Seizure Onset Research Articles

A multicenter, cross‐sectional analysis to assess the safety and usage pattern of brivaracetam in the management of partial‐onset seizure with BAEs—BREEZE study: A post‐hoc analysis

AbstractObjectiveBrivaracetam (BRV), a third‐generation anti‐seizure medication (ASM) offers strong conformational receptor domain binding, faster blood brain barrier (BBB) permeability and better tolerability making it potential therapeutic option as an initial line or initial line add‐on strategy for focal onset seizure (FoS). The following study was planned to further understand the role and relevance of BRV in the real world settings of India.MethodThis was a multicentric, cross‐sectional, and non‐interventional study conducted in patients with FoS across India. The study was approved by central independent ethics committee. Descriptive and analytical statistics employed using SPSS version 29.0.1.0.ResultsPer protocol (PP) analysis included 8479 eligible patients from 1069 sites, gender; 5771 (68.06%) male and 2708 (31.94%) female with mean age 41.21 ± 12.74 years. Total 8019 (94.57%) patients had FoS and 460 (5.43%) patients had focal to bilateral tonic–clonic seizures (FBTCs). In FoS, 4105 (51.19%) patients switched from LEV to BRV whereas 3914 (48.81%) switched from other ASMs to BRV. BAEs accounted for 2059 (50.16%) patients in LEV to BRV switch versus 133 (3.39%) in other ASM to BRV switch. Post switch, LEV‐associated BAEs reduced irrespective of being used as monotherapy 85.65% (p < 0.001) or as an adjuvant therapy 83.71% (p < 0.001) at BRV dosage of 50 to 100 mg BID. This RWE showed the utility of BRV as mono component as an initial add‐on strategy in FoS cases.SignificanceBRV remains a pertinent therapeutic choice for FoS for the treatment naïve and/or BAE cases. Exposure of LEV leads to considerable BAEs compared to patients without LEV exposure. Patients who switched to BRV due to LEV‐induced BAEs significantly improved tolerability with BRV irrespective being used as monotherapy or as adjuvant therapy.Plain Language SummaryCurrent study was planned to understand the clinical role and relevance of third‐generation anti‐seizure medication (ASM), brivaracetam (BRV) in the real world settings of India. Outcome of the study highlighted that BRV is an emerging, potential and safe ASM treatment option for epilepsy in Indian context. Many patients with epilepsy who are not able to tolerate the other ASM including levetiracetam (LEV) primarily due to behavioral side effects improves tolerability post switch to BRV, additionally results are consistent either BRV being used as an adjuvant therapy or as monotherapy therapy.

Methods for Identifying Epilepsy Surgery Targets Using Invasive EEG: A Systematic Review

Background: The pre-surgical evaluation for drug-resistant epilepsy achieves seizure freedom in only 50–60% of patients. Efforts to identify quantitative intracranial EEG (qEEG) biomarkers of epileptogenicity are needed. This review summarizes and evaluates the design of qEEG studies, discusses barriers to biomarker adoption, and proposes refinements of qEEG study protocols. Methods: We included exploratory and prediction prognostic studies from MEDLINE and Scopus published between 2017 and 2023 that investigated qEEG markers for identifying the epileptogenic network as the surgical target. Cohort parameters, ground truth references, and analytical approaches were extracted. Results: Out of 1789 search results, 128 studies were included. The study designs were highly heterogeneous. Half of the studies included a non-consecutive cohort, with sample sizes ranging from 2 to 166 patients (median of 16). The most common minimum follow-up was one year, and the seizure onset zone was the most common ground truth. Prediction studies were heterogeneous in their analytical approaches, and only 25 studies validated the marker through post-surgical outcome prediction. Outcome prediction performance decreased in larger cohorts. Conversely, longer follow-up periods correlated with higher prediction accuracy, and connectivity-based approaches yielded better predictions. The data and code were available in only 9% of studies. Conclusions: To enhance the validation qEEG markers, we propose standardizing study designs to resemble clinical trials. This includes using a consecutive cohort with long-term follow-up, validating against surgical resection as ground truth, and evaluating markers through post-surgical outcome prediction. These considerations would improve the reliability and clinical adoption of qEEG markers.

