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Background: Patients with end-stage renal disease undergoing dialysis suffer from muscle cramps, a prevalent and burdensome symptom for which there is a paucity of efficient and safe treatments., Aim: What is the efficacy and safety of pharmacological interventions for the treatment of dialysis-related muscle cramps?, Design: A systematic review was conducted in OVID, CINAHL, PubMed, Web of Science, and Central Cochrane databases up to August 25, 2023., Data Sources: Experimental studies reporting on a pharmacological intervention for the treatment of dialysis-related muscle cramps were included. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, and the studies quality was assessed with the RoB2 tool., Results: A total of 4660 studies were retrieved, and 13 articles were included. The studies reported on nine interventions: vitamin C, vitamin E, vitamin K2, vitamin B7, dextrose solutions, gabapentin, sodium chloride, creatine monohydrate, and L-carnitine. The studies testing L-carnitine and creatine monohydrate were the only ones deemed to have a low risk of bias. Side effects were reported in only two trials, consisting primarily of gastrointestinal discomfort and hyperglycemia. Vitamins C and E are the two most studied interventions that showed positive results in reducing the frequency, severity, and duration of dialysis-related muscle cramps. L-carnitine is a promising intervention that warrants further investigation., Conclusion: Our review consolidates the existing evidence, elucidating the range of treatments along with their potential benefits and limitations. Future studies should uphold high-quality standards, incorporate patient-reported outcomes, and utilize well-defined, robust samples to improve patient care., (© 2024 Wiley Periodicals LLC.)

The status of parsley as a well-known folk medicine noted for its nutritional and medicinal properties prompted the exploration of its potential as a functional food and natural remedy. The paper aims to investigate the potential of parsley to enhance muscle function and alleviate psoriasiform dermatitis, eventually establishing it as a natural, well-tolerated alternative with specific benefits for both muscles and skin. This study examines the tolerability of parsley in a cohort of 937 participants by assessing immunoglobulin G (IgG) reactions. The findings reveal high tolerability, as 96.26% of participants experienced no adverse effects. Among the 902 individuals lacking hypersensitivity, 37.02% reported muscle cramps, with a notable 15.02% reduction observed in the subgroup consuming parsley juice. In the subset of 32 subjects with dermatitis, the application of parsley extract ointment led to a significant decrease in dermatological parameters (redness, thickness, scaling). While the control group exhibited improvements, statistical significance was not observed. Notably, four categories of affected area reduction were identified, with scaling demonstrating the most pronounced impact. The results propose that parsley holds promise for favorable tolerability, contributing to the alleviation of muscle cramps and presenting an effective alternative in dermatitis treatment. Nonetheless, sustained validation through long-term studies is imperative to substantiate these preliminary findings.

Chronic musculoskeletal pain (CMP) is associated with an increased risk of cardiovascular disease (CVD). This study aimed to determine the factors associated with the intensity of CMP in patients with underlying CVD and to evaluate the efficacy of Ice Power Magnesium In Strong Cream in patients with muscle cramps. We investigated 396 patients with or without CMP who visited an outpatient cardiology clinic and analyzed the features of CMP and factors associated with pain intensity and specific types of CVD in study 1. We also analyzed 73 patients who had muscle cramps in the lower extremities in study 2 to evaluate the efficacy of Ice Power Magnesium In Strong Cream in reducing pain intensity. In study 1, multivariable linear regression analysis showed that older age (regression coefficient [B] = 0.66, 95% confidence interval [CI], 0.07-1.24), female sex (B = 1.18, 95% CI, 0.59-1.76), presence of hypertension (B = 0.69, 95% CI, 0.05-1.33), and use of calcium supplements (B = 1.27, 95% CI, 0.31-2.24) were significantly associated with a higher intensity of CMP. In study 2, the mean pain scores at baseline, week 2 and week 4 after treatment were 5.99 ± 2.12, 2.92 ± 2.63, and 1.90 ± 2.41, respectively, and the reductions were significant at both week 2 and week 4 after treatment (P < .05). Older age, female sex, hypertension, and use of calcium supplements were associated with an increased intensity of CMP. Ice Power Magnesium In Strong Cream was effective in reducing the pain intensity of muscle cramps in the lower extremities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction/aims: Muscle cramps are a common and often disabling symptom in amyotrophic lateral sclerosis (ALS), a devastating and incurable neurodegenerative disorder. To date, there are no medications specifically approved for the treatment of muscle cramps. Ameliorating muscle cramps in ALS may improve and sustain quality of life. A widely prescribed traditional Japanese (Kampo) medicine against muscle cramps, shakuyakukanzoto (TJ-68), has been studied in advanced liver disease, spinal stenosis, kidney failure, and diabetic neuropathy. The Japanese ALS Management Guideline mentions TJ-68 for difficult muscle cramps in ALS. Therefore, the rationale of our trial is to investigate the safety and effectiveness of TJ-68 in treating painful and disabling muscle cramps in people with ALS outside of Japan. Accordingly, we are conducting a randomized clinical trial to test the safety and efficacy of TJ-68 in participants with ALS reporting frequent muscle cramps using an innovative, personalized N-of-1 design. If successful, TJ-68 may be used for muscle cramps in a broader population of people with ALS., Methods: This is a two-site, double-blind, randomized personalized N-of-1 early clinical trial with TJ-68. At least 22 participants with ALS and daily muscle cramps will receive drug or placebo for 2 weeks (one treatment period) followed by a 1-week washout in a four-period cross-over design. While the primary objective is to evaluate the safety of TJ-68, the study has 85% power to detect a one-point shift on the Visual Analog Scale for Muscle Cramps Affecting Overall Daily Activity of the Columbia Muscle Cramp Scale (MCS). Secondary outcomes include the full MCS score, a Cramp Diary, Clinical Global Impression of Changes, Goal Attainment Scale, quality of life scale and ALS functional rating scale-revised (ALSFRS-R)., Discussion: The study is underway. A personalized N-of-1 trial design is an efficient approach to testing medications that alleviate muscle cramps in rare disorders. If TJ-68 proves safe and efficacious then it may be used to treat cramps in ALS, and help to improve and sustain quality of life., Trial Registration: This clinical trial has been registered with ClinicalTrials.gov (NCT04998305), 8/9/2021., (© 2023. The Author(s).)

