Advances in Ketogenic Diet Therapies in Pediatric Epilepsy: A Systematic Review.

Objective: To review the effects of the ketogenic diet on epilepsy in children and adolescents.Data Sources: A literature search was conducted in PubMed with no publication date or language restrictions based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. Keywords used included children, adolescent, ketogenic diet, epilepsy, and seizure.Study Selection: After excluding articles that did not meet the inclusion criteria, such as missing variables of study, adult population, and nonrandomized clinical trials, a total of 12 studies were included in the final review.Data Extraction: Data on study design, duration, sample size, population, and type of intervention were collected using a standard template.Results: The ketogenic diet and its modified versions were noted to have beneficial effects in reduction of seizure frequency and severity, with manageable adverse effects such as gastrointestinal disturbances, dehydration, dyslipidemia, hyperuricemia, infection, and metabolic acidosis.Conclusions: Depending on patient compliance and comorbidities, all variations of the ketogenic diet were found to be helpful for seizure treatment, whether as an additive or an alternative treatment option, for children and adolescents with epilepsy.Prim Care Companion CNS Disord 2024;26(3):23r03661. Author affiliations are listed at the end of this article.

Neuropsychological profile in tuberous sclerosis complex: a study of clinical and cognitive variables in a cohort from Brazil.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with a wide clinical, cognitive, and behavioral expressivity. OBJECTIVE: To assess the neuropsychological profile of individuals clinically diagnosed with TSC and the factors that could significantly impact their cognitive development. METHODS: A total of 62 individuals with ages ranging from 3 to 38 years were followed up in a tertiary attention hospital in Southern Brazil, and they were assessed using a standard battery and the Vineland Adaptive Behavior Scales, when intellectual disability was observed. RESULTS: History of epilepsy was found in 56 participants (90.3%), and 31 (50%) presented an intellectual disability. Among the other half of TSC individuals without intellectual disability, 8 (12.9%) presented borderline classification, 20 (32.2%) presented average scores, and 3 (4.8%) were above average. In total, 17 participants (27.4%) fulfilled the diagnostic criteria for autism spectrum disorder. The results of the multiple linear regression analysis suggested that seizures, age at diagnosis, visual perception, and general attention significantly impact cognitive performance indexes. CONCLUSION: The present study suggests that the occurrence of epileptic seizures and older age at diagnosis contribute to higher impairment in the domains of cognitive development, underlining the importance of early diagnosis and the prevention of epileptic seizures or their rapid control. The development of attentional skills, visual perception, and executive functions must be followed up.

ANTECEDENTES: O complexo da esclerose tuberosa (CET) é uma doença genética autossômica dominante com ampla expressividade clínica, cognitiva e comportamental. OBJETIVO: Avaliar o perfil neuropsicológico de indivíduos com diagnóstico clínico de CET e os fatores que poderiam impactar significativamente o seu desenvolvimento cognitivo. MéTODOS: Ao todo, 62 indivíduos com idades entre 3 e 38 anos foram acompanhados em um hospital terciário do Sul do Brasil e avaliados por meio de uma bateria padrão e das Escalas de Comportamento Adaptativo Vineland, quando observada deficiência intelectual. RESULTADOS: Encontrou-se histórico de epilepsia em 56 participantes (90,3%) e de deficiência intelectual em 31 (50%). Quanto à outra metade dos indivíduos com CET sem deficiência intelectual, 8 (12,9%) apresentaram classificação limítrofe, 20 (32,2%) apresentaram pontuações médias e 3 (4,8%) estavam acima da média. No total, 17 participantes (27,4%) preenchiam os critérios diagnósticos para o transtorno do espectro autista. Os resultados da análise de regressão linear múltipla sugeriram que as crises epilépticas, a idade ao diagnóstico, a percepção visual e a atenção geral impactam significativamente os índices de desempenho cognitivo. CONCLUSãO: Este estudo sugere que a ocorrência de crises epilépticas e a maior idade ao diagnóstico contribuem para um maior comprometimento nos domínios do desenvolvimento cognitivo, e destaca-se a importância do diagnóstico precoce e da prevenção das crises epilépticas ou do seu rápido controle. O desenvolvimento de habilidades de atenção, percepção visual e funções executivas deve ser acompanhado.

