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The article focuses on a case of a previously healthy 17-year-old boy admitted to the hospital after a generalized tonic-clonic seizure following fever, malaise, and headache. Topics include the patient's clinical presentation, including disorientation and memory loss, laboratory investigations showing elevated white blood cell count and abnormal cerebrospinal fluid findings, and imaging findings revealing bilateral basal ganglia lesions progressing to involve other brain regions.

Background and Purpose: GRIN‐related disorders are neurodevelopmental disorders caused by mutations in N‐methyl‐D‐aspartate receptor (NMDAR) subunit genes. A large fraction of these mutations lead to a 'gain of function' (GoF) of the NMDAR. Patients present with a range of symptoms including epilepsy, intellectual disability, behavioural and motor. Controlling seizures is a significant unmet medical need in most patients with GRIN‐related disorders. Although several hundred GRIN mutations have been identified in humans, until recently none of the mouse models carrying Grin mutations/deletions showed an epileptic phenotype. The two recent exceptions both carry mutations of GluN2A. The aim of this study was to assess the efficacy of radiprodil, a selective negative allosteric modulator of GluN2B‐containing NMDARs, in counteracting audiogenic seizures (AGS) in a murine model carrying the GluN2A(N615S) homozygous mutation (Grin2aS/S mice). Experimental Approach: Grin2aS/S mice were acutely treated with radiprodil at different doses before the presentation of a high‐frequency acoustic stimulus commonly used for AGS induction. Key Results: Radiprodil significantly and dose‐dependently reduced the onset and severity of AGS in Grin2aS/S mice. Surprisingly, the results revealed a sex‐dependent difference in AGS susceptibility and in the dose‐dependent protection of radiprodil in the two genders. Specifically, radiprodil was more effective in female versus male mice. Conclusion and Implications: Overall, our data clearly show that radiprodil, a GluN2B selective negative allosteric modulator, may have the potential to control seizures in patients with GRIN2A GoF mutations. Further studies are warranted to better understand the sex‐dependent effects observed in this study. [ABSTRACT FROM AUTHOR]

The article discusses the case of a male patient with bilateral temporal lobe epilepsy that was misdiagnosed as non-epileptic spells. Topics discussed include the patient's cardiac and psychological history, electroclinical seizures observed in the patient which were associated with bradycardia, and the diagnostic value of in-home ambulatory electroencephalography.

The identification of the epileptogenic zone (EZ) boundaries is crucial for effective focal epilepsy surgery. We verify the value of a neurophysiological biomarker of focal ictogenesis, characterized by a low‐voltage fast‐activity ictal pattern (chirp) recorded with intracerebral electrodes during invasive presurgical monitoring (stereoelectroencephalography [SEEG]). The frequency content of SEEG signals was retrospectively analyzed with semiautomatic software in 176 consecutive patients with focal epilepsies that either were cryptogenic or presented with discordant anatomoelectroclinical findings. Fast activity seizure patterns with the spectrographic features of chirps were confirmed by computer‐assisted analysis in 95.4% of patients who presented with heterogeneous etiologies and diverse lobar location of the EZ. Statistical analysis demonstrated (1) correlation between seizure outcome and concordance of sublobar regions included in the EZ defined by visual analysis and chirp‐generating regions, (2) high concordance in contact‐by contact analysis of 68 patients with Engel class Ia outcome, and (3) that discordance between chirp location and the visually outlined EZ correlated with worse seizure outcome. Seizure outcome analysis confirms the fast activity chirp pattern is a reproducible biomarker of the EZ in a heterogeneous group of patients undergoing SEEG. [ABSTRACT FROM AUTHOR]

Objective: Due to the high clinical heterogeneity of epilepsy, there is a critical need for novel metrics aimed at capturing its biological and phenotypic complexity. Frailty is increasingly recognized in various medical disciplines as a useful construct to understand differences in susceptibility to adverse outcomes. Here, we develop a frailty index (FI) for patients with epilepsy (PwE) and explore its association with demographic and clinical features. Methods: In this cross‐sectional study, we consecutively enrolled 153 PwE from an outpatient epilepsy clinic. Participants were assessed for various health deficits to calculate the FI. Associations between FI and demographic/clinical features, antiseizure medications (ASMs), and patient‐reported outcomes were analyzed using general linear models and Spearman correlation. Results: The median age at the time of study visit was 47 years (interquartile range = 33–60), and 89 (58.2%) patients were females. Multiple linear regression revealed that the developed 33‐item FI showed an independent association with age, female sex, higher body mass index, family history of epilepsy, intellectual disability, and the number of ASMs used. A robust analysis of covariance showed higher FI levels in patients using cytochrome P450 3A4‐inducer ASMs. We found a moderate positive correlation between FI and psychological distress, lower quality of life, and physical frailty, measured by the Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy Inventory‐10, and handgrip strength, respectively. Finally, a weak association was observed between higher FI scores and an increased number of epileptic falls. Significance: This study highlights the significance of frailty as a comprehensive health measure in epilepsy. It suggests that frailty in this specific population is not only a manifestation of aging but is inherently linked to epilepsy and treatment‐related factors. Future research is warranted to validate and refine the FI in diverse epilepsy populations and investigate its impact on specific adverse outcomes in longitudinal studies. [ABSTRACT FROM AUTHOR]

Objective: Focal to bilateral tonic–clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge‐wise approach that allowed for identification of the individual connections unique to FBTCS. Methods: T1‐weighted and diffusion‐weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex‐matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor‐derived STRs in an edge‐wise approach to determine specific structural connectivity changes associated with seizure generalization in FBTCS compared to matched FS and HPs. Graph theory metrics were computed on both node‐ and edge‐based connectivity matrices. Results: Edge‐wise analyses demonstrated that all significantly abnormal cross‐hemispheric connections belonged to the FBTCS group. Abnormal connections associated with FBTCS were mostly housed in the contralateral hemisphere, with graph metric values generally decreased compared to HPs. In FBTCS, the contralateral amygdala showed selective decreases in the structural connection pathways to the contralateral frontal lobe. Abnormal connections in TLE involved the amygdala, with the ipsilateral side showing increases and the contralateral decreases. All the FS findings indicated higher graph metrics for connections involving the ipsilateral amygdala. Data also showed that some FBTCS connectivity effects are moderated by aging, recent seizure frequency, and longer illness duration. Significance: Data showed that not all STR pathways are equally affected by the seizure propagation of FBTCS. We demonstrated two key biases, one indicating a large role for the amygdala in the propagation of seizures, the other pointing to the prominent role of cross‐hemispheric and contralateral hemisphere connections in FBTCS. We demonstrated topographic reorganization in FBTCS, pointing to the specific WM tracts involved. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of epilepsy in World Health Organization (WHO) grade 2 glioma is high, with seizures being the presenting symptom in 60%–90%. We explore the epidemiology of seizures in this patient population in a regional neurosurgical center. Methods: Electronic health records of patients with histologically‐proven WHO grade 2 glioma (n = 228) were reviewed between 1997 and 2021, with data collected including patient demographics, epilepsy prevalence, and seizure semiology. The influence of seizure type on overall survival was calculated using a Cox proportional hazards model. Results: Overall, 197 of 228 patients (86.4%) were diagnosed with epilepsy—either at presentation or during the course of their disease. Male patients were more likely than female patients to be diagnosed with epilepsy (91.1% vs 77.1%, p =.003) and, in those with epilepsy, more likely to experience at least one focal to bilateral tonic–clonic seizure (69.4% vs 54.1%, p =.05). Patients with left‐sided tumors were twice as likely to have experienced a focal to bilateral tonic–clonic seizure (p =.02, odds ratio [OR] =.47). Predominantly experiencing seizures with motor activity appeared to confer better overall survival, with a 65% decrease in the risk of death 10 years post diagnosis (hazard ratio [HR] =.35, p =.02). This is despite accounting for previously described prognostic markers including tumor histology/genetics, time from diagnosis to surgery, and the extent of tumor resection. Significance: Motor seizure activity is a frequent feature in WHO grade 2 glioma and appears to confer a survival benefit regardless of histology or surgical factors. Seizures due to dominant hemisphere tumors may be more likely to propagate and cause bilateral tonic–clonic activity. [ABSTRACT FROM AUTHOR]

