Status Epilepticus Research Articles

Moxibustion pre-treatment attenuates seizure severity during status epilepticus and counteracts the proconvulsant function of the purinergic P2X7 receptor.

Moxibustion, traditional Chinese medicine treatment, involves the warming of specific acupuncture points of the body using ignited herbal materials. Evidence suggests beneficial effects of moxibustion in several brain diseases including epilepsy, however, whether moxibustion pretreatment impacts on seizures and what are the underlying mechanisms remains to be established. Evidence has suggested the purinergic ATP-gated P2X7 receptor (P2X7R) to be involved in the actions of moxibustion. Moreover, P2X7R signalling is now well established to contribute to long-lasting brain hyperexcitability underlying epilepsy development. Whether P2X7R signalling is involved in the seizure-reducing actions of moxibustion has not been investigated to date. For our studies we used C57BL/6 male mice that received moxibustion pre-treatments at the acupoints Zusanli (ST36) and Dazhui (GV14) once daily for either 7, 14, or 21days. This was followed by an intraperitoneal injection of kainic acid (KA, 30mg/kg) to induce status epilepticus. Behavioral changes during KA-induced status epilepticus were analyzed according to the Racine scale. Changes in electrographic seizures were analyzed via cortical implanted electroencephalogram (EEG) electrodes. While no effect on seizure severity was observed following 7days of moxibustion pre-treatment, moxibustion pre-treatment at both ST36 and GV14 for 14 or 21days significantly reduced KA-induced behavior seizures at a similar rate. Cortical EEG recordings showed that 14days of moxibustion pre-treatments also reduced electrographic seizures, confirming the anticonvulsant actions of moxibustion pre-treatment. To determine whether moxibustion impacts the pro-convulsant actions of P2X7R signaling, mice were treated with the P2X7R agonist BzATP or P2X7R antagonist A438079. While treatment with the P2X7R agonist BzATP exacerbated seizure severity, treatment with the P2X7R antagonist reduced seizure severity. We further found that moxibustion pre-treatment attenuated epileptic seizures by counteracting the effects ofBzATP. These results suggest that moxibustion pre-treatment at the acupoints ST36 and GV14 for 14days has anti-epileptic effects, which may counteract the proconvulsant functions of the P2X7R.

Anti-epileptic drug (AED) loading in status epilepticus: an audit and introduction of levetiracetam loading protocol

Anti-epileptic drug (AED) loading in status epilepticus: an audit and introduction of levetiracetam loading protocol

Elevated cerebrospinal fluid neuronal injury biomarkers within 24 hours of onset in infection-triggered acute encephalopathy compared to complex febrile seizures

ObjectiveThis study aimed to measure and compare cerebrospinal fluid neuronal injury biomarkers in the acute phase of complex febrile seizure (CFS) and infection-triggered acute encephalopathy (AE). Furthermore, we determined the pathogenesis of AE with biphasic seizures and late reduced diffusion (AESD). MethodsPediatric patients with febrile status epilepticus who visited Hyogo Prefectural Kobe Children's Hospital from November 1, 2016, to December 31, 2022, and whose cerebrospinal fluid samples were collected within 24 h of neurological symptom onset were included. Patients were classified as having CFS or infection-triggered AE according to their definitions. Patients with AE were further categorized into AESD or unclassified AE. Cerebrospinal fluid biomarkers (neuron-specific enolase, growth differentiation factor 15 [GDF-15], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein, and tau protein were measured and compared among the groups. ResultsTotal of 63 patients (45 with CFS and 18 with AE) were included. Among the AE patients, nine were classified as having AESD and nine as having unclassified AE. S100B levels were significantly higher in patients with AESD than in patients with CFS (485 pg/ml vs. 175.3 pg/ml) and were even higher in patients with AESD and neurological sequelae (702.4 pg/ml). GDF-15 levels were significantly elevated in patients with AE compared to patients with CFS (85.8 pg/ml vs. 23.6 pg/ml). ConclusionsThe elevation of S100B suggests that activated astrocytes may be closely associated with the early pathology of AESD. Elevated GDF-15 levels in infection-triggered AE suggest the activation of defense mechanisms caused by stronger neurological injury.