ECG‐based epileptic seizure prediction: Challenges of current data‐driven models

AbstractObjectiveUp to a third of patients with epilepsy fail to achieve satisfactory seizure control. A reliable method of predicting seizures would alleviate psychological and physical impact. Dysregulation in heart rate variability (HRV) has been found to precede epileptic seizures and may serve as an extracerebral predictive biomarker. This study aims to identify the preictal HRV dynamics and unveil the factors impeding the clinical application of ECG‐based seizure prediction.MethodsThirty‐nine adult patients (eight women; median age: 38, [IQR = 31, 56.5]) with 252 seizures were included. Each patient had more than three recorded epileptic seizures, each at least 2 hours apart. For each seizure, one hour of ECG prior to seizure onset was analyzed and 97 HRV features were extracted from overlapping three‐minute windows with 10s stride. Two separate patient‐specific experiments were performed using a support vector machine (SVM). Firstly, the separability of training data was examined in a non‐causal trial. Secondly, the prediction was attempted in pseudo‐prospective conditions. Finally, visualized HRV data, clinical metadata, and results were correlated.ResultsThe mean receiver operating characteristic (ROC) area under the curve (AUC) for the non‐causal experiment was 0.823 (±0.12), with 208 (82.5%) seizures achieving an improvement over chance (IoC) classification score (p < 0.05, Hanley & McNeil test). In pseudo‐prospective classification, the ROC‐AUC was 0.569 (±0.17), and 86 (49.4%) seizures were classified with IoC. Off‐sample optimized SVMs failed to improve performance. Major limiting factors identified include non‐stationarity, variable preictal duration and dynamics. The latter is expressed as both inter‐seizure onset zone (SOZ) and intra‐SOZ variability.SignificanceThe pseudo‐prospective preictal classification achieving IoC in approximately half of tested seizures suggests the presence of genuine preictal HRV dynamics, but the overall performance does not warrant clinical application at present. The limiting factors identified are often overlooked in non‐causal study designs. While current deterministic prediction methods prove inadequate, probabilistic approaches may offer a promising alternative.Plain Language SummaryMany patients with epilepsy suffer from uncontrollable seizures and would greatly benefit from a reliable seizure prediction method. Currently, no such system is available to meet this need. Previous studies suggest that changes in the electrocardiogram (ECG) precede seizures by several minutes. In our work, we evaluated whether variations in heart rate could be used to predict epileptic seizures. Our findings indicate that we are still far from achieving results suitable for clinical application and highlight several limiting factors of present seizure prediction approaches.

ANTICONVULSANT EFFECT OF ISOLATED COMPOUNDS FROM THE LEAVES OF GLOBIMETULA BRAUNII ENGLER VAN TIEGH (LORANTHACEAE) IN MICE AND CHICKS

The anticonvulsant evaluation of globrauneine A (1), globrauneine C (2) globrauneine D (3), globrauneine F (4), lupeol (5), β-sitosterol (6), (1R,5S,7S)-7-[2-(4-hydroxyphenyl) ethyl]-2,6-dioxabi-cyclo [3. 3.1]-nonan-3-one (7), dodoneine (8), quercetin (9) and rutin (10) from Globimetula braunii leaves were analyzed with the aid of pentylenetetrazole-induced seizure test in mice (PTZ) and maximal electroshock seizure test in chicks (MEST), while the neurotoxicity was evaluated using the beam walking assay in mice. 50% of the tested mice were protected by Globrauneine A (1) and dodoneine (8) against PTZ-induced mortality. The mean onset of clonic spasm of the unprotected animals was increased by Quercetin (9) and also the mice were differentially protected against mortality. The tested compounds also produced significant (p<0.05) increase in the mean onset of seizure against pentylenetetrazole-induced seizure. The chicks were not protected by the tested compounds against MEST and the recovery time was not significantly reduced. In the beam assay, with the exception of dodoneine (8), the number of foot slips and the time taken to complete the task was not significantly changed by the tested isolated compounds, suggesting that the observed activities are not due to general CNS depression. The results suggest mild protective effects of these isolated compounds against seizure which might be useful in the control of petit mal epilepsy.

