Spasticity Research Articles (Page 1)

Introduction: The impact of global ischemia and reperfusion on the brain in resuscitation animal models is well investigated whereas the spinal cord and its protection are rarely reported. We investigated the spinal cord in our ventricular fibrillation cardiac arrest (VFCA) extracorporeal cardiopulmonary resuscitation (eCPR) rat model and hypothesized that an untreated VFCA of 8 minutes will lead to dysfunction and histological damage in the spinal cord and that treatment with hypothermic temperature (HT) control for 12 hours to 33°C will minimize these pathological findings. Methods: Adult male Sprague-Dawley rats (n=16, 400-800 g) were subjected to 8 min of VFCA and resuscitated with eCPR and drugs (epinephrine, bicarbonate, heparin). After defibrillation and restoration of spontaneous circulation (ROSC), rats were randomized in normothermic (NT) (n=9) and HT group (n=7). After 24h of survival the neurologic damage score (NDS, 0-100%) was assessed and the spine was fixed in formalin. The spinal cord was removed after fixation and cervical, thoracic, and lumbar transverse sections were embedded in paraffin. Hematoxylin and Eosin (HE)-staining and immunohistochemistry with an antibody against Iba1 were performed. Sections were evaluated in a semiquantitative way (mild, moderate, marked lesions) and compared to sham animals (n=7) by a pathologist blinded to treatment regimens. Results: All animals achieved ROSC, but two NT animals died before the study endpoint. NT animals showed consistent spastic paralysis of all extremities and urinary retention, while motoric function was improved in the HT group. Accordingly, the NDS in the HT group was significantly better compared to the NT group (HT Median 26 [IQR11] % / NT Median 40 [IQR16] % (p-value = 0.014)). In HE-staining, four of seven HT animals showed scattered to mild neuronal necrosis (NN) in the gray matter. In contrast, all animals of the NT group showed moderate to marked NN, which is a significant increase compared to both, the HT group and the sham group. In both VFCA groups activation of microglia was significantly increased compared to sham. Conclusions: We found consistent NN in the spinal cord of rats kept under normothermic conditions for 24h after 8 min of untreated VFCA and eCPR. In the HT group these lesions were significantly reduced, which correlates with the neurological outcome. However, the microglial reaction after this short survival time did not differ between the VFCA groups.

Stroke-related long-term disability is primarily due to impaired motor function. Rehabilitation efforts have traditionally focused on central strategies while ignoring the affected muscles. Regenerative medicine approaches have emerged as a promising option for treating various conditions, including muscular disorders. The present study aims to compare the effects of intramuscular injections of mesenchymal stromal cells (MSCs) and Platelet-rich plasma (PRP) on motor recovery in poststroke survivors. A single-blind, randomized, controlled trial will be followed. Fifteen stroke patients who meet the eligibility criteria will be randomly assigned to the cell therapy, PRP, or waiting-list control groups. Patients in each group will receive a single injection of MSCs or PRP into their affected biceps brachii muscle. Patients in the waiting list control group will receive no intervention. The outcome measures include the Modified Modified Ashworth Scale (MMAS), Brunnstrom recovery stages for the upper limb, elbow range of motion, and sonographic evaluations. All outcome measures will be assessed at baseline, 1, 2, and 3 months after injection. The findings of this study will provide initial supportive evidence regarding the efficacy of MSCs and PRP therapy in improving biceps brachii muscle spasticity and function in patients with chronic stroke. IRCT20230208057351N1.

This meta-analysis attempted to rigorously delineate the efficacy of intermittent theta burst stimulation (iTBS) as a neuromodulatory intervention for post-stroke motor impairments by integrating evidence exclusively from randomized controlled trials (RCTs). Seven databases, namely, PubMed, Web of Science, Embase, the Cochrane Library, Wanfang, VIP, and China National Knowledge Infrastructure (CNKI), were searched. Eligible studies covered RCTs that directly compared the influences of iTBS with sham or placebo interventions in cases recovering from stroke. Two independent reviewers conducted screened the studies, extracted the data, and assessed the risk of bias. Primary outcome measures involved the Fugl-Meyer Assessment (FMA), Barthel Index (BI), and Berg Balance Scale (BBS). The Modified Ashworth Scale (MAS), assessing muscle tone and spasticity, was regarded as a secondary outcome. A random-effects model was employed to account for between-study variability. Totally, 19 RCTs satisfied inclusion criteria, collectively substantiating that iTBS yields statistically and clinically significant improvements in upper extremity motor control (FMA), static balance capacity (BBS), functional independence in activities of daily living (BI), and fine motor performance assessed by the Action Research Arm Test (ARAT) relative to control interventions. Conversely, the meta-analysis revealed a lack of significant benefit of iTBS on lower limb motor outcomes, dynamic mobility as assessed by the Timed Up and Go (TUG) test, and neuromuscular tone measured by the MAS. iTBS exhibited a significant therapeutic benefit in boosting the motor function in the upper limbs, assessed by the FMA, as well as static balance, activities of daily living, and performance on the action research arm test in stroke rehabilitation. However, its influences on lower limb motor function, muscle spasticity (as assessed by the MAS), and dynamic balance could be limited and not statistically significant.