Fluidized spanlastics for intranasal brain delivery of lacosamide aiming to control Status Epilepticus: Design, Characterization, Ex-vivo permeation, Radioiodination and In-vivo biodistribution studies

Status Epilepticus (SE) is a neurological condition characterized by anomalous brain activity, causing repetitive seizures lasting for more than 5 min or periods of unusual behavior without returning to a normal level of consciousness between episodes. Chitosan has shown various pharmaceutical benefits, particularly in intranasal administration. In the current manuscript, novel ultra-deformable vesicles (fluidized spanlastics) loaded with lacosamide (LCM), a model anti-epileptic drug, were formulated and compared with their chitosan containing counterparts. The formed vesicles were assessed for their particle size (PS), zeta potential (ZP), entrapment efficiency (EE%) and storage stability. Surface morphology, pH and viscosity measurements, in-vitro release study and release kinetics, and ex-vivo permeation across nasal sheep mucosa were carried out on the optimized formulations. The bio-distribution and pharmacokinetic studies were performed using the radioiodinated-LCM (131I-LCM) utilizing different routes of administration to assess the in-vivo performance of intravenous solutions (IVs), intranasal solutions (INs) and the intranasal administered optimized formula (INFS). LCM-vesicles showed PS ranging from 109.90 to 418.4 nm, negative ZP values ranging from −28.00 to −48.30 mV in case of regular vesicles and shifted to +16.70 to +18.72 mV in case of chitosan coated vesicles, high EE% values having a range of 65.76–97.25 % and good storage stability properties. The optimized formulation showed spherical shape and enhanced ex-vivo permeation approximately 4-fold higher compared to LCM solution. The results of the in-vivo study demonstrated that the brain/blood ratio (B/B) of INs was 3.3-fold higher than IVs and INs of 131I-LCM in the first 5 min. Accordingly, the prepared system has been shown to possess a promising potential for brain diagnosis and/or therapy.

Increasing adult-born neurons protects mice from epilepsy.

Neurogenesis occurs in the adult brain in the hippocampal dentate gyrus, an area that contains neurons which are vulnerable to insults and injury, such as severe seizures. Previous studies showed that increasing adult neurogenesis reduced neuronal damage after these seizures. Because the damage typically is followed by chronic life-long seizures (epilepsy), we asked if increasing adult-born neurons would prevent epilepsy. Adult-born neurons were selectively increased by deleting the pro-apoptotic gene Bax from Nestin-expressing progenitors. Tamoxifen was administered at 6 weeks of age to conditionally delete Bax in Nestin-CreERT2 Bax fl/fl mice. Six weeks after tamoxifen administration, severe seizures (status epilepticus; SE) were induced by injection of the convulsant pilocarpine. After mice developed epilepsy, seizure frequency was quantified for 3 weeks. Mice with increased adult-born neurons exhibited fewer chronic seizures. Postictal depression was reduced also. These results were primarily in female mice, possibly because they were the more affected by Bax deletion than males, consistent with sex differences in Bax. The female mice with enhanced adult-born neurons also showed less neuronal loss of hilar mossy cells and hilar somatostatin-expressing neurons than wild type females or males, which is notable because these two hilar cell types are implicated in epileptogenesis. The results suggest that selective Bax deletion to increase adult-born neurons can reduce experimental epilepsy, and the effect shows a striking sex difference. The results are surprising in light of past studies showing that suppressing adult-born neurons can also reduce chronic seizures.

Intravenous lacosamide for acute repetitive seizures and convulsive status epilepticus in critically ill children.

Acute repetitive seizures and convulsive status epilepticus are common neurological emergencies in critically ill children. The aim of the study was to evaluate the effectiveness and safety of intravenous lacosamide in critically ill children with acute repetitive seizures and convulsive status epilepticus. This retrospective study included children who received intravenous lacosamide for acute repetitive seizures or convulsive status epilepticus from October 2017 to September 2022 and were admitted to the pediatric intensive care unit at a tertiary medical center. Children who were newly started on intravenous lacosamide were included and divided into two groups: (a) previously healthy, and (b) history of epilepsy and receiving antiseizure medications. Efficacy was defined as the cessation of seizures within 72 h of administering lacosamide. Adverse effects were defined using predefined criteria, and most were evaluated during the first 7 days. Sixty-seven children were enrolled, including 25 (37.3%) girls and 42 (62.7%) boys with a mean age of 7.20 ± 5.66 years. Among them, 30 (44.8%) had acute repetitive seizures, and 37 (55.2%) had convulsive status epilepticus. The seizure types were focal onset (n = 34, 50.7%), generalized onset (n = 27, 40.3%), and mixed type (n = 6, 9.0%). In the previously healthy group, 9 patients had acute repetitive seizures and 23 had convulsive status epilepticus, and the rates of seizure cessation when lacosamide was used as the first to fourth choice of antiseizure medication were 100.0%, 85.7%, 40.0%, and 50.0%, respectively, compared to 73.7%, 54.5%, 100.0%, and 0.0% in the patients with epilepsy (21 had acute repetitive seizures and 14 had convulsive status epilepticus). Sixteen (23.9%) patients developed bradycardia and 1 (1.5%) patient developed a rash. The early use of intravenous lacosamide was effective with acceptable side effects in treating acute repetitive seizures and convulsive status epilepticus in critically ill children, including young infants and children less than 4 years old and those with different etiologies. Acute repetitive seizures and convulsive status epilepticus are common neurological emergencies in pediatric intensive care units (PICUs), traditional intravenous antiseizure medications (ASMs) include phenytoin, valproic acid, levetiracetam, and phenobarbital. In this study, we categorized patients based on their epilepsy history and different etiologies. We observed that early use of lacosamide, even in young infants, demonstrated good efficacy and safety.