Peri‐ictal yawning: A potential lateralizing sign in temporal lobe epilepsy

AbstractObjectiveThe primary objective of this retrospective analysis was to evaluate the incidence and lateralization value of peri‐ictal yawning (PY) in people with temporal lobe epilepsy (TLE). PY has only occasionally been reported as a manifestation of focal epilepsy. We aimed to determine whether PY could serve as an indicator to help lateralize seizure onset during epileptic seizures.MethodsAmong 236 consecutive TLE patients admitted for video‐EEG monitoring, we analyzed the clinical characteristics, along with scalp video‐EEG, magnetic resonance imaging (MRI), fluorodeoxyglucose‐positron emission tomography (FDG‐PET), Wada test, and stereo EEG (SEEG) in patients with PY.ResultsAmong the 236 patients, 26 (11.0%) exhibited PY, and 36 of 1018 recorded seizures (3.5%) were associated with PY. Of the 26 patients with PY, 19 (73.1%) had non‐dominant TLE, while 7 (26.9%) had dominant TLE. The majority of these patients presented with staring, arrest, and automatisms during their seizures with accompanying vegetative signs. PY occurred either during the ictal or postictal phase in all patients. Exception for 10 seizures (10/36, 27.8%) at the early stage (less than 25% total duration), PY was primarily linked to the late ictal and postictal phases. Surgical intervention was performed in 12 patients, 9 of whom (75%) achieved seizure freedom (Engel class I), with 7 of these 9 (77.8%) having non‐dominant TLE.SignificanceYawning is a physiological phenomenon typically not associated with epilepsy. The present series suggests that PY is relatively uncommon in TLE, but may represent a rare vegetative sign, particularly in cases with non‐dominant TLE. Further investigation with a larger cohort of surgically confirmed cases and using intracranial EEG is essential to deepen our understanding of this phenomenon.Plain Language SummaryYawning is a typical physiological response that is generally not linked to epilepsy. However, it can occasionally indicate seizure activity, particularly in TLE. PY happens more often observed in non‐dominant TLE and usually occurs in the later stages of a seizure or just after it. It may hold potential as a lateralizing marker in TLE.

Case Report: Multi drug resistant tuberculosis in an 18-month-old boy with seizure, vomiting, and loss of vision

Multi drug resistant tuberculosis (MDR-TB) in children is rare and requires tremendous skill and knowledge of clinicians for early detection and treatment. This case highlights the complexities in diagnosing and treating MDR-TB in young children. An 18-month-old immunocompetent boy presented with prolonged fever, sudden onset of vision loss, vomiting, and seizures, which led to a suspicion of meningitis. Given his family history of treated pulmonary TB (TB) in the father and uncle one year ago, the initial treatment followed the Nepali national protocol for non-MDR tuberculous meningitis (TBM). However, the child's lack of response to this treatment raised concerns about MDR-TB, particularly after discovering on close questioning that the uncle, who lived with the boy’s family, had actually been diagnosed with MDR-TB. The diagnosis was confirmed by molecular tests of cerebrospinal fluid (CSF) and customized treatment for MDR TBM administered. The boy then slowly improved and became less irritable, afebrile, seizure-free, developed spontaneous movements of all four limbs, and was discharged after one month. Delays in suspicion, confirmation, and treatment of MDR TBM led to complications of leptomeningitis with non-communicating hydrocephalus and bilateral optic atrophy, which was confirmed by magnetic resonance imaging (MRI) scan of the brain. This case highlights the importance of taking a very thorough and proper history and considering the possibility of MDR, especially in countries like Nepal where TB in general is rampant so that timely diagnosis and treatment is possible and complications are avoided.

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.

Whole exome sequencing-based testing of adult epilepsy in a Polish population.

