Department of Neurology, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, MA 02215, USA.
J Neurol Neurosurg Psychiatry. 2010 Nov;81(11):1288-91. doi: 10.1136/jnnp.2009.179002. Epub 2010 Aug 14.
Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the polyomavirus JC (JCV) in immunosuppressed people. There is no cure for PML but 1-year survival has increased from 10% to 50% in HIV-infected individuals treated with highly active antiretroviral therapy. We describe herein the clinical outcome of 24 PML patients whose survival exceeded 5 years, with a mean follow-up of 94.2 months (range, 60-188 months). Of all patients, only two were females including one who had non-Hodgkin's lymphoma and was HIV negative. All 23 HIV-positive patients received highly active antiretroviral therapy, and additional experimental therapies were not associated with a better clinical outcome. Marked neurological improvement occurred in 4/24 (17%) of patients, while 11/24 (46%) had partial improvement and 9/24 (37%) remained stable. By the end of the period of observation, 8/24 (33%) of patients had no significant disability despite persistent symptoms (modified Rankin disability scale (MRDS) =1), 6/24 (25%) had slight disability and were living independently (MRDS=2), 5/24 (21%) were moderately disabled, requiring some help during activities of daily living (MRDS=3) and 5/24 (21%) had moderately severe disability, requiring constant help or institutionalisation (MRDS=4). Patients with cerebellar lesions tended to have a worse clinical outcome. MRI showed leukomalacia with ventricular enlargement secondary to destruction of the white matter at the site of previous PML lesions, and focal areas of subcortical atrophy with preservation of the cortical ribbon. Of 20 patients tested, 19(95%) had detectable CD8+ cytotoxic T-lymphocytes against JCV in their blood. In absence of a specific treatment, immunotherapies aiming at boosting the cellular immune response against JCV may improve the prognosis of PML.
进行性多灶性白质脑病（PML）是一种由免疫抑制人群中的多瘤病毒 JC（JCV）引起的脑脱髓鞘疾病。目前尚无针对 PML 的治愈方法，但在接受高效抗逆转录病毒治疗的 HIV 感染者中，1 年生存率已从 10%提高到 50%。我们在此描述了 24 例 PML 患者的临床结果，这些患者的存活时间超过 5 年，平均随访时间为 94.2 个月（范围为 60-188 个月）。所有患者中，仅有 2 例为女性，其中 1 例患有非霍奇金淋巴瘤且 HIV 阴性。所有 23 例 HIV 阳性患者均接受了高效抗逆转录病毒治疗，而额外的实验性治疗与更好的临床结局无关。24 例患者中有 4 例（17%）出现明显的神经功能改善，11 例（46%）有部分改善，9 例（37%）保持稳定。在观察期结束时，尽管症状持续存在（改良 Rankin 残疾量表（MRDS）=1），24 例患者中有 8 例（33%）无明显残疾，6 例（25%）有轻度残疾且能够独立生活（MRDS=2），5 例（21%）中度残疾，日常生活活动需要一定帮助（MRDS=3），5 例（21%）中度严重残疾，需要持续帮助或住院治疗（MRDS=4）。有小脑病变的患者倾向于出现更差的临床结局。MRI 显示脱髓鞘性白质病，伴有脑室扩大，继发于先前 PML 病变部位的白质破坏，以及局灶性皮质下萎缩伴皮质带保留。在 20 例接受检测的患者中，19 例（95%）的血液中可检测到针对 JCV 的 CD8+细胞毒性 T 淋巴细胞。在没有特定治疗方法的情况下，旨在增强针对 JCV 的细胞免疫反应的免疫疗法可能改善 PML 的预后。
