Raised Creatine Kinase Levels Research Articles

Creatine kinase and prognosis in amyotrophic lateral sclerosis: a literature review and multi-centre cohort analysis

BackgroundAmyotrophic lateral sclerosis (ALS) is a prognostically heterogeneous neurodegenerative disease. Blood creatine kinase (CK) level has been inconsistently reported as a prognostic biomarker and raised levels in some ALS patients have been presumed to reflect muscle wasting, which is also variable.MethodsMEDLINE was systematically searched for papers related to CK in ALS and the relevant studies were reviewed. Using data from 222 ALS patients in a multi-centre, prospective, longitudinal cohort, survival analyses using Kaplan–Meier and Cox proportional hazards models were undertaken in relation to CK and other prognostic factors.ResultsTwenty-five studies investigating CK in ALS were identified, of which 10 specifically studied the link between CK and survival. Five studies observed no association, four found that higher CK levels were associated with longer survival and one, the opposite. In our cohort (n = 222), 39% of patients had a CK level above the laboratory reference range. Levels were higher in males compared to females (p < 0.001), in patients with limb versus bulbar onset of symptoms (p < 0.001) and in patients with higher lower motor neuron burden (p < 0.001). There was no significant trend in longitudinal CK values. Although a higher standardised log (CK) at first visit was associated with longer survival in univariate analysis (hazard ratio 0.75, p = 0.003), there was no significant association after adjusting for other prognostic covariates.ConclusionWhile raised CK levels in ALS do reflect lower motor neuron denervation to a large extent, they are not independently associated with survival when measured in the symptomatic phase of the disease.

Contrast-Induced Rhabdomyolysis Occurring after ERCP in a Patient with Pancreatic Cancer: A Case Report.

ObjectiveWe present a patient with pancreatic cancer who developed weakness, acute renal failure and significantly raised creatine kinase levels post-ERCP and who was assessed as having contrast-induced rhabdomyolysis.ResultsThe patient underwent haemofiltration and ultimately succumbed to his condition.ConclusionRhabdomyolysis is a potentially life-threatening condition which occurs because of damage to skeletal muscle, with release of myoglobin and electrolytes into the circulation. The mortality rate is 59% in severe cases, despite appropriate treatment.LEARNING POINTSIodine-based contrast can cause rhabdomyolysis by reducing blood flow to the muscle.Renal replacement therapy does not improve the mortality rate of rhabdomyolysis.<10% of patients present with the classic triad of myalgia, muscle weakness and tea-coloured urine; creatine kinase levels greater than 5 times the upper limit of normal are the gold standard for diagnosing rhabdomyolysis that is not related to statin use.

A novel case of MSTO1 gene related congenital muscular dystrophy with progressive neurological involvement

Recessive mutations in the MSTO1 gene, encoding for a mitochondrial distribution and morphology regulator, have been recently described in a very limited number of patients with multisystem involvement, mostly characterized by myopathy or dystrophy, cerebellar ataxia, pigmentary retinopathy and raised creatine kinase levels. Here we report an additional patient with recessive MSTO1-related muscular dystrophy (MSTO1-RD), and clinical and radiological evidence of progressive cerebellar involvement. Whole-exome sequencing identified two novel MSTO1 missense variants, c.766C > T (p. (Arg256Trp) and c.1435C > T (p. (Pro479Ser), predicted as damaging by in silico tools. We also report a distinct pattern of selective involvement on muscle MRI in MSTO1-RD. This case confirms a consistent MSTO1-related neuromuscular phenotype and in addition suggests a progressive neurological component at least in some patients, in keeping with the mitochondrial role of the defective protein.

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.

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.

PRIMARY (GENETICALLY DETERMINED) DILATION CARDIOMYOPATHY IN A PATIENT WITH NOVEL MUTATION OF LAMIN GENE: CLINICAL AND MORPHOLOGICAL MANAGEMENT

The primary diagnosis of “dilation cardiomyopathy” is syndromal, and demands clarification of nosological origins. In the article, the specifics of such diagnostics is discussed. Clinical case is provided that illustrates the ways of management, diagnostics and treatment of the essential (primary, genetically determined) dilation cardiomyopathy. Patient of 22 year old with no family history, at the ages 20 and 21 y.o. had cardioembolic strokes. Paroxysmal atrial fibrillation was found, raised creatine kinase levels up to 349-1045 U/L, decreased ejection fraction 17%. Heart failure rapidly progressed. In endomyocardial biopsy there was homogenisation of cardiomyocytes, subendocardial lipomatosis with borderline virus-negative myocarditis. By Senger direct sequencing, the novel variant p.E372 in gene LMNA was found, heterozygous. Implantation of CRT-D was done, and in 4 months — cardiac transplant.

