Search Results (568)

Epilepsy affects over 50 million people worldwide, yet automated seizure detection systems either achieve moderate sensitivity with excessive false alarms or rely on uninterpretable deep networks. This study presents a patient-independent EEG-based seizure detection framework that achieved zero false alarms in 24 h with 95% sensitivity in a retrospective evaluation on a CHB–MIT pediatric cohort (n = 6 seizure-positive patients). The pipeline extracts 27 time-, frequency-, and nonlinear-domain features from 5 s windows and trains five ensemble classifiers (XGBoost, CatBoost, LightGBM, Extra Trees, Random Forest) using strict leave-one-subject-out cross-validation. All models achieved segment-level AUC ≥ 0.99. Under zero-false-alarm constraints, XGBoost attained perfect specificity with 0.922 sensitivity. SHAP and LIME analyses suggested candidate EEG biomarkers that appear consistent with known ictal signatures, including temporo-parietal theta-band power, amplitude variability (IQR, RMS), and Hjorth activity. External validation on the Siena Scalp EEG Database (12 adult patients, 37 seizures) demonstrated cross-dataset generalization with 95% event-level sensitivity (Extra Trees) and AUC of 0.86 (Random Forest). Temporal lobe channels dominated feature importance in both datasets, confirming consistent biomarker identification across pediatric and adult populations. These findings demonstrate that calibrated gradient-boosted ensembles using interpretable EEG features achieve clinically safe seizure detection with cross-dataset generalizability. Full article

Disputes over episcopal temporalities provide a crucial lens through which to view complex Church–Crown relations in medieval England. The secular estates endowed by the Crown formed the backbone of ecclesiastical wealth, sustaining diocesan administration and judicial operations. As the principal patron, the king frequently intervened in episcopal property disputes. By drawing them into the royal courts, the Crown was able to diminish episcopal authority within bishops’ temporal jurisdiction and to consolidate control over ecclesiastical lands and benefice appointments, thereby contributing to the institutionalization of secular judicial interventions in ecclesiastical affairs. Confiscation of temporalities functioned as a key royal instrument for disciplining recalcitrant bishops, carrying both fiscal and political implications. A micro-level analysis of three major fourteenth-century seizures of episcopal temporalities reveals that the process of “seizure—negotiation—conditional restitution” fostered a pattern of “negotiated obedience” between the king and the episcopate. At the same time, conflicts between bishops and lay magnates over landholdings expose the multi-layered configuration of Church–Crown relations. In these contests, both sides petitioned the king and offered strategic concessions to seek royal support, generating a tripartite form of “competitive compromise” that further entrenched royal supremacy in the adjudication of ecclesiastical and secular property. Full article

Epileptic seizures arise from abnormally synchronized neural activity and remain a major global health challenge, affecting more than 50 million people worldwide. Despite advances in pharmacological interventions, a significant proportion of patients continue to experience uncontrolled seizures, underscoring the need for alternative neuromodulation strategies. Rhythmic neural entrainment has recently emerged as a promising mechanism for disrupting pathological synchrony, but most existing systems rely on complex analog electronics or high-power stimulation hardware. This study investigates a proof-of-concept digital custom-designed chip that generates a stable 6 Hz oscillation capable of imposing a stable rhythmic pattern onto digitized seizure-like EEG dynamics. Using a publicly available EEG seizure dataset, we extracted and averaged analog seizure waveforms, digitized them to emulate neural front-ends, and directly interfaced the digitized signals with digital output recordings acquired from the chip using a Saleae Logic analyser. The chip’s pulse train was resampled and low-pass-reconstructed to produce an analog 6 Hz waveform, allowing direct comparison between seizure morphology, its digitized representation, and the entrained output. Frequency-domain and time-domain analyses demonstrate that the chip imposes a narrow-band 6 Hz rhythm that overrides the broadband spectral profile of seizure activity. These results provide a proof-of-concept for low-power digital custom-designed entrainment as a potential pathway toward simplified, wearable neuromodulation device for future healthcare diagnostics. Full article

