Mesial Temporal Lobe Epilepsy Patients Research Articles

Quantitative analysis of visually normal EEG reveals spectral power abnormalities in temporal lobe epilepsy

ObjectiveTo compare quantitative spectral parameters of visually-normal EEG between Mesial Temporal Lobe Epilepsy (MTLE) patients and healthy controls (HC). MethodWe enrolled 26 MTLE patients and 26 HC. From each recording we calculated total power of all frequency bands and determined alpha-theta (ATR) and alpha-delta (ADR) power ratios in different brain regions. Group-wise differences between spectral parameters were investigated (p < 0.05). To test for associations between spectral-power and cognitive status, we evaluated correlations between neuropsychological tests and quantitative EEG (qEEG) metrics. ResultsIn all comparisons, ATR and ADR were significantly decreased in MTLE patients compared to HC, particularly over the hemisphere ipsilateral to epileptic activity. A positive correlation was seen in MTLE patients between ATR in ipsilateral temporal lobe, and results of neuropsychological tests of auditory verbal learning (RAVLT and RAVLT-D), short term verbal memory (Digit span backwards), and executive function (Weigl's sorting test). ADR values in the contralateral posterior region correlated positively with RAVLT-D and Digit span backwards tests. DiscussionResults confirmed that the power spectrum of qEEG is shifted towards lower frequencies in MTLE patients compared to HC. ConclusionOf note, our results were found in visually-normal recordings, providing further evidence of the value of qEEG for longitudinal monitoring of MTLE patients over time. Exploratory analysis of associations between qEEG and neuropsychological data suggest this could be useful for investigating effects of antiseizure medications on cognitive integrity in patients.

PETSurfer-Based Brain Segmentation in Patients with Temporal Lobe Epilepsy and Associated Hippocampal Sclerosis

PurposeIn a homogeneous cohort of mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS), this study utilizes the PETSurfer method to quantify and localize areas of cerebral hypometabolism. MethodsWe selected patients from the University Clinical Center of Serbia who all underwent anterior temporal lobectomy with amygdalohippocampectomy and achieved seizure freedom (Engel class I). Our analysis involved integrating FDG-PET and MRI imaging to compare glucose metabolism between the hemispheres ipsilateral and contralateral to HS. ResultsThe quantitative PETSurfer approach identified significant hypometabolism restricted to the ipsilateral temporal lobe structures—the amygdala, hippocampus, temporal pole, superior and middle temporal gyrus—and the ipsilateral thalamus. The lack of significant hypometabolism in extratemporal regions indicates that these 'pure' mTLE cases may not involve the broader network disruptions typically associated with more extensive epileptic pathologies. The effect sizes ranged from small to medium, indicating variable degrees of metabolic reduction across different structures. ConclusionThese findings highlight the localized nature of the epileptogenic focus in HS-related mTLE with good surgical outcome. However, the small sample size and potential cohort bias, necessitate caution in generalizing these results. Future research would benefit from a comparative approach incorporating a control group, providing a broader context for interpreting these hypometabolic patterns.

May anti-seizure medications alter brain structure in temporal lobe epilepsy? A prospective study.

Mild mesial temporal lobe epilepsy (MTLE) patients may remain untreated for a considerable time after disease onset or achieve seizure control with a single anti-seizures medication (ASM). Thus, they represent an optimal population to investigate whether ASMs might have influence on brain structure. We consecutively enrolled 56 mild MTLE patients (22/56 untreated, 34/56 on-monotherapy) and 58 healthy controls, matched for age and gender. All subjects underwent 3T-brain MRI, using FreeSurfer for automated morphometry. Differences in gray matter were assessed using one-way Analysis of Covariance (ANCOVA), adjusting for age, disease duration and intracranial volume. No significant change was observed between treated and untreated patients. We observed a significant reduction in cortical thickness of left inferior parietal, inferior temporal, middle temporal gyri, and right inferior parietal gyrus, temporal pole in monotherapy patients compared to healthy controls, as well as an increase in left isthmus of cingulate gyrus in untreated MTLE subjects compared to controls. Surface and subcortical volumes analysis revealed no differences among groups. Our study demonstrated no substantial morphological abnormalities between untreated mild MTLE patients and those undergoing monotherapy. Although exploratory, these results may reassure about safety of commonly used drugs and their marginal role in influencing neuroimaging results. PLAIN LANGUAGE SUMMARY: This study investigated the following question: can medications against epileptic seizures have an effect on brain structure in mild mesial temporal lobe? Preliminary results from our analyses suggest not, as we did not find any difference in brain gray matter between untreated patients and those treated with a single anti-seizures medication. On the other hand, epilepsy patients presented cortical thinning compared to healthy controls in several regions of the temporal and parietal lobes, in line with previous studies investigating the disease.

