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Case Presentation: A 19-year-old male presented for evaluation of breakthrough seizures after inability to refill his medication following recent immigration from Haiti. Previously, the patient had never received neuroimaging due to financial constraints and resource scarcity. Computed tomography and magnetic resonance imaging obtained in the emergency department was significant for large right frontoparietal open-lip schizencephaly with mass effect, a rare congenital neurologic disorder previously undiagnosed in this patient with intractable epilepsy.  Discussion: Schizencephaly is a rare congenital neurodevelopmental disorder, which has diverse presentations ranging from intractable epilepsy to variable degrees of neurocognitive dysfunction. Treatment is generally focused on seizure management and rehabilitation. Furthermore, emergency physicians must be cognizant of patients with social determinants of health, which may have formerly prevented thorough evaluation and aid in appropriate treatment of these patients.

Idiopathic epilepsy (IE) has been known to be inherited in the Belgian Tervuren for many decades. Risk genotypes for IE in this breed have recently been identified on Canis familiaris chromosomes (CFA) 14 and 37. In the current study, the allele frequencies of these loci were analyzed to determine whether dog breeders had employed a purposeful selection against IE, leading to a reduction in risk-associated allele frequency within the breed over time. The allele frequencies of two generational groupings of Belgian Tervuren with and without IE were compared. Allele frequencies for risk-associated alleles on CFA14 were unchanged between 1985 and 2015, whereas those on CFA37 increased during that time in the control population (p < 0.05). In contrast, dogs with IE showed a decrease (p < 0.05) in the IE risk-associated allele frequency at the CFA37 locus. Seizure prevalence in the Belgian Tervuren appears to be increasing. These results suggest that, despite awareness that IE is inherited, selection against IE has not been successful.

Objective Methods Results Significance To explore seizure control and offspring outcomes associated with antiseizure medication (ASM) withdrawal during the first trimester of pregnancy.Based on a prospective multicenter study in China, pregnancies followed up between 2009 and 2023 at the neurology outpatient clinic of 50 hospitals were included in this study. Information on demographics, epileptic characteristics, treatment during pregnancy, and offspring outcomes was collected. Pregnancies were categorized into an ASM withdrawal group and an ASM continuation group. Balance tests and univariate log‐binomial regression analysis were conducted to identify imbalanced factors between groups and potential risk factors for seizure deterioration during pregnancy. Multivariate log‐binomial regression was then used to estimate the adjusted effects of ASM withdrawal on seizure deterioration during pregnancy and fetal outcomes. In addition, exploratory subgroup analysis was conducted to identify high‐risk patients who should avoid ASM withdrawal.Of the 695 pregnancies enrolled, 14.2% withdrew ASMs in the first trimester of pregnancy. ASM withdrawal during this period was associated with a risk of seizure deterioration during pregnancy (adjusted risk ratio [aRR] 1.405, 95% confidence interval [CI] 1.009–1.876). Subgroup analysis revealed a significant risk of seizure deterioration in pregnancies with seizures in 9 months (aRR 1.590, 95% CI 1.079–2.344). After adjusting the folic acid dose, no evidence of protective effects on fetus after ASM withdrawal was observed compared to patients with continued treatment, whereas seizure deterioration during pregnancy increased the risk of fetal death (aRR 3.577, 95% CI 1.086–11.651).ASM withdrawal in the first trimester of pregnancy did not show a protective effect on fetal outcomes but rather resulted in increased seizure frequency during pregnancy. However, this finding requires a larger sample for validation. Furthermore, seizure deterioration during pregnancy was associated with an increased risk of fetal death. [ABSTRACT FROM AUTHOR]

Despite an abundance of pharmacologic and surgical epilepsy treatments, there remain millions of patients suffering from poorly controlled seizures. One approach to closing this treatment gap may be found through a deeper mechanistic understanding of the network alterations that underly this aberrant activity. Functional optical imaging in vertebrate models provides powerful advantages to this end, enabling the spatiotemporal acquisition of individual neuron activity patterns across multiple seizures. This coupled with the advent of genetically encoded indicators, be them for specific ions, neurotransmitters or voltage, grants researchers unparalleled access to the intact nervous system. Here, we will review how in vivo functional optical imaging in various vertebrate seizure models has advanced our knowledge of seizure dynamics, principally seizure initiation, propagation and termination. [ABSTRACT FROM AUTHOR]

Graphogenic, or writing epilepsy, is a rare type of reflex epilepsy (RE) in which seizures are provoked by the act of writing. RE is a condition that affects between 4% and 7% of all patients diagnosed with epilepsy. In this case study, we provide a case report on a patient whose seizures were generated by the act of writing. We also present evidence that the cortical mechanisms by which writing-induced seizures occur are focal with possible secondary generalization. [ABSTRACT FROM AUTHOR]

This case report details the clinical presentation, diagnosis, management and prognosis of paroxysmal dyskinesia (PD) in four small‐breed dogs, each weighing under 6 kg: A 7‐year‐old spayed female Pomeranian, an 8‐year‐old female mixed breed, a 1‐year‐old female Pomeranian and a 9‐year‐old castrated male Poodle. These dogs were referred to our hospital due to movement disorders. Diagnosis was facilitated by video recordings of the episodes, assessing motor activity, consciousness, episode duration, any pre‐ or post‐episodic behaviour as well as the presence of autonomic signs. Magnetic resonance imaging conducted on two of the dogs returned unremarkable results. Treatment trials included a gluten‐free diet for all four dogs, with two also receiving acetazolamide. This intervention led to a decrease in the frequency of abnormal movement in all patients. Our findings suggest that PD in dogs can be effectively diagnosed through detailed symptom description using videos and questionnaires. Furthermore, once diagnosed, a combination of nutritional and medical management can be beneficial. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic neurological disorder characterized by recurrent seizures that affects over 70 million people worldwide. Although many antiepileptic drugs that block seizures are available, they have little effect on preventing and curing epilepsy, and their side effects sometimes lead to serious morbidity. Therefore, prophylactic agents with anticonvulsant properties and no adverse effects need to be identified. Recent studies on probiotic administration have reported a variety of beneficial effects on the central nervous system via the microbiota–gut–brain axis. In this study, we investigated the effects of the oral administration of Bifidobacterium breve strain A1 [MCC1274] (B. breve A1) on tonic–clonic seizure in a pentylenetetrazole (PTZ)-induced kindling mouse (KD mouse) model. We found that the oral administration of B. breve A1 every other day for 15 days significantly reduced the seizure score, which gradually increased with repetitive injections of PTZ in KD mice. The administration of B. breve A1, but not saline, to KD mice significantly increased the level of Akt Ser473 phosphorylation (p-Akt) in the hippocampus; this increase was maintained for a minimum of 24 h after PTZ administration. Treatment of B. breve A1-administered KD mice with the selective inhibitor of integrin-linked kinase (ILK) Cpd22 significantly increased the seizure score and blocked the antiepileptic effect of B. breve A1. Moreover, Cpd22 blocked the B. breve A1-induced increase in hippocampal p-Akt levels. These results suggest that the ILK-induced phosphorylation of Akt Ser473 in the hippocampus might be involved in the antiepileptic effect of B. breve A1. [ABSTRACT FROM AUTHOR]

Current recommendations for refractory status epilepticus (SE) unresponsive to benzodiazepines suggest a loading dose of levetiracetam (LEV) of 60 mg/kg to a maximum of 4500 mg. LEV therapeutic drug monitoring can help guide therapy and is garnering increasing attention. The objective of this study is to simulate the probability of target attainment (PTA) of fixed dose and weight‐based loading doses of LEV with respect to established therapeutic target concentrations. Meta‐regression of the current literature was performed to evaluate the relationship between intravenous LEV loading dose and seizure cessation in refractory SE patients. A previously published pharmacokinetic model was used to simulate the PTA capacity of competing single intravenous dosing schemes (fixed vs weight‐based dosing) to achieve maximum (Cpeak) and 12‐h (C12h) plasma concentrations that exceed 12 mg/L. The meta‐regression indicated that dosage was not a statistically significant modulator of seizure control at dosages between 20 and 60 mg/kg. Stochastic simulations showed all dosing schemes achieved plasma Cpeak >12 mg/L, but C12h levels were <12 mg/L in subjects over 60 kg with a fixed dose ≤2000 mg or in subjects <60 kg with a weight‐based dose <30 mg/kg. Dosages of 40 and 60 mg/kg provided ≥90% PTAs across all weights. Using a weight‐based loading dose of 40 mg/kg, up to a suggested maximum of 4500 mg, improves the likelihood of achieving a sustained therapeutic drug concentration after the initial LEV dose, whereas fixed <3000 mg may not achieve the desired concentration before maintenance dosing. [ABSTRACT FROM AUTHOR]

