Cramp-Fasciculation Syndrome Associated with Natural and Added Chemicals in Popular Food Items.

Cramp-fasciculation syndrome (CFS) is a rare and benign neuromuscular disorder that may initially masquerade as motor neuron disease/amyotrophic lateral sclerosis. While CFS may have a familial disposition, we report on cases associated with high consumption of popular food items. One set of patients reversibly experienced acute onset of headache, flushing, muscle stiffness and fasciculations following the consumption of umami-flavored food containing a large concentration of monosodium glutamate. A second group of patients consuming food derived from lupin seed developed acute cholinergic toxicity, CFS, and, with chronic intake, significant, self-limiting, but incompletely reversible upper and lower motor neuron deficits. While these cases may improve our knowledge about the possible causes of CFS, our series also demonstrates that excessive consumption of some popular foods is not harmless. This warrants further research on their safety at all stages of human development from a neurological point of view.

Efficacy of Acupuncture on Pain Severity and Frequency of Calf Cramps in Dialysis Patients: a Randomized Clinical Trial.

Background: Patients with chronic kidney disease, as a common disorder, usually necessitate the implementation of hemodialysis. Muscle cramps are one of the most disabling complications affecting their quality of life. Objectives: We aimed to investigate the efficacy of acupuncture as a safe alternative to the management of pain severity and frequency of calf cramps in dialysis patients compared to a control group. Methods: Fifty dialysis patients experiencing calf cramps who met the eligibility criteria were randomly allocated to two groups. Group A received routine management, including analgesic consumption, stretching exercises, and nine acupuncture sessions, including acupoints BL57, GV26, CV4, CV6, LV3, KI 1, LU7, LU9, and GB34. Group B underwent sham acupuncture therapy at locations other than the primary acupoints in addition to following the specified routine management. The pain severity was measured using the visual analog scale (VAS), and the daily frequency of calf cramps was evaluated at baseline and one month after treatment completion. Results: VAS scores and the frequency of calf cramps were improved one month after treatment completion in both groups. However, the improvement was significant in group A (p < 0.001), while it was not statistically significant in group B (p > 0.05). There was also a significant difference between both groups regarding reducing pain and the frequency of calf cramps, which showed the efficacy of acupuncture compared to the control group (p < 0.0001). Conclusion: Acupuncture can decrease pain and frequency of calf cramps in dialysis patients.

Comprehensive Analysis of a Japanese Pedigree with Biallelic ACAGG Expansions in RFC1 Manifesting Motor Neuronopathy with Painful Muscle Cramps.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive multisystem neurologic disorder caused by biallelic intronic repeats in RFC1. Although the phenotype of CANVAS has been expanding via diagnostic case accumulation, there are scant pedigree analyses to reveal disease penetrance, intergenerational fluctuations in repeat length, or clinical phenomena (including heterozygous carriers). We identified biallelic RFC1 ACAGG expansions of 1000 ~ repeats in three affected siblings having sensorimotor neuronopathy with spinocerebellar atrophy initially presenting with painful muscle cramps and paroxysmal dry cough. They exhibit almost homogeneous clinical and histopathological features, indicating motor neuronopathy. Over 10 years of follow-up, painful intractable muscle cramps ascended from legs to trunks and hands, followed by amyotrophy and subsequent leg pyramidal signs. The disease course combined with the electrophysical and imagery data suggest initial and prolonged hyperexcitability and the ensuing spinal motor neuron loss, which may progress from the lumbar to the rostral anterior horns and later expand to the corticospinal tract. Genetically, heterozygous ACAGG expansions of similar length were transmitted in unaffected family members of three successive generations, and some of them experienced muscle cramps. Leukocyte telomere length assays revealed comparatively shorter telomeres in affected individuals. This comprehensive pedigree analysis demonstrated a non-anticipating ACAGG transmission and high penetrance of manifestations with a biallelic state, especially motor neuronopathy in which muscle cramps serve as a prodromal and disease progress marker. CANVAS and RFC1 spectrum disorder should be considered when diagnosing lower dominant motor neuron disease, idiopathic muscle cramps, or neuromuscular hyperexcitability syndromes.

Re-survey of 16 Japanese patients with advanced-stage hereditary motor sensory neuropathy with proximal dominant involvement (HMSN-P): Painful muscle cramps for early diagnosis.

