MRI-Derived Modeling of Disease Progression Patterns in Patients With Temporal Lobe Epilepsy.

BACKGROUND AND OBJECTIVES: Temporal lobe epilepsy (TLE) is assumed to follow a steady course that is similar across patients. To date, phenotypic and temporal diversities of TLE evolution remain unknown. In this study, we aimed at simultaneously characterizing these sources of variability based on cross-sectional data. METHODS: We studied consecutive patients with TLE referred for evaluation by neurologists to the Montreal Neurological Institute epilepsy clinic, who underwent in-patient video EEG monitoring and multimodal imaging at 3 Tesla, comprising 3D T1 and fluid-attenuated inversion recovery and 2D diffusion-weighted MRI. The cohort included patients with drug-resistant epilepsy and patients with drug-responsive epilepsy. The neuropsychological evaluation included Wechsler Adult Intelligence Scale-III and Leonard tapping task. The control group consisted of participants without TLE recruited through advertisement and who underwent the same MRI acquisition as patients. Based on surface-based analysis of key MRI markers of pathology (gray matter morphology and white matter microstructure), the Subtype and Stage Inference algorithm estimated subtypes and stages of brain pathology to which individual patients were assigned. The number of subtypes was determined by running the algorithm 100 times and estimating mean and SD of disease trajectories and the consistency of patients' assignments based on 1,000 bootstrap samples. Effect of normal aging was subtracted from patients. We examined associations with clinical and cognitive parameters and utility for individualized predictions. RESULTS: We studied 82 patients with TLE (52 female, mean age 35 ± 10 years; 11 drug-responsive) and 41 control participants (23 male, mean age 32 ± 8 years). Among 57 operated, 43/37/20 had Engel-I outcome/hippocampal sclerosis/hippocampal isolated gliosis, respectively. We identified 3 trajectory subtypes: S1 (n = 35), led by ipsilateral hippocampal atrophy and gliosis, followed by white-matter damage; S2 (n = 27), characterized by bilateral neocortical atrophy, followed by ipsilateral hippocampal atrophy and gliosis; and S3 (n = 20), typified by bilateral limbic white-matter damage, followed by bilateral hippocampal gliosis. Patients showed high assignability to their subtypes and stages (>90% bootstrap agreement). S1 had the highest proportions of patients with early disease onset (effect size d = 0.27 vs S2, d = 0.73 vs S3), febrile convulsions (χ2 = 3.70), drug resistance (χ2 = 2.94), a positive MRI (χ2 = 8.42), hippocampal sclerosis (χ2 = 7.57), and Engel-I outcome (χ2 = 1.51), pFDR < 0.05 across all comparisons. S2 and S3 exhibited the intermediate and lowest proportions, respectively. Verbal IQ and digit span were lower in S1 (d = 0.65 and d = 0.50, pFDR < 0.05) and S2 (d = 0.76 and d = 1.09, pFDR < 0.05), compared with S3. We observed progressive decline in sequential motor tapping in S1 and S3 (T = -3.38 and T = -4.94, pFDR = 0.027), compared with S2 (T = 2.14, pFDR = 0.035). S3 showed progressive decline in digit span (T = -5.83, p = 0.021). Supervised classifiers trained on subtype and stage outperformed subtype-only and stage-only models predicting drug response in 73% ± 1.0% (vs 70% ± 1.4% and 63% ± 1.3%) and 76% ± 1.6% for Engel-I outcome (vs 71% ± 0.8% and 72% ± 1.1%), pFDR < 0.05 across all comparisons. DISCUSSION: Cross-sectional MRI-derived models provide reliable prognostic markers of TLE disease evolution, which follows distinct trajectories, each associated with divergent patterns of hippocampal and whole-brain structural alterations, as well as cognitive and clinical profiles.

Associations of Cerebral Blood Flow Patterns With Gray and White Matter Structure in Patients With Temporal Lobe Epilepsy.