Background: ALG13-CDG is an X-linked N-linked glycosylation disorder caused by pathogenic variants in the glycosyltransferase ALG13, leading to severe neurological manifestations. Despite the clear CNS involvement, the impact of ALG13 dysfunction on human brain glycosylation and neurodevelopment remains unknown. We hypothesize that ALG13-CDG causes brain-specific hypoglycosylation that disrupts neurodevelopmental pathways and contributes directly to cortical network dysfunction. Methods: We generated iPSC-derived human cortical organoids (hCOs) from individuals with ALG13-CDG to define the impact of hypoglycosylation on cortical development and function. Electrophysiological activity was assessed using MEA recordings and integrated with multiomic profiling, including scRNA-seq, proteomics, glycoproteomics, N-glycan imaging, lipidomics, and metabolomics. X-inactivation status was evaluated in both iPSCs and hCOs. Results: ALG13-CDG hCOs showed reduced glycosylation of proteins involved in ECM organization, neuronal migration, lipid metabolism, calcium homeostasis, and neuronal excitability. These pathway disruptions were supported by proteomic and scRNA-seq data and included altered intercellular communication. Trajectory analyses revealed mistimed neuronal maturation with early inhibitory and delayed excitatory development, indicating an E/I imbalance. MEA recordings demonstrated early network hypoactivity with reduced firing rates, immature burst structure, and shortened axonal projections, while transcriptomic and proteomic signatures suggested emerging hyperexcitability. Altered lipid and GlcNAc metabolism, along with skewed X-inactivation, were also observed. Conclusions: Our study reveals that ALG13-CDG is a disorder of brain-specific hypoglycosylation that disrupts key neurodevelopmental pathways and destabilizes cortical network function. Through integrated multiomic and functional analyses, we identify early network hypoactivity, mistimed neuronal maturation, and evolving E/I imbalance that progresses to compensatory hyperexcitability, providing a mechanistic basis for seizure vulnerability. These findings redefine ALG13-CDG as disorders of cortical network instability, offering a new framework for targeted therapeutic intervention. Full article

Background: Cenobamate (CNB) is an anti-seizure medication (ASM) approved for the treatment of drug-resistant focal epilepsy in adults. Notwithstanding significant proof of efficacy, real-world pharmacokinetics (PK) data are lacking, particularly regarding sex-based variations and the effect of concomitant ASMs. This exploratory study aimed to investigate the PK profile of CNB in responder adults with drug-resistant focal epilepsy and assess potential relationship with concomitant ASMs and clinical variables. Methods: We enrolled 17 patients receiving add-on CNB. The concentration-to-dose ratio (C/D), incremental slope (ΔC/ΔD), and dose-to-concentration AUC were calculated. Enrolled individuals were stratified into three exposure clusters (low, medium, and high). Univariate ANOVA was used to explore associations between PK parameters, clinical variables and concomitant ASMs. Results: Sex appeared to be associated with AUC cluster classification (p = 0.026), showing females predominating in the high-exposure group. A nonlinear dose-concentration relationship emerged from the ΔC/ΔD analysis, showing steeper slopes at low doses (12.5–50 mg), great variability at higher doses (100–200 mg), and a negative slope in some individuals. Higher CNB concentrations were observed in patients co-treated with lacosamide, while concomitant topiramate was associated with lower exposure. Carbamazepine and valproate showed non-significant trends consistent with their known enzyme-inducing and inhibiting properties. Conclusions: PK of CNB appears highly variable and seems to be influenced by sex and concomitant ASMs. These findings highlight the importance of therapeutic drug monitoring and individualized titration strategies to optimize efficacy and safety in clinical practice. These results should be regarded as exploratory and hypothesis-generating due to the small and monocentric sample size and need to be confirmed in larger, multicenter cohorts. Full article

