Raised Serum Creatine Kinase Research Articles

The Refinement of Home Exercise Program for Children and Adolescents With Muscular Dystrophy in the Present COVID-19 Pandemic Scenario: A Scoping Review.

Muscular dystrophies (MDs) are a category of hereditary illnesses characterized by the gradual malfunction and/or weakening of the skeletal muscles. This disease of the muscles also results in hypotonia and joint contracture, along with raised serum creatine kinase (CK) levels. To prevent complications, continuous physiotherapy is advised for children with muscular dystrophy, which is even asked to perform at home as a home exercise program (HEP). As a result, the home exercise program (HEP) is critical in maintaining the optimal health of children with Duchenne muscular dystrophy (DMD). The present coronavirus (COVID-19) pandemic has adversely affected these children as there was very little scope to get direct help from a physiotherapist. Meanwhile, the home program was continued by many to compensate for the direct benefit. However, because of the lack of specific guidelines and structured methodology to follow for a home program, there was a deterioration in the health status of many children. There is a need to understand how the children are getting affected and the way the home program can be refined to help needy children with muscular dystrophy. Our scoping review aims to identify the present home program patterns being followed for children with DMD and their scope for refinement. The data were collected from electronic databases including PubMed, ProQuest, Cochrane, and Web of Science. We searched four electronic databases until September 2021. We included the published case studies, observational and experimental studies that described the positive impact of home exercise programs, and the methodology they followed as an alternative to institution-based physiotherapy. One hundred thirty-eight titles were screened, and 58 met the inclusion criteria. Along with regular physiotherapy, the incorporation of HEP helped in early complication prevention in patients with muscular dystrophy. The HEP was found to be a successful adjunct in the COVID-19 scenario. This review presents different therapeutic measures that can be taken for the prevention of complications in patients with MD and how the HEP plays an important role in removing the gaps on how HEP is beneficial in the COVID-19 scenario and a scope to refine the present methodologies for more accurate management.

Carrier screening model for Duchenne muscular dystrophy for women of reproductive age based on a pre-pregnancy birth defect control platform

To establish a screening model for females of reproductive age carrying Duchenne muscular dystrophy (DMD) variants based on a current community health examination platform. A total of 61 870 participants were recruited between October 2017 and October 2019. Serum creatine kinase (CK) was measured with a Roche Cobasc 701/702 using an enzymatic rate method. Genetic testing was offered to those with a CK level of ≥ 200 U/L. For carriers of DMD variants, genetic counseling and follow up were provided. For the 61 870 females participating in the program, 1078 were found with raised serum CK (≥ 200 U/L), of which 618 (57.33%) accepted CK re-measurement after at least a two-week interval. One hundred and twenty cases were found with sustained serum CK elevation, of which 6 were confirmed to be definite DMD carriers regardless of family history. Genetic testing was provided to 33 females with a family history for DMD, and 13 were determined as definite carriers. An affected fetus was detected by prenatal diagnosis. After genetic counseling, the parents had opted induced abortion. Large-scale DMD carrier screening through a three-step approach based on the current community health examination platform is both feasible and cost effective.

Muscle biopsy: what and why and when?

Skeletal muscle biopsy remains an important investigative tool in the diagnosis of a variety of muscle disorders. Traditionally, someone with a limb-girdle muscle weakness, myopathic changes on electrophysiology and raised...

Intra-operative rhabdomyolysis during upper limb surgery

Intra-operative rhabdomyolysis during upper limb surgery

Linear Analysis of Autonomic Activity and Its Correlation with Creatine Kinase-MB in Overt Thyroid Dysfunctions

