Waggle needling wields preferable neuroprotective and anti-spastic effects on post-stroke spasticity rats by attenuating γ-aminobutyric acid transaminase and enhancing γ-aminobutyric acid.

Waggle needling, a classical anti-spastic needling technique characterized by combination of acupuncture with joint movement, has gained increasing popularity of spasticity treatment in China. This study was designed to compare the anti-spastic effect of waggle needling to the routine needling and to explore its underlying mechanism. We established post-stroke spasticity model based on ischemia stroke operation (middle cerebral artery occlusion). Rats were divided into six groups: normal control group, sham-operated control group, ischemia stroke model group, waggle needling group, routine needling group and baclofen group. Neurological function and muscle tone were assessed by the Zea Longa score and modified Ashworth scale, respectively. Indirect muscle tone was testified with electrophysiological recording. Cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride staining. The concentrations and expressions of γ-aminobutyric acid transaminase (GABAT) and γ-aminobutyric acid (GABA) were detected by enzyme-linked immunosorbent assay and western blot assay. Waggle needling markedly alleviated neurological deficits, decreased cerebral infarction and eased muscle tone; simultaneously, attenuated GABAT and enhanced GABA expression in the cortical infarct regions in comparison with the routine needling (P < 0.01), yet showed similar therapeutic effect to the baclofen group (P > 0.05). These results preliminary supported that waggle needling as a potential promising non-pharmacological intervention for the treatment of cerebral ischemia and spasticity.

Localization of the center of the intramuscular nerve dense region of the medial femoral muscles and the significance for blocking spasticity.

PURPOSE: To identify the body surface position and depth of the center of the intramuscular nerves dense region (CINDR) of the medial femoral muscles. METHODS: Utilizing twelve Chinese adult cadavers (six men and six women), with an age range from 35 to 75 (66.5±5.4) years, the body surface curves between the greater trochanter of the femur and the pubic tubercle and lateral femoral epicondyle were designated as horizontal (H) and longitudinal (L) reference lines, respectively. Sihler's staining was performed on one side of the medial femoral muscles to show the intramuscular nerve dense regions, and the contralateral CINDR was labeled with barium sulfate and scanned by computed tomography, and three-dimensional reconstruction was performed. The body surface projection point of CINDR was designated as P. Projection of P in the opposite direction was identified as P'. The intersection of the longitudinal line from P to line H, and that of the horizontal line from P to line L was designated as PH and PL, respectively. The percentage positions of PH and PL on the H and L lines and the depth of the CINDRs were determined under the Syngo system. RESULTS: The pectineus, gracilis, adductor longus, and adductor brevis muscles each possess one intramuscular nerve dense region; the adductor magnus muscle has two. The PH was located at 80.32%, 95.67%, 85.64%, 94.92%, 84.48%, and 88.83% of line H, respectively. PL was at 12.76%, 40.68%, 33.26%, 23.39%, 25.57%, and 35.29% of line L, respectively. The depth of CINDRs was at 17.58%, 27.89%, 23.05%, 30.45%, 34.09%, and 29.52% of PP' line, respectively. These percentage values are all means. No statistical difference was observed neither between the left and right sides nor between the male and female cadavers (P>0.05). CONCLUSION: These results may help improve the efficiency and efficacy of botulinum toxin A injection in the treatment of medial femoral muscle spasticity.

Early delivery and prolonged treatment with nimodipine prevents the development of spasticity after spinal cord injury in mice.

Spasticity, one of the most frequent comorbidities of spinal cord injury (SCI), disrupts motor recovery and quality of life. Despite major progress in neurorehabilitative and pharmacological approaches, therapeutic strategies for treating spasticity are lacking. Here, we show in a mouse model of chronic SCI that treatment with nimodipine-an L-type calcium channel blocker already approved from the European Medicine Agency and from the U.S. Food and Drug Administration-starting in the acute phase of SCI completely prevents the development of spasticity measured as increased muscle tone and spontaneous spasms. The aberrant muscle activities associated with spasticity remain inhibited even after termination of the treatment. Constitutive and conditional silencing of the L-type calcium channel CaV1.3 in neuronal subtypes demonstrated that this channel mediated the preventive effect of nimodipine on spasticity after SCI. This study identifies a treatment protocol and suggests that targeting CaV1.3 could prevent spasticity after SCI.

