Role of Nrf2 in Epilepsy Treatment.

Oxidative stress is a consequence of the disruption of the balance between the generation of reactive nitrogen and oxygen species and the biological system's ability to neutralize those reactive products. Oxidative stress is involved in the generation of many disorders, including epilepsy, which is a prevalent chronic neurological disease that affects the lives of millions of people around the world. Epilepsy is characterized by unforeseeable and repeated seizures that can be very disturbing. Studies have reported that oxidative stress occurs before and after seizures. A transcription factor named Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) controls genes related to the induction of oxidative stress and defends cells against oxidative stress. The Nrf2 protein has seven different domains, ranging from Neh1 to Neh7. Each domain is responsible for a distinctive function of this protein. Keap1 binds to Nrf2, but during oxidative stress, Nrf2 detaches from the Keap1 protein, moves to the nucleus, and binds to DNA. The result of this translocation and binding is the initiation of transcription of detoxifying genes to control the harmful effects of oxidative stress. There is some evidence of oxidative stress involvement in epilepsy. In this review, we have listed potential Nrf2-related therapeutic targets for treating and controlling epilepsy, such as Berberis alkaloids, pentoxifylline, lovastatin, progesterone, and chrysin nanoparticles. These activators were tested in animals (in vivo) and cells (in vitro), and most of these experiments showed promising results in different epilepsy models. Finally, the results have suggested that the activation of Nrf2 can be an option for controlling epilepsy.

A single exposure to brivaracetam or perampanel does not cause cell death in neonatal rats.

Introduction: Exposure to a range of anti-seizure medications (ASMs) during early brain development adversely impacts neurodevelopmental outcomes in both animal models and in clinical studies. Many ASMs, including phenobarbital, phenytoin, valproate (VPA), and benzodiazepines, are associated with acute neurotoxicity (cell death), impaired synaptic development, and long-term behavioral changes following gestational or neonatal exposure in animals. This is mirrored in clinical studies which show lasting neurodevelopmental deficits following early-life or gestational exposure to these drugs. Brivaracetam (BRV) and perampanel (PER) are two newer generation anti-seizure medications and are of interest based on their mechanisms of action (SV2A modulator, AMPA antagonist, respectively), as other drugs with these mechanisms of action do not trigger acute neurotoxicity. Both BRV and PER show anti-seizure efficacy in developing animals, but potential neurotoxicity of these drugs is unexplored. Methods: To address this gap, we treated postnatal day (P)7 Sprague-Dawley rats with BRV (20, 40, 80 mg/kg) and PER (0.1, 0.9, 2.7 mg/kg), and assessed the induction of cell death across a range of vulnerable brain regions 24 h after exposure. Cell death was assessed using pathogreen staining. Results: In each of the regions examined (dorsal striatum, nucleus accumbens, motor cortex, cingulate cortex, lateral thalamus, septum, hippocampus), VPA, which served as a positive control, significantly increased cell death as measured by the numer of pathogreen positive cells. By contrast, neither BRV nor PER increased the number of pathogreen positive cells in any region examined. Discussion: Our results suggest that BRV and PER may have a positive safety profile-at least with respect to acute induction of cell death - and therefore may offer a safer option for the treatment of early life seizures.

Efficacy of a mitochondrial drug cocktail in preventing acute encephalopathy with biphasic seizures and late reduced diffusion.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is difficult to differentiate from prolonged febrile seizures during the acute phase. Mitochondrial dysfunction-induced energy depletion is among the key mechanisms underlying acute encephalopathy. Therefore, this study aimed to examine the efficacy of a "mitochondrial cocktail" in preventing AESD. We retrospectively studied children experiencing status epilepticus associated with fever lasting more than 30 min, focusing on those who received the mitochondrial cocktail between February 2016 and December 2020, and those who did not receive it within 24 h between February 2012 and January 2014. The mitochondrial cocktail contained vitamins B1, C, and E; biotin; coenzyme Q10; and l-carnitine. AESD occurred in 1 of 41 (2.4 %) patients in the administration group and 7 of 39 (17.9 %) patients in the non-administration group. The incidence of AESD was lower in the administration group than in the non-administration group, with a significant difference (p = 0.027). The incidence of encephalopathy, including cases classified as AESD and unclassified, was 7/41 (17.1 %) and 7/39 (17.9 %) in the administration and non-administration groups, respectively, with no significant difference. However, the number of cases with worsening pediatric cerebral performance category scores was significantly lower in the administration group compared to the non-administration group (p = 0.015). In conclusion, early administration of the mitochondrial cocktail may help prevent AESD. Some encephalopathy cases do not progress to a biphasic state or develop AESD. Thus, the mitochondrial cocktail should be administered as early as possible to prevent AESD.