Autonomic activity may be deranged in thyroid dysfunctions and may lead to cardiovascular morbidity and mortality. Myopathy is a common manifestation in thyroid disorders and may be associated with raised serum creatine kinase (CK). We hypothesized that cardiovascular abnormality in thyroid dysfunction may manifest as raised CK-MB. This study was designed to investigate the correlation of CK and its isoform CK-MB with thyroid profile and linear parameters of heart rate variability (HRV). The study was conducted on 35 hypothyroid and hyperthyroid patients each, and 25 age-matched healthy controls. Autonomic activity was assessed by simple short term 5-min HRV. Biochemical evaluation of serum thyroid profile, CK-NAC and CK-MB were estimated in all the subjects. Our results demonstrated low HRV in hypo- as well as hyperthyroid patients. We observed significantly higher serum CK levels in hypothyroid patients when compared to hyperthyroids and controls. However, no significant differences were observed in CK-MB levels in the three groups. Significant positive correlation of CK with TSH and negative correlation with some HRV parameters (LF power, HF power, total power, SDNN, RMSSD) was observed in hypothyroid patients. Whereas correlation of CK-MB with thyroid profile as well as HRV parameters was non-significant in all the groups. Based on the CK and CK-MB findings and their correlation, we conclude that the cardiovascular changes seen in thyroid dysfunctions may primarily be due to autonomic imbalance without apparent cardiac muscle involvement. Whereas, raised CK levels indicate predominantly skeletal muscle involvement in hypothyroid patients.

Axonal Neuropathies due to Mutations in Small Heat Shock Proteins: Clinical, Genetic, and Functional Insights into Novel Mutations.

In this study, we describe the phenotypic spectrum of distal hereditary motor neuropathy caused by mutations in the small heat shock proteins HSPB1 and HSPB8 and investigate the functional consequences of newly discovered variants. Among 510 unrelated patients with distal motor neuropathy, we identified mutations in HSPB1 (28 index patients/510; 5.5%) and HSPB8 (four index patients/510; 0.8%) genes. Patients have slowly progressive distal (100%) and proximal (13%) weakness in lower limbs (100%), mild lower limbs sensory involvement (31%), foot deformities (73%), progressive distal upper limb weakness (29%), mildly raised serum creatine kinase levels (100%), and central nervous system involvement (9%). We identified 12 HSPB1 and four HSPB8 mutations, including five and three not previously reported. Transmission was either dominant (78%), recessive (3%), or de novo (19%). Three missense mutations in HSPB1 (Pro7Ser, Gly53Asp, and Gln128Arg) cause hyperphosphorylation of neurofilaments, whereas the C-terminal mutant Ser187Leu triggers protein aggregation. Two frameshift mutations (Leu58fs and Ala61fs) create a premature stop codon leading to proteasomal degradation. Two mutations in HSPB8 (Lys141Met/Asn) exhibited increased binding to Bag3. We demonstrate that HSPB1 and HSPB8 mutations are a major cause of inherited motor axonal neuropathy. Mutations lead to diverse functional outcomes further demonstrating the pleotropic character of small heat shock proteins.

A study of acute muscle dysfunction with particular reference to dengue myopathy.

