Painful Muscle Cramps Research Articles

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 10years 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.

Non-pharmacological Interventions for Muscle Cramps and Pain in Patients With Cirrhosis: A Systematic Review.

Despite the high prevalence of pain and challenges associated with traditional pharmacological pain management in patients with cirrhosis, little is known about the safety and effectiveness of non-pharmacological management of pain in this patient population. A systematic literature search of published studies was conducted in nine databases from inception through January 11, 2023, including any clinical trial, cohort, or case-control study of non-pharmacological pain interventions in adult patients with cirrhosis. Studies using nutritional supplements were included. The primary and secondary outcomes for this review were pain/analgesic effect and safety, respectively. Two reviewers independently performed data extraction and risk of bias assessment. Of the 4,087 studies initially screened, 11 studies representing 340 patients ultimately met inclusion criteria, including seven observational and four randomized controlled trials. Five studies reported muscle cramp severity, four reported muscle cramp frequency, and two reported non-cramp pain. Oral zinc sulfate, L-carnitine, and taurine were reported to decrease cramp frequency. Oral vitamin E, oral zinc sulfate, L-carnitine, taurine, and pickle juice decreased cramp severity. Curcumin supplementation, resistance training, and stretching and walking programs improved non-cramp pain. Mild adverse events were reported in four studies. The risk of bias was moderate to high for all studies, largely due to missing data, study design, and a lack of blinding of participants. Numerous nutritional and non-pharmacological interventions have been reported to be safe and effective for the treatment of pain and painful muscle cramps in patients with cirrhosis. However, further research is needed to better determine the efficacy, safety, and optimal frequency and dosage of interventions.

Anti-IgLON5 disease as a differential diagnosis of multiple system atrophy

IntroductionAnti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a rare autoimmune encephalitis that can mimic progressive supranuclear palsy or corticobasal syndrome. Moreover, anti-IgLON5 disease can present with symptoms characteristic of multiple system atrophy (MSA), such as cerebellar ataxia and autonomic dysfunction. However, the clinical features of anti-IgLON5 disease resembling MSA have not been well established. MethodsWe enrolled 35 patients with suspected MSA for whom anti-IgLON5 antibody tests were requested. We evaluated immunoglobulin G (IgG) against IgLON5 using cell-based assays. We also summarized the clinical characteristics of patients who were positive for anti-IgLON5 antibodies. ResultsWe identified serum and cerebrospinal fluid anti-IgLON5 antibodies in three patients. These patients had many clinical features characteristic of MSA, including parkinsonism, cerebellar ataxia, severe orthostatic hypotension, acute respiratory failure, sleep parasomnia, vocal cord paralysis, and pyramidal tract signs. Clinical features atypical for MSA were myorhythmia, horizontal eye movement restriction, fasciculations, and painful muscle cramps. ConclusionAnti-IgLON5 disease may be an important differential diagnosis of MSA. A comprehensive physical examination, including assessments of eye movement, lower motor neuron signs, and atypical involuntary movements, is important to avoid misdiagnosis.

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.

Sympathetic Sudomotor Ganglionopathy Following Envenomation from a Northern Australia Jellyfish Irukandji Syndrome

The oceans of northern Australia coastal beaches harbor numerous venomous jellyfish. Several species cause Irukandji Syndrome, a severe disorder (developing within an hour after a sting) consisting painful muscle cramps, vomiting, sweating, agitation, vasoconstriction, prostration, hypertension, cardiac irregularities. The jellyfish toxin may modulate neuronal sodium channels leading to a massive release of endogenous catecholamines. Segmental sympathetic cardiovascular hyperactivity has been emphasized but this case report portrays a dramatic effect on segmental sympathetic sudomotor function.

Patient-centred approaches for the management of unpleasant symptoms in kidney disease.