BACKGROUND AND OBJECTIVES: Neuroimaging studies in patients with temporal lobe epilepsy (TLE) show widespread brain network alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. Here, we studied whole-brain perfusion and vascular network alterations in TLE and assessed its associations with gray and white matter compromises and various clinical variables. METHODS: We included individuals with and without pharmaco-resistant TLE who underwent multimodal 3T MRI, including arterial spin labelling, structural, and diffusion-weighted imaging. Using surface-based MRI mapping, we generated individualized cortico-subcortical profiles of perfusion, morphology, and microstructure. Linear models compared regional CBF in patients with controls and related alterations to morphological and microstructural metrics. We further probed interregional vascular networks in TLE, using graph theoretical CBF covariance analysis. The effects of disease duration were explored to better understand the progressive changes in perfusion. We assessed the utility of perfusion in separating patients with TLE from controls using supervised machine learning. RESULTS: Compared with control participants (n = 38; mean ± SD age 34.8 ± 9.3 years; 20 females), patients with TLE (n = 24; mean ± SD age 35.8 ± 10.6 years; 12 females) showed widespread CBF reductions predominantly in fronto-temporal regions (Cohen d -0.69, 95% CI -1.21 to -0.16), consistent in a subgroup of patients who remained seizure-free after surgical resection of the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partially constrained by gray and white matter changes (8.11% reduction in Cohen d) and topologically segregated from whole-brain perfusion networks (area under the curve -0.17, p < 0.05). Negative effects of progressive disease duration further targeted regional CBF profiles in patients (r = -0.54, 95% CI -0.77 to -0.16). Perfusion-derived classifiers discriminated patients from controls with high accuracy (71% [70%-82%]). Findings were robust when controlling for several methodological confounds. DISCUSSION: Our multimodal findings provide insights into vascular contributions to TLE pathophysiology affecting and extending beyond mesiotemporal structures and highlight their clinical potential in epilepsy diagnosis. As our work was cross-sectional and based on a single site, it motivates future longitudinal studies to confirm progressive effects, ideally in a multicentric setting.

HB-EGF activates EGFR to induce reactive neural stem cells in the mouse hippocampus after seizures.

Hippocampal seizures mimicking mesial temporal lobe epilepsy cause a profound disruption of the adult neurogenic niche in mice. Seizures provoke neural stem cells to switch to a reactive phenotype (reactive neural stem cells, React-NSCs) characterized by multibranched hypertrophic morphology, massive activation to enter mitosis, symmetric division, and final differentiation into reactive astrocytes. As a result, neurogenesis is chronically impaired. Here, using a mouse model of mesial temporal lobe epilepsy, we show that the epidermal growth factor receptor (EGFR) signaling pathway is key for the induction of React-NSCs and that its inhibition exerts a beneficial effect on the neurogenic niche. We show that during the initial days after the induction of seizures by a single intrahippocampal injection of kainic acid, a strong release of zinc and heparin-binding epidermal growth factor, both activators of the EGFR signaling pathway in neural stem cells, is produced. Administration of the EGFR inhibitor gefitinib, a chemotherapeutic in clinical phase IV, prevents the induction of React-NSCs and preserves neurogenesis.

Dissociation Between the Epileptogenic Lesion and Primary Seizure Onset Zone in the Tetanus Toxin Model of Temporal Lobe Epilepsy.

