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Background: Temporal lobe epilepsy is the most common type of focal epilepsy, but hereditary factors are usually overlooked. Reelin (RELN) is considered to be the second most common pathogenic gene implicated in autosomal dominant lateral temporal epilepsy (ADLTE). However, this mutation is not frequently discovered in the Chinese population. Additionally, there are few clinical studies regarding the connection between RELN and glioma. Case presentation: The healthcare records of an 8-year-old child who experienced generalized tonic-clonic seizures (GTCS) during sleep for 7 years were retrospectively analyzed. In addition to experiencing his first seizure at the age of one, his mother also suffered from GTCS during her pregnancy, and a glioma was discovered. An investigation involving gene sequencing was conducted on the proband and his parents. He was diagnosed with ADLTE once a missense mutation in RELN (c.1799 C > T) was identified as the causal factor. The mutation was inherited from his mother. He was taking levetiracetam (500 mg twice a day) to avoid seizures, but his mother died of status epilepticus caused by glioma recurrence two years earlier. Conclusions: Genetic issues should be given more consideration in cases of temporal lobe epilepsy. If the source of the seizures is determined to be inherited, anti-seizure medications should be used for prolonged periods. Furthermore, more research is required to determine whether mutations in RELN are related to the occurrence and progression of gliomas. [ABSTRACT FROM AUTHOR]

Among patients with epilepsy, 30–40% experience recurrent seizures even after adequate antiseizure medications therapies, making them refractory. The early identification of refractory epilepsy is important to provide timely surgical treatment for these patients. In this study, we analyze interictal electroencephalography (EEG) data to predict drug refractoriness in patients with temporal lobe epilepsy (TLE) who were treated with monotherapy at the time of the first EEG acquisition. Various EEG features were extracted, including statistical measurements and interchannel coherence. Feature selection was performed to identify the optimal features, and classification was conducted using different classifiers. Functional connectivity and graph theory measurements were calculated to identify characteristics of refractory TLE. Among the 48 participants, 34 (70.8%) were responsive, while 14 (29.2%) were refractory over a mean follow-up duration of 38.5 months. Coherence feature within the gamma frequency band exhibited the most favorable performance. The light gradient boosting model, employing the mutual information filter-based feature selection method, demonstrated the highest performance (AUROC = 0.821). Compared to the responsive group, interchannel coherence displayed higher values in the refractory group. Interestingly, graph theory measurements using EEG coherence exhibited higher values in the refractory group than in the responsive group. Our study has demonstrated a promising method for the early identification of refractory TLE utilizing machine learning algorithms. [ABSTRACT FROM AUTHOR]

Epilepsy, affecting 0.5%‐1% of the global population, presents a significant challenge with 30% of patients resistant to medical treatment. Temporal lobe epilepsy, a common cause of medically refractory epilepsy, is often caused by hippocampal sclerosis (HS). HS can be divided further by subtype, as defined by the International League Against Epilepsy (ILAE). Type 1 HS, the most prevalent form (60%‐80% of all cases), is characterized by cell loss and gliosis predominantly in the subfields cornu ammonis (CA1) and CA4. Type 2 HS features cell loss and gliosis primarily in the CA1 sector, and type 3 HS features cell loss and gliosis predominantly in the CA4 subfield. This literature review evaluates studies on hippocampal subfields, exploring whether observable atrophy patterns from in vivo and ex vivo magnetic resonance imaging (MRI) scans correlate with histopathological examinations with manual or automated segmentation techniques. Our findings suggest only ex vivo 1.5 Tesla (T) or 3T MRI with manual segmentation or in vivo 7T MRI with manual or automated segmentations can consistently correlate subfield patterns with histopathologically derived ILAE‐HS subtypes. In conclusion, manual and automated segmentation methods offer advantages and limitations in diagnosing ILAE‐HS subtypes, with ongoing research crucial for refining hippocampal subfield segmentation techniques and enhancing clinical applicability. [ABSTRACT FROM AUTHOR]

Objective: To predict one‐year seizure freedom, using a combination of relevant clinical variables, following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a series of 101 patients. Methods: Eight predictors of seizure freedom were selected based on their association with medial temporal lobe epilepsy: (1) MRI evidence of mesial temporal sclerosis (MTS); (2) unitemporal interictal epileptiform discharges; (3) absence of generalized tonic–clonic seizures; (4) history of febrile seizures; (5) onset of epilepsy ≤16 years; (6) absence of an auditory, visual, or vertiginous aura; and (7) unitemporal ictal onset; (8) unitemporal PET hypometabolism. We compared four multivariate models: "MTS," using just evidence of MTS; "FULL," using all eight binary predictors; "AIC" using backwards selection of variables; and "SCORE," using a 0‐to‐8‐point ordinal score awarding one point for each binary predictor. Results: In univariate analysis, significant predictors for seizure freedom were evidence of mesial temporal sclerosis (p = 0.011, Fisher exact) and unitemporal interictal discharges (p = 0.005). For multivariate prediction (using leave one‐out cross‐validation), the ordinal SCORE model had a significantly higher area under the curve (AUC 0.70) than the other three models: MTS (AUC 0.54, p = 0.002, Delong's test), FULL (AUC 0.62, p = 0.003), or AIC (AUC 0.53, p < 0.001). Interpretation: An ordinal score incorporating eight independent binary clinical variables predicted seizure freedom better on novel data than a model using MTS alone, a full multivariate model, or a backwards selected model. The ordinal score model represents a simple clinical heuristic to identify which patients should be offered minimally invasive laser surgery. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate whether alterations in white matter topological networks are associated with focal to bilateral tonic–clonic seizures (FBTCS) in temporal lobe epilepsy (TLE). Additionally, we investigated the variables contributing to memory impairment in TLE. Methods: This cross‐sectional study included 88 unilateral people with TLE (45 left/43 right), and 42 healthy controls. Graph theory analysis was employed to compare the FBTCS (+) group (n = 51) with the FBTCS (−) group (n = 37). The FBTCS (+) group was subcategorized into current‐FBTCS (n = 31) and remote‐FBTCS (n = 20), based on the history of FBTCS within 1 year or longer than 1 year before scanning, respectively. We evaluated the discriminatory power of topological network properties by receiver operating characteristic (ROC) analysis. Generalized linear models (GLMs) were employed to investigate variables associated with memory impairment in TLE. Results: Global efficiency (Eg) was significantly reduced in the FBTCS (+) group, especially in the current‐FBTCS subgroup. Greater disruption of regional properties in the ipsilateral occipital and temporal association cortices was observed in the FBTCS (+) group. ROC analysis revealed that Eg, normalized characteristic shortest path length, and nodal efficiency of the ipsilateral middle temporal gyrus could distinguish between FBTCS (+) and FBTCS (−) groups. Additionally, GLMs linked the occurrence of current FBTCS with poorer verbal memory outcomes in TLE. Interpretation: Our study suggests that abnormal networks could be the structural basis of seizure propagation in FBTCS. Strategies aimed at reducing the occurrence of FBTCS could potentially improve the memory outcomes in people with TLE. [ABSTRACT FROM AUTHOR]

Objective: Anterior temporal lobe resection (ATLR) effectively controls seizures in medically refractory temporal lobe epilepsy but risks significant episodic memory decline. Beyond 1 year postoperatively, the influence of preoperative clinical factors on episodic memory and long‐term network plasticity remain underexplored. Ten years post‐ATLR, we aimed to determine biomarkers of successful memory network reorganization and establish presurgical features' lasting impact on memory function. Methods: Twenty‐five ATLR patients (12 left‐sided) and 10 healthy controls underwent a memory‐encoding functional magnetic resonance imaging paradigm alongside neuropsychometry 10 years postsurgery. Generalized psychophysiological interaction analyses modeled network functional connectivity of words/faces remembered, seeding from the medial temporal lobes (MTLs). Differences in successful memory connectivity were assessed between controls and left/right ATLR. Multivariate regressions and mixed‐effect models probed preoperative phenotypes' effects on long‐term memory outcomes. Results: Ten years post‐ATLR, lower baseline functioning (verbal and performance intelligence quotient) and a focal memory impairment preoperatively predicted worse long‐term memory outcomes. Poorer verbal memory was significantly associated with longer epilepsy duration and earlier onset age. Relative to controls, successful word and face encoding involved increased functional connectivity from both or remnant MTL seeds and contralesional parahippocampus/hippocampus after left/right ATLR. Irrespective of surgical laterality, successful memory encoding correlated with increased MTL‐seeded connectivity to frontal (bilateral insula, right anterior cingulate), right parahippocampal, and bilateral fusiform gyri. Ten years postsurgery, better memory performance was correlated with contralateral frontal plasticity, which was disrupted with longer epilepsy duration. Significance: Our findings underscore the enduring nature of functional network reorganizations to provide long‐term cognitive support. Ten years post‐ATLR, successful memory formation featured stronger connections near resected areas and contralateral regions. Preoperative network disruption possibly influenced effectiveness of postoperative plasticity. These findings are crucial for enhancing long‐term memory prediction and strategies for lasting memory rehabilitation. [ABSTRACT FROM AUTHOR]

