Mesial Temporal Lobe Research Articles

SURG-09. IMPACT OF RESPONSIVE NEUROSTIMULATION IN PATIENTS WITH MESIAL TEMPORAL EPILEPSY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract BACKGROUND Brain-responsive neurostimulation, known as the RNS therapy, proves to be a safe and effective adjuvant therapy in decreasing seizure frequency among medically refractory adults with partial-onset seizures who are either seizure-prone post-surgery or are not eligible candidates for surgery. Nevertheless, previous publications have not presented outcomes specifically on subjects with Mesial temporal lobe epilepsy (MTLE). This meta-analysis aims to evaluate the effectiveness of RNS therapy in patients with medically refractory MTLE. METHODS A comprehensive search was conducted across the PubMed, Cochrane, and Scopus databases for studies evaluating the impact of RNS on seizure frequency in patients with mesial temporal epilepsy. Relevant studies published up to March 2024 were included. The statistical analysis assessed the mean seizure reduction, responder rate, and seizure freedom. RESULTS We applied a random-effects model to data from 7 cohort studies with 207 patients, which revealed a significant mean reduction in seizures among individuals who received RNS therapy (68.76%, 95%CI=57.16-80.37%, p-value<0.01). A sub-analysis of 5 studies involving 164 patients demonstrated a substantial response rate (67%, 95%CI= 47-88%, p-value<0.01). Furthermore, an analysis of 4 studies comprising 154 patients indicated a considerable proportion of patients achieved seizure freedom after treatment (Proportion=0.29, 95%CI=0.03-0.55, p-value=0.03). Notably, there was moderate to high heterogeneity across the studies. CONCLUSION This single-arm meta-analysis demonstrates that responsive neurostimulation could be an effective therapeutic option for patients with MTLE, significantly reducing seizure frequency and a high proportion of patients achieving seizure freedom. Further research, including randomized controlled trials with control groups, larger sample sizes, and longer follow-up periods, is warranted to validate these results and optimize patient outcomes. Keywords: neurostimulation; mesial temporal epilepsy; systematic review; meta-analysis.

CNSC-39. INTEGRATED CLINICAL GENETIC ANALYSIS REVEALS NEUROTRANSMITTER RECEPTOR DYSREGULATION IN MENINGIOMAS CAUSING SEIZURE

Abstract Molecular correlates of seizures in meningioma remain unexplored. Previously, we identified MenG molecular grouping, wherein MenG C meningiomas recur more than MenG A or B. We therefore sought to identify molecular and clinical drivers of seizures in meningioma. We identified 144 primary supratentorial meningiomas, excluding those with pre-existing epilepsy. Whole exome sequencing assessed somatic mutation burden. Bulk RNA-sequencing identified differentially expressed genes and gene ontologies (GO). Immunohistochemistry confirmed protein levels. No differences in canonical gene mutation burden (NF2, TRAF7, AKT1, KLF4, SMO, SMARC) was found between seizure and non-seizure groups. MenG C tumors had higher seizure incidence compared to MenG A or B (p=0.03). Seizure causing meningiomas, though extra-axial, exhibited dysregulated neuronal signaling genes. GABAA receptor subunit genes GABRA3 and GABRG1 were downregulated in tumors causing seizure (Log2FC=-1.67, padj=0.014; Log2FC=-2.24, padj=0.009). Immunohistochemistry confirmed expression of GABRB2 subunit, the first documentation of GABA receptor expression in meningiomas. Neuropeptide Y Receptor Y1 (NPY1R) is downregulated in seizure causing meningiomas (Log2FC=-1.64, padj=0.002). NPY1R loss correlates is observed in mesial temporal lobe epilepsy and post-electroconvulsive shock mouse brains. In GO analysis, the terms “GABA signaling pathway,” “neuropeptide signaling,” “excitatory postsynaptic membrane potential,” and “ionotropic glutamate pathway,” were downregulated in meningiomas with seizure (padj<0.05). We assessed which alterations within MenG C tumors caused seizures by identifying genes associated with both seizure presentation and MenG C classification. Glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) is downregulated in MenG C tumors (Log2FC=-2.29, padj=6.02E-07) and seizure causing tumors (Log2FC=-1.75, padj=0.03). Clinically, patients experiencing pre-operative seizures more frequently had cerebral edema, non-homogenous enhancement, intratumoral calcification, higher MIB-1, atypical grade 1, reduced GCS, and ER presentation; they were less likely to have incidental or headache presentation (p<0.05 for all). MenG classification predicts seizure presentation whereas somatic mutation status does not. Meningiomas causing seizures show pathologic neurotransmitter receptor dysregulation.

