Seizure Lateralization Research Articles

SCOPE-mTL: A non-invasive tool for identifying and lateralizing mesial temporal lobe seizures prior to scalp EEG ictal onset.

In mesial temporal lobe (mTL) epilepsy, seizure onset can precede the appearance of a scalp EEG ictal pattern by many seconds. The ability to identify this early, occult mTL seizure activity could improve lateralization and localization of mTL seizures on scalp EEG. Using scalp EEG spectral features and machine learning approaches on a dataset of combined scalp EEG and foramen ovale electrode recordings in patients with mTL epilepsy, we developed an algorithm, SCOPE-mTL, to detect and lateralize early, occult mTL seizure activity, prior to the appearance of a scalp EEG ictal pattern. Using SCOPE-mTL, 73% of seizures with occult mTL onset were identified as such, and no seizures that lacked an occult mTL onset were identified as having one. Predicted mTL seizure onset times were highly correlated with actual mTL seizure onset times (r=0.69). 50% of seizures with early mTL onset were lateralizable prior to scalp ictal onset, with 94% accuracy. SCOPE-mTL can identify and lateralize mTL seizures prior to scalp EEG ictal onset, with high sensitivity, specificity, and accuracy. Quantitative analysis of scalp EEG can provide important information about mTL seizures, even in the absence of a visible scalp EEG ictal correlate.

Differences in sleep architecture between left and right temporal lobe epilepsy.

To investigate whether seizure lateralization affects sleep macrostructure in patients with left and right temporal lobe epilepsy (TLE), as rapid eye movement (REM) sleep is shorter in patients with right hemispheric cerebral infarction than with left. We retrospectively analyzed data from 16 patients with TLE (6 men and 10 women aged 34.9±11.4years) who underwent polysomnography as well as long-term video electroencephalography. Ten patients were diagnosed with left TLE and six patients with right TLE. Sleep stages and respiratory events were scored based on the American Academy of Sleep Medicine criteria. Sleep and respiratory parameters were compared between the patient groups. Percentage of REM stage sleep was significantly (p<0.05) lower in patients with left TLE (median 8.8%, interquartile range 5.5-13.8%) than in patients with right TLE (median 17.0%, interquartile range 14.1-18.3%). The other parameters showed no significant differences. Shorter REM sleep in patients with left TLE sharply contrasts with the previous report of shorter REM sleep in patients with right cerebral infarction. Laterality of the irritative epileptic focus versus destructive lesion may have different effects on the sleep macrostructures.

Epilepsy coexisting with depression

Depression episodes in epilepsy is the most common commorbidity, affecting between 11% and 62% of patients with epilepsy. Although researchers have documented a strong association between epilepsy and psychiatric comorbidities, the nature of this relationship is poorly understood. The manifestation of depression in epilepsy is a complex issue having many interacting neurobiological and psychosocial determinants, including clinical features of epilepsy (seizure frequency, type, foci, or lateralization of foci) and neurochemical or iatrogenic mechanisms. Other risk factors are a family history of psychiatric illness, particularly depression, a lack of control over the seizures and iatrogenic causes (pharmacologic and surgical). In addition, treatment with antiepileptic drugs (AEDs) as well as social coping and adaptation skills have also been recognised as risk factors of depression associated with epilepsy. Epilepsy may foster the development of depression through being exposed to chronic stress. The uncertainty and unpredictability of seizures may instigate sadness, loneliness, despair, low self-esteem, and self-reproach in patients with epilepsy and lead to social isolation, stigmatization, or disability. Often, depression is viewed as a reaction to epilepsy's stigma and the associated poor quality of life. Moreover, patients with epilepsy display a 4-5 higher rate of depression and suicide compared with healthy population.

Resting-state functional MRI distinguishes temporal lobe epilepsy subtypes.

