Spasticity In Multiple Sclerosis Research Articles

Effectiveness, Safety and Patients’ Satisfaction of Nabiximols (Sativex®) on Multiple Sclerosis Spasticity and Related Symptoms in a Swiss Multicenter Study

Background: Cannabinoid oro-mucosal spray nabiximols is approved for patients with moderate to severe multiple sclerosis spasticity (MSS) resistant to other antispastic medications. Few real-world data are available on the effectiveness, safety and patients’ satisfaction in MS patients treated with nabiximols as monotherapy. Methods: To investigate the effectiveness, tolerability and satisfaction of nabiximols in a real-life multicentric Swiss cohort as monotherapy or with stable doses of other antispastic medications, and explore clinical features which may predict treatment response. The following data were collected at treatment start (baseline) and 12 weeks thereafter: Modified Ashworth scale (MAS), scores at numerical rating scales ranging from 0 (absent) to 10 (considerable) for effect on spasticity (sNRS), pain (pNRS), gait (gNRS), urinary symptoms (uNRS), tolerability (tNRS) as assessed by the treating neurologist, and overall treatment satisfaction (TsNRS) and tolerability (tNRS) as assessed by the patient. Results: Ninety-five patients (44 relapsing remitting, 37 secondary progressive and 14 primary progressive MS; median age = 53 (IQR 45–62); female 70%; median EDSS 6 (IQR 4–6), concomitant antispastic treatments in 54% of patients) were included. From baseline to week 12, median MAS score decreased from 3.0 to 2.0 (p < 0.001). Median scores of the each NRS also significantly decreased (p < 0.001 for all comparisons). At week 12, the median TsNRS and tTS scores were 8/10 (IQR: 6–9) and 9/10 (IQR: 7–10), respectively, and 93.7% of patients continued to use nabiximols at the average dose of six sprays/day. No clinical factors, including use of nabiximols as add on vs. monotherapy, were associated with responder status. Conclusions: Our first Swiss, multicentric, observational, real-life study supports and enhances previous finding of nabiximols as monotherapy and as add-on therapy, being an effective, safe and well-tolerated treatment option for resistant MS spasticity and spasticity-related symptoms (pain, bladder dysfunction and gait).

Chitosan-based buccal mucoadhesive bilayer tablets enhance the bioavailability of tizanidine hydrochloride by bypassing the first-pass metabolism

Tizanidine hydrochloride (TZN) is an antimuscarinic agent used in the treatment of pain-related spasms, multiple sclerosis, and stroke-related spasticity. It has low oral bioavailability (40 %) due to excessive first-pass metabolism in the liver. The aim of this project was to enhance the systemic bioavailability of TZN by developing buccal mucoadhesive bilayer tablet formulations using chitosan salts with molecular weights of 136 kDa (7 cP) and 169 kDa (10 cP). Structural characterisation of chitosans and their salts was performed by FTIR, 1H NMR, DSC, TGA, and XRD analyses. Soluble chitosan salts, chitosan glutamate and chitosan chloride, for the adhesive layer, and insoluble ethyl cellulose for the impermeable backing layer were selected as polymers to fabricate the buccal tablets by direct compression method. The tablets containing TZN demonstrated high swelling and good mucoadhesion characteristics as well as released all the drug within 8 h. While TC10, formulated with 10 cP chitosan chloride, showed the highest swelling properties, TG10, prepared with 10 cP chitosan glutamate, exhibited the highest mucoadhesion. Chitosan glutamate tablets (TG7 and TG10) demonstrated better mucoadhesive characteristics and stability than chitosan chloride ones (TC7 and TC10) in the buccal medium based on the results of swelling and drug release studies. The permeability studies performed by Franz diffusion cell demonstrated that the amount of TZN passing through the bovine buccal mucosa was between 13.4 and 14.4 %. Stability studies conducted at 5 ± 2 °C, 25 ± 2 °C and 40 ± 2 °C for 6 months showed that no changes in the content uniformity and pH were observed. The in vivo comparative bioavailability studies in female New Zealand rabbits were performed and TZN-containing buccal mucoadhesive bilayer tablets fabricated with both chloride (TC10) and glutamate (TG10) salts of chitosan demonstrated three times higher bioavailability than the commercial TZN product (Sirdalud® oral tablet) administered by the gastrointestinal route.

