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Epilepsy, a neurological disorder characterized by excessive neuronal activity and synchronized electrical discharges, ranks among the most prevalent global neurological conditions. Despite common use, antiepileptic drugs often result in adverse effects and lack effectiveness in controlling seizures in temporal lobe epilepsy (TLE) patients. Recent research explored the potential of occidentalin-1202, a peptide inspired by Polybia occidentalis venom, in safeguarding Wistar rats from chemically induced seizures. The present study evaluated the new analog from occidentalin-1202 named NOR-1202 using acute and chronic pilocarpine-induced models and an acute kainic acid (KA) male mice model. NOR-1202 was administered through the intracerebroventricular (i.c.v.), subcutaneous, or intraperitoneal routes, with stereotaxic procedures for the i.c.v. injection. In the acute pilocarpine-induced model, NOR-1202 (i.c.v.) protected against generalized seizures and mortality but lacked systemic antiepileptic activity. In the KA model, it did not prevent generalized seizures but improved survival. In the chronic TLE model, NOR-1202′s ED50 did not differ significantly from the epileptic or healthy groups regarding time spent in spontaneous recurrent seizures during the five-day treatment. However, the NOR-1202 group exhibited more seizures than the healthy group on the second day of treatment. In summary, NOR-1202 exhibits antiepileptic effects against chemoconvulsant-induced seizures, but no effect was observed when administered systemically. [ABSTRACT FROM AUTHOR]

This research aimed to investigate Information Processing Speed (IPS) and Visual-Working Memory (VWM) abilities among three distinct groups: children diagnosed with Frontal Lobe Epilepsy (FLE), Temporal Lobe Epilepsy (TLE), and children without epilepsy (Non-Epileptic (NE)). A descriptive, causal-comparative design was employed, involving a sample of 45 children (15 FLE, 15 TLE, and 15 NE children), aged 7 to 12 years, selected from patients referred to Razi Psychiatric Hospital in Tabriz, Iran, in 2020. Notably, non-epileptic (NE) cases were not recruited from the mentioned hospital. The Computerized Stroop Test (CST) was used to assess information processing speed, while Corsi's Blocks Test (CBT) evaluated visual-working memory. The Multivariate Analysis of Variance (MANOVA) revealed significant differences in both information processing speed (IPS) (congruent and incongruent conditions) (p < 0.001) and visual-working memory (forward and backward conditions) (p = 0.004) across groups. Post-hoc analyses showed that non-epileptic (NE) children had significantly higher information processing speed (IPS) (both congruent and incongruent) than those with temporal lobe epilepsy (TLE). Additionally, children with temporal lobe epilepsy (TLE) demonstrated significantly higher information processing speed (IPS) (both congruent and incongruent) compared to those with frontal lobe epilepsy (FLE). For visual-working memory (VWM), both frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE) children exhibited markedly lower performance in forward and backward tasks compared to NE children. This study offers insights into the cognitive characteristics of children with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE), highlighting distinct cognitive functions. Slower information processing speed (IPS) is observed in frontal lobe epilepsy (FLE), and impaired information processing speed (IPS) is noted in temporal lobe epilepsy (TLE), coupled with deficits in visual-working memory (VWM) across both epilepsy subcategories. These findings emphasize the need for customized interventions to address specific cognitive challenges in children with different types of epilepsy. [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]

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]

Epilepsy, a neurological disorder characterized by excessive neuronal activity and synchronized electrical discharges, ranks among the most prevalent global neurological conditions. Despite common use, antiepileptic drugs often result in adverse effects and lack effectiveness in controlling seizures in temporal lobe epilepsy (TLE) patients. Recent research explored the potential of occidentalin-1202, a peptide inspired by Polybia occidentalis venom, in safeguarding Wistar rats from chemically induced seizures. The present study evaluated the new analog from occidentalin-1202 named NOR-1202 using acute and chronic pilocarpine-induced models and an acute kainic acid (KA) male mice model. NOR-1202 was administered through the intracerebroventricular (i.c.v.), subcutaneous, or intraperitoneal routes, with stereotaxic procedures for the i.c.v. injection. In the acute pilocarpine-induced model, NOR-1202 (i.c.v.) protected against generalized seizures and mortality but lacked systemic antiepileptic activity. In the KA model, it did not prevent generalized seizures but improved survival. In the chronic TLE model, NOR-1202′s ED50 did not differ significantly from the epileptic or healthy groups regarding time spent in spontaneous recurrent seizures during the five-day treatment. However, the NOR-1202 group exhibited more seizures than the healthy group on the second day of treatment. In summary, NOR-1202 exhibits antiepileptic effects against chemoconvulsant-induced seizures, but no effect was observed when administered systemically.

The intrahippocampal kainic acid (IHKA) mouse model is an extensively used in vivo model to investigate the pathophysiology of mesial temporal lobe epilepsy (mTLE) and to develop novel therapies for drug-resistant epilepsy. It is characterized by profound hippocampal sclerosis and spontaneously occurring seizures with a major role for the injected damaged hippocampus, but little is known about the excitability of specific subregions. The purpose of this study was to electrophysiologically characterize the excitability of hippocampal subregions in the chronic phase of the induced epilepsy in the IHKA mouse model. We recorded field postsynaptic potentials (fPSPs) after electrical stimulation in the CA1 region and in the dentate gyrus (DG) of hippocampal slices of IHKA and healthy mice using a multielectrode array (MEA). In the DG, a significantly steeper fPSP slope was found, reflecting higher synaptic strength. Population spikes were more prevalent with a larger spatial distribution in the IHKA group, reflecting a higher degree of granule cell output. Only minor differences were found in the CA1 region. These results point to increased neuronal excitability in the DG but not in the CA1 region of the hippocampus of IHKA mice. This method, in which the excitability of hippocampal slices from IHKA mice is investigated using a MEA, can now be further explored as a potential new model to screen for new interventions that can restore DG function and potentially lead to novel therapies for mTLE. [ABSTRACT FROM AUTHOR]

Background: Accumulation of reactive oxygen species (ROS) exacerbates neuronal loss during seizure-induced excitotoxicity. Keap1 (Kelch-like ECH-associated protein1)-nuclear factor erythroid 2–related factor 2 (Nrf2) axis is one of the known active antioxidant response mechanisms. Our study focused on finding the factors influencing Keap1-Nrf2 axis regulation in temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) patients. Methods: Based on post-surgical follow-up data, patient samples (n = 26) were categorized into class 1 (completely seizure-free) and class 2 (only focal-aware seizures/auras), as suggested by International League Against Epilepsy (ILAE). For molecular analyses, double immunofluorescence assay and Western blot analysis were employed. Results: A significant decrease in expression of Nrf2 (p < 0.005), HO-1; p < 0.02) and NADPH Quinone oxidoreductase1 (NQO1; p < 0.02) was observed in ILAE class 2. Keap1 (p < 0.02) and histone methyltransferases (HMTs) like SetD7 (SET7/9; SET domain-containing 7 histone lysine methyltransferase) (p < 0.009) and enhancer of zeste homolog 2 (EZH2; p < 0.02) and methylated histones viz., H3K4me1 (p < 0.001), H3K9me3 (p < 0.001), and H3K27me3 (p < 0.001) was upregulated in ILAE class 2. Nrf2-interacting proteins viz., p21 (p < 0.001) and heat shock protein 90 (HSP90; p < 0.03) increased in class 1 compared to class 2 patients. Conclusion: Upregulation of HMTs and methylated histones can limit phase II antioxidant enzyme expression. Also, HSP90 and p21 that interfere with Keap1-Nrf2 interaction could contribute to a marginal increase in HO-1 and NQO1 expression despite histone methylation and Keap1. Based on our findings, we conclude that TLE-HS patients prone to seizure recurrence were found to have dysfunctional antioxidant response, in part, owing to Keap1-Nrf2 axis. [ABSTRACT FROM AUTHOR]

