Normal Serum Creatine Kinase Levels Research Articles

Association between hyperCKemia and axonal degeneration in Guillain–Barré syndrome

BackgroundElevated serum creatine kinase (CK) levels have been reported in patients with Guillain–Barré syndrome (GBS), more frequently in patients with acute motor axonal neuropathy (AMAN) than in those with acute inflammatory demyelinating polyneuropathy (AIDP). However, some patients with AMAN show reversible conduction failure (RCF), characterized by rapid recovery without axonal degeneration. The present study tested the hypothesis that hyperCKemia is associated with axonal degeneration in GBS, regardless of the subtype.MethodsWe retrospectively enrolled 54 patients with AIDP or AMAN whose serum CK levels were measured within 4 weeks from symptom onset between January 2011 and January 2021. We divided them into hyperCKemia (serum CK ≥ 200 IU/L) and normal CK (serum CK < 200 IU/L) groups. Patients were further classified into axonal degeneration and RCF groups based on more than two nerve conduction studies. The clinical features and frequency of axonal degeneration and RCF were compared between groups.ResultsClinical characteristics were similar in the hyperCKemia and normal CK groups. Compared with that in the RCF subgroup, the frequency of hyperCKemia was significantly higher in the axonal degeneration group (p = 0.007). Patients with normal serum CK levels showed better clinical prognosis, evaluated by the Hughes score at 6 months from admission (p = 0.037).ConclusionHyperCKemia is associated with axonal degeneration in GBS, regardless of the electrophysiological subtype. HyperCKemia within 4 weeks from symptom onset might be a marker of axonal degeneration and poor prognosis in GBS. Serial nerve conduction studies and serum CK measurements will help clinicians understand the pathophysiology of GBS.

Anti-SAE autoantibody-positive Japanese patient with juvenile dermatomyositis complicated with interstitial lung disease - a case report

BackgroundClinical phenotypes and outcomes in juvenile dermatomyositis (JDM) have been defined by various myositis-specific autoantibodies (MSAs). One of the recently described MSAs associated with DM is targeted against the small ubiquitin-like modifier 1 activating enzyme (SAE). We report an anti-SAE autoantibody-positive JDM patient complicated with interstitial lung disease (ILD).Case presentationAn 8-year-8-month-old Japanese girl presented with bilateral eyelid edema and facial erythema. At 8 years 4 months, she had dry cough and papules with erythema on the dorsal side of the interphalangeal joints of both hands. Her facial erythema gradually worsened and did not improve with topical steroids. At the first visit to our department at 8 years 8 months of age, she had a typical heliotrope rash and Gottron’s papules, with no fever or weight loss, and a chest computed tomography scan showed ground-glass opacity under visceral pleura. There was no clinical evidence of myositis, muscle weakness, myalgia, or muscle magnetic resonance imaging (MRI) findings. She had mild dry cough, without any signs of respiratory distress. Laboratory tests showed no elevated inflammatory markers. She had a normal serum creatine kinase level with a slightly elevated aldolase level, and serum anti-SAE autoantibody was detected by immunoprecipitation—western blotting. She was diagnosed with juvenile amyopathic DM complicated by ILD and received two courses of methylprednisolone pulse therapy followed by oral corticosteroid and cyclosporin A. We gradually reduced the corticosteroid dose as her skin rash improved after treatment initiation. There was no progression of muscle symptoms, dysphagia, or disease flare during a 24-month follow-up period.ConclusionsWe report a patient with anti-SAE autoantibody-positive JDM complicated by interstitial pneumonia. This patient had no progression of muscle symptoms and dysphagia during a 24-month follow-up period, which differs from previous reports in adult patients with MSAs. There have been no previous reports of pediatric patients with SAE presenting with ILD. However, ILD seen in this case was not rapidly progressive and did not require cytotoxic agents. To prevent overtreatment, appropriate treatment choices are required considering the type of ILD.

Enzyme replacement therapy in Hunter syndrome (MPS II): A systematic review with narrative synthesis and meta-analysis

We describe the first child with guanidinoacetate methyltransferase (GAMT) deficiency who developed neuroleptic malignant syndrome (NMS) after the treatment of risperidone without elevated creatine kinase (CK) levels.The patient presented with lethargy, hyperthermia, generalized tremor and rigidity with normal serum CK levels. After cessation of risperidone and adding clonezepam to the supportive treatment, symptoms of NMS were ameliorated.We conclude that although serum CK elevation is a useful indicator for the early detection of NMS, normal serum CK levels may be seen during the NMS course in the presence of GAMT deficiency.