Genetic panel testing in paediatric and mixed adult and children populations has demonstrated clinical utility and provided a diagnostic yield of 18-40%. The data on adult epilepsies is limited. We aimed to investigate the diagnostic yield and analyse genetic diagnoses in whole exome sequenced adult patients with epilepsies in Poland. We recruited 151 patients from 42 clinical centres across Poland. The patients had a diagnosis of epilepsy/ seizures, were 18 or older at the time of the genetic testing, and did not have a genetic diagnosis. All patients were tested with whole exome sequencing after an initial testing with a panel of 47 epilepsy-related genes. We reached a diagnostic yield when considering pathogenic/probably pathogenic variants according to ClinVar of 8.6% (n = 13) and 17% (n = 26) when applying the American College of Medical Genetics (ACMG) criteria. Most patients had a pathogenic/probably pathogenic variant in epilepsy-related genes (54%), followed by potential epilepsy-related genes (19%), and neurodevelopment-associated epilepsy genes (15%). Our study shows that whole exome sequencing-based testing reaches a slightly higher diagnostic yield that the traditional 300 gene panel. Genes related to childhood onset neurodevelopmental disorders and epilepsy should be considered as well. Clinical implications/future directions. Patients may have had a diagnosis related to a childhood syndrome, but due to limited diagnostic possibilities, it was not possible to diagnose them in childhood. We would consider testing adult patients with epilepsy with whole exome or genome sequencing (or if not possible with a panel) in cases of a diagnosis of epilepsy with no hints suggesting secondary epilepsy, and especially with clinical features indicating a genetic epilepsy diagnosis, such as neurodevelopmental delay and early onset of seizures.

SLC2A1 variants cause late-onset epilepsy and the genetic-dependent stage feature

BackgroundThe SLC2A1 gene plays a vital role in brain energy metabolism. SLC2A1 variants have been reported to be associated with early-onset refractory seizures. This study aims to explore the association between the SLC2A1 gene and late-onset epilepsy.MethodsTrios-based whole-exome sequencing was performed on patients with epilepsy without acquired etiologies. The pathogenicity of the variants was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.ResultsA total of 14 heterozygous SLC2A1 variants were identified in 16 unrelated families. The variants were evaluated as “pathogenic” or “likely pathogenic” according to the ACMG guidelines. Ten cases (62.5%) presented with infantile onset seizures and developmental delay/intellectual disability and were diagnosed with developmental and epileptic encephalopathy (DEE). The other six cases (37.5%) exhibited late-onset seizures and normal development. They were diagnosed with idiopathic partial epilepsy (n = 2) or idiopathic generalized epilepsy (n = 4). Further analysis showed that DEE-associated variants tended to cluster in the transmembrane region, whereas the mild epilepsy-associated variants tended to locate in regions outside the transmembrane region, suggesting a potential molecular sub-regional effect. A total of 15 cases had delayed diagnosis, with the longest delay being 22 years. The SLC2A1 expression stage, which is expressed at relatively high level throughout the whole life span, from the embryonic to adult stages with two peaks at approximately four and 14 years, is generally consistent with the seizure onset age. In addition, patients with early-onset age had variants that were potentially associated with severe damage, suggesting a potential correlation between the age of disease onset and the damaging effects of the variants.ConclusionsSLC2A1 variants are associated with late-onset epilepsy, which is consistent with the genetic-dependent stage feature of SLC2A1. Early genetic diagnosis is important for treatment of patients with SLC2A1 variants.

Response to amoxicillin and perampanel in infantile Alexander disease.