Impact of intracranial subclinical seizures on seizure outcomes after SLAH in patients with mesial temporal lobe epilepsy

ObjectiveTo investigate the association between subclinical seizures detected on intracranial electroencephalographic (i-SCSs)recordings and mesial temporal sclerosis (MTS), as well as their impact on surgical outcomes of stereotactic laser amygdalohippocampotomy (SLAH). MethodsA retrospective review was conducted on 27 patients with drug-resistant mesial temporal lobe epilepsy (MTLE) who underwent SLAH. The number of seizures detected on scalp EEG and iEEG was assessed. Patients were followed for a minimum of 3 years after SLAH. ResultsOf the 1715 seizures recorded from mesial temporal regions, 1640 were identified as i-SCSs. Patients with MTS were associated with favorable short- and long-term surgical outcomes. Patients with MTS had a higher number of i-SCSs compared to patients without MTS. The numbers of i-SCSs were higher in patients with Engel I-II outcomes, but no significant statistical difference was found. However, it was observed that patients with MTS who achieved Engel I-II classification had higher numbers of i-SCSs than patients without MTS (P < 0.05). ConclusionPatients with MTS exhibited favorable short-term and long-term surgical outcome after SLAH. A higher number of i-SCSs was significantly associated with MTS in patients with MTLE. The number of i-SCSs tended to be higher in patients with Engel Ⅰ-Ⅱ surgical outcomes. SignificanceThe association between i-SCSs, MTS, and surgical outcomes in MTLE patients undergoing SLAH has significant implications for understanding the underlying mechanisms and identifying potential therapeutic targets to enhance surgical outcomes.

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.

Downregulation of Ubiquitin-Specific Protease 15 (USP15) Does Not Provide Therapeutic Benefit in Experimental Mesial Temporal Lobe Epilepsy

Structural epilepsies display complex immune activation signatures. However, it is unclear which neuroinflammatory pathways drive pathobiology. Transcriptome studies of brain resections from mesial temporal lobe epilepsy (mTLE) patients revealed a dysregulation of transforming growth factor β, interferon α/β, and nuclear factor erythroid 2-related factor 2 pathways. Since these pathways are regulated by ubiquitin-specific proteases (USP), in particular USP15, we hypothesized that USP15 blockade may provide therapeutic relief in treatment-resistant epilepsies. For validation, transgenic mice which either constitutively or inducibly lack Usp15 gene expression underwent intrahippocampal kainate injections to induce mTLE. We show that the severity of status epilepticus is unaltered in mice constitutively lacking Usp15 compared to wild types. Cell death, reactive gliosis, and changes in the inflammatory transcriptome were pronounced at 4 days after kainate injection. However, these brain inflammation signatures did not differ between genotypes. Likewise, induced deletion of Usp15 in chronic epilepsy did not affect seizure generation, cell death, gliosis, or the transcriptome. Concordantly, siRNA-mediated knockdown of Usp15 in a microglial cell line did not impact inflammatory responses in the form of cytokine release. Our data show that a lack of USP15 is insufficient to modulate the expression of relevant neuroinflammatory pathways in an mTLE mouse model and do not support targeting USP15 as a therapeutic approach for pharmacoresistant epilepsy.