Efficacy of acupuncture combined with traditional Chinese herbal for primary epilepsy patients with cognitive impairment: A protocol for systematic review and meta-analysis.

BACKGROUND: Epilepsy is a common and serious chronic neurological disorder, and some patients suffer from cognitive dysfunction. We aim to assess the efficacy and safety of acupuncture combined with traditional Chinese herbal for primary epilepsy patients with cognitive impairment. METHODS: To search the randomized control trials (RCTs) published before April 20, 2023 from PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Web of science, and Wanfang Database. The risk of bias within each individual trial was evaluated using the Cochrane Collaboration tool. RevMan5.3 software was used for statistical analysis. The odds ratio (OR) or weighted mean difference (WMD) with a 95% confidence interval (CI) was calculated for each RCT before data pooling. RESULTS: The primary outcomes involve changes in cognitive function and behavioral disturbances. The secondary outcomes focused on quality of life and adverse effects. CONCLUSION: The results of this review are expected to provide new guidelines for the treatment of primary epilepsy patients with cognitive impairment. TRIAL REGISTRATION: This systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (Registration number: CRD42023415355).

Epilepsy, Antiepileptic Drugs, and Adverse Pregnancy Outcomes, 2: Major Congenital Malformations With Antiepileptic Drug Monotherapy.

Women with epilepsy (WWE) are usually advised antiepileptic drug (AED) treatment even during pregnancy. It is therefore important to know what the major congenital malformation (MCM) risks might be with untreated epilepsy, and with first-trimester exposure to different AEDs in monotherapy. This article reviews recent findings from a large multinational registry, a large multinational population based study, and a large meta-analysis. In summary, data from the meta-analysis suggest that the MCM rate is 2%-3% in women without epilepsy and about 3% in WWE who were unexposed to AEDs during pregnancy. Data from the meta analysis also suggest that the MCM rate is approximately population level at 2.6%-3.5% with levetiracetam and lamotrigine and that it is about 4%-5% with carbamazepine, 2.8%-4.8% with oxcarbazepine, about 4% with topiramate, about 5%-7% with phenytoin, about 6%-9% with phenobarbital, and nearly 10% with valproate. The MCM risk with valproate is significantly higher than that with other AEDs (including topiramate and phenobarbital) that significantly increase the risk. Data from the registry suggest that risks are dose-dependent with valproate, phenobarbital, and carbamazepine and that the risk with valproate may be as high as 25% at doses >1,450 mg/d. Valproate is also associated with a wide range of MCMs. Data from the population-based study were generally confirmatory. Strengths and limitations of the studies are considered. The findings of these studies encourage the consideration of levetiracetam or lamotrigine monotherapy for WWE who are pregnant and strongly discourage the consideration of the older AEDs, especially phenytoin and phenobarbitone, and most especially valproate. These considerations also apply to all WWE of childbearing age because it may not be easy to change AEDs when pregnancy is planned and because pregnancy is often unplanned.

Exploring the Anticonvulsant Properties of a Celecoxib-Phospholipid Conjugate: Synthesis, Activation, and Evaluation of Cytotoxicity.

BACKGROUND: Epilepsy poses a significant global health challenge, particularly in regions with limited financial resources hindering access to treatment. Recent research highlights neuroinflammation, particularly involving cyclooxygenase-2 (COX-2) pathways, as a promising avenue for epilepsy management. METHODS: This study aimed to develop a Cyclooxygenase-2 inhibitor with potential anticonvulsant properties. A promising drug candidate was identified and chemically linked with phospholipids through docking analyses. The activation of this prodrug was assessed using phospholipase A2 (PLA2)-mediated hydrolysis studies. The conjugate's confirmation and cytotoxicity were evaluated using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and Sulphoramide B (SRB) assays. RESULTS: Docking studies revealed that the Celecoxib-Phospholipid conjugate exhibited a superior affinity for PLA2 compared to other drug-phospholipid conjugates. FT-IR spectroscopy confirmed the successful synthesis of the conjugate, while DSC analysis confirmed its purity and formation. PLA2-mediated hydrolysis experiments demonstrated selective activation of the prodrug depending on PLA2 concentration. SRB experiments indicated dose-dependent cytotoxic effects of Celecoxib, phospholipid non-toxicity, and efficient celecoxib-phospholipid conjugation. CONCLUSION: This study successfully developed a Celecoxib-phospholipid conjugate with potential anticonvulsant properties. The prodrug's specific activation and cytotoxicity profile makes it a promising therapeutic candidate. Further investigation into underlying mechanisms and in vivo studies is necessary to assess its translational potential fully.