Introduction: MetforminHydrochloride is an antidiabetic used for many years, currently; it considered the first choice in treatment of type 2 diabetes (T2D). It decreases insulin resistance, does not induce hypoglycaemia, increases glucose utilization in the liver and skeletal muscle, and decreases hepatic glucose production. Its adverse effects (AE) are gastrointestinal, decrease in vitamin B12 absorption, abnormalities of hemogram and rarely skin reactions. The objective of this study was to report the type and frequency of AEs of Metformin Hydrochloride used in the therapeutic management of T2D patients admitted to the medical center and the diabetes home of Sidi Bel-Abbès in Algeria., Materials and Methods: A cross-sectional descriptive study was carried out over a period of four months, from January 1st, 2017 to April 30th, 2017, involving 130 patients treated with Metformin Hydrochloride consulting at Mimoun City Diabetes Home and Gambetta Diabetes Center in the town of Sidi Bel-Abbès. The primary outcome measure was the determination of the type and frequency of AEs related to normal dosages or overdose use of Metformin Hydrochloride in T2D. Data were collected from patient records, using a questionnaire, and analyzed using Statistical Package for the Social Sciences, version 20 software., Results: 130 patients were included, including 82 women, with a mean age of 51.08±8.85 years (30-66). One hundred and ninety-eight (198) AEs were reported, an average of 1.52 AEs per patient. Among them, 95 (47.98%) AEs are digestive disorders (30.77% of patients suffered from diarrhea, 10.77% had nausea and vomiting, 8.46% suffered from abdominal pain and bloating, 3.85% lost their taste, 7.69% complained of epigastric cramps and 11.54% of anorexia), 29 (14.65%) AEs are hypoglycaemia, 73 (36.87%) AEs are other symptoms and 1 (0.50%) EI is vitamin B12 deficiency and no cases of lactic acidosis or allergic reaction were reported. Five (3.85%) patients had a total and lasting intolerance to Metformin Hydrochloride leading to its discontinuation following persistent diarrhoea., Conclusion: AEs of Metformin Hydrochloride used in the management of T2D patients consulting at the medical center and the Diabetes home of Sidi Bel-Abbès are frequent. Digestive disorders were the most frequent, diarrhea was very frequent and led to discontinuation of treatment in 3.85% of T2D patients, followed by nausea and vomiting, then abdominal pain, bloating and epigastric cramps, and rarely taste metallic. Hypoglycaemia was frequent following its association with insulin, the onset of headaches and fatigue were frequent, but no case of lactic acidosis or allergic reaction was reported. Due to a lack of means, the dosage of homocysteine and methylmalonic acid had not been carried out to confirm the vitamin B12 deficiency in the patient whose level was less than 200ng/mL. A precise assessment of the imputability of reported AEs is necessary., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Muscle cramps and fatigue are common complications in hemodialysis patients and have been associated with reduced patient comfort. Among the complementary therapies advocated for the management of these complications have been the application of warm or cold compresses to the extremities during a hemodialysis treatment. In this study, we compared the effects of warm or cold compresses application on cramping, fatigue, and patient comfort., Methods: This placebo-controlled randomized trial was done in 69 patients, who were stratified and randomly allocated to three treatment arms. Two of the three groups included an intervention; application of either warm (n = 23) or cold (n = 23) compresses to the extremities during dialysis. The third group served as a placebo control (n = 23). The study period comprised 12 hemodialysis sessions. One week after the completion of the intervention, a follow-up dialysis session was also evaluated. Data were collected at baseline (t 0 ), during each of 12 intervention sessions (t 1 -t 12 ), and at the follow-up session t 13 . Cramps, fatigue, and patient comfort were evaluated using the Cramp Episode Follow-up Chart, Piper's Fatigue Scale, and the Hemodialysis Comfort Scale, respectively., Results: In both the intervention and follow-up sessions, cramping and fatigue were lower, and comfort was higher in each of the intervention groups compared to placebo controls Application of warm compresses was superior to use of cold compresses., Discussion: Both warm and cold compress administration reduced muscle cramps, fatigue, and hemodialysis comfort in hemodialysis patients., (© 2023 International Society for Hemodialysis.)

Quinine has been used in Western medicine since the 16th century, and far longer in South America. It has gained an undeserved reputation as an effective treatment for leg cramps and continues to be widely used in the United Kingdom and elsewhere despite warnings from the Medicines and Healthcare products Regulatory Agency (MHRA) and the US Food and Drug Administration (FDA). The effects in overdose are outlined and a personal perspective of scientific investigation of treatments at one time advocated provided.

Background: Dialysis patients have been shown to have low serum carnitine due to poor nutrition, deprivation of endogenous synthesis from kidneys, and removal by hemodialysis. Carnitine deficiency leads to impaired cardiac function and dialysis-related hypotension which are associated with increased mortality. Supplementing with levocarnitine among hemodialysis patients may diminish incidence of intradialytic hypotension. Data on this topic, however, lacks consensus., Methods: We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to 19th November 2021 to identify randomized controlled studies (RCTs), which examined the effects of oral or intravenous levocarnitine (L-carnitine) on dialysis-related hypotension among hemodialysis patients. The secondary outcome was muscle cramps. Study results were pooled and analyzed utilizing the random-effects model. Trial sequential analysis (TSA) was performed to assess the strength of current evidence., Results: Eight trials with 224 participants were included in our meta-analysis. Compared to control group, L-carnitine reduced the incidence of dialysis-related hypotension among hemodialysis patients (pooled OR = 0.26, 95% CI [0.10-0.72], p = 0.01, I2 = 76.0%). TSA demonstrated that the evidence was sufficient to conclude the finding. Five studies with 147 participants showed a reduction in the incidence of muscle cramps with L-carnitine group (pooled OR = 0.22, 95% CI [0.06-0.81], p = 0.02, I2 = 74.7%). However, TSA suggested that further high-quality studies were required. Subgroup analysis on the route of supplementation revealed that only oral but not intravenous L-carnitine significantly reduced dialysis-related hypotension. Regarding dose and duration of L-carnitine supplementation, the dose > 4,200 mg/week and duration of at least 12 weeks appeared to prevent dialysis-related hypotension., Conclusion: Supplementing oral L-carnitine for at least three months above 4,200 mg/week helps prevent dialysis-related hypotension. L-carnitine supplementation may ameliorate muscle cramps. Further well-powered studies are required to conclude this benefit., Competing Interests: The authors have declared that no competing interests exist.

Introduction/aims: Neuronal hyperexcitability (manifested by cramps) plays a pathological role in amyotrophic lateral sclerosis (ALS), and drugs affecting it may help symptomatic management and slow disease progression. We aimed to determine safety and tolerability of two doses of ranolazine in patients with ALS and evaluate for preliminary evidence of drug-target engagement by assessing muscle cramp characteristics., Methods: We performed an open-label dose-ascending study of ranolazine in 14 individuals with ALS in two sequential cohorts: 500 mg (cohort 1) and 1000 mg (cohort 2) orally twice daily. Each had a 2-week run-in period, 4-week drug administration, and 6-week safety follow-up. Primary outcome was safety and tolerability. Exploratory measures included cramp frequency and severity, fasciculation frequency, cramp potential duration, ALS Functional Rating Scale---Revised score, and forced vital capacity., Results: Six and eight participants were enrolled in cohorts 1 and 2, respectively. There were no serious adverse events. Two subjects in cohort 2 discontinued the drug due to constipation. The most frequent drug-related adverse event was gastrointestinal (40%). Cramp frequency decreased by 54.8% (95% confidence interval [CI], 39%-70.8%) and severity decreased by 46.3% (95% CI, 29.5-63.3%), which appeared to be dose-dependent, with decreased awakening due to cramps. Other outcomes showed no change., Discussion: Ranolazine was well tolerated in ALS up to 2000 mg/day, with gastrointestinal side effects being the most frequent. Ranolazine reduced cramp frequency and severity, supporting its investigation for muscle cramps in a future placebo-controlled trial., (© 2022 Wiley Periodicals LLC.)

