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In the present study patients with previously diagnosed MRI-negative temporal lobe epilepsy (TLE) on long-term video electroencephalography (VEEG) monitoring were re-evaluated with high resolution 3T MRI brain to look out for a skull base temporal lobe encephalocoele (TE). A total of 234 VEEGs were analyzed. TLE had been diagnosed in 104 patients based on semiology, ictal, interictal EEG data, and brain positron emission tomography (PET) studies. Of these, 99 patients had temporal lobe abnormality (78 had mesial temporal sclerosis, 8 had tumor, 3 had focal cortical dysplasia, and 10 had mixed pathology). Out of the five 1.5T MRI-negative TLE patients, two patients were diagnosed with TE on subsequent 3T MRI brain scans and one patient underwent electrocorticography-guided tailored resection for complete removal of epileptogenic tissue; with Engels class I seizure freedom at one year follow-up. We propose that TE should be carefully searched for, as a cause of refractory TLE, using high-resolution MRI sequences. [ABSTRACT FROM AUTHOR]

• MTS was associated with a higher number of intracranial subclinical seizures in patients with MTLE. • The patients with MTS exhibited favorable short-term and long-term surgical outcomes. • Patients with MTS who achieved Engel I - II classification had higher numbers of i-SCSs than patients without MTS. To 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). A 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. Of 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). Patients 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. The 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. [ABSTRACT FROM AUTHOR]

Background: Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and increases the risk of cognitive impairment, negatively impacting the quality of life of affected individuals. Objectives: This study aimed to investigate cognitive function in patients with low socioeconomic status affected by TLE and identify factors influencing such function. Methods: This case-control study, conducted between July 2021 and August 2022, compared the cognitive function of 40 patients affected by TLE to 92 healthy controls. The Montreal cognitive assessment (MoCA) was used for neurocognitive evaluation. Data analysis was performed using SPSS 25.0 for Windows. Results: The mean age of the patient group was 33.35 years, compared to 35.37 years in the control group. Moreover, 70% of patients affected by TLE displayed cognitive impairment and demonstrated lower performance in cognitive functions than the control group (P < 0.05). Significant correlations were identified between overall MoCA scores and several factors, including seizure frequency, educational level, polytherapy, disease duration, and self-esteem scores (P < 0.05). Multivariate analysis revealed that seizure control and higher educational level were statistically significant predictors of overall MoCA scores in patients affected by TLE. Conclusions: In low-income patients affected by TLE, seizure control and a higher educational level emerged as predictors of cognitive performance. These findings underscore the importance of identifying and managing comorbidities and the need for tailored cognitive rehabilitation programs for this population. [ABSTRACT FROM AUTHOR]

The osteoplastic flap is an under-utilized craniotomy approach in pediatric temporal lobe epilepsy treatment. By preserving the myofascial attachment of the temporalis muscle, the flap is allowed the remain vascularized while subdural and intracranial electrodes are in place. The process in which the flap is made and handled throughout this process can be complicated. We herein detail our surgical technique for the osteoplastic flap in the setting of pediatric temporal lobe epilepsy treatment, and highlight the surgical nuances specific to our 2-stage protocol in treating pediatric temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Purpose: Atractylenolide III (ATR III) is known for its anti-inflammatory and neuroprotective activities. In this study, we aimed to investigate the effects of ATR III on neuronal damage in temporal epileptic rats caused by kainic acid. Materials and Methods: 16-week-old Wistar Albino rats were divided into three groups; control (C, n=8), kainic acid (KA, n=8), ATR III+ kainic acid (KA+ATR, n=8). After 21 days of injections of kainic acid, learning, and memory behavior, anxiety, and locomotor activity were evaluated. Neuron morphologies in the hippocampus were examined, the total number of neurons, and the number of degenerated neurons were determined, and the thickness of these regions was also measured. Changes in biochemical parameters such as MDA, SOD, GSHPx, AChE, and CAT were investigated to detect oxidative stress in the brain. Results: There was no significant difference in the learning and memory function and locomotor activity. However, KA increased anxiety behavior without any effect of ATR III (closed arm duration, 244.90±25.17). There was no degeneration in the neurons of the control group. In the KA group, there was an increase in the number of degenerated neurons. In this group, the thicknesses in CA1, CA3, and DG regions were 37.39±1.90, 45.64±6.26 and 46.02±5.72 µm, respectively. In the ATR III+KA group, there were fewer degenerated neurons, less thinning of the hippocampus, and a higher number of normal neurons compared to the KA group. In this group, CA1, CA3, and DG thicknesses were calculated as 36.05±4.13, 47.09±7.09 and 43.07±5.91 µm, respectively. Conclusion: These findings suggest that ATR III may have the potential as a therapeutic agent for reducing neuronal damage in temporal epilepsy. Further research is warranted to explore the underlying mechanisms and evaluate the clinical implications of ATR III in the treatment of epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Structural–functional coupling (SFC) has shown great promise in predicting postsurgical seizure recurrence in patients with temporal lobe epilepsy (TLE). In this study, we aimed to clarify the global alterations in SFC in TLE patients and predict their surgical outcomes using SFC features. Methods: This study analyzed presurgical diffusion and functional magnetic resonance imaging data from 71 TLE patients and 48 healthy controls (HCs). TLE patients were categorized into seizure‐free (SF) and non‐seizure‐free (nSF) groups based on postsurgical recurrence. Individual functional connectivity (FC), structural connectivity (SC), and SFC were quantified at the regional and modular levels. The data were compared between the TLE and HC groups as well as among the TLE, SF, and nSF groups. The features of SFC, SC, and FC were categorized into three datasets: the modular SFC dataset, regional SFC dataset, and SC/FC dataset. Each dataset was independently integrated into a cross‐validated machine learning model to classify surgical outcomes. Results: Compared with HCs, the visual and subcortical modules exhibited decoupling in TLE patients (p <.05). Multiple default mode network (DMN)‐related SFCs were significantly higher in the nSF group than in the SF group (p <.05). Models trained using the modular SFC dataset demonstrated the highest predictive performance. The final prediction model achieved an area under the receiver operating characteristic curve of.893 with an overall accuracy of.887. Significance: Presurgical hyper‐SFC in the DMN was strongly associated with postoperative seizure recurrence. Furthermore, our results introduce a novel SFC‐based machine learning model to precisely classify the surgical outcomes of TLE. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy patients are often grouped together by clinical variables. Quantitative neuroimaging metrics can provide a data‐driven alternative for grouping of patients. In this work, we leverage ultra‐high‐field 7‐T structural magnetic resonance imaging (MRI) to characterize volumetric atrophy patterns across hippocampal subfields and thalamic nuclei in drug‐resistant focal epilepsy. Methods: Forty‐two drug‐resistant epilepsy patients and 13 controls with 7‐T structural neuroimaging were included in this study. We measured hippocampal subfield and thalamic nuclei volumetry, and applied an unsupervised machine learning algorithm, Latent Dirichlet Allocation (LDA), to estimate atrophy patterns across the hippocampal subfields and thalamic nuclei of patients. We studied the association between predefined clinical groups and the estimated atrophy patterns. Additionally, we used hierarchical clustering on the LDA factors to group patients in a data‐driven approach. Results: In patients with mesial temporal sclerosis (MTS), we found a significant decrease in volume across all ipsilateral hippocampal subfields (false discovery rate‐corrected p [pFDR] <.01) as well as in some ipsilateral (pFDR <.05) and contralateral (pFDR <.01) thalamic nuclei. In left temporal lobe epilepsy (L‐TLE) we saw ipsilateral hippocampal and some bilateral thalamic atrophy (pFDR <.05), whereas in right temporal lobe epilepsy (R‐TLE) extensive bilateral hippocampal and thalamic atrophy was observed (pFDR <.05). Atrophy factors demonstrated that our MTS cohort had two atrophy phenotypes: one that affected the ipsilateral hippocampus and one that affected the ipsilateral hippocampus and bilateral anterior thalamus. Atrophy factors demonstrated posterior thalamic atrophy in R‐TLE, whereas an anterior thalamic atrophy pattern was more common in L‐TLE. Finally, hierarchical clustering of atrophy patterns recapitulated clusters with homogeneous clinical properties. Significance: Leveraging 7‐T MRI, we demonstrate widespread hippocampal and thalamic atrophy in epilepsy. Through unsupervised machine learning, we demonstrate patterns of volumetric atrophy that vary depending on disease subtype. Incorporating these atrophy patterns into clinical practice could help better stratify patients to surgical treatments and specific device implantation strategies. [ABSTRACT FROM AUTHOR]

Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross‐sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA‐Epilepsy working group. Methods: A state‐of‐the‐art deep learning‐based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Results: Across all epilepsies, reduced total cerebellar volume was observed (d =.42). Maximum volume loss was observed in the corpus medullare (dmax =.49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax =.47), crus I/II (dmax =.39), VIIIA (dmax =.45), and VIIIB (dmax =.40). Earlier age at seizure onset (ηρmax2 =.05) and longer epilepsy duration (ηρmax2 =.06) correlated with reduced volume in these regions. Findings were most pronounced in TLE‐HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy. [ABSTRACT FROM AUTHOR]

To (i) determine whether accelerated long-term forgetting (ALF) can be found using standardized verbal memory test materials in children with genetic generalized epilepsy (GGE) and temporal lobe epilepsy (TLE), and (ii) to establish whether ALF is impacted by executive skills and repeat testing over long delays. One hundred and twenty-three children aged 8 to 16, (28 with GGE, 23 with TLE, and 72 typically developing; TD) completed a battery of standardized tests assessing executive functioning and memory for two stories. Stories were recalled immediately and after a 30-min delay. To examine whether repeat testing impacts long-term forgetting, one story was tested via free recall at 1-day and 2-weeks, and the other at 2-weeks only. Recognition was then tested for both stories at 2-weeks. Children with epilepsy recalled fewer story details, both immediately and after 30-min relative to TD children. Compared to TD children, the GGE group, but not the TLE group, showed ALF, having significantly poorer recall of the story tested only at the longest delay. Poor executive skills were significantly correlated with ALF for children with epilepsy. Standard story memory materials can detect ALF in children with epilepsy when administered over long delays. Our findings suggest that (i) ALF is related to poor executive skills in children with epilepsy, and (ii) repeated testing may ameliorate ALF in some children. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) represents the most common form of refractory focal epilepsy. The identification of innovative clinical biomarkers capable of categorizing patients with TLE, allowing for improved treatment and outcomes, still represents an unmet need. Circulating microRNAs (c-miRNAs) are short non-coding RNAs detectable in body fluids, which play crucial roles in the regulation of gene expression. Their characteristics, including extracellular stability, detectability through non-invasive methods, and responsiveness to pathological changes and/or therapeutic interventions, make them promising candidate biomarkers in various disease settings. Recent research has investigated c-miRNAs in various bodily fluids, including serum, plasma, and cerebrospinal fluid, of TLE patients. Despite some discrepancies in methodologies, cohort composition, and normalization strategies, a common dysregulated signature of c-miRNAs has emerged across different studies, providing the basis for using c-miRNAs as novel biomarkers for TLE patient management. [ABSTRACT FROM AUTHOR]

Background: Single‐cell RNA sequencing analysis has been usually conducted on post‐traumatic epilepsy (PET) and hereditary epilepsy (HE) patients; however, the transcriptome of patients with traumatic temporal lobe epilepsy has rarely been studied. Materials and Methods: Hippocampus tissues isolated from one patient with PTE and one patient with HE were used in the present study. Single cell isolates were prepared and captured using a 10× Genomics Chromium Single‐Cell 3′ kit (V3) according to the manufacturer's instructions. The libraries were sequenced on an Illumina NovaSeq 6000 sequencing system. Raw data were processed, and the cells were filtered and classified using the Seurat R package. Uniform Manifold Approximation and Projection was used for visualization. Differentially expressed genes (DEGs) were identified based on a p‐value ≤0.01 and log fold change (FC) ≥0.25. Gene Ontology (GO, http://geneontology.org/) and KEGG (Kyoto Encyclopedia of Genes and Genomes, www.genome.jp/kegg) analyses were performed on the DEGs for enrichment analysis. Results: The reads obtained from the 10× genomic platform for PTE and HE were 39.56 M and 30.08 M, respectively. The Q30 score of the RNA reads was >91.6%. After filtering, 7479 PTE cells and 9357 HE cells remained for further study. More than 96.4% of the reads were mapped to GRCh38/GRCm38. The cells were differentially distributed in two groups, with higher numbers of oligodendrocytes (6522 vs. 2532) and astrocytes (133 vs. 52), and lower numbers of microglial cells (2242 vs. 3811), and neurons (3 vs. 203) present in the HE group than in the PTE group. The DEGs in four cell clusters were identified, with 25 being in oligodendrocytes (13 upregulated and 12 downregulated), 87 in microglia cells (42 upregulated and 45 downregulated), 222 in astrocytes (115 upregulated and 107 downregulated), and 393 in neurons (305 upregulated and 88 downregulated). The genes MTND1P23 (downregulated), XIST (downregulated), and RPS4Y1 (upregulated) were commonly expressed in all four cell clusters. The DEGs in microglial cells and astrocytes were enriched in the IL‐17 signaling pathway. Conclusion: Our study explored differences in cells found in a patient with PE compared to a patient with HE, and the transcriptome in the different cells was analyzed for the first time. Studying inflammatory and immune functions might be the best approach for investigating traumatic temporal lobe epilepsy in neurons. [ABSTRACT FROM AUTHOR]