Background and Clinical Significance: Giant sphenoid wing meningiomas are generally viewed as skull base masses that compress frontal centers and their respective pathways gradually enough to cause a dysexecutive–apathetic syndrome, which can mimic primary neurodegenerative disease. The aim of this report is to illustrate how bedside phenotyping and multimodal imaging can disclose similar clinical presentations as surgically treatable network lesions. Case Presentation: An independent, right-handed older female developed an incremental, two-year decline of her ability to perform executive functions, extreme apathy, lack of instrumental functioning, and a frontal-based gait disturbance, culminating in a first generalized seizure and a newly acquired left-sided upper extremity pyramidal sign. Standardized neuropsychological evaluation revealed a predominant frontal-based dysexecutive profile with intact core language skills, similar to behavioral-variant frontotemporal dementia (bvFTD). MRI demonstrated a large, right fronto-temporo-basal extra-axial tumor attached to the sphenoid wing with homogeneous postcontrast enhancement, significant vasogenic edema within the frontal projection pathways, and a marked midline displacement of structures with an open venous pathway. With the use of a skull-base flattening pterional craniotomy with early devascularization followed by staged internal debulking, arachnoid preserving dissection, and conservative venous preservation, the surgeon accomplished a Simpson Grade I resection. Sequential improvements in the patient’s frontal “re-awakening” were demonstrated through postoperative improvements on standardized stroke, cognitive and functional assessment scales that correlated well with persistent decompression and symmetric ventricles on follow-up images. Conclusions: This case illustrates the possibility of a non-dominant sphenoid wing meningioma resulting in a pseudo-degenerative frontal syndrome and its potential for reversal if recognized as a network lesion and treated with tailored, venous-sparing skull-base surgery. Contrast-enhanced imaging and routine frontal testing in atypical “dementia” presentations may aid in identifying additional patients with potentially surgically remediable cases. Full article

Background/Objectives: Asthma, type 1 diabetes mellitus (T1DM), and epilepsy are prevalent chronic diseases among school-aged children, affecting safety, attendance, and academic performance. This systematic review evaluated school teachers’ knowledge, attitudes, and preparedness regarding these conditions and identified gaps that hinder effective management and inclusion. Methods: Following PRISMA guidelines, PubMed, Cochrane Library, Scopus, and Google Scholar were searched between 20 September and 9 October 2025. Forty-nine quantitative cross-sectional studies assessing teachers’ knowledge, attitudes, or preparedness toward asthma, T1DM, or epilepsy were included. The AXIS tool assessed methodological quality, focusing on clarity of objectives, sample justification, ethical transparency, and instrument validation. Results: Teachers’ knowledge was generally moderate and varied by region. Studies on epilepsy (n = 21) highlighted misconceptions and limited understanding of seizure first aid. Diabetes studies (n = 9) indicated moderate awareness but insufficient preparedness for hypoglycemia and insulin management. Asthma studies (n = 19) revealed inconsistent knowledge, particularly regarding symptom recognition and emergency response. AXIS assessment identified recurring limitations, including unjustified sample sizes, limited instrument validation, and poor reporting of non-responders. Conclusions: These findings emphasize the need to enhance school preparedness through targeted, evidence-based teacher training, clear health policies and emergency protocols, awareness and inclusion initiatives, improved collaboration among teachers, parents, and healthcare providers, and strengthened school health infrastructure. Addressing these areas is critical to ensure safe, inclusive, and supportive learning environments for children with chronic illnesses. Full article