Enhancement of Glutamate Uptake as Novel Antiseizure Approach: Preclinical Proof of Concept.

Excitotoxicity is a common hallmark of epilepsy and other neurological diseases associated with elevated extracellular glutamate levels. Thus, here, we studied the protective effects of (R)-AS-1, a positive allosteric modulator (PAM) of glutamate uptake in epilepsy models. (R)-AS-1 was evaluated in a range of acute and chronic seizure models, while its adverse effect profile was assessed in a panel of standard tests in rodents. The effect of (R)-AS-1 on glutamate uptake was assessed in COS-7 cells expressing the transporter. WAY 213613, a selective competitive EAAT2 inhibitor, was used to probe the reversal of the enhanced glutamate uptake in the same transporter expression system. Confocal microscopy and Western blotting analyses were used to study a potential influence of (R)-AS-1 on GLT-1 expression in mice. (R)-AS-1 showed robust protection in a panel of animal models of seizures and epilepsy, including the maximal electroshock- and 6 Hz-induced seizures, corneal kindling, mesial temporal lobe epilepsy, lamotrigine-resistant amygdala kindling, as well as seizures induced by pilocarpine or Theiler's murine encephalomyelitis virus. Importantly, (R)-AS-1 displayed a favorable adverse effect profile in the rotarod, the minimal motor impairment, and the Irwin tests. (R)-AS-1 enhanced glutamate uptake in vitro and this effect was abolished by WAY 213613, while no influence on GLT-1 expression in vivo was observed after repeated treatment. Collectively, our results show that (R)-AS-1 has favorable tolerability and provides robust preclinical efficacy against seizures. Thus, allosteric enhancement of EAAT2 function could offer a novel therapeutic strategy for treatment of epilepsy and potentially other neurological disorders associated with glutamate excitotoxicity. ANN NEUROL 2024.

Lateralization of memory function in temporal lobe epilepsy using scene memory fMRI.

Functional magnetic resonance imaging (fMRI) offers an alternative to the traditional Wada test for presurgical language and memory lateralization that carries almost no risk. However, fMRI lateralization of episodic memory remains challenging because the hippocampus, which is fundamental to episodic memory, is smaller, more prone to susceptibility artifact, and harder to functionally modulate than language regions. We previously showed that a complex scene memory task can lateralize memory function in the mesial temporal lobe. Using data acquired from N = 45 patients with temporal lobe epilepsy acquired with an improved stimulus paradigm and high-resolution fMRI, we now demonstrate that memory activation can be successfully lateralized within hippocampus proper. PLAIN LANGUAGE SUMMARY: Epilepsy surgery can improve seizure control in patients with temporal lobe epilepsy (TLE) that cannot be controlled with medications also, but ablation or removal of temporal lobe brain tissue can also cause cognitive deficits. Functional MRI (fMRI) can noninvasively map brain activation and perform well in lateralizing and localizing language function, but localizing and lateralizing memory function is more challenging. Building upon prior work using complex scene encoding to map memory function, we demonstrate that the use of high-resolution fMRI along with an optimized task paradigm allows memory activation to be detected within the hippocampus. Because the hippocampus is both a common site of TLE and a key region underlying memory, this approach is expected to contribute to presurgical evaluation of TLE.

