Causes and Implications of Isolated Small Fiber Neuropathy

Peripheral neuropathy is a highly prevalent condition that leads to significant morbidity.1 Usually, length-dependent nerve damage occurs to both large- and small-diameter axons. Damage to large fiber nerves can result in numbness, tingling, poor balance, or weakness, leading to an increased fall risk. The neurologic examination shows abnormalities in vibration, proprioception, deep tendon reflexes, and strength. In contrast, damage to small-diameter lightly myelinated or unmyelinated fibers can result in paresthesias, neuropathic pain, and autonomic symptoms. Abnormalities on neurologic examination are often less pronounced, with changes in pinprick and temperature sensation or allodynia. Electrodiagnostic tests have long been available and provide the gold standard to quantify large fiber function, but they are unable to assess for small fiber involvement. Limitations of electrodiagnostic testing and limited examination findings may be the reason that neurologists have focused primarily on neuropathies with mixed or large fiber involvement. A more recent diagnostic procedure, 3-mm punch skin biopsies analyzed for nerve fiber density in the epidermis, quantifies distal small fiber nerve injury and has led to a new focus on isolated small fiber neuropathy (SFN).

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