The neurobiology of cognitive disorders in temporal lobe epilepsy

Department of Neurology, University of Wisconsin School of Medicine and Public Health, 600 North Highland Avenue, Madison, WI 53792, USA.
Nature Reviews Neurology (Impact Factor: 14.1). 02/2011; 7(3):154-64. DOI: 10.1038/nrneurol.2011.3
Source: PubMed

ABSTRACT Cognitive impairment, particularly memory disruption, is a major complicating feature of epilepsy. This Review will begin with a focus on the problem of memory impairment in temporal lobe epilepsy (TLE). We present a brief overview of anatomical substrates of memory disorders in TLE, followed by a discussion of how our understanding of these disorders has been improved by studying the outcomes of anterior temporal lobectomy. The clinical efforts made to predict which patients are at greatest risk of experiencing adverse cognitive outcomes following epilepsy surgery are also considered. Finally, we examine the vastly changing view of TLE, including findings demonstrating that anatomical abnormalities extend far outside the temporal lobe, and that cognitive impairments extend beyond memory function. Linkage between these distributed cognitive and anatomical abnormalities point to a new understanding of the anatomical architecture of cognitive impairment in epilepsy. Clarifying the origin of these cognitive and anatomical abnormalities, their progression over time and, most importantly, methods for protecting cognitive and brain health in epilepsy, present a challenge to neurologists.

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Available from: Jack Lin, Dec 18, 2013
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    • "typically showed lower reliability in mTL, with ICCs typically below 0.5, and sometimes much lower [Clement and Belleville, 2009; Putcha et al., 2011; Wagner et al., 2005]. Furthermore, a verbal memory task may be less reliable than other memory fMRI tasks [Harrington et al., 2006]. "
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    ABSTRACT: fMRI is increasingly implemented in the clinic to assess memory function. There are multiple approaches to memory fMRI, but limited data on advantages and reliability of different methods. Here, we compared effect size, activation lateralisation, and between-sessions reliability of seven memory fMRI protocols: Hometown Walking (block design), Scene encoding (block design and event-related design), Picture encoding (block and event-related), and Word encoding (block and event-related). All protocols were performed on three occasions in 16 patients with temporal lobe epilepsy (TLE). Group T-maps showed activity bilaterally in medial temporal lobe for all protocols. Using ANOVA, there was an interaction between hemisphere and seizure-onset lateralisation (P = 0.009) and between hemisphere, protocol and seizure-onset lateralisation (P = 0.002), showing that the distribution of memory-related activity between left and right temporal lobes differed between protocols and between patients with left-onset and right-onset seizures. Using voxelwise intraclass Correlation Coefficient, between-sessions reliability was best for Hometown and Scenes (block and event). The between-sessions spatial overlap of activated voxels was also greatest for Hometown and Scenes. Lateralisation of activity between hemispheres was most reliable for Scenes (block and event) and Words (event). Using receiver operating characteristic analysis to explore the ability of each fMRI protocol to classify patients as left-onset or right-onset TLE, only the Words (event) protocol achieved a significantly above-chance classification of patients at all three sessions. We conclude that Words (event) protocol shows the best combination of between-sessions reliability of the distribution of activity between hemispheres and reliable ability to distinguish between left-onset and right-onset patients. Hum Brain Mapp, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
    Human Brain Mapping 03/2015; 36(4). DOI:10.1002/hbm.22726 · 6.92 Impact Factor
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    • "Regional atrophy has been identified in several subcortical gray matter structures, including the amygdala and thalamus (Bernasconi et al. 2003; McDonald et al. 2008), the ipsilateral temporal cortex (Moran et al. 2001; Doherty et al. 2003; Bernasconi et al. 2005), and a number of fronto-limbic cortical regions (Duzel et al. 2006; Voets et al. 2011). Such widespread brain atrophy explains the array of cognitive deficits exhibited by patients (Bell et al. 2011) and may underpin failure in achieving seizure freedom in some refractory patients who undergo selective surgical treatment (Bonilha et al. 2012). Therefore, the relevance of this extra-hippocampal atrophy has been increasingly recognized; however, its relationship to the underlying mechanisms remains poorly understood. "
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    ABSTRACT: Temporal cortex abnormalities are common in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE+HS) and believed to be relevant to the underlying mechanisms. In the present study, we set out to determine the familiarity of temporal cortex morphologic alterations in a cohort of MTLE+HS patients and their asymptomatic siblings. A surface-based morphometry (SBM) method was applied to process MRI data acquired from 140 individuals (50 patients with unilateral MTLE+HS, 50 asymptomatic siblings of patients, and 40 healthy controls). Using a region-of-interest approach, alterations in temporal cortex morphology were determined in patients and their asymptomatic siblings by comparing with the controls. Alterations in temporal cortex morphology were identified in MTLE+HS patients ipsilaterally within the anterio-medial regions, including the entorhinal cortex, parahippocampal gyrus, and temporal pole. Subtle but similar pattern of morphology changes with a medium effect size were also noted in the asymptomatic siblings. These localized alterations were related to volume loss that appeared driven by shared contractions in cerebral cortex surface area. These findings indicate that temporal cortex morphologic alterations are common to patients and their asymptomatic siblings and suggest that such localized traits are possibly heritable. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    Cerebral Cortex 01/2015; DOI:10.1093/cercor/bhu315 · 8.67 Impact Factor
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    • "TLE is the most common form of focal epilepsy. Cognitive impairment is a major concern for patients as well as clinicians [46]. "
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    ABSTRACT: Epilepsy is a mystery even though it affects an estimated 50 million people worldwide. Its management is enigmatic and as such, is not curative, but rather aims to attain freedom from seizures without side-effects. However, an approach for the selection of the most effective drugs and doses for individual patients is lacking. Almost all of the antiepileptic drugs in current use are associated with adverse reactions, some of which are severe and life-threatening. A more comprehensive treatment strategy requires improved research on epilepsy. This is the key to developing a treatment plan focused on the individual needs of each patient. Pharmacogenetics can offer a novel line of attack in the treatment of epilepsy. The potential advantages of gene therapy in the management of epilepsy are manifold. It encompasses the principle of testing as to how genetic variation among individuals affects variation in drug response, efficacy, and potential adverse drug events. Pharmacogenomics is the investigation of relationships between patient genotype and responses to drug treatment. It holds the promise of selecting the right drug at the right dose for the right person. A conceptual framework that outlines the pharmacogenetic and pharmacogenomic aspects of epilepsy presented here. Future directions for research and the application of these technologies to the clinical practice of individualising treatment for epilepsy are also discussed. A combination of research strategies and prudent policies from government may lead to a better understanding of treatment effects and futuristic but realistic management in epilepsy.
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