Acupuncture waggle needling alleviates spastic movement disorder in post-stroke rats via GLT-1 activation to modulate Glu/GABA-Gln cycle.

Pediatric torticollis, predominantly resulting from congenital muscular torticollis, is characterized by unilateral shortening of the sternocleidomastoid muscle, leading to head tilt and limited cervical mobility. Conventional management primarily involves physical therapy and repositioning strategies, with most infants achieving full recovery. However, a subset of patients exhibits persistent symptoms despite conservative treatment. Botulinum toxin type A (BoNT-A) has emerged as a minimally invasive adjunct intervention that targets muscular hypertonicity by inhibiting acetylcholine release at neuromuscular junctions. This scoping review synthesizes clinical evidence from six studies, including randomized controlled trials and case reports, assessing the efficacy and safety of BoNT-A in pediatric torticollis. Results indicate consistent improvements in range of motion, head posture correction, and patient satisfaction, with rare and mild adverse events such as local bruising and transient muscle weakness. Despite promising outcomes, variability in dosing, injection protocols, and follow-up durations underscores the need for standardized treatment guidelines and further high-quality research. These findings support BoNT-A as a valuable therapeutic option for refractory pediatric torticollis, warranting integration into multidisciplinary care frameworks.

Novel efficacy evidence and mechanistic explorations of motion-style scalp acupuncture in post-stroke muscle spasticity management: Systematic review and meta-analysis of randomized controlled trials.

The article highlights that cerebral palsy is a disorder of the nervous system characterized by persistent motor impairments and postural abnormalities resulting from brain damage at the early stages of its development. In Ukraine, there is a growing number of children diagnosed with this pathology, which determines the need for effective programs of physical culture and sports rehabilitation. Particular attention is paid to enhancing the functional independence and social adaptation of primary school-aged children with cerebral palsy in specialized rehabilitation centers for persons with disabilities. The study emphasizes that physical culture and sports rehabilitation of preschool children with cerebral palsy is an urgent issue that includes a complex set of tasks and provides opportunities to significantly improve the physical and psycho- emotional state of patients, facilitating their adaptation to social needs. The developed program of physical culture and sports rehabilitation is based on the principles of individualization, an interdisciplinary approach, and the active participation of the child in the recovery process. The program includes aquatic exercises, massage techniques (classical, segmental, and acupressure), breathing exercises, as well as the use of modern computerized simulators Tera-vital and Tera-balance, which contribute to the development of coordination skills, reduction of muscle spasticity, and improvement of balance. During the sessions, a pedagogical concept of motor function development is implemented, aimed at fostering independence, initiative, and positive motivation for physical activity.

This study analyzed the changes in the composition of thin filaments in spastic muscles after stroke to investigate the mechanism underlying changes in the sarcomeres. Twenty-four rats were randomly divided into four groups: normal, and 3, 6, and 9 days after stroke. A model of post-stroke gastrocnemius muscle spasm was created. Quantitative proteomic procedure and bioinformatics analysis revealed significant changes in cytoskeletal protein expressions in gastrocnemius muscles of each stroke group, particularly those on thin filaments. On the 3rd day after stroke, proteins upregulated within the thin filaments included actin-binding LIM protein 1, tropomyosin 3, leiomodin 2, drebrin-like protein, parvin beta, capping actin protein-gelsolin like, actinin alpha 2, and PDZ-LIM-domain protein 1, while downregulated proteins included tropomyosin 1, gelsolin, actinin alpha 3, and PDZ-LIM-domain protein 7. On the sixth day, upregulation of tropomyosin 2 was newly added while parvin alpha, destrin, PDZ-LIM-domain protein 3, leiomodin 3 were downregulated. On the 9th day, actinin alpha 2, PDZ-LIM-domain protein 7, and cofilin 2 were downregulated. These altered proteins are capable of promoting actin filament elongation and regulating Z-disc growth, and changes in their expression may be responsible for the changes in spastic muscle sarcomere after stroke.