We assessed whether presurgical resting state functional magnetic resonance imaging (fMRI) provides information for distinguishing temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE-MTS) from TLE without MTS (TLE-noMTS). Thirty-four patients with TLE and 34 sex-/age-matched controls consented to a research imaging protocol. MTS status was confirmed by histologic evaluation of surgical tissue (TLE-MTS = 16; TLE-noMTS = 18). The fractional amplitude of low-frequency fluctuations (fALFFs) in the blood oxygen level-dependent (BOLD) resting-state fMRI signal, a marker of local metabolic demand at rest, was averaged at five regions of interest (ROIs; hippocampus, amygdala, frontal, occipital, and temporal lobe), along with corresponding volume and cortical thickness estimates. ROIs were labeled ipsilateral or contralateral according to seizure lateralization and compared across TLE-MTS, TLE-noMTS, and healthy controls (HCs). MTS status was regressed on ipsilateral hippocampal volume and fALFF to test for independent contributions. The TLE-MTS group had reduced fALFF in the ipsilateral amygdala and hippocampus; whereas, the TLE-noMTS group had marginally reduced fALFF in the ipsilateral amygdala but not hippocampus. These results were consistently obtained with and without application of global signal regression (GSR). Ipsilateral hippocampal volume contributed to 37% of the variance in MTS status (p < 0.001) and fALFF contributed an additional 10% (p = 0.021). Two MTS cases were accurately classified with fALFF but not volume, and three were accurately classified with volume but not fALFF. At the lobar level, fALFF (with GSR) was reduced in the ipsilateral temporal and bilateral frontal lobes of patients with TLE-MTS and bilateral frontal lobes of patients with TLE-noMTS in the context of normal cortical thickness. This study indicates that resting-state fMRI provides complementary functional information for MTS classification. Findings validate fALFF as a measure of regional brain integrity in TLE and highlight the value of using multi-modal imaging to provide independent diagnostic information in presurgical epilepsy evaluations.

Ictal unilateral blinking is an unreliable lateralizing sign in tuberous sclerosis complex

ObjectiveIctal unilateral blinking is an uncommon but reportedly reliable lateralizing sign, indicating an ipsilateral seizure focus. We aimed to determine its lateralizing utility in patients with tuberous sclerosis complex (TSC). MethodsWe reviewed the video-EEGs of 92 children with TSC and drug-resistant epilepsy. Eleven (12%) had seizures with unilateral blinking, of which 10 underwent epilepsy surgery. Lateralization of seizures was inferred from other semiology, ictal scalp EEG and outcome following tuberectomy. ResultsSeizures manifesting with unilateral blinking were focal motor in four patients, focal motor evolving into epileptic spasms in six, and epileptic spasms with focal features in one. Associated unilateral facial contraction was seen in five patients and arm jerking in four. Lateralized scalp ictal rhythms were seen in seven patients. Following tuberectomies, seven patients are seizure free and two had >90% reduction. Overall lateralization of seizures with unilateral blinking was contralateral in six patients and ipsilateral in four. When unilateral blinking was early in seizures, overall lateralization was more often contralateral (6/7 patients, PPV 85%). SignificanceIctal unilateral blinking is not infrequent but unreliable in lateralizing seizures in TSC. Unrecognized seizure propagation to contralateral symptomatogenic regions and potentially different mechanisms may account for the variable lateralization.

Drug-resistant focal epilepsy in women of childbearing age: Reproduction and the effect of epilepsy surgery.