Monoallelic de novo AJAP1 loss-of-function variants disrupt trans-synaptic control of neurotransmitter release.

Adherens junction-associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses in the brain. Here, we show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs, resulting in the inability to recruit them. Ultrastructural analysis revealed significantly decreased presynaptic GBR levels in Ajap1-/- and Ajap1W183C/+ mice. Consequently, these mice exhibited reduced GBR-mediated presynaptic inhibition at excitatory and inhibitory synapses, along with impaired synaptic plasticity. Our study reveals that AJAP1 enables the postsynaptic neuron to regulate the level of presynaptic GBR-mediated inhibition, supporting the clinical relevance of loss-of-function AJAP1 variants.

Monitoring levetiracetam concentration in saliva during pregnancy is stable and feasible.

AIMS: This multicenter prospective cohort study (registration no. ChiCTR2000032089) aimed to investigate the relationship between saliva and plasma levetiracetam concentrations to determine whether saliva could be used for routine monitoring of levetiracetam during pregnancy. METHODS: The slot concentrations of levetiracetam in simultaneously obtained saliva and plasma samples were measured using UPLC-MS/MS. The correlations between saliva and plasma levetiracetam concentrations and the dose-normalized concentrations were compared among pregnant women in different stages and nonpregnant control participants with epilepsy. RESULTS: In total, 231 patients with 407 plasma and saliva sample pairs were enrolled from 39 centers. Linear relationships between salivary and plasma levetiracetam concentrations were reported in the enrolled population (r = 0.898, p < 0.001), including pregnant (r = 0.935, p < 0.001) and nonpregnant participants (r = 0.882, p < 0.001). Plasma concentrations were moderately higher than saliva concentrations, with ratios of saliva to plasma concentrations of 0.98 for nonpregnant women, 0.98, 1, and 1.12 for pregnant women during the first trimester, the second trimester, the and third trimester, respectively. The effective range of saliva levetiracetam concentration was found to be 9.98 µg/mL (lower limit) with an area under the curve (AUC) of 0.937 (95% confidence intervals, 0.915-0.959), sensitivity of 88.9%, specificity of 86.8%, and p < 0.001, to 24.05 µg/mL (upper limit) with an AUC of 0.952 (0.914-0.99), sensitivity of 100%, specificity of 92.3%, and p = 0.007. CONCLUSION: The saliva/plasma concentration ratio of levetiracetam remains constant during pregnancy and is similar to that in non-pregnant individuals. Monitoring levetiracetam concentration in saliva during pregnancy should be widely promoted.

EEG/MEG source imaging of deep brain activity within the maximum entropy on the mean framework: Simulations and validation in epilepsy.