Patients with chronic kidney disease (CKD) frequently experience unpleasant symptoms. These can be gastrointestinal (constipation, nausea, vomiting and diarrhoea), psychological (anxiety and sadness), neurological (lightheadedness, headache and numbness), cardiopulmonary (shortness of breath and oedema), dermatological (pruritus and dry skin), painful (muscle cramps, chest pain and abdominal pain) or involve sexual dysfunction, sleep disorders and fatigue. These symptoms often occur in clusters, with one of them as the lead symptom and others as secondary symptoms. Uraemic toxins (also called uremic toxins) are often considered to be the main cause of CKD-associated symptom burden, but treatment of uraemia by dialysis often fails to resolve them and can engender additional symptoms. Indeed, symptoms can be exacerbated by comorbid conditions, pharmacotherapies, lifestyle and dietary regimens, kidney replacement therapy and ageing. Patients with kidney disease, including those who depend on dialysis or transplantation, should feel actively supported in their symptom management through the identification and targeting of unpleasant symptoms via a tailored palliative care approach. Such an approach may help minimize the burden and consequences of kidney disease, and lead to improved patient outcomes including health-related quality of life and better life participation.

Treatment Possibilities of Muscle Cramps in Patients with Liver Cirrhosis

Abstract Muscle cramps appearing in liver cirrhosis substantially affect the quality of life of these patients. The prevalence of painful muscle cramps can be up to 88%. The exact mechanism by which these muscle cramps occur is unknown. The management of this symptom is not easy because there is no uniformly accepted recommendation about what kind of supplementation or medicine (or both) can be used exactly. The aim of our study is to review the treatment options for muscle cramps in liver cirrhosis. We found in the literature (using the keywords „liver cirrhosis", „muscle cramps", „treatment" and „quality of life") 32 articles of this topic. Treatment options currently are: vitamin supplementations (vitamin E, 1 - α hydroxy vitamin D), amino acid supplementations (taurine, branched - chain amino acids, L - carnitine, albumin), mixed herbal medicines (Niuche-Shen-Qui-Wan), zinc and medications (eperisone hydrochloride, quinine and quinidine sulphate, baclofen, methocarbamol, orphenadrine). Vitamin supplementations and amino acid supplementations are targeting the possible pathophysiological causes of muscle cramps (nerve function or energy metabolism alterations which are unique to liver cirrhosis). New aspects started to use medications especially antispasmodic agents (methocarbamol, orphenadrine) and antispasticity agents (baclofen) to relieve muscle cramps. We also found a multicenter study and two systematic reviews (performed in 2013 and 2014). From 2014 there is no systematic article appeared in this topic and we considered it important to survey the new treatment options next to the treatment options already known.

Systemic AAV8-mediated delivery of a functional copy of muscle glycogen phosphorylase (Pygm) ameliorates disease in a murine model of McArdle disease.

McArdle disease is a disorder of carbohydrate metabolism that causes painful skeletal muscle cramps and skeletal muscle damage leading to transient myoglobinuria and increased risk of kidney failure. McArdle disease is caused by recessive mutations in the muscle glycogen phosphorylase (PYGM) gene leading to absence of PYGM enzyme in skeletal muscle and preventing access to energy from muscle glycogen stores. There is currently no cure for McArdle disease. Using a preclinical animal model, we aimed to identify a clinically translatable and relevant therapy for McArdle disease. We evaluated the safety and efficacy of recombinant adeno-associated virus serotype 8 (rAAV8) to treat a murine model of McArdle disease via delivery of a functional copy of the disease-causing gene, Pygm. Intraperitoneal injection of rAAV8-Pygm at post-natal day 1-3 resulted in Pygm expression at 8weeks of age, accompanied by improved skeletal muscle architecture, reduced accumulation of glycogen and restoration of voluntary running wheel activity to wild-type levels. We did not observe any adverse reaction to the treatment at 8weeks post-injection. Thus, we have investigated a highly promising gene therapy for McArdle disease with a clear path to the ovine large animal model endemic to Western Australia and subsequently to patients.