Serum levels of oxidative stress biomarkers is changed in pharmacoresistant mesial temporal lobe epilepsy patients with or without psychiatric disorders

The objective of the present study was to assess the levels of oxidative stress biomarkers (OSB) in patients with pharmacoresistant temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS) in order to investigate a possible role of oxidative stress (OS) in the pathophysiology of such disease. Ninety-eight participants were included and distributed in three groups: group 1 (G1) - 25 patients with pharmacoresistant TLE-MTS, without comorbid PD; Group 2 (G2) - 21 patients with pharmacoresistant TLE-MTS with PD; Group 3 (G3) - 52 healthy control subjects. Serum levels of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione plus oxidated glutathione (total GSH), glucose-6-phosphate dehydrogenase (G6PD), Trolox-equivalent antioxidant capacity (TEAC), and thiobarbituric acid reactive substances (TBARS) were analyzed through spectrometry. The significance level was set at P<0.05. Sociodemographic data were similar in all groups (P>0.05). A family history of epilepsy was more frequent among G1 and G2 groups when compared to G3 (P = 0.0002). Compared to controls, G1 and G2 presented higher CAT (P<0.0001) and TBARS levels (P = 0.001), as well as lower GPx (P<0.0001), G6PD (P = 0.005) and total GSH levels (P = 0.04). The presence of psychiatric disorders (PD), analyzed both separately and together, was not associated with significant differences in OSB levels (P>0.05). The lower levels of GPx, G6PD, and total GSH, as well as the higher CAT and TBARS levels observed in pharmaco-resistant TLE-MTS patients can indicate an imbalance between oxidizing agent production and elimination, supporting the hypothesis of a possible role of OS in the pathogenesis of this condition.

Altered Metabolic Networks in Mesial Temporal Lobe Epilepsy with Focal to Bilateral Seizures.

This study was designed to identify whether the metabolic network changes in mesial temporal lobe epilepsy (MTLE) patients with focal to bilateral tonic-clonic seizures (FBTCS) differ from changes in patients without FBTCS. This retrospective analysis enrolled 30 healthy controls and 54 total MTLE patients, of whom 27 had FBTCS. Fluorodeoxyglucose positron emission tomography (FDG-PET) data and graph theoretical analyses were used to examine metabolic connectivity. The differences in metabolic networks between the three groups were compared. Significant changes in both local and global network topology were evident in FBTCS+ patients as compared to healthy controls, with a lower assortative coefficient and altered betweenness centrality in 15 brain regions. While global network measures did not differ significantly when comparing FBTCS- patients to healthy controls, alterations in betweenness centrality were evident in 13 brain regions. Significantly altered betweenness centrality was also observed in four brain regions when comparing patients with and without FBTCS. The study revealed greater metabolic network abnormalities in MTLE patients with FBTCS as compared to FBTCS- patients, indicating the existence of distinct epileptogenic networks. These findings can provide insight into the pathophysiological basis of FBTCS.

[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.

E2730, an uncompetitive γ-aminobutyric acid transporter-1 inhibitor, suppresses epileptic seizures in a rat model of chronic mesial temporal lobe epilepsy.

