Search Results (46)

Introduction: Patients with generalized epilepsy are rarely referred for advanced diagnostics like magnetoencephalography (MEG). This is due to the assumption that generalized seizures cannot be localized noninvasively. Methods: We present simultaneous MEG (306 channels) and EEG (64 channels) data from seven patients with drug-resistant generalized epilepsy. Three patients experienced typical generalized seizures during their MEG clinical evaluation. In total, 38 epileptiform events (three seizures, 35 interictal discharges) were analyzed using two software platforms and three localization methods: equivalent current dipole (ECD), sLORETA (via SWARM), and dynamic statistical parametric mapping (dSPM). Individual head models were created from each patient’s MRI. Results: MEG successfully localized seizure onset zones, showing distinct hypersynchronous discharges on all sensors as well as alternately during interictal discharges. Localization was consistent across methods and generalized events within subjects, revealing cortical sources in all cases, with rapid propagation (27–60 ms) across networks. Conclusions: This study demonstrates that MEG can meaningfully localize both seizures and interictal discharges in generalized epilepsy. This supports a broader use for MEG beyond focal epilepsy. Incorporating MEG in drug-resistant cases including generalized epilepsies may improve diagnosis and guide treatments including non-surgical options. Full article

Giant somatosensory evoked potentials (gSEPs) are abnormally high-amplitude cortical responses to peripheral nerve stimulation, traditionally regarded as electrophysiological hallmarks of progressive myoclonic epilepsies (PMEs). However, accumulating evidence shows their presence in a broader range of non-epileptic conditions, including focal lesions, metabolic encephalopathies, neurodegenerative diseases, and even functional disorders. This review offers a comprehensive analysis of the physiological mechanisms, diagnostic criteria, and clinical significance of gSEPs, integrating data from both classical and emerging neurophysiological techniques. gSEPs are mainly produced in the primary somatosensory cortex through mechanisms involving cortical disinhibition, impaired GABAergic transmission, and altered thalamocortical connectivity. In epileptic syndromes such as Unverricht–Lundborg disease and other PMEs, gSEPs reflect cortical hyperexcitability and are closely linked to cortical myoclonus. Conversely, in non-epileptic contexts, they may indicate transient or chronic cortical dysfunction. The diagnostic utility of gSEPs ranges from differential diagnosis of myoclonus to monitoring disease. However, heterogeneity in amplitude definitions and recording protocols hinders the standardization of these measurements. This may result in the identification of the right threshold to differentiate conditions associated with simple increased versus giant SEP, the latter of which may help identify truly epileptic conditions from other disorders simply associated with increased SEP amplitude. Full article

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

mTORopathies represent a group of neurodevelopmental disorders linked to dysregulated mTOR signaling, resulting in conditions such as tuberous sclerosis complex, focal cortical dysplasia, hemimegalencephaly, and Smith–Kingsmore Syndrome. These disorders often manifest with epilepsy, cognitive impairments, and, in some cases, structural brain anomalies. The mTOR pathway, a central regulator of cell growth and metabolism, plays a crucial role in brain development, where its hyperactivation leads to abnormal neuroplasticity, tumor formation, and heightened neuronal excitability. Current treatments primarily rely on mTOR inhibitors, such as rapamycin, which reduce seizure frequency and tumor size but fail to address underlying genetic causes. Advances in gene editing, particularly via CRISPR/Cas9, offer promising avenues for precision therapies targeting the genetic mutations driving mTORopathies. New delivery systems, including viral and non-viral vectors, aim to enhance the specificity and efficacy of these therapies, potentially transforming the management of these disorders. While gene editing holds curative potential, challenges remain concerning delivery, long-term safety, and ethical considerations. Continued research into mTOR mechanisms and innovative gene therapies may pave the way for transformative, personalized treatments for patients affected by these complex neurodevelopmental conditions. Full article

