From the Division of Neurovirology, Department of Neurology (CW, SG, EN, XD, IJK), and Center for Virology and Vaccine Research, Department of Medicine (CW, SG, EN, XD, IJK), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Anatomy and Cell Biology (BFGhP, MT), and Cameco MS Neuroscience Research Center (BFGh.P, MT), University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Providence Saint Joseph Medical Center, The Hycy and Howard Hill Neuroscience Institute, Movement Disorder Center, Burbank (MM); David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (RZ); Department of Medicine, Northridge Hospital Medical Center, Northridge (RZ); and Buddhist Tzu Chi Medical Center, Alhambra, California (SPD); and Department of Laboratory Medicine and Pathology (JEP), and Department of Neurology (CFL), Mayo Clinic, Rochester, Minnesota.
J Neuropathol Exp Neurol. 2013 Nov;72(11):1043-51. doi: 10.1097/NEN.0000000000000005.
Natalizumab, a monoclonal antibody directed against α4 integrins, has, to date, been associated with 399 cases of progressive multifocal leukoencephalopathy (PML) worldwide in patients receiving treatment for multiple sclerosis (MS). Because of the limited number of histologic studies, the possible interplay between MS and PML lesions has not been investigated. We report the clinical, radiologic, and histologic findings of an MS patient who developed PML after 32 months of natalizumab monotherapy. After withdrawal of natalizumab, she received plasma exchange, mefloquine, and mirtazapine but died soon thereafter. Postmortem examination was restricted to examination of the brain and spinal cord. Extensive PML lesions, characterized by the presence of JC virus DNA were found in the cerebral white matter and neocortex. Sharply demarcated areas of active PML lesions contained prominent inflammatory infiltrates composed of approximately equal numbers of CD4-positive and CD8-positive T cells, consistent with an immune reconstitution inflammatory syndrome. Conversely, all MS lesions identified were hypocellular, long-standing inactive plaques characterized by myelin loss, relative axonal preservation, and gliosis and, importantly, were devoid of JC virus DNA and active inflammation. Chronic inactive MS lesions were separate and distinct from nearby PML lesions. This case demonstrates the coexistence and apparent lack of interplay between chronic inactive MS and PML lesions, and that immune reconstitution inflammatory syndrome seems to affect the shape and appearance of PML but not MS lesions.
那他珠单抗，一种针对 α4 整合素的单克隆抗体，迄今为止，已在全球接受多发性硬化症（MS）治疗的患者中与 399 例进行性多灶性脑白质病（PML）相关。由于组织学研究数量有限，尚未研究 MS 和 PML 病变之间的可能相互作用。我们报告了一名 MS 患者的临床，放射和组织学发现，该患者在接受那他珠单抗单药治疗 32 个月后发生了 PML。那他珠单抗停药后，她接受了血浆置换，甲氟喹和米氮平，但随后不久死亡。尸检仅限于大脑和脊髓的检查。在大脑白质和新皮层中发现了广泛的 PML 病变，其特征是存在 JC 病毒 DNA。明显界定的活跃 PML 病变区域包含明显的炎症浸润，由大约相等数量的 CD4 阳性和 CD8 阳性 T 细胞组成，符合免疫重建炎症综合征。相反，所有鉴定的 MS 病变均为细胞减少，长期处于不活跃状态的斑块，特征为髓鞘丢失，相对轴突保留和神经胶质增生，重要的是，缺乏 JC 病毒 DNA 和活跃的炎症。慢性不活跃的 MS 病变与附近的 PML 病变分开且不同。该病例表明慢性不活跃的 MS 和 PML 病变共存且似乎没有相互作用，并且免疫重建炎症综合征似乎影响 PML 的形态和外观，但不影响 MS 病变。
