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Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

Miller, Thomas D.; Chong, Trevor T.-J.; Aimola Davies, Anne M.; Ng, Tammy W.C.; Johnson, Michael R.; Irani, Sarosh R.; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A.; Rosenthal, Clive R.

Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis Thumbnail


Thomas D. Miller

Trevor T.-J. Chong

Anne M. Aimola Davies

Tammy W.C. Ng

Michael R. Johnson

Sarosh R. Irani

Angela Vincent

Masud Husain

Saiju Jacob

Paul Maddison

Christopher Kennard

Clive R. Rosenthal


© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. 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) 7.0T 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 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.

Journal Article Type Article
Acceptance Date Jan 29, 2017
Online Publication Date Mar 28, 2017
Publication Date May 1, 2017
Deposit Date Apr 25, 2017
Publicly Available Date Apr 25, 2017
Journal Brain
Print ISSN 0006-8950
Electronic ISSN 1460-2156
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 140
Issue 5
Pages 1212-1219
Keywords Limbic encephalitis, Hippocampus, Ultra-high resolution 7.0 T MRI, Hippocampal subfields, Amnesia
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