Objective: Focal epilepsy is the most frequent type of epilepsy in childhood, particularly after the first year of life. This study aims to analyze the clinical aspects, electrophysiological and neuroimaging findings, and genetic predispositions in pediatric focal epilepsy. Specifically, we investigate the association between these parameters and evaluate their impact on therapeutic decisions. Methods: This is a retrospective study, in which we enrolled 39 patients currently receiving follow-up in our unit, 20 male and 19 female. Using the Chi-squared test, we compared them considering several genetic traits, pre/peri/postnatal risk factors, family history, clinical and instrumental features, and treatments. Differences are considered significant with a p value < 0.005. Results: Our findings highlight the multifactorial nature of focal epilepsy, with a combination of genetic and environmental contributions. EEG demonstrated the highest sensitivity among diagnostic tools, being non-significant in only 12.8% of cases, while MRI (p < 0.001), CT (p < 0.04), and brain ultrasound had lower detection rates. MRI findings were significant in 43.6% of patients, predominantly showing vascular malformations (35.8%). MRI-negative findings were more common in temporal and occipital epilepsy, whereas MRI-positive results were observed in 100% of frontal seizures. Importantly, some MRI-negative cases may still be lesional, particularly in temporal lobe epilepsy, where focal cortical dysplasia could be present but undetected with standard imaging. Valproic acid remains the most commonly used anti-seizure medication, and, despite guideline recommendations, it was still prescribed as a first-line treatment in 34.3% of cases and is being used in 23.5% of female patients, raising concerns about its appropriateness. Conclusions: This study highlights the role of genetic and environmental risk factors in pediatric focal epilepsy. EEG showed superior diagnostic sensitivity over MRI, particularly in MRI-negative cases. While high-resolution MRI (3T or 7T) could improve lesion detection, its cost limits accessibility. Valproate was the most prescribed drug, despite its recommended use in generalized epilepsy, emphasizing the need for improved adherence to treatment guidelines. Together with other studies, these findings can contribute to optimizing diagnostic and therapeutic strategies for pediatric focal epilepsy. Full article

Background: Pharmacoresistant epilepsy affects approximately one-third of all epilepsy patients, and resective surgery may offer favorable outcomes for carefully selected patients with focal epilepsy. The accurate identification of the epileptogenic zone (EZ) is essential for successful surgery, particularly in cases where non-invasive diagnostics are inconclusive. Invasive diagnostics with stereoelectroencephalography (SEEG) offer a reliable approach to localizing the EZ, especially in MRI-negative cases. Methods: This retrospective study analyzed the data of 22 patients with pharmacoresistant epilepsy who underwent frameless stereotactic SEEG electrode implantation with automated CT-based registration between September 2016 and November 2024. For measuring accuracy, Euclidean distance, radial deviation, angular deviation, and depth deviation were calculated for each electrode. Results: A total of 153 depth electrodes were implanted, targeting various cortical regions. The median Euclidean distance at the entry point was 1.54 mm (IQR 1.31), with a radial deviation of 1.33 mm (IQR 1.32). At the target level, the median Euclidean distance was 2.61 mm (IQR 1.53), with a radial deviation of 1.67 mm (IQR 1.54) and depth deviation of 0.95 mm (IQR 2.43). Accuracy was not significantly affected by electrode order, anatomical location, skull thickness, or intracranial length. Conclusions: These findings demonstrate that frameless stereotactic SEEG electrode implantation is safe and feasible for identifying the EZ. The integration of automatic intraoperative CT-based registration ensures precision. While maintaining workflow efficiency, it achieves accuracy comparable to frame-based methods. Further studies with larger cohorts are warranted to validate these results and assess their impact on surgical outcomes. Full article

Developing interfaces for seizure diagnosis, often challenging to detect visually, is rising. However, their effectiveness is constrained by the need for diverse and extensive databases. This study aimed to create a seizure detection methodology incorporating detailed information from each EEG channel and accounts for frequency band variations linked to the primary brain pathology leading to ICU admission, enhancing our ability to identify epilepsy onset. This study involved 460 video-electroencephalography recordings from 71 patients under monitoring. We applied signal preprocessing and conducted a numerical quantitative analysis in the frequency domain. Various machine learning algorithms were assessed for their efficacy. The k-nearest neighbours (KNN) model was the most effective in our overall sample, achieving an average F1 score of 0.76. For specific subgroups, different models showed superior performance: Decision Tree for ‘Epilepsy’ (average F1 score of 0.80) and ‘Craniencephalic Trauma’ (average F1 score of 0.84), Random Forest for ‘Cardiorespiratory Arrest’ (average F1 score of 0.89) and ‘Brain Haemorrhage’ (average F1 score of 0.84). In the categorisation of seizure types, Linear Discriminant Analysis was most effective for focal seizures (average F1 score of 0.87), KNN for generalised (average F1 score of 0.84) and convulsive seizures (average F1 score of 0.88), and logistic regression for non-convulsive seizures (average F1 score of 0.83). Our study demonstrates the potential of using classifier models based on quantified EEG data for diagnosing seizures in ICU patients. The performance of these models varies significantly depending on the underlying cause of the seizure, highlighting the importance of tailored approaches. The automation of these diagnostic tools could facilitate early seizure detection. Full article