Assessment of arousal recovery after cardiac arrest using diffusion kurtosis MRI with higher b-values: a pilot study

ABSTRACT Objective Comatose survivors of cardiac arrest (CA) pose a complex challenge for physicians reliant on imperfect studies to determine the extent of neurologic injury. Clinically available imaging is frequently relied upon despite limited sensitivity. We conducted a prospective pilot study comparing diffusion kurtosis imaging (DKI)-MRI and somatosensory evoked potentials (SSEPs) in comatose survivors of CA to investigate the benefit of utilizing higher diffusion b-values to enhance prediction of arousal recovery. Methods Survivors of CA admitted from June 2015 through November 2019 with DKI-MRI and SSEPs were evaluated. Advanced diffusion metrics differentiating present or absent SSEPs were analyzed using whole-brain voxelwise nonparametric permutation inference with threshold-free cluster enhancement. Results Twenty survivors of CA were included, mean age 52, 45% female and out-of-hospital arrests accounting for 75% of cases. Baseline characteristics and examination findings were not statistically different between groups at admission or 48 h after achieving normothermia. A decrease in mean diffusivity (MD) and increase in mean kurtosis (MK) was demonstrated in subjects without arousal recovery potential, most prominently in the posterior mesial temporal, parietal and occipital lobes. Conclusion DKI-MRI may improve early arousal recovery prediction during the immediate phase of post-CA care, especially where SSEPs are unavailable or unreliable.

Compartment-specific small non-coding RNA changes and nucleolar defects in human mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (mTLE) is a debilitating disease characterized by recurrent seizures originating from temporal lobe structures such as the hippocampus. The pathogenic mechanisms underlying mTLE are incompletely understood but include changes in the expression of non-coding RNAs in affected brain regions. Previous work indicates that some of these changes may be selective to specific sub-cellular compartments, but the full extent of these changes and how these sub-cellular compartments themselves are affected remains largely unknown. Here, we performed small RNA sequencing (RNA-seq) of sub-cellular fractions of hippocampal tissue from mTLE patients and controls to determine nuclear and cytoplasmic expression levels of microRNAs (miRNAs). This showed differential expression of miRNAs and isomiRs, several of which displayed enriched nuclear expression in mTLE. Subsequent analysis of miR-92b, the most strongly deregulated miRNA in the nucleus, showed accumulation of this miRNA in the nucleolus in mTLE and association with snoRNAs. This prompted us to further study the nucleolus in human mTLE which uncovered several defects, such as altered nucleolar size or shape, mis-localization of nucleolar proteins, and deregulation of snoRNAs, indicative of nucleolar stress. In a rat model of epilepsy, nucleolar phenotypes were detected in the latency period before the onset of spontaneous seizures, suggesting that nucleolar changes may contribute to the development of seizures and mTLE. Overall, these data for the first time implicate nucleolar defects in the pathogenesis of mTLE and provide a valuable framework for further defining the functional consequences of altered sub-cellular RNA profiles in this disease.

Ictal asystole is a rare complication of epilepsy

Ictal bradyarrhythmia (IB) and ictal asystole (IA) are rare complications of epilepsy. Onset latency of IB/IA implicates central nervous parasympathetic pathways, causing asystole, subsequent cerebral hypoxaemia, and potentially inducing a paradoxal, therapeutic effect by terminating both the seizure and the IA. This is a case report of a 68-year-old woman with mesial temporal lobe epilepsy and hippocampal sclerosis and IA. Association of IB/IA and sudden unexpected death in epilepsy lacks evidence and pacemaker therapy is rarely indicated. Treatment aims to minimize seizures and reduce the risk of falls.

Distinguishing seizures in autoimmune limbic encephalitis from mesial temporal lobe epilepsy with hippocampal sclerosis: Clues of a temporal plus network

