Histopathological features of peripheral nerve and muscle in mitochondrialdisease

Despite enormous strides in the molecular diagnosis of mitochondrial diseas e, this approach is currently applicable to only a minority of patients who are affected with these disorders. The phenotypic spectrum in this categor y of disease is large and, in the absence of genotypic confirmation, a patt ern recognition paradigm is probably the most sensitive means to reinforce the suspicion of mitochondrial disease. Along with clinical, biochemical, r adiographic, and electrophysiological markers, histopathological features f rom nerve and muscle biopsy are useful indices to factor into a complex equ ation permitting a presumptive diagnosis or to justify more elaborate diagn ostic undertakings. The combination of electrophysiological evidence of dem yelinating neuropathy on nerve conduction studies and mild myopathic featur es on electromyography is one such constellation that should instigate a hi gh index of suspicion for mitochondrial disease. The histopathological hall marks of mitochondrial cytopathies on muscle biopsy are the "ragged-red fib er" on light level evaluation and paracrystalline inclusions at the electro n microscopic level. Neither of these is exclusive to mitochondrial disease and both may be identified among other nonspecific changes seen in biopsy specimens. Histopathological evaluation of muscle and nerve can provide inf ormation to reinforce the likelihood of mitochondrial disease or to indicat e an alternative diagnosis as the more probable cause of a patient's sympto ms.