About 40–50% of patients with drug-resistant epilepsy do not properly respond to pharmacological therapy with antiseizure medications (ASMs). Recently approved by the US Food and Drug Administration and European Medicines Agency as an add-on drug for focal seizures, cenobamate is an ASM sharing two basic mechanisms of action and exhibiting a promising profile of clinical efficacy. The drug preferably inhibits persistent sodium current and activates GABA-mediated events via extrasynaptic, non-benzodiazepine receptors. Thus, its antiseizure potential is dependent on both reducing excitation and enhancing inhibition in the central nervous system. In experimental seizure models, cenobamate exhibited a clear-cut activity in many of them with promising protective indexes, with only bicuculline-induced seizures being unaffected. Randomized clinical trials indicate that combinations of cenobamate, with already prescribed ASMs, resulted in significant percentages of seizure-free patients and patients with a significant reduction in seizure frequency, compared to other ASMs in the form of an add-on therapy. Its greater antiseizure efficacy was accompanied by adverse events comparable to other ASMs. Cenobamate has also been shown to possess neuroprotective activity, which may be of importance in affecting the process of epileptogenesis and, thus, modifying the course of epilepsy. Full article

Background and Objectives: The objective of this paper is to determine the rate and predictors of non-adherence to antiseizure medications in Saudi Arabia. Materials and Methods: A cross-sectional study which involved questionnaires and data collection from patients’ medical records was conducted at neurology clinics. The rate of non-adherence to antiseizure medications was measured using “the Medication Adherence Rating Scale” (MARS). Predictors of non-adherence to antiseizure medications were evaluated using a multidimensional questionnaire specific to epilepsy. Results: One hundred and sixty-two patients participated in the study. The mean (SD) age was 34.1 (10.4) years, and 56% were male. Epilepsy was controlled (i.e., seizure-free ≥ 1 year) in 42% of patients. The mean ± SD (range) MARS scores were 7.80 ± 1.59 (2–10). Out of 162 patients, 58 (36%) patients had MARS scores ≤ 7 out of 10. The most frequently rated predictor for non-adherence was poor seizure control, which was reported by around 36% of patients. Forgetfulness, dosing frequency, and social stigma were also among the commonest predictors of non-adherence to antiseizure medications that were rated by approximately 27%, 24%, and 22% of the patients, respectively. The impacts of several socio-demographic and clinical factors on adherence were assessed. In the regression analysis, the odds of non-adherence in a patient who experienced adverse effects were twice that of a patient who did not have adverse effects (p = 0.113). Furthermore, females, employers, and patients who had comorbidity, those with focal epilepsy, those on polytherapy of antiseizure medication, and those receiving multiple doses per day, were all more likely (but not significantly, p > 0.05) to be non-adherent compared to their counterparts. Conclusions: The significance of this study is that it reveals that adherence to antiseizure medications is suboptimal in Saudi Arabia. Poor seizure control, forgetfulness, dosing frequency, and social stigma were the primary patient-reported predictors of non-adherence in epilepsy. This emphasizes the importance of routine evaluation of adherence in practice to identify and address what individual patients perceive as a barrier to adherence with antiseizure medications. Full article

Objectives: To review the evidence on the clinical value of magnetic source imaging (MSI) in patients with refractory focal epilepsy without evidence for an epileptogenic lesion on magnetic resonance imaging (“MRI-negative” or “non-lesional MRI”). Methods: We conducted a systematic literature search on PUBMED, which was extended by researchrabbit.ai using predefined criteria to identify studies that applied MSI in MRI-negative patients with epilepsy. We extracted data on patient characteristics, MSI methods, localization results, surgical outcomes, and correlation with other modalities. Results: We included 23 studies with a total of 512 non-lesional epilepsy patients who underwent MSI. Most studies used equivalent current dipole (ECD) models to estimate the sources of interictal epileptic discharges (IEDs). MEG detected IEDs in 32–100% of patients. MSI results were concordant with other modalities, such as EEG, PET, and SPECT, in 3892% of cases. If MSI concordant surgery was performed, 52–89% of patients achieved seizure freedom. MSI contributed to the decision-making process in 28–75% of cases and altered the surgical plan in 5–33% of cases. Conclusions: MSI is a valuable diagnostic tool for MRI-negative patients with epilepsy, as it can detect and localize IEDs with high accuracy and sensitivity, and provides useful information for surgical planning and predicts outcomes. MSI can also complement and refine the results of other modalities, such as EEG and PET, and optimize the use of invasive recordings. MSI should be considered as part of the presurgical evaluation, especially in patients with non-lesional refractory epilepsy. Full article

Hyperventilation (HV) is an activation technique performed during clinical practices to trigger epileptiform activities, supporting the neurophysiological evaluation of patients with epilepsy. Although the role of HV has often been questioned, especially in the case of focal epilepsy, no studies have ever assessed how cortical structures respond to such a maneuver via intracranial EEG recordings. This work aims to fill this gap by evaluating the HV effects on the Stereo-EEG (SEEG) signals from a cohort of 10 patients with drug-resistant focal epilepsy. We extracted multiple quantitative metrics from the SEEG signals and compared the results obtained during HV, awake status, non-REM sleep, and seizure onset. Our findings show that the cortical connectivity, estimated via the phase transfer entropy (PTE) algorithm, strongly increases during the HV maneuver, similar to non-REM sleep. The opposite effect is observed during seizure onset, as ictal transitions involve the desynchronization of the brain structures within the epileptogenic zone. We conclude that HV promotes a conductive environment that may facilitate the propagation of epileptiform activities but is not sufficient to trigger seizures in focal epilepsy. Full article

