Spasticity In Multiple Sclerosis Patients Research Articles

Transcranial direct current stimulation for spasticity in patients with multiple sclerosis: Exploring novel routes

BackgroundPatients with Multiple sclerosis (MS) usually suffer from severe neurological disabilities. Spasticity is one of the most bothering and disabling manifestations that MS patients suffer from. Owing to being a chronic inflammatory demyelinating disorder; finding new modalities to alleviate some of the disabilities related to MS became a desired objective. Transcranial direct current stimulation (tDCS), a relatively new tool for modulating cortical excitability has been recently considered as a tool to provide symptomatic treatment for many neurologic and psychiatric diseases. In our study, we used tDCS to assess its effect on spasticity in MS patients. Methods5 consecutive daily sessions of 20 minutes duration of active anodal tDCS over the ipsilesional motor cortex were given to 10 relapsing remitting MS (RRMS) patients with at least 1 spastic lower limb (active group) who were compared with other matched10 RRMS patients who received sham stimulation (sham group). The outcome was to measure the effect on spasticity both clinically using the Modified Ashworth Scale (MAS) and through neurophysiological assessment (H reflex latency and H/M amplitude ratio). ResultsPatients who received active anodal tDCS showed significant improvement (p< 0.05) in the H/M amplitude ratio as compared to the sham group. However, there was no significant difference between the two groups in the MAS. H latency showed significant stability in active group when compared to the sham group. ConclusionAnodal direct current stimulation of the ipsilesional motor cortex in patients with MS, resulted in reduced spasticity as per neurophysiological assessment.

Impact of Lockdown during COVID-19 Pandemic on Central Activation, Muscle Activity, Contractile Function, and Spasticity in People with Multiple Sclerosis.

Background People with multiple sclerosis (MS) suffer from symptoms related to neural control, such as reduced central activation, lower muscle activity, and accentuated spasticity. A forced 9-week home confinement related to COVID-19 in Spain may have worsened these symptoms. However, no study has demonstrated the impact of home confinement on neuromuscular mechanisms in the MS population. This study was aimed at analyzing the effects of a 9-week home confinement on central activation, muscle activity, contractile function, and spasticity in MS patients. Methods Eighteen participants were enrolled in the study. Left and right knee extensor maximum voluntary isometric contraction (MVIC), maximal neural drive via peak surface electromyography (EMG) of the vastus lateralis, central activation ratio (CAR), and muscle contractile function via electrical stimulation of the knee extensor muscles, as well as spasticity using the pendulum test, were measured immediately before and after home confinement. Results Seventeen participants completed the study. CAR significantly decreased after lockdown (ES = 1.271, p < 0.001). Regarding spasticity, there was a trend to decrease in the number of oscillations (ES = 0.511, p = 0.059) and a significant decrease in the duration of oscillations (ES = 0.568, p = 0.038). Furthermore, in the left leg, there was a significant decrease in the first swing excursion (ES = 0.612, p = 0.027) and in the relaxation index (ES = 0.992, p = 0.001). Muscle contractile properties, MVIC, and EMG variables were not modified after confinement. Conclusions The results suggest that a home confinement period of 9 weeks may lead to an increase in lower limb spasticity and a greater deficit in voluntary activation of the knee extensors.

A Pilot Study of the Government Pharmaceutical Organization (GPO) Cannabis Extract for Multiple Sclerosis (MS) Spasticity Treatment in Thailand

