Elevated Serum Creatine Kinase Research Articles

Use of an Electronic Medical Record to Characterize Cases of Intermediate Statin‐Induced Muscle Toxicity

Statin use can be accompanied by a variety of musculoskeletal complaints. The authors describe the clinical characteristics of case patients who experienced adverse statin-induced musculoskeletal symptoms within a large population-based cohort in Central Wisconsin. Case status was determined based on elevated serum creatine kinase (CK) levels and the presence of at least 1 physician note reflecting an increased index of suspicion for statin intolerance. From the medical records of nearly 2 million unique patients, the authors identified more than 20,000 potential study patients ( approximately 1%) having CK data and at least 1 exposure to a statin drug. Manual screening was completed on 2227 patients with CK levels in the upper 10th percentile. Of those screened, 267 met inclusion criteria (12.0% eligibility) and 218 agreed to participate in a retrospective study characterizing the risk determinants of statin-induced muscle toxicity. Three categoric pain variables were graded retrospectively (distribution, location, and severity of pain). The presenting complaints of the case patients were extremely heterogeneous. The number of patients with a compelling pain syndrome (diffuse, proximal muscle pain of high intensity) increased at higher serum CK levels; the number of patients with indeterminate pain variables decreased at higher serum CK levels. The lines reflecting these relationships cross at a CK level of approximately 1175 U/L, approximately half the threshold level needed to make a clinical diagnosis of "myopathy" (ie, CK >10-fold the upper limit of normal).

Visual Hallucinations in a Patient with Adult Onset Acid Maltase Deficiency Disorder

A 66-year-old male presented with visual hallucinations. He had chronically elevated serum creatine kinase (CK) levels without muscle weakness. His hospital course was complicated by hypercapnic respiratory failure requiring mechanical ventilation. His hallucinations completely subsided on mechanical ventilation. Elevated CK levels prompted a muscle biopsy, which showed myopathy consistent with acid maltase deficiency disorder (AMDD). This is the first reported case of adult onset AMDD presenting with psychiatric symptoms. Our objective in reporting this case is to encourage early recognition of neuromuscular respiratory failure in AMDD and to reinforce that respiratory failure may develop without associated extremity muscle weakness.

A rare case of neuroleptic malignant syndrome presenting with serious hyperthermia treated with a non-invasive cooling device: a case report.

IntroductionA rare side effect of antipsychotic medication is neuroleptic malignant syndrome, mainly characterized by hyperthermia, altered mental state, haemodynamic dysregulation, elevated serum creatine kinase and rigor. There may be multi-organ dysfunction including renal and hepatic failure as well as serious rhabdomyolysis, acute respiratory distress syndrome and disseminated intravascular coagulation. The prevalence of neuroleptic malignant syndrome is between 0.02% and 2.44% for patients taking neuroleptics and it is not necessary to fulfil all cardinal features characterizing the syndrome to be diagnosed with neuroleptic malignant syndrome. Because of other different life-threatening diseases matching the various clinical findings, the correct diagnosis can sometimes be hard to make. A special problem of intensive care treatment is the management of severe hyperthermia. Lowering of body temperature, however, may be a major clinical problem because hyperthermia in neuroleptic malignant syndrome is typically unresponsive to antipyretic agents while manual cooling proves difficult due to peripheral vasoconstriction.Case presentationA 22-year-old Caucasian man was admitted unconscious with a body temperature of 42°C, elevated serum creatine phosphokinase, tachycardia and hypotonic blood pressure. In addition to intensive care standard therapy for coma and shock, a non-invasive cooling device (Arctic Sun 2000®, Medivance Inc., USA), originally designed to induce mild therapeutic hypothermia in patients after cardiopulmonary resuscitation, was used to lower body temperature. After successful treatment it became possible to obtain information from the patient about his recent ambulant treatment with Olanzapin (Zyprexa®) for schizophrenia.ConclusionNumerous case reports have been published about patients who developed neuroleptic malignant syndrome due to Olanzapin (Zyprexa®) medication. Frequently hyperthermia has been observed in these cases with varying outcomes. In our case the only residual impairment for the patient is dysarthria with corresponding symmetric cerebellar pyramidal cell destruction demonstrated by increased signal intensity in T2-weighted magnetic resonance imaging, most likely caused by the excessive hyperthermia.