Comparison of the effects of modified constraint-induced movement therapy and intensive conventional therapy with a botulinum-a toxin injection on upper limb motor function recovery in patients with stroke.

Stroke is the second leading cause of mortality worldwide and one of the main causes of adult disability. Many studies have suggested that combination therapies provide better outcomes in patients with stroke than monotherapies. The combination of botulinum-A toxin (BTX) injection with rehabilitation methods, such as modified constraint-induced movement therapy (BTX-mCIMT), has emerged as a highly promising intervention for promoting motor recovery after stroke. Thus, the present study compared the effectiveness of the combination of BTX with high-dose conventional therapy (BTX-ICT) and BTX-mCIMT for improving motor recovery and reducing spasticity of the upper limb in patients with stroke. This study recruited 64 patients with stroke. The patients were randomly allocated to two groups, namely, BTX-ICT and BTX-mCIMT. Modified Ashworth scale (MAS), Fugl-Meyer assessment (FMA), and Barthel index (BI) assessment scores were determined for the patients in both the groups before and at 4 weeks after the BTX injection. After four weeks of treatment, the MAS, FMA, and BI assessment scores of the patients in both groups were significantly higher than the scores before the treatments (P < 0.05). At the end of 4 weeks, the patients in the BTX-mCIMT group showed significantly higher mean FMA and BI assessment scores than the patients in the BTX-ICT group (P < 0.05). However, no significant statistical difference was observed in the MAS score of the patients in the two groups (P > 0.05). Our results indicated that while both BTX-mCIMT and BTX-ICT promoted motor function recovery in patients with stroke, BTX-mCIMT exerted higher therapeutic effects than BTX-ICT on motor function recovery and in the activities of daily living of patients with stroke.

Use of Kinesio taping in lower-extremity rehabilitation of post-stroke patients: A systematic review and meta-analysis.

BACKGROUND: and purpose: The benefits of Kinesio taping (KT) in post-stroke rehabilitation have not been determined. This study aimed to evaluate its effects on lower-extremity rehabilitation in patients after a stroke. METHODS: A literature search was performed using EBSCOhost, Embase, Physiotherapy Evidence Database (PEDro), PubMed, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), SinoMed, and Wanfang Data through June 2018. Randomized controlled trials (RCTs) on the use of KT during lower-extremity, post-stroke rehabilitation were selected. Meta-analysis was conducted. RESULTS: A total of 14 RCTs of low to moderate quality were reviewed and included 783 participants. Results indicated that KT significantly improved patients' lower extremity spasticity, motor function, balance, ambulation, gait parameters, and daily activities, with few adverse effects. CONCLUSION: KT may have positive effects on lower-extremity, post-stroke rehabilitation. Due to the limited number and quality of the research, additional studies are needed to identify KT benefits.

Experimental Study on Nerve Signals Block for Spasticity Based on Antimissile Strategy.

A method of blocking neural signal for spasticity which is based on the antimissile strategy was proposed. When the pathological nerve action potential signal is detected at the proximal end of the nerve, such a potential signal that is opposite to the signal of the primary neural activity is applied at the distal end of the nerve at a proper delay so as to block the pathological nerve signal. Preliminary tests were performed on toad sciatic nerve-gastrocnemius specimens. Firstly, the effect of the distance between blocking electrodes on the blocking pulse voltage threshold was studied based on the electrical tension induced by the nerve signal on the controlled muscle. Then, the effective parameters of the blocking waveform were studied. Finally, the delay range of the blocking pulse compared to the pathogen action potential was studied. The results showed that in the sciatic nerve-gastrocnemius specimens, the most effective distance between the blocking electrode pairs was 5 mm and the anodic block required an inverted triangle waveform. The voltage threshold of an effective anodic blocking pulse was 1 V and the minimum pulse width was 90 ms. Under the condition of voltage threshold and minimum pulse width, the time shifting value of blocking pulse was greater than 1ms. It is concluded from the study that the spastic action potential caused by the disease can be effectively blocked, and limb muscle spasms can be eliminated under the action of appropriate electrode configuration and blocking signal waveforms.