Leg cramping is a common side effect of hemodialysis, and this is frequently treated by the administration of carnitine, but this is not effective in every patient. Alkalosis is a key component of the etiology of leg cramping during hemodialysis sessions. This is mediated through the binding of calcium ions to serum albumin, which causes hypocalcemia, and an increase in the release of calcium ions from the sarcoplasmic reticulum. Normally the calcium pump on the sarcoplasmic reticulum consumes ATP and quickly reuptakes the released calcium ions, which rapidly stops excessive muscle contractions. Thus, carnitine deficiency results in prolonged muscle contraction because of ATP depletion. However, during ATP production, carnitine is only involved up to the stage of acyl-CoA transport into mitochondria, and for the efficient generation of ATP, the subsequent metabolism of acyl-CoA is also important. For example, β-oxidation and the tricarboxylic acid cycle may be affected by a deficiency of water-soluble vitamins and the electron transport chain requires coenzyme Q10, but statins inhibit its production. The resulting accumulation of excess long-chain acyl-CoA in mitochondria inhibits enzymes involved in energy production. Thus, carnitine administration may be used more effectively if clinicians are aware of its specific physiologic roles., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Competing Interests: The author declares no conflicts of interest.

Purpose: Painful muscle cramps are a common complication in liver cirrhosis patients, and no effective treatment is available. This pilot study aimed to evaluate whether taurine supplementation improves muscle cramps in Korean cirrhotic patients., Materials and Methods: Ten cirrhotic patients who experienced muscle cramps one or more times/week were enrolled in this prospective single-arm study and administered with an oral taurine solution (1 g/50 mL) thrice a day for 4 weeks. Taurine was discontinued for the subsequent 4 weeks. The frequency and intensity of muscle cramps were evaluated using a questionnaire at weeks 0, 2, 4, 6, and 8 after the start of treatment., Results: At baseline, the median frequency of muscle cramps was six times/week, and all patients had severe pain. Muscle cramp scores (frequency×intensity) decreased in seven patients by weeks 4 and 8 after treatment initiation. Compared to baseline muscle cramp scores [median 21, interquartile range (IQR): 8-84], median muscle cramp scores were lower at week 4 (6.5, IQR: 3-12, p =0.126) and week 8 (5, IQR: 1.5-56, p =0.066). All five patients whose baseline plasma taurine levels were below the normal limit showed increased taurine levels at week 4; 60% of them experienced improvements in their muscle cramps. Of the five patients with normal or higher taurine levels, 80% experienced an improvement in symptoms at week 4. The safety and tolerability of the 4-week taurine therapy were excellent., Conclusion: Oral taurine therapy for 4 weeks improved muscle cramps safely in cirrhotic patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2021.)

Background: Muscle cramps are suddenly occurring involuntary, mostly painful contractions of a single muscle, rarely of a muscle group. They can be idiopathic or occur in various neuromuscular diseases and can sometimes substantially impair the quality of life due to the frequency and strength. Only a few drugs are available for the effective treatment of cramps., Results: In this case series we report on five patients with cramps of different origin who responded well to treatment with brivaracetam., Discussion: Brivaracetam is actually used for the treatment of epileptic seizures. It binds to the synaptic vesicle protein 2A (SV2A), which also occurs in nerves and nerve roots. The SV2A regulates the exocytotic release of neurotransmitters, which could explain the effect of brivaracetam on muscle cramps., Conclusion: Further studies are needed to demonstrate the effect of brivaracetam on muscle cramps.

Background: Mexiletine is a potential drug in amyotrophic lateral sclerosis (ALS) that has been tested in clinical trials. The objective of this study was to determine the efficacy and safety of mexiletine in ALS via systematic review of existing evidences. Materials & methods: Relevant records were searched using major healthcare electronic databases. Data on functional disability, impairment, survival, muscle cramp frequency and severity, and adverse events were obtained. Results & conclusion: Three relevant randomized controlled trials with 141 patients were included in this review. Mexiletine has no effect on the functional disability, impairment and survival in ALS. However, significant improvement in reducing muscle cramp severity and frequency was shown. The most common adverse effect associated with mexiletine intake among ALS patients are nausea (n = 11, 7.8%) and tremors (n = 5, 3.6%).

