Registration data EudraCT(2010-021257-39) and ClinicalTrials.gov-Identifier:NCT01882556.

Nabiximols effect on blood pressure and heart rate in post-stroke patients of a randomized controlled study.

Cannabinoids may be useful to treat pain, epilepsy and spasticity, although they may bear an increased risk of cardiovascular events. This study aims to evaluate the cardiovascular safety of nabiximols, a cannabis-based drug, in patients with spasticity following stroke, thus presenting an increased cardiovascular risk. This is an ancillary study stemming from the SativexStroke trial: a randomized double-blind, placebo-controlled, crossover study aimed at assessing the effect of nabiximols on post-stroke spasticity. Patients were treated with nabiximols oromucosal spray or placebo and assessed before and after two phases of 1-month duration each. Only the phase with the active treatment was considered for each patient who completed the study. The average values of blood pressure (diastolic, systolic, differential) and heart rate from the first 5 days of the phase (lowest nabiximols dosage) were compared to the average values recorded during the last 5 days at the end of the phase (highest nabiximols dosage). Baseline comparisons between gender, stroke type and affected side and correlation between age and blood pressure and heart rate were performed. The study was registered with the EudraCT number 2016-001034-10. Thirty-four patients completed the study and were included in the analysis. Thirty-one were taking antihypertensive drugs and, among these, 12 were taking beta-blockers. During the study, no arrhythmic events were recorded, blood pressure and heart rate did not show pathological fluctuations, and no cardiovascular or cerebrovascular events occurred. At baseline blood pressure and heart rate were comparable concerning gender, stroke type and affected side. A significant direct correlation emerged between differential blood pressure and age and an inverse correlation between diastolic blood pressure and age. No correlation emerged between systolic blood pressure or heart rate and age. Blood pressure and heart rate did not change during nabiximols treatment compared to the baseline condition. This ancillary study adds evidence that, in patients who already underwent a cerebrovascular accident, nabiximols does not determine significant blood pressure and heart rate variation or cardiovascular complications. These data support the cardiovascular safety of nabiximols, encouraging more extensive studies involving cannabinoids characterized by slow absorption rates.

Lesions causing post-stroke spasticity localize to a common brain network.

The efficacy of clinical interventions for post-stroke spasticity (PSS) has been consistently unsatisfactory, probably because lesions causing PSS may occur at different locations in the brain, leaving the neuroanatomical substrates of spasticity unclear. Here, we investigated whether heterogeneous lesions causing PSS were localized to a common brain network and then identified the key nodes in this network. We used 32 cases of PSS and the Human Connectome dataset (n = 1,000), using a lesion network mapping method to identify the brain regions that were associated with each lesion in patients with PSS. Functional connectivity maps of all lesions were overlaid to identify common connectivity. Furthermore, a split-half replication method was used to evaluate reproducibility. Then, the lesion network mapping results were compared with those of patients with post-stroke non-spastic motor dysfunction (n = 29) to assess the specificity. Next, both sensitive and specific regions associated with PSS were identified using conjunction analyses, and the correlation between these regions and PSS was further explored by correlation analysis. The lesions in all patients with PSS were located in different cortical and subcortical locations. However, at least 93% of these lesions (29/32) had functional connectivity with the bilateral putamen and globus pallidus. These connections were highly repeatable and specific, as compared to those in non-spastic patients. In addition, the functional connectivity between lesions and bilateral putamen and globus pallidus in patients with PSS was positively correlated with the degree of spasticity. We identified that lesions causing PSS were localized to a common functional connectivity network defined by connectivity to the bilateral putamen and globus pallidus. This network may best cover the locations of lesions causing PSS. The putamen and globus pallidus may be potential key regions in PSS. Our findings complement previous neuroimaging studies on PSS, contributing to identifying patients with stroke at high risk for spasticity at an early stage, and may point to PSS-specific brain stimulation targets.