Effect of adding upper limb rehabilitation to botulinum toxin-A on upper limb activity after stroke: Protocol for the InTENSE trial.

Rationale Although clinical practice guidelines recommend that management of moderate to severe spasticity include the use of botulinum toxin-A in conjunction with therapy, there is currently no evidence to support the addition of therapy. Aims To determine the effect and cost-benefit of adding evidence-based movement training to botulinum toxin-A. Sample size estimate A total of 136 participants will be recruited in order to be able to detect a between-group difference of seven points on the Goal Attainment Scale T-score with 80% power at a two-tailed significance level of 0.05. Methods and design The InTENSE trial is a national, multicenter, Phase III randomized trial with concealed allocation, blinded assessment and intention-to-treat analysis. Stroke survivors who are scheduled to receive botulinum toxin-A in any muscle(s) that cross the wrist because of moderate to severe spasticity after a stroke greater than three months ago, who have completed formal rehabilitation and have no significant cognitive impairment will be randomly allocated to receive botulinum toxin-A plus evidence-based movement training or botulinum toxin-A alone. Study outcomes The primary outcomes are goal attainment (Goal Attainment Scaling) and upper limb activity (Box and Block Test) at three months (end of intervention) and at 12 months (beyond the intervention). Secondary outcomes are spasticity, range of motion, strength, pain, burden of care and health-related quality of life. Direct costs, personal costs and health system costs will be collected at 12 months. Discussion The results of the InTENSE trial are anticipated to directly influence intervention for moderate to severe spasticity after stroke. Trial Registration ANZCTR12615000616572.

Effects of high-frequency transcranial magnetic stimulation on functional performance in individuals with incomplete spinal cord injury: study protocol for a randomized controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been investigated as a new tool in neurological rehabilitation of individuals with spinal cord injury (SCI). However, due to the inconsistent results regarding the effects of rTMS in people with SCI, a randomized controlled double-blind crossover trial is needed to clarify the clinical utility and to assess the effect size of rTMS intervention in this population. Therefore, this paper describes a study protocol designed to investigate whether the use of rTMS can improve the motor and sensory function, as well as reduce spasticity in patients with incomplete SCI. METHODS: A double-blind randomized sham-controlled crossover trial will be performed by enrolling 20 individuals with incomplete SCI. Patients who are at least six months post incomplete SCI (aged 18-60 years) will be recruited through referral by medical practitioners or therapists. Individuals will be randomly assigned to either group 1 or group 2 in a 1:1 ratio, with ten individuals in each group. The rTMS protocol will include ten sessions of high-frequency rTMS (5 Hz) over the bilateral lower-limb motor area positioned at the vertex (Cz). Clinical evaluations will be performed at baseline and after rTMS active and sham. DISCUSSION: rTMS has produced positive results in treating individuals with physical impairments; thus, it might be promising in the SCI population. The results of this study may provide new insights to motor rehabilitation thereby contributing towards the better usage of rTMS in the SCI population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02899637 . Registered on 25 August 2016.

Effects of whole-body vibration on neuromuscular performance in individuals with spinal cord injury: a systematic review.

OBJECTIVE: To examine the effects of whole-body vibration on neuromuscular performance in people with spinal cord injury and evaluate the safe and effective vibration protocols. METHODS: PubMed, EMBASE, CINAHL and PEDro were mainly searched for English literatures. Other data sources were ClinicalTrials.gov , Current Controlled Trials and reference lists of all relevant articles. The PEDro scale was used to evaluate the methodological quality, and the Oxford Centre for Evidence-based Medicine level of evidence was used to assess the level of evidence. Basic information and whole-body vibration protocols were extracted by two independent researchers. Any disagreements were resolved by the third researcher. RESULTS: Of the eight included studies involving 94 individuals with spinal cord injury and 24 able-bodied participants, six of them reported beneficial effects of whole-body vibration on muscle activation and the other two on muscle spasticity. Based on the reviewed studies, an intermittent mode of whole-body vibration (frequency: 10-50 Hz; amplitude: 0.6-4 mm) is less likely to cause adverse events when applying to spinal cord injury subjects standing on platform (knees flexed at 10°-40°). CONCLUSIONS: The strength of evidence is insufficient in supporting the benefits of whole-body vibration on neuromuscular performance in individuals with spinal cord injury. The intermittent vibration (frequency: 10-50 Hz; amplitude: 0.6-4 mm; knee flexion: 10°-40°) may be the possible effective range and have good compliance.