In status epilepticus (SE), "time is brain." Currently, first‐line therapy consists of benzodiazepines (BDZs) and SE is classified by the response to treatment; stage 2 or established SE is defined as "BDZ‐resistant SE." Nonetheless, this classification does not always work, especially in the case of prolonged convulsive SE, where many molecular changes occur and γ‐aminobutyric acid signaling becomes excitatory. Under these circumstances, BDZ therapy might not be optimal, and might be possibly detrimental, if given alone; as the duration of SE increases, so too does BDZ resistance. Murine models of SE showed how these cases might benefit more from synergistic combined therapy from the start. The definition of Stage 1 plus is suggested, as a stage requiring combined therapy from the start, which includes prolonged SE with seizure activity going on for >10 min, the time that marks the disruption of receptor homeostasis, with increased internalization. This specific stage might require a synergistic approach from the start, with a combination of first‐ and second‐line treatment. [ABSTRACT FROM AUTHOR]

Objective: Patients with focal, lesional epilepsy present with seizures at variable ages. Larger lesion size and overlap with sensorimotor or default mode network (DMN) have been associated with younger age at seizure onset in cohorts with mixed types of focal cortical dysplasia (FCD). Here, we studied determinants of age at seizure onset in patients with bottom‐of‐sulcus dysplasia (BOSD), a discrete type of FCD with highly localized epileptogenicity. Methods: Eighty‐four patients (77% operated) with BOSD were studied. Demographic, histopathologic, and genetic findings were recorded. BOSD volume and anatomical, primary versus association, rostral versus caudal, and functional network locations were determined. Normative functional connectivity analyses were performed using each BOSD as a region of interest in resting‐state functional magnetic resonance imaging data of healthy children. Variables were correlated with age at seizure onset. Results: Median age at seizure onset was 5.4 (interquartile range = 2–7.9) years. Of 50 tested patients, 22 had somatic and nine had germline pathogenic mammalian target of rapamycin (mTOR) pathway variants. Younger age at seizure onset was associated with greater BOSD volume (p =.002), presence of a germline pathogenic variant (p =.04), DMN overlap (p =.04), and increased functional connectivity with the DMN (p <.05, false discovery rate corrected). Location within sensorimotor cortex and networks was not associated with younger age at seizure onset in our relatively small but homogenous cohort. Significance: Greater lesion size, pathogenic mTOR pathway germline variants, and DMN connectivity are associated with younger age at seizure onset in small FCD. Our findings strengthen the suggested role of DMN connectivity in the onset of FCD‐related focal epilepsy and reveal novel contributions of genetic etiology. [ABSTRACT FROM AUTHOR]

Objective: Brain infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6J mice can induce acquired epileptogenesis. Diet alters acute seizure incidence in TMEV‐infected mice; yet it is unclear whether intestinal dysbiosis may also impact acute or chronic behavioral comorbidities. This study thus assessed the impact of diet formulation and sterilization on acute seizure presentation, gut microbiome composition, and epilepsy‐related chronic behavioral comorbidities. Methods: Baseline fecal samples were collected from male C57BL/6J mice (4‐ to 5‐weeks‐old; Jackson Labs) upon facility arrival. Mice were randomized to either autoclaved (AC) or irradiated diet (IR) (Prolab RMH 3000) or IR (Picolab 5053). Three days later, mice underwent intracerebral TMEV or phosphate‐buffered saline (PBS) injection. Fecal samples were collected from a subset of mice at infection (Day 0) and Day 7 post‐infection. Epilepsy‐related working memory deficits and seizure threshold were assessed 6 weeks post‐infection. Gut microbiome diversity was determined by 16S rRNA amplicon sequencing of fecal samples. Results: TMEV‐infected mice displayed acute handling‐induced seizures, regardless of diet: 28 of 57 IR Picolab 5053 (49.1%), 30 of 41 IR Prolab RMH 3000 (73.2%), and 47 of 77 AC Prolab RMH 3000 (61%) mice displayed seizures. The number of observed seizures differed significantly by diet: IR Picolab 5053 diet‐fed mice had 2.2 ± 2.8 seizures (mean ± standard deviation), IR Prolab RMH 3000 diet‐fed mice had 3.5 ± 2.9 seizures, and AC Prolab RMH 3000 diet‐fed mice had 4.4 ± 3.8 seizures during the 7‐day monitoring period. Gut microbiome composition differed significantly in TMEV‐infected mice fed the AC Prolab RMH 3000 diet, with measured differences in gram‐positive bacteria. These mice also displayed worsened long‐term working memory deficits. Significance: Diet‐induced differences in intestinal dysbiosis in the TMEV model are associated with marked changes in acute seizure presentation, symptomatic recovery, and onset of chronic behavioral comorbidities of epilepsy. Our study reveals a novel disease‐modifying impact of dietary manipulation on intestinal bacterial species after TMEV‐induced acute seizures. [ABSTRACT FROM AUTHOR]

We present two cases, in which end-of-life patients were inadvertently treated with bolus infusions of undiluted subcutaneous levetiracetam. The patients were treated for three and four days respectively. In both cases, the course of treatment was uneventful. Especially, no seizures, nor local irritation was observed. Administration of undiluted subcutaneous levetiracetam as intermittent bolus infusions by hand holds alluring properties for end-of-life patients. Amongst others reducing patient discomfort, increasing freedom of movement, and accessibility to essential seizure prophylaxis by eliminating the need for a syringe driver, thereby helping accommodate many patients wish to die in their own home. However, pharmacokinetics, efficacy, and safety, including the optimum dilution and administration time of the subcutaneous preparation remains to be determined in clinically controlled trials. [ABSTRACT FROM AUTHOR]

Approximately 22% of Alzheimer's disease (AD) patients suffer from seizures, and the co-occurrence of seizures and epileptiform activity exacerbates AD pathology and related cognitive deficits, suggesting that seizures may be a targetable component of AD progression. Given that alterations in neuronal excitatory:inhibitory (E:I) balance occur in epilepsy, we hypothesized that decreased markers of inhibition relative to those of excitation would be present in AD patients. We similarly hypothesized that in 5XFAD mice, the E:I imbalance would progress from an early stage (prodromal) to later symptomatic stages and be further exacerbated by pentylenetetrazol (PTZ) kindling. Post-mortem AD temporal cortical tissues from patients with or without seizure history were examined for changes in several markers of E:I balance, including levels of the inhibitory GABAA receptor, the sodium potassium chloride cotransporter 1 (NKCC1) and potassium chloride cotransporter 2 (KCC2) and the excitatory NMDA and AMPA type glutamate receptors. We performed patch-clamp electrophysiological recordings from CA1 neurons in hippocampal slices and examined the same markers of E:I balance in prodromal 5XFAD mice. We next examined 5XFAD mice at chronic stages, after PTZ or control protocols, and in response to chronic mTORC1 inhibitor rapamycin, administered following kindled seizures, for markers of E:I balance. We found that AD patients with comorbid seizures had worsened cognitive and functional scores and decreased GABAA receptor subunit expression, as well as increased NKCC1/KCC2 ratios, indicative of depolarizing GABA responses. Patch clamp recordings of prodromal 5XFAD CA1 neurons showed increased intrinsic excitability, along with decreased GABAergic inhibitory transmission and altered glutamatergic neurotransmission, indicating that E:I imbalance may occur in early disease stages. Furthermore, seizure induction in prodromal 5XFAD mice led to later dysregulation of NKCC1/KCC2 and a reduction in GluA2 AMPA glutamate receptor subunit expression, indicative of depolarizing GABA receptors and calcium permeable AMPA receptors. Finally, we found that chronic treatment with the mTORC1 inhibitor, rapamycin, at doses we have previously shown to attenuate seizure-induced amyloid-β pathology and cognitive deficits, could also reverse elevations of the NKCC1/KCC2 ratio in these mice. Our data demonstrate novel mechanisms of interaction between AD and epilepsy and indicate that targeting E:I balance, potentially with US Food and Drug Administration-approved mTOR inhibitors, hold therapeutic promise for AD patients with a seizure history. [ABSTRACT FROM AUTHOR]