A practical guide to botulinum neurotoxin treatment of shoulder spasticity 1: Anatomy, physiology, and goal setting

Botulinum neurotoxin type A (BoNT-A) is a first-line treatment option for post-stroke spasticity, reducing pain and involuntary movements and helping to restore function. BoNT-A is frequently injected into the arm, wrist, hand and/or finger muscles, but less often into the shoulder muscles, despite clinical trials demonstrating improvements in pain and function after shoulder BoNT-A injection. In part 1 of this two-part practical guide, we present an experts' consensus on the use of BoNT-A injections in the multi-pattern treatment of shoulder spasticity to increase awareness of shoulder muscle injection with BoNT-A, alongside the more commonly injected upper limb muscles. Expert consensus was obtained from five European experts with a cumulative experience of more than 100 years of BoNT-A use in post-stroke spasticity. A patient-centered approach was proposed by the expert consensus: to identify which activities are limited by the spastic shoulder and consider treating the muscles that are involved in hindering those activities. Two patterns of shoulder spasticity were identified: for Pattern A (adduction, elevation, flexion and internal rotation of the shoulder), the expert panel recommended injecting the pectoralis major, teres major and subscapularis muscles; in most cases injecting only the pectoralis major and the teres major is sufficient for the first injection cycle; for Pattern B (abduction or adduction, extension and internal rotation of the shoulder), the panel recommended injecting the posterior part of the deltoid, the teres major and the latissimus dorsi in most cases. It is important to consider the local guidelines and product labels, as well as discussions within the multidisciplinary, multiprofessional team when deciding to inject shoulder muscles with BoNT-A. The choice of shoulder muscles for BoNT-A injection can be based on spastic pattern, but ideally should also firstly consider the functional limitation and patient expectations in order to establish better patient-centered treatment goals. These recommendations will be of benefit for clinicians who may not be experienced in evaluating and treating spastic shoulders.

Experience of using gait adaptability training in medical rehabilitation of patients after cerebrovascular accident in the late recovery period

The article presents the treatment data of 80 patients who had an ischemic stroke with movement disorders in the form of hemiparesis with increased muscle tone in the lower limb due to spasticity. The patients were divided into 2 groups comparable in terms of clinical and functional characteristics: group 1 included patients who, in addition to standard treatment, had gait adaptability training with video reconstruction on the C–Mill biofeedback system (BFB), and group 2 consisted of 40 people who underwent a course of standard drug therapy and medical rehabilitation (exercise therapy and medical massage). The characteristics of the main static and locomotor parameters were assessed according to the C–Mill data and the Tinetti assessment tool, and the range of motion in the lower extremities was assessed according to goniometry data at all control points (before and after treatment, 3 and 6 months after treatment). The obtained data indicate the benefit of including gait adaptability training in the standard complex of medical rehabilitation of patients who have undergone acute cerebrovascular accident with motor disorders in the form of hemiparesis with post-stroke spasticity of the lower extremity. This was confirmed by the normalization of the parameters of the gait adaptability, namely, a decrease in the duration of free gait (step cycle) by an average of 32 %, an increase in the frequency of a free gait step by an average of 30 % and in the length of a free gait step by 16 % immediately after treatment, with the results maintained at all control points.

Reasons and Determinants of BoNT-A Treatment Discontinuation in Patients Living with Spasticity: A 10-Year Retrospective Analysis.

Background: The present study aimed to evaluate the reasons and determinants of BoNT-A discontinuation in patients with stroke, multiple sclerosis, spinal cord injury, and traumatic brain injury. Methods: It is a retrospective study of 56 discontinuer patients treated with botulinum toxin between January 2011 and December 2021. Discontinuation rates and their predictors were estimated using Kaplan–Meier, Log rank test, and Cox’s regression method of analyses. Results: The mean age was 56.54 years, 53.57% were affected by post-stroke spasticity, 17.86% by spinal cord injury, 12.5% and 16.07% by traumatic brain injury and multiple sclerosis, respectively. The median discontinuation time was 5 months. The main reason for discontinuation were logistic problems (37%) and orthopedic surgeries or intrathecal baclofen (27%). Discontinuers were more likely to have severe spasticity (R = 1.785), have no pain (HR = 1.320), no access to rehabilitation services (HR = 1.402), and have cognitive impairment (HR = 1.403). Conclusions: The main reasons for discontinuation are related to logistic issues (due to distance or the absence of an adequate caregiver) and surgical interventions for spasticity, including intrathecal baclofen. It is crucial to identify possible predictors of discontinuation to improve the effectiveness of a multidisciplinary management. The study confirms the crucial role of rehabilitation and caregivers in achieving better long-term outcomes.

