Safety of baclofen versus tizanidine for older adults with musculoskeletal pain.

BACKGROUND: Baclofen and tizanidine are both muscle relaxants that carry the risk for neuropsychiatric events in older adults but there is a lack of data directly comparing their safety. This study aimed to investigate the relative risk between these two medications in causing injury and delirium in older adults. METHODS: This was a retrospective cohort study that was completed in an integrated healthcare system in the United States and included patients aged 65 years or older who started baclofen or tizanidine for the treatment of musculoskeletal pain from January 2016 through December 2018. Outcomes included new incidence of injury (concussion, contusion, dislocation, fall, fracture, or other injuries) and delirium. The cohort was followed from the initiation of therapy until the first occurrence of any of the following events: end of the index drug exposure, end of health plan membership, death, or the study end date of December 31st, 2019. Descriptive statistics were used to compare baseline patient characteristics between baclofen and tizanidine treatment groups. Cox proportional hazards model was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals. RESULTS: The final study cohort included 12,101 and 6,027 older adults in the baclofen and tizanidine group respectively (mean age 72.2 ± 6.2 years old, 59% female). Older adults newly started on baclofen had a greater risk of injury (HR = 1.54, 95% CI = 1.21-1.96, P = < 0.001) and delirium (HR = 3.33, 95% CI = 2.11-5.26, p = <0.001) compared to those started on tizanidine. CONCLUSION: The results of this study suggest that baclofen is associated with higher incidences of injury and delirium compared to tizanidine when used for the treatment of musculoskeletal pain. Future studies should investigate if these risks are dose-related and include a comparison group not exposed to either drug.

Surgical Treatment for Spasticity: Selective Dorsal Rhizotomy ­ Technique and Literature Review

Spasticity is amotor disorder that leads to a resistance to passive jointmovement. Cerebral palsy is the most important cause of spasticity and can be caused by several factors, including multiple gestations, alcoholism, infections, hemorrhages, drowning, and traumatic brain injuries, among others. There aremany scales that help tomeasure andmonitor the degree of impairment of these patients. The initial treatment should focus on the causal factor, such as tumors, inflammation, degenerative diseases, hydrocephalus, etc. Subsequently, the treatment of spastic musculature includes oral or intrathecal myorelaxants, spinal cord electrostimulation, neurotomies, Lissauer tract lesion, dentatotomy and selective dorsal rhizotomy. The latter is a safetechnique, possibleto beperformed inmost centers with neurosurgical support, and it is effective in the treatment of severe spasticity. In this article, the authors describe the surgical technique and conduct a review the literature.

Physical Compatibility of Nafamostat with Analgesics, Sedatives, and Muscle Relaxants for Treatment of Coronavirus Disease 2019.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) may require continuous administration of analgesics, sedatives, and muscle relaxants. Nafamostat has recently been reported as a therapeutic agent for COVID-19. However, there is a lack of information on the compatibility of nafamostat with the aforementioned drug classes. This study evaluated the physical compatibility of nafamostat with these drug classes. METHODS: Nafamostat was combined with 1-3 target drugs (fentanyl, morphine, midazolam, dexmedetomidine, and rocuronium). Fifteen physical compatibility tests were conducted. Nafamostat was dissolved in 5% glucose solution; the final concentration was 10 mg/mL. All other medications were diluted in 0.9% sodium chloride to obtain clinically relevant concentrations. The power of hydrogen (pH) of all medications was measured during each test. Compatibility tests were conducted with 4 test solutions in which nafamostat and the target drugs were compounded at equal volume ratios (1:1, 1:1:1, or 1:1:1:1). Visual appearance, turbidity, and pH were evaluated immediately after mixing and at 1 and 3 hours. Physical incompatibilities were defined as gross precipitation, cloudiness, appearance of the Tyndall effect, or a turbidity change of ≥0.5 nephelometric turbidity units (NTU) based on nafamostat. RESULTS: The mean pH of nafamostat was 3.13 ± 0.03. The combination of nafamostat, fentanyl, and dexmedetomidine had the highest pH (3.39 ± 0.01; 3 hours after mixing). All drugs were compatible with nafamostat until 3 hours after admixture, with a mean turbidity value of ≤0.03 NTU. CONCLUSIONS: Infusions combining nafamostat with the tested sedatives, analgesics, and muscle relaxants could be safely administered.