Despite extensive temporal lobe epilepsy (TLE) research, understanding the specific limbic structures' roles in seizures remains limited. This weakness can be attributed to the complex nature of TLE and the existence of various TLE subsyndromes, including non-lesional TLE. Conventional TLE models like kainate and pilocarpine hinder precise assessment of the role of individual limbic structures in TLE ictogenesis due to widespread limbic damage induced by the initial status epilepticus. In this study, we used a non-lesional TLE model characterized by the absence of initial status and cell damage to determine the spatiotemporal profile of seizure initiation and limbic structure recruitment in TLE. Epilepsy was induced by injecting a minute dose of tetanus toxin into the right dorsal hippocampus in seven animals. Following injection, animals were implanted with bipolar recording electrodes in the amygdala, dorsal hippocampus, ventral hippocampus, piriform, perirhinal, and entorhinal cortices of both hemispheres. The animals were video-EEG monitored for four weeks. In total, 140 seizures (20 seizures per animal) were analyzed. The average duration of each seizure was 53.2+/-3.9 s. Seizure could initiate in any limbic structure. Most seizures initiated in the ipsilateral (41 %) and contralateral (18 %) ventral hippocampi. These two structures displayed a significantly higher probability of seizure initiation than by chance. The involvement of limbic structures in seizure initiation varied between individual animals. Surprisingly, only 7 % of seizures initiated in the injected dorsal hippocampus. The limbic structure recruitment into the seizure activity wasn't random and displayed consistent patterns of early recruitment of hippocampi and entorhinal cortices. Although ventral hippocampus represented the primary seizure onset zone, the study demonstrated the involvement of multiple limbic structures in seizure initiation in a non-lesional TLE model. The study also revealed the dichotomy between the primary epileptogenic lesion and main seizure onset zones and points to the central role of ventral hippocampi in temporal lobe ictogenesis.

Association of interleukin-1 and interleukin-6 levels in lateralized temporal epilepsy patients.

Objectives: To explore the clinical significance of interleukin-1 and interleukin-6 in the development of lateralized temporal epilepsy. METHODS: The prospective study was conducted from January to April of 2022 at the Neurology Department of Training and Research Hospital, Istanbul Medeniyet University, Turkey, and comprised patients with lateralized temporal epilepsy aged 18-86 years who were in the interictal period in group A and healthy controls in group B. The levels of interleukin-1 and interleukin-6 of patients in both groups were compared. Data was analysed using SPSS 25. RESULTS: Of the 92 subjects, 60(65.2%) were in group A; 35(58.3%) were males and 25(41.7%) were females with a median age of 37.5 years (interquartile range: 2.2-42.7 years). There were 32(34.8%) subjects in group B; 19(40.6%) females and 13(40.6%) males with a median age of 40.5 years (interquartile range: 25-50 years) (p>0.05). Within group A, 41(68.3%) patients had left-sided epilepsy and 19(31.7%) had right-sided epilepsy (p<0.001). Both interleukin-1 and interleukin-6 levels were lower in group A than in group B (p<0.001). Both interleukin levels did not significantly differ between right and leftlateralised temporal seizures (p=0.44). In the left-lateralized temporal seizures, interleukin-1 levels correlated with epilepsy duration (p<0.006), lower onset age (p<0.050), and presence of prenatal risk (p<0.028). Interleukin-1 and interleukin-6 levels were positively correlated with each other for lateralized temporal epileptic hemispheres (p<0.001). CONCLUSIONS: Interleukin-1 level was correlated with epilepsy duration, lower onset age, and presence of prenatal risk in the left-lateralized temporal epilepsy.

Peri-ictal Water Drinking in an Omani Patient with Bilateral Mesial Temporal Sclerosis.

Peri-ictal water drinking (PIWD) is a rare vegetative manifestation of temporal lobe epilepsy without a definite lateralisation value. We report a case of PIWD in a 22-year-old Omani male patient with post-concussion syndrome and epilepsy presented to a tertiary care hospital in Muscat, Oman, in 2021 for evaluation of paroxysmal events. His behaviour of PIWD was misinterpreted by his family until characterised in the epilepsy-monitoring unit as a manifestation of epilepsy that was treated medically. To the best of the authors' knowledge, this is the second reported case in the region.

Memory changes in patients with hippocampal sclerosis submitted to surgery to treat mesial temporal lobe epilepsy.