Recognition, Description, and Variability of Spasticity in Individuals With Multiple Sclerosis and Potential Barriers to Clinician-Patient Dialogue: Results From SEEN-MSS, a Large-Scale, Self-Reported Survey.

The experience with spasticity varies among individuals with multiple sclerosis and spasticity (MSS), as they may not recognize it as spasticity or have the language to describe their symptoms. This can lead to potential delays in diagnosis and treatment. Symptoms and Emotions Exploration Needed in Multiple Sclerosis Spasticity was an online survey completed by 1177 individuals with MSS in 2021. It sought to capture symptoms of spasticity, variability of symptoms, specific spasticity triggers, and how conversations with physicians were initiated. The mean age of the cohort was 56.8 years and it was 78% women. Prior to spasticity onset, 65% of respondents felt minimally prepared or unprepared for possibly developing spasticity and were unaware that spasticity manifests as part of MS. Eighty percent experienced spasticity daily, which was variable in severity and duration. Spasticity was triggered by a range of factors and 90% of those surveyed were unable to predict when it would occur or its severity. Day-to-day variability of spasticity prevented 65% of respondents from doing things they wished to do. Sixty percent were confused by their symptoms, not recognizing them as spasticity. Although 91% reported experiencing muscle spasms, only 69% used "muscle spasms" to describe their symptoms. Other descriptors included "muscle tightness," "stiffness," "cramping," and "pain." After recognizing spasticity, 78% proactively initiated discussions with their physicians, 52% wished they had done so sooner, and 42% delayed the conversation by up to or more than a year. Results emphasize the variable nature of spasticity and the lack of a common language to describe symptoms, underscoring the importance of education, earlier recognition, and customized treatments tailored to the severity and duration of spasticity symptoms.

The Use of Long-Arm Serial Casting to Manage Multiple Sclerosis Spasticity: A Case Report

Abstract Spasticity is common among individuals with multiple sclerosis (MS) and can have negative implications. Casting is a treatment intervention that is used to manage spasticity. The use of casting has been studied in individuals with brain injury and stroke, but no publications were found for its use in persons with MS. An individual with MS with upper extremity spasticity participated in long-arm serial casting, bivalve cast fabrication, and additional targeted therapeutic interventions over the course of 17 visits. Spasticity, pain, strength, passive range of motion (PROM), skin, and function were assessed. Spasticity and PROM improved. Increased strength was found in shoulder flexion, elbow flexion/extension, and supination. Active range of motion with resistance was possible and pain-free after the intervention for abduction, horizontal abduction, horizontal adduction, and external rotation. Furthermore, increased functional use including feeding, dressing, and bathing was achieved.

Stretching is not essential for managing MS spasticity: A randomized controlled trial

Background: Clinical practice, expert opinion, and evidence-based guidelines recommend daily stretching as first-line treatment for multiple sclerosis (MS) spasticity, but this has not been evaluated by fully powered clinical trials. Objective: To determine whether MS Spasticity: Take Control (STC), a guideline-based program of spasticity education and stretching exercises has different effects on the impact of spasticity than a control program of different spasticity education and range of motion (ROM) exercises. Methods: Ambulatory people with self-reported MS spasticity were randomly assigned to STC or ROM, delivered in same duration, facilitator-led, group classes, face-to-face (F2F) initially and later virtually, due to coronavirus disease 2019 (COVID-19). Multiple Sclerosis Spasticity Scale (MSSS) scores were compared between groups at 1 (primary outcome) and 6 months after interventions. Results: A total of 231 people enrolled. There was no significant difference in MSSS scores between STC and ROM at 1 month (mean difference = 0.28, 95% (confidence interval (CI)) = [−9.45 to 10.01], p = 0.955). There were significant group mean improvements in MSSS scores and most other outcomes at 1 and 6 months. Conclusion: Education with stretching exercises, the first-line recommended treatment for MS spasticity, and education with ROM exercises may both improve MS spasticity to a similar degree. This study debunks the belief that stretching is essential to managing MS spasticity.