General Anesthesia for a Patient With Pelizaeus-Merzbacher Disease.

We report the successful management of general anesthesia for a patient with Pelizaeus-Merzbacher disease (PMD). PMD is one of a group of progressive, degenerative disorders of the cerebral white matter. The typical clinical manifestations of PMD include psychomotor retardation, nystagmus, abnormal muscle tone, seizures, and cognitive impairment. General anesthesia for a patient with PMD may be difficult mainly because of seizures and airway complications related to poor pharyngeal muscle control. In addition, the possibility of exacerbation of spasticity should be considered. A 20-year-old man with PMD required removal of impacted wisdom teeth under general anesthesia. General anesthesia was induced with thiamylal, fentanyl, and desflurane. Anesthesia was maintained with desflurane and continuous intravenous remifentanil under bispectral index and train-of-4 monitoring. Anesthesia lasted 1 hour 20 minutes and was completed uneventfully. Airway complications, seizures, and exacerbation of spasticity did not occur postoperatively. Preoperatively, our patient had no history of epilepsy attacks or aspiration pneumonia, and no clinical symptoms of gastroesophageal reflux disease. Therefore, exacerbation of spasticity was one of the most likely potential complications. Identification of these associated conditions and evaluation of risk factors during preoperative examination is important for performing safe anesthesia in these patients.

Reconstructive surgery and patients with spinal cord injury: Perioperative considerations for the plastic surgeon.

BACKGROUND: Patients with spinal cord injury (SCI) requiring reconstructive surgery, particularly for pressure ulcers, are ubiquitous in Plastic and Reconstructive Surgery practices. Much of the current literature focuses on operative techniques, antibiotic indications, sitting protocols, and dressing and bedding choices. METHODS: This paper reviews normal neuroanatomy, outlines changes in neurophysiology observed in spinal cord injury, and addresses concepts related to perioperative care that are highly relevant but often under-emphasised. RESULTS: Vascular disturbances such as autonomic dysreflexia and orthostatic hypotension are dangerous phenomena occurring in this patient population that, if not properly recognised and treated, may result in complications such as haematoma, flap loss, inadequate tissue perfusion, and death. The management of spasticity, deep venous thrombosis, and perioperative pain are also relevant and discussed in this paper. CONCLUSION: A basic understanding of these concepts is essential for the Plastic Surgeon involved in the care of patients with SCI and pressure ulcers, particularly before and after debridement or reconstruction.

Tetraplegia Management Update.

Tetraplegia is a profound impairment of mobility manifesting as a paralysis of all 4 extremities owing to cervical spinal cord injury. The purpose of this article is to provide an update and analyze current management, treatment options, and outcomes of surgical reconstruction of arm and hand function. Surgical restoration of elbow and wrist extension or handgrip has tremendous potential to improve autonomy, mobility, and critical abilities, for example, eating, personal care, and self-catheterization and productive work in at least 70% of tetraplegic patients. Tendon and nerve transfers, tenodeses, and joint stabilizations reliably enable improved arm and hand usability, reduce muscle imbalance and pain in spasticity, and prevent joint contractures. One-stage combined procedures have proven considerable advantages over traditional multistage approaches. Immediate activation of transferred muscles reduces the risk of adhesions, facilitates relearning, avoids adverse effects of immobilization, and enhances functional recovery. Transfer of axillary, musculocutaneous, and radial nerve fascicles from above the spinal cord injury are effective and promising options to enhance motor outcome and sensory protection, especially in groups with limited resources. Improved communication between medical disciplines, therapists, patients, and their relatives should help that more individuals can benefit from these advances and could empower many thousands tetraplegic individuals "to take life into their own hands" and live more independently.

Sativex in the management of multiple sclerosis-related spasticity: role of the corticospinal modulation.

Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, and Hmax/Mmax ratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability.