Introduction: There is limited data in the scientific literature using quantitative methods to assess response of golfer's cramp to intervention. The objective of this pilot study was to use quantitative measures to study the effect of propranolol and looking at the hole when putting., Methods: 14 golfers completed 50 10' putts (10 each x 5 conditions): two-handed looking at the ball, right hand only looking at the ball, two-handed looking at the hole, then following a single 10 mg oral dose of propranolol two-handed and right hand only putts looking at the ball. Quantitative measurements of putter movement and surface EMG to assess wrist muscle co-contraction were measured., Results: Based on video review of the putting, five golfers with dystonic golfer's cramp and nine with non-dystonic yips were compared. Those with dystonic golfer's cramp had more putts with the yips and yips with co-contraction when two-handed putting looking at the ball, no increase when putting right hand only, less smoothness of putter movement, and all of these improved following propranolol and when looking at the hole. The non-dystonic group had an increase in yipped putts and yipped putts with co-contraction putting right hand only and no improvement with either intervention., Conclusion: Yipped putts with co-contraction, right hand only putting, and smoothness of putter movement differed between dystonic golfer's cramp and non-dystonic yips. Propranolol and looking at the hole only improved dystonic golfer's cramp putting. This is the first pilot study of oral medication treatment for this task-specific dystonia., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Skeletal muscle cramps are common and often occur in association with pregnancy, advanced age, exercise or motor neuron disorders (such as amyotrophic lateral sclerosis). Typically, such cramps have no obvious underlying pathology, and so are termed idiopathic. Magnesium supplements are marketed for the prophylaxis of cramps but the efficacy of magnesium for this purpose remains unclear. This is an update of a Cochrane Review first published in 2012, and performed to identify and incorporate more recent studies., Objectives: To assess the effects of magnesium supplementation compared to no treatment, placebo control or other cramp therapies in people with skeletal muscle cramps.   SEARCH METHODS: On 9 September 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, CINAHL Plus, AMED, and SPORTDiscus. We also searched WHO-ICTRP and ClinicalTrials.gov for registered trials that might be ongoing or unpublished, and ISI Web of Science for studies citing the studies included in this review., Selection Criteria: Randomized controlled trials (RCTs) of magnesium supplementation (in any form) to prevent skeletal muscle cramps in any patient group (i.e. all clinical presentations of cramp). We considered comparisons of magnesium with no treatment, placebo control, or other therapy., Data Collection and Analysis: Two review authors independently selected trials for inclusion and extracted data. Two review authors assessed risk of bias. We attempted to contact all study authors when questions arose and obtained participant-level data for four of the included trials, one of which was unpublished. We collected all data on adverse effects from the included RCTs., Main Results: We identified 11 trials (nine parallel-group, two cross-over) enrolling a total of 735 individuals, amongst whom 118 cross-over participants additionally served as their own controls. Five trials enrolled women with pregnancy-associated leg cramps (408 participants) and five trials enrolled people with idiopathic cramps (271 participants, with 118 additionally crossed over to control). Another study enrolled 29 people with liver cirrhosis, only some of whom suffered muscle cramps. All trials provided magnesium as an oral supplement, except for one trial which provided magnesium as a series of slow intravenous infusions. Nine trials compared magnesium to placebo, one trial compared magnesium to no treatment, calcium carbonate or vitamin B, and another trial compared magnesium to vitamin E or calcium. We judged the single trial in people with liver cirrhosis and all five trials in participants with pregnancy-associated leg cramps to be at high risk of bias. In contrast, we rated the risk of bias high in only one of five trials in participants with idiopathic rest cramps. For idiopathic cramps, largely in older adults (mean age 61.6 to 69.3 years) presumed to have nocturnal leg cramps (the commonest presentation), differences in measures of cramp frequency when comparing magnesium to placebo were small, not statistically significant, and showed minimal heterogeneity (I² = 0% to 12%). This includes the primary endpoint, percentage change from baseline in the number of cramps per week at four weeks (mean difference (MD) -9.59%, 95% confidence interval (CI) -23.14% to 3.97%; 3 studies, 177 participants; moderate-certainty evidence); and the difference in the number of cramps per week at four weeks (MD -0.18 cramps/week, 95% CI -0.84 to 0.49; 5 studies, 307 participants; moderate-certainty evidence). The percentage of individuals experiencing a 25% or better reduction in cramp rate from baseline was also no different (RR 1.04, 95% CI 0.84 to 1.29; 3 studies, 177 participants; high-certainty evidence). Similarly, no statistically significant difference was found at four weeks in measures of cramp intensity or cramp duration. This includes the number of participants rating their cramps as moderate or severe at four weeks (RR 1.33, 95% CI 0.81 to 2.21; 2 studies, 91 participants; moderate-certainty evidence); and the percentage of participants with the majority of cramp durations of one minute or more at four weeks (RR 1.83, 95% CI 0.74 to 4.53, 1 study, 46 participants; low-certainty evidence). We were unable to perform meta-analysis for trials of pregnancy-associated leg cramps. The single study comparing magnesium to no treatment failed to find statistically significant benefit on a three-point ordinal scale of overall treatment efficacy. Of the three trials comparing magnesium to placebo, one found no benefit on frequency or intensity measures, another found benefit for both, and a third reported inconsistent results for frequency that could not be reconciled. The single study in people with liver cirrhosis was small and had limited reporting of cramps, but found no difference in terms of cramp frequency or cramp intensity. Our analysis of adverse events pooled all studies, regardless of the setting in which cramps occurred. Major adverse events (occurring in 2 out of 72 magnesium recipients and 3 out of 68 placebo recipients), and withdrawals due to adverse events, were not significantly different from placebo. However, in the four studies for which it could be determined, more participants experienced minor adverse events in the magnesium group than in the placebo group (RR 1.51, 95% CI 0.98 to 2.33; 4 studies, 254 participants; low-certainty evidence). Overall, oral magnesium was associated with mostly gastrointestinal adverse events (e.g. diarrhoea), experienced by 11% (10% in control) to 37% (14% in control) of participants., Authors' Conclusions: It is unlikely that magnesium supplementation provides clinically meaningful cramp prophylaxis to older adults experiencing skeletal muscle cramps. In contrast, for those experiencing pregnancy-associated rest cramps the literature is conflicting and further research in this population is needed. We found no RCTs evaluating magnesium for exercise-associated muscle cramps or disease-state-associated muscle cramps (for example amyotrophic lateral sclerosis/motor neuron disease) other than a single small (inconclusive) study in people with liver cirrhosis, only some of whom suffered cramps., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: Many patients of liver cirrhosis are complaining of muscle cramps, which are annoying to them. There is no effective treatment for muscle cramps in cirrhotic patients till now. This study purposed to evaluate efficacy and safety of orphenadrine in the treatment of muscle cramps in cirrhotic patients., Methods: One hundred and twenty four patients who had muscle cramps three or more times weekly were included. They were divided into two arms: 62 patients administrated orphenadrine and 62 administrated placebo. They were followed up till 2 weeks after the end of therapy. Muscle cramps were evaluated using questionnaire as regards severity, duration, and frequency. Also, side effects of orphenadrine were recorded., Results: Frequency, duration of muscle cramps, and pain score improved significantly after 1 month of orphenadrine therapy in comparison to placebo. Few side effects were recorded in the form of dry mouth, drowsiness, and nausea., Conclusion: Orphenadrine is considered as promising safe drug for treatment of muscle cramps associated with liver cirrhosis.

The study analyzes the medication rules of Xin&apos;an Wang&apos;s internal medicine for treating stomach cramps by data mining technology,in order to provide reference for clinical medication. Through the summarization of the medical cases of stomach cramps treated by Xin&apos;an Wang&apos;s doctors( Wang Ren-zhi,Wang Zhong-qi,Wang Le-tao),statistics was made for the frequency of symptoms,signs,syndromes and drugs in Office 2010. Apriori algorithm in IBM SPSS Modeler 14. 1,and SPSS Statistics 22. 0 were used for association rule analysis and cluster analysis. The results showed that the 310 prescriptions collected involved totally 322 syndromes( including symptoms and signs) and 336 drugs,with the cumulative dose of 4 072 times; the symptoms were correlated to the spleen and stomach,liver and gallbladder,and the heart system; syndrome differentiation was mainly based on liver-Qi invasion of the stomach,diet impairment to the stomach,deficiency of spleen and stomach and cold syndrome; commonly used drugs were Qi regulating drugs,phlegm eliminating drugs and blood circulation promoting and stasis removing drugs; high-frequency drug complex network diagram showed that Pinelliae Rhizoma,Aurantii Fructus,Trichosanthis Fructus,Allii Macrostemonis Bulbus were closely related; the analysis showed 12,20,and 17 two,three,and four association rules; cluster analysis showed 10 pairs of Trichosanthis Fructus-Allii Macrostemonis Bulbus,Pinelliae Rhizoma-Aurantii Fructus,and Aspongopus-Toosendan Fructus drug combinations. According to Xin&apos; an Wang&apos;s doctors,stomach cramps are closely related to liver and spleen,Qi stagnation,phlegm and blood stasis are the standard.Xin&apos;an Wang&apos;s doctors give the first priority on &quot; deoppilation&quot;,focus on soothing the liver and spleen,activating Qi and eliminating phlegm,and promoting blood circulation,and refer to use modified Xiaoxianxiong Decoction and modified Gualou Xiebai Banxia Decoction based on symptoms.