Prevalence and factors influencing the occurrence of spasticity in stroke patients: a retrospective study

ABSTRACT Background To describe the prevalence and clinical characteristics of stroke patients withoutspasticity, and simultaneously analyse the factors related to post-strokenon-spasticity. Methods In this retrospective study, information on patients hospitalized in thedepartment of rehabilitation, Daping Hospital, over the past eight years wascollected. Demographic information and clinical characteristics werestatistically analysed. Results A total of 819 stroke patients with an average age of 61.66±13.72 years old wereanalysed, including 561 males (68.5%), and 258 females (31.5%). In this study,201 (24.5%) patients developed spasticity, and 618 (75.5%) patients had nospasticity. Patients without spasticity were older than those with spasticity.Patients with ischemic stroke and mild functional impairment were also lesslikely to have spasticity. Post-stroke spasticity may be related to age [oddratio (OR): 0.982; 95% CI:0.965 to 0.999; P = 0.042), hemorrhagic stroke (OR:1.643; 95% CI: 1.029 to 2.626; P = 0.038), National Institute of Health StrokeScale (NIHSS) Scores (OR: 1.132; 95% CI: 1.063 to 1.204; P = 0.000]. Conclusion Most stroke patients do not have spasticity, especially the elderly, patients withischemic stroke, and those with mild functional impairment, suggesting that notall upper motor nerve injuries lead to increased muscle tension. For youngindividuals, patients with hemorrhagic stroke, and those with moderate tosevere functional impairment, close follow-up is necessary to identify theoccurrence of spasticity early on and then formulate corresponding rehabilitationstrategies for prompt intervention.

PET/CT imaging of post-stroke upper extremity spasticity without and with botulinum toxin A

PET/CT imaging of post-stroke upper extremity spasticity without and with botulinum toxin A

Efficacy and Safety of Botulinum Toxin Type A (NABOTA) for Post-stroke Upper Extremity Spasticity: A Multicenter Phase IV Trial.

ObjectiveTo evaluate the efficacy and safety of Daewoong botulinum toxin type A (NABOTA) after its launch in South Korea.MethodsThis prospective, multicenter, open-label phase IV clinical trial included 222 patients with stroke. All patients visited the clinic at baseline and at weeks 4, 8, and 12 after injection of upto 360 units of NABOTA into the wrist, elbow, and finger flexor muscles at the first visit. The primary outcome was the change in Modified Ashworth Scale (MAS) score for the wrist flexor muscles between baseline and week 4. The secondary outcomes were the changes in MAS, Disability Assessment Scale (DAS), and Caregiver Burden Scale (CBS) scores between baseline and each visit, and the Global Assessment Scale (GAS) score at week 12.ResultsThere was a statistically significant decrease in the MAS score for the wrist flexors between baseline and week 4 (−0.97±0.66, p<0.001). Compared with baseline, the MAS, DAS and CBS scores improved significantly during the study period. The GAS was rated as very good or good by 86.8% of physicians and by 60.0% of patients (or caregivers). The incidence of adverse events was 14.4%, which is smaller than that in a previous trial.ConclusionNABOTA showed considerable efficacy and safety in the management of upper limb spasticity in stroke patients.

Effect of electroacupuncture of Governor Vessel on expression of GAD67 and GABA-T in cerebral cortex of rats with post-stroke limb spasticity

To observe the effect of electroacupuncture (EA) of Governor Vessel (GV) on the expressions of glutamate decarboxylase 67 (GAD67) and γ-aminobutyric acid transaminase (GABA-T) in the cerebral cortex of rats with post-stroke limb spasticity, so as to explore its mechanism underlying improvement of limb spasticity. Twenty four male SD rats were randomly and equally divided into control, sham operation, model, and EA groups. The cerebral ischemia model was established by occlusion of the middle cerebral artery (MCAO). EA (100 Hz, 1-3 mA) was applied to "Dazhui"(GV14), "Jizhong"(GV6) and "Houhui"( anteromedial of transverse process of the sixth lumbar vertebra) for 30 min, once daily for 7 consecutive days. The neurologic deficit score (0-5 points) was evaluated according to Zea Longa's method, and the muscular tension severity (0-5 points) was assessed according to the modified Ashworth muscle tone rating scale, and the tension signals of the quadriceps ferroris of the affected limb were recorded using tonotransducer and BL-420F electrophysiological recorder. The expression levels of GAD67 and GABA-T proteins and mRNAs in the cerebral cortex were detected by immunohistochemistry, fluorescence quantitative real-time PCR and Western blot, separately. After modeling, the neurological deficit score, muscle tone score, and the expression levels of GABA-T mRNA and protein in cerebral cortex were significantly increased (P<0.01, P<0.05), tension signal value and the expression levels of GAD67 mRNA and protein in cerebral cortex were significantly decreased (P<0.01) in the model group relevant to the control and sham operation groups. Following the intervention, the neurological deficit score, muscle tone score, and expression levels of GABA-T mRNA and protein in cerebral cortex were significantly decreased (P<0.01), tension signal value and the expression levels of GAD67 mRNA and protein in cerebral cortex were significantly increased (P<0.01, P<0.05) in the EA group in contrast to the model group. EA stimulation of Governor Vessel can ameliorate the limb spasticity symptom in MCAO rats, which may be associated with its functions in increasing the expressions of GAD67 protein and mRNA and inhibiting the expressions of GABA-T protein and mRNA, thereby playing the inhibitory role of GABA.