Investigating the potential risk of cadmium exposure on seizure severity and anxiety-like behaviors through the ferroptosis pathway in epileptic mice: An integrated multi-omics approach.

Cadmium, a toxic heavy metal from industrial activities, poses a neurotoxic risk, especially to children. While seizures are common in children, the link between cadmium and seizure activity is unclear. Ferroptosis, an iron-dependent cell death, is key in seizure-induced hippocampal damage and related anxiety. This study aims to elucidate these mechanisms and assess the broader implications of cadmium exposure. Our research contributes in three significant areas: Firstly, through a combination of observational studies in long-term cadmium-exposed workers, Mendelian randomization analysis, NHANES analysis, urinary metabolomics, and machine learning analysis, we explored the impact of long-term cadmium exposure on inflammatory cytokines, ferroptosis-related gene expression, and lipid and iron metabolism. Secondly, by harnessing public databases for human disorders and metal-associated gene targets, alongside therapeutic molecular analyses, we identified critical human gene targets for cadmium toxicity in seizures and proposed melatonin as a promising therapeutic agent. Finally, utilizing mouse behavioral assays, T2 MRI, and MRS, we provide evidence of how prolonged cadmium exposure disrupts iron and lipid metabolism in the brain, triggering ferroptosis in the hippocampus.

Pentylenetetrazole-Induced Seizures Cause Short-Term Changes in the Phenotype of Microglial and Astroglial Cells in the Hippocampus and Temporal Cortex of Young Male Wistar Rats.

Astrocytes and microglia can adopt two distinct phenotypes in various pathological processes: neurotoxic A1/M1 and neuroprotective A2/M2. Recent evidence suggests that these cells play a significant role in epileptogenesis. The objective of this study was to characterize the phenotype of astrocytes and microglial cells in the hippocampus and temporal cortex of young male Wistar rats at 3 h, 1, 3, and 7 days after pentylenetetrazole-induced seizures. RT-qPCR was employed to examine the expression of glial genes (Gfap, Aif1, Slc1a1, Slc1a2, Slc1a3, Itpr2, Gdnf, Bdnf, Fgf2, Tgfb, Il1b, Tnf, Il1rn, Lcn2, S100a10, Nlrp3, Arg1). The most notable alterations in the expression of glial genes were observed on the first day following seizures in the temporal cortex. An increase in the expression of the Gfap, Slc1a2, Slc1a1, Il1b, Tnfa, Bdnf, and Fgf2 genes, and the A2 astrocyte condition marker S100a10, was observed. An increase in the expression of the Gfap and Slc1a2 genes was observed in the hippocampus on the first day after seizures. However, in contrast to the changes observed in the cortex, the changes in the hippocampus were opposite for the Il1rn, Bdnf, Tgfb, and Arg1 genes. Nevertheless, the alterations in GFAP and EAAT2 protein levels were not corroborated by Western blot analysis. Conversely, a more comprehensive immunohistochemical analysis confirmed an augmentation in the number of GFAP-positive cells in the hippocampus 1 day after seizures. Based on the presented evidence, we can conclude that a single convulsive seizure episode in 3-week-old rats results in transient astroglial activation and polarization to a neuroprotective phenotype (A2).

Risk factors for secondary epilepsy following febrile seizures in children: A meta-analysis.

