Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans.
Date Issued
2017-03-28
Date Acceptance
2017-01-29
Citation
BRAIN, 2017, 140 (5), pp.1212-1219
ISSN
0006-8950
Publisher
OXFORD UNIVERSITY PRESS
Start Page
1212
End Page
1219
Journal / Book Title
BRAIN
Volume
140
Issue
5
Copyright Statement
© 2017 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse,
distribution, and reproduction in any medium, provided the original work is properly cited.
distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000400069900013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
RDA03
Subjects
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
limbic encephalitis
hippocampus
ultra-high resolution 7.0 T MRI
hippocampal subfields
amnesia
POTASSIUM CHANNEL-COMPLEX
AUTOBIOGRAPHICAL MEMORY
LEUCINE-RICH
COGNITIVE DEFICITS
SEIZURES
IMPAIRMENT
EPILEPSY
AMNESIA
DAMAGE
Neurology & Neurosurgery
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Publication Status
Published