Objective This study aimed to use machine learning to evaluate the risk factors of seizures and develop a model and nomogram to predict seizures in children with coronavirus disease 2019 (COVID-19). Material and methods A total of 519 children with COVID-19 were assessed to develop predictive models using machine learning algorithms, including extreme gradient boosting (XGBoost), random forest (RF) and logistic regression (LR). The performance of the models was assessed using area under the receiver operating characteristic curve (AUC) values. Importance matrix plot and SHapley Additive exPlanations (SHAP) values were calculated to evaluate feature importance and to show the visualization results. The nomogram and clinical impact curve were used to validate the final model. Results Two hundred and seventeen children with COVID-19 had seizures. According to the AUC, the RF model performed the best. Based on the SHAP values, the top three most important variables in the RF model were neutrophil percentage, cough and fever duration. The nomogram and clinical impact curve also verified that the RF model possessed significant predictive value. Conclusions Our research indicates that the RF model demonstrates excellent performance in predicting seizures, and our novel nomogram can facilitate clinical decision-making and potentially offer benefit for clinicians to prevent and treat seizures in children with COVID-19. [ABSTRACT FROM AUTHOR]

Familial hemiplegic migraine (FHM), an autosomal dominant subtype of hemiplegic migraine, is a channelopathy presenting with severe headache, visual field defect, paresthesia, unilateral motor deficit, encephalopathy, seizures and aphasia. This cross-sectional study was conducted over 10 months in children aged 1–18 years suspected of hemiplegic migraine at a tertiary care pediatric hospital. Fourteen children were screened and five children with genetically confirmed FHM were included. The symptoms in the study population were paroxysmal hemiparesis (5/5), headache (5/5) and focal seizures (1/5). The hemiplegia episodes lasted from 4 h to 7 days. The mean age at the onset of neurological symptoms was 6.8 ± 0.7 years and the mean age at diagnosis was 12.8 ± 1.7 years, with a mean delay of 6.1 ± 1.9 years for the diagnosis. Neuroimaging during acute episodes revealed accentuated gray, white differentiation in the contralateral cerebral hemisphere with mild effacement of sulcal spaces in T2/fluid-attenuated inversion recovery (FLAIR) images. Genetic testing revealed ATP1A2 mutations (FHM2) in 4/5 and SCN1A (FHM3) in 1/5 patients. All of them (5/5) were initiated on oral topiramate and had favorable treatment responses with a mean follow-up duration of 7 ± 1.4 months. Diagnosis of FHM is mainly clinical and can be confirmed by genetic analysis. Perfusion and diffusion-weighted MRI should be considered during acute headache episodes, as it is mostly normal in symptom-free periods. Routine MRI sequences like T1 weighted, T2 weighted, FLAIR and contrast remain normal even during acute attacks. [ABSTRACT FROM AUTHOR]

Epilepsy is a neurological disorder experienced as seizures, which can occur at intermittent times along a continuum of severity. Currently, there is a need for scholarship exploring how epilepsy impacts career development. This reflective lifeworld phenomenological study examined, "How is career development experienced in individuals living with epilepsy? Eight participants were interviewed to explore the intersubjective contextual experience of the phenomenon. The resulting structural essence, running on ice in the midst of the fog, contains four constituents: existence of epilepsy, running on ice, the fog, and gaining traction. Implications for career development counseling and scholarship are described. [ABSTRACT FROM AUTHOR]

Purpose: Alcohol is implicated in epileptogenesis and seizures attack. An increasing number of studies about alcohol and epilepsy have been published. We aimed to assess research trends and hot spots in the field of alcohol and epilepsy. Patients and Methods: Literature concerning alcohol and epilepsy was systemically searched through the Web of Science database. Collaborative maps were quantitatively analyzed by using the VOSviewer and CiteSpace tools. Results: A total of 1578 papers about the field of alcohol and epilepsy were taken into analysis, which was written by 6840 authors from 2153 institutions in 85 countries, published in 676 journals, and cited 79 667 references from 10 750 journals. The United States was the leading country and had close ties with others. The University of Toronto was the most productive institution. Alcoholism‐clinical and experimental research was the fastest‐growing journal. Richard J. Bodnar was the author contributing the most literature. Analysis of keywords showed epilepsy, alcohol, seizures, alcohol withdrawal, and management were common themes. Conclusion: The presented study conducted the first bibliometric analysis of the field of alcohol and epilepsy, which will provide insights into the latest progress, evolution paths, frontier research hot spots, and future research trends in the field. [ABSTRACT FROM AUTHOR]

The article addresses the recognition of motor versus nonmotor seizures in adolescents, highlighting the frequent misidentification of nonmotor seizures in emergency department settings, potentially delaying diagnosis and treatment. Topics include the high rate of misrecognition of nonmotor seizures, particularly among adolescents, and the importance of improving interviewing techniques in emergency departments to expedite diagnosis.

Background: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate–severe traumatic brain injury (TBI). Methods: We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate–severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate–severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. Results: The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. Conclusions: Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate–severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence). [ABSTRACT FROM AUTHOR]

Background: Iatrogenic malnutrition is a significant burden to patients, clinicians, and health care systems. Compared with well-nourished patients, underfed patients (those who receive less than 80% of their daily energy requirement) have more adverse outcomes related to nutritional status. Volume-based protocols allow for catch-up titrations, are consistently superior to rate-based protocols, and can be implemented in most settings. Local Problem: This project was conducted in an 8-bed neuroscience intensive care unit in which up to 41% of patients who required enteral feeding were underfed. Methods: This quality improvement clinical practice change project used a before-and-after design to evaluate (1) the effect of implementing a volume-based feeding protocol on the delivery of enteral feeds and (2) the effect of a nutrition-based project on staff members' attitudes regarding nutrition in critical care. The effectiveness of a volume-based feeding titration protocol was compared with that of a rate-based feeding protocol for achieving delivery of at least 80% of prescribed nutrition per 24-hour period. Staff members' attitudes were assessed using a survey before and after the project. Results: During 241 enteral feeding days (n = 40 patients), the percentage of delivered enteral feeding volume and the percentage of days patients received at least 80% of the prescribed volume increased after volume-based feeding was implemented. After project implementation, 74 staff members reported increased emphasis on nutrition delivery in their practice and a higher level of agreement that nutrition is a priority when caring for critically ill patients. Conclusions: Using a volume-based feeding protocol with supplemental staff education resulted in improved delivery of prescribed enteral feeding. [ABSTRACT FROM AUTHOR]

ADPRHL2 is involved in posttranslational modification and is known to have a role in physiological functions such as cell signaling, DNA repair, gene control, cell death, and response to stress. Recently, a group of neurological disorders due to ADPRHL2 variants is described, characterized by childhood-onset, stress-induced variable movement disorders, neuropathy, seizures, and neurodegenerative course. We present the diagnostic pathway of two pediatric patients with episodic dystonia and ataxia, who later had a neurodegenerative course complicated by central hypoventilation syndrome due to the same homozygous ADPRHL2 variant. We conducted a systematic literature search and data extraction procedure following the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 statement in terms of patients with ADPRHL2 variants, from 2018 up to 3 February, 2023. In total, 12 articles describing 47 patients were included in the final analysis. Median age at symptom onset was 2 (0.7–25) years, with the most common presenting symptoms being gait problems (n = 19, 40.4%), seizures (n = 16, 34%), ataxia (n = 13, 27.6%), and weakness (n = 10, 21.2%). Triggering factors (28/47; 59.5%) and regression (28/43; 60.4%), axonal polyneuropathy (9/23; 39.1%), and cerebral and cerebellar atrophy with white matter changes (28/36; 77.7%) were the other clues. The fatality rate and median age of death were 44.6% (n = 21) and 7 (2–34) years, respectively. ADPRHL2 variants should be considered in the context of episodic, stress-induced pediatric and adult-onset movement disorders and seizures. [ABSTRACT FROM AUTHOR]