ObjectiveDiagnosing autoimmune limbic encephalitis (ALE) in adults with new-onset seizures can be challenging, especially when seizures represent the predominant manifestation and MRI findings are not straightforward. By comparison with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), this study aimed to identify ictal electro-clinical features that might help clinicians recognize ALE-related seizures. MethodsThis retrospective, multi-centre study analysed the ictal semiology and EEG correlate of 116 video-EEG-captured seizures in 40 ALE patients and 45 ones recorded in 21 MTLE-HS subjects. The proportion of patients presenting each clinical feature on at least one occasion was compared between the study groups. Latent class analysis (LCA) was also performed. ResultsIctal features were overall more numerous in ALE than in MTLE-HS (33 vs 22), and LCA confirmed the intrinsic variability of ALE-related seizures. Hyperventilation served as a trigger only in ALE (4/40). Awareness impairment (p = 0.032), limb dystonic posturing (p = 0.009) and manual automatisms (p < 0.001) were significantly less common in ALE cases. Conversely, piloerection was observed only in ALE subjects, although it did not reach statistical significance (p = 0.289), as was the case for déjà-vu (p = 0.084), and sensory symptoms (p = 0.079). Regarding EEG, the type of ictal pattern differed significantly (p = 0.007). SignificanceThis study shows that, despite the wide overlap with MTLE-HS, some ictal electro-clinical features could help clinicians suspect the autoimmune origin of adult-onset seizures. Moreover, autoimmune limbic seizures apparently shared similarities with ‘temporal plus’ epilepsy, which could partly account for the poor surgical outcomes and provide an interesting conceptual framework for future research.

Detection and staging of Alzheimer's disease by plasma pTau217 on a high throughput immunoassay platform

Plasma phospho-tau 217 (pTau217) assays can accurately detect Alzheimer's disease (AD) pathology, but clinical application is limited by the need for specialised equipment. This study tests the performance of a plasma pTau217 assay performed on the Lumipulse-G® platform, that is in widespread clinical use, for selecting patients for therapy based on β-amyloid (Aβ) status and tau staging. Participants included 388 individuals with 18F-NAV4694 Aβ-PET and 18F-MK6240 tau-PET. Association of pTau217 with PET was examined using Spearman's correlation. Discriminative performance for Aβ and tau PET status as well as tau staging was assessed using Receiver Operating Characteristic analysis. Plasma pTau217 had a high correlation with both Aβ Centiloid (r=0.76) and tau SUVRmeta-temporal (r=0.78). Area under curve (AUC) was 0.93 for Aβ- vs Aβ+ and 0.94 for tau- vs tau+. Applying one threshold (Youden's index), pTau217 was 87% accurate in classification of participants to Aβ- vs Aβ+. Applying two thresholds to classify participants into Low, Indeterminate, and High zones, 17.8% had Indeterminate results and among Low/High zone participants, 92% were correctly classified as Aβ- or Aβ+. The assay accurately discriminated moderate/high neocortical tau from no tau or tau limited to mesial-temporal lobe (AUC 0.97) and high neocortical tau from all others (AUC 0.94). Plasma pTau217, measured by the widely-available, fully-automated Lumipulse®, was a strong predictor of both Aβ and tau PET status and demonstrated strong predictive power in identifying individuals likely to benefit the most from anti-Aβ treatments. NHMRC grants 1132604, 1140853, 1152623 and AbbVie.

Frequency and Longitudinal Course of Behavioral and Neuropsychiatric Symptoms in Participants With Genetic Frontotemporal Dementia.

