Mesial Temporal Lobe Epilepsy Group Research Articles

Inhibitory control deficits in patients with mesial temporal lobe epilepsy: an event-related potential analysis based on Go/NoGo task.

Neuropsychiatric comorbidities are common among patients with mesial temporal lobe epilepsy (MTLE). One of these comorbidities, impulsivity, can significantly impact the quality of life and prognosis. However, there have been few studies of impulsivity in these patients, and the existing findings are inconsistent. The present study investigates impulsivity in MTLE patients from the perspective of inhibitory control and its underlying processes using event-related potentials (ERPs) initiated using a Go/NoGo task. A total of 25 MTLE patients and 25 age-, gender-, and education-matched healthy controls (HCs) completed an unequal visual Go/NoGo task. Different waveforms as well as behavioral measures were analyzed between Go and NoGo conditions (N2d and P3d). Impulsivity was also assessed using self -rating scales, and clinical variables that may be related to ERPs were explored. Compared with HCs, MTLE patients exhibited significantly longer reaction time (RT) (p = 0.002) and lower P3d especially at the frontal electrode sites (p = 0.001). In the MTLE group, the seizure frequency (p = 0.045) and seizure types (p < 0.001) were correlated with the P3d amplitude. A self-rated impulsivity assessment revealed that MTLE patients had higher non-planning (p = 0.017) and total scores (p = 0.019) on the BIS-11 as well as higher DI (p = 0.010) and lower FI (p = 0.007) on the DII. The findings demonstrate that the presence of inhibitory control deficits in patients with MTLE are characterized by deficits in the late stage of inhibition control, namely the motor inhibition stage. This study improves our understanding of impulsivity in MTLE patients and suggests that ERPs may constitute a sensitive means of detecting this trait.

Performance of hippocampal radiomics models based on T2-FLAIR images in mesial temporal lobe epilepsy with hippocampal sclerosis

PurposePreoperative identification of hippocampal sclerosis (HS) is crucial to successful surgery for mesial temporal lobe epilepsy (MTLE). We aimed to investigate the diagnostic performance of hippocampal radiomics models based on T2 fluid-attenuated inversion recovery (FLAIR) images in MTLE with HS. MethodsWe analysed 210 cases, including 172 HS pathology-confirmed cases (100 magnetic resonance imaging [MRI]-positive cases [MRI + HS], 72 MRI-negative HS cases [MRI − HS]), and 38 healthy controls (HC). The hippocampus was delineated slice by slice on an oblique coronal plane by a T2-FLAIR sequence, perpendicular to the hippocampus’s long axis, to obtain a three-dimensional region of interest. Radiomics were processed using Artificial Intelligence Kit software; logistic regression radiomics models were constructed. The model evaluation indexes included the area under the curve (AUC), accuracy, sensitivity, and specificity. ResultsThe respective AUC, accuracy, sensitivity, and specificity were 0.863, 81.4%, 78.0%, and 84.6% between the MRI − HS and HC groups in the training set and 0.855, 75.0%, 68.2%, and 81.8% in the test set; 0.975, 95.0%, 92.9%, and 98.0% between the MRI + HS and HC groups in the training set and 0.954, 88.7%, 90.0%, and 87.0% in the test set; and 0.912, 84.3%, 83.3%, and 86.5% between the MTLE and HC groups in the training set and 0.854, 79.7%, 80.8%, and 77.3% in the test set. The AUC values of the comparative radiomics models were > 0.85, indicating good diagnostic efficiency. ConclusionThe hippocampal radiomics models based on T2-FLAIR images can help diagnose MTLE with HS. They can be used as biological markers for MTLE diagnosis.

18F]FDG PET metabolic patterns in mesial temporal lobe epilepsy with different pathological types.