Objective: To discuss the ameliorative effect of a novel antiepileptic drug Q808 on neuronal injury in temporal lobe epilepsy (TLE) rats, and to clarify its mechanism of action. Methods: TLE rat model was prepared by intraperitoneal injection of the innovative antiepileptic drug candidate 6- (4-chlorophenoxy) - tetrazolo (5, 1-a) phthalazine (Q808). Forty-five successfully modeled rats were randomly divided into model group, low dose of Q808 group, and high dose of Q808 group, and there were 15 rats in each group. The rats in low dose of Q808 group and high dose of Q808 group were gavaged with 20 and 80 mg·kg-1 Q808, respectively, and the rats in model group were gavaged with an equal amount of 0. 3% sodium carboxymethyl cellulose. Another 15 healthy SD rats were selected as control group. After 4 weeks of continuous gavage treatment, the morphology of the rats in varioius groups was observed; PONEMAH 6. X experimental animal telemetry platform was used to record the electroencephalogram of the rats in various groups; Golgi staining was used to observe the morphology of dendritic and dendritic spine density of hippocampal CA1 neurons of the rats in various groups; Western blotting method was used to detect the expression levels of synaptic plasticity-specific protein calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) in hippocampus tissue of the rats in various groups. Results: The rats in control group showed normal activity without convulsions or other abnormal manifestations. The rats in model group, low dose of Q808 group, and high dose of Q808 group showed varying degrees of reduced activity, trembling and nodding, loss of balance, muscle rigidity and forelimb convulsions, gradually transforming into whole-body muscle rigidity and standing, followed by falling backwards, and there were no convulsions during the interictal period. Compared with control group, the total durations of epileptic seizures of the rats in model group, low dose of Q808 group, and high dose of Q808 group were significantly prolonged (P<0. 01). Compared with model group, the total durations of epileptic seizures in low dose of Q808 group and high dose of Q808 group were significantly shortened (P<0. 01). The hippocampal CA1 neurons of the rats in control group showed regular distribution of dendrites with dense and orderly dendritic networks. The hippocampal CA1 neurons of the rats in model group showed disordered arrangement of dendrites with massive dendritic entanglement, forming thicker nerve fiber bundles. Compared with model group, the dendritic networks of hippocampal CA1 neurons of the rats in low dose of Q808 group and high dose of Q808 group were partially recovered with relatively regular arrangement. Compared with control group, the dendritic spine density of hippocampal CA1 neurons of the rats in model group was significantly decreased (P<0. 01). Compared with model group, the dendritic spine densities of hippocampal CA1 neurons in low dose of Q808 group and high dose of Q808 group significantly increased (P<0. 01). Compared with control group, the expression levels of CaMKⅡ protein in hippocampus tissue of the rats in model group, low dose of Q808 group, and high dose of Q808 group were significantly decreased (P< 0. 01). Compared with model group, the expression levels of CaMKⅡ protein in hippocampus tissue of the rats in low dose of Q808 group and high dose of Q808 group were significantly increased (P<0. 01). Conclusion: The novel antiepileptic drug Q808 has an ameliorating effect on the TLE model rats; its mechanism may be related to Q808's ability to reduce the dendritic lesions in hippocampal CA1 neurons and increase the expression level of synaptic plasticity-related protein CaMKⅡ protein. [ABSTRACT FROM AUTHOR]

The global health concern of pharmacoresistant epilepsy necessitates innovative therapeutic strategies. Drug resistance often arises due to complex pharmacokinetic challenges. Beta-cyclodextrin, known for enhancing drug solubility and stability, offers a potential solution for improving the efficacy of antiseizure medications. This study aims to investigate the impact of beta-cyclodextrin-complexed rufinamide on seizure-like activity using an in vitro model of temporal lobe epilepsy. Seizure-like neuronal activity was induced using a low-magnesium model. Local field potentials were recorded from transverse rat hippocampal slices. Rufinamide was solubilized using beta-cyclodextrin and administered at 100 micromolar concentration. The impact on various seizure-like parameters and time-resolved phase-amplitude coupling was assessed. Rufinamide increased the duration of the preictal phase while reducing the duration of ictal and postictal phases. The frequency of seizure-like events was higher in rufinamide. No significant change was observed in the firing rate of the first 10 ictal spikes, but the firing frequency of the second set of 10 ictal spikes was higher during rufinamide perfusion. Time-resolved phase-amplitude coupling maximum analysis did not reveal significant differences between the control and rufinamide treatment. Beta-cyclodextrin-solubilized rufinamide significantly modulates seizure-like event dynamics, exhibiting both anticonvulsant and proconvulsant effects. While the compound shortened seizure-like activity, it increased the frequency of seizure-like events. Our observations suggest a need for further investigation into the solubilization method and its impact on rufinamide's bioavailability. Dose-dependent effects and underlying molecular mechanisms should also be explored to enhance the pharmacological properties of antiseizure medications. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate mesial temporal lobe abnormalities in mesial temporal lobe epilepsy (MTLE) patients with hypersynchronous (HYP) and low‐voltage fast rhythms (LVF) onset identified by stereotactic electroencephalography (SEEG) and evaluate their diagnostic and prognostic value. Methods: Fifty‐one MTLE patients were categorized as HYP or LVF by SEEG. High‐resolution MRI volume‐based analysis and 18F‐FDG‐PET standard uptake values of hippocampal and amygdala subfields were quantified and compared with 57 matched controls. Further analyses were conducted to delineate the distinct pathological characteristics differentiating the two groups. Diagnostic and prognostic prediction performance of these biomarkers were assessed using receiver operating characteristic curves. Results: LVF‐onset individuals demonstrated ipsilateral amygdala enlargement (p = 0.048) and contralateral hippocampus hypermetabolism (p = 0.042), pathological results often accompany abnormalities in the temporal lobe cortex, while HYP‐onset subjects had significant atrophy (p < 0.001) and hypometabolism (p = 0.013) in ipsilateral hippocampus and its subfields, as well as amygdala atrophy (p < 0.001), pathological results are highly correlated with hippocampal sclerosis. Severe fimbria atrophy was observed in cases of HYP‐onset MTLE with poor prognosis (AUC = 0.874). Conclusion: Individuals with different seizure‐onset patterns display specific morphological and metabolic abnormalities in the amygdala and hippocampus. Identifying these subfield abnormalities can improve diagnostic and prognostic precision, guiding surgical strategies for MTLE. [ABSTRACT FROM AUTHOR]

Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p < 0.001, Duncan's new multiple range test) and their total duration (p < 0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p < 0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest that cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose. [ABSTRACT FROM AUTHOR]

Aim: Temporal lobe epilepsy surgery is the most common type of epilepsy surgery. This study evaluates the relationship between preoperative auras and surgical prognosis. Materials and Methods: The follow-up data of 100 patients who underwent anterior temporal lobectomy surgery after 2 years was reviewed. The patients were divided into two groups based on the presence or absence of abdominal-emotional (AE) aura. Each patient was evaluated with a detailed history, video-electroencephalography (EEG), neuroimaging, and postsurgical outcomes according to Engel classification to predict postsurgical seizure freedom. Results: After 2 years of follow-up, 71 patients were seizure-free. Based on aura types, univariate analysis showed that the age of disease onset and history of febrile convulsion were higher in the AE (+) group (p=0.013, p<0.001). Additionally, MTS was more frequently observed in the MRI, MRS, and pathology results (p= <0.001, p=0.01, p=0.009). No correlation was found between the presence or type of aura and postoperative seizurefree state. Conclusion: Our results showed that the presence or type of aura had no prognostic significance for seizure freedom after TLE surgery. However, further studies with larger patient numbers are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