• Long-term follow-up of 84 treatment-naïve patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). • ASM provided encouraging treatment outcomes in drug-naïve MTLE-HS patients, with 64 % achieving seizure freedom (SF) and 41 % achieving complete SF in the last year of follow-up. • Remission and relapse were common in MTLE-HS, with 46 % and 51 % of patients experiencing a fluctuating course with periods of SF and complete SF, respectively. • Patients with MTLE-HS may require more ASMs for seizure control. This study aimed to describe long-term treatment outcomes of treatment-naïve patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). A retrospective review was conducted of treatment-naïve patients with MTLE-HS who visited the Yonsei Epilepsy Clinic from April 2000 to April 2022 and were followed up for at least 2 years. Seizure freedom (SF) was defined as no seizures or auras only for >1 year, and complete SF was defined as no seizures including auras for >1 year. Eighty-four treatment-naïve patients with MTLE-HS with a median follow-up of 122 months were included. Except for one patient who underwent early surgical treatment, of the remaining 83 patients, 31 (37.3 %) achieved SF and remained in remission, 38 (45.8 %) had fluctuations in seizure control, and 14 (16.9 %) never achieved SF. Additionally, 18 (21.7 %) patients achieved complete SF and remained in remission, 42 (50.6 %) showed fluctuations, and 23 (27.7 %) never achieved complete SF. Fifty-three (63.9 %) patients achieved SF and 34 (41.0 %) achieved complete SF at their last visit. Older age at epilepsy onset, male sex, low pretreatment seizure density, history of central nervous system infection before age 5, absence of aura, and fewer antiseizure medications in the final regimen were associated with favorable outcome. Of the 84 patients, 11 (13.1 %) underwent temporal lobectomy. Medical treatment outcomes in treatment-naïve MTLE-HS were relatively better than previously reported outcomes in MTLE-HS, although frequent fluctuations in seizure control were observed. [ABSTRACT FROM AUTHOR]

A ketogenic diet (KD) is often used in the treatment of refractory epilepsy. Many studies have found that it also has a positive impact on cognitive comorbidities, but the specific mechanism remains unclear. In many disease models, endoplasmic reticulum stress (ERS) and synaptic plasticity is considered a new therapeutic target for improving cognitive impairment, and it has become a research focus in recent years. Recently, studies have found that a KD has a certain regulatory effect on both ERS and synaptic plasticity, but this result has not been confirmed in epilepsy. To investigate the effect of a KD on ERS and synaptic plasticity. In this study, a rat model of temporal lobe epilepsy (TLE) induced by lithium chloride–pilocarpine was used. After the model was successfully established, the rats in each group were fed a normal diet or a KD for 28 days, and the effect of a KD on the latency and seizure frequency of spontaneous recurrent seizures (SRSs) was observed via video monitoring. Subsequently, a Morris water maze was used to evaluate the spatial learning and memory abilities of the rats in each group; the ultrastructure of the ER and the synapses of the hippocampus were observed by transmission electron microscopy, and the dendritic spine density of the hippocampus was analysed by Golgi staining. Long-term potentiation (LTP) was used to detect the synaptic plasticity of the rats' hippocampi, and the expression of ERS-related proteins and synapse-related proteins was detected by Western blotting. A KD effectively reduced the frequency of SRSs in rats with TLE and improved their learning and memory impairment. Further investigations found that a KD inhibited the up-regulation of glucose-regulated protein 78, phospho-protein kinase-like ER kinase, phosphorylated α subunit of eukaryotic initiation factor 2, activating transcription factor 4 and C/EBP homologous protein expression in the hippocampi of rats with TLE and protected the ultrastructure of the neuronal ER, suggesting that a KD suppressed excessive ERS induced by epilepsy. Concurrently, we also found that a KD not only improved the synaptic ultrastructure and increased the density of dendritic spines in rats with TLE but also reversed the epilepsy-induced LTP deficit to some extent. More importantly, the expression of postsynaptic density protein 95, synaptotagmin-1 and synaptosomal-associated protein 25 in the hippocampi of rats with epilepsy was significantly increased after KD intervention. The study findings indicate that a KD improves learning and memory impairment in rats with epilepsy, possibly by regulating ERS and synaptic plasticity. [ABSTRACT FROM AUTHOR]

Motor proteins, encoded by Kinesin superfamily (KIF) genes, are critical for brain development and plasticity. Increasing studies reported KIF's roles in neurodevelopmental disorders. Here, a 6 years and 3 months‐old Chinese boy with markedly symptomatic epilepsy, intellectual disability, brain atrophy, and psychomotor retardation was investigated. His parents and younger sister were phenotypically normal and had no disease‐related family history. Whole exome sequencing identified a novel heterozygous in‐frame deletion (c.265_267delTCA) in exon 3 of the KIF5C in the proband, resulting in the removal of evolutionarily highly conserved p.Ser90, located in its ATP‐binding domain. Sanger sequencing excluded the proband's parents and family members from harboring this variant. The activity of ATP hydrolysis in vitro was significantly reduced as predicted. Immunofluorescence studies showed wild‐type KIF5C was widely distributed throughout the cytoplasm, while mutant KIF5C was colocalized with microtubules. The live‐cell imaging of the cargo‐trafficking assay revealed that mutant KIF5C lost the peroxisome‐transporting ability. Drosophila models also confirmed p.Ser90del's essential role in nervous system development. This study emphasized the importance of the KIF5C gene in intracellular cargo‐transport as well as germline variants that lead to neurodevelopmental disorders and might enable clinicians for timely and accurate diagnosis and disease management in the future. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) is a common form of refractory epilepsy in adulthood. The metabolic profile of epileptogenesis is still poorly investigated. Elucidation of such a metabolic profile using animal models of epilepsy could help identify new metabolites and pathways involved in the mechanisms of epileptogenesis process. In this study, we evaluated the metabolic profile during the epileptogenesis periods. Using a pilocarpine model of epilepsy, we analyzed the global metabolic profile of hippocampal extracts by untargeted metabolomics based on ultra‐performance liquid chromatography–high‐resolution mass spectrometry, at three time points (3 h, 1 week, and 2 weeks) after status epilepticus (SE) induction. We demonstrated that epileptogenesis periods presented different hippocampal metabolic profiles, including alterations of metabolic pathways of amino acids and lipid metabolism. Six putative metabolites (tryptophan, N‐acetylornithine, N‐acetyl‐L‐aspartate, glutamine, adenosine, and cholesterol) showed significant different levels during epileptogenesis compared to their respective controls. These putative metabolites could be associated with the imbalance of neurotransmitters, mitochondrial dysfunction, and cell loss observed during both epileptogenesis and epilepsy. With these findings, we provided an overview of hippocampal metabolic profiles during different stages of epileptogenesis that could help investigate pathways and respective metabolites as predictive tools in epilepsy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between left epileptiform activity and language laterality indices (LI) in patients with right mesial temporal sclerosis (MTS). Methods: Twenty‐two patients with right MTS and 22 healthy subjects underwent fMRI scanning while performing a language task. LI was calculated in multiple regions of interest (ROI). Data on the presence of left epileptiform abnormalities were obtained during prolonged video‐EEG monitoring. Results: After correction for multiple comparisons, LI was reduced in the middle temporal gyrus in the left interictal epileptiform discharges (IED+) group, compared with the left IED− group (p < 0.05). Significance: Using a responsive reading naming fMRI paradigm, right MTS patients who presented left temporal interictal epileptiform abnormalities on video‐EEG showed decreased LI in the middle temporal gyrus, indicating decreased left middle temporal gyrus activation, increased right middle temporal gyrus activation or a combination of both, demonstrative of language network reorganization, specially in the MTG, in this patient population. Plain Language Summary: This research studied 22 patients with right mesial temporal sclerosis (a specific type of epilepsy) comparing them to 22 healthy individuals. Participants were asked to perform a language task while undergoing a special brain imaging technique (fMRI). The findings showed that patients with epilepsy displayed a change in the area of the brain typically responsible for language processing. This suggests that their brains may have adapted due to their condition, altering the way language is processed. [ABSTRACT FROM AUTHOR]

