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The mesial temporal lobe epilepsy (MTLE) seizures are believed to originate from medial temporal structures, including the amygdala, hippocampus, and temporal cortex. Thus, the seizures onset zones (SOZs) of MTLE locate in these regions. However, whether the neural features of SOZs are specific to different medial temporal structures are still unclear and need more investigation. To address this question, the present study tracked the features of two different high frequency oscillations (HFOs) in the SOZs of these regions during MTLE seizures from 10 drug-resistant MTLE patients, who received the stereo electroencephalography (SEEG) electrodes implantation surgery in the medial temporal structures. Remarkable difference of HFOs features, including the proportions of HFOs contacts, percentages of HFOs contacts with significant coupling and firing rates of HFOs, could be observed in the SOZs among three medial temporal structures during seizures. Specifically, we found that the amygdala might contribute to the generation of MTLE seizures, while the hippocampus plays a critical role for the propagation of MTLE seizures. In addition, the HFOs firing rates in SOZ regions were significantly larger than those in NonSOZ regions, suggesting the potential biomarkers of HFOs for MTLE seizure. Moreover, there existed higher percentages of SOZs contacts in the HFOs contacts than in all SEEG contacts, especially those with significant coupling to slow oscillations, implying that specific HFOs features would help identify the SOZ regions. Taken together, our results displayed the features of HFOs in different medial temporal structures during MTLE seizures, and could deepen our understanding concerning the neural mechanism of MTLE.

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OBJECTIVE: To expand the clinical phenotype and mutation spectrum of familial mesial temporal lobe epilepsy (FMTLE) and provide a new perspective for exploring the pathological mechanisms of epilepsy caused by leucine-rich glioma inactivated 1 (LGI1) variants. METHODS: We reported clinical data from two families with FMTLE and screened patients for variants in the LGI1 gene using Whole-exome sequencing and Sanger sequencing. The clinical features of FMTLE were analysed. The pathogenicity of the causative loci was assessed according to the American College of Medical Genetics and Genomics guidelines, and potential pathogenic mechanisms were predicted through multiple bioinformatics and molecular dynamics software. RESULTS: We identified two novel LGI1 truncating variants within two large families with FMTLE: LGI1 (c.1174C>T, p.Q392X) and LGI1 (c.703C>T, p.Q235X). Compared to previous reports, we found that focal to bilateral tonic-clonic seizures are a common type of seizure in FMTLE. The clinical phenotypes of patients with FMTLE caused by LGI1 variants were relatively mild, and all patients responded well to valproic acid. Bioinformatics analyses and molecular dynamics simulations showed that protein structure and interactions were considerably weakened or damaged as a result of both variants. CONCLUSION: This study presents the first report identifying LGI1 as a potential novel pathogenic gene within FMTLE families, thereby broadening the mutation spectrum associated with FMTLE. The findings of this study offer novel insights and avenues for understanding the intricate molecular mechanisms underlying LGI1 variants and their correlations with patient phenotypes. This study proposes the possibility of familial focal epilepsy syndromes overlapping.

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Mesial temporal lobe epilepsy (MTLE) is characterized by recurring focal seizures that arise from limbic areas and are often refractory to pharmacological interventions. We have reported that optogenetic stimulation of PV-positive cells in the medial septum at 0.5 Hz exerts seizure-suppressive effects. Therefore, we compared here these results with those obtained by optogenetic stimulation of medial septum PV-positive neurons at 8 Hz in male PV-ChR2 mice (P60-P100) undergoing an initial, pilocarpine-induced status epilepticus (SE). Optogenetic stimulation (5 min ON, 10 min OFF) was performed from day 8 to day 12 after SE at a frequency of 8 Hz (n = 6 animals) or 0.5 Hz (n = 8 animals). Surprisingly, in both groups, no effects were observed on the occurrence of interictal spikes and interictal high frequency oscillations (HFOs). However, 0.5 Hz stimulation induced a significant decrease of seizure occurrence (p < 0.05). Such anti-ictogenic effect was not observed in the 8 Hz protocol that instead triggered seizures (p < 0.05); these seizures were significantly longer under optogenetic stimulation compared to when optogenetic stimulation was not implemented (p < 0.05). Analysis of ictal HFOs revealed that in the 0.5 Hz group, but not in the 8 Hz group, seizures occurring under optogenetic stimulation were associated with significantly lower rates of fast ripples compared to when optogenetic stimulation was not performed (p < 0.05). Our results indicate that activation of GABAergic PV-positive neurons in the medial septum exerts seizure-suppressing effects that are frequency-dependent and associated with low rates of fast ripples. Optogenetic activation of medial septum PV-positive neurons at 0.5 Hz is efficient in blocking seizures in the pilocarpine model of MTLE, an effect that did not occur with 8 Hz stimulation.