Optimal management of severe symptomatic gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common disorder, and empirical proton pump inhibitor (PPI) treatment is often the first step of management; however, up to 40% of patients remain symptomatic despite PPI treatment. Refractory reflux refers to continued symptoms despite an adequate trial of PPI, and management remains challenging. The differential diagnosis is important; other oesophageal (e.g. eosinophilic oesophagitis) and gastroduodenal disorders (e.g. functional dyspepsia) should be ruled out, as this changes management. A combination of clinical assessment, endoscopic evaluation and in selected cases oesophageal function testing can help characterize patients with refractory reflux symptoms into oesophageal phenotypes so appropriate therapy can be more optimally targeted. Medical options then may include adding a H2 receptor antagonist, alginates, baclofen or antidepressant therapy, and there is emerging evidence for bile acid sequestrants and diaphragmatic breathing. The demonstration of a temporal association of symptoms with reflux events on pH-impedance testing (reflux hypersensitivity) serves to focus the management on modulating oesophageal perception and reducing the reflux burden, or identifies those with no obvious pathophysiologic abnormalities (functional heartburn). Anti-reflux surgery based on randomized controlled trial evidence has a role in reflux hypersensitivity or continued pathological acid reflux despite PPI in carefully considered, fully worked up cases that have failed medical therapy; approximately two of three cases will respond but there is a small risk of complications. In patients with persistent volume reflux despite medical therapy, given the lack of alternatives, anti-reflux surgery is a consideration. Promising newer approaches include endoscopic techniques. This review aims to summarize current diagnostic approaches and critically evaluates the evidence for the efficacy of available treatments.

Ehlers-Danlos Syndrome: An Analysis of the Current Treatment Options.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a multifaceted disease that can present with a variety of types of pain. Unfortunately, both the mechanisms and treatments for pain are poorly understood. The proposed treatments for the various musculoskeletal pain syndromes in EDS have had variable success, and it becomes much more imperative to better define and evaluate the current treatment modalities in treating this debilitating disease. OBJECTIVES: The purpose of this study was to investigate the currently available treatment modalities for patients with EDS and their efficacies in pain and symptom relief. STUDY DESIGN: Retrospective cohort study. SETTING: Institutional physical medicine and rehabilitation primary care clinic. METHODS: All patients were seen between January 2015 and April 2019, in which 98 patients with EDS were identified through retrospective chart review. Institutional review board approval was obtained, and all patients provided written consent to be included in the study. We reviewed various treatment modalities, including complimentary/alternative treatments, opioids/opioid-like medications, nonsteroidal antiinflammatory drugs, physical therapy, occupational therapy, muscle relaxants, neuropathic modulators, steroids, surgery/procedures, and acetaminophen. Treatment methods were extracted from individual patient charts, and efficacy was grouped into 3 categories: improvement, no effect, or worsened symptoms. RESULTS: The most common treatments used were complimentary/alternative treatments (n = 88). Occupational therapy and bracing were the most effective options with 70% of patients reporting improvement. Neuropathic modulators were the least well tolerated with 47% of patients reporting adverse effects. LIMITATIONS: Men were a small percentage of the study. Patients were not randomized, and pain score reporting was subjective. Patient data were extracted from a single practice setting. Timing and symptom onset were not measured. CONCLUSIONS: There is a relative paucity of published literature regarding the various treatment methods for EDS. Although our study is able to identify positive and negative trends with certain modalities, it is vital to understand that EDS is not a uniform diagnosis among patients, and that a combination of several different treatments usually is needed for optimal symptom control. Further research and investigation are necessary to develop a comprehensive treatment database for this complex condition. KEY WORDS: Ehlers-Danlos syndrome, pain, hypermobility, arthralgia, subluxation, genetic, physical therapy, interventional pain.

Methanol Extract of Dicranopteris linearis Leaves Attenuate Pain via the Modulation of Opioid/NO-Mediated Pathway.

