Sural Nerve Morphometry in Diabetic Autonomic and Painful Sensory Neuropathy

Abstract

Observations have been made on a selected series of insulin-dependent patients with neuropathy, subdivided into three groups: (1) severe autonomic neuropathy with an accompanying painless sensory neuropathy; (2) severe autonomic neuropathy with a chronic painful sensory neuropathy; and (3) chronic or acute painful sensory neuropathy with no autonomic neuropathy. All three groups showed a loss of large and small myelinated nerve fibres in sural nerve biopsy specimens which was greater in Groups 1 and 2. Regenerative activity was prominent in all three groups, but least in Group 3. Teased fibre studies showed evidence both of axonal regeneration and remyelination. Active fibre degeneration was rare. Measurements of g ratio (axon diameter:total fibre diameter) gave no indication of axonal atrophy. The density of unmyelinated axons was reduced in all three groups, as was their median diameter. Vibration sense threshold was positively correlated with the total number of myelinated fibres and thermal sensory threshold with median unmyelinated axon diameter but not with total unmyelinated axon numbers. No correlation between the occurrence of pain and active degeneration of myelinated fibres or with regenerative activity either in myelinated or unmyelinated axons was detectable. Assessment of differential loss of large or small myelinated nerve fibres was difficult because of the presence of large numbers of small regenerating myelinated axons. The results are discussed in relation to the concept of 'diabetic small fibre neuropathy' and the causation of pain in diabetic neuropathy.

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 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.…”

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

“…Alterations in nerve conduction velocity and amplitude have been considered to reflect underlying structural pathology of the myelinated fibres [30]. Such pathology includes demyelination and a significant loss of myelinated fibres due to axonal degeneration [9,10]. In addition axonal atrophy and axo-glial dysjunction have also been demonstrated in some [31,32] but not in other [20,21,33] studies.…”

“…Detailed neurophysiological studies in diabetic patients have shown that demyelination precedes axonal loss and that the latter may be responsible for the symptoms [8]. Whilst studies in patients with established neuropathy demonstrate a combination of demyelination and axonal degeneration of myelinated fibres and degeneration with regeneration of unmyelinated fibres [9][10][11] and endoneurial microangiopathy [12][13][14][15], the early pathological features of patients with diabetic neuropathy are not clearly defined.…”