Background: Iatrogenic cerebral amyloid angiopathy (iCAA) is a rare form of CAA occurring decades after neurosurgical procedures involving cadaveric dural grafts. While typically associated with recurrent lobar intracerebral hemorrhages, recent reports suggest a possible overlap with CAA-related inflammation (CAAri). We report a case of iCAA with features indicative of active neuroinflammation that demonstrated a positive response to immunosuppressive therapy. Methods: Over a 12-year natural history, the patient underwent a comprehensive work-up, including serial clinical assessments, brain MRIs, core CSF biomarker analysis, amyloid PET imaging, and next-generation sequencing panel testing. Results: Previous clinical charts confirmed the use of cadaveric graft (Lyodura) in a neurosurgical intervention thirty years before. During hospitalization for seizures, brain MRI revealed, along with a severe form of CAA, an area of vasogenic edema. Given the suspicion of an active inflammatory process, corticosteroid and subsequent methotrexate maintenance therapy were introduced, leading to clinical and radiological improvement. Over 30 months of follow-up, the patient has remained clinically and radiologically stable, with no new hemorrhagic or inflammatory events. Conclusions: This case highlights the potential interplay between iCAA and neuroinflammation. The absence of new hemorrhages following immunosuppression suggests a possible disease-modifying effect, warranting further investigation into the role of neuroinflammation in iCAA and its therapeutic implications. Full article

Background and Clinical Significance: Paroxysmal extreme pain disorder (PEPD) is an extremely rare autosomal dominant sodium channelopathy caused by SCN9A gain-of-function variants. It is characterized by infantile-onset excruciating paroxysmal pain, typically in rectal, ocular, or mandibular regions, triggered by innocuous stimuli and accompanied by autonomic flares. Carbamazepine is dramatically effective in most reported cases. To date, only two genetically confirmed cases have been documented in Chinese patients, and fewer than 20 disease-causing variants are reported worldwide. We report the third Chinese case harboring a novel likely pathogenic SCN9A variant (p.Leu1623Gln), notable for its unusually severe, progressive, and carbamazepine-refractory phenotype, as well as life-threatening psychiatric sequelae, highlighting phenotypic heterogeneity and the devastating impact when standard therapy fails. Case Presentation: A Chinese male proband with positive family history presented with lifelong trigger-induced catastrophic burning and tearing pain in the perineum and lower limbs, associated with erythema, swelling, and occasional non-epileptic seizures. Attacks worsened with age despite escalating polypharmacy, including high-dose opioids, benzodiazepines, topical lidocaine and carbamazepine. Both the proband and his father developed profound psychosocial sequelae including severe depression and suicidal attempts. Next-generation sequencing in the proband revealed a novel heterozygous likely pathogenic variant NM_001365536.1 (SCN9A): c.4868T>A p.(Leu1623Gln). Conclusions: This third reported ethnic Chinese PEPD case expands the genotypic and phenotypic spectrum of SCN9A-related channelopathies, demonstrating that some variants can produce carbamazepine-refractory, progressive, and profoundly disabling disease with high suicidality risk. Early genetic diagnosis is critical in family planning and cascade testing, and has the potential in guiding targeted therapy that is under active research. Full article

Background: Standard ketogenic diets (KD) and fish oil have established efficacy for drug-resistant epilepsy (DRE), but adherence and variability remain challenging. Objective: The objective of this study is to provide the first systematic evaluation of clinical evidence for emerging dietary interventions for epilepsy—specifically those other than standard KD and fish oil—and to rigorously evaluate their effectiveness and certainty of evidence to address the current gap in dietary management literature. Unlike prior reviews focused on standard KD or carbohydrate-modified versions, this study is the first to synthesize evidence for “non-standard” interventions—including olive oil-based KDs, probiotics, and restrictive gluten/glutamate-free diets—which are typically excluded from traditional dietary meta-analyses. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Web of Science, Cochrane, and Google Scholar up to March 2025. Randomized Controlled Trials (RCTs) and Non-Randomized Studies of Interventions (NRSIs) were included, with quality assessed using RoB 2 and ROBINS-I tools. Results: Eight studies (total n = 675) were identified, comprising 2 RCTs and 6 NRSIs. These included olive oil-based KDs (n = 1), probiotic/synbiotic supplementation (n = 2), medium-chain triglyceride (MCT) additions (n = 2), and gluten-free (n = 1) or glutamate-free (n = 1) diets. Evidence quality is generally low, with 75% of studies at high risk of bias. Preliminary responder rates reached 83.1% in uncontrolled olive oil-based KD studies, whereas the only RCT evaluating a low-glutamate diet showed no significant seizure reduction (p = 0.57). Conclusion: Evidence for emerging dietary interventions beyond standard KD is nascent and of low certainty. Interpretation: While preliminary signals exist for olive oil-based KDs and probiotics, current data are insufficient for clinical recommendation; this review identifies these as promising exploratory targets requiring validation through rigorous, blinded RCTs. Full article