OBJECTIVE: To systematically assess the risk factors for secondary epilepsy in children with febrile seizures, in order to promptly identify early signs of epilepsy and establish a reliable foundation for timely clinical intervention and improved prognosis. METHODS: The databases, including CNKI, WanFang, VIP, CBM, PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant studies, up to October 2023. Two researchers independently collected and extracted data from selected studies, adhering to predefined criteria. Statistical analysis was performed using Stata 15.0. RESULTS: A total of 23 studies included 714 cases in the case group and 5269 cases in the control group. The results of Meta-analysis showed that preterm birth (OR=3.30, P=0.02), history of perinatal asphyxia (OR=3.94, P=0.001), age at the first seizure < 12 months (OR=2.93, P=0.003), peak temperature < 39℃ (OR=2.51, P<0.001), onset of fever to seizure < 1 h (OR=5.61, P<0.001), Complex FS(OR=4.08, P<0.001), duration of the seizure > 15 min (OR=6.21, P<0.001), Multiple seizures (≥2/episode) in one attack (OR=2.92, P<0.001), focal seizures (OR=2.53, P=0.018), recurrent FS (≥2) (OR=3.49, P<0.001), neurodevelopmental abnormality(OR=8.68, P<0.001), developmental delay(OR=10.04, P<0.001), family history of epilepsy (OR=2.74, P=0.004), family history of FS (OR=2.07, P=0.022), electroencephalogram (EEG) abnormal(OR=4.06, P<0.001)and Brain imaging abnormalities (OR=2.84, P=0.002)were Risk factors for secondary epilepsy following FS in Children. Notably, gender (female) was not a significant factor. CONCLUSIONS: This study provides a comprehensive and systematic discussion of the risk factors associated with secondary epilepsy in children with febrile seizures. It actively formulates intervention measures for modifiable risk factors and conducts early detection and continuous follow-up observation for non-modifiable high-risk children, thereby reducing the risk of epilepsy.

Role of comorbidities in epilepsy surgery outcomes of older adults.

We lack knowledge about prognostic factors of resective epilepsy surgery (RES) in older adults (≥60 years), especially the role of comorbidities, which are a major consideration in managing the care of people with epilepsy (PWE). We analyzed a single-center cohort of 94 older adults (median age = 63.5 years, 52% females) who underwent RES between 2000 and 2021 with at least 6 months of postsurgical follow-up. Three fourths of the study cohort had lesional magnetic resonance imaging and underwent temporal lobectomy. Fifty-four (57%) PWE remained seizure-free during a median follow-up of 3.5 years. Cox proportional hazard multivariable analysis showed that aura (hazard ratio [HR] = .52, 95% confidence interval [CI] = .27-1.00), single ictal electroencephalographic pattern (HR = .33, 95% CI = .17-.660), and Elixhauser Comorbidity Index (HR = 1.05, 95% CI = 1.00-1.10) were independently associated with seizure recurrence at last follow-up. A sensitivity analysis using the Charlson Combined Score (HR = 1.38, 95% CI = 1.03-1.84, p = .027) confirmed the association of comorbidities with worse seizure outcome. Our findings provide a framework for a better informed discussion about RES prognosis in older adults. More extensive, multicenter cohort studies are needed to validate our findings and reduce hesitancy in pursuing RES in suitable older adults.

Characteristics of motion signal profiles of tonic-clonic, tonic, hyperkinetic, and motor seizures extracted from nocturnal video recordings.

OBJECTIVE: In this study, characteristics of signal profiles formed by motion, oscillation, and sound signals were analyzed to evaluate generalizability and variability in a single patient setting (intra-patient variability) and between patients (inter-patient variability). As a secondary objective, the effect of brivaracetam intervention on signal profiles was explored. METHODS: Patient data included 13 hyperkinetic seizures, 65 tonic seizures, 13 tonic-clonic seizures, and 138 motor seizures from 11 patients. All patients underwent an 8-week monitoring, and after a 3-week baseline, brivaracetam was initiated. Motion, oscillation, and sound features extracted from the video were used to form signal profiles. Variance of signals was calculated, and combined median and quartile visualizations were used to visualize the results. Similarly, the effect of intervention was visualized. RESULTS: Hyperkinetic motion signals showed a rapid increase in motion and sound signals without oscillations and achieved low intra-patient variance. Tonic component created a recognizable peak in motion signal typical for tonic and tonic-clonic seizures. For tonic seizures, inter-patient variance was low. Motor signal profiles were varying, and they did not form a generalizable signal profile. Visually recognizable changes were observed in the signal profiles of two patients. SIGNIFICANCE: Video-based motion signal analysis enabled the extraction of motion features characteristic for different motor seizure types which might be useful in further development of this system. Tonic component formed a recognizable seizure signature in the motion signal. Hyperkinetic and motor seizures may have not only significantly different motion signal amplitude but also overlapping signal profile characteristics which might hamper their automatic differentiation. Motion signals might be useful in the assessment of movement intensity changes to evaluate the treatment effect. Further research is needed to test generalizability and to increase reliability of the results.