Autoantibody to transcriptional intermediary factor-1β as a myositis-specific antibody: clinical correlation with clinically amyopathic dermatomyositis or dermatomyositis with mild myopathy.

Myositis-specific autoantibodies (MSAs) are associated with unique clinical subsets in polymyositis/dermatomyositis (PM/DM). Autoantibodies against transcriptional intermediary factor (TIF)-1γ and TIF-1α are known to be MSAs. Previously, we reported that TIF-1β is also targeted in patients with DM with or without concomitant anti-TIF-1α/γ antibodies. To evaluate the clinical features of seven cases with anti-TIF-1β antibodies alone. Serum autoantibody profiles were determined, and protein and RNA immunoprecipitation studies were conducted. Western blotting was performed to confirm autoantibody reactivity against TIF-1β. Anti-TIF-1β antibody was identified by immunoprecipitation assay in 24 cases. Among them, seven patients were positive for anti-TIF-1β antibody alone. Six of the seven patients were classified as having DM. Among the six cases of DM, two patients had no muscle weakness and normal creatine kinase (CK) levels, and were classified as having clinically amyopathic DM. Four patients had muscle weakness, but three of them had normal serum CK levels that responded well to systemic steroids. Characteristic features of DM included skin rashes, such as Gottron sign, periungual erythema, punctate haemorrhage on the perionychium and facial erythema including heliotrope, which were observed in 86%, 57%, 86% and 71% of our cases, respectively. One of the seven patients had appendiceal cancer. None of the patients had interstitial lung disease. Seven patients were confirmed to have anti-TIF-1β antibody without any other MSAs, including TIF-1α/γ antibodies, and six of them were diagnosed with DM. We suggest that anti-TIF-1β antibody is an MSA, and that it is associated with clinically amyopathic DM or DM with mild myopathy.

Biopsy-Proven Dermatomyositis with Normal Creatine Kinase

Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterized by skeletal muscle inflammation and typical skin manifestations. Creatine kinase (CK) has traditionally been considered to be the most useful serum enzyme for the diagnosis and assessment of adult patients with IIM. To our knowledge, there has been no reported case of biopsy-proven DM without CK elevation in Korea, to date. Panniculitis is an uncommon cutaneous manifestation in adult patients with DM. A search of the PubMed database reveals fewer than 30 reported cases of panniculitis in adult patients with DM. Here, we report a case of a 42-year-old female who was diagnosed with biopsy-proven DM with normal serum CK levels and panniculitis. (Korean J Med 2016;90:274-279)

Is It Statin Induced Polymyalgia Rheumatica or Just a Coincidence?

©2015 Turkish League Against Rheumatism. All rights reserved. A 53-year-old female presented with pain in her bilateral shoulders, hips and neck, stiffness (lasting one hour), and proximal weakness for three months. She declared that her symptoms had ensued one week after the usage of daily 40 mg atorvastatin for hyperlipidemia. As such, atorvastatin was discontinued; however, her complaints did not decline. Physical examination revealed painful and restricted shoulder and neck movements, weakness in shoulder and hip muscles, and a swollen, warm right knee. Laboratory investigations including creatine kinase (CK), rheumatoid factor and anti-nuclear antibody levels were within normal values, except for the increased C-reactive protein (0.744 mg/dL, N: 0-0.5) and erythrocyte sedimentation rate (75 mm/h, N: 0-20). X-rays of the hand, knee, hip and shoulder were non-contributory. Ultrasound illustrated biceps tenosynovitis and trochanteric bursitis bilaterally, and increased suprapatellar fluid in right knee (Figure 1). Overall, the patient was diagnosed with polymyalgia rheumatica (PMR) according to the 2012 European League Against Rheumatism/American College of Rheumatology classification criteria.1 Her symptoms and clinical findings (erythrocyte sedimentation rate and C-reactive protein levels) responded to medium dose of prednisolone (20 mg/d) treatment dramatically. Although statins have been reported to be associated with some musculoskeletal side effects such as myalgia, myositis, myopathy, and elevated CK, statin induced PMR is a very rare condition which has been reported only in a few anecdotal reports.2-4 Likewise, statin treatment might trigger the development of PMR in our patient. Since statin induced PMR and myalgia have similar clinical features, the exact diagnosis can be challenging. Statin induced myalgia presents with/without increased CK levels with normal erythrocyte sedimentation rate and C-reactive protein levels. Therefore, patients with statin induced myalgia may have normal serum CK levels, which sometimes make it difficult to distinguish PMR from myopathy syndromes. In case of drug discontinuation, symptoms heal in a period of one-week to four-month in statin, myopathy and treatment of steroid is rarely required.5 PMR patients do not recover spontaneously and corticosteroid treatment is usually needed.6