Electro/Magneto-EncephaloGraphy (EEG/MEG) source imaging (EMSI) of epileptic activity from deep generators is often challenging due to the higher sensitivity of EEG/MEG to superficial regions and to the spatial configuration of subcortical structures. We previously demonstrated the ability of the coherent Maximum Entropy on the Mean (cMEM) method to accurately localize the superficial cortical generators and their spatial extent. Here, we propose a depth-weighted adaptation of cMEM to localize deep generators more accurately. These methods were evaluated using realistic MEG/high-density EEG (HD-EEG) simulations of epileptic activity and actual MEG/HD-EEG recordings from patients with focal epilepsy. We incorporated depth-weighting within the MEM framework to compensate for its preference for superficial generators. We also included a mesh of both hippocampi, as an additional deep structure in the source model. We generated 5400 realistic simulations of interictal epileptic discharges for MEG and HD-EEG involving a wide range of spatial extents and signal-to-noise ratio (SNR) levels, before investigating EMSI on clinical HD-EEG in 16 patients and MEG in 14 patients. Clinical interictal epileptic discharges were marked by visual inspection. We applied three EMSI methods: cMEM, depth-weighted cMEM and depth-weighted minimum norm estimate (MNE). The ground truth was defined as the true simulated generator or as a drawn region based on clinical information available for patients. For deep sources, depth-weighted cMEM improved the localization when compared to cMEM and depth-weighted MNE, whereas depth-weighted cMEM did not deteriorate localization accuracy for superficial regions. For patients' data, we observed improvement in localization for deep sources, especially for the patients with mesial temporal epilepsy, for which cMEM failed to reconstruct the initial generator in the hippocampus. Depth weighting was more crucial for MEG (gradiometers) than for HD-EEG. Similar findings were found when considering depth weighting for the wavelet extension of MEM. In conclusion, depth-weighted cMEM improved the localization of deep sources without or with minimal deterioration of the localization of the superficial sources. This was demonstrated using extensive simulations with MEG and HD-EEG and clinical MEG and HD-EEG for epilepsy patients.

Dissimilar Changes in Serum Cortisol after Epileptic and Psychogenic Non-Epileptic Seizures: A Promising Biomarker in the Differential Diagnosis of Paroxysmal Events?

The hypothalamic-pituitary-adrenal axis is known to be involved in the pathogenesis of epilepsy and psychiatric disorders. Epileptic seizures (ESs) and psychogenic non-epileptic seizures (PNESs) are frequently differentially misdiagnosed. This study aimed to evaluate changes in serum cortisol and prolactin levels after ESs and PNESs as possible differential diagnostic biomarkers. Patients over 18 years with ESs (n = 29) and PNESs with motor manifestations (n = 45), captured on video-EEG monitoring, were included. Serum cortisol and prolactin levels as well as hemograms were assessed in blood samples taken at admission, during the first hour after the seizure, and after 6, 12, and 24 h. Cortisol and prolactine response were evident in the ES group (but not the PNES group) as an acute significant increase within the first hour after seizure. The occurrence of seizures in patients with ESs and PNESs demonstrated different circadian patterns. ROC analysis confirmed the accuracy of discrimination between paroxysmal events based on cortisol response: the AUC equals 0.865, with a prediction accuracy at the cutoff point of 376.5 nmol/L 0.811 (sensitivity 86.7%, specificity 72.4%). Thus, assessments of acute serum cortisol response to a paroxysmal event may be regarded as a simple, fast, and minimally invasive laboratory test contributing to differential diagnosis of ESs and PNESs.

Has Treatment Seeking Behaviour Changed in People Living with Epilepsy? Experience of People Living with Epilepsy Attending Adult Neurology Clinics in Enugu.

BACKGROUND: Over the years efforts has been made through public health education to change the knowledge, attitude and practice of epilepsy and seizures among the populace in Nigeria. One surrogate method of reviewing the impact of these educational interventions includes changes in treatment-seeking behavior of People Living With Epilepsy and the reasons for their choices of treatment. METHODS: This was a cross-sectional descriptive study. Data were collected from People Living With Epilepsy attending the medical outpatient clinics in two tertiary hospitals in Enugu, Enugu State southeast Nigeria. RESULTS: A total 276 people living with epilepsy were recruited with a mean age of 30.1 years and a median age of 25 years. After the onset of epilepsy, 76(27.5%) and 70(25.4%) visited general hospitals and teaching hospitals respectively, while prayer houses and traditional healing centers were first visited by 54(19.6%) and 40(14.5%) respectively. As a second choice of care 9(3.3%) and 13(4.7%) visited prayer houses and traditional healing centers. Only 42(15.2%) selected their treatment center because they were confident of getting a cure however, this was highest for those that visited traditional healing centers 11(27.5%). The age of onset of epilepsy positively correlated with selecting orthodox treatment at the choice of care, while occupational status negatively correlated with selecting orthodox care at the same period. CONCLUSIONS: Health care seeking behaviors among PLWE in Southeast Nigeria might have changed over the years as more people living with epilepsy were more likely to select orthodox treatment compared to non-orthodox means of treatment.