Women with epilepsy (WWE) have lower birth rates than expected. The reasons for this are multifactorial and involve a complex interaction between reproductive endocrine and psychosocial factors. The effect of epilepsy surgery on reproduction in women with drug-resistant focal epilepsy has not previously been studied. Adult women of childbearing age (18-45years old) with drug-resistant focal epilepsy who had undergone a focal cortical resection between 1997 and 2008 at the Mayo Clinic in Rochester, MN were included in the study. Patients who had a history of hysterectomy or tubal ligation or who were menopausal at the time of surgery were excluded. Data on prior pregnancies and births, epilepsy history, surgical treatment, hormonal dysfunction, and socioeconomic status were obtained using a retrospective chart review. Associations between various clinical and demographic variables with changes in pregnancies and births from pre- to postsurgery were assessed using Chi-square or Fisher's exact test for categorical variables and Wilcoxon rank sum test for continuous variables. All tests were 2-sided, and p-values less than 0.05 were considered statistically significant. All analyses were performed using SAS software version 9.2 (SAS INC, Cary NC). One hundred and thirteen women (average age: 30.5years) were included in the study. Average length of follow-up was 5.7years (SD-3.90). Sixty-four patients (57.5%) were nulliparous at the time of surgery. Sixty-one patients (54%) had never been married. Average number of pregnancies per patient prior to surgery was 0.93, and average number of births prior to surgery was 0.73. After surgery, a total of 17 women had a total of 35 pregnancies and 25 births. The average number of pregnancies and births after surgery was 1.27 and 0.96, respectively. Infertility was reported in one patient postoperatively. Patients who were younger at the time of surgery experienced a greater change in the number of pregnancies and births after surgery (p=0.0036 and 0.0060, respectively). Patients who received fewer antiepileptic drug medication trials by the time of surgery also had a greater change in the number of births after surgery (p=0.0362). Seizure onset localization and lateralization, presurgical seizure frequency, age at seizure onset, duration of epilepsy, and postoperative seizure outcome were not statistically significant factors. The present retrospective observational study provides additional evidence for the importance of early surgical treatment in women with drug-resistant focal epilepsy. Patients who had received fewer medications prior to surgery were more likely to experience an increase in births following surgery. The significance of these findings requires further investigation but may support a role for earlier surgical intervention in the management of drug-resistant focal epilepsy.

Applications of global quantitative 18F-FDG-PET analysis in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a prevalent neurodegenerative disease associated with various neuropsychiatric disorders and decreased quality of life. Much has been said about the use of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET), magnetic resonance imaging (MRI), and computed tomography in the qualitative assessment of TLE. However, research into the applications of quantitative measurements to treat and diagnose TLE is severely lacking in the literature. Global quantitative analysis using 18F-FDG-PET is a powerful tool in the metabolic assessment of TLE, and can more accurately identify seizure lateralization and the potential effects of treatment as compared with visual assessments and traditional biopsy region-of-interest quantification. Therefore, there is a pressing need to introduce these novel methods to the treatment of TLE. Although 18F-FDG-PET is most commonly used for visual assessments, qualitative analysis is associated with high levels of interobserver and intraobserver variability. Semiquantitative analysis using standardized uptake value is a more consistently accurate measure of the hypometabolic patterns seen in TLE patients. Novel methods of global quantitative analysis developed in our laboratory have the potential to improve TLE assessment by limiting variability and correcting for the partial volume effect. It is of great importance to adopt these techniques into the mainstream diagnosis and treatment of TLE in order to improve patient care worldwide.

Classification of ictal and seizure-free HRV signals with focus on lateralization of epilepsy.

Epileptic onsets often affect the autonomic function of the body during a seizure, whether it is in ictal, interictal or post-ictal periods. The different effects of localization and lateralization of seizures on heart rate variability (HRV) emphasize the importance of autonomic function changes in epileptic patients. On the other hand, the detection of seizures is of primary interests in evaluating the epileptic patients. In the current paper, we analyzed the HRV signal to develop a reliable offline seizure-detection algorithm to focus on the effects of lateralization on HRV. We assessed the HRV during 5-min segments of continuous electrocardiogram (ECG) recording with a total number of 170 seizures occurred in 16 patients, composed of 86 left-sided and 84 right-sided focus seizures. Relatively high and low-frequency components of the HRV were computed using spectral analysis. Poincaré parameters of each heart rate time series considered as non-linear features. We fed these features to the Support Vector Machines (SVMs) to find a robust classification method to classify epileptic and non-epileptic signals. Leave One Out Cross-Validation (LOOCV) approach was used to demonstrate the consistency of the classification results. Our obtained classification accuracy confirms that the proposed scheme has a potential in classifying HRV signals to epileptic and non-epileptic classes. The accuracy rates for right-sided and left-sided focus seizures were obtained as 86.74% and 79.41%, respectively. The main finding of our study is that the patients with right-sided focus epilepsy showed more reduction in parasympathetic activity and more increase in sympathetic activity. It can be a marker of impaired vagal activity associated with increased cardiovascular risk and arrhythmias. Our results suggest that lateralization of the seizure onset zone could exert different influences on heart rate changes. A right-sided seizure would cause an ictal tachycardia whereas a left-sided seizure would result in an ictal bradycardia.

