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: 15.36). 02/2011; 7(3):154-64. DOI: 10.1038/nrneurol.2011.3
Source: PubMed


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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    • "Among patients with temporal lobe epilepsy (TLE), 14% – 31% develop depression (Adams et al. 2008; Sanchez-Gistau et al. 2010) and 30% cognitive deficits (Jones et al. 2007). Comorbidities are often considered as more detrimental by patients for their quality of life than seizures themselves (Hermann et al. 2000; Bell et al. 2011). The general mechanisms underlying depression and cognitive deficits remain unknown. "

    Full-text · Chapter · Jan 2016
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    • "Recurrent seizures and interictal activity contribute to fluctuating and progressive memory deficits in MTS. Higher seizure frequency negatively impacts on memory performance [1] [3] [4] [5]. The impact of contralateral electrographic involvement on memory function in unilateral MTS has not been studied. "
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    ABSTRACT: Purpose: To evaluate the effect of contralateral electrographic involvement on memory performance (measured by neuropsychological and Wada memory testing) in patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS). Methods: We studied 51 patients with medically-refractory epilepsy associated with unilateral MTS (27 women, 30/51, left MTS) submitted to prolonged non-invasive video-EEG monitoring and bilateral Wada testing. According to ictal electrographic involvement, patients were classified as: Contralateral ictal involvement, when one or more seizures evolved with rhythmic activity in the temporal region contralateral to the MTS or exclusive ipsilateral ictal involvement if all seizures showed ictal EEG activity exclusively on the MTS side. Wada testing involved a twelve-item memory paradigm. Wada memory asymmetry score was calculated for each patient subtracting the number of recalled items after injection on the lesion side from the number of recalled items after contralateral injection. Expected asymmetry (EA) was considered if Wada memory asymmetry>0, and Symmetrical or Reversed memory asymmetry (S-RA) when ≤0. Neuropsychological testing was applied in the 51 patients and in 40 healthy controls. Verbal Memory was evaluated with the Rey Auditory Verbal Learning Test (RAVLT), considering the number of recalled items on immediate recall after the initial five consecutive encoding trials (RAVLT 6), a post-interference delayed (30min) recall (RAVLT 7), and recall after 7days. Nonverbal memory was tested with Wechsler Memory Scale-III (WMS-III) Faces subtests 1 e 2. Results: Groups did not differ in demographic, clinical and video-EEG monitoring variables. S-RA was observed more frequently in the group with contralateral ictal involvement (57.2% vs. 27.0%; p: 0.03). Logistic regression analysis considering demographic, clinical, hippocampal volume and video-EEG monitoring variables showed contralateral ictal involvement as the only independent variable associated with S-RA (coefficient=1.32, p=0.029, odds ratio 3.77; 95% CI 1.1-12.47). Additionally, the patient group with contralateral ictal EEG involvement displayed worse verbal and nonverbal memory scores compared to healthy controls. Conclusion: In this cohort of unilateral MTS patients, contralateral ictal involvement was associated with decreased memory performance on Wada and on neuropsychological testing.
    Full-text · Article · Dec 2015 · Journal of the Neurological Sciences
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    • "Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults (Engel, 2001). Cognitive deficits and psychotic symptoms are more frequently observed in TLE vs. other epilepsies and the general population (Gaitatzis et al., 2004; Bell et al., 2011). Imaging studies in TLE patients have indicated atrophy in various extratemporal sites, including the limbic thalamus and prefrontal cortex (Keller and Roberts, 2008; Bonilha et al., 2010; Diniz et al., 2011). "
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    ABSTRACT: Cognitive deficits and psychotic symptoms are highly prevalent in patients with temporal lobe epilepsy (TLE). Imaging studies in humans have suggested that these comorbidities are associated with atrophy in temporal lobe structures and other limbic regions. It remains to be clarified whether TLE comorbidities are due to the frequency of spontaneous seizures or to limbic structural damage per se. Here, we used the pilocarpine model of chronic spontaneous seizures to evaluate the possible association of seizure frequency with sensorimotor gating, spatial working memory, and neuropathology throughout limbic regions. For TLE modeling, we induced a 2-h status epilepticus by the systemic administration of lithium-pilocarpine. Once spontaneous seizures were established, we tested the locomotor activity (open field), spatial working memory (eight-arm radial maze), and sensorimotor gating (prepulse inhibition of acoustic startle). After behavioral testing, the brains were sectioned for hematoxilin-eosin staining (cell density) and parvalbumin immunohistochemistry (GABAergic neuropil) in the prefrontal cortex, nucleus accumbens, thalamus, amygdala, hippocampus, and entorhinal cortex. The animal groups analyzed included chronic epileptic rats, their controls, and rats that received lithium-pilocarpine but eventually failed to express status epilepticus or spontaneous seizures. Epileptic rats showed deficits in sensorimotor gating that negatively correlated with the radial maze performance, and impairments in both behavioral tests correlated with seizure frequency. In addition to neuronal loss at several sites, we found increased parvalbumin immunostaining in the prefrontal cortex (infralimbic area), thalamus (midline and reticular nuclei), amygdala, Ammon's horn, dentate gyrus, and entorhinal cortex. These tissue changes correlated with seizure frequency and impairments in sensorimotor gating. Our work indicates that chronic seizures might impact the inhibitory-excitatory balance in the temporal lobe and its interconnected limbic regions, which could increase the likelihood of cognitive deficits and interictal psychiatric disorders.
    Full-text · Article · Nov 2015 · Neuroscience
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