More than one third of mesial temporal lobe epilepsy (MTLE) patients are resistant to current antiseizure medications (ASMs), and half experience mild-to-moderate adverse effects of ASMs. There is therefore a strong need to develop and test novel ASMs. The objective of this work is to evaluate the pharmacokinetics and neurological toxicity of E2730, a novel uncompetitive inhibitor of γ-aminobutyric acid transporter-1, and to test its seizure suppression effects in a rat model of chronic MTLE. We first examined plasma levels and adverse neurological effects of E2730 in healthy Wistar rats. Adult male rats were implanted with osmotic pumps delivering either 10, 20, or 100 mg/kg/day of E2730 subcutaneously for 1 week. Blood sampling and behavioral assessments were performed at several timepoints. We next examined whether E2730 suppressed seizures in rats with chronic MTLE. These rats were exposed to kainic acid-induced status epilepticus, and 9 weeks later, when chronic epilepsy was established, were assigned to receive one of the three doses of E2730 or vehicle for 1 week in a randomized crossover design. Continuous video-electroencephalographic monitoring was acquired during the treatment period to evaluate epileptic seizures. Plasma levels following continuous infusion of E2730 showed a clear dose-related increase in concentration. The drug was well tolerated at all doses, and any sedation or neuromotor impairment was mild and transient, resolving within 48 h of treatment initiation. Remarkably, E2730 treatment in chronically epileptic rats led to seizure suppression in a dose-dependent manner, with 65% of rats becoming seizure-free at the highest dose tested. Mean seizure class did not differ between the treatment groups. This study shows that continuous subcutaneous infusion of E2730 over 7 days results in a marked, dose-dependent suppression of spontaneous recurrent seizures, with minimal adverse neurological effects, in a rat model of chronic MTLE. E2730 shows strong promise as an effective new ASM to be translated into clinical trials.

More extensive structural damage in temporal lobe epilepsy with hippocampal sclerosis type 1

ObjectiveTo explore clinical and structural differences between mesial temporal lobe epilepsy (mTLE) patients with different hippocampal sclerosis (HS) subtypes. MethodsHigh-resolution T1-weighted MRI and diffusion tensor imaging data were obtained in 41 refractory mTLE patients and 52 age- and sex-matched healthy controls. Postoperative histopathological examination confirmed HS type 1 in 30 patients and HS type 2 in eleven patients. Clinical features, postoperative seizure outcomes, hippocampal subfields volumes, fractional anisotropy (FA) values of white matter regions and graph theory parameters were explored and compared between the HS type 1 and HS type 2 groups. ResultsNo significant differences in clinical features and postsurgical seizure outcomes were found between the HS type 1 and type 2 groups. However, the HS type 1 group showed extra atrophy in ipsilateral parasubiculum than healthy controls and more severe atrophy in contralateral hippocampal fissure than the HS type 2 group. More extensive FA decrease were also observed in the HS type 1 group, involving ipsilateral optic radiation, superior fronto-occipital fasciculus, contralateral uncinate fasciculus, tapetum, bilateral hippocampal cingulum, corona radiata, etc. Furthermore, in spite of similar impairments in characteristic path length, global efficiency and local efficiency in two HS groups, the HS type 1 group showed additional decrease of clustering coefficient than healthy controls. ConclusionsHS type 1 and 2 groups had similar clinical characteristics and postoperative seizure outcomes. More widespread neuronal cell loss in the HS type 1 group contributed to more extensive structural damage and connectivity abnormality. These results shed new light on the imaging correlates of different HS pathology.

Biohybrid restoration of the hippocampal loop re-establishes the non-seizing state in an in vitro model of limbic seizures

Objective. The compromise of the hippocampal loop is a hallmark of mesial temporal lobe epilepsy (MTLE), the most frequent epileptic syndrome in the adult population and the most often refractory to medical therapy. Hippocampal sclerosis is found in >50% of drug-refractory MTLE patients and primarily involves the CA1, consequently disrupting the hippocampal output to the entorhinal cortex (EC). Closed-loop deep brain stimulation is the latest frontier to improve drug-refractory MTLE; however, current approaches do not restore the functional connectivity of the hippocampal loop, they are designed by trial-and-error and heavily rely on seizure detection or prediction algorithms. The objective of this study is to evaluate the anti-ictogenic efficacy and robustness of an artificial bridge restoring the dialog between hippocampus and EC. Approach. In mouse hippocampus-EC slices treated with 4-aminopyridine and in which the Schaffer Collaterals are severed, we established an artificial bridge between hippocampus and EC wherein interictal discharges originating in the CA3 triggered stimulation of the subiculum so to entrain EC networks. Combining quantification of ictal activity with tools from information theory, we addressed the efficacy of the bridge in controlling ictogenesis and in restoring the functional connectivity of the hippocampal loop. Main results. The bridge significantly decreased or even prevented ictal activity and proved robust to failure; when operating at 100% of its efficiency (i.e., delivering a pulse upon each interictal event), it recovered the functional connectivity of the hippocampal loop to a degree similar to what measured in the intact circuitry. The efficacy and robustness of the bridge stem in mirroring the adaptive properties of the CA3, which acts as biological neuromodulator. Significance. This work is the first stepping stone toward a paradigm shift in the conceptual design of stimulation devices for epilepsy treatment, from function control to functional restoration of the salient brain circuits.