Type I Alexander disease (AxD) presents with paroxysmal neurodegeneration, refractory epilepsy, and encephalopathy in the first years of life and is associated with a poor prognosis. Although there is no treatment, mild symptomatic improvement has been reported in one case of adult Alexander treated with ceftriaxone, given its interaction with the mutant glial fibrillary acid protein (GFAP) responsible for the disease's pathogenesis. We describe a patient presenting with irritability starting at 2 months of age, initially attributed to gastroesophageal reflux. A ventriculoperitoneal shunt was placed at 3 months of age due to hydrocephalus secondary to aqueduct stenosis detected through an MRI scan, but the irritability persisted. At 5 months, a new brain MRI was performed due to irritability worsening, onset of abnormal ocular movements and seizures. In addition genetic testing was performed. AxD was diagnosed due to the mutation c.716G>A (p.Arg239His) in GFAP. Since irritability had worsened and had not responded to levomepromazine, treatment with amoxicillin (80 mg/kg/day) was attempted to modulate glutamate levels. The patient showed a striking improvement of irritability in 48 h that persisted over the next months. The patient had frequent daily seizures which did not respond to valproate, clonazepam, or phenobarbital. Perampanel, a postsynaptic AMPA receptor antagonist, was added to phenobarbital and he was seizure free for more than 3 months. Drugs modulating glutamate levels in the central nervous system, including β-lactam antibiotics and perampanel, may have an important role in the symptomatic treatment of AxD and other neurodegenerative diseases where glutamatergic excitotoxicity is a pathogenic determinant. PLAIN LANGUAGE SUMMARY: Alexander disease is a rare and serious condition that affects the brain, often leading to neurodegeneration (brain damage), seizures, and other problems in early childhood. The disease is caused by a mutation in a gene called GFAP. There is no cure, and current treatments mainly focus on relieving symptoms. This article discusses the case of a baby who showed signs of irritability and seizures from a young age. The baby was diagnosed with Alexander disease after brain scans and genetic testing. Despite treatment with various drugs, the baby continued to experience seizures and irritability. The doctors decided to try amoxicillin, a common antibiotic, because of its potential to help control the disease by affecting a brain chemical called glutamate. Surprisingly, the baby's irritability improved within 2 days of starting amoxicillin, and the improvement lasted for several months. However, the seizures persisted until another medication, perampanel, was added. This combination controlled the baby's seizures for over 3 months. Unfortunately, the baby passed away at 13 months due to complications from the disease. However, doctors believe that drugs like amoxicillin and perampanel could be promising treatments for managing symptoms of Alexander disease and other similar brain conditions in the future, especially where excess glutamate plays a role in the damage. This case suggests that these treatments may help control irritability and seizures, offering hope for better management of this challenging disease.

Imaging blood-brain barrier dysfunction in drug-resistant epilepsy: A multi-center feasibility study.

Blood-brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals. We scanned 50 drug-resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE-MRI. The presence and extent of BBBD were analyzed and compared between PWE and healthy controls. Both greater brain volume and higher number of brain regions with BBBD were significantly present in PWE compared to healthy controls (p < 10-7). No differences in total brain volume with BBBD were observed in patients diagnosed with either focal seizures or generalized epilepsy, despite variations in the affected regions. Overall brain volume with BBBD did not differ in PWE with MRI-visible lesions compared with non-lesional cases. BBBD was observed in brain regions suspected to be related to the onset of seizures in 82% of patients (n = 39) and was typically identified in, adjacent to, and/or in the same hemisphere as the suspected epileptogenic lesion (n = 10). These findings are consistent with pre-clinical studies that highlight the role of BBBD in the development of DRE and identify microvascular stabilization as a potential therapeutic strategy.

An Unobtrusive and Lightweight Ear-worn System for Continuous Epileptic Seizure Detection

Epilepsy is one of the most common neurological diseases globally (around 50M people globally). Fortunately, up to 70% of people with epilepsy could live seizure-free if properly diagnosed and treated, and a reliable technique to monitor the onset of seizures could improve the quality of life of patients who are constantly facing the fear of random seizure attacks. The current gold standard, video-EEG (v-EEG), involves attaching over 20 electrodes to the scalp, is costly, requires hospitalization, trained professionals, and is uncomfortable for patients. To address this gap, we developed EarSD , a lightweight and unobtrusive ear-worn system to detect seizure onsets by measuring physiological signals behind the ears. This system can be integrated into earphones, headphones, or hearing aids, providing a convenient solution for continuous monitoring. EarSD is an integrated custom-built sensing - computing - communication ear-worn platform to capture seizure signals, remove the noises caused by motion artifacts and environmental impacts, and stream the collected data wirelessly to the computer/mobile phone nearby. EarSD 's ML algorithm, running on a server, identifies seizure-associated signatures and detects onset events. We evaluated the proposed system in both in-lab and in-hospital experiments at the University of Texas Southwestern Medical Center with epileptic seizure patients, confirming its usability and practicality.

Machine learning for forecasting initial seizure onset in neonatal hypoxic-ischemic encephalopathy.

