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).

周围神经病变是一种非常普遍的疾病，会导致显着的发病率。¹通常，大直径和小直径轴突都会发生长度依赖性神经损伤。大纤维神经受损会导致麻木、刺痛、平衡不良或虚弱，从而增加跌倒风险。神经系统检查显示振动、本体感觉、深腱反射和力量异常。相比之下，小直径轻度有髓或无髓纤维的损伤可导致感觉异常、神经性疼痛和自主神经症状。神经系统检查的异常通常不太明显，有针刺和温度感觉或异常性疼痛的变化。电诊断测试早已可用并提供量化大纤维功能的金标准，但它们无法评估小纤维的参与。电诊断测试的局限性和有限的检查结果可能是神经科医生主要关注混合或大纤维受累的神经病的原因。最近的诊断程序，3 毫米穿孔皮肤活检分析了表皮中的神经纤维密度，量化了远端小纤维神经损伤，并导致了对孤立性小纤维神经病变 (SFN) 的新关注。