To investigate [18F]FDG PET patterns of mesial temporal lobe epilepsy (MTLE) patients with distinct pathologic types and provide possible guidance for predicting long-term prognoses of patients undergoing epilepsy surgery. This was a retrospective review of MTLE patients who underwent anterior temporal lobectomy between 2016 and 2021. Patients were classified as having chronic inflammation and gliosis (gliosis, n = 44), hippocampal sclerosis (HS, n = 43), or focal cortical dysplasia plus HS (FCD-HS, n = 13) based on the postoperative pathological diagnosis. Metabolic patterns and the severity of metabolic abnormalities were investigated among MTLE patients and healthy controls (HCs). The standardized uptake value (SUV), SUV ratio (SUVr), and asymmetry index (AI) of regions of interest were applied to evaluate the severity of metabolic abnormalities. Imaging processing was performed with statistical parametric mapping (SPM12). With a mean follow-up of 2.8years, the seizure freedom (Engel class IA) rates of gliosis, HS, and FCD-HS were 54.55%, 62.79%, and 69.23%, respectively. The patients in the gliosis group presented a metabolic pattern with a larger involvement of extratemporal areas, including the ipsilateral insula. SUV, SUVr, and AI in ROIs were decreased for patients in all three MTLE groups compared with those of HCs, but the differences among all three MTLE groups were not significant. MTLE patients with isolated gliosis had the worst prognosis and hypometabolism in the insula, but the degree of metabolic decrease did not differ from the other two groups. Hypometabolic regions should be prioritized for [18F]FDG PET presurgical evaluation rather than [18F]FDG uptake values. This study proposes guidance for optimizing the operation scheme in patients with refractory MTLE and emphasizes the potential of molecular neuroimaging with PET using selected tracers to predict the postsurgical histology of patients with refractory MTLE epilepsy. • MTLE patients with gliosis had poor surgical outcomes and showed a distinct pattern of decreased metabolism in the ipsilateral insula. • In the preoperative assessment of MTLE, it is recommended to prioritize the evaluation of glucose hypometabolism areas over [18F]FDG uptake values. • The degree of glucose hypometabolism in the epileptogenic focus was not associated with the surgical outcomes of MTLE.

Exploring the impact of hippocampal sclerosis on white matter tracts and memory in individuals with mesial temporal lobe epilepsy.

To investigate how the presence/side of hippocampal sclerosis (HS) are related to the white matter structure of cingulum bundle (CB), arcuate fasciculus (AF), and inferior longitudinal fasciculus (ILF) in mesial temporal lobe epilepsy (MTLE). We acquired diffusion-weighted magnetic resonance imaging (MRI) from 86 healthy and 71 individuals with MTLE (22 righ-HS; right-HS, 34 left-HS; left-HS, and 15 nonlesional MTLE). We utilized two-tensor tractography and fiber clustering to compare fractional anisotropy (FA) of each side/tract between groups. Additionally, we examined the association between FA and nonverbal (WMS-R) and verbal (WMS-R, RAVLT codification) memory performance for MTLE individuals. White matter abnormalities depended on the side and presence of HS. The left-HS demonstrated widespread abnormalities for all tracts, the right-HS showed lower FA for ipsilateral tracts and the nonlesional MTLE group did not differ from healthy individuals. Results indicate no differences in verbal/nonverbal memory performance between the groups, but trend-level associations between higher FA of visual memory and the left CB (r = 0.286, P = 0.018), verbal memory (RAVLT) and -left CB (r = 0.335, P = 0.005), -right CB (r = 0.286, P = 0.016), and -left AF (r = 0.287, P = 0.017). Our results highlight that the presence and side of HS are crucial to understand the pathophysiology of MTLE. Specifically, left-sided HS seems to be related to widespread bilateral white matter abnormalities. Future longitudinal studies should focus on developing diagnostic and treatment strategies dependent on HS's presence/side.

Memory characteristics in mesial temporal lobe epilepsy: Insights from an eye tracking memory game and neuropsychological assessments.

To compare different patterns of memory impairment in patients with two subtypes of mesial temporal lobe epilepsy (MTLE) and healthy controls. Thirty-five healthy controls and 41 patients with MTLE were recruited, of which 25 patients were diagnosed as hippocampal sclerosis (HS-MTLE), and the rest 16 patients were lesion-negative (MRI-neg MTLE). Participants completed the Wechsler memory assessment and a short-term memory game on an automated computer-based memory assessment platform with an eye tracker. Both the MRI-neg MTLE and HS-MTLE groups took longer time to complete the short-term memory game than healthy controls (p < 0.001, Cohen's d = 1.087; p = 0.047, Cohen's d = 0.787). During the memory encoding phase, the MRI-neg MTLE group spent significantly shorter time than healthy controls on the difficult levels with three (p = 0.004, Cohen's d = 0.993) and four targets (p = 0.016, Cohen's d = 0.858). During the memory decoding phase, the HS-MTLE group spent less time looking on the targets compared to controls when recalling and finding four targets (p = 0.004, Cohen's d = -0.793), while the MRI-neg MTLE group spent significantly longer time on the distractors and shorter time on the region of interests (ROIs) for all difficulty levels (all p < 0.05) than controls. Furthermore, the eye tracking data were correlated with the scores of the Wechsler Memory Scale after Bonferroni correction (p < 0.05). Patients with MRI-neg MTLE demonstrate impaired memory mostly due to attention deficits, while those with HS-MTLE show memory impairment with relative sparing of attention. Eye tracking technology has the potential of facilitating the investigation of the mechanism of memory defect in MTLE and can serve as a supplementary neuropsychological tool for clinical diagnosis and long-term monitoring.

