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It is well known that transthyretin-related familial amyloidotic polyneuropathy (TTR-FAP) and diabetic peripheral neuropathy are characterized by early selective involvement of small nerve fibers. However, early diagnosis of these diseases is not easy because prominent early diagnostic markers for small fiber neuropathies have not established. Thus, we adopted several methods to evaluate autonomic function accurately for detecting the onset of small-fiber neuropathy, such as laser-Doppler flowmetry, sweating tests using capsule type sweating ratemeter, morphological check of sweat gland, electrogastrography, density check of small-fiber and gastrointestinal interstitial cells of Cajal, R-R interval study, (123)I-MIBG myocardial scintigraphy, and head-up tilt test to check the overshoot phenomenon. These tests may indicate very early stage of small-fiber neuropathies in asymptomatic mutated TTR carriers or impaired glucose tolerance patients. Moreover, assessment of the pain thresholds by preferential stimulation of C and Aδ fibers are particularly useful tools for diagnosing the onset of small-fiber neuropathies in addition to the autonomic testing.

Diagnosis of small-fiber neuropathy using various autonomic function tests.