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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]

[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]

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]

• Metabolic PET radiomics features were strong predictors of seizure recurrence. • PET-based radiomics score, SGS, and Durmon were significant predictors of seizure-free outcomes. • A nomogram incorporating PET-based radiomics and clinical risk factors demonstrated good performance in predicting surgery outcomes. To establish and validate a novel nomogram based on clinical characteristics and [18F]FDG PET radiomics for the prediction of postsurgical seizure freedom in patients with temporal lobe epilepsy (TLE). 234 patients with drug-refractory TLE patients were included with a median follow-up time of 24 months after surgery. The correlation coefficient redundancy analysis and LASSO Cox regression were used to characterize risk factors. The Cox model was conducted to develop a Clinic-PET nomogram to predict the relapse status in the training set (n = 171). The nomogram's performance was estimated through discrimination, calibration, and clinical utility. The prognostic prediction model was validated in the test set (n = 63). Eight radiomics features were selected to assess the radiomics score (radscore) of the operation side (Lat_radscore) and the asymmetric index (AI) of the radiomics score (AI_radscore). AI_radscor, Lat_radscor, secondarily generalized seizures (SGS), and duration between seizure onset and surgery (Durmon) were significant predictors of seizure-free outcomes. The final model had a C-index of 0.68 (95 %CI: 0.59–0.77) for complete freedom from seizures and time-dependent AUROC was 0.65 at 12 months, 0.65 at 36 months, and 0.59 at 60 months in the test set. A web application derived from the primary predictive model was displayed for economic and efficient use. A PET-based radiomics nomogram is clinically promising for predicting seizure outcomes after temporal lobe epilepsy surgery. [ABSTRACT FROM AUTHOR]

• The NLRP3 inflammasome is a biomarker of temporal lobe epilepsy. • NLRP3 inflammasome creates a pro-inflammatory and pro-convulsive environment. • Intervention of NLRP3 inflammasome shows antiepileptic and neuroprotective effects. • Regulating NLRP3 inflammasome is a novel strategy for antiepileptic drug discovery. Epilepsy is one of the most widespread and complex diseases in the central nervous system (CNS), affecting approximately 65 million people globally, an important factor resulting in neurological disability-adjusted life year (DALY) and progressive cognitive dysfunction. Medication is the most essential treatment. The currently used drugs have shown drug resistance in some patients and only control symptoms; the development of novel and more efficacious pharmacotherapy is imminent. Increasing evidence suggests neuroinflammation is involved in the occurrence and development of epilepsy, and high expression of NLRP3 inflammasome has been observed in the temporal lobe epilepsy (TLE) brain tissue of patients and animal models. The inflammasome is a crucial cause of neuroinflammation by activating IL-1β and IL-18. Many preclinical studies have confirmed that regulating NLRP3 inflammasome pathway can prevent the development of epilepsy, reduce the severity of epilepsy, and play a neuroprotective role. Therefore, regulating NLRP3 inflammasome could be a potential target for epilepsy treatment. In summary, this review describes the priming and activation of inflammasome and its biological function in the progression of epilepsy. In addition, we reviewes the current pharmacological researches for epilepsy based on the regulation of NLRP3 inflammasome, aiming to provide a basis and reference for developing novel antiepileptic drugs. [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]

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

In Africa, epilepsy is a real burden. Temporal lobe epilepsy is the most common drug-resistant focal epilepsy disorder, and temporal lobectomy is the most common effective treatment for patients with drug-resistant epilepsy. We aim to highlight the Moroccan experience in epilepsy surgery and to ascertain its long-term outcome. Through the results of surgical treatment in our series, we hope to raise awareness of the need for epilepsy surgery in Africa and contribute to its development. We present a retrospective study of 132 patients who underwent surgery for epilepsy from January 2005 to December 2021 at our institution. The presurgical evaluation was based on clinical screening, interictal electroencephalography, video-electroencephalography, neuropsychological tests, magnetic resonance imaging, and positron emission tomography in some cases. Data are presented as the median and ranges. For all analyses, P values <0.05 were considered statistically significant. Our series includes 132 patients (69 males; 52.27%); the median age at surgery was 24 years (range, 1–64). One hundred and fifteen patients (87%) were operated on for temporal lobe epilepsy, of whom 98 (85%) had anterior temporal lobectomy and 17 (15%) had lesionectomy. Seventeen patients (13%) were operated on for extratemporal epilepsy, of whom 4 had lesionectomy, 7 functional hemispherotomy, and 5 Gamma Knife stereotactic radiosurgery. Our postoperative outcomes 3 months after surgery found 113 patients (85.6%) seizure-free (Engel class I), 16 with Engel class II (12.1%), and 3 with Engel class III (2.3%) in temporal lobe epilepsy. In extratemporal lobe epilepsy, 12 patients (70.5%) showed Engel class I, seizure-free, 4 Engel class II (23.5%), and 1 Engel class III (6%). These results confirm that most patients with drug-resistant epilepsy may benefit from surgical treatment without submitting to preoperative invasive explorations. This finding should help develop epilepsy surgery widely in Africa. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy is the most common reason behind drug-resistant seizures and temporal lobectomy (TL) is performed after all other efforts have been taken for a Temporal lobe epilepsy. Our study aims to develop multiple machine learning (ML) models capable of predicting postoperative outcomes following TL surgery. Data from the American College of Surgeons National Surgical Quality Improvement Program database identified patients who underwent TL surgery. We focused on 3 outcomes: prolonged length of stay (LOS), nonhome discharges, and 30-day readmissions. Six ML algorithms, TabPFN, XGBoost, LightGBM, Support Vector Machine, Random Forest, and Logistic Regression, coupled with the Optuna optimization library for hyperparameter tuning, were tested. Models with the highest area under the receiver operating characteristic (AUROC) values were included in the web application. SHapley Additive exPlanations was used to evaluate importance of predictor variables. Our analysis included 423 patients. Of these patients, 111 (26.2%) experienced prolonged LOS, 33 (7.8%) had nonhome discharges, and 29 (6.9%) encountered 30-day readmissions. The top-performing models for each outcome were those built with the Random Forest algorithm. The Random Forest models yielded AUROCs of 0.868, 0.804, and 0.742 in predicting prolonged LOS, nonhome discharges, and 30-day readmissions, respectively. Our study uses ML to forecast adverse postoperative outcomes following TL. We developed accessible predictive models that enhance prognosis prediction for TL surgery. Making ML models available for this purpose represents a significant advancement in shifting toward a more patient-centric, data-driven paradigm. [ABSTRACT FROM AUTHOR]

• Low-frequency integration and segregation of IED-free resting state networks are higher in TLE patients than in healthy subjects. • Network changes are less visible in N2 and unrelated to epilepsy, likely because physiologic theta waves mask pathologic activity. • In absence of IEDs, it might be easier to detect epilepsy-related alterations during wakefulness than N2 sleep. Investigate sleep and temporal lobe epilepsy (TLE) effects on brain networks derived from electroencephalography (EEG). High-density EEG was recorded during non-rapid eye movement (NREM) sleep stage 2 (N2) and wakefulness in 23 patients and healthy controls (HC). Epochs without epileptic discharges were source-reconstructed in 72 brain regions and connectivity was estimated. We calculated network integration and segregation at global (global efficiency, GE; average clustering coefficient, avgCC) and hemispheric level. These were compared between groups across frequency bands and correlated with the individual proportion of wakefulness- or sleep-related seizures. At the global level, patients had higher delta GE, delta avgCC and theta avgCC than controls, irrespective of the vigilance state. During wakefulness, theta GE of patients was higher than controls and, for patients, theta GE during wakefulness was higher than during N2. Wake-to-sleep differences in TLE were notable only in the ipsilateral hemisphere. Only measures from wakefulness recordings correlated with the proportion of wakefulness- or sleep-related seizures. TLE network alterations are more prominent during wakefulness and at lower frequencies. Increased integration and segregation suggest a pathological 'small world' configuration with a possible inhibitory role. Network alterations in TLE occur and are easier to detect during wakefulness. [ABSTRACT FROM AUTHOR]

