Involvement of the thalamocortical network in TLE with and without mesiotemporal sclerosis

Purpose: The thalamus plays an important role in seizure propagation in temporal lobe epilepsy (TLE). This study investigated how structural abnormalities in the focus, ipsilateral thalamus and extrafocal cortical structures relate to each other in TLE with mesiotemporal sclerosis (TLE‐MTS) and without hippocampal sclerosis (TLE‐no). Methods: T₁ and high‐resolution T₂ images were acquired on a 4T magnet in 29 controls, 15 TLE‐MTS cases, and 14 TLE‐no. Thalamus volumes were obtained by warping a labeled atlas onto each subject’s brain. Deformation‐based morphometry was used to identify regions of thalamic volume loss and FreeSurfer for cortical thickness measurements. CA1 volumes were obtained from high‐resolution T₂ images. Multiple regression analysis and correlation analyses for voxel‐ and vertex‐based analyses were performed in SPM2 and FreeSurfer. Results: TLE‐MTS had bilateral volume loss in the anterior thalamus, which was correlated with CA1 volume and cortical thinning in the mesiotemporal lobe. TLE‐no had less severe volume loss in the dorsal lateral nucleus, which was correlated with thinning in the mesiotemporal region but not with extratemporal thinning. Discussion: The findings suggest that seizure propagation from the presumed epileptogenic focus or regions close to it into the thalamus occurs in TLE‐MTS and TLE‐no and results in circumscribed neuronal loss in the thalamus. However, seizure spread beyond the thalamus seems not to be responsible for the extensive extratemporal cortical abnormalities in TLE.     

Voxel-based optimized morphometry (VBM) of gray and white matter in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis

PURPOSE: In temporal lobe epilepsy (TLE) with evidence of hippocampal sclerosis (TLE-MTS) volumetric gray (GM) and white (WM) matter abnormalities are not restricted to the hippocampus but also are found in extrahippocampal structures. Less is known about extrahippocampal volumetric abnormalities in TLE without hippocampal sclerosis (TLE-no). In this study, we used optimized voxel-based morphometry (VBM) with and without modulation with the following aims: (a) to identify WM and GM abnormalities beyond the hippocampus in TLE-MTS and TLE-no; and (b) to determine whether extratemporal WM and GM abnormalities differ between TLE-MTS and TLE-no. METHODS: Optimized VBM of GM and WM with and without modulation was performed in 26 TLE-MTS (mean age, 35.6 +/- 9.7 years), 17 TLE-no (mean age, 35.6 +/- 11.1 years), and 30 healthy controls (mean age, 30.3 +/- 11.1 years). RESULTS: In TLE-MTS, GM/WM volume and concentration reductions were found in the ipsilateral limbic system, ipsi- and contralateral neocortical regions, thalamus, cerebellum, internal capsule, and brainstem when compared with controls. In contrast, no differences of GM/WM volumes/concentrations were found between TLE-no and controls or between TLE-no and TLE-MTS. CONCLUSIONS: In TLE-MTS, optimized VBM showed extensive GM and WM volume reductions in the ipsilateral hippocampus and in ipsi- and contralateral extrahippocampal regions. In contrast, no GM/WM volume or concentration reductions were found in TLE-no. This further supports the hypothesis that TLE-no is a distinct clinicopathologic entity from TLE-MTS and probably heterogeneous in itself.     

