Myovascular innervation: Axon loss in small-fiber neuropathies

Introduction: Vascular denervation occurs in some neuropathies, but measurement of small perivascular axons has been difficult. Methods: 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. Results: 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. Conclusions: 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.