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Frontiers in Neurology 2024Muscle cramps are typically regarded as benign muscle overactivity in healthy individuals, whereas spasms are linked to spasticity resulting from central motor lesions.... (Review)
Review
BACKGROUND
Muscle cramps are typically regarded as benign muscle overactivity in healthy individuals, whereas spasms are linked to spasticity resulting from central motor lesions. However, their striking similarities made us hypothesize that cramping is an under-recognized and potentially misidentified aspect of spasticity.
METHODS
A systematic search on spasms and cramps in patients with Upper Motor Neuron Disorder (spinal cord injury, cerebral palsy, traumatic brain injury, and stroke) was carried out in Embase/Medline, aiming to describe the definitions, characteristics, and measures of spasms and cramps that are used in the scientific literature.
RESULTS
The search identified 4,202 studies, of which 253 were reviewed: 217 studies documented only muscle spasms, 7 studies reported only cramps, and 29 encompassed both. Most studies ( = 216) lacked explicit definitions for either term. One-half omitted any description and when present, the clinical resemblance was significant. Various methods quantified cramp/spasm frequency, with self-reports being the most common approach.
CONCLUSION
Muscle cramps and spasms probably represent related symptoms with a shared pathophysiological component. When considering future treatment strategies, it is important to recognize that part of the patient's spasms may be attributed to cramps.
PubMed: 38497037
DOI: 10.3389/fneur.2024.1360521 -
Journal of Neuromuscular Diseases 2024The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1...
BACKGROUND
The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography, and genetic confirmation.
METHODS
Next-generation sequencing including the CLCN1 and SCN4A genes was performed in patients with clinical neuromuscular disorders. Electromyography, Short Exercise Test, in vivo and in vitro electrophysiology, site-directed mutagenesis and heterologous expression were collected.
RESULTS
A heterozygous point mutation (c.1775C > T, p.Thr592Ile) of muscle voltage-gated sodium channel α subunit gene (SCN4A) has been identified in five female patients over three generations, in a family with non-dystrophic myotonia. The muscle stiffness and myotonia involve mainly the face and hands, but also affect walking and running, appearing early after birth and presenting a clear cold sensitivity. Very hot temperatures, menstruation and pregnancy also exacerbate the symptoms; muscle pain and a warm-up phenomenon are variable features. Neither paralytic attacks nor post-exercise weakness has been reported. Muscle hypertrophy with cramp-like pain and increased stiffness developed during pregnancy. The symptoms were controlled with both mexiletine and acetazolamide. The Short Exercise Test after muscle cooling revealed two different patterns, with moderate absolute changes of compound muscle action potential amplitude.
CONCLUSIONS
The p.Thr592Ile mutation in the SCN4A gene identified in this Sardinian family was responsible of clinical phenotype of myotonia.
Topics: Adult; Female; Humans; Middle Aged; Electromyography; Italy; Myotonia; Myotonia Congenita; NAV1.4 Voltage-Gated Sodium Channel; Pedigree; Point Mutation
PubMed: 38427496
DOI: 10.3233/JND-230134 -
Comparative Biochemistry and... 2024In response to seasonal droughts, the green striped burrowing frog Cyclorana alboguttata enters a reversible hypometabolic state called aestivation where heart rate and...