Background: There has been a small number of reports mention the clinical features including quality of life (QOL) in liver cirrhosis (LC) patients with muscle cramping and therapeutic efficacy for muscle cramping. We evaluated clinical features of muscle cramping and treatments in such patients., Patients and Methods: Two-hundred and eighty-nine LC outpatients (70.6 ± 10.5 years old; male: female = 149: 140) were questioned regarding the presence or absence of muscle cramps within the last 3 months, including frequency, severity of related pain using a visual analogue scale, cramp locations, time of day, duration, sleep disturbance, daily activity decline, and being conscious of QOL decline. At the next hospital-visit, 3 or 4 months later, the subjects, who treated with medical intervention, received the same questionnaire., Results: Patients with muscle cramps (n = 160) included a higher percentage of females (53.8 vs. 41.9%, P = 0.045), worse Child-Pugh score (5: 6: 7: 8: 9: 10 = 91: 36: 15: 10: 4: 4 vs. 85: 25: 12: 5: 0: 2, P = 0.043) and lower platelet count (10.2 ± 4.7 vs. 11.8 ± 5.0 × 104/µl, P = 0.006) as compared to those without cramps (n = 129). Of the 160 with cramping, 82 (51.3%), received treatment with several types of medication, with l-carnitine the most administered drug (n = 66: 80.5%), and those also showed a tendency to complain about muscle cramps at night, sleep disturbance, reduced daily activity, and being conscious of QOL decline (each P < 0.01). We observed that frequency, visual analogue scale, sleep disturbance, daily activity, duration of muscle cramping, and being conscious of QOL decline were improved after the intervention (each P < 0.001, respectively)., Conclusion: Intervention for muscle cramping improves total QOL in LC patients with such symptom.

Background: Frequent and painful nocturnal leg cramps (NLC) require an effective therapy to improve quality of life and sleep performance in patients., Method: In a multicenter, prospective, non-interventional study (NIS) data on the effectiveness, tolerability and safety of quinine sulfate were collected in daily medical management in adult patients with frequent and painful nocturnal leg cramps., Results: In total 596 patients were included into the study. Of these, 568 patients finished the study as planned (95.3%). Number, duration and pain intensity of NLC were reduced in the majority of patients after 2 weeks of therapy with quinine sulfate 200 mg OD. Physicians rated global assessment of treatment effect as "good" and "very good" in 535 patients (92.4%) which was concurrent with the patients' rating ("good" and "very good" by 534 patients = 92.2%), based on the full analysis set of 579 patients. Furthermore, quality of life and sleep were improved. Adverse drug reactions were reported in 35/592 patients (5.9%). Severe adverse events were not observed. The total incidence of therapy-associated adverse effects was comparable in the subgroup of patients with concomitant ß-blocker therapy (149/592 patients, 25.2%; totally 10%, subgroup 10.1%). Efficacy and tolerability of quinine sulfate were evaluated as "very good" or "good" by the majority of physicians and patients., Conclusions: The present NIS confirms effectiveness and tolerability of the therapy with quinine sulfate in daily clinical routine for adult patients with frequent and painful nocturnal leg cramps.

Background: Muscle cramps occur in 29-88% of patients with liver cirrhosis. They adversely affect quality of life. This study aimed to evaluate the efficacy and safety of methocarbamol as a novel therapy in controlling muscle cramps in cirrhotic patients., Patients and Methods: This study was carried on 100 patients with liver cirrhosis in addition to chronic hepatitis C who presented with frequent muscle cramps (≥three cramps per week). Half of these patients received methocarbamol and the other half received placebo. This was done through equal randomization. Questionnaires on muscle cramp were answered. Patients were evaluated before, after 1 month of treatment, and 2 weeks after washout of treatment in terms of severity, duration, and frequency of cramps. Liver, renal functions, and electrolytes were analyzed. Also, any side effect was detected., Results: Patients who were treated with methocarbamol showed a significant decrease in the frequency and duration of cramps. Also, the pain score improved significantly. However, no significant changes were observed in the placebo group. Few side effects of methocarbamol were recorded, including dry mouth and drowsiness., Conclusion: Methocarbamol seems to be a promising safe and well-tolerated medication, and plays a role in the treatment of muscle cramps in patients with liver cirrhosis.

Objective: Muscle cramps occur in >50% of diabetic patients and reduce the quality of life. No effective treatment is available. We evaluated the clinical effectiveness of botulinum toxin A (BTX-A) injections for treating cramps in diabetic patients with neuropathy., Methods: This single-center, double-blind, placebo-controlled perspective study investigated the efficacy and safety of BTX-A intramuscular injection for treating calf or foot cramps refractory to common pharmacological drugs. Fifty diabetic patients with peripheral neuropathy and cramps were randomly assigned to 2 matched groups. BTX-A (100 or 30 units) or saline was injected on each side into the gastrocnemius or the small flexor foot muscles. Changes in pain intensity (primary outcome) and cramp frequency were evaluated over the course of 20 weeks after BTX-A administration. Cramp interference in daily life and the electrophysiological cramp threshold frequency were also measured. The treatment was repeated 5 months after first injection in 19 responders., Results: All outcome measures improved significantly after BTX-A compared with placebo. The changes with respect to baseline were already significant after 1 week and persisted up to week 14. Only 5 of 25 (20%) patients were nonresponders (<50% decrease of the primary outcome). The responses to a second BTX-A injection provided results similar to the first administration. Mild pain at the injection site (4/25 cases) was the only adverse event, and it disappeared within 2 to 3 days., Interpretation: Local BTX-A infiltration is an efficacious and safe procedure for obtaining a sustained amelioration of muscle cramps associated with diabetic neuropathy. Ann Neurol 2018;84:682-690., (© 2018 American Neurological Association.)