Metabolic profiles and correlation with surgical outcomes in mesial versus neocortical temporal lobe epilepsy.

Differentiating mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE) remains challenging. Our study characterized the metabolic profiles between MTLE and NTLE and their correlation with surgical prognosis using 18 F-FDG-PET. A total of 137 patients with intractable temporal lobe epilepsy (TLE) and 40 age-matched healthy controls were recruited. Patients were divided into the MTLE group (N = 91) and the NTLE group (N = 46). 18 F-FDG-PET was used to measure the metabolism of regional cerebra, which was analyzed using statistical parametric mapping. The volume of abnormal metabolism in cerebral regions and their relationship with surgical prognosis were calculated for each surgical patient. The cerebral hypometabolism of MTLE was limited to the ipsilateral temporal and insular lobes (p < 0.001, uncorrected). The NTLE patients showed hypometabolism in the ipsilateral temporal, frontal, and parietal lobes (p < 0.001, uncorrected). The MTLE patients showed extensive hypermetabolism in cerebral regions (p < 0.001, uncorrected). Hypermetabolism in NTLE was limited to the contralateral temporal lobe and cerebellum, ipsilateral frontal lobe, occipital lobe, and bilateral thalamus (p < 0.001, uncorrected). Among patients who underwent resection of epileptic lesions, 51 (67.1%) patients in the MTLE group and 10 (43.5%) in the NTLE group achieved Engel class IA outcome (p = 0.041). The volumes of metabolic increase for the frontal lobe or thalamus in the MTLE group were larger in non-Engel class IA patients than Engel class IA patients (p < 0.05). The spatial metabolic profile discriminated NTLE from MTLE. Hypermetabolism of the thalamus and frontal lobe in MTLE may facilitate preoperative counseling and surgical planning.

The comparison of decision-making in ambiguous situations and galvanic skin responses as somatic markers in patients with posterior cortex epilepsy and mesial temporal lobe epilepsy with hippocampal sclerosis

ABSTRACT Introduction Decision-making behaviors of patients with mesial temporal lobe epilepsy (MTLE) is a subject that has been studied frequently. However, determining the neuropsychological profiles of patients with different types of epilepsy is also important. Our main purpose was to examine the decision-making behaviors of patients with posterior cortex epilepsy (PCE) through the assumptions of somatic marker hypothesis (SMH) and to compare their performances with those of a MTLE group and a control group. Method Participants comprised of 13 patients with PCE (mean age 30.92 ± 9.99 years); 14 patients with MTLE with hippocampal sclerosis (MTLE-HS) (mean age 25.53 ± 7.40 years) and 15 controls (mean age 24.60 ± 8.45 years). Decision-making performances were assessed with the Iowa gambling test (IGT) and anticipatory skin responses before each choice were recorded. A comprehensive neuropsychological test battery was also given to all participants in order to examine the relationship of decision-making with other cognitive functions. Results Anticipatory responses before choosing from disadvantageous decks were significantly larger than choosing from advantageous decks in the PCE group (p = 0.00). No significant difference was found between the PCE and control group’s total net scores. IGT total net scores was significantly correlated with Stroop test interference time (p = 0.03). Conclusion The study reveals that cognitive impairments of patients with PCE are not limited to brain’s posterior areas’ functions, and provides evidence for the current paradigm which understands epilepsy as a network disorder.

