Impaired consciousness in epilepsy

Departments of Neurology, Neurobiology, and Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.
The Lancet Neurology (Impact Factor: 21.9). 09/2012; 11(9):814-26. DOI: 10.1016/S1474-4422(12)70188-6
Source: PubMed


Consciousness is essential to normal human life. In epileptic seizures consciousness is often transiently lost, which makes it impossible for the individual to experience or respond. These effects have huge consequences for safety, productivity, emotional health, and quality of life. To prevent impaired consciousness in epilepsy, it is necessary to understand the mechanisms that lead to brain dysfunction during seizures. Normally the consciousness system-a specialised set of cortical-subcortical structures-maintains alertness, attention, and awareness. Advances in neuroimaging, electrophysiology, and prospective behavioural testing have shed light on how epileptic seizures disrupt the consciousness system. Diverse seizure types, including absence, generalised tonic-clonic, and complex partial seizures, converge on the same set of anatomical structures through different mechanisms to disrupt consciousness. Understanding of these mechanisms could lead to improved treatment strategies to prevent impairment of consciousness and improve the quality of life of people with epilepsy.

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    • "Focal seizures may impair consciousness, likely mediated, in part, by the spread of ictal activity to the thalamus [1] [2]. The precise thalamic regions involved and their roles with respect to the maintenance of consciousness , however, are unclear. "
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    ABSTRACT: Impaired consciousness during seizures may be mediated by ictal propagation to the thalamus. Functions of individual thalamic nuclei with respect to consciousness, however, are largely unknown. The dorsomedial (DM) nucleus of the thalamus likely plays a role in arousal and cognition. We propose that alterations of firing patterns within the DM nucleus contribute to impaired arousal during focal seizures. Electroencephalograph data were collected from electrodes within the left DM thalamus and midcingulate cortex (MCC) in a patient undergoing seizure monitoring. Spectral power was computed across ictal states (preictal, ictal, and postictal) and level of consciousness (stupor/sleep vs. awake) in the DM nucleus and MCC. Eighty-seven seizures of multifocal left frontal and temporal onsets were analyzed, characterized by loss of consciousness. At baseline, the left DM nucleus demonstrated rhythmic bursts of gamma activity, most frequently and with greatest amplitude during wakefulness. This activity ceased as ictal discharges spread to the MCC, and consciousness was impaired, and it recurred at the end of each seizure as awareness was regained. The analysis of gamma (30-40Hz) power demonstrated that when seizures occurred during wakefulness, there was lower DM ictal power (p<0.0001) and higher DM postictal power (p<0.0001) relative to the preictal epoch. This spectral pattern was not evident within the MCC or when seizures occurred during sleep. Data revealed a characteristic pattern of DM gamma bursts during wakefulness, which disappeared during partial seizures associated with impaired consciousness. The findings are consistent with studies suggesting that the DM nucleus participates in cognition and arousal. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Aug 2015 · Epilepsy & Behavior
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    • "Here, we further demonstrated the altered functional connectivity between these RSNs, suggesting that the abnormality in the two anticorrelated systems might reflect the disturbed management of introspective and extrospective information, thereby facilitating the loss of consciousness during absence seizures. This finding is consistent with previous suggestions of network inhibition or network disruption as a plausible mechanism for impaired consciousness during epilepsy seizure [3]. In addition, many studies have shown that the methods used in functional connectivity analyses would influence the anti-correlation in fMRI data [43] [44] [45]. "
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    ABSTRACT: Altered functional connectivity has been associated with the influence of epileptic activity. Abnormalities in connectivity, particularly in dorsal attention (DAN), salience (SN) and default mode (DMN) networks, might contribute to the loss of consciousness during seizures and cognitive deficits in patients with children absence epilepsy (CAE). The objective of the present study was to identify whether the functional network connectivity (FNC) is changed between patients with CAE and healthy controls. Using independent component analysis, twelve resting state networks (RSNs) were identified in resting state functional magnetic resonance imaging data sets in eighteen CAE patients and twenty-one healthy controls. Analyses of the group differences in FNC strength were conducted, controlling for age and gender effects. The findings showed that some functional networks were clustered into two subgroups, correlated within subgroups and antagonized with each other. Compared with the controls, patients with CAE demonstrated abnormal FNC strength among three networks: DMN, DAN and SN. In addition, the antagonism of two subgroups was altered. These results might reflect the underlying neuronal functional impairment or altered integration among these RSNs in CAE, suggesting that the abnormal functional connectivity is likely to imply the pathological mechanism associated with the accumulative influence of epileptic activity. These findings contribute to the understanding of the behavior abnormality in CAE, such as disturbed executive and attentional functions and the loss of consciousness during absence seizures. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · May 2015 · Journal of the neurological sciences
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    • "Looking at the particular brain regions in TLE with increased connectivity variance, we speculate that (1) the hippocampal activity interferes with language (39) and memory function (40), both interictally and ictally and that (2) the increased dynamic connectivity to the precuneus and frontal cortex is ictally associated with impaired consciousness (4, 41) and executive functioning (42). We also propose that (3) the increased dynamics in functional connectivity between the hippocampus and the sensorimotor cortices might pave the way for ictal sensory and motor dysfunction and – probably tightly related to the supplementary motor area – in particular motor automatisms (43). "
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    ABSTRACT: Temporal lobe epilepsy (TLE) can be conceptualized as a network disease. The network can be characterized by inter-regional functional connectivity, i.e., blood oxygen level-dependent (BOLD) signal correlations between any two regions. However, functional connectivity is not constant over time, thus computing correlation at a given time and then at some later time could give different results (non-stationarity). We hypothesized (1) that non-stationarities can be induced by epilepsy (e.g., interictal epileptic activity) increasing local signal variance and that (2) these transient events contribute to fluctuations in connectivity leading to pathological functioning, i.e., TLE semiology. We analyzed fMRI data from 27 patients with TLE and 22 healthy controls focusing on EEG-confirmed wake epochs only to protect against sleep-induced connectivity changes. Testing hypothesis (1), we identified brain regions where the BOLD signal variance was significantly greater in TLE than in controls: the temporal pole - including the hippocampus. Taking the latter as the seed region and testing hypothesis (2), we calculated the time-varying inter-regional correlation values (dynamic functional connectivity) to other brain regions and found greater connectivity variance in the TLE than the control group mainly in the precuneus, the supplementary and sensorimotor, and the frontal cortices. We conclude that the highest BOLD signal variance in the hippocampi is highly suggestive of a specific epilepsy-related effect. The altered connectivity dynamics in TLE patients might help to explain the hallmark semiological features of dyscognitive seizures including impaired consciousness (precuneus, frontal cortex), sensory disturbance, and motor automatisms (sensorimotor cortices, supplementary motor cortex). Accounting for the non-stationarity and state-dependence of functional connectivity are a prerequisite in the search for potential connectivity-derived biomarkers in TLE.
    Full-text · Article · Sep 2014 · Frontiers in Neurology
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