Benzodiazepines are the recommended first-line treatment of acute seizures. We wished to compare the efficacy, side effects, and satisfaction after midazolam administration by the buccal, intranasal, or intramuscular route in the treatment of acute seizures in children at homes and in emergency room (ER). A prospective, randomized, controlled trial was performed in children aged one month to 17 years with acute seizures lasting longer than five minutes. The primary end point was seizure cessation within 10 minutes of drug administration and no seizure recurrence within 30 minutes. In the home group, 67 patients received midazolam via buccal route, 60 via intranasal route, and 69 via intramuscular route, whereas in the ER group, 37 patients received buccal, 34 received intranasal, and 34 received intramuscular midazolam. The primary end point was achieved in 94.2% and 85.3% after intramuscular midazolam in the home and ER groups, respectively. The intranasal midazolam was successful in stopping seizures in 93.3% in the home group and 88.2% in the ER group. The buccal route was effective in 91% in the home group and 78.4% in the ER group. There were no significant differences in efficacy between all groups (P = 0.763 and P = 0.509) among the home and ER groups, respectively. There were no significant cardiorespiratory events in all groups. Intramuscular, intranasal, and buccal doses of midazolam resolved most seizures in prehospital and emergency settings. Our results indicate that there is no statistically significant difference detected between different routes of midazolam. Intranasal route showed the highest satisfaction rate among caregivers. [ABSTRACT FROM AUTHOR]

Background: Levetiracetam has a favorable pharmacology profile to be used subcutaneously. However, its subcutaneous use is still considered off-label as this is beyond its license. The evidence base for its safety, tolerability, and efficacy is limited to observational studies. Objectives: To report the safety and efficacy of subcutaneous levetiracetam in Latino patients on home care. Design: Observational retrospective case series study. Subjects: Consecutive sample of Latino adults with life-limiting illnesses. Methods: A case series framework with 4 domains (selection, ascertainment, causality, and reporting) to ensure reporting quality was used. Additionally, 8 relevant outcomes established in a previous comprehensive review, were collected and reported. Adverse reactions were documented using the Common Terminology Criteria for Adverse Events. Results: Fifteen Latino patients with oncological and non-oncological diagnoses received subcutaneous levetiracetam for a mean of 21 days on home care. Levetiracetam was most frequently initiated subcutaneously due to loss of the oral route. The average dosage of subcutaneous levetiracetam was 1200 mg. Only 1 patient required a dose adjustment, and only 2 patients experienced a total of 5 seizures during the therapy trial. No adverse reactions were reported. Conclusions: Subcutaneous levetiracetam appears to be effective and safe. This case series of Latino patients in home care expands the evidence of its use in the home care setting. The preliminary data reported by now on multiple case series warrants robust trials. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Seizures have been reported as an adverse event of the COVID‐19 vaccine. However, there is no solid evidence of increased seizure occurrence compared to the general population. This study was undertaken to investigate seizure occurrence among COVID‐19 vaccine recipients compared to unvaccinated controls.A systematic search was made of PubMed, Web of Science, Scopus, and Cochrane Library up to April 9, 2024. Studies reporting seizure occurrence following COVID‐19 vaccination were included. This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses framework and was conducted using random‐ and common‐effect models. The risk of bias in the studies was evaluated by the Newcastle–Ottawa Scale. The outcome of interest was new onset seizure incidence proportion compared among (1) COVID‐19 vaccine recipients, (2) unvaccinated cohorts, and (3) various types of COVID‐19 vaccines.Forty studies were included, of which seven entered the meta‐analysis. Results of the pooled analysis of the new onset seizure incidence (21‐ or 28‐day period after vaccination) in 13 016 024 vaccine recipients and 13 013 262 unvaccinated individuals by pooling the cohort studies did not show any statistically significant difference between the two groups (odds ratio [OR] = .48, 95% confidence interval [CI] = .19–1.20, p = .12, I2 = 95%, τ2 = .7145). Pooling four studies accounting for 19 769 004 mRNA versus 47 494 631 viral vector vaccine doses demonstrated no significant difference in terms of new onset seizure incidence between the groups (OR = 1.18, 95% CI = .78–1.78, p = .44, I2 = 0%, τ2 = .004).This systematic review and meta‐analysis shows no statistically significant difference in the risk of new onset seizure incidence between COVID‐19 vaccinated individuals and unvaccinated individuals. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Among motor vehicle crashes (MVCs), little is known about whether the characteristics and collision features involving drivers with epilepsy differ from those involving drivers without any history of epilepsy. We assessed MVC features and the effect of epilepsy diagnosis on the risk of severe crash‐related injuries among drivers.A total of 33 174 MVC events among people with epilepsy (PWE) and 663 480 MVC events of age‐ and sex‐matched non‐PWE (1:20) were selected. Crash‐related features that involved drivers with and without epilepsy were compared, including driver eligibility, medical history of comorbidities and medications, road and environmental conditions, and accident causes. Cox and logistic regression analyses were used to examine the risks of fatality and severe injury among drivers with and without epilepsy.PWE involved in MVCs were more likely to have lower socioeconomic status, comorbidities, scooter drivers without a qualified driver's license, driving under the influence of alcohol, and be involved in single‐vehicle accidents than non‐PWE. Drivers with epilepsy also had a higher risk of fatality within 30 days of MVC, with an adjusted hazard ratio (aHR) of 1.37 (95% confidence interval [CI], 1.20–1.57) and a higher risk of hospital admission within 3 days after MVC (aHR, 1.33; 95% CI, 1.29–1.38) compared to that of non‐PWE.The characteristics of MVCs of drivers with epilepsy were distinct from those of non‐affected drivers. And higher fatality and injury rates were observed among drivers with epilepsy, which should be considered in further policymaking regarding safe driving of PWE. [ABSTRACT FROM AUTHOR]

Protein phosphatase 2 regulatory subunit B56δ related neurodevelopmental disorder (PPP2R5D‐related NDD) is largely caused by de novo heterozygous missense PPP2R5D variants. We report medical characteristics, longitudinal adaptive functioning, and in‐person neurological, motor, cognitive, and electroencephalogram (EEG) activity for PPP2R5D‐related NDD. Forty‐two individuals (median age 6 years, range = 0.8–25.3) with pathogenic/likely pathogenic PPP2R5D variants were assessed, and almost all variants were missense (97.6%) and de novo (85.7%). Common clinical symptoms were developmental delay, hypotonia, macrocephaly, seizures, autism, behavioral challenges, and sleep problems. The mean Gross motor functional measure‐66 was 60.2 ± 17.3% and the mean Revised upper limb module score was 25.9 ± 8.8. The Vineland‐3 adaptive behavior composite score (VABS‐3 ABC) at baseline was low (M = 61.7 ± 16.8). VABS‐3 growth scale value scores increased from baseline in all subdomains (range = 0.6–5.9) after a mean follow‐up of 1.3 ± 0.3 years. EEG beta and gamma power were negatively correlated with VABS‐3 score; p < 0.05. Individuals had a mean Quality‐of‐life inventory‐disability score of 74.7 ± 11.4. Twenty caregivers (80%) had a risk of burnout based on the Caregiver burden inventory. Overall, the most common clinical manifestations of PPP2R5D‐related NDD were impaired cognitive, adaptive function, and motor skills; and EEG activity was associated with adaptive functioning. This clinical characterization describes the natural history in preparation for clinical trials. [ABSTRACT FROM AUTHOR]