Abstract Global neuropsychological impairments with intellectual disability (ID) seem to play a major role in the occurrence of psychogenic non‐epileptic seizures (PNES) in epilepsy. Conversely, the pathophysiology underlying PNES combined with epilepsy without ID remains elusive. We investigated the neuropsychiatric profile in 26 average intelligent subjects (15 women, mean age: 40.04 ± 13.53 years) with temporal lobe epilepsy (TLE) plus PNES (TLE + PNES), compared with 28 with TLE and 22 with PNES alone, matched for age and sex. All subjects underwent neuropsychiatric assessment, including Beck Depression Inventory‐2 (BDI‐2), State‐Trait Anxiety Inventory (STAI), Dissociative Experiences Scale (DES), Toronto Alexithymia Scale (TAS‐20), Traumatic Experience Checklist (TEC), and cognitive evaluation. TLE + PNES and PNES groups shared a similar psychiatric profile with higher levels of depression (BDI‐2, P

Introduction: Prospective memory (PM) is the ability to remember future intentions, and PM function is closely related to independence in daily life, particularly in patients with temporal lobe epilepsy (TLE). As PM involves various cognitive components of attention, working memory, inhibition and other executive functions, this study investigated how TLE may affect PM components and the underlying neural mechanisms. Methods: Sixty-four subjects were recruited, including 20 refractory TLE patients, 18 well-controlled TLE patients and 26 age-matched healthy controls. A set of neuropsychological tests was administered to assess specific brain functions. An event-related potential (ERP) task was used to further explore how PM and its components would be differentially affected in the two TLE types. Results: Our findings revealed that: (1) refractory TLE patients scored lower than the healthy controls in the digit span, Verbal Fluency Test and Symbol Digit Modalities Test; (2) refractory TLE patients exhibited impaired PM performance and reduced prospective positivity amplitudes over the frontal, central and parietal regions in ERP experiments when compared to the healthy controls; and (3) decreased P3 amplitudes in the nogo trials were observed over the frontal-central sites in refractory but not in well-controlled TLE patients. Discussion: To our knowledge, this is the first ERP study on PM that has specifically identified PM impairment in refractory but not in well-controlled TLE patients. Our finding of double dissociation in PM components suggests that inhibition dysfunction may be the main reason for PM deficit in refractory TLE patients. The present results have clinical implications for neuropsychological rehabilitation in TLE patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of current resistance on therapeutic outcomes, and the mechanism of current conduction treatment in a rat model of temporal lobe epilepsy (TLE). Methods: Rats were randomly divided into four groups: normal control, epileptic group, low-resistance conduction (LRC) and high-resistance conduction (HRC) group. The content of glutamate (Glu) and gamma-amino butyric acid (GABA) in the hippocampus was determined using a neurotransmitter analyzer. mRNA and protein expression of interleukin 1β (IL-1β) /IL-1 receptor 1(IL-1R1) and high mobility group protein B1 (HMGB-1)/toll-like receptor-4 (TLR-4) in hippocampal neurons were tested. Video electroencephalogram monitoring was used to record seizures and EEG discharges. Cognitive function in the rats was tested using the Morris water maze. Results: Glu/GABA ratio in the epileptic control and HRC groups was significant differences from LRC group. The levels of HMGB1/TLR4 and IL-1β/IL-1R1 in the LRC group and normal control group were significantly lower than those in epileptic control group (p < 0.01) and the HRC group. The mRNA levels of HMGB1/TLR4 and IL-1β/IL-1R1 in the LRC group and normal control group were significantly lower than those in epileptic control group. The frequency of total and propagated seizures was lower in the LRC group than in the epileptic control and HRC groups (p < 0.01). The numbers of platform crossings in the LRC group and normal control group were significantly higher than those in the epileptic control and HRC groups in the space exploration experiment. Conclusion: Current resistance affected seizure control and cognitive protection in rats with TLE treated by current conduction. The lower current resistance, the better seizure control and cognitive protection in rats with TLE treated by current conduction. Glu/GABA, IL-1β/IL-1R1, and HMGB1/TLR-4 may participate in the anti-seizure mechanism of current conduction treatment. [ABSTRACT FROM AUTHOR]

Global neuropsychological impairments with intellectual disability (ID) seem to play a major role in the occurrence of psychogenic non‐epileptic seizures (PNES) in epilepsy. Conversely, the pathophysiology underlying PNES combined with epilepsy without ID remains elusive. We investigated the neuropsychiatric profile in 26 average intelligent subjects (15 women, mean age: 40.04 ± 13.53 years) with temporal lobe epilepsy (TLE) plus PNES (TLE + PNES), compared with 28 with TLE and 22 with PNES alone, matched for age and sex. All subjects underwent neuropsychiatric assessment, including Beck Depression Inventory‐2 (BDI‐2), State‐Trait Anxiety Inventory (STAI), Dissociative Experiences Scale (DES), Toronto Alexithymia Scale (TAS‐20), Traumatic Experience Checklist (TEC), and cognitive evaluation. TLE + PNES and PNES groups shared a similar psychiatric profile with higher levels of depression (BDI‐2, P < 0.001), anxiety (STAI‐S, P < 0.001; STAI‐T, P < 0.001), dissociation (DES, P < 0.001), and alexithymia (TAS, P = 0.005) scales than the TLE group. Nonetheless, like individuals with TLE, patients with TLE + PNES had a lower rate of a potentially traumatizing event than PNES. The very low rate of potentially traumatizing event in subjects with TLE + PNES leads us to hypothesize that epilepsy itself may be the psychophysiological distress that contributed to PNES. A psychopathological assessment in subjects with epilepsy is crucial to identify those more likely to develop PNES. [ABSTRACT FROM AUTHOR]

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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 Interictal 18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) is used in the workup for epilepsy surgery when MRI and EEG video monitoring are not conclusive. Timing of FDG‐PET is crucial to avoid the metabolically dynamic (post)ictal state that complicates interpretation, but the exact time window is unclear. We performed a systematic review to provide an evidence‐based recommendation for the minimal time interval between last seizure and FDG‐PET acquisition. We searched PubMed and Embase for articles on the effect of time since last seizure on FDG‐PET outcome. Quality assessment was conducted with the Critical Appraisal Skills Programme Cohort Study Checklist. We identified five studies. Three studies were classified as of low to moderate quality, mainly due to undocumented data or insufficient statistical measurements. Two high‐quality studies included only adults with Temporal Lobe Epilepsy (TLE). The metabolic interictal phase is 24 or 48 hours after the last seizure, depending on seizure type. The recommendation is based on the best available evidence from two small study populations for TLE. If clinically possible, interictal FDG‐PET in adults should be performed at least 24 hours after focal aware seizures and 48 hours after focal impaired awareness and focal to bilateral tonic–clonic seizures.

Objective: The evaluation to determine candidacy and treatment for epilepsy surgery in persons with drug‐resistant epilepsy (DRE) is not uniform. Many non‐invasive and invasive tests are available to ascertain an appropriate treatment strategy. This study examines expert response to clinical vignettes of magnetic resonance imaging (MRI)–positive lesional focal cortical dysplasia in both temporal and extratemporal epilepsy to identify associations in evaluations and treatment choice. Methods: We analyzed annual report data and a supplemental epilepsy practice survey reported in 2020 from 206 adult and 136 pediatric epilepsy center directors in the United States. Non‐invasive and invasive testing and surgical treatment strategies were compiled for the two scenarios. We used chi‐square tests to compare testing utilization between the two scenarios. Multivariable logistic regression modeling was performed to assess associations between variables. Results: The supplemental survey response rate was 100% with 342 responses included in the analyses. Differing testing and treatment approaches were noted between the temporal and extratemporal scenarios such as chronic invasive monitoring selected in 60% of the temporal scenario versus 93% of the extratemporal scenario. Open resection was the most common treatment choice; however, overall treatment choices varied significantly (p <.001). Associations between non‐invasive testing, invasive testing, and treatment choices were present in both scenarios. For example, in the temporal scenario stereo‐electroencephalography (SEEG) was more commonly associated with fluorodeoxyglucose–positron emission tomography (FDG‐PET) (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.06–3.29; p =.033), magnetoencephalography (MEG) (OR 2.90; 95% CI 1.60–5.28; p = <.001), high density (HD) EEG (OR 2.80; 95% CI 1.27–6.24; p =.011), functional MRI (fMRI) (OR 2.17; 95% CI 1.19–4.10; p =.014), and Wada (OR 2.16; 95% CI 1.28–3.66; p =.004). In the extratemporal scenario, choosing SEEG was associated with increased odds of neuromodulation over open resection (OR 3.13; 95% CI 1.24–7.89; p =.016). Significance: In clinical vignettes of temporal and extratemporal lesional DRE, epilepsy center directors displayed varying patterns of non‐invasive testing, invasive testing, and treatment choices. Differences in practice underscore the need for comparative trials for the surgical management of DRE. [ABSTRACT FROM AUTHOR]