Stability of face recognition abilities after left or right anterior temporal lobectomy.

Patients with anterior temporal lobe (ATL) resection due to mesial temporal lobe epilepsy (MTLE) have difficulties at identifying familiar faces and explicitly remembering newly learned faces but their ability to individuate unfamiliar faces remains largely unknown. Moreover, the extent to which their difficulties with familiar face identity recognition and learning is truly due to the ATL resection remains unknown. Here, we report a study of 24 MTLE patients and matched healthy controls tested with an extensive set of seven face and visual object recognition tasks (including three tasks evaluating unfamiliar face individuation) before and about 6 months after unilateral (nine left, 15 right) ATL resection. We found that ATL resection has little or no effect on the patients' preserved pre-surgical ability to perform unfamiliar face individuation, both at the group and individual levels. More surprisingly, ATL resection also has little effect on the patients' performance at recognizing and naming famous faces as well as at learning new faces. A substantial proportion of right MTLE patients (33%) even improved their response times on several tasks, which may indicate a functional release of visuo-spatial processing after resection in the right ATL. Altogether this study shows that face recognition abilities are mainly unaffected by ATL resection in MTLE, either because the critical regions for face recognition are spared or because performance at some tasks is already lower than normal preoperatively. Overall, these findings urge caution when interpreting the causal effect of brain lesions on face recognition ability in patients with ATL resection due to MTLE. They also illustrate the complexity of predicting cognitive outcomes after epilepsy surgery because of the influence of many different intertwined factors.

Altered metabolic-functional coupling in the epileptogenic network could predict surgical outcomes of mesial temporal lobe epilepsy.

To investigate the relationship between glucose metabolism and functional activity in the epileptogenic network of patients with mesial temporal lobe epilepsy (MTLE) and to determine whether this relationship is associated with surgical outcomes. 18F-FDG PET and resting-state functional MRI (rs-fMRI) scans were performed on a hybrid PET/MR scanner in 38 MTLE patients with hippocampal sclerosis (MR-HS), 35 MR-negative patients and 34 healthy controls (HC). Glucose metabolism was measured using 18F-FDG PET standardized uptake value ratio (SUVR) relative to cerebellum; Functional activity was obtained by fractional amplitude of low-frequency fluctuation (fALFF). The betweenness centrality (BC) of metabolic covariance network and functional network were calculated using graph theoretical analysis. Differences in SUVR, fALFF, BC and the spatial voxel-wise SUVR-fALFF couplings of the epileptogenic network, consisting of default mode network (DMN) and thalamus, were evaluated by Mann-Whitney U test (using the false discovery rate [FDR] for multiple comparison correction). The top ten SUVR-fALFF couplings were selected by Fisher score to predict surgical outcomes using logistic regression model. The results showed decreased SUVR-fALFF coupling in the bilateral middle frontal gyrus (PFDR = 0.0230, PFDR = 0.0296) in MR-HS patients compared to healthy controls. Coupling in the ipsilateral hippocampus was marginally increased (PFDR = 0.0802) in MR-HS patients along with decreased BC of metabolic covariance network and functional network (PFDR = 0.0152; PFDR = 0.0429). With Fisher score ranking, the top ten SUVR-fALFF couplings in regions from DMN and thalamic subnuclei could predict surgical outcomes with the best performance being a combination of ten SUVR-fALFF couplings with an AUC of 0.914. These findings suggest that the altered neuroenergetic coupling in the epileptogenic network is associated with surgical outcomes of MTLE patients, which may provide insight into their pathogenesis and help with preoperative evaluation.