Statin-Induced Musculoskeletal Problems: Disconcerting Reports and Data

Statins are molecules of fungal origin, which inhibit the hydroxymethylglutaryl-CoA (HMG-CoA) reductase enzyme, a key step in the sterol biosysnthesis, rendering them powerful cholesterol lowering medications contributing to significant prevention of cardiovascular disease. 1 Statins are characterized by differences in bioavailability, lipo/hydrophilicity, cytochrome P-450 mediated metabolism and cellular transport mechanisms, differences that are reflected in their relative capacity in LDL-cholesterol lowering and possibly in parenchymal or muscular toxicities. 2 Statin intolerance comprises, among others, musculoskeletal problems, such as statin-induced muscle and tendon disorders which are the most common cause of statin discontinuation. 3-10 Musculoskeletal Problems Statin therapy has long been associated with musculoskeletal (MS) problems in approximately 10% - 25% of patients treated in real-world clinical practice, but such problems have rarely been reported in controlled clinical trials, 3,4 and their incidence has thus far been underestimated. 5 Studies have concentrated on creatine kinase (CK) elevations to identify myopathy. However, many patients can have normal serum CK levels despite myalgia and persistent weakness and muscle biopsy - proven myopathy. Discontinuation of statin and rechalllenge may be required to prove that it is statin-related. Several risk factors may predispose patients to statin-related MS problems, including advanced age, family history of myopathy, statin dose, and interacting medications (e.g., azole antifungals, cimetidine, fibrates, macrolide antibiotics, protease inhibitors and cyclosporine) (Table 1). 5,6,8 Musculoskeletal conditions, arthropathies, injuries, and pain appear to be more common among statin users than among similar nonusers... (excerpt)

AB0649 Clinical Features of Spontaneous Pneumomediastinum in Dermatomyositis

BackgroundSpontaneous pneumomediastinum is a rare complication and a poor prognostic factor of dermatomyositis (DM). But the mechanisms, outcome, and prognostic factors of DM associated pneumomediastinum have not yet been evaluated.ObjectivesTo...

多発筋炎様症状を呈した高齢発症サルコイドミオパチーの1例

A 75-year-old woman was admitted with a history of acute muscle weakness of her legs for two weeks. Physical examination showed no abnormal findings. Neurological examination revealed symmetrical proximal muscle weakness of legs with muscle pain on grasping. Laboratory data showed normal serum creatine kinase level and marked increases in the levels of serum ACE and soluble interleukin 2. Electromyography showed no myopathic changes. MRI T2 weighted imaging (T2WI) imaging for femoral skeletal muscle demonstrated scattered high and low intensity signals. Muscle biopsy from the right rectus femoris muscle showed granuloma with giant cells of Langhans. She was given a diagnosis of sarcoid myopathy, and motor weakness and abnormal intensity signals on T2WI in this patient were dramatically improved with oral administration of prednisolone (40 mg/day).

An unusual case of congenital muscular dystrophy with normal serum CK level, external ophtalmoplegia, and white matter changes on brain MRI

We report a sporadic case of congenital muscular dystrophy (CMD) in a 13-year-old girl with early manifestation of muscle weakness and hypotonia, severe contractures, bulbar syndrome, progressive external ophtalmoplegia, and white matter changes on magnetic resonance imaging (MRI) of the brain, but no mental defect. Serum creatine kinase (CK) level was normal. Muscle biopsy revealed a dystrophic picture with a prominent inflammatory infiltrate mimicking inflammatory myopathy—typical histological findings in CMD. Immunostaining showed normal expression of merosin, α and β-dystroglycans. Mutation analyses of calpain3, dysferlin, and SEPN1 genes were negative. An electron microscopy revealed the accumulation of abnormally enlarged mitochondria located under the sarcolemma. Measurement of respiratory chain enzyme activities did not reveal any biochemical defect and mitochondrial genetic studies, including sequencing of the entire mitochondrial genome, were unremarkable. Phenotypic presentation of our patient is very unusual and differs considerably from other CMD variants.