[Display omitted] • Wnt/β-catenin signaling is downregulated in acute stage of status epilepsy (SE). • Wnt/β-catenin signaling is upregulated at chronic stage post SE induction. • Upregulated Wnt signaling in chronic epilepsy might involve in epileptogenesis. • Gsk-3β inhibitors can be used to improve the acute status epilepticus condition. • Dvl and β-catenin inhibitors can be used to improve the chronic epilepsy. Epilepsy is a chronic neurological complication characterized by unprovoked seizure episodes due to the imbalance between excitatory and inhibitory neurons. The epileptogenesis process has been reported to be involved in chronic epilepsy however, the mechanism underlying epileptogenesis remains unclear. Recent studies have shown the possible involvement of Wnt/β-catenin signaling in the neurogenesis and neuronal reorganization in epileptogenesis. In this study, we used repeated low dose lithium-pilocarpine model of status epilepsy (SE) to study the involvement of Wnt/β-catenin signaling at acute and chronic stages post SE induction. The acute study ranged from day 0 to day 28 post SE induction and the chronic study ranged from day 0 to day 56 post SE induction. Several neurobehavioral parameters and seizure score and seizure frequency was analysed until the end of the study. The proteins involved in the regulation of Wnt/β-catenin signaling and downstream cascading were analysed using western blot and quantitative real-time PCR analysis. The Wnt/β-catenin pathway was found inactive in acute SE, while the same was found activated at the chronic stage. Our findings suggest that the activated Wnt/β-catenin signaling in chronic epilepsy might be the possible mechanism underlying epileptogenesis as indicated by increased neuronal count, increased synaptic density, astrogliosis and apoptosis in chronic epilepsy. These findings can help target the Wnt/β-catenin pathway differentially depending upon the type of epilepsy. The acute stage characterized by SE can be improved by targeting GSK-3β levels and the chronic stage characterized by temporal lobe epilepsy can be improved by targeting β-catenin and disheveled proteins. [ABSTRACT FROM AUTHOR]

• Preoperative dSPM of language MEG signals showed right-shifted lateralization in the supramarginal gyrus in left mesial TLE. • Right shift in supramarginal gyrus was correlated with postoperative verbal memory increase in HS+ group of left mesial TLE. • Regional language lateralization in dSPM of MEG signals may be useful to predict postoperative verbal memory in left HS+ group. To clarify whether preoperative language magnetoencephalography (MEG) predicts postoperative verbal memory (VM) changes in left mesial temporal lobe epilepsy (LMTLE). We reviewed 18 right-handed patients with LMTLE who underwent anterior temporal lobectomy or selective amygdala hippocampectomy, 12 with (HS+) and 6 without hippocampal sclerosis (HS−). Patients underwent neuropsychological assessment before and after surgery. MEG was measured with an auditory verbal learning task in patients preoperatively and in 15 right-handed controls. Dynamic statistical parametric mapping (dSPM) was used for source imaging of task-related activity. Language laterality index (LI) was calculated by z-score of dSPM in language-related regions. LI in the region of HS+ and HS− was compared to controls. The correlation between LI and postoperative VM change was assessed in HS+ and HS−. Preoperative LI in supramarginal gyrus showed greater right-shifted lateralization in both HS+ and HS− than in controls. Right-shifted LI in supramarginal gyrus was correlated with postoperative VM increase in HS+ (p = 0.019), but not in HS−. Right-shifted language lateralization in dSPM of MEG signals may predict favorable VM outcome in HS+ of LMTLE. Findings warrant further investigation of the relation between regional language laterality index and postoperative verbal memory changes. [ABSTRACT FROM AUTHOR]

Epilepsy surgery is traditionally difficult to pursue in resource-limited countries but is nevertheless essential in the treatment of medication-refractory, surgically amenable epilepsy. With the help of international collaboration, a successful epilepsy program was started in Vietnam. This article comprises a retrospective chart review, combined with prospective longitudinal follow-up of 35 cases of unilateral drug-resistant epilepsy in the temporal lobe who underwent temporal lobectomy, in Viet Duc University Hospital from May 2018 to September 2022. The female/male ratio was 0.6:1, and focal seizures with impaired awareness accounted for 97.14% of patients. Of patients with focal awareness seizures, 51.41% were localized and detected by electroencephalography. Postoperatively, 80% of patients were seizure free (Engel I) at 1 year, and the remaining 20% had worthwhile seizure improvement (Engel II). Postoperative temporal lobe pathology was categorized as follows: mesial temporal sclerosis (48.57%), focal cortical dysplasia (25.71%), and low-grade neoplasms (25.71%). Of patients, 17.14% had postoperative complications (5 infections and 1 transient extremity paresis), and there were no deaths. Even in low-resource environments, effective and safe surgical care can be provided for drug-resistant epilepsy caused by temporal lobe disease. This study serves as a model of international collaboration and support for future hospitals in low-resource environments to replicate. [ABSTRACT FROM AUTHOR]

• Structure-function coupling of interictal epileptic discharges (IEDs) was studied with graph signal processing for the first time. • The predominance of smooth vs coarse spatial maps changes during the IED and points at stronger integration mechanisms during IEDs. • This effect was localized in the ipsilateral mesial temporal regions of patients with temporal lobe epilepsy. Structure-function coupling remains largely unknown in brain disorders. We studied this coupling during interictal epileptic discharges (IEDs), using graph signal processing in temporal lobe epilepsy (TLE). We decomposed IEDs of 17 patients on spatial maps, i.e. network harmonics, extracted from a structural connectome. Harmonics were split in smooth maps (long-range interactions reflecting integration) and coarse maps (short-range interactions reflecting segregation) and were used to reconstruct the part of the signal coupled (Xc) and decoupled (Xd) from the structure, respectively. We analysed how Xc and Xd embed the IED energy over time, at global and regional level. For Xc, the energy was smaller than for Xd before the IED onset (p <.001), but became larger around the first IED peak (p <.05, cluster 2, C2). Locally, the ipsilateral mesial regions were significantly coupled to the structure over the whole epoch. The ipsilateral hippocampus increased its coupling during C2 (p <.01). At whole-brain level, segregation gives way to integrative processes during the IED. Locally, brain regions commonly involved in the TLE epileptogenic network increase their reliance on long-range couplings during IED (C2). In TLE, integration mechanisms prevail during the IED and are localized in the ipsilateral mesial temporal regions. [ABSTRACT FROM AUTHOR]

Recent studies suggest that although children with epilepsy may show normal learning and memory performance, accelerated long-term forgetting (ALF) may become evident over time. Our study examined associations between delayed episodic memory performance (recall 1-week after learning) and executive functions. A consecutive sample of children with a diagnosis of idiopathic epilepsy with focal or generalized seizures, without morphologic or metabolic abnormalities (n = 20, mean age: 11.70 years) was compared to an IQ-matched healthy control group (n = 20, mean age: 11.55 years). We also assessed parents' and children's rating of forgetting in everyday life and explored its association with delayed episodic memory recall. Similar to results from recent studies of pediatric patients with temporal lobe epilepsy or genetic generalized epilepsy, our pediatric epilepsy patients showed a significantly elevated recall loss over time, although verbal learning, immediate and 30-minute recall was comparable to the matched control group. Additionally, delayed memory recall in patients was moderately associated with their subjective rating of forgetting, as well as with executive functions (verbal fluency and switching) and divided attention. We assume that executive functions play a crucial role in deep memory encoding, facilitating stronger and more enduring memory traces. Given that approximately 20% of epilepsy patients – compared to a healthy reference sample – had a significantly reduced delayed recall and due to the clinical relevance of long-term memory, age-appropriate standard norms for free memory recall after 1-week are desirable. [ABSTRACT FROM AUTHOR]

• S193/T196 (S202/T205 human) tau showed progressive dephosphorylation in epilepsy. • No change in phosphorylation at T172 (T181 human) or T222 (T231 human) was seen. • At 2 months post-SE, total tau expression was transiently decreased. • Tau expression and phosphorylation at 3 loci differ between chronic epilepsy and AD. Tau is an intracellular protein known to undergo hyperphosphorylation and subsequent neuro-toxic aggregation in Alzheimer's disease (AD). Here, tau expression and phosphorylation at three canonical loci known to be hyperphosphorylated in AD (S202/T205, T181, and T231) were studied in the rat pilocarpine status epilepticus (SE) model of temporal lobe epilepsy (TLE). We measured tau expression at two time points of chronic epilepsy: two months and four months post-SE. Both time points parallel human TLE of at least several years. In the whole hippocampal formation at two months post-SE, we observed modestly reduced total tau levels compared to naïve controls, but no significant reduction in S202/T205 phosphorylation levels. In the whole hippocampal formation from four month post-SE rats, total tau expression had reverted to normal, but there was a significant reduction in S202/T205 tau phosphorylation levels that was also seen in CA1 and CA3. No change in phosphorylation was seen at the T181 and T231 tau loci. In somatosensory cortex, outside of the seizure onset zone, no changes in tau expression or phosphorylation were seen at the later time point. We conclude that total tau expression and phosphorylation in an animal model of TLE do not show hyperphosphorylation at the three AD canonical tau loci. Instead, the S202/T205 locus showed progressive dephosphorylation. This suggests that changes in tau expression may play a different role in epilepsy than in AD. Further study is needed to understand how these changes in tau may impact neuronal excitability in chronic epilepsy. [ABSTRACT FROM AUTHOR]