Brain volumes and white matter diffusion across the adult lifespan in temporal lobe epilepsy.

Typical aging is associated with gradual cognitive decline and changes in brain structure. The observation that cognitive performance in mesial temporal lobe epilepsy (TLE) patients diverges from controls early in life with subsequent decline running in parallel would suggest an initial insult but does not support accelerated decline secondary to seizures. Whether TLE patients demonstrate similar trajectories of age-related gray (GM) and white matter (WM) changes as compared to healthy controls remains uncertain. 3D T1-weighted and diffusion tensor images were acquired at a single site in 170 TLE patients (aged 23-74 years) with MRI signs of unilateral hippocampal sclerosis (HS, 77 right) and 111 healthy controls (aged 26-80 years). Global brain (GM, WM, total brain, and cerebrospinal fluid) and regional volumes (ipsi- and contralateral hippocampi), and fractional anisotropy (FA) of 10 tracts (three portions of corpus callosum, inferior longitudinal, inferior fronto-occipital and uncinate fasciculi, body of fornix, dorsal and parahippocampal-cingulum, and corticospinal tract) were compared between groups as a function of age. There were significant reductions of global brain and hippocampi volumes (greatest ipsilateral to HS), and FA of all 10 tracts in TLE versus controls. For TLE patients, regression lines run in parallel to those from controls for brain volumes and FA (for all tracts except the parahippocampal-cingulum and corticospinal tract) versus age across the adult lifespan. These results imply a developmental hindrance occurring earlier in life (likely in childhood/neurodevelopmental stages) rather than accelerated atrophy/degeneration of most brain structures herein analyzed in patients with TLE.

Pre-ictal fluctuation of EEG functional connectivity discriminates seizure phenotypes in mesial temporal lobe epilepsy

ObjectiveWe explored whether quantifiable differences between clinical seizures (CSs) and subclinical seizures (SCSs) occur in the pre-ictal state. MethodsWe analyzed pre-ictal stereo-electroencephalography (SEEG) retrospectively across mesial temporal lobe epilepsy patients with recorded CSs and SCSs. Power spectral density and functional connectivity (FC) were quantified within and between the seizure onset zone (SOZ) and the early propagation zone (PZ), respectively. To evaluate the fluctuation of neural connectivity, FC variability was computed. Measures were further verified by a logistic regression model to evaluate their classification potentiality through the area under the receiver-operating-characteristics curve (AUC). ResultsFifty-four pre-ictal SEEG epochs (27 CSs and 27 SCSs) were selected among 14 patients. Within the SOZ, pre-ictal FC variability of CSs was larger than SCSs in 1–45 Hz during 30 seconds before seizure onset. Pre-ictal FC variability between the SOZ and PZ was larger in SCSs than CSs in 55–80 Hz within 1 minute before onset. Using these two variables, the logistic regression model achieved an AUC of 0.79 when classifying CSs and SCSs. ConclusionsPre-ictal FC variability within/between epileptic zones, not signal power or FC value, distinguished SCSs from CSs. SignificancePre-ictal epileptic network stability possibly marks seizure phenotypes, contributing insights into ictogenesis and potentially helping seizure prediction.

SEEG-based reevaluation of epileptogenic networks and the predictive role for reoperation in MTLE patients with surgical failure.

