Infantile epileptic spasms syndrome in a child with lissencephaly associated with de novo PAFAH1B1 variant and coincidental CMV infection.

Type 1 lissencephaly is a brain malformation characterized by agyria and pachygyria and is known to be caused by congenital infections and genetic variations. Here we present a case of a 4-month-old female with new onset infantile epileptic spasms syndrome (IESS) with initial etiology concerned for congenital cytomegalovirus (cCMV) due to a positive urine CMV PCR and maternal viral syndrome during pregnancy. Her brain MRI was significant for type 1 lissencephaly without other radiographical features of cCMV. The patient initially responded to high dose Prednisolone but had relapse of spasms at 9-month-old and required an ACTH course. She later developed generalized tonic seizures and focal impaired awareness seizures. Subsequent whole exome sequencing (WES) trio revealed a de novo PAFAH1B1 (c.405G > A, p.W135*) heterozygous nonsense variant which is pathogenic and thus solved the diagnostic puzzle. This case demonstrates that the absence of cCMV stigmata should raise concern for alternative etiology in cases of lissencephaly and the importance of genetic evaluation for subsequent management and family counseling.

Effects of Anti-Seizure Medication on Neuregulin-1 Gene and Protein in Patients with First-Episode Focal Epilepsy.

Introduction: Neuregulin-1 (NRG-1) appears to play a role in the pathogenesis of several neuropsychiatric disorders, including epilepsy. We conducted a study to investigate the effect of anti-seizure medication on NRG-1 mRNA and NRG-1 protein levels in patients with first-episode focal epilepsy. Methods: The levels of NRG-1 mRNA isoforms (type I, II, III, and IV) in peripheral blood mononuclear cells (PBMCs) of 39 healthy controls, 39 first-episode focal epilepsy patients before anti-seizure medication (ASM) therapy and four weeks after administration of ASM were measured by RT-qPCR, and the levels of NRG-1 protein in the serum of samples of each group were determined using ELISA. In addition the relationship between efficacy, NRG-1 mRNA expression, and NRG-1 protein expression was analyzed. Results: The levels of NRG-1 mRNA progressively increased in patients with first-episode focal epilepsy treated with ASM and were distinctly different from those before medication, but remained lower than in healthy controls (all P < 0.001). Before and after drug administration, NRG-1 protein levels were substantially higher in epileptic patients than in healthy controls, and no significant changes were detected with prolonged follow-up (P < 0.001). Patients with epilepsy who utilized ASM were able to control seizures with an overall efficacy of 97.4%. There was a negative correlation between NRG-1 mRNA levels and efficacy: as NRG-1 mRNA levels increased, seizures reduced (all P < 0.05). Conclusion: Our research indicated that NRG-1 may play a role in the pathophysiology of epilepsy. NRG-1 mRNA may provide ideas for the discovery of novel epilepsy therapeutic markers and therapeutic targets for novel ASM.

Stereo-EEG features of temporal and frontal lobe seizures with loss of consciousness.

The loss of consciousness (LOC) during seizures is one of the most striking features that significantly impact the quality of life, even though the neuronal network involved is not fully comprehended. We analyzed the intracerebral patterns in patients with focal drug-resistant epilepsy, both with and without LOC. We assessed the localization, lateralization, stereo electroencephalography (SEEG) patterns, seizure duration, and the quantification of contacts exhibiting electrical discharge. The degree of LOC was quantified using the Consciousness Seizure Scale. Thirteen patients (40 seizures) with focal drug-resistant epilepsy underwent SEEG. In cases of temporal lobe epilepsy (TLE, 6 patients and 15 seizures), LOC occurred more frequently in seizures with mesial rather than lateral temporal lobe onset. On the other hand, in cases of frontal lobe epilepsy (7 patients; 25 seizures), LOC was associated with pre-frontal onset, a higher number of contacts with epileptic discharge compared to the onset count and longer seizure durations. Our study revealed distinct characteristics during LOC depending on the epileptogenic zone. For temporal lobe seizures, LOC was associated with mesial seizure onset, whereas in frontal lobe epilepsy, seizure with LOC has a significant increase in contact showing epileptiform discharge and a pre-frontal onset. This phenomenon may be correlated with the broad neural network required to maintain consciousness, which can be affected in different ways, resulting in LOC.

