Search Results (38)

Background: Hippocampal sclerosis (HS) is a hallmark of mesial temporal lobe epilepsy (MTLE). However, genetic studies on MTLE patients with HS (MTLE-HS) remain limited, especially in East Asian populations. This study aimed to identify genetic variants associated with MTLE-HS and elucidate their biological relevance through integrative genomic and transcriptomic analyses. Methods: We conducted a genome-wide association study (GWAS) on 157 Korean epilepsy patients, including 52 MTLE-HS subjects and 105 non-acquired focal epilepsy individuals without HS as controls. The splicing and expression quantitative trait locus (sQTL and eQTL, respectively) effects of significant variants were analyzed using GTEx datasets. Transcriptomic data from the hippocampi of MTLE-HS subjects and an epilepsy mouse model were examined to assess TMEM14A expression. Gene correlation enrichment analysis was performed to investigate potential associations with epilepsy-related phenotypes. Results: The GWAS identified rs6924849, located downstream of TMEM14A, as significantly associated with MTLE-HS. The sQTL analysis revealed that rs6924849 induces abnormal TMEM14A splicing in hippocampal tissue. Transcriptomic analyses showed reduced TMEM14A expression in MTLE-HS hippocampi, while mice with pilocarpine-induced epilepsy exhibited a transient increase in TMEM14A expression during the acute phase post-status epilepticus. Gene correlation enrichment analyses linked TMEM14A to seizure-related phenotypes in both humans and mice. Conclusions: This study identifies rs6924849 as a novel genetic variant associated with MTLE-HS in an East Asian population. The dysfunctional splicing and altered expression of TMEM14A may contribute to the neuronal loss characteristic of HS, as TMEM14A regulates apoptosis. These findings emphasize the potential role of TMEM14A in MTLE-HS pathogenesis from genomic and transcriptomic perspectives. Full article

This study investigated the striatopallidal complex’s involvement in status epilepticus (SE) caused by morphological neurodegenerative changes in a post-natal immature developing brain in a lithium−pilocarpine male Wistar albino rat model of mesial temporal lobe epilepsy. One hundred experimental pups were grouped by age as follows: 12, 15, 18, 21, and 25 days. SE was induced by lithium−pilocarpine. Brain sections were microscopically examined by Fluoro-Jade B fluorescence stain at intervals of 4, 12, 24, and 48 h and 1 week after SE. Each interval was composed of four induced SE pups and a control. Fluoro-Jade B positive neurons in the dorsal striatum (DS) were screened and plotted on stereotaxic rat brain maps. The DS showed consistent neuronal damage in pups aged 18, 21, and 25 days. The peak of the detected damage was observed in pups aged 18 days, and the start of the morphological sequela was observed 12 h post SE. The neuronal damage in the DS was distributed around its periphery, extending medially. The damaged neurons showed intense Fluoro-Jade B staining at the intervals of 12 and 24 h post SE. SE neuronal damage was evidenced in the post-natal developing brain selectively in the DS and was age-dependent with differing morphological sequela. Full article

Background/Objectives: Temporal lobe epilepsy (TLE) responds well to surgical treatment, although a considerable percentage of patients experience seizure recurrence after resection. Relapse from the contralateral mesial temporal lobe, extratemporal lobe epilepsy mimicking TLE, or temporal plus epilepsy might account for surgical failures. Methods: We included patients with a pre-implantation hypothesis suggesting TLE, who underwent stereo-EEG (SEEG) evaluation at our institution and had an individual SEEG exploration paradigm with at least twelve stereo-electrodes placed to sixteen brain regions allowing exploration of limbic and paralimbic networks. We analyzed the prevalence of TLE subtypes based on ictal onset localization with SEEG and response to resective surgery. Results: Twenty-four subjects met the inclusion criteria. Seven patients had unilateral mesial temporal epilepsy (UMTE), five had bilateral mesial temporal epilepsy (BMTE), five had unilateral neocortical temporal epilepsy (UNTE), six had temporal-plus epilepsy (TPE), one had extratemporal epilepsy (ETE). The number of patients who underwent destructive surgeries and surgical outcomes are as follows: UMTE—all seven patients, Engel I; BMTE- three out of five, Engel I, III, and IV, respectively; UNTE—three out of five, Engel I; TLE mimic (ETE)—one, Engel I; TPE—all six patients, Engel I–three, Engel III–two, Engel IV—one. Conclusions: In our study, UMTE was the most frequent TLE subtype (29%), and all patients proceeded to resective surgery with good outcomes. TPE comprised a substantial component (25%) of this cohort with initially presumed TLE, who had a notable proportion of unfavorable outcomes. Larger studies are needed to create guidelines for rational counseling of patients with presumed TLE regarding surgical outcomes. Full article