Aim: To investigate the seizure course of PCDH19 clustering epilepsy (PCDH19‐CE) in a cohort of female children in China. Method: This ambidirectional cohort study examined 113 female patients with PCDH19‐CE through multicentre collaboration. Prognostic factors for seizure freedom were evaluated by multivariate Cox regression analysis. Results: The median seizure course period from seizure onset was 6 years 6 months. Of 113 patients, 78% and 56% experienced seizure freedom for at least 1 year and at least 2 years respectively. In patients younger than 5 years (n = 30), 5 to 10 years (n = 52), and older than 10 years (n = 31), 57%, 81%, and 94% experienced at least 1 year of seizure freedom, and 32%, 52%, and 84% experienced at least 2 years of seizure freedom, respectively. However, 58% (65 out of 113) relapsed at least once after more than 1 year of seizure freedom without trigger exposure (40%) or because of common triggers, including fever (43%) and antiseizure medication (ASM) reduction (29%). There was an 84% risk of seizure relapse after ASM reduction attempts. The likelihood of seizure freedom decreased with early age at seizure onset and developmental delay. Interpretation: Patients with PCDH19‐CE exhibit increasing seizure freedom with age, but there is a risk of relapse. ASM reduction in children younger than 10 years old requires caution. Patients with early seizure onset and developmental delay have a reduced chance of seizure freedom. What this paper adds: The seizure freedom rate in PCDH19 clustering epilepsy gradually increases with age.The disease course is characterized by relapsing–remitting seizures.Antiseizure medication reduction requires caution for patients younger than 10 years of age.Patients with early seizure onset and developmental delay are less likely to achieve seizure freedom. [ABSTRACT FROM AUTHOR]

• Automated EEG software detected focal IEDs during long-term video EEG monitoring in all included patients with IGE (n = 32). • Almost a quarter of all detected IEDs showed a negative focal maximum. • Focal seizure symptoms were seen in three-quarter of IGE patients in our study. Focal seizure symptoms (FSS) and focal interictal epileptiform discharges (IEDs) are common in patients with idiopathic generalized epilepsies (IGEs), but dedicated studies systematically quantifying them both are lacking. We used automatic IED detection and localization algorithms and correlated these EEG findings with clinical FSS for the first time in IGE patients. 32 patients with IGEs undergoing long-term video EEG monitoring were systematically analyzed regarding focal vs. generalized IEDs using automatic IED detection and localization algorithms. Quantitative EEG findings were correlated with FSS. We observed FSS in 75% of patients, without significant differences between IGE subgroups. Mostly varying/shifting lateralizations of FSS across successive recorded seizures were seen. We detected a total of 81,949 IEDs, whereof 19,513 IEDs were focal (23.8%). Focal IEDs occurred in all patients (median 13% focal IEDs per patient, range 1.1 – 51.1%). Focal IED lateralization and localization predominance had no significant effect on FSS. All included patients with IGE showed focal IEDs and three-quarter had focal seizure symptoms irrespective of the specific IGE subgroup. Focal IED localization had no significant effect on lateralization and localization of FSS. Our findings may facilitate diagnostic and treatment decisions in patients with suspected IGE and focal signs. [ABSTRACT FROM AUTHOR]

Bovine familial convulsions and ataxia (BFCA) is considered an autosomal dominant syndrome with incomplete penetrance. Nine Angus calves from the same herd were diagnosed with BFCA within days of birth. Necropsy revealed cerebellar and spinal cord lesions associated with the condition. Parentage testing confirmed that all affected calves had a common sire. The sire was then bred to 36 cows across two herds using artificial insemination, producing an additional 14 affected calves. The objective of this investigation was to identify hypothesized dominant genetic variation underlying the condition. Whole‐genome sequencing was performed on the sire, six affected and seven unaffected paternal half‐sibling calves and combined with data from 135 unrelated controls. The sire and five of the six affected calves were heterozygous for a nonsense variant (Chr7 g.12367906C>T, c.5073C>T, p.Arg1681*) in CACNA1A. The other affected calves (N = 8) were heterozygous for the variant but it was absent in the other unaffected calves (N = 7) and parents of the sire. This variant was also absent in sequence data from over 6500 other cattle obtained via public repositories and collaborator projects. The variant in CACNA1A is expressed in the cerebellum of the ataxic calves as detected in the transcriptome and was not differentially expressed compared with controls. The CACNA1A protein is part of a highly expressed cerebellar calcium voltage gated channel. The nonsense variant is proposed to cause haploinsufficiency, preventing proper transmission of neuronal signals through the channel and resulting in BFCA. [ABSTRACT FROM AUTHOR]

To evaluate EEG monitoring during neonatal ECMO and to identify any correlations between seizure detection to abnormal neuroimaging. Eight-year, service evaluation of neonates who received at least one continuous EEG (cEEG) whilst on ECMO at Great Ormond Street Hospital. Pearson's chi-square test and multivariate logistic regression analysis were used to assess clinical and EEG variables association with seizures and neuroimaging findings. Fifty-seven neonates were studied; 57 cEEG recordings were reviewed. The incidence of seizures was 33% (19/57); of these 74% (14/19) were electrographic-only. The incidence of status epilepticus was 42%, (8/19 with 6 neonates having electrographic-only status and 2 electro-clinical status. Seizures were detected within an hour of recording in 84%, (16/19). The overall mortality rate was 39% (22/57). Seizure detection was strongly associated with female gender (OR 4.8, 95% CI: 1.1–20.4, p = 0.03), abnormal EEG background activity (OR 2.8, 95% CI: 1.1–7.4, p = 0.03) and abnormal EEG focal features (OR 23.6, 95% CI: 5.4–103.9, p = 0.001). There was a strong association between the presence of seizures and abnormal neuroimaging findings (OR 10.9, 95% CI: 2.8–41.9, p = 0.001). Neonates were highly likely to have abnormal neuroimaging findings in the presence of severely abnormal background EEG (OR 9.5, 95% CI 1.7–52.02, p = 0.01) and focal EEG abnormalities (OR 6.35, 95% CI 1.97–20.5, p = 0.002) Conclusion: The study highlights the importance of cEEG in neonates undergoing ECMO. An association between seizure detection and abnormal neuroimaging findings was described. What is Known: • Patients on ECMO are at a higher risk of seiures. • Continuous EEG monitoring is recommended by the ACNS for high risk and ECMO patients. What is New: • In this cohort, neonates with sezirues were 11 times more likely of having abnromal neuroimaging findings. • Neonates with burst suppressed or suppressed EEG background were 9.5 times more likely to have abnormal neuroimaging findings. What does this study add? • This study reports a 33% incidence of neonatal seizures during ECMO. • Neonates with seizures were 11 times more likely to have an abnormal brain scan. • The study captures the real-time approach of EEG monitoring. • Recommended cEEG monitoring should last at least 24 h for ECMO patients. • This is the first study to assess this in neonates only. [ABSTRACT FROM AUTHOR]

