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Cited by 40Epilepsy research and treatmentMemory and Neural MechanismsPharmacological Effects and Toxicity Studies

Characterising subtypes of hippocampal sclerosis and reorganization: correlation with pre and postoperative memory deficit.

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Prada Jardim, Anaclara, Liu, Joan, Baber, Jack, Michalak, Zuzanna, Reeves, Cheryl, Ellis, Matthew, Novy, Jan, de Tisi, Jane +6 more·2018·Brain Pathology
DOI 10.1111/bpa.12514PMC PMC5893935
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Abstract

Neuropathological subtypes of hippocampal sclerosis (HS) in temporal lobe epilepsy (The 2013 International League Against Epilepsy classification) are based on the qualitative assessment of patterns of neuronal loss with NeuN. In practice, some cases appear indeterminate between type 1 (CA1 and CA4 loss) and type 2 HS (CA1 loss) and we predicted that MAP2 would enable a more stringent classification. HS subtypes, as well as the accompanying alteration of axonal networks, regenerative capacity and neurodegeneration have been previously correlated with outcome and memory deficits and may provide prognostic clinical information. We selected 92 cases: 52 type 1 HS, 15 type 2 HS, 18 indeterminate-HS and 7 no-HS. Quantitative analysis was carried out on NeuN and MAP2 stained sections and a labeling index (LI) calculated for six hippocampal subfields. We also evaluated hippocampal regenerative activity (MCM2, nestin, olig2, calbindin), degeneration (AT8/phosphorylated tau) and mossy-fiber pathway re-organization (ZnT3). Pathology measures were correlated with clinical epilepsy history, memory and naming test scores and postoperative outcomes, at 1 year following surgery. MAP2 LI in indeterminate-HS was statistically similar to type 2 HS but this clustering was not shown with NeuN. Moderate verbal and visual memory deficits were noted in all HS types, including 54% and 69% of type 2 HS. Memory deficits correlated with several pathology factors including lower NeuN or MAP2 LI in CA4, CA1, dentate gyrus (DG) and subiculum and poor preservation of the mossy fiber pathway. Decline in memory at 1 year associated with AT8 labeling in the subiculum and DG but not HS type. We conclude that MAP2 is a helpful addition in the classification of HS in some cases. Classification of HS subtype, however, did not significantly correlate with outcome or pre- or postoperative memory dysfunction, which was associated with multiple pathology factors including hippocampal axonal pathways, regenerative capacity and degenerative changes.

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  • In younger temporal lobe epilepsy patients, an association between post-operative naming decline and subtle tau hyperphosphorylation localized to only the subiculum and dentate gyrus suggests that tau-associated pathological changes in relevant brain regions over time may underlie progressive cognitive impairment seen in temporal lobe epilepsy.

    “In younger TLE patients, an association between post-operative naming decline and subtle tau hyperphosphorylation localized to only the subiculum and dentate gyrus suggest that tau-associated pathological changes in relevant brain regions over time may underlie progressive cognitive impairment seen in TLE (Prada Jardim et al., 2018).”

    From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Prada Jardim et al., 2018

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Authors
Prada Jardim, A., Liu, J., Baber, J., Michalak, Z., Reeves, C., Ellis, M., Novy, J., de Tisi, J., McEvoy, A., Miserocchi, A., Targas Yacubian, E. M., Sisodiya, S., Thompson, P., & Thom, M.
Affiliations
  • Department of Clinical and Experimental Epilepsy UCL Institute of Neurology Queen Square London WCN1BG UK
  • National Hospital for Neurology and Neurosurgery (GB)
  • Department of Neurology and Neurosurgery Universidade Federal de Sao Paulo, UNIFESP Sao Paulo Brazil
Corresponding author
Thom, Maria
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
2017-04-24
Volume
28
Issue
2
Pages
143-154
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/bpa.12514
PMC
PMC5893935
OpenAlex
W2604552217
Cited by
40
References
3
Citations by year
2026: 6 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 2
FWCI
2.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Pathology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, cc-by)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • WestminsterResearch (University of Westminster) (acceptedVersion, cc-by)
  • IRIS (submittedVersion, cc-by)
  • UCL Discovery (University College London) (submittedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Funders
Medical Research Council (MR/JO127OX/1)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Keywords
hippocampal sclerosis, temporal lobe epilepsy, MAP2, NeuN, hippocampal neurodegeneration, phosphorylated tau, epilepsy surgery outcomes, dentate gyrus, subiculum
MeSH terms
Adolescent, Adult, Epilepsy, Temporal Lobe, Female, Hippocampus, Humans, Immunohistochemistry, Male, Memory Disorders, Microtubule-Associated Proteins, Middle Aged, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Sclerosis, Disease Progression, Neurosurgical Procedures, Antigens, Nuclear, Young Adult

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