Diagnostic Utility of Muscle Biopsies in the Age of Molecular Genetics
Diagnostic Utility of Muscle Biopsies in the Age of Molecular Genetics
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports he has no financial relationships relevant to this field of study.
Synopsis: Muscle biopsy still remains an important test for determining correct diagnosis and treatment of patients with suspected muscle disease.
Source: Lai CH, et al. Open muscle biopsy in suspected myopathy: diagnostic yield and clinical utility. Eur J Neurol doi:10.1111/j.1468-1331.2009.02765.
With the advent of molecular genetics, is there a diagnostic role for open muscle biopsy? In a retrospective review performed by the Neuromuscular Division of The Johns Hopkins Hospital to address this question, all muscle biopsies performed between July 1, 1998 and June 30, 2001 were reviewed. Of 575 biopsies carried out, 317 were excluded, as they were either part of an autopsy or a combined nerve muscle biopsy, leaving 258 samples that formed the basis of this study.
Clinical history and examination findings, family history, electrodiagnostic studies (EMG), creatine kinase (CK) values, pre-biopsy diagnosis, MRC (Medical Research Council) grade of muscle strength at biopsy site, pathology, and post-biopsy diagnosis were collected from the medical record on all patients. Univariate and multivariate modeling provided statistical analysis.
Among the 258 patients, mean age was 47 years and men composed 53% (n = 137). Weakness was present in 78% (n = 201), and CK was elevated in 55% (143 of the 227 patients in whom it was performed). EMG, performed in 227 patients, was normal in 43 (17%) and nonspecific in 12% (n = 32), but in the remainder showed myopathic motor units with (n = 56, 22%) or without (n = 96, 37%) positive waves, fibrillation potentials, or myotonic discharges. Family history was positive in 11% (n = 29). Most common muscles biopsied included the quadriceps (42%), biceps or deltoid (23% each), and calf muscle (5%). Muscle strength was normal, or almost so, in the biopsied muscle in 36% (n = 92), severely weak (MRC 3+ or less) in 10% (n = 26), and moderately weak (MRC 4- to 4+) in 40% (n = 102). Myopathy was diagnosed pathologically in 52% (n = 134), with nonspecific abnormalities described in 20% (n = 52), neurogenic abnormalities in 12% (n = 31), mixed abnormalities in 2.3% (n = 6), and no abnormalities in 14% (n = 35). Consequent to the biopsy, a change in diagnosis occurred in 47% (n = 120), more often in those with normal CK and no family history of muscle disease, and less so in those with a myopathic EMG prior to biopsy. Post biopsy, a specific diagnosis was made in 43% (n = 112), most commonly inclusion body myositis, mitochondrial myopathy, or dermatomyositis, and treatment was altered as a result of the biopsy in 33% (n = 84). In the age of DNA analysis, muscle biopsy still plays a critical role in the diagnosis and management of muscle disease.
Commentary
Is percutaneous muscle biopsy a reliable alternative to open biopsy? Percutaneous biopsy can be quickly arranged, is easily performed in the clinic or at the bedside, is well tolerated, and complications are rare. But is the diagnostic sensitivity and specificity as good? Among 900 consecutive percutaneous muscle biopsies performed between 1993-2007 and identified retrospectively through the London Health Sciences Center, Department of Pathology database, in London, Ontario, Canada, it appears that it is (Can J Neurol Sci 2009;36;201-206). High-quality specimens were obtained and only rarely (1.8%) was tissue inadequate for diagnosis, usually due to edema, cachexia, or marked obesity. Biopsies had to be repeated in 3%, either due to nonspecific findings, suspected focal disease not seen on initial biopsy, or to perform additional testing. Final diagnoses included myositis, mitochondrial myopathy, muscular dystrophy, and metabolic myopathy. Diagnostic range is not impaired with percutaneous needle muscle biopsy and patients are able to resume full activities following biopsy. Unless nerve biopsy or extensive biochemical analysis is also being considered, percutaneous muscle biopsy offers a satisfactory alternative to open biopsy in the evaluation of suspected muscle disease.
Muscle biopsy still remains an important test for determining correct diagnosis and treatment of patients with suspected muscle disease.Subscribe Now for Access
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