Abstract Background Temporal lobe epilepsy (TLE), a prevalent neurological disorder, is associated with hippocampal oxidative stress and inflammation. A recent study reveals that the long noncoding RNA ILF3 divergent transcript (ILF3‐AS1) level is elevated in the hippocampus of TLE patients; however, the functional roles of ILF3‐AS1 in TLE and underlying mechanisms deserve further investigation. Hence, this study aimed to elucidate whether ILF3‐AS1 is involved in the pathogenesis of TLE by regulating oxidative stress and inflammation and to explore its underlying mechanism in vitro. Methods Human hippocampal neurons were subjected to a magnesium‐free (Mg2+‐free) solution to establish an in vitro model of TLE. The potential binding sites between ILF3‐AS1 and miRNA were predicted by TargetScan/Starbase and confirmed by dual luciferase reporter assay. Cell viability and damage were assessed by cell counting kit‐8 and lactate dehydrogenase assay kits, respectively. Levels of reactive oxygen species, malondialdehyde, and superoxide dismutase were determined by commercial kits. Levels of Interleukin‐6 (IL‐6), IL‐1β, and tumor necrosis factor‐alpha were quantified by enzyme‐linked immunosorbent assay. The expressions of gene and protein were determined by quantitative real‐time polymerase chain reaction and Western blot analysis. Results In Mg2+‐free‐treated hippocampal neurons, both ILF3‐AS1 and HMGB1 were highly up‐regulated, whereas miR‐504‐3p was down‐regulated. ILF3‐AS1 knockdown ameliorated Mg2+‐free‐induced cellular damage, oxidative stress, and inflammatory response. Bioinformatics analysis revealed that miR‐504‐3p was a target of ILF3‐AS1 and was negatively regulated by ILF3‐AS1. MiR‐504‐3p inhibitor blocked the protection of ILF3‐AS1 knockdown against Mg2+‐free‐induced neuronal injury. Further analysis presented that ILF3‐AS1 regulated HMGB1 expression by sponging miR‐504‐3p. Moreover, HMGB1 overexpression reversed the protective functions of ILF3‐AS1 knockdown. Conclusion Our findings indicate that ILF3‐AS1 contributes to Mg2+‐free‐induced hippocampal neuron injuries, oxidative stress, and inflammation by targeting the miR‐504‐3p/HMGB1 axis. These results provide a novel mechanistic understanding of ILF3‐AS1 in TLE and suggest potential therapeutic targets for the treatment of epilepsy.

Abstract Introduction Emerging evidence illustrates that temporal lobe epilepsy (TLE) involves network disruptions represented by hyperexcitability and other seizure‐related neural plasticity. However, these associations are not well‐characterized. Our study characterizes the whole brain white matter connectome abnormalities in TLE patients compared to healthy controls (HCs) from the prospective Epilepsy Connectome Project study. Furthermore, we assessed whether aberrant white matter connections are differentially related to cognitive impairment and a history of focal‐to‐bilateral tonic–clonic (FBTC) seizures. Methods Multi‐shell connectome MRI data were preprocessed using the DESIGNER guidelines. The IIT Destrieux gray matter atlas was used to derive the 162 × 162 structural connectivity matrices (SCMs) using MRTrix3. ComBat data harmonization was applied to harmonize the SCMs from pre‐ and post‐scanner upgrade acquisitions. Threshold‐free network‐based statistics were used for statistical analysis of the harmonized SCMs. Cognitive impairment status and FBTC seizure status were then correlated with these findings. Results We employed connectome measurements from 142 subjects, including 92 patients with TLE (36 males, mean age = 40.1 ± 11.7 years) and 50 HCs (25 males, mean age = 32.6 ± 10.2 years). Our analysis revealed overall significant decreases in cross‐sectional area (CSA) of the white matter tract in TLE group compared to controls, indicating decreased white matter tract integrity and connectivity abnormalities in addition to apparent differences in graph theoretic measures of connectivity and network‐based statistics. Focal and generalized cognitive impaired TLE patients showcased higher trend‐level abnormalities in the white matter connectome via decreased CSA than those with no cognitive impairment. Patients with a positive FBTC seizure history also showed trend‐level findings of association via decreased CSA. Conclusions Widespread global aberrant white matter connectome changes were observed in TLE patients and characterized by seizure history and cognitive impairment, laying a foundation for future studies to expand on and validate the novel biomarkers and further elucidate TLE's impact on brain plasticity.

BackgroundPrevious structural neuroimaging studies linked cerebellar deficits to temporal lobe epilepsy (TLE). The functions of various cerebellar regions are increasingly being valued, and their changes in TLE patients warrant further in-depth investigation. In this study, we used the Spatially Unbiased Infratentorial (SUIT) toolbox with a new template to evaluate the cerebellar structural abnormalities in patients with TLE, and further explored the relationship between the changes of different cerebellar regions and cognition.MethodsThirty-two patients with TLE were compared with 39 healthy controls (HC) matched according to age, gender, handedness, and education level. All participants underwent a high-resolution T1-weighted MRI scan on a 3.0 Tesla scanner. We used a voxel-based morphometry (VBM) approach utilizing the SUIT toolbox to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with TLE.ResultsCompared with HC, TLE patients showed a significant reduction in the volume of gray matter in the Left lobule VI and white matter in the Right Crus II. In the TLE patient group, we conducted partial correlation analysis between the volumes of different cerebellar regions and cognitive rating scale scores, such as MMSE and MoCA. The volume of the Left lobule VI (GM) exhibited a positive correlation with the MMSE score, but no significant correlation was found with the MoCA score. On the other hand, there was no significant correlation observed between the volume of the Right Crus II (WM) and the two cognitive scale scores mentioned above. Furthermore, it was observed that the MMSE was more effective than the MoCA in identifying epilepsy patients with cognitive impairment.ConclusionThis study supported previous research indicating that temporal lobe epilepsy (TLE) is linked to structural changes in the cerebellum, specifically affecting the volume of both gray and white matter. These findings offer valuable insights into the neurobiology of TLE and hold potential to inform the development of enhanced diagnostic methods and more effective treatment approaches.