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an intractable neurological disease with autosomal dominant inheritance, four-limb weakness, sensory impairment, and a slowly progressive course. HMSN-P patients develop four-limb paralysis at the advanced-stage, as in amyotrophic lateral sclerosis (ALS). There is a natural 20- to 30-year course from initial painful muscle cramps and four-limb paralysis to respiratory dysfunction. A delay in the diagnosis of HMSN-P occurs due to the 20- to 30-year span from the initial symptom(s) to typical quadriplegia. Its early diagnosis is important, but the involvement of painful muscle cramps as an early symptom has not been clear. Following our earlier survey, we conducted a re-survey focusing on painful muscle cramps, assistive-device use, and hope for specific therapies in 16 Japanese patients with advanced-stage HMSN-P. Fifteen patients presented painful muscle cramps as the initial symptom, and muscle cramps in the lower abdomen including the flank were described by 10 of the patients. The presence of painful muscle cramps including those in the abdominal region may be a clue for the early diagnosis of HMSN-P. Painful abdominal cramps have not described in related diseases, e.g., ALS, spinal muscular atrophy, and Charcot-Marie-Tooth disease. Recent patient-welfare improvements and advances in assistive devices including robot-suit assistive limbs are delaying the terminal state of HMSN-P. Regarding specific therapies for HMSN-P, many patients choose both nucleic acid medicine and the application of induced pluripotent stem cells as a specific therapy for HMSN-P.

Randomized double-blind personalized N-of-1 clinical trial to test the safety and potential efficacy of TJ-68 for treating muscle cramps in amyotrophic lateral sclerosis (ALS): study protocol for a TJ-68 trial.

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.

Clinical characteristics of muscle cramps in hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome associated with a novel COL4A1 pathogenic variant: A family case study.

BACKGROUND: Muscle cramps are a common problem characterized by a sudden, painful, and involuntary contraction of a muscle or muscle group. Most muscle cramps develop in the calf muscles, particularly in situations of prolonged exercise; however, some may be related to underlying systemic conditions such as the hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome. Muscle cramps appear to be the initial symptom of the HANAC syndrome; however, the clinical characteristics of these muscle cramps have rarely been described in detail. CASE PRESENTATION: We report a familial case of autosomal-dominant muscle cramps in four members of a Japanese family spanning across three generations. The muscle cramps were recognized as systemic symptoms of the HANAC syndrome associated with a novel COL4A1 pathogenic variant, NM_001845:c.1538G > A, p.(Gly513Asp). The four affected individuals indicated that the first episodes of the muscle cramps occurred in early childhood. In addition, they reported that the muscle cramps are characterized by an abrupt onset of severe pain without muscle contraction. The painful recurrent attacks occurred spontaneously in various muscles throughout the body, but rarely in the calf muscle. The muscle pain lasts for several minutes, cannot be ameliorated by stretching the affected muscle, and leaves a feeling of discomfort that lasts for 24-48 h. The serum creatine kinase levels of the patients were persistently elevated; however, their electromyography results did not reveal any specific abnormalities. CONCLUSIONS: Recognition of the clinical characteristics of the muscle cramps in the HANAC syndrome may facilitate early diagnosis of the syndrome and enable proper treatment of the patients, improve their long-term outcomes, and facilitate the design and adaption of appropriate genetic counseling.

Effects of warm or cold compresses applied to the legs during hemodialysis on cramps, fatigue, and patient comfort: A placebo-controlled randomized trial.

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 (t0 ), during each of 12 intervention sessions (t1 -t12 ), and at the follow-up session t13 . 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.

Characteristics of spinal and bulbar muscular atrophy in South Korea: a cross-sectional study of 157 patients.

Spinal and bulbar muscular atrophy, namely Kennedy disease, is a rare progressive neurodegenerative disorder caused by the expansion of a CAG repeat in the first exon of the androgen receptor gene on the X chromosome. We assessed the clinical history, laboratory findings, functional scales and electrophysiological data, as well as the levels of luteinizing hormone, follicle-stimulating hormone and testosterone, in 157 Korean patients with genetically confirmed spinal and bulbar muscular atrophy (mean age at data collection = 56.9 years; range = 33-83 years). Hand tremor was the first symptom noticed by patients at a median age of 35 years, followed by gynaecomastia, orofacial fasciculation, cramps and fatigability in ascending order. Clinical symptoms such as paraesthesia and dysphagia appeared during the later stages of the disease. Cane use during ambulation began at a median age of 62 years. There were statistically significant differences between patients and controls in the results of sensory nerve studies, motor conduction velocity, and distal latencies. Furthermore, among the hormone markers analysed, the level of luteinizing hormone exhibited a negative correlation with the spinal and bulbar muscular atrophy functional rating scale, Korean version. However, among the patients with a disease duration of ≤5 years, the levels of luteinizing hormone showed a significant correlation with assessments using the amyotrophic lateral sclerosis functional rating scale-revised, spinal and bulbar muscular atrophy functional rating scale, Korean version and the 6-minute walk test. In conclusion, our findings provide clinical information from a substantial number of patients with spinal and bulbar muscular atrophy in Korea that accorded with that of patients with this disease worldwide but with updated clinical features.

Electromyographic changes in a patient with hypocalcemia after thyroidectomy: A case report.