Introduction: Pattern separation (PS) is a fundamental aspect of memory creation that defines the ability to transformsimilarmemory representations into distinct ones, so they do not overlap when storing and retrieving them. Experimental evidence in animalmodels and the study of other human pathologies have demonstrated the role of the hippocampus in PS, in particular of the dentate gyrus (DG) and CA3. Patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HE) commonly report mnemonic deficits that have been associated with failures in PS. However, the link between these impairments and the integrity of the hippocampal subfields in these patients has not yet been determined. The aim of this work is to explore the association between the ability to perform mnemonic functions and the integrity of hippocampal CA1, CA3, and DG in patients with unilateral MTLE-HE. Method: To reach this goal we evaluated the memory of patients with an improved object mnemonic similarity test. We then analyzed the hippocampal complex structural and microstructural integrity using diffusion weighted imaging. Results: Our results indicate that patients with unilateral MTLE-HE present alterations in both volume and microstructural properties at the level of the hippocampal subfields DG, CA1, CA3, and the subiculum, that sometimes depend on the lateralization of their epileptic focus. However, none of the specific changes was found to be directly related to the performance of the patients in a pattern separation task, which might indicate a contribution of various alterations to the mnemonic deficits or the key contribution of other structures to the function. Discussion: we established for the first time the alterations in both the volume and the microstructure at the level of the hippocampal subfields in a group of unilateral MTLE patients. We observed that these changes are greater in the DG and CA1 at the macrostructural level, and in CA3 and CA1 in the microstructural level. None of these changes had a direct relation to the performance of the patients in a pattern separation task, which suggests a contribution of various alterations to the loss of function. [ABSTRACT FROM AUTHOR]

Background. Temporal lobe epilepsy (TLE) is a complex neuropsychiatric illness that alters patient's behavior and social well-being. Early and accurate diagnosis of TLE is a key factor in its treatment. Currently, magnetic resonance spectroscopy (MRS) is recommended due to its high sensitivity and specificity in the detection of seizures. However, some studies have reported on its limited role in lesion detection. Objectives. The present meta-analysis aims to analyze different studies thoroughly and investigate the role of MRS in the detection of TLE. Materials and methods. A systematic literature review was conducted using Medline (via PubMed), Cinahl (via EBSCO), Scopus, and Web of Sciences databases for case-control, retrospective and prospective studies regarding the use of MRS in detecting TLE. Studies were included using the Population, Intervention, Comparison, Outcomes and Study (PICOS) criteria and relevant event data were extracted. The risk of publication bias was analyzed using the Begg and Mazumdar test. A risk of bias assessment was conducted using RevMan software. The Mantel-Haenszel method was used to calculate the sensitivity, pooled odds ratio (OR), and risk ratio (RR), also using RevMan software. Results. A total of 16 studies published between 2000 and 2022 were included, which encompassed a total of 645 patients. We obtained a high sensitivity of 84.8%, which shows a high efficiency of MRS, and a pooled OR value of 0.37 (95% confidence interval (95% CI): 0.14-0.97) with a tau2 value of 2.63, χ2 value of 84.99, degrees of freedom (df) value of 15, I2 value of 82%, Z-value of 2.03, and p < 0.05. The pooled RR was 0.82 (95% CI: 0.69-0.97) with a tau2 value of 0.10, χ2 value of 122.11, df of 15, I2 value of 88%, Z-value of 2.25, and p < 0.05. These results were statistically significant for a low risk of publication bias. Conclusions. The current meta-analysis highly recommends the use of MRS in the accurate detection of alterations seen in the brain in patients with TLE. [ABSTRACT FROM AUTHOR]

Previous research has linked epilepsy of the temporal lobe (TLE) with comorbidities of psychiatric nature, yet few studies have investigated personality psychopathology in patients with TLE. This is the first study on the topic in the Arab world and the first study using the Personality Inventory for DSM-5-Brief From (PID-5-BF). Thus, this study, which is cross-sectional by nature, aims to explore the potential relationship between TLE and personality psychopathology. Utilizing the validated Arabic version of the Personality Inventory for DSM-5 − Brief Form (PID-5-BF), this study compared average total scores and domain scores among 24 TLE patients and 48 controls from the general population, using the Independent Samples t -test. Binary logistic regression used to assess the impact of gender and age on personality psychopathology in both the TLE and control group. Following adjustment for age and gender, notable disparities emerged in average total scores (p < 0.001), as well as negative affect (p < 0.0001), disinhibition (p < 0.04), and psychoticism scores (p < 0.01), with TLE patients exhibiting higher scores across these domains with a score of 1.28, 2.00, 1.08 and 1.25 respectively compared to controls with a score of 0.85, 1.08, 0.69 and 0.69 respectively. Nevertheless, analyses investigating age and gender as predictors for personality psychopathology yielded non-significant results in both groups. The study hints at a possible positive link between TLE and personality psychopathology, possibly attributable to limbic system involvement. This is the first study of its kind in the Arab world, highlighting a neglected topic in the region. While these results hold clinical implications, further research is warranted to validate these relationships. [ABSTRACT FROM AUTHOR]

IntroductionPattern separation (PS) is a fundamental aspect of memory creation that defines the ability to transform similar memory representations into distinct ones, so they do not overlap when storing and retrieving them. Experimental evidence in animal models and the study of other human pathologies have demonstrated the role of the hippocampus in PS, in particular of the dentate gyrus (DG) and CA3. Patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HE) commonly report mnemonic deficits that have been associated with failures in PS. However, the link between these impairments and the integrity of the hippocampal subfields in these patients has not yet been determined. The aim of this work is to explore the association between the ability to perform mnemonic functions and the integrity of hippocampal CA1, CA3, and DG in patients with unilateral MTLE-HE.MethodTo reach this goal we evaluated the memory of patients with an improved object mnemonic similarity test. We then analyzed the hippocampal complex structural and microstructural integrity using diffusion weighted imaging.ResultsOur results indicate that patients with unilateral MTLE-HE present alterations in both volume and microstructural properties at the level of the hippocampal subfields DG, CA1, CA3, and the subiculum, that sometimes depend on the lateralization of their epileptic focus. However, none of the specific changes was found to be directly related to the performance of the patients in a pattern separation task, which might indicate a contribution of various alterations to the mnemonic deficits or the key contribution of other structures to the function.Discussionwe established for the first time the alterations in both the volume and the microstructure at the level of the hippocampal subfields in a group of unilateral MTLE patients. We observed that these changes are greater in the DG and CA1 at the macrostructural level, and in CA3 and CA1 in the microstructural level. None of these changes had a direct relation to the performance of the patients in a pattern separation task, which suggests a contribution of various alterations to the loss of function.

ObjectiveThe objective of this study was to explore the relation between interictal epileptiform discharge (IED) source connectivity and cortical structural couplings (SCs) in temporal lobe epilepsy (TLE).MethodsHigh-resolution 3D-MRI and 32-sensor EEG data from 59 patients with TLE were collected. Principal component analysis was performed on the morphological data on MRI to obtain the cortical SCs. IEDs were labeled from EEG data and averaged. The standard low-resolution electromagnetic tomography analysis was performed to locate the source of the average IEDs. Phase-locked value was used to evaluate the IED source connectivity. Finally, correlation analysis was used to compare the IED source connectivity and the cortical SCs.ResultsThe features of the cortical morphology in left and right TLE were similar across four cortical SCs, which could be mainly described as the default mode network, limbic regions, connections bilateral medial temporal, and connections through the ipsilateral insula. The IED source connectivity at the regions of interest was negatively correlated with the corresponding cortical SCs.SignificanceThe cortical SCs were confirmed to be negatively related to IED source connectivity in patients with TLE as detected with MRI and EEG coregistered data. These findings suggest the important role of intervening IEDs in treating TLE.