Background:Acute myopathy is a common cause of acute motor quadriparesis which has various etiologies with different courses of illness and prognosis depending on the cause. Understanding this diversity helps us in proper approach toward diagnosis, predicting the prognosis, and possible complications and in improving the treatments that are being provided. This study was planned to study the clinical, electrophysiological, and etiological profile of patients presenting with acute myopathy. We also studied how dengue-related acute myopathy differs from other causes and also difference between myopathy due to myositis and hypokalemia in cases of dengue.Materials and Methods:This was a prospective, observational study involving all clinically suspected cases of acute myopathy of not more than 4 weeks duration with raised serum creatine kinase (CK) level. They were subjected to detailed clinical evaluation along with hematological, biochemical, microbiological, and electrophysiological studies and followed-up for outcome at 1 and 3 months. Muscle biopsy and histopathological examination were done in selected patients after taking informed consent. Statistical analysis was performed by appropriate methods using SPSS version 16.0 (Chicago, IL, USA).Results:We evaluated thirty patients of acute myopathy with raised CK level. Seventeen patients had fever, 11 had myalgia, and 5 had skin lesions. All presented with symmetric weakness, 17 (56.7%) patients having predominantly proximal weakness, neck or truncal weakness in 6 (20%), hyporeflexia in 12 (40%), with mean Medical Research Council (MRC) sum score of 46.67 ± 6.0. Eight (mean modified Barthel index [MBI] at presentation - 15 ± 3.7) patients had poor functional status according to MBI and 15 according to modified Rankin scale (MRS) (mean MRS score - 2.5 ± 1.2). Etiology was dengue viral infection in 14 patients; hypokalemia due to various causes other than dengue in 8; pyomyositis in 3; dermatomyositis, polymyositis, thyrotoxicosis, systemic lupus erythematosus, and unknown etiology in one each. Only eight patients had abnormal electrophysiology and seven among nine biopsies done were abnormal. At 1 month, 24 (80.0%) and 23 (76.7%) patients had achieved normal MBI and MRS scores with 28 (93.3) and 27 (90%) patients, respectively, at 3 months. Dengue with hypokalemia had less myalgia, more of hyporeflexia, and lower serum CK compared to those without hypokalemia.Conclusion:Dengue infection and hypokalemia due to various causes are the most common causes of acute myopathy and are associated with rapid and complete recovery within 1 month. Shorter duration of illness, higher MRC sum score, better disability status at presentation, lower serum CK correlate with better outcome. Biopsy was decisive in <20% cases; hence, it is not primary investigation in acute myopathy.

Statin therapy for acute respiratory distress syndrome: an individual patient data meta-analysis of randomised clinical trials

We performed an individual patient data meta-analysis to assess the possible benefits and harms of statin therapy in adults with acute respiratory distress syndrome (ARDS) and to investigate effects in specific ARDS subgroups. We identified randomised clinical trials up to 31 October 2016 that had investigated statin therapy versus placebo in patients with ARDS. Individual patient data from each trial were compiled. Conventional two-stage meta-analyses were performed for primary and secondary outcomes, and one-stage regression models with single treatment-covariate interactions for subgroup analyses. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Six trials with a total of 1755 patients were included. For the primary outcomes, there was no significant effect of statin therapy on 28-day mortality [relative risk (RR) 1.03, 95% CI 0.86-1.23], ventilator-free days (mean difference 0.34days, 95% CI -0.68 to 1.36) or serious adverse events (RR 1.14, 95% CI 0.84-1.53). There was a significantly increased incidence of raised serum creatine kinase or transaminase levels with statin therapy (106/879; 12.1%) versus control (78/876; 8.9%) (RR 1.40, 95% CI 1.07-1.83, p=0.015). There were no significant treatment-covariate interactions in the predefined subgroups investigated. We found no clinical benefit from initiation of statin therapy in adult patients with ARDS, either overall or in predefined subgroups. While there was an increased incidence of raised serum creatine kinase and transaminase levels, there was no difference in serious adverse events among groups. Therefore, we do not recommend initiation of statin therapy for the treatment of ARDS.

Clinicopathological Features of Telbivudine-Associated Myopathy.

Telbivudine, a thymidine nucleoside analog, is a common therapeutic option for chronic hepatitis B infection. While raised serum creatine kinase is common, myopathy associated with telbivudine is rare. Reports on its myopathological features are few and immunohistochemical analyses of inflammatory cell infiltrates have not been previously described. We describe the clinical, myopathological and immunohistochemical features of four patients who developed myopathy after telbivudine therapy for chronic hepatitis B infection. All four patients presented with progressive proximal muscle weakness, elevation of serum creatine kinase and myopathic changes on electromyography. Muscle biopsies showed myofiber degeneration/necrosis, regeneration, and fibers with cytoplasmic bodies and cytochrome c oxidase deficiency. There was minimal inflammation associated with strong sarcolemmal overexpression of class I major histocompatibility complex (MHC class I). Upon withdrawal of telbivudine, muscle weakness improved in all patients and eventually completely resolved in three. In our series, telbivudine-associated myopathy is characterized by necrotizing myopathy which improved on drug withdrawal. Although the occasional loss of cytochrome c oxidase is consistent with mitochondrial toxicity, the overexpression of MHC class I in all patients could suggest an underlying immune-mediated mechanism which may warrant further investigation.

