Abstract

Most peripheral neuropathies involve large as well as small-fiber dysfunction. A small subset of neuropathies present with restricted or predominant small-fiber involvement. In this review, we discuss the differential diagnosis, clinical presentation, evaluation, and treatment of small-fiber neuropathies. Although these neuropathies are rare, their differential diagnosis is broad, and includes many disorders, including metabolic, toxic, inflammatory, infectious, and genetic etiologies. As small fibers subserve pain and autonomic functions, these neuropathies usually present with pain and temperature loss, painful dysesthesias, autonomic dysfunction, or a combination. These neuropathies are especially challenging as nerve conductions and EMG, which help guide the evaluation of most peripheral neuropathies, may have normal findings in patients with small-fiber neuropathies. Other specialized studies, including tests of autonomic function, intraepidermal nerve fiber analysis, and quantitative sensory testing, are often required to confirm the presence of a small-fiber neuropathy. In some cases, the underlying etiology can be directly treated. In most, management is limited to symptomatic treatment of sensory and autonomic dysfunction. Small-fiber neuropathies are a heterogeneous group of disorders. They vary in etiologies and require special attention, as many disorders are rare and the differential diagnosis is broad. Evaluation is often extensive and may need pathologic specimen. Many patients respond to symptomatic therapy, but some are difficult to treat.

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