Temporal lobe epilepsy with sensory aura: interictal glucose hypometabolism

Patients with mesial temporal lobe epilepsy (mTLE) exhibit marked depressions of the regional cerebral glucose metabolism (rCMRGlu) in the mesiotemporal region. We hypothesised that patients with temporal lobe epilepsy (TLE) who have a bilateral somatosensory or acoustic ( = temporolateral/SII-) aura can be differentiated from mTLE by rCMRGlu depressions primarily involving temporo-perisylvian locations. We therefore used this ictal semiology as a clinical criterion to define a subgroup of such patients and measured the rCMRGlu in 16 patients with TLE as evident from interictal and ictal EEG-video monitoring. Clinically, they presented with medically refractory complex partial seizures and were subjected to presurgical evaluation. The pattern of the interictal rCMRGlu in the TLE patients was different from that observed in patients with mTLE and showed significant depressions ipsilateral to the epileptic focus in mesial temporal and lateral temporal regions but spared the thalamus. The neocortical metabolic depressions were spatially more extended in right than in left TLE patients. Magnetic resonance images (MRI) were either normal (n = 5) or revealed unilateral or bilateral hippocampal atrophy/sclerosis (n = 7), or temporal or extratemporal focal cortical dysplasia (n = 4). The selected TLE patients presented here comprise a heterogeneous group showing most pronounced metabolic depressions in the lateral temporal cortex. Thus, our data suggest that non-invasive metabolic imaging can assist in identifying the neocortical symptomatogenic zone in putative temporo-perisylvian lobe epilepsy.     

Thalamic diffusion and volumetry in temporal lobe epilepsy with and without mesial temporal sclerosis

PURPOSE: As an important connection within the limbic system, considerable attention has been paid to thalamic pathology in temporal lobe epilepsy (TLE). Magnetic resonance imaging (MRI) volumetric studies have yielded variable results and have largely been focused on TLE with mesial temporal sclerosis (TLE+). Diffusion tensor imaging (DTI) provides unique information on microstructure based on the measurement of water diffusion. To date, DTI properties of thalamus have not been well characterized in adult TLE patients with unilateral MTS or without MTS (TLE-). The purpose of this study was to investigate the status of thalamic integrity by using DTI as well as volumetric MRI in adult TLE+ and TLE- patients. METHOD: In 17 unilateral TLE+ patients, 10 TLE- patients and 26 controls, the thalamus was segmented by using an automated atlas-based method. Mean diffusivity (MD), fractional anisotropy (FA) and volume were then quantified from DTI and 3D T1-weighted scans. RESULTS: No significant changes were found in either DTI parameters or volume of thalamus in TLE- patients, as compared to healthy controls. However, both DTI parameters and MRI volumetry showed bilateral thalamic pathology in TLE+ patients, as compared to healthy controls. Also, TLE+ patients showed significant reduction of thalamic volume as compared to TLE- patients. In addition, thalamic FA ipsilateral to seizure focus showed significant correlation with age at onset of epilepsy in TLE+ patients. CONCLUSION: Our finding demonstrates bilateral pathology of thalamus in unilateral TLE+ patients. The discrepancy in thalamic pathology between TLE+ and TLE- patients suggests that along with differences in mesial temporal pathology, TLE+ and TLE- have unique extratemporal structural abnormalities.     

Neocortical thinning in "benign" mesial temporal lobe epilepsy

Purpose : In refractory mesial temporal lobe epilepsy (MTLE) extrahippocampal and neocortical abnormalities have been described in patients with or without mesial temporal sclerosis (MTS). Recently we observed gray matter reductions in regions outside the hippocampus in benign MTLE with or without MTS. Cortical thickness has been proposed as a viable methodologic alternative for assessment of neuropathologic changes in extratemporal regions. Herein, we aimed to use this technique to describe cortical abnormalities in patients with benign TLE. Methods : Whole‐brain cortical thickness analysis (FreeSurfer) was performed in 32 unrelated patients with benign TLE [16 patients with signs of MTS on magnetic resonance imaging (MRI), pMTLE; 16 without, nMTLE] and 44 healthy controls. Key Findings : In the pMTLE group, the most significant thinning was found in the sensorimotor cortex bilaterally but was more extensive in the left hemisphere (false discovery rate, p < 0.05). Other areas were localized in the occipital cortex, left supramarginal gyrus, left superior parietal gyrus, left paracentral sulcus, left inferior/middle/superior frontal gyrus, left inferior frontal sulcus, right cingulate cortex, right superior frontal gyrus, right inferior parietal gyrus, right fusiform gyrus, and cuneus/precuneus. In the nMTLE, a similar neurodegenerative pattern was detected, although not surviving correction for multiple comparisons. Direct comparison between pMTLE and nMTLE did not reveal significant changes. Significance : Patients with either benign pMTLE or nMTLE showed comparable cortical thinning, mainly confined to the sensorimotor cortex. This finding that is not appreciated on routine MRI supports the hypothesis that similar to refractory MTLE, even in benign MTLE, pathology in neocortical regions maybe implicated in the pathophysiology of this syndrome.     