Perampanel for the treatment of Asian people with epilepsy: Real-world evidence from the PERMIT extension study.

This post-hoc analysis of the PERMIT Extension study compared the effectiveness and safety/tolerability of perampanel (PER) between Asian and non-Asian participants. Retention rates, adverse events (AEs), seizure frequency, responder rate (≥50% seizure frequency reduction), and seizure freedom rate (no seizures since at least the prior visit) were assessed. Retention was assessed after 3, 6 and 12 months. Effectiveness assessments were evaluated at 3, 6 and 12 months and the last visit by seizure type (total, focal and generalised). PERMIT Extension included 730 Asian and 1662 non-Asian individuals. Significant differences in demographic/baseline characteristics were reported for the Asian versus non-Asian subgroups including higher median age at epilepsy onset, longer median duration of epilepsy, higher mean number of previous and concomitant ASMs and lower mean monthly seizure frequency (total, focal and generalised). Retention rates were similar between the two subgroups at 3 and 12 months, but significantly lower in the Asian versus non-Asian subgroup at 6 months (65.6% vs. 71.8%; p = 0.004). At last visit, seizure freedom rate was significantly higher in the Asian versus non-Asian for total (35.9% vs. 25.4%; p = 0.001) and focal seizures (32.4% vs. 18.9%; p = 0.001) as was responder rate for both total (63.9% vs. 52.3%; p = 0.001) and focal seizures (62.2% vs. 44.7%; p < 0.001). Seizure freedom and responder rates for generalised seizures were similar between the two subgroups at the last visit. Rates of AEs were similar between the two subgroups (Asian, 47.6%; non-Asian, 45.4%). PER was effective and generally well-tolerated in Asian and non-Asian individuals.

The Utility of 24-h Video-EEG Monitoring in the Diagnosis of Epilepsy in Children.

Objectives: Evaluate the diagnostic yield of 24-h video-EEG monitoring in a group of children admitted in our epilepsy monitoring unit (EMU). Methods: 232 children who underwent 24-h video-EEG monitoring was analysed. We divided each patient's monitoring duration into the first 1, 2, 4, 8, 16 h, relative to the whole 24 h monitoring period. The detection of the first interictal epileptiform discharges (IEDs), epileptic seizures (ES), and psychogenic non-epileptic seizures (PNES) were analysed relative to the different monitoring time subdivision. Results: Our findings revealed that: (1) there was no significant difference in the prevalence of detecting initial IEDs between the first 4-h and 24-h monitoring periods (73.7% vs 81%); (2) clinical events detection rate was statistically similar between the first 8-h and 24-h monitoring periods (15.5% vs 19.3%); (4) an 8-h monitoring was sufficient to capture IEDs, ES and PNES in focal epilepsy children; (5) a 1-h monitoring was sufficient to capture IEDs, ES and PNES in generalized epilepsy children; and (6) IEDs were detected within the first 1-h of monitoring in 96.7% self-limited focal epilepsies (SeLFEs) patient. Conclusion: Our study suggests that a 4-h monitoring has more value in increasing the detection rate of IEDs compared to the traditional shorter routine EEG. And in the case of SeLFEs, a 1-h of monitoring might be sufficient in detecting IEDs. A 24-h VEEG monitoring can detect clinical events in 19.3% of patients. Overall, the yield of IEDs and clinical events detection is adequate in children in children undergoing 24-h video-EEG monitoring.

Unusual MRI abnormality in patients with nonketotic hyperglycaemia-associated seizures.