Temporal lobe epilepsy (TLE) stands as the predominant adult focal epilepsy syndrome, characterized by dysfunctional intrinsic brain dynamics. However, the precise mechanisms underlying seizures in these patients remain elusive. Our study encompassed 116 TLE patients compared with 51 healthy controls. Employing microstate analysis, we assessed brain dynamic disparities between TLE patients and healthy controls, as well as between drug-resistant epilepsy (DRE) and drug-sensitive epilepsy (DSE) patients. We constructed dynamic functional connectivity networks based on microstates and quantified their spatial and temporal variability. Utilizing these brain network features, we developed machine learning models to discriminate between TLE patients and healthy controls, and between DRE and DSE patients. Temporal dynamics in TLE patients exhibited significant acceleration compared to healthy controls, along with heightened synchronization and instability in brain networks. Moreover, DRE patients displayed notably lower spatial variability in certain parts of microstate B, E and F dynamic functional connectivity networks, while temporal variability in certain parts of microstate E and G dynamic functional connectivity networks was markedly higher in DRE patients compared to DSE patients. The machine learning model based on these spatiotemporal metrics effectively differentiated TLE patients from healthy controls and discerned DRE from DSE patients. The accelerated microstate dynamics and disrupted microstate sequences observed in TLE patients mirror highly unstable intrinsic brain dynamics, potentially underlying abnormal discharges. Additionally, the presence of highly synchronized and unstable activities in brain networks of DRE patients signifies the establishment of stable epileptogenic networks, contributing to the poor responsiveness to antiseizure medications. The model based on spatiotemporal metrics demonstrated robust predictive performance, accurately distinguishing both TLE patients from healthy controls and DRE patients from DSE patients.

IntroductionNeuropsychological assessment forms an integral part of the presurgical evaluation for patients with medically refractory focal epilepsy. Our understanding of cognitive impairment in epilepsy is based on seminal lesional studies that have demonstrated important structure-function relationships within the brain. However, a growing body of literature demonstrating heterogeneity in the cognitive profiles of patients with focal epilepsy (e.g., temporal lobe epilepsy; TLE) has led researchers to speculate that cognition may be impacted by regions outside the seizure onset zone, such as those involved in the interictal or “irritative” network.MethodsNeuropsychological data from 48 patients who underwent stereoelectroencephalography (SEEG) monitoring between 2012 and 2023 were reviewed. Patients were categorized based on the site of seizure onset, as well as their irritative network, to determine the impact of wider network activity on cognition. Neuropsychological data were compared with normative standards (i.e., z = 0), and between groups.ResultsThere were very few distinguishing cognitive features between patients when categorized based purely on the seizure onset zone (i.e., frontal lobe vs. temporal lobe epilepsy). In contrast, patients with localized irritative networks (i.e., frontal or temporal interictal epileptiform discharges [IEDs]) demonstrated more circumscribed profiles of impairment compared with those demonstrating wider irritative networks (i.e., frontotemporal IEDs). Furthermore, the directionality of propagation within the irritative network was found to influence the manifestations of cognitive impairment.DiscussionThe findings suggest that neuropsychological assessment is sensitive to network activity beyond the site of seizure onset. As such, an overly focal interpretation may not accurately reflect the distribution of the underlying pathology. This has important implications for presurgical work-up in epilepsy, as well as subsequent surgical outcomes.

Asynchronous distributed multielectrode stimulation (ADMES) is a novel approach to deep brain stimulation for medication resistant temporal lobe epilepsy that has shown promise in rodent and in vitro seizure models. To further evaluate its effects on a pre-clinical model, we characterized the effect of unilateral ADMES in an NHP model of temporal lobe seizures induced by intra-hippocampal injection of penicillin (PCN). Four non-human primates were used for this study in two contemporaneous cohorts. One cohort (n = 3 hemispheres) was implanted with the Medtronic RC + S stimulation (GIN cohort) and recording system connected to two 4-contact ring electrodes to evaluate three unilateral stimulation patterns: 7 Hz Ring ADMES, 20 Hz Dual Ring, and 125 Hz Dual Ring (analog of clinical stimulation). In an additional cohort (EPC cohort, n = 2), two 12-contact segmented electrodes were implanted in the right hippocampus and connected to an externalized recording and stimulation system to allow more flexibility in the stimulation pattern. In this second cohort, 4 variations of stimulation were evaluated (7 Hz Full ADMES, 7 Hz Ring ADMES, 31 Hz Wide Ring, and 31 Hz Dual Ring). In the GIN cohort, we found an increase in seizure frequency and time spent in seizure during the 7 Hz Ring ADMES stimulation compared to the respective post-stimulation. A similar post-stimulation effect was found in the EPC cohort. We also found an increase in seizure frequency during the 7Hz full ADMES compared to the respective post-stimulation. However, we did not find a difference between pre-stimulation and stimulation conditions suggesting a possible post stimulation effect of the 7Hz hippocampal stimulation. In conclusion, in the NHP PCN model of temporal lobe seizures, acute asynchronous hippocampal stimulation was not therapeutic, however, our findings related to the post-stimulation effect can support future studies using hippocampal stimulation for the treatment of temporal lobe epilepsy.