The network nature of focal epilepsy is exemplified by mesial temporal lobe epilepsy (mTLE), characterized by focal seizures originating from the mesial temporal neocortex, amygdala, and hippocampus. The mTLE network hypothesis is evident in seizure semiology and interictal comorbidities, both reflecting limbic network dysfunction. The network generating seizures also supports essential physiological functions, including memory, emotion, mood, and sleep. Pathology in the mTLE network often manifests as interictal behavioral disturbances and seizures. The limbic circuit is a vital network, and here we review one of the most common focal epilepsies and its comorbidities. We describe two people with drug resistant mTLE implanted with an investigational device enabling continuous hippocampal local field potential sensing and anterior nucleus of thalamus deep brain stimulation (ANT-DBS) who experienced reversible psychosis during continuous high-frequency stimulation. The mechanism(s) of psychosis remain poorly understood and here we speculate that the anti-epileptic effect of high frequency ANT-DBS may provide insights into the physiology of primary disorders associated with psychosis. [ABSTRACT FROM AUTHOR]

There is currently no efficacious intervention for preventing post-traumatic epilepsy (PTE). Preclinical studies support the potential use of anticholinergics for this condition. The purpose of this study was to evaluate the effects of biperiden as an intervention for preventing PTE. A randomized, double-blinded clinical trial was conducted at HC/FMUSP between 2018-2022. Adults with acute traumatic brain injury (TBI) were randomly assigned to receive biperiden or placebo, for 10 days. The primary outcome was the incidence of PTE while the secondary outcomes included the frequency of seizures, the frequency of any adverse events and mortality after 24 months. The study was powered at a planned enrolment of 132 patients. The trial began in January 2018 and was halted by researchers on March 2020 (and terminated in December 2022) in the face of the global COVID-19 pandemic. Overall, 123 participants were randomized and 112 contributed with data for modified mITT analysis, being that 61 (49.5%) participants completed the 24-month follow-up consult. Data analysis indicated lack of evidence of biperiden for either, the incidence of post-traumatic epilepsy (2.6, 95%CI, 0.65-10.57; p = 0.170) or the mortality rate (1.57, 95%CI, 0.73-3.38; p = 0.248). The frequency of late post-traumatic seizures was higher for biperiden group (2.03, 95%CI = 0.912-3.1597; p <0.001). The present study suggests that there was insufficient evidence regarding the effect of biperiden in preventing PTE after TBI, which underpins the need for larger studies. [ABSTRACT FROM AUTHOR]

Objective: Preclinical models of seizures and epilepsy in rodents contributed substantially to the discovery of currently available antiseizure medications. These were also broadly used for investigation of processes of epileptogenesis. Nevertheless, rodent models pose some limitations, thus, new models using alternative species are in high demand. The aim of this study was to describe a new model of seizures/epilepsy induced by the cholinomimetic agent, pilocarpine (PILO), in larval zebrafish. Methods: Local field potential (LFP) recordings were conducted to analyze electroencephalographic discharges and correlate it with larval behavior. Hematoxylin and eosin (H&E) staining, as well as TUNEL staining were performed to analyze morphology and apoptosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) was undertaken for gene expression analysis. Results: Acute exposure to PILO, in a concentration-dependent manner, induces electroencephalographic discharges in larval zebrafish, which behaviorally manifest as decreased locomotion and moving time, but enhanced movement velocity. The PILO-induced seizure-like activity is behaviorally distinct from this induced by the application of chemoconvulsant pentylenetetrazole (PTZ). Zebrafish larvae previously exposed to PILO (2 h), after a washing out period, exhibit spontaneous, unprovoked discharges and apoptotic changes in their brains. Significance: Here, we comprehensively investigated a new model of PILOinduced seizures/epilepsy in larval zebrafish. We propose that this model may be used to study epileptogenesis and for antiseizure drug screening purposes. [ABSTRACT FROM AUTHOR]

Background Hypothesis Animals Methods Results Conclusions and Clinical Importance Electroencephalography (EEG) recording protocols have been standardized for humans. Although the utilization of techniques in veterinary medicine is increasing, a standard protocol has not yet been established.Assessment of a sedation‐awakening EEG protocol in dogs.Electroencephalography examination was performed in a research colony of 6 nonepileptic dogs (control [C]) and 12 dogs with epilepsy admitted to the clinic because of the epileptic seizures.It was a prospective study with retrospective control. Dogs with epilepsy were divided into 2 equal groups, wherein EEG acquisition was performed using a “sedation” protocol (IE‐S, n = 6) and a “sedation‐awakening” protocol (IE‐SA, n = 6). All animals were sedated using medetomidine. In IE‐SA group, sedation was reversed 5 minutes after commencing the EEG recording by injecting atipamezole IM. Type of background activity (BGA) and presence of EEG‐defined epileptiform discharges (EDs) were evaluated blindly. Statistical significance was set at P > 0.05.Epileptiform discharges were found in 1 of 6 of the dogs in group C, 4 of 6 of the dogs in IE‐S group, and 5 of 6 of the dogs in IE‐SA group. A significantly greater number of EDs (spikes, P = .0109; polyspikes, P = .0109; sharp waves, P = .01) were detected in Phase 2 in animals subjected to the “sedation‐awakening” protocol, whereas there was no statistically significant greater number of discharges in sedated animals.A “sedation‐awakening” EEG protocol could be of value for ambulatory use if repeated EEG recordings and monitoring of epilepsy in dogs is needed. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine differences in factors influencing quality of life (QOL) in people with extratemporal lobe epilepsy (ETLE) and mesial temporal lobe epilepsy (MTLE). Methods: We obtained data from the medical records of 84 (47 ETLE and 37 MTLE) people with epilepsy. The data included age, sex, employment, seizure frequency, number of antiseizure medication (ASM), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) score, and Quality of Life in Epilepsy Inventory-31 (QOLIE-31) score. Multiple regression analyses were performed using QOLIE-31 as the dependent variable and age, sex, employment, seizure frequency, number of ASM, and NDDI-E score as the independent variables in ETLE or MTLE. Results: From the results of the multiple regression analyses, QOLIE-31 in ETLE was associated with NDDI-E (β = -0.757, p < 0.001) and employment (β = 0.388, p = 0.008). Meanwhile, QOLIE-31 in MTLE was associated with NDDI-E (β = -0.625, p < 0.001), employment (β = 0.396, p = 0.041), and number of ASMs (β = -0.399, p = 0.018). Conclusion: Overall, our findings indicate that the number of ASMs is potentially an influence on QOL of MTLE but similar effect is not observed in ETLE. [ABSTRACT FROM AUTHOR]

