Recent Advances and Controversies in Myopathology

Abstract

The first unequivocal microscopic description of autopsy muscle histopathology was presented by Edward Meryon in 1851 at a meeting of the Royal Medical and Chirurgical Society in London, and the study was published a year later [1]. Von Griesinger was the first to perform a muscle biopsy in 1864. In the following year, Guillaume-Benjamin-Amand Duchenne developed his own tool for performing a muscle biopsy. Enzyme histochemistry and electron microscopy were later added to the arsenal for evaluating muscle biopsies. These methods help visualize the morphological and functional features that can broadly categorize neuromuscular disorders into dystrophy, congenital myopathy, inflammatory myopathy, metabolic myopathy, mitochondrial myopathy, myofibrillar myopathy, neurogenic atrophy, etc. The use of ancillary techniques such as immunohistochemistry (IHC) and immunofluorescence (IF) to detect proteins (presence, absence, excess, deficiency, etc.) has greatly refined the results of morphology and enzyme histochemistry and, in fact, has nailed down the diagnosis in most inherited causes of myopathy. Of special note, IHC and IF play a major role in the diagnosis and classification of idiopathic inflammatory myopathies and their mimics [2]. Protein extracted from muscle can be subjected to Western blotting and functional biochemical assays. Functional assays are an essential component of inherited metabolic myopathy work-up. Genetic studies from the DNA extracted from muscle biopsy can be utilized to detect mutations in both genomic as well as mitochondrial DNA (mtDNA). RNA extracted from a muscle biopsy sample can be utilized to study gene expression at the mRNA level. Genetic studies can also be performed on DNA extracted from peripheral blood. However, in some cases, especially mitochondrial myopathies, mutated mtDNA is only found in muscle mitochondria and hence requires muscle mtDNA to be tested.