CONTEXTE: Au fil des ans, des efforts ont été déployés par le biais de l'éducation en santé publique pour changer les connaissances, les attitudes et les pratiques concernant l'épilepsie et les crises d'épilepsie parmi la population au Nigeria. Une méthode indirecte pour examiner l'impact de ces interventions éducatives comprend les changements dans le comportement de recherche de traitement des personnes vivant avec l'épilepsie et les raisons de leurs choix de traitement. MÉTHODES: Il s'agit d'une étude descriptive transversale. Les données ont été collectées auprès de personnes vivant avec l'épilepsie fréquentant les cliniques de consultations externes médicales dans deux hôpitaux tertiaires à Enugu, dans l'État d'Enugu, au sud-est du Nigeria. RÉSULTATS: Au total, 276 personnes vivant avec l'épilepsie ont été recrutées, avec un âge moyen de 30,1 ans et un âge médian de 25 ans. Après le début de l'épilepsie, 76 (27,5 %) et 70 (25,4 %) ont consulté respectivement des hôpitaux généraux et des hôpitaux universitaires, tandis que les lieux de prière et les centres de guérison traditionnelle ont été les premiers consultés par respectivement 54 (19,6 %) et 40 (14,5 %). Comme deuxième choix de soins, 9 (3,3 %) et 13 (4,7 %) ont consulté des lieux de prière et des centres de guérison traditionnelle. Seuls 42 (15,2 %) ont choisi leur centre de traitement parce qu'ils étaient confiants d'obtenir une guérison, cependant, ce taux était le plus élevé pour ceux qui ont consulté les centres de guérison traditionnelle (11 soit 27,5 %). L'âge de début de l'épilepsie était positivement corrélé avec la sélection d'un traitement orthodoxe comme choix de soins, tandis que le statut professionnel était négativement corrélé avec la sélection de soins orthodoxes au même moment. CONCLUSIONS: Les comportements de recherche de soins parmi les personnes vivant avec l'épilepsie dans le sud-est du Nigeria ont peut-être changé au fil des ans, car davantage de personnes vivant avec l'épilepsie étaient plus susceptibles de choisir un traitement orthodoxe par rapport aux moyens de traitement non orthodoxes. MOTS-CLÉS: Épilepsie, Comportement de recherche de soins, Guérisseurs traditionnels, Lieux de prière, Médecine orthodoxe, sud-est du Nigeria.

A scheme combining feature fusion and hybrid deep learning models for epileptic seizure detection and prediction.

Epilepsy is one of the most well-known neurological disorders globally, leading to individuals experiencing sudden seizures and significantly impacting their quality of life. Hence, there is an urgent necessity for an efficient method to detect and predict seizures in order to mitigate the risks faced by epilepsy patients. In this paper, a new method for seizure detection and prediction is proposed, which is based on multi-class feature fusion and the convolutional neural network-gated recurrent unit-attention mechanism (CNN-GRU-AM) model. Initially, the Electroencephalography (EEG) signal undergoes wavelet decomposition through the Discrete Wavelet Transform (DWT), resulting in six subbands. Subsequently, time-frequency domain and nonlinear features are extracted from each subband. Finally, the CNN-GRU-AM further extracts features and performs classification. The CHB-MIT dataset is used to validate the proposed approach. The results of tenfold cross validation show that our method achieved a sensitivity of 99.24% and 95.47%, specificity of 99.51% and 94.93%, accuracy of 99.35% and 95.16%, and an AUC of 99.34% and 95.15% in seizure detection and prediction tasks, respectively. The results show that the method proposed in this paper can effectively achieve high-precision detection and prediction of seizures, so as to remind patients and doctors to take timely protective measures.

The effect of the HMGB1/RAGE/TLR4/NF-κB signalling pathway in patients with idiopathic epilepsy and its relationship with toxoplasmosis.