Voxel-based morphometry of temporal lobe epilepsy: an introduction and review of the literature

We review the applications and results of voxel-based morphometry (VBM) studies that have reported brain changes associated with temporal lobe epilepsy (TLE). A PubMed search yielded 18 applications of VBM to study brain abnormalities in patients with TLE up to May 2007. Across studies, 26 brain regions were found to be significantly reduced in volume relative to healthy controls. There was a strong asymmetrical distribution of temporal lobe abnormalities preferentially observed ipsilateral to the seizure focus, particularly of the hippocampus (82.35% of all studies), parahippocampal gyrus (47.06%), and entorhinal (23.52%) cortex. The contralateral hippocampus was reported as abnormal in 17.65% of studies. There was a much more bilateral distribution of extratemporal lobe atrophy, preferentially affecting the thalamus (ipsilateral = 61.11%, contralateral = 50%) and parietal lobe (ipsilateral = 47.06%, contralateral = 52.94%). VBM generally reveals a distribution of brain abnormalities in patients with TLE consistent with the region-of-interest neuroimaging and postmortem literature. It is unlikely that VBM has any clinical utility given the lack of robustness for individual comparisons. However, VBM may help elucidate some unresolved important research questions such as how recurrent temporal lobe seizures affect hippocampal and extrahippocampal morphology using serial imaging acquisitions.     

Neocortical abnormalities of [11C]-flumazenil PET in mesial temporal lobe epilepsy

OBJECTIVE: To characterize abnormalities in neocortical central benzodiazepine receptor (cBZR) binding in patients with mesial temporal lobe epilepsy (mTLE) with unilateral hippocampal sclerosis (HS) using [(11)C]-flumazenil-(FMZ) PET and complementary voxel-based and quantitative volume-of-interest (VOI) methods. METHODS: The authors studied 13 control subjects and 15 patients with refractory mTLE and unilateral HS with [(11)C]-FMZ PET. Data were corrected for partial volume effect in the interactively outlined hippocampus and in 28 cortical VOI using an individualized template. A voxel-based analysis was also performed using statistical parametric mapping (SPM). RESULTS: Fourteen patients with mTLE had reduced [(11)C]-FMZ volume distribution (V(d)) in the hippocampus ipsilateral to the EEG focus, extending into the amygdala in four. Five patients showed additional significant neocortical abnormalities of [(11)C]-FMZ binding: temporal neocortical increases (1), extratemporal decreases (2), extratemporal increases only (1), and temporal and extratemporal neocortical increases (1). Group VOI analysis revealed significant reductions only in the ipsilateral hippocampus. SPM showed decreased [(11)C]-FMZ-V(d) in the ipsilateral hippocampus in 13 of 15 patients, extending into the amygdala in eight. Five patients showed additional neocortical abnormalities: temporal neocortical increases only (3), extratemporal decreases (1), or both temporal neocortical and extratemporal decreases (1). Group analysis showed significant reductions in the ipsilateral hippocampus only. CONCLUSIONS: A combination of VOI- and voxel-based analysis of [(11)C]-FMZ PET detected extrahippocampal changes of cBZR binding in eight of 15 patients with mTLE due to HS. The finding of abnormalities in patients who were thought to have unilateral HS only based on MRI suggests that more widespread abnormalities are present in HS.     