Multi-scale modelling of the epileptic brain: advantages of computational therapy exploration.

Epilepsy is a complex disease spanning across multiple scales, from ion channels in neurons to neuronal circuits across the entire brain. Over the past decades, computational models have been used to describe the pathophysiological activity of the epileptic brain from different aspects. Traditionally, each computational model can aid in optimizing therapeutic interventions, therefore, providing a particular view to design strategies for treating epilepsy. As a result, most studies are concerned with generating specific models of the epileptic brain that can help us understand the certain machinery of the pathological state. Those specific models vary in complexity and biological accuracy, with system-level models often lacking biological details. Here, we review various types of computational models of epilepsy and discuss their potential for different therapeutic approaches and scenarios, including drug discovery, surgical strategies, brain stimulation, and seizure prediction. We propose that we need to consider an integrated approach with a unified modelling framework across multiple scales to understand the epileptic brain. Our proposal is based on the recent increase in computational power, which has opened up the possibility of unifying those specific epileptic models into simulations with an unprecedented level of detail. A multi-scale epilepsy model can bridge the gap between biologically detailed models, used to address molecular and cellular questions, and brain-wide models based on abstract models which can account for complex neurological and behavioral observations. With these efforts, we move toward the next generation of epileptic brain models capable of connecting cellular features, such as ion channel properties, with standard clinical measures such as seizure severity.

Ketogenic diet therapies as a non-pharmacological adjuvant in resistant epilepsy: retrospective analysis of adult outpatients in Colombia.

Twelve patients between 18 and 53 years of age were included. MAD plus nutritional supplementation was administered to 75% (n = 10) of the participants, one (8.3%) received MAD alone, and 16.7 (n = 2) received Classic Ketogenic Diet (cKD) plus nutritional supplementation. Oral nutritional supplementation, administered in the outpatient setting, provided patients with between 31 and 55% of the total caloric value. In the first month of KDT treatment, 83.3% (n = 10) of patients reduced the number of weekly seizures by 40% (median). At six months of treatment, 75% of patients had at least halved the number of weekly seizures. At 12 months of treatment, the number of weekly seizures had been reduced by 85.7% (median). KDT was well tolerated, and there was no need to discontinue treatment. This study provides real-world information on the use of KDT, particularly MAD in adults, in developing countries. Future studies in larger cohorts will provide further information on different types of KDT, adherence, and patient-reported outcomes.

Rehabilitation in patients with newly diagnosed epilepsy: A controlled, 1-year follow-up study on a specialized inpatient rehabilitation program.

OBJECTIVES: To evaluate the efficacy of a specialized inpatient rehabilitation program in patients with newly diagnosed epilepsy (NDE), who had been referred within 1 year after diagnosis. METHODS: We performed an open, prospective, controlled study comparing a 1-year follow-up assessment of patients with NDE after completing a rehabilitation program at an epilepsy center (rehabilitation group) with a control group of patients with similar epilepsy duration, but without rehabilitation in the first year after diagnosis. Primary outcome measures comprised emotional adaptation to epilepsy, depression and anxiety; and secondary outcome measures were overall quality of life (QoL), overall health, perceived restrictions because of epilepsy, level of information about epilepsy, and employment status. RESULTS: Comparison of the admission data of 74 rehabilitation group patients (mean age and SD 47.7 ± 13.0 years) with the pre-rehabilitation assessment of 56 control patients (45.5 ± 12.1 years) revealed no significant differences concerning sociodemographic and health data. Comparison of the follow-up assessment of the rehabilitation group and the pre-rehabilitation assessment of the control group showed significantly better values for the rehabilitation group on emotional adaptation to epilepsy (p = .003), overall QoL (p = .006) and overall health (p = .011), perceived restrictions because of epilepsy, and subjective level of information about epilepsy (both p's < .001). There were no statistically significant differences concerning depression and anxiety or employment status (all p's > .50). One year after rehabilitation, patients in the rehabilitation group were more often seizure-free and less often on sickness absence than control group patients (both p's < .001). SIGNIFICANCE: Since reduced QoL shortly after diagnosis of NDE is associated with seizure recurrence, an early identification of patients with a greater need for support seems important. This epilepsy-related rehabilitation program showed lasting effects on several aspects of adaptation to epilepsy and QoL.