Bent spine syndrome as the initial symptom of late-onset Pompe disease.

Late-onset Pompe disease (LOPD) is a rare disorder characterized by progressive proximal muscle weakness and early respiratory insufficiency, for which enzyme replacement therapy (ERT) is available. Having diagnosed a case of LOPD presenting with bent spine syndrome, we conducted a brief survey in the French centers involved in management of Pompe disease, from which we collected data on 3 other cases. The patients (3 women and 1 man) had a mean age of 64 years (range 51-77 years) and a delay in diagnosis of approximately 10 years (range 8-42 years). At diagnosis, 3 patients already had respiratory symptoms. All had normal or very mildly raised creatine kinase levels and magnetic resonance imaging abnormalities in the paraspinal muscles. They exhibited the most frequent mutation in Pompe disease (c.-32-13 T>G). Clinicians should be aware of this atypical presentation of LOPD to enable earlier diagnosis and treatment. Muscle Nerve 56: 167-170, 2017.

Clinical features of the myasthenic syndrome arising from mutations in GMPPB

BackgroundCongenital myasthenic syndrome (CMS) due to mutations in GMPPB has recently been reported confirming the importance of glycosylation for the integrity of neuromuscular transmission.MethodsReview of case notes of patients with...

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

Viral myositis as a close mimicker of polymyositis

Viruses can induce myositis through persistent infections, molecular mimicry, production of immune complexes, immune dysregulation, or other mechanisms. Self limited viral myositis is more common among children and has been seen to be mostly associated with influenza A and B. We report a case of 15-year-old boy who presented with proximal muscle weakness following 3 weeks after an episode of fever. Muscle necrosis was evident from the raised creatine kinase levels and myoglobinuria. The patient improved slowly over a period of weeks without any treatment except for adequate hydration.

S.P.56 Early neurodevelopmental findings in young children with Duchenne muscular dystrophy

Abstract Cognitive abilities have been extensively studied in children and adults with Duchenne muscular dystrophy (DMD) but less has been reported on younger children. This is not surprising as the diagnosis of DMD remains at a mean age of 4 and 6 months. The aim of this study was to assess neurodevelopmental abilities before the age of 4 years in a cohort of DMD patients in whom early diagnosis was possible because of incidental raised creatine kinase levels, family history or neonatal screenings. Sixty-six children with a diagnosis of DMD of age between 7 and 43 months (mean 27 months) were included in the study. All children were assessed using the Griffiths Mental Development Scales, establishing both total scores and subscores for each of the subscales. Thirty-six of the 66 children had a developmental quotient (DQ) > 85, 21 had a DQ between 70 and 84 and 9 below 70. The mean total DQ was 86 (SD 16.07) and the mean scores for each subscale were as follows: (A) locomotor: 79 (19.47), (B) personal social: 91 (18.48), (C) hearing and speech: 85 (23.59), (D) eye hand coordination: 87 (17.20), (E) performance: 88 (18.40), (F) practical reasoning: 95 (16.08). (Scale F only for patients older than 2 years.) Details of mutations were available in 58 of the 66 children included. Low DQ were found in five of the 26 (18.5 %) patients with mutations before exon 44, in 15 of the 29 with mutations between 44 and 55 (51.7 %) and in all three with mutations in the exons beyond exon 55. it Conclusions: The DQ found in our cohort was on average one SD below a DQ of 100 with approximately 45% of the children having a DQ below 85. The locomotor scale had the lowest scores but even when we excluded the locomotor scale, a DQ below 85 was found in 28 patients (43%).