Modelling Long-Term Outcomes and Risk of Death for Patients with Post-Stroke Spasticity Receiving Abobotulinumtoxina Treatment and Rehabilitation Therapy.

ObjectiveStroke is associated with a high risk of death and cardiovascular events. Rehabilitation therapy is critical for functional recovery, to reduce hospital readmissions, all-cause and cardiovascular mortality, and stroke recurrence (long-term outcomes). Post-stroke spasticity may prevent effective recovery by restricting mobility. AbobotulinumtoxinA is an adjunctive therapy to physical therapy for post-stroke spasticity, but its long-term effects are unknown. The objective was to model the long-term clinical and economic outcomes of abobotulinumtoxinA for post-stroke spasticity.MethodsEffects of abobotulinumtoxinA on treating post-stroke spasticity and evidence linking functional outcomes with long-term outcomes were collected in a focused literature review. A model was developed to estimate health benefits on long-term outcomes, direct medical costs, life- and quality-adjusted life-years for abobotulinumtoxinA injections plus rehabilitation therapy compared with rehabilitation therapy alone, from a UK perspective over a 10-year time-period.ResultsAbobotulinumtoxinA + rehabilitation therapy led to a risk reduction of 8.8% for all-cause mortality, and an increase of 13% in life-years and 59% in quality-adjusted life-years compared with rehabilitation therapy alone. AbobotulinumtoxinA + rehabilitation therapy was considered cost-effective compared with rehabilitation therapy alone (incremental cost-effectiveness ratio: £24,602).ConclusionAbobotulinumtoxinA + rehabilitation therapy may improve long-term outcomes, including post-stroke survival, while being cost-effective for the treatment of post-stroke spasticity.LAY ABSTRACTHere we developed a model to explore and compare the long-term benefits and overall costs of two interventions for the treatment of post-stroke spasticity (PSS): abobotulinumtoxinA injections plus rehabilitation therapy (aboBoNT-A+RT) vs. RT alone. Stroke survivors are known to be at a higher risk of recurrent stroke and death, and more than 25% are affected by spasticity. PSS significantly reduces patients’ mobility, physical functioning, and subsequently their ability to recover after a stroke. AboBoNT-A+RT is an effective treatment for spasticity. This model is the first to highlight that combining aboBoNT-A injections with RT could improve the overall survival of stroke survivors with spasticity by 8.8% and their overall quality of life, while being considered good value for money by UK payers.

Experiences of patients with poststroke spasticity throughout a botulinum toxin treatment cycle: Results from a prospective ethnographic study.

This study was conducted to capture the experience of patients with poststroke spasticity (PSS) throughout one botulinum neurotoxin A (BoNT-A) treatment cycle. The REBOT study (NCT03995524) was a prospective, observational ethnographic study conducted in France, Italy, the UK, and the USA. It combined a mixed-method ethnography (including semi-structured qualitative interviews within a week of a BoNT-A injection) with completion of a longitudinal quantitative patient-reported outcome questionnaire and sharing of video and images, both reported weekly over a 12–14-week period throughout the BoNT-A treatment cycle. The study recruited 30 adult patients with PSS who were receiving BoNT-A treatment. The most commonly used BoNT-A product was onabotulinumtoxinA (Botox®), which was administered to 21 patients (70%), whereas two patients (6.7%) received abobotulinumtoxinA (Dysport®) and seven patients (23.3%) did not specify the BoNT-A medication that they received. Patients reported a high, continuous burden of PSS, with spasms, sleeping difficulties, stiffness, and pain being the most commonly reported symptoms. In line with an observed waning effect of BoNT-A injections, spasticity symptoms initially were improved at Weeks 4–6 after injection but reemerged after 9–11 weeks. Treatment satisfaction levels decreased over the BoNT-A treatment cycle, as reflected by the worsening of symptoms and the need to self-medicate and consult a physician. The psychological impact of PSS was high. Patients acknowledged the benefits of BoNT-A treatment but wished for more individualized treatment plans with flexible dosing and injection intervals. Additionally, only 10% of patients reported that they had a trusting relationship with their physician and believed that their needs were considered by those managing their PSS. To our knowledge, this was the first ethnographic study in patients with PSS who were treated with BoNT-A. This ethnographic approach to patient surveys complements traditional research methods and allows improved identification of patients' unmet needs by capturing their weekly experience of treatment. The findings of this study confirm previous observations of the diminishing effectiveness of BoNT-A injections between treatment sessions, highlighting the need for agents with a longer duration of action and/or a more flexible treatment pattern that allows for more frequent injections.

