Nobile-Orazio Eduardo, Bianco Mariangela, Nozza Andrea
Neuromuscular and Neuroimmunology Service, Department of Medical Biotechnology and Translational Medicine, Humanitas Clinical and Research Institute, Milan University, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
Department of Medical Oncology and Haematology, Humanitas Cancer Center, Humanitas Clinical and Research Institute, IRCCS, Rozzano, Milan, Italy.
Curr Treat Options Neurol. 2017 Oct 16;19(12):43. doi: 10.1007/s11940-017-0479-9.
Purpose of review Several advances have been made on the pathogenesis and therapy of neuropathies associated with paraproteinemia (monoclonal gammopathy). It is important for the neurologist to understand the pathogenetic relevance of this association especially when the hematological disease does not require per se any therapy. Recent findings Treatment of the neuropathy in patients with malignant paraproteinemia is mainly addressed by the hematologist while the neurologist is mainly involved in the initial diagnosis and in deciding whether the neuropathy is caused by the disease or by the chemotherapy used for the disease. There is little evidence that the neuropathy is caused by the hematological condition in patients with IgG or IgA monoclonal gammopathy of undetermined significance (MGUS) unless there is an evidence of a reactivity of the paraprotein with nerve or evidence of its presence in the nerve. Patients with a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)-like presentation should be treated as CIDP while there is no evidence that immune or chemotherapy may be effective in the other patients. In most patients with IgM paraproteinemia, that is usually a MGUS or an indolent Waldenström's macroglobulinemia, the neuropathy is induced by an immune reactivity of the paraprotein with nerve and particularly with the myelin-associated glycoprotein. There are now consistent data also from controlled studies that the anti-CD20 monoclonal antibody rituximab may improve the neuropathy in these patients. POEMS syndrome is a severe condition characterized by a disabling neuropathy whose prognosis has improved in the last few years with therapies against the proliferating plasma cell clone or vascular endothelial growth factor including local radiotherapy and chemotherapy followed by autologous stem cell transplantation. Other therapies are also available for patients not eligible or resistant to transplantation, including lenalidomide and possibly thalidomide or bortezomib. Summary Several new therapies are now available for patients with paraproteinemic neuropathy consistently improving the prognosis of these neuropathies. In most instances, however, their efficacy needs to be confirmed in controlled trials.
综述目的 与副蛋白血症（单克隆丙种球蛋白病）相关的神经病变的发病机制和治疗方面已取得了多项进展。对于神经科医生而言，了解这种关联的发病机制相关性非常重要，尤其是当血液系统疾病本身不需要任何治疗时。最新发现 恶性副蛋白血症患者神经病变的治疗主要由血液科医生负责，而神经科医生主要参与初始诊断以及判断神经病变是由疾病本身还是用于治疗该疾病的化疗引起的。几乎没有证据表明意义未明的IgG或IgA单克隆丙种球蛋白病（MGUS）患者的神经病变是由血液系统疾病引起的，除非有证据表明副蛋白与神经有反应性或其存在于神经中。具有慢性炎症性脱髓鞘性多发性神经根神经病（CIDP）样表现的患者应按CIDP进行治疗，而没有证据表明免疫治疗或化疗对其他患者有效。在大多数IgM副蛋白血症患者中（通常为MGUS或惰性华氏巨球蛋白血症），神经病变是由副蛋白与神经尤其是与髓鞘相关糖蛋白的免疫反应性引起的。现在，对照研究也有一致的数据表明，抗CD20单克隆抗体利妥昔单抗可能会改善这些患者的神经病变。POEMS综合征是一种严重疾病，其特征是致残性神经病变，在过去几年中，通过针对增殖性浆细胞克隆或血管内皮生长因子的治疗，包括局部放疗和化疗，然后进行自体干细胞移植，其预后有所改善。对于不符合移植条件或对移植耐药的患者，也有其他治疗方法，包括来那度胺，可能还有沙利度胺或硼替佐米。总结 现在有几种新的治疗方法可用于副蛋白血症性神经病变患者，持续改善这些神经病变的预后。然而，在大多数情况下，它们的疗效需要在对照试验中得到证实。
