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Epilepsy surgery has seen numerous technological advances in both diagnostic and therapeutic procedures in recent years. This has increased the number of patients who may be candidates for intervention and potential improvement in quality of life. However, the expansion of the field also necessitates a broader understanding of how to incorporate both traditional and emerging technologies into the care provided at comprehensive epilepsy centers. This review summarizes both old and new surgical procedures in epilepsy using an example algorithm. While treatment algorithms are inherently oversimplified, incomplete, and reflect personal bias, they provide a general framework that can be customized to each center and each patient, incorporating differences in provider opinion, patient preference, and the institutional availability of technologies. For instance, the use of minimally invasive stereotactic electroencephalography (SEEG) has increased dramatically over the past decade, but many cases still benefit from invasive recordings using subdural grids. Furthermore, although surgical resection remains the gold-standard treatment for focal mesial temporal or neocortical epilepsy, ablative procedures such as laser interstitial thermal therapy (LITT) or stereotactic radiosurgery (SRS) may be appropriate and avoid craniotomy in many cases. Furthermore, while palliative surgical procedures were once limited to disconnection surgeries, several neurostimulation treatments are now available to treat eloquent cortical, bitemporal, and even multifocal or generalized epilepsy syndromes. An updated perspective in epilepsy surgery will help guide surgical decision making and lay the groundwork for data collection needed in future studies and trials.
Copyright © 2018 Elsevier Inc. All rights reserved.
Over the past 20 years, a large body of experimental and epidemiologic evidence has linked sleep duration and quality to glucose homeostasis, although the mechanistic pathways remain unclear. The aim of the current study was to determine whether genetic variation influencing both sleep and glucose regulation could underlie their functional relationship. We hypothesized that the genetic regulation of electroencephalographic (EEG) activity during non-rapid eye movement sleep, a highly heritable trait with fingerprint reproducibility, is correlated with the genetic control of metabolic traits including insulin sensitivity and β-cell function. We tested our hypotheses through univariate and bivariate heritability analyses in a three-generation pedigree with in-depth phenotyping of both sleep EEG and metabolic traits in 48 family members. Our analyses accounted for age, sex, adiposity, and the use of psychoactive medications. In univariate analyses, we found significant heritability for measures of fasting insulin sensitivity and β-cell function, for time spent in slow-wave sleep, and for EEG spectral power in the delta, theta, and sigma ranges. Bivariate heritability analyses provided the first evidence for a shared genetic control of brain activity during deep sleep and fasting insulin secretion rate.
© 2017 by the American Diabetes Association.
EEG acquired simultaneously with fMRI (EEG-fMRI) is a multimodal method that has shown promise in mapping the seizure onset zone in patients with focal epilepsy. However, there are many instances when this method is unsuccessful or not applicable, and other data driven fMRI methods may be utilized. One such method is the two-dimensional temporal clustering analysis (2dTCA). In this study we compared the classic EEG-fMRI and 2dTCA performance in mapping regions related to the seizure onset region in 18 focal epilepsy patients (12 presenting interictal epileptiform discharges (IEDs), during EEG-fMRI acquisition) with Engel I or II surgical outcome. Activation maps of both 2dTCA timing outputs (positive and negative histograms) and EEG detected IEDs were computed and compared to the region of epilepsy surgical resection. Patients were evaluated in three categories based on frequency of EEG detected spiking during the MRI. EEG-fMRI maps were concordant to the epilepsy region in 5/12 subjects, four with frequent IEDs on EEG. The 2dTCA was successful in mapping 13/18 patients including 3/6 with no IEDs detected (10/12 with IEDs detected). The epilepsy-related activities were successfully mapped by both methods in only 4/12 patients. This work suggests that the epilepsy-related information detected by each method may be different: while EEG-fMRI is more accurate in patients with high rather than lower numbers of EEG detected IEDs; 2dTCA can be useful in evaluating patients even when no concurrent EEG spikes are detected or EEG-fMRI is not effective. Therefore, our results support that 2dTCA might be an alternative for mapping epilepsy-related BOLD activity in negative EEG-fMRI (6/7 patients) and spike-less patients.
OBJECTIVE - Medically refractory epilepsy is a debilitating disorder that is particularly challenging to treat in patients who have already failed a surgical resection. Evidence regarding outcomes of further epilepsy surgery is limited to small case series and reviews. Therefore, our group performed the first quantitative meta-analysis of the literature from the past 30 years to assess for rates and predictors of successful reoperations.
