Seizure Onset Research Articles

Gastrodin Attenuates Neuroinflammation and Injury in Young Rats with LiCl/Pilocarpine-Induced Status Epilepticus.

Status epilepticus is a severe neurological emergency that often leads to long-term neuronal damage and functional impairment. Gastrodin is a compound widely used in traditional Chinese medicine with potential neuroprotective effects. This study aims to investigate the effects of GAS on neuroinflammation and injury caused by LiCl/pilocarpine-induced SE in young rats. SE in rats was induced using the LiCl/pilocarpine model. Morris water maze and Y-maze experiments were used for the behavioral test of rats. Enzyme-linked immunosorbent assay was utilized to quantify the levels of interleukin (IL)-1β, IL-6, and IL-8 levels, and biochemical kits assessed the levels of malondialdehyde, superoxide dismutase and glutathione peroxidase (GSH-px) in hippocampus tissues. Additionally, Western blot analysis was performed to evaluate the protein expression levels of p-p65, p65, p-IκBα and IκBα, which are key factors of the nuclear factor kappa B (NF-κB) signaling pathway. Compared to the control group, the SE group rats exhibited reduced learning and memory abilities. Markedly elevated levels of inflammatory factors (IL-1β, IL-6, and IL-8). The expression levels of p-p65 and p-IκBα were significantly upregulated, while IκBα levels were notably decreased. Following GAS treatment, the latency of seizure onset was significantly shortened, the incidence of SE was significantly reduced and the severity of nerve injury was alleviated. Additionally, both the inflammation levels and the oxidative stress were significantly decreased, primarily through inhibition NF-κB signaling pathway. These findings suggest that GAS may be a potential therapeutic agent for treating SE.

A Prospective Observational Study on Incidence, Implications and Management of Seizures Following Stroke

Background: Seizures following a stroke often indicate a more severe incident, typically resulting in extended hospital stays and a heightened risk of long-term disability. Management strategies generally include the use of anti-epileptic drugs to mitigate the frequency and severity of seizures. Objectives: this study aims to evaluate the incidence and risk factors assosciated for seizures after stroke, differentiating between acute symptomatic seizures and late seizures. Additionally, it assess dependency levels of patients after stroke and management of seizures after stroke. Methodology: We conducted prospective observational study for 6 months which includes patients who were diagnosed with cerebrovascular accident, past history of cerebrovascular accident, experienced single or recurrent seizures of different types. Results: Out of 150 patients observed, 67 experienced seizures following stroke. Majority of these patients were male (99) predominantly aged between 50-75. Hypertension was found to be the major risk factor affecting 106(75.2%) individuals.Ischemic stroke were common. In terms of seizure occurrence, 27 patients experienced acute symptomatic seizure and 40 late onset seizure. Activity of daily living was assessed using Barthel Index Scale in which total dependency showed statistically significant relevance (P =0.01). Conclusion: In summary, the leading cause of seizure in adults is stroke. While both ischemic and hemorrhagic stroke may increase the risk of seizure, our study reveals that occurrence of seizure is greater following ischemic compared to hemorrhagic. A clinical pharmacist plays a vital role in determining prophylactic AED treatment for stroke patients and monitor to improve patient’s quality of life.

Comparison Between Different Source Localization and Connectivity Metrics of Spiky and Oscillatory MEG Activities