Becker muscular dystrophy caused by an intronic mutation reducing the efficiency of the splice donor site of intron 26 of the dystrophin gene

We describe an 11-year-old boy with dystrophinopathy who presented with a history of progressive proximal muscle weakness and elevated serum creatine kinase levels at age 6. Sequence analysis of the dystrophin ( DMD) gene did not identify a mutation in the coding regions but revealed a nucleotide substitution in intron 26 (c.3603+3A>T). Since computer algorithms did not conclusively indicate that this sequence variant inactivated the splice site, we analyzed the DMD mRNA from a muscle biopsy of the patient to determine its functional significance. PCR and sequence analysis of the cDNA demonstrated that the mutation reduced the efficiency of the donor splice site and caused activation of a cryptic donor site 113 bp downstream. Activation of the cryptic donor site led to inclusion of 116 bp of intronic sequence containing a stop codon producing a truncated dystrophin protein. Residual wild-type splicing was also detected, which would explain the milder Becker rather than Duchenne phenotype in this patient. We highlight the importance of mRNA analysis for determination of pathogenicity in patients with ambiguous sequence variants in the DMD gene.

Cardiac magnetic resonance imaging and management of dilated cardiomyopathy in a Duchenne muscular dystrophy manifesting carrier

JO N 3055 muscles. Most DMD boys initially present delayed motor milestones, elevated serum creatine kinase (CK), respiratory impairment and 25 % of those surviving the age of 15 present dilated cardiomyopathy and arrhythmias [3, 4, 8, 10]. Echocardiography describes left ventricular dysfunction, but cardiac magnetic resonance (CMR) can detect the earliest signs of cardiomyopathy: occult regional cardiac asynergy; tissue degeneration; fibrosis [1, 9, 12]. Standard therapy for heart failure is effective in DMD cardiomyopathy [7, 10]. Female carriers show a mosaic pattern of dystrophin-positive and dystrophin-negative muscular fibres. About 50 % of patients present skeletal muscular symptoms and 18 % present dilated cardiomyopathy, because of a “skewed Xinactivation”, with most cells having an active faulty X-chromosome [5, 6]. A 27-year old woman was referred to our hospital in 2005 because of fatigue, effort dyspnoea (NYHA class IIb), episodes of palpitations and near syncope. Two brothers with a typical history of DMD without heart involvement died in their teens due to respiratory failure. Her asymptomatic 6year old daughter had a mild increase of CK (640 U/L). DNA analysis revealed dystrophin gene deletion of exons 3–17. Electromyography showed small duration motor unit potentials and reduced amplitude interference pattern during voluntary contraction. In 2003, she had already been diagnosed with a dilated cardiomyopathy, with an echocardiographic ejection fraction (EF) of 40 %, treated discontinuously with carvedilol 6.25 mg b.i.d. She was a smoker (5 cigarettes/d) and showed only calf pseudohypertrophy. She had high plasmatic concentrations of CK (1745 U/L, n.v. 22– 269), normal levels of cardiac troA. Barison G. D. Aquaro C. Passino M. Falorni A. Balbarini M. Lombardi L. Pasquali M. Emdin G. Siciliano

Single Nucleotide Polymorphisms Associated with Increased Risk for Statin Myopathy

Approximately 2% to 7% of statin users develop myalgias. Elevated serum creatine kinase (CK) levels occur in 0.1% to 1.0% of users, whereas the

Side-Alternating Vibration Training Improves Muscle Performance in a Patient with Late-Onset Pompe Disease