Cerebral palsy (CP) is a condition that often presents with altered muscle tone affecting function. The purpose of this case report is to describe the clinical application of transcutaneous electrical nerve stimulation (TENS) to manage the impact of muscle tone during gait in 2 children with CP. Two children with CP, who are gait, received TENS to manage spasticity and dystonia. Gait was analyzed using a two-dimensional gait analysis with and without TENS. Results demonstrated medium and large minimally clinically important differences in velocity, cadence, and stride length with TENS. Using TENS parameters may be a modality to manage tone and improve gait for children with CP. A larger study is needed to determine the effects of TENS. Clinicians may use TENS on spastic or dystonic muscles as an intervention to improve gait for children with CP.

Background: Konzo is a neurological disorder caused by prolonged consumption of poorly processed bitter cassava, leading to upper motor neuron damage and spastic paralysis. Nutritional deficiency, particularly low sulphur amino acids, exacerbates cyanide toxicity. This study evaluated the effects of bitter cassava and dietary rehabilitation on body weight, motor performance, muscle mass, and cerebral cortex histology in Wistar rats. Methods: Twenty-five female Wistar rats were randomly assigned to five groups (n=5): control, cassava only, cassava + animal feed, cassava + eggshell and brown beans, and eggshell and brown beans only. Rats were fed for four weeks, with body weight measured weekly. Motor function was assessed using the single-pellet reach-to-grasp task. Muscle wet weight (biceps and flexor carpi radialis) was determined post-dissection, and cerebral cortex histology was analyzed using Nissl staining. Data were analyzed with ANOVA and Tukey’s post hoc test (p < 0.05). Results: Cassava-only rats showed weight loss (−2.94%), decreased reach-to-grasp success (46.92 ± 5.07%), and mild muscle atrophy. Dietary supplementation improved outcomes: cassava + animal feed rats gained +9.77% body weight and showed enhanced motor performance (+8.11%), while cassava + eggshell and brown beans rats demonstrated +12.13% improvement in reach-to-grasp and increased muscle mass (biceps: 0.20 ± 0.02 g; flexor carpi radialis: 0.20 ± 0.01 g). Histology revealed disorganized cortical layers, pyknotic pyramidal cells, and chromatolysis in cassava-only rats, whereas amino acid supplementation largely restored cortical cytoarchitecture. Conclusion: Poorly processed bitter cassava induces neurotoxicity, motor deficits, and muscle atrophy in rats. Sulphur amino acid-rich diets mitigate these effects and promote neuronal restoration. Proper cassava processing and dietary protein supplementation are crucial to prevent Konzo.

Friedreich's ataxia is a rare, neurodegenerative, multisystem disorder. While ataxia is a hallmark, non-ataxia signs, including muscle weakness, spasticity, and dysphagia are equally disabling. The Inventory of Non-Ataxia Signs (INAS) is a symptom list transformable to a 16-item count. To evaluate the responsiveness of a modified INAS in this population. Participants were drawn from the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS). The modified INAS count (presence/absence, 0-16 scale) and modified INAS sum (severity-weighted, 0-84 scale) were evaluated using linear mixed-models and standardized response means (SRMs). Items rare (<5%) and uncharacteristic in Friedreich's ataxia were excluded (chorea, myoclonus, fasciculations, resting tremor, rigidity) RESULTS: A total of 1129 participants (mean age, 32.3 years) were assessed for up to 12 years. The mean modified INAS count was 4.6 (±2.2) and modified INAS sum 15.1 (± 9.9). Both correlated strongly with existing outcome measures. Longitudinally, the modified INAS count increased by 0.13 points/year (95% CI 0.12, 0.14; P < 0.001) and modified INAS sum by 0.68 points/year (95% CI 0.64, 0.72; P < 0.001). The modified INAS sum demonstrated greater responsiveness, with SRMs of 0.26, 0.38, 0.53, and 0.80 at 1, 2, 3, and 5 years, respectively, compared with 0.16, 0.27, 0.31, and 0.46 for the modified INAS count. In non-ambulatory patients and children, responsiveness of the modified INAS sum was higher (SRM 0.82 and 1.7 at 5 years, respectively). The modified INAS sum showed good responsiveness over 5 years but not over 1-3 years. It may supplement existing outcome measures, contributing to holistic assessment of this multisystem disease, especially in non-ambulatory patients, in whom ataxia-focused measures may show ceiling effects, and children, who typically progress faster. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Spasticity results from upper motor neuron lesions and can create a deforming force and pain, and is often accompanied by contracture. Although the origin of spasticity is neural, there is ample evidence of secondary muscle changes. Here, we use direct measurement of the force-frequency relationship (FFR) to characterize human muscle's physiological properties. This study directly quantified the FFR of both healthy and spastic human skeletal muscles. Muscle force was measured intraoperatively in healthy gracilis (n = 13; aged 39.4 ± 10.6 yr; surgery due to brachial plexus injury) and spastic biceps brachii muscle (n = 8; aged 53.3 ± 10.3 yr; surgery due to stroke or traumatic brain injury). Nerve stimulation was applied at frequencies ranging from 1 to 70 Hz. Twitch contraction parameters, including time to peak tension (TPT) and half-relaxation time (HRT), were also compared. The FFR of the two muscles was modeled with sigmoid functions, and differences between muscles were assessed with an extra sum-of-squares F test. TPT did not significantly differ between groups (P = 0.12), whereas HRT was prolonged in the spastic biceps (P < 0.05). Despite small differences in twitch kinetics, both muscles exhibited nearly identical FFR profiles. This study represents the first direct in vivo report of spastic human muscle kinetic properties and shows that these contractile kinetics are similar in healthy and spastic muscles. This may suggest that there are no dramatic calcium handling or myosin heavy chain changes in the biceps muscle secondary to spasticity.NEW & NOTEWORTHY This study presents the first in vivo intraoperative measurement of the kinetic properties of spastic human muscle. Despite slower relaxation in spastic biceps, the force-frequency relationship was similar to that of the healthy gracilis muscle. This suggests that spasticity does not substantially alter frequency-dependent force summation, possibly due to similar fiber-type compositions and limited changes in calcium handling or myosin isoforms in human spastic muscle.