METHODS - A PubMed search was conducted for studies reporting outcomes of repeat epilepsy surgery. Studies were excluded if they reported fewer than five eligible patients or had average follow-ups < 1 year, and patients were excluded from analysis if they received a nonresective intervention. Outcomes were stratified by each variable of interest, and quantitative meta-analysis was performed to generate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS - Seven hundred eighty-two patients who received repeat resective epilepsy surgery from 36 studies were included. Engel I outcome was observed in 47% (n = 369) of patients. Significant predictors of seizure freedom included congruent over noncongruent electrophysiology data (OR = 3.6, 95% CI = 1.6-8.2), lesional over nonlesional epilepsy (OR = 3.2, 95% CI = 1.9-5.3), and surgical limitations over disease-related factors associated with failure of the first surgery (OR = 2.6, 95% CI = 1.3-5.3). Among patients with at least one of these predictors, seizure freedom was achieved in 58%. Conversely, the use of invasive monitoring was associated with worse outcome (OR = 0.4, 95% CI = 0.2-0.9). Temporal lobe over extratemporal/multilobe resection (OR = 1.5, 95% CI = 0.8-3.0) and abnormal over normal preoperative magnetic resonance imaging (OR = 1.9, 95% CI = 0.6-5.4) showed nonsignificant trends toward seizure freedom.
SIGNIFICANCE - This analysis supports considering further resection in patients with intractable epilepsy who continue to have debilitating seizures after an initial surgery, especially in the context of factors predictive of a favorable outcome.
Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
It has been proposed that early differences in sensory responsiveness arise from atypical neural function and produce cascading effects on development across domains. This longitudinal study prospectively followed infants at heightened risk for autism spectrum disorder (ASD) based on their status as younger siblings of children diagnosed with ASD (Sibs-ASD) and infants at relatively lower risk for ASD (siblings of typically developing children; Sibs-TD) to examine the developmental sequelae and possible neurophysiological substrates of a specific sensory response pattern: unusually intense interest in nonsocial sensory stimuli or "sensory seeking." At 18 months, sensory seeking and social orienting were measured with the Sensory Processing Assessment, and a potential neural signature for sensory seeking (i.e., frontal alpha asymmetry) was measured via resting state electroencephalography. At 36 months, infants' social symptomatology was assessed in a comprehensive diagnostic evaluation. Sibs-ASD showed elevated sensory seeking relative to Sibs-TD, and increased sensory seeking was concurrently associated with reduced social orienting across groups and resting frontal asymmetry in Sibs-ASD. Sensory seeking also predicted later social symptomatology. Findings suggest that sensory seeking may produce cascading effects on social development in infants at risk for ASD and that atypical frontal asymmetry may underlie this atypical pattern of sensory responsiveness.
Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Individuals differ greatly in their sensitivity to rewards and punishments. In the extreme, these differences are implicated in a range of psychiatric disorders from addiction to depression. However, it is unclear how these differences influence the recruitment of attention, working memory, and long-term memory when responding to potential rewards. Here, we used a rewarded memory-guided visual search task and ERPs to examine the influence of individual differences in self-reported reward/punishment sensitivity, as measured by the Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) scales, on the recruitment of cognitive mechanisms in conditions of potential reward. Select subscales of the BAS, including the fun seeking and reward responsiveness scales, showed unique relationships with context updating to reward cues and working memory maintenance of potentially rewarded stimuli. In contrast, BIS scores showed unique relationships with deployment of attention at different points in the task. These results suggest that sensitivity to rewards (i.e., BAS) and to punishment (i.e., BIS) may play an important role in the recruitment of specific and distinct cognitive mechanisms in conditions of potential rewards.
© 2017 Society for Psychophysiological Research.
Dravet syndrome, an early onset epileptic encephalopathy, is most often caused by de novo mutation of the neuronal voltage-gated sodium channel gene SCN1A. Mouse models with deletion of Scn1a recapitulate Dravet syndrome phenotypes, including spontaneous generalized tonic-clonic seizures, susceptibility to seizures induced by elevated body temperature, and elevated risk of sudden unexpected death in epilepsy. Importantly, the epilepsy phenotype of Dravet mouse models is highly strain-dependent, suggesting a strong influence of genetic modifiers. We previously identified Cacna1g, encoding the Cav3.1 subunit of the T-type calcium channel family, as an epilepsy modifier in the Scn2a transgenic epilepsy mouse model. In this study, we asked whether transgenic alteration of Cacna1g expression modifies severity of the Scn1a Dravet phenotype. Scn1a mice with decreased Cacna1g expression showed partial amelioration of disease phenotypes with improved survival and reduced spontaneous seizure frequency. However, reduced Cacna1g expression did not alter susceptibility to hyperthermia-induced seizures. Transgenic elevation of Cacna1g expression had no effect on the Scn1a epilepsy phenotype. These results provide support for Cacna1g as a genetic modifier in a mouse model of Dravet syndrome and suggest that Cav3.1 may be a potential molecular target for therapeutic intervention in patients.
Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
OBJECTIVE - Currently, approximately 60-70% of patients with unilateral temporal lobe epilepsy (TLE) remain seizure-free 3 years after surgery. The goal of this work was to develop a presurgical connectivity-based biomarker to identify those patients who will have an unfavorable seizure outcome 1-year postsurgery.
METHODS - Resting-state functional and diffusion-weighted 3T magnetic resonance imaging (MRI) was acquired from 22 unilateral (15 right, 7 left) patients with TLE and 35 healthy controls. A seizure propagation network was identified including ipsilateral (to seizure focus) and contralateral hippocampus, thalamus, and insula, with bilateral midcingulate and precuneus. Between each pair of regions, functional connectivity based on correlations of low frequency functional MRI signals, and structural connectivity based on streamline density of diffusion MRI data were computed and transformed to metrics related to healthy controls of the same age.
RESULTS - A consistent connectivity pattern representing the network expected in patients with seizure-free outcome was identified using eight patients who were seizure-free at 1-year postsurgery. The hypothesis that increased similarity to the model would be associated with better seizure outcome was tested in 14 other patients (Engel class IA, seizure-free: n = 5; Engel class IB-II, favorable: n = 4; Engel class III-IV, unfavorable: n = 5) using two similarity metrics: Pearson correlation and Euclidean distance. The seizure-free connectivity model successfully separated all the patients with unfavorable outcome from the seizure-free and favorable outcome patients (p = 0.0005, two-tailed Fisher's exact test) through the combination of the two similarity metrics with 100% accuracy. No other clinical and demographic predictors were successful in this regard.
SIGNIFICANCE - This work introduces a methodologic framework to assess individual patients, and demonstrates the ability to use network connectivity as a potential clinical tool for epilepsy surgery outcome prediction after more comprehensive validation.
Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
BACKGROUND - Occipital lobe epilepsy (OLE) is an uncommon but debilitating focal epilepsy syndrome with seizures often refractory to medical management. While surgical resection has proven a viable treatment, previous studies examining postoperative seizure freedom rates are limited by small sample size and patient heterogeneity, thus exhibiting significant variability in their results.
OBJECTIVE - To review the medical literature on OLE so as to investigate rates and predictors of both seizure freedom and visual outcomes following surgery.
METHODS - We reviewed manuscripts exploring surgical resection for drug-resistant OLE published between January 1990 and June 2015 on PubMed. Seizure freedom rates were analyzed and potential predictors were evaluated with separate meta-analyses. Postoperative visual outcomes were also examined.
RESULTS - We identified 27 case series comprising 584 patients with greater than 1 yr of follow-up. Postoperative seizure freedom (Engel class I outcome) was observed in 65% of patients, and was significantly predicted by age less than 18 yr (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.13-2.18), focal lesion on pathological analysis (OR 2.08, 95% CI 1.58-2.89), and abnormal preoperative magnetic resonance imaging (OR 3.24, 95% 2.03-6.55). Of these patients, 175 also had visual outcomes reported with 57% demonstrating some degree of visual decline following surgery. We did not find any relationship between postoperative visual and seizure outcomes.
CONCLUSION - Surgical resection for OLE is associated with favorable outcomes with nearly two-thirds of patients achieving postoperative seizure freedom. However, patients must be counseled regarding the risk of visual decline following surgery.
Copyright © 2017 by the Congress of Neurological Surgeons
RATIONALE - Hypermotor seizures are most often reported from the frontal lobe but may also have temporal, parietal, or insular origin. We noted a higher proportion of patients with temporal lobe epilepsy in our surgical cohort who had hypermotor seizures. We evaluated the anatomic localization and surgical outcome in patient with refractory hypermotor seizures who had epilepsy surgery in our center.
METHODS - We identified twenty three patients with refractory hypermotor seizures from our epilepsy surgery database. We analyzed demographics, presurgical evaluation including semiology, MRI, PET scan, interictal/ictal scalp video-EEG, intracranial recording, and surgical outcomes. We evaluated preoperative variables as predictors of outcome.
RESULTS - Most patients (65%) had normal brain MRI. Intracranial EEG was required in 20 patients (86.9%). Based on the presurgical evaluation, the resection was anterior temporal in fourteen patients, orbitofrontal in four patients, cingulate in four patients, and temporoparietal in one patient. The median duration of follow-up after surgery was 76.4months. Fourteen patients (60%) had been seizure free at the last follow up while 3 patients had rare disabling seizures.
CONCLUSIONS - Hypermotor seizures often originated from the temporal lobe in this series of patients who had epilepsy surgery. This large proportion of temporal lobe epilepsy may be the result of a selection bias, due to easier localization and expected better outcome in temporal lobe epilepsy. With extensive presurgical evaluation, including intracranial EEG when needed, seizure freedom can be expected in the majority of patients.
Copyright © 2016. Published by Elsevier Inc.