Background: Breakthrough seizures and status epilepticus require urgent management. Administration of intravenous push (IVP) levetiracetam has been demonstrated to be safe as compared to intravenous piggyback (IVPB). This transition can potentially offer faster time to administration and reduced drug and material cost. The objective of this study was to observe safety of administration in patients receiving levetiracetam via IVP compared to IVPB in acute care settings. Methods: This is a multi-center, observational, retrospective cohort study of 1214 adult patients who received levetiracetam pre- and post-implementation of IVP over a 6 month timespan. Primary outcome was time from order verification to administration of urgent first-time doses. Secondary outcomes included time to administration of loading doses and cost. Safety outcome was infusion site related reactions. Results: Time from order verification to administration of urgent first-time doses pre- and post-implementation of IVP administration was reduced from 61 minutes to 47 minutes (P =0.0002). Infusion site related reactions were observed in 6 out of 5432 doses in the IVPB arm and in 5 out of 4700 doses in the IVP arm (P =1). Total estimated cost was $76,171.96 for the 5449 IVPB total doses and $11,484.33 for the 4721 IVP total doses. Conclusions: Transition from IVPB to IVP administration reduced time from order verification to administration of urgent first-time doses with both administrations having similar incidence of infusion site related reactions. Cost savings and improved workflow were observed. Levetiracetam administered via IVP may be considered as a safe alternative method of administration in the acute care setting. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy of stiripentol in Dravet syndrome children was evidenced in two randomized, double-blind, placebo-controlled, phase 3 studies, namely STICLO France (October 1996–August 1998) and STICLO Italy (April 1999–October 2000), but data were not fully exploited at the time. Methods: This post-hoc analysis used additional information, notably collected during the open-label extension (OLE) month, or reported by caregivers in individual diaries, to evaluate new outcomes. Results: Overall, 64 patients were included (31 in the placebo group, 33 in the stiripentol group) of whom 34 (53.1%) were female. Patients' mean and median (25%; 75%) age were 9.2 years (range 3.0–20.7 years) and 8.7 years (6.0; 12.1) respectively. At the end of the double-blind treatment period, 72% of the patients in the stiripentol group had a ≥ 50% decrease in generalized tonic–clonic seizure (GTCS) frequency, versus 7% in the placebo group (P < 0.001), 56% had a profound (≥ 75%) decrease versus 3% in the placebo group (P < 0.001), and 38% were free of GTCS, but none in the placebo group (P < 0.001). The onset of stiripentol efficacy was rapid, significant from the fourth day of treatment onwards. The median longest period of consecutive days with no GTCS was 32 days in the stiripentol group compared to 8.5 days in the placebo group (P < 0.001). Further to the switch to the third month OLE, an 80.2% decrease in seizure frequency from baseline was observed in patients previously receiving placebo, while no change in efficacy was observed in those already on stiripentol. Adverse events were more frequent in the stiripentol group, with significantly more episodes of somnolence, anorexia, and weight decrease than in the placebo group. Conclusion: Altogether these new analyses of the STICLO data reinforce the evidence for a remarkable efficacy of stiripentol in Dravet syndrome, with a demonstrated rapid onset of action and sustained response, as also evidenced in further post-randomized trials. [ABSTRACT FROM AUTHOR]

Introduction: It is important to assess the effectiveness of an antiseizure medication in treating different epilepsy aetiologies to optimise individualised therapeutic approaches. Data from the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) Extension study were used to assess the effectiveness and safety/tolerability of perampanel (PER) when used to treat individuals with a range of epilepsy aetiologies in clinical practice. Methods: A post hoc analysis was conducted of PERMIT Extension data from individuals with a known aetiology. Retention was assessed after 3, 6 and 12 months. Effectiveness was assessed after 3, 6 and 12 months and at the last visit (last observation carried forward). Effectiveness assessments included responder rate (≥ 50% seizure frequency reduction) and seizure freedom rate (no seizures since at least the prior visit). Safety/tolerability was assessed by evaluating adverse events (AEs) and AEs leading to discontinuation. Results: PERMIT Extension included 1945 individuals with structural aetiology, 1012 with genetic aetiology, 93 with an infectious aetiology, and 26 with an immune aetiology. Retention rates at 12 months were 61.1% (structural), 65.9% (genetic), 56.8% (infectious) and 56.5% (immune). At the last visit, responder rates (total seizures) were 43.3% (structural), 68.3% (genetic), 37.0% (infectious) and 20.0% (immune), and corresponding seizure freedom rates were 15.8%, 46.5%, 11.1% and 5.0%, respectively. AE incidence rates were 58.0% (structural), 46.5% (genetic), 51.1% (infectious) and 65.0% (immune), and corresponding rates of discontinuation due to AEs over 12 months were 18.9%, 16.4%, 18.5% and 21.7%, respectively. The types of AEs reported were generally consistent across aetiology subgroups, with no idiosyncratic AEs emerging. Conclusion: Although PER was effective and generally well tolerated when used to treat individuals with a range of epilepsy aetiologies in clinical practice, variability in its effectiveness and tolerability across the subgroups indicates that PER may be particularly useful for individuals with specific epilepsy aetiologies. [ABSTRACT FROM AUTHOR]

Meningeal carcinomatosis (MC) has an extremely poor prognosis and can present with various neurological symptoms. A 68-year-old man presented to our hospital with a 1 month history of headache and nausea followed by sudden decrease in vision in both eyes. Whilst being examined in the ophthalmology department he lost consciousness and had a generalised tonic clonic seizure. Accordingly, he was transferred to the Emergency Department. Head magnetic resonance imaging showed hydrocephalus. Abdominal contrast-enhanced computed tomography scanning reported changes suggestive of gastric carcinoma. Cerebrospinal fluid cytological examination showed numerous atypical cells, leading to the diagnosis of MC. An upper gastrointestinal endoscopy revealed an advanced gastric tumour. Systemic chemotherapy was initiated, however, he died within 16 days of admission. At autopsy, poorly differentiated adenocarcinoma was identified in the subarachnoid space, however it had not invaded the brain parenchyma or optic chiasm. This is the first report of loss of vision being the first presenting symptom of new-onset gastric carcinoma with MC. Although rare, MC should be suspected in cases where patients present with sudden loss of vision and symptoms of meningeal irritation, where there are no ophthalmological findings to explain the vision loss. [ABSTRACT FROM AUTHOR]

Various factors contribute to the development of infection-related acute encephalopathy (AE) in children, such as infectious agents and chronic underlying disorders. We studied underlying disorders in children with AE to identify predisposing factors of AE. We investigated underlying disorders or past histories in patients with two types of AE from the database in the Tokai area of Japan between 2009 and 2022: 204 patients with AE with reduced subcortical diffusion (AED) and 137 with clinically mild encephalopathy with a reversible splenial lesion (MERS). We compared them with 89 patients with acute disseminated encephalomyelitis (ADEM) to clarify the specific disorders in the two AE types. The prevalence of underlying disorders in AED (34%, 70 patients) was significantly higher than that in ADEM (12%, 11 patients) (P < 0.01). The prevalence of underlying disorders in MERS was 23% (32 patients). The underlying disorders included seizure disorders, premature birth, genetic/congenital disorders, and endocrine/renal diseases. In patients with seizure disorders in AED, five patients (18%) had Dravet syndrome and four (15%) had West syndrome, whereas none with MERS had these syndromes. Twenty-five (12%) of 204 patients with AED, three (2%) with MERS, and one (1%) with ADEM were preterm or low birth weight. The high prevalence of seizure disorders suggests that seizure susceptibility is an important predisposing factor in AED. Premature birth also has an impact on the development of AED. Caution is required regarding the development of AE in patients with chronic seizure disorders or premature birth. [ABSTRACT FROM AUTHOR]

There is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and explore the electroencephalographic seizure response to lacosamide in neonates. A retrospective cohort study was conducted using data from seven pediatric hospitals from January 2009 to February 2020. For safety outcomes, neonates were followed for ≤30 days from index date. Electroencephalographic response of lacosamide was evaluated based on electroencephalographic reports for ≤3 days. Among 47 neonates, 98% received the first lacosamide dose in the intensive care units. During the median follow-up of 12 days, 19% of neonates died, and the crude incidence rate per 1000 patient-days (95% confidence interval) of the adverse events by diagnostic categories ranged from 2.8 (0.3, 10.2) for blood or lymphatic system disorders and nervous system disorders to 10.5 (4.2, 21.6) for cardiac disorders. Electroencephalographic seizures were observed in 31 of 34 patients with available electroencephalographic data on the index date. There was seizure improvement in 29% of neonates on day 1 and also in 29% of neonates on day 2. On day 3, there was no change in 50% of neonates and unknown change in 50% of neonates. The results are reassuring regarding the safety of lacosamide in neonates. Although some neonates had fewer seizures after lacosamide administration, the lack of a comparator arm and reliance on qualitative statements in electroencephalographic reports limit the preliminary efficacy results. [ABSTRACT FROM AUTHOR]