In response to seasonal droughts, the green striped burrowing frog Cyclorana alboguttata enters a reversible hypometabolic state called aestivation where heart rate and oxygen consumption can be reduced despite warm (>25C°) ambient temperatures. With a view to understanding molecular mechanisms we profiled aestivating versus control gastrocnemius muscle using mRNA sequencing. This indicated an extensive metabolic reprogramming, with nearly a quarter of the entire transcriptome (3996 of 16,960 mRNA) exhibiting a nominal >2-fold change. Consistent with a physiological adaptation to spare carbohydrate reserves, carbohydrate catabolism was systemically downregulated. A 630-fold downregulation of ENO3 encoding the enolase enzyme was most striking. The 590 frog orthologs of mRNA encoding the mitoproteome were, viewed as a population, significantly downregulated during aestivation, although not to the same extent as mRNA encoding carbohydrate catabolism. Prominent examples include members of the TCA cycle (IDH2), electron transport chain (NDUFA6), the ATP synthase complex (ATP5F1B) and ADP/ATP intracellular transport (SLC25A4). Moreover, mRNA derived from the mt genome itself (e.g. mt-ND1) were also downregulated. Most prominent among the upregulated mRNA are those encoding aspects of regulated proteolysis including the proteosome (e.g. PSME4L), peptidases (USP25), atrogins (FBXO32) and ubiquitination (VCP). Finally, we note the ∼5-fold upregulation of the mRNA EIFG3 that encodes part of the EIF4F complex. This possesses global control of protein synthesis. Given protein synthesis is repressed in aestivating frogs this indicates the skeletal musculature is poised for accelerated translation of mRNA upon emergence, supporting a strategy to rapidly restore function when the summer rains come.
Topics: Animals; Muscle, Skeletal; Anura; Carbohydrates; Adenosine Triphosphate; Estivation
PubMed: 38355035
DOI: 10.1016/j.cbpb.2024.110952 -
Molecules (Basel, Switzerland) Jan 2024The 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...
Exploring the Therapeutic Efficacy of Parsley ( Mill.) as a Functional Food: Implications in Immunological Tolerability, Reduction of Muscle Cramps, and Treatment of Dermatitis.
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.
Topics: Humans; Functional Food; Petroselinum; Muscle Cramp; Plant Extracts; Dermatitis
PubMed: 38338356
DOI: 10.3390/molecules29030608 -
Journal of the International Society of... Dec 2024The purpose of this study was to examine the acute effects of a multi-ingredient, low calorie dietary supplement (MIDS, XTEND® Healthy Hydration) on 5-kilometer (5-km)... (Clinical Trial)
Clinical Trial
The effects of a sugar-free amino acid-containing electrolyte beverage on 5-kilometer performance, blood electrolytes, and post-exercise cramping versus a conventional carbohydrate-electrolyte sports beverage and water.
OBJECTIVE
The purpose of this study was to examine the acute effects of a multi-ingredient, low calorie dietary supplement (MIDS, XTEND® Healthy Hydration) on 5-kilometer (5-km) time trial performance and blood electrolyte concentrations compared to a carbohydrate-electrolyte beverage (CE, GATORADE® Thirst Quencher) and distilled water (W).
METHODS
During visit 1 (V1), participants (10 men and 10 women, 20-35 years old, BMI ≤ 29 kg/m, recreationally active) reported to the laboratory whereby the following tests were performed: i) height and weight measurements, ii) body composition analysis, iii) treadmill testing to measure maximal aerobic capacity, and iv) 5-km time trial familiarization. The second visit (V2) was one week after V1 in the morning (0600 - 0900) and participants arrived 12-14 h fasted (no food or drink). The first battery of assessments (V2-T1) included nude body mass, urine specific gravity (USG), a profile of mood states (POMS) questionnaire, and the completion of a visual analogue scale (VAS) questionnaire to quantify cramping. Then heart rate (HR), blood pressure (BP), total body hydration (via bioelectrical impedance spectroscopy [BIS]) were examined. Finally, a measurement of blood markers via finger stick was performed. Participants consumed a randomized beverage (16 fl. oz. of MIDS, 16 fl. oz. of W, or 16 fl. oz. of CE) within 3 min followed by a 45-min rest. Following the rest period, a second battery (V2-T2) was performed whereby participants' USG was assessed and they completed the POMS and VAS questionnaires, and HR, BP, and blood markers were measured. The participants then performed a 5-km treadmill time trial. Immediately following the 5-km time trial, participants completed a third testing battery (V2-T3) that began with blood markers, HR and BP assessments, followed by nude body weight assessment, and the POMS and VAS questionnaires. After 60 min, a fourth battery (V2-T4) was performed that included HR, BP, and blood markers. After sitting quietly for another 60 min a fifth battery assessment was performed (V2-T5) that included participants' USG, POMS and VAS questionnaires, HR, BP, blood markers, and total body hydration. Visits 3 (V3) and 4 (V4) followed the same protocol except a different randomized drink (16 oz. of CE, MIDS, or W) was consumed; all of which were separated by approximately one week.
