Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine.
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 cm(3)) 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.
Department of Neurology, Inselspital, Bern University Hospital, Freiburgstrasse 10, 3010, Bern, Switzerland.|University of Bern, Bern, Switzerland.
Rebekka
R
Kurmann
University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, Bern, Switzerland.|University of Bern, Bern, Switzerland.
Christian
C
Weisstanner
Transplantation & Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, Basel, Switzerland.
Piotr
P
Kardas
Transplantation & Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, Basel, Switzerland.|Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
Hans H
HH
Hirsch
University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, Bern, Switzerland.|University of Bern, Bern, Switzerland.
Roland
R
Wiest
Department of Hematology, Inselspital, Bern University Hospital, Bern, Switzerland.|Center for Thrombosis and Hemostasis, Mainz University Medical Center, Mainz, Germany.|University of Bern, Bern, Switzerland.
Bernhard
B
Lämmle
Department of Infectious Diseases, Inselspital, Bern University Hospital, Bern, Switzerland.|University of Bern, Bern, Switzerland.
Hansjakob
H
Furrer
Department of Neurology, Lausanne University Hospital, Lausanne, Switzerland.|Department of Clinical Neurosciences, University of Lausanne, Lausanne, Switzerland.
Renaud
R
Du Pasquier
Department of Neurology, Inselspital, Bern University Hospital, Freiburgstrasse 10, 3010, Bern, Switzerland.|University of Bern, Bern, Switzerland.
Claudio L
CL
Bassetti
Department of Neurology, Inselspital, Bern University Hospital, Freiburgstrasse 10, 3010, Bern, Switzerland.|University of Bern, Bern, Switzerland.
Mathias
M
Sturzenegger
Department of Neurology, Inselspital, Bern University Hospital, Freiburgstrasse 10, 3010, Bern, Switzerland. heinz-krestel@bluewin.ch.|University of Bern, Bern, Switzerland. heinz-krestel@bluewin.ch.
Heinz
H
Krestel
D000998:Antiviral Agents / Q000627:therapeutic use*; D017074:Common Variable Immunodeficiency / Q000150:complications*; D004279:DNA, Viral / Q000097:blood; D006801:Humans; D007577:JC Virus; D007968:Leukoencephalopathy, Progressive Multifocal / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000627:therapeutic use*; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D014766:Viremia
D000998:Antiviral Agents; D004279:DNA, Viral; D008803:Mianserin; D000078785:Mirtazapine; D015767:Mefloquine
CD4+ T lymphocytopenia; Idiopathic primary hypogammaglobulinemia; Mefloquine; Mirtazapine; Noncoding control region; Progressive multifocal leukoencephalopathy