To present the expression of calsyntenin‐1 (Clstn1) in the brain and investigate the potential mechanism of Clstn1 in lithium–pilocarpine rat seizure models. Thirty‐five male SD adult rats were induced to have seizures by intraperitoneal injection of lithium chloride pilocarpine. Rats exhibiting spontaneous seizures were divided into the epilepsy (EP) group (n = 15), whereas those without seizures were divided into the control group (n = 14). Evaluate the expression of Clstn1 in the temporal lobe of two groups using Western blotting, immunohistochemistry, and immunofluorescence. Additionally, 55 male SD rats were subjected to status epilepticus (SE) using the same induction method. Rats experiencing seizures exceeding Racine's level 4 (n = 48) were randomly divided into three groups: SE, SE + control lentivirus (lentiviral vector expressing green fluorescent protein [LV‐GFP]), and SE + Clstn1‐targeted RNA interference lentivirus (LV‐Clstn1‐RNAi). The LV‐GFP group served as a control for the lentiviral vector, whereas the LV‐Clstn1‐RNAi group received a lentivirus designed to silence Clstn1 expression. These lentiviral treatments were administered via hippocampal stereotactic injection 2 days after SE induction. Seven days after SE, Western blot analysis was performed to evaluate the expression of Clstn1 in the hippocampus and temporal lobe. Meanwhile, we observed the latency of spontaneous seizures and the frequency of spontaneous seizures within 8 weeks among the three groups. The expression of Clstn1 in the cortex and hippocampus of the EP group was significantly increased compared to the control group (p <.05). Immunohistochemistry and immunofluorescence showed that Clstn1 was widely distributed in the cerebral cortex and hippocampus of rats, and colocalization analysis revealed that it was mainly co expressed with neurons in the cytoplasm. Compared with the SE group (11.80 ± 2.17 days) and the SE + GFP group (12.40 ± 1.67 days), there was a statistically significant difference (p <.05) in the latency period of spontaneous seizures (15.14 ± 2.41 days) in the SE + Clstn1 + RNAi group rats. Compared with the SE group (4.60 ± 1.67 times) and the SE + GFP group (4.80 ± 2.05 times), the SE + Clstn1 + RNAi group (2.0 ±.89 times) showed a significant reduction in the frequency of spontaneous seizures within 2 weeks of chronic phase in rats (p <.05). Elevated Clstn1 expression in EP group suggests its role in EP onset. Targeting Clstn1 may be a potential therapeutic approach for EP management. [ABSTRACT FROM AUTHOR]

Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant–antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant–antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups' oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state. [ABSTRACT FROM AUTHOR]

Despite the benefits of anterior temporal lobectomy with amygdalohippocampectomy in patients with temporal lobe epilepsy (TLE), approximately up to 5% may have hemiparesis as its postoperative complication. This paper aims to describe which step/s of the anterior temporal lobectomy with amygdalohippocampectomy have the highest probability of having the greatest decrease in motor evoked potential (MEP) amplitude. This study used a cross-sectional design of obtaining data from TLE patients who underwent anterior temporal lobectomy with amygdalohippocampectomy with transcranial MEP monitoring. Each of the following steps were evaluated for reduction in MEP amplitude: 1) dural opening, 2) opening the inferior horn, 2) vertical temporal lobe resection 3) subpial dissection, 4) temporal lobe stem resection, 5) lateral temporal lobe resection, 6) hippocampal resection, 7) amygdala resection, 8) uncus resection, and 9) dural closure. Nineteen patients were included in the study. Based on the Friedman Test, 1 or more steps had significantly different average MEP amplitude reductions (Friedman = 50.7, P = 0.0001). When compared with baseline (100%, cutoff P = 0.005), hippocampal resection (z = –3.81, P < 0.0001), T1 subpial dissection (z = –3.2, P = 0.0010), uncus resection (z = –3.48, P = 0.0002), temporal stem resection (z = –3.26, P = 0.001), lateral temporal lobe resection (z = –3.13, P = 0.002), and amygdalectomy (–z = –3.37, P = 0.0005) were significantly lower. Of these, hippocampal resection, uncus resection, and amygdalectomy were deemed highly significant. MEP amplitude tends to decrease during amygdala, hippocampal, and uncal resection because of surgical manipulation of anterior choroidal arteries, which can potentially cause hemiparesis. Careful attention should be paid to changes in MEP during these steps. [ABSTRACT FROM AUTHOR]

Background: Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE/HS) is the most common cause of drug-resistant focal seizures and surgical resection is the primary treatment option, with seizure-free rates ranging from 60 to 80%. However, data on postsurgical seizure outcomes in patients ≥ 50 years of age are limited. This study aimed to assess the efficacy and safety of surgery in this age group compared to younger patients. Methods: We performed a retrospective analysis of data from resective surgeries conducted in patients with MTLE/HS between 1990 and 2022. We focused on patients aged ≥ 50 years and compared the surgical safety and efficacy variables between this group and a control group of patients aged < 50 years through a case–control study. Results: Among the 450 MTLE/HS patients who underwent surgery during the inclusion period, 61 (13.6%) were aged ≥ 50 years and matched with 183 younger patients, totaling 244 study participants. The two groups had similar characteristics. At the last follow-up (median 5.7 years), Engel I outcomes were achieved in 80.3% of the older patients and 81.4% of the younger patients, with no significant difference (p = 0.85). Postoperative cognitive and psychiatric outcomes did not differ between the groups. Major complication rates were also comparable, at 3.3% in the older group and 2.7% in the younger group (p = 0.83). The extratemporal ictal abnormalities observed on video-EEG were the only variable that demonstrated a significant association with an unfavorable seizure outcome in the older group (OR 9.3, 95% CI [1.8–47.6], p = 0.005). Conclusions: This study provides grade 3 evidence that resective surgery for MTLE/HS patients aged ≥ 50 years is as effective and safe as it is for younger patients, and thus should be considered as the primary treatment option for drug-resistant cases. [ABSTRACT FROM AUTHOR]

Rodents and human studies indicate that the hippocampus, a brain region necessary for memory processing, responds to noxious stimuli. However, the hippocampus has yet to be considered a key brain region directly involved in the human pain experience. One approach to answer this question is to perform quantitative sensory testing on patients with hippocampal damage--ie, medial temporal lobe epilepsy. Some case studies and case series have performed such tests in a handful of patients with various types of epilepsy and have reported mixed results. Here, we aimed to determine whether mechanical pain sensitivity was altered in patients diagnosed with temporal lobe epilepsy. We first investigated whether mechanical pain sensitivity in patients with temporal lobe epilepsy differs from that of healthy individuals. Next, in patients with temporal lobe epilepsy, we evaluated whether the degree of pain sensitivity is associated with the degree of hippocampal integrity. Structural integrity was based on hippocampal volume, and functional integrity was based on verbal and visuospatial memory scores. Our findings show that patients with temporal lobe epilepsy have lower mechanical pain sensitivity than healthy individuals. Only left hippocampal volume was positively associated with mechanical pain sensitivity--the greater the hippocampal damage, the lower the sensitivity to mechanical pain. Hippocampal measures of functional integrity were not significantly associated with mechanical pain sensitivity, suggesting that the mechanisms of hippocampal pain processing may be different than its memory functions. Future studies are necessary to determine the mechanisms of pain processing in the hippocampus. [ABSTRACT FROM AUTHOR]

Olfactory oscillations may enhance cognitive processing through coupling with beta (β, 15–30 Hz) and gamma (γ, 30–160 Hz) activity in the hippocampus (HPC). We hypothesize that coupling between olfactory bulb (OB) and HPC oscillations is increased by cholinergic activation in control rats and is reduced in kainic‐acid‐treated epileptic rats, a model of temporal lobe epilepsy. OB γ2 (63–100 Hz) power was higher during walking and immobility‐awake (IMM) compared to sleep, while γ1 (30–57 Hz) power was higher during grooming than other behavioral states. Muscarinic cholinergic agonist pilocarpine (25 mg/kg ip) with peripheral muscarinic blockade increased OB power and OB‐HPC coherence at β and γ1 frequency bands. A similar effect was found after physostigmine (0.5 mg/kg ip) but not scopolamine (10 mg/kg ip). Pilocarpine increased bicoherence and cross‐frequency coherence (CFC) between OB slow waves (SW, 1–5 Hz) and hippocampal β, γ1 and γ2 waves, with stronger coherence at CA1 alveus and CA3c than CA1 stratum radiatum. Bicoherence further revealed a nonlinear interaction of β waves in OB with β waves at the CA1‐alveus. Beta and γ1 waves in OB or HPC were segregated at one phase of the OB‐SW, opposite to the phase of γ2 and γ3 (100–160 Hz) waves, suggesting independent temporal processing of β/γ1 versus γ2/γ3 waves. At CA1 radiatum, kainic‐acid‐treated epileptic rats compared to control rats showed decreased theta power, theta‐β and theta‐γ2 CFC during baseline walking, decreased CFC of HPC SW with γ2 and γ3 waves during baseline IMM, and decreased coupling of OB SW with β and γ2 waves at CA1 alveus after pilocarpine. It is concluded that β and γ waves in the OB and HPC are modulated by a slow respiratory rhythm, in a cholinergic and behavior‐dependent manner, and OB‐HPC functional connectivity at β and γ frequencies may enhance cognitive functions. [ABSTRACT FROM AUTHOR]

