PMID- 31672142 OWN - NLM STAT- MEDLINE DCOM- 20200122 LR - 20200122 IS - 1471-2377 (Electronic) IS - 1471-2377 (Linking) VI - 19 IP - 1 DP - 2019 Oct 31 TI - Probable progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation: a case report and literature review. PG - 263 LID - 10.1186/s12883-019-1493-1 [doi] LID - 263 AB - BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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. FAU - Ishii, Kazuhiro AU - Ishii K AUID- ORCID: 0000-0003-2059-4670 AD - Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan. kazishii@md.tsukuba.ac.jp. FAU - Yamamoto, Fumiko AU - Yamamoto F AD - Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan. FAU - Homma, Shinsuke AU - Homma S AD - Department of Pulmonology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan. FAU - Okada, Yoshinori AU - Okada Y AD - Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryomachi, Aoba-ku Sendai, 980-8575, Japan. FAU - Nakamichi, Kazuo AU - Nakamichi K AD - Department of Virology 1, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo, 162-8640, Japan. FAU - Saijo, Masayuki AU - Saijo M AD - Department of Virology 1, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo, 162-8640, Japan. FAU - Tamaoka, Akira AU - Tamaoka A AD - Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan. LA - eng GR - 17K09768/Japan Society for the Promotion of Science/ GR - H29-Nanchitou (Nan)-Ippan-036/Ministry of Health, Labour and Welfare/ PT - Case Reports PT - Journal Article PT - Review DEP - 20191031 PL - England TA - BMC Neurol JT - BMC neurology JID - 100968555 RN - 0 (Immunosuppressive Agents) SB - IM MH - Brain/diagnostic imaging/pathology MH - Female MH - Humans MH - *Immune Reconstitution Inflammatory Syndrome MH - Immunocompromised Host MH - Immunosuppressive Agents/administration & dosage/adverse effects/therapeutic use MH - JC Virus MH - *Leukoencephalopathy, Progressive Multifocal MH - *Lung Transplantation MH - Middle Aged PMC - PMC6822459 OTO - NOTNLM OT - CD4 positive cell OT - Immune reconstitution inflammatory syndrome OT - JC polyomavirus OT - Lung transplantation OT - Mefloquine OT - Progressive multifocal leukoencephalopathy COIS- The authors declare that they have no competing interests. EDAT- 2019/11/02 06:00 MHDA- 2020/01/23 06:00 PMCR- 2019/10/31 CRDT- 2019/11/02 06:00 PHST- 2018/10/29 00:00 [received] PHST- 2019/10/09 00:00 [accepted] PHST- 2019/11/02 06:00 [entrez] PHST- 2019/11/02 06:00 [pubmed] PHST- 2020/01/23 06:00 [medline] PHST- 2019/10/31 00:00 [pmc-release] AID - 10.1186/s12883-019-1493-1 [pii] AID - 1493 [pii] AID - 10.1186/s12883-019-1493-1 [doi] PST - epublish SO - BMC Neurol. 2019 Oct 31;19(1):263. doi: 10.1186/s12883-019-1493-1.