Immediate and short-term effects of continuous theta burst transcranial magnetic stimulation over contralesional premotor area on post-stroke spasticity in patients with severe hemiplegia: Study protocol for a randomized controlled trial.

BackgroundPost-stroke spasticity is an important complication that greatly affects survivors' functional prognosis and daily activities. Increasing evidence points to aberrant contralesional neuromodulation compensation after brain injury as a possible culprit for increased spasticity in patients with severe stroke. Hyperactivity of the contralesional premotor area (cPMA) was supposed to be highly correlated with this progression. This study aims to demonstrate the immediate and short-term efficacy of continuous theta-burst stimulation (cTBS) targeting cPMA on upper limb spasticity in severe subacute stroke patients.MethodsThis trial is a single-center, prospective, three-group randomized controlled trial. Forty-five eligible patients will be recruited and randomized into three groups: the sham-cTBS group (sham cTBS targeting contralesional PMA), the cTBS-cM1 group (cTBS targeting contralesional M1), and the cTBS-cPMA group (cTBS targeting contralesional PMA). All subjects will undergo comprehensive rehabilitation and the corresponding cTBS interventions once a day, five times a week for 4 weeks. Clinical scales, neurophysiological examinations, and neuroimaging will be used as evaluation tools in this study. As the primary outcome, clinical performance on muscle spasticity of elbow/wrist flexor/extensors and upper-limb motor function will be evaluated with the modified Ashworth scale and the Fugl-Meyer Assessment of Upper Extremity Scale, respectively. These scale scores will be collected at baseline, after 4 weeks of treatment, and at follow-up. The secondary outcomes were neurophysiological examinations and Neuroimaging. In neurophysiological examinations, motor evoked potentials, startle reflex, and H reflexes will be used to assess the excitability of the subject's motor cortex, reticulospinal pathway, and spinal motor neurons, respectively. Results of them will be recorded before and after the first cTBS treatment, at post-intervention (at 4 weeks), and at follow-up (at 8 weeks). Neuroimaging tests with diffusion tensor imaging for all participants will be evaluated at baseline and after the 4-week treatment.DiscussionBased on the latest research progress on post-stroke spasticity, we innovatively propose a new neuromodulation target for improving post-stroke spasticity via cTBS. We expected that cTBS targeting cPMA would have significant immediate and short-term effects on spasticity and related neural pathways. The effect of cTBS-cPMA may be better than that of cTBS via conventional cM1. The results of our study will provide robust support for the application of cTBS neuromodulation in post-stroke spasticity after a severe stroke.Clinical trial registrationThis trial was registered with chictr.org.cn on June 13, 2022 (protocol version). http://www.chictr.org.cn/showproj.aspx?proj=171759.

The Lack of Systemic and Subclinical Side Effects of Botulinum Neurotoxin Type-A in Patients Affected by Post-Stroke Spasticity: A Longitudinal Cohort Study.

Botulinum Neurotoxin type-A (BoNT-A) is the treatment of choice for focal post-stroke spasticity (PSS). Due to its mechanism of action and the administration method, some authors raised concern about its possible systemic diffusion leading to contralateral muscle weakness and autonomic nervous system (ANS) alterations. Stroke itself is a cause of motor disability and ANS impairment; therefore, it is mandatory to prevent any source of additional loss of strength and adjunctive ANS disturbance. We enrolled 15 hemiparetic stroke survivors affected by PSS already addressed to BoNT-A treatment. Contralateral handgrip strength and ANS parameters, such as heart rate variability, impedance cardiography values, and respiratory sinus arrythmia, were measured 24 h before (T0) and 10 days after (T1) the ultrasound (US)-guided BoNT-A injection. At T1, neither strength loss nor modification of the basal ANS patterns were found. These findings support recent literature about the safety profile of BoNT-A, endorsing the importance of the US guide for a precise targeting and the sparing of “critical” structures as vessels and nerves.