Toxic myopathies: muscle biopsy features

Several drugs and toxic substances can cause muscular abnormalities and are frequent causes of acquired myopathies. We present a series of 32 patients, predominance of young adult patients, diagnosed with toxic myopathy. The most common substances inducing myopathy were corticosteroids (56.2%) followed by the propoxyphene, neuroleptics, zidovudine and drug-induced hypokalemia. The investigation showed normal serum creatine kinase levels in 65.4%, myopathic pattern of the needle electromyography in 40% and the more frequent histological diagnosis of the muscle biopsy was type 2 fiber atrophy (59.3%). Clinical features, etiology, course of the disease, serum levels of muscular enzymes, electromyographic features and, especially, muscle biopsy features are discussed.

A Patient With Polymyositis and Normal Serum Creatine Kinase Level

A Patient With Polymyositis and Normal Serum Creatine Kinase Level

Hydroxychloroquine causes severe vacuolar myopathy in a patient with chronic graft‐versus‐host disease

A 51-year-old man developed progressive debilitating limb and respiratory muscle weakness while undergoing treatment for chronic graft-versus-host disease secondary to allogeneic bone marrow transplant for mantle cell lymphoma. He had a normal serum creatine kinase level and acetylcholine receptor antibodies were negative. Electromyography showed a severe, nonirritable myopathy and a sensory motor axonal polyneuropathy. A muscle biopsy showed a necrotizing, vacuolar myopathy with many fibers containing autophagic and red-rimmed vacuoles, suggestive of an amphiphilic drug myopathy. The patient's strength and function improved significantly after discontinuation of hydroxychloroquine.

Congenital muscular dystrophy in Israeli families.

Twelve patients from 11 Israeli families with congenital muscular dystrophy were evaluated between 1991 and 2001. There were six males and six females, of whom six were merosin negative and six were merosin positive. Serum creatine kinase levels were highly elevated in the merosin-negative group. Four of the children were cognitively normal but nonambulant. Two had unusual clinical findings of severe cognitive and motor developmental dysfunction. Four infants in the merosin-positive group who had normal serum creatine kinase levels had early-onset severe motor weakness and died within the first year of life owing to ventilatory insufficiency. The other two were ambulant and had normal cognitive development and elevated serum creatine kinase levels. Noteworthy, two of the six children with merosin-negative congenital muscular dystrophy had cognitive impairment, and four of the six children with merosin-positive congenital muscular dystrophy had a severe form of the disease with ventilatory insufficiency and death during infancy.

Infantile polymyositis with normal serum creatine kinase level

A 30-month-old boy who has been suffering progressive proximal muscle weakness and severe atrophy in shoulder and hip muscles from 11 months of age had prominent perivascular inflammatory cellular infiltration in his muscle biopsy and myopathic EMG changes. But his serum creatine kinase (CK) levels were repeatedly found to be within normal ranges. Oral prednisolone therapy (2 mg/kg/d) brought a complete recovery of muscle power and normalization of EMG and muscle biopsy findings. This report provides an additional support that the cases of infantile polymyositis with normal serum CK levels may respond well to steroid therapy.

Myalgia and cramps: dystrophinopathy with wide-ranging laboratory findings.

We present 12 cases of males with myalgia and cramps and a normal muscle strength examination. All the patients had muscle dystrophin values consistent with Becker muscular dystrophy. Five of the patients had a normal electromyogram, and five had normal light microscopic muscle biopsy results. Of particular note, four of the 12 patients had normal serum creatine kinase levels, and four others had only mild elevations (less than twice the upper limit of normal). These patients establish an identifiable dystrophinopathy of adolescent boys and young men that can present with muscle pain and, in some cases, normal routine laboratory evaluations.

In utero fetal muscle biopsy for the diagnosis of Duchenne muscular dystrophy in a female fetus “suddenly at risk”

DNA methods to diagnose Duchenne muscular dystrophy (DMD) are not always informative, and we have published previously the first instance of in utero muscle biopsy to assess dystrophin in a male fetus having the same "X" as an affected sib. We present here a female fetus with a de novo X,1 translocation with breakpoint at Xp21, detected on amniocentesis for advanced maternal age. The translocation breakpoint placed her at high risk for DMD. In utero muscle biopsy at 20 weeks of gestation produced a specimen positive for dystrophin immunofluorescence indicating a likely normal fetus. The pregnancy was continued, and at term the baby girl was found to have normal serum creatine kinase levels, and was therefore unaffected with DMD. Our experiences add de novo Xp21 translocation to the indications for in utero muscle biopsy for diagnosis of DMD.