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British Medical Journal Jul 1962
Topics: Anus Diseases; Disease; Humans; Muscle Cramp; Pain; Rectal Diseases; Rectum; Sacrococcygeal Region
PubMed: 13887589
DOI: 10.1136/bmj.2.5298.164 -
Journal of Neurology, Neurosurgery, and... Feb 1993
Review
Topics: Humans; Muscle Cramp; Muscle Rigidity; Muscles; Osteochondrodysplasias; Peripheral Nerves; Spasm; Spinal Cord; Stiff-Person Syndrome
PubMed: 8436998
DOI: 10.1136/jnnp.56.2.121 -
JAMA Neurology Jun 2015Dystonia is a heterogeneous neurologic disorder characterized by abnormal muscle contractions for which standard medical therapy is often inadequate. For such patients,... (Review)
Review
IMPORTANCE
Dystonia is a heterogeneous neurologic disorder characterized by abnormal muscle contractions for which standard medical therapy is often inadequate. For such patients, therapeutic brain stimulation is becoming increasingly used.
OBJECTIVES
To review the evidence and effect sizes for treating different types of dystonia with different types of brain stimulation and to discuss recent advances relevant to patient selection, surgical approach, programming, and mechanism of action.
EVIDENCE REVIEW
PubMed was searched for publications on the clinical effect of brain stimulation in dystonia up through December 31, 2014. Recent meta-analyses, consensus statements, and evidence-based guidelines were incorporated. Emphasis was placed on deep brain stimulation (DBS) and randomized clinical trials; however, other stimulation modalities and trial designs were included. For each intervention the mean change in dystonia severity, number of patients studied, and evidence of efficacy based on American Academy of Neurology criteria were determined.
FINDINGS
Strong (level B) evidence supports the use of DBS for the treatment of primary generalized or segmental dystonia, especially when due to mutation in the DYT1 gene, as well as for patients with cervical dystonia. Large effect sizes have also been reported for DBS treatment of tardive dystonia, writer's cramp, cranial dystonia, myoclonus dystonia, and off-state dystonia associated with Parkinson disease. Lesser benefit is generally seen in dystonia secondary to structural brain damage. Other brain stimulation techniques, including epidural cortical stimulation and noninvasive brain stimulation, have been investigated, but generally report smaller effect sizes in fewer patients.
CONCLUSIONS AND RELEVANCE
Patients with dystonia that is not adequately controlled with standard medical therapy should be referred for consideration of DBS, especially patients with generalized, segmental, or cervical dystonia. Other less-invasive stimulation modalities require further research before being considered a therapeutic alternative.
Topics: Deep Brain Stimulation; Dystonia Musculorum Deformans; Humans
PubMed: 25894231
DOI: 10.1001/jamaneurol.2015.51 -
Journal of Veterinary Internal Medicine Jan 2021Muscle cramps (MCs) are prolonged, involuntary, painful muscle contractions characterized by an acute onset and short duration, caused by peripheral nerve hyperactivity.
BACKGROUND
Muscle cramps (MCs) are prolonged, involuntary, painful muscle contractions characterized by an acute onset and short duration, caused by peripheral nerve hyperactivity.
OBJECTIVES
To provide a detailed description of the clinical features and diagnostic findings in dogs affected by MCs.
ANIMALS
Fourteen dogs.
METHODS
Multicenter retrospective case series. Cases were recruited by a call to veterinary neurologists working in referral practices. Medical records and videotapes were searched for dogs showing MCs. The follow-up was obtained by telephone communication with the owner and the referring veterinarian.
RESULTS
Three patterns of presentation were identified depending on the number of affected limbs and presence/absence of migration of MCs to other limbs. In 9/14 (64%) of dogs, MCs were triggered by prompting the dogs to move. 8/14 (58%) dogs were overtly painful with 6/14 (42%) showing mild discomfort. The cause of MCs was hypocalcemia in 11/14 (79%) dogs: 9 dogs were affected by primary hypoparathyrodism, 1 dog by intestinal lymphoma and 1 dog by protein losing enteropathy. In 3/14 cases (21%) the cause was not identified, and all 3 dogs were German Shepherds.