Background: The prevalence of spasticity in multiple sclerosis (MS) patients is nearly 90%. Most patients do not respond to current anti-spastic medications. Objective: To evaluate the efficacy and safety of Government Pharmaceutical Organization cannabis extract (GPOCE) in the treatment of spasticity in MS patients in Thailand. Materials and Methods: This prospective pilot study in patients diagnosed with MS whose spasticity was not relieved under current spasticity treatments, was performed between November 2019 and June 2020. The GPOCE formulation of THC:CBD 1:1 was administered to all patients. The treatment outcomes were determined at 12 weeks and compared with their baseline. Results: Seven patients participated in the present study. Among these, two patients withdrew after receiving only a small dose of GPOCE. Finally, five patients were included in the final analysis. The primary outcome was a reduction in the Modified Ashworth Score (MAS), which decreased among participants from a baseline of 15 (IQR 12 to 19) to 6 (IQR 1 to 12) (p=0.043). The key secondary outcome was a clinically relevant response (CRR), which was defined as a reduction of the spasticity Numeric Rating Scale (NRS) of more than thirty percent compared to baseline. Four patients (80%) achieved CRR. Moreover, the overall spasticity NRS decreased from a median of 6 (IQR5 to 7) to 2 (IQR2 to 3). A reduction of other NRS parameters, including fatigue, pain, tremor, sleep, spasm, anxiety, and depression, was also observed after treatment. Moreover, GPOCE was generally well tolerated. Conclusion: GPOCE is useful in treating spasticity in patients with MS. The safety profile is acceptable under the supervision of a health care provider. Keywords: Multiple sclerosis (MS), Cannabis extract, Spasticity

The inter- and intra-rater reliability of Modified Tardieu Scale in assessing spasticity of knee extensors in patients with multiple sclerosis

IntroductionSpasticity is one of the most common and disabling symptoms in Multiple sclerosis (MS). The is a clinical tool for assessing spasticity. This study aimed to investigate the inter- and intra-rater reliability of the modified Tardieu scale for assessing knee extensors spasticity in MS patients. MethodsTwenty-six patients with MS (12 females and 14 males) with a mean age of 40 ± 11.39 years participated in this study. The extensor muscles of both knees were evaluated using the MTS in two sessions. At first session, two examiners randomly assessed the knee extensor spasticity to study the inter-rater reliability and 3–4 days later the first examiner assessed the patients again, to determine intra-rater reliability. Intra-class Correlation Coefficient (ICC) analysis, two-way random effect model was used to determine the reliability of various components of the modified Tardieu scale. ResultsThe inter-rater reliability for quality of muscle reaction of knee extensor muscles was very good (ICC = 0.89) and for the difference between the angle of muscle response (R1) and full range(R2) of movement (R2- R1), as spasticity intensity criterion, was good (ICC = 0.73). ICC values for R2-R1 and muscle response quality assessments by one rater were 0.73 and 0.82, respectively. ConclusionThe findings of the current study showed that the MTS has good to very good inter- and intra-rater reliability for assessing knee extensors spasticity in MS patients.

The Effect of Repetitive Transcranial Magnetic Stimulation on Spasticity in Patients with Multiple Sclerosis.

Background and PurposeThis randomized controlled study examined the effect of repetitive transcranial magnetic stimulation (rTMS) on spasticity in patients with multiple sclerosis (MS).MethodsThis study included 16 patients with a history of MS and spasticity in the adductor hip muscles according to the Modified Ashworth Scale (MAS). The participants were randomized into the active group (n=10) and control group (n=6), in which active rTMS and sham rTMS were applied in 10 sessions, respectively. A physical therapy and rehabilitation program was applied along with rTMS sessions in both groups. The evaluation parameters were assessed at baseline and then 1 week and 1 month after applying rTMS.ResultsStatistical analyses with post-hoc correction revealed statistically significant improvements in the active group compared to the control group in the bilateral MAS score, Penn Spasm Frequency Scale score, patient satisfaction, amount of urine leakage, actual health status, perceived health status, energy and fatigue, role limitations due to physical problems, social function, overall quality of life, cognitive functioning, physical health composite score, mental health composite score, and total score on the Multiple Sclerosis Quality of Life-54 (MSQOL-54) (p<0.05). Statistically significant changes were detected in the MSQOL-54 social function and physical health composite scores of patients in the control group (p<0.05).ConclusionsActive rTMS combined with a physical therapy program reduced spasticity in MS patients compared to the control group that received only physical therapy. Further comprehensive and more advanced studies are needed to confirm the present findings.

