Pediatric Nerve Biopsy Diagnostic and Treatment Utility in Tertiary Care Referral  Cristiane M. Ida, MD, Peter J. Dyck, MD, P. James B. Dyck, MD, Janean K. Engelstad, HT, Wei Wang, MD, Duygu Selcen, MD, John B. Bodensteiner, MD, Michelle L. Mauermann, MD, Christopher J. Klein, MD  Pediatric Neurology  Volume 58, Pages 3-11 (May 2016) DOI: 10.1016/j.pediatrneurol.2016.01.021 Copyright © 2016 Terms and Conditions

Figure 1 Illustrative case 1 where unsuspected large arteriole vasculitis was found on nerve biopsy. Osmium-stained teased nerve fiber preparation demonstrated fibers with axonal degeneration (A). Paraffin-embedded trichrome-stained sections showed large collections of epineural perivascular inflammatory mononuclear cells associated with vessel wall fibrinoid necrosis and intraluminal thrombus (B). Epoxy-embedded methylene blue-stained semithin sections revealed moderate multifocal decrease in myelinated fiber density, which was more prominent in the center of the fascicle (central fascicular degeneration) (C). Pediatric Neurology 2016 58, 3-11DOI: (10.1016/j.pediatrneurol.2016.01.021) Copyright © 2016 Terms and Conditions

Figure 2 Illustrative case 2 where chronic inflammatory demyelinating polyradiculoneuropathy was thought more likely than an inherited demyelinating process based on the nerve biopsy findings. Osmium-stained teased nerve fiber preparation demonstrates fibers with demyelinating segments (A). Paraffin-embedded immunoreaction to lymphocytes (CD-45) showing endoneurial paravascular inflammatory infiltrates (B). Epoxy-embedded methylene blue-stained semithin sections revealed subperineurium edema (C) and thinly myelinated fibers with multifocal onion bulbs (D). Pediatric Neurology 2016 58, 3-11DOI: (10.1016/j.pediatrneurol.2016.01.021) Copyright © 2016 Terms and Conditions

Figure 3 Illustrative case 3 of an idiopathic hypertrophic brachial plexopathy where fascicular targeted biopsy led to the diagnosis of a benign tumor, i.e., perineurioma. (A) Paraffin-embedded hematoxylin and eosin- and (B) epoxy-embedded methylene blue-stained sections revealed loss of normal fascicular architecture with virtually all fibers surrounded by concentric layers of cells forming tightly packed whorls that were immunoreactive to epithelial membrane antigen immunostain (C) and negative for S-100 immunostain (D). Pediatric Neurology 2016 58, 3-11DOI: (10.1016/j.pediatrneurol.2016.01.021) Copyright © 2016 Terms and Conditions

Figure 4 Illustrative case 4 where immune treatable versus inherited demyelinating polyneuropathy was considered, with biopsy supporting an inherited form and eventual DNA discovery of a causal PMP22 point mutation. Epoxy-embedded methylene blue-stained semithin sections revealed fascicles with diffuse onion-bulb formations characterized by multiple circumferential layers of Schwann cell processes surrounding fibers with abnormally thin myelin, without evidence of inflammation. Pediatric Neurology 2016 58, 3-11DOI: (10.1016/j.pediatrneurol.2016.01.021) Copyright © 2016 Terms and Conditions

Figure 5 Illustrative case 5 where acquired versus inherited neuropathy was considered, with nerve biopsy identifying giant axons leading to genetic testing for causal GAN DNA mutation. Osmium-stained teased nerve fiber preparation demonstrated fibers with homogenous axonal swellings (A). Epoxy-embedded methylene blue-stained semithin sections revealed axonal swellings with homogenous material involving large and small myelinated fibers characteristic of giant axons (B). Electron micrographs showed collections of densely packed neurofilaments, large dark collections within axon surrounded by thinner myelin (C,D). Pediatric Neurology 2016 58, 3-11DOI: (10.1016/j.pediatrneurol.2016.01.021) Copyright © 2016 Terms and Conditions