Behavioral and neuropsychiatric symptoms are frequent in patients with genetic frontotemporal dementia (FTD). We aimed to describe behavioral and neuropsychiatric phenotypes in genetic FTD, quantify their temporal association, and investigate their regional association with brain atrophy. We analyzed data of pathogenic variant carriers in the chromosome 9 open reading frame 72 (c9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT) gene from the Genetic Frontotemporal dementia Initiative cohort study that enrolls both symptomatic pathogenic variant carriers and first-degree relatives of known carriers. Principal component analysis was performed to identify behavioral and neuropsychiatric clusters that were compared with respect to frequency and severity between groups. Associations between neuropsychiatric clusters and MRI-assessed atrophy were determined using voxel-based morphometry. We applied linear mixed effects and generalized linear mixed effects models to assess the longitudinal course of symptoms. A total of 522 participants were included: 221 c9orf72 (138 presymptomatic), 213 GRN (157 presymptomatic), and 88 MAPT (62 presymptomatic) pathogenic variant carriers. Principal component analysis revealed 5 phenotypic clusters (67.6% of variance), labeled diverse behavioral, affective, psychotic, euphoric/hypersexual, and tactile hallucinations phenotype. In participants presenting behavioral or neuropsychiatric symptoms, affective symptoms were most frequent across groups (83.6%-88.1%), followed by diverse behavioral symptoms (68.4%-77.9%). In c9orf72 and GRN pathogenic variant carriers, psychotic symptoms (32.0% and 19.4%, respectively) were more frequent than euphoric/hypersexual symptoms (28.7% and 14.2%, respectively), which was the other way around in MAPT pathogenic variant carriers (28.6% and 23.8%). Although diverse behavioral symptoms were associated with gray and white matter frontotemporal atrophy, only a small atrophy cluster in the right thalamus was associated with psychotic symptoms. Euphoric/hypersexual symptoms were associated with atrophy in mesial temporal lobes, basal forebrain structures, and the striatum (p < 0.05). Estimated time to symptom onset, genetic group, education, and sex influenced behavioral and neuropsychiatric symptoms (p < 0.05). Particularly, in c9orf72 pathogenic variant carriers, psychotic symptoms may be starting decades before recognition of onset of illness. We identified multiple clusters of behavioral and neuropsychiatric symptoms in participants with genetic FTD that relate to distinct cerebral atrophy patterns. Their severity depends on time, affected gene, sex, and education. These clinical-genetic associations can guide diagnostic evaluations and the design of clinical trials for new disease-modifying and preventive treatments.

Associations between neurolinguistic deficits and personality traits in people with epilepsy.

People with epilepsy (PWE) have been hypothesized to have higher prevalence of personality disorders and cognitive disorders. The objective of this study was to investigate the controversial notion of "epileptic personality," a series of supposedly specific personality traits of people with epilepsy (PWE). For this purpose, 29 individuals with Mesial Temporal lobe Epilepsy (MTLE) and 23 with Juvenile myoclonic epilepsy (JME) as confirmed by electroencephalography (EEG), MRI scans and clinical examination, underwent a thorough neuropsychological and personality assessment. The resulting neuropsychological profiles were statistically analyzed considering possible personality disorders, character traits, cognitive and linguistic deviations from 20 healthy controls (HC). Our findings suggest accumulative cognitive and linguistic deficits in individuals with epilepsy compared to controls. It is possible that these might be misinterpreted as personality disorders. Specifically, personality traits (p = 0.049) and verbal fluency (p = 0.013), were significantly different between PWEs and controls. Also, the type of epilepsy and lateralization seem to affect executive function (p = 0.049) and pragmatology scores (p < 0.001), exhibiting differences in subgroup analysis. Different theories are considered as plausible pathophysiological explanations for the aforementioned differences. This research might serve as a basis to further investigate the cognitive aspects of epilepsy and possible pharmacological interventions, which are currently lacking.

Anatomy-guided resections for paralimbic tumors in the temporo-insular region: combining tumor and epilepsy surgery concepts.

Tumors in the temporo-mesial region often extend into the insula and vice versa. The present study investigated the results of a surgical strategy that combines principles of tumor and epilepsy surgery. We retrospectively analyzed 157 consecutive patients with intrinsic brain tumors in the temporo-mesial region, with varying degrees of extensions into the insula (44 patients, 28.0%). The surgical strategy utilized "anatomy-guided resection," targeting specific anatomical compartments infiltrated by the tumor (e.g., temporal pole, anterior temporo-mesial region = uncus and hippocampal head, posterior temporo-mesial, insula) rather than treating the tumor as a single mass. The most frequent histologies were ganglioglioma CNS WHO grade 1 (55 patients, 35.0%) and IDH1 wildtype glioblastoma (36 patients, 22.9%). Tumor infiltration was most commonly found in the anterior temporo-mesial compartment (145 patients, 92.4%). An anterior temporal lobectomy was part of the surgical strategy in 131 cases (83.4%). Seventy-six patients (48.4%) with drug-resistant epilepsy underwent a formal presurgical epilepsy work-up, including depth electrode placement in three cases. Complete resections were achieved in 117 patients (74.5%), with supramarginal resections performed in 89 cases (56.7%). Four patients experienced non-temporary neurological complications (CTCAE grade 3-5). At 6 months, 127 of 147 assessable patients (86.4%) were free from seizures or auras (ILAE class 1), excluding early postoperative seizures (<30 days). At 24 months, 122 of 144 assessable cases (84.7%) remained seizure-free (ILAE class 1). Kaplan-Meier estimates for 5-year overall survival were 98.5% for non-recurrent glioneuronal tumors. The 2-year overall survival estimates were 96.0% for 24 primary diffuse CNS WHO grade 2 and 3 gliomas and 55.2% for 30 patients undergoing first surgeries for glioblastomas/astrocytomas CNS WHO grade 4. Combining both epilepsy and tumor surgery concepts in the surgical treatment of intrinsic brain tumors involving the mesial temporal lobe, often extending into the insula, led to more extensive resections, improved seizure outcomes, and potentially even better patient survival outcomes.

