-
Muscle & Nerve Jul 2022Neuronal hyperexcitability (manifested by cramps) plays a pathological role in amyotrophic lateral sclerosis (ALS), and drugs affecting it may help symptomatic...
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.
Topics: Amyotrophic Lateral Sclerosis; Humans; Muscle Cramp; Pilot Projects; Ranolazine
PubMed: 35466411
DOI: 10.1002/mus.27560 -
Acta Myologica : Myopathies and... Mar 2022McArdle's disease is an autosomal recessive glycogenosis due to mutation in the myophosphorylase gene () resulting in a pure myopathy. The clinical onset typically...
McArdle's disease is an autosomal recessive glycogenosis due to mutation in the myophosphorylase gene () resulting in a pure myopathy. The clinical onset typically occurs in childhood with cramps, myalgia, and intolerance to physical exercise, although late onset forms are also reported. We describe a case of a 17-year-old male complaining of cramps and myalgia following brief and intense exercise. The patient reported marked improvement in muscle fatigability few minutes after starting aerobic exercise. When he was a child, he had experienced few episodes of vomiting, nausea, and black colored urine following physical activity. Laboratory testings revealed high creatine kinase serum levels. Genetic testings for metabolic myopathies demonstrated a compound heterozygous for two mutations (p.R570Q and p.K754Nfs*49) allowing the diagnosis of McArdle's disease. To date, 183 mutations in the PYGM gene are listed in Human Gene Mutation Database Professional 2021.2, but this novel compound heterozygosis has never been reported before.
Topics: Adolescent; Glycogen Phosphorylase, Muscle Form; Glycogen Storage Disease Type V; Humans; Male; Muscle Cramp; Mutation; Myalgia
PubMed: 35465342
DOI: 10.36185/2532-1900-067 -
The American Journal of Gastroenterology Jun 2022Muscle cramps are common among persons with cirrhosis and associated with poor health-related quality of life. Treatment options are limited. We sought to determine... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Muscle cramps are common among persons with cirrhosis and associated with poor health-related quality of life. Treatment options are limited. We sought to determine whether pickle juice can improve muscle cramp severity.
METHODS
We enrolled 82 patients with cirrhosis and a history of >4 muscle cramps in the previous month from December 2020 to December 2021. Patients were randomized 1:1 to sips of pickle juice vs tap water at cramp onset. Our primary outcome assessed at 28 days was the change in cramp severity measured by the visual analog scale for cramps (VAS-cramps, scaled 0-10). Cramps were assessed 10 times over 28 days using interactive text messages. Secondary outcomes included the proportion of days with VAS-cramps <5, change in sleep quality, and global health-related quality of life measured using the EQ-5D.
RESULTS
Overall, 74 patients completed the trial, aged 56.6 ± 11.5 years, 54% male, 41% with ascites, 38% with encephalopathy, and model for end-stage liver disease-sodium score 11.2 ± 4.9. Many patients were receiving other cramp therapies at baseline. The baseline VAS for cramps was 4.2 ± 3.4, the EQ-5D was 0.80 ± 0.10, and 43% rated sleep as poor. At trial completion, the respective values for the pickle juice and control arms were -2.25 ± 3.61 points on the VAS for cramps, compared with control tap water (-0.36 ± 2.87), P = 0.03; a proportion of cramp-days with VAS-cramps <5 were 46% vs 35% (P = 0.2); and the change in sleep quality was not different (P = 0.1). The end-of-trial EQ-5D was 0.78 ± 0.10 vs 0.80 ± 0.10 (P = 0.3). No differences in weight change were observed for those with and without ascites.
DISCUSSION
In a randomized trial, sips of pickle brine consumed at cramp onset improve cramp severity without adverse events.
Topics: Ascites; End Stage Liver Disease; Female; Fermented Foods; Humans; Liver Cirrhosis; Male; Muscle Cramp; Quality of Life; Severity of Illness Index; Water
PubMed: 35416793
DOI: 10.14309/ajg.0000000000001781 -
BMJ Case Reports Apr 2022A 45-year-old woman was evaluated for right-sided hemicorporal scar-like skin lesions on her arm and thoracic and inguinal areas that appeared shortly after reduction...
A 45-year-old woman was evaluated for right-sided hemicorporal scar-like skin lesions on her arm and thoracic and inguinal areas that appeared shortly after reduction mammoplasty. Five years later, she developed spontaneous cramps and involuntary abnormal, painful, twitching movements in the same areas. With time, the cramps worsened and disabled the patient. The use of her right arm triggered contractures of muscles and abnormal movements. A diagnosis of neuromyotonia (NMT) was established on the basis of clinical findings and on electromyographic findings of a burst of high-frequency motor unit potentials recorded in the right triceps in the area of skin lesions. The results of medullary, encephalic MRI as well as a comprehensive metabolic panel were normal. She was positive for antinuclear antibodies without specificity. Neither antineural antibodies nor antivoltage-gated potassium channel complex antibodies (specifically, leucine-rich glioma inactivated protein 1 and contactin-associated protein-like-2) were detected. Her skin lesions were diagnosed as morphea. Two combined strategies of treatment were initiated: antiepileptic drugs for NMT and corticosteroids and methotrexate for morphea. NMT is a rare, debilitating neurological complication of morphea.