Adult neural stem cells (NSCs) in the hippocampal dentate gyrus continuously proliferate and generate new neurons throughout life. Although various functions of organelles are closely related to the regulation of adult neurogenesis, the role of endoplasmic reticulum (ER)-related molecules in this process remains largely unexplored. Here we show that Derlin-1, an ER-associated degradation component, spatiotemporally maintains adult hippocampal neurogenesis through a mechanism distinct from its established role as an ER quality controller. Derlin-1 deficiency in the mouse central nervous system leads to the ectopic localization of newborn neurons and impairs NSC transition from active to quiescent states, resulting in early depletion of hippocampal NSCs. As a result, Derlin-1-deficient mice exhibit phenotypes of increased seizure susceptibility and cognitive dysfunction. Reduced Stat5b expression is responsible for adult neurogenesis defects in Derlin-1-deficient NSCs. Inhibition of histone deacetylase activity effectively induces Stat5b expression and restores abnormal adult neurogenesis, resulting in improved seizure susceptibility and cognitive dysfunction in Derlin-1-deficient mice. Our findings indicate that the Derlin-1-Stat5b axis is indispensable for the homeostasis of adult hippocampal neurogenesis. Synopsis: Derlin-1, an endoplasmic reticulum (ER)-associated degradation component, regulates seizure susceptibility and cognitive function through Stat5b-mediated maintenance of adult neurogenesis, and this function is distinct from its role in ER quality control. Derlin-1 is essential for the appropriate localization of newborn neurons and the transition of neural stem cells from active to quiescent states. Mice with a loss of Derlin-1 in the central nervous system exhibit increased seizure susceptibility and cognitive dysfunction. Derlin-1 maintains adult neurogenesis homeostasis through the regulation of Stat5b expression. Histone deacetylase inhibition effectively induces Stat5b expression and restores abnormal adult neurogenesis. Derlin-1, an endoplasmic reticulum (ER)-associated degradation component, regulates seizure susceptibility and cognitive function through Stat5b-mediated maintenance of adult neurogenesis, and this function is distinct from its role in ER quality control. [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy is a widespread disease requiring long-term drug treatment. The aim of this study was to collect information on reported suspected adverse drug reactions (sADRs) of antiseizure medications (ASMs) and study their seriousness and outcomes in various system organ classifications (SOCs). We intended to compare old and new ASMs’ ADRs. Methods: Using EudraVigilance (EV) database, we extracted line listings of reported sADRs with different ASMs over the period from January 2012 to December 2021. The list of ASMs was compiled according to the Anatomical therapeutic chemical classification system. The Medical Dictionary for Regulatory Activities version 24.0 was used for determining the SOCs of individual reported preferred terms (PTs) sADRs. In addition, we calculated the Reporting Odds Ratio (ROR), 95% confidence interval (95% CI), p-value (statistically significant if p< 0.05) and chi-square statistics. Results: A total of 276,694 reports were contained in the exported line listings which included 1,051,142 individual sADRs reported as PTs such as seizure (3.49%), drug ineffective (2.46%), somnolence (1.32%), dizziness (1.29%) and represented four SOCs: nervous system disorders (19.26%), general disorders and administration site conditions (14.39%), psychiatric disorders (11.29%) and injury, poisoning and procedural complications (9.79). Among patients, the age group between 18 and 64 years had the highest percentage (52.40%), followed by those aged over 64 years (18.75%). Of all the reported PTs, 882,706 (83.98%) had reported seriousness. Old ASMs had a significant positive association with “caused/prolonged hospitalisation”, “congenital anomaly”, “disabling”, “life threatening” and “results in death”, while new ASMS with ‘other medically important condition’. There were 386 (0.04%) PTs related to Sudden Unexpected Death in Epilepsy (SUDEP). Conclusion: In our study, we examined 10 years’ reported sADRs of ASMs in the EV international database. The majority of PTs were serious. Old ASMs were generally more commonly associated with undesired outcomes and seriousness. Considering their expected seriousness and outcomes, the safety profile of the different ASMs, can play a cardinal role in the selection of ASMs. [ABSTRACT FROM AUTHOR]

Objective: Seizures significantly affect quality of life among patients with epilepsy while employment significantly contributes to the quality of life in general. Thus, in our study, we aimed to determine how the demographic and disease-related characteristics of patients with epilepsy impact quality of life and employment. Material and Methods: Our sample included 202 patients who had been diagnosed with epilepsy for at least a year and admitted to the Neurology Polyclinic between October 2023 and March 2024. Data about patients’ characteristics were collected using a sociodemographic information form while quality of life was measured using the Turkish Quality of Life in Epilepsy Inventory-31 (QOLIE-31). Results: On average, patients were 29.07 ± 10.84 years old and had had epilepsy for 10.5 ± 8.92 years. Patients’ lowest mean score on the QOLIE-31’s subscales was for “Total Quality of Life” whereas their highest mean score was for “Social Function”. The total quality of life score of patients with low education level and low income was found significantly lower. Among other results, patients with a seizure frequency of 6 or more per month had significantly lower scores on all subscales except “Emotional Well-Being”, and patients with refractory epilepsy and/or receiving polytherapy had significantly lower total scores and scores on all subscales. Conclusion: Our results indicate that employment does not significantly affect quality of life among patients with epilepsy whereas their clinical features do. Even so, physicians should take all conditions into account to ensure the highest-possible quality of life for patients with epilepsy. [ABSTRACT FROM AUTHOR]

Aim: Patients with a background of cerebrospinal fluid (CSF)-diverting shunts are frequently investigated for shunt malfunction when presenting with seizures. However, there is very limited evidence in the literature regarding the association of seizures and shunt malfunction. We sought to determine the incidence of shunt malfunction in our cohort of shunted paediatric patients presenting with seizures, and the utility of seizures as a marker of shunt malfunction. Methods: We retrospectively identified all shunted patients presenting with seizures, as well as all patients undergoing shunt revision following a presentation with seizures from our hospital database over a 14-year period from 2009 to 2023. Data gathered included demographics, de novo seizures or change in pattern of seizures, the aetiology of hydrocephalus and the segment of shunt requiring revision. Exclusion criteria included infected cases requiring shunt externalisation. A literature review of all papers discussing seizures as a presentation of shunt malfunction was also carried out. Results: Overall, over a 14-year period of study, 338 shunted patients presented with seizures and were referred as suspected shunt malfunction with 10 having confirmed shunt malfunction requiring revision (2.9%). This group represented 6.2% of 161 cases of shunt revision carried out during the 14-year period of study. Post-haemorrhagic hydrocephalus secondary to prematurity was the commonest aetiology of shunted hydrocephalus presenting with seizures. Out of 10 patients presenting with seizures with shunt malfunction, 4 presented with de novo seizures, while 6 presented with a change in seizure pattern or frequency in already known epileptic patients. Shunt revision surgeries included 5 distal catheter, 2 proximal catheter, 1 proximal catheter-valve, 1 valve only and 1 case of whole shunt change. Conclusion: Our data supports that seizures are rare manifestation of shunt malfunction and can present either de novo or with a change in seizure frequency in already-known epileptic patients. [ABSTRACT FROM AUTHOR]

Developmental and epileptic encephalopathies (DEEs) are characterized by pharmacoresistant seizures and developmental delay. Patients with DEEs experience multiple seizure types, including tonic–clonic seizures (TCS) that can be generalized tonic–clonic (GTCS) or focal evolving to bilateral tonic–clonic (FBTCS). Fenfluramine (FFA) has demonstrated efficacy in reduction of TCS in patients with Dravet syndrome (DS), Lennox–Gastaut syndrome (LGS), and other DEEs. Using the PRISMA‐ScR (Preferred Reporting Items for Systematic Review and Meta‐Analyses extension for Scoping Review) guidelines, we performed a scoping review to describe changes in TCS in patients treated with FFA. A comprehensive search of five literature databases was conducted up to February 14, 2023. Studies were included if they reported change in GTCS or TCS (but not FBTCS) after treatment with FFA in patients with DEEs. Duplicate patients and studies with unclear efficacy data were excluded. Fourteen of 422 studies met the eligibility criteria. Data extracted and evaluated by expert clinicians identified 421 unique patients with DS (in nine studies), CDKL5 deficiency disorder, SCN8A‐related disorder, LGS, SCN1B‐related disorder, and other DEEs. The median percent reduction in GTCS or TCS from baseline was available in 10 studies (n = 328) and ranged from 47.2% to 100%. Following FFA treatment, 10 studies (n = 144) reported ≥50% reduction in GTCS or TCS from baseline in 72% of patients; in nine of those (n = 112), 54% and 29% of patients achieved ≥75% and 100% reduction in GTCS or TCS from baseline, respectively. Overall, this analysis highlighted improvements in GTCS or TCS frequency when patients were treated with FFA regardless of the DEE evaluated. Future studies may confirm the impact of FFA on TCS reduction and on decreased premature mortality risk (including sudden unexpected death in epilepsy), improvement in comorbidities and everyday executive function, decreased health care costs, and improvement in quality of life. [ABSTRACT FROM AUTHOR]

Understanding the correlation between genotype and phenotype remains challenging for modern genetics. Digenic network analysis may provide useful models for understanding complex phenotypes that traditional Mendelian monogenic models cannot explain. Clinical data, whole exome sequencing data, in silico, and machine learning analysis were combined to construct a digenic network that may help unveil the complex genotype–phenotype correlations in a child presenting with inherited seizures and thrombocytopenia. The proband inherited a maternal heterozygous missense variant in SCN1A (NM_001165963.4:c.2722G>A) and a paternal heterozygous missense variant in MYH9 (NM_002473.6:c.3323A>C). In silico analysis showed that these two variants may be pathogenic for inherited seizures and thrombocytopenia in the proband. Moreover, focusing on 230 epilepsy-associated genes and 35 thrombopoiesis genes, variant call format data of the proband were analyzed using machine learning tools (VarCoPP 2.0) and Digenic Effect predictor. A digenic network was constructed, and SCN1A and MYH9 were found to be core genes in the network. Further analysis showed that MYH9 might be a modifier of SCN1A, and the variant in MYH9 might not only influence the severity of SCN1A-related seizure but also lead to thrombocytopenia in the bone marrow. In addition, another eight variants might also be co-factors that account for the proband's complex phenotypes. Our data show that as a supplement to the traditional Mendelian monogenic model, digenic network analysis may provide reasonable models for the explanation of complex genotype–phenotype correlations. [ABSTRACT FROM AUTHOR]