Temporal lobe epilepsy (TLE) is the most prevalent and treatment-refractory type of epilepsy. Among the different mechanisms associated with epileptogenesis, overstimulation of glutamatergic neurotransmission has been associated with the onset and progression of seizures in TLE. Experimental evidence indicates that blocking the N-methyl-D-aspartate (NMDA) receptor or suppressing the expression of its subunit, mainly GluN1, may be effective in preventing epileptic seizures. Small interfering RNA (siRNA) has received attention as a potential therapeutic tool due to the inhibition of gene expression in some diseases. The present work evaluated the potential silencing effect of intranasal administration of an siRNA conjugate against the GluN1 subunit in animals submitted to the pilocarpine model of epilepsy. The results showed that the siRNA conjugate transfection system silences the GluN1 subunit in the hippocampus of rats when administered intranasally. As demonstrated by the RT-qPCR and Western blotting approaches, the silencing of GluN1 was specific for this subunit without affecting the amount of mRNA for other subunits. Silencing increased the latency time for the first tonic–clonic seizure when compared to controls. The overlapping of findings and the validation of the intranasal route as a pharmacological route of siRNA targeting the GluN1 subunit give the work a significant biotechnological interest. [ABSTRACT FROM AUTHOR]

[Display omitted] • Spire2 is decreased in the brains of epileptic individuals. • Spire2 has an inhibitory role on epilepsy development and progression. • In mice, Spire2 knock-down aggravated abnormal firing. • In mice, Spire2 overexpression normalized firing. Epilepsy is a neurological disorder caused by abnormally elevated neuronal firing and excitability. Spire2, also known as the nucleating factor of F-actin, plays an important role in long-range vesicle transport. This study showed that Spire2 was highly expressed in neurons in the cortex and hippocampus. Its knockdown significantly reduced the initiation current of the evoked action potential and the frequency of action potential, suggesting that Spire2 knockdown inhibits the threshold current of the neuron. In the cortex of patients with refractory temporal lobe epilepsy (TLE), Spire2 expression was significantly reduced. Decreased expression levels of Spire2 were also observed in kainic acid (KA) and pentylenetetrazole (PTZ) animal models. In the KA and PTZ models, Spire2-knockdown mice showed significantly increased seizures and shortened intervals between seizures, with a tendency to increase seizure duration. In contrast, Spire2-overexpressing mice showed reduced numbers of spontaneous seizures. In conclusion, this study revealed a significantly decreased expression of Spire2 in the brain tissues of epileptic individuals and an inhibitory role for this protein in the development of epilepsy. In addition, knockdown of Spire2 aggravated abnormal firing in epileptic mice, while its overexpression had the opposite effect. These findings provide new insights into the mechanism of epileptogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Temporal lobe epilepsy (TLE), a debilitating neurological disorder, necessitates refined diagnostic and treatment strategies. This comprehensive review appraises the potential of positron emission tomography (PET) in enhancing the presurgical planning of Anterior Temporal Lobectomy (ATL) for patients afflicted with TLE., Methods: A comprehensive literature search was conducted using the PubMed, SCOPUS, and ScienceDirect databases from 1985 to 2022, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies investigating PET and ATL. This review studied a range of radiotracers, including FDG, H 2 O, FMZ, MPPF, and FCWAY, analyzing their efficacy in detecting epileptogenic foci, establishing resection boundaries, and predicting postoperative outcomes. The study paid special attention to cases where MRI findings were inconclusive., Results: A total of 52 studies were included in the final analysis. Our analysis revealed that FDG-PET imaging was instrumental in identifying seizure foci and predicting postoperative results. It exhibited significant value in situations where structural abnormalities were absent on MRI scans. Furthermore, newer radiotracers such as 5-HT 1A antagonists, FCWAY and MPPF, presented promising potential for localizing seizure foci, particularly in MRI-negative TLE, despite their comparatively limited current usage., Conclusion: PET imaging, although challenged by issues such as radiation exposure, limited accessibility, and high costs, offers considerable promise. Integration with other imaging modalities, such as EEG and MRI, has contributed to improved localization of epileptogenic foci and subsequently, enhanced surgical outcomes. Further research must focus on establishing the relative efficacy and optimal combinations of these radiotracers in the orchestration of ATL surgical planning and prognostication of postoperative outcomes for TLE patients. Encouragingly, these advancements hold the potential to revolutionize the management of TLE, delivering a better quality of life for patients., Competing Interests: Declaration of Competing Interest The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Using magnetic resonance (MR) images to evaluate changes in the shape of the hippocampus has been an active research topic. This paper presents a new shape analysis approach to quantify and visualize deformations of the hippocampus in epilepsy. The proposed method is based on Laplace–Beltrami (LB) eigenvalues and eigenfunctions as isometric invariant shape features, and thus, the procedure does not require any image registration. In addition to the LB-based shape features, total hippocampal volume and surface area are calculated using manually segmented images. Theses shape and volumetric descriptors are used to distinguish the patients with temporal lobe epilepsy (TLE) (N = 55) from healthy control subjects (N = 12, age = 32.2 ± 9.1, sex (M/F) = 6/6) and patients with right TLE (N = 26, age = 45.1 ± 11.0, sex (M/F) = 9/17) from left TLE (N = 29, age = 45.4 ± 11.9, sex (M/F) = 10/19). Experimental results illustrate the usefulness of the proposed approach for the diagnosis and lateralization of TLE with 93.0% and 86.4% of the cases, respectively. Moreover, the proposed method outperforms the volumetric analysis in terms of both sensitivity (94.9% vs. 88.1%) and specificity (83.3% vs. 50.0%) of the lateralization. The analysis of local hippocampal thickness variations suggests significant deformation in both ipsilateral and contralateral hippocampi of epileptic patients, while there were no differences between right and left hippocampi in controls. It is anticipated that the proposed method could be advantageous in the presurgical evaluation of patients with drug-resistant epilepsy; however, further validation of the method using a larger dataset is required. [ABSTRACT FROM AUTHOR]

Interictal 18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) is used in the workup for epilepsy surgery when MRI and EEG video monitoring are not conclusive. Timing of FDG‐PET is crucial to avoid the metabolically dynamic (post)ictal state that complicates interpretation, but the exact time window is unclear. We performed a systematic review to provide an evidence‐based recommendation for the minimal time interval between last seizure and FDG‐PET acquisition. We searched PubMed and Embase for articles on the effect of time since last seizure on FDG‐PET outcome. Quality assessment was conducted with the Critical Appraisal Skills Programme Cohort Study Checklist. We identified five studies. Three studies were classified as of low to moderate quality, mainly due to undocumented data or insufficient statistical measurements. Two high‐quality studies included only adults with Temporal Lobe Epilepsy (TLE). The metabolic interictal phase is 24 or 48 hours after the last seizure, depending on seizure type. The recommendation is based on the best available evidence from two small study populations for TLE. If clinically possible, interictal FDG‐PET in adults should be performed at least 24 hours after focal aware seizures and 48 hours after focal impaired awareness and focal to bilateral tonic–clonic seizures. [ABSTRACT FROM AUTHOR]

Background: Patients with temporal lobe epilepsy (TLE) frequently complain of poor sleep quality, which is a condition that clinicians are typically neglecting. In this study, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Athens Insomnia Scale (AIS) were used to assess the sleep status of patients with temporal lobe epilepsy (TLE). Simultaneously diffusion kurtosis imaging (DKI) was applied to examine the white matter microstructure abnormalities in patients with TLE and sleep disorders. Methods: TLE patients who have been diagnosed in the cardio-cerebrovascular ward of the Yanan University Affiliated Hospital from October 2020 to August 2021 were recruited. Finally, 51 patients and 30 healthy controls were enrolled in our study, with all subjects completing the sleep evaluation questionnaire and undergoing a DKI examination. Using independent sample t -test, analysis of variance (ANOVA), and Mann-Whitney U test to compare groups. Results: Thirty patients (58.82%) complained of long-term sleep difficulties. The overall differences among the evaluation of AIS, ESS, and PSQI are significant (P = 0.00, P = 0.00, P = 0.03). The scores of AIS, ESS in Left and Right-TLE (L/R-TLE) with sleep disorders, as well as PSQI in L-TLE, are statistically higher than the control group (P = 0.00, P = 0.00, P = 0.00, P = 0.00, P = 0.02). L-TLE with sleep disorders showed decreased MK on affected sides (P = 0.01). However, statistical differences in MD and FA have not been observed (P = 0.34, P = 0.06); R-TLE with sleep disorders showed significantly decreased MK and increased MD on affected sides (P = 0.00, P = 0.00), but FA's statistical difference has not been observed (P = 0.20). Conclusions: TLE patients with sleep disorders have different DKI parameters than individuals who do not have sleep issues. During this process, the kurtosis parameter (MK) was more sensitive than the tensor parameters (MD, FA) in detecting the patient's aberrant white matter diffusion. DKI may be a better choice for in vivo investigation of anomalous craniocerebral water diffusion. [ABSTRACT FROM AUTHOR]