Lesion side matters — An fMRI study on the association between neural correlates of watching dynamic fearful faces and their evaluation in patients with temporal lobe epilepsy

Most studies assessing facial affect recognition in patients with TLE reported emotional disturbances in patients with TLE. Results from the few fMRI studies assessing neural correlates of affective face processing in patients with TLE are divergent. Some, but not all, found asymmetrical mesiotemporal activations, i.e., stronger activations within the hemisphere contralateral to seizure onset. Little is known about the association between neural correlates of affect processing and subjective evaluation of the stimuli presented. Therefore, we investigated the neural correlates of processing dynamic fearful faces in 37 patients with mesial temporal lobe epilepsy (TLE; 18 with left-sided TLE (lTLE), 19 with right-sided TLE (rTLE)) and 20 healthy subjects. We additionally assessed individual ratings of the fear intensity and arousal perception of the fMRI stimuli and correlated these data with the activations induced by the fearful face paradigm and activation lateralization within the mesiotemporal structures (in terms of individual lateralization indices, LIs). In healthy subjects, whole-brain analysis showed bilateral activations within a widespread network of mesial and lateral temporal, occipital, and frontal areas. The patient groups activated different parts of this network. In patients with lTLE, we found predominantly right-sided activations within the mesial and lateral temporal cortices and the superior frontal gyrus. In patients with rTLE, we observed bilateral activations in the posterior regions of the lateral temporal lobe and within the occipital cortex. Mesiotemporal region-of-interest analysis showed bilateral symmetric activations associated with watching fearful faces in healthy subjects. According to the region of interest and LI analyses, in the patients with lTLE, mesiotemporal activations were lateralized to the right hemisphere. In the patients with rTLE, we found left-sided mesiotemporal activations. In patients with lTLE, fear ratings were comparable to those of healthy subjects and were correlated with relatively stronger activations in the right compared to the left amygdala. Patients with rTLE showed significantly reduced fear ratings compared to healthy subjects, and we did not find associations with amygdala lateralization. Although we found stronger activations within the contralateral mesial temporal lobe in the majority of all patients, our results suggest that only in the event of left-sided mesiotemporal damage is the right mesial temporal lobe able to preserve intact facial fear recognition. In the event of right-sided mesiotemporal damage, fear recognition is disturbed. This underlines the hypothesis that the right amygdala is biologically predisposed to processing fear, and its function cannot be fully compensated in the event of right-sided mesiotemporal damage.     

Hippocampal deformation-based shape analysis in epilepsy and unilateral mesial temporal sclerosis

PURPOSE: To assess shape changes in patients with mesial temporal sclerosis (MTS) and temporal lobe epilepsy (TLE), by using deformation-based hippocampal shape analysis. METHODS: We retrospectively reviewed magnetic resonance imaging (MRI) studies in 30 subjects with unilateral MTS (15 right-sided MTS, 15 left-sided MTS) and TLE. We defined the "average" hippocampus in the right- and left-MTS groups by generating a mean transformation for the 15 deformation images in each group. Further to quantify the difference between the hippocampi, we coregistered the mean transformation of the involved hippocampus (with MTS) to the contralateral hippocampus, considering the left- and right-MTS groups independently. We generated a color "flame" scale showing degrees of outward and inward deviation of the coregistered hippocampi. RESULTS: Both the right- and left-MTS groups showed similar shape changes, with maximal inward deformation in the medial and lateral hippocampal head and the hippocampal tail. However, more extensive involvement was seen in the lateral hippocampal body in the right-MTS group as compared with the left. CONCLUSIONS: Deformation-based hippocampal shape analysis shows specific regions of hippocampal surface anatomy that are most affected in MTS. This technique may aid in detection of clinically significant anatomic abnormalities of the hippocampus in patients with epilepsy.     

