The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
OBJECTIVE - Seizures in temporal lobe epilepsy (TLE) disturb brain networks and lead to connectivity disturbances. We previously hypothesised that recurrent seizures in TLE may lead to abnormal connections involving subcortical activating structures including the ascending reticular activating system (ARAS), contributing to neocortical dysfunction and neurocognitive impairments. However, no studies of ARAS connectivity have been previously reported in patients with epilepsy.
METHODS - We used resting-state functional MRI recordings in 27 patients with TLE (67% right sided) and 27 matched controls to examine functional connectivity (partial correlation) between eight brainstem ARAS structures and 105 cortical/subcortical regions. ARAS nuclei included: cuneiform/subcuneiform, dorsal raphe, locus coeruleus, median raphe, parabrachial complex, pontine oralis, pedunculopontine and ventral tegmental area. Connectivity patterns were related to disease and neuropsychological parameters.
RESULTS - In control subjects, regions showing highest connectivity to ARAS structures included limbic structures, thalamus and certain neocortical areas, which is consistent with prior studies of ARAS projections. Overall, ARAS connectivity was significantly lower in patients with TLE than controls (p<0.05, paired t-test), particularly to neocortical regions including insular, lateral frontal, posterior temporal and opercular cortex. Diminished ARAS connectivity to these regions was related to increased frequency of consciousness-impairing seizures (p<0.01, Pearson's correlation) and was associated with impairments in verbal IQ, attention, executive function, language and visuospatial memory on neuropsychological evaluation (p<0.05, Spearman's rho or Kendell's tau-b).
CONCLUSIONS - Recurrent seizures in TLE are associated with disturbances in ARAS connectivity, which are part of the widespread network dysfunction that may be related to neurocognitive problems in this devastating disorder.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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.
Current approaches separately analyze concurrently acquired diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) data. The primary limitation of these approaches is that they do not take advantage of the information from DTI that could potentially enhance estimation of resting-state functional connectivity (FC) between brain regions. To overcome this limitation, we develop a Bayesian hierarchical spatiotemporal model that incorporates structural connectivity (SC) into estimating FC. In our proposed approach, SC based on DTI data is used to construct an informative prior for FC based on resting-state fMRI data through the Cholesky decomposition. Simulation studies showed that incorporating the two data produced significantly reduced mean squared errors compared to the standard approach of separately analyzing the two data from different modalities. We applied our model to analyze the resting state DTI and fMRI data collected to estimate FC between the brain regions that were hypothetically important in the origination and spread of temporal lobe epilepsy seizures. Our analysis concludes that the proposed model achieves smaller false positive rates and is much robust to data decimation compared to the conventional approach.
Quantification of volumetric correlation may be sensitive to disease alterations undetected by standard voxel based morphometry (VBM) such as subtle, synchronous alterations in regional volumes, and may provide complementary evidence of the structural impact of temporal lobe epilepsy (TLE) on the brain. The purpose of this study was to quantify differences of regional volumetric correlation in right (RTLE) and left (LTLE) TLE patients compared to healthy controls. A T1 weighted 3T MRI was acquired (1mm(3)) in 44 drug resistant unilateral TLE patients (n=26 RTLE, n=18 LTLE) and 44 individually age and gender matched healthy controls. Images were processed using a standard VBM framework and volumetric correlation was calculated across subjects in 90 regions and compared between patients and controls. Results were summarized across hemispheres and region groups. There was increased correlation involving the contralateral homologues of the seizure foci/network in the limbic, subcortical and temporal regions in both RTLE and LTLE. Outside these regions, results implied widespread correlated alterations across several contralateral lobes in LTLE, with more focal changes in RTLE. These findings complement previous volumetric studies in TLE describing more ipsilateral atrophy, by revealing subtle coordinated volumetric changes to identify a more widespread effect of TLE across the brain.
Copyright © 2016 Elsevier B.V. All rights reserved.
OBJECTIVE - Temporal lobe epilepsy is associated with functional changes throughout the brain, particularly including a putative seizure propagation network involving the hippocampus, insula, and thalamus. We identified a specified frequency range where functional connectivity in this network was related to duration of disease. Then, to identify specific thalamic nuclei involved in seizure propagation, we determined the subregions of the thalamus that have increased resting functional oscillations in this frequency range.