Dicranopteris linearis leaf has been reported to exert antinociceptive activity. The present study elucidates the possible mechanisms of antinociception modulated by the methanol extract of D. linearis leaves (MEDL) using various mouse models. The extract (25, 150, and 300 mg/kg) was administered orally to mice for 30 min priot to subjection to the acetic acid-induced writhing-, hot plate- or formalin-test to establish the antinociceptive profile of MEDL. The most effective dose was then used in the elucidation of possible mechanisms of action stage. The extract was also subjected to the phytochemical analyses. The results confirmed that MEDL exerted significant (p < 0.05) antinociceptive activity in those pain models as well as the capsaicin-, glutamate-, bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced paw licking model. Pretreatment with naloxone (a non-selective opioid antagonist) significantly (p < 0.05) reversed MEDL effect on thermal nociception. Only l-arginine (a nitric oxide (NO) donor) but not N(ω)-nitro-l-arginine methyl ester (l-NAME; a NO inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a specific soluble guanylyl cyclase inhibitor) significantly (p < 0.05) modified MEDL effect on the writhing test. Several polyphenolics and volatile antinociceptive compounds were detected in MEDL. In conclusion, MEDL exerted the opioid/NO-mediated antinociceptive activity, thus, justify D. linearis as a potential source for new analgesic agents development.

Involvement of Potassium Channels, Nitric Oxide Synthase, and Guanylate Cyclase in the Spasmolytic Effect of Simaba ferruginea A.St.-Hil on Rat Isolated Ileum.

BACKGROUND AND AIM: Simaba ferruginea A.St.-Hil. Popularly known as "calunga," is a typical Brazilian cerrado plant whose rhizomes are popular for treating diarrhea. AIMS: The aim of this study was to evaluate the spasmolytic activity and the antidiarrheal effect of the ethanolic extract obtained from S. ferruginea (Sf-EtOH). METHODS: Ileal segments (1-2 cm) from male Wistar rats were mounted in isolated organ baths and connected to a force transducer, and then to an amplifier which was connected to a computer (AVS Projetos/São Paulo-SP). After stabilization for 60 min, under tension (1 gf), two submaximal contractions were induced with KCl 40 mM or carbachol 10-6 M on ileal segments. During the third tonic and sustained contraction, Sf-EtOH was added in cumulative concentrations to the organ bath. Incubations with L-NAME (10-4 M), ODQ (10-5 M), TEA+ (5 or 1 mM), glibenclamide (10-5 M), or apamine (100 nM) were prepared (n = 5), separately and used to verify the involvement of the nitric oxide synthase, guanylate cyclase, and potassium channels in the relaxing effect. The results were expressed as mean ± standard error of the mean and were statistically evaluated using one-way ANOVA followed by Bonferroni test, when necessary *p < 0.05. RESULTS: Sf-EtOH promotes relaxation on rat isolated ileum pre-contracted with CCh and KCl in a concentration-dependent manner. Sf-EtOH also inhibited ileum contractions against cumulative concentrations of carbachol (CCh), KCl, and CaCl2, shifting the curves to the right in a non-parallel manner with an Emax reduction. In the presence of potassium channel blockers, Sf-EtOH shifted the curves to the right with a reduction of Emax, suggesting the involvement of BKCa, KATP, and SKCa in its spasmolytic effect. In the presence of L-NAME or ODQ, the relaxation curves were shifted to the right, suggesting the involvement of this pathway in Sf-EtOH spasmolytic effect. CONCLUSIONS: Sf-EtOH acts in a concentration-dependent manner, involving the positive modulation of K+ channels and NO pathway.

Role of dantrolene in dinitrophenol (DNP) overdose: A continuing question?