Anticipatory anxiety of seizures in epilepsy: A common, complex, and underrecognized phenomenon?

The diagnosis of epilepsy is associated with loss of predictability, which invariably results in the fear of when and if future seizures will occur. For a subset of patients with epilepsy (PWE), there may be a pathological persistent fear of seizure occurrence, resulting in limitations to daily activities through avoidant behaviors. Paradoxically, the research of anticipatory anxiety of seizures (AAS; also referred to as seizure phobia) has been practically nonexistent and, not surprisingly, this condition remains underrecognized by clinicians. The available data are derived from three small case series of patients followed in tertiary epilepsy centers. In this study, we review the available data on the reported clinical manifestations of AAS in PWE, and of the potential role of variables associated with it, such as personal and family psychosocial and psychiatric history and epilepsy-related variables. In addition, we review the need for the creation of screening tools to identify patients at risk of AAS and discuss potential treatment strategies, which could be considered as part of the comprehensive management for PWE.

Functional Connectivity Alterations in Patients with Post-stroke Epilepsy Based on Source-level EEG and Graph Theory.

We investigated the differences in functional connectivity based on the source-level electroencephalography (EEG) analysis between stroke patients with and without post-stroke epilepsy (PSE). Thirty stroke patients with PSE and 35 stroke patients without PSE were enrolled. EEG was conducted during a resting state period. We used a Brainstorm program for source estimation and the connectivity matrix. Data were processed according to EEG frequency bands. We used a BRAPH program to apply a graph theoretical analysis. In the beta band, radius and diameter were increased in patients with PSE than in those without PSE (2.699 vs. 2.579, adjusted p = 0.03; 2.261 vs. 2.171, adjusted p = 0.03). In the low gamma band, radius was increased in patients with PSE than in those without PSE (2.808 vs. 2.617, adjusted p = 0.03). In the high gamma band, the radius, diameter, average eccentricity, and characteristic path length were increased (1.828 vs. 1.559, adjusted p < 0.01; 2.653 vs. 2.306, adjusted p = 0.01; 2.212 vs. 1.913, adjusted p < 0.01; 1.425 vs. 1.286, adjusted p = 0.01), whereas average strength, mean clustering coefficient, and transitivity were decreased in patients with PSE than in those without PSE (49.955 vs. 55.055, adjusted p < 0.01; 0.727 vs. 0.810, adjusted p < 0.01; 1.091 vs. 1.215, adjusted p < 0.01). However, in the delta, theta, and alpha bands, none of the functional connectivity measures were different between groups. We demonstrated significant alterations of functional connectivity in patients with PSE, who have decreased segregation and integration in brain network, compared to those without PSE.

Thalamic stereoelectroencephalography for neuromodulation target selection: Proof of concept and review of literature of pulvinar direct electrical stimulation.

In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, various thalamic nuclei, including the anterior, centromedian, and pulvinar nuclei, have been extensively investigated as targets for neuromodulation. However, the therapeutic effects of different targets for thalamic neuromodulation on various types of epilepsy are not well understood. Here, we present a 32-year-old patient with multifocal bilateral temporoparieto-occipital epilepsy and bilateral malformations of cortical development (MCDs) who underwent bilateral stereoelectroencephalographic (SEEG) recordings of the aforementioned three thalamic nuclei bilaterally. The change in the rate of interictal epileptiform discharges (IEDs) from baseline were compared in temporal, central, parietal, and occipital regions after direct electrical stimulation (DES) of each thalamic nucleus. A significant decrease in the rate of IEDs (33% from baseline) in the posterior quadrant regions was noted in the ipsilateral as well as contralateral hemisphere following DES of the pulvinar. A scoping review was also performed to better understand the current standpoint of pulvinar thalamic stimulation in the treatment of DRE. The therapeutic effect of neuromodulation can differ among thalamic nuclei targets and epileptogenic zones (EZs). In patients with multifocal EZs with extensive MCDs, personalized thalamic targeting could be achieved through DES with thalamic SEEG electrodes.

Impact of depressive symptoms on adverse effects in people with epilepsy on antiseizure medication therapy.