Hypocalcemia is a rather uncommon condition that may be encountered in the outpatient setting. It may be associated with a wide range of clinical symptoms and signs. It is unclear that the primary cause of symptom is hypocalcemia, as these symptoms are usually discrete and ambiguous. Signs of muscle cramp and tetany are considered the expressions of overexcitability of peripheral nerves or central nervous system in case of hypocalcemia in the nerve. In this case, we present a 59-year-old female who presented with persistent muscle cramp and pain of both upper and lower extremities and underwent an investigation that revealed electromyographic changes due to hypocalcemia during an electromyographic study.

Treatment of Muscle Cramps in Patients With Cirrhosis of Liver: A Systematic Review.

Background: Muscle 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. Methods: A 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. Results: Twenty-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. Conclusion: Taurine, 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.

Injuries in Medium to Long-Distance Triathlon: A Retrospective Analysis of Medical Conditions Treated in Three Editions of the Ironman Competition.

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.

Efficacy and Safety of Pregabalin for Muscle Cramps in Liver Cirrhosis: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Muscle 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. METHODS: We 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. RESULTS: This 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. CONCLUSION: With 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 REGISTRATION: ClinicalTrials.gov Identifier: NCT01271660.

Vitamin K2 as a potential therapeutic candidate for the prevention of muscle cramps in hemodialysis patients: A prospective multicenter, randomized, controlled, crossover pilot trial.

OBJECTIVES: Muscle cramps occur in 33% to 78% of patients with dialysis. The etiology of muscle cramps is poorly understood, and no clear evidence-based prevention or treatment strategies exist. Improved interventions are urgently needed. The aim of this study was to investigate the effect of vitamin K2 in reducing the frequency and severity of muscle cramps in hemodialysis (HD) patients. METHODS: This multicenter, randomized, placebo-controlled, crossover clinical trial was conducted from June 2019 to May 2020. Each participant received vitamin K2 (360 µg/d) or placebo for two 4-wk phases, and then crossed to the alternative arm for two 4-wk phases after a 2-wk washout. The primary endpoint was the frequency of muscle cramps during HD. The secondary endpoints were severity and duration of muscle cramps during HD. RESULTS: A total of 523 patients with maintenance HD were screened for muscle cramps, including 41 patients with muscle cramps refractory to conventional interventions, were enrolled. Nineteen patients in the vitamin K2-initial group and 20 in the placebo-initial group completed the protocol, and were included in the final analysis. Vitamin K2 reduced the frequency, duration, and severity of muscle cramps in HD patients (all P < 0.05). The frequency, duration, and severity of muscle cramps in HD patients increased again after crossing over to the placebo. There were no serious adverse events. One patient experienced gastrointestinal discomfort when taking vitamin K2. CONCLUSIONS: This pilot trial demonstrated that vitamin K2 supplementation could decrease the frequency, duration, and severity of muscle cramps in HD patients.

Translation of Runge's 1873 publication "On the etiology and treatment of writer's cramp": The first description of "tennis elbow".

This publication by Dr Ferdinand Runge is ubiquitously credited as first to describe the symptoms, pathology, and treatment of patients with lateral epicondylosis (tennis elbow). However, the main focus of his work was to provide insight into causes of writer's cramp and treatments for the condition, elegantly illustrated in four case reports. This work, recently cited as unavailable, is written in German. Given the high frequency of citations in the English literature, it was considered useful to translate it into English to widen access to a broader readership. The purpose of this project was briefly to introduce the life and clinical expertise of Dr. Ferdinand Runge and the content of his work, followed by a translation of the entire manuscript into English. The paper was translated by the three authors using a process of sequential consensus. All are proficient in German and English, with clinical expertise in both topics. A brief reflection is provided to place Dr Runge's observations, clinical reasoning, and contemporaneously available treatments in the context of current thinking about lateral epicondylalgia. Dr. Runge shares his expertise, carefully reporting pertinent examination findings for each case, sharing hypotheses about the etiology of writer's cramp, and using the effectiveness of his applied treatment as confirmation. He concludes that careful evaluation of the patient's activities that hindered writing prior to the onset of the writer's cramp is key to managing this ailment. The topics addressed in this classic work are still thought-provoking.

Proposal for new sleep disorder criteria in patients with chronic liver disease: Influence of liver-related complications.