McArdle's disease in a Turkish woman due to an intronic variant of PYGM gene

Objective: Glycogen storage disease type 5, also known as McArdle disease, is a hereditary disorder with progressive myopathy. It is characterized by onset of exercise intolerance with premature fatigue and painful muscle cramps in childhood or adolescence. Temporary myoglobinuria may occur after exercise due to rhabdomyolysis. Patients may have mild muscle weakness since childhood. Muscular atrophy with fatty replacement may develop in adult life. McArdle disease is a relatively benign disease and rarely severe myoglobinuria can cause acute renal failure as a complication of widespread rhabdomyolysis. This autosomal recessive disease is caused a homozygous mutation of the PYGM gene encoding muscle enzyme myophosphorylase C. Case: A 36-year-old woman admitted to the Physical Medicine and Rehabilitation polyclinic of Giresun University Hospital with a complaint of gradually increasing progressive weakness and tiredness since 13 years age. CK serum level has been found to in normal range; even after exercise. The findings demonstrated myogenic abnormalities on electromyography, multiple glycogen-containing vacuoles and undetectable muscle myophosphorylase activity on muscle biopsy. The genetic analysis revealed no pathogenic mutations in exon regions of PYGM gene. But in sequencing analysis, the rs71049658, insertion/ deletion variation in intron 17 was determined. Coenzyme Q10 (CoQ-10) 30mg/day, vitamin B6 250mg/day and L-carnitine 1gr/day treatment protocol has been applied and after two months the treatment, clinical improvement has been achieved. Conclusion: In this case report, an atypical McArdle case with a diagnostic challenge has been presented. We thought that this polymorphism in the myophosphorylase gene may lead to a severe mosaic alteration in mRNA splicing, including exon skipping, activation of cryptic splice-sites, and exon-intron reorganizations.

SAT-114 Problems In Postoperative Hypothyroidism And Hypoparathyrosis Treatment Because Of Bariatric Surgery

Background: Bariatric surgery remains the most effective method of weight loss and can result in partial or complete resolution of multiple obesity-related comorbidities. Bariatric surgery should be performed in conjunction with a comprehensive preoperative assessment and a follow-up plan consisting of nutritional, behavioral, and medical programs. The bariatric surgical procedures are associated with significant long-term complications, primarily malnutrition. Clinical case: A 56-year-old woman was presented with complaints about tingling in her fingertips, painful muscle cramps, and difficulties with finger extension. It was found out from medical history that total thyroidectomy with parathyroidectomy because of papillary thyroid cancer was performed in 2007 and oral levothyroxine was prescribed. Bariatric surgery SADI-S (sleeve gastrectomy, duodeno-ileal anastomosis) was performed because of morbid obesity in September 2018. On physical examination Chvostek and Trousseau signs were noted. BMI was 39 kg/m2. Laboratory examination was carried out. Increased level of TSH and decreased value of calcium and 25-OH vitamin D were revealed. Laboratory results demonstrated postoperative hypothyroidism decompensation due to abnormal gastric acid secretion because of sleeve gastrectomy and postoperative hypoparathyrosis decompensation due to reduced calcium absorption because of duodeno-ileal anastomosis. So, the dosage of calcium, vitamin D and levothyroxine was increased. Also 10% calcium gluconate was prescribed. But compensation of postoperative hypothyroidism and hypoparathyrosis was not achieved. Thus, reconstructive operation was recommended due to ineffective medical treatment of hypothyroidism and hypoparathyrosis. Conclusion: This clinical case demonstrates that lack of comprehensive preoperative assessment indications to bariatric surgery leads to complication in compensation of comorbid states, such as postoperative hypothyroidism and hypoparathyrosis. Reference: (1) Nancy Puzziferri, MD, MS, Thomas B. Roshek III, MD, Helen G. Mayo, BS, MLS, Ryan Gallagher, BA, Steven H. Belle, PhD, MScHyg, and Edward H. Livingston, MD Long-term Follow-up After Bariatric Surgery: A Systematic Review. JAMA. 2014 September 3; 312(9): 934-942. (2) Improved levothyroxine pharmacokinetics after bariatric surgery. Thyroid 2013; 3; 23: 414-9.