This study was undertaken to develop a machine learning (ML) model to forecast initial seizure onset in neonatal hypoxic-ischemic encephalopathy (HIE) utilizing clinical and quantitative electroencephalogram (QEEG) features. We developed a gradient boosting ML model (Neo-GB) that utilizes clinical features and QEEG to forecast time-dependent seizure risk. Clinical variables included cord blood gas values, Apgar scores, gestational age at birth, postmenstrual age (PMA), postnatal age, and birth weight. QEEG features included statistical moments, spectral power, and recurrence quantification analysis (RQA) features. We trained and evaluated Neo-GB on a University of California, San Francisco (UCSF) neonatal HIE dataset, augmenting training with publicly available neonatal electroencephalogram (EEG) datasets from Cork University and Helsinki University Hospitals. We assessed the performance of Neo-GB at providing dynamic and static forecasts with diagnostic performance metrics and incident/dynamic area under the receiver operating characteristic curve (iAUC) analyses. Model explanations were performed to assess contributions of QEEG features and channels to model predictions. The UCSF dataset included 60 neonates with HIE (30 with seizures). In subject-level static forecasting at 30 min after EEG initiation, baseline Neo-GB without time-dependent features had an area under the receiver operating characteristic curve (AUROC) of .76 and Neo-GB with time-dependent features had an AUROC of .89. In time-dependent evaluation of the initial seizure onset within a 24-h seizure occurrence period, dynamic forecast with Neo-GB demonstrated median iAUC = .79 (interquartile range [IQR] .75-.82) and concordance index (C-index) = .82, whereas baseline static forecast at 30 min demonstrated median iAUC = .75 (IQR .72-.76) and C-index = .69. Model explanation analysis revealed that spectral power, PMA, RQA, and cord blood gas values made the strongest contributions in driving Neo-GB predictions. Within the most influential EEG channels, as the preictal period advanced toward eventual seizure, there was an upward trend in broadband spectral power. This study demonstrates an ML model that combines QEEG with clinical features to forecast time-dependent risk of initial seizure onset in neonatal HIE. Spectral power evolution is an early EEG marker of seizure risk in neonatal HIE.

Olfactory Dysfunction and Limbic Hypoactivation in Temporal Lobe Epilepsy.

The epileptogenic network in temporal lobe epilepsy (TLE) contains structures of the primary and secondary olfactory cortex such as the piriform and entorhinal cortex, the amygdala, and the hippocampus. Olfactory auras and olfactory dysfunction are relevant symptoms of TLE. This study aims to characterize olfactory function in TLE using olfactory testing and olfactory functional magnetic resonance imaging (fMRI). We prospectively enrolled 20 individuals with unilateral TLE (age 45 ± 20 years [mean ± SD], 65% female, 90% right-handed) and 20 healthy individuals (age 33 ± 15 years [mean ± SD], 35% female, 90% right-handed). In the TLE group, the presumed seizure onset zone was left-sided in 75%; in 45% of the individuals with TLE limbic encephalitis was the presumed etiology; and 15% of the individuals with TLE reported olfactory auras. Olfactory function was assessed with a Screening Sniffin' Sticks Test (Burkhart, Wedel, Germany) during a pre-assessment. During a pre-testing, all individuals were asked to rate the intensity, valence, familiarity, and associated memory of five different odors (eugenol, vanillin, phenethyl alcohol, decanoic acid, valeric acid) and a control solution. During the fMRI experiment, all individuals repeatedly smelled eugenol (positively valenced odor), valeric acid (negatively valenced odor), and the control solution and were asked to rate odor intensity on a five-point Likert scale. We acquired functional EPI sequences and structural images (T1, T2, FLAIR). Compared to healthy individuals, individuals with TLE rated the presented odors as more neutral (two-sided Mann-Whitney U tests, FDR-p < 0.05) and less familiar (two-sided Mann-Whitney U tests, FDR-p < 0.05). fMRI data analysis revealed a reduced response contrast in secondary olfactory areas (e.g., hippocampus) connected to the limbic system when comparing eugenol and valeric acid in individuals with TLE when compared with healthy individuals. However, no lateralization effect was obtained when calculating a lateralization index by the number of activated voxels in the olfactory system (two-sided Mann-Whitney U test; U = 176.0; p = 0.525). TLE is characterized by olfactory dysfunction and associated with hypoactivation of secondary olfactory structures connected to the limbic system. These findings contribute to our understanding of the pathophysiology of TLE. This study was preregistered on OSF Registries (www.osf.io).