Epilepsy is considered the second neurological disease in a coma after stroke. Famous markers of epilepsy are repetitive seizures, their origin is stroma and cortical deformation. A neurologist would be assisted by identifying Epileptogenic Zones EZ when diagnosing epilepsy.. Source localization is utilized to identify regions known as EZ, which are of excessive discharges. It consists of both forward and inverse problems. The forward problem models the head through analytical and numerical methods. The inverse problem can be resolved using several techniques to locate the cerebral abnormal sources, via the electrophysiological recording biomarkers. In our study, we will investigate four distributed inverse problem methods: minimum norm estimation MNE, standardized low-resolution brain electromagnetic tomography sLORETA, maximum entropy on the mean MEM, Dynamic statistical parametric maps dSPM, to define epileptic networks connectivity of spiky and oscillatory events. We will examine the epileptic network connectivity using Phase Locking Value (PLV), Phase Transfert Entropy (PTE) for oscillatory events, cross-correlation (CC), and Granger Causality (GC) for spiky events applied on 5 pharmaco resistant subjects. We suggest rating the effectiveness of these networks in locating EZ through a phase of confrontation within iEEG transitory and oscillatory networks connectivity by exploring concordant nodes, their distance, propagation delays connection strength, and their cooperation in recognition of seizure onset zone. All studied techniques of the inverse problem, connection metrics, for both biomarkers of the 5 patients succeed in detecting at least one part of SOZ. sLORETA provides the highest concordant nodes and the closed one for spiky events using CC and GC. sLORETA also depicts the lowest propagation delay for oscillatory events using PTE. Through the 5 patients, MEM, dSPM, and MNE using CC, CG for spiky events, and PTE, PLV for oscillatory activities provide about 72 % of concordant nodes between MEG and iEEG.

Cerebral cortical encephalitis in adults with myelin oligodendrocyte glycoprotein antibody-associated disease: A national case series.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a relatively recently described disease, most commonly presenting with optic neuritis and longitudinally extensive transverse myelitis. Cerebral cortical encephalitis is a rare manifestation of MOGAD. We identified patients presenting with cerebral cortical encephalitis with positive MOG antibodies in serum across a large specialized service. Demographic and clinical information were collected. We describe clinical and laboratory characteristics, treatment response, and subsequent relapse risk in adults presenting with this phenotype. We identified eight patients meeting clinical criteria for cerebral cortical encephalitis with MOG antibodies. All had seizures; four had focal onset seizures with or without secondary generalization. Two patients exhibited encephalopathy, and six demonstrated focal neurological deficits at presentation. All had fluid-attenuated inversion recovery hyperintensities. Five of eight displayed cerebral swelling, and two of eight displayed leptomeningeal enhancement. Where cerebrospinal fluid (CSF) results were available, five of seven had CSF pleocytosis, protein was raised in two of seven, and one patient had oligoclonal bands unique to CSF. Median time to seizure control was 1.25 months, and all clinical features and magnetic resonance imaging abnormalities resolved. Four of eight patients (50%) had a clinical relapse, with a median time to relapse of 6.4 months. Cerebral cortical encephalitis appears to share similar CSF findings, steroid responsiveness, and risk of relapse with other clinical manifestations of MOGAD. This informs treatment decisions and patient counselling.

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.

Brivaracetam (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. This 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. Per 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. BRV 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. Current 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.

Is an earlier onset of focal epilepsy associated with atypical language lateralization? A systematic review, meta-analysis and new data.

Right and bilateral language representation is common in focal epilepsy, possibly reflecting the influence of epileptogenic lesions and/or seizure activity in the left hemisphere. Atypical language lateralization is assumed to be more likely in cases of early seizure onset, due to greater language plasticity in childhood. However, evidence for this association is mixed, with most research based on small samples and heterogenous cohorts. In this preregistered meta-analysis we examined the association between age at seizure onset and fMRI-derived language lateralization in individuals with focal epilepsy. The pooled effect size demonstrated a correlation between an earlier onset and rightward language lateralization in the total sample (r=0.1, p=.005, k=58, n=1240), with no difference in the correlation between left and right hemisphere epilepsy samples (Q=62.03, p=.302). In exploratory analyses of the individual participant data (n=1157), we demonstrated strong evidence that a logarithmic model fits the data better than a linear (BF=350) or categorical model with 6 years of age as a cut-off (BF=36). These findings indicate that there is a small but significant relationship between age at seizure onset and language lateralization. The relationship was consistent with theories of language plasticity proposing an exponential decline in plasticity over early childhood. However, given that this effect was subtle and only found in larger sample sizes, an early age at seizure onset would not serve as a good indicator of atypical language lateralization on the individual patient level.

