PMID- 34562035
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20231115
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Linking)
VI  - 90
IP  - 5
DP  - 2021 Nov
TI  - Neuropathological Variability within a Spectrum of NMDAR-Encephalitis.
PG  - 725-737
LID - 10.1002/ana.26223 [doi]
AB  - OBJECTIVE: To describe the neuropathological features of N-methyl-D-aspartate 
      receptor (NMDAR)-encephalitis in an archival autopsy cohort. METHODS: We examined 
      four autopsies from patients with NMDAR-encephalitis; two patients were 
      untreated, three had comorbidities: small cell lung cancer, brain post-transplant 
      lymphoproliferative disease (PTLD), and overlapping demyelination. RESULTS: The 
      two untreated patients had inflammatory infiltrates predominantly composed of 
      perivascular and parenchymal CD3(+) /CD8(-) T cells and CD79a(+) B cells/plasma 
      cells in basal ganglia, amygdala, and hippocampus with surrounding white matter. 
      The hippocampi showed a significant decrease of NMDAR-immunoreactivity that 
      correlated with disease severity. The patient with NMDAR-encephalitis and 
      immunosuppression for kidney transplantation developed a brain monomorphic PTLD. 
      Inflammatory changes were compatible with NMDAR-encephalitis. Additionally, 
      plasma cells accumulated in the vicinity of the necrotic tumor along with 
      macrophages and activated microglia that strongly expressed pro-inflammatory 
      activation markers HLA-DR, CD68, and IL18. The fourth patient developed 
      demyelinating lesions in the setting of a relapse 4 years after 
      NMDAR-encephalitis. These lesions exhibited the hallmarks of classic multiple 
      sclerosis with radially expanding lesions and remyelinated shadow plaques without 
      complement or immunoglobulin deposition, compatible with a pattern I 
      demyelination. INTERPRETATION: The topographic distribution of inflammation in 
      patients with NMDAR-encephalitis reflects the clinical symptoms of movement 
      disorders, abnormal behavior, and memory dysfunction with inflammation dominantly 
      observed in basal ganglia, amygdala, and hippocampus, and loss of 
      NMDAR-immunoreactivity correlates with disease severity. Co-occurring pathologies 
      influence the spatial distribution, composition, and intensity of inflammation, 
      which may modify patients' clinical presentation and outcome. ANN NEUROL 
      2021;90:725-737.
CI  - (c) 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on 
      behalf of American Neurological Association.
FAU - Zrzavy, Tobias
AU  - Zrzavy T
AUID- ORCID: 0000-0001-8909-1591
AD  - Department of Neurology, Medical University of Vienna, Vienna, Austria.
FAU - Endmayr, Verena
AU  - Endmayr V
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Bauer, Jan
AU  - Bauer J
AD  - Department of Neuroimmunology, Center for Brain Research, Medical University of 
      Vienna, Vienna, Austria.
FAU - Macher, Stefan
AU  - Macher S
AUID- ORCID: 0000-0001-8068-1528
AD  - Department of Neurology, Medical University of Vienna, Vienna, Austria.
FAU - Mossaheb, Nilufar
AU  - Mossaheb N
AD  - Department of Psychiatry and Psychotherapy, Clinical Division of Social 
      Psychiatry, Medical University of Vienna, Vienna, Austria.
FAU - Schwaiger, Carmen
AU  - Schwaiger C
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Ricken, Gerda
AU  - Ricken G
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Winklehner, Michael
AU  - Winklehner M
AUID- ORCID: 0000-0003-4938-7827
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Glatter, Sarah
AU  - Glatter S
AD  - Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 
      Vienna, Austria.
FAU - Breu, Markus
AU  - Breu M
AD  - Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 
      Vienna, Austria.
FAU - Wimmer, Isabella
AU  - Wimmer I
AD  - Department of Neurology, Medical University of Vienna, Vienna, Austria.
FAU - Kovacs, Gabor G
AU  - Kovacs GG
AUID- ORCID: 0000-0003-3841-5511
AD  - Department of Laboratory Medicine and Pathobiology and Tanz Centre for Research 
      in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada.
FAU - Risser, Daniele U
AU  - Risser DU
AD  - Center for Forensic Medicine, Medical University of Vienna, Vienna, Austria.
FAU - Klupp, Nikolaus
AU  - Klupp N
AD  - Center for Forensic Medicine, Medical University of Vienna, Vienna, Austria.
FAU - Simonitsch-Klupp, Ingrid
AU  - Simonitsch-Klupp I
AD  - Department of Pathology, Medical University of Vienna, Vienna, Austria.
FAU - Roetzer, Thomas
AU  - Roetzer T
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Rommer, Paulus
AU  - Rommer P
AD  - Department of Neurology, Medical University of Vienna, Vienna, Austria.
FAU - Berger, Thomas
AU  - Berger T
AD  - Department of Neurology, Medical University of Vienna, Vienna, Austria.
FAU - Gelpi, Ellen
AU  - Gelpi E
AUID- ORCID: 0000-0003-2948-4187
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
AD  - Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Barcelona, 
      Spain.
FAU - Lassmann, Hans
AU  - Lassmann H
AD  - Department of Neuroimmunology, Center for Brain Research, Medical University of 
      Vienna, Vienna, Austria.
FAU - Graus, Francesc
AU  - Graus F
AD  - Neuroimmunology Programme, Institut d'Investigacions Biomediques August Pi i 
      Sunyer Hospital Clinic, University of Barcelona, Barcelona, Spain.
FAU - Dalmau, Josep
AU  - Dalmau J
AD  - Neuroimmunology Programme, Institut d'Investigacions Biomediques August Pi i 
      Sunyer Hospital Clinic, University of Barcelona, Barcelona, Spain.
AD  - Department of Neurology, University of Pennsylvania, Philadelphia, PA.
AD  - Institucio Catalana de Recerca i Estudis Avancats, Barcelona, Spain.
FAU - Hoftberger, Romana
AU  - Hoftberger R
AUID- ORCID: 0000-0002-5769-1100
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
LA  - eng
GR  - DOC 33/FWF_/Austrian Science Fund FWF/Austria
GR  - I 4685/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211009
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 9007-36-7 (Complement System Proteins)
SB  - IM
MH  - Anti-N-Methyl-D-Aspartate Receptor Encephalitis/*diagnosis/*pathology
MH  - Brain/pathology
MH  - Complement System Proteins/metabolism
MH  - Humans
MH  - Male
MH  - Neoplasm Recurrence, Local/*pathology
MH  - Nervous System Diseases/pathology
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
EDAT- 2021/09/26 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/09/25 08:37
PHST- 2021/09/12 00:00 [revised]
PHST- 2021/07/09 00:00 [received]
PHST- 2021/09/19 00:00 [accepted]
PHST- 2021/09/26 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/09/25 08:37 [entrez]
AID - 10.1002/ana.26223 [doi]
PST - ppublish
SO  - Ann Neurol. 2021 Nov;90(5):725-737. doi: 10.1002/ana.26223. Epub 2021 Oct 9.