Side-alternating vibration training (SAVT) was used for 15 weeks in a patient with Late-onset Pompe disease who had never used enzyme replacement or chaperone therapy. Prior to the use of SAVT, the patient had experienced declining muscle performance and her 6-minute walk distance decreased from 210 to 155 metres in 6 months. After SAVT, her 6-minute walk distance increased 70% from 166 to 282 metres, muscle jumping power increased by 64% from 83 to 166 watts, isometric knee extensor strength increased 17% from 38 to 44 Nm, and she achieved a more normal pattern of ankle, knee, and joint kinematics and kinetics. Her functional ability measured through the Rotterdam 9-item score was unchanged at 19/36. There were no elevations in serum creatine kinase or lactate. This is the first report, to our knowledge, of a performance improvement in a patient with Pompe disease using SAVT.

軸索型ギランバレー症候群に対する急性期理学療法の経験

We describe four male patients suffering from quadriplegia caused by axonal Guillain-Barré syndrome. They were diagnosed with axonal Guillain-Barré syndrome based on their clinical course and electrophysiological findings. Three patients had severe pain, two had marked elevation of serum creatine kinase, one had finger contracture, and two required mechanical ventilation. Two of the patients recovered during the period from nadir to discharge in the Hughes functional grading scale and Barthel index. A physical therapist should understand the characteristics of severe axonal Guillain-Barré syndrome in an acute stage, and consider the psychological status of the patients.

Exercise induced rhabdomyolysis

Rhabdomyolysis is a potentially life-threatening disease, characterized by the release of intracellular calcium from skeletal muscles and can result in acute renal failure. A nineteen year old boy was admitted to the Clinic for Infective Diseases of Clinical Center Novi Sad. The disease was developing gradually and the symptoms were dizziness, muscle pain and dark color of urine. Due to the pathological level of aminotransferase he was hospitalized on the fourth day of the disease beginning with a suspicious diagnosis of acute viral hepatitis. In the hospital course of the disease, a further elevation of serum aminotransferases, creatine kinase and lactate dehydrogenase were registered. Additional serological analyses were done to exclude other possible causes of acute liver lesion. In the neurological status prolonged decontraction of quadriceps muscle was detected and the electromyography was suspicious on neuromyositis. Excessive muscular activity with the strenuous exercise is the leading, but very frequently overlooked, cause of rhabdomyolysis in healthy people. Excessive physical exercise may lead to elevation of the serum activity of aminotransferases and to suspicion of hepatitis.

Statin-Induced Ca<sup>2+</sup> Release was Increased in B Lymphocytes in Patients who Showed Elevated Serum Creatine Kinase During Statin Treatment

Statins are effective in lowering cholesterol levels, but cause fatal rhabdomyolysis in susceptible individuals. Because it has been hypothesized that muscle damage could result from alterations in Ca(2+) homeostasis in muscle cells, we tested whether measuring statin-induced changes in intracellular calcium ([Ca(2+)](i)) is useful for predicting susceptibility to statin-muscle damage, using human CD19+ primary B lymphocytes. Statin-induced alterations in [Ca(2+)](i) were studied using the human THP-1 cell line and CD19+ primary B lymphocytes. Changes in [Ca(2+)](i) were measured directly in fluo-3- loaded cells using either single or dual-color flow cytometry. The Ca(2+) release study suggested that statin-induced changes in [Ca(2+)](i) were due to Ca(2+) release from ryanodine-sensitive Ca(2+) stores and mitochondrial compartments. Further, statin users who experienced elevated creatine kinase (n=8) exhibited significantly greater statin-induced Ca(2+) release in B cells than healthy volunteers (n=45) and statin users without elevated creatine kinase (n=16), while no difference was seen between the latter two groups. Statin-induced Ca(2+) release from ryanodine-sensitive stores and mitochondria may contribute to myotoxicity. The laboratory test for Ca(2+) release using CD19+ primary B lymphocytes may be useful to predict susceptibility to statin-induced muscle toxicity prior to statin use.