Patterns of verbal learning and memory in children with intractable temporal lobe or frontal lobe epilepsy.

The objective of this study was to provide a better understanding of the verbal learning and memory (VLM) patterns that might differentiate children with frontal lobe epilepsy (FLE) from children with temporal lobe epilepsy (TLE) and to examine the impact of variables thought to influence outcomes (seizure laterality, age at seizure onset, age at assessment, epilepsy duration, number of antiepileptic drugs). Retrospective analyses were carried out for children with intractable unilateral TLE (n=100) and FLE (n=27) who completed standardized measures of VLM entailing lists of single words or lists of word pairs. Mean intelligent quotients and VLM scores on single words fell within the average range for both groups, whereas scores fell within the low average to borderline range on word pairs. No significant overall differences in VLM were found between the group with TLE and the group with FLE. Older age at assessment and older age at seizure onset were generally associated with better VLM in both groups but were related to better performance in a number of indices in the group with TLE and only fewer intrusions in the group with FLE. The VLM profiles of children with TLE and FLE are generally similar. Older age at assessment and older age at seizure onset have a favorable impact on both groups but are related to better encoding, retrieval, and monitoring processes for the group with TLE and improved memory monitoring (i.e., as indicated by fewer intrusions) in the group with FLE.

Biceps electromyography in dialeptic and automotor seizures with and without secondary generalization

ObjectiveLocalization of seizure onset during presurgical video-EEG monitoring is indispensable for successful epilepsy surgery. Sometimes analysis of ictal EEG and video fails to identify this zone. Therefore, this study explored the hypothesis that ictal EMG recordings contribute to the lateralization or localization of focal epilepsy. MethodsAll patients with automotor or dialeptic seizures with or without secondary generalization were prospectively included during presurgical video-EEG monitoring over a 5years study period. We analyzed characteristics of ictal biceps EMG and compared the results to EEG and video findings. Results79 patients with 185 seizures were included (51.9% male; 73.5% automotor and 26.5% dialeptic seizures; 24.3% seizures secondarily generalized). Even in dialeptic seizures, muscle tone increased bilaterally within seconds after EEG seizure onset (66.7%) without clinical movements. Bilateral “spindle-shaped” EMG activity during the automotor phase predicted secondary generalization in 88.7%. Increase of muscle activity in the contralateral side of the body in the beginning of the secondarily generalized tonic–clonic phase was detected in 78.1% after automotor seizures whereas this phenomenon was less pronounced after dialeptic seizures (69.2%). 38.5% of dialeptic seizures evolved into generalized tonic–unilateral clonic seizures. ConclusionIctal EMG recordings provide lateralizing signs especially in secondarily generalized automotor seizures. In addition, the study suggested that secondary generalization in automotor seizures is determined early already during the automotor phase. Dialeptic seizures can evolve only unilaterally into a tonic–clonic seizure while the other side of the body remains tonic. SignificanceIctal biceps EMG can provide further information regarding lateralization of epileptic seizures.

Susceptibility-weighted imaging in acute-stage pediatric convulsive disorders.