Nabiximols is Efficient as Add-On Treatment for Patients with Multiple Sclerosis Spasticity Refractory to Standard Treatment: A Systematic Review and Meta-Analysis of Randomised Clinical Trials.

Spasticity affects 54% of multiple sclerosis (MS) patients at disease onset, but this rate gradually increases with disease progression. Spasticity does not fully respond to standard treatment in one-third of the patients. Our systematic review and meta-analysis assessed whether add-on nabiximols, can improve MS-associated refractory spasticity. The systematic literature search was performed in Web of Science, MEDLINE, Scopus, CENTRAL, and Embase, on 15/10/2021, without restrictions. We included in the review blinded, randomized, placebo-controlled trials evaluating the efficacy of nabiximols in adult MS patients with refractory spasticity, by comparison with placebo. The primary outcome was responder rate by spasticity numerical rating scale (NRS). Secondary outcomes were spasticity-related parameters. We used random effect models to calculate odds ratios (OR) or mean differences and the corresponding 95% CI. Bias-factors were assessed with Cochrane risk of bias tool (RoB2). (PROSPERO ID: CRD42021282177). We identified 9 eligible articles, of which 7 (1128 patients) were included in the meta-analysis. The spasticity numerical rating scale (NRS) was significantly higher in the nabiximols group than in the placebo group (OR 2.41 (95% CI 1.39; 4.18)). Secondary outcomes were in accordance with our primary results. At least some concerns were detected in the risk of bias analysis. Our results indicate that nabiximols is efficient in MS associated spasticity, refractory to standard treatment and it may be considered as add-on symptomatic therapy. Nevertheless, further studies are needed to establish the optimal treatment protocol - dose, duration, moment of initiation, disease type.

Regulation and control of the use of Cannabis and Cannabidiol in „novel foods”

Cannabis sativa L. is a medicinal plant from family Cannabaceae with many pharmacological activities. The recent appearance of a number of cannabis products in the pharmaceutical market has led to increased requirements for regulation and quality control. The control of Cannabis sativa L. is subject to the Psychotropic Substances Convention, which includes the addictive psychoactive delta-9-tetrahydrocannabinol (THC), and to the Narcotic Drugs Convention, which includes the illicit products: herbal and liquid cannabis, resin, extracts and tinctures of flowering or fruiting tops containing THC. Approved by the FDA for use in chemotherapy are Marinol caps. (THC) and Cesamet caps., containing the synthetic THC-derivative Nabilon. There is no harmonized European Union legislation on the use of cannabis and Cannabidiol (CBD), which antagonizes the THC-psychotropic effect. Legitimate products include seeds, oil, extracts, and seed tinctures of the industrial cannabis chemotype, containing primarily Cannabidiol and less than 0.2% THC. Sativex oral spray (THC/CBD = 1:1) is approved for muscle spasticity in multiple sclerosis. Cannabidiol was not used as a food ingredient in the European Union before 15.05.1997 and is a „novel food” according to Regulation 2015/2283. Flour; protein powder and cannabis seed oil are not „novel foods”. Cannabidiol as Epidiolex is FDA approved for epilepsy forms Lennox-Gastaut and Dravet.

