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. 2021 Dec 14;97(24):e2392–e2403. doi: 10.1212/WNL.0000000000012932

Figure 2. Interstitial Histologic Alternations in NF155-IgG4-Positive and NF155-IgG-Positive (IgG4-Negative) Patients.

Figure 2

Representative photomicrographs from neurofascin-155 (NF155)–immunoglobulin G4 (IgG4) (A–F) and NF155–immunoglobulin G (IgG) (G–H) patients. Semithin epoxy sections (methylene blue) from a sural nerve biopsy show myelinated nerve fiber loss, active axonal degeneration, and slight multifocality. Sections B–F are taken from a targeted fascicular sciatic nerve biopsy of a 53-year-old man, NF155-IgG4-positive, with rapid onset of numbness, sensory and cerebellar ataxia, cranial nerve involvement, dysarthric speech, tremor, and pseudoathetosis, who was refractory to IV immunoglobulin (IVIg) treatment. However, with prolonged ongoing (several times per week) plasma exchange, he had dramatic recovery and regained independence and ability to ambulate. Semithin epoxy section (methylene blue) (B) shows subperineural edema and reduced density of myelinated nerve fibers with degenerating profiles (mild to moderate degree). Serial paraffin cross-sections (C–F) show a large perineurial inflammatory cell collection on hematoxylin & eosin (C) and on CD-45 (D) that was positive for T cells (CD3) (E) and B cells (CD20) (F). Photomicrographs G and H come from a 35-year-old man with progressive chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and progressive onset of proximal more than distal weakness with falls who was NF155-IgG-positive (NF155-IgG4-negative). He initially was responsive to IVIg but over 3 years required increasing IVIg doses and was not helped with rituximab, and worsened with plasma exchange. (G) Teased nerve fiber preparations show chronic de- and remyelination with onion bulbs formations (arrows) and tomaculae (myelin reduplication, Asterix) as well as active axonal degeneration (arrowheads). (H) Methylene blue epoxy section shows the mixed pattern of onion bulbs (moderate sized onion bulbs interspersed among myelinated fibers without onion bulb), the typical pattern seen in inflammatory demyelinating neuropathies (CIDP). These findings show the different pathologic patterns seen in NF155-IgG4 (no onion bulbs) compared to non NF155-IgG4 disease (frequent onion bulb formations).