Human herpesvirus 6B infection in mesial temporal lobe epilepsy: a meta-analysis

BackgroundWhether human herpesvirus 6B (HHV-6B) can affect mesial temporal lobe epilepsy (MTLE) remains controversial. The present meta-analysis was aimed to evaluate whether HHV-6B is significantly associated with MTLE.MethodsSix studies were included in this meta-analysis, comprising 183 MTLE patients and 75 controls. In these studies, HHV-6B infection in astrocytes and brain samples of MTLE patients and controls was investigated by polymerase chain reaction and immunofluorescence.ResultsThe frequency of HHV-6B infection detection is significantly higher in the MTLE group than in the control group (OR = 9.42, 95%CI: 3.66–24.25), P < 0.00001). Although febrile convulsion is strongly associated with MTLE, the formation of febrile convulsion leading to MTLE is not associated with HHV-6B infection (OR = 2.68, 95%CI: 0.93–7.73), P = 0.07). Moreover, the HHV-6B-specific antigen is co-localized to cells positive for GFAP that morphologically resemble astrocytes. HHV-6B mainly infects astrocytes, oligodendrocytes and microglia, and could damage the vascular endothelial cells of the central nervous system.ConclusionsThere is an association between HHV-6B infection and MTLE. Future large-scale, multi-center, controlled, prospective studies are required to confirm these findings. In addition, the exact mechanism underlying the effects of HHV-6B infection on MTLE needs to be further investigated.

Quantitative evaluation of gray matter alterations in patients with mesial temporal lobe epilepsy (MTLE)

Objective: The purpose of this study was to evaluate the gray matter (GM) alterations in patients with mesial temporal lobe epilepsy (MTLE) based on statistical models. Methods: High-resolution MRI data were collected from 64 adult MTLE patients and 100 healthy participants. Voxel Based Morphometry (VBM) and Surfaced Based Morphometry (SBM) analysis were used to detect the alterations of cerebral GM of MTLE. We also built general linear models (GLM) for quantitatively evaluating regions of interest (ROIs) from the corrected VBM, SBM analysis. Results: The corrected VBM and SBM analyses identified discriminable GM alterations in the left and right MTLE groups located in the ipsilateral hippocampus, the perisylvian cortex in the left MTLE group and the bilateral orbitofrontal cortex in the right MTLE group. We extracted the ipsilateral hippocampal volume GLM of both unilateral MTLE groups. History of febrile convulsions and an increased number of AEDs were recognized as risk factors for ipsilateral hippocampus atrophy of unilateral MTLE. Moreover, early onset age was also considered a risk factor for left hippocampus atrophy in left MTLE. Significance: The current study established a quantitative assessment of unilateral MTLE based solely on GM alterations, without any influence of demographic risk factors. By using this GM-based protocol, we found that regions both inside and outside of the temporal lobes may be associated with the epileptic network of MTLE.

The Rolandic operculum generates different semiologies in insulo-opercular and temporal lobe epilepsies

PurposeThe role of the Rolandic operculum in in mesial temporal lobe epilepsy (MTLE) is to produce oroalimentary automatisms (OAAs). In insulo-opercular epilepsy (IOE), the Rolandic operculum may produce perioral muscle clonic or tonic movements or contractions. This paper aims to confirm the symptomatogenic zone of facial symptoms in IOE and to explain this phenomenon. MethodsA total of 45 IOE patients and 15 MTLE patients were analyzed. The patients with IOE were divided into facial (+) and (-) groups according to the facial symptoms. The interictal positron emission tomography (PET) data were compared among groups. Furthermore, electroclinical correlation, functional connectivity and energy ratio (ER) were analyzed with stereo-electroencephalography (SEEG). ResultsIntergroup PET differences were observed mainly in the Rolandic operculum. Electroclinical correlation showed that the Rolandic operculum was the only brain area showing any correlations. Compared with the facial (-) group, the facial (+) group showed stronger functional connectivity and a higher ER in the alpha 1, alpha 2 and beta sub-bands. In the Rolandic operculum, compared with those of the MTLE group, the h2 and ER of the facial (+) group were higher in the high frequency sub-bands. Intergroup comparison of the ER in the seizure onset zones (SOZ) showed no significant difference. SignificanceThe symptomatogenic zone of facial symptoms in IOE is the Rolandic operculum. Seizure propagation to the Rolandic operculum generates different semiologies because of the different synchronization frequencies and energies of the sub-bands depending on the site of seizure origin. This may be due to the complex spreading pathway from the SOZ to the symptomatogenic zone.