Marijuana: Forensics of Abuse, Medical Uses, Controversy, and AI

Motor vehicle accidents are a significant consequence of marijuana abuse. Limitations of its roadside detection and the forensic problems with establishing impairment require innovations that are scientifically achievable. Marijuana abuse currently is at an all-time high in the United States and its physiological effects make it a popular recreational drug that is reported to be a leading cause of preventable morbidity and mortality among the youth in the 18 most affluent nations. The medical benefits of drugs derived from marijuana complicate its forensic regulation. In an extensive 2017 report by The American Academy of Sciences, the evidence for the medical benefits of delta-9 tetrahydrocannabinol (derived from marijuana) were stated to be conclusive or substantial for the treatment of chronic pain in adults, as an antiemetic for treatment of chemotherapy-induced nausea and vomiting, and for improving patient-reported multiple sclerosis spasticity symptoms. The benefits from treatment for many other medical conditions were inconclusive or absent. The evidence is clear that safely driving a motor vehicle is significantly impaired while under the influence of marijuana. However, there is no roadside forensic test that reliably detects impairment, and there is an urgent need for such to protect the public while insuring the legal rights of users. There is strong societal pressure to relax marijuana’s forensic regulation, including removing it from Schedule I of the Controlled Substances Act. Artificial intelligence (AI) should be implemented with appropriate human control to resolve controversies.

Development of an integrated conceptual model of multiple sclerosis spasticity

Purpose Spasticity is common in multiple sclerosis (MS), often leading to functional limitations and disability. We developed a conceptual model of spasticity in MS integrating expert opinion, recent literature, and experiences of clinicians and people with MS spasticity. Methods A conceptual model was developed based on a targeted literature review of articles published between 2014 and 2019, followed by input from clinicians, then input from participants with MS spasticity. Multidisciplinary experts on spasticity provided guidance at each step. Results Key concepts of the integrated spasticity conceptual model included: moderators; triggers; modifiers; treatment; objective manifestations; subjective experience; physical, functional, social, and emotional/psychological impacts; and long-term consequences. Participants with MS spasticity most frequently endorsed spasms, tightness, and pain as descriptors of spasticity. Some participants with MS spasticity had difficulty distinguishing spasticity from other MS symptoms (e.g. muscle weakness). Some triggers, emotional/psychological impacts, and long-term consequences of spasticity reported by participants with MS spasticity were not previously identified in the published literature. Conclusions This conceptual model of spasticity, integrating published literature with the experience of clinicians, people with MS spasticity, and experts, demonstrates the complex, multidimensional nature of MS spasticity. This model may be used to improve clinician–patient dialogue, research, and patient care.

Assessment of Impact of Spasticity on Activities of Daily Living in Multiple Sclerosis Patients from Saudi Arabia: A Cross-sectional Study

Introduction: Multiple sclerosis (MS) is a chronic progressive autoimmune disease with several symptoms, including spasticity. This study aimed to illustrate the impact of spasticity on the daily activities of MS patients. Subjects and Methods: A cross-sectional study was conducted using a self-administered questionnaire consisting of demographic, clinical characteristics, and MS spasticity scale. A total of 286 patients from Saudi Arabia participated in this study. Results: Muscle stiffness occurring due to spasticity in most cases does not bother the patient, except for muscle tightness (32.9%) and stiffness when staying in the same position for a long time (36.7%), which cause extreme discomfort to the patients. Five items of pain and discomfort have been reported to extremely bother the patients (28.0-33.6%). The highest percentage of patients claimed not to be affected by muscle spasm items (29.4%-66.1%), including activities of dressing and sleeping (36.7%-57.7%). More than 30% of the patients found spasticity to affect their walking speed and going up/downstairs. About 36% to 49% did not experience any difficulties with their body movements. The patients also did not exhibit any feelings of discomfort, except for irritation (30.4%) and nervousness (29.4%). Conclusion: MS patients are significantly affected by spasticity, and a considerable percentage of these patients experience problems with their movements and activities.

Repetitive transcranial magnetic stimulation for treatment of limb spasticity following multiple sclerosis: a systematic review and meta-analysis.