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

The National Academies of Sciences, Engineering, and Medicine has published “The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research,” which summarizes available scientific literature on the therapeutic effects of cannabis, other health effects, cannabis use and abuse and research opportunities. The 468-page book serves as an excellent initial source on the current state of research and provides summaries and recommendations for further research on a number of topics. While not exhaustive, this resource provides an excellent starting place for medical regulators, who face a complex landscape of often-confiicting information when addressing the topic of cannabis for medical use. It is a remarkably approachable, well-organized snapshot of the current state of research on these topics.Particularly helpful for the clinician is the section on the therapeutic effects of cannabis, including a summary of current research and strength of recommendations for cannabis use in the treatment of 21 medical conditions. These topics range from chronic pain to Huntington's Disease and Schizophrenia. As with all sections, the authors provide here an identification of research gaps, a summary and references to primary literature. This section is particularly useful for helping guide policy decisions, as in many state and local jurisdictions there is vigorous debate regarding the expansion of medical indications for cannabis. The references to medical literature (both primary literature and systematic reviews) provide insight into which conditions likely are benefited by the use of cannabis. For example, the authors note that oral cannabinoids are found to be modestly effective antiemetics for chemotherapy-induced nausea and vomiting and patient-reported spasticity in multiple sclerosis patients. However, they also acknowledge that there is “insufficient evidence to support the conclusion that cannabinoids are an effective treatment for cancers, including glioma.”For medical regulators, the section on other health effects of cannabis is particularly helpful. Here, regulators will find in-depth discussion of current literature on a variety of topics, including cannabis and its effect on cancer, cardio-metabolic risk, respiratory disease and immunity. Notable is a summary of cancer risks associated with cannabis use. Interestingly, there is limited evidence of a statistical association with cannabis use and germ cell tumors, but not esophageal or lung cancers. From a public health perspective, topics also include associated abuse of other drugs and association with injury and death.In keeping with the well-organized nature of this work, each chapter concludes with a single-page highlighted “Summary of Chapter Conclusion.” For the busy reader, this summary provides an evidence-based summary of the topic in bullet-point format.Finally, the book touches on cannabis research priorities, noting that they should include population-health impacts, basic science studies regarding harms and benefits and social effects on behavioral change. Challenges and barriers to research include regulatory and supply issues, funding issues and policy divides between state and federal regulations. While this section is likely most applicable to researchers and universities, it provides a glimpse of likely future work to be done.Recognizing that regulatory and policy decisions are undertaken after careful consideration of many available information sources, this reference book is a very valuable addition to discussions regarding cannabis for medical use. By collecting and summarizing — and critiquing by level of evidence — currently available research, this work fills a need for an approachable and organized reference.

Effect of repetitive transcranial magnetic stimulation on leg spasticity in primary progressive and secondary progressive form of multiple sclerosis

Lower limb spasticity is one of the most common symptoms in multiple sclerosis (MS) patients with an increasing severity as the disease progresses. Previous clinical and experimental results of excitatory repetitive transcranial magnetic stimulation (rTMS) highlighted possible role in reducing of lower limb spasticity in MS patients. The aim of our pilot study was to explore effects of rTMS on leg spasticity in MS patients. Our pilot study included 20 MS patients with secondary progressive (SP) and primary progressive form (PP) of disease with Expanded Disability Status Scale (EDDS) score 4–6.5 and lower limb spasticity, that were referred to Clinic for Rehabilitation Dr Miroslav Zotovic, Belgrade. They were simple randomized in two groups: first group included ten patients with rTMS and second group was placebo group with sham rTMS. For rTMS intervention, we used the intermittent theta burst stimulation over M1 leg area for the worst affected leg. Both group had exercise therapy (ET) session after the rTMS (real/sham) intervention during the three weeks. Primary outcome measure for spasticity was Modified Ashworth Scale (MAS). Secondary outcome measures included clinical assessment of spasticity Multiple Sclerosis Spasticity Scale (MSSS88) and the Timed-25-foot walk. Outcome measures were evaluated before and after three weeks of treatment, and compared within the group and between two groups. There were no statistically differences between the group regarding age, gender, education, form and duration of disease, EDSS. A statistically significant difference was found in the group of patients treated with the rTMS for MAS (W = 2.714; P = 0.007), T25 W (Z = 2.813; P = 0.005) and MSSS88 (Z = 2.803; P = 0.005). In placebo group these changes were not statistically significant. rTMS associated with short period of ET may induce significant reduction of spasticity in SP and PP form of disease.