Duration-dependent extensive volume and shape changes of mesolimbic structures in surgically treated unilateral patients with temporal lobe epilepsy

PurposeAlthough surgical treatment of drug-resistant mesial temporal lobe epilepsy (MTLE) has proven efficacy, surgical referrals are often delayed. Knowledge of the abnormalities of mesolimbic structures beyond the hippocampus may be important for patients with MTLE because of its usefulness in the understanding of progressive disabilities in affected structures. This study aimed to identify volume and shape changes of mesolimbic structures in surgically treated patients with unilateral MTLE and their correlation with various clinical parameters. MethodsTwenty-four patients with unilateral MTLE (12 with left MTLE [LMTLE] and 12 with right MTLE [RMTLE]) who were surgically treated with standard temporal lobectomy, including amygdalohippocampectomy, and 24 age- and sex-matched healthy individuals were enrolled. Preoperatively, volumetric analysis using magnetic resonance imaging (MRI) of 27 mesolimbic substructures (11 from each hemisphere and 5 from the midline) was performed. We also investigated the three-dimensional morphometric differences of the mesolimbic structures between the unilateral MTLE and control groups using shape analyses. ResultsPatients with LMTLE showed significant volume reductions in various ipsilateral mesolimbic (72.7%, 8/11) and contralateral structures (27.3%, 3/11). Patients with RMTLE had also significant reduced volumes in ipsilateral (63.6%, 7/11) and contralateral structures (73.3%, 3/11). Among the clinical parameters, only the duration of epilepsy had a statistically significant inverse correlation with the volumes of the hippocampus, parahippocampus, entorhinal cortex, cingulate, and corpus callosum. In the shape analysis of the bilateral hippocampus, amygdala, parahippocampus, and entorhinal cortex, after accounting for the effects of age and total intracranial volume, significant shape changes in the anterolateral area of the ipsilateral hippocampus were noted, which corresponds to the cornu ammonis (CA)1 and subiculum of the hippocampus. ConclusionsThe extensive volume reductions in the multiple mesolimbic structures and the substantial inverse correlation between the duration of epilepsy and the volumes of the various mesolimbic structures in our study supports that MTLE is not restricted to the hippocampus, but it progressively involves extensive mesolimbic structures. The duration-dependent atrophic changes in multiple subcortical structures seen in this study also suggest a positive role of early surgical intervention for patients with drug-resistant TLE.

Looking for indicative magnetic resonance imaging signs of hippocampal developmental abnormalities in patients with mesial temporal lobe epilepsy and healthy controls

To evaluate the frequency of qualitative features for hippocampal developmental abnormalities (HiDeA) definition on magnetic resonance imaging (MRI) in mesial temporal lobe epilepsy (MTLE) patients and healthy controls, highlighting which were more sensitive and specific to the epileptic syndrome. We enrolled 93 healthy controls and 187 MTLE patients. Among patients, 133 were MRI-negative and 54 had hippocampal sclerosis (HS). Two blinded, trained investigators defined HiDeA if three signs were present, including at least one of the following: (1) globular hippocampal shape (HCS), (2) verticalized collateral sulcus, and (3) medial positioning of hippocampus (HCP). After evaluating the prevalence of HiDeA in MTLE and controls, we assessed the frequency of each sign. Then, we classified differences in type or number of HiDeA diagnostic features, calculating their sensitivity and specificity. Fisher exact test was used to assess statistical significance. HiDeA was detected in 36 of 187 MTLE cases (19.25%) and in eight of 93 (8.6%) controls. In particular, HiDeA was present in 25 of 133 (18.8%) patients with MRI-negative MTLE. Among all visual criteria here considered, HCS showed higher sensitivity both in the MRI-negative MTLE group (88%) and in the HS-MTLE group (91%). HCP, thickened subiculum, and reduction of the upper horizontal portion of the parahippocampal gyrus (HCTH) signs demonstrated a 100% specificity in both groups. In healthy controls, HCS was confirmed to have the highest sensitivity (100%), whereas HCP showed the highest specificity (98.8%). All these criteria were statistically associated with HiDeA. Electroencephalographic focus was concordant with the HiDeA side in 52.2% of MTLE patients. An association was not found among signs of HiDeA and treatment responsiveness. We identified characteristic signs of HiDeA, such as HCTH or HCP, differentiating HiDeA features between MTLE and healthy controls. The identification of sensitive and, more importantly, specific criteria of HiDeA could be helpful to make a more confident visual diagnosis.