Pilot trials have suggested that repetitive transcranial magnetic stimulation (rTMS) may reduce limb spasticity in multiple sclerosis (MS). We carried out the current meta-analysis to synthesize currently available evidence regarding such correlation. Up to November 2022, five international electronic databases (Cochrane CENTRAL, PubMed, Embase, Web of Science, and CINAHL) and four Chinese electronic databases (CBM, CNKI, WanFang Data, and VIP) were systematically searched to identify randomized trials comparing active rTMS and sham stimulation in patients with MS-related spasticity. Two reviewers independently selected studies and extracted data on study design, quality, clinical outcomes, and time points measured. The primary outcome was clinical spasticity relief after intervention. Secondary outcomes included spasticity at the follow-up visit 2 weeks later and post-treatment fatigue. Of 831 titles found, we included 8 studies (181 participants) in the quantitative analysis. Pooled analyses showed that rTMS therapy was associated with significant spasticity relief in the early post-intervention period [standardized mean differences (SMD): -0.67; 95%CI: -1.12 to -0.21], but there was insufficient evidence for rTMS in reducing spasticity at the follow-up visit 2 weeks later (SMD: -0.17; 95%CI: -0.52 to 0.17) and fatigue (SMD: -0.26; 95%CI: -0.84 to 0.31). This evidence supports the recommendations to treat MS-related spasticity with rTMS, but underlines the need for further large randomized trials.

The Efficacy of Spinal Cord Stimulators in the Reduction of Multiple Sclerosis Spasticity: A Narrative Systematic Review.

A systematic review was employed utilizing Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, to analyze all primary clinical data on the efficacy of spinal cord stimulation (SCS) in the treatment of multiple sclerosis (MS) induced spasticity. Databases include: Embase, PubMed, Scopus, Cochrane, and Web of Science. The review included case series, case studies, and clinical trials. Outcomes of interest were spasticity reduction. Grading of Recommendations Assessment, Development and Evaluation criteria was utilized to grade the certainty of evidence. Five hundred thirty-two articles were retrieved following database systematic review. One hundred eighty-eight articles were removed as duplicates utilizing the "Detect Duplicates" function on Rayyan.ai. A further 344 articles were excluded following abstract and title appraisal. As a result, 16 articles were subjected to full text appraisal. The dates of publication ranged from 1973 to 2019. Although a unique modality, there is not enough evidence to support the employment of SCS over current medical standard of care. Further high-quality randomized control trials are required to elucidate SCS's role in MS induced spasticity algorithm.

Arbaclofen extended-release tablets for spasticity in multiple sclerosis: open-label extension study.

Baclofen, a racemic γ-aminobutyric acid B receptor agonist, is commonly used for the management of multiple sclerosis-related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the γ-aminobutyric acid B receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets allow a dosing interval of 12 h and have shown a favourable safety and efficacy profile in early clinical development. A 12-week, randomized, placebo-controlled Phase 3 trial in adults with multiple sclerosis-related spasticity demonstrated that arbaclofen extended-release 40 mg/day significantly reduced spasticity symptoms compared with placebo and was safe and well tolerated. The current study is an open-label extension of the Phase 3 trial designed to evaluate the long-term safety and efficacy of arbaclofen extended-release. In a 52-week, open-label, multicentre study, adults with a Total Numeric-transformed Modified Ashworth Scale score ≥2 in the most affected limb received oral arbaclofen extended-release titrated over 9 days up to 80 mg/day based on tolerability. The primary objective was assessment of arbaclofen extended-release safety and tolerability. Secondary objectives included an assessment of efficacy using the Total Numeric-transformed Modified Ashworth Scale-most affected limb, the Patient Global Impression of Change and Expanded Disability Status Scale. Of 323 patients enrolled, 218 (67.5%) completed 1 year of treatment. Most patients (74.0%) achieved an arbaclofen extended-release maintenance dose of 80 mg/day. At least one treatment-emergent adverse event was reported by 278 patients (86.1%). The most common adverse events were [n patients (%)]: urinary tract disorder [112 (34.7)], muscle weakness [77 (23.8)], asthenia [61 (18.9)], nausea [70 (21.7)], dizziness [52 (16.1)], somnolence [41 (12.7)], vomiting [29 (9.0)], headache [24 (7.4)] and gait disturbance [20 (6.2)]. Most adverse events were of mild-moderate severity. Twenty-eight serious adverse events were reported. One death occurred during the study, a myocardial infarction that was considered by investigators as unlikely to be related to treatment. Overall, 14.9% of patients discontinued due to adverse events, primarily muscle weakness, multiple sclerosis relapse, asthenia and nausea. Evidence of improvement in multiple sclerosis-related spasticity was observed across arbaclofen extended-release dosages. Arbaclofen extended-release treatment (up to 80 mg/day) was well tolerated and reduced symptoms of spasticity in adult patients with multiple sclerosis for 1 year. Clinical Trial Identifier: ClinicalTrials.gov, NCT03319732.