Structural and functional asymmetry of medial temporal subregions in unilateral temporal lobe epilepsy: A 7T MRI study

Mesial temporal lobe epilepsy (TLE) is a common neurological disorder affecting the hippocampus and surrounding medial temporal lobe (MTL). Although prior studies have analyzed whole‐brain network distortions in TLE patients, the functional network architecture of the MTL at the subregion level has not been examined. In this study, we utilized high‐resolution 7T T2‐weighted magnetic resonance imaging (MRI) and resting‐state BOLD‐fMRI to characterize volumetric asymmetry and functional network asymmetry of MTL subregions in unilateral medically refractory TLE patients and healthy controls. We subdivided the TLE group into mesial temporal sclerosis patients (TLE‐MTS) and MRI‐negative nonlesional patients (TLE‐NL). Using an automated multi‐atlas segmentation pipeline, we delineated 10 MTL subregions per hemisphere for each subject. We found significantly different patterns of volumetric asymmetry between the two groups, with TLE‐MTS exhibiting volumetric asymmetry corresponding to decreased volumes ipsilaterally in all hippocampal subfields, and TLE‐NL exhibiting no significant volumetric asymmetries other than a mild decrease in whole‐hippocampal volume ipsilaterally. We also found significantly different patterns of functional network asymmetry in the CA1 subfield and whole hippocampus, with TLE‐NL patients exhibiting asymmetry corresponding to increased connectivity ipsilaterally and TLE‐MTS patients exhibiting asymmetry corresponding to decreased connectivity ipsilaterally. Our findings provide initial evidence that functional neuroimaging‐based network properties within the MTL can distinguish between TLE subtypes. High‐resolution MRI has potential to improve localization of underlying brain network disruptions in TLE patients who are candidates for surgical resection.     

A case of adult-onset type II citrullinemia with comorbid epilepsy even after liver transplantation

The current study using single case voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) and 1H-MR-spectroscopy (1H-MRS) explores the neural background of unexplained seizure attacks and electroencephalography (EEG) abnormalities persisting even after liver transplantation in a patient with adult-onset type II citrullinemia (CTLN2). Although the MRI had shown no gross abnormality, the VBM revealed significantly smaller-than-normal regional volume in the left hippocampus of the patient as compared with 111 age-matched controls. 1H-MRS further indicated reduction of all metabolite concentrations in the left hippocampus compared with those in the right homolog region, with the single exception of elevated glutamate concentration. These results are similar to those of patients with mesial temporal lobe epilepsy (TLE), although CTLN2-complicated mesial TLE has rarely been reported. In contrast to TLE, periictal asterixis and interictal slow activities on EEG support another possibility that the patient might have slight metabolic encephalopathy even after the liver transplantation.     

Hippocampus‐associated causal network of structural covariance measuring structural damage progression in temporal lobe epilepsy

In mesial temporal lobe epilepsy (mTLE), the causal relationship of morphometric alterations between hippocampus and the other regions, that is, how the hippocampal atrophy leads to progressive morphometric alterations in the epileptic network regions remains largely unclear. In this study, a causal network of structural covariance (CaSCN) was proposed to map the causal effects of hippocampal atrophy on the network‐based morphometric alterations in mTLE. It was hypothesized that if cross‐sectional morphometric MRI data could be attributed temporal information, for example, by sequencing the data according to disease progression information, GCA would be a feasible approach for constructing a CaSCN. Based on a large cohort of mTLE patients (n = 108), the hippocampus‐associated CaSCN revealed that the hippocampus and the thalamus were prominent nodes exerting causal effects (i.e., GM reduction) on other regions and that the prefrontal cortex and cerebellum were prominent nodes being subject to causal effects. Intriguingly, compensatory increased gray matter volume in the contralateral temporal region and post cingulate cortex were also detected. The method unraveled richer information for mapping network atrophy in mTLE relative to the traditional methods of stage‐specific comparisons and structured covariance network. This study provided new evidence on the network spread mechanism in terms of the causal influence of hippocampal atrophy on progressive brain structural alterations in mTLE. Hum Brain Mapp 38:753–766, 2017. © 2016 Wiley Periodicals, Inc.     

