Neuropathy A Review

Michelle L. Mauermann, MD1; Nathan P. Staff, MD, PhD1

2025년 11월 17일

JAMA Published Online: November 17, 2025

DOI: 10.1001/jama.2025.19400

Abstract

Importance  Peripheral neuropathy, defined as damage to peripheral nerves, affects approximately 1% of adults worldwide. More than 200 causes of peripheral neuropathy exist, with symptoms ranging in severity from mild toe numbness to debilitating symptoms that can require a wheelchair. Diabetes is the most common cause of neuropathy, affecting approximately 206 million people worldwide.

Observations   Peripheral neuropathy is typically length-dependent, which means that symptoms appear in the longest nerve axons (toes) and progress proximally over time. Peripheral neuropathy is typically symmetric and affects sensory axons more than motor axons. Diabetic neuropathy, which is often associated with both sensory symptoms, such as pain, tingling, or numbness; mild weakness; and autonomic symptoms, such as orthostatic hypotension, accounts for more than 50% of peripheral neuropathy in Western populations. Other causes of neuropathy include hereditary causes, such as Charcot-Marie-Tooth disease, toxic neuropathy from medications (chemotherapies [eg, cisplatin, paclitaxel, vincristine], amiodarone, or HIV nucleotide reverse transcriptase inhibitors [eg, stavudine, zalcitabine]); alcohol; vitamin deficiencies such as vitamin B₁₂; and monoclonal gammopathies. Up to 27% of adults with neuropathy have no identifiable etiology for their neuropathy after diagnostic testing. Recommended initial testing includes blood glucose (for diabetes), serum B₁₂ with metabolites (methylmalonic acid with or without homocysteine), and serum protein electrophoresis with immunofixation (for monoclonal gammopathies). First-line medications for neuropathic pain are the α2-δ calcium channel subunit ligands, such as gabapentin and pregabalin; serotonin norepinephrine reuptake inhibitors, such as duloxetine and venlafaxine; and tricyclic antidepressants, such as amitryptyline and nortriptyline. Pain often persists despite medical management. At least a 50% reduction in pain was observed in 38% of those with painful diabetic peripheral neuropathy receiving 1200 mg of gabapentin daily. Combination drug therapies for neuropathic pain may provide added benefit. The prognosis of peripheral neuropathy depends on its underlying cause, but complete reversal of nerve damage is uncommon even in cases for which there are available treatments.

Conclusions and Relevance    Peripheral neuropathy affects approximately 1% of adults worldwide and may cause sensory, motor, and autonomic symptoms. Diabetes is the most common cause of peripheral neuropathy in Western countries. First-line therapies for neuropathic pain include gabapentin, pregabalin, duloxetine, and amitriptyline.

Figure 1.  Anatomic Basis for Peripheral Neuropathy Symptoms

Figure 2.  Diagnostic Algorithm for Peripheral Neuropathy

요약

·         중요성   말초신경병증은 말초신경의 손상으로 정의되며, 전 세계 성인의 약 1%에서 발생한다. 말초신경병증에는 200가지가 넘는 원인이 존재하며, 증상은 경미한 발가락 저림부터 휠체어가 필요할 정도의 심각한 장애까지 다양하다. 당뇨병은 가장 흔한 원인이며, 전 세계 약 2억 600만 명의 사람들에게 영향을 미친다.

·         관찰  말초신경병증은 일반적으로 길이 의존적(length-dependent) 양상을 보이며, 이는 가장 긴 신경축삭(발가락)에서 증상이 먼저 나타나 시간이 지나면서 몸쪽으로 진행하는 것을 의미한다. 말초신경병증은 대체로 대칭적이며, 감각신경 축삭이 운동신경 축삭보다 더 많이 영향을 받는다.

당뇨병성 신경병증은 통증, 저림, 무감각과 같은 감각 증상뿐 아니라 경미한 근력저하, 기립성 저혈압과 같은 자율신경 증상을 특징으로 하며, 서구 지역 말초신경병증의 50% 이상을 차지한다. 그 외 원인으로는 샤르코-마리-투스병과 같은 유전성 질환, 약물(항암제: 시스플라틴, 파클리탁셀, 빈크리스틴 / 아미오다론 / HIV 역전사효소 억제제(스타부딘, 잘시타빈))에 의한 독성 신경병증, 알코올, 비타민 B12 결핍, 단클론 감마병증 등이 있다.

성인의 최대 27%에서는 진단 검사를 시행해도 원인을 찾을 수 없다. 권고되는 초기 검사는 혈당(당뇨병 확인), 혈중 비타민 B12 및 대사산물(메틸말론산 ± 호모시스테인), 단클론 감마병증을 확인하기 위한 혈청 단백 전기영동 및 면역고정검사이다.

신경병증  통증의 1차 치료약물은 α2-δ 칼슘채널 서브유닛 리간드(가바펜틴, 프레가발린), 세로토닌-노르에피네프린 재흡수 억제제(둘록세틴, 벤라팍신), 삼환계 항우울제(아미트립틸린, 노르트립틸린)이다.약물 치료에도 불구하고 통증이 지속되는 경우가 흔하다. 하루 1200 mg의 가바펜틴을 복용한 통증성 당뇨병성 말초신경병증 환자의 38%에서 통증이 50% 이상 감소한 것으로 보고되었다. 약물 병용요법은 추가적인 이득을 제공할 수 있다.말초신경병증의 예후는 원인 질환에 따라 달라지지만, 치료가 가능한 원인이라 하더라도 신경 손상이 완전히 회복되는 경우는 드물다.

·         결론 및 임상적 의의   말초신경병증은 전 세계 성인의 약 1%에서 발생하며 감각, 운동, 자율신경 증상을 유발할 수 있다. 서구 국가에서 당뇨병은 말초신경병증의 가장 흔한 원인이다. 신경병증 통증의 1차 치료는 가바펜틴, 프레가발린, 둘록세틴, 아미트립틸린이다.