Arbaclofen extended-release tablets for spasticity in multiple sclerosis: randomized, controlled clinical trial.

Baclofen, a racemic GABA-B (GABAB) receptor agonist, is commonly used for the management of multiple sclerosis-related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the GABAB receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets have a dosing interval of 12 hours and have shown a favourable safety and efficacy profile in early-phase clinical development. The current Phase 3 study was designed to evaluate the efficacy and safety of arbaclofen extended-release tablets in patients with multiple sclerosis-related spasticity. In this multicentre, double-blind, placebo-controlled study, adults with multiple sclerosis-related spasticity were randomized to arbaclofen extended-release 40 mg/day, arbaclofen extended-release 80 mg/day or placebo for 12 weeks. The co-primary end-points were the change from baseline to Week 12 in the Total Numeric-transformed Modified Ashworth Scale in the Most Affected Limb score and the Clinical Global Impression of Change score. A hierarchical testing procedure was used to evaluate the co-primary end-points; analyses for the 80 mg/day group were considered inferential only if the arbaclofen extended-release 40 mg/day and placebo groups demonstrated a statistically significant difference (P ≤ 0.05) for both end-points. Five hundred thirty-six patients were included in the study. At Week 12, the least squares mean change from baseline in Total Numeric-transformed Modified Ashworth Scale in the Most Affected Limb score was -1.67 (95% confidence interval: -1.97 to -1.36) and -1.28 (95% confidence interval: -1.57 to -0.99) in the arbaclofen extended-release 40 mg/day and placebo groups, respectively (least squares mean difference: -0.39; P < 0.048). Improvements were seen in the mean Clinical Global Impression of Change scores for both the arbaclofen extended-release 40 mg/day and placebo groups; however, no statistically significant difference was observed between them (least squares mean difference: -0.10; P = 0.43). Most adverse events were of mild-moderate severity. Arbaclofen extended-release 40 mg/day for 12 weeks significantly reduced multiple sclerosis-related spasticity compared with placebo and was safe and well tolerated over the 12-week treatment period. Although arbaclofen extended-release 40 mg/day improved Clinical Global Impression of Change scores, a significant difference from placebo was not observed.

Symptom burden, management and treatment goals of people with MS spasticity: Results from SEEN-MSS, a large-scale, self-reported survey

BackgroundSpasticity occurs frequently in people with multiple sclerosis (PwMS) and may affect non-physical aspects of life. However, there is a paucity of data assessing the full impact of spasticity in PwMS. ObjectiveThis survey of PwMS and spasticity (PwMSS) was undertaken to understand the impact of spasticity in physical, functional, emotional, and social domains. MethodsSEEN-MSS (Symptoms and Emotions Exploration Needed in Multiple Sclerosis Spasticity), an online survey, was developed in collaboration with three US-based MS organizations (conducted February-April 2021). ResultsSurvey was completed by 1,177 PwMSS, 78% female, mean age 56.8yrs, 16.8yrs from MS diagnosis, 11.5yrs with spasticity. Considering day-to-day goals of treatment, respondents reported that managing symptoms(46%) was nearly as important as slowing disease progression(54%). Most reported spasticity was a constant reminder of their MS. Participants reported that spasticity limited daily activities (92%), caused pain (92%), impaired sleep (89%) and negatively impacted emotional well-being (87%). Spasticity fostered a sense of dependence (61%), isolation (40%), decline in self-confidence (75%), self-image (70%), and social connection (62%). ConclusionsSpasticity has wide-reaching negative impacts on multiple aspects of life, causing substantial burden for PwMSS. Results emphasize the need to fully understand the burden of spasticity and addressing individual needs of PwMSS.

Isokinetic Resistance Training for Ankle Plantarflexor Spasticity and Muscle Weakness in People With Multiple Sclerosis: A Proof-of-Concept Case Series.