Objective: Analgesic/anti-inflammatory medication (AAIM) increases the risk of medical complications during endurance races. We determined how many runners use AAIM before or during races, AAIM types, and factors associated with AAIM use., Design: Cross-sectional study., Setting: 21.1-km and 56-km races., Participants: Seventy-six thousand six hundred fifty-four race entrants., Methods: Participants completed pre-race medical screening questions on AAIM use, running injury or exercise-associated muscle cramping (EAMC) history, and general medical history., Main Outcome Measures: Analgesic/anti-inflammatory medication use, types of AAIM (% runners; 95% confidence interval), and factors associated with AAIM use (sex, age, race distance, history of running injury or EAMC, and history of chronic diseases) [prevalence ratio (PR)]., Results: Overall, 12.2% (12.0-12.5) runners used AAIM 1 week before and/or during races (56 km = 18.6%; 18.0-19.1, 21.1 km = 8.3%; 8.1-8.6) (P < 0.0001). During races, nonsteroidal anti-inflammatory drugs (NSAIDs) (5.3%; 5.1-5.5) and paracetamol (2.6%; 2.4-2.7) were used mostly. Independent factors (adjusted PR for sex, age, and race distance; P < 0.0001) associated with AAIM use were running injury (2.7; 2.6-2.9), EAMC (2.0; 1.9-2.1), cardiovascular disease (CVD) symptoms (2.1; 1.8-2.4), known CVD (1.7; 1.5-1.9), CVD risk factors (1.6; 1.5-1.6), allergies (1.6; 1.5-1.7), cancer (1.3; 1.1-1.5), and respiratory (1.7; 1.6-1.8), gastrointestinal (2.0; 1.9-2.2), nervous system (1.9; 1.7-2.1), kidney/bladder (1.8; 1.6-2.0), endocrine (1.5; 1.4-1.7), and hematological/immune (1.5; 1.2-1.8) diseases., Conclusions: 12.2% runners use AAIM before and/or during races, mostly NSAIDs. Factors (independent of sex, age, and race distance) associated with AAIM use were history of injuries, EAMC, and numerous chronic diseases. We suggest a pre-race screening and educational program to reduce AAIM use in endurance athletes to promote safer races.

Diabetic patients often suffer from muscle cramps. This study aimed to compare the quality of life (QOL) of diabetic patients with and without muscle cramps and to investigate the effect of L-carnitine supplementation in diabetic patients with muscle cramps. A total of 91 patients with diabetes were enrolled in this study: 69 patients with muscle cramps and 22 patients without muscle cramps. Muscle cramps and QOL were evaluated using the muscle cramp questionnaire and the Short Form 36 health survey version 2 (SF-36), respectively. Clinical characteristics were compared between diabetic patients with and without muscle cramps. In the prospective portion of the study, 25 diabetic patients with muscle cramps received L-carnitine supplementation (600 mg/day orally) for 4 months. The questionnaires were administered before and after supplementation. The SF-36 scores in diabetic patients with muscle cramps were lower than those in patients without muscle cramps on the subscales of physical function, role physical, bodily pain, vitality, general health, and social function. In the 25 patients with muscle cramps who received L-carnitine supplementation, the monthly frequency of muscle cramps and Wong-Baker FACES ® Pain Rating Scale scores were significantly decreased. Scores on the following SF-36 subscales improved after L-carnitine supplementation: body pain, vitality, social function, and role emotional. This study demonstrated that muscle cramps decrease the QOL in patients with diabetes, and L-carnitine supplementation may improve the QOL by reducing the frequency and severity of muscle cramps in these patients.

Quinine has long been used for the treatment of conditions such as malaria and leg cramps, and is also present at low levels in some beverages; however, it can cause serious side effects. We describe a patient who developed severe haemolysis, thrombocytopaenia, and acute kidney injury following the ingestion of a single dose of quinine. This case demonstrates the importance of awareness of such potentially life-threatening consequences of exposure to this agent.

Bites of tiger spiders belonging to Poecilotheria genus cause moderate to severe pain and long-lasting local or generalized muscle cramps in humans. Bites occur in regions of the spiders' natural habitat, India and Sri Lanka, but the popularity of these colorful tarantulas as pets leads to reports of envenomation cases worldwide. Treatment is predominantly symptomatic and often inadequate since there is almost no clinical or toxicology research data available, and physicians outside India or Sri Lanka typically have no experience in treating such cases. We report toxicity studies of venom from nine Poecilotheria species in laboratory mice (Mus musculus Balb/C males). LD 50 values are 5-14 mg of lyophilized crude venom per 1 kg (i.v.). The major symptoms of envenomation include tonic-clonic seizures, jerks, characteristic motor stereotypy, and hyperalgesia and point to voltage-gated sodium channels as a potential target of the venom components. Poecilotheria fasciata venom effects were studied in detail at a sub-lethal dose of 5 mg/kg (LD 50  = 12 mg/kg). 13 widely used pharmacological agents (atropine, chloropyramine, chlorpromazine, diazepam, ethanol, flupirtine, haloperidol, ketotifen, lamotrigine, oxcarbazepine, tolperisone, xylazine, and CaCl 2 ) were checked for ability to suppress the envenomation symptoms. Chlorpromazine (10 mg/kg, i.p.), oxcarbazepine (60 mg/kg, p.o.), tolperisone (50 mg/kg, s.c.) and xylazine (2.5 mg/kg, i.p.) were found effective as a pretreatment to mitigate muscle cramps and motor stereotypy. When administered after envenomation chlorpromazine (5 mg/kg, i.v.) effectively reduced the cramps, while oxcarbazepine (30 mg/kg, i.v.) and xylazine (1 mg/kg, i.v.) suppressed the stereotypy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Exercise-associated muscle cramping (EAMC) is a poorly understood problem that is neuromuscular in origin. Ingestion of transient receptor potential (TRP) channel agonists has been efficacious in attenuating electrically induced muscle cramps. This study examines the effect of TRP agonist ingestion on voluntarily induced EAMC and motor function., Methods: Study 1: Thirty-nine participants completed 2 trials after ingesting TRP agonist-containing active treatment (A), or vehicle (V) control. Cramping in the triceps surae muscle was induced via voluntary isometric contraction. Study 2: After ingesting A or V, 31 participants performed kinematic and psychomotor tests of manual dexterity., Results: A increased precramp contraction duration (A, 36.9 ± 4.1 s; V, 27.8 ± 3.1 s), decreased cramp EMG area under the curve (A, 37.3 ± 7.7 %EMG max ·s; V, 77.2 ± 17.7 %EMG max ·s), increased contraction force to produce the cramp (A, 13.8 ± 1.8 kg; V, 9.9 ± 1.6 kg), and decreased postcramp soreness (A, 4.1 ± 0.3 arbitrary units (a.u.); V, 4.7 ± 0.3 a.u.). Kinematic and psychomotor tests were not affected., Discussion: TRP agonist ingestion attenuated EAMC characteristics without affecting motor function. Muscle Nerve 56: 379-385, 2017., (© 2017 Wiley Periodicals, Inc.)