Comparison of two different rest intervals on drop jump: effects on muscle damage markers

Comparison of two different rest intervals on drop jump: effects on muscle damage markers Study aim: To determine the effects of 60- or 180-s rest intervals between sets of drop jump (DJ) exercise on serum creatine kinase (CK) activity and perceived muscle soreness. Materials and methods: A group of 36 healthy male subjects aged 18 - 19 years performed 4 sets of 10 DJ, the rest intervals between sets amounting to 60 (Group A) or 180 s (Group B). Before, as well as 3, 24, 48, and 72 h post-exercise, blood was sampled for determining the activity of in serum CK activity and the perceived muscle soreness was reported. Two-way ANOVA (time x rest interval) was used in data analysis. Results: The DJ sessions induced muscle soreness and elevated serum CK activity (p<0.05). No significant between-group differences were found. Conclusion: Rest intervals of 1 - 2 min duration had no effect on the magnitude of changes in CK activity or perceived muscle soreness. This may be of practical importance when designing training which includes drop jumps.

Immune‐mediated myositis in Crohn's disease

We report a patient with uncontrolled Crohn's disease who presented with progressive weakness of proximal muscles and a marked elevation of serum creatine kinase. Muscle biopsy from the left deltoid exhibited myositic changes with inflammatory infiltrates in the perimysium, endomysium, and perivascular locations. Most were stained as CD68-positive macrophages, whereas some were CD4- and CD8-positive T lymphocytes. Due to uncontrolled bowel inflammation, several fistulae were found in the descending colon, and partial colectomy was performed. An examination of the resected colon exhibited inflammation of the bowel structure surrounded mainly by CD68-positive macrophages. The histopathological findings of the descending colon were analogous to those of the muscle. After an increased dose of mesalazine and partial colectomy, her muscle symptoms improved. These findings suggest that the myositis in Crohn's disease is immune-mediated and that treatment of bowel inflammation should be emphasized as opposed to steroid or other immunosuppressive therapy.

Dominant-negative inhibition of Ca2+ influx via TRPV2 ameliorates muscular dystrophy in animal models

Muscular dystrophy is a severe degenerative disorder of skeletal muscle characterized by progressive muscle weakness. One subgroup of this disease is caused by a defect in the gene encoding one of the components of the dystrophin-glycoprotein complex, resulting in a significant disruption of membrane integrity and/or stability and, consequently, a sustained increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)). In the present study, we demonstrate that muscular dystrophy is ameliorated in two animal models, dystrophin-deficient mdx mice and delta-sarcoglycan-deficient BIO14.6 hamsters by dominant-negative inhibition of the transient receptor potential cation channel, TRPV2, a principal candidate for Ca(2+)-entry pathways. When transgenic (Tg) mice expressing a TRPV2 mutant in muscle were crossed with mdx mice, the [Ca(2+)](i) increase in muscle fibers was reduced by dominant-negative inhibition of endogenous TRPV2. Furthermore, histological, biochemical and physiological indices characterizing dystrophic pathology, such as an increased number of central nuclei and fiber size variability/fibrosis/apoptosis, elevated serum creatine kinase levels, and reduced muscle performance, were all ameliorated in the mdx/Tg mice. Similar beneficial effects were also observed in the muscles of BIO14.6 hamsters infected with adenovirus carrying mutant TRPV2. We propose that TRPV2 is a principal Ca(2+)-entry route leading to a sustained [Ca(2+)](i) increase and muscle degeneration, and that it is a promising therapeutic target for the treatment of muscular dystrophy.

Biphasic creatine kinase elevation in pseudoephedrine overdosage

Biphasic creatine kinase elevation in pseudoephedrine overdosage

G.P.14.06 LGMD2H patients of non Hutterite origin with mutations in TRIM32 gene

Limb-girdle muscular dystrophies (LGMD) include a broad group of genetically determined progressive muscle disorders. By definition, patients should present primary or predominant symmetrical atrophy of the pelvic and/or shoulder girdle musculature, elevated serum creatine kinase and a necrotic regeneration pattern. The term now includes many different phenotypes ranging from severe forms, with onset in the first decade and rapid progression, to milder forms with later onset and atypical presentation.