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

• Own voice perception might be a complex process including emotional, memory, somatosensory, auditory, and facial recognition processing. • Right superior temporal gyrus, transverse temporal gyrus, amygdala, hippocampus, and fusiform gyrus (FG) are likely part of the neural network subjacent to own human voice perception. • Cortico-cortical evoked potentials might help to understand neurophysiological bases of own voice perception. • Own voice perception seem to be related to facial perception as well. The neural bases for language perception have been studied elsewhere using Transcranial Magnetic Stimulation, functional Magnetic Resonance Imaging and Direct Cortical Stimulation. However, to our knowledge, there is no previous report about a patient identifying the change in his voice tone, speed, and prosody because of right temporal cortical stimulation. Nor has there been a cortico-cortical evoked potential (CCEP) assessment of the network underlying this process. We present CCEP from a patient with right focal refractory temporal lobe epilepsy of tumoral etiology who reported changes in the perception of his own speech prosody during stimulation. This report will serve as a complement to the understanding of the neural networks of language and prosody. The present report shows that right superior temporal gyrus, transverse temporal gyrus, right amygdala, hippocampus, and fusiform gyrus (FG) are part of the neural network subjacent to own human voice perception. [ABSTRACT FROM AUTHOR]

Expression of immediate early genes (IEGs) in the brain is important for synaptic plasticity, and probably also in neurodegenerative conditions. To understand the cellular mechanisms of the underlying neuropathophysiological processes in epilepsy, we need to pinpoint changes in concentration of synaptic plasticity-related proteins at subsynaptic levels. In this study, we examined changes in synaptic expression of Activity-regulated cytoskeleton-associated (Arc) and Brai Derived Neurotrophic Factor (BDNF) in a rat model of kainate-induced temporal lobe epilepsy (TLE). Western blotting showed reduced concentrations of Arc and increased concentrations of BDNF in hippocampal synaptosomes in chronic TLE rats. Then, using quantitative electron microscopy, we found corresponding changes in subsynaptic regions in the hippocampus. Specifically, we detected significant reductions in the concentrations of Arc in the presynaptic terminal of Schaffer collateral glutamatergic synapses in the stratum radiatum of the CA1 area in TLE, as well as in their adjacent postsynaptic spines. In CA3, there was a significant reduction of Arc only in the presynaptic terminal cytoplasm. Conversely, in CA3, there was a significant increase in the expression of BDNF in the presynaptic terminal, but not in the postsynaptic spine. Significant increase in BDNF concentration in the CA1 postsynaptic density was also obtained. We hypothesize that the observed changes in Arc and BDNF may contribute to both cognitive impairment and increased excitotoxic vulnerability in chronic epilepsy. • Expression of Arc is reduced in hippocampal Schaffer collateral glutamatergic synapses in temporal lobe epilepsy. • The concentration of BDNF is increased in hippocampal Schaffer collateral glutamatergic synapses in temporal lobe epilepsy. • Synaptic changes in Arc and BDNF may contribute to increased excitotoxicity and cognitive impairments in chronic epilepsy. [ABSTRACT FROM AUTHOR]

Limited hippocampal radiofrequency thermocoagulation (RFTC) for patients with mesial temporal lobe epilepsy was associated with good short-term seizure control and few complications. We aimed to demonstrate the neuropsychologic outcomes and assess the prognostic factors of long-term seizure control in these patients. We included all patients with mesial temporal lobe epilepsy who underwent limited hippocampal RFTC from January 2016 to December 2020. Clinical data of age, sex, seizure control before and after operation were all corrected. Pre- and postoperative neuropsychologic function including full-scale intelligence quotient (FSIQ), memory quotient, and the Mini-Mental State Examination was used. Thirty-one patients (17 female and 14 male) with a mean epilepsy duration of 22.3 years and seizure frequency of 5.7 times per month were included. The intraoperative seizure rate was 19.3%, and a higher preoperative seizure frequency (P = 0.001) and longer duration of epilepsy (P = 0.042) were associated with the occurrence of intraoperative seizures. The postoperative FSIQ scores were significantly better than preoperative scores (mean 92.1 vs. 89.7, P = 0.014). Nine patients (29%) who underwent limited hippocampal RFTC were seizure-free at 1 year of follow-up. Responders represented 58% (n = 18) of patients at 1 year. The mean follow-up period was 34.7 ± 13.3 months. Five patients remained seizure free and 13 patients are still responders at the last follow-up visits. Long-term seizure frequency was 2.32 ± 2.86 times per month. Limited hippocampal RFTC is a safe stereotactic minimal invasive procedure with good neuropsychologic outcome and acceptable efficacy of seizure reduction in appropriately selected patients. [ABSTRACT FROM AUTHOR]

Temporal lobe encephaloceles (TEs) are a rare cause of drug-resistant temporal lobe epilepsy (DR-TLE), with head trauma and obesity identified as risk factors in adults. This study evaluated the clinical characteristics of childhood-onset DR-TLE due to TE. This is a single-institution retrospective review of childhood-onset DR-TLE with radiographic TE identified between 2008 and 2020. The epilepsy history, brain imaging features, and surgical outcomes were collected. Eleven children with DR-TLE due to TE were included (median age at epilepsy onset was 11 years, interquartile range 8.5 to 13.5 years). Median latency between epilepsy diagnosis and TE detection was 3 years (range of 0 to 13 years). None had history of head trauma. Body mass index greater than 85 percentile for age and sex was seen in 36% of the children. No patient had bilateral TE identified. TEs were diagnosed based on epilepsy surgery conference re-review of imaging in 36% of cases. All herniations were contained defects without osseous dehiscence. Regional fluorodeoxyglucose (FDG) hypometabolism ipsilateral to the encephalocele was seen in all children who had FDG-positron emission tomography (PET) of the brain. Of the children who had surgery, 70% were seizure free or had nondisabling seizures at last follow-up (mean follow-up 52 months). TE is a surgically remediable etiology of DR-TLE in childhood. TEs are often overlooked at pediatric epilepsy diagnosis, calling for the need to increase awareness of this entity. FDG-PET temporal hypometabolism in children with presumed nonlesional DR-TLE should be carefully examined for occult TEs. [ABSTRACT FROM AUTHOR]

It is unknown whether ultrasound-induced blood–brain barrier (BBB) disruption can promote epileptogenesis and how BBB integrity changes over time after sonication. To gain more insight into the safety profile of ultrasound (US)-induced BBB opening, we determined BBB permeability as well as histological modifications in C57BL/6 adult control mice and in the kainate (KA) model for mesial temporal lobe epilepsy in mice after sonication with low-intensity pulsed ultrasound (LIPU). Microglial and astroglial changes in ipsilateral hippocampus were examined at different time points following BBB disruption by respectively analyzing Iba1 and glial fibrillary acidic protein immunoreactivity. Using intracerebral EEG recordings, we further studied the possible electrophysiological repercussions of a repeated disrupted BBB for seizure generation in nine non-epileptic mice. LIPU-induced BBB opening led to transient albumin extravasation and reversible mild astrogliosis, but not to microglial activation in the hippocampus of non-epileptic mice. In KA mice, the transient albumin extravasation into the hippocampus mediated by LIPU-induced BBB opening did not aggravate inflammatory processes and histologic changes that characterize the hippocampal sclerosis. Three LIPU-induced BBB opening did not induce epileptogenicity in non-epileptic mice implanted with depth EEG electrodes. Our experiments in mice provide persuasive evidence of the safety of LIPU-induced BBB opening as a therapeutic modality for neurological diseases. [ABSTRACT FROM AUTHOR]

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

• Abnormality of intrinsic brain activity in the temporal neocortex, mainly lateralized to the epileptic side, was detected by various indicators. • The application of dynamic indicators played a complementary role, further revealing the temporal variability decline of the occipital lobe. • Alteration of several indicators in the temporal neocortex, especially fALFF, may help in the diagnosis and lateralization of MRI-negative TLE. To comprehensively explore the potential brain activity abnormalities affected by MRI-negative temporal lobe epilepsy (TLE) and to detect whether the changes were associated with cognition and help in the diagnosis or lateralization. Six static intrinsic brain activity (IBA) indicators (ALFF, fALFF, ReHo, DC, GSCorr, VMHC) and their corresponding six temporal dynamic indicators in 39 unilateral MRI-negative TLE patients and 42 healthy volunteers were compared. Correlation analyses were performed between these indicators in areas displaying group differences, cognitive function, and epilepsy duration. ROC analyses were performed to test the diagnostic and lateralization ability of the IBA parameters. Considerable overlap was present among the abnormal brain regions detected by different static and dynamic indicators, including (1) alteration of fALFF, Reho, DC, VMHC, dfALFF, dReHo, and dDC in the temporal neocortex (predominately ipsilateral to the epileptogenic foci); (2) decreased dGSCorr and dVMHC in the occipital lobe. Meanwhile, the ReHo and VMHC values in the temporal neocortex correlated with the cognition scores or epilepsy duration (P < 0.01). The ROC analysis results revealed moderate diagnosis or lateralization efficiency of several IBA indicators (fALFF, dfALFF, ReHo, DC, dDC, and VMHC). The abnormal condition of neuronal activity in the temporal neocortex, predominately lateralized to the epileptic side, was a crucial feature in patients with MRI-negative TLE and might offer diagnosis or lateralization information. The application of dynamic intrinsic brain activity indicators played a complementary role, further revealing the temporal variability decline of the occipital lobe in MRI-negative TLE patients. [ABSTRACT FROM AUTHOR]