The ability of the Auditory Verbal Learning Test (AVLT) to lateralize hippocampal sclerosis (HS) in mesial temporal lobe epilepsy (MTLE) was explored in a sample of 50 patients with MTLE-HS (23 right and 27 left). Patients' AVLT scores were adjusted to the demographic characteristics of each individual in accordance with the Portuguese normative data. The laterality of the HS was determined by consensus by two neuroradiologists. ROC curves were used to identify the best AVLT cutoff scores to differentiate right vs. left HS. Diagnostic statistics were applied to different AVLT measures. The study results revealed that four AVLT scores can correctly classify the laterality of HS in the total sample and a sub-group of 39 right-handed patients (Edinburgh Laterality Inventory +100): delayed recall trial (76 and 80%, respectively), delayed recognition trial (64 and 67%, respectively), learning over trials index (64 and 74%, respectively), and long-term percent retention index (68 and 72%, respectively). In right-handed patients, the diagnostic capability of the delayed recall trial was improved by pairing it with the learning over trials index (accuracy of 85%). In sum, AVLT measures of verbal memory differentiate left from right HS in MTLE. The delayed recall trial demonstrated good diagnostic capacity. [ABSTRACT FROM AUTHOR]

Background Multiple hippocampal transection (MHT) is a surgical technique used for the treatment of drug-resistant mesial temporal lobe epilepsy in situations where standard procedures would pose a high risk for memory deterioration. During MHT, the longitudinal fibers of the hippocampus, implicated in epilepsy spreading, are interrupted, while the transverse memory circuits are spared. The extent of MHT is governed by intraoperative electrocorticography; abolition of epileptic discharges serves as an end point to terminate the transection. In other words, the aim of MHT is not the anatomical completeness of hippocampal transection. In contrast, we hypothesize that only the complete transection of hippocampal cross-section is needed to durably terminate epilepsy, avoiding possible postoperative reorganization of longitudinal pathways. Here, we report an anatomical study designed to evaluate the feasibility of complete transection of hippocampus with the aid of ultrasound neuronavigation and we propose new instruments to reach this goal. Methods Five cadaveric brains were analyzed in this study. MHT was performed on both sides of each brain either with or without ultrasound neuronavigation. The percentage of transected cross-section of the hippocampus was measured using magnetic resonance imaging (MRI) and both sides were compared. Results The ultrasound-guided MHTs were more likely to achieve complete hippocampal transection compared with the nonnavigated MHT transection (73 vs 58%; p < 0.01). Our study also allowed us to propose specialized transectors to minimize invasivity of this procedure. Conclusion Completeness of MHT can be better reached with the aid of an ultrasound neuronavigation system; modified instruments for this procedure were also designed. [ABSTRACT FROM AUTHOR]

Background: SPG18 is caused by mutations in the endoplasmic reticulum lipid raft associated 2 (ERLIN2) gene. Autosomal recessive (AR) mutations are usually associated with complicated hereditary spastic paraplegia (HSP), while autosomal dominant (AD) mutations use to cause pure SPG18. Aim: To define the variegate clinical spectrum of the SPG18 and to evaluate a dominant negative effect of erlin2 (encoded by ERLIN2) on oligomerization as causing differences between AR and AD phenotypes. Methods: In a four-generation pedigree with an AD pattern, a spastic paraplegia multigene panel test was performed. Oligomerization of erlin2 was analyzed with velocity gradient assay in fibroblasts of the proband and healthy subjects. Results: Despite the common p.V168M mutation identified in ERLIN2, a phenoconversion to amyotrophic lateral sclerosis (ALS) was observed in the second generation, pure HSP in the third generation, and a complicated form with psychomotor delay and epilepsy in the fourth generation. Erlin2 oligomerization was found to be normal. Discussion: We report the first AD SPG18 family with a complicated phenotype, and we ruled out a dominant negative effect of V168M on erlin2 oligomerization. Therefore, our data do not support the hypothesis of a relationship between the mode of inheritance and the phenotype, but confirm the multifaceted nature of SPG18 on both genetic and clinical point of view. Clinicians should be aware of the importance of conducting an in-depth clinical evaluation to unmask all the possible manifestations associated to an only apparently pure SPG18 phenotype. We confirm the genotype–phenotype correlation between V168M and ALS emphasizing the value of close follow-up. [ABSTRACT FROM AUTHOR]

The subiculum is a key region of the brain involved in the initiation of pathological activity in temporal lobe epilepsy, and local GABAergic inhibition is essential to prevent subicular‐originated epileptiform discharges. Subicular pyramidal cells may be easily distinguished into two classes based on their different firing patterns. Here, we have compared the strength of the GABAa receptor‐mediated inhibitory postsynaptic currents received by regular‐ vs. burst‐firing subicular neurons and their dynamic modulation by the activation of μ opioid receptors. We have taken advantage of the sequential re‐patching of the same cell to initially classify pyramidal neurons according to their firing patters, and then to measure GABAergic events triggered by the optogenetic stimulation of parvalbumin‐ and somatostatin‐expressing interneurons. Activation of parvalbumin‐expressing cells generated larger responses in postsynaptic burst‐firing neurons whereas the opposite was observed for currents evoked by the stimulation of somatostatin‐expressing interneurons. In all cases, events depended critically on ω‐agatoxin IVA‐ but not on ω‐conotoxin GVIA‐sensitive calcium channels. Optogenetic GABAergic input originating from both parvalbumin‐ and somatostatin‐expressing cells was reduced in amplitude following the exposure to a μ opioid receptor agonist. The kinetics of this pharmacological sensitivity was different in regular‐ vs. burst‐firing neurons, but only when responses were evoked by the activation of parvalbumin‐expressing neurons, whereas no differences were observed when somatostatin‐expressing cells were stimulated. In conclusion, our results show that a high degree of complexity regulates the organizing principles of subicular GABAergic inhibition, with the interaction of pre‐ and postsynaptic diversity at multiple levels. Key points: Optogenetic stimulation of parvalbumin‐ and somatostatin‐expressing interneurons (PVs and SOMs) triggers inhibitory postsynaptic currents (IPSCs) in both regular‐ and burst‐firing (RFs and BFs) subicular pyramidal cells.The amplitude of optogenetically evoked IPSCs from PVs (PV‐opto IPSCs) is larger in BFs whereas IPSCs generated by the light activation of SOMs (SOM‐opto IPSCs) are larger in RFs.Both PV‐ and SOM‐opto IPSCs critically depend on ω‐agatoxin IVA‐sensitive P/Q type voltage‐gated calcium channels, whereas no major effects are observed following exposure to ω‐conotoxin GVIA, suggesting no significant involvement of N‐type channels.The amplitude of both PV‐ and SOM‐opto IPSCs is reduced by the probable pharmacological activation of presynaptic μ opioid receptors, with a faster kinetics of the effect observed in PV‐opto IPSCs from RFs vs. BFs, but not in SOM‐opto IPSCs.These results help us understand the complex interactions between different layers of diversity regulating GABAergic input onto subicular microcircuits. [ABSTRACT FROM AUTHOR]