Randomised clinical trial: oral taurine supplementation versus placebo reduces muscle cramps in patients with chronic liver disease.

Painful muscle cramps occur in the majority of patients with cirrhosis impacting significantly on quality of life and sleep patterns. They are frequently unrecognised or overlooked. Current management is based on anecdotal evidence or case study reports. To investigate the effect of oral taurine supplementation on frequency, duration, and intensity of muscle cramps in patients with chronic liver disease. Patients with chronic liver disease who experienced three or more muscle cramps/week were enrolled in a double-blinded, randomised control, crossover, taurine dose-variable study. Each participant received either taurine supplementation or placebo for 4weeks then crossed to the alternative arm. Primary outcome data for frequency, duration, and intensity of muscle cramps was recorded by participants. Participants recorded frequency, duration, and location of muscle cramps. Biochemical parameters, including serum taurine and methionine levels, were measured at each time point. Linear mixed models were used to analyse outcomes. Forty-nine patients were enrolled in the study and 30 patients completed the protocol. Participants who were unable to complete the protocol were not included in the final analysis due to the absence of outcome data. The mean age of participants was 54.7years and 70% were males. Oral taurine supplementation increased serum taurine levels (P<0.001). There were no adverse side effects associated with taurine supplementation. Participants receiving 2g taurine/d experienced a reduction in cramp frequency (seven cramps fewer/fortnight, P=0.03), duration (89minutes less/fortnight P=0.03), and severity (1.4 units less on a Likert scale P<0.004) compared to placebo. Oral supplementation with 2g taurine/d results in a clinically significant reduction in the frequency, duration, and intensity of muscle cramps in patients with chronic liver disease. Taurine should be considered as a safe and effective intervention in the management of muscle cramps in individuals with chronic liver disease. This study was registered with the Australian New Zealand Clinical Trials Register: ACTRN12612000289819.

USE OF THREE-COMPONENT LEVODOPA (LEVODOPA/CARBIDOPA/ENTACAPONE) TO CORRECT NOCTURNAL SYMPTOMS OF PARKINSON,S DISEASE

Objective: to describe a clinical case of late-stage Parkinson’s disease (PD) with nocturnal symptoms and fluctuations and to present successful experience in using the three-component drug Stalevo (levodopa/carbidopa/entacapone) as a single dose prior to sleep. Patient V. aged 72 years took medical advice at the Department of Neurology, Russian Medical Academy of Postgraduate Education, for complaints of constrained movements, inability to turn in bed independently, painful muscle cramps, light sleep with nocturnal awakenings, and frequent (5–6 times) urinations at night. The first symptoms of the disease appeared 12 years ago when the patient began to notice sluggishness, altered handwriting, and clumsiness during small movements of the right hand. By taking into account symptoms (obvious nocturnal akinesia, overactive bladder, sleep disorders, and cramps) and the results of his examination, the patient was diagnosed with the akinetic-rigid form of PD (4 Hoehn-Yarh scores). Therapy was corrected as follows: the dose of amantadine remained the same (300 mg); its last administration is recommended to be at 16:00; the daily dose of levodopa was 700 mg; that of levodopa/benserazide was 550 mg/day (1 tablet × 3/4 tablet × 1 tablet). The evening intake of levodopa was changed for that of the three-component drug Stalevo (levodopa 150 mg/ carbidopa 37.5 mg/entacapone 200 mg). Results. After 3 months, the patient was observed to have significant health improvement: reduced nocturnal and morning akinesia, better gait, a considerably smaller number of nocturnal urinations (less than once per night), regression of painful calf muscle cramps, and improved sleep. Conclusion. The three-component drug Stalevo (levodopa/carbidopa/entacapone) is effective in treating late-stage PD. Its use as a single dose before going to bed has led to regressive nocturnal symptoms, better sleep, and lower motor fluctuations.