This study validates an automated seizure detection algorithm for multi-channel neonatal EEG, adapting a previously published method to a dataset with fewer electrodes. The Python-based implementation, SDApy, was applied to EEG recordings from 23 neonates to classify seizure and non-seizure epochs using a support vector machine trained on an independent dataset. The algorithm employs time- and frequency-domain features and maintains high generalization across different recording setups, achieving robust performance despite using only nine electrodes instead of nineteen. Evaluation metrics, including F1 scores and precision—recall curves, confirmed strong agreement between algorithm predictions and expert annotations for most patients. SDApy’s open-source implementation enhances accessibility compared with earlier MatLab versions, offering a transparent and cost-effective approach to clinical EEG analysis. The pipeline can operate with labels from a single expert, supports data pre-labeling for deep learning, and integrates well into neonatal intensive care unit monitoring workflows. Overall, SDApy demonstrates reliable adaptation to reduced-channel EEG and shows potential for real-time seizure detection, personalized threshold optimization, and integration into multimodal neurophysiological monitoring systems. Full article

Background/Objectives: Post-varicella arteriopathy (PVA) is a significant cause of pediatric arterial ischemic stroke (AIS) that typically involves previously healthy children within 12 months of primary varicella infection, mostly with a monophasic course. Diagnosis is based on clinical and imaging findings, and cerebrospinal fluid analysis may confirm it; treatment is empirical and heterogeneous. We describe a typical case of PVA and present a systematic review of its clinical, radiological, therapeutic, and outcome features. Methods: Following PRISMA 2020 and AMSTAR-2 guidelines, data on demographics, clinical presentation, imaging, laboratory confirmation, treatment, and outcomes were extracted across databases (PubMed, Embase, Scopus). Results: Forty-seven studies, encompassing 312 pediatric patients, were included. Mean age was 4 years with a median latency of 3.82 months from varicella to neurologic symptoms. Common presentation included hemiparesis, language impairment, and seizures. Imaging findings showed unilateral focal involvement of anterior circulation arteries, basal ganglia infarctions, and, rarely, bilateral or posterior circulation involvement. CSF VZV-DNA PCR and anti-VZV IgG were positive in 39% and 48% of tested patients. Treatment included intravenous acyclovir (34%), corticosteroids (20%), and low-dose aspirin (77%); two patients underwent acute reperfusion therapy (rt-PA or thrombectomy). Outcomes tended to be moderately favorable: 43% achieved full recovery, 45% had residual deficit, and 11% experienced recurrence. Prothrombotic state was reported, and it may influence disease severity. Conclusions: PVA is a rare distinct cause of pediatric stroke, with a generally favorable prognosis quoad vitam. Standardized guidelines and prospective studies are needed to establish evidence-based management. Clinicians should maintain a high suspicion for its diagnosis. Full article

