抗 MAG 神经病:历史沿革、临床病理相关性以及未来治疗试验的考虑因素。

IF 1 4区 医学 Q4 NEUROSCIENCES
Arquivos de neuro-psiquiatria Pub Date : 2024-06-01 Epub Date: 2024-02-07 DOI:10.1055/s-0043-1777728
Norman Latov, Thomas H Brannagan, Howard W Sander, Francisco de Assis Aquino Gondim
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引用次数: 0

摘要

背景:抗MAG神经病变患者表现为远端脱髓鞘性多发性神经病变、IgM单克隆丙种球蛋白病和抗MAG抗体滴度升高:本文回顾了抗 MAG 神经病的临床表现、病程、病理生理学和治疗方法,并对治疗试验的设计进行了思考:方法:回顾与抗MAG神经病变相关的医学和科学文献,以及外周神经病变治疗性临床试验的设计:结果:抗-MAG神经病可在多年内保持不发作,但随后会进入进展期。抗体滴度的高度升高具有诊断意义,但在慢性炎症性脱髓鞘性多发性神经病(CIDP)中也会出现中等滴度的抗体。周围神经会变得不兴奋,从而掩盖脱髓鞘异常。有充分证据表明,抗 MAG 抗体会导致神经病变。据报道,通过针对 B 细胞的药物降低自身抗体浓度,可在病例系列和非对照试验中改善临床症状,但在对照临床试验中却没有改善,这可能是由于试验设计不当所致:我们建议抗 MAG 神经病的治疗试验应包括具有典型表现、一定程度的乏力、抗 MAG 抗体滴度高度升高以及至少有一根神经出现脱髓鞘范围异常的患者。使用一种或多种抗 B 细胞药物进行治疗的目的是将自身抗体浓度降低至少 60%。可能需要进行为期两年的试验才能显示疗效。下肢神经病变损伤评分(NIS-LL)和下肢功能评分(LLF)将是一个合适的主要结果衡量指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anti-MAG neuropathy: historical aspects, clinical-pathological correlations, and considerations for future therapeutical trials.

Background:  Patients with anti-MAG neuropathy present with distal demyelinating polyneuropathy, IgM monoclonal gammopathy, and elevated titers of anti-MAG antibodies.

Objective:  This paper reviews what is known about the clinical presentation, course, pathophysiology, and treatment of anti-MAG neuropathy, with considerations for the design of therapeutic trials.

Methods:  A literature review of the medical and scientific literature related to anti-MAG neuropathy, and the design of therapeutic clinical trials in peripheral neuropathy.

Results:  Anti-MAG neuropathy can remain indolent for many years but then enter a progressive phase. Highly elevated antibody titers are diagnostic, but intermediate titers can also occur in chronic inflammatory demyelinating polyneuropathy (CIDP). The peripheral nerves can become inexcitable, thereby masking the demyelinating abnormalities. There is good evidence that the anti-MAG antibodies cause neuropathy. Reduction of the autoantibody concentration by agents that target B-cells was reported to result in clinical improvement in case series and uncontrolled trials, but not in controlled clinical trials, probably due to inadequate trial design.

Conclusion:  We propose that therapeutic trials for anti-MAG neuropathy include patients with the typical presentation, some degree of weakness, highly elevated anti-MAG antibody titers, and at least one nerve exhibiting demyelinating range abnormalities. Treatment with one or a combination of anti-B-cell agents would aim at reducing the autoantibody concentration by at least 60%. A trial duration of 2 years may be required to show efficacy. The neuropathy impairment score of the lower extremities (NIS-LL) plus the Lower Limb Function (LLF) score would be a suitable primary outcome measure.

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来源期刊
Arquivos de neuro-psiquiatria
Arquivos de neuro-psiquiatria 医学-精神病学
CiteScore
2.10
自引率
7.10%
发文量
262
审稿时长
4-8 weeks
期刊介绍: Arquivos de Neuro-Psiquiatria is the official journal of the Brazilian Academy of Neurology. The mission of the journal is to provide neurologists, specialists and researchers in Neurology and related fields with open access to original articles (clinical and translational research), editorials, reviews, historical papers, neuroimages and letters about published manuscripts. It also publishes the consensus and guidelines on Neurology, as well as educational and scientific material from the different scientific departments of the Brazilian Academy of Neurology. The ultimate goals of the journal are to contribute to advance knowledge in the areas of Neurology and Neuroscience, and to provide valuable material for training and continuing education for neurologists and other health professionals working in the area. These goals might contribute to improving care for patients with neurological diseases. We aim to be the best Neuroscience journal in Latin America within the peer review system.
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