PURPOSE: This study was performed with the purpose of analysing the relationship between epileptological and surgical variables and post-operative memory performance, following surgery for refractory mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS). METHODS: Logical memory (LM) and visual memory (VM) scores for immediate and late follow-up of 201 patients operated for MTLE/HS were reviewed. Scores were standardized with a control group of 54 healthy individuals matched for age and education. The Reliable Change Index (RCI) was calculated to verify individual memory changes for late LM and VM scores. A multiple linear regression analysis was carried out with the RCI, using LM and VM scores as well as the clinical variables. RESULTS: A total of 112 (56%) patients had right HS. The RCI of the right HS group demonstrated that 6 (7%) patients showed improvement while 5 (6%) patients showed decreased scores in late LM; for late VM, 7 (8%) patients presented improvement, and 2 (3%) patients showed poorer scores. RCI of the left HS group showed that 3 (3%) individuals showed improved scores, while scores of 5 (4%) patients worsened for late LM; for late VM, 3 (3%) patients presented higher scores and 6 (5%) showed lower scores. Left HS and advanced age at onset of the first epileptic seizure were predictors of late LM loss (p<.05). CONCLUSION: Left MTLE/HS and seizure onset at advanced ages were predictive factors for the worsening of late LM. We observed poorer baseline LM function in the left HS group and improvement of LM in some patients who had resection of the right MTL. Patients in the right HS group showed a higher percentage of reliable post-operative improvement for both VM and LM scores.

Molecular Genetics of Acquired Temporal Lobe Epilepsy.

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

Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy-A Preliminary Study in a Brazilian Cohort Sample.

The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy-Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06-3.37); OR = 1.38 (95%CI = 1.04-1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25-5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01-2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08-5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04-17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.

Connectome-based prediction of cognitive performance in patients with temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) patients often exhibit varying degrees of cognitive impairments. This study aims to predict cognitive performance in TLE patients by applying a connectome-based predictive model (CPM) to whole-brain resting-state functional connectivity (RSFC) data. METHODS: A CPM was established and leave-one-out cross-validation was employed to decode the cognitive performance of patients with TLE based on the whole-brain RSFC. RESULTS: Our findings indicate that cognitive performance in TLE can be predicted through the internal and network connections of the parietal lobe, limbic lobe, and cerebellum systems. These systems play crucial roles in cognitive control, emotion processing, and social perception and communication, respectively. In the subgroup analysis, CPM successfully predicted TLE patients with and without focal to bilateral tonic-clonic seizures (FBCTS). Additionally, significant differences were noted between the two TLE patient groups and the normal control group. CONCLUSION: This data-driven approach provides evidence for the potential of predicting brain features based on the inherent resting-state brain network organization. Our study offers an initial step towards an individualized prediction of cognitive performance in TLE patients, which may be beneficial for diagnosis, prognosis, and treatment planning.

Microstate-based brain network dynamics distinguishing temporal lobe epilepsy patients: A machine learning approach.

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

Neuronal avalanches in temporal lobe epilepsy as a noninvasive diagnostic tool investigating large scale brain dynamics.

The epilepsy diagnosis still represents a complex process, with misdiagnosis reaching 40%. We aimed at building an automatable workflow, helping the clinicians in the diagnosis of temporal lobe epilepsy (TLE). We hypothesized that neuronal avalanches (NA) represent a feature better encapsulating the rich brain dynamics compared to classically used functional connectivity measures (Imaginary Coherence; ImCoh). We analyzed large-scale activation bursts (NA) from source estimation of resting-state electroencephalography. Using a support vector machine, we reached a classification accuracy of TLE versus controls of 0.86 ± 0.08 (SD) and an area under the curve of 0.93 ± 0.07. The use of NA features increase by around 16% the accuracy of diagnosis prediction compared to ImCoh. Classification accuracy increased with larger signal duration, reaching a plateau at 5 min of recording. To summarize, NA represents an interpretable feature for an automated epilepsy identification, being related with intrinsic neuronal timescales of pathology-relevant regions.

Altered immune pathways in patients of temporal lobe epilepsy with and without hippocampal sclerosis.