A randomized double-blind controlled study protocol on the efficacy and safety of Sangdantongluo granule in the treatment of post-stroke spasticity

IntroductionStroke is the first leading cause of mortality and disability worldwide, and post-stroke spasticity (PSS) is the common complication of stroke. Sangdantongluo Granule (Z20210481000), a modern patent Chinese medicine, is widely used in clinical practice to treat PSS. Whereas, there is limited evidence of effectiveness for Sangdantongluo Granule to treat PSS. This study will evaluate the clinical efficacy and safety of Sangdantongluo granule in the treatment of PSS. Methodsand Analysis This multicenter, randomized, double-blind and placebo-controlled study will recruit 132 participants in China who develops PSS 15 days–90 days after stroke. Participants will be randomly assigned in an equal ratio to receive either Sangdantongluo granule or placebo for 2 months twice a day orally. The primary measure is the Modified Ashworth Scale (MAS), Secondary outcome measures include Composite Spasticity Scale (CSS), Simplified Fugl-Meyer Motor Scale (S-FM), National Institute of Health stroke scale (NIHSS), Modified Rankin Scale (mRS), Modified Barther Index (MBI), and Surface electromyography. Adverse events will be supervised throughout the trial. SPSS V. 26.0 statistical software will be used for statistical analysis. Enrolment will be started in April 2022. Ethics and disseminationThe trial and protocol were approved by the Ethics Committee of Hunan Academy of Chinese Medicine Affiliated Hospital (No. [202102]20). We will report the results of this trial in a peer-reviewed journal. Trial registrationClinicalTrials.gov ChiCTR2100044544. Registered on 23 March 2021.

Motor unit distribution and recruitment in spastic and non-spastic bilateral biceps brachii muscles of chronic stroke survivors

Objective. This study aims to characterize the motor units (MUs) distribution and recruitment pattern in the spastic and non-spastic bilateral biceps brachii muscles (BBMs) of chronic stroke survivors. Approach. High-density surface electromyography (HD-sEMG) signals were collected from both spastic and non-spastic BBMs of fourteen chronic stroke subjects during isometric elbow flexion at 10%, 30%, 50% and 100% maximal voluntary contractions (MVCs). By combining HD-sEMG decomposition and bioelectrical source imaging, MU innervation zones (MUIZs) of the decomposed MUs were first localized in the 3D space of spastic and non-spastic BBMs. The MU depth defined as the distance between the localized MUIZ and its normal projection on the skin surface was then normalized to the arm radius of each subject and averaged at given contraction level. The averaged MU depth at different contraction levels on a specific arm side (intra-side) and the bilateral depths under a specific contraction level (inter-side) were compared. Main results. The average depth of decomposed MUs increased with the contraction force and significant differences observed between 10% vs 50% (p < 0.0001), 10% vs 100% (p < 0.0001) and 30% vs 100% MVC (p = 0.0017) on the non-spastic side, indicating that larger MUs with higher recruitment threshold locate in deeper muscle regions. In contrast, no force-related difference in MU depth was observed on the spastic side, suggesting a disruption of orderly recruitment of MUs with increase of force level, or the MU denervation and the subsequent collateral reinnervation secondary to upper motor neuron lesions. Inter-side comparison demonstrated significant MU depth difference at 10% (p= 0.0048) and 100% force effort (p= 0.0026). Significance. This study represents the first effort to non-invasively characterize the MU distribution inside spastic and non-spastic bilateral BBM of chronic stroke patients by combining HD-sEMG recording, EMG signal decomposition and bioelectrical source imaging. The findings of this study advances our understanding regarding the neurophysiology of human muscles and the neuromuscular alterations following stroke. It may also offer important MU depth information for botulinum toxin injection in clinical post-stroke spasticity management.

Effect of Early Radial Shock Wave Treatment on Spasticity in Subacute Stroke Patients: A Pilot Study.

