PMID- 34377151
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210812
IS  - 1756-2856 (Print)
IS  - 1756-2864 (Electronic)
IS  - 1756-2856 (Linking)
VI  - 14
DP  - 2021
TI  - Progressive multifocal leukoencephalopathy and immune reconstitution inflammatory 
      syndrome in seven patients with sarcoidosis: a critical discussion of treatment 
      and prognosis.
PG  - 17562864211035543
LID - 10.1177/17562864211035543 [doi]
LID - 17562864211035543
AB  - Progressive multifocal leukoencephalopathy (PML) is a subacute brain infection by 
      the opportunistic John Cunningham (JC) virus. Herein, we describe seven patients 
      with PML, lymphopenia, and sarcoidosis, in three of whom PML was the first 
      manifestation of sarcoidosis. At onset, the clinical picture comprised rapidly 
      progressive spastic hemi- or limb pareses as well as disturbances of vision, 
      speech, and orientation. Cerebral magnetic resonance imaging showed 
      T2-hyperintense, confluent, mainly supratentorial lesions. Four patients 
      developed punctate contrast enhancement as a radiological sign of an immune 
      reconstitution inflammatory syndrome (IRIS), three of them having a fatal course. 
      In the cerebrospinal fluid, the initial JC virus load (8-25,787 copies/ml) did 
      not correlate with interindividual severity; however, virus load corresponded to 
      clinical dynamics. Brain biopsies (n = 2), performed 2 months after symptom 
      onset, showed spotted demyelination and microglial activation. All patients had 
      lymphopenia in the range of 270-1150/microl. To control JC virus, three patients 
      received a combination of mirtazapine and mefloquine, another two patients 
      additionally took cidofovir. One patient was treated with cidofovir only, and one 
      patient had a combined regimen with mirtazapine, mefloquine, cidofovir, 
      intravenous interleukin 2, and JC capsid vaccination. To treat sarcoidosis, the 
      four previously untreated patients received prednisolone. Three patients had 
      taken immunosuppressants prior to PML onset, which were subsequently stopped as a 
      potential accelerator of opportunistic infections. After 6-54 months of follow 
      up, three patients reached an incomplete recovery, one patient progressed, but 
      survived so far, and two patients died. One further patient was additionally 
      diagnosed with lung cancer, which he died from after 24 months. We conclude that 
      the combination of PML and sarcoidosis is a diagnostic and therapeutic challenge. 
      PML can occur as the first sign of sarcoidosis without preceding 
      immunosuppressive treatment. The development of IRIS might be an indicator of 
      poor outcome.
CI  - (c) The Author(s), 2021.
FAU - Dohrn, Maike F
AU  - Dohrn MF
AUID- ORCID: 0000-0002-5320-9807
AD  - Department of Neurology, Medical Faculty of the RWTH Aachen University, 
      Pauwelsstr. 30, Aachen, 52074, Germany.
FAU - Ellrichmann, Gisa
AU  - Ellrichmann G
AD  - Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, 
      Germany.
FAU - Pjontek, Rastislav
AU  - Pjontek R
AD  - Department of Diagnostic and Interventional Neuroradiology, Medical Faculty of 
      the RWTH Aachen University, Aachen, Germany.
FAU - Lukas, Carsten
AU  - Lukas C
AD  - Department of Radiology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, 
      Germany.
FAU - Panse, Jens
AU  - Panse J
AD  - Department of Oncology, Hematology and Stem Cell Transplantation, Medical Faculty 
      of the RWTH Aachen University, Aachen, Germany.
FAU - Gold, Ralf
AU  - Gold R
AD  - Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, 
      Germany.
FAU - Schulz, Jorg B
AU  - Schulz JB
AD  - Department of Neurology, Medical Faculty of the RWTH Aachen University, Aachen, 
      Germany.
FAU - Gess, Burkhard
AU  - Gess B
AD  - Department of Neurology, Medical Faculty of the RWTH Aachen University, Aachen, 
      Germany.
FAU - Tauber, Simone C
AU  - Tauber SC
AD  - Department of Neurology, Medical Faculty of the RWTH Aachen University, Aachen, 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20210731
PL  - England
TA  - Ther Adv Neurol Disord
JT  - Therapeutic advances in neurological disorders
JID - 101480242
PMC - PMC8326823
OTO - NOTNLM
OT  - John Cunningham (JC) virus
OT  - cidofovir
OT  - lymphopenia
OT  - mefloquine
OT  - mirtazapine
COIS- Conflict of interest statement: Ralf Gold is the editor-in-chief of Therapeutic 
      Advances in Neurological Disorders. The remaining authors declare that they have 
      no conflicts of interest relevant for this work.
EDAT- 2021/08/12 06:00
MHDA- 2021/08/12 06:01
PMCR- 2021/07/31
CRDT- 2021/08/11 06:36
PHST- 2021/03/18 00:00 [received]
PHST- 2021/07/05 00:00 [accepted]
PHST- 2021/08/11 06:36 [entrez]
PHST- 2021/08/12 06:00 [pubmed]
PHST- 2021/08/12 06:01 [medline]
PHST- 2021/07/31 00:00 [pmc-release]
AID - 10.1177_17562864211035543 [pii]
AID - 10.1177/17562864211035543 [doi]
PST - epublish
SO  - Ther Adv Neurol Disord. 2021 Jul 31;14:17562864211035543. doi: 
      10.1177/17562864211035543. eCollection 2021.