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Introduction: Mesial temporal lobe epilepsy (MTLE) is one of the most prevalent forms of focal epilepsy in surgical series, particularly among adults. Over the decades, different surgical strategies have been developed to address drug-resistant epilepsy while safeguarding neurological and cognitive functions. Among these strategies, anterior temporal lobectomy (ATL), involving the removal of the temporal pole and mesial temporal structures, has emerged as a widely employed technique. Numerous modifications have been proposed to mitigate the risks associated with aphasia, cognitive issues, and visual field defects. Methods: Our approach is elucidated through intraoperative and cadaveric dissections, complemented by neuroradiological and cadaveric measurements of key anatomical landmarks. A retrospective analysis of patients with drug-resistant MTLE who were treated using our ATL technique at IRCCS Neuromed (Pozzilli) is presented. Results: A total of 385 patients were treated with our ATL subpial technique anatomically focused on the anterior Sylvian point (ASyP). The mean FU was 9.9 ± 5.4 years (range 1-24). In total, 84%of patients were free of seizures during the last follow-up, with no permanent neurological deficits. Transient defects were as follows: aphasia in 3% of patients, visual field defects in 2% of patients, hemiparesis in 2% of patients, and cognitive/memory impairments in 0.8% of patients. In cadaveric dissections, the ASyP was found at a mean distance from the temporal pole of 3.4 ± 0.2 cm (range 3-3.8) at the right side and 3.5 ± 0.2 cm (3.2-3.9) at the left side. In neuroimaging, the ASyP resulted anterior to the temporal horn tip in all cases at a mean distance of 3.2 ± 0.3 mm (range 2.7-3.6) at the right side and 3.5 ± 0.4 mm (range 2.8-3.8) at the left side. Discussion: To the best of our knowledge, this study first introduces the ASyP as a reliable and reproducible cortical landmark to perform the ATL to overcome the patients' variabilities, the risk of Meyer's loop injury, and the bias of intraoperative measurements. Our findings demonstrate that ASyP can be a safe cortical landmark that is useful in MTLE surgery because it is constantly present and is anterior to risky temporal regions such as temporal horn and language networks.

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An epilepsy diagnosis reduces a patient's quality of life tremendously, and it is a fate shared by over 50 million people worldwide. Temporal lobe epilepsy (TLE) is largely considered a nongenetic or acquired form of epilepsy that develops in consequence of neuronal trauma by injury, malformations, inflammation, or a prolonged (febrile) seizure. Although extensive research has been conducted to understand the process of epileptogenesis, a therapeutic approach to stop its manifestation or to reliably cure the disease has yet to be developed. In this review, we briefly summarize the current literature predominately based on data from excitotoxic rodent models on the cellular events proposed to drive epileptogenesis and thoroughly discuss the major molecular pathways involved, with a focus on neurogenesis-related processes and transcription factors. Furthermore, recent investigations emphasized the role of the genetic background for the acquisition of epilepsy, including variants of neurodevelopmental genes. Mutations in associated transcription factors may have the potential to innately increase the vulnerability of the hippocampus to develop epilepsy following an injury-an emerging perspective on the epileptogenic process in acquired forms of epilepsy.