OBJECTIVE: We studied the impact of depressive symptoms on adverse effects (AEs) in people with epilepsy (PWE) on antiseizure medication (ASM) therapy. An effect of depression on the AE burden has already been reported. We studied the correlation of various depressive symptoms with specific AEs to assess which AEs are especially prone to being confounded by particular depressive symptoms. METHODS: PWE filled in a variety of questionnaires including the "Neurological Disorder Depression Inventory for Epilepsy" (NDDI-E), "Emotional Thermometers 4" (ET4) and "Liverpool Adverse Events Profile" (LAEP). Depression was defined by a NDDI-E score > 13. Depressive symptoms consisted of NDDI-E and ET4 items. Discriminant analysis identified those AEs (=LAEP items) that were most highly influenced by depression. Logistic regression analysis yielded correlations of different depressive symptoms with specific AEs. RESULTS: We included 432 PWE. The strongest discriminators for depression were the LAEP items "Depression", "Nervousness/agitation," and "Tiredness". Out of all depressive symptoms "Everything I do is a struggle" most strongly correlated with total LAEP score (odds ratio [OR] = 3.1) and correlated with all but one LAEP item. Other depressive symptoms correlated to varying degrees with total LAEP and item scores. The number of ASMs, lack of seizure remission, and female gender correlated with high LAEP scores. SIGNIFICANCE: To the best of our knowledge, we are the first to show that various depressive symptoms correlate with specific LAEP items. This information can be helpful for quick evaluation of whether the reporting of different LAEP items may be confounded by particular depressive symptoms. This is relevant because changes in therapy may differ depending on if AEs are confounded by depressive symptoms. Simply reporting a particular depressive symptom may give a clue to whether specific AEs are confounded by depression. Our findings confirm the importance of screening for depression in all PWE. PLAIN LANGUAGE SUMMARY: In this study we measured depressive disorder and side effects caused by medication used to treat epilepsy with self-reported questionnaires in a cohort of people with epilepsy. We found depressive disorder to influence the perception of side effects that are caused by drugs used to treat epilepsy. This knowledge can help to identify if the reporting of side effects is influenced by depression. Treating depression may help to reduce side effects and may thus increase the tolerability of anti-epileptic medication. People who tolerate their medication are more likely to take it and are thus less likely to develop epileptic seizure.

COVID-19 vaccinations for patients with epilepsy in Guizhou Province, China: A cross-sectional study.

Several COVID-19 vaccines have been approved for emergency use according to China's immunization programs. These vaccines has created hope for patients with epilepsy, because the vaccines can help to reduce their risk of becoming infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to investigate the COVID-19 vaccine safety in patients with epilepsy. Here, we assessed the time of symptom control and the features of adverse events of seizure patients following their COVID-19 vaccinations. The results showed that adverse events of COVID-19 vaccinations for epilepsy patients included local pain at the injection site, dizziness and headache, epileptic attack, somnolence, limb weakness, limb pain, allergy, and fever. In addition, the average recovery time of the adverse events was approximately 42 h. More importantly, our study showed that it was relatively safe to vaccinate epilepsy patients who did not experience seizures for approximately 12 months prior to the immunization date.

Focal-to-bilateral tonic-clonic seizures and High-grade CMV-infection are poor survival predictors in Tumor-related Epilepsy Adult-type diffuse gliomas-A single-center study and literature review.

