Progressive Centripetal Degeneration of Axons in Small Fibre Diabetic Polyneuropathy

Abstract

A clinicopathological study is presented of 5 patients with a pseudosyringomyelic dissociation of sensory loss and severe autonomic disturbances related to diabetic polyneuropathy. Sensory loss which followed a pattern that suggested a length-related degeneration of fibres was associated with spontaneous pains in 3 patients. Plantar ulcers and neurogenic arthropathies were also present in 3 patients. The pathological changes in sural nerve biopsies included a severe loss of unmyelinated and small myelinated axons which appeared to be involved earlier than larger myelinated fibres. Distal degeneration of single fibres with subsequent axonal sprouting from the proximal axon was demonstrated in all patients. This severe axonal neuropathy was associated with primary and secondary segmental demyelination. Our observations are consistent with a progressive centripetal degeneration of axons in predominantly sensory diabetic polyneuropathy.

Magnetic resonance neurography detects diabetic neuropathy early and with Proximal Predominance

“…In accord with the distal dominance of symptoms and signs, the longitudinal gradient of fiber loss along lower extremity nerve trunks is also directed from distal (where it is most severe) to proximal 4, 5, 6, 7, 9. Such a distally marked reduction in fiber density appears not only in sural nerve biopsies, but also in skin punch biopsies, which reveal the density of cutaneous innervation by small fibers (intraepidermal nerve fiber density; IENF).…”

“…It is generally agreed that fiber loss in lower extremity peripheral nerves is the most prominent histological fingerprint of DPN and involves large myelinated and/or small fibers 3, 4, 5, 6, 7, 8, 9. In accord with the distal dominance of symptoms and signs, the longitudinal gradient of fiber loss along lower extremity nerve trunks is also directed from distal (where it is most severe) to proximal 4, 5, 6, 7, 9.…”

“…One view holds that axons degenerate “centripetally” or in a “dying‐back” fashion (ie, from distal to more proximal levels) 9, 17. This concept is mainly based on fascicular biopsies taken from distal sural nerves at the ankle level.…”

“…One important aspect of DPN pathogenesis that remains poorly understood is the spatiotemporal distribution and propagation of microstructural nerve alteration. The most prominent histological fingerprint of DPN is a distally dominant, mixed axonal loss involving all types of nerve fibers 3, 4, 5, 6, 7, 8, 9. However, where along the lower extremity peripheral nerves, including their terminal fibers, and the microvascular and/or metabolic pathologic mechanisms by which axon structure degeneration occurs first remain controversial issues.…”

“…However, where along the lower extremity peripheral nerves, including their terminal fibers, and the microvascular and/or metabolic pathologic mechanisms by which axon structure degeneration occurs first remain controversial issues. One view holds that early axon degeneration occurs distally 9. Accordingly, the term dying‐back degeneration has been coined to reflect this assumption that primary/early structural degeneration occurs with distal predominance and propagates over time from distal to more proximal levels.…”