Periodontal status and serum creatine kinase levels among young soccer players: A preliminary report.

It is hypothesized that soccer players with periodontal disease exhibit raised serum creatine kinase (CK) levels as compared to those without periodontal disease. We assessed the clinical gingival status and serum CK levels among young soccer players. Demographic data were collected through a structured questionnaire. Full mouth bleeding on probing (BOP) and probing pocket depth (PPD) were assessed. Blood samples (4 mL) were collected for measurement of serum CK levels. All blood samples were collected from a vein in the antecubital region. Total CK activities in serum were determined with an optimized spectrophotometric method. Statistical analysis was performed using one-way analysis of variance, and P< 0.05 was considered statistically significant. Twenty-seven male soccer players volunteered to participate in the present study. The mean age of the participants in Groups 1 (n = 14) and 2 (n = 13) were 18.2 ± 2.3 years and 19.1 ± 0.6 years, respectively. Mean scores of BOP were significantly higher among individuals in Group 2 (56.8%) compared with individuals in Group 1 (19.4%) (P < 0.001). Mean scores of PPD ≥4 mm were significantly higher among subjects in Group 2 (12.1%) as compared to individuals in Group 1 (0.8%) (P < 0.001). Levels of CK were significantly higher among individuals in Group 2 (292.7 U/L) as compared to those in Group 1 (52.3 U/L) (P < 0.01). Increased BOP and PPD are associated with increased serum CK levels in young soccer players.

Immune-mediated necrotising myopathy linked to statin use

In December, 2013, a 59-year-old man presented to the Neurology Department with progressive pelvic girdle myalgia and proximal weakness so severe that he needed help walking. His myalgia had started in March, 2012, 4 months after starting atorvastatin, and had persisted despite discontinuation of the statin in September, 2013. On examination we noted severe proximal paraparesis. Laboratory tests revealed substantially raised serum creatine kinase concentration (3453 U/L, normal range <171 U/L) but no sign of systemic infl ammation. Electromyography showed widespread acute myopathic changes. T1-weighted pelvic MRI (fi gure) showed widespread muscle atrophy. Biopsy sample from the right glutaeus maximus showed prominent necrosis without signifi cant infl ammation, a cytoplasmic pattern with perinuclear reinforcement of indirect immunofl uorescence on human HEp-2 cells, and strong positivity of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) auto-antibody (256 AU/mL, normal range <14 AU/mL; fi gure). These fi ndings were consistent with statin-associated immune-mediated necrotising myopathy. After 6 months of treatment with high dose oral corticosteroids, subcutaneous methotrexate, and intravenous immunoglobulins, the patient’s symptoms resolved, creatinine kinase concentrations returned to normal, and HMGCRantibody level dropped substantially (to 70 AU/mL). Statins are HMGCR inhibitors that show a good safety profi le despite frequent occurrence of benign myalgia that usually resolves after discontinuation of therapy. Nevertheless, severe side-eff ects such as myopathy (0·4 cases per 10 000 person-years) can occur. As in our patient, immune-mediated myopathy linked to statin use arises from an autoimmune mechanism that involves production of anti-HMGCR auto-antibodies. Thereafter myopathy is progressive, even after discontinuation of the the statin. Randomised controlled trials provide little evidence on the benefi ts of immunosuppressive therapy in such cases, but, as in our patient, some studies suggest immediate introduction of high-dose corticosteroids associated with other immunosuppressive agents and plasma exchange might be helpful (appendix).