Topics: Antibodies; Female; Humans; Isaacs Syndrome; Leucine; Middle Aged; Muscle Cramp; Scleroderma, Localized
PubMed: 35410943
DOI: 10.1136/bcr-2020-237959 -
Diabetes, Metabolic Syndrome and... 2022Patients with type 2 diabetes (T2DM) often suffer from muscle cramps of varying severity. Studies have shown that muscle cramp is closely related to local...
AIM
Patients with type 2 diabetes (T2DM) often suffer from muscle cramps of varying severity. Studies have shown that muscle cramp is closely related to local microcirculation perfusion disorders. Diabetic retinopathy can not only reflect the microcirculation perfusion in the eye but also the systemic microcirculation in patients with diabetes. The aims of this study were to investigate the relationship between muscle cramps and diabetic retinopathy in patients with type 2 diabetes.
METHODS
A total of 150 adult patients with type 2 diabetes were enrolled and administered a questionnaire on muscle cramping, along with a visual analogue scale for pain. Diabetic retinopathy (DR) was determined by using fundus photography and graded as non-proliferative DR (NPDR) and proliferative DR (PDR). To assess whether there was an association between the muscle cramps and diabetic retinopathy, we conducted binomial logistic regression analysis.
RESULTS
Our study revealed that 48% of patients with T2DM experienced muscle cramps in the past three months. Patients self-reported suffering from muscle cramps exhibited a higher prevalence of DR (61% vs 38%, P < 0.05) and PDR (22% vs 4%, P < 0.05) compared with patients without muscle cramps. Serum 25-(OH) vitamin D, calcium, and magnesium levels were not significantly different between patients with and without muscle cramps. After adjusting for age, duration of diabetes, HbA1c, vitamin D, potassium, calcium, and magnesium, we demonstrated that diabetic retinopathy (OR, 2.18; 95% CI, 1.01-4.69; P< 0.05) and albumin (OR, 0.90; 95% CI, 0.82-1.00; P< 0.05) were highly associated with muscle cramps. Binomial logistic regression analysis also indicated that severity of DR is associated with muscle cramps. In addition, DR and PDR were found to be associated with muscle cramp frequency (P for trend < 0.05), duration (P for trend < 0.05), and pain severity (P for trend < 0.05).
CONCLUSION
Muscle cramps occur frequently in diabetes and are correlated with diabetic retinopathy and albumin. Patients with PDR exhibited a higher frequency, severity, and longer duration relative to those with NPDR or without DR. Our findings suggested that muscle cramps in individuals with T2DM might be a result of microvascular dysfunction. Modulation of microvascular perfusion might thus provide a therapeutic target for alleviating muscle cramps.
PubMed: 35313678
DOI: 10.2147/DMSO.S352735 -
Scientific Reports Mar 2022This is a prospective, observational community cohort study with the objective of investigating menstrual cramp occurrence related to ovulatory characteristics. Women... (Observational Study)
Observational Study
This is a prospective, observational community cohort study with the objective of investigating menstrual cramp occurrence related to ovulatory characteristics. Women reported cramp intensity on daily Menstrual Cycle Diary© records over one year. Ovulation and luteal phase lengths were assessed by validated Quantitative Basal Temperature© (QBT) analysis. Healthy, normal-weight, non-smoking community dwelling premenopausal women ages 21-41 years with two consecutive, normally ovulatory, normal-length menstrual cycles were enrolled. All 53 women, with 13.6 ± 2.8 cycles per woman, reported at least one cramp episode of median intensity 1.5 [0-4 scale; range 1.0-3.5], and 2.2 days' [range 1.0-10.2] duration. Within the 49 women who experienced all ovulatory cycle types (normal, short luteal length [SLL < 10 days] and anovulatory), median cramp intensity was greater in normal-length cycles having subclinical ovulatory disturbances (SLL and anovulatory; median 1.4 [range 0.0-2.8]) than in normally ovulatory cycles (median 1.2 [range 0.0-2.3]) (P = 0.023). Cramp Scores did not differ by ovulatory status within the 19 women having both normally ovulatory and anovulatory cycles (P = 0.222). Within-woman 1-year Cramp Scores were not different in anovulatory and normally ovulatory menstrual cycles but were more intense with ovulatory disturbances.
Topics: Adult; Anovulation; Cohort Studies; Dysmenorrhea; Female; Humans; Male; Menstrual Cycle; Muscle Cramp; Ovulation; Prospective Studies; Young Adult
PubMed: 35304559
DOI: 10.1038/s41598-022-08658-3 -
Clinical Journal of the American... Oct 2022Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for...