Hippocampal dentate granule cells in temporal lobe epilepsy: A morphometry and transcriptomic study.

The dentate gyrus (DG) plays a critical role in hippocampal circuitry, providing a "gate-like" function to the downstream cornu ammonis (CA) sectors. Despite this critical role, pathologies in DG are less commonly described than those in the CA sectors in the diagnosis of mesial temporal lobe epilepsy (mTLE). To elucidate the role of the DG in mTLE, we analysed hippocampal sclerosis (HS), no-HS, non-TLE epilepsy control, and non-epilepsy control cohorts using morphometry and gene expression profiling techniques. Morphometry techniques analysed DG cell spacing, nucleus size, and nucleus circularity. Our data show distinct DG morphometry and RNA expression profiles between HS and No-HS. Dentate granule cells are more dispersed in patients with HS, and the DG shows an elevated expression of the complement system, apoptosis, and extracellular matrix remodelling-related RNA. We also observe an overall decrease in neurogenesis-related RNA in HS DG. Interestingly, regardless of the pathological diagnosis, the DG morphometry correlates with post-operative outcomes. Increased cell spacing is observed in the DG of mTLE cases that achieve seizure freedom post-operatively. This study reveals the possible prognostic value of DG morphometry, as well as supporting the notion that HS and no-HS TLE may be distinct disease entities with differing contributing mechanisms.

Machine learning localization to identify the epileptogenic side in mesial temporal lobe epilepsy

BackgroundMesial temporal sclerosis (MTS) is the most common pathology associated with drug-resistant mesial temporal lobe epilepsy (mTLE) in adults.Most atrophic hippocampi can be identified using MRI based on standard epilepsy protocols; however, difficulties can arise in cases where sclerotic changes in the hippocampus are subtle or non-epilepsy-specific protocols have been implemented. In such cases, quantitative methods, such as T1-weighted axial series MRIs, are valuable additional tools to complement epilepsy-specific protocols. In the current study, we applied machine learning (ML) techniques to the analysis of brain regions of interest (ROIs), including the hippocampus, thalamus, and cortical areas, to enhance the accuracy of lesion lateralization in MRI. MethodsThis study included 104 patients diagnosed with mTLE, including 55 with lesions on the right side and 49 with lesions on the left side. FreeSurfer software was used to extract features from high-resolution T1-weighted axial brain MRI scans for use in computing lateralization indices (LI) for various brain regions. After using feature selection to pinpoint critical ROIs, the corresponding LI values were used as parameters in training the ML model. ResultsThe proposed ML model demonstrated exceptional performance in the lateralization of mTLE, achieving test accuracy of 92.38 % with an AUROC of 0.97. ConclusionThis study demonstrated the efficacy of ML in detecting instances of MTS from thin-slice T1 images. The proposed method provides valuable insights for surgical planning and treatment. Nonetheless, additional research will be required to enhance the robustness of the model and rigorously validate its effectiveness and applicability in clinical settings.

Evaluating cortical excitatory and inhibitory activity through interictal intracranial electroencephalography in mesial temporal lobe epilepsy.