Levels of soluble adhesion molecules and their associations in inflammatory myositis

Vidya S. Limaye, Claudine S. Bonder, Wai Y. Sun, Susan Lester, Peter J. Roberts-Thomson And Peter Blumbergs

A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy

Neurodegeneration with brain iron accumulation is clinically and genetically heterogeneous because of mutations in at least 7 nuclear genes. We performed homozygosity mapping and whole-exome sequencing in 2 brothers with brain iron accumulation from a consanguineous family. We identified a homozygous missense mutation in both brothers in the very recently identified chromosome 19 open-reading frame 12 gene. The disease presented before age 10 with slowly progressive tremor, dystonia, and spasticity. Additional features were optic atrophy, peripheral neuropathy, and learning difficulties. A raised serum creatine kinase indicated neuromuscular involvement, and compensatory mitochondrial proliferation implicated mitochondrial dysfunction as a pathological mechanism. Further studies are needed to explore the function of the chromosome 19 open-reading frame 12 gene, and extended genetic analysis on larger patient cohorts will provide more information about the presentation and frequency of this disease.

Paroxysmal neuromyotonia: A new sporadic channelopathy

Neuromyotonia is a heterogeneous group of genetic and autoimmune channelopathies resulting in hyperexcitability of peripheral nerves. We report an unusual case of neuromyotonia, which to our knowledge has not been previously described. The patient developed intermittent attacks of severe painful muscle stiffness accompanied by sweating, myokymia and raised serum creatine kinase. Genetic analysis of KCNA1, KCNQ2 and SCN4A genes did not identify pathogenic mutation. Serum voltage-gated potassium channel antibody was also negative. He was successfully treated with acetazolamide and carbamazepine. This appears to be a new neuromuscular disease, “paroxysmal neuromyotonia”, the etiology of which is still unknown.

Single-fiber electromyography in hyperCKemia: the value of fiber density

Although persistently raised serum creatine kinase (sCK), or hyperCKemia, is considered the biological hallmark of neuromuscular diseases, pauci- or asymptomatic- or isolated-hyperCKemia can often be found. Single-fiber electromyography (SFEMG) is an electrophysiological technique of great value in the assessment of neuromuscular, neuropathic and myopathic disorders. We hypothesize that SFEMG fiber density (FD) evaluation is able to detect subclinical electrophysiological abnormalities indicating a myopathic process in subjects with hyperCKemia. Nineteen subjects with hyperCKemia without evident clinical signs of muscle involvement and 15 healthy controls were studied. Electrophysiological investigations including nerve conduction studies (NCS), quantitative EMG (QEMG), SFEMG with focus on FD measurements, and muscle biopsy were performed. NCS, QEMG, SFEMG were normal in all controls. In subjects with hyperCKemia, NCS were normal; QEMG was abnormal in 5, while both SFEMG and muscle biopsy disclosed abnormalities in 12 subjects. The mean FD value was 2.6 ± 0.5 in the control and 4 ± 1.4 (p = 0.003) in the hyperCKemia group. SFEMG revealed subclinical changes in the majority of subjects with hyperCKemia. To the best of our knowledge, this is the first study demonstrating that SFEMG FD evaluation is able to detect the presence of muscle diseases, which are in a subclinical phase and would remain unidentified otherwise. SFEMG may be used to distinguish hyperCKemia associated to asymptomatic muscle disorders from idiopathic hyperCKemia. We believe that SFEMG FD evaluation should be added to the routine examinations in the screening of idiopathic hyperCKemia.

Statin Myopathy: A Lipid Clinic Experience on the Tolerability of Statin Rechallenge

Statin myopathy is a generally encountered side effect of statin usage. Both muscle symptoms and a raised serum creatine kinase (CK) are used in case definition, but these are common manifestations of other conditions, which may not be statin related. Statin rechallenge assuming no contraindication in selected cases is an option before considering a different class of lipid-lowering agent. We aim to characterize retrospectively the patients referred to our Lipid Clinic with a diagnosis of statin myopathy. The tolerability of different statins was assessed to determine a strategy for rechallenging statins in such patients in the future. Patients with statin myopathy constitute 10.2% of our Lipid Clinic workload. They are predominantly female (62.0%), Caucasian (63.9%), with a mean age of 58.3 years and mean body mass index (BMI) of 29.3 kg/m(2). The serum CK and erythrocyte sedimentation rate (ESR) were statistically higher compared to patients with statin intolerances with no muscular component or CK elevations. Secondary causes of statin myopathy were implicated in 2.7% of cases. Following statin myopathy to simvastatin we found no statistical difference between the tolerability rates between atorvastatin, rosuvastatin, pravastatin, and fluvastatin. Fibrates, cholestyramine, and ezetimibe were statistically better tolerated in these patients. Statin rechallenge is a real treatment option in patients with statin myopathy. Detailed history and examination is required to exclude muscle diseases unrelated to statin usage. In patients developing statin myopathy on simvastatin, we did not find any statistical difference between subsequent tolerability rates to rosuvastatin, pravastatin, and fluvastatin.

