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Three transcription factors, Krox20 (EGR2), Oct6 (SCIP/Tst1) and Sox10, are considered necessary for transition from the nonmyelinating to the myelinating stage of Schwann cell development. We immunohistochemically studied Oct6 expression in peripheral nerve specimens from 25 patients with various diseases including Charcot-Marie-Tooth disease type 1A (CMT1A). Oct6 was present in cytoplasm of Schwann cells associated with normal-appearing myelinated nerve fibers, but not in nuclei. Expression was seen in nuclei of Schwann cells in the early phase of acute axonal degeneration; nuclear expression peaked at the regenerative stage. Schwann cells forming "onion bulbs" expressed Oct6 in chronic inflammatory demyelinating polyneuropathy (CIDP), but showed minimal expression in CMT1A, reflecting their proliferative activity in CIDP. Nerves showing chronic axonal loss had no expression. Oct6, then, may be a marker for dedifferentiation of adult Schwann cells and active nerve regeneration.

Immunocytochemical expression of tumor necrosis factor-alpha (TNF-alpha) was examined in nerve biopsy samples of patients with various disorders, focusing on nerve injury. TNF-alpha was mainly associated with phagocytosing macrophages in acute axonal injury, but the staining was more frequently seen in sections from patients with vasculitis than with metabolic neuropathy. Ramifield macrophages outside nerve fibers were also positive for TNF-alpha in the acute stage of vasculitis. In active demyelinating lesions from patients with chronic inflammatory demyelinating neuropathy (CIDP), macrophages outside nerve fibers showed weak staining with TNF-alpha, but the cells adhering to myelinated nerve fibers showed definite staining. This may be due, in part, to the smouldering course of CIDP, and expression may be up-regulated transiently during the demyelinating process. These results indicate that macrophages, as the effector cells for both axonal injury and active demyelination, express TNF-alpha, buth their activation mechanisms may vary among vasculitis, metabolic axonopathy and inflammatory demyelination.

We performed histochemical and ultrastructural studies on a sural nerve biopsy specimen obtained from a 31-year-old man with late-onset Krabbe's disease. Myelin sheaths were uniformly thin for the fiber diameter, with a moderate reduction in the myelinated fiber population. Despite a few small onion-bulb formations, quantitative studies demonstrated uniformly thin myelin sheaths and less variability in internodal lengths. This suggests that the main pathophysiology of the peripheral neuropathy observed in late-onset Krabbe's disease is hypomyelination rather than segmental demyelination as in infantile Krabbe's disease. Ultrastructurally, curvilinear lamellar cytoplasmic inclusions were observed in Schwann cells and fibroblasts.