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APPROACH TO PATIENTS WITH NEUROMUSCULAR DISEASE
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Figure 3 15 Variability in muscle ber size, increased internalized nuclei, muscle ber splitting, and small intracytoplasmic vacuoles are nonspeci c myopathy features appreciated on this modi ed Gomori-trichrome stain
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Figure 3 17 Segmental necrosis is best appreciated on paraf n sections in which large, longitudinal segments can be visualized The striations of the sarcomeres can be appreciated in normal bers while the necrotic segment of an adjacent ber loses the striations The necrotic segment is invaded by macrophages Paraf n sections, H&E stain
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have a featureless ground-glass appearance Semithin and EM sections reveal degeneration of the Z disk and myo brillar network as well as abnormal mitochondria Macrophages are recruited into the area and in ltrate the necrotic segments in order to digest the disintegrating muscle tissue damaged tissue In certain diseases (polymyositis and inclusion body myositis), macrophages and lymphocytes may invade nonnecrotic tissue such that a muscle ber can be severed into distinct segments Repair of necrotic segments can occur and begins with the proliferation of adjacent satellite cells in the region of the destroyed portion of the ber19 The satellite
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cells align next to each other to form myotubes Several myotubes form per segment and adhere to the surrounding basal lamina The expansion of myotubes occurs laterally and longitudinally, eventually reaching and fusing with the healthy muscle tissue stumps The regenerating muscle bers can be appreciated by their large internalized nuclei with prominent nucleoli, and their basophilic cytoplasm that is laden with ribonucleic acid (RNA) (Fig 3 18) Old damage can be ascertained by the increase in the number of internalized nuclei (Fig 3 15) Myonuclei,
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Figure 3 16 A necrotic muscle ber is pale staining in comparison to surround muscle bers on H&E stain H&E stain
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Figure 3 18 Regenerating muscle bers are smaller and more basophilic than normal bers and contain enlarged nuclei sometimes with nucleoli, as these are very active in trying to replenish necessary muscle proteins H&E stain
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MUSCLE AND NERVE HISTOPATHOLOGY
which usually lie along the subsarcolemmal membrane, are more internalized in regenerated segments Other characteristics of myopathic injury include alterations in structural proteins or organelles, formation of vacuoles, and accumulation of intracytoplasmic deposits Increased endomysial connective tissue is a common feature of muscular dystrophies In ammatory cell in ltrates are seen in the different types of myositides but can also be seen in dystrophies and other types of myopathy and thus are not speci c for an immune-mediated process These various histopathologic abnormalities are discussed in more detail in subsequent chapters with the diseases in which these appear
other autoimmune in ammatory conditions (eg, sarcoidosis), possible infectious processes (eg, leprosy), and tumor in ltration (eg, lymphoma and leukemia) Also, a nerve biopsy may be required for diagnosis of a tumor of the peripheral nerve (eg, perineurioma) Less commonly, nerve biopsy may be warranted to diagnose uncommon forms of hereditary neuropathy when DNA testing is not available or is negative (eg, giant axonal neuropathy and polyglucosan body neuropathy)
TECHNIQUES
We usually biopsy a super cial sensory nerve that is clinically affected and also abnormal on sensory nerve conduction studies The most common nerve biopsied is the sural nerve We prefer to biopsy the sural nerve in the mid-shin approximately one-third to one-fourth of the distance from ankle to knee, as opposed to the lateral ankle itself where the nerve may be more prone to trauma and healing may not be as good (Fig 3 19) Patients should be warned that following the sural nerve biopsy, there is often pain for several months as well permanent loss of sensation on the lateral aspect of the ankle and foot20 A super cial peroneal nerve biopsy is particularly useful when vasculitic neuropathy is suspected because the underlying peroneus brevis muscle can also be biopsied through the same incision site, thereby increasing the diagnostic yield (Fig 3 20) Biopsy of the super cial peroneal nerve will lead to numbness of the dorsum of the foot and again often neuropathic pain for several months20 If only the upper extremities are involved, the super cial radial nerve can be biopsied; however, this leads to numbness of the dorsum of the hand, which is problematic for most patients Importantly, because of sampling error, the single small segment of distal sensory nerve may not be representative of focal disease processes elsewhere in the peripheral nervous system, especially in processes with predominant motor involvement On rare occasions when a patient has a multifocal process and the lesion appears proximal (eg, amyloidomas, in ammatory process, and tumors), a fascicular nerve biopsy of a lesion in the root, plexus, or proximal nerve may be required This procedure should only be performed, however, by neurosurgeons experienced in the technique and where the tissue can be processed appropriately in the neuropathology laboratory Nerve biopsies are performed under local anesthesia in adults; general anesthesia is often required to obtain an adequate specimen from children or when a proximal nerve segment needs to be biopsied (eg, root, plexus, or proximal nerve) Ideally, the pathology laboratory should be contacted in advance of the surgery so that the tissue can be picked up directly from the operating room and processed immediately Local
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