• Astrocytic markers GFAP, vimentin, S100B and Aldh1L1, but not GS, are differentially increased following KA treatment. • Both A1-like and A2-like astrocyte markers are increased in KA-treated animals. • KA treatment transiently enhances the levels of total/phospho-tau. • KA treatment enhances the level/expression of cleaved tau in a subset of astrocytes. Kainic acid (KA), an analogue of the excitatory neurotransmitter glutamate, when administered systemically can trigger seizures and neuronal loss in a manner that mirrors the neuropathology of human mesial temporal lobe epilepsy (mTLE), which affects ∼50 million people globally. Evidence suggests that changes in astrocytes which precede neuronal damage play an important role in the degeneration of neurons and/or development of seizures in TLE pathogenesis. Additionally, a role for microtubule associated tau protein, involved in various neurodegenerative diseases including Alzheimer's disease, has also been suggested in the development of seizure and/or neurodegeneration in TLE pathogenesis. At present, possible alterations of different subtypes of astrocytes and their association, if any, with tau protein in TLE remain unclear. In this study, we evaluated alterations of different subtypes of astrocytes and phospho-/cleaved-tau levels in KA-treated rat model of TLE. Our results reveal that levels/expression of various astrocyte markers such as GFAP, vimentin, S100B, Aldh1L1, but not GS, are increased in the hippocampus of KA-treated rats. The levels/expression of both A1(C3+) and A2(S100A10+)-like astrocytes are also increased in KA-treated rats. Concurrently, the total (Tau1 and Tau5) and phospho-tau (AT270 and PHF1) levels are transiently enhanced following KA administration. Furthermore, the level/expression of cleaved-tau, which is apparent in a subset of GFAP-, S100B- and A2-positive astrocytes, are increased in KA-treated rats. These results, taken together, suggest a differential role for various astrocytic subpopulations and tau protein in the development of seizure and/or loss of neurons in KA model of TLE and possibly in human mTLE pathogenesis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Modulation index(MI) Ripples/3–4 Hz and MI Ripples/4–8 Hz in the hippocampus were significantly higher than in other regions at seizure onset. • MI Ripples/3–4 Hz and MI Ripples/4–8 Hz showed chronological changes corresponding to the phase of the seizure. • Continuous measurement of MI Ripples/3–4 Hz and MI Ripples/4–8 Hz during the ictal phase could help identify epileptogenic zones. To analyze chronological changes in phase-amplitude coupling (PAC) and verify whether PAC analysis can diagnose epileptogenic zones during seizures. We analyzed 30 seizures in 10 patients with mesial temporal lobe epilepsy who had ictal discharges with preictal spiking followed by low-voltage fast activity patterns on intracranial electroencephalography. We used the amplitude of two high-frequency bands (ripples: 80–200 Hz, fast ripples: 200–300 Hz) and the phase of three slow wave bands (0.5–1 Hz, 3–4 Hz, and 4–8 Hz) for modulation index (MI) calculation from 2 minutes before seizure onset to seizure termination. We evaluated the accuracy of epileptogenic zone detection by MI, in which a combination of MI was better for diagnosis and analyzed patterns of chronological changes in MI during seizures. MI Ripples/3–4 Hz and MI Ripples/4–8 Hz in the hippocampus were significantly higher than those in the peripheral regions from seizure onset. Corresponding to the phase on intracranial electroencephalography, MI Ripples/3–4 Hz decreased once and subsequently increased again. MI Ripples/4–8 Hz showed continuously high values. Continuous measurement of MI Ripples/3–4 Hz and MI Ripples/4–8 Hz could help identify epileptogenic zones. PAC analysis of ictal epileptic discharges can help epileptogenic zone identification. [ABSTRACT FROM AUTHOR]

• A multi-level discourse analysis examined language in temporal lobe epilepsy (TLE). • When retelling personal memories, disturbed fluency, cohesion, and coherence emerges. • Over repetitions they consistently produce a vague account. • This possibly relates to the neurolinguistic demands of recalling personal events. Aside from deficits identified in single-word level retrieval, individuals with temporal lobe epilepsy (TLE) exhibit clinical oddities, such as circumstantiality in their language production. Circumstantiality refers to the use of language which is pedantic, repetitive, and overly detailed. This becomes particularly evident when elicitation tasks impose minimal structure, or when impersonal narratives are retold over consecutive occasions. Personal reminiscence is highly specific and localised in time, placing unique demands on cognitive-linguistic systems. It is hypothesised that the nature of this elicitation paradigm will produce a unique psycholinguistic phenotype in those with TLE. Among controls there is a compression of output for impersonal narratives, meaning that they use fewer words over less time and are more fluent. The opposite effect is observed when personal narratives are retold. To investigate the micro- and macrolinguistic processes underpinning personal discourse production in TLE, we examined the elicited language output of 15 surgically naïve individuals with TLE and 14 healthy controls. Participants were asked to recall and re-tell an autobiographical memory on four immediately consecutive occasions, representing an alternative unstructured elicitation. Following transcription and coding of output, a detailed multi-level discourse analysis of output volume, fluency, cohesion, and coherence was conducted. As anticipated, a distinctly different pattern emerged in TLE when compared with controls who did not compress their output volume across repetitions but instead produced greater novelty, and a more coherent and refined account over time. Individuals with TLE consistently told a less distinct story across repetitions, with disturbances in fluency, cohesion, and coherence. This reflects a reduced capacity to produce a coherent mental representation, in all likelihood related to the neurolinguistic demands of recalling and retelling specific personal events. [ABSTRACT FROM AUTHOR]

Focused ultrasound (FUS) has the potential to modulate regional brain excitability and possibly aid seizure control; however, effects on behavior of FUS used as a seizure therapy are unknown. This study explores behavioral effects and hippocampal restoration induced by pulsed FUS in a kainic acid (KA) animal model of temporal lobe epilepsy. Twenty-nine male Sprague–Dawley rats were observed for 20 weeks with anatomical magnetic resonance imaging (MRI) and behavioral performance evaluations, comprising measures of anxiety, limb usage, sociability, and memory. FUS targeted to the right hippocampus was given 9 and 14 weeks after KA was delivered to the right amygdala. Ultrasound pulsations were delivered with the acoustic settings of 0.25 of mechanical index, 0.5 W/cm2 of intensity spatial peak temporal average (ISPTA), 100 Hz of pulse repetition frequency, and 30% of duty cycle, during three consecutive pulse trains of 10 min separated by 5-min rests. Controls included normal animals with sham injections and KA-exposed animals without FUS exposure. Longitudinal MRI observations showed that FUS substantially protected hippocampal and striatal structures from KA-induced atrophy. KA alone increased anxiety, impaired contralateral limb usage, and reduced sociability and learning. Two courses of FUS sonications partially ameliorated these impairments by enhancing exploring and learning, balancing limb usage, and increasing social interaction. The histology results indicated that two sonications enhanced neuroprotection effect and decreased the inflammation markers induced by KA. This study supports existence of both neuroprotective and beneficial behavioral effects from low-intensity pulsed ultrasound in the KA animal model of epilepsy. [ABSTRACT FROM AUTHOR]