Gamma oscillation regularity (GOR) indicates the synchronization of inhibitory interneurons, while the reactivity of cortico-cortical evoked potentials (CCEPs) is supposed to reflect local cortical excitability. Under the assumption that the early response of CCEP near the stimulation site also indicates excitatory activity primarily mediated by pyramidal cells, we aimed to visualize the cortical inhibitory and excitatory activities using GOR and CCEP in combination and to use them to predict the epileptogenic zone (EZ) in mesial temporal lobe epilepsy (MTLE). In five patients who underwent intracranial electrode implantation, GOR and CCEP reactivity in the vicinity of the stimulation site was quantified. The interictal GOR was calculated using multiscale entropy (MSE), the decrease of which was related to the enhanced GOR. These parameters were compared on an electrode-and-electrode basis, and spatially visualized on the brain surface. As a result, elevated GOR and CCEP reactivities, indicative of enhanced inhibitory and excitatory activities, were observed in the epileptogenic regions. Elevated CCEP reactivity was found to be localized to a restricted area centered on the seizure onset region, whereas GOR elevation was observed in a broader region surrounding it. Although these parameters independently predicted the EZ with high specificity, we combined the two to introduce a novel parameter, the excitatory and inhibitory (EI) index. The EI index predicted EZ with increased specificity compared with GOR or CCEP reactivity alone. Our results demonstrate that GOR and CCEP reactivity provided a quantitative visualization of the distribution of cortical inhibitory and excitatory activities and highlighted the relationship between the two parameters. The combination of GOR and CCEP reactivities are expected to serve as biomarkers for localizing the epileptogenic zone in MTLE from interictal intracranial electroencephalograms.

Selective Amygdalohippocampectomy versus Anterior Temporal Lobectomy in Mesial Temporal Lobe Epilepsy: A Meta-Analysis of Seizure Control and Cognitive Outcomes

Background: Mesial temporal lobe epilepsy (MTLE) is a common form of drug-resistant epilepsy often necessitating surgical intervention. The choice between selective amygdalohippocampectomy (SelAH) and anterior temporal lobectomy (ATL) remains a subject of debate, with each procedure offering potential advantages and disadvantages in terms of seizure control and cognitive outcomes. Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Springer databases to identify studies published between 2013 and September 2024 that compared SELAH and ATL in patients with MTLE. The primary outcomes of interest were seizure freedom rates and changes in cognitive function, particularly IQ scores. A meta-analysis was performed using a random-effects model to pool the results of included studies. Results: The meta-analysis encompassed 5 studies involving 218 patients with MTLE (105 underwent SelAH, 113 underwent ATL). The pooled results demonstrated a statistically significant reduction in the odds of achieving seizure freedom following ATL compared to SelAH (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.24-0.81, p = 0.008). Regarding cognitive outcomes, no significant difference was observed in Performance IQ (PIQ) between the two groups. However, a trend towards improved Verbal IQ (VIQ) was noted in the SelAH group, although this did not reach statistical significance. Conclusion: The findings suggest that SelAH may offer superior seizure control compared to ATL in patients with MTLE. While both procedures appear to have comparable effects on PIQ, SelAH may be associated with a trend towards better preservation or even improvement in VIQ. The choice between SelAH and ATL should be individualized based on patient-specific factors, including preoperative cognitive profile and the relative importance of seizure control versus cognitive preservation.

A novel AAV9-dual microRNA-vector targeting GRIK2 in the hippocampus as a treatment for mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (mTLE) is the most prevalent type of epilepsy in adults. First and subsequent generations of anti-epileptic therapy regimens fail to decrease seizures in a large number of patients suffering from mTLE, leaving surgical ablation of part of the hippocampus as the only therapeutic option to potentially reach seizure freedom. GluK2 has recently been identified as a promising target for the treatment of mTLE using gene therapy. Here, we engineered an adeno-associated virus serotype 9 vector expressing a cluster of two synthetic microRNAs (miRNAs), expressed from the human synapsin promoter, that target GRIK2 mRNA. Intra-hippocampal delivery of this vector in a mouse model of mTLE significantly reduced GRIK2 expression and daily seizure frequency. This treatment also improved the animals' health, reduced their anxiety, and restored working memory. Focal administration of the vector to the hippocampus of cynomolgus monkeys in GLP toxicology studies led to the selective transduction of hippocampal neurons with little exposure elsewhere in the brain and no transduction outside the central nervous system. Expression of miRNAs in hippocampal neurons resulted in substantially decreased GRIK2 mRNA expression. These data suggest that the intra-hippocampal delivery of a GMP-grade AAV9 coding for a synthetic miRNAs targeting GRIK2 is a promising treatment strategy for mTLE.