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Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy. The main pathological changes primarily involve hippocampal sclerosis (HS). Early resective surgery of the sclerotic hippocampus is typically associated with favorable clinical outcomes. However, not all patients are suitable candidates for resective surgery of mesial temporal lobe structures. Therefore, alternative treatment modalities should be considered. We present the case of a 50-year-old right-handed woman with left HS who underwent unilateral subiculum stimulation for drug-resistant epilepsy (DRE). Since the age of 10, the patient had been experiencing focal to bilateral tonic-clonic seizures (FBTCS). Despite multiple antiseizure medications, she experienced 12 to 17 FBTCS per month in the last two years. Due to concerns about potential memory decline and personal preferences, she refused resective surgery. As an alternative, the patient underwent left unilateral subiculum stimulation. The stimulation resulted in a nearly 67 % reduction in seizure frequency at the last follow-up (20 months after surgery). This case highlights that drug-resistant epilepsy may be effectively treated with subicular stimulation in patients with HS.

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Objective: Mesial temporal lobe epilepsy (mTLE) is a complex neurological disorder that has been recognized as a widespread global network disorder. The group-level structural covariance network (SCN) could reveal the structural connectivity disruption of the mTLE but could not reflect the heterogeneity at the individual level. Methods: This study adopted a recently proposed individual structural covariance network (IDSCN) method to clarify the alternated structural covariance connection mode in mTLE and to associate IDSCN features with the clinical manifestations and regional brain atrophy. Results: We found significant IDSCN abnormalities in the ipsilesional hippocampus, ipsilesional precentral gyrus, bilateral caudate, and putamen in mTLE patients than in healthy controls. Moreover, the IDSCNs of these areas were positively correlated with the gray matter atrophy rate. Finally, we identified several connectivities with weak associations with disease duration, frequency, and surgery outcome. Significance: Our research highlights the role of hippo-thalamic-basal-cortical circuits in the pathophysiologic process of disrupted whole-brain morphological covariance networks in mTLE, and builds a bridge between brain-wide covariance network changes and regional brain atrophy.

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OBJECTIVE: The aim of this study was to identify features of responsive neurostimulation (RNS) lead configuration and contact placement associated with greater seizure reduction in mesial temporal lobe epilepsy (MTLE). METHODS: A single-center series of patients with MTLE treated with RNS were retrospectively analyzed to assess the relationship between anatomical targeting and seizure reduction. Targeting was determined according to both the preoperatively conceived lead configuration and the actual placement of RNS contacts. Three lead configurations were used: 1) single bilateral, with 1 depth lead in each hippocampus; 2) single unilateral, with 1 hippocampal depth lead and another implant outside the mesial temporal lobe; and 3) dual unilateral, with 2 leads in 1 hippocampus. Contact placement on postoperative imaging was measured according to the number of hippocampal contacts per targeted hippocampus (contact density) and per patient (contact count), distribution throughout the hippocampus, and proximity to the anteromedial hippocampus. RESULTS: Dual unilateral lead placement resulted in significantly higher hippocampal contact density compared with the single hippocampal approaches, but only showed a nonsignificant trend toward a higher rate of response. However, those patients with more than 4 contacts in a single hippocampus, achievable only with dual unilateral leads, had a significantly higher rate of response. The higher likelihood of response was poorly explained by more widespread hippocampal coverage, but well correlated with proximity to the anteromedial hippocampus. CONCLUSIONS: Dual unilateral hippocampal implantation increased RNS contact density in patients with unilateral MTLE, which contributed to improved outcomes, not by stimulating more of the hippocampus, but instead by being more likely to stimulate a latent subtarget in the anterior hippocampus. It remains to be explored whether a single electrode targeted selectively to this region would also result in improved outcomes.

