Department of Neurology, MS Center Amsterdam, Neuroscience Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
Department of Radiology and Nuclear Medicine, MS Center Amsterdam, Neuroscience Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
J Neurol. 2020 Sep;267(9):2599-2602. doi: 10.1007/s00415-020-09880-7. Epub 2020 May 8.
To compare the available diagnostic criteria for progressive multifocal leukoencephalopathy (PML) diagnosis in a real-world cohort of patients with natalizumab-associated PML and to explore opportunities for improvement of such criteria in the context of pharmacovigilance of immunosuppressive therapies.
We applied the "Mentzers PML case definition" to a dataset of 28 patients with natalizumab-associated PML (many of whom were identified through MRI screening in the context of pharmacovigilance), who were previously rated according to the American Academy of Neurology (AAN) PML diagnostic criteria, and compared the response to both sets of criteria.
The "Mentzers case definition" resulted in a level of certainty 1-3 in patients with a positive JC virus PCR, termed 'definite' and 'probable' PML according to the AAN diagnostic criteria. Patients that tested negative for JC virus in CSF (29%) were classified level 4 by the "Mentzers case definition", neglecting the longitudinal clinical and radiological signs of PML available, while the AAN diagnostic criteria separated these patients in 'possible' and 'not PML'.
Both the AAN PML diagnostic criteria and the "Mentzers case definition" require the positive detection of JC virus DNA in CSF to define patients at a higher degree of suspicion of PML. However, as sensitivity of JC virus PCR in CSF is limited and often returns negative in particular in early cases of PML with a mere MRI-based PML suspicion, both criteria have obvious limitations when frequent MRI is used for pharmacovigilance purposes. Thus, revision of PML diagnostic criteria is needed, including the incorporation of lesion evolution, and longitudinal CSF studies that also assess for the presences of intrathecally produced anti-JC virus antibodies.
比较纳武单抗相关性进行性多灶性白质脑病（PML）诊断的现有诊断标准，探索在免疫抑制治疗药物警戒背景下，改进这些标准的机会。
我们将“Mentzers PML 病例定义”应用于 28 例纳武单抗相关性 PML 患者的数据集（其中许多是通过药物警戒背景下的 MRI 筛查发现的），这些患者之前根据美国神经病学学会（AAN）PML 诊断标准进行了评估，并比较了这两种标准的反应。
“Mentzers 病例定义”导致阳性 JC 病毒 PCR 的患者的确定性水平为 1-3，根据 AAN 诊断标准称为“明确”和“可能”PML。CSF 中检测到 JC 病毒阴性的患者（29%）根据“Mentzers 病例定义”被归类为 4 级，忽略了 PML 可用的纵向临床和放射学迹象，而 AAN 诊断标准将这些患者分为“可能”和“非 PML”。
AAN PML 诊断标准和“Mentzers 病例定义”都需要在 CSF 中检测到 JC 病毒 DNA 阳性，以定义更有可能患有 PML 的患者。然而，由于 CSF 中 JC 病毒 PCR 的敏感性有限，并且在基于 MRI 的 PML 可疑的早期 PML 病例中往往返回阴性，因此，当频繁使用 MRI 进行药物警戒目的时，这两种标准都存在明显的局限性。因此，需要修订 PML 诊断标准，包括纳入病变演变和纵向 CSF 研究，以评估鞘内产生的抗-JC 病毒抗体的存在。
