Pue Farooque

Impaired consciousness in epilepsy investigated by a prospective responsiveness in epilepsy scale (RES)

Purpose:  Impaired consciousness in epileptic seizures has a major negative impact on patient quality of life. Prior work on epileptic unconsciousness has mainly used retrospective and nonstandardized methods. Our goal was to validate and to obtain initial data using a standardized prospective testing battery.

A Prospective Study of Loss of Consciousness in Epilepsy Using Virtual Reality Driving Simulation and Other Video Games

Patients with epilepsy are at risk of traffic accidents when they have seizures while driving. However, driving is an essential part of normal daily life in many communities, and depriving patients of driving privileges can have profound consequences for their economic and social well-being. In the current study, we collected ictal performance data from a driving simulator and two other video games in patients undergoing continuous video/EEG monitoring. We captured 22 seizures in 13 patients and found that driving impairment during seizures differed in terms of both magnitude and character, depending on the seizure type. Our study documents the feasibility of a prospective study of driving and other behaviors during seizures through the use of computer-based tasks. This methodology may be applied to further describe differential driving impairment in specific types of seizures and to gain data on anatomical networks disrupted in seizures that impair consciousness and driving safety.

Altered functional connectivity in seizure onset zones revealed by fMRI intrinsic connectivity

Objective: The purpose of this study was to investigate functional connectivity (FC) changes in epileptogenic networks in intractable partial epilepsy obtained from resting-state fMRI by using intrinsic connectivity contrast (ICC), a voxel-based network measure of degree that reflects the number of connections to each voxel. Methods: We measured differences between intrahemispheric- and interhemispheric-ICC (ICCintra−inter) that could reveal localized connectivity abnormalities in epileptogenic zones while more global network changes would be eliminated when subtracting these values. The ICCintra−inter map was compared with the seizure onset zone (SOZ) based on intracranial EEG (icEEG) recordings in 29 patients with at least 1 year of postsurgical follow-up. Two independent reviewers blindly interpreted the icEEG and fMRI data, and the concordance rates were compared for various clinical factors. Results: Concordance between the icEEG SOZ and ICCintra−inter map was observed in 72.4% (21/29) of the patients, which was higher in patients with good surgical outcome, especially in those patients with temporal lobe epilepsy (TLE) or lateral temporal seizure localization. Concordance was also better in the extratemporal lobe epilepsy than the TLE group. In 85.7% (18/21) of the cases, the ICCintra−inter values were negative in the SOZ, indicating decreased FC within the epileptic hemisphere relative to between hemispheres. Conclusions: Assessing alterations in FC using fMRI-ICC map can help localize the SOZ, which has potential as a noninvasive presurgical diagnostic tool to improve surgical outcome. In addition, the method reveals that, in focal epilepsy, both intrahemispheric- and interhemispheric-FC may be altered, in the presence of both regional as well as global network abnormalities.

Testing for minimal consciousness in complex partial and generalized tonic-clonic seizures

Impaired consciousness in epilepsy has a major negative impact on quality of life. Prior work suggests that complex partial seizures (CPS) and generalized tonic–clonic seizures (GTCS), which both cause loss of consciousness, affect similar frontoparietal networks. Milder involvement in CPS than in GTCS may spare some simple behavioral responses, resembling the minimally conscious state. However, this difference in responses has not been rigorously tested previously. During video–electroencephalography (EEG) monitoring, we administered a standardized prospective testing battery including responses to questions and commands, as well as tests for reaching/grasping a ball and visual tracking in 27 CPS (in 14 patients) and 7 GTCS (in six patients). Behavioral results were analyzed in the ictal and postictal periods based on video review. During both CPS and GTCS, patients were unable to respond to questions or commands. However, during CPS, patients often retained minimally conscious ball grasping and visual tracking responses. Patients were able to successfully grasp a ball in 60% or to visually track in 58% of CPS, and could carry out both activities in 52% of CPS. In contrast, during GTCS, preserved ball grasp (10%), visual tracking (11%), or both (7%), were all significantly less than in CPS. Postictal ball grasping and visual tracking were also somewhat better following CPS than GTCS. These findings suggest that impaired consciousness in CPS is more similar to minimally conscious state than to coma. Further work may elucidate the specific brain networks underlying relatively spared functions in CPS, ultimately leading to improved treatments aimed at preventing impaired consciousness.

Ictal spread of medial temporal lobe seizures with and without secondary generalization: An intracranial electroencephalography analysis

Secondary generalization of seizures has devastating consequences for patient safety and quality of life. The aim of this intracranial electroencephalography (icEEG) study was to investigate the differences in onset and propagation patterns of temporal lobe seizures that remained focal versus those with secondary generalization, in order to better understand the mechanism of secondary generalization.