RESULTS
No differences occurred between conditions for 5-km time trial completion, indirect calorimetry outcomes during 5-km time trials, USG, or nude mass measurements ( > 0.05 for all relevant statistical tests). However, blood potassium and the sodium/potassium ratio displayed significant interactions ( < 0.05), and post hoc testing indicated these values were better maintained in the MIDS versus other conditions. Post-exercise cramp prevalence was greater in the CE ( < 0.05) and trended higher with W ( = 0.083) compared to the MIDS condition. Post-exercise cramp severity was also elevated with the W and CE beverages ( < 0.05) but not the MIDS ( = 0.211).
CONCLUSIONS
The MIDS did not affect 5-km time trial performance but exhibited favorable effects on blood electrolyte and post-exercise self-reporting cramp outcomes compared to the CE and W drinks.
Topics: Adult; Female; Humans; Male; Young Adult; Amino Acids; Beverages; Dietary Carbohydrates; Electrolytes; Muscle Cramp; Potassium; Water; Water-Electrolyte Balance; Random Allocation
PubMed: 38131124
DOI: 10.1080/15502783.2023.2296888 -
JPMA. the Journal of the Pakistan... Dec 2023McArdle's disease (Glycogen storage disease type V) is a rare inherited autosomal recessive disease involving defect in enzyme, glycogen phosphorylase (PYGM) which...
McArdle's disease (Glycogen storage disease type V) is a rare inherited autosomal recessive disease involving defect in enzyme, glycogen phosphorylase (PYGM) which results in accumulation of glycogen mainly affecting skeletal muscles. It commonly presents in childhood and rarely in adults with symptoms like exercise intolerance, muscle weakness, cramps and fatigue. Herein, we report an unusual case of a 22 years old male in Pakistan with probable McArdle's Disease presenting with repeated episodes of generalized cramping muscle pain, exercise intolerance and haematuria. The diagnostic approach to identifying this disease as well as the differentials of other rare types of skeletal muscle disorders that should be kept in mind while dealing with a similar clinical picture, irrespective of the age of presentation, have been discussed.
Topics: Humans; Male; Young Adult; Adult; Glycogen Storage Disease Type V; Muscle, Skeletal; Muscle Weakness; Fatigue; Muscle Cramp
PubMed: 38083936
DOI: 10.47391/JPMA.8401 -
Phytomedicine : International Journal... Jan 2024Although chronic treatment with glucocorticoids, such as dexamethasone, is frequently associated with muscle atrophy, effective and safe therapeutics for treating muscle...
BACKGROUND
Although chronic treatment with glucocorticoids, such as dexamethasone, is frequently associated with muscle atrophy, effective and safe therapeutics for treating muscle atrophy remain elusive. Jakyak-gamcho-tang (JGT), a decoction of Paeoniae Radix and Glycyrrhizae Radix et Rhizoma, has long been used to relieve muscle tension and control muscle cramp-related pain. However, the effects of JGT on glucocorticoid-induced muscle atrophy are yet to be comprehensively clarified.
PURPOSE
The objective of the current study was to validate the protective effect of JGT in dexamethasone-induced muscle atrophy models and elucidate its underlying mechanism through integrated in silico - in vitro - in vivo studies.
STUDY DESIGN AND METHODS
Differential gene expression was preliminarily analyzed using the RNA-seq data to determine the effects of JGT on C2C12 myotubes. The protective effects of JGT were further validated in dexamethasone-treated C2C12 myotubes by assessing cell viability, myotube integrity, and mitochondrial function or in C57BL/6 N male mice with dexamethasone-induced muscle atrophy by evaluating muscle mass and physical performance. Transcriptomic pathway analysis was also performed to elucidate the underlying mechanism.