Gait alterations following a one-year surgical deferral in children with cerebral palsy exhibiting flexed knee gait.

The effect of mechanical digit sensory stimulation on upper limb motor function recovery in convalescent stroke patients with hemiplegia.

Hyperselective neurectomy (HSN) involves transection of most terminal nerve branches supplying a spastic muscle with subsequent recovery of strength resulting from collateral regeneration of spared motor neurons. However, the underlying mechanisms driving spasticity reduction have not been defined. This study aimed to address this knowledge gap and compare the efficacy of HSN to other forms of nerve injury as a therapy for spasticity in a rodent model of spinal cord injury. Six weeks after T8 spinal transection, rats (n=90) were randomized into 5 groups: sham (n=18), HSN of the nerves to gastrocnemius and soleus (n=17), transection-without-repair (n=18), transection-with-repair (n=19) and crush (n=18) of the tibial nerve. Muscle resistance, modified-Ashworth scale (MAS) and changes in spindle innervation and VGLUT1 density in the spinal cord were analyzed at 2- and 12-weeks post-nerve injury. At 12 weeks, muscle resistance and MAS scores were reduced in transection-with-repair, but not HSN. Reinnervated muscle spindles in both groups presented with atypical morphology. VGLUT1 density representing Ia afferent synapses in the spinal cord was not different between groups. Nerve transection with primary epineural repair demonstrated enhanced long-term spasticity reduction in spinal cord-injured rats. However, differences in functional synapses on spinal cord motor neurons between groups were not found. Loss of the stretch reflex may alternatively be explained by atypical muscle spindle morphology or central processing in a spinal cord injury cohort. Future studies are needed to further elucidate how peripheral nerve injury modulates disruption of the stretch reflex and treatment of spasticity.

Some pseudoscorpions produce venom to subdue prey and their venom components may be of translational interest in agronomy and beyond. However, only very few pseudoscorpion venom peptides have been functionally characterized as of yet. Here, we carry out a bioactivity profiling of Ammogarypin, a linear venom peptide recently identified in the venom of Ammogarypus lawrencei. We show, that the peptide causes signs of spastic paralysis and fatalities when injected in Drosophila suzukii flies and low toxicity when injected in Myzus persicae aphids, while no effects were recovered when fed to both insects. The toxin further has marginal effects on growth of E. coli and S. aureus bacteria and no effect on the viability of mammalian MDCKII cells and equine erythrocytes. While our assessment revealed low potential for agricultural translation of the peptide, our data shows that Ammogarypin appears to fulfill a function in prey capture. In contrast to other linear pseudoscorpion toxins, it seems to serve only a single biological function and does not defend the venom gland against microbial colonization, nor serving as spreading factor. This study adds to the growing body of literature revolving around the biodiscovery and biochemical ecology of pseudoscorpions, some of earths smallest and least understood venomous animal lineages.