Genetic and Cellular Basis of Impaired Phagocytosis and Photoreceptor Degeneration in CLN3 Disease.

CLN3 Batten disease (also known as juvenile neuronal ceroid lipofuscinosis) is a lysosomal storage disorder that typically initiates with retinal degeneration but is followed by seizure onset, motor decline and premature death. Patient-derived CLN3 disease induced pluripotent stem cell-RPE cells show defective phagocytosis of photoreceptor outer segment (POS). Because modifier genes are implicated in CLN3 disease, our goal here was to investigate a direct link between CLN3 mutation and POS phagocytosis defect. Isogenic control and CLN3 mutant stem cell lines were generated by CRISPR-Cas9-mediated biallelic deletion of exons 7 and 8. A transgenic CLN3Δ7-8/Δ7-8 (CLN3) Yucatan miniswine was also used to study the impact of CLN3Δ7-8/Δ7-8 mutation on POS phagocytosis. POS phagocytosis by cultured RPE cells was analyzed by Western blotting and immunohistochemistry. Electroretinogram, optical coherence tomography and histological analysis of CLN3Δ7-8/Δ7-8 and wild-type miniswine eyes were carried out at 6, 36, or 48 months of age. CLN3Δ7-8/Δ7-8 RPE (CLN3 RPE) displayed decreased POS binding and consequently decreased uptake of POS compared with isogenic control RPE cells. Furthermore, wild-type miniswine RPE cells phagocytosed CLN3Δ7-8/Δ7-8 POS less efficiently than wild-type POS. Consistent with decreased POS phagocytosis, lipofuscin/autofluorescence was decreased in CLN3 miniswine RPE at 36months of age and was followed by almost complete loss of photoreceptors at 48months of age. CLN3Δ7-8/Δ7-8 mutation (which affects ≤85% of patients) affects both RPE and POS and leads to photoreceptor cell loss in CLN3 disease. Furthermore, both primary RPE dysfunction and mutant POS independently contribute to impaired POS phagocytosis in CLN3 disease.

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

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. 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. 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. 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.

Up 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. Thirty-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. The 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. The 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. Many 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&lt;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.

The 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. Among 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. Among 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. Yawning 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. Yawning 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.

Magnetic Resonance Imaging of Adults Presenting with First Onset Seizure

Magnetic Resonance Imaging of Adults Presenting with First Onset Seizure

Self-Supervised Data-Driven Approach Defines Pathological High-Frequency Oscillations in Human.

Interictal high-frequency oscillations (HFOs) are a promising neurophysiological biomarker of the epileptogenic zone (EZ). However, objective criteria for distinguishing pathological from physiological HFOs remain elusive, hindering clinical application. We investigated whether the distinct mechanisms underlying pathological and physiological HFOs are encapsulated in their signal morphology in intracranial EEG (iEEG) recordings and whether this mechanism-driven distinction could be simulated by a deep generative model. In a retrospective cohort of 185 epilepsy patients who underwent iEEG monitoring, we analyzed 686,410 HFOs across 18,265 brain contacts. To learn morphological characteristics, each event was transformed into a time-frequency plot and input into a variational autoencoder. We characterized latent space clusters containing morphologically defined putative pathological HFOs (mpHFOs) using interpretability analysis, including latent space disentanglement and time-domain perturbation. mpHFOs showed strong associations with expert-defined spikes and were predominantly located within the seizure onset zone (SOZ). Discovered novel pathological features included high power in the gamma (30-80 Hz) and ripple (>80 Hz) bands centered on the event. These characteristics were consistent across multiple variables, including institution, electrode type, and patient demographics. Predicting 12-month postoperative seizure outcomes using the resection ratio of mpHFOs outperformed unclassified HFOs (F1=0.72 vs. 0.68) and matched current clinical standards using SOZ resection (F1=0.74). Combining mpHFO data with demographic and SOZ resection status further improved prediction accuracy (F1=0.83). Our data-driven approach yielded a novel, explainable definition of pathological HFOs, which has the potential to further enhance the clinical use of HFOs for EZ delineation.

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.