This study aims to investigate the relationship between toxoplasmosis and this pathway, which may be effective in the formation of epilepsy by acting through the HMGB1/RAGE/TLR4/NF-κB signalling pathway in patients with idiopathic epilepsy. In the study, four different experimental groups were formed by selecting Toxoplasma gondii IgG positive and negative patients with idiopathic epilepsy and healthy controls. Experimental groups were as follows: Group 1: Epilepsy+/Toxo- (E+, T-) (n = 10), Group 2: Epilepsy-/Toxo- (E-, T-) (n = 10), Group 3: Epilepsy-/Toxo+ (E-, T+) (n = 10), Group 4: Epilepsy+/Toxo+ (E+, T+) (n = 10). HMGB1, RAGE, TLR4, TLR1, TLR2, TLR3, IRAK1, IRAK2, IKBKB, IKBKG, BCL3, IL1ß, IL10, 1 L8 and TNFα mRNA expression levels in the HMGB/RAGE/TLR4/NF-κB signalling pathway were determined by quantitative simultaneous PCR (qRT-PCR) after collecting blood samples from all patients in the groups. Statistical analysis was performed by one-way ANOVA followed by LSD post-hoc tests, and p < 0.05 was considered to denote statistical significance. The gene expression levels of HMGB1, TLR4, IL10, IL1B, IL8, and TLR2 were significantly higher in the G1 group than in the other groups (p < 0.05). In the G3 group, RAGE and BCL3 gene expression levels were significantly higher than in the other groups (p < 0.05). In the G4 group, however, IRAK2, IKBKB, and IKBKG gene expression levels were significantly higher than in the other groups (p < 0.05). HMGB1, TLR4, IRAK2, IKBKB, IL10, IL1B, IL1B, and IL8 in this signalling pathway are highly expressed in epilepsy patients in G1 and seizures occur with the stimulation of excitatory mechanisms by acting through this pathway. The signalling pathway in epilepsy may be activated by HMGB1, TLR4, and TLR2, which are considered to increase the level of proinflammatory cytokines. In T. gondii, this pathway is activated by RAGE and BCL3.

Speech and music recruit frequency-specific distributed and overlapping cortical networks.

To what extent does speech and music processing rely on domain-specific and domain-general neural networks? Using whole-brain intracranial EEG recordings in 18 epilepsy patients listening to natural, continuous speech or music, we investigated the presence of frequency-specific and network-level brain activity. We combined it with a statistical approach in which a clear operational distinction is made between shared, preferred, and domain-selective neural responses. We show that the majority of focal and network-level neural activity is shared between speech and music processing. Our data also reveal an absence of anatomical regional selectivity. Instead, domain-selective neural responses are restricted to distributed and frequency-specific coherent oscillations, typical of spectral fingerprints. Our work highlights the importance of considering natural stimuli and brain dynamics in their full complexity to map cognitive and brain functions.

Knowledge, attitudes, and practices of caregivers with children diagnosed with epilepsy attending a pediatric outpatient clinic: a descriptive, cross-sectional, questionnaire-based study in Addis Ababa, Ethiopia.

BACKGROUND: Caregivers' knowledge and attitudes influence help-seeking behavior and treatment decisions of patients with epilepsy, which in turn significantly impacts epilepsy care. In Ethiopia, epilepsy is often misunderstood, associated with misconceptions and accompanied by persistent negative attitudes. The objective of this study is to assess the knowledge, attitude, and practice of caregivers of children with epilepsy. METHODS: We conducted a hospital-based survey at the Yekatit 12 Hospital Pediatric Neurology Clinic, Addis Ababa, Ethiopia, between May and July 2022. We invited caregivers of children with epilepsy taking one or more daily anti-seizure medications to participate. Caregivers were invited to complete a structured questionnaire with guidance from a trained nurse to estimate knowledge and attitudes towards epilepsy and its treatment. Knowledge and attitudes were categorized as "good" and "favorable" (correct answers to ≥ 50% of questions) or "bad" and "unfavorable" (< 50% correct answers), respectively. Attitudes towards standard care versus non-standard (e.g., spiritual) care were also estimated. RESULTS: A total of 120 caregivers completed the questionnaire. Many caregivers were familiar with the term 'epilepsy', with more than half (51.7%) having heard or read about it previously. The reported causes of epilepsy varied, with birth injury being the most common cause (44 out of 120 caregivers). Notably, there was association between the caregiver's gender and their knowledge score, with a p-value = 0.05. Caregivers exposed to information about epilepsy through hearing or reading demonstrated significantly higher levels of knowledge, with a p-value < 0.001. Additionally, knowing someone with epilepsy other than the index child was significantly associated with higher knowledge scores (p-value < 0.001). The study also revealed negative attitudes toward epilepsy: for example, 56.7% of surveyed caregivers believed it is unlikely that a child with epilepsy has normal cognitive abilities and 39.1% believed they should never be allowed to attend regular school. Additionally, a high proportion of caregivers (70%) sought alternative treatments (e.g., spiritual help) alongside standard medical care. CONCLUSIONS: A significant knowledge gap was identified among caregivers, revealing prevalent misconceptions and negative attitudes. Improving epilepsy awareness, attitudes, and practices among caregivers will potentially contribute to overall improved quality of life for children with epilepsy.

