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25 High-resolution MRI Reveals Selective Patterns of Hippocampal Subfield Atrophy in Focal Epilepsy
- Adam Schadler, Erik Kaestner, Alena Stasenko, Christine N. Smith, Catherine Tallman, Nigel P. Pedersen, Shahin Hakimian, Michelle S. Kim, Daniel J Peterson, Thomas J. Grabowski, Daniel L. Drane, Carrie R. McDonald
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 25-26
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- Article
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Objective:
Hippocampal pathology is a consistent feature in persons with temporal lobe epilepsy (TLE) and a strong biomarker of memory impairment. Histopathological studies have identified selective patterns of cell loss across hippocampal subfields in TLE, the most common being cellular loss in the cornu ammonis 1 (CA1) and dentage gyrus (DG). Structural neuroimaging provides a non-invasive method to understand hippocampal pathology, but traditionally only at a whole-hippocampal level. However, recent methodological advances have enabled the non-invasive quantification of subfield pathology in patients, enabling potential integration into clinical workflow. In this study, we characterize patterns of hippocampal subfield atrophy in patients with TLE and examine the associations between subfield atrophy and clinical characteristics.
Participants and Methods:High-resolution T2 and T1-weighted MRI were collected from 31 participants (14 left TLE; 6 right TLE; 11 healthy controls [HC], aged 18-61 years). Reconstructions of hippocampal subfields and estimates of their volumes were derived using the Automated Segmentation of Hippocampal Subfields (ASHS) pipeline. Total hippocampal volume was calculated by combining estimates of the subfields CA1-3, DG, and subiculum. To control for variations in head size, all volume estimates were divided by estimates of total brain volume. To assess disease effects on hippocampal atrophy, hippocampi were recoded as either ipsilateral or contralateral to the side of seizure focus. Two sample t-tests at a whole-hippocampus level were used to test for ipsilateral and contralateral volume loss in patients relative to HC. To assess whether we replicated the selective histopathological patterns of subfield atrophy, we carried out mixed-effects ANOVA, coding for an interaction between diagnostic group and hippocampal subfield. Finally, to assess effects of disease load, non-parametric correlations were performed between subfield volume and age of first seizure and duration of illness.
Results:Patients had significantly smaller total ipsilateral hippocampal volume compared with HC (d=1.23, p<.005). Contralateral hippocampus did not significantly differ between TLE and HC. Examining individual subfields for the ipsilateral hemisphere revealed significant main-effects for group (F(1, 29)=8.2, p<0.01), subfields (F(4, 115)=550.5, p<0.005), and their interaction (F(4, 115)=8.1, p<0.001). Post-hoc tests revealed that TLE had significantly smaller volume in the ipsilateral CA1 (d=-2.0, p<0.001) and DG (d = -1.4, p<0.005). Longer duration of illness was associated with smaller volume of ipsilateral CA2 (p=-0.492, p<0.05) and larger volume of contralateral whole-hippocampus (p=0.689, p<0.001), CA1 (p=0.614, p < 0.005), and DG (p=0.450, p<0.05).
Conclusions:Histopathological characterization after surgery has revealed important associations between hippocampal subfield cell loss and memory impairments in patients with TLE. Here we demonstrate that non-invasive neuroimaging can detect a pattern of subfield atrophy in TLE (i.e., CA1/DG) that matches the most common form of histopathologically-observed hippocampal sclerosis in TLE (HS Type 1) and has been linked directly to both verbal and visuospatial memory impairment. Finally, we found evidence that longer disease duration is associated with larger contralateral hippocampal volume, driven by increases in CA1 and DG. This may reflect subfield-specific functional reorganization to the unaffected brain tissue, a compensatory effect which may have important implications for patient function and successful treatment outcomes.
1 - Definition, clinical features and neuroanatomical basis of dementia
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- By Thomas J. Grabowski, Department of Neurology, Division of Behavioral Neurology and Cognitive Neuroscience, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, USA, Antonio R. Damasio, Department of Neurology, Division of Behavioral Neurology and Cognitive Neuroscience, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, USA
- Edited by Margaret M. Esiri, University of Oxford, Virginia M. -Y. Lee, University of Pennsylvania School of Medicine, John Q. Trojanowski, University of Pennsylvania School of Medicine
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- Book:
- The Neuropathology of Dementia
- Published online:
- 12 October 2009
- Print publication:
- 22 July 2004, pp 1-33
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Summary
Introduction
Dementia is a frequent consequence of neurodegenerative diseases involving the cerebral cortex. Unlike stroke, encephalitis or head injury, which lead to relatively circumscribed and stable brain damage, degenerative disorders often affect many regions of the brain. The widespread changes in brain structure and the multiple signs of cognitive impairment that result from such changes have led to a conceptualization of the degenerative dementias, and especially of Alzheimer's disease, as ‘diffuse’ pathological processes, but this is not strictly true. The degenerative dementias, including Alzheimer's disease, do not affect the entire cerebral cortex equally. Instead, the degenerative dementias are associated with varied profiles of anatomic involvement, which can be tracked by quantitative histopathological and neuroimaging techniques. Association and limbic regions suffer the brunt of the damage.
It is widely accepted that cognition is supported by distributed neural systems, and that it is susceptible to dissociation by focal brain damage. Despite continued uncertainties about the physiology underlying normal cognition, locally and globally, the pathological functional anatomy of many cognitive disorders is beginning to be elucidated. Classic examples of such disorders and their anatomic correlates include anterograde declarative amnesia, which is due to lesions of the hippocampal formation and adjacent mesial temporal lobe structures; aphasia, which is due to lesions in the left perisylvian cerebral cortex; ideomotor apraxia, which is due to lesions of the left parietal lobe; and simultanagnosia, which is due to bilateral lesions of the dorsal occipital and parietal lobes. The clinical manifestations of degenerative processes clearly depend in part on which neural structures and systems are affected earliest and most extensively. It is now apparent that degenerative dementia can present with impairments resembling any of the classic ‘focal’ disorders listed above.