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Abstract

Introduction:

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating brain infection caused by JC polyomavirus (JCV), primarily seen in patients with severely compromised cellular immunity. Clinical presentation varies depending on the affected white matter. PML prognosis is variable and effective treatments are lacking.

Case presentation:

A 75-year-old Chinese woman with type 2 diabetes mellitus, chronic kidney disease and rheumatoid arthritis, treated with low-dose methotrexate and prednisolone for 2.5 years, developed a infection of her left arm. After 6 months of treating this rare black fungus infection with voriconazole, surgery and immunosuppression discontinuation, she presented with progressive afebrile encephalopathy with right-sided hemiparesis. There were no signs of inflammation or metabolic abnormalities. Brain magnetic resonance imaging revealed diffuse frontal white matter lesions and a cerebrospinal fluid PCR confirmed PML due to JC virus. Severe lymphopenia was never present, and at PML diagnosis, CD4 and CD8 T-cell counts were 454 mm and 277 mm. CD8 T-cells were able to respond to JCV VP1 peptide stimulation with TNFα secretion. Peripheral B-cell count was only 8 mm. Mirtazapine and Maraviroc were started, but unfortunately, she rapidly deteriorated and died 5 weeks after PML diagnosis.

Conclusion:

Although peripheral lymphocyte counts were never low and CD4 T-cell count was close to normal, the persistent black fungus infection was a hallmark of severely compromised cellular immunity. The unexpected extremely low absolute B-cell count might suggest a protective role for B-cells. The paradoxical, clinical PML onset months after immunosuppressive discontinuation suggests that it was only discovered in the context of an immune reconstitution inflammatory syndrome.

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/content/journal/jmmcr/10.1099/jmmcr.0.005053
2016-07-11
2020-01-23
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References

  1. Breuer J., Schwab N., Schneider-Hohendorf T., Marziniak M., Mohan H., Bhatia U., Gross C. C., Clausen B. E., Weishaupt C. et al. 2014; Ultraviolet B light attenuates the systemic immune response in central nervous system autoimmunity. Ann Neurol75:739–758 [CrossRef][PubMed]
    [Google Scholar]
  2. Dammeier N., Schubert V., Hauser T. K., Bornemann A., Bischof F.. 2015; Case report of a patient with progressive multifocal leukoencephalopathy under treatment with dimethyl fumarate. BMC Neurol15:108 [CrossRef][PubMed]
    [Google Scholar]
  3. Du Pasquier R. A., Schmitz J. E., Jean-Jacques J., Zheng Y., Gordon J., Khalili K., Letvin N. L., Koralnik I. J.. 2004; Detection of JC virus-specific cytotoxic T lymphocytes in healthy individuals. J Virol78:10206–10210 [CrossRef][PubMed]
    [Google Scholar]
  4. Giacomini P. S., Rozenberg A., Metz I., Araujo D., Arbour N., Bar-Or A.. Maraviroc in Multiple Sclerosis–Associated PML–IRIS (MIMSAPI) Group 2014; Maraviroc and JC virus-associated immune reconstitution inflammatory syndrome. N Engl J Med370:486–488 [CrossRef][PubMed]
    [Google Scholar]
  5. Hirsch H. H., Kardas P., Kranz D., Leboeuf C.. 2013; The human JC polyomavirus (JCPyV): virological background and clinical implications. APMIS121:685–727 [CrossRef][PubMed]
    [Google Scholar]
  6. Hoepner R., Faissner S., Klasing A., Schneider R., Metz I., Bellenberg B., Lukas C., Altmeyer P., Gold R., Chan A.. 2015; Progressive multifocal leukoencephalopathy during fumarate monotherapy of psoriasis. Neurol Neuroimmunol Neuroinflamm2:e85 [CrossRef][PubMed]
    [Google Scholar]
  7. Koralnik I. J., Du Pasquier R. A., Letvin N. L.. 2001; JC virus-specific cytotoxic T lymphocytes in individuals with progressive multifocal leukoencephalopathy. J Virol75:3483–3487 [CrossRef][PubMed]
    [Google Scholar]
  8. Middel A., Arends J. E., van Lelyveld S. F., Otto S., Schuurman R., Frijns C. J., Tesselaar K., Hoepelman A. I.. 2015; Clinical and immunologic effects of maraviroc in progressive multifocal leukoencephalopathy. Neurology85:104–106 [CrossRef][PubMed]
    [Google Scholar]
  9. Nieuwkamp D. J., Murk J. L., van Oosten B. W., Cremers C. H., Killestein J., Viveen M. C., Van Hecke W., Frijlink D. W., Wattjes M. P.. PML in Dutch MS Patients Consortium 2015; PML in a patient without severe lymphocytopenia receiving dimethyl fumarate. N Engl J Med372:1474–1476 [CrossRef][PubMed]
    [Google Scholar]
  10. Palazzo E., Yahia S. A.. 2012; Progressive multifocal leukoencephalopathy in autoimmune diseases. Joint Bone Spine79:351–355 [CrossRef][PubMed]
    [Google Scholar]
  11. Wattjes M. P., Vennegoor A., Steenwijk M. D., de Vos M., Killestein J., van Oosten B. W., Mostert J., Siepman D. A., Moll W. et al. 2015; MRI pattern in asymptomatic natalizumab- associated PML. J Neurol Neurosurg Psychiatry86:793–798 [CrossRef][PubMed]
    [Google Scholar]
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