Journal
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
Volume 90, Issue 9, Pages 965-974Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/jnnp-2018-320168
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Funding
- NIHR Oxford Biomedical Research Centre
- Alzheimer's Research UK
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centres based at Oxford University Hospitals NHS Trust
- University of Oxford
- Wellcome Trust [104079/Z/14/Z]
- UCB-Oxford University Alliance
- Epilepsy Research UK [P1201]
- Fulbright UK-US commission
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)
- Medical Research Council Clinician Scientist Fellowship [MR/K010395/1]
- Oxford Health NHS Foundation Trust
- BMA Research Grants-Vera Down grant
- Margaret Temple
- MRC [MR/K010395/1] Funding Source: UKRI
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Objective Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment. Method A cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined. Results Patients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531). Conclusion VGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy.
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