Pseudohypoparathyroidism (PHP) comprises a cluster of heterogeneous diseases characterized by hypocalcemia and hyperphosphatemia due to parathyroid hormone (PTH) resistance. PHP type 1B (PHP1B) is caused by heterozygous maternal deletions within GNAS or STX16. STX16 exon 2–6 deletion is commonly observed in autosomal dominant (AD)-PHP1B, while sporadic PHP1B commonly results from methylation abnormalities of maternal differentially methylated regions and remains unclear at the molecular level. A 39-year-old male patient with PHP1B, who had his first seizure at 15 years of age, presented to our hospital. The methylation-specific multiplex ligation-dependent probe amplification results showed a half-reduced copy number of STX16 exon 5–7 and loss of methylation at GNAS exon A/B. His mother also had a half-reduced copy number of STX16 exon 5–7 but with normal methylation of GNAS. His father has a normal copy number of STX16 and normal methylation of GNAS. For the recognition and early diagnosis of this kind of disease, here we report the clinical symptoms, auxiliary examinations, genetic testing characteristics, and treatment of the patient. [ABSTRACT FROM AUTHOR]

Background: Following the standardized nomenclature proposed by the American Clinical Neurophysiology Society (ACNS), rhythmic high-amplitude delta activity with superimposed spikes (RHADS) can be reported as an extreme delta brush (EDB). The clinical implications of similar electrographic patterns being reported as RHADS versus EDB are important to highlight. We aim to review the electrographic characteristics of RHADS, evaluate whether RHADS is seen in other neurological disorders, and identify the similar and unique characteristics between RHADS and EDB to ultimately determine the most accurate way to differentiate and report these patterns. We believe that the differentiation of RHADS and EDB is important as there is a vast difference in the diagnostic approach and the medical management of associated underlying etiologies. Data source: We conducted an extensive search on MEDLINE and Pubmed utilizing various combinations of keywords. Searching for "gamma polymerase and EEG", or "RHADS" or "Alpers syndrome and EEG" or "EEG" AND "Alpers–Huttenlocher syndrome". Results: Three articles were found to be focused on the description of "RHADS" pattern in Alpers Syndrome. No publication to date were found when searching for the terms "EDB" AND "children", AND "infant" AND "adolescent" excluding "encephalitis" and "neonate". Although RHADS and EDB appear as similar EEG patterns, meticulous analysis can differentiate them. RHADS is not exclusive to patients with Alpers–Huttenlocher syndrome and may manifest in regions beyond the posterior head region. Reactivity to eye-opening and response to anesthesia can be two other elements that help in the differentiation of these patterns. Conclusion: RHADS is not exclusive to patients with AHS and may manifest in regions beyond the posterior head region. Reactivity to eye-opening and response to anesthesia are features that help in the differentiation of these patterns. [ABSTRACT FROM AUTHOR]

Purpose: To delineate the characteristics of probable antibody-negative pediatric autoimmune encephalitis (probable Ab-negative AE), we compared the clinical features of probable Ab-negative AE to those of major antibody-positive AE. Methods: We retrospectively reviewed the clinical features of 18 patients with probable Ab-negative AE, 13 with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), and 13 with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Clinical characteristics, neuroimaging findings, treatments, and outcomes were analyzed. Results: The age of onset and length of hospital stay were significantly higher in the NMDARE group than in the other groups (p = 0.02 and p < 0.01). Regarding initial neurological symptoms, acute symptomatic seizures in the probable Ab-negative AE group (67%) were significantly more frequent than in the NMDARE (15%) and MOGAD (23%) groups (p<0.01). Paraclinical evidence of neuroinflammation within 1 month of disease onset revealed that single-photon emission computed tomography (SPECT) detected abnormal alterations in 14/14 (100%), cerebrospinal fluid (CSF) analysis in 15/18 (83%), and magnetic resonance imaging (MRI) in 11/18 (61%) in patients with probable Ab-negative AE. In the probable Ab-negative AE group, seven patients (39%) developed autoimmune-associated epilepsy, whereas one patient (8%) had both NMDARE and MOGAD (not statistically significant, p = 0.07). Conclusion: Patients with probable Ab-negative AE exhibited acute symptomatic seizures as initial neurological symptoms significantly more frequently. They developed autoimmune-associated epilepsy more frequently than those with NMDARE and MOGAD, which was not statistically significant. SPECT within 1 month of disease onset might be a valuable surrogate marker of ongoing neuroinflammation and neuronal dysfunction, even in patients with negative MRI findings. [ABSTRACT FROM AUTHOR]

This narrative review aims to summarise the information available on the use of subcutaneous (SC) levetiracetam (LEV) in the adult palliative care setting using clinical texts, databases, journals, and grey literature. A search strategy utilising Embase, Medline CINALH and Cochrane databases, as well as Google Scholar, was conducted with the mapped search terms "levetiracetam", "subcutaneous" and "palliative". LEV intravenous (IV) proprietary products are used subcutaneously, including as continuous subcutaneous infusions (CSCIs), in the adult palliative care setting. The total LEV daily dose ranged from 250 mg to 5000 mg and LEV was administered with various diluents at varying volumes. The data identified a clinical desire to mix LEV with other medications; however, the current evidence on combination compatibility is observational only and drug stability in combinations is lacking. The majority of information in the literature on SC LEV use is based on case reports and retrospective audits. Case reports, whilst at times offering more clinical detail, represent specific circumstances not necessarily applicable to a larger patient cohort. The findings of retrospective audits are limited by the documentation and detail reported at the time of patient care that may not be designed for data collection. [ABSTRACT FROM AUTHOR]

This work presents a novel approach that harnesses the capabilities of field programmable gate arrays (FPGA) to enable instantaneous monitoring of electroencephalography (EEG) signals for the detection and prediction of seizure patterns. The integration of FPGA technology with the perceptron learning algorithm holds promises for enhancing real-time healthcare monitoring systems and contributing to improved patient care and safety. The proposed work addresses the challenges presented at predicting seizures from EEG data. The first challenge is to handle massive EEG data that poses memory issues. To tackle this, the research employs cellular automata (Rule 90 and Rule 150) to reduce data size by 85.71%, making it more manageable. The second is to implement a linearly classified perceptron algorithm using FPGA to predict and detect seizures from real-time EEG data. The third is clock synchronization between stored data and real EEG data for comparison purposes. The proposed system is continuously compared to real-time EEG signals using a single perceptron neural network, and alert signals are generated based on preactivation values, with a continuous alert issued when the value reaches 3/4th sample match. These early alerts empower individuals to take preventive actions. The model is implemented using an FPGA Zynq-7000 series, which consumes 270mW of power. The design utilizes 118 Lookup Tables (LUTs).Article Highlights: First one is data compression which was successfully achieved with Cellular Automata techniques and 85% memory is saved. Second the compressed data set trained to the machine learning algorithm was developed and implemented in the FPGA with very negligible delay and very high accuracy. The seizure affected people will have very less time to take the medical diagnosis. So the proposed work will be helpful to detect the abnormal states so they can react early for damage prevention. [ABSTRACT FROM AUTHOR]

The blood–brain barrier (BBB) is a barrier protecting the brain and a milieu of continuous exchanges between blood and brain. There is emerging evidence that the BBB plays a major role in epileptogenesis and drug‐resistant epilepsy, through several mechanisms, such as water homeostasis dysregulation, overexpression of drug transporters, and inflammation. Studies have shown abnormal water homeostasis in epileptic tissue and altered aquaporin‐4 water channel expression in animal epilepsy models. This review focuses on abnormal water exchange in epilepsy and describes recent non‐invasive MRI methods of quantifying water exchange. Plain Language Summary: Abnormal exchange between blood and brain contribute to seizures and epilepsy. The authors describe why correct water balance is necessary for healthy brain functioning and how it is impacted in epilepsy. This review also presents recent MRI methods to measure water exchange in human brain. These measures would improve our understanding of factors leading to seizures. [ABSTRACT FROM AUTHOR]