AIM: Sleep disorder is common in patients with chronic liver disease (CLD). Liver-related silent complications, including muscle cramps, covert hepatic encephalopathy (HE), and sarcopenia, often reduce the quality of life of patients with CLD and have been reported to cause sleep disorders. In this study, we clarified the prevalence of liver-related complications associated with sleep disorders in patients with CLD. METHODS: We conducted a multicenter cohort study of 271 patients with CLD. The Athens Insomnia Scale, muscle cramps questionnaires, and Stroop test were used to assess insomnia, muscle cramps, and covert HE, respectively. In addition, sarcopenia, dynapenia, and myopenia were diagnosed according to the guidelines of the Japan Society of Hepatology. RESULTS: In total, 136 patients (50.2%) had sleep disorders. Serum albumin and hemoglobin levels and prothrombin time activity were significantly lower in patients with sleep disorders than in those without sleep disorders. On univariate and multivariate analyses adjusted with inverse probability weighting, muscle cramps, covert HE, and dynapenia were associated with a sleep disorder. Sleep disorder was categorized as follows: cramp, covert HE, dynapenia, multiple complications, and others. In total, 106 of 136 patients (77.9%) with sleep disorder had at least one liver-related complication, whereas 75 patients had multiple liver-related complications. CONCLUSION: Sleep disorder in patients with CLD was classified into four categories (muscle cramp, covert HE, dynapenia, and others). Questionnaire for sleep disorder might be an easy primary step for surveillance of high-risk patients with silent complications associated CLD.

Fasciculaciones y calambres: bases fisiológicas y enfrentamiento clínico de un fenómeno complejo / Fasciculations and cramps: physiological bases and clinical approach of a complex phenomenon

Fasciculations and cramps originate in the motor unit, a functional unit that includes the lower motor neuron and their innervated muscle fibres. Both are common complaints in outpatient practice. These symptoms can be secondary to neurological or medical pathology, presenting a broad differential diagnosis and a complex approach. Recent neurophysiological studies have increased the knowledge of their origin mainly in amyotrophic lateral sclerosis. The symptomatic management of fasciculations and cramps depends on their etiology and includes pharmacological and non-pharmacological treatments. This article aims to present an updated review of the most relevant aspects of physiopathology, clinical approach, and differential diagnosis of both phenomena.

Prevention of leg cramps by using compression stockings or magnesium supplements in the 50-84 age group: study protocol for a randomised controlled trial.

BACKGROUND: Leg cramps are painful sensations of tightening in the muscles of the legs that commonly appear during the night and are often associated with secondary insomnia. They are common especially in older age. There is no evidence that any method of prevention of nocturnal leg cramps is both safe and effective. There are no previous trials concerning cramp prevention by using compression stockings. The objective of this study is to assess in a prospective randomised controlled trial whether leg cramps can be prevented by the daily use of knee-length compression stockings or magnesium supplements. METHODS: The study will be set in Finland, and 50-84-year-old volunteers will be recruited through Google Ads, the Finnish health library website and Finnish primary health care centres. The participants must have a minimum of two episodes of leg cramps per week for the past 4 weeks to be included in the study. The participants (n = 225) will be allocated to three equal groups: the compression stocking arm, the magnesium supplement arm and the placebo arm. The participants will go through 4 weeks of follow-up without intervention and then another 4 weeks of follow-up with the assigned intervention. The material for the study will be collected through electronic questionnaires. DISCUSSION: This protocol describes a study that compares compression stockings, magnesium supplements and placebo for the prevention of leg cramps. The results of this study can significantly improve knowledge on the methods of preventing leg cramps. TRIAL REGISTRATION: ClinicalTrials.gov NCT04694417. Registered on Jan 4, 2021.

The pathophysiology of leg cramping during dialysis and the use of carnitine in its treatment.

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, ß-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.

Development and validation of a real-time method characterizing spontaneous pain in women with dysmenorrhea.

AIM: Prior research has primarily focused on static pain assessment, largely ignoring the dynamic nature of pain over time. We used a novel assessment tool for characterizing pain duration, frequency, and amplitude in women with dysmenorrhea and evaluated how these metrics were affected by naproxen treatment. METHODS: Dysmenorrheic women (n = 25) rated their menstrual pain by squeezing a pressure bulb proportional to the magnitude of their pain. To evaluate whether bulb squeezing was affected by naproxen, we compared parameters before and after naproxen. We also analyzed the correlation between pain relief on a numerical rating scale to changes in bulb squeezing parameters. Random bulb-squeezing activity in pain-free participants (n = 14) was used as a control for nonspecific effects or bias. RESULTS: In dysmenorrheic women, naproxen reduced the duration of the squeezing during a painful bout, the number of painful bouts and bout intensity. Before naproxen, the correlation between these bulb squeeze parameters and self-reported pain on numeric rating scale was not significant (R2 = 0.12, p = 0.304); however, there was a significant correlation between changes in bulb squeeze activity and self-reported pain relief after naproxen (R2 = 0.55, p < 0.001). CONCLUSION: Our study demonstrates a convenient technique for continuous pain assessment, capturing three different dimensions: duration, frequency, and magnitude. Naproxen may act by reducing the duration and frequency of episodic pain in addition to reducing the severity. After further validation, these methods could be used for other pain conditions for deeper phenotyping and assessing novel treatments.