Introduction: Previous studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored. The aim of our study is to examine the correlation between the dregree of CMV infection and seizure types on the survival of TRE Adult-type-diffuse-glioma. To achieve this objective, we conducted a comprehensive literature review to assess our results regarding previous publications. Methods: We conducted a retrospective-observational study on TRE Adult-type-diffuse-gliomas treated at a single center in Mexico from 2010 to 2018. Tumor tissue and cDNA were analyzed by immunochemistry (IHC) for CMV (IE and LA antigens) at the Karolinska Institute in Sweden, and RT-PCR for CMV-gB in Torreon Mexico, respectively. Bivariate analysis (X2-test) was performed to evaluate the association between subtypes of Adult-type-diffuse-glioma (IDH-mut grade 4 astrocytoma vs. IDH-wt glioblastoma) and the following variables: type of hemispheric involvement (mesial vs. neocortical involvement), degree of CMV infection (<25%vs. >25% infected-tumoral cells) and seizure types [Focal awareness, focal impaired awareness, and FBTCS]. Kaplan Meier and Cox analyses were performed to determine the risk, p < 0.05 was considered statistically significant. Results: Sixty patients with TRE Adult type diffuse gliomas were included (80% IDH-wt glioblastoma and 20% IDH-mut grade 4astrocytomas). The mean age was 61.5 SD ± 18.4, and 57% were male. Fifty percent of the patients presented with mesial involvement of the hemysphere. Seizure types included focal awareness (15%), focal impaired awareness (43.3%), and FBTCS (41.7%). Ninety percent of cases were treated with Levetiracetam and 33.3% presented Engel-IA postoperative seizure control. More than 90% of samples were positive for CMV-immunohistochemistry (IHC). However, all cDNA analyzed by RT-PCR return negative results. The median of overall survival (OS) was 15 months. High-grade CMV-IE infection (14 vs. 25 months, p<0.001), mesial involvement (12 vs. 18 months, p<0.001), and FBTCS were associated with worse OS (9 vs.18 months for non-FBTCS). Multivariate analysis demonstrated that high-grade CMV infection (HR = 3.689, p=0.002) and FBTCS (HR=7.007, p<0.001) were independent unfavorable survival factors. Conclusions: CMV induces a proinflammatory tumoral microenvironment that contributes to the developmet of epilepsy. Tumor progression could be associated not only with a higher degree of CMV infection but also to epileptogenesis, resulting in a seizure phenotype chracterized by FBTCS and poor survival outcomes. This study represents the first survival analysis in Latin America to include a representative sample of TRE Adult-type diffuse gliomas considering CMV-infection-degree and distinguishing features (such as FBTCS) that might have potential clinical relevance in this group of patients. Further prospective studies are required to validate these results.

Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

Analysis of prognostic factors and the role of epilepsy in neurosurgical patients with brain metastases.

Background: Brain metastases (BMs) represent the most frequent brain tumors in adults. The identification of key prognostic factors is essential for choosing the therapeutic strategy tailored to each patient. Epilepsy can precede several months of other clinical presentations of BMs. This work aimed to study the impact of epilepsy and other prognostic factors on BMs patients' survival. Methods: This retrospective study included 51 patients diagnosed with BMs and who underwent neurosurgery between 2010 and 2021. The impact of BM features and patient's clinical characteristics on the overall survival (OS) was analyzed through uni- and multivariate analysis. Results: The average OS was 25.98 months and differed according to the histology of the primary tumor. The primary tumor localization and the presence of extracranial metastases had a statistically significant impact on the OS, and patients with single BM showed a superior OS to those with multifocal lesions. The localization of BMs in the temporal lobe correlated with the highest OS. The OS was significantly higher in patients who presented seizures in their clinical onset and in those who had better post-surgical Karnofsky performance status, no post-surgical complications, and who underwent post-surgical treatment. Conclusion: Our study has highlighted prognostically favorable patient and tumor factors. Among those, a clinical onset with epileptic seizures can help identify brain metastasis hitherto silent. This could lead to immediate diagnostic-therapeutic interventions with more aggressive therapies after appropriate multidisciplinary evaluation.

Efficacy of Personalized Postoperative Epilepsy Management in Patients with Glioblastoma Utilizing IDH1 Gene Assessment.

Objective: We explored the correlation between the presence of isocitrate dehydrogenase-1 (IDH1) mutations and the incidence of postoperative epilepsy in patients with glioblastoma, as well as assessed the efficacy of preemptive administration of antiepileptic medications in mitigating the occurrence of postoperative epilepsy. Methods: Fifty-three patients who received a postoperative pathological diagnosis of glioblastoma, were enrolled in this study. Tumor specimens were subjected to IDH1 gene analysis. The patient cohort was stratified based on their IDH1 mutation status and the administration of prophylactic antiepileptic drugs during the postoperative phase. We subsequently conducted a comparative analysis of postoperative epileptic complications within each patient subgroup. Results: In the cohort of 53 patients under study, the occurrence of epilepsy was observed in 10 out of 21 patients carrying IDH1 mutations, while 5 out of 32 patients with wild-type IDH1 also experienced epilepsy, revealing a statistically significant difference (P < 0.05). Among the 27 patients who received prophylactic antiepileptic drugs, 6 of them developed epilepsy, whereas 9 out of 26 patients who did not receive prophylactic antiepileptic drugs exhibited concurrent epilepsy, with no statistically significant difference (P > 0.05). However, when performing a subgroup analysis, it was found that 3 out of 12 patients with IDH1 mutations who received prophylactic antiepileptic drugs experienced epilepsy, whereas 7 out of 9 patients who did not receive prophylactic antiepileptic drugs developed epilepsy, demonstrating a statistically significant difference (P < 0.05). Furthermore, within the group of 15 patients with wild-type IDH1, 3 patients who received prophylactic antiepileptic drugs developed epilepsy, while 2 cases of epilepsy occurred among the 17 patients who did not receive prophylactic antiepileptic drugs, with no statistically significant difference (P > 0.05). Conclusion: In individuals with IDH1 mutant glioblastoma who have undergone surgical resection, the implementation of preventive antiepileptic therapy demonstrates a potential to diminish the occurrence of postoperative epilepsy.