CONCLUSIONS AND CLINICAL IMPORTANCE
Muscle cramps can manifest in 1 of 3 clinical patterns. Muscle cramps are elicited when dogs are encouraged to move and do not always appear as painful events, showing in some cases only discomfort. The main cause of MCs in this study was hypocalcemia consequent to primary hypoparathyroidism. In dogs having MCs of unknown etiology, idiopathic disease or paroxysmal dyskinesia could not be ruled out.
Topics: Animals; Dog Diseases; Dogs; Hypocalcemia; Muscle Cramp; Protein-Losing Enteropathies; Retrospective Studies
PubMed: 33247617
DOI: 10.1111/jvim.15965 -
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 -
Clinical Gastroenterology and... Nov 2013Muscle cramps are common in patients with liver disease and adversely influence quality of life. The exact mechanisms by which they occur remain unclear, although a... (Review)
Review
Muscle cramps are common in patients with liver disease and adversely influence quality of life. The exact mechanisms by which they occur remain unclear, although a number of pathophysiological events unique to liver disease may contribute. Clinical studies have identified alterations in 3 areas: nerve function, energy metabolism, and plasma volume/electrolytes. Treatments have focused on these particular areas with varied results. This review will focus on the clinical features of muscle cramps in patients with liver disease and review potential mechanisms and current therapies.
Topics: Humans; Liver Diseases; Muscle Cramp
PubMed: 23542334
DOI: 10.1016/j.cgh.2013.03.017 -
JHEP Reports : Innovation in Hepatology Apr 2023Acetaminophen (APAP)-induced acute liver injury (AILI) is a leading cause of acute liver failure (ALF). -acetylcysteine (NAC) is only effective within 24 h after APAP...
BACKGROUND & AIMS
Acetaminophen (APAP)-induced acute liver injury (AILI) is a leading cause of acute liver failure (ALF). -acetylcysteine (NAC) is only effective within 24 h after APAP intoxication, raising an urgent need for alternative approaches to treat this disease. This study aimed to test whether cathelicidin (), which is a protective factor in chronic liver diseases, protects mice against APAP-induced liver injury and ALF.
METHODS
A clinically relevant AILI model and an APAP-induced ALF model were generated in mice. Genetic and pharmacological approaches were used to interfere with the levels of cathelicidin .
RESULTS
An increase in hepatic pro-CRAMP/CRAMP (the precursor and mature forms of mouse cathelicidin) was observed in APAP-intoxicated mice. Upregulated cathelicidin was derived from liver-infiltrating neutrophils. Compared with wild-type littermates, knockout had no effect on hepatic injury but dampened hepatic repair in AILI and reduced survival in APAP-induced ALF. CRAMP administration reversed impaired liver recovery observed in APAP-challenged knockout mice. Delayed CRAMP, CRAMP(1-39) (the extended form of CRAMP), or LL-37 (the mature form of human cathelicidin) treatment exhibited a therapeutic benefit for AILI. Co-treatment of cathelicidin and NAC in AILI displayed a stronger hepatoprotective effect than NAC alone. A similar additive effect of CRAMP(1-39)/LL-37 and NAC was observed in APAP-induced ALF. The pro-reparative role of cathelicidin in the APAP-damaged liver was attributed to an accelerated resolution of inflammation at the onset of liver repair, possibly through enhanced neutrophil phagocytosis of necrotic cell debris in an autocrine manner.
CONCLUSIONS
Cathelicidin reduces APAP-induced liver injury and ALF in mice by promoting liver recovery via facilitating inflammation resolution, suggesting a therapeutic potential for late-presenting patients with AILI with or without ALF.
IMPACT AND IMPLICATIONS
Acetaminophen-induced acute liver injury is a leading cause of acute liver failure. The efficacy of -acetylcysteine, the only clinically approved drug against acetaminophen-induced acute liver injury, is significantly reduced for late-presenting patients. We found that cathelicidin exhibits a great therapeutic potential in mice with acetaminophen-induced liver injury or acute liver failure, which makes up for the limitation of -acetylcysteine therapy by specifically promoting liver repair after acetaminophen intoxication. The pro-reparative role of cathelicidin, as a key effector molecule of neutrophils, in the APAP-injured liver is attributed to an accelerated resolution of inflammation at the onset of liver repair, possibly through enhanced phagocytic function of neutrophils in an autocrine manner.
