Department of Neurology, University of Kentucky College of Medicine, 740 S. Limestone St., Room L-445, Lexington, KY, 40536-0284, USA,
Curr Neurol Neurosci Rep. 2013 Dec;13(12):408. doi: 10.1007/s11910-013-0408-6.
AIDS generated a significantly increased interest in the pathogenesis, clinical manifestations, and treatment of progressive multifocal leukoencephalopathy (PML), a disease previously considered to be very rare. Scrutiny increased after a second wave of PML following the introduction of biological agents, in particular, natalizumab and efalizumab. While efalizumab, a lymphocyte function-associated antigen 1 inhibitor marketed for use in psoriasis, has been removed from the market, natalizumab, an α4β1 and α4β7 integrin inhibitor, remains widely used in the treatment of multiple sclerosis (MS). Approximately 400 cases of natalizumab-associated PML have been reported from 2005 to August 2013. Additionally, other therapies currently employed or under development for the treatment of MS may also be associated with PML, such as mycophenolate mofetil, rituximab, and alemtuzumab. Therefore, practitioners using these medications need to understand the risks associated with these agents, ways to mitigate the risk, and treatment of PML and the related condition PML immune reconstitution inflammatory syndrome. PML associated with the use of therapeutic agents, especially, natalizumab, does share similarities with HIV-related PML; however, distinct differences exist. Radiographically isolated PML is seen more commonly with natalizumab-associated PML and the disease appears to be heralded more often by cognitive and behavior disturbances. Furthermore, the mortality of natalizumab-associated PML is substantially lower. Risk mitigation strategies have been developed for the natalizumab-associated PML, which has been convincingly demonstrated to be linked to duration of therapy, JC virus seropositivity, and the prior use of immunosuppressive agents.
艾滋病的出现极大地增加了人们对进行性多灶性白质脑病（PML）的发病机制、临床表现和治疗的兴趣，这种疾病以前被认为非常罕见。在生物制剂（特别是那他珠单抗和依法利珠单抗）引入后，PML 出现了第二波疫情，因此对 PML 的研究也有所增加。虽然用于治疗银屑病的淋巴细胞功能相关抗原 1 抑制剂依法利珠单抗已退出市场，但作为 α4β1 和 α4β7 整合素抑制剂的那他珠单抗仍广泛用于多发性硬化症（MS）的治疗。自 2005 年至 2013 年 8 月，已报告了约 400 例那他珠单抗相关 PML 病例。此外，目前用于治疗 MS 的其他疗法或正在开发的疗法也可能与 PML 相关，如霉酚酸酯、利妥昔单抗和阿仑单抗。因此，使用这些药物的临床医生需要了解这些药物的相关风险、降低风险的方法以及 PML 和相关疾病 PML 免疫重建炎症综合征的治疗方法。与治疗剂（尤其是那他珠单抗）相关的 PML 与 HIV 相关的 PML 有一些相似之处，但也存在明显的差异。与那他珠单抗相关的 PML 更常出现放射学孤立性 PML，且疾病通常更常以认知和行为障碍为前兆。此外，那他珠单抗相关 PML 的死亡率明显较低。已经为那他珠单抗相关 PML 制定了风险缓解策略，该策略已被证明与治疗持续时间、JC 病毒血清阳性和先前使用免疫抑制剂有关。