ObjectivePatients with temporal lobe epilepsy (TLE) often exhibit neurocognitive disorders; however, we still know very little about the pathogenesis of cognitive impairment in patients with TLE. Therefore, our aim is to detect changes in the structural connectivity networks (SCN) of patients with TLE.MethodsThirty-five patients with TLE were compared with 47 normal controls (NC) matched according to age, gender, handedness, and education level. All subjects underwent thin-slice T1WI scanning of the brain using a 3.0 T MRI. Then, a large-scale structural covariance network was constructed based on the gray matter volume extracted from the structural MRI. Graph theory was then used to determine the topological changes in the structural covariance network of TLE patients.ResultsAlthough small-world networks were retained, the structural covariance network of TLE patients exhibited topological irregularities in regular architecture as evidenced by an increase in the small world properties (p

BackgroundEpilepsy-associated psychoses are poorly understood, and management is focused on treating epilepsy. Chronic, interictal psychosis that persists despite seizure control is typically treated with antipsychotics. Whether resection of a mesial temporal lobe lesion may improve interictal psychotic symptoms that persist despite seizure control remains unknown.ObservationsIn a 52-year-old man with well-controlled epilepsy and persistent comorbid psychosis, brain magnetic resonance imaging (MRI) revealed an infiltrative, intraaxial, T2 fluid-attenuated inversion recovery intense mass of the left amygdala. The patient received an amygdalectomy for oncological diagnosis and surgical treatment of a presumed low-grade glioma. Pathology was ganglioglioma, World Health Organization grade I. Postoperatively, the patient reported immediate resolution of auditory hallucinations. Patient has remained seizure-free on 2 antiepileptic drugs and no antipsychotic pharmacotherapy and reported lasting improvement in his psychotic symptoms.LessonsThis report discusses improvement of psychosis symptoms after resection of an amygdalar glioma, independent of seizure outcome. This case supports a role of the amygdala in psychopathology and suggests that low-grade gliomas of the limbic system may represent, at minimum, partially reversible etiology of psychotic symptoms.

Objective To investigate the role of transient receptor potential melatonin 2 （TRPM2） ion channels in microglia and astrocytes in temporal lobe epilepsy （TLE） -associated neuroinflammation. Methods Rats were randomly divided into the control group and epilepsy group. Seizure models were induced by lithium chloride-pilocarpine in the epilepsy group， and those in the control group were injected with the same dose of saline. The TLE rats were randomly divided into 7 subgroups according to the observation time after model establishment： acute phase （3 h group， 6 h group， 1 d group， 2 d group）， latent phase （14 d group） and chronic phase （30 d group， 90 d group） subgroups （n = 5）. The expression level of TRPM2 in the hippocampus of TLE rats at different stages were detected， and the cellular localization of TRPM2 in the brain of TLE rats was investigated. BV2 and C8 cell lines were induced by hydrogen peroxide （H2O2）. The levels of IL1-β， IL-6 and TNF-α released by BV2 and C8 cells were observed by ELISA. The levels of TRPM2， poly （ADP-ribose） polymerase 1 （PARP-1）， glycogen synthase kinase-3β （GSK-3β） and phosphorylated nuclear factor-κb p65 （p-NF-κb p65） were measured in H2O2-induced BV2 and C8 cells. Meantime， the activity of Calcineurin （CaN） in H2O2-induced BV2 was observed. Results The TRPM2 expression in 2d epileptic rat hippocampus was increased （P < 0.05）. The expression of TRPM2 and the release of inflammatory cytokines were increased in H2O2 induced-BV2 and C8 cells （both P < 0.05）. H2O2 could up-regulate the expression of PARP-1 and p-NF-κB p65 and enhance the activity of CaN in BV2 cells （all P < 0.05）. Conclusions Oxidative stress can up-regulate the expression levels of TRPM2 and pro-inflammatory cytokines in microglia and astrocytes. Oxidative stress caused by recurrent epilepsy may mediate the occurrence of TLE-associated neuroinflammation through the TRPM2/ CaN/p-NF-κB p65 pathway in microglia.

Abstract Introduction This research aimed to see how well magnetic resonance spectroscopy (MRS) could identify the lateralization side in individuals with temporal lobe epilepsy (TLE) compared to electroencephalography (EEG) and magnetic resonance imaging (MRI) results. Methods Twenty‐three individuals were included in this research and diagnosed with TLE (both clinically and by EEG). Clinical exams, interictal EEG, and MRI were performed on all patients. In addition, the individuals were also subjected to proton MRS. Results The age range of 23 participants was 20–55 years (mean = 34.6 ± 8.5); 10 were male (44%), and 13 were female (56%). The right temporal lobe MRI showed a sensitivity and specificity of 60% and 55% for detecting mesial temporal lobe sclerosis (MTS) foci, respectively (positive predictive value (PPV) of 27% and negative predictive value (NPV) of 83%). MRI showed 83% sensitivity and 35% specificity for MTS foci in the left temporal lobe (PPV of 31% and NPV of 86%). MRS showed 61% sensitivity and 100% specificity in the right temporal lobe (PPV 100%) and 80% sensitivity and specificity in the left temporal lobe (PPV 100%) for identifying MTS foci. Overall, MRS (both left and right) results matched EEG findings. Conclusion MRS is a potential noninvasive neuroradiology technique for assessing epilepsy patients because it is more sensitive than structural MRI in identifying MTS. The results of the study overall appears to be of interest but still need further support from future studies with larger sample sizes.

Abstract Objective We aimed to investigate differences in episodic memory networks between patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis and healthy controls, especially with regards to the parietal memory network (PMN), as well as their relation to neuropsychological memory performance after mesial temporal resection. Methods 28 healthy subjects as well as 21 patients with TLE (12 left, 9 right) were investigated using a spatial memory fMRI paradigm, which has been shown to activate the PMN. Regions of interest (ROI) were defined based on the results of the second‐level analyses and activations within the predefined ROIs were compared across groups and correlated with postoperative verbal and nonverbal memory scores. Results Healthy subjects showed activations within regions belonging to the dorsal visual stream and the PMN as well as the bilateral parahippocampal place area, the bilateral frontal eye field, and the bilateral middle frontal gyrus. Comparison between groups revealed that TLE patients activated significantly less in the left middle occipital gyrus and the right precuneus. The activation pattern in left TLE patients showed further reductions, mainly in areas belonging to the dorsal visual stream and the PMN within the left hemisphere. Activations within the left superior parietal lobulus, bilateral inferior parietal lobulus, bilateral middle temporal gyrus, left precuneus, left frontal eye field, and left middle frontal gyrus correlated significantly with postoperative verbal memory scores, and activations within the left superior parietal lobulus, left inferior parietal lobulus, left middle temporal gyrus, and left precuneus correlated significantly with higher performance in postoperative nonverbal memory scores. Significance The PMN is involved in episodic memory encoding. Higher activations in areas belonging to the PMN and the dorsal visual stream, especially within the left hemisphere, before amygdalohippocampectomy may result in higher postoperative memory scores. Plain language summary This study aims to investigate the effects of epilepsy due to hippocampal sclerosis, i.e. scarring in the temporal lobe, on memory networks in the brain. We discovered that especially patients with left‐sided hippocampal sclerosis show reduced brain activations in visual areas and memory networks within the left hemisphere of the brain during orientation in space. Importantly, higher activations within these areas may result in better memory after epilepsy surgery.