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The purpose of this study was to systematically examine three different surgical approaches in treating left medial temporal lobe epilepsy (mTLE) (viz., subtemporal selective amygdalohippocampectomy [subSAH], stereotactic laser amygdalohippocampotomy [SLAH], and anterior temporal lobectomy [ATL]), to determine which procedures are most favorable in terms of visual confrontation naming and seizure relief outcome. This was a retrospective study of 33 adults with intractable mTLE who underwent left temporal lobe surgery at three different epilepsy surgery centers who also underwent pre-, and at least 6-month post-surgical neuropsychological testing. Measures included the Boston Naming Test (BNT) and the Engel Epilepsy Surgery Outcome Scale. Fisher's exact tests revealed a statistically significant decline in naming in ATLs compared to SLAHs, but no other significant group differences. 82% of ATL and 36% of subSAH patients showed a significant naming decline whereas no SLAH patient (0%) had a significant naming decline. Significant postoperative naming improvement was seen in 36% of SLAH patients in contrast to 9% improvement in subSAH patients and 0% improvement in ATLs. Finally, there were no statistically significant differences between surgical approaches with regard to seizure freedom outcome, although there was a trend towards better seizure relief outcome among the ATL patients. Results support a possible benefit of SLAH in preserving visual confrontation naming after left TLE surgery. While result interpretation is limited by the small sample size, findings suggest outcome is likely to differ by surgical approach, and that further research on cognitive and seizure freedom outcomes is needed to inform patients and providers of potential risks and benefits with each.

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BACKGROUND: We aimed to analyze potentially prognostic factors which could have influence on postoperative seizure, neuropsychological and psychiatric outcome in a cohort of patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS) after selective amygdalohippocampectomy (SAHE) via transsylvian approach. METHODS: Clinical variables of 171 patients with drug-resistant MTLE with HS (88 females) who underwent SAHE between 1994 and 2019 were evaluated using univariable and multivariable logistic regression models, to investigate which of the explanatory parameters can best predict the outcome. RESULTS: At the last available follow-up visit 12.3 ± 6.3 years after surgery 114 patients (67.9%) were seizure-free. Left hemispheric MTLE was associated with worse postoperative seizure outcome at first year after surgery (OR = 0.54, p = 0.01), female sex-with seizure recurrence at years 2 (OR = 0.52, p = 0.01) and 5 (OR = 0.53, p = 0.025) and higher number of preoperative antiseizure medication trials-with seizure recurrence at year 2 (OR = 0.77, p = 0.0064), whereas patients without history of traumatic brain injury had better postoperative seizure outcome at first year (OR = 2.08, p = 0.0091). All predictors lost their predictive value in long-term course. HS types had no prognostic influence on outcome. Patients operated on right side performed better in verbal memory compared to left (VLMT 1-5 p < 0.001, VLMT 7 p = 0.001). Depression occurred less frequently in seizure-free patients compared to non-seizure-free patients (BDI-II Z = - 2.341, p = 0.019). CONCLUSIONS: SAHE gives an improved chance of achieving good postoperative seizure, psychiatric and neuropsychological outcome in patients with in MTLE due to HS. Predictors of short-term outcome don't predict long-term outcome.

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OBJECTIVE: The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology of malformations of cortical development. The aim of this study was to determine the diagnostic yield of somatic variants in genes that have been previously associated with a somatic or germline epilepsy model, ascertained from resected brain tissue from patients with multidrug-resistant focal epilepsy. METHODS: Forty-two patients were recruited across three categories: (1) malformations of cortical development, (2) mesial temporal lobe epilepsy with hippocampal sclerosis, and (3) nonlesional focal epilepsy. Participants were subdivided based on histopathology of the resected brain. Paired blood- and brain-derived DNA samples were sequenced using high-coverage targeted next generation sequencing to high depth (585× and 1360×, respectively). Variants were identified using Genome Analysis ToolKit (GATK4) MuTect-2 and confirmed using high-coverage Amplicon-EZ sequencing. RESULTS: Sequence data on 41 patients passed quality control. Four somatic variants were validated following amplicon sequencing: within CBL, ALG13, MTOR, and FLNA. The diagnostic yield across 41 patients was 10%, 9% in mesial temporal lobe epilepsy with hippocampal sclerosis and 20% in malformations of cortical development. SIGNIFICANCE: This study provides novel insights into the etiology of mesial temporal lobe epilepsy with hippocampal sclerosis, highlighting a potential pathogenic role of somatic variants in CBL and ALG13. We also report candidate diagnostic somatic variants in FLNA in focal cortical dysplasia, while providing further insight into the importance of MTOR and related genes in focal cortical dysplasia. This work demonstrates the potential molecular diagnostic value of variants in both germline and somatic epilepsy genes.