Decision making under ambiguity and under risk in mesial temporal lobe epilepsy

Decision making is essential in everyday life. Though the importance of the mesial temporal lobe in emotional processing and feedback learning is generally recognized, decision making in mesial temporal lobe epilepsy (mTLE) is almost unexplored so far. Twenty-eight consecutive epilepsy patients with drug resistant mTLE and fifty healthy controls performed decision tasks under initial ambiguity (participants have to learn by feedback to make advantageous decisions) and under risk (advantageous choices may be made by estimating risks and by rational strategies). A subgroup analysis compared the performance of patients affected by MRI-verified abnormalities of the hippocampus or amygdala. The effect of lesion side was also assessed. In decision under ambiguity, mTLE patients showed marked deficits and did not improve over the task. Patients with hippocampus abnormality and patients with amygdala abnormality showed comparable deficits. No difference was found between right and left TLE groups. In decision under risk, mTLE patients performed at the same level as controls. Results suggest that mTLE patients have difficulties in learning from feedback and in making decisions in uncertain, ambiguous situations. By contrast, they are able to make advantageous decisions when full information is given and risks, possible gains and losses are exactly defined.     

Atypical intrinsic neural timescales in temporal lobe epilepsy

Objective

Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy in adults. Here we profiled local neural function in TLE in vivo, building on prior evidence that has identified widespread structural alterations. Using resting-state functional magnetic resonance imaging (rs-fMRI), we mapped the whole-brain intrinsic neural timescales (INT), which reflect temporal hierarchies of neural processing. Parallel analysis of structural and diffusion MRI data examined associations with TLE-related structural compromise. Finally, we evaluated the clinical utility of INT.

Methods

We studied 46 patients with TLE and 44 healthy controls from two independent sites, and mapped INT changes in patients relative to controls across hippocampal, subcortical, and neocortical regions. We examined region-specific associations to structural alterations and explored the effects of age and epilepsy duration. Supervised machine learning assessed the utility of INT for identifying patients with TLE vs controls and left- vs right-sided seizure onset.

Results

Relative to controls, TLE showed marked INT reductions across multiple regions bilaterally, indexing faster changing resting activity, with strongest effects in the ipsilateral medial and lateral temporal regions, and bilateral sensorimotor cortices as well as thalamus and hippocampus. Findings were similar, albeit with reduced effect sizes, when correcting for structural alterations. INT reductions in TLE increased with advancing disease duration, yet findings differed from the aging effects seen in controls. INT-derived classifiers discriminated patients vs controls (balanced accuracy, 5-fold: 76% ± 2.65%; cross-site, 72%–83%) and lateralized the focus in TLE (balanced accuracy, 5-fold: 96% ± 2.10%; cross-site, 95%–97%), with high accuracy and cross-site generalizability. Findings were consistent across both acquisition sites and robust when controlling for motion and several methodological confounds.

Significance

Our findings demonstrate atypical macroscale function in TLE in a topography that extends beyond mesiotemporal epicenters. INT measurements can assist in TLE diagnosis, seizure focus lateralization, and monitoring of disease progression, which emphasizes promising clinical utility.     

Resection extent versus postoperative outcomes of seizure and memory in mesial temporal lobe epilepsy

OBJECTIVES: To investigate the effects of the resection of hippocampus and temporal neocortex on postsurgical seizure and memory outcomes in mesial temporal lobe epilepsy (mTLE) patients. METHODS: Sixty-eight mTLE patients underwent pre- and postsurgical brain magnetic resonance imaging (MRI). The patients were divided into seizure-free group (SF, N=54) and non-seizure-free group (NSF, N=14). The resection length of hippocampus was determined by the difference between presurgical and postsurgical hippocampus lengths in MRIs. The lengths of resected temporal gyri were measured on three-dimensional MRI reconstruction. Among SF group, 37 patients performed pre- and postsurgical neuropsychological tests. The postsurgical memory decline (PMD) was calculated by subtracting postsurgical memory score from presurgical one in verbal and visual memory tests. RESULTS: The resection length of hippocampus in SF was significantly longer than in NSF (32.7 +/- 7.7 mm versus 25.1 +/- 7.3 mm, t-test, p=0.002), regardless of intersubject difference in the extent of hippocampal sclerosis (logistic regression, p=0.003) while the resection lengths of the lateral temporal gyri were not different between SF and NSF. Overall postsurgical change of verbal or visual memory was not significant. However, regression analysis showed a significant correlation between the resection length of inferior or basal temporal gyrus and verbal PMD (p<0.001) in left TLE patients with seizure-free outcome. CONCLUSION: More resection of hippocampus may predict a better postsurgical seizure-free outcome. The larger resection of inferior or basal temporal gyrus seems to be related to a postsurgical verbal memory decline in left TLE patients.     

