Min Young Gi, Visentin Andrea, Briani Chiara, Rajabally Yusuf A
Department of Translational Medicine, Seoul National University College of Medicine, Seoul, The Republic of Korea.
Haematology Unit, Department of Medicine, University of Padova, Padova, Italy.
J Neurol Neurosurg Psychiatry. 2025 Mar 24;96(4):340-349. doi: 10.1136/jnnp-2024-334678.
Antimyelin-associated glycoprotein (MAG) neuropathy is a rare autoimmune demyelinating peripheral neuropathy caused by IgM autoantibodies targeting MAG. The typical presentation is that of a slowly progressive, distal, length-dependent, predominantly sensory, sometimes ataxic neuropathy, frequently accompanied by upper limb tremor. Distal motor weakness may subsequently occur. The clinical presentation may vary and rarely be consistent with that of typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), as well as have an aggressive and rapidly disabling course. The diagnosis of anti-MAG neuropathy is based on the detection of anti-MAG antibodies through ELISA or western blot analysis, primarily in presence of an IgM monoclonal gammopathy. Anti-MAG neuropathy may occur without or with haematological malignancy. Electrophysiology is characteristic of a predominantly distal demyelinating neuropathy. Intravenous immunoglobulins and plasma exchange have unproven benefits, but may provide short-term effects. Cytotoxic therapies are commonly used, although without an evidence base. Rituximab, an anti-B-cell monoclonal antibody was studied in two randomised controlled trials, neither of which achieved their primary outcome. However, a meta-analysis of these two studies demonstrated improvement of disability at 8-12 months. A recent trial with lenalidomide was interrupted prematurely due to a high rate of venous thromboembolism. There are currently two ongoing trials with Bruton's tyrosine kinase inhibitors. Symptom control is otherwise frequently needed. Outcome measures used for other inflammatory neuropathies present limitations in anti-MAG neuropathy. International registries such as the planned IMAGiNe study may, in future, provide answers to the many remaining questions.
抗髓鞘相关糖蛋白（MAG）神经病是一种罕见的自身免疫性脱髓鞘性周围神经病，由靶向MAG的IgM自身抗体引起。典型表现为缓慢进展的、远端的、长度依赖性的、以感觉为主的、有时伴有共济失调的神经病，常伴有上肢震颤。随后可能出现远端肌无力。临床表现可能有所不同，很少与典型的慢性炎症性脱髓鞘性多发性神经根神经病（CIDP）一致，也可能有侵袭性且迅速致残的病程。抗MAG神经病的诊断主要基于通过ELISA或蛋白质印迹分析检测抗MAG抗体，主要是在存在IgM单克隆丙种球蛋白病的情况下。抗MAG神经病可在无血液系统恶性肿瘤或伴有血液系统恶性肿瘤的情况下发生。电生理学表现为以远端脱髓鞘为主的神经病。静脉注射免疫球蛋白和血浆置换的益处尚未得到证实，但可能有短期效果。细胞毒性疗法虽无循证依据但常用。抗B细胞单克隆抗体利妥昔单抗在两项随机对照试验中进行了研究，但均未达到其主要结局。然而，对这两项研究的荟萃分析表明，在8至12个月时残疾情况有所改善。最近一项使用来那度胺的试验因静脉血栓栓塞发生率高而提前中断。目前有两项关于布鲁顿酪氨酸激酶抑制剂的试验正在进行。否则经常需要进行症状控制。用于其他炎性神经病的结局指标在抗MAG神经病中存在局限性。诸如计划中的IMAGiNe研究等国际注册研究未来可能会为许多悬而未决的问题提供答案。