The reality of epilepsy in primary care in Rio de Janeiro: the importance of educational projects for better patient care.

BACKGROUND: The Basic Health Unit (Unidade Básica de Saúde - UBS, in Portuguese) is the first point of contact in the public healthcare system for people with epilepsy. Primary care professionals need to appropriately diagnose, treat, and refer, if necessary, to tertiary services. OBJECTIVE: To evaluate the knowledge of UBS professionals on the management of patients with epilepsy in Rio de Janeiro. METHODS: Online questionnaires were performed on the topic of epilepsy before and after exposure to classes taught by epileptologists. RESULTS: A total of 66 doctors participated, 54.5% of whom were residents or trained in family medicine. The majority had from 1 to 3 years of practice. Insecurity prevailed in the management of pregnant women and the elderly. Around 59.1% of the participants referred patients with seizures without examinations. A total of 78% of the participants did not correctly classify seizure types, and 2/3 did not define drug-resistant epilepsy. Induction and broad-spectrum drugs were common. The therapeutic decision depended on availability in the basic health unit (UBS) (81.8%), dosage (60.6%), side effects (34.8%), and age (36.4%). Comorbidities and sex influenced 1/4 of the sample. For 23% of the participants, the type of crisis did not affect the choice. Regarding typical non-pharmacological options, 75% of the participants were aware of cannabidiol, 40.9% of surgery, 22.7% of ketogenic diet, and 22.8% of deep brain stimulation/vagus nerve stimulation (DBS/VNS). A total of 90.2% indicated the need for training. CONCLUSION: There are deficits in the knowledge of UBS professionals in the management of epilepsy. Specialized training is imperative to optimize the care offered within SUS.

ANTECEDENTES: A Unidade Básica de Saúde (UBS) é o primeiro contato no sistema público de saúde para pessoas com epilepsia. Profissionais de atenção primária precisam diagnosticar, tratar e encaminhar adequadamente, se necessário, a serviços terciários. OBJETIVO: Avaliar o conhecimento dos profissionais das UBSs sobre o manejo de pacientes com epilepsia no Rio de Janeiro. MéTODOS: Foram realizados questionários online sobre o tema da epilepsia pré e pós exposição a aulas ministradas por epileptólogos. RESULTADOS: Participaram 66 médicos, sendo 54,5% residentes ou formados em medicina da família. A maioria tinha de 1 a 3 anos de prática. A insegurança prevaleceu no manejo de gestantes e idosos. Cerca de 59,1% dos participantes encaminhavam pacientes com crises sem exames. Um total de 78% dos participantes não classificou corretamente tipos de crises, e 2/3 não definiram epilepsia farmacorresistente. Fármacos indutores e de amplo espectro foram comuns. A decisão terapêutica dependeu da disponibilidade na Unidade Básica de Saúde (UBS) (81,8%), posologia (60,6%), efeitos colaterais (34,8%) e idade (36,4%). Comorbidades e sexo influenciaram 1/4 da amostra. Para 23% dos participantes, o tipo de crise não afetou a escolha. Quanto a opções não farmacológicas típicas, 75% conheciam o canabidiol, 40,9% a cirurgia, 22,7% a dieta cetogênica, 22,8% a estimulação cerebral profunda/estimulação do nervo vago (ECP/ENV). Um total de 90,2% dos participantes indicou necessidade de treinamento. CONCLUSãO: Há déficits no conhecimento dos profissionais das UBSs no manejo da epilepsia. O treinamento especializado é imperativo para otimizar o cuidado oferecido no âmbito do SUS.