METHODS - Resting-state functional magnetic resonance imaging (fMRI) was acquired from 20 patients with unilateral temporal lobe epilepsy (TLE; 14 right and 6 left) and 20 healthy controls who were each age and gender matched to a specific patient. Wavelet-based fMRI connectivity mapping across the network was computed at each frequency to determine those frequencies where connectivity significantly decreases with duration of disease consistent with impairment due to repeated seizures. The voxel-wise power of the spontaneous blood oxygenation fluctuations of this frequency band was computed in the thalamus of each subject.
RESULTS - Functional connectivity was impaired in the proposed seizure propagation network over a specific range (0.0067-0.013 Hz and 0.024-0.032 Hz) of blood oxygenation oscillations. Increased power in this frequency band (<0.032 Hz) was detected bilaterally in the pulvinar and anterior nucleus of the thalamus of healthy controls, and was increased over the ipsilateral thalamus compared to the contralateral thalamus in TLE.
SIGNIFICANCE - This study identified frequencies of impaired connectivity in a TLE seizure propagation network and used them to localize the anterior nucleus and pulvinar of the thalamus as subregions most susceptible to TLE seizures. Further examinations of these frequencies in healthy and TLE subjects may provide unique information relating to the mechanism of seizure propagation and potential treatment using electrical stimulation.
Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Surgery can be a highly effective treatment for medically refractory temporal lobe epilepsy (TLE). The emergence of minimally invasive resective and nonresective treatment options has led to interest in epilepsy surgery among patients and providers. Nevertheless, not all procedures are appropriate for all patients, and it is critical to consider seizure outcomes with each of these approaches, as seizure freedom is the greatest predictor of patient quality of life. Standard anterior temporal lobectomy (ATL) remains the gold standard in the treatment of TLE, with seizure freedom resulting in 60-80% of patients. It is currently the only resective epilepsy surgery supported by randomized controlled trials and offers the best protection against lateral temporal seizure onset. Selective amygdalohippocampectomy techniques preserve the lateral cortex and temporal stem to varying degrees and can result in favorable rates of seizure freedom but the risk of recurrent seizures appears slightly greater than with ATL, and it is not clear whether neuropsychological outcomes are improved with selective approaches. Stereotactic radiosurgery presents an opportunity to avoid surgery altogether, with seizure outcomes now under investigation. Stereotactic laser thermo-ablation allows destruction of the mesial temporal structures with low complication rates and minimal recovery time, and outcomes are also under study. Finally, while neuromodulatory devices such as responsive neurostimulation, vagus nerve stimulation, and deep brain stimulation have a role in the treatment of certain patients, these remain palliative procedures for those who are not candidates for resection or ablation, as complete seizure freedom rates are low. Further development and investigation of both established and novel strategies for the surgical treatment of TLE will be critical moving forward, given the significant burden of this disease.
Copyright © 2015 Elsevier Inc. All rights reserved.
BACKGROUND - Due to pharmacoresistant seizures and the underutilization of surgical treatments, a large number of temporal lobe epilepsy (TLE) patients experience seizures for years or decades. The goal of this study was to generate a predictive model of duration of disease with the least number of parameters possible in order to identify and quantify the significant volumetric and functional indicators of TLE progression.
METHODS - Two cohorts of subjects including 12 left TLE, 21 right TLE and 20 healthy controls (duration = 0) were imaged on a 3T MRI scanner using high resolution T1-weighted structural MRI and 20 min of resting functional MRI scanning. Multivariate linear regression methods were used to compute a predictive model of duration of disease using 49 predictors including functional connectivity and gray matter volumes computed from these images.
RESULTS - No model developed from the full set of data accurately predicted the duration of disease across the entire range from 3 to 50 years. We then performed the regression on 35 subjects with durations of disease in the range 10 to 35 years. The resulting predictive model showed that longer durations were associated with reductions in functional connectivity from the ipsilateral temporal lobe to the contralateral temporal lobe, precuneus and mid cingulate, and with decreases in volume of the ipsilateral hippocampus and pallidum.
CONCLUSIONS - Functional and volumetric parameters accurately predicted duration of disease in TLE. The findings suggest that TLE is associated with a gradual functional isolation and significant progressive structural atrophy of the ipsilateral temporal lobe over years of duration in the range of 10-35 years. Furthermore, these changes can also be detected in the contralateral hemisphere in these patients, but to a lesser degree.
Copyright © 2014 Elsevier B.V. All rights reserved.
OBJECT - Resection is a safe and effective treatment option for children with pharmacoresistant focal epilepsy, but some patients continue experience seizures after surgery. While most studies of pediatric epilepsy surgery focus on predictors of postoperative seizure outcome, these factors are often not modifiable, and the reasons for surgical failure may remain unclear.
