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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Contributors CL and CRB were responsible for study concept and design. CL, GPDA, ARF, CLM, and FS were responsible for data acquisition and analysis. GPDA, CL, ARF, CLM, FS, SA, GZ, CEM, SRI, and CRB were responsible for drafting the manuscript or preparing figures.
Funding CL, GPDA, AR-F, CLM, and FS report no disclosures. SA is supported by the NIHR Oxford Biomedical Research Centre and Alzheimer’s Research UK and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centres based at Oxford University Hospitals NHS Trust, Oxford Health NHS Foundation Trust, and the University of Oxford. GZ and CM are supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centres based at Oxford University Hospitals NHS Trust, Oxford Health NHS Foundation Trust, and the University of Oxford. SRI is supported by the Wellcome Trust (104079/Z/14/Z), the UCB-Oxford University Alliance, BMA Research Grants- Vera Down grant (2013) and Margaret Temple (2017), Epilepsy Research UK (P1201) and by the Fulbright UK-US commission (MS-SOCIETY research AWARD). The research was funded/supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC; The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health). CRB is supported by a Medical Research Council Clinician Scientist Fellowship (MR/K010395/1). The authors reported no biomedical financial interests or potential conflicts of interest. The study was funded by Medical Research Council Clinician Scientist Fellowship (MR/K010395/1) awarded to CRB.
Competing interests SRI is a co-applicant and receives royalties on patent application WO/2010/046716 (UK patent no, PCT/GB2009/051441) entitled ‘Neurological Autoimmune Disorders’. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies.
Patient consent for publication All participants provided written informed consent according to the Declaration of Helsinki.
Ethics approval Ethical approval was received from South Central Oxford Research Ethics Committee (REC no: 08/H0606/133).
Provenance and peer review Not commissioned; externally peer reviewed.
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