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

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.

SUBMITTER: Prada Jardim A

PROVIDER: S-EPMC5893935 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTemporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored.MethodsWe studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively.Key findingsIndividuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of both frontal lobes and white matter integrity within the frontoparietal network and contralateral temporal lobe.SignificanceOur data provide further evidence that working memory is disrupted in HS and impaired integrity of both gray and white matter is seen in functionally relevant areas. We suggest this forms the structural basis of the impairment of working memory, indicating widespread and functionally significant structural changes in patients with apparently isolated HS.

Project description:ObjectiveAs many as 65% of people with multiple sclerosis (MS) have clinically significant memory impairment, but the nature of this deficit is controversial. Some investigations suggest that an inability to retrieve newly learned information from memory is prominent, whereas others imply that compromised acquisition accounts for impairment. Prior research has not simultaneously evaluated acquisition and retrieval processes in MS, and fewer have attempted to account for initial acquisition when studying retrieval. The Item Specific Deficit Approach (ISDA) offers a method of quantifying acquisition, retrieval, and retention processes, with the latter two mechanisms being adjusted for initial acquisition. To simultaneously quantify acquisition and retrieval abilities, the ISDA was applied to list learning performance in two independent samples of people with MS and corresponding healthy comparison groups.Participants and methodsStudy 1 included 85 people with MS and 47 healthy individuals. Study 2 involved a separate sample of 79 people with MS and 22 healthy people. They were administered neuropsychological batteries, and participants with MS were classified as globally impaired or unimpaired. The California Verbal Learning Test-II was administered to assess new-learning in both studies, and responses were scored using the ISDA.ResultsBoth studies revealed that cognitively impaired people with MS manifest weaknesses involving acquisition and retrieval. Nearly identical effect sizes emerged across samples, with cognitive impairment achieving a medium effect upon acquisition and a large effect upon retrieval.ConclusionsThese findings accord well with previous research showing diminished acquisition and retrieval among people with MS. The results may also reconcile contradictory findings in the extant literature by showing that memory impairment in MS is not exclusively attributable to either acquisition or retrieval. Rather, both processes may manifest across people with MS. The replication across samples with nearly identical effect sizes implies that these effects are reliable and possess external validity. These data hold implications for memory rehabilitation interventions involving people with MS, and suggest that acquisition and retrieval processes should be addressed in treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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

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