• Interoperative electrocorticography (iECoG) is a potential biomarker to determine adequacy of laser ablation in mesial TLE (mTLE). • A robust reduction (>70%) of epileptiform discharges on iECoG after MR guided laser ablation (MRLT) therapy is associated with better outcomes in mTLE. • The robust reduction post-MRLT may suggest that the ablation has correctly targeted the epileptogenic tissue in these patients. Magnetic resonance-guided laser interstitial thermal therapy (MRLiTT) for treating temporal lobe epilepsy has recently gained popularity. We aimed to investigate the predictive value of pre-and post-MRLiTT epileptiform discharges (EDs) on intraoperative electrocorticography (iECoG) in seizure outcomes for patients with mesial temporal lobe epilepsy (mTLE). We conducted a pilot, prospective single-center cohort study on seven consecutive patients with mTLE that underwent MRLiTT. Pre- and post-MRLiTT iECoG was performed using a 1x8 contact depth electrode along the same trajectory used for the laser catheter. The responders had a robust reduction in ED frequency compared to pre-MRLiTT iECoG (86% vs 13%, p < 0.01). Clinical characteristics, including risk factors for epilepsy, duration of epilepsy, presence of mesial temporal lobe sclerosis, prior intracranial monitoring, the absolute frequency of pre- or post-MRLiTT EDs, and ablation volume were not significantly associated with responder status. This is the first demonstration that intraoperative reduction in EDs during mesial temporal lobe MRLiTT may potentially predict seizure outcomes and may serve as an intraoperative biomarker for satisfactory ablation. However, larger prospective studies are needed to confirm our findings and evaluate the utility of iECoG during MRLiTT. iECoG during mesial temporal lobe MRLiTT may help assess seizure outcomes. [ABSTRACT FROM AUTHOR]

Anteromesial resection is an effective method for treating seizures arising from the medial temporal lobe, as these cases are often the most straightforward and have the best outcomes. Nevertheless, some patients who go on to have a mesial resection are recommended to have an implantation of electrodes before surgery. Whether the need for such an implant alters the rate of seizure freedom is not well-studied in this particular subgroup of epilepsy patients. We performed a retrospective review of consecutive anteromesial surgeries for medial temporal lobe epilepsy performed between 2005 and 2020. Of a total of 39 patients, 19 required electrode implantation (electrode group) and 20 did not (no-electrode group). The primary outcomes assessed were reduction in seizure frequency and Engel score. Complication rates were also compared. Postresection seizure frequency reduction was nonsignificantly higher in the no-electrode group (97.0 ± 10.3%) than in the electrode group (88.5 ± 23.7%, P = 0.15). The rate of Engel I outcome was nonsignificantly higher in the no-electrode group (84.2%) than in the electrode group (65.0%, P = 0.17). Major complication rates were nonsignificantly higher in the no-electrode group (15.8 ± 1.9%) than in the electrode group (5.0 ± 1.1%, P = 0.26). Power analysis revealed that 74 patients would need to be included in each group to reach statistical significance. Although not statistically significant, our study showed a trend for improved seizure control if a decision was made not to implant electrodes prior to potentially curative anteromesial resection. Engel I outcome in this group reached approximately 85%. A larger multi-instiutional study may be required to reach statistical significance. [ABSTRACT FROM AUTHOR]

Meningoencephalocele (ME) of the temporal lobe through a bone defect in the middle cranial fossa is a rare known cause of refractory temporal lobe epilepsy (TLE). ME-induced drug-resistant TLE has been described in adults; however, its incidence in children is very rare. A 7-year-old girl presented at our hospital with brief episodes of impaired consciousness and enuresis. Initial brain MRI results were interpreted as normal. Her seizures could not be controlled even with multiple anti-seizure medications. She was diagnosed with drug-resistant TLE, which presented with prolonged impaired awareness seizures for 30–60 s and secondary bilateral tonic seizures. At 9 years of age, brain MRI revealed a left temporal anteroinferior ME with a congenital bone defect in the left middle cranial fossa. She was referred for presurgical epilepsy evaluation. Long-term video electroencephalography (EEG) failed to reveal regional abnormality in the left temporal lobe; invasive evaluation using stereoelectroencephalography (SEEG) was thus indicated. Ictal onset SEEG was identified in the temporal pole near the ME which was rapidly propagated to the mesial temporal structures and other cortical regions. The left temporal pole including the ME was micro-surgically disconnected while preserving the hippocampus and amygdala. The patient's seizures have been completely controlled for 1 year and 6 months post-operatively. SEEG revealed rapid propagation of ictal activity in this patient's case, confirming that the ME was epileptogenic. Since the majority of patients with refractory epilepsy caused by ME have favorable postoperative seizure outcomes, it is important to carefully check for ME in drug-resistant TLE patients with apparently normal MRI. [ABSTRACT FROM AUTHOR]

Introduction: Temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) is one of the most common drug-resistant epilepsy. Surgery is currently accepted as an effective and safe therapeutic approach compared to antiseizure medications (ASMs). The study aims to evaluate the effect of surgical treatment of TLE-HS on sleep profile and architecture by subjective and objective evaluation of sleep in basal condition after one month and one year.Methods: Thirteen patients with TLE-HS were recruited to undergo overnight polysomnography and a subjective evaluation of nocturnal sleep utilizing the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence through the Epworth Sleepiness Scale (ESS) in basal condition (T0), one month (T1) and one year after surgery (T2), respectively. Thirteen healthy controls (HC) matched for age, sex and BMI were recruited. Scoring and analysis of sleep macrostructure and cyclic alternating pattern (CAP) parameters were performed.Results: The comparison between patients in basal condition (T0) and HC showed a significant lower sleep efficiency (p = 0.003) and REM percentage (p < 0.001). Regarding CAP, patients at T0 showed higher total CAP rate (p < 0.001), CAP rate in N2 (p < 0.001), higher A3 (%) (p = 0.001), higher mean duration of A1 (p = 0.002), A3 index (p < 0.001), cycle in sequences (p < 0.001), lower B duration (p < 0.001), cycle mean duration (p < 0.001) than HC. Surgery did not induce significant changes in nocturnal macrostructural polysomnographic variables in T1 and T2. Lower CAP rate (T1 vs T0 and T2 vs T0 p < 0.001), CAP rate in N3 (T1 vs T0 and T2 vs T0 p < 0.001), A3 (%) (T1 vs T0 and T2 vs T0 p < 0.001); lower phase A2 index (T1 vs T0 p < 0.001) and A3 index (T1 vs T0 p < 0.001), lower phase A1 index (T2 vs T0 p < 0.001) and cycle in sequences (T2 vs T0 p = 0.002) higher B mean duration (T2 vs T0 p = 0.002). No significant differences were found between T1 and T2 in CAP parameters.Conclusion: We found a significant NREM sleep instability in patients with TLE-HS compared with HC. In addition, anterior temporal lobectomy (ATL) induced a significant improvement in sleep continuity as evaluated by cyclic alternating pattern already one month later and this effect persisted after one year. ALT seems to restore a more resilient sleeping brain. [ABSTRACT FROM AUTHOR]

Ictal stereo-encephalography (sEEG) biomarkers for seizure onset zone (SOZ) localization can be classified depending on whether they target abnormalities in signal power or functional connectivity between signals, and they may depend on the frequency band and time window at which they are estimated. This work aimed to compare and optimize the performance of a power and a connectivity-based biomarker to identify SOZ contacts from ictal sEEG recordings. To do so, we used a previously introduced power-based measure, the normalized mean activation (nMA), which quantifies the ictal average power activation. Similarly, we defined the normalized mean strength (nMS), to quantify the ictal mean functional connectivity of every contact with the rest. The optimal frequency bands and time windows were selected based on optimizing AUC and F2-score. The analysis was performed on a dataset of 67 seizures from 10 patients with pharmacoresistant temporal lobe epilepsy. Our results suggest that the power-based biomarker generally performs better for the detection of SOZ than the connectivity-based one. However, an equivalent performance level can be achieved when both biomarkers are independently optimized. Optimal performance was achieved in the beta and lower-gamma range for the power biomarker and in the lower- and higher-gamma range for connectivity, both using a 20 or 30 s period after seizure onset. The results of this study highlight the importance of this optimization step over frequency and time windows when comparing different SOZ discrimination biomarkers. This information should be considered when training SOZ classifiers on retrospective patients' data for clinical applications. • Power-based biomarker outperforms connectivity-based one for SOZ detection in sEEG. • Comparable performance is achievable by optimizing both biomarkers independently. • Optimal power-based biomarker performance in beta and lower-gamma range. • Optimal connectivity-based biomarker performance in gamma range. • Maximal performance for both biomarkers occurs 20–30 s post-seizure onset. [ABSTRACT FROM AUTHOR]