RESULTS
Based on preliminary gene set enrichment analysis using the RNA-seq data, JGT regulated various pathways related to muscle differentiation and regeneration. Dexamethasone-treated C2C12 myotubes and muscle tissues of atrophic mice displayed substantial muscle protein degradation and muscle loss, respectively, which was efficiently alleviated by JGT treatment. Importantly, JGT-mediated protective effects were associated with observations such as preservation of mitochondrial function, upregulation of myogenic signaling pathways, including protein kinase B/mammalian target of rapamycin/forkhead box O3, inhibition of ubiquitin-mediated muscle protein breakdown, and downregulation of inflammatory and apoptotic pathways induced by dexamethasone.
CONCLUSION
To the best of our knowledge, this is the first report to demonstrate that JGT could be a potential pharmaceutical candidate to prevent muscle atrophy induced by chronic glucocorticoid treatment, highlighting its known effects for relieving muscle spasms and pain. Moreover, transcriptomic pathway analysis can be employed as an efficient in silico tool to predict novel pharmacological candidates and elucidate molecular mechanisms underlying the effects of herbal medications comprising diverse biologically active ingredients.
Topics: Male; Mice; Animals; Glucocorticoids; Paeonia; Mice, Inbred C57BL; Muscular Atrophy; Muscle Fibers, Skeletal; Muscle Proteins; Dexamethasone; Pain; Mammals; Drugs, Chinese Herbal; Glycyrrhiza
PubMed: 37984121
DOI: 10.1016/j.phymed.2023.155057 -
Human Genetics Dec 2023Machado-Joseph disease (MJD/SCA3) is the most frequent dominant ataxia worldwide. It is caused by a (CAG) expansion. MJD has two major ancestral backgrounds: the Machado...
Machado-Joseph disease (MJD/SCA3) is the most frequent dominant ataxia worldwide. It is caused by a (CAG) expansion. MJD has two major ancestral backgrounds: the Machado lineage, found mainly in Portuguese families; and the Joseph lineage, present in all five continents, probably originating in Asia. MJD has been described in a few African and African-American families, but here we report the first diagnosed in Sudan to our knowledge. The proband presented with gait ataxia at age 24; followed by muscle cramps and spasticity, and dysarthria, by age 26; he was wheel-chair bound at 29 years of age. His brother had gait problems from age 20 years and, by age 21, lost the ability to run, showed dysarthria and muscle cramps. To assess the mutational origin of this family, we genotyped 30 SNPs and 7 STRs flanking the ATXN3_CAG repeat in three siblings and the non-transmitting father. We compared the MJD haplotype segregating in the family with our cohort of MJD families from diverse populations. Unlike all other known families of African origin, the Machado lineage was observed in Sudan, being shared with 86 Portuguese, 2 Spanish and 2 North-American families. The STR-based haplotype of Sudanese patients, however, was distinct, being four steps (2 STR mutations and 2 recombinations) away from the founder haplotype shared by 47 families, all of Portuguese extraction. Based on the phylogenetic network constructed with all MJD families of the Machado lineage, we estimated a common ancestry at 3211 ± 693 years ago.
Topics: Male; Humans; Young Adult; Adult; Machado-Joseph Disease; Portugal; Muscle Cramp; Dysarthria; Phylogeny; Africa, Eastern
PubMed: 37957369
DOI: 10.1007/s00439-023-02611-8 -
Medicine Oct 2023Chronic musculoskeletal pain (CMP) is associated with an increased risk of cardiovascular disease (CVD). This study aimed to determine the factors associated with the...
Factors affecting the intensity of chronic musculoskeletal pain in patients with cardiovascular disease and evaluation of the efficacy of magnesium emulsion cream for muscle cramps.
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.
Topics: Humans; Female; Muscle Cramp; Magnesium; Cardiovascular Diseases; Musculoskeletal Pain; Emulsions; Calcium; Ice; Hypertension; Chronic Pain
PubMed: 37904395
DOI: 10.1097/MD.0000000000035532 -
Deutsches Arzteblatt International Sep 2023
Topics: Female; Humans; Muscle Cramp; Dysmenorrhea
PubMed: 37811847
DOI: 10.3238/arztebl.m2023.0165