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OBJECTIVE: To compare quantitative spectral parameters of visually-normal EEG between Mesial Temporal Lobe Epilepsy (MTLE) patients and healthy controls (HC). METHOD: We 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. RESULTS: In 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. DISCUSSION: Results confirmed that the power spectrum of qEEG is shifted towards lower frequencies in MTLE patients compared to HC. CONCLUSION: Of 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.

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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.

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PURPOSE: In 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: These 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.

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Posterior reversible encephalopathy syndrome is often linked to conditions like hypertension and is characterized by reversible brain edema. The development of mesial temporal sclerosis as a consequence of posterior reversible encephalopathy syndrome is an uncommon clinical outcome.  We report a 48-year-old female who initially presented with severe iron deficiency anemia, hypertension, and septic tenosynovitis requiring surgical drainage with subsequent development of posterior reversible encephalopathy syndrome accompanied by endocarditis. Although there was a question of one seizure episode during one of her hospital days, the patient experienced multiple seizure episodes three months after she left the hospital. Subsequent MRI demonstrated atrophy of the left mesial temporal lobe suggesting mesial temporal sclerosis.  The temporal development of mesial temporal sclerosis in a patient with posterior reversible encephalopathy syndrome highlights mesial temporal sclerosis as a potential long-term consequence of posterior reversible encephalopathy syndrome, and the need for imaging surveillance in patients diagnosed with posterior reversible encephalopathy syndrome.

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OBJECTIVE: The aim of this investigation was to determine whether a correlation could be discerned between perfusion acquired through ASL MRI and metabolic data acquired via 18F-fluorodeoxyglucose (18F-FDG) PET in mesial temporal lobe epilepsy (mTLE). METHODS: ASL MRI and 18F-FDG PET data were gathered from 22 mTLE patients. Relative cerebral blood flow (rCBF) asymmetry index (AIs) were measured using ASL MRI, and standardized uptake value ratio (SUVr) maps were obtained from 18F-FDG PET, focusing on bilateral vascular territories and key bitemporal lobe structures (amygdala, hippocampus, and parahippocampus). Intra-group comparisons were carried out to detect hypoperfusion and hypometabolism between the left and right brain hemispheres for both rCBF and SUVr in right and left mTLE. Correlations between the two AIs computed for each modality were examined. RESULTS: Significant correlations were observed between rCBF and SUVr AIs in the middle temporal gyrus, superior temporal gyrus, and hippocampus. Significant correlations were also found in vascular territories of the distal posterior, intermediate anterior, intermediate middle, proximal anterior, and proximal middle cerebral arteries. Intra-group comparisons unveiled significant differences in rCBF and SUVr between the left and right brain hemispheres for right mTLE, while hypoperfusion and hypometabolism were infrequently observed in any intracranial region for left mTLE. CONCLUSION: The study's findings suggest promising concordance between hypometabolism estimated by 18F-FDG PET and hypoperfusion determined by ASL perfusion MRI. This raises the possibility that, with prospective technical enhancements, ASL perfusion MRI could be considered an alternative modality to 18F-FDG PET in the future.

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OBJECTIVE: The study investigated metabolic connectivity (MC) differences between patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) and healthy controls (HCs), based on [18 F]-fluorodeoxyglucose (FDG)-PET data. We focused on the MC changes dependent on the lateralization of the epileptogenic lobe and on correlations with postoperative outcomes. METHODS: FDG-PET scans of 47 patients with unilateral MTLE with histopathologically proven HS and 25 HC were included in the study. All the patients underwent a standard anterior temporal lobectomy and were more than 2 years after the surgery. MC changes were compared between the two HS groups (left HS, right HS) and HC. Differences between the metabolic network of seizure-free and non-seizure-free patients after surgery were depicted afterward. Network changes were correlated with clinical characteristics. RESULTS: The study showed widespread metabolic network changes in the HS patients as compared to HC. The changes were more extensive in the right HS than in the left HS. Unfavorable surgical outcomes were found in patients with decreased MC within the network including both the lesional and contralesional hippocampus, ipsilesional frontal operculum, and contralesional insula. Favorable outcomes correlated with decreased MC within the network involving both orbitofrontal cortices and the ipsilesional temporal lobe. SIGNIFICANCE: There are major differences in the metabolic networks of left and right HS, with more extensive changes in right HS. The changes within the metabolic network could help predict surgical outcomes in patients with HS. MC may identify patients with potentially unfavorable outcomes and direct them to a more detailed presurgical evaluation. PLAIN LANGUAGE SUMMARY: Metabolic connectivity is a promising method for metabolic network mapping. Metabolic networks in mesial temporal lobe epilepsy are dependent on lateralization of the epileptogenic lobe and could predict surgical outcomes.

