Muscle Biopsy in Benign HyperCKemia
Abstract & Commentary
Source: Simmons Z, et al. Muscle biopsy in the evaluation of patients with modestly elevated creatine kinase levels. Muscle Nerve. 2003;27:242-244.
Benign hyperCKemia may be defined as serum elevation of creatine kinase (CK) in an asymptomatic patient or in a patient with nonspecific symptoms, including muscle pain, fatigue, cramps, stiffness, normal neurological examination, and normal or nondiagnostic electrodiagnostic (nerve conduction studies and electromyography) studies. Rarely does a treatable disorder underlie such CK elevation, and the use of muscle biopsy remains questionable.
Over a 9-year period, 20 patients, 14 men and 6 women, demonstrated modest serum CK elevation (< 1000 U/L) on at least 2 occasions with no history of myoglobinuria. All had normal muscle strength, negative family history for neuromuscular disease or malignant hyperthermia, and nondiagnostic EMG studies. All underwent biopsy with extensive evaluation of the tissue to determine if such studies contributed to their diagnosis and treatment. Muscle stains included hematoxylin-eosin, Gomori trichrome, oil-red-O, periodic acid-Schiff, adenosine triphosphatase, succinate dehydrogenase, NADH-tetrazolium reductase, cytochrome oxidase, myophosphorylase, myoadenylate deaminase, and stains for dystrophin, sarcoglycans, laminin (merosin), and dysferlin. Absent a diagnosis by these techniques, biochemical analysis was pursued, including phosphorylase, phosphorylase b kinase, phosphofructokinase, phosphoglycerate kinase, phosphoglycerate mutase, lactate dehydrogenase, and carnitine palmitoyltransferase.
Myoadenylate deaminase deficiency was demonstrated in 1 patient. In the remainder, biopsy was normal in 9, nonspecific in 6 (minor muscle fiber atrophy and fiber type predominance), and mildly myopathic in 4 (rare degenerating or regenerating fibers, internal nuclei, or split fibers). Immunohistochemistry was normal in all. Biochemically, phosphorylase b kinase was deficient in 3 and carnitine palmitoyltransferase in 2. Neither muscle biopsy findings nor biochemical abnormalities predicted an abnormality in the other. Extensive evaluation of muscle biopsy in benign CK elevation is warranted for diagnostic purposes but will not alter patient management.
Commentary
Among 114 patients with benign hyperCKemia, a diagnosis of disease was made in 18.4%, with nonspecific skeletal muscle abnormalities found in 38.6% and completely normal muscle biopsy findings in 31.6%.1 Long-term follow-up of 31 such patients revealed that although symptoms tend to persist with no substantial change in myalgia or fatigue, deterioration is not seen.2 Importantly, even in the absence of established myopathy, such patients may be at risk for malignant hyperthermia, as demonstrated by in vitro sensitivity to caffeine.3 Patients must be so informed. Elevation of CK is well recognized following exercise. Such elevation is less pronounced in well-trained athletes as compared to untrained persons.4 Despite serum elevation, athletes were asymptomatic for muscle pain or chest discomfort. — Michael Rubin
Dr. Rubin is Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus.
References
1. Prelle A, et al. J Neurol. 2002;249:305-311.
2. Reijneveld JC, et al. Muscle Nerve. 2000;23:575-579.
3. Sunohara N, et al. Neurology. 1984;34:544-547.
4. Garry JP, McShane JM. MedGenMed. 2000:E4.
Benign hyperckemia may be defined as serum elevation of creatine kinase (CK) in an asymptomatic patient or in a patient with nonspecific symptoms, including muscle pain, fatigue, cramps, stiffness, normal neurological examination, and normal or nondiagnostic electrodiagnostic (nerve conduction studies and electromyography) studies.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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