Project description:BackgroundMuscle cramps are witnessed in 22-88% of patients with cirrhosis of liver and frequently lead to sleep disturbance with an appalling impact on quality of life. Despite such a high prevalence, there is lack of evidence-based management protocol due to scarcity of trials on treatment options in the literature. This study aimed to review systematically the available therapeutic options for muscle cramps in patients with cirrhosis of liver.MethodsA systematic review of the relevant databases (PubMed, Scopus, Embase, and Web of Science) to identify treatments for muscle cramps in patients with hepatic cirrhosis was performed. Studies meeting the selection criteria were reviewed and assessed for risk of bias and analyzed.ResultsTwenty-four publications were identified as eligible for inclusion in this systematic review. Seven randomized controlled trials (RCTs) and 17 prospective studies were included. Taurine, methocarbamol, baclofen, and orphenadrine are relatively safer and effective treatment option for muscle cramps in cirrhosis on the basis of recently conducted RCTs. Moreover, l-carnitine, branched-chain amino acids (BCAAs), pregabalin, zinc, and vitamin D are also safe and showed beneficial effects on muscle cramps. However, studies on vitamin E revealed contradictory results.ConclusionTaurine, BCAAs, orphenadrine, and baclofen are safe and well-tolerated treatment options for muscle cramps in cirrhosis. However, well-designed randomized controlled clinical trials are the need of the hour to determine the most suitable treatment options for skeletal muscle cramps in patients with cirrhosis of liver.
Project description:Background and aimsMuscle cramps markedly affect the quality of life in cirrhotic patients with no available highly effective treatment. The aim of this study was to assess the safety and efficacy of orphenadrine in the treatment of muscle cramps in cirrhotic patients.MethodsThe study enrolled 30 liver cirrhosis patients complaining of frequent muscle cramps (≥3 per week), who were randomized to receive either orphenadrine 100 mg or calcium carbonate 500 mg twice daily as a control for one month. Severity, frequency, and duration of the muscle cramps were assessed before and after treatment as well as recurrence after washout of the drug for two weeks. Side effects were recorded.ResultsOne month after treatment with orphenadrine; the frequency of muscle cramps decreased significantly to 0.6 ± 0.74 per week compared to 12.53 ± 6.01 at baseline (p < 0.001), the duration of muscle cramps decreased from 1 min to 0.1 min after treatment (p < 0.001). The pain score improved significantly from a score of 8/10 to 0/10 (p < 0.001). The side effects were few, such as dry mouth, drowsiness, and nausea, with no significant difference between their occurrences in the two groups.ConclusionOrphenadrine is safe and effective in treatment of muscle cramps in patients with liver cirrhosis.
Project description:BackgroundMuscle cramp is possibly related to peripheral nerve hyperexcitability (PNH), and one of the most debilitating symptoms frequently encountered in patients with liver cirrhosis. We investigated whether pregabalin, a gamma-aminobutyric acid analogue, can suppress neuronal excitability and reduce muscle cramps in cirrhotic patients.MethodsWe conducted a randomized, double-blind, placebo-controlled trial in which study participants with cirrhosis from a single tertiary center were enrolled. Primary endpoint was the relative change in cramp frequency from the run-in to standard dose treatment phase (4 weeks per each). Secondary endpoints included the responder rate, and the changes in cramp frequency during sleep, pain intensity, health-related quality of life (Liver Disease Quality of Life Instrument, Short Form-36) and electrophysiological measures of PNH.ResultsThis study was terminated early because of insufficient accrual. 80% (n = 56) of the target number of participants (n = 70) were randomized to pregabalin (n = 29) or placebo (n = 27). Median baseline frequency of muscle cramps (interquartile range) was 5.8 (3.5-10) per week in the pregabalin group and 6.5 (4.0-10) in the placebo group (P = 0.970). The primary analysis showed a significant reduction in cramp frequency with pregabalin compared to placebo (-36% vs. 4.5% for the percentage change, P = 0.010). Secondary outcomes did not differ significantly between the two groups. Adverse effects with pregabalin were mainly dizziness and lethargy.ConclusionWith multiple problems emerging from premature termination in mind, the results suggested an acceptable safety profile and favorable effect of pregabalin in reducing muscle cramps compared to placebo in cirrhotic patients.Trial registrationClinicalTrials.gov Identifier: NCT01271660.