Diethylcarbamazine is a classic anthelmintic that is used for the prevention and treatment of lymphatic filariasis. The mode of action of diethylcarbamazine is still not well understood with the consensus that it acts on the host immune system, rather than directly acting on the adult parasite. Recent studies, have found that diethylcarbamazine acts on the muscle of adult female Brugia malayi, generating temporary spastic paralysis mainly through the Transient Potential Receptor C (TRPC) orthologue TRP-2. Activation of TRP-2 leads to inward currents on the muscle, an increase in intracellular calcium and subsequent muscle contraction. These studies have demonstrated that Brugia malayi TRP-2 is activated by diethylcarbamazine. In this study, we heterologously expressed the Brugia malayi TRP-2b channel in the Human Embryonic Kidney (HEK) 293 cell line. Application of diethylcarbamazine to Bma-trp-2b transfected HEK293 cells leads to larger and more frequent increases in intracellular calcium compared to non-transfected cells. This increase can be inhibited using the TRPC specific antagonist SKF96365. Our study shows that diethylcarbamazine’s action is dependent upon the Brugia malayi TRP-2 channel and may also, in addition, activate endogenous mammalian TRP channels.

Stroke and traumatic brain injury lead to upper motor neuron syndrome, which is characterized by muscle spasticity or paresis of varying severity depending on the lesion's location and extent. Current treatments are mostly symptomatic with limited efficacy and significant side effects. Nerve transfer techniques, such as the contralateral L4 ventral root transfer in animal models and C7 root transfer in both animal and clinical studies, have been shown to reduce spasticity and improve function in upper motor neuron syndrome; however, they lack selectivity. Our hypothesis is that using a selective peripheral donor nerve from the contralateral side, rather than the entire nerve root, may represent an effective nerve transfer and provide a robust basis for future research on selective muscle reinnervation in upper motor neuron syndrome. Ten rats underwent a contralateral ulnar-to-ulnar nerve transfer procedure. Electrophysiological measurements were conducted twelve weeks post-surgery to assess successful reinnervation of the contralateral flexor carpi ulnaris muscle. Additionally, muscle biopsies of the reinnervated flexor carpi ulnaris were harvested to examine the muscle fiber type composition, cross-sectional area, and collagen content as well as compare them to naive counterparts. Axon quantification of the reinnervated nerves was also performed. All rats recovered uneventfully, maintaining the use of both paws post-surgery. Electrophysiological tests confirmed the successful reinnervation of the flexor carpi ulnaris muscle. Muscle fiber type composition, cross-sectional area, and collagen content did not show statistically significant changes. Axon counts indicated successful nerve regeneration without architectural disruption. In conclusion, we were able to demonstrate this novel contralateral nerve transfer model's feasibility, reproducibility, and safety as well as achieve effective muscle reinnervation. This model provides a valuable tool for further research on selective muscle reinnervation and treatment of upper motor neuron syndrome, with potential implications for improving clinical outcomes in stroke and traumatic brain injury patients.

We aimed to assess whether spinal motoneurons received and sent the same neural information during involuntary and voluntary activation following stroke. High-density surface electromyography (HD-sEMG) signals of biceps brachii muscle were recorded, while 14 stroke survivors and 10 age-matched controls performed passive stretch and active contraction. Populational motor unit (MU) activity was extracted from HD-sEMG recordings with decomposition algorithms. The MU discharge rate, discharge variability and spatial distribution of MU action potentials (MUAP) were used to detect neural drive to muscles. The cross-correlation analysis between MU discharge timings was performed to detect common synaptic input (CSI) to motoneurons. In stroke survivors, involuntary activation exhibited higher discharge rate and lower discharge variability than voluntary activation (18.41 ± 2.05 Hz vs. 14.99 ± 1.50 Hz, p = 0.000, d = 1.392; 0.04 ± 0.02 vs. 0.12 ± 0.04, p = 0.000, d = 1.775). The opposite MUAP distribution patterns were observed between involuntary and voluntary activation (lateral-medial: 3.91 ± 1.01 vs. 4.85 ± 0.57, p = 0.000, d = 1.304; distal-proximal: 5.16 ± 0.80 vs. 4.01 ± 0.73, p = 0.001, d = 1.222). CSI was lower in involuntary activation than voluntary activation (0.42 ± 0.07 vs. 0.55 ± 0.08, p = 0.004). The discharge variability was significantly positively correlated with CSI. Our decoding results demonstrated that information flow between supraspinal and spinal cord was unbalanced following stroke. The determinants of MU discharge in reflex activity depend more on intrinsic properties of spinal motoneurons than on brain.

Intrathecal monovalent fragments from two human monoclonal antibodies block tetanus neurotoxin in rodents