BackgroundPatients with temporal lobe epilepsy (TLE) frequently complain of poor sleep quality, which is a condition that clinicians are typically neglecting. In this study, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Athens Insomnia Scale (AIS) were used to assess the sleep status of patients with temporal lobe epilepsy (TLE). Simultaneously diffusion kurtosis imaging (DKI) was applied to examine the white matter microstructure abnormalities in patients with TLE and sleep disorders.MethodsTLE patients who have been diagnosed in the cardio-cerebrovascular ward of the Yanan University Affiliated Hospital from October 2020 to August 2021 were recruited. Finally, 51 patients and 30 healthy controls were enrolled in our study, with all subjects completing the sleep evaluation questionnaire and undergoing a DKI examination. Using independent sample t-test, analysis of variance (ANOVA), and Mann-Whitney U test to compare groups.ResultsThirty patients (58.82%) complained of long-term sleep difficulties. The overall differences among the evaluation of AIS, ESS, and PSQI are significant (P = 0.00, P = 0.00, P = 0.03). The scores of AIS, ESS in Left and Right-TLE (L/R-TLE) with sleep disorders, as well as PSQI in L-TLE, are statistically higher than the control group (P = 0.00, P = 0.00, P = 0.00, P = 0.00, P = 0.02). L-TLE with sleep disorders showed decreased MK on affected sides (P = 0.01). However, statistical differences in MD and FA have not been observed (P = 0.34, P = 0.06); R-TLE with sleep disorders showed significantly decreased MK and increased MD on affected sides (P = 0.00, P = 0.00), but FA's statistical difference has not been observed (P = 0.20).ConclusionsTLE patients with sleep disorders have different DKI parameters than individuals who do not have sleep issues. During this process, the kurtosis parameter (MK) was more sensitive than the tensor parameters (MD, FA) in detecting the patient's aberrant white matter diffusion. DKI may be a better choice for in vivo investigation of anomalous craniocerebral water diffusion.

Temporal lobe epilepsy (TLE) is the most prevalent and treatment-refractory type of epilepsy. Among the different mechanisms associated with epileptogenesis, overstimulation of glutamatergic neurotransmission has been associated with the onset and progression of seizures in TLE. Experimental evidence indicates that blocking the N-methyl-D-aspartate (NMDA) receptor or suppressing the expression of its subunit, mainly GluN1, may be effective in preventing epileptic seizures. Small interfering RNA (siRNA) has received attention as a potential therapeutic tool due to the inhibition of gene expression in some diseases. The present work evaluated the potential silencing effect of intranasal administration of an siRNA conjugate against the GluN1 subunit in animals submitted to the pilocarpine model of epilepsy. The results showed that the siRNA conjugate transfection system silences the GluN1 subunit in the hippocampus of rats when administered intranasally. As demonstrated by the RT-qPCR and Western blotting approaches, the silencing of GluN1 was specific for this subunit without affecting the amount of mRNA for other subunits. Silencing increased the latency time for the first tonic–clonic seizure when compared to controls. The overlapping of findings and the validation of the intranasal route as a pharmacological route of siRNA targeting the GluN1 subunit give the work a significant biotechnological interest.

• Temporal and frontal epilepsy maybe related to decrease in OB volume. • Temporal and frontal epilepsy may cause olfactory impairment. • Olfactory deficit maybe related to central epileptic focus. • Olfactory impairment may help early diagnosis of the epilepsy. We investigated peripheric smell regions of olfactory bulb (OB) volume and olfactory sulcus (OS) depth in temporal and frontal lobe epilepsy patients by cranial magnetic resonance imaging (MRI). In this retrospective study, cranial MRI images of 150 adult patients were included. Group 1 was consisted of 50 adult patients with temporal lobe epilepsy (TLE). Group 2 was consisted of 50 adult patients with frontal lobe epilepsy (FLE). The control group (Group 3) was consisted of 50 healthy subjects without epilepsy. OB volume and OS depth were measured in all groups. OB volumes of the temporal and frontal epilepsy groups were significantly lower than those of the control group (p adjusted < 0.0175). However, OS depths were not different between groups 1–3 (p > 0.05). In the temporal and frontal epilepsy groups, there were positive correlations between OB volumes; OS depths; left OB volume and bilateral OS depths p < 0.05). There were no significant correlations between OB volume and OS depth; and age and gender of the epilepsy group (p > 0.05). We concluded that temporal and frontal epilepsy maybe related to decrease in OB volume and may cause olfactory impairment. Olfactory deficit maybe related to central epileptic focus. Therefore, early diagnosis and appropriate treatment of epilepsy are important to prevent olfactory impairment. [ABSTRACT FROM AUTHOR]

• Failure to account for ATL following LITT provides an underestimate of costs. • LITT costs more if the ratio of subsequent ATLs exceeds the cost reduction of LITT. • Cost per seizure-free patient will be higher in LITT if certain relationships are met. Laser interstitial thermal therapy (LITT) is an alternative to anterior temporal lobectomy (ATL) for the treatment of temporal lobe epilepsy that has been found by some to have a lower procedure cost but is generally regarded as less effective and sometimes results in a subsequent procedure. The goal of this study is to incorporate subsequent procedures into the cost and outcome comparison between ATL and LITT. This single-center, retrospective cohort study includes 85 patients undergoing ATL or LITT for temporal lobe epilepsy during the period September 2015 to December 2022. Of the 40 patients undergoing LITT, 35 % (N = 14) underwent a subsequent ATL. An economic cost model is derived, and difference in means tests are used to compare the costs, outcomes, and other hospitalization measures. Our model predicts that whenever the percentage of LITT patients undergoing subsequent ATL (35% in our sample) exceeds the percentage by which the LITT procedure alone is less costly than ATL (7.2% using total patient charges), LITT will have higher average patient cost than ATL, and this is indeed the case in our sample. After accounting for subsequent surgeries, the average patient charge in the LITT sample ($103,700) was significantly higher than for the ATL sample ($88,548). A second statistical comparison derived from our model adjusts for the difference in effectiveness by calculating the cost per seizure-free patient outcome, which is $108,226 for ATL, $304,052 for LITT only, and $196,484 for LITT after accounting for the subsequent ATL surgeries. After accounting for the costs of subsequent procedures, we found in our cohort that LITT is not only less effective but also results in higher average costs per patient than ATL as a first course of treatment. While cost and effectiveness rates will vary across centers, we also provide a model for calculating cost effectiveness based on individual center data. [ABSTRACT FROM AUTHOR]

Background and Importance: Arachnoid cysts are developmental cystic lesions which may be found as an incidental finding on neuroimaging or present with symptoms of headache, seizure and neurologic deficit. Presentation with seizure is more common with larger sizes and temporal location. Presentation with Temporal Lobe Epilepsy (TLE) is rare, and fenestration of cysts has variable results for seizure control. We reported controlling TLE symptoms following endoscopic transsphenoidal fenestration of an arachnoid cyst. The anteromedial location in middle fossa, extension toward sphenoid sinus and normal appearance of mesial temporal structures on MRI encouraged us to consider this surgical approach. Case Presentation: A 26-year-old patient with a 13-year history of TLE with uncontrolled symptoms despite taking a combination of AEDs (LTG, CBZ, LEV, CLB) was referred to our clinic. Neuroimaging revealed an arachnoid cyst in anteromedial part of temporal fossa which extended to sphenoid sinus, but showed no abnormality in mesial temporal structures. Endoscopic endonasal transsphenoidal fenestration of the arachnoid cyst was performed, and followed by reconstruction of the skull base. The procedure improved the seizure control during the 9-month follow-up and no sign of radiologic recurrence was observed. Conclusion: Transsphenoidal endoscopic fenestration is a safe and feasible surgical approach for treatment of symptomatic arachnoid cysts in anteromedial part of middle fossa especially when they extend toward lateral wall of sphenoid sinus. This surgical corridor has the privilege of avoiding cortical injury accompanied by transcranial approaches, which is deleterious in epileptic patients.