Background: Temporal lobe epilepsy is the most common pharmaco-resistant type of epilepsy. The chance of obtaining seizure freedom after resective surgery in pharmaco-resistant mesial temporal lobe patients (mTLE) is significantly higher compared to pharmaceutical treatment (at least 50–60% compared to less than 15%). However, some factors (e.g., craniotomy) may prevent epilepsy patients undergoing surgery. A recent advancement in epilepsy surgery, i.e., magnetic resonance guided laser interstitial thermal therapy (MRgLITT), has become an attractive alternative for performance of selective amygdala-hippo-campectomy, especially because of its minimal invasiveness. Among other medial temporal lobe structures, the hippocampus is particularly important for successful processing of vestibular inputs. Nevertheless, it is still unclear whether mTLE patients who underwent MRgLITT perform worse on vestibular-dependent tests, including balancing, spatial orientation and rotational memory. Methods: Nine patients (Age 40.1 ± 14.5; 2 females) underwent vestibular-dependent assessments before and after MRgLITT using the following test battery: (I) clinical balancing test (CBT), (II) triangle completion test (TCT) and (III) rotational memory test (RM). Results: We found significant improvement from pre- to post-surgery in the vestibular-dependent spatial orientation test, namely in the wheelchair condition of the triangle completion test. Additionally, the obtained effect sizes were medium to large in favor of post-surgery assessment for the majority of conditions in the three tests applied in this study, indicating that the assessment of a larger number of patients could also, potentially, lead to significant results in these cases. Conclusions: This plausibility study is the first to assess vestibular-dependent balancing, spatial orientation and rotational memory functions before and after MRgLITT in mTLE patients. Even with a small sample of nine patients, significant changes and medium to high effect sizes in favor of surgery were observed. Nevertheless, prospective studies with larger sample sizes are necessary for appropriate estimation of MRgLITT effectiveness in these functional domains. Full article

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. Full article

Novelty detection, crucial to episodic memory formation, is impaired in epileptic patients with mesial temporal lobe resection. Mismatch novelty detection, that activates the hippocampal CA1 area in humans and is vital for memory reformulation and reconsolidation, is also impaired in patients with hippocampal lesions. In this work, we investigated the response to mismatch novelty, as occurs with the new location of known objects in a familiar environment, in the Li²⁺-pilocarpine rat model of TLE and its correlation with hippocampal monoaminergic markers. Animals showing spontaneous recurrent seizures (SRSs) for at least 4 weeks at the time of behavioural testing showed impaired spatial learning in the radial arm maze, as described. Concurrently, SRS rats displayed impaired exploratory responses to mismatch novelty, yet novel object recognition was not significantly affected in SRS rats. While the levels of serotonin and dopamine transporters were mildly decreased in hippocampal membranes from SRS rats, the levels on the norepinephrine transporter, tyrosine hydroxylase and dopamine-β-hydroxylase were enhanced, hinting for an augmentation, rather than an impairment in noradrenergic function in SRS animals. Altogether, this reveals that mismatch novelty detection is particularly affected by hippocampal damage associated to the Li²⁺-pilocarpine model of epilepsy 4–8 weeks after the onset of SRSs and suggests that deficits in mismatch novelty detection may substantially contribute to cognitive impairment in MTLE. As such, behavioural tasks based on these aspects of mismatch novelty may prove useful in the development of cognitive therapy strategies aiming to rescue cognitive deficits observed in epilepsy. Full article