Objective: Deep brain stimulation (DBS) is a promising approach for the treatment of epilepsy. However, the optimal target for DBS and underlying mechanisms are still not clear. Here, we compared the therapeutic effects of DBS on distinct septal subregions, aimed to find the precise targets of septal DBS and related mechanisms for the clinical treatment. Methods: Assisted by behavioral test, electroencephalography (EEG) recording and analyzing, selectively neuronal manipulation and immunohistochemistry, we assessed the effects of DBS on the three septal subregions in kainic acid (KA)‐induced mouse seizure model. Results: DBS in the medial septum (MS) not only delayed generalized seizure (GS) development, but reduced the severity; DBS in the vertical diagonal band of Broca (VDB) only reduced the severity of GS, while DBS in the horizontal diagonal band of Broca (HDB) subregion showed no anti‐seizure effect. Notably, DBS in the MS much more efficiently decreased abnormal activation of hippocampal neurons. EEG spectrum analysis indicated that DBS in the MS and VDB subregions mainly increased the basal hippocampal low‐frequency (delta and theta) rhythm. Furthermore, ablation of cholinergic neurons in the MS and VDB subregions blocked the anti‐seizure and EEG‐modulating effects of septal DBS, suggesting the seizure‐alleviating effect of DBS was dependent on local cholinergic neurons. Significance: DBS in the MS and VDB, rather than HDB, attenuates hippocampal seizure by activation of cholinergic neurons‐augmented hippocampal delta/theta rhythm. This may be of great therapeutic significance for the clinical treatment of epilepsy with septal DBS. Plain Language Summary: The optical target of deep brain stimulation in the septum is still not clear. This study demonstrated that stimulation in the medial septum and vertical diagonal band of Broca subregions, but not the horizontal diagonal band of Broca, could alleviate hippocampal seizure through cholinergic neurons‐augmented hippocampal delta/theta rhythm. This study may shed light on the importance of precise regulation of deep brain stimulation therapy in treating epileptic seizures. [ABSTRACT FROM AUTHOR]

Objective: GABAA receptor subunit mutations pose a significant risk for genetic generalized epilepsy; however, there are over 150 identified variants, many with unknown or unvalidated pathogenicity. We aimed to develop in vivo models for testing GABAA receptor variants using the model organism, Caenorhabditis elegans. Methods: CRISPR‐Cas9 gene editing was used to create a complete deletion of unc‐49, a C. elegans GABAA receptor, and to create homozygous epilepsy‐associated mutations in the endogenous unc‐49 gene. The unc‐49 deletion strain was rescued with transgenes for either the C. elegans unc‐49B subunit or the α1, β3, and γ2 subunits for the human GABAA receptor. All newly created strains were analyzed for phenotype and compared against existing unc‐49 mutations. Results: Nematodes with a full genetic deletion of the entire unc‐49 locus were compared with existing unc‐49 mutations in three separate phenotypic assays—coordinated locomotion, shrinker frequency and seizure‐like convulsions. The full unc‐49 deletion exhibited reduced locomotion and increased shrinker frequency and PTZ‐induced convulsions, but were not found to be phenotypically stronger than existing unc‐49 mutations. Rescue with the unc‐49B subunit or creation of humanized worms for the GABAA receptor both showed partial phenotypic rescue for all three phenotypes investigated. Finally, two epilepsy‐associated variants were analyzed and deemed to be loss of function, thus validating their pathogenicity. Significance: These findings establish C. elegans as a genetic model to investigate GABAA receptor mutations and delineate a platform for validating associated variants in any epilepsy‐associated gene. Plain Language Summary: Epilepsy is a complex human disease that can be caused by mutations in specific genes. Many possible mutations have been identified, but it is unknown for most of them whether they cause the disease. We tested the role of mutations in one specific gene using a small microscopic worm as an animal model. Our results establish this worm as a model for epilepsy and confirm that the two unknown mutations are likely to cause the disease. [ABSTRACT FROM AUTHOR]

Objective: Hospital‐acquired infections are a common complication for patients with moderate or severe traumatic brain injury (TBI), contributing to morbidity and mortality. As infection‐mediated immune responses can predispose towards epilepsy, we hypothesized that post‐injury hospital‐acquired infections increase the risk of post‐traumatic epilepsy (PTE). Methods: A retrospective cohort study of adults with moderate to severe TBI was conducted using data from the Victorian State Trauma Registry in Australia. Infections were identified from the International Statistical Classification of Diseases and Related Health Problems 10th Revision–Australian Modification (ICD‐10‐AM) codes, and diagnosis of PTE was determined by the Glasgow Outcome Scale – Extended questionnaire regarding epileptic fits at 24 months follow‐up. Results: Of all TBI patients (n = 15 152), 24% had evidence of having had any type of infection, with the most common being pneumonia, urinary tract, and respiratory infections. Of those who responded to the PTE question at 24 months (n = 1361), 11% had developed PTE. Univariable analysis found that the incidence of PTE was higher in patients who had any type of infection compared to patients without an infection (p < 0.001). After adjustment for covariates associated with both development of PTE and risk of infection, multivariable analysis found a solid association between infection and PTE (adjusted RR = 1.59; 95% CI: 1.11–2.28; p = 0.011). Having any type of complicating infection acquired during admission was also associated with poor GOSE outcomes at subsequent follow‐ups (adjusted OR = 0.20; 95% CI: 0.11–0.35, p < 0.001). Significance: These findings suggest that hospital‐acquired infections contribute to PTE development after TBI. Future investigation into infections as a modifiable target to reduce poor outcomes after TBI is warranted. Plain Language Summary: Hospital‐acquired infections are common in patients with traumatic brain injuries. A database study of adults with moderate or severe brain injuries in Australia examined whether these infections are associated with the development of epilepsy after a brain injury. 24% of patients had infections, with pneumonia and urinary tract infections being the most common. Of those surveyed 2 years after the injury, 11% developed post‐traumatic epilepsy. Patients with infections had a significantly higher risk of epilepsy, even when accounting for other known risk factors, and infections were also linked to poor outcomes more broadly. The study suggests that preventing hospital‐acquired infections could be a crucial target for improving outcomes after traumatic brain injuries. [ABSTRACT FROM AUTHOR]

Introduction: Magnesium sulfate is the most utilized anticonvulsant for treating patients with eclampsia and pre-eclampsia. The purpose of this study is to determine whether the 12-h regimen of magnesium sulfate outweighs the 24-h regimen in both efficacy and safety in the management of patients with mild or severe pre-eclampsia and eclampsia. Methods: We searched six electronic databases: PubMed, Scopus, Web of Science, Cochrane Library, Ovid, and Google Scholar. This search was conducted to yield any studies that were published until 15 January 2023. We did the statistical analysis plan by Review Manager Software version 5.4. Results: We included 13 randomized control trials with 2813 patients in this systematic review. Our meta-analysis revealed that there were no statistically significant differences between the 12-h regimen of the magnesium sulfate group and the 24-h regimen of the magnesium sulfate group in our outcome of interest: occurrence of seizure (RD: -0.00, 95% CI [-0.01, 0.00], P = 0.56), diminished deep tendon reflexes (RD: -0.00, 95% CI [-0.01, 0.01], P = 0.80), respiratory depression (RD: -0.00, 95% CI [-0.02, 0.01], P = 0.57), and pulmonary edema (RD: -0.00, 95% CI [-0.01, 0.01], P = 0.85). Conclusion: Our study showed no statistically significant difference in effectiveness and toxicity risk between the 12-h and 24-h regimens. [ABSTRACT FROM AUTHOR]

