Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan.
Department of Pulmonology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan.
BMC Neurol. 2019 Oct 31;19(1):263. doi: 10.1186/s12883-019-1493-1.
Progressive multifocal leukoencephalopathy (PML) is a rapidly developing demyelinating disease in the cerebral white matter and is often caused by JC polyomavirus (JCV). PML after lung transplantation is rare and has a poor prognosis, with no established therapies. Reducing the patient's immunosuppressant doses, thereby restoring immunity, could be used to treat PML. However, some patients develop immune reconstitution inflammatory syndrome (IRIS) with this treatment, an immune-induced inflammatory response to JCV that results in serious neuronal damage. We herein report a case of a 60-year-old female who suffered from PML 5 years after lung transplantation, had worsened brain lesions thought to be related to PML-IRIS at the time of immunosuppressant reduction, and missed treatment opportunities.
A 60-year-old female developed PML 5 years after lung transplantation. Fluid-attenuated inversion recovery and diffusion-weighted brain magnetic resonance imaging (MRI) revealed multiple high-signal lesions, mainly in the cerebral white matter. Polymerase chain reaction found 0.32 million copies/mL of JCV in the cerebrospinal fluid. Thus, she was given a diagnosis of PML. Mycophenolate mofetil and tacrolimus dosages were reduced, and CD4-positive cell counts and the blood concentration of each immunosuppressant were monitored. Mefloquine was also orally administered at a daily dose of 275 mg for 3 days and was then administered at a dose of 275 mg per week. Although the patient's CD4-positive cell counts increased and her immune system recovered, her symptoms and brain MRI findings worsened. We suspected PML progression or a transition to PML-IRIS. Steroid pulse therapy to suppress the inflammatory lesions was not possible but was retrospectively indicated. The patient rapidly began to exhibit akinetic mutism and died 4 months after the onset of neurologic symptoms.
When neurologic symptoms and abnormal brain MRI findings are noted during immune recovery, it is often difficult to distinguish between progressed PML and PML-IRIS. However, the pathogenesis of brain lesions usually involves inflammation and immune-reactive mechanisms for JCV. Steroid pulse therapy, which can reduce inflammation, should thus be administered in organ transplantation cases with differential diagnoses including PML-IRIS.
进行性多灶性白质脑病（PML）是一种大脑白质中迅速发展的脱髓鞘疾病，通常由 JC 多瘤病毒（JCV）引起。肺移植后的 PML 较为罕见且预后不良，尚无既定疗法。降低患者的免疫抑制剂剂量，从而恢复免疫，可用于治疗 PML。然而，一些患者在这种治疗下会发生免疫重建炎症综合征（IRIS），这是一种针对 JCV 的免疫诱导炎症反应，会导致严重的神经元损伤。我们在此报告一例 60 岁女性，肺移植 5 年后发生 PML，在免疫抑制剂减少时脑病变恶化，被认为与 PML-IRIS 有关，从而错失了治疗机会。
一名 60 岁女性，肺移植 5 年后发生 PML。液体衰减反转恢复和弥散加权脑磁共振成像（MRI）显示多处高信号病变，主要位于大脑白质。聚合酶链反应发现脑脊液中 JCV 为 0.32×10⁶拷贝/ml。因此，她被诊断为 PML。减少霉酚酸酯和他克莫司的剂量，并监测 CD4⁺阳性细胞计数和每种免疫抑制剂的血药浓度。还口服甲氟喹，每天 275mg，连续 3 天，然后每周 275mg。尽管患者的 CD4⁺阳性细胞计数增加，免疫系统恢复，但她的症状和脑 MRI 表现恶化。我们怀疑是 PML 进展或向 PML-IRIS 转变。抑制炎症病灶的类固醇脉冲疗法不可行，但事后被认为是必要的。患者迅速出现无动性缄默症，发病后 4 个月死亡。
在免疫恢复期间出现神经症状和异常脑 MRI 表现时，通常难以区分进展性 PML 和 PML-IRIS。然而，脑病变的发病机制通常涉及炎症和针对 JCV 的免疫反应机制。对于包括 PML-IRIS 在内的具有鉴别诊断的器官移植病例，应使用类固醇脉冲疗法来减轻炎症。