Background: Temporal lobe epilepsy is a common neurological disease that affects many areas of patients’ lives, including social competence. The aim of the study was to assess theory of mind in patients with temporal lobe epilepsy and to investigate the demographic and clinical factors associated with this function. Methods: A total of 65 participants took part in the study, which included 44 patients with epilepsy and 21 demographically matched healthy individuals. The following neuropsychological tests were used to examine theory of mind: the Faux Pas Test, the Hinting Task, the Emotion Comprehension Test, and a cognitive function screen, the Montreal Cognitive Assessment. Results: Patients with epilepsy scored lower on all measures of the theory-of-mind tests. Moreover, in the clinical group, numerous moderate and strong correlations were found between the theory-of-mind tests and education, age at onset of epilepsy, lateralization of epileptic focus, cognitive status, and, to a lesser degree, number of anti-epileptic drugs, frequency of seizures, and age. In contrast, in the control group, significant correlations were found mostly between the theory-of-mind tests and sex, and, to a lesser degree, age. Education and cognitive functioning were not associated. Conclusions: Patients with epilepsy experience difficulties in theory of mind, which may have a negative impact on the quality of their social relationships. The level of theory-of-mind abilities correlates with particular clinical and demographic indicators. Recognizing these issues allows clinicians to implement tailored interventions, potentially improving patients’ quality of life. Full article

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT–qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT–qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1, Adam8, Slc24a1, and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca²⁺ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients. Full article

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

The identification of reliable brain-specific biomarkers in periphery contributes to better understanding of normal neurophysiology and neuropsychiatric diseases. The neurospecific proteins BDNF, NSE, VILIP-1, and S100B play an important role in the pathogenesis of neuropsychiatric disorders, including epilepsy. This study aimed to assess the correspondence of the expression of BDNF, NSE, VILIP-1, and S100B in the blood (serum and peripheral blood mononuclear cells (PBMCs)) to the in vivo hippocampal levels of subjects with drug-resistant epilepsy who underwent neurosurgery (N = 44) using multiplex solid-phase analysis, ELISA, and immunohistochemical methods, as well as to analyze the correlations and associations of the blood and hippocampal levels of these proteins with clinical parameters. We first studied the concordance between in vivo brain and blood levels of BDNF, NSE, VILIP-1, and S100B in epileptic patients. A positive correlation for NSE between hippocampal and PBMC levels was revealed. NSE levels in PBMCs were also significantly correlated with average seizure duration. BDNF levels in PBMCs were associated with seizure frequency and hippocampal sclerosis. Thus, NSE and BDNF levels in PBMCs may have potential as clinically significant biomarkers. Significant correlations between the levels of the neurospecific proteins studied herein suggest interactions between BDNF, NSE, VILIP-1, and S100B in the pathophysiology of epilepsy. Full article

(1) Objective: This study aimed to explore the efficacy of conventional invasive techniques in confirming unilateral seizure onset localization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to investigate the association between electrode type and intracranial electroencephalography (EEG) pattern. (2) Methods: This retrospective study encompasses patients diagnosed with MTLE-HS who underwent an invasive study prior to an anterior temporal lobectomy (ATL). Intracranial EEG features were assessed for 99 seizure events from 25 selected patients who achieved seizure remission with ATL after an invasive study using bilateral combined depth and subdural electrodes. Their findings were compared to those of 21 seizure events in eight patients who exhibited suboptimal seizure outcomes. (3) Results: For the distribution of electrodes that recorded the ictal onset, hippocampal depth electrodes recorded 96% of all seizure events, while subdural electrodes recorded 52%. Among the seizures recorded in subdural electrodes, 49% were localized in medial electrodes, with only 8% occurring in lateral electrodes. The initiation of seizures exclusively detected in hippocampal depth electrodes was associated with successful seizure remission, whereas those solely recorded in the lateral strip electrodes were often linked to refractory seizures after ATL. (4) Conclusions: These findings emphasize the importance of employing a combination of depth and subdural electrodes in invasive studies for patients with MTLE-HS to enhance the accuracy of lateralization. This also cautions against sole reliance on subdural electrodes without depth electrodes, which could lead to inaccurate localization. Full article

Epilepsy is a chronic brain disease with recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is the most common pathological cause of epilepsy. With the development of computer-aided diagnosis technology, there are many auxiliary diagnostic approaches based on deep learning algorithms. However, the causes of epilepsy are complex, and distinguishing different types of epilepsy accurately is challenging with a single mode of examination. In this study, our aim is to assess the combination of multi-modal epilepsy medical information from structural MRI, PET image, typical clinical symptoms and personal demographic and cognitive data (PDC) by adopting a multi-channel 3D deep convolutional neural network and pre-training PET images. The results show better diagnosis accuracy than using one single type of medical data alone. These findings reveal the potential of a deep neural network in multi-modal medical data fusion. Full article

