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

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

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.

Adolescent, Adult, Antigens, Nuclear, Disease Progression, Epilepsy, Temporal Lobe, Female, Hippocampus, Humans, Immunohistochemistry, Male, Memory Disorders, Microtubule-Associated Proteins, Middle Aged, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Neurosurgical Procedures, Sclerosis, Young Adult, Journal Article, Research Support, Non-U.S. Gov't
1015-6305
143-154
Prada Jardim, Anaclara
0aa86404-29fc-4977-92f6-3c772dc1b919
Liu, Joan
0e68a532-ba7f-451a-944c-461e1585c47e
Baber, Jack
e9f1b9a9-fdb1-465b-a52a-d49dd8d60c37
Michalak, Zuzanna
6396a6ff-f48c-4fef-a528-41420a0c0df5
Reeves, Cheryl
6912b99a-1a85-4ad3-860f-de808d19aca9
Ellis, Matthew
afbca752-ced4-40dd-b0af-d9ecffbd5b63
Novy, Jan
53e922fd-bbc5-44a8-add1-3b5f0bfa4970
de Tisi, Jane
11ae411b-ca4b-4247-9356-afdd14d81176
McEvoy, Andrew
879f5889-d763-401b-bdc6-605140c47aeb
Miserocchi, Anna
6dc25cf8-a6ee-4460-b963-9ef4e469e0aa
Targas Yacubian, Elza Marcia
2bcc5829-452b-4e0e-a13c-17cfaefd9a0a
Sisodiya, Sanjay
322a3ac6-b8ab-44d8-bc9e-af9a2ba75d1f
Thompson, Pamela
69df292d-f664-42f0-aec1-58d0cab4962a
Thom, Maria
a9f63dd8-ba68-4ea1-a945-e4bbd18525d2
Prada Jardim, Anaclara
0aa86404-29fc-4977-92f6-3c772dc1b919
Liu, Joan
0e68a532-ba7f-451a-944c-461e1585c47e
Baber, Jack
e9f1b9a9-fdb1-465b-a52a-d49dd8d60c37
Michalak, Zuzanna
6396a6ff-f48c-4fef-a528-41420a0c0df5
Reeves, Cheryl
6912b99a-1a85-4ad3-860f-de808d19aca9
Ellis, Matthew
afbca752-ced4-40dd-b0af-d9ecffbd5b63
Novy, Jan
53e922fd-bbc5-44a8-add1-3b5f0bfa4970
de Tisi, Jane
11ae411b-ca4b-4247-9356-afdd14d81176
McEvoy, Andrew
879f5889-d763-401b-bdc6-605140c47aeb
Miserocchi, Anna
6dc25cf8-a6ee-4460-b963-9ef4e469e0aa
Targas Yacubian, Elza Marcia
2bcc5829-452b-4e0e-a13c-17cfaefd9a0a
Sisodiya, Sanjay
322a3ac6-b8ab-44d8-bc9e-af9a2ba75d1f
Thompson, Pamela
69df292d-f664-42f0-aec1-58d0cab4962a
Thom, Maria
a9f63dd8-ba68-4ea1-a945-e4bbd18525d2

Prada Jardim, Anaclara, Liu, Joan, Baber, Jack, Michalak, Zuzanna, Reeves, Cheryl, Ellis, Matthew, Novy, Jan, de Tisi, Jane, McEvoy, Andrew, Miserocchi, Anna, Targas Yacubian, Elza Marcia, Sisodiya, Sanjay, Thompson, Pamela and Thom, Maria (2018) Characterising subtypes of hippocampal sclerosis and reorganization: correlation with pre and postoperative memory deficit. Brain Pathology, 28 (2), 143-154. (doi:10.1111/bpa.12514).

Record type: Article

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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Accepted/In Press date: 28 March 2017
e-pub ahead of print date: 5 April 2017
Published date: March 2018
Keywords: Adolescent, Adult, Antigens, Nuclear, Disease Progression, Epilepsy, Temporal Lobe, Female, Hippocampus, Humans, Immunohistochemistry, Male, Memory Disorders, Microtubule-Associated Proteins, Middle Aged, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Neurosurgical Procedures, Sclerosis, Young Adult, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 429123
URI: http://eprints.soton.ac.uk/id/eprint/429123
ISSN: 1015-6305
PURE UUID: bcb500af-8080-4055-96ce-fe77f90f48c1

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Date deposited: 21 Mar 2019 17:30
Last modified: 16 Mar 2024 00:08

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Contributors

Author: Anaclara Prada Jardim
Author: Joan Liu
Author: Jack Baber
Author: Zuzanna Michalak
Author: Cheryl Reeves
Author: Matthew Ellis
Author: Jan Novy
Author: Jane de Tisi
Author: Andrew McEvoy
Author: Anna Miserocchi
Author: Elza Marcia Targas Yacubian
Author: Sanjay Sisodiya
Author: Pamela Thompson
Author: Maria Thom

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