Epilepsy is a type of brain disorder triggered by an abrupt electrical imbalance of neuronal networks. An electroencephalogram (EEG) is a diagnostic tool to capture the underlying brain mechanisms and detect seizure onset in epileptic patients. To detect seizures, neurologists need to manually monitor EEG recordings for long periods, which is challenging and susceptible to errors depending on expertise and experience. Therefore, automatic identification of seizure and seizure-free EEG signals becomes essential. This study introduces a method based on the features extracted from the phase space reconstruction for classifying seizure and seizure-free EEG signals. The computed features are derived from the elliptical area and interquartile range of the Euclidean distance by varying percentage values of data points ranging from 50 to 100%. We consider two public datasets and evaluate these features in each EEG epoch that includes the healthy, interictal, preictal, and ictal stages of epileptic subjects, utilizing the K-nearest neighbor classifier for classification. Results show that the features have higher values during the seizure than the seizure-free EEG signals and healthy subjects. Furthermore, the proposed features can effectively discriminate seizure EEG signals from the seizure-free and normal subjects with 100% accuracy, sensitivity, and specificity in both datasets. Likewise, the classification between the preictal stage and seizure EEG signals attains 98% accuracy. Overall, the reconstructed phase space features significantly enhance the accuracy of detecting epileptic EEG signals compared with existing methods. This advancement holds great potential in assisting neurologists in swiftly and accurately diagnosing epileptic seizures from EEG signals. [ABSTRACT FROM AUTHOR]

Companions (i.e., friends, family members, and other accompanying persons) play an important role in seizure clinic consultations, providing information that patients cannot. The COVID-19 pandemic has seen an increase in these consultations being conducted via telephone. Little is known, however, about how this shift might affect companion participation. Using conversation analysis applied to a set of recorded telephone neurologist-patient-companion consultations (n = 9) and comparable moments drawn from a set of face-to-face consultations (n = 37) (both collected in the UK), we aimed to explore this impact and to identify communication methods that clinicians can use to manage companion participation during telephone consultations. We identified four ways in which participation was observably affected by the telephone. Telephone consultations could make it unclear whether a companion was present and make it difficult for the companion to communicate directly with the neurologist. Passing the floor from one speaker to another was more complex remotely, which could also restrict the patient's own participation once the companion had the floor. These issues are rooted in the limitations of the telephone as a communication medium. Based on the issues identified, we conclude our analysis by highlighting some of the ways in which neurologists and other health professionals can manage companion participation in telephone consultations. These include encouraging the use of speakerphone, checking whether a companion is present throughout the call, keeping track of who can hear what throughout the call, and directing questions using given names to avoid ambiguity. [ABSTRACT FROM AUTHOR]

Objective: The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy. Methods: Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video‐electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4). Results: Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body‐turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002). Interpretation: This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age‐dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138–1148 [ABSTRACT FROM AUTHOR]

Objective: In the era of stereoelectroencephalography (SEEG), many studies have been devoted to understanding the role of interictal high‐frequency oscillations. High‐frequency activity (HFA) at seizure onset has been identified as a marker of epileptogenic zone. We address the physiological significance of ictal HFAs and their relation to clinical semiology. Methods: We retrospectively identified patients with pure focal primary motor epilepsy. We selected only patients in whom SEEG electrodes were optimally placed in the motor cortex as confirmed by electrical stimulation. Based on these narrow inclusion criteria, we extensively studied 5 patients (3 males and 2 females, mean age = 22.4 years) using time–frequency analysis and time correlation with motor signs onset. Results: A total of 157 analyzable seizures were recorded in 5 subjects. The first 2 subjects had tonic or clonic semiology with rare secondary generalization. Subject 3 had atonic onset followed by clonic hand/arm flexion. Subject 4 had clusters of tonic and atonic facial movements. Subject 5 had upper extremity tonic movements. The median frequency of the fast activity extracted from the Epileptogenic Zone Fingerprint pipeline in the first 4 subjects was 76 Hz (interquartile range = 21.9Hz). Positive motor signs did not occur concomitantly with high gamma activity developing in the motor cortex. Motor signs began at the end of HFAs. Interpretation: This study supports the hypothesis of an inhibitory effect of ictal HFAs. The frequency range in the gamma band was associated with the direction of the clinical output effect. Changes from inhibitory to excitatory effect occurred when discharge frequency dropped to low gamma or beta. ANN NEUROL 2024;95:1127–1137 [ABSTRACT FROM AUTHOR]

Pathogenic variants in genes encoding ion channels are causal for various pediatric and adult neurological conditions. In particular, several epilepsy syndromes have been identified to be caused by specific channelopathies. These encompass a spectrum from self-limited epilepsies to developmental and epileptic encephalopathies spanning genetic and acquired causes. Several of these channelopathies have exquisite responses to specific antiseizure medications (ASMs), while others ASMs may prove ineffective or even worsen seizures. Some channelopathies demonstrate phenotypic pleiotropy and can cause other neurological conditions outside of epilepsy. This review aims to provide a comprehensive exploration of the pathophysiology of seizure generation, ion channels implicated in epilepsy, and several genetic epilepsies due to ion channel dysfunction. We outline the clinical presentation, pathogenesis, and the current state of basic science and clinical research for these channelopathies. In addition, we briefly look at potential precision therapy approaches emerging for these disorders. [ABSTRACT FROM AUTHOR]

Objective: Preterm neonates encounter hyperoxia relatively early, and are more exposed to hyperoxic stress due to their insufficient antioxidant defense mechanisms. This study was planned around the hypothesis that this hyperoxic effect may cause a disposition to future acute seizures. Methods: This study was composed of two main groups Hyperoxy and Control (Room air with normal O2 levels) Groups. Group 1 – hyperoxia (Study): The experimental group consisted of premature newborn rats exposed to hyperoxia with their dams from birth to postnatal day 5. Group 2 – room air (Control): The group was not exposed to hyperoxia and housed the same room air and temperature as their dams. Female, Acute Epilepsy Female, Male, Acute Epilepsy Male, and a total of eight subgroups were formed in both the control and hyperoxia groups. When the rats were two months old, intracranial electrodes were attached to obtain electrocorticography (ECoG) recordings. Pre-model recordings were taken, after which an acute pentylenetetrazole (PTZ) model of absence seizure was induced by the intraperitoneal administration of PTZ at 50 mg/kg. ECoG records were examined using the PowerLab system for 180 min. Spike wave number and duration, Spike wave frequency and amplitude data were evaluated.Results: Seven female and three male rats were exposed to hyperoxia, and a control group of five female and three male rats were included in the study. The median interquartile range for spike wave latency in the hyperoxia and control groups were 1112 (644–1545) and 654 (408–1152), frequency 4476 (3120–7421) and 3934 (2264–4704), and amplitude data 0.68 (0.59–0.79) and 0.52 (0.37–0.67), respectively. Although a difference was observed in median values capable of constituting susceptibility to epilepsy, the difference was not statistically significant (p > 0.05). In terms of gender, spike-wave counts were significantly higher in female rats (p < 0.05). Females exposed to hyperoxia were more susceptible to epilepsy than both males and females in the control group (p < 0.05).Conclusion: Exposure to hyperoxia in the first days of life of premature neonates due to their susceptibility to oxidative stress and insufficient antioxidant mechanisms, can cause a disposition to acute seizures. As a result, females exposed to hyperoxia during the neonatal period may be prone to epilepsy in maturity. [ABSTRACT FROM AUTHOR]

