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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.
    Nature Communications 03/2015; 6:6606. DOI:10.1038/ncomms7606 · 10.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Normal brain functioning is presumed to depend upon interacting regions within large-scale neuronal networks. Increasing evidence exists that interictal network alterations in focal epilepsy are associated with cognitive and behavioral deficits. Nevertheless, the reported network alterations are inconclusive and prone to low statistical power due to small sample sizes as well as modest effect sizes. We therefore systematically reviewed the existing literature and conducted a meta-analysis to characterize the changes in whole-brain interictal focal epilepsy networks at sufficient power levels. We focused on the two most commonly used metrics in whole-brain networks: average path length and average clustering coefficient. Twelve studies were included that reported whole-brain network average path length and average clustering coefficient characteristics in patients and controls. The overall group difference, quantified as the standardized mean average path length difference between epilepsy and control groups, corresponded to a significantly increased average path length of 0.29 (95% confidence interval (CI): 0.12 to 0.45, p = 0.0007) in the epilepsy group. This suggests a less integrated interictal whole-brain network. Similarly, a significantly increased standardized mean average clustering coefficient of 0.35 (CI: 0.05 to 0.65, p = 0.02) was found in the epilepsy group in comparison with controls, pointing towards a more segregated interictal network. Sub-analyses revealed similar results for functional and structural networks in terms of effect size and directionality for both metrics. In addition, we found individual network studies to be prone to low power due to the relatively small group differences in average path length and average clustering coefficient in combination with small sample sizes. The pooled network characteristics support the hypothesis that focal epilepsy has widespread detrimental effects, that is, reduced integration and increased segregation, on whole brain interictal network organization, which may relate to the co-morbid cognitive and behavioral impairments often reported in patients with focal epilepsy.
    PLoS ONE 12/2014; 9(12):e114606. DOI:10.1371/journal.pone.0114606 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Accumulation of stressful events can render individuals susceptible to develop epilepsy and comorbidities. Whether such vulnerability can be predicted and reversed is not known. Here we show that social defeat, whilst not producing depression by itself, produced in 50% of rats reduced threshold for status epilepticus (SE), accelerated epileptogenesis and once epilepsy was induced, depression-like profile and cognitive deficits. Low serum BDNF levels measured before SE identified this vulnerable population. Treatment with a BDNF analog before SE prevented the occurrence of comorbidities. Thus, vulnerability to comorbidities after epilepsy onset due to unresolved past stressful events may be predicted and reversed. This article is protected by copyright. All rights reserved. © 2015 American Neurological Association.
    Annals of Neurology 04/2015; DOI:10.1002/ana.24414 · 11.91 Impact Factor

Full-text (2 Sources)

Available from
May 17, 2014