Neuroinflammation represents a dynamic process of defense and protection against the harmful action of infectious agents or other detrimental stimuli in the central nervous system (CNS). However, the uncontrolled regulation of this physiological process is strongly associated with serious dysfunctional neuronal issues linked to the progression of CNS disorders. Moreover, it has been widely demonstrated that neuroinflammation is linked to epilepsy, one of the most prevalent and serious brain disorders worldwide. Indeed, NLRP3, one of the most well-studied inflammasomes, is involved in the generation of epileptic seizures, events that characterize this pathological condition. In this context, several pieces of evidence have shown that the NLRP3 inflammasome plays a central role in the pathophysiology of mesial temporal lobe epilepsy (mTLE). Based on an extensive review of the literature on the role of NLRP3-dependent inflammation in epilepsy, in this review we discuss our current understanding of the connection between NLRP3 inflammasome activation and progressive neurodegeneration in epilepsy. The goal of the review is to cover as many of the various known epilepsy models as possible, providing a broad overview of the current literature. Lastly, we also propose some of the present therapeutic strategies targeting NLRP3, aiming to provide potential insights for future studies. Full article

This study was designed to identify whether the metabolic network changes in mesial temporal lobe epilepsy (MTLE) patients with focal to bilateral tonic-clonic seizures (FBTCS) differ from changes in patients without FBTCS. This retrospective analysis enrolled 30 healthy controls and 54 total MTLE patients, of whom 27 had FBTCS. Fluorodeoxyglucose positron emission tomography (FDG-PET) data and graph theoretical analyses were used to examine metabolic connectivity. The differences in metabolic networks between the three groups were compared. Significant changes in both local and global network topology were evident in FBTCS+ patients as compared to healthy controls, with a lower assortative coefficient and altered betweenness centrality in 15 brain regions. While global network measures did not differ significantly when comparing FBTCS− patients to healthy controls, alterations in betweenness centrality were evident in 13 brain regions. Significantly altered betweenness centrality was also observed in four brain regions when comparing patients with and without FBTCS. The study revealed greater metabolic network abnormalities in MTLE patients with FBTCS as compared to FBTCS− patients, indicating the existence of distinct epileptogenic networks. These findings can provide insight into the pathophysiological basis of FBTCS. Full article

Mesial temporal lobe epilepsy is the most common type of epilepsy. For most patients suffering from TLE, the only treatment option is surgery. However, there is a high possibility of relapse. Invasive EEG as a method for predicting the outcome of surgical treatment is a very complex and invasive manipulation, so the search for outcome biomarkers is an urgent task. MicroRNAs as potential biomarkers of surgical outcome are the subject of this study. For this study, a systematic search for publications in databases such as PubMed, Springer, Web of Science, Scopus, ScienceDirect, and MDPI was carried out. The following keywords were used: temporal lobe epilepsy, microRNA, biomarkers, surgery, and outcome. Three microRNAs were studied as prognostic biomarkers of surgical outcome: miR-27a-3p, miR-328-3p, and miR-654-3p. According to the results of the study, only miR-654-3p showed a good ability to discriminate between patients with poor and good surgical outcomes. MiR-654-3p is involved in the following biological pathways: ATP-binding cassette drug transporters, glutamate transporter SLC7A11, and TP53. A specific target for miR-654-3p is GLRA2, the glycine receptor subunit. MicroRNAs, which are diagnostic biomarkers of TLE, and epileptogenesis, miR-134-5p, MiR-30a, miRs-143, etc., can be considered as potential biomarkers of surgical outcome, as they can be indicators of early and late relapses. These microRNAs are involved in the processes characteristic of epilepsy: oxidative stress and apoptosis. The study of miRNAs as potential predictive biomarkers of surgical outcome is an urgent task and should be continued. However, when studying miRNA expression profiles, it is important to take into account and note a number of factors, such as the type of sample under study, the time of sampling for the study, the type and duration of the disease, and the type of antiepileptic treatment. Without taking into account all these factors, it is impossible to assess the influence and involvement of miRNAs in epileptic processes. Full article