Background: Assessment of wild edible vegetables (WEVs) from the ethnobotanical approach is a significant key to understanding indigenous knowledge systems. The available literature has revealed a tremendous decline in knowledge of WEVs over the last few decades. The main purpose of this study was to document and analyse the traditional knowledge of WEVs among the two major ethnic groups of Mizoram regarding their use and the diversity associated with the importance of traditional medicines. Secondly, a market survey will be conducted to determine the status of available WEVs. Methods: This study conducted an ethnobotanical survey among 72 informants through semi-structured interviews and questionnaires besides direct field observations. The documented data were quantitatively analysed using various ethnobotanical indices, including Informant's consensus factor (ICF), Fidelity level value (Fl), and Direct matrix ranking (DMR). A marketing survey was conducted in the Bara Bazar, Mizoram's most prominent local market. A total of 38 vendor informants were interviewed to observe and collect the price of commonly sold WEVs. Results: A total of 70 WEVs, distributed in 58 genera under 36 families, were documented and identified. Of these, 33 WEVs were of medicinal importance. Leafy vegetables were documented as the most frequently consumed parts (55.71%). The majority (44.29%) of the plants documented were consumed in fried form. The highest level of agreement among informants for food used categories was observed for plants combined with dry fish (ICF = 1). The Informant's consensus factor (ICF) of disease categories ranges from 0.75 to 1, with the highest being reported for convulsion (ICF = 1), sleep inducer (ICF = 1), and antiseptic (ICF = 1). Picria fel-terrae was the most preferred plant for hypertension treatment (100% FL). Direct matrix ranking (DMR) indicated that Dysoxylum excelsum was highly utilized by the inhabitant for multipurpose species (DMR = 64). Jaccard similarity index (JI) between the two ethnic groups was revealed at 1.26. Forty-seven WEVs were found to be commercialized in the Bara Bazar market, Aizawl, with a price range from 0.1 to 2.4 USD. Ensete superbum was reported as near threatened per the IUCN Red List of Threatened Species. Conclusion: This work highlighted the importance and rich diversity of WEVs in Mizoram, which are presently used among different age groups for food and medicine. Informants have good knowledge of WEVs, which was shared to a great extent among the inhabitants; this legacy of traditional culture must be conserved. This study further suggests a priority setting for conserving multipurpose WEVs in human-inhabited sites, investigating the recorded species' nutritional properties and pharmacological activities. [ABSTRACT FROM AUTHOR]

Background: Paediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid–base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment. Methods: A double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as 'carbogen'. Due to the urgent need to treat the seizure, deferred consent is used. The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality. Discussion: If safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff. Trial registration: EudraCT: 2021-005367-49. CTA: 17136/0300/001. ISRCTN: 52731862. Registered on July 2022. [ABSTRACT FROM AUTHOR]

The placebo response is a common phenomenon. Limited evidence is available about its magnitude in canine epilepsy trials, even though it can significantly influence the efficacy evaluation of new treatments. It was hypothesised that the placebo response is diminished when epilepsy trials are conducted in a prospective crossover design. Seizure data spanning six months from three previous multicenter epilepsy studies were analysed. The monthly seizure frequency of 60 dogs diagnosed with idiopathic epilepsy was calculated, comparing baseline data with placebo treatment. Furthermore, differentiation was made between dogs randomised to the placebo group early (Phase 1: first 3 months) or later during the study (Phase 2: second 3 months). The analysis did not reveal any placebo response in terms of monthly seizure frequency. Instead, an increase was noted during the placebo treatment period, with a mean of 2.95 seizures per month compared to 2.30 seizures per month before study entry (p = 0.0378). Additionally, a notable phase effect was observed. Dogs receiving the placebo in the second study phase exhibited a significant increase in monthly seizure frequency compared to baseline (p = 0.0036). Conversely, no significant difference from baseline was observed for dogs receiving the placebo in the first study phase. These findings underscore the considerable variability in placebo responses observed in trials for canine epilepsy, contrasting with previous limited data. The identified phase effect should be carefully considered in the design and evaluation of canine epilepsy trials to ensure a more accurate assessment of efficacy for new treatments. [ABSTRACT FROM AUTHOR]

Background: Progressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics. Case report: We report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures. Discussion: Myoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7. [ABSTRACT FROM AUTHOR]

Objective: Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) with ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies suggest high efficacy with unusually high seizure-free rates. The authors sought to investigate the plasma levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. Methods: Blood samples were collected from adult PWEs who were treated with adjunct cenobamate under steady-state conditions. Daily doses, concomitant medications, efficacy, and tolerability were assessed. The plasma cenobamate levels of seizure-free versus non-responding PWEs and between PWEs with and those without clinical adverse events were compared. Results: Samples from 101 PWEs were included. Thirty-six PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. A linear correlation was found between the daily doses (range: 100 mg–400 mg) and the plasma levels (3.8 mg/L–54.6 mg/L). Neither the daily doses nor the plasma levels differed significantly between the investigated subgroups. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Conclusions: To evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful. A general therapeutic range cannot be defined. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic neurological disease, characterized by spontaneous, unprovoked, recurrent seizures that may lead to long-term disability and premature death. Despite significant efforts made to improve epilepsy detection clinically and pre-clinically, the pervasive presence of noise in EEG signals continues to pose substantial challenges to their effective application. In addition, discriminant features for epilepsy detection have not been investigated yet. The objective of this study is to develop a hybrid model for epilepsy detection from noisy and fragmented EEG signals. We hypothesized that a hybrid model could surpass existing single models in epilepsy detection. Our approach involves manual noise rejection and a novel statistical channel selection technique to detect epilepsy even from noisy EEG signals. Our proposed Base-2-Meta stacking classifier achieved notable accuracy (0.98 ± 0.05), precision (0.98 ± 0.07), recall (0.98 ± 0.05), and F1 score (0.98 ± 0.04) even with noisy 5-s segmented EEG signals. Application of our approach to the specific problem like detection of epilepsy from noisy and fragmented EEG data reveals a performance that is not only superior to others, but also is translationally relevant, highlighting its potential application in a clinic setting, where EEG signals are often noisy or scanty. Our proposed metric DF-A (Discriminant feature-accuracy), for the first time, identified the most discriminant feature with models that give A accuracy or above (A = 95 used in this study). This groundbreaking approach allows for detecting discriminant features and can be used as potential electrographic biomarkers in epilepsy detection research. Moreover, our study introduces innovative insights into the understanding of these features, epilepsy detection, and cross-validation, markedly improving epilepsy detection in ways previously unavailable. [ABSTRACT FROM AUTHOR]

Background. Ictal arrhythmia is a rare condition that causes arrhythmic manifestations induced by epileptic seizures, including asystole or bradycardia. Ictal asystole (IA) is a very rare condition found in patients undergoing video-encephalography (EEG) monitoring. It is often related to temporal lobe epilepsy and can cause syncope, which can lead to injury or even death. Case Presentation. Two patients with epilepsy showed symptoms of syncope. Both patients underwent 4-day ambulatory EEG tests and were diagnosed with IA. Following the tests, the patients were implanted with a permanent pacemaker, and one of them underwent a temporal lobectomy. As a result of these procedures, the patients experienced a reduction in episodes of symptomatic syncope. Conclusion. Patients with ictal asystole and symptomatic ictal bradycardia are at increased risk of falls due to seizures. Although there are no specific guidelines for managing this condition, antiseizure medications, epilepsy surgery, and cardiac pacemaker implantation have been effective treatments. [ABSTRACT FROM AUTHOR]