BACKGROUND: 2,4-Dinitrophenol (DNP) is a known uncoupler of oxidative phosphorylation that clinically results in hyperthermia, tachycardia, tachypnea, and metabolic acidosis. Overdoses of DNP are often fatal and there is no specific reversal therapy. Dantrolene interferes with calcium release in skeletal muscle and is traditionally used to treat malignant hyperthermia. There has been limited published data on its use in DNP toxicity. We present two cases of DNP toxicity that were treated with dantrolene. CASE 1: A 22-year-old male presented following an overdose of his bodybuilding supplements including DNP. He became altered, tachycardic, and hyperthermic to 40.0C. He required intubation and aggressive cooling. He received multiple doses of dantrolene over the initial 36 h with resolution of his hyperthermia. He was extubated and discharged home on hospital day 6. CASE 2: A 20-year-old male presented following a staggered ingestion of DNP. He was tachypneic and tachycardic on arrival. He became hyperthermic to 40.2C and required intubation. He underwent aggressive cooling and received 200 mg of IV dantrolene. His temperature normalized, however, he expired 4 h after ED arrival. CONCLUSION: DNP toxicity has limited treatment options. Dantrolene may ameliorate the hypermetabolic state in DNP toxicity by lessening excitation-contraction coupling in muscle cells and improving the associated hyperthermia. Our cases demonstrate the hyperthermia reducing effects of dantrolene in DNP toxicity and contribute to the existing literature on this topic. Being aware of the possible use of dantrolene to treat the associated hyperthermia could assist emergency physicians in the treatment of DNP toxicity.

Opioid Adjuncts: Optimizing Opioid Therapy With Nonopioid Medications.

In this article, we describe a variety of medications that physicians managing outpatient chronic pain should familiarize themselves with to better aid their approach to multimodal pain therapy. Physicians should always consider the use of an adjuvant or coanalgesic drug as first-line treatments. Although many of these medications are not primarily analgesics, in clinical practice they have independent analgesic effects or synergistic analgesic properties when used with opioids. The use of adjunct analgesics reduces opioid-related adverse effects and optimizes pain management. Although there may be some medication overlap with this section and the ERAS section, the purpose of this article is to understand prolonged use in the outpatient setting to reduce opioid use or limit opioid dose with adjuvant therapy.

A review of the effects of baclofen and of THC:CBD oromucosal spray on spasticity-related walking impairment in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a complex disease with a heterogeneous and unpredictable clinical course. Mobility impairment after progressive paralyses and muscle tone spasticity is common. Areas covered: The prevalence, assessment, and pharmacological management of gait impairment and spasticity in MS and their effects on health-related quality of life (HRQoL) are discussed. The roles of oral and intrathecal baclofen and of delta-9-tetrahydrocannabinol/cannabidiol (THC:CBD) oromucosal spray in treating MS spasticity-related gait impairment are reviewed. Expert commentary: Mobility impairment and spasticity are experienced by approximately 90% and 80% of MS patients, respectively, during the disease course. Prevalence and severity of gait impairment and spasticity increase as disease progresses. The symptoms are related and both impact negatively on HRQoL. Oral baclofen and tizanidine are generally used for first-line treatment of MS spasticity but are ineffective in approximately 40% of cases. Second-line therapy includes add-on THC:CBD spray for patients with resistant MS spasticity. Results of studies evaluating baclofen for treating MS spasticity gait impairment are equivocal. In studies of patients with resistant MS spasticity, THC:CBD spray consistently improved the timed 10-meter walk test and significantly improved multiple spatial-temporal and kinematic gait parameters. THC:CBD oromucosal spray warrants further investigation as a treatment for MS spasticity-related gait impairment.

Vaginal diazepam plus transcutaneous electrical nerve stimulation to treat vestibulodynia: A randomized controlled trial.

OBJECTIVE: To assess the effectiveness of vaginal diazepam in addition to transcutaneous electrical nerve stimulation (TENS) in the treatment of vestibulodynia (VBD). STUDY DESIGN: This study was a randomized, double-blind, placebo-controlled trial. Forty-two patients with VBD were randomized, 21 underwent diazepam and TENS (diazepam group) and 21 received placebo and TENS (placebo group). Vulvar pain was assessed on a on a 10-cm visual analogue scale (VAS) and dyspareunia according to the Marinoff dyspareunia scale. Vaginal surface electromyography (EMG) and vestibular current perception threshold (CPT) testing were performed at baseline and 60 days after treatment. The primary endpoints included the change in pain and dyspareunia from baseline to 60 days of pain and dyspareunia. The secondary endpoints was the variation in objectivity of pelvic floor muscle (PFM) function and vestibular nerve fiber current perception threshold (CPT). RESULTS: The VAS scores for pain from basal values of 7.5 and 7.2 for the diazepam and placebo, respectively, showed significant (p 0.01) decreases from 4.7 to 4.3, but this difference was not statistically significant. The Marinoff dyspareunia scores in the diazepam group showed a significant difference (p 0.05) from values measured in the placebo group. The ability to relax the PFM after contraction (difference between maximal contraction and rest tone) was significantly greater for the diazepam group versus the placebo group (3.8 µv and 2.4 µv, respectively, p 0.01). The CPT values for all of the nerve fibers increased after the treatment, but this increase was significant in the diazepam group only for the values at a 5-Hz stimulation (C fibers) with a change of 47.8% vs 26.9% (p < 0.05). Only two patients reported a mild drowsiness in the diazepam group. CONCLUSIONS: The present study provided indications that vaginal diazepam plus TENS is useful to improve pain and PFM instability in women with VBD.

