Progressive Multifocal Leukoencephalopathy.
Progressive Multifocal Leukoencephalopathy.
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DOI：
10.1007/s11940-000-0053-7
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发表时间：
2000-07-01
影响因子：
2
通讯作者：
Berger
中科院分区：
文献类型：
--
作者：
Berger
在进行进行性多灶性白质脑病（PML）的实验性治疗之前，诊断需要明确确定。改善潜在的免疫缺陷状态是治疗PML的最佳初始方法。免疫抑制治疗应在可行时停止。对于艾滋病患者，应给予高活性抗逆转录病毒治疗；这似乎延长了生存时间。目前，没有一种治疗方法在精心设计的前瞻性试验中被证明是有效的。阿糖胞嘧啶在体外已被证明对JC病毒有效，但对艾滋病和PML患者静脉注射或鞘内注射无效。在PML中使用阿糖胞嘧啶治疗方案的失败可能是由于药物未充分渗透到大脑感染部位的结果。其他具有体外抗JC病毒活性的药物，如拓扑异构酶和喜树碱，耐受性差。西多福韦在艾滋病和PML患者中的使用仍然是传闻，尽管目前正在调查中。干扰素α可能提高艾滋病和PML患者的生存率，并且可能对PML具有普遍适用性，而不考虑潜在免疫缺陷状态的原因。大约7%至9%的PML患者在没有特异性治疗的情况下表现出延长的生存期（约12个月）和相关的临床和影像学异常改善。在与艾滋病相关的PML患者中，延长生存时间与PML作为艾滋病的表现、CD4 t淋巴细胞计数升高以及PML病变在x线影像上的对比增强有关。活跃的炎症反应也可能与生存率的提高有关。对JC病毒病理生理学认识的增加为治疗策略的发展提供了希望。受PML影响的人越来越多，这使得组织精心设计的治疗试验能够解决这一问题。
Before embarking on experimental therapies for progressive multifocal leukoencephalopathy (PML), the diagnosis needs to be unequivocally established. Improving the underlying immunodeficiency state is the best initial approach to the management of PML. Immunosuppressive therapies should be discontinued when feasible. In the patient with AIDS, highly active antiretroviral therapy should be administered; this appears to prolong survival. At present, no therapy has been demonstrated to be effective in a well-designed prospective trial. Cytosine arabinoside, which has demonstrated efficacy in vitro against JC virus, has not been effective when administered intravenously or intrathecally to patients with AIDS and PML. The failure of regimens employing cytosine arabinoside in PML may have been the consequence of inadequate penetration of the drug to sites of infection in the brain. Other drugs with established in vitro activity against JC virus, such as topoisomerase and camptothecin, are poorly tolerated. The use of cidofovir in patients with AIDS and PML remains anecdotal, although it is currently under investigation. Interferon alfa may improve survival in patients with AIDS and PML and may have general applicability to PML regardless of the cause of the underlying immunodeficient state. Approximately 7% to 9% of patients with PML demonstrate prolonged survival (>12 months) and associated improvement in clinical and radiographic abnormalities in the absence of specific therapy. In patients with AIDS-related PML, prolonged survival correlates with PML as the presenting manifestation of AIDS, higher CD4 T-lymphocyte counts, and contrast enhancement of PML lesions on radiographic imaging. A brisk inflammatory response may also be associated with improved survival. The increased understanding of the pathophysiology of JC virus provides hope for the development of curative strategies. The growing number of persons affected with PML has allowed the organization of carefully designed therapeutic trials to address this issue.