Sensory integration is the province of the parietal lobe. The non-dominant hemisphere is responsible for both body sides, while the dominant hemisphere is responsible for the contralateral hemi-body. Furthermore, the posterior cingulate cortex (PCC) participates in a network involved in spatial orientation, attention, and spatial and episodic memory. Laser interstitial thermotherapy (LiTT) is a minimally invasive surgery for focal drug-resistant epilepsy (DRE) that can target deeper brain regions, and thus, region-specific symptoms can emerge. Here, we present an 18-year-old right-handed male with focal DRE who experienced seizures characterized by sensations of déjà vu, staring spells, and language disruption. A comprehensive evaluation localized the seizure focus and revealed a probable focal cortical dysplasia (FCD) in the left posterior cingulate gyrus. The patient underwent uneventful LiTT of the identified lesion. Post-operatively, he developed transient ipsilateral spatial neglect and contralateral sensory loss, as well as acalculia. His sensory symptoms gradually improved after the surgery, and he remained seizure-free after the intervention for at least 10 months (until the time of this writing). This rare case of ipsilateral spatial and visual hemineglect post-LiTT in epilepsy underscores the importance of recognizing atypical neurosurgical outcomes and considering individual variations in brain anatomy and function. Understanding the dynamics of cortical connectivity and handedness, particularly in pediatric epilepsy, may be crucial in anticipating and managing neurocognitive effects following epilepsy surgery. Full article

Background: Evaluating the differential impact of vagus nerve stimulation (VNS) therapy across various seizure types, our study explores its efficacy specifically in patients with categorized minor and major seizures. Methods: We conducted a retrospective cohort study involving 76 patients with pharmacoresistant epilepsy treated at the University Emergency Hospital of Bucharest between 2021 and 2024. Seizures were classified as ‘minor’ (including focal-aware and non-motor/absence seizures) and ‘major’ (including focal to bilateral tonic-clonic and generalized motor seizures), based on modified International League Against Epilepsy (ILAE) criteria. This classification allowed us to assess the response to VNS therapy, defined by a 50% or greater reduction in seizure frequency at the 12-month follow-up. Results: Our findings reveal that major seizures respond more favorably to VNS therapy, significantly reducing both frequency and intensity. In contrast, minor seizures showed a less pronounced response in frequency reduction but noted improvements in neurocognitive functions, suggesting a nuanced benefit of VNS in these cases. Conclusion: The study underscores the importance of seizure type in determining the efficacy of VNS therapy, advocating for personalized treatment approaches based on seizure classification. This approach could potentially enhance clinical outcomes by tailoring VNS settings to specific seizure types, improving overall management strategies in pharmacoresistant epilepsy. Full article

Objective: Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) with ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies suggest high efficacy with unusually high seizure-free rates. The authors sought to investigate the plasma levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. Methods: Blood samples were collected from adult PWEs who were treated with adjunct cenobamate under steady-state conditions. Daily doses, concomitant medications, efficacy, and tolerability were assessed. The plasma cenobamate levels of seizure-free versus non-responding PWEs and between PWEs with and those without clinical adverse events were compared. Results: Samples from 101 PWEs were included. Thirty-six PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. A linear correlation was found between the daily doses (range: 100 mg–400 mg) and the plasma levels (3.8 mg/L–54.6 mg/L). Neither the daily doses nor the plasma levels differed significantly between the investigated subgroups. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Conclusions: To evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful. A general therapeutic range cannot be defined. Full article

Temporal lobe epilepsy (TLE) represents the most common form of refractory focal epilepsy. The identification of innovative clinical biomarkers capable of categorizing patients with TLE, allowing for improved treatment and outcomes, still represents an unmet need. Circulating microRNAs (c-miRNAs) are short non-coding RNAs detectable in body fluids, which play crucial roles in the regulation of gene expression. Their characteristics, including extracellular stability, detectability through non-invasive methods, and responsiveness to pathological changes and/or therapeutic interventions, make them promising candidate biomarkers in various disease settings. Recent research has investigated c-miRNAs in various bodily fluids, including serum, plasma, and cerebrospinal fluid, of TLE patients. Despite some discrepancies in methodologies, cohort composition, and normalization strategies, a common dysregulated signature of c-miRNAs has emerged across different studies, providing the basis for using c-miRNAs as novel biomarkers for TLE patient management. Full article