Table of Contents
Washington University Experience | MUSCLE | Myopathies with Mitochondrial Pathology | 18E1 Case 18 Denoument
Comment: The mitochondria in this paraspinal muscle biopsy are quite abnormal in numbers, shapes and paracrystalline parking lot inclusions. In appendicular deltoid muscle such accumulation would suggest mitochondrial myopathy and presage dysfunction in enzyme activity or mitochondrial genome changes. However, the fact that this specimen is a paraspinal muscle tempers the interpretation. Our examination of the deltoid muscle in this case performed at the same time and processed together showed significantly less mitochondrial pathology and, in particular, no parking lot inclusions. Studies of the current case performed in the neuromuscular laboratory showed that mitochondrial cytochrome oxidase and SDH activities/histochemistry are reduced and increased, respectively, in the paraspinal muscle and not in the deltoid muscle biopsy. Scattered ragged red fibers were seen in the paraspinal muscle on Gomori trichrome stain. From past experience the mitochondrial changes seen here would appear excessive from aging alone and we think these findings suggested genuine pathology; however, the lack of deltoid muscle patthology muddies the interpretation. Paraspinal muscle fibers represent a different population from appendicular muscle (Fiber type I rich oxidative slow twitch fibers vs glycolytic fiber type 2 rich). Because the paraspinal muscles are richer in Type I (slow-twitch) fibers, they naturally have a higher baseline mitochondrial density than the type 2 fast-twitch-dominant muscles found in more balanced numbers in parts of the limbs. Studies have shown that paraspinal muscle fibers have abnormal numbers of mitochondria and abnormal shapes as patients age. Paraspinal muscles appear to be more prone to mitochondrial respiratory chain defects with aging compared to limb muscles. The density of respiratory-deficient fibers (fibers that cannot produce energy efficiently) in paraspinal muscles is significantly higher than what has been reported in control limb muscles. A subpopulation of respiratory-deficient fibers in paraspinal muscles are caused by clonally expanded mitochondrial DNA (mtDNA) deletions. An additional subpopulation of these deficient fibers is linked to a depletion of the total amount of mitochondrial DNA. When paraspinal muscles are affected by conditions like chronic low back pain, disc herniation, or scoliosis, their EM appearance reveals significant deviations from healthy skeletal muscle: (see PMID: 22762368 and the neuromuscular website (https://neuromuscular.wustl.edu/) ---- Not shown: A paraspinal cytochrome oxidase preparation shows a number of fibers with reduced or absent staining. SDH shows fibers with increased staining. The end stage (Trapezius) muscle cytochrome oxidase and SDH is normal. Cytochrome oxidase and SDH are normal in the deltoid muscle.