Failing Hearts Are More Vulnerable to Sympathetic, but Not Vagal Stimulation-Induced, Atrial Fibrillation-Ameliorated with Dantrolene Treatment.

BACKGROUND: Both vagal (VS) and sympathetic (SS) stimulations can increase atrial fibrillation (AF) inducibility, with VS being known as more arrhythmogenic in normal hearts. Heart failure (HF) results in autonomic dysfunction (characterized by sympathetic activation and vagal withdrawal) and is associated with an increased AF incidence. This study investigated whether failing hearts, compared with normal control hearts, respond differently to autonomic stimulation-induced AF arrhythmogenesis and the effect of dantrolene on SS-enhanced AF in HF. METHODS AND RESULTS: A rat myocardial infarction (MI) HF model was used. In experiment 1, AF inducibility was compared in 9 MI-HF rats versus 10 sham-control animals at baseline, during VS, and during SS with isoproterenol infusion. In experiment 2, dantrolene treatment (n = 8) was compared with placebo-control (n = 9) on SS-induced AF inducibility in HF. Compared with the sham-control, baseline AF inducibility was higher in the MI-HF group. AF inducibility was augmented in both groups by autonomic stimulation. However, under VS the increased magnitude was less in the MI-HF group (49% ± 11% vs 80% ± 10%; P = .029), but under SS was significantly more (53% ± 8% vs 6% ± 7%; P < .001), compared with sham-control. Dantrolene significantly attenuated SS-enhanced AF in HF (69% ± 6% vs 29% ± 9%; P = .006). CONCLUSIONS: Failing hearts are less sensitive to VS, but more vulnerable to SS-induced AF compared with normal-control hearts. Dantrolene can significantly attenuate SS-enhanced AF in HF, indicating that cardiac ryanodine receptor dysfunction may play a critical role in SS-enhanced AF in HF, and stabilizing leaky ryanodine receptor with the use of dantrolene may be a new treatment option in this condition.

A mixed treatment comparison on efficacy and safety of treatments for spasticity caused by multiple sclerosis: a systematic review and network meta-analysis.

OBJECTIVES: This study is aimed at providing a quantitative evaluation on different therapies of spasticity caused by multiple sclerosis. DATA SOURCES: PubMed and Embase database. REVIEW METHODS: We searched for randomized controlled trials that met the requirements. Percentages of improved patients' spasticity scale, mild adverse effect and severe adverse effect were extracted as outcomes. The forest plots accompanied with surface under the cumulative ranking curves were used to reveal the efficacy and safety of these therapies. RESULTS: In all, 23 randomized controlled trials with a total of 2720 patients were included in our study. Cannabinoids and botulinum toxin had shown a significantly better efficacy than placebo in the percentage of improved patients. Botulinum toxin also showed such significant difference compared with tizanidine and baclofen. No significant difference was found in spasticity scale. Cannabinoids, tizanidine and diazepam had significantly more mild adverse effect reports than placebo. Surface under the cumulative ranking curves suggested that cannabinoids, botulinum toxin and transcutaneous electric nerve stimulation were preferable therapies. CONCLUSIONS: We recommended botulinum toxin as the optimal intervention for multiple sclerosis-related spasticity. Cannabinoids and transcutaneous electric nerve stimulation could also be considered as multiple sclerosis-related spasticity treatments but their safety remained to be verified.

Results of the post-registration clinical study "PARUS" on efficiency and safety assessment of Mydocalm-Richter for local injection therapy of a myofascial trigger zone.