Abstract Biallelic CNTNAP2 variants have been associated with Pitt‐Hopkins‐like syndrome. We describe six novel and one previously reported patients from six independent families and review the literature including 64 patients carrying biallelic CNTNAP2 variants. Initial reports highlighted intractable focal seizures and the failure of epilepsy surgery in children, but subsequent reports did not expand on this aspect. In all our patients (n = 7), brain MRI showed bilateral temporal gray/white matter blurring with white matter high signal intensity, more obvious on the T2‐FLAIR sequences, consistent with bilateral temporal lobe dysplasia. All patients had focal seizures with temporal lobe onset and semiology, which were recorded on EEG in five, showing bilateral independent temporal onset in four. Epilepsy was responsive to anti‐seizure medications in two patients (2/7, 28.5%), and pharmaco‐resistant in five (5/7, 71.5%). Splice‐site variants identified in five patients (5/7, 71.5%) were the most common mutational finding. Our observation expands the phenotypic and genetic spectrum of biallelic CNTNAP2 alterations focusing on the neuroimaging features and provides evidence for an elective bilateral anatomoelectroclinical involvement of the temporal lobes in the associated epilepsy, with relevant implications on clinical management.

Abstract Background This study was performed to test the hypothesis that systemic leukocyte gene expression has prognostic value differentiating low from high seizure frequency refractory temporal lobe epilepsy (TLE). Methods A consecutive series of patients with refractory temporal lobe epilepsy was studied. Based on a median baseline seizure frequency of 2.0 seizures per month, low versus high seizure frequency was defined as ≤ 2 seizures/month and > 2 seizures/month, respectively. Systemic leukocyte gene expression was analyzed for prognostic value for TLE seizure frequency. All differentially expressed genes were analyzed, with Ingenuity® Pathway Analysis (IPA®) and Reactome, to identify leukocyte gene expression and biological pathways with prognostic value for seizure frequency. Results There were ten males and six females with a mean age of 39.4 years (range: 16 to 62 years, standard error of mean: 3.6 years). There were five patients in the high and eleven patients in the low seizure frequency cohorts, respectively. Based on a threshold of twofold change (p 2.0, FDR

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory, resistant to antiepileptic drugs, and has a high recurrence rate. The pathogenesis of temporal lobe epilepsy is complex and is not fully understood. Intracellular calcium dynamics have been implicated in temporal lobe epilepsy. However, the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown, and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice. In this study, we used a multi-channel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process. We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes. In particular, cortical spreading depression, which has recently been frequently used to represent the continuously and substantially increased calcium signals, was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from grade II to grade V. However, vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures. Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to grade I episodes. In addition, the latency of cortical spreading depression was prolonged, and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced. Intriguingly, it was possible to rescue the altered intracellular calcium dynamics. Via simultaneous analysis of calcium signals and epileptic behaviors, we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced, and that the end-point behaviors of temporal lobe epilepsy were improved. Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades. Furthermore, the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy, thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

This article explores the role of the immune system in the development of epilepsy and spontaneous seizures. It emphasizes the need for a better understanding of the underlying pathological processes in order to identify more effective targeted therapies. The article discusses various factors that may contribute to epileptogenesis, such as complement C3, neuroinflammation, and early-life environmental insults. It also examines the conditions of new onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) and their association with immune-mediated inflammatory processes. The authors stress the importance of studying neuroinflammation in the context of epilepsy development and call for collaboration among experts in different fields to improve patient outcomes. The article acknowledges funding sources and expresses gratitude to the authors who contributed to the research topic. [Extracted from the article]

Canonical Wnt activator Chir99021 prevents epileptogenesis in the intrahippocampal kainate mouse model of temporal lobe epilepsy Mardones MD Rostam KD Nickerson MC Gupta K. Experimental Neurology. 2024 Mar 21;376:114767. The Wnt signaling pathway mediates the development of dentate granule cell neurons in the hippocampus. These neurons are central to the development of temporal lobe epilepsy and undergo structural and physiological remodeling during epileptogenesis, which results in the formation of epileptic circuits. The pathways responsible for granule cell remodeling during epileptogenesis have yet to be well defined, and represent therapeutic targets for the prevention of epilepsy. The current study explores Wnt signaling during epileptogenesis and for the first time describes the effect of Wnt activation using Wnt activator Chir99021 as a novel anti-epileptogenic therapeutic approach. Focal mesial temporal lobe epilepsy was induced by intrahippocampal kainate (IHK) injection in wild-type and POMC-eGFP transgenic mice. Wnt activator Chir99021 was administered daily, beginning 3 h after seizure induction, and continued up to 21-days. Immature granule cell morphology was quantified in the ipsilateral epileptogenic zone and the contralateral peri-ictal zone 14 days after IHK, targeting the end of the latent period. Bilateral hippocampal electrocorticographic recordings were performed for 28-days, 7-days beyond treatment cessation. Hippocampal behavioral tests were performed after the completion of Chir99021 treatment. Consistent with previous studies, IHK resulted in the development of epilepsy after a 14 day latent period in this well-described mouse model. Activation of the canonical Wnt pathway with Chir99021 significantly reduced bilateral hippocampal seizure number and duration. Critically, this effect was retained after treatment cessation, suggesting a durable antiepileptogenic change in epileptic circuitry. Morphological analyses demonstrated that Wnt activation prevented pathological remodeling of the primary dendrite in both the epileptogenic zone and peri-ictal zone, changes in which may serve as a biomarker of epileptogenesis and anti-epileptogenic treatment response in pre-clinical studies. These findings were associated with improved object location memory with Chir99021 treatment after IHK. This study provides novel evidence that canonical Wnt activation prevents epileptogenesis in the IHK mouse model of mesial temporal lobe epilepsy, preventing pathological remodeling of dentate granule cells. Wnt signaling may therefore play a key role in mesial temporal lobe epileptogenesis, and Wnt modulation may represent a novel therapeutic strategy in the prevention of epilepsy. [ABSTRACT FROM AUTHOR]