Therapeutic benefit of uncobotulinum toxin A for spasticity of the triceps surae in patients with multiple sclerosis: An observational study on gait spatiotemporal parameters

Few data are available on the use of botulinum toxin for spasticity treatment in multiple sclerosis (MS). In a previous study we found that one of the main therapeutic goals in patients suffering from spasticity of the triceps surae was improvement in walking. In this pilot observational study, we assessed the benefit of an injection of incobotulinumtoxinA in patients with MS suffering from spasticity of the triceps surae. This study enrolled MS patients with Expanded Disability Status Scale (EDSS) scores < 6 who required botulinum toxin for focal spasticity of the triceps surae. Treatment consisted of 200 IU of incobotulinumtoxinA (Xeomin) (100 units in 3 milliliters) injected into the triceps surae at 5 sites. A second injection was allowed, but after a 3 months delay. Outcome measures were assessed before injection, and at 6 weeks and 3 months post-injection, using the Goal Attainment Scale (GAS), Twelve Item MS Walking (MSWS-12) Scale, Timed Up and Go (TUG) Test, and 6 Minute Walk Test (6MWT). Spatiotemporal gait data were obtained by GAITRite. Twenty-two patients with a mean age of 48.2 ± 12 years and a mean EDSS of 4.2 (median 4.7). At 6 weeks, spatiotemporal parameters and the results of the 6MWT were not significantly different even though we observed a significant improvement for the GAS, the MSWS-12 score ( P = 0.015), and the TUG Test ( P = 0.003). However, at 3 months, there was a significant benefit on injected (0.005) and non-injected (0.01) step length measured by GaitRITE but not on support distribution (0.18; 0.38). This may explain the decrease in gait fatigability and the increase of speed on the 6MWT (0.02), although neither the TUG Test nor the MSWS-12 Scale showed improvement. Eighty percent of patients had reached their objective on GAS. These results confirm the interest of toxin as a treatment for focal spasticity of the triceps surae with a significant improvement of gait. Further studies are needed to clarify guidelines for administration (dosage, intervals). The best results on gait parameters are obtained after 3 months, confirmation of the hypothesis of central effect of toxin. Botulinum toxin should probably be discussed early in the management of spasticity in MS patients.

Is there a link between ultrasonography measurements of thigh muscles, clinical and isokinetic parameters in MS patients?

The aim of the study was to investigate the relations between ultrasound measurements of thigh muscles, isokinetic muscle strength and clinical parameters in a sample of multiple sclerosis (MS) patients. We included 12 adult MS patients with a significant disability (EDSS: 5.2 ± 1.5). We assessed ultrasound measurements of vastus lateralis (VL) and biceps femoris (BF), with computer image processing (thickness, pennation angle and fascicle length). The muscle strength was assessed with isokinetic dynamometry for both VL and BF (muscle peak torque in N·m −1 ) We also recorded clinical parameters such as spasticity (Ashworth scale), gait speed and fatigue (Fatigue Severity Scale). All the parameters were recorded twice: at the baseline and after three weeks of follow-up and muscle-strengthening in a neurological rehabilitation hospitalization unit. The weakest muscle of both was used in the analysis for a better clinical accuracy. A linear Pearson regression analysis showed a moderate significant correlation between the weakest VL thickness and sustained gait speed after 3 weeks of routine physical therapy ( r = 0.590, P = 0.044). We also found both strong significant correlations between VL pennation angle of fibers and spasticity ( r = 0.653, P = 0.021), as well as fascicle length and spasticity ( r = 0.647, P = 0.023). A secondary analysis showed that a strong link was found between VL muscle thickness and sustained gait speed when we included the mean thickness value of both muscles in each patient, instead of the weakest muscle alone ( r = 0.606, P = 0.037). Our analysis did not show any significant correlation between ultrasound measurements and muscle peak torque measured on an isokinetic device for VL and BF muscles. We also did not find any significant link between BF ultrasound parameters and clinical parameters. This work suggests that architectural changes in thigh muscles, especially the VL, seem to be linked with a gain in sustained gait speed whereas it might enhance spasticity in MS patients. This result might assess that a bigger muscle thickness could be the consequence of a higher density of slow twitch oxidative type I muscle fibers. This assessment could be confirmed in a higher evidence level study.