The aim of this preliminary study was to investigate the clinical use of acute-stage susceptibility-weighted imaging (SWI) in children with prolonged convulsive disorder. Ten children with prolonged convulsive disorder who underwent SWI within 2 h after termination of seizure (acute-stage SWI group) and 15 control children who underwent SWI > 2 h after their seizures terminated or for other purposes were enrolled. The cerebral venous vasculature was compared between the groups. The acute-stage SWI group was further divided into three subgroups: normal group, those with regional low signals in the cerebral veins (regional group) and those with diffuse low signals in the cerebral veins (generalized group). Inter-ictal electroencephalography (EEG) and venous blood gas findings during seizure activity were compared between these subgroups. All patients in the acute-stage SWI group had low cerebral vein signal. Four patients were assigned to the regional group and six patients to the generalized group. Decrease of venous pH and the increase of venous pCO2 during seizure activity was more prominent in the regional group than in the generalized group. In the regional group, low-signal areas in the cerebral veins were consistent with abnormal areas on EEG; these low-signal areas resolved completely in all patients on follow-up SWI. Ten patients in the control group had normal SWI, and five had a generalized low signal. Acute-stage SWI may be a useful alternative for identifying lateralization of seizures in children with prolonged convulsive disorder.

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography.

ObjectivePatients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video–electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions.MethodsAmbulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded.ResultsEighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0–376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording.SignificanceAbout one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions.

Predicting the laterality of temporal lobe epilepsy from PET, MRI, and DTI: A multimodal study.

Pre-surgical evaluation of patients with temporal lobe epilepsy (TLE) relies on information obtained from multiple neuroimaging modalities. The relationship between modalities and their combined power in predicting the seizure focus is currently unknown. We investigated asymmetries from three different modalities, PET (glucose metabolism), MRI (cortical thickness), and diffusion tensor imaging (DTI; white matter anisotropy) in 28 left and 30 right TLE patients (LTLE and RTLE). Stepwise logistic regression models were built from each modality separately and from all three combined, while bootstrapped methods and split-sample validation verified the robustness of predictions. Among all multimodal asymmetries, three PET asymmetries formed the best predictive model (100% success in full sample, >95% success in split-sample validation). The combinations of PET with other modalities did not perform better than PET alone. Probabilistic classifications were obtained for new clinical cases, which showed correct lateralization for 7/7 new TLE patients (100%) and for 4/5 operated patients with discordant or non-informative PET reports (80%). Metabolism showed closer relationship with white matter in LTLE and closer relationship with gray matter in RTLE. Our data suggest that metabolism is a powerful modality that can predict seizure laterality with high accuracy, and offers high value for automated predictive models. The side of epileptogenic focus can affect the relationship of metabolism with brain structure. The data and tools necessary to obtain classifications for new TLE patients are made publicly available.

Sex differences in lateralization of semantic verbal fluency in temporal lobe epilepsy

When differences exist, women tend to outperform men on measures of verbal fluency, possibly due to greater bilateral language representation. Patients with temporal lobe epilepsy (TLE) have a higher rate of atypical cortical language representation than the general population, making them a population of interest for the study of language. For the current study, 78 TLE patients (51% male, 51% left temporal focus) underwent pre-surgical neuropsychological evaluations. Retrospective data analyses investigated the impact of seizure laterality and sex on letter and semantic verbal fluency. Results indicated an interaction between sex and laterality for semantic, but not letter, verbal fluency. Males with left TLE exhibited significantly worse semantic fluency than males with right TLE, whereas females’ semantic fluency did not differ by seizure focus. These data indicate that females with TLE may indeed engage in more bilateral hemispheric processing of semantic verbal fluency, whereas males may be more reliant on left temporal cortical function for this task.

Epilepsy surgery in patients with bilateral temporal lobe seizures: a systematic review.