AIM: The "PARUS" program included investigation of the analgesic, muscle relaxant and sedative effects of Mydocalm-Richter which acts as central muscle relaxant in patients with myofascial pain syndrome, taking into account its registered indication for use - the hypertonus and cross-striated muscle spasm. MATERIALS AND METHODS: Fifty patients with myofascial trigger points, the mean age of 41.67±11.86 years, have been enrolled in the study. All patients had undergone clinical examination that allowed the diagnosis of myofascial pain syndrome. The intensity of pain syndrome was evaluated using the pain visual analogue scales and McGill pain questionnaire. Visualization of area in spasm and evaluation of blood circulation was carried out using the ultrasound scan of target muscle. In order to objectively evaluate any conceivable hypotensive and sedative effects of Mydocalm-Richter we used the orthostatic test, Schulte's test for attention span and perfor-mance distribution and Munsterberg's test for attention discrimination and concentration. RESULTS: The analgesic and muscle relaxant effects of Mydocalm-Richter become apparent by day 3 post-injection, and the muscle relaxation effect is reaching its maximum on day 10 post-injection. Cardiovascular function following administration of Mydocalm-Richter was evaluated using the orthostatic test which revealed good orthostatic tolerance. Single injection of tolperisone hydrochloride possessing a central muscle relaxant activity has no sedative effect and does not influence patient response time. The ultrasound examination data demonstrated the improvement and in some cases restoration of blood circulation in the myofascial trigger points. CONCLUSION: Clinical study "PARUS" conducted in patients with myofascial pain has demonstrated a positive muscle relaxant and analgesic effect of Mydocalm-Richter that resulted in restoration of peripheral circulation in the myofascial trigger pointsconfirmed by ultrasound examination. An important benefit of this drug product is the absence of sedative effect and arterial hypotension.

Colonic perforation by an intrathecal baclofen pump catheter causing delayed Escherichia coli meningitis.

Intrathecal baclofen (ITB) delivery via an implanted pump is frequently used for the treatment of spasticity. This is an effective and safe neurosurgical and pharmacological intervention associated with an improvement in patient quality of life. There is, however, a risk of device-related infection. We present a patient with pump-site infection and Escherichia coli meningitis secondary to transcolonic perforation of an intrathecal baclofen pump catheter. While this is rare, we review the intraoperative precautions and best practices that should be taken to prevent and manage this unusual complication.

Acute and Subchronic Toxicity Studies of Aqueous Extract of Desmodium adscendens (Sw) DC.

Extracts of Desmodium adscendens (Sw) DC are used for the treatment of various diseases but limited toxicological evaluations have been done on the medicinal plant. This study investigates toxicity effects of the leave extract of D adscendens, and the possibility of drug-drug interaction of the plant extract when co-administered with other drugs. Oral administrations of leaf extract of D adscendens to white Wistar rats in an acute toxicity studies allowed the estimation of an LD50 (median lethal dose) value of 1122 mg/kg body weight. In a subchronic toxicity studies, the plant extract caused a decrease in zoxazolamine paralysis time and prevented thiopentone from causing sleep in test animals compared to controls. Overall, the results are consistent with the plant extract being safe at the doses administered in humans. However, the induction of the CYP enzymes is an indication of a possible drug interaction when the plant extract is co-administered with other drugs.

Neuromodulation in multiple sclerosis.

Neuromodulation, or the utilization of advanced technology for targeted electrical or chemical neuronal stimulation or inhibition, has been expanding in several neurological subspecialties. In the past decades, immune-modulating therapy has been the main focus of multiple sclerosis (MS) research with little attention to neuromodulation. However, with the recent advances in disease-modifying therapies, it is time to shift the focus of MS research to neuromodulation and restoration of function as with other neurological subspecialties. Preliminary research supports the value of intrathecal baclofen pump and functional electrical stimulation in improving spasticity and motor function in MS patients. Deep brain stimulation can improve MS-related tremor and trigeminal neuralgia. Spinal cord stimulation has been shown to be effective against MS-related pain and bladder dysfunction. Bladder overactivity also responds to sacral neuromodulation and posterior tibial nerve stimulation. Despite limited data in MS, transcranial magnetic stimulation and brain-computer interface are promising neuromodulatory techniques for symptom mitigation and neurorehabilitation of MS patients. In this review, we provide an overview of the available neuromodulatory techniques and the evidence for their use in MS.