[Display omitted] • Alox5 deficiency in neuron alleviates seizure activity and epileptogenesis. • Neuronal Alox5 deletion reverses neuron loss and astrogliosis. • The development of comorbidities in the chronic phase of epilepsy was alleviated by Alox5 deletion. • Anti-epileptic effect of neuronal Alox5 deletion may be linked with reducing glutamate. • The identification of Alox5 as a potential therapeutic target suggests its promising role in the management of epilepsy. Our previous work reveals a critical role of activation of neuronal Alox5 in exacerbating brain injury post seizures. However, whether neuronal Alox5 impacts the pathological process of epilepsy remains unknown. To prove the feasibility of neuron-specific deletion of Alox5 via CRISPR-Cas9 in the blockade of seizure onset and epileptic progression. Here, we employed a Clustered regularly interspaced short-palindromic repeat-associated proteins 9 system (CRISPR/Cas9) system delivered by adeno-associated virus (AAV) to specifically delete neuronal Alox5 gene in the hippocampus to explore its therapeutic potential in various epilepsy mouse models and possible mechanisms. Neuronal depletion of Alox5 was successfully achieved in the brain. AAV delivery of single guide RNA of Alox5 in hippocampus resulted in reducing seizure severity, delaying epileptic progression and improving epilepsy-associated neuropsychiatric comorbidities especially anxiety, cognitive deficit and autistic-like behaviors in pilocarpine- and kainic acid-induced temporal lobe epilepsy (TLE) models. In addition, neuronal Alox5 deletion also reversed neuron loss, neurodegeneration, astrogliosis and mossy fiber sprouting in TLE model. Moreover, a battery of tests including analysis of routine blood test, hepatic function, renal function, routine urine test and inflammatory factors demonstrated no noticeable toxic effect, suggesting that Alox5 deletion possesses the satisfactory biosafety. Mechanistically, the anti-epileptic effect of Alox5 deletion might be associated with reduction of glutamate level to restore excitatory/inhibitory balance by reducing CAMKII-mediated phosphorylation of Syn ISer603. Our findings showed the translational potential of AAV-mediated delivery of CRISPR-Cas9 system including neuronal Alox5 gene for an alternative promising therapeutic approach to treat epilepsy. [ABSTRACT FROM AUTHOR]

Objective To explore the approach to establish a temporal lobe epilepsy model via intraperitoneal pilocarpine injection in C57BL/6J mice, and to summarize behavioral indicators predicting successful modeling during the acute phase of epileptic seizures after pilocarpine administration, aiming to offer a practical mice model for future epilepsy research.MethodsThirty C57BL/6J substrain mice (primary subjects) and forty C57BL/6N substrain mice (control subjects) were selected to establish a temporal lobe epilepsy model by inducing seizures through a single intraperitoneal injection of pilocarpine. The mice from the two substrains were each divided into 3 groups, and were injected intraperitoneally with 300 mg/kg, 330 mg/kg, or 360 mg/kg of pilocarpine, respectively. Motor seizure behaviors were observed and compared between the two substrains of C57BL/6 mice post pilocarpine injection, and the spontaneous recurrent seizures (SRS) were continuously monitored from the 7th day after injection. On the 28th day post-injection, the mice were euthanized and the histopathological changes in their hippocampi were examined. ResultsAfter pilocarpine administration, C57BL/6N mice displayed characteristic motor seizures followed by the onset of status epilepticus (SE). Conversely, C57BL/6J mice showed fewer instances of typical motor seizure behavior and the subsequent SE. Instead, they more often exhibited systemic tremors lasting several seconds to tens of seconds following limb twitching. This behavior is classified as “severe seizure (SS)” in current study. Following intraperitoneal injection of 330 mg/kg and 360 mg/kg pilocarpine, C57BL/6J mice displaying SS during the acute phase of seizure might exhibit SRS after a latency period. The percentage of spontaneous seizures observed in C57BL/6J mice post-modeling (70%) was comparable to that seen in C57BL/6N mice (75%) which developed SRS subsequent to SE. C57BL/6J mice displayed characteristic pathological alterations associated with temporal lobe epilepsy in the hippocampi after 28 d following pilocarpine injection, including increased mossy fiber sprouting and neuronal death. ConclusionsWhen inducing an epilepsy model via intraperitoneal pilocarpine injection in C57BL/6J mice, the behavioral criteria to predict the successful establishment of the model could be either the occurrence of SE or the manifestation of SS.

Abstract Transient global amnesia (TGA) is characterized by sudden and temporary memory impairment, while transient epileptic amnesia (TEA) represents amnestic attacks as the main manifestation of focal epilepsy with presumed temporal origin. We present a 48‐year‐old patient who experienced transient amnesia 10 weeks after right selective amygdalo‐hippocampectomy for right temporal lobe epilepsy. Despite TEA being a plausible explanation for amnesia in patients with temporal lobe epilepsy, no epileptiform discharges were found during the amnestic episode and key features indicative of TGA, including long duration, isolated occurrence, and dense anterograde amnesia of the episode, argued against a diagnosis of TEA in this case. Notably, the patient has remained seizure‐free (now 4,5 years) and stopped taking antiseizure medication 32 months after surgery. Although TGA clinical criteria formally exclude patients with recent active epilepsy, neurologists should be aware that TGA can occur after epilepsy surgery in the temporal lobe. Therefore, we consider it of high clinical relevance to establish a careful differential diagnosis between TGA and epileptic amnestic attacks after epilepsy surgery to avoid unnecessary reintroduction or continuation of antiseizure medication. Additionally, this case presents the first comparison of detailed neuropsychological test results before and after a presumed TGA episode, revealing a complete recovery of anterograde memory functions within 1 day. Plain Language Summary A 48‐year‐old patient experienced an episode of transient amnesia 10 weeks after epilepsy surgery. Given the patient's history, an epileptic origin of the episode initially seemed likely. However, tests revealed no seizure activity during the episode and the characteristics matched a condition called transient global amnesia. This case highlights the importance of correctly diagnosing memory impairments after epilepsy surgery to prevent unnecessary treatment.

Abstract Background Temporal lobe epilepsy (TLE) is among the most common types of epilepsy and often leads to cognitive, emotional, and psychiatric issues due to the frequent seizures. A notable pathological change related to TLE is hippocampal sclerosis (HS), which is characterized by neuronal loss, gliosis, and an increased neuron fibre density. The mechanisms underlying TLE-HS development remain unclear, but the reactive transcriptomic changes in glial cells and neurons of the hippocampus post-epileptogenesis may provide insights. Methods To induce TLE, 200 nl of kainic acid (KA) was stereotactically injected into the hippocampal CA1 region of mice, followed by a 7-day postinjection period. Single-cell RNA sequencing (ScRNA-seq), single-nucleus RNA sequencing (SnRNA-seq), and Xenium-based spatial transcriptomics analyses were employed to evaluate the changes in mRNA expression in glial cells and neurons. Results From the ScRNA-seq and SnRNA-seq data, 31,390 glial cells and 48,221 neuronal nuclei were identified. Analysis of the differentially expressed genes (DEGs) revealed significant transcriptomic alterations in the hippocampal cells of mice with TLE, affecting hundreds to thousands of mRNAs and their signalling pathways. Enrichment analysis indicated notable activation of stress and inflammatory pathways in the TLE hippocampus, while pathways related to axonal development and neural support were suppressed. Xenium analysis demonstrated the expression of all 247 genes across mouse brain sections, revealing the spatial distributions of their expression in 27 cell types. Integrated analysis of the DEGs identified via the three sequencing techniques revealed that Spp1, Trem2, and Cd68 were upregulated in all glial cell types and in the Xenium data; Penk, Sorcs3, and Plekha2 were upregulated in all neuronal cell types and in the Xenium data; and Tle4 and Sipa1l3 were downregulated in all glial cell types and in the Xenium data. Conclusion In this study, a high-resolution single-cell transcriptomic atlas of the hippocampus in mice with TLE was established, revealing potential intrinsic mechanisms driving TLE-associated inflammatory activation and altered cell interactions. These findings provide valuable insights for further exploration of HS development and epileptogenesis.

Abstract Among patients with epilepsy, 30–40% experience recurrent seizures even after adequate antiseizure medications therapies, making them refractory. The early identification of refractory epilepsy is important to provide timely surgical treatment for these patients. In this study, we analyze interictal electroencephalography (EEG) data to predict drug refractoriness in patients with temporal lobe epilepsy (TLE) who were treated with monotherapy at the time of the first EEG acquisition. Various EEG features were extracted, including statistical measurements and interchannel coherence. Feature selection was performed to identify the optimal features, and classification was conducted using different classifiers. Functional connectivity and graph theory measurements were calculated to identify characteristics of refractory TLE. Among the 48 participants, 34 (70.8%) were responsive, while 14 (29.2%) were refractory over a mean follow-up duration of 38.5 months. Coherence feature within the gamma frequency band exhibited the most favorable performance. The light gradient boosting model, employing the mutual information filter-based feature selection method, demonstrated the highest performance (AUROC = 0.821). Compared to the responsive group, interchannel coherence displayed higher values in the refractory group. Interestingly, graph theory measurements using EEG coherence exhibited higher values in the refractory group than in the responsive group. Our study has demonstrated a promising method for the early identification of refractory TLE utilizing machine learning algorithms.