Epilepsia Partialis Continua as Late Sequelae in Chronic Cerebral Paragonimiasis

Paragonimiasis is a parasitic infection that occurs after ingesting freshwater crayfish or crabs, and &lt;i&gt;Paragonimus westermani&lt;/i&gt; (&lt;i&gt;P. westermani&lt;/i&gt;) species are the most important in clinical practice. Cerebral paragonimiasis is one of the most important extra-pulmonary forms with severe outcomes and higher mortality compared to the pulmonary forms. Epilepsia partialis continua (EPC) is defined as a variant of focal motor status epilepticus in which frequent repetitive muscle jerks, usually arrhythmic, continue over 1 hour. Cerebral infections of &lt;i&gt;P. westermani&lt;/i&gt; often cause simple epileptic seizures, but cases progressing to EPC are very rare. The authors report a case of confirming and treating a newly developed recurrent focal onset seizures in a patient with chronic cerebral paragonimiasis treated over 30 years ago.

Seizure solver- pyridoxine dependent seizures

Pyridoxine dependency is a rare cause of seizures. Pyridoxine dependent seizures (PDS) occur despite normal vitamin B6 levels and is due to defective binding of pyridoxine to its apoenzyme, glutamate decarboxylase, which converts glutamic acid to gamma aminobutyric acid (GABA). Pyridoxine-dependent seizure is a rare autosomal recessive disorder that usually presents with neonatal intractable seizures. Parenteral pyridoxine injection test is a highly effective and reproducible test in confirming the diagnosis. Hunt, et al.(l) described the first case of PDS with autosomal recessive inheritance. Since then, several cases have been reported with onset of seizures after neonatal period (2-6). Pyridoxine-dependent epilepsy – ALDH7A1 (PDE-ALDH7A1) is characterized by seizures not well controlled with anti-seizure medication that are responsive clinically and electrographically to large daily supplements of pyridoxine (vitamin B6). This is true across a phenotypic spectrum that ranges from classic to atypical PDE-ALDH7A1. Intellectual disability is common, particularly in classic PDE-ALDH7A1.(7)

Accumulated seizure burden predicts neurodevelopmental outcome at 36 months of age in patients with tuberous sclerosis complex.

Epilepsy and intellectual disability are common in tuberous sclerosis complex (TSC). Although early life seizures and intellectual disability are known to be correlated in TSC, the differential effects of age at seizure onset and accumulated seizure burden on development remain unclear. Daily seizure diaries, serial neurodevelopmental testing, and brain magnetic resonance imaging were analyzed for 129 TSC patients followed from 0 to 36 months. We used machine learning to identify subgroups of patients based on neurodevelopmental test scores at 36 months of age and assessed the stability of those subgroups at 12 months. We tested the ability of candidate biomarkers to predict 36-month neurodevelopmental subgroup using univariable and multivariable logistic regression. Candidate biomarkers included age at seizure onset, accumulated seizure burden, tuber volume, sex, and earlier neurodevelopmental test scores. Patients clustered into two neurodevelopmental subgroups at 36 months of age, higher and lower scoring. Subgroup was mostly (75%) the same at 12 months. Significant univariable effects on subgroup were seen only for accumulated seizure burden (largest effect), earlier test scores, and tuber volume. Neither age at seizure onset nor sex significantly distinguished 36-month subgroups, although for girls but not boys there was a significant effect of age at seizure onset. In the multivariable model, accumulated seizure burden and earlier test scores together predicted 36-month neurodevelopmental group with 82% accuracy and an area under the curve of .86. These results untangle the contributions of age at seizure onset and accumulated seizure burden to neurodevelopmental outcomes in young children with TSC. Accumulated seizure burden, rather than the age at seizure onset, most accurately predicts neurodevelopmental outcome at 36 months of age. These results emphasize the need to manage seizures aggressively during the first 3 years of life for patients with TSC, not only to promote seizure control but to optimize cognitive function.