Impact of White Matter Networks on Risk for Memory Decline Following Resection Versus Ablation in Temporal Lobe Epilepsy Kaestner E, Stasenko A, Schadler A, Roth R, Hewitt K, Reyes A, Qiu D, Bonilha L, Voets N, Hu R, Willie J, Pedersen N, Shih J, Ben-Haim S, Gross R, Drane D, McDonald C R. J Neurol Neurosurg Psychiatry. 2024 Jan;11: jnnp-2023-332682. doi: 10.1136/jnnp-2023-332682. Online ahead of print. Background: With expanding neurosurgical options in epilepsy, it is important to characterize each option's risk for postoperative cognitive decline. Here, we characterize how patients' preoperative white matter (WM) networks relate to postoperative memory changes following different epilepsy surgeries. Methods: Eighty-nine patients with temporal lobe epilepsy with T1-weighted and diffusion-weighted imaging as well as preoperative and postoperative verbal memory scores (prose recall) underwent either anterior temporal lobectomy (ATL; n = 38) or stereotactic laser amygdalohippocampotomy (SLAH; n = 51). We computed laterality indices (ie, asymmetry) for volume of the hippocampus and fractional anisotropy (FA) of 2 deep WM tracts (uncinate fasciculus [UF]) and inferior longitudinal fasciculus [ILF]). Results: Preoperatively, left-lateralized FA of the ILF was associated with higher prose recall (P <.01). This pattern was not observed for the UF or hippocampus (P s > 0.05). Postoperatively, right-lateralized FA of the UF was associated with less decline following left ATL (P <.05) but not left SLAH (P >.05), while right-lateralized hippocampal asymmetry was associated with less decline following both left ATL and SLAH (P s < 0.05). After accounting for preoperative memory score, age of onset, and hippocampal asymmetry, the association between UF and memory decline in left ATL remained significant (P <.01). Conclusions: Asymmetry of the hippocampus is an important predictor of risk for memory decline following both surgeries. However, asymmetry of UF integrity, which is only severed during ATL, is an important predictor of memory decline after ATL only. As surgical procedures and pre-surgical mapping evolve, understanding the role of frontal-temporal WM in memory networks could help to guide more targeted surgical approaches to mitigate cognitive decline. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Pharmacology titled "Recent advances in the treatment of epilepsy." It discusses the complexities of epilepsy and the different treatment options available. The editorial highlights the use of anti-seizure medications as the first line of treatment but acknowledges that some patients are resistant to these medications. It explores new pharmacological and non-pharmacological approaches, such as specific drugs, neurostimulation techniques, and the ketogenic diet. The editorial also mentions the potential role of the gut microbiota and natural compounds in epilepsy treatment. It provides valuable insights for clinicians and researchers in the field of neuroscience. The article titled "Nutrients" published in Frontiers in Pharmacology emphasizes the importance of nutrients in maintaining good health. It discusses the role of various nutrients in supporting bodily functions and preventing diseases. The article provides a comprehensive overview of different types of nutrients, their sources, and their impact on specific health conditions. [Extracted from the article]

Seizure Progression Is Slowed by Enhancing Neurosteroid Availability in the Brain of Epileptic Rats Gol M, Costa AM, Biagini G, Lucchi C. Epilepsia. 2024;65(3):e41-e46. doi:10.1111/epi.17887. PMID: 38243753 Trilostane is a 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase inhibitor able to produce a manyfold increase in brain levels of various neurosteroids, including allopregnanolone. We previously found that treatment with trilostane can slow down epileptogenesis in the kainic acid (KA) model of temporal lobe epilepsy. It is unknown whether trilostane may have a similar effect on the progression of epilepsy severity, as observed in KA-treated rats. Consequently, we investigated the effects of trilostane (50 mg/kg/day, 1 week) in epileptic rats, given 64 days after KA administration. Seizures were monitored by video-electrocorticographic recordings before and during the treatment with trilostane or vehicle (sesame oil), and neurosteroid levels were measured in serum and cerebral tissue using liquid chromatography-electrospray tandem mass spectrometry after treatment. Pregnenolone sulfate, pregnenolone, progesterone, 5α-dihydroprogesterone, and allopregnanolone peripheral levels were massively increased by trilostane. With the only exception of hippocampal pregnenolone sulfate, the other neurosteroids augmented in both the neocortex and hippocampus. Only pregnanolone levels were not upregulated by trilostane. As expected, a significant increase in the seizure occurrence was observed in rats receiving the vehicle, but not in the trilostane group. This suggests that the increased availability of neurosteroids produced a disease-modifying effect in the brain of epileptic rats. [ABSTRACT FROM AUTHOR]

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue Sanders MW, Van der Wolf I, Jansen FE, Aronica E, Helmstaedter C, Racz A, Surges R, Grote A, Becker AJ, Rheims S, Catenoix H, Duncan JS, De Tisi J, Jacques TS, Cross JH, Kalviainen R, Rauramaa T, Chassoux F, Devaux BC, Di Gennaro G, Esposito V, Bodi I, Honavar M, Bien CG, Cloppenborg T, Coras R, Hamer HM, Marusic P, Kalina A, Pieper T, Kudernatsch M, Hartlieb TS, Von Oertzen TJ, Aichholzer M, Dorfmuller G, Chipaux M, Noachtar S, Kaufmann E, Schulze-Bonhage A, Scheiwe CF, Özkara C, Grunwald T, Koenig K, Guerrini R, Barba C, Buccoliero AM, Giordano F, Rosenow F, Menzler K, Garbelli R, Deleo F, Krsek P, Straka B, Arzimanoglou AA, Toulouse J, Van Paesschen W, Theys T, Pimentel J, Loução De Amorim IM, Specchio N, De Palma L, Feucht M, Scholl T, Roessler K, Toledano Delgado R, Gil-Nagel A, Raicevic S, Ristic AJ, Schijns O, Beckervordersandforth J, San Antonio-Arce V, Rumia J, Blumcke I, Braun KP; as the European Epilepsy Brain Bank Consortium (EEBB). Neurology. 2024;102(4): e208007. doi:10.1212/WNL.0000000000208007. PMID: 38290094 Background and Objectives: Patients with presumed nonlesional focal epilepsy—based on either MRI or histopathologic findings—have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. Methods: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. Results: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings—versus nonspecific reactive gliosis—(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. Discussion: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways. [ABSTRACT FROM AUTHOR]

This scientific commentary discusses the importance of investigating network reorganization after epilepsy surgery. The commentary highlights that focal epilepsy is a network disorder with widespread functional and anatomical alterations throughout the brain. However, there are challenges in studying the effects of surgery, such as acquiring pre- and post-surgical scans and overcoming technical difficulties. The study mentioned in the commentary used diffusion MRI and dimensionality reduction methodologies to examine the global effects of anterior temporal lobectomy surgery in patients with temporal lobe epilepsy. The results showed changes in connectivity patterns before and after surgery, suggesting reorganization and compensation in the brain. Further research is needed to understand the effects of different resections, individual patient phenotypes, and outcomes. [Extracted from the article]

Background/Objectives: In this study, a medical decision support system is presented to assist physicians in epileptic focus detection by correlating MRI and EEG data of temporal lobe epilepsy patients. Methods: By exploiting the asymmetry in the hippocampus in MRI images and using voxel-based morphometry analysis, gray matter reduction in the temporal and limbic lobes is detected, and epileptic focus prediction is realized. In addition, an epileptic focus is also determined by calculating the asymmetry score from EEG channels. Finally, epileptic focus detection was performed by associating MRI and EEG data with a decision tree. Results: The results obtained from the proposed algorithm provide 100% overlap with the physician’s finding on the EEG data. Conclusions: MRI and EEG correlation in epileptic focus detection was improved compared with physicians. The proposed algorithm can be used as a medical decision support system for epilepsy diagnosis, treatment, and surgery planning.