Management of symptoms associated with spasticity in patients with multiple sclerosis

To describe the role of nurses in the management of symptoms related to spasticity in patients with multiple sclerosis (MS). A descriptive study was developed based on a questionnaire on spasticity in MS patients. The questionnarie was completed through an anonymous tele-voting system at a national meeting with nurses involved in the management of these patients. Apart from fatigue, according to the opinion of the participants, the spasticity symptom associated with MS most notified by patients was difficulty in walking, followed by spasms and pain. Participants thought that it is important that nursing takes: 1) a role in identifying these symptoms, 2) should focus on the detection of the triggering or aggravating factors, and 3) on providing support in the assessment of the level of spasticity. It is important to inform about the correct use of anti-spasticity drugs, how to adjust the dosage and side effects of treatments, including cannabinoids via an oromucosal spray, titrating its doses according to each patient, and monitoring its tolerability, efficacy and adherence. Although there are usually resources to follow up these patients, there are still important gaps, including the lack of a specific follow-up protocol. Although all the participants are experts in the management of patients with MS, there is still diversity in the functions they perform, and the available resources they have in their hospitals. Nurses act as a key element in the process of identification of symptoms, training and monitoring of these patients with spasticity in EM.

87. Anodal transcranial direct current stimulation of motor cortex does not ameliorates spasticity in multiple sclerosis

Spasticity is a common disorder and a major cause of a long-term disability in patients with multiple sclerosis (MS). Transcranial direct current stimulation (tDCs) is a potential tool to improve motor deficits in several neurological disease and, recently, it has been proposed as effective in decreasing spasticity after stroke. To assess whether anodal tDCS is effective in modulating lower limb spasticity in MS patients. We performed a single-centre randomized, double-blind, sham-controlled study to investigate efficacy of anodal vs sham tDCs in 20 relapsing-remitting MS patients. Ten patients received anodal tDCS stimulation to the primary sensorymotor cortex of the more affected side, 20 min for day, 5 days per week, for 2 weeks. Ten patients received sham tDCS stimulation. Spasticity was assessed by using the modified Ashworth scale (MAS) and the self-scoring MSSS-88 at baseline and at the end of protocol stimulation. No significant change in lower limb spasticity was observed for both anodal and sham tDCS stimulation. Anodal tDCS seems to be not effective in decreasing lower limb spasticity in MS patients.

Characterizations of reflex and nonreflex changes in spastic multiple sclerosis

Spasticity, an increased resistance of a limb to movement, is associated with functional limitations and a major source of disability in neurological disorders, including multiple sclerosis (MS) and stroke. Despite the clinical significance of spasticity in brain and spinal cord injuries, it is often not clear whether the spasticity is due to reflex or non-reflex changes. Reflex and nonreflex properties of the human knee joint were studied in eight MS patients with spasticity and ten healthy subjects. A digitally controlled joint driving device was used to apply small-amplitude, and band-limited white-noise perturbations to the knee to manifest the reflex and nonreflex properties. The subjects were asked to maintain a steady level of background muscle torque during the perturbation. A nonlinear delay differential equation model was used to characterize the reflex and intrinsic properties of the knee in terms of phasic stretch reflex gain, tonic stretch reflex gain, joint elastic stiffness, and coefficient of viscosity. It was found that joint coefficient of viscosity and tonic stretch reflex gain of the spastic MS patients were significantly lower than those of normal controls. On the other hand, spastic MS patients showed higher phasic stretch reflex gains than normal controls and a trend of increased joint stiffness. Simultaneous characterizations of changes in tonic and phasic reflexes and nonreflex changes in joint elastic stiffness and viscosity in neurological disorders may help us gain insight into mechanisms underlying spasticity and develop impairment-specific treatment.