Due to the abundance of ACE2 receptors in nervous system cells, the SARS-CoV-2 virus can cause damage to this system. This study aims to examine the prevalence of neurological symptoms in COVID-19 patients. In this cross-sectional observational study, 75 COVID-19 positive patients admitted to Golestan Hospital’s neurology department in Ahvaz, Iran, from March 2020 to March 2023, were investigated. Neurological clinical symptoms were categorized into three groups: central nervous system, peripheral, and muscular symptoms. The relevant information was collected from patient files, including medical history, imaging data, and laboratory test results. Statistical analysis was performed using SPSS software, employing the rank-biserial correlation coefficient (r), Mann–Whitney U tests, Phi correlation, Cramer’s V, and Kendall’s Tau to evaluate the prevalence and significance of neurological symptoms. The most common clinical symptoms observed were hemiparesis, dysarthria, Central Facial Palsy (CFP), ataxia, and nausea, respectively. Among these symptoms, headaches (p = 0.001), seizures (p = 0.024), and nausea (p = 0.046) were found to be more prevalent in younger patients. Additionally, a significant relationship was identified between the level of serum Creatine phosphokinase (CPK) and seizures (p = 0.024), with lower levels observed in individuals with vomiting (p = 0.024), and higher levels observed in individuals with CFP (p = 0.040). This study highlights that patients with COVID-19 may experience serious neurological symptoms. The clinical spectrum and range of neurological symptoms associated with COVID-19 were found to be diverse and extensive, emphasizing the importance of considering this infection as a potential cause of neurological disorders. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) in an integral part of the diagnostic workup in canines with idiopathic epilepsy (IE). While highly sensitive and specific in identifying structural lesions, conventional MRI is unable to detect changes at the microscopic level. Utilizing more advanced neuroimaging techniques may provide further information on changes at the neuronal level in the brain of canines with IE, thus providing crucial information on the pathogenesis of canine epilepsy. Additionally, earlier detection of these changes may aid clinicians in the development of improved and targeted therapies. Advances in MRI techniques are being developed which can assess metabolic, cellular, architectural, and functional alterations; as well alterations in neuronal tissue mechanical properties, some of which are currently being applied in research on canine IE. This mini-review focuses on novel MRI techniques being utilized to better understand canine epilepsy, which include magnetic resonance spectroscopy, diffusion-weighted imaging, diffusion tensor imaging, perfusionweighted imaging, voxel based morphometry, and functional MRI; as well as techniques applied in human medicine and their potential use in veterinary species. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the comparative efficacy and safety of various doses of oral cannabidiol (CBD) in treating refractory epilepsy indications, thus providing more informative evidence for clinical decision-making. Methods: A literature search of PubMed, Embase, the Cochrane library, and Web of Science (WoS) was performed to retrieve relevant randomized controlled trials (RCTs) that compared different doses of oral CBD with placebo or each other in refractory epilepsy indications. The search was limited from the inception of each database to January 3, 2023. Relative risk [RR] with a 95% confidence interval [CI] was used to express results. STATA/SE 14 was employed for network meta-analysis. Results: Six RCTs involving 972 patients were included in the final data analysis. Network meta-analysis showed that, CBD10 (10  mg/kg/day) (RR: 1.77, 95%CI: 1.28 to 2.44), CBD20 (20  mg/kg/day) (RR: 1.91, 95%CI: 1.49 to 2.46), CBD25 (25  mg/kg/day) (RR: 1.61, 95%CI: 0.96 to 2.70), and CBD50 (50  mg/kg/day) (RR: 1.78, 95%CI: 1.07 to 2.94) were associated with higher antiseizure efficacy although the pooled result for CBD25 was only close to significant. In addition, in terms of the risk of treatment-emergent adverse events (TEAEs), the difference between different doses is not significant. However, CBD20 ranked first in terms of antiseizure efficacy, followed by CBD50, CBD10, and CBD25. For TEAEs, CBD25 ranked first, followed by CBD10, CBD50, CBD5, and CBD20. Conclusion: For refractory indications, CBD20 may be optimal option for antiseizure efficacy; however, CBD25 may be best for TEAEs. Therefore, an appropriate dose of oral CBD should be selected based on the actual situation. Due to the limitations of eligible studies and the limited sample size, more studies are needed in the future to validate our findings. [ABSTRACT FROM AUTHOR]

Bromide is the first effective antiseizure medication used in human medicine since the XIX century. Initially met with skepticism, bromide quickly gained enthusiasm within the medical field until being largely replaced by newer antiseizure medications with significantly fewer adverse effects in people. In veterinary medicine, bromide continues to be used in the management of epileptic patients for over 30  years, yet adverse effects can impact owners and patients alike. We sought to provide the general practitioner and veterinary neurologist with insightful information on both the positive and negative attributes of bromide, explore factors that may influence its desirability as an antiseizure medication in specific veterinary cases and elucidate its current role in modern epilepsy treatment for veterinary patients. It’s also our endeavor to discuss the current use as an alternative or add-on with other known antiseizure medications and potential future studies that might enhance our understanding and use of this medication. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is one of the most common neurological diseases that affects people of different ages, ethnicities, and geographical locations. The objective of the present study was to determine the demographic and clinical characteristics of epilepsy in west Algerian population. Patients and methods: We enrolled 226 patients with epilepsy and collected data from medical records. We analyzed socio-demographic data, personal and family history, age at onset, seizure types, neurological and psychological findings, etiologies, syndromic classification and comorbidities. Results: In our cohort, the mean age was 27.26 ± 17.57 years and there was no gender predominance. The mean age of seizure onset was 17.11 ± 16.27 years. Genetic epilepsy was the most observed (45.13%). Focal seizures (69.02%) were more frequent than generalized seizures which were mostly represented by absence and tonic–clonic seizures. We reported 51.45% of patients with comorbidities and 16.65% with a history of traumatic brain injury. Conclusion: This is the first report describing the clinical profile and the socio-demographic features in a cohort of patients with epilepsy in the western Algeria. Our results could help to offer personalized care to our patients based on the clinical particularities of their epileptic disorders. [ABSTRACT FROM AUTHOR]

Background: Déjà vu, French for “already seen,” is a phenomenon most people will experience at least once in their lifetime. Emerging evidence suggests that déjà vu occurs in healthy individuals (as “non-ictal déjà vu”) and in epilepsy patients during seizures (as “ictal déjà vu”) and between seizures (as “interictal déjà vu”). Although the ILAE has recognized déjà vu as a feature of epileptic seizures, it is notably absent from the ICD-11. A lack of evidence-based research may account for this omission. To our knowledge, this study represents the first systematic review and meta-analysis on déjà vu experiences. Through detailed examinations of non-ictal, interictal and ictal déjà vu, we seek to highlight possible clinical implications. Rethinking the status quo of ictal déjà vu could potentially lead to earlier interventions and improve outcomes for epilepsy patients. Methods: This study was registered in PROSPERO (ID: CRD42023394239) on 5 February 2023. Systematic searches were conducted across four databases: EMBASE, MEDLINE, PsycINFO, and PubMed, from inception to 1 February 2023, limited to English language and human participants. Studies were included/ excluded based on predefined criteria. Data was extracted according to the PICO framework and synthesized through a thematic approach. Meta-analyses were performed to estimate prevalence’s of the phenomena. Study quality, heterogeneity, and publication bias were assessed. Results: Database searching identified 1,677 records, of which 46 studies were included. Meta-analyses of prevalence showed that non-ictal déjà vu was experienced by 0.74 (95% CI [0.67, 0.79], p  <  0.001) of healthy individuals, whereas interictal déjà vu was experienced by 0.62 (95% CI [0.48, 0.75], p  =  0.0 9 9 ) and ictal déjà vu by 0.22 (95% CI [0.15, 0.32], p  =  0.001) of epilepsy patients. Examinations of phenomenological (sex, age, frequency, duration, emotional valence, and dissociative symptoms) and neuroscientific (brain structures and functions) data revealed significant variations between non-ictal, interictal and ictal déjà vu on several domains. Conclusion: This systematic review and meta-analysis do not support the notion that non-ictal, interictal and ictal déjà vu are homogenous experiences. Instead, it provides insight into ictal déjà vu as a symptom of epilepsy that should be considered included in future revisions of the ICD-11. [ABSTRACT FROM AUTHOR]

Epilepsy affects over 65 million people worldwide. One-third of people with epilepsy do not respond to medication and may benefit from surgery. Vagus nerve stimulation (VNS) is the first neuromodulation therapy for the treatment of drug-resistant epilepsy. This method is used in combination with anti-seizure medications in adults and in the pediatric population. VNS has also been demonstrated to have benefits for some epilepsy comorbidities, such as depression, and can be used in combination with other neuromodulation therapies in epilepsy. The authors present an overview of VNS physiology, patient selection, surgery and risks, neuromodulation therapy, and application to epilepsy comorbidities. [ABSTRACT FROM AUTHOR]