We explored the association between magnetic resonance imaging (MRI) lesion, degree of seizure laterality on intracranial electroencephalography (iEEG), and seizure outcome in patients with ambiguous or presumed bilateral temporal lobe epilepsy (BiTLE) on scalp EEG. We systematically reviewed the literature using Embase and MEDLINE up to May 31, 2012. Patients with bilateral iEEG, temporal lobe surgery, and follow-up ≥1 year were included. We undertook three separate analyses on patients whose scalp EEG showed ambiguous onset or BiTLE (1) group data of those whose iEEG demonstrated unilateral TLE, (2) group data of those whose iEEG demonstrated BiTLE, (3) individual patient analysis in those with BiTLE for whom iEEG seizure laterality data were provided. Of 1,403 patients with ambiguous or presumed BiTLE on scalp EEG, 1,027 (73%) proved to have unilateral TLE on iEEG and contributed to the first analysis. Of these, 58% had Engel class I and 9% Engel class II outcomes. Of 132 patients in the second analysis (true BiTLE), Engel class I and II outcomes were achieved in 23% and 14%, respectively. Of 41 patients in the third analysis, 66% and 2% had Engel class I and II outcomes, respectively. The median proportion of seizures ipsilateral to the resection on iEEG did not differ between BiTLE patients with Engel class I-II (76%) and Engel III-IV (78%) outcomes (p = 0.87). Patients with ambiguous or independent bitemporal seizure onset on scalp EEG achieved good surgical outcomes. Overall, a significantly higher proportion of patients achieved good outcomes when iEEG showed unilateral TLE (67%) than when it showed true BiTLE (45%). However, the degree of seizure lateralization in those with BiTLE was not associated with seizure outcome, and it has a limited role in selecting the side of surgery.

Clinical utility of the Wechsler Memory Scale—Fourth Edition (WMS-IV) in predicting laterality of temporal lobe epilepsy among surgical candidates

This study evaluated the accuracy of the Wechsler Memory Scale—Fourth Edition (WMS-IV) in identifying functional cognitive deficits associated with seizure laterality in localization-related temporal lobe epilepsy (TLE) relative to a previously established measure, the Rey Auditory Verbal Learning Test (RAVLT). Emerging WMS-IV studies have highlighted psychometric improvements that may enhance its ability to identify lateralized memory deficits. Data from 57 patients with video-EEG-confirmed unilateral TLE who were administered the WMS-IV and RAVLT as part of a comprehensive presurgical neuropsychological evaluation for temporal resection were retrospectively reviewed. We examined the predictive accuracy of the WMS-IV not only in terms of verbal versus visual composite scores but also using individual subtests. A series of hierarchal logistic regression models were developed, including the RAVLT, WMS-IV delayed subtests (Logical Memory, Verbal Paired Associates, Designs, Visual Reproduction), and a WMS-IV verbal–visual memory difference score. Analyses showed that the RAVLT significantly predicted laterality with overall classification rates of 69.6% to 70.2%, whereas neither the individual WMS-IV subtests nor the verbal–visual memory difference score accounted for additional significant variance. Similar to previous versions of the WMS, findings cast doubt as to whether the WMS-IV offers significant incremental validity in discriminating seizure laterality in TLE beyond what can be obtained from the RAVLT.

Thalamic functional connectivity predicts seizure laterality in individual TLE patients: application of a biomarker development strategy.

Noninvasive markers of brain function could yield biomarkers in many neurological disorders. Disease models constrained by coordinate-based meta-analysis are likely to increase this yield. Here, we evaluate a thalamic model of temporal lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended in a diffusion tractography study of an independent patient population. Specifically, we evaluated whether thalamic functional connectivity (resting-state fMRI-BOLD) with temporal lobe areas can predict seizure onset laterality, as established with intracranial EEG. Twenty-four lesional and non-lesional temporal lobe epilepsy patients were studied.No significant differences in functional connection strength in patient and control groups were observed with Mann-Whitney Tests (corrected for multiple comparisons). Notwithstanding the lack of group differences, individual patient difference scores (from control mean connection strength) successfully predicted seizure onset zone as shown in ROC curves: discriminant analysis (two-dimensional) predicted seizure onset zone with 85% sensitivity and 91% specificity; logistic regression (four-dimensional) achieved 86% sensitivity and 100% specificity. The strongest markers in both analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex functional connection strength. Thus, this study shows that thalamic functional connections are sensitive and specific markers of seizure onset laterality in individual temporal lobe epilepsy patients. This study also advances an overall strategy for the programmatic development of neuroimaging biomarkers in clinical and genetic populations: a disease model informed by coordinate-based meta-analysis was used to anatomically constrain individual patient analyses.