Identifying Morphological Patterns of Hippocampal Atrophy in Patients With Mesial Temporal Lobe Epilepsy and Alzheimer Disease.

Purpose: Mesial temporal lobe epilepsy (MTLE) and Alzheimer's disease (AD) are two distinct neurological disorders associated with hippocampal atrophy. Our goal is to analyze the morphologic patterns of hippocampal atrophy to better understand the underlying pathological and clinical characteristics of the two conditions.Methods: Twenty-five patients with AD and 20 healthy controls with matched age and gender were recruited into the AD group. Twenty-three MTLE patients and 28 healthy controls with matched age and gender were recruited into the MTLE group. All subjects were scanned on 3T-MRI scanner. Automated volumetric analysis was applied to measure and compare the hippocampal volume of the two respective groups. Vertex-based morphologic analysis was applied to characterize the morphologic patterns of hippocampal atrophy within and between groups, and a correlation analysis was performed.Results: Volumetric analysis revealed significantly decreased hippocampal volume in both AD and MTLE patients compared to the controls. In the patients with AD, the mean total hippocampal volume was 32.70% smaller than that of healthy controls, without a significant difference between the left and the right hippocampus (p < 0.05). In patients with MTLE, a significant reduction in unilateral hippocampal volume was observed, with a mean volume reduction of 28.38% as compared with healthy controls (p < 0.05). Vertex-based morphologic analysis revealed a generalized shrinkage of the hippocampi in AD patients, especially in bilateral medial and lateral regions. In MTLE group, atrophy was seen in the ipsilateral head, ipsilateral lateral body and slightly contralateral tail of the hippocampus (FWE-corrected, p < 0.05).Conclusions: MTLE and AD have distinctive morphologic patterns of hippocampal atrophy, which provide new insight into the radiology-pathology correlation in these diseases.

Evaluation of olfactory and gustatory changes in patients with mesial temporal lobe epilepsy

PurposeThe temporal lobe plays an important role in the perception of odors. Another important anatomical structure involved in the perception of smell is the olfactory bulb. The relationship between olfactory bulb volume (OBV) and olfactory function is unclear, however. In our study, we aimed to evaluate the relationship between OBV and olfactory function in patients with mesial temporal lobe epilepsy (MTLE). MethodForty-eight patients with MTLE who were managed in the Cerrahpaşa Medical Faculty Neurology Department’s epilepsy outpatient clinic were recruited for the study. Tests with Sniffin’ Sticks and Taste Strips were performed and OBV measured in all patients. Two control groups were recruited, one for the Sniffin' Sticks and Taste Strip tests and one for OBV measurement. ResultsIn the smell tests; the threshold, discrimination and identification scores were significantly lower in the MTLE group than in the control group. The mean taste test scores did not differ significantly between the MTLE and control groups.In the MTLE group, the mean right OBV was 40.2 ± 12.54 and the left OBV was 39.3 ± 10.54, both of which were significantly lower those in the control group. The mean OBVs of patients with hyposmia were significantly smaller bilaterally than the OBVs of those with normosmia. There was no correlation between the gustatory scores and OBV. ConclusionsOlfactory function was significantly impaired in patients with MTLE compared with healthy controls in all domains, namely threshold, discrimination, and identification. In addition, olfactory bulbus volume was smaller in patients with olfactory dysfunction.

Hippocampal involvement in nonpathological déjà vu: Subfield vulnerability rather than temporal lobe epilepsy equivalent.