Epilepsy is a prevalent disorder of the central nervous system. Approximately, one-third of patients show resistance to pharmacological interventions. The pathogenesis of epilepsy is complex, and neuronal apoptosis plays a critical role. Aberrantly reactive astrocytes, induced by cytokine release from activated microglia, may lead to neuronal apoptosis. This study investigated the role of glucagon-like peptide 1 receptor (GLP1R) in microglial activation in epilepsy and its impact on astrocyte-mediated neurotoxicity. We used human hippocampal tissue from patients with temporal lobe epilepsy and a pilocarpine-induced epileptic mouse model to assess neurobiological changes in epilepsy. BV2 microglial cells and primary astrocytes were used to evaluate cytokine release and astrocyte activation in vitro. The involvement of GLP1R was explored using the GLP1R agonist, Exendin-4 (Ex-4). Our findings indicated that reduced GLP1R expression in hippocampal microglia in both epileptic mouse models and human patients, correlated with increased cytokine release and astrocyte activation. Ex-4 treatment restored microglial homeostasis, decreased cytokine secretion, and reduced astrocyte activation, particularly of the A1 phenotype. These changes were associated with a reduction in neuronal apoptosis. In addition, Ex-4 treatment significantly decreased the frequency and duration of seizures in epileptic mice. This study highlights the crucial role of microglial GLP1R in epilepsy pathophysiology. GLP1R downregulation contributes to microglial- and astrocyte-mediated neurotoxicity, exacerbating neuronal death and seizures. Activation of GLP1R with Ex-4 has emerged as a promising therapeutic strategy to reduce neuroinflammation, protect neuronal cells, and control seizures in epilepsy. This study provides a foundation for developing novel antiepileptic therapies targeting microglial GLP1R, with the potential to improve outcomes in patients with epilepsy. GLP1R activation by Exendin-4 is a novel therapeutic approach to attenuate neuroinflammation, prevent neuronal loss in epilepsy, and reduce seizure frequency and severity. [Display omitted] [ABSTRACT FROM AUTHOR]

The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining. Results revealed that acute electrophysiological (EEG) profiling of the ASD cocktail markedly halted sharp ictogenic spikes as well as altered dynamics of brain wave oscillations thus validating the need for polytherapy vs. monotherapy. In TLE animals, pharmacological intervention for 6 weeks with topiramate 10 mg/kg in combination with PREG and LAC at the dose of 20 mg/kg exhibited marked protection from SRS incidence, improved body weight, offensive aggression, anxiety-like behavior, cognitive impairments, and depressive-like behavior (p < 0.05). Moreover, combination therapy impeded redox impairments as evidenced by decreased MDA and AchE levels and increased activity of antioxidant SOD, GSH enzymes. Furthermore, polytherapy rescued animals from SE-induced neurodegeneration with increased neuronal density in CA1, CA3c, CA3ab, hilus, and granular cell layer (GCL) of the dentate gyrus. In conclusion, early polytherapy with topiramate in combination with pregabalin and lacosamide prompted synergy and prevented epileptogenesis with associated psychological and neuropathologic alterations. [Display omitted] [ABSTRACT FROM AUTHOR]

In medial temporal lobe epilepsy (MTLE), the benefits of surgery must be balanced against the risk of post-operative memory decline. Prediction of postoperative outcomes based on functional magnetic resonance imaging (fMRI) tasks is increasingly common but remains uncertain. The aim of this retrospective study was to determine whether hippocampal activations elicited by fMRI language tasks could enhance or refine memory fMRI in MTLE patients candidates to surgery. Forty-six patients were included: 30 right and 16 left MTLE, mostly with hippocampal sclerosis. Preoperative assessment included neuropsychological tests and fMRI with language (syntactic verbal fluency) and memory tasks (encoding, delayed, and immediate recognition of images of objects). Thirty patients underwent surgery and had neuropsychological evaluations one year after surgery. Worsening was defined as a degradation of more than 10 % in postoperative forgetting scores compared to preoperative scores in verbal, non-verbal and global memory. Memory fMRI had the best sensitivity with hippocampal activations obtained in 95 % of patients, versus 65 % with language fMRI. Considering the patients who elicited an hippocampal activation, language fMRI led to 80 %, 65 % and 85 % of correct predictions for respectively global, verbal and non verbal memory (versus 71 %, 64 % and 68 % with memory fMRI). Memory and language fMRI predictions outperformed those made by neuropsychological tests. In summary, language fMRI was less sensitive than memory fMRI to elicit hippocampal activations but when it did, the proportion of correct memory predictions was better. Moreover, it proved to be an independent predictive factor regardless of the side of the epileptic focus. Given the ease of setting up a language task in fMRI, we recommend the systematic combination of memory and language tasks to predict the post-operative memory outcome of MTLE patients undergoing epilepsy surgery. • The aim of this retrospective study was to determine whether hippocampal activations elicited by fMRI language tasks could enhance or refine memory fMRI in MTLE patients candidates to surgery. • Language fMRI was less sensitive than memory fMRI to elicit hippocampal activations but when it did, the proportion of correct memory predictions was better. Moreover, it proved to be an independent predictive factor regardless of the side of the epileptic focus. • Given the ease of setting up a language task in fMRI, we recommend the systematic combination of memory and language tasks to predict the post-operative memory outcome of MTLE patients. [ABSTRACT FROM AUTHOR]

To explore the utility of high frequency oscillations (HFO) and long-range temporal correlations (LRTCs) in preoperative assessment of epilepsy. MEG ripples were detected in 59 drug-resistant epilepsy patients, comprising 5 with parietal lobe epilepsy (PLE), 21 with frontal lobe epilepsy (FLE), 14 with lateral temporal lobe epilepsy (LTLE), and 19 with mesial temporal lobe epilepsy (MTLE) to identify the epileptogenic zone (EZ). The results were compared with clinical MEG reports and resection area. Subsequently, LRTCs were quantified at the source-level by detrended fluctuation analysis (DFA) and life/waiting -time at 5 bands for 90 cerebral cortex regions. The brain regions with larger DFA exponents and standardized life-waiting biomarkers were compared with the resection results. Compared to MEG sensor-level data, ripple sources were more frequently localized within the resection area. Moreover, source-level analysis revealed a higher proportion of DFA exponents and life-waiting biomarkers with relatively higher rankings, primarily distributed within the resection area (p <0.01). Moreover, these two LRCT indices across five distinct frequency bands correlated with EZ. HFO and source-level LRTCs are correlated with EZ. Integrating HFO and LRTCs may be an effective approach for presurgical evaluation of epilepsy. • High frequency oscillations enhance precision in identifying epileptogenic zone. • Long-range temporal correlations across bands aid in localizing epileptogenic zone. • Combining the above two points is more effective than using them separately. [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]

• HHV-6B triggers immune modulatory factors in MTLE. • Increased IL-1a, IL-2 and IL-7 mRNA levels are associated with early antigen expression. • IL-1a and IL-7 may be taken as indirect biomarker of HHV-6B infection in CSF. • Co-localization of HHV-6B antigen with astrocytes and oligodendrocytes. Background: Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity. Methods: Nested polymerase chain reaction (nPCR), real-time PCR, immunohistochemistry (IHC) and suspension bead array for cytokines were performed. Results : Nested polymerase chain reaction (nPCR) in brain tissue revealed HHV-6B DNA in 19 of 49 MTLE patients (39%) and 1 of 19 controls (5%) (P < 0.001), but not in CSF. ICH showed HHV-6B early antigen (P41) positivity in 3 patients (6%), late antigen (gp116/54/64) positivity in 5 patients (10%), latent antigen (U94) positivity in 8 patients (16%), and multiple antigen (early and late or/and latent) positivity in 9 patients (18%). None of these HHV-6B related proteins were found positive in control brain tissue. PCR revealed significant up-regulation of IL-1a, IL-2 and IL-7 mRNA levels in the brain tissue from MTLE patients expressing early antigens compared to those expressing late, latent, multiple antigens, negative antigens and the controls. Suspension bead array of the CSF confirmed significant up-regulation of IL-1a and IL-7 protein expression from MTLE patients expressing early antigens compared to the other groups. Conclusions: Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection. [ABSTRACT FROM AUTHOR]

