Figure 5. Loss of Large Myelinated Fibers and Onion-Bulbs in Limb Nerves of Chronic Immune Sensory Polyradiculopathy (CISP)–Plus.

Nerve biopsies (A.a, B.a, C.a, D.a) taken from proximal and distal limb nerves from a normal control (A) and from 3 patients with CISP-plus (B–D) and their corresponding myelinated fiber histograms (A.b, B.b, C.b, D.b). The biopsies are methylene blue–stained epoxy sections. All CISP-plus biopsies have reduced numbers of large myelinated fibers and a unimodal size distribution with a small fiber peak at about 3.5 μm on the histograms. (A) Normal control sural nerve shows normal myelinated fiber density (MF) and bimodal size distribution (with peaks at 3.5 μm and 9 μm). CISP-plus biopsies of sural (B) and superficial radial nerves (C) show increased regenerating nerve clusters in (C) (arrowheads). (D) CISP-plus fascicular sciatic nerve biopsy shows occasional onion-bulb formations (arrows). The CISP-plus nerve biopsies demonstrate that large myelinated fiber loss and onion-bulb formation are not restricted to the sensory root level (as in CISP) but extend to more distal nerves to a lesser degree. Morphologic analysis for 2 fascicular sciatic biopsies showed the mean MF was 6,656/mm² (6,742 and 6,570/mm²), for the superficial radial biopsy the MF was 9,153/mm², and for 5 sural nerve biopsies the mean MF was 5,724/mm² (SD ± 1,864/mm²). Individual sural densities were 4,107, 4,413, 5,114, 6,280, and 8,706/mm²; 4 of the sural nerves were mildly reduced (4,000–6,500/mm²) and 1 was normal (6,500–13,000/mm²) per our laboratory MF density values.