PML surveillance registration system in Japan and DMD–associated PML

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by JC polyomavirus (JCV). In Japan, the incidence of PML has been investigated by us, a Health and Labour Sciences Research Grant for Research on Measures for Intractable Diseases (Prion Disease and Slow Virus Infections) from the Ministry of Health, Labour and Welfare of the Japanese government. Recently, we have established registration system on PML Surveillance Committee. This system makes epidemiological investigation effective and exact. In Japan the basic disease of PML are changing variously. The major basic diseases are hematologic disease/malignancy such as lymphoma, collagen disease/autoimmune disease as SLE, HIV infection, MS and kidney disease. Four fingolimod–associated PML cases and one natalizumab–associated PML are reported in Japan. Next, we have established new criteria for the diagnosis of PML by PML Practice guideline 2017. Clinical diagnosis criteria consist of clinical feature, neuroradiographic imaging, excluded criteria, and the presence of the virus in the CSF compartment. In histopathological diagnosis criteria, Definitive diagnosis of PML requires neuropathologic demonstration of the typical histopathologic triad (demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei) coupled with the techniques to show the presence of JC virus. Furthermore, Nakamichi et al established ultrasensitive PCR assay in detection of JCV DNA in the cerebrospinal fluid. Shishido–Hara et al are accepting of consultation of pathological examination form attending doctors and pathologists. These measures will be helpful for the new DMD–associated PML.