Background: Intraoperative electrocorticography is used to tailor epilepsy surgery by analysing interictal spikes or spike patterns that can delineate epileptogenic tissue. High-frequency oscillations (HFOs) on intraoperative electrocorticography have been proposed as a new biomarker of epileptogenic tissue, with higher specificity than spikes. We prospectively tested the non-inferiority of HFO-guided tailoring of epilepsy surgery to spike-guided tailoring on seizure freedom at 1 year.Methods: The HFO trial was a randomised, single-blind, adaptive non-inferiority trial at an epilepsy surgery centre (UMC Utrecht) in the Netherlands. We recruited children and adults (no age limits) who had been referred for intraoperative electrocorticography-tailored epilepsy surgery. Participants were randomly allocated (1:1) to either HFO-guided or spike-guided tailoring, using an online randomisation scheme with permuted blocks generated by an independent data manager, stratified by epilepsy type. Treatment allocation was masked to participants and clinicians who documented seizure outcome, but not to the study team or neurosurgeon. Ictiform spike patterns were always considered in surgical decision making. The primary endpoint was seizure outcome after 1 year (dichotomised as seizure freedom [defined as Engel 1A-B] vs seizure recurrence [Engel 1C-4]). We predefined a non-inferiority margin of 10% risk difference. Analysis was by intention to treat, with prespecified subgroup analyses by epilepsy type and for confounders. This completed trial is registered with the Dutch Trial Register, Toetsingonline ABR.NL44527.041.13, and ClinicalTrials.gov, NCT02207673.Findings: Between Oct 10, 2014, and Jan 31, 2020, 78 individuals were enrolled to the study and randomly assigned (39 to HFO-guided tailoring and 39 to spike-guided tailoring). There was no loss to follow-up. Seizure freedom at 1 year occurred in 26 (67%) of 39 participants in the HFO-guided group and 35 (90%) of 39 in the spike-guided group (risk difference -23·5%, 90% CI -39·1 to -7·9; for the 48 patients with temporal lobe epilepsy, the risk difference was -25·5%, -45·1 to -6·0, and for the 30 patients with extratemporal lobe epilepsy it was -20·3%, -46·0 to 5·4). Pathology associated with poor prognosis was identified as a confounding factor, with an adjusted risk difference of -7·9% (90% CI -20·7 to 4·9; adjusted risk difference -12·5%, -31·0 to 5·9, for temporal lobe epilepsy and 5·8%, -7·7 to 19·5, for extratemporal lobe epilepsy). We recorded eight serious adverse events (five in the HFO-guided group and three in the spike-guided group) requiring hospitalisation. No patients died.Interpretation: HFO-guided tailoring of epilepsy surgery was not non-inferior to spike-guided tailoring on intraoperative electrocorticography. After adjustment for confounders, HFOs show non-inferiority in extratemporal lobe epilepsy. This trial challenges the clinical value of HFOs as an epilepsy biomarker, especially in temporal lobe epilepsy. Further research is needed to establish whether HFO-guided intraoperative electrocorticography holds promise in extratemporal lobe epilepsy.Funding: UMCU Alexandre Suerman, EpilepsieNL, RMI Talent Fellowship, European Research Council, and MING Fund. [ABSTRACT FROM AUTHOR]

• Reduction in SV2A binding in the first days after status epilepticus. • SV2A is reduced earlier and stronger in the hippocampus and the piriform cortex. • SV2A levels returned to control levels in all areas in the chronic phase. • SV2A is likely a marker of epileptogenesis. Synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein that binds levetiracetam and is involved in neurotransmission via an unknown mechanism. SV2A-immunoreactivity is reduced in animal models of epilepsy, and in postmortem hippocampi from patients with temporal lobe epilepsy. It is not known if other regions outside the hippocampus are affected in epilepsy, and whether SV2A expression is permanently reduced or regulated over time. In this study, we induced a generalized status epilepticus (SE) by systemic administration of lithium-pilocarpine to adult female rats. The brains from all animals experiencing SE were collected at different time points after the treatment. The radiotracer, [11C]-UCB-J, binds to SV2A with high affinity, and has been used for in vivo imaging as an a-proxy marker for synaptic density. Here we determined the level of tritiated UCB-J binding by semiquantitative autoradiography in the cerebral cortex, hippocampus, thalamus, and hypothalamus, and in cortical subregions. A prominent and highly significant reduction in SV2A binding capacity was observed over the first days after SE in the cerebral cortex and the hippocampus, but not in the thalamus and hypothalamus. The magnitude in reduction was larger and occurred earlier in the hippocampus and the piriform cortex, than in other cortical subregions. Interestingly, in all areas examined, the binding capacity returned to control levels 12 weeks after the SE comparable to the chronic epileptic phase. These data indicate that lithium-pilocarpine-induced epileptogenesis involves both loss and gain of synapses in the in a time-dependent manner. [ABSTRACT FROM AUTHOR]

Neuronal nitric oxide synthase (nNOS) plays a pivotal role in the pathological process of neuronal injury in the development of epilepsy. Our previous study has demonstrated that nitric oxide (NO) derived from nNOS in the epileptic brain is neurotoxic due to its reaction with the superoxide radical with the formation of peroxynitrite. Neuropeptide Y (NPY) is widely expressed in the mammalian brain, which has been implicated in energy homeostasis and neuroprotection. Recent studies suggest that nNOS may act as a mediator of NPY signaling. Here in this study, we sought to determine whether NPY expression is regulated by nNOS, and if so, whether the regulation of NPY by nNOS is associated with the neuronal injuries in the hippocampus of epileptic brain. Our results showed that pilocarpine-induced temporal lobe epilepsy (TLE) mice exhibited an increased level of nNOS expression and a decreased level of NPY expression along with hippocampal neuronal injuries and cognition deficit. Genetic deletion of nNOS gene, however, significantly upregulated hippocampal NPY expression and reduced TLE-induced hippocampal neuronal injuries and cognition decline. Knockdown of NPY abolished nNOS depletion-induced neuroprotection and cognitive improvement in the TLE mice, suggesting that inhibition of nNOS protects against hippocampal neuronal injuries by increasing neuropeptide Y expression in TLE mice. Targeting nNOS-NPY signaling pathway in the epileptic brain might provide clinical benefit by attenuating neuronal injuries and preventing cognitive deficits in epilepsy patients. [Display omitted] • NOS enzymatic activity is increased in the hippocampus of TLE mice. • Inhibition of nNOS suppresses TLE-induced cognitive impairment. • Inhibition of nNOS suppresses TLE-induced neuroinflammation and neuronal injuries. • nNOS negatively regulates NPY expression in the hippocampus of TLE mice. • Inhibition of nNOS suppresses TLE-induced neural injuries in a NPY-dependent manner. [ABSTRACT FROM AUTHOR]

To assess hippocampal function during stereoelectroencephalography (SEEG) investigations through the study of the medial temporal lobe event-related potential (ERP) MTL-P300. We recorded the MTL-P300 during a visual oddball task, using hippocampal electrodes implanted for SEEG in 71 patients, in a preoperative epilepsy investigation. The presence of an MTL-P300 and its amplitude were correlated with hippocampal involvement during seizures and memory function. Analysis using ROC curves revealed that an MTL-P300 amplitude below -46 µV, has a specificity of 93.3% in detecting the epileptogenic zone, and absence of the MTL-P300 in the left hippocampus of patients with typical language organization was associated with marked alteration of verbal memory scores. There was a significant correlation between performance in non-verbal memory tests and the amplitude of the MTL-P300 in the right hippocampus of patients with left hemispheric seizures (immediate visual recall: r = 0.67, p = 0.005; delayed visual recall: r = 0.56, p = 0.025). Using a linear regression, we confirmed that the absence of the MTL-P300 in the left hippocampus, the involvement of the left hippocampus during seizures, and the duration of epilepsy were predictors of verbal memory deficits. Analysis of the MTL-P300 during SEEG recording provides relevant information for the analysis of hippocampal functionality and can help to localize the epileptogenic zone. [ABSTRACT FROM AUTHOR]

Purpose: Ictal hypoxemia is accepted as one of the mechanisms underlying sudden unexpected death in epilepsy (SUDEP). Although ictal hypoxemia is more common in generalized seizures, it also occurs in focal seizures with or without generalization. In this study, we aimed to show the relationship between clinical and electroencephalographic findings of seizures in patients with temporal lobe epilepsy (TLE) with periictal oxygen saturation.Methods: The data of 55 adult patients who were hospitalized in the Video EEG Monitoring Unit (VEMU) and operated on for drug-resistant TLE between January 2017 and December 2020 were examined. Forty-five seizures from 21 patients with ictal peripheral arterial saturation information and that were seizure-free for at least a year during the follow-up were included in the study.Results: The median patient age was 28 (IQR 25-39.5) years (women: 9, men: 12). Age at epilepsy onset was negatively correlated with saturation at seizure onset. Moreover, the age at VEMU admission was also negatively correlated with saturation at seizure onset and the lowest levels of saturation. The saturation at the end of the seizures and the lowest saturation measured in the periictal period with generalization of EEG were significantly lower than those without generalization. The onset of ictal EEG with the rhythmic theta pattern was significantly associated with the lowest level of saturation (<90%), postictal generalized electroencephalographic suppression (PGES), and the presence of generalization.Conclusion: According to the study, rhythmic ictal theta activity, older age, nocturnal seizure, and generalization in ictal EEG might increase the potential risk of SUDEP. Further studies including a greater number of subjects and different epilepsy syndromes may provide more comprehensive information about potential biomarkers for SUDEP. [ABSTRACT FROM AUTHOR]