To the best of the authors' knowledge, no data are available about the use of isokinetic resistance training for managing ankle plantarflexor spastic hypertonia in people with multiple sclerosis (MS). The aim of this proof-of-concept study was to explore the feasibility and effects of concentric contractions on spasticity-related resistance to passive motion, strength, and mobility in people with MS and ankle plantarflexor spasticity. In this pretest/posttest case series, 5 people with MS (mean age = 53.6 [SD = 8.8] years; median Expanded Disability Status Scale score = 5; Modified Ashworth Scale range = 1-4) received 6weeks of isokinetic resistance training of the spastic plantarflexors. Before and after the intervention, the following outcomes were assessed: average peak torque during passive robotic mobilization, isometric strength, surface electromyography (sEMG) from the spastic muscles, time to complete the 10-m Walk Test, and the Timed "Up & Go" Test. The standardized effect size was used to test pretest and posttest effects at the individual level. Group-level analyses were also performed. Following the training, the average peak torque recorded from the plantarflexors during passive motion at a velocity of 150 degrees per second was found to be decreased by at least 1 SD in all participants but 1, with a significant reduction at the group level of 23.8%. Conversely, no changes in sEMG activity were detected. Group-level analyses revealed that the maximal strength of the trained plantarflexors increased significantly (31.4%). Fast walking speed increased and time to complete the Timed "Up & Go" Test decreased in 4 participants, although not significantly at the group level. Isokinetic resistance training proved safe and feasible in people who had MS and ankle plantarflexor spasticity. The observed reductions in resistance to passive motion from the spastic plantarflexors in the absence of sEMG changes might suggest a mechanical rather than a neural effect of the training. Based on these preliminary findings, isokinetic resistance training does not exacerbate hypertonia in people with MS and ankle plantarflexor spasticity and could be safely used to manage muscle weakness in this population.

Effect of Dynamic Neuromuscular Stabilization on Balance, Trunk Function, Falling, and Spasticity in People With Multiple Sclerosis: A Randomized Controlled Trial

ObjectiveTo compare the effects of core stabilization (CS) and dynamic neuromuscular stabilization (DNS) on balance, trunk function, mobility, falling, and spasticity, in people with multiple sclerosis (PWMS). DesignTwo-group randomized controlled trial. SettingGeneral community and referral center. ParticipantsA total of 64 PWMS, between 30 and 50 years old, and an expanded disability status scale between 2 and 5, participated in this study (N=64). InterventionsParticipants were randomly assigned to CS (n=32) and DNS (n=32) groups. Both groups received a total of 15 sessions of CS or DNS exercises, 60 minutes per session, 3 times a week during the 5 weeks. Outcome MeasuresBalance function was measured as the primary outcome measure. Trunk function, postural stability, falling rate, fear of falling, falling index, mobility, and spasticity were measured as secondary outcomes. ResultsDNS group had significant improvement in Berg balance scale, trunk impairment scale, postural stability, activities-specific balance confidence, reduced falling rate, the timed Up and Go (TUG), multiple sclerosis walking scale-12, and multiple sclerosis spasticity scale in PWMS compared with the CS group, (P<.0001) after 5 weeks of intervention and 17 weeks of follow-up. Except for the modified Ashworth scale (MAS), significant improvements were seen in all outcome measures in both groups after 5 weeks of intervention. ConclusionThis is the first clinical evidence to support the importance of DNS exercise in improving balance, trunk function, and fall prevention in PWMS. This study provides clinical evidence that DNS may be more effective for PWMS than CS.

Cannabinoids and PPAR Ligands: The Future in Treatment of Polycystic Ovary Syndrome Women with Obesity and Reduced Fertility.

