Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Division of Neuroradiology and Neurophysics, UCL Institute of Neurology, and Lysholm Department of Neuroradiology, London, UK.
Lancet Neurol. 2018 May;17(5):467-480. doi: 10.1016/S1474-4422(18)30040-1.
Progressive multifocal leukoencephalopathy (PML) is a rare, devastating demyelinating disease of the CNS caused by the JC virus (JCV) that occurs in patients with compromised immune systems. Detection of PML in systemically immunocompetent patients with multiple sclerosis treated with natalizumab points to a role for this drug in the pathophysiology of PML. Emerging knowledge of the cellular and molecular biology of JCV infection and the pathogenesis of PML-including interplay of this common virus with the human immune system and features of natalizumab that might contribute to PML pathogenesis-provides new opportunities to monitor viral status and predict risk of JCV-associated disease. In the absence of an effective treatment for PML, early detection of the disease in patients with multiple sclerosis who are receiving natalizumab or other immunomodulatory treatments is vital to minimize CNS injury and avoid severe disability. Frequent MRI, stratified along a clinical and virus-specific immune risk profile, can be used to detect presymptomatic PML. Improved approaches to PML risk stratification are needed to guide treatment choices and surveillance of patients with multiple sclerosis.
进行性多灶性白质脑病（PML）是一种由 JC 病毒（JCV）引起的罕见且具破坏性的中枢神经系统脱髓鞘疾病，发生于免疫系统受损的患者中。在接受那他珠单抗治疗的多发性硬化症系统免疫功能正常的患者中检测到 PML，表明该药物在 PML 的病理生理学中发挥了作用。JCV 感染的细胞和分子生物学以及 PML 的发病机制（包括这种常见病毒与人类免疫系统的相互作用以及可能导致 PML 发病机制的那他珠单抗的特征）的新知识为监测病毒状态和预测与 JCV 相关疾病的风险提供了新的机会。由于没有有效的 PML 治疗方法，对于正在接受那他珠单抗或其他免疫调节治疗的多发性硬化症患者，早期检测疾病对于最小化中枢神经系统损伤和避免严重残疾至关重要。经常进行 MRI 检查，并根据临床和病毒特异性免疫风险概况进行分层，可以用于检测出有症状前的 PML。需要改进 PML 风险分层的方法，以指导多发性硬化症患者的治疗选择和监测。