Elevated basal glutamate and unchanged glutamine and gaba in refractory epilepsy

Aberrant glutamate and γ‐aminobutyric acid (GABA) neurotransmission contribute to seizure generation and the epileptic state. However, whether levels of these neurochemicals are abnormal in epileptic patients is unknown. Here, we report on interictal levels of glutamate, glutamine, and GABA in epilepsy patients at seizure onset and nonepileptic sites, cortical lesions, and from patients with poorly localized neocortical epilepsies.

Elevated basal glutamate and unchanged glutamine and GABA in refractory epilepsy: Microdialysis study of 79 patients at the yale epilepsy surgery program.

Aberrant glutamate and γ‐aminobutyric acid (GABA) neurotransmission contribute to seizure generation and the epileptic state. However, whether levels of these neurochemicals are abnormal in epileptic patients is unknown. Here, we report on interictal levels of glutamate, glutamine, and GABA in epilepsy patients at seizure onset and nonepileptic sites, cortical lesions, and from patients with poorly localized neocortical epilepsies.

Automatic detection of prominent interictal spikes in intracranial EEG: validation of an algorithm and relationsip to the seizure onset zone.

OBJECTIVE To develop an algorithm for the automatic quantitative description and detection of spikes in the intracranial EEG and quantify the relationship between prominent spikes and the seizure onset zone. METHODS An algorithm was developed for the quantification of time-frequency properties of spikes (upslope, instantaneous energy, downslope) and their statistical representation in a univariate generalized extreme value distribution. Its performance was evaluated in comparison to expert detection of spikes in intracranial EEG recordings from 10 patients. It was subsequently used in 18 patients to detect prominent spikes and quantify their spatial relationship to the seizure onset area. RESULTS The algorithm displayed an average sensitivity of 63.4% with a false detection rate of 3.2 per minute for the detection of individual spikes and an average sensitivity of 88.6% with a false detection rate of 1.4% for the detection of intracranial EEG contacts containing the most prominent spikes. Prominent spikes occurred closer to the seizure onset area than less prominent spikes but they overlapped with it only in a minority of cases (3/18). CONCLUSIONS Automatic detection and quantification of the morphology of spikes increases their utility to localize the seizure onset area. Prominent spikes tend to originate mostly from contacts located in the close vicinity of the seizure onset area rather than from within it. SIGNIFICANCE Quantitative analysis of time-frequency characteristics and spatial distribution of intracranial spikes provides complementary information that may be useful for the localization of the seizure-onset zone.

The importance of early immunotherapy in patients with faciobrachial dystonic seizures

Faciobrachial dystonic seizures (FBDS) are the first adult-onset autoantibody-mediated epilepsy. Thompson et al. describe 103 patients with FBDS, and show that seizures are responsive to immunotherapy, with early seizure cessation reducing long-term disability and preventing cognitive impairment. Potential pathogenic mechanisms include complement fixation and LGI1-ADAM22 complex internalisation.

Seizure localization using three-dimensional surface projections of intracranial EEG power.

Intracranial EEG (icEEG) provides a critical road map for epilepsy surgery but it has become increasingly difficult to interpret as technology has allowed the number of icEEG channels to grow. Borrowing methods from neuroimaging, we aimed to simplify data analysis and increase consistency between reviewers by using 3D surface projections of intracranial EEG poweR (3D-SPIER). We analyzed 139 seizures from 48 intractable epilepsy patients (28 temporal and 20 extratemporal) who had icEEG recordings, epilepsy surgery, and at least one year of post-surgical follow-up. We coregistered and plotted icEEG β frequency band signal power over time onto MRI-based surface renderings for each patient, to create color 3D-SPIER movies. Two independent reviewers interpreted the icEEG data using visual analysis vs. 3D-SPIER, blinded to any clinical information. Overall agreement rates between 3D-SPIER and icEEG visual analysis or surgery were about 90% for side of seizure onset, 80% for lobe, and just under 80% for sublobar localization. These agreement rates were improved when flexible thresholds or frequency ranges were allowed for 3D-SPIER, especially for sublobar localization. Interestingly, agreement was better for patients with good surgical outcome than for patients with poor outcome. Localization using 3D-SPIER was measurably faster and considered qualitatively easier to interpret than visual analysis. These findings suggest that 3D-SPIER could be an improved diagnostic method for presurgical seizure localization in patients with intractable epilepsy and may also be useful for mapping normal brain function.