Myovascular innervation: axon loss in small-fiber neuropathies.

Abstract

Vascular denervation occurs in some neuropathies, but measurement of small perivascular axons has been difficult. We evaluated 31 consecutive patients who had both muscle and skin biopsies. We quantitated myovascular innervation by staining unmyelinated axons with peripherin and non-myelinating Schwann cells with neural cell adhesion molecule and comparing their areas. Perivascular unmyelinated axon-Schwann (UAS) ratios correlated with axon density in skin (r = 0.679; P < 0.0001). Low UAS ratios (≤0.25) had a sensitivity of 90% and specificity of 91% for a clinical diagnosis of small-fiber neuropathy (P < 0.0001). Autonomic features were more common in patients with low perivascular UAS ratios (P = 0.002). A patient subgroup with myovascular, but not skin, denervation commonly had muscle discomfort and autonomic features. UAS ratio measurements, comparing axons and associated non-myelinating Schwann cells, can quantitate perivascular innervation. Small-fiber neuropathies are often associated with myovascular denervation. Some patients with muscle discomfort have selective myovascular denervation.