Is there a clustering effect on electroencephalographic seizure localization?

Long-term video-EEG monitoring (LTM) is the gold standard for initial lateralization and localization of seizures in the workup for neurosurgical treatment of medically intractable epilepsy. Previous studies have yielded contradictory results as to whether seizures that occur in clusters tend to arise from the same brain region and may lead to the incorrect conclusion that seizures arise from a single focus. To determine whether seizure clustering affects localization in an LTM setting, the authors performed an observational study over 6 years at a large regional epilepsy center on those undergoing LTM for seizure diagnosis, characterization, or presurgical workup. Excluding repeat studies and LTMs with generalized or nonepileptic seizures resulted in 479 monitorings with 2774 focal seizures for analysis. Sequential pairs of consecutive focal seizures were classed as "concordant", "discordant," or "other," based on EEG localization. ANOVA analysis on the logarithm of the interseizure interval (LISI) among the three seizure pair groups showed no significant difference, p=0.47, nor did analysis defining concordance as lateralization to the same hemisphere (p=0.34). Analyses on subgroups with multifocal seizures, bilateral seizures, and extratemporal seizures all failed to show a significant difference. In conclusion, seizures have the same localizing value whether occurring in a cluster over a few hours or sporadically over a few days. This could potentially lead to shorter monitoring times.

Out-of-body experiences associated with seizures

Alterations of consciousness are critical factors in the diagnosis of epileptic seizures. With these alterations in consciousness, some persons report sensations of separating from the physical body, experiences that may in rare cases resemble spontaneous out-of-body experiences. This study was designed to identify and characterize these out-of-body-like subjective experiences associated with seizure activity. Fifty-five percent of the patients in this study recalled some subjective experience in association with their seizures. Among our sample of 100 patients, 7 reported out-of-body experiences associated with their seizures. We found no differentiating traits that were associated with patients' reports of out-of-body experiences, in terms of either demographics; medical history, including age of onset and duration of seizure disorder, and seizure frequency; seizure characteristics, including localization, lateralization, etiology, and type of seizure, and epilepsy syndrome; or ability to recall any subjective experiences associated with their seizures. Reporting out-of-body experiences in association with seizures did not affect epilepsy-related quality of life. It should be noted that even in those patients who report out-of-body experiences, such sensations are extremely rare events that do not occur routinely with their seizures. Most patients who reported out-of-body experiences described one or two experiences that occurred an indeterminate number of years ago, which precludes the possibility of associating the experience with the particular characteristics of that one seizure or with medications taken or other conditions at the time.

Using multivariate data reduction to predict postsurgery memory decline in patients with mesial temporal lobe epilepsy

Predicting postsurgery memory decline is crucial to clinical decision-making for individuals with mesial temporal lobe epilepsy (mTLE) who are candidates for temporal lobe excisions. Extensive neuropsychological testing is critical to assess risk, but the numerous test scores it produces can make deriving a formal prediction of cognitive change quite complex. In order to benefit from the information contained in comprehensive memory assessment, we used principal component analysis (PCA) to simplify neuropsychological test scores (presurgical and pre- to postsurgical change) obtained from a cohort of 56 patients with mTLE into a few easily interpretable latent components. We next performed discriminant analyses using presurgery latent components to categorize seizure laterality and then regression analyses to assess how well presurgery latent components could predict postsurgery memory decline. Finally, we validated the predictive power of these regression models in an independent sample of 18 patients with mTLE. Principal component analysis identified three significant latent components that reflected IQ, verbal memory, and visuospatial memory, respectively. Together, the presurgery verbal and visuospatial memory components classified 80% of patients with mTLE correctly according to their seizure laterality. Furthermore, the presurgery verbal memory component predicted postsurgery verbal memory decline, while the presurgery visuospatial memory component predicted visuospatial memory decline. These regression models also predicted postsurgery memory decline successfully in the independent cohort of patients with mTLE. Our results demonstrate the value of data reduction techniques in identifying cognitive metrics that can characterize laterality of damage and risk of postoperative decline.