Awake surgery with mapping-based resection to treat focal epilepsy in eloquent brain areas.

Resective surgery is a potential therapeutic option for select patients with intractable focal epilepsy. However, the presence of ictal onset zones within or surrounding highly functional brain areas presents a surgical challenge, leading to poor seizure and functional outcomes. This report describes our experiences with awake mapping-tailored resection of epileptogenic areas involving eloquent cortices and evaluates their feasibility, tolerance, limitations, and significance. The study included patients who underwent surgery for drug-resistant focal epilepsy at our center under awake conditions. The surgical approach aimed to achieve maximum resection of preoperatively defined epileptogenic zones, considering the boundaries defined by surrounding functional areas. We collected data on preoperative evaluations, intraoperative tests and seizures, postoperative status epilepticus, and neurological functional outcomes. We included 22 patients, 10 of whom had non-lesional epilepsy. Language, motor function, and sensory function were at risk in 19, 9, and 4 patients, respectively. Resection was performed as planned in 14 (63.6%) patients, while modifications were necessary in 8 (36.4%) patients due to functional constraints. The mean follow-up duration was 29.8months. Sixteen (72.7%) patients achieved Engel class Ia outcomes, indicating seizure freedom, while none of the patients experienced clinically significant permanent postoperative neurological deficits. Resective surgery with intraoperative brain mapping under awake conditions was a valid treatment option for achieving a cure in cases of drug-resistant focal epilepsy, even in situations in which the condition is considered inoperable due to the risk of significant postoperative neurological deficits.

Seizure Onset Zone Detection Based on Convolutional Neural Networks and EEG Signals

Background: The localization of seizure onset zones (SOZs) is a critical step before the surgical treatment of epilepsy. Methods and Results: In this paper, we propose an SOZ detection method based on convolutional neural networks and EEG signals. This method aims to locate SOZs through the seizure status of each channel in multi-channel EEG signals. First, we preprocess the data with filtering, segmentation, resampling, and standardization to ensure their quality and consistency. Then, the single-channel UCI epilepsy seizure recognition dataset is used to train and test the convolutional neural network (CNN) model, achieving an accuracy of 98.70%, a sensitivity of 97.53%, and a specificity of 98.98%. Next, the multi-channel clinical EEG dataset collected by a hospital is divided into 21 single-channel site datasets and input into the model for detection, and then the seizure results of 21 sites per second are obtained. Finally, the seizure sites are visualized through the international 10–20 system electrode distribution map, diagrams of the change process of the seizure sites during seizures are drawn, and patients’ SOZs are located. Conclusions: Our proposed method well classifies seizure and non-seizure data and successfully locates SOZs by detecting the seizure results of 21 sites through a single-channel model. This study can effectively assist doctors in locating the SOZs of patients and provide help for the diagnosis and treatment of epilepsy.

Seizure Sources Can Be Imaged from Scalp EEG by Means of Biophysically Constrained Deep Neural Networks.

Seizure localization is important for managing drug-resistant focal epilepsy. Here, the capability of a novel deep learning-based source imaging framework (DeepSIF) for imaging seizure activities from electroencephalogram (EEG) recordings in drug-resistant focal epilepsy patients is investigated. The neural mass model of ictal oscillations is adopted to generate synthetic training data with spatio-temporal-spectra features similar to ictal dynamics. The trained DeepSIF model is rigorously validated using computer simulations and in a cohort of 33 drug-resistant focal epilepsy patients with high-density (76-channel) EEG seizure recordings, by comparing DeepSIF estimates with surgical resection outcome and seizure onset zone (SOZ) . These findings show that the trained DeepSIF model outperforms other methods in estimating the spatial and temporal information of origins of ictal activities. It achieves a high spatial specificity of 96% and a low spatial dispersion of 3.80±5.74mm when compared to the resection region. The source imaging results also demonstrate good coverage of SOZ, with an average distance of 10.89±10.14mm (from the SOZ to the reconstruction). These promising results suggest that DeepSIF has significant potential for advancing noninvasive imaging of the origins of ictal activities in patients with focal epilepsy, aiding management of intractable epilepsy.