2021 年 38 巻 4 号 p. 551-557
Progressive multifocal leukoencephalopathy (PML) is a JC virus infection that is an inapparent infection under normal immune conditions ; however, the JC virus is pathologically reactivated when the immunocompetence of the host declines, causing infectious demyelinating encephalopathy. There are three types of disease–modifying drugs (DMDs) associated with PML in multiple sclerosis treatment. Fingolimod (FGM) and siponimod (SPM) are sphingosine–1–phosphate receptor agonists. Natalizumab (NTZ) is an antibody against the integrin alpha–4 beta–1 subunit of T lymphocytes. Dimethyl fumarate (DMF) is a nuclear factor (erythroid–derived 2)–related factor 2 that has antioxidant and anti–inflammatory effects that are thought to be mediated by the activation of the transcription pathway. The risk of NTZ–related PML depends on the JC virus antibody index, history of immunosuppressant use, and duration of NTZ administration. In recent years, extended interval dosing therapy, which extends the NTZ administration interval, has attracted attention as an optional treatment method that maintains adequate blood levels of NTZ while reducing the risk of PML. The mechanism of FGM–related PML is unknown, but FGM and SPM cause a decrease in lymphocytes in the blood, and administration in elderly patients and the long–term use of these drugs are associated with a high risk of PML. The frequency of PML in Japan may be statistically higher than that worldwide. It has been pointed out that the risk factors of DMF–related PML include a persistent decrease in the blood lymphocyte count (less than 500/mm3) and age older than 50 years.
Since immune reconstitution inflammatory syndrome (IRIS) is nearly inevitable in cases of DMD–related PML, it is important to administer steroids according to the conditions to control central nervous inflammation after IRIS onset. It is also important to adjust the imaging interval according to the risk of detecting the asymptomatic stage of PML and to avoid the development of IRIS, and if a physician considers it necessary, the cerebrospinal fluid should be checked as well.