Nonketotic hyperglycaemia (NKH) is a metabolic disorder typically observed in individuals with inadequately managed or undiagnosed diabetes mellitus (DM). Seizures are a common clinical presentation in NKH, and they tend to respond better to glucose correction than anticonvulsant therapy. MRI scans may reveal both subcortical T2/fluid-attenuated inversion recovery (FLAIR) imaging hypointensity and cortical changes, including cortical grey matter T2/FLAIR imaging hyperintensity and cortical or leptomeningeal enhancement, although cortical abnormalities are less frequently observed. These alterations are reversible when the underlying metabolic disturbance is effectively addressed. We suggest the role of iron accumulation as a mechanism for subcortical T2 hypointensity using T2* weighted imaging. Our cases substantiate the significance of subcortical T2/FLAIR hypointensity as a fundamental feature of this condition. In the appropriate clinical context, the recognition of these MRI abnormalities can help prevent misdiagnosis and facilitate timely treatment.

Pathomechanism of infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion evaluated by MR spectroscopy.

BACKGROUND: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has recently been reported as a distinct type of TBI in infancy. However, the pathological and prognostic factors of TBIRD remain unknown. We aimed to compare patients with and without TBIRD and evaluate the pathomechanism of TBIRD using magnetic resonance spectroscopy (MRS). METHODS: Ten Japanese patients with TBI were admitted to our hospital and underwent MRS between September 2015 and September 2022 (age range, 3-15 months; median age, 8.5 months). TBIRD was diagnosed in six patients. MRS data were compared among patients with TBIRD, patients without TBIRD, and controls. Neurological prognosis was classified into grades 1 (normal) to 3 (severe). RESULTS: In patients with TBIRD, MRS revealed an increase in the glutamine (Gln) level on days 3-29, which subsequently became close to normal. The degree of Gln elevation in the non-TBIRD group was smaller (117-158 % of controls) than that in the TBIRD group (210-337 %) within 14 days. MRS in the TBIRD group showed decreased N-acetyl aspartate (NAA) concentrations. The degree of NAA decrease was more prominent in grade 3 than in grades 1 and 2. NAA levels in the non-TBIRD group were almost normal. CONCLUSIONS: Patients with TBI and markedly elevated Gln levels on MRS may develop TBIRD. Neuro-excitotoxicity is a possible pathological mechanism of TBIRD. Decreased NAA levels may be useful for predicting the prognosis of patients with TBIRD.

Amplitude-Integrated Electroencephalography: A Readily Available Tool for Neonatologists.

Hypoxic-ischemic encephalopathy (HIE) is a common condition occurring at birth, impairing central nervous system function. Therapeutic hypothermia is beneficial for suspected HIE as it reduces mortality and disability in survivors but not for other types of encephalopathy (e.g., metabolic). Amplitude-integrated electroencephalography (aEEG) complements limited resource Neonatal Intensive Care Units as a screening tool that can provide information regarding the degree of encephalopathy and electrographic seizures. Patients with HIE are at increased risk for seizures, which are subclinical in half of the cases. The aEEG emphasizes electroencephalographic amplitude differences, whereas continuous video electroencephalography (cEEG) provides a high-resolution picture of cerebral electrical activity, making it the most accurate method for detecting subclinical seizures. Still, its interpretation demands extensive training beyond the scope of neonatologists. Any infant in whom aEEG is suspicious for seizures should undergo cEEG to confirm the findings because even very low-amplitude artifacts might be misdiagnosed as seizures. We report a case and review the utility of aEEG in detecting subclinical seizures in neonates with HIE during therapeutic hypothermia while cEEG is not available.

Dyke-Davidoff-Masson-like syndrome in an adult cat.

Case summary: A 4-year-old cat was presented with acute onset of lateralised neurological central nervous system (CNS) signs and seizures. Haematological and serum biochemical parameters were within normal limits. Imaging diagnostics revealed severe CT and MRI abnormalities of the right brain, similar to Dyke-Davidoff-Masson syndrome (DDMS) in human medicine. This syndrome includes cerebral hemiatrophy with compensatory calvarial hyperostosis and ventriculomegaly. Such changes have previously been reported only once in a single feline case of approximately the same age. In humans, DDMS is described as an embryonic and perinatal developmental disturbance or an acquired injury in early childhood. Relevance and novel information: This case report shows that without further imaging diagnostics, congenital disorders can be overlooked in some rare cases of adult cats with later onset of their first clinical signs.

VPS13D affects epileptic seizures by regulating mitochondrial fission and autophagy in epileptic rats.