Background: Clinical and experimental evidence indicates that olfactory stimulation modulates limbic seizures, either blocking or inducing ictal activity.Objective: We aim to evaluate the behavioral and electroencephalographic (EEGraphic) effects of dihydro-2,4,5-trimethylthiazoline (TMT) olfactory exposure on limbic seizures induced by amygdala rapid kindling (ARK).Materials and Methods: Wistar male rats (280–300 g) underwent stereotaxic surgery for electrode implantation in piriform cortex (PC), hippocampal formation (HIP), and amygdaloid complex (AMYG). Part of the animals was exposed to a saturated chamber with water or TMT, while others had ARK and olfactory exposure prior to the 21st stimulus. Behavioral responses were measured by traditional seizure severity scales (Racine and Pinel and Rovner) and/or by sequential analysis/neuroethology. The electrographic activity of epileptogenic limbic networks was quantified by the occurrence of the first and second EEG afterdischarges, comparing the 1st and 21st stimulus. The spectral analysis [Fast Fourier Transform (FFT)] of the first afterdischarge was performed at the 21st stimulus.Results: TMT olfactory exposure reduced the seizure severity in kindled rats, altering the displayed behavioral sequence. Moreover, TMT decreased the occurrence of first and second afterdischarges, at the 21st stimulus, and altered the spectral features.Conclusions: Both behavioral and EEGraphic evaluations indicated that TMT, a potent molecule with strong biological relevance, in fact, “predator odor,” suppressed the epileptiform activity in limbic networks.

Temporal lobe epilepsy (TLE) is one of the most common and refractory forms of epilepsy, with a different etiology. According to experimental and clinical studies, the transformation of the normal pattern of brain neuron activity into paroxysmal one 3 is accompanied by changes in the expression of cytokines and neurotrophins in the hippocampus and temporal cortex. Modulation of the expression of the neurotrophic brain factor (Brain-Derived Neurotrophic Factor, BDNF) may be associated with the carrier of the single nucleotide polymorphism (SNP) of the rs6265 BDNF gene. The research groups have shown increased expression of BDNF in the hippocampus and temporal cortex in patients with drug resistant epilepsy. Independent studies have demonstrated the role of the Il1B gene, encoding pro-inflammatory cytokine interleukin (IL) 1β, in the development of inflammatory reactions and structural mediobasal temporal epilepsy with hippocampal sclerosis.The purpose of the research is to study the association of the carriers of the SNP rs16944 and rs1143634 of the IL1B gene and rs6265 of the BDNF gene with the development of temporal lobe epilepsy.Patients and methods. We carried out a molecular genetic study of the carrier of SNPs rs1143634 and rs16944 of the Il1B and rs6265 gene of the BDNF gene using real-time polymerase chain reaction (RT-PCR) in 84 patients with TLE and 203 Caucasian healthy volunteers living in the Siberian Federal Region.Results. The carriage of a high-producing allele C (odds ratio, OR 2.01; 95% confidence interval, CI 1.31–3.08; p = 0.001) and the homozygous genotype CC (OR 2.48; 95% CI 1.47–4, 17; p = 0.001) of SNPs of the IL1B gene (rs1143634) are statistically significantly associated with the development of TLE in the population under study. No statistically significant differences in the carriers of the SNPs of the Il1B (rs1143634 and rs16944) gene and BDNF (rs6265) with the clinical features and course of TLE were revealed (p> 0.05). The association of carriers of SNPs rs6265 of the BDNF gene with the development of TLE was not detected (χ2 = 0.3; p = 0.86) as well.Conclusion The association of the high-producing allele C carrier and the homozygous genotype CC (rs1143634) of the IL1B gene with TLE has been established.

Temporal lobe epilepsy (TLE) is one of the most common and refractory forms of epilepsy, with a different etiology. According to experimental and clinical studies, the transformation of the normal pattern of brain neuron activity into paroxysmal is accompanied by changes in the expression of cytokines and neurotrophins in the hippocampus and temporal cortex. Modulation of the expression of the brainderived neurotrophic factor (BDNF) may be associated with the carriage of the single nucleotide polymorphism (SNP) rs6265 in BDNF gene. Research groups have shown increased expression of BDNF in the hippocampus and temporal cortex in patients with pharmacoresistant epilepsy. Independent studies have demonstrated the role of the Il-1B gene encoding the proinflammatory cytokine IL1B in the development of inflammatory reactions and structural mediobasal TLE with hippocampal sclerosis.Objective: to study the association of the carrier SNPs rs16944, rs1143634 of IL-1B gene and rs6265 of BDNF gene in the development of TLE.Patients and methods: using RT-PCR, we identified carriers of SNPs rs1143634 and rs16944 in Il-1B gene and rs6265 in BDNF gene, from samples of 84 patients with TLE and 203 Caucasian healthy volunteers in the Siberian Federal District.Results: we have shown that the carriage of a high-producing allele C (OR = 2.01; 95% CI: 1.31-3.08; p = 0.001) and the homozygous genotype CC (OR = 2.48; 95% CI: 1.47-4.17; p = 0.001) SNPs in IL-1B gene (rs1143634) are statistically significantly associated with TLE in Siberian population. There were no statistically significant differences in the carriers of SNPs in IL-1B gene (rs1143634 and rs16944) and in BDNF gene (rs6265) with clinical and anamnestic features of TLE (p> 0.05). Association of carriers of SNPs rs6265 in BDNF gene with the development of TLE was not detected (χ2 = 0.3; p = 0.86).Conclusions: we detected association of carriers of the high-producing allele C and the homozygous genotype CC (rs1143634) in IL1B gene with temporal lobe epilepsy.

Patients suffering from temporal lobe epilepsy (TLE) show severe problems in hippocampus dependent memory consolidation. Memory consolidation strongly depends on an intact dialog between the hippocampus and neocortical structures. Deficits in hippocampal signal transmission are known to provoke disturbances in memory formation. In the present study, we investigate changes of synaptic plasticity at hippocampal output structures in an experimental animal model of TLE. In pilocarpine-treated rats, we found suppressed long-term potentiation (LTP) in hippocampal and parahippocampal regions such as the subiculum and the entorhinal cortex (EC). Subsequently we focused on the subiculum, serving as the major relay station between the hippocampus proper and downstream structures. In control animals, subicular pyramidal cells express different forms of LTP depending on their intrinsic firing pattern. In line with our extracellular recordings, we could show that LTP could only be induced in a minority of subicular pyramidal neurons. We demonstrate that a well-characterized cAMP-dependent signaling pathway involved in presynaptic forms of LTP is perturbed in pilocarpine-treated animals. Our findings suggest that in TLE, disturbances of synaptic plasticity may influence the information flow between the hippocampus and the neocortex.

