Prospective evaluation of somatic and autonomic small fibers in selected autonomic neuropathies

Background: There are a number of distal and generalized small-fiber neuropathies. The neuropathologic basis is poorly understood as somatic and autonomic C fibers are not usually studied in the same region of the body. Objective: To evaluate prospective somatic and autonomic C-fiber function in 11 healthy control subjects and 38 patients with different clinical patterns of neuropathy. Methods: Distal small-fiber neuropathy (DSFN), peripheral neuropathy (PN), diabetic neuropathy (DN), neuropathic postural tachycardia syndrome (POTS), and idiopathic autonomic neuropathy (IAN) were evaluated. Intraepidermal nerve fiber density was used to evaluate distal somatic C fibers. Both quantitative sudomotor axon reflex test and skin norepinephrine content were measured for the biopsy site to assess distal autonomic C-fiber function. Postganglionic sudomotor, adrenergic, and cardiovagal functions were evaluated by autonomic reflex testing and quantified using a-Composite Autonomic Severity Scale. Results: Skin norepinephrine concentration was significantly related to CASS. DN was associated with somatic and autonomic C-fiber impairment with good agreement. POTS was associated with selective distal autonomic deficit. DSFN had combined distal somatic and C-fiber impairment. IAN showed combined and selective distal and generalized autonomic C-fiber impairment. The somatic neuropathies had C-fiber impairment affecting both populations to varying degrees. Conclusion: Although a general agreement exists between the loss of somatic C fibers and autonomic deficits, selective involvement occurs for specific autonomic neuropathies.