Approximately 20%-30% of mesial temporal lobe epilepsy (MTLE) patients got unfavorable seizure control after surgery, and there was a discrepancy about the reasons for the surgical failure. The functional connectivity (FC) patterns obtained from stereo-electroencephalography (SEEG) reveal information about the dynamics of the epileptic brain and the added value of extracting information that was not identifiable in the SEEG data using FC analysis. This study aims to find out the patterns of the potential epileptogenic network of failure patients and the electrophysiological predictors of reoperation. From January 2012 to December 2019, the MTLE patients with surgical failure were reviewed, and all patients underwent SEEG-guided reoperation. The epileptogenic network was quantified by calculating FC indicators, including phase slope index (PSI), mutual information (MI) strength, imaginary coherence (icoh), and Granger causality. Ten patients with 13 seizures were included in the analysis, and 7 of them achieved a favorable outcome after the SEEG-guided reoperation. The surgical zone (SZ) with a favorable prognosis showed greater outward information flow than the non-SZ, whereas the SZ with an unfavorable prognosis showed greater inward information flow. The recurrent patients with favorable prognosis had strong connectivity between the posterior hippocampus, temporal neocortex, and insula, whereas the patients with unfavorable prognosis showed strong functional connectivity between the insula and temporal-parietal-occipital junction. The power spectrum of patients with favorable prognosis was significantly lower than that of patients with unfavorable prognosis, especially showing a more oscillation power of low frequency. The SEEG-guided reoperation could achieve favorable seizure control outcomes for recurrent patients. The FCs were a potential indicator to help construct the temporal epileptic network and predictor for the reoperative prognosis in the recurrent patients.

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.

Epilepsy surgery for dominant-side mesial temporal lobe epilepsy without hippocampal sclerosis

Although anterior temporal lobectomy (ATL) is an established surgery for medically intractable mesial temporal lobe epilepsy (MTLE), it can harm memory function, especially in dominant-side MTLE patients without hippocampal sclerosis (HS). To avoid this complication, multiple hippocampal transection (MHT) was developed, but its efficacy has not been fully elucidated. We report the detailed treatment results of MHT compared with that of ATL. We retrospectively analysed the records of 30 patients who underwent surgery for dominant-side MTLE. ATL was completed for 23 patients with HS, and MHT was completed for 7 patients without HS. The seizure control status, number of anti-seizure medicines, neurocognitive function, and psychiatric disorders of each patient were reviewed. The mean follow-up period was 70 months. Seizure control of Engel class I was achieved in 16 patients (70%) in the ALT group versus 5 patients (71%) in the MHT group. The mean number of anti-seizure medicines administered in the ATL group changed significantly from 2.4 to 1.9 (p = 0.01), while that in the MHT group was unchanged (from 2.1 to 2.0, p = 0.77). Eleven patients (48%) in the ATL group developed psychiatric disorders during the postoperative follow-up period, whereas no psychological complications were observed in the MHT group. Neither group showed neurocognitive decline after the surgery in any of the WAIS-III or WMS-R subtests. In conclusion, MHT may achieve reasonable postoperative seizure reduction, preserve neurocognitive function, and reduce postoperative psychiatric complications. Therefore, it can be considered as a therapeutic option for dominant-side MTLE without HS.

Reelin Signaling Pathway and Mesial Temporal Lobe Epilepsy: A Causative Link.

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis. The aim of this study was to investigate the Reelin signalling pathway in the MTLE patients. Therefore, we studied each step in the Reelin signalling pathway for the gene and protein expressions, in the hippocampal tissue obtained from patients undergoing surgery for MTLE and compared it with age matched normal autopsy cases. We found statistically significant decrease (P<0.001) in the Reelin mRNA expression in MTLE patients. Among the two reelin receptors, apolipoprotein E receptor 2 (ApoER2) was significantly increased whereas very low density lipoprotein receptor (VLDLR) was decreased among the patients. Disabled 1 (Dab1), the downstream target of reelin, was found to be decreased. Dab1 in turn inhibits Cofilin, which is responsible for cytoskeletal reorganization, thus limiting aberrant neuronal migration. Statistically significant over expression of Cofilin protein was found in the patient group. Matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteases-1 (TIMP-1), both of which are involved in processing of Reelin, were down regulated in 70-85% of cases. The whole pathway was found to be deranged in MTLE. These results indicate that Reelin signalling pathway is disturbed at various points in the MTLE patients and might be involved in the pathogenesis & progression of MTLE. Our results extend the existing information regarding the components of the Reelin pathway and further, establish a link between pathway disturbance and MTLE.