Background: Clinical and experimental evidence indicates that olfactory stimulation modulates limbic seizures, either blocking or inducing ictal activity. Objective: We aim to evaluate the behavioral and electroencephalographic (EEGraphic) effects of dihydro-2,4,5-trimethylthiazoline (TMT) olfactory exposure on limbic seizures induced by amygdala rapid kindling (ARK). Materials and Methods: Wistar male rats (280–300 g) underwent stereotaxic surgery for electrode implantation in piriform cortex (PC), hippocampal formation (HIP), and amygdaloid complex (AMYG). Part of the animals was exposed to a saturated chamber with water or TMT, while others had ARK and olfactory exposure prior to the 21st stimulus. Behavioral responses were measured by traditional seizure severity scales (Racine and Pinel and Rovner) and/or by sequential analysis/neuroethology. The electrographic activity of epileptogenic limbic networks was quantified by the occurrence of the first and second EEG afterdischarges, comparing the 1st and 21st stimulus. The spectral analysis [Fast Fourier Transform (FFT)] of the first afterdischarge was performed at the 21st stimulus. Results: TMT olfactory exposure reduced the seizure severity in kindled rats, altering the displayed behavioral sequence. Moreover, TMT decreased the occurrence of first and second afterdischarges, at the 21st stimulus, and altered the spectral features. Conclusions: Both behavioral and EEGraphic evaluations indicated that TMT, a potent molecule with strong biological relevance, in fact, "predator odor," suppressed the epileptiform activity in limbic networks. [ABSTRACT FROM AUTHOR]

Purpose: This is a cross-sectional study without an unexposed group. We elucidated the effects of sevoflurane anesthesia on high-frequency oscillations (HFOs) to examine the usefulness of assessing intraoperative HFOs.Methods: We recorded electrocorticography in seven patients with medication-resistant temporal lobe epilepsy (TLE) caused by unilateral hippocampal sclerosis who were seizure-free after temporal lobectomy. We analyzed the number of intraoperative spikes and HFOs on spikes in the epileptogenic parahippocampal gyrus and nonepileptogenic superior temporal gyrus with sevoflurane concentrations of 1.5%, 2.0%, 2.5%, and 3.0%.Results: The number of spikes and HFOs in the epileptogenic area significantly increased with an increase in the sevoflurane concentration. In the nonepileptogenic area, spikes and HFOs did not significantly increase with increases in the sevoflurane concentration. However, 2.5% sevoflurane markedly induced spikes and ripples but no fast ripples (FRs) in one patient, and 3.0% sevoflurane induced marked increases in both ripples and FRs in two patients.Conclusions: The proconvulsant effect of sevoflurane on intraoperative HFOs in patients with TLE depends on the concentration. While HFOs induced by higher sevoflurane concentrations may be a useful biomarker for epileptogenic areas, careful interpretation is also needed because a higher sevoflurane concentration can also induce false-positive HFOs in nonepileptogenic areas. [ABSTRACT FROM AUTHOR]

In medical refractory temporal lobe epilepsy (TLE), the epileptogenic zone can be difficult to identify and therefore difficult to treat, especially in the absence of clear MRI pathologies and specific results from presurgical evaluation. Invasive monitoring with stereo-electroencephalography (sEEG) is a tool for a better determination of the epileptogenic zone. Here, we investigate the impact of sEEG on decision-making in temporal lobe epilepsy surgery. We reviewed patients with TLE who underwent further investigation with sEEG in our epilepsy unit. We examined specifically how sEEG findings influenced our decision regarding indication for a surgical procedure and resection volume. From 2013 to 2017, we performed 152 temporal resections in epilepsy patients. Twenty-one of these patients were designated for further preoperative investigation with sEEG due to incongruent findings in presurgical evaluation. Six patients were implanted bitemporally. In five cases, the hypothesis for the epileptogenic zone and localization had to be changed due to sEEG findings and resulted in a different tailored resection than intended. In three cases, sEEG findings led to the cancelation of the originally intended temporal resection as the epileptogenic zone was not definable or bilateral. In another three cases, the prognosis for reduction of seizures postoperatively had to be reduced due to the sEEG findings. However, the resection was performed after interdisciplinary discussion and informed consent of the patient. The examination by sEEG led to a change of plan for further treatment in 13 patients (61.9%) suffering TLE in total. Invasive monitoring with sEEG electrodes had a strong impact on decision-making for further treatment in patients suffering from temporal lobe epilepsy with incongruent findings in presurgical examination designated for epilepsy surgery. This applies to resection volumes as well as to prediction of seizure outcome. [ABSTRACT FROM AUTHOR]

Patients suffering from temporal lobe epilepsy (TLE) show severe problems in hippocampus dependent memory consolidation. Memory consolidation strongly depends on an intact dialog between the hippocampus and neocortical structures. Deficits in hippocampal signal transmission are known to provoke disturbances in memory formation. In the present study, we investigate changes of synaptic plasticity at hippocampal output structures in an experimental animal model of TLE. In pilocarpine-treated rats, we found suppressed long-term potentiation (LTP) in hippocampal and parahippocampal regions such as the subiculum and the entorhinal cortex (EC). Subsequently we focused on the subiculum, serving as the major relay station between the hippocampus proper and downstream structures. In control animals, subicular pyramidal cells express different forms of LTP depending on their intrinsic firing pattern. In line with our extracellular recordings, we could show that LTP could only be induced in a minority of subicular pyramidal neurons. We demonstrate that a well-characterized cAMP-dependent signaling pathway involved in presynaptic forms of LTP is perturbed in pilocarpine-treated animals. Our findings suggest that in TLE, disturbances of synaptic plasticity may influence the information flow between the hippocampus and the neocortex. [ABSTRACT FROM AUTHOR]

• Cognitive impairment in people with epilepsy is common but access to neuropsychological screenings is limited by cost and time. • We evaluated cognition in people with temporal lobe epilepsy using neuropsychological screening tools and robotic (Kinarm) assessment. • Robotic assessment can assess executive function, attention, visuospatial and motor performance in a comparable manner to neuropsychological screenings in patients with temporal lobe epilepsy. • Technology-based assessment of cognition may be an effective tool to screen for cognitive impairment in people with epilepsy. Individuals with temporal lobe epilepsy (TLE) frequently demonstrate impairments in executive function, working memory, and/or declarative memory. It is recommended that screening for cognitive impairment is undertaken in all people newly diagnosed with epilepsy. However, standard neuropsychological assessments are a limited resource and thus not available to all. Our study investigated the use of robotic technology (the Kinarm robot) for cognitive screening. 27 participants with TLE (17 left) underwent both a brief neuropsychological screening and a robotic (Kinarm) assessment. The degree of impairments and correlations between standardized scores from both approaches to assessments were analysed across different neurocognitive domains. Performance was compared between people with left and right TLE to look for laterality effects. Finally, the association between the duration of epilepsy and performance was assessed. Across the 6 neurocognitive domains (attention, executive function, language, memory, motor and visuospatial) assessed by our neuropsychological screening, all showed scores that significantly correlated with Kinarm tasks assessing the same cognitive domains except language and memory that were not adequately assessed with Kinarm. Participants with right TLE performed worse on most tasks than those with left TLE, including both visuospatial (typically considered right hemisphere), and verbal memory and language tasks (typically considered left hemisphere). No correlations were found between the duration of epilepsy and either the neuropsychological screening or Kinarm assessment. Our findings suggest that Kinarm may be a useful tool in screening for neurocognitive impairment in people with TLE. Further development may facilitate an easier and more rapid screening of cognition in people with epilepsy and distinguishing patterns of cognitive impairment. [ABSTRACT FROM AUTHOR]

Background/Aims: Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients. Methods: Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients. Total RNA was isolated, and high-throughput sequencing was used to profile the transcriptome of dysregulated circRNAs. Quantitative PCR was performed for the validation of changed circRNAs. Results: In total, 78983 circRNAs, including 15.29% known and 84.71% novel circRNAs, were detected in this study. Intriguingly, 442 circRNAs were differentially expressed between the TLE and non-TLE groups (fold change≥2.0 and FDR≤0.05). Of these circRNAs, 188 were up-regulated, and 254 were down-regulated in the TLE patient group. Eight circRNAs were validated by real-time PCR. Remarkably, circ-EFCAB2 was intensely up-regulated, while circ-DROSHA expression was significantly lower in the TLE group than in the non-TLE group (P

This study explored the taxonomy of cognitive impairment within temporal lobe epilepsy and characterized the sociodemographic, clinical and neurobiological correlates of identified cognitive phenotypes. 111 temporal lobe epilepsy patients and 83 controls (mean ages 33 and 39, 57% and 61% female, respectively) from the Epilepsy Connectome Project underwent neuropsychological assessment, clinical interview, and high resolution 3T structural and resting-state functional MRI. A comprehensive neuropsychological test battery was reduced to core cognitive domains (language, memory, executive, visuospatial, motor speed) which were then subjected to cluster analysis. The resulting cognitive subgroups were compared in regard to sociodemographic and clinical epilepsy characteristics as well as variations in brain structure and functional connectivity. Three cognitive subgroups were identified (intact, language/memory/executive function impairment, generalized impairment) which differed significantly, in a systematic fashion, across multiple features. The generalized impairment group was characterized by an earlier age at medication initiation (P

