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Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and is responsible for 15%-20% of epilepsy cases in children. Class I evidence strongly supports the use of temporal lobectomy for intractable TLE in adults, but fewer studies have examined seizure outcomes and predictors of seizure freedom after temporal lobectomy in pediatric patients. The authors performed a systematic review and meta-analysis of studies including 10 or more pediatric patients (age ≤ 19 years) published over the last 20 years examining seizure outcomes after temporal lobectomy for TLE. Thirty-six studies met their inclusion criteria. These 36 studies included 1318 pediatric patients with a mean age (± SEM) of 10.7 ± 0.3 years. Overall, seizure freedom (Engel Class I outcome) was achieved in 1002 cases (76%); 316 patients (24%) continued to have seizures (Engel Class II-IV outcome). All patients had at least 1 year of follow-up. Statistically significant predictors of seizure freedom after surgery included lesional epilepsy etiology (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.02-1.15), abnormal findings on preoperative MRI (OR 1.27, 95% CI 1.16-1.40), and lack of generalized seizures (OR 1.36, 95% CI 1.20-1.56). Among lesional epilepsy cases, there was a trend toward better outcome with gross-total lesionectomy than with subtotal resection. Approximately three-fourths of pediatric patients with TLE attain seizure freedom after temporal lobectomy. Favorable outcomes may be predicted by lesional epilepsy etiology, abnormal MRI, and lack of generalized seizures. Pediatric patients with medically refractory TLE should be referred to a comprehensive pediatric epilepsy center for surgical evaluation.
PURPOSE - Most children with medically refractory temporal lobe epilepsy (TLE) become seizure free after temporal lobectomy, but some individuals continue to seize. As studies of temporal lobectomy typically focus on seizure freedom, the effect of surgery on seizure type and frequency among children with persistent seizures is poorly understood. Seizures which impair consciousness are associated with increased morbidity compared to consciousness-sparing seizures.
METHODS - A retrospective cohort study was performed to evaluate the effects of temporal lobectomy on seizure type and frequency in children with intractable TLE.
RESULTS - Among 58 pediatric TLE patients with a mean (±SEM) age of 14.0 ± 0.7 years who received temporal lobectomy, 46 (79.3%) individuals achieved an Engel class I seizure outcome, including 38 (65.5%) children who became completely seizure free (Engel IA). Mean follow-up was 2.7 ± 0.4 years. While the number of patients experiencing simple partial seizures (SPSs) (consciousness sparing) decreased by only 23 % after surgery, the number of children having complex partial seizures and generalized tonic-clonic seizures (consciousness impairing) diminished by 87 and 83%, respectively (p < 0.01). SPS was the predominant seizure type in only 11.3% of patients before resection, but in 42.1% of patients with postoperative seizures (p < 0.01). Children with postoperative seizures experienced a 70% reduction in overall seizure frequency compared to baseline (p < 0.05), having consciousness-impairing seizures 94% less frequently (p < 0.05), but having consciousness-sparing seizures 35% more frequently (p = 0.73).
CONCLUSIONS - Seizure type and frequency are important considerations in the medical and surgical treatment of children with epilepsy, although complete seizure freedom remains the ultimate goal.
Temporal-lobe epilepsy (TLE) involves seizures that typically originate in the hippocampus. There is evidence that seizures involve anatomically and functionally connected brain networks within and beyond the temporal lobe. Many studies have explored the effect of TLE on gray matter and resting-state functional connectivity in the brain. However, the relationship between structural and functional changes has not been fully explored. The goal of this study was to investigate the relationship between gray matter concentration (GMC) and functional connectivity in TLE at the voxel level. A voxel-wise linear regression analysis was performed between GMC maps and whole-brain resting-state functional connectivity maps to both the left thalamus (Lthal) and the left hippocampus (LH) in a group of 15 patients with left TLE. Twenty regions were found that exhibited GMC decreases linearly correlated with resting-state functional connectivity to either the LH or the Lthal in the patient group only. A subset of these regions had significantly reduced GMC, and one of these regions also had reduced functional connectivity to the LH in TLE compared to the controls. These results suggest a network of impairment in left TLE where more severe reductions in GMC accompany decreases (LH, Lthal, right midcingulate gyrus, left precuneus, and left postcentral gyrus) or increases (LH to right thalamus) in resting functional connectivity. However, direct relationships between these imaging parameters and disease characteristics in these regions have yet to be established.