Pre-treatment risk predictors of valproic acid-induced dyslipidemia in pediatric patients with epilepsy.

Background: Valproic acid (VPA) stands as one of the most frequently prescribed medications in children with newly diagnosed epilepsy. Despite its infrequent adverse effects within therapeutic range, prolonged VPA usage may result in metabolic disturbances including insulin resistance and dyslipidemia. These metabolic dysregulations in childhood are notably linked to heightened cardiovascular risk in adulthood. Therefore, identification and effective management of dyslipidemia in children hold paramount significance. Methods: In this retrospective cohort study, we explored the potential associations between physiological factors, medication situation, biochemical parameters before the first dose of VPA (baseline) and VPA-induced dyslipidemia (VID) in pediatric patients. Binary logistic regression was utilized to construct a predictive model for blood lipid disorders, aiming to identify independent pre-treatment risk factors. Additionally, The Receiver Operating Characteristic (ROC) curve was used to evaluate the performance of the model. Results: Through binary logistic regression analysis, we identified for the first time that direct bilirubin (DBIL) (odds ratios (OR) = 0.511, p = 0.01), duration of medication (OR = 0.357, p = 0.009), serum albumin (ALB) (OR = 0.913, p = 0.043), BMI (OR = 1.140, p = 0.045), and aspartate aminotransferase (AST) (OR = 1.038, p = 0.026) at baseline were independent risk factors for VID in pediatric patients with epilepsy. Notably, the predictive ability of DBIL (AUC = 0.690, p < 0.0001) surpassed that of other individual factors. Furthermore, when combined into a predictive model, incorporating all five risk factors, the predictive capacity significantly increased (AUC = 0.777, p < 0.0001), enabling the forecast of 77.7% of dyslipidemia events. Conclusion: DBIL emerges as the most potent predictor, and in conjunction with the other four factors, can effectively forecast VID in pediatric patients with epilepsy. This insight can guide the formulation of individualized strategies for the clinical administration of VPA in children.

Machine learning applied to epilepsy: bibliometric and visual analysis from 2004 to 2023.

Background: Epilepsy is one of the most common serious chronic neurological disorders, which can have a serious negative impact on individuals, families and society, and even death. With the increasing application of machine learning techniques in medicine in recent years, the integration of machine learning with epilepsy has received close attention, and machine learning has the potential to provide reliable and optimal performance for clinical diagnosis, prediction, and precision medicine in epilepsy through the use of various types of mathematical algorithms, and promises to make better parallel advances. However, no bibliometric assessment has been conducted to evaluate the scientific progress in this area. Therefore, this study aims to visually analyze the trend of the current state of research related to the application of machine learning in epilepsy through bibliometrics and visualization. Methods: Relevant articles and reviews were searched for 2004-2023 using Web of Science Core Collection database, and bibliometric analyses and visualizations were performed in VOSviewer, CiteSpace, and Bibliometrix (R-Tool of R-Studio). Results: A total of 1,284 papers related to machine learning in epilepsy were retrieved from the Wo SCC database. The number of papers shows an increasing trend year by year. These papers were mainly from 1,957 organizations in 87 countries/regions, with the majority from the United States and China. The journal with the highest number of published papers is EPILEPSIA. Acharya, U. Rajendra (Ngee Ann Polytechnic, Singapore) is the authoritative author in the field and his paper "Deep Convolutional Neural Networks for Automated Detection and Diagnosis of Epileptic Seizures Using EEG Signals" was the most cited. Literature and keyword analysis shows that seizure prediction, epilepsy management and epilepsy neuroimaging are current research hotspots and developments. Conclusions: This study is the first to use bibliometric methods to visualize and analyze research in areas related to the application of machine learning in epilepsy, revealing research trends and frontiers in the field. This information will provide a useful reference for epilepsy researchers focusing on machine learning.