Pain is a largely neglected symptom in patients with amyotrophic lateral sclerosis (ALS) although it is reported by most of these patients. It occurs at all stages of the disease and can be an onset symptom preceding motor dysfunction. Pain is correlated with a deterioration in patients' quality of life and increased prevalence of depression. In the later stages of ALS, pain can be severe enough to require increased use of sedative and analgesic drugs, and is among the events that predict clinical deterioration and death. The site of pain depends on the pain type or underlying mechanism (eg, painful cramps, nociceptive pain, or neuropathic pain). Given the multifactorial nature of pain in patients with ALS, different treatments have been suggested, ranging from non-steroidal anti-inflammatory drugs, drugs for neuropathic pain, opioids, and cannabinoids, to physical therapy strategies and preventive assistive devices. Further understanding of the pathophysiology is crucial to drive assessment in clinical trials of therapeutic strategies targeted at specific mechanisms and studies of individualised therapies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited., Objectives: To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND., Methods: We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND. We assessed the methodological quality of the included reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the GRADE approach. We followed standard Cochrane study (review) selection and data extraction procedures. We reported findings narratively and in tables., Main Results: We included nine Cochrane Systematic Reviews of interventions to treat symptoms in people with MND. Three were empty reviews with no included randomised controlled trials (RCTs); however, all three reported on non-RCT evidence and the remaining six included mostly one or two studies. We deemed all of the included reviews of high methodological quality. Drug therapy for painThere is no RCT evidence in a Cochrane Systematic Review exploring the efficacy of drug therapy for pain in MND. Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data.The review reported adverse effects of riluzole, but it is not clear whether other interventions had adverse effects. Treatment for spasticityIt is uncertain whether an endurance-based exercise programme improved spasticity or quality of life, measured at three months after the programme, as the quality of evidence is very low (1 RCT, comparison "usual activities", N = 25). The review did not evaluate other approaches, such as use of baclofen as no RCTs were available. Mechanical ventilation for supporting respiratory functionNon-invasive ventilation (NIV) probably improves median survival and quality of life in people with respiratory insufficiency and normal to moderately impaired bulbar function compared to standard care, and improves quality of life but not survival for people with poor bulbar function (1 RCT, N = 41, moderate-quality evidence; a second RCT did not provide data). The review did not evaluate other approaches such as tracheostomy-assisted ('invasive') ventilation, or assess timing of NIV initiation. Treatment for sialorrhoeaA single session of botulinum toxin type B injections to parotid and submandibular glands probably improves sialorrhoea and quality of life at up to 4 weeks compared to placebo injections, but not at 8 or 12 weeks after the injections (moderate-quality evidence from 1 placebo-controlled RCT, N = 20). The review authors found no trials of other approaches. Enteral tube feeding for supporting nutritionThere is no RCT evidence in a Cochrane Systematic Review to support benefit or harms of enteral tube feeding in supporting nutrition in MND. Repetitive transcranial magnetic stimulationIt is uncertain whether repetitive transcranial magnetic stimulation (rTMS) improves disability or limitation in activity in MND in comparison with sham rTMS (3 RCTs, very low quality evidence, N = 50). Therapeutic exerciseThere is evidence that exercise may improve disability in MND at three months after the exercise programme, but not quality of life, in comparison with "usual activities" or "usual care" including stretching (2 RCTs, low-quality evidence, N = 43). Multidisciplinary careThere is no RCT evidence in a Cochrane Systematic Review to demonstrate any benefit or harm for multidisciplinary care in MND.None of the reviews, other than the review of treatment for cramps, reported that adverse events occurred. However, the trials were too small for reliable adverse event reporting., Authors' Conclusions: This overview has highlighted the lack of robust evidence in Cochrane Systematic Reviews on interventions to manage symptoms resulting from MND. It is important to recognise that clinical trials may fail to demonstrate efficacy of an intervention for reasons other than a true lack of efficacy, for example because of insufficient statistical power, the wrong choice of dose, insensitive outcome measures or inappropriate participant eligibility. The trials were mostly too small to reliably assess adverse effects of the treatments. The nature of MND makes it difficult to research clinically accepted or recommended practice, regardless of the level of evidence supporting the practice. It would not be ethical, for example, to design a placebo-controlled trial for treatment of pain in MND or to withhold multidisciplinary care where such care is available. It is therefore highly unlikely that there will ever be classically designed placebo-controlled RCTs in these areas.We need more research with appropriate study designs, robust methodology, and of sufficient duration to address the changing needs-of people with MND and their caregivers-associated with MND disease progression and mortality. There is a significant gap in studies assessing the effectiveness of interventions for symptoms relating to MND, such as pseudobulbar emotional lability and cognitive and behavioural difficulties. Future studies should use appropriate outcome measures that are reliable, have internal and external validity, and are sensitive to change in what is being measured (such as quality of life).

Background and Aims: Muscle cramps adversely influence the quality of life of patients with liver cirrhosis. Indeed, to date, a well-established therapy for this complication is still lacking. This is the first randomized placebo-controlled trial of baclofen in the treatment of muscle cramps in patients with liver cirrhosis., Patients and Methods: A total of 100 patients with liver cirrhosis and muscle cramps signed an informed consent to participate in this study. They were recruited from the Department of Tropical Medicine-Tanta University Hospital. They were randomized to receive either baclofen or placebo for 3 months. Patients were followed monthly and 1 month after withdrawal. At each visit, the clinicoepidemiological data were recorded, the muscle cramp questionnaire was filled, and any drug-related side effects were reported., Results: In the baclofen group, the frequency of muscle cramps decreased significantly after 1 and 3 months of treatment (P<0.005), with a significant relapse after withdrawal (P<0.001). Patients receiving baclofen showed a significant decrease in the severity and duration of muscle cramps (P<0.001). After 3 months of baclofen therapy at a dose of 30 mg/day, muscle cramps disappeared completely in 72%, reduced in 20%, and led to no change in 8% of patients. No significant changes in the frequency, severity, and duration of muscle cramps were noted in the placebo group. There were few but nonsignificant side effects in the baclofen group compared with the placebo group., Conclusion: Baclofen was well tolerated, safe, and effective in the treatment of muscle cramps in patients with liver cirrhosis.

A 91-year-old woman presented to the emergency department by ambulance after her family found her minimally responsive. Telemetry monitoring demonstrated episodes of non-sustained polymorphic ventricular tachycardia (PMVT) associated with significantly prolonged repolarization. Her medical history revealed that she was taking quinine or a derivative in three different forms: hydroxychloroquine, quinine sulfate (for leg cramps), and her gin mixed with tonic water (containing quinine). The present case is illustrative of classic etiologies and findings of acquired long QT syndrome, and serves as an important reminder for providers to take a complete medication history, including use of duplicative and alternative medicines and type of alcohol consumption., Competing Interests: The authors declare that they do not have a conflict of interest.