Background Spasticity is a complication that can start immediately after stroke. Radial extracorporeal shock wave therapy (rESWT) is a physical therapy tool used to manage chronic spasticity. However, the effect of rESWT's early use to treat spasticity after stroke is still not clearly investigated. The aim of this study is to evaluate the efficacy of rESWT in improving poststroke spasticity of the upper limb in patients with a recent onset of spasticity compared to conventional physiotherapy alone. Methods 40 stroke patients were randomly assigned to experimental (EG) or control group (CG). Both groups underwent two daily sessions of conventional rehabilitation therapy (CRT) 5 days per week; the EG underwent one rESWT session a week for 4 weeks. The modified Ashworth scale (MAS) tested at the shoulder, elbow, and wrist was used as outcome measure. MAS was evaluated at baseline, after 2 and 4 rESWT session, and one month after the last session (follow-up). Results No significant differences between groups were found at baseline in terms of age, days from onset of spasticity after stroke, and MAS at each body segment. The sample lost eight drop-out patients. Except for the shoulder MAS values, the EG showed statistically significant lower MAS values already after the second rESWT session compared to CG. This significant difference was maintained until the follow-up. The CG showed a significant increase of wrist spasticity after the second evaluation, while the EG maintained constant MAS values throughout the observational period. The elbow spasticity was significantly higher in the CG at the follow-up evaluation. Conclusion The rESWT combined with CRT seems to be effective in avoiding the increasing progression of spasticity after stroke.

The Necessity of a Locally Active Antidote in the Clinical Practice of Botulinum Neurotoxin Therapy: Short Communication.

Recently, it was demonstrated that copper complexes and 3,4-diaminopyridine can effectively reduce the activity of the botulinum neurotoxin light chain. The aim of the present study was to indicate that treatment with an antidote may have a major influence, not only on the extremely rare disease of botulism, but also on the much more frequently occurring side effects experienced during BoNT therapy. This was a retrospective chart review of patients who were regularly treated with BoNT for various indications. The percentage of patients with clinical signs of overdosing was determined. In patients with facial dystonia, double vision and ptosis occurred as side effects. In patients with cervical dystonia, neck weakness and dysphagia were observed as the most frequent side effects. In oromandibular and oropharyngeal dystonia, abnormal tongue movements and dysphagia occurred frequently. In writer’s cramp and mild post-stroke hand spasticity, severe paresis of the injected and non-injected finger muscles was observed. Additionally, in the BoNT treatment of pain syndromes (such as tension headaches or migraines), neck weakness may occur. Across all indications for clinical BoNT applications, clinical signs of BoNT overdosing may occur in up to 5% of the BoNT-treated patients. Therefore, the development of an antidote for BoNT overdoses would be very much appreciated and would have a major influence on the management of BoNT therapy.

Practical value and thought on "co-regulation of body and mind" in treatment of post-stroke spasticity with acupuncture

This paper reviews the application of "co-regulation of body and mind" of acupuncture for post-stroke spasticity. It is found that acupoints on the head and the back of the governor vessel, as well as Jiaji (Ex-B 2) points are mainly used for regulating the mind, and the local sites of spastic muscles and the points on the antagonistic muscles are for regulating the body specially. It is believed that regulating the mind should be integrated with regulating the body, while, the acupoint selection be associated with needling methods so as to fully achieve the "co-regulation of body and mind" and enhance the practical value of acupuncture for post-stroke spasticity. It is proposed that the classical anti-spastic needling techniques, such as huici (relaxing needling) and guanci (joint needling), should be more considered.

A Practical Post-Stroke Elbow Spasticity Assessment Using an Upper Limb Rehabilitation Robot: A Validation Study.

Spasticity is a motor disorder characterised by a velocity-dependent increase in muscle tone, which is critical in neurorehabilitation given its high prevalence and potential negative influence among the post-stroke population. Accurate measurement of spasticity is important as it guides the strategy of spasticity treatment and evaluates the effectiveness of spasticity management. However, spasticity is commonly measured using clinical scales which may lack objectivity and reliability. Although many technology-assisted measures have been developed, showing their potential as accurate and reliable alternatives to standard clinical scales, they have not been widely adopted in clinical practice due to their low usability and feasibility. This paper thus introduces an easy-to-use robotic based measure of elbow spasticity and its evaluation protocol. Preliminary results collected with one post-stroke patient and one healthy control subject are presented and demonstrate the feasibility of the approach.