Decision making in patients with temporal lobe epilepsy

The mesiotemporal lobe is involved in decision making processes because bilateral amygdala damage can cause impairments in decision making that is mainly based on the processing of emotional feedback. In addition to executive functions, previous studies have suggested the involvement of feedback processing in decision making under risk when explicit information about consequences and their probabilities is provided. In the current study, we investigated whether unilateral mesiotemporal damage, comprising of the hippocampus and/or the amygdala, results in alterations of both kinds of decision making. For this purpose, we preoperatively examined 20 patients with refractory unilateral mesiotemporal lobe epilepsy (TLE) and a comparison group (CG) of 20 healthy volunteers with the Iowa Gambling Task to assess decision making based on feedback processing, the Game of Dice Task to assess decision making under risk, and with a neuropsychological test battery. Results indicate that TLE patients performed normally in decision making under risk, but can exhibit disturbances in decision making on the Iowa Gambling Task. A subgroup analysis revealed that those patients with a preference for the disadvantageous alternatives performed worse on executive subcomponents and had seizure onset at an earlier age in comparison to the patient subgroup without disadvantageous decision making. Furthermore, disadvantageous decision making can emerge in patients with selective hippocampal sclerosis not extended to the amygdala. Thus, our results demonstrate for the first time that presurgical patients with TLE can have selective reductions in decision making and that these deficits can result from hippocampal lesions without structural amygdala abnormalities.     

The overall pathological status of the left hippocampus determines preoperative verbal memory performance in left mesial temporal lobe epilepsy

Studies on hippocampal cell loss in epilepsy have produced diverging evidence as to which subfields are specifically related to memory. This may be due to rather small and often heterogeneous samples, or to different memory measures. Therefore, the current study examined hippocampal cell densities and memory in a large sample of patients with solely mesial temporal lobe epilepsy (mTLE), employing measures with proven sensitivity to mesiotemporal pathology. In 104 patients who had undergone epilepsy surgery for mTLE, we evaluated the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical verbal and figural memory while controlling for side‐of‐surgery and hemispheric dominance. First of all, patients showed material‐specific memory impairment concordant with the lateralization of epilepsy. Factor analysis of segmental cell loss revealed a single factor reflecting the overall integrity of the hippocampus. The overall pathological status of the left hippocampus correlated with verbal memory parameters (r = 0.33–0.34, P < 0.05), especially when controlling for atypical hemispheric dominance (r = 0.50–0.57, P < 0.01), and explained up to 33% of the observed variance. Further analyses revealed no superior role of a single subfield or cell loss pattern for memory performance. No systematic relations between neuronal cell densities of the right hippocampus and memory function were found, nor did left or right hippocampal pathology explain figural memory parameters. The results suggest that the overall pathological status of the left hippocampus – rather than a specific subfield pathology – is predictive for verbal memory in mTLE. The finding that figural memory parameters, although sensitive to right mTLE, were not related to neuronal cell densities of the right hippocampus, puts the left/right hippocampus verbal/nonverbal memory dichotomy into perspective. © 2014 Wiley Periodicals, Inc.     