What to do … When the treatment does not work: polymyositis

Although patients with polymyositis or dermatomyositis may respond to treatment with corticosteroids alone, in many cases a combination of steroids and an immunosuppressive agent is required to achieve satisfactory disease...

Case Report of Olanzapine-Associated Elevation of Serum Creatine Kinase in a 16-Year-Old Boy With Heat Stroke

Case Report of Olanzapine-Associated Elevation of Serum Creatine Kinase in a 16-Year-Old Boy With Heat Stroke

Truncation of Caveolin-3 causes autosomal-recessive Rippling Muscle Disease

Mutations in the Caveolin-3 gene ( CAV3 ) have been associated with heterogeneous overlapping phenotypes, including: Limb Girdle Muscular Dystrophy type 1C (LGMD-1C), Isolated Elevated Serum Creatine Kinase (HyperCKemia), Distal...

Metabolic Myopathies Discovered During Investigations of Statin Myopathy

The statins have emerged as the dominant class of drug for the treatment of hypercholesterolemia. These medications are generally well tolerated. However, myalgias, the most frequent side-effect, occur in up to 7% of patients. Transaminitis and skeletal myotoxicity, with elevated serum creatine kinase (CK) levels (i.e., >10 times the upper limit of normal), occur with reported frequencies of 1% and 0.1%, respectively. Various hypotheses have been proposed to explain the relationship between statin therapy and the spectrum of muscle dysfunction manifested by myalgia, myopathy, and rhabdomyolysis.Statin-mediatd inhibition of mevalonate metabolism impairs the synthesis of isoprenylated products–the most notable of which is ubiquinone. However, isoprenylation is responsible for the post-translational modification of up to 2% of cellular proteins. Therefore, numerous metabolic pathways are potentially modified by statin-mediated hypoprenylation. Subclinical defects in one or more energy-deriving pathways may be unmasked upon exposure to the pleotropic effects of statins. Such pharmacogenomic synergism may underlie the development of “statin myopathy” in a subset of patients. In this regard, we describe four patients with mutations in the myophosphorylase (PYGM; MIM 232600), myoadenylate deaminase (AMPD1; MIM 102770), and carnitine palmitoyltransferase (CPT2; MIM 600650) genes whose diagnoses became apparent during the course of investigations for statin-induced myalgias and hyperCKemia.

ADULTS WITH EOSINOPHILIC MYOSITIS AND CALPAIN-3 MUTATIONS

A recent report found that six patients who presented with eosinophilic myositis in childhood actually had a calpainopathy (LGMD 2A).1 I have encountered two patients previously diagnosed with adult-onset eosinophilic polymyositis who had mutations in the calpain-3 gene ( CAPN3 ). ### Case reports. #### Case 1. A 22-year-old woman presented with a 1-year history of progressive arm and leg weakness and elevated serum creatine kinase (CK) levels as high as 5,528 U/L. There was no family history of myopathy. She was initially evaluated elsewhere and a quadriceps muscle biopsy was interpreted as an inflammatory myopathy with prominent eosinophilic infiltrates. There was no peripheral eosinophilia. She was treated with prednisone, azathioprine, methotrexate, IV immunoglobulin, and rituximab without improvement. She was referred to me for management of her myositis. Manual muscle testing revealed the following Medical Research Council (MRC) grades: neck flexion 4−/5, neck extension 4/5, deltoids, biceps, and triceps 4/5, wrist extension 4+/5, wrist flexors and fingers 5/5, hip flexion/extension/abduction 2/5, knee flexion 3/5, knee extension 4+/5, ankle dorsiflexion and plantar flexion 4+/5. There was no facial weakness, muscle atrophy, or hypertrophy. Serum CK was 845 U/L. Review of her outside muscle biopsy slides demonstrated many necrotic and …