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Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine

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Abstract

Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm3) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy.

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Acknowledgments

We thank the nurses, physiotherapists, and residents of our neurological ward for their support with clinical data collection.

Contributors

RK, MS, and HK were involved in diagnosis and treatment of the patient. RK, MS, and HK designed the study. RK, CW, and PK conducted the examinations and laboratory studies. RK, BL, MS, and HK drafted the manuscript. RW, HF, RDP, and HHH intellectually contributed to data interpretation and the manuscript. The version to be published was approved by all of the authors. HK accepts full responsibility for the data as guarantor.

Funding

No extra funds were used in this study.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, Inselspital, Bern University Hospital, Freiburgstrasse 10, 3010, Bern, Switzerland

    Rebekka Kurmann, Claudio L. Bassetti, Mathias Sturzenegger & Heinz Krestel

  2. University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, Bern, Switzerland

    Christian Weisstanner & Roland Wiest

  3. Transplantation & Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, Basel, Switzerland

    Piotr Kardas & Hans H. Hirsch

  4. Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland

    Hans H. Hirsch

  5. Department of Hematology, Inselspital, Bern University Hospital, Bern, Switzerland

    Bernhard Lämmle

  6. Department of Infectious Diseases, Inselspital, Bern University Hospital, Bern, Switzerland

    Hansjakob Furrer

  7. Department of Neurology, Lausanne University Hospital, Lausanne, Switzerland

    Renaud Du Pasquier

  8. Center for Thrombosis and Hemostasis, Mainz University Medical Center, Mainz, Germany

    Bernhard Lämmle

  9. University of Bern, Bern, Switzerland

    Rebekka Kurmann, Christian Weisstanner, Roland Wiest, Bernhard Lämmle, Hansjakob Furrer, Claudio L. Bassetti, Mathias Sturzenegger & Heinz Krestel

  10. Department of Clinical Neurosciences, University of Lausanne, Lausanne, Switzerland

    Renaud Du Pasquier

Authors
  1. Rebekka Kurmann
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  2. Christian Weisstanner
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  3. Piotr Kardas
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  4. Hans H. Hirsch
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  5. Roland Wiest
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  6. Bernhard Lämmle
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  7. Hansjakob Furrer
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  8. Renaud Du Pasquier
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  9. Claudio L. Bassetti
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  11. Heinz Krestel
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Corresponding author

Correspondence to Heinz Krestel.

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Supplementary Table 1

Shown are patients with PML and CVID reported in the literature from 1996 to 2013 (see reference list in this figure legend). References in the table, marked with an asterisk, fulfill the criteria of late onset combined immunodeficiency (LOCID). Of the published cases, clinical symptoms, laboratory parameters (pathological values colored in red, for reference ranges see legend Fig. 1), means of diagnosis, MRI lesions, treatment, survival time, patient age at time of PML diagnosis, and gender are presented. (DOCX 21 kb)

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Kurmann, R., Weisstanner, C., Kardas, P. et al. Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine. J. Neurovirol. 21, 694–701 (2015). https://doi.org/10.1007/s13365-015-0340-4

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  • DOI: https://doi.org/10.1007/s13365-015-0340-4

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