Irregular Tremulous Movements and Infrequent Seizures: A Clinical-Electrophysiological Diagnosis of Benign Adult Familial Myoclonus Epilepsy.

We report a case involving a 31-year-old male without any known precipitating injuries presenting with involuntary finger movements and rare seizures. There was a noted family history of tremulous movements. Yet the characteristics of his finger movements were irregular and not typical of essential tremor (ET). Electrophysiological examinations, including video EEG, showed no epileptic discharges, and brain MRI results were normal. However, somatosensory evoked potentials (SEP) revealed the presence of giant SEP, and a positive cortical (C)-reflex was observed, leading to a clinical diagnosis of benign adult familial myoclonus epilepsy (BAFME). Management with valproic acid and perampanel resulted in a significant reduction of symptoms. This case highlights the necessity of considering BAFME in the differential diagnosis for atypical tremorous finger movements, especially with a relevant family history, and the critical role of electrophysiological findings indicative of cortical hyperexcitability.

Mapping combinatorial expression of non-clustered protocadherins in the developing brain identifies novel PCDH19-mediated cell adhesion properties.

Non-clustered protocadherins (ncPcdhs) are adhesive molecules with spatio-temporally regulated overlapping expression in the developing nervous system. Although their unique role in neurogenesis has been widely studied, their combinatorial role in brain physiology and pathology is poorly understood. Using probabilistic cell typing by in situ sequencing, we demonstrate combinatorial inter- and intra-familial expression of ncPcdhs in the developing mouse cortex and hippocampus, at single-cell resolution. We discovered the combinatorial expression of Protocadherin-19 (Pcdh19), a protein involved in PCDH19-clustering epilepsy, with Pcdh1, Pcdh9 or Cadherin 13 (Cdh13) in excitatory neurons. Using aggregation assays, we demonstrate a code-specific adhesion function of PCDH19; mosaic PCDH19 absence in PCDH19+9 and PCDH19 + CDH13, but not in PCDH19+1 codes, alters cell-cell interaction. Interestingly, we found that PCDH19 as a dominant protein in two heterophilic adhesion codes could promote trans-interaction between them. In addition, we discovered increased CDH13-mediated cell adhesion in the presence of PCDH19, suggesting a potential role of PCDH19 as an adhesion mediator of CDH13. Finally, we demonstrated novel cis-interactions between PCDH19 and PCDH1, PCDH9 and CDH13. These observations suggest that there is a unique combinatorial code with a cell- and region-specific characteristic where a single molecule defines the heterophilic cell-cell adhesion properties of each code.

Heparin-Modified Superparamagnetic Iron Oxide Nanoparticles Suppress Lithium Chloride/Pilocarpine-Induced Temporal Lobe Epilepsy in Rats through Attenuation of Inflammation and Oxidative Stress.

The development of antiepileptic drugs is still a long process. In this study, heparin-modified superparamagnetic iron oxide nanoparticles (UFH-SPIONs) were prepared, and their antiepileptic effect and underlying mechanism were investigated. UFH-SPIONs are stable, homogeneous nanosystems with antioxidant enzyme activity that are able to cross the blood-brain barrier (BBB) and enriched in hippocampal epileptogenic foci. The pretreatment with UFH-SPIONs effectively prolonged the onset of seizures and reduced seizure severity after lithium/pilocarpine (LP)-induced seizures in rats. The pretreatment with UFH-SPIONs significantly decreased the expression of inflammatory factors in hippocampal tissues, including IL-6, IL-1ß, and TNF-α. LP-induced oxidative stress in hippocampal tissues was in turn reduced upon pretreatment with UFH-SPIONs, as evidenced by an increase in the levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and a decrease in the level of lipid peroxidation (MDA). Moreover, the LP-induced upregulation of apoptotic cells was decreased upon pretreatment with UFH-SPIONs. Together, these observations suggest that the pretreatment with UFH-SPIONs ameliorates LP-induced seizures and downregulates the inflammatory response and oxidative stress, which exerts neuronal protection during epilepsy.