Background: We hypothesized that right and left temporal lobe epilepsy (RTLE and LTLE, respectively) have distinctive spatial patterns of white matter (WM) changes that can be differentiated and interpreted with the use of multiple diffusion parameters. We compared the global microstructure of fiber bundles with regard to WM alterations in both RTLE and LTLE, addressing some of the methodological issues of previous studies.Methods: Diffusion tensor imaging data from 17 patients with RTLE (age: 40.7 ± 10.4), 15 patients with LTLE (age: 37.3 ± 10.4), and 15 controls (age: 34.8 ± 11.2) were used in the study. WM integrity was quantified by fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity (LD), and radial diffusivity (RD). The diffusion parameters were compared between the groups in tracts representing the core of the fiber bundles. The volumes of hippocampi and amygdala were subsequently compared across the groups, while the data were adjusted for the effect of hippocampal sclerosis.Results: Significantly reduced FA and increased MD, LD, and RD were found bilaterally over widespread brain regions in RTLE. An increase in MD and RD values was observed in widespread WM fiber bundles ipsilaterally in LTLE, largely overlapping with regions where FA was lower, while no increase in LD was observed. We also found a difference between the LTLE and RTLE groups for the right hippocampal volume (with and without adjustment for HS), whereas no significant volume differences were found between patients and controls.Conclusions: It appears that patients with RTLE exhibit a more widespread pattern of WM alterations that extend far beyond the temporal lobe in both ipsilateral and contralateral hemisphere; furthermore, these changes seem to reflect more severe damage related to chronic degeneration. Conversely, more restrained changes in the LTLE may imply a pattern of less severe axonal damage, more restricted to ipsilateral hemisphere. Comprehensive finding of more prominent hippocampal atrophy in the RTLE raises an interesting issue of seizure-induced implications on gray matter and WM microstructure that may not necessarily mean a straightforward causal relationship. Further correlations of diffusion-derived metrics with neuropsychological and functional imaging measures may provide complementary information on underlying WM abnormalities with regard to functional hemispheric specialization.

Electroconvulsive therapy (ECT) was established based on Meduna's hypothesis that there is an antagonism between schizophrenia and epilepsy, and that the induction of a seizure could alleviate the symptoms of schizophrenia. However, subsequent investigations of the mechanisms of ECT have largely ignored this originally established relationship between these two disorders. With the development of functional magnetic resonance imaging (fMRI), brain-network studies have demonstrated that schizophrenia and epilepsy share common dysfunctions in the default-mode network (DMN), saliency network (SN), dorsal-attention network (DAN), and central-executive network (CEN). Additionally, fMRI-defined brain networks have also been shown to be useful in the evaluation of the treatment efficacy of ECT. Here, we compared the ECT-induced changes in the pathological conditions between schizophrenia and epilepsy in order to offer further insight as to whether the mechanisms of ECT are truly based on antagonistic and/or affinitive relationships between these two disorders.

Bumetanide (BTN or BUM) is a FDA-approved potent loop diuretic (LD) that acts by antagonizing sodium-potassium-chloride (Na-K-Cl) cotransporters, NKCC1 (SLc12a2) and NKCC2. While NKCC1 is expressed both in the CNS and in systemic organs, NKCC2 is kidney-specific. The off-label use of BTN to modulate neuronal transmembrane Cl− gradients by blocking NKCC1 in the CNS has now been tested as an anti-seizure agent and as an intervention for neurological disorders in pre-clinical studies with varying results. BTN safety and efficacy for its off-label use has also been tested in several clinical trials for neonates, children, adolescents, and adults. It failed to meet efficacy criteria for hypoxic-ischemic encephalopathy (HIE) neonatal seizures. In contrast, positive outcomes in temporal lobe epilepsy (TLE), autism, and schizophrenia trials have been attributed to BTN in studies evaluating its off-label use. NKCC1 is an electroneutral neuronal Cl− importer and the dominance of NKCC1 function has been proposed as the common pathology for HIE seizures, TLE, autism, and schizophrenia. Therefore, the use of BTN to antagonize neuronal NKCC1 with the goal to lower internal Cl− levels and promote GABAergic mediated hyperpolarization has been proposed. In this review, we summarize the data and results for pre-clinical and clinical studies that have tested off-label BTN interventions and report variable outcomes. We also compare the data underlying the developmental expression profile of NKCC1 and KCC2, highlight the limitations of BTN’s brain-availability and consider its actions on non-neuronal cells.

Magnetic Resonance Spectroscopy (MRS) has at least two major roles in the evaluation of epileptic patients. First, MRS can help to understand the interaction between seizures and metabolic function. Thus, MRS is particularly interesting for basic science studies of seizures and epilepsy. Second, MRS can explain the nature of seizure control and/or provide localization information by measuring metabolic changes. So MRS can be used as a powerful complementary technique to structural MRI for diagnosis and assessment of response to therapy, and measurement of disease progression. The aim of this paper is to review the methodological aspects of 1H-MRS publications between 1994 to 2016, which utilized 1H-MRS in lateralizing the epileptogenic zone in lesional and non-lesional Temporal Lobe Epilepsy (TLE), Extra-Temporal Lobe Epilepsy (ETLE), and generalized epileptic patients to help the spectroscopist, magnetic resonance imaging technologists, and radiologists to improve the overall diagnostic sensitivity in epileptic patients.

Persons with drug refractory TLE have the option of being managed by surgery. They may develop memory impairment with specific etiology of mesial temporal sclerosis and anterior temporal lobe resection (ATLR). The study evaluated the semantic verbal memory outcomes in pre- and post-surgery temporal lobe epilepsy (TLE) patients using functional MRI and voxel morphometric methods. Twenty consecutive persons with drug-resistant epilepsy (DRE) and 20 healthy controls were recruited after obtaining the institute ethics approval. The fMRI scans were performed on a 1.5 T MR Scanner using standardized semantic verbal memory tasks using a native Hindi paradigm, before and after an anterior temporal lobectomy (in cases). A task-based functional connectivity (FC) was estimated using a conn toolbox. Data analysis was carried out using the statistical parametric imaging (SPM12) and CAT12 toolbox. Post-surgery TLE group showed increased robust FC in the right middle and posterior temporal regions as compared to pre-surgery session. A significant reduction in grey matter volume was observed in the left temporal lobe post-operatively as compared to pre-surgery and healthy control groups. In the post-surgery TLE group, neuropsychological scores were reduced in specific PGI domains such as visuospatial, working memory, and executive functioning. Our results may help in understanding of memory reorganization in TLE post-operatively. [ABSTRACT FROM AUTHOR]

Responsive neurostimulation (RNS) is becoming a promising therapy in refractory epilepsy control. In a RNS system, a critical challenge is how to detect seizure onsets accurately with low computational costs. In this study, an energy efficient AdaBoost cascade method for robust long-term seizure detection from local field potential (LFP) signals was proposed and evaluated in a portable neurostimulator. The AdaBoost cascade method included two stages: a seizure candidate detection stage (stage1) and a false alarm rejection stage (stage2). Since seizure activities occurred occasionally in most cases, most normal signal segments can be efficiently classified in stage1. A small percent of suspicious segments were fed into stage2 for more strict examination, where more sophisticated features were extracted to precisely identify seizure activities and reduce false alarms. To further optimize energy efficiency for hardware implementation, we proposed a soft-cascade algorithm for stage2 to reduce the computational costs. Our method was implemented in a generalized neurostimulator and evaluated online with four rats with chronic temporal lobe epilepsy (TLE). A total of 2280.1 hours of LFP signals were recorded and analyzed. Our approach achieves a detection rate of 91.6%, 3.85/h false alarm rate, and 2.31 second detection delay. With the two-stage cascade approach, 98.13% of computational costs could be reduced, with respect to the time of calculation of all features. Our method can detect seizure onsets precisely with high energy efficiency, which is suitable for hardware implementation in portable neuro-stimulators. Therefore, this proposed approach is promising to provide effective and robust performances in long-term seizure detection in neurostimulators for responsive seizure control. [ABSTRACT FROM AUTHOR]