PubMed: 36923240
DOI: 10.1016/j.jhepr.2023.100687 -
Journal of Women's Health (2002) Aug 2022The menstrual cycle may influence vulvodynia through hormonal pathways or vulvar irritation due to menstruation or menstrual hygiene. We assessed menstrual cycle...
The menstrual cycle may influence vulvodynia through hormonal pathways or vulvar irritation due to menstruation or menstrual hygiene. We assessed menstrual cycle characteristics in those with and without clinically confirmed vulvodynia. Participants were recruited from the administrative database of a health care network serving ∼27% of Minneapolis-Saint Paul residents. For 220 clinically confirmed cases and 224 controls, menstrual cycle characteristics were retrospectively assessed at three time points: before age 18, the year before onset of vulvar pain, and 3 months before study participation. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between menstrual characteristics at all three time points and vulvodynia. Models adjusted for prespecified confounders were evaluated against crude effect estimates. Women with heavier menstrual flows had higher odds of vulvodynia compared with women with lighter menstrual flows during their adolescent years (OR 1.62, 95% CI 0.91-2.86), the year before onset of vulvar pain (OR = 2.11, 95% CI 1.10-4.02), and during the 3 months before study participation (OR = 1.67, 95% CI 0.91-3.06). Women with more severe cramps also had higher odds of vulvodynia compared with women with no or mild cramps during their adolescent years (OR = 2.45, 95% CI 1.45-4.15), the year before onset of vulvar pain (OR = 3.30, 95% CI 1.67-6.51), and during the 3 months before study participation (OR = 4.96, 95% CI 1.99-12.36). Women with specific premenstrual symptoms also reported higher odds of vulvodynia. Among those with vulvodynia, half reported a change in vulvar pain across the menstrual cycle, with 60% of these reporting greater pain just before and during menstruation. Furthermore, we observe a trend of decreased tampon use and increased use of sanitary pads as women with vulvodynia moved closer to their date of diagnosis. Menstrual cycle characteristics were associated with vulvodynia, and associations were consistent across different phases of the reproductive life cycle.
Topics: Adolescent; Female; Humans; Hygiene; Menstrual Cycle; Menstruation; Muscle Cramp; Pain; Retrospective Studies; Vulvodynia
PubMed: 35041490
DOI: 10.1089/jwh.2020.9011 -
The Cochrane Database of Systematic... May 2021Lower limb muscle cramps are common and painful. They can limit exercise participation, and reduce quality of sleep, and quality of life. Many interventions are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lower limb muscle cramps are common and painful. They can limit exercise participation, and reduce quality of sleep, and quality of life. Many interventions are available for lower limb cramps; some are controversial or could cause harm, and often, people experience no benefit from the interventions used. This is an update of a Cochrane Review first published in 2012. We updated the review to incorporate new evidence.
OBJECTIVES
To assess the effects of non-drug, non-invasive therapies for lower limb muscle cramps.
SEARCH METHODS
In August 2018 and May 2020, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and reference lists of included studies. We imposed no restrictions by language or publication date.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of non-drug, non-invasive interventions tested over at least four weeks, for lower limb muscle cramps in any group of people, except pregnant women. The primary outcome was cramp frequency. Secondary outcomes were cramp pain severity, cramp duration, health-related quality of life, quality of sleep, participation in activities of daily living, proportion of participants reporting lower limb muscle cramps, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed risk of bias, and cross-checked data extraction and analyses according to standard Cochrane procedures.