Interventions for managing skeletal muscle spasticity following traumatic brain injury.

BACKGROUND: Skeletal muscle spasticity is a major physical complication resulting from traumatic brain injury (TBI), which can lead to muscle contracture, joint stiffness, reduced range of movement, broken skin and pain. Treatments for spasticity include a range of pharmacological and non-pharmacological interventions, often used in combination. Management of spasticity following TBI varies from other clinical populations because of the added complexity of behavioural and cognitive issues associated with TBI. OBJECTIVES: To assess the effects of interventions for managing skeletal muscle spasticity in people with TBI. SEARCH METHODS: In June 2017, we searched key databases including the Cochrane Injuries Group Specialised Register, CENTRAL, MEDLINE (Ovid), Embase (Ovid) and others, in addition to clinical trials registries and the reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cross-over RCTs evaluating any intervention for the management of spasticity in TBI. Only studies where at least 50% of participants had a TBI (or for whom separate data for participants with TBI were available) were included. The primary outcomes were spasticity and adverse effects. Secondary outcome measures were classified according to the World Health Organization International Classification of Functioning, Disability and Health including body functions (sensory, pain, neuromusculoskeletal and movement-related functions) and activities and participation (general tasks and demands; mobility; self-care; domestic life; major life areas; community, social and civic life). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Data were synthesised narratively; meta-analysis was precluded due to the paucity and heterogeneity of data. MAIN RESULTS: We included nine studies in this review which involved 134 participants with TBI. Only five studies reported between-group differences, yielding outcome data for 105 participants with TBI. These five studies assessed the effects of a range of pharmacological (baclofen, botulinum toxin A) and non-pharmacological (casting, physiotherapy, splints, tilt table standing and electrical stimulation) interventions, often in combination. The studies which tested the effect of baclofen and tizanidine did not report their results adequately. Where outcome data were available, spasticity and adverse events were reported, in addition to some secondary outcome measures.Of the five studies with results, three were funded by governments, charities or health services and two were funded by a pharmaceutical or medical technology company. The four studies without useable results were funded by pharmaceutical or medical technology companies.It was difficult to draw conclusions about the effectiveness of these interventions due to poor reporting, small study size and the fact that participants with TBI were usually only a proportion of the overall total. Meta-analysis was not feasible due to the paucity of data and heterogeneity of interventions and comparator groups. Some studies concluded that the intervention they tested had beneficial effects on spasticity, and others found no difference between certain treatments. The most common adverse event was minor skin damage in people who received casting. We believe it would be misleading to provide any further description of study results given the quality of the evidence was very low for all outcomes. AUTHORS' CONCLUSIONS: The very low quality and limited amount of evidence about the management of spasticity in people with TBI means that we are uncertain about the effectiveness or harms of these interventions. Well-designed and adequately powered studies using functional outcome measures to test the interventions used in clinical practice are needed.

[Update on muscle relaxation : What comes after succinylcholine, rocuronium and sugammadex?] / Update Muskelrelaxation : Was kommt nach Succinylcholin, Rocuronium und Sugammadex?

Due to the great advantages, it is not possible to imagine current practice in anesthesia without the adminstration of muscle relaxants. For a long time the administration of succinylcholine for rapid sequence induction (RSI) was considered to be the state of the art for patients at risk for aspiration. The favorable characteristics are, however, accompanied by many, sometimes severe side effects. Due to the development of non-depolarizing muscle relaxants, in particular rocuronium in combination with sugammadex, there is the possibility to achieve a profile of action similar to succinylcholine with low side effects. After the introduction of sugammadex onto the market, further substances were conceived, which enable a complete encapsulation of muscle relaxants. Calabadion is a very promising new substance for the antagonization of muscle relaxants, which can antagonize the action of steroid as well as benzylisoquinoline types. In the USA new muscle relaxants are currently being tested, which have a rapid onset and the effect can be reversed by L­cysteine. One of the most promising substances is gantacurium, which is currently being tested in the USA in phase III trials. It remains to be seen whether these muscle relaxants, which are not yet on the market and drugs for reversal of neuromuscular blockade have the potential to become a real alternative to the combination of rocuronium and sugammadex.