PMID- 31916298
OWN - NLM
STAT- MEDLINE
DCOM- 20210708
LR  - 20210904
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 30
IP  - 3
DP  - 2020 May
TI  - Extensive subpial cortical demyelination is specific to multiple sclerosis.
PG  - 641-652
LID - 10.1111/bpa.12813 [doi]
AB  - Cortical demyelinated lesions are frequent and widespread in chronic multiple 
      sclerosis (MS) patients, and may contribute to disease progression. Inflammation 
      and related oxidative stress have been proposed as central mediators of cortical 
      damage, yet meningeal and cortical inflammation is not specific to MS, but also 
      occurs in other diseases. The first aim of this study was to test whether 
      cortical demyelination was specific for demyelinating CNS diseases compared to 
      other CNS disorders with prominent meningeal and cortical inflammation. The 
      second aim was to assess whether oxidative tissue damage was associated with the 
      extent of neuroaxonal damage. We studied a large cohort of patients diagnosed 
      with demyelinating CNS diseases and non-demyelinating diseases of autoimmune, 
      infectious, neoplastic or metabolic origin affecting the meninges and the cortex. 
      Included were patients with MS, acute disseminated encephalomyelitis (ADEM), 
      neuromyelitis optica (NMO), viral and bacterial meningoencephalitis, progressive 
      multifocal leukoencephalopathy (PML), subacute sclerosing panencephalitis (SSPE), 
      carcinomatous and lymphomatous meningitis and metabolic disorders such as 
      extrapontine myelinolysis, thus encompassing a wide range of adaptive and innate 
      cytokine signatures. Using myelin protein immunohistochemistry, we found cortical 
      demyelination in MS, ADEM, PML and extrapontine myelinolysis, whereby each 
      condition showed a disease-specific histopathological pattern. Remarkably, 
      extensive ribbon-like subpial demyelination was only observed in MS, thus 
      providing an important pathogenetic and diagnostic cue. Cortical oxidative injury 
      was detected in both demyelinating and non-demyelinating CNS disorders. Our data 
      demonstrate that meningeal and cortical inflammation alone accompanied by 
      oxidative stress are not sufficient to generate the extensive subpial cortical 
      demyelination found in MS, but require other MS-specific factors.
CI  - (c) 2020 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf 
      of International Society of Neuropathology.
FAU - Junker, Andreas
AU  - Junker A
AUID- ORCID: 0000-0002-8063-9765
AD  - Institute of Neuropathology, University Medical Center Gottingen, Georg August 
      University Gottingen, Robert-Koch-Str. 40, 37075, Gottingen, Germany.
AD  - Department of Neuropathology, University Hospital Essen, Hufelandstr. 55, 45147, 
      Essen, Germany.
FAU - Wozniak, Jadwiga
AU  - Wozniak J
AD  - Institute of Neuropathology, University Medical Center Gottingen, Georg August 
      University Gottingen, Robert-Koch-Str. 40, 37075, Gottingen, Germany.
FAU - Voigt, David
AU  - Voigt D
AD  - Institute of Neuropathology, University Medical Center Gottingen, Georg August 
      University Gottingen, Robert-Koch-Str. 40, 37075, Gottingen, Germany.
FAU - Scheidt, Uta
AU  - Scheidt U
AD  - Institute of Neuropathology, University Medical Center Gottingen, Georg August 
      University Gottingen, Robert-Koch-Str. 40, 37075, Gottingen, Germany.
FAU - Antel, Jack
AU  - Antel J
AD  - Montreal Neurological Institute, McGill University Health Centre, 2155 Guy 
      Street, Montreal, Canada.
FAU - Wegner, Christiane
AU  - Wegner C
AD  - Institute of Neuropathology, University Medical Center Gottingen, Georg August 
      University Gottingen, Robert-Koch-Str. 40, 37075, Gottingen, Germany.
AD  - Department of Child and Adolescent Psychiatry/Psychotherapy, University Medical 
      Center Gottingen, Georg August University Gottingen, Robert-Koch-Str. 40, 37075, 
      Gottingen, Germany.
FAU - Bruck, Wolfgang
AU  - Bruck W
AD  - Institute of Neuropathology, University Medical Center Gottingen, Georg August 
      University Gottingen, Robert-Koch-Str. 40, 37075, Gottingen, Germany.
FAU - Stadelmann, Christine
AU  - Stadelmann C
AD  - Institute of Neuropathology, University Medical Center Gottingen, Georg August 
      University Gottingen, Robert-Koch-Str. 40, 37075, Gottingen, Germany.
LA  - eng
GR  - National Multiple Sclerosis Society/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200203
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
SB  - IM
MH  - Cerebral Cortex/*pathology
MH  - Demyelinating Diseases/*pathology
MH  - Disease Progression
MH  - Humans
MH  - Inflammation/pathology
MH  - Meninges/*pathology
MH  - Multiple Sclerosis/*pathology
MH  - Myelin Sheath/*pathology
PMC - PMC8018087
OTO - NOTNLM
OT  - acute disseminated encephalomyelitis (ADEM)
OT  - carcinomatous and lymphomatous meningitis
OT  - cortical demyelination
OT  - meningitis
OT  - multiple sclerosis (MS)
OT  - neuromyelitis optica (NMO)
OT  - oxidative stress
OT  - progressive multifocal leukoencephalopathy (PML)
OT  - subpial lesions
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/01/10 06:00
MHDA- 2021/07/09 06:00
PMCR- 2020/02/03
CRDT- 2020/01/10 06:00
PHST- 2019/10/24 00:00 [received]
PHST- 2020/01/02 00:00 [accepted]
PHST- 2020/01/10 06:00 [pubmed]
PHST- 2021/07/09 06:00 [medline]
PHST- 2020/01/10 06:00 [entrez]
PHST- 2020/02/03 00:00 [pmc-release]
AID - BPA12813 [pii]
AID - 10.1111/bpa.12813 [doi]
PST - ppublish
SO  - Brain Pathol. 2020 May;30(3):641-652. doi: 10.1111/bpa.12813. Epub 2020 Feb 3.