A - 147 Patient-Centric Considerations for Selecting the Language of Procedure Administration in Candidates for Epilepsy Surgery: Implications for Data Interpretation, Prognostication and Outcomes

Abstract Objective Selecting the language of pre-surgical neuropsychological testing (NPT), intracarotid amobarbital procedure, and intra/extra functional language mapping (ESM) in bi−/multi-lingual patients is a high-stakes neuropsychological decision point. Though a patient’s self-selection of language is an integral consideration, both patient and provider must fully understand the potential implications of language selection on a patient’s data interpretation and overall case conceptualization. Method A 26-year-old, right-handed, bilingual (L1 = Mandarin-, L2 = English-speaking) female received pre-operative NPT, Wada test, and ESM to guide resective surgery targeting medically-refractory epilepsy involving the right superior temporal gyrus (STG) and mesial (MTL) temporal lobe. All procedures were conducted in English at the patient’s request with alternate forms of verbally-mediated NPT administered in Mandarin. Results Confrontation naming and verbal fluencies were impaired in both English and Mandarin. Wada testing administered in English revealed bilateral language and greater left hemisphere memory support. Following considerable psychoeducation regarding possible functional language loss in Mandarin post-operatively, the patient agreed to ESM in L1 with auditory and picture naming disruption after right STG stimulation. Conclusion Despite strong English-language fluency, assessment in Mandarin was of critical importance, as eloquent cortices essential for tonal language production may have been resected if mapping procedures were completed in English-only, as requested. Balancing factors informed by functional and structural neuroanatomy, patient worldview, and cross-cultural neuropsychology requires a tailored, patient-centric approach to case conceptualization.

Delineating structural and metabolic abnormalities in amygdala and hippocampal subfields for different seizure-onset patterns via stereotactic electroencephalography.

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

The impact of visual field defects following anterior temporal lobectomy

Objective: This prospective study aimed to quantify visual field defects (VFDs) along with other defects in ophthalmic functions after anterior temporal lobectomy (ATL) in patients with mesial temporal lobe epilepsy (MTLE) and their impact on quality of life using a VFQ-25 questionnaire. Methods: Ophthalmic evaluation was done during pre-operative evaluation as well as 3 months after surgery. It included the Best Corrected Visual Acuity (BCVA), visual field evaluation, colour vision examination, fundoscopy, extraocular movements and diplopia charting. Visual field evaluation was done using a Humphrey field analyser. The foveal threshold (FT), mean deviation (MD) and pattern standard deviation (PSD) were calculated for each patient. Quality of life assessment was done using the Visual Functioning Questionnaire-25 (VFQ-25). Two-tailed independent T-tests and Chi-square tests were performed for comparison of results. Results: Thirty-four patients were included in this study (23 men and 11 women). The mean age was 26.6 years (range 9-44 years). Post-operatively, none complained of a visual field disturbance. Thirty-one (91.17%) of 34 patients had a new quantifiable superior quadrantanopia. FT, MD and PSD of patients ranged between 29db to 40db, -1.23 to -14.28 and 1.75 to 15.34, respectively. There was no detectable abnormality in visual acuity, colour vision, fundoscopy, diplopia charting or extraocular movements. VFQ-25 scores ranged from 84 to 100. The difference between VFQ scores of patients with and without quadrantanopia was not significant. Conclusion: Standard ATL produces asymptomatic VFDs that do not affect quality of life. A combined effort of the neurologist and ophthalmologist is recommended to counsel the patient before surgery.