Abnormal mitochondrial dynamics can lead to seizures, and improved mitochondrial dynamics can alleviate seizures. Vacuolar protein sorting 13D (VPS13D) is closely associated with regulating mitochondrial homeostasis and autophagy. However, further investigation is required to determine whether VPS13D affects seizures by influencing mitochondrial dynamics and autophagy. We aimed to investigate the influence of VPS13D on behavior in a rat model of acute epileptic seizures. Hence, we established an acute epileptic seizure rat model and employed the CRISPR/CAS9 technology to construct a lentivirus to silence the Vps13d gene. Furthermore, we used the HT22 mouse hippocampal neuron cell line to establish a stable strain with suppressed expression of Vps13d in vitro. Then, we performed quantitative proteomic and bioinformatics analyses to confirm the mechanism by which VPS13D influences mitochondrial dynamics and autophagy, both in vitro and in vivo using the experimental acute epileptic seizure model. We found that knockdown of Vps13d resulted in reduced seizure latency and increased seizure frequency in the experimental rats. Immunofluorescence staining and western blot analysis revealed a significant increase in mitochondrial dynamin-related protein 1 expression following Vps13d knockdown. Moreover, we observed a significant reduction in LC3II protein expression levels and the LC3II/LC3I ratio (indicators for autophagy) accompanied by a significant increase in P62 expression (an autophagy adaptor protein). The proteomic analysis confirmed the up-regulation of P62 protein expression. Therefore, we propose that VPS13D plays a role in modulating seizures by influencing mitochondrial dynamics and autophagy.

Incidence and pattern of neurological emergencies in Ramadan.

BACKGROUND: The impact of Ramadan fasting on various neurological emergencies remains relatively unexplored. This study aimed to clarify the incidence and pattern of the different neurological emergencies in Ramadan compared to Shaaban. METHODS: In this cross-sectional study, all adult patients attending the emergency room at two Egyptian centers with neurological emergencies during Shaaban and Ramadan were evaluated. Clinical, laboratory, and radiological assessments were made on an individual basis upon which the diagnosis of neurological disorder was made. IBM SPSS Version 25 was used to analyze the data. RESULTS: Seventy-twenty patients were included, 382 during Shaaban and 338 during Ramadan. Among causes of delirium, the frequency of dehydration was significantly higher, and the frequency of illicit drug abuse was significantly lower during Ramadan compared to Shaaban (P = 0.004, 0.030, respectively). The incidence of ICH was significantly reduced during Ramadan compared to Shaaban (10.8% vs 19.7%, P = 0.031). The incidence of cardioembolic strokes significantly increased during Ramadan than Shaaban (40.5% vs 26.4%, P = 0.014), whereas the incidence of small vessel disease (SVD) significantly decreased during Ramadan than Shaaban (21.6% vs. 42.1%, P < 0.001). The incidence of a single seizure was significantly higher in Ramadan than in Shaaban (69.4% vs. 34.6%, P = 0.007). The incidence of functional neurological disorders was significantly reduced in Ramadan than in Shaaban (P < 0.001). CONCLUSION: The incidence of delirium caused by illicit drug abuse, ICH, SVD, and functional neurological disorders declined during Ramadan, while the incidence of delirium triggered by dehydration, cardioembolic strokes, and a single seizure increased during Ramadan.

Clinical correlates of perceived stigma among people living with epilepsy enrolled in a self-management clinical trial.

BACKGROUND AND PURPOSE: Stigma is a pervasive barrier for people living with epilepsy (PLWE) and can have substantial negative effects. This study evaluated clinical correlates of perceived stigma in a research sample of PLWE considered to be at high risk due to frequent seizures or other negative health events. METHODS: Analyses were derived from baseline data from an ongoing Centers for Disease Control and Prevention (CDC)-funded randomized controlled trial (RCT) testing an epilepsy self-management approach. Standardized measures assessed socio-demographics, perceived epilepsy stigma, epilepsy-related self-efficacy, epilepsy self-management competency, health literacy, depressive symptom severity, functional status, social support and epilepsy-related quality of life. RESULTS: There were 160 individuals, mean age of 39.4, (Standard deviation/SD=12.2) enrolled in the RCT, 107 (66.9 %) women, with a mean age of epilepsy onset of 23.9 (SD 14.0) years. The mean seizure frequency in the prior 30 days was 6.4 (SD 21.2). Individual factors correlated with worse perceived stigma were not being married or cohabiting with someone (p = 0.016), lower social support (p < 0.0001), lower self-efficacy (p < 0.0001), and lower functional status for both physical health (p = 0.018) and mental health (p < 0.0001). Perceived stigma was associated with worse depressive symptom severity (p < 0.0001). Multivariable linear regression found significant independent associations between stigma and lower self-efficacy (ß -0.05; p = 0.0096), lower social support (ß -0.27; p = 2.4x10-5, and greater depression severity (ß 0.6; p = 5.8x10-5). CONCLUSIONS: Perceived epilepsy stigma was positively correlated with depression severity and negatively correlated with social support and self-efficacy. Providers caring for PLWE may help reduce epilepsy stigma by screening for and treating depression, encouraging supportive social relationships, and providing epilepsy self-management support. Awareness of epilepsy stigma and associated factors may help reduce some of the hidden burden borne by PLWE.