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We analyzed peripheral blood mononuclear cells (PBMCs) and serum inflammatory biomarkers in patients with mesial temporal lobe epilepsy (drug-resistant - DR, vs. drug-sensitive - DS). Patients with epilepsy showed higher levels of serum CCL2, CCL3, IL-8 and AOPP, and lower levels of FRAP and thiols compared to healthy controls (HC). Although none of the serum biomarkers distinguished DR from DS patients, when analysing intracellular cytokines after in vitro stimulation, DR patients presented higher percentages of IL-1ß and IL-6 positive monocytes compared to DS patients and HC. Circulating innate immune cells might be implicated in DR epilepsy and constitute potential new targets for treatments.

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Objective: Several clinical studies have explored the feasibility and efficacy of radiosurgical treatment for mesial temporal lobe epilepsy, but the long-term safety of this treatment has not been fully characterized. This study aims to report and describe radiation-induced cavernous malformation as a delayed complication of radiosurgery in epilepsy patients. Methods: The series includes 20 patients with mesial temporal lobe epilepsy who underwent Gamma Knife radiosurgery (GKRS). The majority received a prescribed isodose of 24 Gy as an adjuvant treatment after anterior temporal lobectomy. Results: In this series, we identified radiation-induced cavernous malformation in three patients, resulting in a cumulative incidence of 18.4% (95% CI, 6.3 to 47.0%) at an eight-year follow-up. These late sequelae of vascular malformation occurred between 6.9 and 7.6 years after GKRS, manifesting later than other delayed radiation-induced changes, such as radiation necrosis. Neurological symptoms attributed to intracranial hypertension were present in those three cases involving cavernous malformation. Of these, two cases, which initially exhibited an insufficient response to radiosurgery, ultimately demonstrated seizure remission following the successful microsurgical resection of the cavernous malformation. Conclusion: All things considered, the development of radiation-induced cavernous malformation is not uncommon in this population and should be acknowledged as a potential long-term complication. Microsurgical resection of cavernous malformation can be preferentially considered in cases where the initial seizure outcome after GKRS is unsatisfactory.

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(1) Objective: This study aimed to explore the efficacy of conventional invasive techniques in confirming unilateral seizure onset localization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to investigate the association between electrode type and intracranial electroencephalography (EEG) pattern. (2) Methods: This retrospective study encompasses patients diagnosed with MTLE-HS who underwent an invasive study prior to an anterior temporal lobectomy (ATL). Intracranial EEG features were assessed for 99 seizure events from 25 selected patients who achieved seizure remission with ATL after an invasive study using bilateral combined depth and subdural electrodes. Their findings were compared to those of 21 seizure events in eight patients who exhibited suboptimal seizure outcomes. (3) Results: For the distribution of electrodes that recorded the ictal onset, hippocampal depth electrodes recorded 96% of all seizure events, while subdural electrodes recorded 52%. Among the seizures recorded in subdural electrodes, 49% were localized in medial electrodes, with only 8% occurring in lateral electrodes. The initiation of seizures exclusively detected in hippocampal depth electrodes was associated with successful seizure remission, whereas those solely recorded in the lateral strip electrodes were often linked to refractory seizures after ATL. (4) Conclusions: These findings emphasize the importance of employing a combination of depth and subdural electrodes in invasive studies for patients with MTLE-HS to enhance the accuracy of lateralization. This also cautions against sole reliance on subdural electrodes without depth electrodes, which could lead to inaccurate localization.