Background: The solute carrier (SLC) superfamily, which transports solutes across biological membranes, includes four members (SLC2A1, SLC6A1, SLC9A64, and SLC35A2) that have been linked to epilepsy. This study sought to examine the DNA methylation patterns near the promoters of these genes in temporal lobe epilepsy (TLE), as DNA methylation is a crucial epigenetic modification that can impact gene expression. Methods: The study comprised 38 individuals with TLE and 38 healthy controls. Methylation experiments were performed using peripheral blood, while demethylation experiments were carried out using SH-SY5Y cells with the DNA methylation inhibitor decitabine. Results: A significant difference was observed in the DNA methylation rate of SLC6A1 between TLE patients and controls, with TLE patients showing a lower rate (4.81% vs. 5.77%, p = 0.0000), which remained significant even after Bonferroni correction (p = 0.0000). Based on the hypomethylated SLC6A1 in TLE, a predictive model was established that showed promise in distinguishing and calibrating TLE. In the TLE group, there were differences in DNA methylation rates of SLC6A1 between the young patients and the older controls (4.42% vs. 5.22%, p = 0.0004). A similar trend (p = 0.0436) was noted after adjusting for sex, age at onset, and drug response. In addition, the study found that DNA methylation had a silencing impact on the expression of the SLC6A1 gene in SH-SY5Y cells, which were treated with decitabine at a set dose gradient. Conclusions: The evidence suggests that lower methylation of SLC6A1 may stimulate transcription in TLE, however, further investigation is necessary to confirm the exact mechanism. [ABSTRACT FROM AUTHOR]

Abstract Introduction There remains a critical need for precise localization of the epileptogenic foci in individuals with drug-resistant epilepsy (DRE). 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging can reveal hypometabolic regions during the interval between seizures in patients with epilepsy. However, visual-based qualitative analysis is time-consuming and strongly influenced by physician experience. CortexID Suite is a quantitative analysis software that helps to evaluate PET imaging of the human brain. Therefore, we aimed to evaluate the efficacy of CortexID quantitative analysis in the localization of the epileptogenic zone in patients with temporal lobe epilepsy (TLE). Methods A total of 102 patients with epilepsy who underwent 18F-FDG-PET examinations were included in this retrospective study. The PET visual analysis was interpreted by two nuclear medicine physicians, and the quantitative analysis was performed automatically using CortexID analysis software. The assumed epileptogenic zone was evaluated comprehensively by two skilled neurologists in the preoperative assessment of epilepsy. The accuracy of epileptogenic zone localization in PET visual analysis was compared with that in CortexID quantitative analysis. Results The diagnostic threshold for the difference in the metabolic Z-score between the right and left sides of medial temporal lobe epilepsy (MTLE) was calculated as 0.87, and that for lateral temporal lobe epilepsy (LTLE) was 2.175. In patients with MTLE, the area under the curve (AUC) was 0.922 for PET visual analysis, 0.853 for CortexID quantitative analysis, and 0.971 for the combined diagnosis. In patients with LTLE, the AUC was 0.842 for PET visual analysis, 0.831 for CortexID quantitative analysis, and 0.897 for the combined diagnosis. These results indicate that the diagnostic efficacy of CortexID quantitative analysis is not inferior to PET visual analysis (p > 0.05), while combined analysis significantly increases diagnostic efficacy (p

Abstract Backgroud Temporal lobe epilepsy (TLE) is associated with abnormal dynamic functional connectivity patterns, but the dynamic changes in brain activity at each time point remain unclear, as does the potential molecular mechanisms associated with the dynamic temporal characteristics of TLE. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 84 TLE patients and 35 healthy controls (HCs). The data was then used to conduct HMM analysis on rs-fMRI data from TLE patients and an HC group in order to explore the intricate temporal dynamics of brain activity in TLE patients with cognitive impairment (TLE-CI). Additionally, we aim to examine the gene expression profiles associated with the dynamic modular characteristics in TLE patients using the Allen Human Brain Atlas (AHBA) database. Results Five HMM states were identified in this study. Compared with HCs, TLE and TLE-CI patients exhibited distinct changes in dynamics, including fractional occupancy, lifetimes, mean dwell time and switch rate. Furthermore, transition probability across HMM states were significantly different between TLE and TLE-CI patients (p

Abstract Objective This study investigates the association of Body Mass Index (BMI) and age of epilepsy onset, in patients with epilepsy associated with temporal encephaloceles (TEs). Methods A comprehensive PubMed literature review was conducted using the keywords “temporal encephaloceles” and “epilepsy” for identifying articles for the analysis. Inclusion criteria encompassed all evidence levels reporting patients with TE-related epilepsy and documented BMI. Logistic regression analyses were performed to examine the effect of BMI on predicting epilepsy onset after the 25th year of age. Spearman’s correlation assessed the relationship between BMI with epilepsy onset. Finally, the association between BMI and postsurgical outcomes, distinguishing between more favourable outcomes (Engel Class I and II) and less favourable outcomes (Engell Class III and IV) was explored. Results Of the initially identified 88 articles, nine were included in the analysis, involving 127 patients with TE-related epilepsy and reported BMI. The mean age of epilepsy onset was 24.9 years (SD = 14.8 years), with a mean BMI of 28.0 kg/m2 (SD = 7.4 kg/m2). A significant positive correlation was observed between BMI and age of epilepsy onset (rho = 0.448, p

Objective: Pharmacoresistant epilepsy represents a significant global health challenge, necessitating novel therapeutic approaches. Despite advances in antiseizure medications, many patients remain treatment-resistant partially due to complex pharmacokinetic issues. Beta-cyclodextrin, known for enhancing drug solubility and stability, offers potential solutions by forming inclusion complexes, thereby improving anti-seizure medication’s efficacy. This study aimed to investigate the effect of beta-cyclodextrin and beta-cyclodextrin-complexed carbamazepine on epileptiform activities, using an in vitro model of temporal lobe epilepsy.

Abstract Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein–protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS.

Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures. Here, we characterize the involvement of the substantia nigra (SN) and somatosensory cortex (SI) during temporal lobe (TL) seizures induced by penicillin injection in the hippocampus (HPC) of two nonhuman primates. The seizure onset and offset patterns were manually classified and spectral power and coherence were calculated. We then compared the 3-second segments recorded in pre-ictal, onset, offset and post-ictal periods based on the seizure onset and offset patterns. Our results demonstrated an involvement of the SN and SI dependent on the seizure onset and offset pattern. We found that low amplitude fast activity (LAF) and high amplitude slow activity (HAS) onset patterns were associated with an increase in activity of the SN while the change in activity was limited to LAF seizures in the SI. However, the increase in HPC/SN coherence was specific to the farther-spreading LAF onset pattern. As for the role of the SN in seizure cessation, we observed that the coherence between the HPC/SN was reduced during burst suppression (BS) compared to other termination phases. Additionally, we found that this coherence returned to normal levels after the seizure ended, with no significant difference in post-ictal periods among the three types of seizure offsets. This study constitutes the first demonstration of TL seizures entraining the SN in the primate brain. Moreover, these findings provide evidence that this entrainment is dependent on the onset and offset pattern and support the hypothesis that the SN might play a role in the maintenance and termination of some specific temporal lobe seizure. [ABSTRACT FROM AUTHOR]

Electrical neurostimulation is currently used to manage epilepsy, but the most effective approach for minimizing seizure occurrence is uncertain. While functional MRI (fMRI) can reveal which brain areas are affected by stimulation, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. In this study, we utilized the intrahippocampal kainatemousemodel ofmesial temporal lobe epilepsy (mTLE) to systematically examine the brain-wide responses to electrical stimulation using fMRI. We compared fMRI responses of saline-injected controls and epileptic mice during stimulation in the septal hippocampus (HC) at 10Hz and demonstrated the effects of different stimulation amplitudes (80-230 µA) and frequencies (1-100Hz) in epileptic mice. Motivated by recent studies exploring 1Hz stimulation to prevent epileptic seizures, we furthermore investigated the effect of prolonged 1Hz stimulation with fMRI. Compared to sham controls, epileptic mice showed less propagation to the contralateral HC, but significantly stronger responses in the ipsilateral HC and a wider spread to the entorhinal cortex and septal region. Varying the stimulation amplitude had little effect on the resulting activation patterns, whereas the stimulation frequency represented the key parameter and determined whether the induced activation remained local or spread from the hippocampal formation into cortical areas. Prolonged stimulation of epileptic mice at 1Hz caused a slight reduction in local excitability. In this way, our study contributes to a better understanding of these stimulation paradigms. [ABSTRACT FROM AUTHOR]