Methylphenidate and the risk of acute central nervous system oxygen toxicity: a rodent model and observational data in human divers.

Introduction: The effects of methylphenidate, a stimulant often prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD), on the development of central nervous system oxygen toxicity (COT) have not been experimentally evaluated. Methods: The records of all pure-oxygen-rebreather divers evaluated at our institution from 1975-2022 were assessed. Cases of COT were defined as a new onset of tinnitus, tunnel vision, myoclonus, headache, nausea, loss of consciousness, or seizures resolving within 15 minutes from breathing normobaric air, and matched 4:1 with similar controls. Any medications issued to the diver in the preceding three months, including methylphenidate, were recorded. In the animal arm of this study, male mice were exposed to increasing doses of methylphenidate orally, with subsequent exposure to hyperbaric O2 until clinically evident seizures were recorded. Results: Seventy-five cases of COT were identified in divers, occurring at a median of 80 (range 2-240) minutes after dive initiation at a median depth of 5 m (2-13). Hypercarbia was documented in 11 (14.7%) cases. Prescription of methylphenidate in the preceding three months was not associated with increased risk (OR 0.72, 95% CI 0.16-3.32) of COT. In mice, increasing methylphenidate exposure dose was associated with significantly longer mean COT latency time being 877 s (95% CI 711-1,043) with doses of 0 mg·kg⁻¹; 1,312 s (95% CI 850-1,773) when given 0.75 mg·kg⁻¹; and 1,500 s (95% CI 988-2,012) with 5 mg·kg⁻¹ (F = 4.635, P = 0.014). Conclusions: Observational human data did not demonstrate an association between methylphenidate and an increased risk of COT. Methylphenidate exposure in mice prolongs COT latency and may have protective effects against COT.

Navigating the Complexities: A Rare Case of Intrahepatic Cholestasis of Pregnancy With Placenta Previa Manifesting With Seizures.

Intrahepatic cholestasis of pregnancy (ICP) is a prevalent and reversible liver disorder that occurs during pregnancy. It is primarily characterized by itching, especially on the palms and soles, and elevated levels of transaminases and bile acids. Some patients may also exhibit hyperbilirubinemia. This condition generally has a good maternal prognosis. The patient, in this case, presented with severe itching, elevated liver enzymes and bile acids, and an ultrasound indicated placenta previa. Uniquely, she experienced an episode of seizure and high blood pressure following surgery. This case report underscores the need for vigilant monitoring of patients with ICP, not only during pregnancy due to the risk of adverse perinatal outcomes but also for antenatal and postpartum complications.

Isolated Partial Absence of the Septum Pellucidum: A Case Report.

The septum pellucidum is an important thin, membranous structure in the brain that separates the anterior horns of the lateral ventricles, essential for maintaining brain anatomy and function. Here, we describe a case of a 38-year-old male with a 20-year history of seizures, occurring approximately three to four times annually and lasting 30 minutes to one hour per episode, who presented with a recent seizure three days prior. Magnetic resonance imaging (MRI) of the brain revealed an absence of the septum pellucidum in its posterior portion, mild prominence of both lateral ventricles, and an abnormal course of the crura of the fornix, leading to a diagnosis of partial absence of the septum pellucidum. This case underscores the importance of comprehensive neuroimaging in detecting structural brain anomalies, which is crucial for effective diagnosis, management, and improving patient outcomes, particularly in long-standing seizure disorders.