METHODS - The authors performed a retrospective cohort study of children and adolescents who received focal resective surgery for pharmacoresistant epilepsy. Both quantitative and qualitative analyses of factors associated with persistent postoperative seizures were conducted.
RESULTS - Records were reviewed from 110 patients, ranging in age from 6 months to 19 years at the time of surgery, who underwent a total of 115 resections. At a mean 3.1-year follow-up, 76% of patients were free of disabling seizures (Engel Class I outcome). Seizure freedom was predicted by temporal lobe surgery compared with extratemporal resection, tumor or mesial temporal sclerosis compared with cortical dysplasia or other pathologies, and by a lower preoperative seizure frequency. Factors associated with persistent seizures (Engel Class II-IV outcome) included residual epileptogenic tissue adjacent to the resection cavity (40%), an additional epileptogenic zone distant from the resection cavity (32%), and the presence of a hemispheric epilepsy syndrome (28%).
CONCLUSIONS - While seizure outcomes in pediatric epilepsy surgery may be improved by the use of high-resolution neuroimaging and invasive electrographic studies, a more aggressive resection should be considered in certain patients, including hemispherectomy if a hemispheric epilepsy syndrome is suspected. Family counseling regarding treatment expectations is critical, and reoperation may be warranted in select cases.
This study presents a cross-sectional investigation of functional networks in temporal lobe epilepsy (TLE) as they evolve over years of disease. Networks of interest were identified based on a priori hypotheses: the network of seizure propagation ipsilateral to the seizure focus, the same regions contralateral to seizure focus, the cross hemisphere network of the same regions, and a cingulate midline network. Resting functional magnetic resonance imaging data were acquired for 20 min in 12 unilateral TLE patients, and 12 age- and gender-matched healthy controls. Functional changes within and between the four networks as they evolve over years of disease were quantified by standard measures of static functional connectivity and novel measures of dynamic functional connectivity. The results suggest an initial disruption of cross-hemispheric networks and an increase in static functional connectivity in the ipsilateral temporal network accompanying the onset of TLE seizures. As seizures progress over years, the static functional connectivity across the ipsilateral network diminishes, while dynamic functional connectivity measures show the functional independence of this ipsilateral network from the network of midline regions of the cingulate declines. This implies a gradual breakdown of the seizure onset and early propagation network involving the ipsilateral hippocampus and temporal lobe as it becomes more synchronous with the network of regions responsible for secondary generalization of the seizures, a process that may facilitate the spread of seizures across the brain. Ultimately, the significance of this evolution may be realized in relating it to symptoms and treatment outcomes of TLE.
BACKGROUND - Temporal lobectomy can lead to favorable seizure outcomes in medically-refractory temporal lobe epilepsy (TLE). Although most studies focus on seizure freedom after temporal lobectomy, less is known about seizure semiology in patients who "fail" surgery. Morbidity differs between seizure types that impair or spare consciousness. Among TLE patients with seizures after surgery, how does temporal lobectomy influence seizure type and frequency?
OBJECTIVE - To characterize seizure types and frequencies before and after temporal lobectomy for TLE, including consciousness-sparing or consciousness-impairing seizures.
METHODS - We performed a retrospective longitudinal cohort study examining patients undergoing temporal lobectomy for epilepsy at our institution from January 1995 to August 2010.
RESULTS - Among 241 TLE patients who received temporal lobectomy, 174 (72.2%) patients achieved Engel class I outcome (free of disabling seizures), including 141 (58.5%) with complete seizure freedom. Overall seizure frequency in patients with persistent postoperative seizures decreased by 70% (P < .01), with larger reductions in consciousness-impairing seizures. While the number of patients experiencing consciousness-sparing simple partial seizures decreased by only 19% after surgery, the number of individuals having consciousness-impairing complex partial seizures and generalized tonic-clonic seizures diminished by 70% and 68%, respectively (P < .001). Simple partial seizure was the predominant seizure type in 19.1% vs 37.0% of patients preoperatively and postoperatively, respectively (P < .001). Favorable seizure outcome was predicted by a lack of generalized seizures preoperatively (odds ratio 1.74, 95% confidence interval 1.06-2.86, P < .5).
CONCLUSION - Given important clinical and mechanistic differences between seizures with or without impairment of consciousness, seizure type and frequency remain important considerations in epilepsy surgery.