Background: Nocturnal leg cramps are painful, involuntary muscle contractions commonly seen in elderly. While mostly harmless, they can severely impair quality of life and often disrupt sleep. Adverse drug effects may be responsible for a fraction of nocturnal leg cramps but often go unrecognized, resulting in additional prescribing intended to deal with adverse effects that might be better addressed by reduction, substitution, or discontinuation of the offending agent., Case Presentation: An 87 year old female presented as outpatient in family medicine with nocturnal leg cramps which had been present for five years and increasingly burdened her quality of life. She had been using quinine 200 mg once daily for symptomatic relief but the cramps kept returning with increasing intensity. During clinical examination we found neither structural nor neurological or metabolic disorders that explained her symptoms. When doing a medication analysis, we found that she was taking a statin together with quinine. Quinine is a cytochrome P450 isoenzyme 3A4 inhibitor, the very enzyme which is involved in the metabolism of most statins. Therefore the use of both substances simultaneously increases blood levels of the statin thereby increasing the risk of side effects including symptomatic myopathy and myalgia. After discontinuing both medications, the patient was, and remained, symptom free., Conclusion: This case report describes a possible medication interaction that has rarely been noted in literature.

Background: Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid-related disorders. PPI-induced hypomagnesaemia, a defect in intestinal absorption of Mg(2+) , can be a severe side effect of chronic PPI use., Aim: To restore serum Mg(2+) concentrations in PPI-induced hypomagnesaemia patients by dietary supplementation with inulin fibres., Methods: Eleven patients with PPI-induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14-day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg(2+) levels served as the primary endpoint., Results: Inulin significantly enhanced serum Mg(2+) levels from 0.60 to 0.68 mmol/L in PPI-induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg(2+) excretion was significantly increased in patients with PPI-induced hypomagnesaemia (0.3-2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin., Conclusion: Inulin increases serum Mg(2+) concentrations under PPI maintenance in patients with PPI-induced hypomagnesaemia., (© 2016 John Wiley & Sons Ltd.)

Objective: To determine the safety and tolerability of mexiletine in a phase II double-blind randomized controlled trial of sporadic amyotrophic lateral sclerosis (SALS)., Methods: Sixty participants with SALS from 10 centers were randomized 1:1:1 to placebo, mexiletine 300 mg/d, or mexiletine 900 mg/d and followed for 12 weeks. The primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetic study from plasma and CSF, ALS Functional Rating Scale-Revised (ALSFRS-R) score, slow vital capacity (SVC), and muscle cramp frequency and severity., Results: The only serious adverse event among active arm participants was one episode of imbalance. Thirty-two percent of participants receiving 900 mg of mexiletine discontinued study drug vs 5% on placebo (p = 0.026). Pharmacokinetic study demonstrated a peak plasma concentration 2 hours postdose and strong correlation between plasma and CSF (p < 0.001). Rates of decline of ALSFRS-R and SVC did not differ from placebo. Analysis of all randomized patients demonstrated significant reductions of muscle cramp frequency (300 mg: rate = 31% of placebo, p = 0.047; 900 mg: 16% of placebo, p = 0.002) and cramp intensity (300 mg: mean = 45% of placebo, p = 0.08; 900 mg: 25% of placebo, p = 0.005)., Conclusions: Mexiletine was safe at both doses and well-tolerated at 300 mg/d but adverse effects at 900 mg/d led to a high rate of discontinuation. Mexiletine treatment resulted in large dose-dependent reductions in muscle cramp frequency and severity. No effect on rate of progression was detected, but clinically important differences could not be excluded in this small and short-duration study., Classification of Evidence: This study provides Class I evidence that mexiletine is safe when given daily to patients with amyotrophic lateral sclerosis at 300 and 900 mg and well-tolerated at the lower dose., (© 2016 American Academy of Neurology.)

Muscle cramps are side effects commonly associated with tyrosine kinase inhibitor (TKI) treatment. Patients suffering from muscle cramps are treated with various medications such as calcium, magnesium and vitamin supplements, but these therapies are often ineffective. We report two patients with chronic myelogenous leukemia who developed muscle cramps caused by TKI. These patients were treated successfully with levocarnitine. Both of our cases revealed the beneficial effects of levocarnitine treatment on TKI-induced muscle cramps.

This case report describes a female with p.Lys4876Arg amino acid change in the ryanodine receptor type 1 (RYR1) and a sibling who died of malignant hyperthermia (MH) during anesthesia. After her diagnosis as MH susceptible, this patient was administered low-dose dantrolene daily for greater than 25 years for treatment of chronic muscle spasm and pain in her lower extremities and back limiting sleep. Her creatine phosphokinase (CPK) was as high as 2390 IU/L during labor and 900 IU at rest. With 25 mg dantrolene daily, muscle cramps were eliminated, and sleep was improved. Gait instability was noted with dantrolene in the morning, but not when taken at bedtime. There was no evidence of liver injury. This case suggests that low dose dantrolene by mouth could be considered for the treatment of chronic muscle pain in individuals with MH susceptibility.

Shakuyakukanzoto (SKT), a traditional Japanese (Kampo) medicine, has been used by patients with muscle cramps and abdominal pains. In this trial, we analyzed plasma concentrations of active components after SKT was administered as a single oral dose of 2.5 or 5.0 g/day per person. The study was a randomized, open-label, two-arm, two-period, crossover trial conducted in healthy Japanese volunteers. Albiflorin (ALB), paeoniflorin (PAE), glycycoumarin (GCM), isoliquiritigenin (ILG), glycyrrhetic acid (GA), and glycyrrhetic acid-3-O-monoglucuronide were targeted, and the plasma concentration of each component was measured using a liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were calculated, and the linearity was assessed. All targeted components were detected in the plasma after oral administration of SKT. ALB, PAE, GCM, and ILG were detected at an early stage. The linearity was observed for the maximum plasma concentration of GCM, ILG, and GA and for the area under the plasma concentration-time curve of GA. In this trial, we demonstrated for the first time in humans that these components were absorbed into the blood after oral administration of SKT. The results of this pharmacokinetic trial in humans are also important and useful for understanding the mechanism of action of SKT, verifying the active components predicted in basic research, and conducting pharmacokinetics and safety studies in the future., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Various medications and behavioral treatments for sleep-related leg cramps have been tried, but the quality of the evidence is low. Quinine seems to be effective, but dangerous. β-Agonists may be one of the more common causes of secondary leg cramps. Statins may not be implicated in leg cramps as much as has been believed. Potassium-sparing diuretics may have a higher incidence of sleep-related leg cramps than potassium-depleting diuretics. Plantar flexion of the feet may elicit most sleep-related leg cramps. More research into behavioral treatments is needed. A standardized sleep-related leg cramp questionnaire would be useful to expand research., (Copyright © 2015 Elsevier Inc. All rights reserved.)