IntroductionMorphological correlates of nonpathological déjà vu (DV) have been identified recently within the human brain. Significantly reduced gray matter volume (GMV) within a set of cortical and subcortical regions reported in subjects experiencing DV seems to mirror the distribution of GMV reduction in mesial temporal lobe epilepsy (MTLE) patients but vary in terms of the hippocampus. Another condition associated with hippocampal GMV reduction and DV alike disturbance in memory processing is schizophrenia (SCH). Here, we tested the hypothesis that hippocampal involvement in nonpathological DV resembles more closely the pattern of GMV decrease observed in MTLE compared with that occurring in SCH.MethodsUsing automated segmentation of the MRI data we compared the medians of GMV within 12 specific hippocampal subfields in healthy individuals that do (DV+; N = 87) and do not report déjà vu experience (DV−; N = 26), and patients with MTLE (N = 47) and SCH (N = 29). By Pearson correlation, we then evaluated the similarity of MTLE and SCH groups to DV+ group with respect to spatial distribution of GMV deviation from DV− group.ResultsSignificant GMV decrease was found in MTLE group in most of the subfields. There were just trends in the hippocampal GMV decrease found in DV+ or SCH groups. Concerning the spatial distribution of GMV decrease, we revealed statistically significant correlation for the left hippocampus for SCH vs DV+. Otherwise there was no statistically significant correlation.ConclusionsOur findings reveal structural features of hippocampal involvement in nonpathological DV, MTLE, and SCH. Despite our expectations, the pattern of GMV reduction in the DV+ relative to the DV− group does not resemble the pattern observed in MTLE any more than that observed in SCH. The highly similar patterns of the three clinical groups rather suggest an increased vulnerability of certain hippocampal subfields; namely, Cornu Ammonis (CA)4, CA3, dentate gyrus granular cell layer (GC‐DG), hippocampal–amygdaloid transition area (HATA) and subiculum.

Mesial temporal lobe epilepsy diminishes functional connectivity during emotion perception

ObjectivesUnilateral mesial temporal lobe epilepsy (MTLE) has been associated with impaired recognition of emotional facial expressions. Correspondingly, imaging studies showed decreased activity of the amygdala and cortical face processing regions in response to emotional faces. However, functional connectivity among regions involved in emotion perception has not been studied so far. MethodsTo address this, we examined intrinsic functional connectivity (FC) modulated by the perception of dynamic fearful faces among the amygdala and limbic, frontal, temporal and brainstem regions. Regions of interest were identified in an activation analysis by presenting a block-design with dynamic fearful faces and dynamic landscapes to 15 healthy individuals. This led to 10 predominately right-hemispheric regions. Functional connectivity between these regions during the perception of fearful faces was examined in drug-refractory patients with left- (n=16) or right-sided (n=17) MTLE, epilepsy patients with extratemporal seizure onset (n=15) and a second group of 15 healthy controls. ResultsHealthy controls showed a widespread functional network modulated by the perception of fearful faces that encompassed bilateral amygdalae, limbic, cortical, subcortical and brainstem regions. In patients with left MTLE, a downsized network of frontal and temporal regions centered on the right amygdala was present. Patients with right MTLE showed almost no significant functional connectivity. A maintained network in the epilepsy control group indicates that findings in mesial temporal lobe epilepsy could not be explained by clinical factors such as seizures and antiepileptic medication. ConclusionFunctional networks underlying facial emotion perception are considerably changed in left and right MTLE. Alterations are present for both hemispheres in either MTLE group, but are more pronounced in right MTLE. Disruption of the functional network architecture possibly contributes to deficits in facial emotion recognition frequently reported in MTLE.

Social cognition in neuropsychiatric populations: a comparison of theory of mind in schizophrenia and mesial temporal lobe epilepsy

Social cognition deficits are observed both in patients with schizophrenia (SCZ) and in patients with mesial temporal lobe epilepsy (MTLE). This may be due to dysfunction of the amygdala network, which is a common feature of both diseases. In this study, SCZ (n = 48) or MTLE (n = 31) and healthy controls (HC, n = 47) completed assessments of mentalising (Reading Mind in the Eyes Test, RMET) and basic cognitive processing, e.g., working memory, executive functions and psychomotor speed (Trail-Making Test B and Digit Symbol). SCZ were also assessed with the Positive And Negative Syndrome Scale (PANSS). We found that the RMET scores of the two clinical groups were similar (p > 0.05) and lower than in the HCs (SCZ: p < 0.05; MTLE: p < 0.001). In the next step, SCZ were split into two groups with respect to the level of symptoms. Analysis of the RMET scores revealed no differences between the HC (M = 25.7 ± 4.1) and POS-LO (M = 25.3 ± 4.8); both groups outperformed the POS-HI group (M = 21.3 ± 5.2) and the MTLE group (M = 20.8 ± 4.6). No differences were found for the median-split with regard to negative symptoms. In SCZ, the mind-reading deficit appears to be associated with the level of positive symptoms. Both POS-HI and MTLE patients present significant mentalising deficits compared to healthy controls.