Muscle phosphorylase kinase deficiency

To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD). Patient 1 (39 years old) had mild exercise-induced forearm pain, and EMG showed a myopathic pattern. Patient 2 (69 years old) had raised levels of creatine kinase (CK) for more than 6 months after statin treatment. Both patients had increased glycogen levels in muscle and PHK activity <11% of normal. Two novel pathogenic nonsense mutations were found in the PHKA1 gene. The metabolic response to anaerobic forearm exercise and aerobic cycle exercise was studied in the patients and 5 healthy subjects. Ischemic exercise showed a normal 5-fold increase in plasma lactate (peak 5.7 and 6.9 mmol/L) but an exaggerated 5-fold increase in ammonia (peak 197 and 171 μmol/L; control peak range 60-113 μmol/L). An incremental exercise test to exhaustion revealed a blunted lactate response (5.4 and 4.8 mmol/L) vs that for control subjects (9.6 mmol/L; range 7.1-14.3 mmol/L). Fat and carbohydrate oxidation rates at 70% of peak oxygen consumption were normal. None of the patients developed a second wind phenomenon or improved their work capacity with an IV glucose infusion. Our findings demonstrate that muscle PHK deficiency may present as an almost asymptomatic condition, despite a mild impairment of muscle glycogenolysis, raised CK levels, and glycogen accumulation in muscle. The relative preservation of glycogenolysis is probably explained by an alternative activation of myophosphorylase by AMP and P(i) at high exercise intensities.

Bitten by the “Flying” Tree Snake, Chrysopelea Paradisi

BackgroundThe paradise tree snake, Chrysopelea paradisi, is a rear-fanged colubrid. Like other members of the genus Chrysopelea, it is able to glide through the air, and thus, is commonly known as a “flying snake.” There are few documented effects of its bite on humans. Case ReportA 16-year-old military college student presented to the Emergency Department (ED) of an urban teaching hospital 2 h after being bitten by C. paradisi. There were multiple bite marks and the patient reported moderate pain on the left index finger. There was no evidence of significant local or systemic envenomation. A transient prolonged coagulation profile and raised creatine kinase level were noted. ConclusionThe full effects of a bite from C. paradisi remain uncharacterized. This case featured only mild local effect. After the administration of first aid, non-sedating analgesia, anti-tetanus toxoid injection, and broad-spectrum antibiotic coverage, a short stay in the ED observation ward with regular monitoring of vital signs and serial wound inspection are recommended. More effort is required to increase awareness of the prevention and management of snakebite with equal emphasis on conservation of wildlife and their natural habitat.

Glycogen storage disease type V (Mc Ardle′s disease): A report on three cases

McArdle's disease (myophosphorylase deficiency), an uncommon autosomal recessive metabolic disorder, is characterized clinically by exercise intolerance beginning in childhood, myalgia, cramps, exercise-induced rhabdomyolysis, "second wind" phenomenon, elevated Creatine Kinase (CK) levels at rest, and previous episodes of raised CK levels following exercise. Several mutations in the PYGM gene and geographic variations have been described. We report three biopsy confirmed cases of McArdle's disease.

A Case of Risperidone‐Associated Neuroleptic Malignant Syndrome in a Patient Receiving Long‐Term Haloperidol Treatment

We report a case of risperidone‐associated neuroleptic malignant syndrome. A 53‐year‐old gentleman with mental retardation, psychosis and hypertension who was on long term haloperidol, lorazepam and atenolol treatment presented to the Department of Emergency Medicine of the Singapore General Hospital with hyperthermia, generalised rigidity, impaired consciousness and diaphoresis five weeks after adding on risperidone. Biochemical investigations revealed hyponatremia, raised creatine kinase levels and myoglobinuria. Chest X‐ray showed consolidative changes in the right upper and middle zones and left middle zone. He was diagnosed as neuroleptic malignant syndrome with rhabdomyolysis, and aspiration pneumonia. He was discharged well after 13 days.

Beware of 'normal' creatine kinase levels in HIV-associated polymyositis

Generalised weakness may be a common complaint of persons infected with HIV, but the development of significant proximal weakness requires specific attention. Polymyositis may occur in HIV infection and is readily treatable with prednisone. Elevated creatine kinase (CK) levels have been regarded as an important criterion for diagnosing polymyositis. A study of HIV-associated polymyositis reported similarly elevated CK levels to those observed in non-HIV settings. However, muscle inflammation can be associated with normal or near-normal CK levels. We report 4 cases of HIV-associated polymyositis in which the diagnosis was almost missed owing to the absence of raised CK levels.

