Myelinated and unmyelinated endoneurial axon quantitation and clinical correlation

Introduction: Different disease patterns result from loss of myelinated and unmyelinated axons, but quantitation to define their loss has been difficult. Methods: We measured large and small endoneurial axons in axonal neuropathies by staining them with peripherin and comparing their area to that of nonmyelinating Schwann cells stained with neural cell adhesion molecule (NCAM). Results: Loss of myelinated and unmyelinated axons was typically proportional, with predominant myelinated or unmyelinated axon loss in a few patients. Myelinated axon loss was associated with loss of distal vibration sense and sensory potentials (P<0.0001) and was selective in patients with bariatric and bowel resection surgery (P<0.001). Unmyelinated axon measurements correlated with skin (ankle P=0.01; thigh P=0.02) and vascular (nerve P<0.0001; muscle P=0.01) innervation. Conclusions: Myelinated and unmyelinated axons can be quantitated by comparing areas of axons and nonmyelinating Schwann cells. Clinical features correlate with myelinated axon loss, and unmyelinated axon loss correlates with skin and vascular denervation.