Takao Masaki
Department of Neuropathology, the Brain Bank for Aging Research, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology.
Brain Nerve. 2013 Nov;65(11):1363-74.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system and is associated with John Cunningham (JC) virus infection in the oligodendrocytes. The number of patients with PML increased after the pandemic of acquired immunodeficiency syndrome. Thereafter, an association between PML and monoclonal antibody therapy has come into light. Thus far, several monoclonal antibodies have been reported to cause PML. Currently, according to the Barts and the London School of Medicine and Dentistry, the number of PML cases due to natalizumab treatment for multiple sclerosis is 395 (incidence is 3.28/1,000). Moreover, the number of individuals with PML due to rituximab treatment is increasing (over 100 cases). Efalizumab, infliximab, adalimumab, etanercept, ibritumomab tiuxetan, bevacizumab, alemtuzumab, cetuximab, and brentuximab are also reported as risk factors of PML. The diagnosis of PML is based on clinical, neuroradiological, pathological, and molecular analyses. In clinical setting, magnetic resonance imaging provides the most important information in the diagnosis of PML. Patients with PML due to monoclonal antibody treatment may present clinical symptoms different from that of the classic PML, such as sensory disturbance and seizure. Once PML is identified in an individual receiving monoclonal antibody therapy, the monoclonal antibody must be immediately discontinued and removed from the body by plasmapheresis. Because most patients may present immune reconstitution inflammatory syndrome (IRIS), steroid therapy must be considered immediately. However, the prognosis of PML is still worse in patients receiving monoclonal antibody therapy. To prevent PML development, sophisticated and well-organized strategies must be established for monoclonal antibody treatment. Besides neurologists, physicians from other fields must be aware of PML associated with resulted from monoclonal antibody therapy.
进行性多灶性白质脑病（PML）是一种中枢神经系统脱髓鞘疾病，与少突胶质细胞中的约翰·坎宁安（JC）病毒感染有关。获得性免疫缺陷综合征大流行后，PML患者数量增加。此后，PML与单克隆抗体治疗之间的关联逐渐显现。迄今为止，已有数种单克隆抗体被报道可引发PML。目前，据巴茨和伦敦医学与牙科学院的数据，因那他珠单抗治疗多发性硬化症导致的PML病例数为395例（发病率为3.28/1000）。此外，因利妥昔单抗治疗导致PML的个体数量也在增加（超过100例）。依法利珠单抗、英夫利昔单抗、阿达木单抗、依那西普、替伊莫单抗、贝伐单抗、阿仑单抗、西妥昔单抗和 Brentuximab也被报道为PML的危险因素。PML的诊断基于临床、神经放射学、病理学和分子分析。在临床环境中，磁共振成像在PML诊断中提供最重要的信息。因单克隆抗体治疗导致PML的患者可能出现与经典PML不同的临床症状，如感觉障碍和癫痫发作。一旦在接受单克隆抗体治疗的个体中确诊PML，必须立即停用单克隆抗体，并通过血浆置换将其从体内清除。由于大多数患者可能出现免疫重建炎症综合征（IRIS），必须立即考虑使用类固醇治疗。然而，接受单克隆抗体治疗的PML患者预后仍然较差。为预防PML的发生，必须为单克隆抗体治疗制定完善且组织有序的策略。除神经科医生外，其他领域的医生也必须意识到与单克隆抗体治疗相关的PML。