Serum creatine kinase and lactic dehydrogenase levels as useful markers of perinatal asphyxia

Objectives To determine the usefulness of creatine kinase (CK) alone or in combination with lactic dehydrogenase (LDH) in identifying, those infants at risk of developing hypoxic ischaemic encephalopathy (HIE) or a major handicap following perinatal asphyxia. Design Prospective observational study. Method CK and LDH in serum were measured in 35 asphyxiated infants and in 30 controls within 6 hours of delivery. The asphyxiated newborns were monitored for evidence of HIE. Both groups were followed up in paediatric outpatients clinic and a developmental assessment was done at the end of one year. Results Both the CK and LDH levels were significantly raised in all asphyxiated newborns. 25.7% of asphyxiated babies developed HIE. The CK and LDH values of those who developed HIE were significantly higher than the rest of the asphyxiated newborns. Five babies had developmental delay and their CK values too were significantly higher. The same relationship was not seen with their LDH values. Conclusion Both the CK and LDH values are raised in birth asphyxia. The increase is more marked among those who developed HIE. However, only the raised CK levels correlated with long-term outcome. Babies with CK values above 2860 IU/ L should be closely monitored for both the immediate and longterm sequelae. Sri Lanka Journal of Child Health , 2000; 29 : 49-52 (Key words: creatine kinase, lactic dehydrogenase, markers of perinatal asphyxia) doi: 10.4038/sljch.v29i2.604

Clinical and Laboratory Analysis of Influenza B Infection in Children in Taichung, Taiwan during the 2006-2007 Flu Season

An epidemic of influenza B/Malaysia/2506/2004 was reported in Taiwan during the 2006-2007 flu season. We investigated the flu vaccination history and clinical and Laboratory characteristics of children with influenza B infection. We enrolled children younger than 18 years old who visited one of two hospitals between November 2006 and February 2007 with influenza-like illnesses. Throat swabs were taken on their first visit and cultured for viruses. Complete and differential blood counts and blood biochemical parameters were analyzed in some children. Influenza virus was cultured from 51.0% of patients (101/198), 87 (86.1%) of who were infected with influenza virus type B. The remaining 14 (13.9%) were infected with influenza virus type AH3. The 87 children (median age 7.8 years) with culture-proven influenza B virus infection were enrolled. Nine parents reported that enrolled children had been vaccinated against influenza. Leukopenia was found in 56.1% (32/57) of patients, leukocytosis in 3.5% (2/57), and thrombocytopenia in 1.8% (1/57). Thirteen of 23 patients (56%) tested for creatine kinase (CK) had elevated levels ( >160 U/L), and 11 of 23 (47.8%) had myalgia associated with raised CK (p < 0.05). Twenty-six children developed complications, including one case of pneumonia with acute respiratory distress syndrome and one case of flu-associated encephalitis. Most children who contracted influenza B infection had not been vaccinated. Almost half the children had leukopenia, and some had leukocytosis, but thrombocytopenia was rare. There was a significant association between raised CK levels and myalgia in influenza B infection.

Myotoxicity of Lipid-Lowering Agents in a Teenager With MELAS Mutation

The use of lipid-lowering statins has been associated with raised serum muscle enzymes and, occasionally, with rhabdomyolysis, especially in patients with pre-existing metabolic myopathies. The A3243G mutation is one of the most common mutations associated with mitochondrial disorders. A teenager harboring the A3243G mutation had the unusual association of hereditary glomerulopathy and recurrent episodes of raised creatine kinase levels with the use of lipid-lowering agents. Muscle biopsy showed both normal respiratory chain enzyme activities and normal coenzyme Q(10) levels, although decreased muscle coenzyme Q(10) concentration had been postulated to have a pathogenic role in statin-related myopathies. The close temporal relationship of statin administration and raised creatine kinase levels in this patient suggests caution in the use of statins in children and teenagers with mitochondrial myopathies.

New onset diabetes complicated by haemolysis and rhabdomyolysis: a case report and review of the literature

IntroductionPreviously undiagnosed glucose-6-phosphate dehydrogenase (G6PD) deficiency can be unmasked by a diabetic crisis and both can be associated with rhabdomyolysis. The relationship between diabetes and G6PD deficiency is discussed and the possible triggers for haemolysis as outlined in this case report. The incidence of G6PD deficiency is 10% in African-American males and up to 35% in parts of Africa so an increased awareness of G6PD deficiency is important when treating diabetes in these populations.Case presentationA 54-year-old Kenyan man presented with a 3-day history of reduced appetite, weakness and reduced level of consciousness as a result of a hyperglycaemic diabetic crisis with both hyperosmolarity and ketoacidosis. The patient then developed haemolysis and a raised creatine kinase level. A diagnosis of G6PD deficiency and rhabdomyolysis was made.ConclusionThis case highlights the importance of simple laboratory investigations in the early identification of the rarer complications of diabetic crisis such as haemolysis secondary to G6PD deficiency and rhabdomyolysis.