Using acupoint-to-acupoint penetrative needling to treat post-stroke spastic paralysis: a clinical progress review.

OBJECTIVE: To determine the characteristics and advantages of acupoint-to-acupoint penetrative needling (AAPN) treatment for post-stroke spastic paralysis (PSSP) to improve the clinical outcomes of this disease in the future. METHODS: Randomized, controlled trials of PSSP patients receiving AAPN treatment were searched from MEDLINE, EMBASE, and China National Knowledge Infrastructure Database between January 2006 and June 2013. Key words included: clinic or clinical, acupuncture, needling, acupoint-to-acupoint, penetrative or penetration or penetrating, stroke or apoplexy or cerebral infarction or cerebral hemorrhage, spastic paralysis or spasticity or palsy, and hypermyotonia. Language was limited to English and Chinese. Case series reports, review articles, and, animal studies were excluded. RESULTS: AAPN showed better clinical results on PSSP than other acupuncture treatments, especially when combined with adjunct therapies such as electroacupuncture, bloodletting, and rehabilitation. The greatest benefit was achieved with rehabilitation combined with penetration from Yang-channel acupoints to Yin-channel acupoints in the upper limbs, and from Yin-channel acupoints to Yang-channel acupoints in the lower limbs with a reinforcing maneuver. CONCLUSION: AAPN is an effective treatment for PSSP, and it can accelerate and enhance functional repair of PSSP patients.

Inhibitory effects of instrument-assisted neuromobilization on hyperactive gastrocnemius in a hemiparetic stroke patient.

An instrument-assisted soft tissue mobilization (IASTM) technique has recently been used specifically to inhibit hypertonic muscles and to lengthen muscle fiber shortness. However, it is unknown whether IASTM will show such promising inhibition effects on excessive ankle plantarflexion following stroke. Therefore, the purpose of this study was to use electromyographic (EMG) analysis to determine the ability of IASTM to reduce gastrocnemius (GCM) hypertonicity and concurrently facilitate tibialis anterior (TA) lengthening in a stroke patient. EMG activity on the patient's TA and GCM was measured before and after applying IASTM. After the intervention, the GCM was deactivated by 43%, and TA activity increased by 150%, indicating IASTM-induced inhibition of the overactive GCM. The neuromobilization technique using IASTM showed a promising improvement of neuromuscular imbalance between TA and GCM activations, which can increase gait performance in a stroke case.

Dysport (botulinum toxin type A) in routine therapeutic usage: a telephone needs assessment survey of European physicians to evaluate current awareness and adherence to product labeling changes.

BACKGROUND: Botulinum neurotoxin type A is a well-established treatment for a number of conditions involving muscle hyperactivity. Dysport (Ipsen Ltd, Wrexham, United Kingdom) is a botulinum neurotoxin type A preparation that has been available for a number of therapeutic uses for over 20 years in the European Union (EU). This survey was part of the EU botulinum toxin risk management plan to identify potential educational needs of injectors by collecting data on their routine practice administration of Dysport and their awareness of potential adverse events (AEs) that are included in the current product labeling. METHODS: Dysport-experienced injectors in 5 EU countries were surveyed via telephone about their experience of Dysport in patients with cervical dystonia, adult upper and lower limb spasticity, pediatric cerebral palsy, and blepharospasm/hemifacial spasm. RESULTS: The reconstitution dilution volume most often used was 2.5 mL per 500 U for all indications. The mean total dose ranged from 387 to 530 U for cervical dystonia, 508 to 773 U for upper limb spasticity, 600 to 832 U for lower limb spasticity, 375 to 700 U for pediatric cerebral palsy, and 54 to 213 U for blepharospasm/hemifacial spasm. The potential AEs most commonly mentioned by surveyed physicians were dysphagia for cervical dystonia, arm muscle weakness for upper limb spasticity, leg muscle weakness for lower limb spasticity, and pediatric cerebral palsy and ptosis for blepharospasm/hemifacial spasm. CONCLUSIONS: The results indicate that product-labeling recommendations are generally applied in clinical practice and that there is a good familiarity with potential AEs based on clinical condition. Nevertheless, the survey shows that experienced injectors do sometimes deviate from the manufacturers labeling recommendations, highlighting the importance of ongoing education.