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

[The association between frontotemporal connecting fibers and seizure severity in patients with temporal lobe epilepsy].

The patients with temporal lobe epilepsy (TLE) admitted in the Department of Neurology, Zhongshan Hospital, Fudan University from June 2009 to February 2012 were prospectively enrolled. The diffusion tensor imaing was performed on the patients at the time of enrollment and 3 years later. The fractional anisotropy (FA) values of the white matter connecting fibers(bilateral hooked, arcuate, cingulate, and superior longitudinal tracts), the connecting fibers of both hemispheres(anterior union, anterior callosal forceps, posterior forceps, and bilateral fornix), and fibers of perirhinal cortices system(bilateral radiating crown and anterior limb of the internal capsule) were measured by the region of interest method. The severity of epilepsy was evaluated using the Veterans Administration Seizure Type and Frequency Rating Scale(VA-2) and National Hospital Seizure Severity Scale (NHS3). A total of 51 patients with TLE were screened, with 27 patients completing the 3-year follow-up. There were 13 males and 14 females with an age of (32±11) years and a follow-up duration of (39.1±1.1) months. During the follow-up, 6 patients had increased/unchanged NHS3 or VA-2 scores, while 21 patients had decreased scores. Three years later, the FA values of the bilateral arcuate fasciculus, the right superior longitudinal fasciculus, the right radial coronal and corpus callosum anterior forceps in TLE patients decreased compared to baseline(P<0.05). However, compared to the patients with decreased VA-2 scores during the follow-up, the degree of increase in FA values (ΔFA, follow-up FA value-baseline FA value) of the ipsilateral hook bundle caused by epilepsy was more significant in the group with increased/unchanged VA-2 scores (decreased score group vs increased/unchanged score group:-0.032±0.063 vs 0.018±0.043, t=2.305, P=0.035). The value of ΔFA in epileptic patients with increased/unchanged NHS3 scores (0.075±0.113) was higher compared to those with decreased scores (-0.079±0.099, t=2.804, P=0.010). Correlation analysis also showed the changes in FA values of epileptic lateral fasciculus (r=0.503, P=0.009) and arcuate fasciculus (r=0.602, P=0.001)were positively correlated with the changes in VA-2 and HNS3 scores, respectively. The seizure severity in patients with TLE was closely associated with the microstructure changes in the frontal and temporal white matter, especially the arcuate and uncinate tracts, on the same side that caused seizures, which may indicate the white matter remodeling and abnormal network reformation associated with seizures.

EEG Ictal Power Dynamics, Function-Structure Associations, and Epilepsy Surgical Outcomes.

BACKGROUND AND OBJECTIVES: Postoperative seizure control in drug-resistant temporal lobe epilepsy (TLE) remains variable, and the causes for this variability are not well understood. One contributing factor could be the extensive spread of synchronized ictal activity across networks. Our study used novel quantifiable assessments from intracranial EEG (iEEG) to test this hypothesis and investigated how the spread of seizures is determined by underlying structural network topological properties. METHODS: We evaluated iEEG data from 157 seizures in 27 patients with TLE: 100 seizures from 17 patients with postoperative seizure control (Engel score I) vs 57 seizures from 10 patients with unfavorable surgical outcomes (Engel score II-IV). We introduced a quantifiable method to measure seizure power dynamics within anatomical regions, refining existing seizure imaging frameworks and minimizing reliance on subjective human decision-making. Time-frequency power representations were obtained in 6 frequency bands ranging from theta to gamma. Ictal power spectrums were normalized against a baseline clip taken at least 6 hours away from ictal events. Electrodes' time-frequency power spectrums were then mapped onto individual T1-weighted MRIs and grouped based on a standard brain atlas. We compared spatiotemporal dynamics for seizures between groups with favorable and unfavorable surgical outcomes. This comparison included examining the range of activated brain regions and the spreading rate of ictal activities. We then evaluated whether regional iEEG power values were a function of fractional anisotropy (FA) from diffusion tensor imaging across regions over time. RESULTS: Seizures from patients with unfavorable outcomes exhibited significantly higher maximum activation sizes in various frequency bands. Notably, we provided quantifiable evidence that in seizures associated with unfavorable surgical outcomes, the spread of beta-band power across brain regions is significantly faster, detectable as early as the first second after seizure onset. There was a significant correlation between beta power during seizures and FA in the corresponding areas, particularly in the unfavorable outcome group. Our findings further suggest that integrating structural and functional features could improve the prediction of epilepsy surgical outcomes. DISCUSSION: Our findings suggest that ictal iEEG power dynamics and the structural-functional relationship are mechanistic factors associated with surgical outcomes in TLE.

Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE).

BACKGROUND AND OBJECTIVES: New-onset refractory status epilepticus (NORSE) occurs in previously healthy children or adults, often followed by refractory epilepsy and poor outcomes. The mechanisms that transform a normal brain into an epileptic one capable of seizing for prolonged periods despite treatment remain unclear. Nonetheless, several pieces of evidence suggest that immune dysregulation could contribute to hyperexcitability and modulate NORSE sequelae. METHODS: We used single-nucleus RNA sequencing to delineate the composition and phenotypic states of the CNS of 4 patients with NORSE, to better understand the relationship between hyperexcitability and immune disturbances. We compared them with 4 patients with chronic temporal lobe epilepsy (TLE) and 2 controls with no known neurologic disorder. RESULTS: Patients with NORSE and TLE exhibited a significantly higher proportion of excitatory neurons compared with controls, with no discernible difference in inhibitory GABAergic neurons. When examining the ratio between excitatory neurons and GABAergic neurons for each patient individually, we observed a higher ratio in patients with acute NORSE or TLE compared with controls. Furthermore, a negative correlation was found between the ratio of excitatory to GABAergic neurons and the proportion of GABAergic neurons. The ratio between excitatory neurons and GABAergic neurons correlated with the proportion of resident or infiltrating macrophages, suggesting the influence of microglial reactivity on neuronal excitability. Both patients with NORSE and TLE exhibited increased expression of genes associated with microglia activation, phagocytic activity, and NLRP3 inflammasome activation. However, patients with NORSE had decreased expression of genes related to the downregulation of the inflammatory response, potentially explaining the severity of their presentation. Microglial activation in patients with NORSE also correlated with astrocyte reactivity, possibly leading to higher degrees of demyelination. DISCUSSION: Our study sheds light on the complex cellular dynamics in NORSE, revealing the potential roles of microglia, infiltrating macrophages, and astrocytes in hyperexcitability and demyelination, offering potential avenues for future research targeting the identified pathways.

Lateralizing value and clinicoradiological features of asymmetric last clonic jerks in temporal and extratemporal epilepsy.

Seizure semiology and electroencephalograph (EEG) are very important for determining seizure type, hemisphere lateralization, or localization. Clinical symptoms of focal seizures, as well as findings at the onset or end of a focal to bilateral tonic-clonic seizure (FBTCS), are highly informative for lateralization. This study aimed to investigate the relationship of asymmetric last clonic jerk in patients with temporal or extratemporal lobe epilepsy with pathologies, localization, lateralization, or other semiological findings detected in neuroimaging or neuro psychometric tests and its positive predictive value for the detection of hemisphere lateralization based on seizure onset ictal EEG activation. 44 patients with asymmetric last clonic jerks (aLCJ) who were followed up in our VEM unit were randomized 1:1 with epilepsy patients without. In patients with ipsilateral automatism and contralateral posture or gustatory and olfactory hallucinations aLCJ was less or absent. In patients with unilateral tonic activity, aLCJ was more common. The positive predictive value of aLCJ for ictal EEG activation lateralization was 86.36%. In conclusion, asymmetric last clonic beat is valuable for lateralization of FBTCS and should be considered. Its presence strongly and reliably lateralizes to the side of seizure onset.