Spasticity improvement in patients with relapsing–remitting multiple sclerosis switching from interferon-β to glatiramer acetate: The Escala Study

BackgroundA recent pilot study suggested spasticity improvement during glatiramer acetate (GA) treatment in multiple sclerosis (MS) patients who previously received interferon-β (IFN-β). ObjectiveTo evaluate changes in spasticity in MS patients switching from IFN-β to GA. MethodsObservational, multicentre study in patients with relapsing–remitting MS (RRMS) and spasticity switching from IFN-β to GA. The primary endpoint comprised changes on Penn Spasm Frequency Scale (PSFS), Modified Ashworth Scale (MAS), Adductor Tone Rating Scale (ATRS), and Global Pain Score (GPS) at months 3 and 6 after starting GA. ResultsSixty-eight evaluable patients were included (mean age,41.7±9.5years; female,70.6%; mean time from MS diagnosis to starting GA,7.6±5.7years). Previous treatments were subcutaneous IFN-β1a in 42.6% patients, intramuscular IFN-β1a in 41.2% and IFN-β1b in 32.4%, whose mean durations were 3.5±3.3, 2.7±2.5 and 4.4±3.6years, respectively. Statistically significant reductions in mean scores on all spasticity measurements were observed from baseline to month 3 (PSFS, 1.7±0.9 vs 1.4±0.6, p<0.01; MAS, 0.7±0.5 vs 0.6±0.5, p<0.01; highest MAS score, 1.9±0.8 vs 1.7±0.8, p<0.01; ATRS, 1.6±0.6 vs 1.4±0.6, p<0.01; GPS, 29.4±22.1 vs 24.7±19.4, p<0.01) and from baseline to month 6 (PSFS, 1.7±0.9 vs 1.3±0.6, p<0.01; MAS, 0.7±0.5 vs 0.5±0.5, p<0.01; highest MAS score, 1.9±0.8 vs 1.5±0.9, p<0.01; ATRS, 1.6±0.6 vs 1.3±0.6, p<0.01; GPS, 29.4±22.1 vs 19.1±14.8, p<0.01). ConclusionSpasticity improvement in terms of spasm frequency, muscle tone and pain can be noted after three months and prolonged for six months of GA treatment.

Cannabinoide zur symptomatischen Therapie der Multiplen Sklerose

Spasticity represents a common troublesome symptom in patients with multiple sclerosis (MS). Treatment of spasticity remains difficult, which has prompted some patients to self-medicate with and perceive benefits from cannabis. Advances in the understanding of cannabinoid biology support these anecdotal observations. Various clinical reports as well as randomized, double-blind, placebo-controlled studies have now demonstrated clinical efficacy of cannabinoids for the treatment of spasticity in MS patients. Sativex is a 1:1 mix of delta-9-tetrahydocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, which recently received a label for treating MS-related spasticity in Germany. The present article reviews the current understanding of cannabinoid biology and the value of cannabinoids as a symptomatic treatment option in MS.

Sativex® (tetrahydrocannabinol + cannabidiol), an endocannabinoid system modulator: basic features and main clinical data

Sativex® (nabiximols, USAN name) oromucosal spray contains the two main active constituents of Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 molecular ratio, and acts as an endocannabinoid system modulator. Randomized, controlled clinical trials of Sativex as add-on therapy provide conclusive evidence of its efficacy in the treatment of more than 1500 patients with multiple sclerosis (MS)-related resistant spasticity. The primary end point in clinical trials was the mean change from baseline in the 0–10 numerical rating scale (NRS) spasticity score. The first pivotal clinical trial included 189 patients treated for 6 weeks with Sativex (n = 124) or placebo (n = 65). At study end, there was a significant reduction from baseline in patient-recorded NRS spasticity scores with Sativex compared with placebo (-1.18 vs -0.63; p = 0.048). In the second pivotal trial, 337 patients with MS-related resistant spasticity received Sativex (n = 167) or placebo (n = 170) over a 15-week period. In the per-protocol analysis (79% of the patient population), mean baseline NRS spasticity score was reduced significantly in patients receiving Sativex compared with placebo: -1.3 versus -0.8 points (p = 0.035). The third pivotal clinical trial, evaluating the sustained efficacy of Sativex, had a two-phase study design: in phase A (n = 572), 47% of patients were initial responders (improvement ≥20%) after 4 weeks of single-blind Sativex treatment who then entered phase B, a randomized, double-blind, 12-week placebo comparison. At the end of phase B, the change in NRS spasticity score improved by a further 0.04 units in initial responders treated with Sativex, but decreased by 0.81 units in placebo recipients (p = 0.0002). Significant improvements in quality-of-life measures from baseline to week 16 were also observed in patients receiving Sativex. The most common treatment-related adverse events with Sativex were mild-to moderate and transient episodes of dizziness, fatigue or somnolence. Sativex does not exhibit the side effects typically associated with recreational cannabis use and there are no signs of drug tolerance or withdrawal syndrome, or any evidence of drug misuse or abuse. Sativex oromucosal spray appears to be a useful and welcomed option for the management of resistant spasticity in MS patients. Although the management of MS has been improved by the availability of disease-modifying agents that target the underlying pathophysiological processes of the disease, a clear need remains for more effective symptomatic treatments, especially as regards MS-related spasticity and pain.