The majority of patients with temporal lobe epilepsy (TLE) experience disturbances of episodic memory from structural damage or dysfunction of the hippocampus. The objective of this study was to use functional Magnetic Resonance Imaging (fMRI) to identify regions where resting state connectivity to the left hippocampus (LH) is correlated with neuropsychological measures of verbal memory retention in TLE patients. Eleven left TLE (LTLE) patients and 15 control subjects participated in resting state fMRI scans. All LTLE patients underwent neuropsychological testing. Resting state functional connectivity maps to the LH were calculated for each patient, and subsequently used in a multiple regression analysis with verbal memory retention scores as a covariate. The analysis identified brain regions whose connectivity to the LH was linearly related to memory retention scores across the group of patients. In LTLE patients, right sided (contralateral) clusters in the precuneus and inferior parietal lobule (IPL) exhibited increased connectivity to the LH with increased memory retention score; left sided (ipsilateral) regions in the precuneus and IPL showed increased connectivity to the LH with decreased retention score. Patients with high memory retention scores had greater connectivity between the LH-right parietal clusters than between the LH-left parietal clusters; in contrast, control subjects had significantly and consistently greater LH-left hemisphere than LH-right hemisphere connectivity. Our results suggest that increased connectivity in contralateral hippocampal functional pathways within the episodic verbal memory network represents a strengthening of alternative pathways in LTLE patients with strong verbal memory retention abilities.
Copyright © 2012 Wiley Periodicals, Inc.
PURPOSE - Early surgical intervention can be advantageous in the treatment of refractory temporal lobe epilepsy (TLE). The success of TLE surgery relies on accurate lateralization of the seizure onset. The purpose of this study was to determine whether resting functional MRI (fMRI) connectivity mapping of the hippocampus has the potential to complement conventional presurgical evaluations in distinguishing left from right TLE. In addition, we sought to determine whether this same network might separate patients with favorable from unfavorable postoperative outcomes.
METHODS - Resting fMRI acquisitions were performed on 21 patients with TLE and 15 healthy controls. The patients included seven patients with left TLE and seven patients with right TLE with seizure-free postoperative outcome, and five patients with left TLE and two patients with right TLE with recurring seizures after surgery. Functional connectivity maps to each hippocampus were determined for each subject and were compared between the controls and the seizure-free patients with left TLE and with right TLE. The one network identified was then quantified in the patients with TLE and recurring seizures.
KEY FINDINGS - The resting functional connectivity between the right hippocampus and the ventral lateral nucleus of the right thalamus was the most statistically significant network to distinguish between seizure-free patients with left TLE and with right TLE with high sensitivity and specificity. This connectivity was also significantly greater in the seizure-free patients with left TLE than the healthy controls. Finally, six of the seven patients in whom seizures recurred after surgery had connectivity values in this network unlike those who were seizure-free.
SIGNIFICANCE - This study identified a region in the ventral lateral nucleus of the right thalamus whose connectivity to the hippocampi separates left from right TLE subjects. This suggests that the quantification of resting-state functional magnetic resonance imaging (MRI) connectivity across this network may be a potential indicator of lateralization of TLE that may be added to other presurgical MRI assessments. Further validation in a larger, independent cohort is required.
Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.
PURPOSE - Mesial temporal lobe epilepsy (mTLE) is a chronic disorder with spontaneous seizures recurring for years, or even decades. Many structural and functional changes have been detected in both the seizure focus and distal regions throughout the brain over this duration that may reflect the development of epileptogenic networks. Resting state functional magnetic resonance imaging (fMRI) connectivity mapping has the potential to elucidate and quantify these networks. The network between the left and right hippocampus may very likely be one of the most susceptible to changes due to long-term seizure propagation effects. Therefore, the objective of this study was to quantify cross hippocampal influence in mTLE using high temporal resolution fMRI, and to determine its relationship with disease duration.
METHODS - fMRI images were acquired in the resting (interictal) state with 500 ms temporal resolution across the temporal lobes of 19 mTLE patients (13 left, 6 right). The left and right hippocampi were identified on each subject's images using both structurally defined and functionally defined boundaries. The cross hippocampal influence was quantified in two ways for each pair of regions: (1) the nondirectional hippocampal functional connectivity calculated as the Pearson's correlation between the average time series in the left and the right hippocampus regions, and (2) the Granger causality (GC) laterality measure, which implies directional influence by determining temporal precedence. Each of these measures was correlated with age, age of onset, and disease duration across subjects to investigate relationship to disease progression.
KEY FINDINGS - The hippocampal connectivity was not significantly different between patients with left and right mTLE using either the structurally or the functionally defined regions. Across all patients, hippocampal connectivity was not correlated significantly with age of onset or duration of disease. However, as duration of disease increased after 10 years (nine patients), the hippocampal connectivity increased linearly. Using the functionally defined regions, the GC laterality was increased in the right mTLE over the left mTLE, indicating that the left hippocampus was influencing the right hippocampus more than the right influencing left. This was also positively correlated with age of onset. Furthermore, like hippocampal connectivity, the relationship between GC laterality and duration of disease changes after 10 years duration of disease. After this duration, the GC laterality was positive in the three of three patients with right mTLE (left influencing right), whereas the GC laterality was negative in five of six patients with left mTLE (right influencing left).
SIGNIFICANCE - This study reveals a relationship between fMRI functional connectivity and causal influence of the left and right hippocampi and duration of disease in mTLE. During the interictal state, the interhemispheric hippocampal connectivity initially is disrupted and then linearly increases as the epilepsy progresses longer than 10 years. This increase in connectivity appears to be due to the hippocampus contralateral to the epileptogenic focus exerting more influence over the ipsilateral hippocampus. These findings may have implications in understanding the functional development of epileptic networks and possibly prediction of surgical outcome of mTLE.
Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in each hemisphere. Finally, we observed that complex-partial seizures were somewhat more common with onset in the language-dominant temporal lobe. These findings provide direct evidence for cortical dysfunction in the form of bilateral frontoparietal slow waves associated with impaired consciousness in temporal lobe seizures. We hypothesize that bilateral temporal lobe seizures may exert a powerful inhibitory effect on subcortical arousal systems. Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy.
The purpose of this study was to determine transient functional signal activity in a small, homogeneous group of left temporal lobe epilepsy (TLE) patients, without the use of EEG; and to use one of these activated regions to identify a possible epileptogenic network across the whole brain in this group. Resting functional MRI scanning was performed on five left TLE patients who underwent selective amygdalohippocampectomy resulting in seizure control and 10 healthy control subjects. Activation maps of functional signal peaks were calculated using a data-driven analysis, 2dTCA, across the group of patients. In addition to the expected region of activation in the left anterior hippocampus, the results of the 2dTCA analysis revealed activity in the bilateral insular cortex and default-mode network which are not commonly reported using fMRI, but are supported by other electrical and functional changes. The region of activation corresponding to the anterior hippocampal region of resection (presumably the epileptogenic region) was used as a seed region for fMRI functional connectivity analysis. This revealed increased negative connectivity in the patients as compared to controls across a network including thalamic, brainstem, frontal and parietal regions consistent with theories of inhibited function in subcortical and cortical structures during ictal propagation.
Why do complex-partial seizures in temporal lobe epilepsy (TLE) cause a loss of consciousness? Abnormal function of the medial temporal lobe is expected to cause memory loss, but it is unclear why profoundly impaired consciousness is so common in temporal lobe seizures. Recent exciting advances in behavioral, electrophysiological, and neuroimaging techniques spanning both human patients and animal models may allow new insights into this old question. While behavioral automatisms are often associated with diminished consciousness during temporal lobe seizures, impaired consciousness without ictal motor activity has also been described. Some have argued that electrographic lateralization of seizure activity to the left temporal lobe is most likely to cause impaired consciousness, but the evidence remains equivocal. Other data correlates ictal consciousness in TLE with bilateral temporal lobe involvement of seizure spiking. Nevertheless, it remains unclear why bilateral temporal seizures should impair responsiveness. Recent evidence has shown that impaired consciousness during temporal lobe seizures is correlated with large-amplitude slow EEG activity and neuroimaging signal decreases in the frontal and parietal association cortices. This abnormal decreased function in the neocortex contrasts with fast polyspike activity and elevated cerebral blood flow in limbic and other subcortical structures ictally. Our laboratory has thus proposed the "network inhibition hypothesis," in which seizure activity propagates to subcortical regions necessary for cortical activation, allowing the cortex to descend into an inhibited state of unconsciousness during complex-partial temporal lobe seizures. Supporting this hypothesis, recent rat studies during partial limbic seizures have shown that behavioral arrest is associated with frontal cortical slow waves, decreased neuronal firing, and hypometabolism. Animal studies further demonstrate that cortical deactivation and behavioral changes depend on seizure spread to subcortical structures including the lateral septum. Understanding the contributions of network inhibition to impaired consciousness in TLE is an important goal, as recurrent limbic seizures often result in cortical dysfunction during and between epileptic events that adversely affects patients' quality of life.
BACKGROUND - Selective amygdalohippocampectomy (SelAH) is increasingly performed in patients with mesial temporal lobe epilepsy and hippocampal sclerosis. To determine whether visual field defects are less pronounced after SelAH than after standard temporal lobectomy (StTL), we retrospectively analyzed postoperative quantitative visual fields after the 2 procedures.
METHODS - Humphrey visual field analysis was obtained postoperatively in 18 patients who had undergone SelAH and in 33 patients who had undergone StTL. The SelAH was performed via a transcortical approach through the middle temporal gyrus and included the amygdala, 3 cm of the hippocampus, and the parahippocampal gyrus. The visual field pattern deviation was used for analysis. We considered a defect clinically significant if there were 3 contiguous coordinates affected at the 5% level or 2 at the 1% level.
RESULTS - All but 2 of 18 patients who had undergone SelAH had homonymous superior quadrantic visual field defects contralateral to the side of the surgery. One patient had no defects by our criteria, and one had a mild defect that reached significance only in the ipsilateral eye. The averaged defect affected mostly coordinates close to the vertical meridian with relative sparing of points close to the horizontal meridian. All but 3 of the 33 patients who had undergone StTL had homonymous superior quadrantic visual field defects. One patient had no defects; 2 had defects that reached significance in only one eye. The averaged defect involved all points in the affected quadrant, but was also greater near the vertical meridian. Of 13 tested visual field coordinates, 4 were significantly less affected by SelAH in the ipsilateral eye and 3 in the contralateral eye. The coordinates close to the horizontal meridian were significantly spared by SelAH.
CONCLUSIONS - Visual field defects are very common after SelAH but are significantly less pronounced than after StTL. In particular, the visual field close to the horizontal meridian is relatively spared in SelAH.