Project description:PurposePainful 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 methodsTen 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.ResultsAt 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.ConclusionOral taurine therapy for 4 weeks improved muscle cramps safely in cirrhotic patients.
Project description:IntroductionMuscle cramping is a common symptom in amyotrophic lateral sclerosis (ALS) that lacks efficacious treatment. The natural history of this symptom is unknown, which hampers efforts to design optimal clinical trials.MethodsWe surveyed early stage ALS patients about their experience with cramps each month by phone for up to 21 months.ResultsCramps developed in 95% of patients over the course of their disease. The number of cramps experienced by an individual varied widely from month-to-month and trended lower after the first year of illness (P = 0.26). Those with limb-onset and age >60 years had more cramps than bulbar-onset (P < 0.0001) and younger patients (P < 0.0001).ConclusionsThe high variability of the number of cramps experienced suggests that clinical trials will need to use crossover designs or large numbers of participants, even when the treatment effect is substantial.
Project description:This study aims to assess the frequency, location, severity, duration, and fluctuation over time of muscle cramps in Charcot-Marie-Tooth disease (CMT).Inherited Neuropathies Consortium Contact Registry participants recorded the occurrence and characteristics of muscle cramps using an 11-question survey administered 3 times over 8 weeks.A total of 110 adult patients with CMT completed the survey. Weekly cramp frequency was 9.3 (SD 12.3), and 23% had daily muscle cramps. Twenty-two percent reported a significant impact on quality of life. Over 8 weeks, the daily frequency and severity of muscle cramps did not change significantly.Patients with CMT have muscle cramps that vary little over an 8-week period, and they may interfere with quality of life. These data may be useful in the planning of clinical trials of agents to treat adults with CMT-associated muscle cramps.
Project description:The objective of this study was to describe muscle cramps in an US sample of amyotrophic lateral sclerosis (ALS) patients. Utilizing an anonymous web based questionnaire we queried ALS patients regarding the severity, frequency, time-course, treatment of muscle cramps and their relationship to pain. The survey had 282 respondents with 92% reporting that they had cramps. For 20% of the sample, cramps were stated to be the presenting ALS symptom. Cramp severity was rated at a mean of 5.2/10 and the mean cramp frequency was 5.3 cramps per day. Cramp intensity and frequency did not correlate with duration or severity of ALS. Pain as measured with the Patient Reported Outcome Measurement Information System (PROMIS) pain scales was not statistically different from the US general population. Cramp severity and frequency significantly and positively correlated with the PROMIS pain scales. Patients with more severe cramps were more likely to use prescription medications for their cramps compared to patients with milder symptoms. Treatments directed at cramps were tried by 57%. In conclusion, cramps are a common symptom in ALS and it does not correlate with disease duration or severity. The severity of cramps is on average moderate and many patients try treatments.
Project description:ObjectiveTo describe clinical, laboratory, and genetic characteristics of three unrelated cases from Chile, Portugal, and Saudi Arabia with severe insulin resistance, SOFT syndrome, and biallelic pathogenic POC1A variants.DesignObservational study.MethodsProbands' phenotypes, including short stature, dysmorphism, and insulin resistance, were compared with previous reports.ResultsCases 1 (female) and 3 (male) were homozygous for known pathogenic POC1A variants: c.649C>T, p.(Arg217Trp) and c.241C>T, p.(Arg81*), respectively. Case 2 (male) was compound heterozygous for p.(Arg217Trp) variant and the rare missense variant c.370G>A, p.(Asp124Asn). All three cases exhibited severe insulin resistance, acanthosis nigricans, elevated serum triglycerides and decreased HDL, and fatty liver, resembling three previously reported cases. All three also reported severe muscle cramps. Aggregate analysis of the six known cases with biallelic POC1A variants and insulin resistance showed decreased birth weight and length mean (s.d.): -2.8 (0.9) and -3.7 (0.9) SDS, respectively), severe short stature mean (s.d.) height: -4.9 (1.7) SDS) and moderate microcephaly (mean occipitofrontal circumference -3.0 (range: -4.7 to -1.2)). These findings were similar to those reported for patients with SOFT syndrome without insulin resistance. Muscle biopsy in Case 3 showed features of muscle involvement secondary to a neuropathic process.ConclusionsPatients with SOFT syndrome can develop severe dyslipidaemic insulin resistance, independent of the exonic position of the POC1A variant. They also can develop severe muscle cramps. After diagnosis, patients should be regularly screened for insulin resistance and muscle complaints.