Background: There is a lack of further exploration of the epileptogenic network of specific types of epilepsy, such as unilateral hippocampal sclerosis (HS), and there is an urgent need to find exact evidence to confirm the consistency of its brain network changes. Methods: We enrolled 22 mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) patients to compare the differences in brain activity between 22 healthy controls (HCs) and them. Resting-state electroencephalography (EEG) was also measured. Then, we calculated the power spectral density and phase locking values in and between these electrodes. Results: The results showed the increased theta power was related to the high severity of epilepsy in the temporal, parietal, and central regions in mTLE-HS patients, and there were positive correlations between theta power in the contralateral temporal region and seizure frequency. Theta power in the ipsilateral parietal lobe is positively correlated with the number of anti-seizure medications (ASMs), but not with the usage of third-generation ASMs. Meanwhile, the temporal lobe of mTLE-HS patients had more connectivity with parietal lobe and central region. Conclusions: Theta power is an important EEG indicator of mTLE-HS, positively correlates with epilepsy severity and seizure frequency, and has network properties that can be observed outside the lesion. Moreover, the usage of third-generation ASMs did not affect the risk of increased theta power. Lastly, the temporoparietal and temporal-central networks are likely to be causative pathways in epilepsy patients with cognitive impairment. This study provides a potential guideline for the treatment of mTLE-HS in clinical practice. [ABSTRACT FROM AUTHOR]

This editorial explores the connection between epilepsy and Alzheimer's disease (AD), focusing on their shared clinical presentations and pathological findings. It discusses cognitive profiles, biomarkers, underlying mechanisms, and treatment implications. The authors present various studies to enhance our understanding of the relationship between epilepsy and AD, with the aim of improving diagnosis and finding effective treatments for cognitive improvement. The document includes declarations of financial support and conflicts of interest, as well as a list of references for further reading. [Extracted from the article]

The network nature of focal epilepsy is exemplified by mesial temporal lobe epilepsy (mTLE), characterized by focal seizures originating from the mesial temporal neocortex, amygdala, and hippocampus. The mTLE network hypothesis is evident in seizure semiology and interictal comorbidities, both reflecting limbic network dysfunction. The network generating seizures also supports essential physiological functions, including memory, emotion, mood, and sleep. Pathology in the mTLE network often manifests as interictal behavioral disturbances and seizures. The limbic circuit is a vital network, and here we review one of the most common focal epilepsies and its comorbidities. We describe two people with drug resistant mTLE implanted with an investigational device enabling continuous hippocampal local field potential sensing and anterior nucleus of thalamus deep brain stimulation (ANT-DBS) who experienced reversible psychosis during continuous high-frequency stimulation. The mechanism(s) of psychosis remain poorly understood and here we speculate that the anti-epileptic effect of high frequency ANT-DBS may provide insights into the physiology of primary disorders associated with psychosis. [ABSTRACT FROM AUTHOR]

MR-guided Laser Interstitial Thermal Therapy (MRgLITT) is a minimally invasive neurosurgical technique increasingly used for the treatment of drug-resistant epilepsy and brain tumors. Utilizing near-infrared light energy delivery guided by real-time MRI thermometry, MRgLITT enables precise ablation of targeted brain tissues, resulting in limited corridor-related morbidity and expedited postoperative recovery. Since receiving CE marking in 2018, the adoption of MRgLITT has expanded to more than 40 neurosurgical centers across Europe. In epilepsy treatment, MRgLITT can be applied to various types of focal lesional epilepsy, including mesial temporal lobe epilepsy, hypothalamic hamartoma, focal cortical dysplasias, periventricular heterotopias, cavernous malformations, dysembryoplastic neuroepithelial tumors (DNET), low-grade gliomas, tuberous sclerosis, and in disconnective surgeries. In neuro-oncology, MRgLITT is used for treating newly diagnosed and recurrent primary brain tumors, brain metastases, and radiation necrosis. This comprehensive review presents an overview of the current evidence and technical considerations for the use of MRgLITT in treating various pathologies associated with drug-resistant epilepsy and brain tumors. [ABSTRACT FROM AUTHOR]

Abnormal brain aging is suggested in epilepsy. Given the brain network dysfunction in epilepsy, the white matter tracts, which primarily interconnect brain regions, could be of special importance. We focused on white matter brain aging in diverse forms of epilepsy and comorbid psychosis. We obtained brain diffusion tensor imaging (DTI) data at 3 T-MRI in 257 patients with epilepsy and 429 healthy subjects. The tract-based fractional anisotropy values of the healthy subjects were used to build a brain-age prediction model, and we calculated the brain-predicted age difference (brain-PAD: predicted age—chronological age) of all subjects. As a result, almost all epilepsy categories showed significantly increased brain-PAD (p < 0.001), including temporal lobe epilepsy (TLE) with no MRI-lesion (+ 4.2 yr), TLE with hippocampal sclerosis (+ 9.1 yr), extratemporal focal epilepsy (+ 5.1 yr), epileptic encephalopathy or progressive myoclonus epilepsy (+ 18.4 yr), except for idiopathic generalized epilepsy (IGE). Patients with psychogenic non-epileptic seizures also presented increased brain-PAD. In TLE, interictal psychosis significantly raised brain-PAD by 8.7 years. In conclusion, we observed increased brain aging in most types of epilepsy, which was generally consistent with brain morphological aging results in previous studies. Psychosis may accelerate brain aging in TLE. These findings may suggest abnormal aging mechanisms in epilepsy and comorbid psychotic symptoms. [ABSTRACT FROM AUTHOR]

Backgroud: Temporal lobe epilepsy (TLE) is associated with abnormal dynamic functional connectivity patterns, but the dynamic changes in brain activity at each time point remain unclear, as does the potential molecular mechanisms associated with the dynamic temporal characteristics of TLE. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 84 TLE patients and 35 healthy controls (HCs). The data was then used to conduct HMM analysis on rs-fMRI data from TLE patients and an HC group in order to explore the intricate temporal dynamics of brain activity in TLE patients with cognitive impairment (TLE-CI). Additionally, we aim to examine the gene expression profiles associated with the dynamic modular characteristics in TLE patients using the Allen Human Brain Atlas (AHBA) database. Results: Five HMM states were identified in this study. Compared with HCs, TLE and TLE-CI patients exhibited distinct changes in dynamics, including fractional occupancy, lifetimes, mean dwell time and switch rate. Furthermore, transition probability across HMM states were significantly different between TLE and TLE-CI patients (p < 0.05). The temporal reconfiguration of states in TLE and TLE-CI patients was associated with several brain networks (including the high-order default mode network (DMN), subcortical network (SCN), and cerebellum network (CN). Furthermore, a total of 1580 genes were revealed to be significantly associated with dynamic brain states of TLE, mainly enriched in neuronal signaling and synaptic function. Conclusions: This study provides new insights into characterizing dynamic neural activity in TLE. The brain network dynamics defined by HMM analysis may deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, indicating a linkage between neural configuration and gene expression in TLE. [ABSTRACT FROM AUTHOR]

Background: Previous 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 indepth 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. Methods: Thirty-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. Results: Compared 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. Conclusion: This 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. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine differences in factors influencing quality of life (QOL) in people with extratemporal lobe epilepsy (ETLE) and mesial temporal lobe epilepsy (MTLE). Methods: We obtained data from the medical records of 84 (47 ETLE and 37 MTLE) people with epilepsy. The data included age, sex, employment, seizure frequency, number of antiseizure medication (ASM), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) score, and Quality of Life in Epilepsy Inventory-31 (QOLIE-31) score. Multiple regression analyses were performed using QOLIE-31 as the dependent variable and age, sex, employment, seizure frequency, number of ASM, and NDDI-E score as the independent variables in ETLE or MTLE. Results: From the results of the multiple regression analyses, QOLIE-31 in ETLE was associated with NDDI-E (β = -0.757, p < 0.001) and employment (β = 0.388, p = 0.008). Meanwhile, QOLIE-31 in MTLE was associated with NDDI-E (β = -0.625, p < 0.001), employment (β = 0.396, p = 0.041), and number of ASMs (β = -0.399, p = 0.018). Conclusion: Overall, our findings indicate that the number of ASMs is potentially an influence on QOL of MTLE but similar effect is not observed in ETLE. [ABSTRACT FROM AUTHOR]