Studies deem that about 1 percent of the human population is affected by epileptic seizures on a global scale. It is characterized as an undue neuronal discharge in the brain and degrades the quality of life of the patients to a large extent. Children being unaware of a sudden onset of seizures could be affected by severe injury or even mortality. Machine-learning-based epileptic seizure detection from EEG (Electro-Encephalogram) signals have always been a hot area of research. However, the majority of the research works rely on correlated non-linear features extracted from the EEG signals, causing a high-computational overhead, and challenging their application in real-time clinical diagnosis. This study proposes a robust seizure detection framework using Gaussian Deep Boltzmann Machine-based classifier and Symplectic Geometric Decomposition (SGD)-based features. The simplified eigenvalues derived through Symplectic Similarity Transform (SST) are employed as feature vectors for the classifier, eliminating the need for a deliberate feature extraction procedure. The study examines the transferability capability of the suggested framework in discriminating seizures in both neonates and pediatric subjects in unison, experimenting with classical annotated datasets. The model yielded a mean accuracy of about 97.91% and an F1 Score of 0.935 in pediatric seizure detection, and mean sensitivity and specificity of 99.05% and 98.28%, in neonatal seizure detection tasks, respectively. Thus, the model can be deemed comparable to the available state-of-the-art seizure detection frameworks. [ABSTRACT FROM AUTHOR]

The problem of multi-class classification is always a challenge in the field of EEG (electroencephalogram)-based seizure detection. The traditional studies focus on computing or learning a set of features from EEG to distinguish between different patterns. However, the extraction of characteristic information becomes increasingly difficult as the number of EEG types increases. To address this issue, a creative EEG classification technique is proposed by employing a principal component analysis network (PCANet) coupled with phase space reconstruction (PSR) and power spectrum density (PSD). We have introduced the PSR and PSD to prepare the inputs, where dynamic and frequency information are exposed from deep within PCANet. It is remarkable that a layered cascade strategy is designed to make a powerful deep learner according to the rule of one network vs one task (OVO). The proposed method has achieved greater effects than the individual models and shown superior performance in comparison with state-of-the-art algorithms, which present 98.0% of sensitivity, 99.90% of specificity, and 99.07% of accuracy. Our ensemble PCANet model works in an assembly line-like manner, obviating the need for hand-craft features. Results demonstrate that the proposed scheme can greatly enhances the accuracy and robustness of seizure detection from EEG signals. [ABSTRACT FROM AUTHOR]

Background: Zonisamide (ZNS) is a newer generation antiseizure medication (ASM) used to treat epilepsy in dogs and cats. However, scientific and clinical information, particularly regarding monotherapy, is limited. Objectives: To evaluate the antiseizure efficacy and tolerability of ZNS monotherapy in dogs with newly diagnosed idiopathic epilepsy (IE). Animals: Study included 56 client‐owned dogs newly diagnosed with IE. Methods: This was a prospective multicenter, open‐label, uncontrolled study. All dogs were ASM‐naïve and had ≥2 seizures within 12 weeks. Dogs were administered 2.7‐14.4 mg/kg ZNS PO q12h and followed up for ≥12 weeks. Data from the 12‐week maintenance treatment period were compared with those from the 4‐ to 12‐week pretreatment period for efficacy evaluation. Data from the entire ZNS administration period were used to assess tolerability. Results: Fifty‐six dogs were included in our study. Of the dogs, 53 were assessed for efficacy; 40 (76%) had a ≥ 50% reduction in seizure frequency, and 29 (55%) achieved seizure freedom. For 90% of the dogs with ≥50% reduction in seizure frequency, the mean ZNS dose was 4.8 (range, 2.7‐8.6) mg/kg q12h and the mean trough plasma ZNS concentration was 18.9 (range, 8.0‐48.0) μg/mL. In 7 of the 56 dogs (13%), reduced activity, decreased appetite, vomiting, hindlimb weakness, soft stools, or constipation was observed, albeit mild and temporary. Laboratory tests revealed no relevant changes. Conclusions and Clinical Importance: Our study suggests that ZNS monotherapy is effective and well‐tolerated in dogs with newly diagnosed IE. [ABSTRACT FROM AUTHOR]

Objective: The mechanistic target of rapamycin (mTOR) pathway has been implicated in promoting epileptogenesis in animal models of acquired epilepsy, such as posttraumatic epilepsy (PTE) following traumatic brain injury (TBI). However, the specific anatomical regions and neuronal populations mediating mTOR's role in epileptogenesis are not well defined. In this study, we tested the hypothesis that mTOR activation in dentate gyrus granule cells promotes neuronal death, mossy fiber sprouting, and PTE in the controlled cortical impact (CCI) model of TBI. Methods: An adeno‐associated virus (AAV)‐Cre viral vector was injected into the hippocampus of Rptorflox/flox (regulatory‐associated protein of mTOR) mutant mice to inhibit mTOR activation in dentate gyrus granule cells. Four weeks after AAV‐Cre or AAV‐vehicle injection, mice underwent CCI injury and were subsequently assessed for mTOR pathway activation by Western blotting, neuronal death, and mossy fiber sprouting by immunopathological analysis, and posttraumatic seizures by video‐electroencephalographic monitoring. Results: AAV‐Cre injection primarily affected the dentate gyrus and inhibited hippocampal mTOR activation following CCI injury. AAV‐Cre‐injected mice had reduced neuronal death in dentate gyrus detected by Fluoro‐Jade B staining and decreased mossy fiber sprouting by ZnT3 immunostaining. Finally, AAV‐Cre‐injected mice exhibited a decrease in incidence of PTE. Significance: mTOR pathway activation in dentate gyrus granule cells may at least partly mediate pathological abnormalities and epileptogenesis in models of TBI and PTE. Targeted modulation of mTOR activity in this hippocampal network may represent a focused therapeutic approach for antiepileptogenesis and prevention of PTE. [ABSTRACT FROM AUTHOR]

PURA syndrome is a congenital developmental disorder caused by de novo mutations in the PURA gene, which encodes a DNA/RNA-binding protein essential for transcriptional and translational regulation. We present the case of an 11-year-old patient with a de novo frameshift variant in the PURA gene, identified through whole exome sequencing (WES). In addition to the classical PURA deficiency phenotype, our patient exhibited pronounced sialorrhea and seizures, which were effectively treated with the ketogenic diet (KD). Our integrative approach, combining a literature review and bioinformatics data, has led to the first documented clinical case showing improvement in both sialorrhea and seizures with KD treatment, a phenomenon not previously reported. Although a direct relationship between the de novo PURA mutation and the KD was not established, we identified a novel frameshift deletion associated with a new clinical phenotype. [ABSTRACT FROM AUTHOR]

Objective(s): Convulsions caused by fever in children and parents not knowing about the nature of this disease cause severe anxiety and inappropriate performance in parents. Due to the cost-effectiveness of the telenursing method, nurses can use it to provide a large amount of information in a short period with distance education. Therefore, the present study was conducted with the aim of determining the effect of telenursing training on the anxiety of mothers with children suffering from febrile convulsions. Methods: This quasi-experimental intervention study was conducted in 2020-2021 among 60 mothers with children suffering from febrile seizures in the hospitals of Birjand, Iran. The sampling method was accessible and then people were randomly divided into two intervention and control groups. After being discharged from the hospital, the intervention group received telenursing (for 2 weeks and 3 sessions each week for 15 minutes via mobile phone and by calling the mothers and sending an educational video). The control group received routine training at discharge. The data collection questionnaire included the demographic and background information and the Spielberger anxiety questionnaire. The Spielberger questionnaire was completed at the beginning and after the end of the intervention. SPSS software version 16 and paired t, independent t and chisquare statistical tests were used for data analysis. Results: Stait and trait anxiety before the intervention was not significant between the control and intervention groups (P=0.865 and P=0.153, respectively). There was a statistically significant difference between the two intervention and control groups in Stait and trait anxiety after the intervention, and it was reduced in the intervention group (P<0.001). Conclusion: Telenursing training was an effective method in reducing the anxiety of mothers with children suffering from febrile convulsions. Therefore, it is suggested to use the telenursing method in order to reduce anxiety among mothers with children suffering from febrile convulsions. [ABSTRACT FROM AUTHOR]

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