MAIN RESULTS
We included three trials, with 201 participants, all 50 years of age and older; none had neurological disease. All trials evaluated a form of stretching for lower limb muscle cramps. A combination of daily calf and hamstring stretching for six weeks may reduce the severity of night-time lower limb muscle cramps (measured on a 10 cm visual analogue scale (VAS) where 0 = no pain and 10 cm = worst pain imaginable) in people aged 55 years and older, compared to no intervention (mean difference (MD) -1.30, 95% confidence interval (CI) -1.74 to -0.86; 1 RCT, 80 participants; low-certainty evidence). The certainty of evidence was very low for cramp frequency (change in number of cramps per night from week zero to week six) comparing the stretching group and the no intervention group (MD -1.2, 95% CI -1.8 to -0.6; 80 participants; very low-certainty evidence). Calf stretching alone for 12 weeks may make little to no difference to the frequency of night-time lower limb muscle cramps in people aged 60 years and older (stretching group median number of cramps in the last four weeks (Md) 4, interquartile range (IQR) 8; N = 48; sham stretching group Md 3, IQR 7.63; N = 46) (U = 973.5, z = -0.995, P = 0.32, r = 0.10; 1 RCT, 94 participants; low-certainty evidence). This trial did not report cramp severity. The evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50- to 60-year-old women with metabolic syndrome (N = 24). It was not possible to fully analyse the frequency data and the scale used to measure cramp severity is not validated. No study reported health-related quality of life, quality of sleep, or participation in activities of daily living. No participant in these three studies reported adverse events. The evidence for adverse events was of moderate certainty as the studies were too small to detect uncommon events. In two of the three studies, outcomes were at risk of recall bias, and tools used to measure outcomes were not validated. Due to limitations in study designs that led to risks of bias, and imprecise findings with wide CIs, we cannot be certain that findings of future studies will be similar to those presented in this review.
AUTHORS' CONCLUSIONS
A combination of daily calf and hamstring stretching for six weeks may reduce the severity of night-time lower limb muscle cramps in people aged 55 years and older, but the effect on cramp frequency is uncertain. Calf stretching alone compared to sham stretching for 12 weeks may make little or no difference to the frequency of night-time lower limb muscle cramps in people aged 60 years and older. The evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50- to 60-year-old women with metabolic syndrome. Overall, use of unvalidated outcome measures and inconsistent diagnostic criteria make it difficult to compare the studies and apply findings to clinical practice. Given the prevalence and impact of lower limb muscle cramps, there is a pressing need to carefully evaluate many of the commonly recommended and emerging non-drug therapies in well-designed RCTs across all types of lower limb muscle cramps. A specific cramp outcome tool should be developed and validated for use in future research.
Topics: Activities of Daily Living; Age Factors; Aged; Bias; Female; Hamstring Muscles; Humans; Leg; Lower Extremity; Male; Middle Aged; Muscle Cramp; Muscle Relaxants, Central; Muscle Stretching Exercises; Pain Measurement; Quinine; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 33998664
DOI: 10.1002/14651858.CD008496.pub3 -
Neurology Dec 2011To identify correlates of calf cramp in children with Charcot-Marie-Tooth disease type 1A (CMT1A).
OBJECTIVES
To identify correlates of calf cramp in children with Charcot-Marie-Tooth disease type 1A (CMT1A).
METHODS
Throughout Australia, 81 children aged 2-16 years with CMT1A were recruited. Measures of strength, ankle range, foot posture, balance, agility, endurance, gait, and neurophysiology were collected. Post hoc logistic regression analyses were performed to identify independent predictors of calf cramp.
RESULTS
Of the 81 children, 26 (32%) reported calf cramp, and 1 child each reported toe, quadriceps, or arm cramp. Calf cramp was associated (p < 0.05) with older age; the presence of hand tremor; stronger foot inversion, eversion, dorsiflexion, and plantarflexion; and better performance in long-jump and 9-hole peg tests. Logistic regression analysis revealed only increasing age (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.11-1.58; p = 0.002) and the presence of hand tremor (OR 3.81, 95% CI 1.18-12.56; p = 0.028) as independent predictors of calf cramp.
CONCLUSION
Calf cramps are common in children with CMT1A and worsen with age. This study revealed a previously unrecognized link between cramp and hand tremor in children with CMT1A. Further investigation of proposed mechanisms and risk factors common to both cramp and tremor will contribute to our understanding of these common complications of CMT1A.
Topics: Adolescent; Charcot-Marie-Tooth Disease; Child; Child, Preschool; Female; Humans; Male; Muscle Cramp; Prevalence
PubMed: 22131544
DOI: 10.1212/WNL.0b013e31823d76aa