A founder mutation in Anoctamin 5 is a major cause of limb girdle muscular dystrophy

The limb-girdle muscular dystrophies are a group of disorders with wide genetic and clinical heterogeneity. Recently, mutations in the ANO5 gene, which encodes a putative calcium-activated chloride channel belonging to the Anoctamin family of proteins, were identified in five families with one of two previously identified disorders, limb-girdle muscular dystrophy 2L and non-dysferlin Miyoshi muscular dystrophy. We screened a candidate group of 64 patients from 59 British and German kindreds and found the truncating mutation, c.191dupA in exon 5 of ANO5 in 20 patients, homozygously in 15 and in compound heterozygosity with other ANO5 variants in the rest. An intragenic single nucleotide polymorphism and an extragenic microsatellite marker are in linkage disequilibrium with the mutation, suggesting a founder effect in the Northern European population. We have further defined the clinical phenotype of ANO5-associated muscular dystrophy. Patients show adult onset proximal lower limb weakness with highly raised serum creatine kinase values (average 4500 IU/l) and frequent muscle atrophy and asymmetry of muscle involvement. Onset varies from the early 20 s to 50 s and the weakness is generally slowly progressive, with most patients remaining ambulant for several decades. Distal presentation is much less common but a milder degree of distal lower limb weakness is often observed. Upper limb strength is only mildly affected and cardiac and respiratory function is normal. Females appear less frequently affected. In the North of England population we have identified eight patients with ANO5 mutations, suggesting a minimum prevalence of 0.27/100,000, twice as common as dysferlinopathy. We suggest that mutations in ANO5 represent a relatively common cause of adult onset muscular dystrophy with high serum creatine kinase and that mutation screening, particularly of the common mutation c.191dupA, should be an early step in the diagnostic algorithm of adult limb-girdle muscular dystrophy patients.

Neuroleptic malignant syndrome during long-term antipsychotic combination treatment: a case report

Neuroleptic malignant syndrome during long-term antipsychotic combination treatment: a case report Neuroleptic malignant sydnrome (NMS) is a rare but potentially life-threatening idiosyncratic adverse reaction, usually seen with antipsychotic treatment. It is characterized by fever, autonomic instability, extrapyramidal syndrome and altered mental state. Raised serum creatine kinase level, impaired liver and kidney function tests, leucocytosis and electrolyte disturbance may be the accompanying laboratory features. Various demographic, patient-medication and environmental factors increase the risk of NMS. In this case report, the clinical characteristics and management of NMS in a patient who has several risk factors such as mental retardation, use of parenteral, high dose typical antipsychotic combination for long

A treatable muscle disease

A 70-year-old woman presented with increasing weakness and fatigue over 4 years. She had suffered motor problems from birth with hypotonia and delayed motor milestones. She walked abnormally in childhood...

New drugs: Daptomycin

Being a cyclic lipopeptide, daptomycin belongs to a new class of antibiotics. It acts by forming a pore in the bacterial membrane thus causing leakage of potassium and subsequent depolarization and arrest of cell function. Daptomycin has a bactericidal action on Gram-positive bacteria and is registered for the treatment of adults with complicated skin and soft tissue infections caused by Gram-positive microorganisms. There is limited experience with treatment of Staphylococcus aureus bacteraemia. Its main adverse effects include gastrointestinal symptoms, skin reactions at the site of infusion, and raised serum creatine kinase.