Patients with hypoparathyroidism can present with concurrent basal ganglia calcifications (BGCs). The exact pathogenesis is unknown, although it is thought to relate to calcium-phosphate deposition from chronic hypocalcemia and hyperphosphatemia. We present the case of a 65-year-old man with known idiopathic primary hypoparathyroidism and concurrent extensive BGC. Thirty years after diagnosis, he presented with focal seizures despite a decade of stable intracranial calcifications on imaging. Serum calcium, phosphate, 25-hydroxyvitamin D, and parathyroid hormone levels were well controlled during this period. He was commenced on lifelong levetiracetam with subsequent seizure remission. Given the scarcity of literature surrounding focal seizures and BGC, it is essential to raise awareness in this area. [ABSTRACT FROM AUTHOR]

This letter discusses the relationship between migraine and epilepsy, specifically a condition called migralepsy. Migralepsy is characterized by a seizure that occurs during or within one hour after a migraine with aura. The letter describes a case of a 22-year-old man who experienced migraines with aura followed by epileptic seizures. The patient initially took topiramate, which reduced the frequency of migraines but did not fully control the seizures. The patient then switched to lamotrigine, which significantly improved both the migraines and seizures. The letter suggests that lamotrigine may be more effective in reducing seizure frequency by targeting the mechanisms underlying cortical spreading depression. Further studies are needed to better understand migralepsy. [Extracted from the article]

Functional seizures (FS), the most common subtype of functional neurological disorder (FND), cause serious neurological disability and significantly impact quality of life. Characterized by episodic disturbances of functioning that resemble epileptic seizures, FS coincide with multiple comorbidities and are treated poorly by existing approaches. Novel treatment approaches are sorely needed. Notably, mounting evidence supports the safety and efficacy of psychedelic-assisted therapy (PAT) for several psychiatric conditions, motivating investigations into whether this efficacy also extends to neurological disorders. Here, we synthesize past empirical findings and frameworks to construct a biopsychosocial mechanistic argument for the potential of PAT as a treatment for FS. In doing so, we highlight FS as a well-defined cohort to further understand the large-scale neural mechanisms underpinning PAT. Our synthesis is guided by a complexity science perspective which we contend can afford unique mechanistic insight into both FS and PAT, as well as help bridge these two domains. We also leverage this perspective to propose a novel analytic roadmap to identify markers of FS diagnostic specificity and treatment success. This endeavor continues the effort to bridge clinical neurology with psychedelic medicine and helps pave the way for a new field of psychedelic neurology. [ABSTRACT FROM AUTHOR]

• Our multimodal quantitative method unveils directional dynamics of epileptic network during interictal to ictal transition. • Epileptogenic zone exhibits maximum outflow during preictal, and at seizure onset. • Regions that are hypoperfused during seizures exhibit maximum outflow during ictal evolution and can serve as a control network. Ictal Single Photon Emission Computed Tomography (SPECT) and stereo-electroencephalography (SEEG) are diagnostic techniques used for the management of patients with drug-resistant focal epilepsies. While hyperperfusion patterns in ictal SPECT studies reveal seizure onset and propagation pathways, the role of ictal hypoperfusion remains poorly understood. The goal of this study was to systematically characterize the spatio-temporal information flow dynamics between differently perfused brain regions using stereo-EEG recordings. We identified seizure-free patients after resective epilepsy surgery who had prior ictal SPECT and SEEG investigations. We estimated directional connectivity between the epileptogenic-zone (EZ), non-resected areas of hyperperfusion, hypoperfusion, and baseline perfusion during the interictal, preictal, ictal, and postictal periods. Compared to the background, we noted significant information flow (1) during the preictal period from the EZ to the baseline and hyperperfused regions, (2) during the ictal onset from the EZ to all three regions, and (3) during the period of seizure evolution from the area of hypoperfusion to all three regions. Hypoperfused brain regions were found to indirectly interact with the EZ during the ictal period. Our unique study, combining intracranial electrophysiology and perfusion imaging, presents compelling evidence of dynamic changes in directional connectivity between brain regions during the transition from interictal to ictal states. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To enhance your understanding of the emotional and psychological effects of epilepsy, and how the condition is linked to mental health issues • To consider how you could address the mental health needs of people with epilepsy in your practice • To recognise the importance of collaborative working between epilepsy professionals and mental health professionals. Epilepsy is a neurological disorder that can have significant emotional and psychological effects on people and may adversely affect their well-being and quality of life. People with epilepsy are at high risk of developing mental health issues such as depression and anxiety due to a range of factors, including the unpredictability of seizures, the risk of sudden unexpected death, limitations to their autonomy and independence, and the side effects of anti-seizure medicines. However, historical links between epilepsy and psychiatry, alongside persisting stigma, may prevent people with epilepsy from seeking support from mental health services. Furthermore, professionals in both fields may lack the relevant skills and knowledge to support people with epilepsy who have mental health issues. Epilepsy services and mental health services need to work together to provide coordinated care and address the mental health needs of people with epilepsy. [ABSTRACT FROM AUTHOR]

Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies. The incidence of PTE after traumatic brain injury (TBI) depends on the severity of injury, approaching one in three in groups with the most severe injuries. The repeated seizures that characterize PTE impair neurological recovery and increase the risk of poor outcomes after TBI. Given this high risk of recurrent seizures and the relatively short latency period for their development after injury, PTE serves as a model disease to understand human epileptogenesis and trial novel anti-epileptogenic therapies. Epileptogenesis is the process whereby previously normal brain tissue becomes prone to recurrent abnormal electrical activity, ultimately resulting in seizures. In this Review, we describe the clinical course of PTE and highlight promising research into epileptogenesis and treatment using animal models of PTE. Clinical, imaging, EEG and fluid biomarkers are being developed to aid the identification of patients at high risk of PTE who might benefit from anti-epileptogenic therapies. Studies in preclinical models of PTE have identified tractable pathways and novel therapeutic strategies that can potentially prevent epilepsy, which remain to be validated in humans. In addition to improving outcomes after TBI, advances in PTE research are likely to provide therapeutic insights that are relevant to all epilepsies. Post-traumatic epilepsy is a major driver of disability associated with traumatic brain injury. This article reviews the epidemiology and clinical features of post-traumatic epilepsy and discusses how an understanding of the underlying epileptogenic mechanisms might inform the development of anti-epileptogenic medications. Key points: Post-traumatic epilepsy (PTE) is highly prevalent after traumatic brain injury, impairing neurological recovery and leading to worse functional outcomes. Current epilepsy therapeutics symptomatically treat seizures but do not modify epileptogenesis, the process by which brain tissue becomes prone to seizures. The unique nature of PTE, occurring after a well-defined epileptogenic insult, makes it a promising model system for understanding epileptogenesis. Future research in individuals with PTE populations might not only reveal novel mechanisms of epileptogenesis but also enable anti-epileptogenic therapies to be tested. [ABSTRACT FROM AUTHOR]

The recent scientific literature abounds in proposals of seizure forecasting methods that exploit machine learning to automatically analyze electroencephalogram (EEG) signals. Deep learning algorithms seem to achieve a particularly remarkable performance, suggesting that the implementation of clinical devices for seizure prediction might be within reach. However, most of the research evaluated the robustness of automatic forecasting methods through randomized cross-validation techniques, while clinical applications require much more stringent validation based on patient-independent testing. In this study, we show that automatic seizure forecasting can be performed, to some extent, even on independent patients who have never been seen during the training phase, thanks to the implementation of a simple calibration pipeline that can fine-tune deep learning models, even on a single epileptic event recorded from a new patient. We evaluate our calibration procedure using two datasets containing EEG signals recorded from a large cohort of epileptic subjects, demonstrating that the forecast accuracy of deep learning methods can increase on average by more than 20%, and that performance improves systematically in all independent patients. We further show that our calibration procedure works best for deep learning models, but can also be successfully applied to machine learning algorithms based on engineered signal features. Although our method still requires at least one epileptic event per patient to calibrate the forecasting model, we conclude that focusing on realistic validation methods allows to more reliably compare different machine learning approaches for seizure prediction, enabling the implementation of robust and effective forecasting systems that can be used in daily healthcare practice. [ABSTRACT FROM AUTHOR]