Objective: We assessed the diagnostic utility of the occurrence rate of high-frequency oscillations and modulation index (MI) from intraoperative electrocorticography (ioECoG) in determining the extent of epileptogenicity in mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS).Methods: We enrolled 17 patients who underwent selective amygdalohippocampectomy (SelAH) for TLE due to HS. We analyzed the occurrence rate of ripples (80-200 Hz) and fast ripples (200-300 Hz); and MI between ripples and 3-4 Hz (MIRipples/3-4 Hz) and fast ripples and 3-4 Hz (MIFRs/3-4 Hz) from the amygdala, hippocampus, and lateral temporal lobe (LTL) pre-SelAH and the LTL post-SelAH, and subsequently categorized the patients into good and poor seizure outcome groups. We compared the occurrence rates and MIs over each region of interest between both groups. Receiver operating characteristic analysis was used to identify the most optimal indicator to predict poor surgical outcomes.Results: In the poor seizure outcome group, an increase in the occurrence rate of ripples was seen in the hippocampus and LTL pre-SelAH and the LTL post-SelAH. The MIRipples/3-4 Hz from the LTL pre-SelAH was the most indicative factor of poor outcome.Conclusions: High occurrence rate of ripples and MIRipples/3-4 Hz from the LTL showed wide epileptogenicity in TLE patients with poor seizure outcomes after SelAH. Our data suggest that the analysis of the occurrence rate of HFOs and MIHFOs/3-4 Hz from ioECoG, especially from the LTL, can indicate the distribution of epileptogenicity in TLE with HS. [ABSTRACT FROM AUTHOR]

[Display omitted] • Chronic epilepsy results in reduced REM sleep duration and prolonged REM latency. • Enriched environment (EE) improves REM sleep in epileptic rats. • EE reversed the altered delta, theta, and gamma oscillations in epileptic rats. • EE normalised PFC–CA1 hypersynchronous activity in epileptic rats. • EE prevented epilepsy-induced further loss of PV+ interneurons. Sleep dysfunctions in epilepsy increase the burden of seizures and cognitive impairments. Seizures and certain anti-seizure drugs (ASDs) can affect sleep quality, leading to excessive daytime sleepiness and poor cognitive performance. Therefore, it is imperative to develop non-pharmacological strategies to curb epilepsy and related sleep dysfunction. Enriched environment (EE) has been demonstrated to ameliorate seizures and associated comorbidity in animal models of epilepsy. However, its effects on epilepsy-induced sleep dysfunctions and altered neural activity remain unexplored. To study the same, chronic epilepsy was induced in male Wistar rats and subjected to standard or enriched housing (6 h/day for 14 days), after which sleep/wake cycle, EEG spectral power and coherence during all vigilance states were analysed. Further, hippocampal parvalbumin-positive (PV+) interneurons were quantified to correlate the functional implications with the electrophysiological changes. Epileptic rats showed decreased rapid eye movement (REM) sleep, prolonged REM latency, and extended wake after sleep onset (WASO). Power spectrum analysis indicated an increase in delta and theta activity with a concomitant decrease in gamma activity during wake, an increase in prefrontal cortex (PFC)– Cornu ammonis (CA1) coherence, and a significant loss of hippocampal PV+ interneuron density. Exposure to EE restored REM sleep duration and latency without altering WASO in epileptic rats. EE also restored delta power during non-rapid eye movement (NREM) and theta, gamma power during wake, PFC–CA1 coherence, and PV+ interneurons density. These results further strengthen the role of EE's positive effects on brain plasticity and aid in developing non-pharmacological strategies to mitigate epilepsy-associated comorbidities. [ABSTRACT FROM AUTHOR]

Focused ultrasound (FUS) has potential utility for modulating regional brain excitability and possibly aiding seizure control; however, the duration of any beneficial effect is unknown. This study explores the efficacy and time course of a short series of pulsed FUS in suppressing EEG epileptiform spikes/bursts in a kainic acid (KA) animal model of temporal lobe epilepsy. Forty-four male Sprague-Dawley rats were recorded for 14 weeks with EEG while software calculated EEG numbers of epileptiform spikes and bursts (≥ 3 spikes/s). Four regimens of FUS given in a single session at week 7 were evaluated, with mechanical index (MI) ranging from 0.25 to 0.75, intensity spatial peak temporal average (ISPTA) from 0.1 to 2.8 W per cm2, duty cycle from 1 to 30%, and three consecutive pulse trains for 5 or 10 min each. Controls included sham injections in four and KA without FUS in eleven animals. Histological analysis investigated tissue effects. All animals receiving KA evidenced EEG spikes, averaging 10,378 ± 1651 spikes per 8 h and 1255 ± 199 bursts per 8 h by weeks 6-7. The KA-only group showed a 30% of increase in spikes and bursts by week 14. Compared to the KA-only group, spike counts were reduced by about 25%, burst counts by about 33%, and burst durations by about 50% with FUS. Behavioral seizures were not analyzed, but electrographic seizures longer than 10 s declined up to 70% after some FUS regimens. Repeated-measure ANOVA showed a significant effect of higher intensity and longer sonication duration FUS treatment using 0.75-MI, ISPTA 2.8 W/cm2, 30% duty cycle for 10-min sonications (group effect, F (4, 15) = 6.321, p < 0.01; interaction effect, F (44, 165) = 1.726, p < 0.01), with the hippocampal protective effect lasting to week 14, accompanied by decreased inflammation and gliosis effect. In contrast, spike and burst suppression were achieved using an FUS regimen with 0.25-MI ISPTA 0.5 W/cm2, 30% duty cycle for 10-min sonications. This regimen reduced inflammation and gliosis at weeks 8-14 and protected hippocampal tissue. This study demonstrates that low-intensity pulsed ultrasound can modulate epileptiform activity for up to 7 weeks and, if replicated in the clinical setting, might be a practical treatment for epilepsy. [ABSTRACT FROM AUTHOR]

We describe a case of severe encephalopathy with reversible splenial lesion associated with parechovirus, followed by intractable temporal lobe epilepsy (TLE), which was improved by epilepsy surgery. A 3-year-old girl was admitted because of fever, consciousness disturbance and generalized tonic clonic seizure. Her seizure lasted for four hours. Fluid-attenuated inversion recovery (FLAIR) showed a hyperintensity in the splenium of the corpus callosum. Electroencephalogram (EEG) demonstarated continuous diffuse epileptic activity represented by synchronous and rhythmic high-amplitude spikes and waves, which led to the diagnosis of status epilepticus. Her consciousness was improved with fosphenytoin, midazolam and methylprednisolone pulse after 3 days. Seven days later, FLAIR hyperintensity in the splenium of the corpus callosum was disappeared; however, a hyperintensity in the right hippocampus was detected. Since the stool examination was positive for parechovirus, her final diagnosis was reversible splenial lesion syndrome (RESLES) associated with parechovirus. At age 8, she experienced epigastric sensation and consciousness disturbance once a week. Based on the scalp EEG and radiological findings, she was diagnosed with intractable right TLE. We performed a right selective amygdalohippocampectomy and anterior temporal disconnection at 10 years of age. One year and 3 months after surgery, she was seizure free. To our knowledge, this is the first report of severe febrile epilepticus status. with RESLES associated with parechovirus, followed by intractable TLE, which was resolved by epilepsy surgery. [ABSTRACT FROM AUTHOR]

[Display omitted] • Glial activation and neurodegeneration contribute to the epilepsy associated cognitive impairment. • Metformin improved the TLE associated cognitive impairment by inhibiting neuroinflammation and neurodegeneration in rats. • Metformin inhibited the microglial and astroglial activation in epileptic rats. • Metformin holds promise as a therapeutic intervention for cognitive impairment associated with epilepsy. Cognitive impairment is a prevalent co-morbidity associated with epilepsy. Emerging studies indicate that neuroinflammation could be a possible link between epilepsy and its comorbidities, including cognitive impairment. In this context, the roles of glial activation, proinflammatory mediators, and neuronal death have been well studied and correlated with epilepsy-associated cognitive impairment in animal studies. While recent reports have demonstrated the anti-epileptogenic and anti-convulsant actions of metformin, its effect on epilepsy associated cognitive deficit remains unknown. Therefore, the current study investigated the effect of metformin treatment on neuroinflammation, neurodegeneration, and cognitive deficits after inducing status epilepticus (SE) with lithium-pilocarpine in rats. Metformin treatment improved the hippocampal-dependent spatial and recognition memory in Morris water maze and Novel object recognition tasks, respectively. Further, metformin treatment attenuated microglial and astroglial activation, accompanied by reduced IL-1β, COX-2 and NF-ĸβ gene expression. Additionally, metformin conferred neuroprotection by inhibiting the neuronal death as assessed by Nissl staining and transmission electron microscopy. These findings suggest that metformin holds promise as a therapeutic intervention for cognitive impairment associated with epilepsy, possibly through its modulation of glial activation and neuronal survival. Further research is needed to elucidate the precise mechanisms and to assess the long-term effect of metformin in epilepsy-associated cognitive impairment. [ABSTRACT FROM AUTHOR]