Intrinsic plasticity, a fundamental process enabling neurons to modify their intrinsic properties, plays a crucial role in shaping neuronal input‐output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. In this study, a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), is identified as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. PTPRN recruits the NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L) to NaV1.2 sodium channels, facilitating NEDD4L‐mediated ubiquitination, and endocytosis of NaV1.2. Knockout of PTPRN in hippocampal granule cells leads to augmented NaV1.2‐mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno‐associated virus‐mediated delivery of PTPRN in the dentate gyrus region decreases intrinsic excitability and reduces seizure susceptibility. Moreover, the present findings indicate that PTPRN exerts a selective modulation effect on voltage‐gated sodium channels. Collectively, PTPRN plays a significant role in regulating intrinsic excitability and seizure susceptibility, suggesting a potential strategy for precise modulation of NaV1.2 channels' function. [ABSTRACT FROM AUTHOR]

Introduction: Neuropsychological 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. Methods: Neuropsychological 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. Results: There 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. Discussion: The 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. [ABSTRACT FROM AUTHOR]

Introduction: Functional magnetic resonance imaging (fMRI) can be used to assess language and memory function as part of pre-surgical decision making in refractory epilepsy. Although language paradigms are well established, memory paradigms are not widely used in clinical practice due to a lack of evidence for robust and reliable methods. Here, we aim to investigate the clinical utility of the Home Town Walk (HTW) paradigm for personalized treatment decisions in medial temporal lobe epilepsy. Methods: A cohort of 123 consecutive patients having HTW-fMRI as part of routine MRI scans over a 7.5 year period were included in this retrospective study. Of these, 111 patients underwent repeated HTW-fMRI in two scanning sessions one to three days apart. fMRI analysis was performed at the time of the scans using clinically approved software and retrospectively validated using FSL. We assessed the test-retest within subject reliability of activations within the posterior parahippocampal gyri (pPHG) at the individual subject level. Results and discussion: Activations within the pPHG region were observed for 101 patients (91%) in at least one of the fMRI sessions and for 88 patients (79%) in both fMRI sessions, with 82 patients showing overlapping unilateral or bilateral activations and 8 further patients showing overlapping activations in one of the hemispheres but not the other. Reproducibility was evaluated using metrics based on the concordance ratios for size (Rsize) and location (Roverlap) within the pPHG region, as well as the lateralization index (LI) metric to reflect the asymmetry of hemispheric activations, which is of crucial relevance to inform surgery. Test-retest reliability of visuospatial memory LIs, assessed by an intraclass correlation coefficient (ICC) yielded a value of 0.76, indicating excellent between session stability of memory lateralization. Conclusion: The HTW-fMRI paradigm shows reproducible activations in the medial temporal lobes of individual epilepsy patients sufficient to consistently lateralize visuospatial memory function, demonstrating the clinical utility of HTW memory fMRI and its potential for application in the pre-surgical assessment of people with temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Fertility treatment, including assisted reproductive technology (ART), is increasingly used. Sex hormones influence seizure control as well as interacting with antiseizure medications, and so the hormonal manipulation involved in fertility treatments has direct implications for people with epilepsy. Here, we summarise the various fertility treatments and consider their important influences on epilepsy care. While early observations raised concerns about seizure exacerbation associated with ART, there are limited data to guide best practice in people with epilepsy, and further research is needed. [ABSTRACT FROM AUTHOR]

Surgery is a good treatment option for drug-resistant temporal lobe epilepsy (TLE). 2-deoxy-2-(18F) fluoro-D-glucose (FDG) positron emission tomography (PET) is used to detect epileptic foci as hypometabolic lesions in presurgical evaluation. Visual field defects (VFDs) in the contralateral homonymous upper quadrant are common postoperative complications in TLE. This study aimed to quantify VFDs using pattern deviation probability plots (PDPPs) and examine the effect of hypometabolism in FDG-PET on VFDs. This study included 40 patients. Both visual fields were assessed using the Humphrey field analyzer preoperatively and 3 months and 2 years postoperatively. PDPPs with <0.5% confidence level counted in the contralateral homonymous upper quadrant. FDG-PET results were compared between groups with (15 patients) and without (24 patients) hypometabolism in the optic radiation. All 40 patients were evaluated by Humphrey field analyzer at 3 months postoperatively and 39 at 2 years postoperatively. The incidence of VFDs 3 months postoperatively was 35/40 (87.5%), and 17/40 (42.5%) patients had severe VFDs. In cases of surgery on the left temporal lobe, ipsilateral eyes appeared to be more significantly affected than contralateral eyes. VFDs were more severe in patients with FDG hypometabolism than in those without hypometabolism in posteromedial temporal and medial occipital cortex (P < 0.01); however, 85% of patients with FDG hypometabolism had a reduced VFD 2 years postoperatively. PDPP counting is useful for quantifying VFDs. Preoperative dysfunction indicated by preoperative FDG-PET in the posteromedial temporal and medial occipital cortex could enhance VFDs early after TLE surgery. [ABSTRACT FROM AUTHOR]

• P2X7R signaling regulates both glial and neuronal genes during seizures. • P2X7R deficiency in microglia reduces seizure severity and leads to an anti-inflammatory phenotype in microglia during seizures. • P2X7R deficiency in neurons increases seizure severity. • Increased expression of P2X7Rs on GABAergic interneurons reduces seizure severity in acquired and genetic models of epilepsy. The purinergic ATP-gated P2X7 receptor (P2X7R) is increasingly recognized to contribute to pathological neuroinflammation and brain hyperexcitability. P2X7R expression has been shown to be increased in the brain, including both microglia and neurons, in experimental models of epilepsy and patients. To date, the cell type-specific downstream effects of P2X7Rs during seizures remain, however, incompletely understood. Effects of P2X7R signaling on seizures and epilepsy were analyzed in induced seizure models using male mice including the kainic acid model of status epilepticus and pentylenetetrazole model and in male and female mice in a genetic model of Dravet syndrome. RNA sequencing was used to analyze P2X7R downstream signaling during seizures. To investigate the cell type-specific role of the P2X7R during seizures and epilepsy, we generated mice lacking exon 2 of the P2rx7 gene in either microglia (P2rx7 : Cx3cr1 -Cre) or neurons (P2rx7 : Thy-1 -Cre). To investigate the protective potential of overexpressing P2X7R in GABAergic interneurons, P2X7Rs were overexpressed using adeno-associated virus transduction under the mDlx promoter. RNA sequencing of hippocampal tissue from wild-type and P2X7R knock-out mice identified both glial and neuronal genes, in particular genes involved in GABAergic signaling, under the control of the P2X7R following seizures. Mice with deleted P2rx7 in microglia displayed less severe acute seizures and developed a milder form of epilepsy, and microglia displayed an anti-inflammatory molecular profile. In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice. Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. Functional studies determined that GABAergic interneurons display increased responses to P2X7R activation in experimental epilepsy. Finally, we show that viral transduction of P2X7R in GABAergic interneurons protects against evoked and spontaneous seizures in experimental temporal lobe epilepsy and in mice lacking Scn1a , a model of Dravet syndrome. Our results suggest a dual and opposing action of P2X7R in epilepsy and suggest P2X7R overexpression in GABAergic interneurons as a novel therapeutic strategy for acquired and, possibly, genetic forms of epilepsy. [ABSTRACT FROM AUTHOR]

Objective: As programs expand globally, epilepsy surgery is becoming increasingly available as an effective treatment for some people with medically intractable seizures. Prospective candidates require careful neuropsychological evaluation and follow-up. The aim of this study was to examine the sex differences in neuropsychological function in presurgical presentation and postoperative outcomes in people with temporal lobe epilepsy referred for epilepsy surgery. Methods: Three hundred and seventy-two patients (202 Female; 170 Male) with a homogenous underlying pathology (hippocampal sclerosis) underwent a preoperative assessment on tests of intellectual, language, and memory function and were followed up one year after undergoing a unilateral temporal lobe resection; n = 169 Right (RTL), n = 203 Left (LTL). Results: There was no impact of sex or laterality of surgery on seizure outcome; 84% of males and 80% of females were seizure free at follow-up. Before surgery, sex effects were evident on tests of verbal memory with females performing better than males. Declines in verbal memory function following surgery were greater in females than males. Being female had a stronger association with postoperative decline on immediate prose recall (partial eta squared η2 = 0.029), than side of surgery (η2 = 0.018) albeit with a small effect size. Conclusions: There are subtle but significant sex differences in the neuropsychological profiles of people with temporal lobe epilepsy, before and following surgery. Whilst females generally perform better than males on tests of verbal memory function before surgery they demonstrate greater post-operative declines on these measures following surgery. [ABSTRACT FROM AUTHOR]