Painful cramps and giant myotonic discharges in a family with the Nav1.4‐G1306A mutation

Two previously reported Norwegian patients with painful muscle cramps and giant myotonic discharges were genotyped and compared with those of members of 21 families harboring the same mutation. Using primers specific for SCN4A and CLCN1, the DNA of the Norwegian family members was amplified and bidirectionally sequenced. Clinical and neurophysiological features of other families harboring the same mutation were studied. A G1306A mutation in the Nav1.4 voltage-gated sodium channel of skeletal muscle was identified. This mutation is known to cause myotonia fluctuans. No giant myotonic discharges or painful muscle cramps were found in the other G1306A families. Ephaptic transmission between neighboring muscle fibers may not only cause the unusual size of the myotonic discharges in this family, but also a more severe type of potassium-aggravated myotonia than myotonia fluctuans.

Effects of shakuyakukanzoto and its absorbed components on twitch contractions induced by physiological Ca2+ release in rat skeletal muscle.

Shakuyakukanzoto (SKT) is a kampo medicine composed of equal proportions of Glycyrrhizae radix (G. radix) and Paeoniae radix (P. radix). A double-blind study reported that SKT significantly ameliorated painful muscle cramp in cirrhosis patients without the typical severe side effects of muscle weakness and central nervous system (CNS) depression. Previous basic studies reported that SKT and its active components induced relaxation by a direct action on skeletal muscle and that SKT did not depress CNS functions; however, why SKT has a lower incidence of muscle weakness remains unknown. In the present study, we investigated which components are absorbed into the blood of rats after a single oral administration of SKT to identify the active components of SKT. We also investigated the effects of SKT and its components on the twitch contraction induced by physiological Ca2+ release. Our study demonstrated that SKT and five G. radix isolates, which are responsible for the antispasmodic effect of SKT, did not inhibit the twitch contraction in contrast to dantrolene sodium, a direct-acting peripheral muscle relaxant, indicating that the mechanisms of muscle contraction of SKT and dantrolene in skeletal muscle differ. These findings suggest that SKT does not reduce the contractile force in skeletal muscle under physiological conditions, i.e., SKT may have a low risk of causing muscle weakness in clinical use. Considering that most muscle relaxants and anticonvulsants cause various harmful side effects such as weakness and CNS depression, SKT appears to have a benign safety profile.

Systematic review: the treatment of muscle cramps in patients with cirrhosis.

Up to 88% of patients with hepatic cirrhosis experience painful muscle cramps resulting in sleep deprivation and impaired quality of life. Management is often based on poor evidence with varying degrees of success in controlling the frequency and severity of muscle cramps in this group. To review systematically the treatment options for muscle cramps in cirrhosis. A systematic review of the relevant databases to identify treatments for muscle cramps in patients with hepatic cirrhosis was performed. Studies meeting the selection criteria were reviewed and quality of the papers was rated using a validated quality rating scale. The results for each treatment are reported. Eighteen publications were identified as eligible for inclusion in this systematic review. The majority (n = 15) of these were treatment/intervention reports. Only three randomised-control studies were identified. A wide range of treatments were identified including zinc, 1-α-hydroxy vitamin D, vitamin E, branched chain amino acids, taurine, l-carnitine, nuiche-shen-qi-wen, eperisone hydrochloride, intravenous albumin and quinidine. There were some reported improvements in muscle cramps with most interventions with the exception of vitamin E but the evidence predominantly relies on case study reports. There is a lack of randomised-controlled clinical studies to support using these interventions. There appear to be a number of promising treatments for muscle cramps in cirrhosis. However, there remains a need for further double-blinded, randomised, controlled clinical investigations to support routine use of these interventions to treat muscle cramps in patients with hepatic cirrhosis.

Hyperexcitability as a potential cause for diffuse lower motor neuron loss in Isaacs’ syndrome

AbstractWe present a patient who initially developed diffuse painful muscle cramps who had elevated antibodies against voltage‐gated potassium channel (VGKC) complex. Despite the initial improvement after immunomodulatory therapy, she later developed progressive atrophy and weakness of the limb muscles whose electrophysiological finding mimicked that in lower motor neuron disease. A potential causal relationship between anti‐VGKC complex antibody‐associated hyperexcitability and lower motor axon loss is discussed.