Parameter estimation in a whole-brain network model of epilepsy: Comparison of parallel global optimization solvers.

The Virtual Epileptic Patient (VEP) refers to a computer-based representation of a patient with epilepsy that combines personalized anatomical data with dynamical models of abnormal brain activities. It is capable of generating spatio-temporal seizure patterns that resemble those recorded with invasive methods such as stereoelectro EEG data, allowing for the evaluation of clinical hypotheses before planning surgery. This study highlights the effectiveness of calibrating VEP models using a global optimization approach. The approach utilizes SaCeSS, a cooperative metaheuristic algorithm capable of parallel computation, to yield high-quality solutions without requiring excessive computational time. Through extensive benchmarking on synthetic data, our proposal successfully solved a set of different configurations of VEP models, demonstrating better scalability and superior performance against other parallel solvers. These results were further enhanced using a Bayesian optimization framework for hyperparameter tuning, with significant gains in terms of both accuracy and computational cost. Additionally, we added a scalable uncertainty quantification phase after model calibration, and used it to assess the variability in estimated parameters across different problems. Overall, this study has the potential to improve the estimation of pathological brain areas in drug-resistant epilepsy, thereby to inform the clinical decision-making process.

TREADS: Target Research for Anti-epileptic Drugs Using Data Science.

CONTEXT: Epilepsy is a common neurological disease and is classified into different types based on features such as the kind of seizure, age of onset, part of brain effected, etc. There are nearly 30 approved anti-epileptic drugs (AEDs) for treating different epilepsies and each drug targets proteins exhibiting a specific molecular mechanism of action. There are many genes, proteins, and microRNAs known to be associated with different epileptic disorders. This rich information on epilepsy-associated data is not available at one single location and is scattered across multiple publicly available repositories. There is a need to have a single platform integrated with the data, as well as tools required for epilepsy research. METHODS AND MATERIAL: Text mining approaches are used to extract data from multiple biological sources. The data is curated and populated within an in-house developed epilepsy database. Machine-learning based models are built in-house to know the probability of a protein being druggable based on the significant protein features. A web interface is provided for the access of the epilepsy database as well as the ML-based tool developed in-house. RESULTS: The epilepsy-associated data is made accessible through a web browser. For a protein of interest, the platform provides all the feature values, and the results generated using different machine learning models are displayed as visualization plots. CONCLUSIONS: To meet these objectives, we present TREADS, a platform for epilepsy research community, having both database and an ML-based tool for the study of AED targets. TO ACCESS TREADS: https://treads-aer.cdacb.in.

The Purinergic P2X7 Receptor as a Target for Adjunctive Treatment for Drug-Refractory Epilepsy.

Epilepsy is one of the most common neurological diseases worldwide. Anti-seizure medications (ASMs) with anticonvulsants remain the mainstay of epilepsy treatment. Currently used ASMs are, however, ineffective to suppress seizures in about one third of all patients. Moreover, ASMs show no significant impact on the pathogenic mechanisms involved in epilepsy development or disease progression and may cause serious side-effects, highlighting the need for the identification of new drug targets for a more causal therapy. Compelling evidence has demonstrated a role for purinergic signalling, including the nucleotide adenosine 5'-triphosphate (ATP) during the generation of seizures and epilepsy. Consequently, drugs targeting specific ATP-gated purinergic receptors have been suggested as promising treatment options for epilepsy including the cationic P2X7 receptor (P27XR). P2X7R protein levels have been shown to be increased in the brain of experimental models of epilepsy and in the resected brain tissue of patients with epilepsy. Animal studies have provided evidence that P2X7R blocking can reduce the severity of acute seizures and the epileptic phenotype. The current review will provide a brief summary of recent key findings on P2X7R signalling during seizures and epilepsy focusing on the potential clinical use of treatments based on the P2X7R as an adjunctive therapeutic strategy for drug-refractory seizures and epilepsy.