Cannabinoids (CBs) are used to treat chronic pain, chemotherapy-induced nausea and vomiting, and multiple sclerosis spasticity. Recently, the medicinal use of CBs has attracted increasing interest as a new therapeutic in many diseases. Data indicate a correlation between CBs and PPARs via diverse mechanisms. Both the endocannabinoid system (ECS) and peroxisome proliferator-activated receptors (PPARs) may play a significant role in PCOS and PCOS related disorders, especially in disturbances of glucose-lipid metabolism as well as in obesity and fertility. Taking into consideration the ubiquity of PCOS in the human population, it seems indispensable to search for new potential therapeutic targets for this condition. The aim of this review is to examine the relationship between metabolic disturbances and obesity in PCOS pathology. We discuss current and future therapeutic interventions for PCOS and related disorders, with emphasis on the metabolic pathways related to PCOS pathophysiology. The link between the ECS and PPARs is a promising new target for PCOS, and we examine this relationship in depth.

Can strength training modify voluntary activation, contractile properties and spasticity in Multiple Sclerosis?: A randomized controlled trial.

BackgroundA randomized controlled trial was conducted to analyze the effects of 10 weeks of strength training (ST) on voluntary activation, muscle activity, muscle contractile properties, and spasticity in people with MS. Methods30 participants were randomized to either an experimental [EG] (n = 18) or a control [CG] (n = 12) group. The EG carried out 10-weeks of ST, where the concentric phase was performed at maximum voluntary velocity. Muscle activity of the vastus lateralis (surface electromyography (sEMG) during the first 200 ms of contraction), maximal neural drive (peak sEMG), voluntary activation (central activation ratio), and muscle contractile function (via electrical stimulation) of the knee extensor muscles, as well as spasticity, were measured pre- and post-intervention. ResultsThe EG showed a significant improvement with differences between groups in muscle activity in EMG0–200 (p = 0.031; ES = -0.8) and maximal neural drive (p = 0.038; ES = -0.8), as well as improvement in the ST group with a trend towards significance in EMG0–100 (p = 0.068; ES = -0.6). CAR increased after intervention in ST group (p = 0.010; ES=-0.4). Spasticity also improved in the ST group, with differences between group after intervention, in first swing excursion (right leg: p = 0.006; ES = -1.4, left leg: p = 0.031; ES = -1.2), number of oscillations (right leg: p = 0.001; ES = -0.4, left leg: p = 0.031; ES = -0.4) and duration of oscillations (left leg: p = 0.002; ES = -0.6). Contractile properties remain unchanged in both ST group and CG. Conclusions10 weeks of ST improves muscle activity during the first 200 ms of contraction, maximal neural conduction, and spasticity in people with MS. However, ST does not produce adaptations in muscle contractile properties in this population.

A real-world evidence study of nabiximols in multiple sclerosis patients with resistant spasticity: Analysis in relation to the newly described 'spasticity-plus syndrome'.

Background and purposeNabiximols is a therapeutic option for patients with multiple sclerosis (MS) spasticity whose symptoms are poorly controlled by conventional oral first‐line medications. This study aimed to assess the relationship between changes in spasticity severity (measured on the 0–10 numeric rating scale [NRS]) and the presence of associated symptoms in patients treated with nabiximols, and to investigate the presence of the newly described ‘spasticity‐plus syndrome’.MethodsWe analyzed real‐world data from the Italian Medicines Agency e‐Registry on 1138 patients with MS spasticity who began treatment with nabiximols. Evaluation time points were baseline, 4 weeks, and 3, 6, 12 and 18 months after treatment start.ResultsCommon symptoms associated with MS spasticity in this cohort were pain (38.4% at baseline), sleep disturbances (32.7%), and spasms/cramps (28.5%). Pain was frequently clustered with sleep disturbances (57.2% of pain cases) and spasms/cramps (43.9%). Approximately one‐third of patients with data at all evaluation time points maintained treatment at 18 months. Nabiximols reduced the baseline mean spasticity 0–10 NRS score by 24.6% at Week 4, and by 33.9% at 18 months in treatment continuers. Nabiximols resolved a range of MS spasticity‐associated symptoms at Week 4, and after 18 months in treatment continuers.ConclusionThis real‐world analysis supports the concept of a spasticity‐plus syndrome and suggests that nabiximols can favorably impact a range of spasticity‐associated symptoms.