Hereditary Motor and Sensory Neuropathy With Proximal Predominance (HMSN-P)

Hereditary motor and sensory neuropathy with proximal predominance (HMSN-P) is a rare disorder inherited in an autosomal dominant fashion. Patients present with slowly progressive proximal-predominant weakness, painful muscle cramps, fasciculations, large-fiber sensory loss, and areflexia. Electrodiagnostic (EDX) studies typically reveal abnormalities consistent with a sensorimotor neuronopathy. A patient with HMSN-P underwent EDX studies, revealing ongoing and chronic neurogenic denervation, motor unit instability, and neuromyotonic discharges, further defining the spectrum of EDX findings in HMSN-P. The clinical, pathological, and genetic features are also reviewed. The appearance of HMSN-P in the United States and elsewhere calls for clinicians in nonendemic regions to be familiar with this rare disorder, which has typically been geographically confined.

沖縄型神経原性筋萎縮症（HMSN-P）の疾患概念の確立と歴史

We established a new disease autosomal dominant hereditary motor and sensory neuropathy with proximal dominant involvement (HMSNP) in 1997, in Okinawa, Japan. This disease is characterized by proximal dominant neurogenic atrophy with fasciculations, painful muscle cramp, obvious sensory nerve involvement, areflexia, high incidence of elevated creatine kinase levels, hyperlipidemia and hyperglycemia. (MIM %604484). HMSNP is so called or HMSNO (HMSN OKINAWA type),. These clinical features resembled those of Kennedy-Alter-Sung syndrome. Most HMSNP patients have severe muscle atrophy and finally the tracheostomy and artificial ventilation are required. Therefore, we initially thought to classify HMSNP into a subtype of motor neuron disease (MND) like familial amyotrophic lateral sclerosis (FALS) or spinal muscular atrophy (SMA). However, the general consensus for MND was no sensory involvement. Therefore, as the disease showed severe sensory involvement, we categorized HMSNP in subtype of HMSN at that time. We also reported the pathology of HMSNP, showing severely decreased anterior horn cells, decreased posterior horn cells, and loss of posterior funiculus in the spinal cord.

Simvastatin-induced nocturnal leg pain disappears with pravastatin substitution

Statins have similar side effects that do not always occur at the same rate among the various statins. We present a case of simvastatin-induced muscle toxicity that disappeared when pravastatin was substituted for the original drug. A 74-year-old male, a nonsmoker, complained of severe nocturnal leg cramps. The patient also complained that similar painful cramping occurred when he walked rapidly or jogged. Because some components of his lipid panel exceeded the'desirable' range, and as he had a history of myocardial infarction, his family physician prescribed simvastatin (40 mg/day). The patient had taken this medication for the past eight years. The painful nocturnal episodes started two years ago and affected either one or the other leg. Four months ago we discontinued his simvastatin and prescribed pravastatin (80 mg/day). At a follow-up visit six weeks later, the patient reported that his leg pains at night and the pain experienced after brisk walking had disappeared. Four months after the substitution of pravastatin for simvastatin, the patient reported that his complete lack of symptoms had continued. These painful muscle cramps were probably caused by an inadequate vascular supply to the calf and foot muscles. Perhaps a combination of advanced age and atherosclerotic changes created a predisposition for the simvastatin-induced leg cramps. Pravastatin differs from simvastatin in several ways.l It is not metabolized by cytochrome P450 (CYP) 3A4 oxidases, and thus is not influenced by CYP 3A4 inhibitors like simvastatin. Also, simvastatin is associated with single-nucleotide polymorphisms located within the SLCO1B1 gene on the chromosome 12 and established myopathy, while pravastatin lacks this association. These differences may contribute to increased tolerance to pravastatin in this particular case.

熱中症に付随した有痛性筋痙攣に対する芍薬甘草湯の治療経験

<b>熱中症に付随した有痛性筋痙攣に対する</b><b>芍薬甘草湯の治療経験 </b>