Mulufocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a lytic infection of oligodendrocytes by the human papovavirus JC. Patients with defects in cell-mediated immunity are at risk for active disease: a usually lethal demyelination of the brain. PML develops in at least 4% of patients with the acquired immunodeficiency syndrome (AIDS). Definitive diagnosis currently requires brain biopsy. Previous attempts to detect JC virus DNA by polymerase chain reaction in cerebrospinal fluid of PML patients, particularly those with human immunodeficiency virus type 1 (HIV-1) infection, have been of low sensitivity. In the present study, cerebrospinal fluid was assayed by polymerase chain reaction from 26 HIV-I-positive patients with PML, 114 HIV-1-positive control subjects, and 16 control subjects who were HIV-1 negative or were without risk factors for HIV disease. Polymerase chain reaction conditions were optimized to detect a single copy of viral DNA in 50 p.1 of cerebrospinal fluid. Specificity of the polymerase chain reaction product was confirmed by size on gel electrophoresis and Southern blot hybridization. JC virus DNA was detected in 24 of 26 samples from patients with PML 8 of 8 with tissue diagnosis and 16 of 18 with strong clinical and magnetic resonance imaging evidence of PML. Among control subjects, 11 of 130 samples were positive for JC virus: 10 of 114 samples from HIV-infected patients and one from an HIV-negative patient with risk factors for PML and an unexplained hemiparesis. Overall sensitivity was 92% (24126); specificity was, at minimum, 92% (1 19/130). Treatments for PML are now in clinical trials. This assay provides a safe, inexpensive means of establishing the diagnosis of a potentially treatable condition. Furthermore, our data suggest that a subgroup of presymptomatic patients who may be at high risk for PML can be identified. Such patients may be particularly suitable for prophylactic interventions.

进行性多灶性白质脑病（PML）是由人类多瘤病毒JC引起的少突胶质细胞溶解性感染。细胞介导免疫有缺陷的患者有患活动性疾病的风险，即一种通常致命的脑脱髓鞘疾病。至少4%的获得性免疫缺陷综合征（艾滋病）患者会发生PML。目前明确诊断需要脑活检。以前通过聚合酶链反应在PML患者（特别是那些感染1型人类免疫缺陷病毒（HIV - 1）的患者）的脑脊液中检测JC病毒DNA的尝试，灵敏度较低。在本研究中，对26例HIV - I阳性的PML患者、114例HIV - 1阳性对照受试者以及16例HIV - 1阴性或无HIV疾病风险因素的对照受试者的脑脊液进行了聚合酶链反应检测。优化了聚合酶链反应条件，以检测50微升脑脊液中单个拷贝的病毒DNA。通过凝胶电泳的大小和Southern杂交确认了聚合酶链反应产物的特异性。在26例PML患者的24个样本中检测到JC病毒DNA，其中8例经组织诊断，16例有强烈的临床和磁共振成像PML证据。在对照受试者中，130个样本中有11个JC病毒呈阳性：114个来自HIV感染患者的样本中有10个，1个来自有PML风险因素且有不明原因偏瘫的HIV阴性患者。总体灵敏度为92%（24/26）；特异性至少为92%（119/130）。PML的治疗目前正在临床试验中。这种检测方法为确诊一种可能可治疗的疾病提供了一种安全、廉价的手段。此外，我们的数据表明，可以识别出可能处于PML高风险的无症状患者亚群。这类患者可能特别适合预防性干预。