Conceptual Framework for Patient-Reported Outcome Measures in Clinical Trials of Skeletal Muscle Cramping Experienced in Dialysis: A Kidney Health Initiative Workgroup Report.
Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to () create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, () construct a conceptual model for developing and evaluating a skeletal muscle cramping-specific patient-reported outcome measure, and () identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping.
Topics: Humans; Renal Dialysis; Kidney Failure, Chronic; Muscle Cramp; Patient Reported Outcome Measures; Kidney; Muscle, Skeletal
PubMed: 35292531
DOI: 10.2215/CJN.11980921 -
Journal of Sports Science & Medicine Mar 2022Triathlon's popularity is rapidly increasing, and epidemiological data relating to its related medical conditions is crucial to the development of proper medical plans...
Triathlon's popularity is rapidly increasing, and epidemiological data relating to its related medical conditions is crucial to the development of proper medical plans and safety guidelines for it. This study examined the data from the medical reports collected during three consecutive editions of Ironman Italy, from 2017 to 2019. Out of 10,653 race-starters, 3.3% required medical attention sustaining 472 medical conditions. A significantly higher injury risk was found for females versus males (χ2 = 9.78, p = 0.02) and in long-distance (IR: 4.09/1,000hours) rather than in Olympic/middle distance races (IR: 1.75/1,000hours). Most (68.4%) conditions (including muscular exhaustion, hypothermia, and dehydration) were systemic, whilst only 10.2% were acute traumatic injuries. Of a total of 357 triathletes requiring medical assistance, 8.1% were a candidate for hospitalisation. The equipment and personnel that are required for the medical assistance in future triathlon events were estimated based on Maurer's algorithm, and ten practical recommendations for triathlon medical support were formulated.
Topics: Bicycling; Female; Humans; Male; Retrospective Studies; Running; Swimming
PubMed: 35250334
DOI: 10.52082/jssm.2022.58 -
Kidney Medicine Feb 2022Recent evidence suggests a role for magnesium as a calcification inhibitor. Increased magnesium abundance may attenuate vascular calcification and promote bone formation.
RATIONALE & OBJECTIVE
Recent evidence suggests a role for magnesium as a calcification inhibitor. Increased magnesium abundance may attenuate vascular calcification and promote bone formation.
STUDY DESIGN
Parallel-group, 1:1-allocation-ratio, quasi-experimental study.
SETTING & PARTICIPANTS
The study was conducted at hemodialysis centers in Bangkok, Thailand. Patients receiving maintenance hemodialysis were screened for coronary artery calcification (CAC) and bone mineral density (BMD), and those with a CAC score of ≥300 were included and matched according to the initial CAC score. The intervention and control groups consisted of 20 patients in each arm.
INTERVENTIONS
A high (1.75 mEq/L) or standard (0.7 mEq/L) dialysate magnesium concentration was delivered for 26 weeks.
OUTCOMES
Changes in the CAC score and BMD and the progression of CAC. The safety outcomes included occurrence of cramps recorded as per usual care.
RESULTS
The median CAC score of all patients was 1,792. Serum and ionized magnesium concentrations increased substantially in the high dialysate magnesium group. At the end of the study, the CAC score increased significantly in both the groups, with no significant difference between the groups. The number of participants with CAC progression was comparable between the 2 groups. In exploratory subgroup analyses stratified by the median CAC score, a significant decline in CAC and fewer participants with CAC progression were observed in the subgroup with lower CAC scores that received the high dialysis magnesium concentration. Bone mineral density was largely unchanged in both groups. The number of participants experiencing cramps and the number of episodes of muscle cramps were markedly lower among patients who received the high dialysis magnesium concentration.
LIMITATIONS
The participants had severe vascular calcification at baseline; therefore, the findings might not apply to those with less-established calcification. Moreover, cramps were not systematically ascertained.
CONCLUSIONS
The high dialysis magnesium concentration did not alleviate the progression of CAC or improve BMD in patients with severe calcification receiving hemodialysis; however, muscle cramps were less frequent among those treated with high dialysate magnesium. Further study is required to determine a possible favorable effect of high dialysis magnesium concentration in individuals with mild-to-moderate calcification.
PubMed: 35243301
DOI: 10.1016/j.xkme.2021.08.009 -
European Journal of Endocrinology Mar 2022To describe clinical, laboratory, and genetic characteristics of three unrelated cases from Chile, Portugal, and Saudi Arabia with severe insulin resistance, SOFT... (Observational Study)
Observational Study
OBJECTIVE
To 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.
DESIGN
Observational study.
METHODS
Probands' phenotypes, including short stature, dysmorphism, and insulin resistance, were compared with previous reports.
RESULTS
Cases 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.
CONCLUSIONS
Patients 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.
Topics: Cell Cycle Proteins; Cytoskeletal Proteins; Dwarfism; Female; Humans; Insulin Resistance; Male; Muscle Cramp
PubMed: 35234134
DOI: 10.1530/EJE-21-0609