Open Access Research article

Characteristics of progressive multifocal leukoencephalopathy clarified through internet-assisted laboratory surveillance in Japan

Kazuo Nakamichi1, Hidehiro Mizusawa2, Masahito Yamada3, Shuji Kishida4, Yoshiharu Miura4, Toshio Shimokawa5, Tomohiko Takasaki1, Chang-Kweng Lim1, Ichiro Kurane1 and Masayuki Saijo1*

Author Affiliations

1 Department of Virology 1, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan

2 Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan

3 Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Ishikawa, Kanazawa, 920-8640, Japan

4 Division of Neurology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, 113-8677, Japan

5 Department of Ecosocial System Engineering, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Kofu, Yamanashi, 400-8511, Japan

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BMC Neurology 2012, 12:121  doi:10.1186/1471-2377-12-121

Published: 15 October 2012

Abstract

Background

Progressive multifocal leukoencephalopathy (PML), a rare but fatal demyelinating disease caused by JC virus (JCV), occurs mainly in immunocompromised patients. As PML develops in individuals with various underlying disorders sporadically and infrequently, a nationwide survey of PML is difficult. This study was conducted to elucidate the characteristics of PML in Japan through an internet-assisted laboratory surveillance program.

Methods

A diagnostic support system for PML was established using a real-time PCR assay of JCV DNA in cerebrospinal fluid (CSF), and requests for testing were received from clinicians via specialized websites. Medical histories of patients were collected through standardized questionnaires, and a database of CSF JCV loads and clinical information was created and analyzed.

Results

For 4 years from April 2007 to March 2011, CSF specimens from 419 patients were tested. Forty-eight individuals were found positive for JCV DNA in their CSF and were diagnosed with PML. PML primarily occurred not only in HIV-positive patients (33.3%) but also in patients with hematologic disorders after receiving stem cell transplantation, chemotherapy, and/or immunosuppressive treatment (39.6%). The frequencies of PML cases among the subjects in these two categories were 20.3% and 23.5%, respectively. Although no significant features were observed with respect to CSF JCV loads in PML patients with an HIV infection or hematologic disorder, males were predominant in both groups (100% and 89.5%, respectively). The proportion of PML cases with autoimmune disorders (6.3%) or solid-organ transplants (2.1%) was smaller than those with HIV infection or hematologic disorders, probably due to the limited availability of therapeutic monoclonal antibodies and transplantation from brain dead donors.

Conclusions

The results suggest that the internet-assisted laboratory surveillance program might be a useful strategy for collecting precise real-time information on PML on a national level. The current database provides important background information for the diagnosis and treatment of patients with risk factors for PML.

Keywords:
Cerebrospinal fluid; Surveillance; Japan; JC virus; Progressive multifocal leukoencephalopathy