Comparison of voxel-based 3-D MRI analysis and subtraction ictal SPECT coregistered to MRI in focal epilepsy

While voxel-based 3-D MRI analysis methods as well as assessment of subtracted ictal versus interictal perfusion studies (SISCOM) have proven their potential in the detection of lesions in focal epilepsy, a combined approach has not yet been reported. The present study investigates if individual automated voxel-based 3-D MRI analyses combined with SISCOM studies contribute to an enhanced detection of mesiotemporal epileptogenic foci. Seven consecutive patients with refractory complex partial epilepsy were prospectively evaluated by SISCOM and voxel-based 3-D MRI analysis. The functional perfusion maps and voxel-based statistical maps were coregistered in 3-D space. In five patients with temporal lobe epilepsy (TLE), the area of ictal hyperperfusion and corresponding structural abnormalities detected by 3-D MRI analysis were identified within the same temporal lobe. In two patients, additional structural and functional abnormalities were detected beyond the mesial temporal lobe. Five patients with TLE underwent epileptic surgery with favourable postoperative outcome (Engel class Ia and Ib) after 3-5 years of follow-up, while two patients remained on conservative treatment. In summary, multimodal assessment of structural abnormalities by voxel-based analysis and SISCOM may contribute to advanced observer-independent preoperative assessment of seizure origin.     

Imaging seizure activity: a combined EEG/EMG-fMRI study in reading epilepsy

Purpose:   To characterize the spatial relationship between activations related to language-induced seizure activity, language processing, and motor control in patients with reading epilepsy.
Methods:   We recorded and simultaneously monitored several physiological parameters [voice-recording, electromyography (EMG), electrocardiography (ECG), electroencephalography (EEG)] during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in nine patients with reading epilepsy. Individually tailored language paradigms were used to induce and record habitual seizures inside the MRI scanner. Voxel-based morphometry (VBM) was used for structural brain analysis. Reading-induced seizures occurred in six out of nine patients.
Results:   One patient experienced abundant orofacial reflex myocloni during silent reading in association with bilateral frontal or generalized epileptiform discharges. In a further five patients, symptoms were only elicited while reading aloud with self-indicated events. Consistent activation patterns in response to reading-induced myoclonic seizures were observed within left motor and premotor areas in five of these six patients, in the left striatum (n = 4), in mesiotemporal/limbic areas (n = 4), in Brodmann area 47 (n = 3), and thalamus (n = 2). These BOLD activations were overlapping or adjacent to areas physiologically activated during language and facial motor tasks. No subtle structural abnormalities common to all patients were identified using VBM, but one patient had a left temporal ischemic lesion.
Discussion:   Based on the findings, we hypothesize that reflex seizures occur in reading epilepsy when a critical mass of neurons are activated through a provoking stimulus within corticoreticular and corticocortical circuitry subserving normal functions.     

Clinical features and pathological characteristics of amygdala enlargement in mesial temporal lobe epilepsy

Although the hippocampus is considered an important site of seizures in mesial temporal lobe epilepsy (mTLE), the amygdala may also have a significant role. Amygdala enlargement is occasionally found in patients with mTLE, and volumetric detection of amygdala enlargement has been documented in "image-negative" patients with TLE. However, only limited data have been reported on the clinical features, surgical outcomes, and pathological characteristics in patients with mTLE with amygdala enlargement. We recruited 12 patients who had undergone surgical treatment for refractory epilepsy with radiological evidence of amygdala enlargement, and 11 became seizure free. All patients showed homogenously increased amygdala volumes on MRI without enhancement and underwent surgical treatment for mTLE. Pathology results revealed that eight patients had focal cortical dysplasia (FCD), two had ganglioglioma, one had oligodendroglioma, and one had astrocytoma. The clinical features and MRI findings were largely indistinguishable between the patients with brain tumors and those with FCD, but the patients with brain tumors tended to be younger at the time of seizure onset. Our study shows that surgical treatment of epilepsy in patients with amygdala enlargement usually has a favorable outcome. FCD was the most frequent pathological diagnosis in these patients. However, a brain tumor should be considered in the differential diagnosis, especially in young patients, because it is often difficult to differentiate FCD from a brain tumor on radiological features.