Control of experimental spasticity by targeting the degradation of endocannabinoids using selective fatty acid amide hydrolase inhibitors.

BACKGROUND: It has been previously shown that CB1 cannabinoid receptor agonism using cannabis extracts alleviates spasticity in both a mouse experimental autoimmune encephalomyelitis (EAE) model and multiple sclerosis (MS) in humans. However, this action can be associated with dose-limiting side effects. OBJECTIVE: We hypothesised that blockade of anandamide (endocannabinoid) degradation would inhibit spasticity, whilst avoiding overt cannabimimetic effects. METHODS: Spasticity eventually developed following the induction of EAE in either wild-type or congenic fatty acid amide hydrolase (FAAH)-deficient Biozzi ABH mice. These animals were treated with a variety of different FAAH inhibitors and the effect on the degree of limb stiffness was assessed using a strain gauge. RESULTS: Control of spasticity was achieved using FAAH inhibitors CAY100400, CAY100402 and URB597, which was sustained following repeated administrations. Therapeutic activity occurred in the absence of overt cannabimimetic effects. Importantly, the therapeutic value of the target could be definitively validated as the treatment activity was lost in FAAH-deficient mice. Spasticity was also controlled by a selective monoacyl glycerol lipase inhibitor, JZL184. CONCLUSIONS: This study demonstrates definitively that FAAH inhibitors provide a new class of anti-spastic agents that may have utility in treating spasticity in MS and avoid the dose-limiting side effects associated with cannabis use.

Multiple sclerosis spasticity daily management: retrospective data from Europe.

Multiple sclerosis (MS) is a distressing and debilitating disease, which often leads to a state of progressive deterioration for the individual. Spasticity is a common and disabling neurological feature with increasing presence and severity throughout the progression of MS. Management of this spasticity is a key component of day-to-day care for patients with MS. Data from recent epidemiological studies in Spain (the '6E' and '5E' studies) and Germany (the 'MOVE 1' study) confirm the frequent occurrence of spasticity symptoms in patients with MS. Despite the difficulties experienced by MS patients with spasticity, the condition is largely undertreated because current treatment options do not provide adequate control of MS spasticity. With worsening MS spasticity there is an increase in individual patient symptoms, worsening of quality of life and impairment of daily living. From a healthcare/societal perspective, MS spasticity has been shown to be associated with substantial costs. Many of these costs relate to the increased disability (and consequent need for rehabilitation and caregiver support) that are associated with moderate-to-severe spasticity. Consequently, newer drugs that can provide better symptomatic relief and may slow progression to more severe forms of disability will be a step forward in the level of care that we can provide for MS patients.

A new multiple sclerosis spasticity treatment option: effect in everyday clinical practice and cost-effectiveness in Germany.

Sativex® (GW Pharmaceuticals PLC, Porton Down, UK; Laboratorios Almirall, SA, Barcelona, Spain), a cannabinoid oromucosal spray containing a 1:1 ratio of 9-δ-tetrahydrocannabinol and cannabidiol, has been licensed in Germany since July 2011 as add-on therapy for moderate-to-severe multiple sclerosis (MS) treatment-resistant spasticity symptoms. The 'MOVE 2' study evaluated clinical outcomes, treatment satisfaction, quality of life (QoL) and provision of care in MS patients with spasticity receiving Sativex in everyday clinical practice. Data from 300 patients were collected from 42 specialized MS centers across Germany and were available for this analysis. Assessments, including the MS spasticity 0-10 numerical rating scale, modified Ashworth scale, patients' and physicians' clinical impressions, and QoL scales were rated at baseline and at 1 and 3 months after starting treatment with Sativex. Sativex provided relief of MS-related spasticity in the majority of patients who were previously resistant to treatment. In addition, clear improvements were noted in MS spasticity-associated symptoms (e.g., sleep quality, bladder function and mobility), activities of daily living and QoL. Sativex was generally well tolerated. The majority of patients (84%) reported no adverse events, and there was only a limited risk of serious adverse reactions. Furthermore, based on data from Sativex clinical trials, a Markov model-based analysis has shown that Sativex is a cost-effective treatment option for patients with MS spasticity in Germany.