New approaches in the management of spasticity in multiple sclerosis patients: role of cannabinoids.

Cannabinoids such as Cannabis-based medicinal extracts (CBMEs) are increasingly being used in the treatment of spasticity associated with multiple sclerosis (MS). They have been shown to have a beneficial effect on spasticity; however, this evidence is largely based on subjective rating scales. Objective measurements using the Ashworth scale have tended to show no significant effect; however, the validity of this scale has been questioned. The available clinical trial data suggest that the adverse side effects associated with using CBMEs are generally mild, such as dry mouth, dizziness, somnolence, nausea and intoxication. However, most of these trials were run over a period of months and it is possible that other adverse side effects could develop with long-term use. There may be reason to be concerned about the use of therapeutic cannabinoids by adolescents, people predisposed to psychosis and pregnant women.

Does cannabis safely reduce spasticity in multiple sclerosis patients?

Does cannabis safely reduce spasticity in multiple sclerosis patients?

The effect of baclofen on the transmission in spinal pathways in spastic multiple sclerosis patients

Objectives: To measure the effect of baclofen on the transmission in different spinal pathways to soleus motoneurones in spastic multiple sclerosis patients.Methods: Baclofen was administered orally in 14 and intrathecally in 8 patients. Hmax/Mmax, presynaptic inhibition by biceps femoris tendon tap of femoral nerve stimulation, depression of the soleus H-reflex following previous activation of the Ia afferents from the soleus muscle (i.e. postactivation depression), disynaptic reciprocal Ia inhibition of the soleus H-reflex and the number of backpropagating action potentials in primary afferents, which may be a sign of presynaptic inhibition, were examined.Results: Baclofen depressed the soleus Hmax/Mmax ratio significantly following oral and intrathecal baclofen. None of the two tests of presynaptic inhibition, or the postactivation depression or the disynaptic reciprocal Ia inhibition of the soleus H-reflex were affected by baclofen administration. Also the action potentials of the primary afferents were unchanged during baclofen administration.Conclusions: The antispastic effect of baclofen is not caused by an effect on the transmitter release from Ia afferents or on disynaptic reciprocal Ia inhibition. One possible explanation of the depression of the H-reflex by baclofen is suggested to be a direct depression of motoneuronal excitability.

Baclofen increases the soleus stretch reflex threshold in the early swing phase during walking in spastic multiple sclerosis patients

Baclofen increases the soleus stretch reflex threshold in the early swing phase during walking in spastic multiple sclerosis patients

Soleus long-latency stretch reflexes during walking in healthy and spastic humans

The present study was carried out to investigate the long-latency soleus stretch reflexes M2 (peak latency of approximately 85 ms) and M3 (peak latency of approximately 115 ms) during walking in healthy and spastic multiple sclerosis (MS) patients. An 8° stretch was applied to the ankle extensors of the left leg in 8 healthy subjects during normal walking speed and 9 spastic MS patients and 10 age-matched healthy subjects during slow walking. When present in walking healthy subjects, M2 and M3 were modulated in a similar way and with the same amplitudes as previously described for the short latency soleus stretch reflex (M1). The spastic patients’ soleus M1 was significantly less modulated during walking. The patients’ M2 long-latency response was modulated in the same way as the age-matched healthy subjects. All patients’ M3 responses were absent or much suppressed during walking. The origin and functional importance of the short- and long-latency stretch reflexes in healthy and spastic persons are discussed in relation to the above findings and the behaviour of the stretch reflexes during matched isometric contractions. M3 is argued to be part of a transcortical reflex in healthy subjects.