Background/Objectives: Medication non-adherence and incomplete seizure documentation remain major challenges in epilepsy care, particularly in drug-resistant forms. Digital health tools may improve self-management by integrating seizure tracking, adherence support, and patient–clinician communication. This narrative review summarizes current mobile applications for seizure monitoring and adherence and outlines opportunities and gaps in clinical translation. Methods: A narrative synthesis (PubMed, Scopus, Google Scholar; 2019–2025; English) summarized functionality, usability, clinical validation, and limitations of epilepsy-focused mobile/wearable applications; no systematic methods or meta-analysis were applied. Results: Existing tools cluster into seizure diary apps, smartwatch-based monitoring systems, and adherence-focused applications. While they improve documentation and treatment regularity, most lack adaptive personalization, language localization and therapeutically active components. Comprehensive platforms combining tracking, adherence analytics and telehealth remain unevenly validated. Validated wearable detectors for generalized tonic–clonic seizures typically report sensitivity in the 80–95% range in real-world or simulated-real-world studies, alongside variable specificity and false-alarm rates, underscoring the need for individualized deployment and calibration. Conclusions: Mobile and wearable applications are promising adjuncts to routine epilepsy care. The field is gradually shifting from passive monitoring toward integrated, user-centered platforms that blend monitoring, predictive analytics and neuromodulation. This review also briefly outlines a conceptual example of an integrated mobile platform that combines seizure documentation, adherence support and patient-initiated rhythmic cueing; this example is presented at a purely exploratory level and requires further clinical validation. Full article

Epileptic seizure (ES) detection is critical for improving clinical outcomes in epilepsy management. While intracranial EEG (iEEG) provides high-quality neural recordings, existing detection methods often rely on large amounts of data, involve high computational complexity, or fail to generalize in low-data settings. In this paper, we propose a lightweight, data-efficient, and high-performance approach for ES detection based on hyperdimensional computing (HDC). Our method first extracts local binary patterns (LBPs) from each iEEG channel to capture temporal–spatial dynamics. These binary sequences are then mapped into a high-dimensional space via HDC for robust representation, followed by a binary Naive Bayes classifier to distinguish ictal and inter-ictal states. The proposed design enables fast inference, low memory requirements, and suitability for hardware implementation. We evaluate the method on the SWEC-ETHZ iEEG short-term dataset. In one-shot learning, it achieves 100% sensitivity and specificity for most patients. In few-shot learning, it maintains 98.88% sensitivity and 93.09% specificity on average. The average latency is 4.31 s, demonstrating that it is much better than state-of-the-art methods. These results demonstrate the method’s potential for efficient, low-resource, and high-performance ES detection. Full article

Epilepsy is a common neurological disorder in cats, but its seizure types, etiologies, and clinical associations remain incompletely characterized compared to dogs. This retrospective study analyzed 118 feline epilepsy cases from two veterinary hospitals in Finland and Lithuania, aiming to evaluate the distribution of seizure types and their associations with demographic, clinical, neurological, diagnostic, and diagnostic test results. Seizures were classified as single generalized (SG), cluster seizures (CS), or status epilepticus (SE). SG and CS occurred with nearly equal frequency (44.9% and 45.8%, respectively), while SE was less common (9.3%). Median age at presentation was 72 months, and no significant differences were found in age, sex, reproductive status, or body weight between seizure types. Abnormal clinical findings (p = 0.009) and neurological abnormalities (p < 0.001) were significantly more frequent in cats with SE, indicating greater neurological compromise in severe seizure forms. MRI was performed in 74.6% of cases and revealed a significant difference in utilization among seizure types (p = 0.004), with lower imaging rates in SE, likely reflecting clinical instability at presentation. Etiology of seizure development was established in 89 cats: idiopathic epilepsy (IE) predominated (80.9%), followed by structural (15.7%) and metabolic/toxic (3.4%) causes. Seizure type and etiology were significantly associated (p = 0.006), with structural epilepsy most common in SE and idiopathic epilepsy prevailing in SG and CS. Among cats with known outcomes (n = 35), seizure control was achieved in 68.6%, while mortality and euthanasia were higher in SE. These findings provide new insight into feline epilepsy by linking seizure type to clinical and etiological profiles, emphasizing that severe presentations are more often associated with neurological abnormalities and structural causes, whereas demographic factors alone do not predict seizure severity. Full article