Blood DNA methylation pattern is altered in mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (MTLE) is a common epileptic disorder; little is known whether it is associated with peripheral epigenetic changes. Here we compared blood whole genomic DNA methylation pattern in MTLE patients (n = 30) relative to controls (n = 30) with the Human Methylation 450 K BeadChip assay, and explored genes and pathways that were differentially methylated using bioinformatics profiling. The MTLE and control groups showed significantly different (P < 1.03e-07) DNA methylation at 216 sites, with 164 sites involved hyper- and 52 sites hypo- methylation. Two hyper- and 32 hypo-methylated sites were associated with promoters, while 87 hyper- and 43 hypo-methylated sites corresponded to coding regions. The differentially methylated genes were largely related to pathways predicted to participate in anion binding, oxidoreductant activity, growth regulation, skeletal development and drug metabolism, with the most distinct ones included SLC34A2, CLCN6, CLCA4, CYP3A43, CYP3A4 and CYP2C9. Among the MTLE patients, panels of genes also appeared to be differentially methylated relative to disease duration, resistance to anti-epileptics and MRI alterations of hippocampal sclerosis. The peripheral epigenetic changes observed in MTLE could be involved in certain disease-related modulations and warrant further translational investigations.

Delta Brush Pattern Is Not Unique to NMDAR Encephalitis: Evaluation of Two Independent Long-Term EEG Cohorts.

Although its specificity has not previously been investigated in other cohorts, delta brush pattern (DBP) is increasingly reported in the EEGs of patients with anti- N-methyl-d-aspartate receptor (NMDAR) encephalitis. We aimed to investigate the DBP in the EEGs of 2 cohorts; patients with change in consciousness for various causes monitored in the intensive care unit (ICU) (n = 106) and patients with mesial temporal lobe epilepsy (MTLE) with or without antineuronal antibodies (n = 76). These patients were investigated for the presence of DBP, defined as an EEG pattern characterized by delta activity at 1 to 3 Hz with superimposed bursts of rhythmic 12- to 30-Hz activity. Two investigators blindfolded for the clinical and immunological data independently analyzed the EEGs for recognition of this pattern. An EEG picture compatible with DBP was observed in 4 patients; only 1 of them (1.3%) belonged to the MTLE group. She did not bear any of the investigated autoantibodies and was seizure-free after epilepsy surgery. In the ICU group, there were 3 additional patients showing DBP with various diagnoses such as hypoxic encephalopathy, brain tumor, stroke, and metabolic derangements. All of them had died in 1-month period. Our results underlined that DBP is not unique to NMDAR encephalitis; it may very rarely occur in MTLE with good prognosis after surgery and second, in ICU patients who have high mortality rate. Therefore, the presence of this pattern should alert the clinician for NMDAR encephalitis but other possible etiologies should not be ignored.

Elevated Expression of VEGF-C and Its Receptors, VEGFR-2 and VEGFR-3, in Patients with Mesial Temporal Lobe Epilepsy.

Mesial temporal lobe epilepsy (MTLE) is a frequent form of focal intractable epilepsy in adults. We previously reported overexpression of vascular endothelial growth factor C (VEGF-C) and its receptors, VEGFR-2 and VEGFR-3, in epilepsy-associated tuberous sclerosis complex. To identify whether VEGF-C and its receptors are involved in epileptogenesis of MTLE, we investigated the levels and expression pattern of VEGF-C and its receptors in temporal neocortex and hippocampus (HPC) from 28 patients with MTLE and ten control (CTX) subjects. Real-time quantitative polymerase chain reaction and Western blotting results revealed upregulated mRNA and immunoreactive protein levels of VEGF-C, VEGFR-2, and VEGFR-3 in the MTLE group compared to the control groups. Immunohistochemistry and double-labeled immunofluorescence showed that VEGF-C was highly expressed in neurons and astrocytes, including reactive astrocytes and vascular endothelial cells, VEGFR-2 was expressed at a high level in reactive astrocytes and vascular endothelial cells, but not in neurons, whereas VEGFR-3 was only overexpressed in reactive astrocytes. Taken together, these findings suggest that VEGF-C and its receptors, VEGFR-2 and VEGFR-3, may contribute to the epileptogenesis of MTLE.