Identification of autosomal dominant lateral temporal epilepsy caused by a novel mutation in RELN in China: a case report

BackgroundTemporal lobe epilepsy is the most common type of focal epilepsy, but hereditary factors are usually overlooked. Reelin (RELN) is considered to be the second most common pathogenic gene implicated in autosomal dominant lateral temporal epilepsy (ADLTE). However, this mutation is not frequently discovered in the Chinese population. Additionally, there are few clinical studies regarding the connection between RELN and glioma.Case presentationThe healthcare records of an 8-year-old child who experienced generalized tonic-clonic seizures (GTCS) during sleep for 7 years were retrospectively analyzed. In addition to experiencing his first seizure at the age of one, his mother also suffered from GTCS during her pregnancy, and a glioma was discovered. An investigation involving gene sequencing was conducted on the proband and his parents. He was diagnosed with ADLTE once a missense mutation in RELN (c.1799 C > T) was identified as the causal factor. The mutation was inherited from his mother. He was taking levetiracetam (500 mg twice a day) to avoid seizures, but his mother died of status epilepticus caused by glioma recurrence two years earlier.ConclusionsGenetic issues should be given more consideration in cases of temporal lobe epilepsy. If the source of the seizures is determined to be inherited, anti-seizure medications should be used for prolonged periods. Furthermore, more research is required to determine whether mutations in RELN are related to the occurrence and progression of gliomas.

Post-hypoxic myoclonus (Lance-Adams Syndrome) in post-cardiorespiratory arrest, a case presentation in elderly

A clinical case report is presented of an elderly adult recovering from cardiac arrest who developed generalized myoclonus or Lance Adams syndrome in a tertiary care hospital. Myoclonus is defined as a sudden, brief muscle contraction (1). The Lance Adams Syndrome is a form of post- hypoxic myoclonus, characterized by action myoclonus that typically involve the trunk, face, and extremities, and whose onset is days to weeks after a hypoxic brain injury. (2) The incidence of post-hypoxic myoclonus is 1. 3 cases per 100,000 people per year, so its differential diagnosis represents a challenge. The etiology may be secondary to cardiorespiratory arrest, anesthetic and surgical accidents, in addition to heart disease and drug overdose. Acute post-hypoxic myoclonus begins hours after the injury, sometimes begins as myoclonic status epilepticus, and if the patient survives, he will progress to a chronic phase with a poor or low life expectancy. Treatment is controversial, several articles agree that patients have shown better response to Levetiracetam, Magnesium Valproate, Lacosamide and Clonazepam.

Metabolic Adaptation in Epilepsy: From Acute Response to Chronic Impairment.

Epilepsy is characterized by hypersynchronous neuronal discharges, which are associated with an increased cerebral metabolic rate of oxygen and ATP demand. Uncontrolled seizure activity (status epilepticus) results in mitochondrial exhaustion and ATP depletion, which potentially generate energy mismatch and neuronal loss. Many cells can adapt to increased energy demand by increasing metabolic capacities. However, acute metabolic adaptation during epileptic activity and its relationship to chronic epilepsy remains poorly understood. We elicited seizure-like events (SLEs) in an in vitro model of status epilepticus for eight hours. Electrophysiological recording and tissue oxygen partial pressure recordings were performed. After eight hours of ongoing SLEs, we used proteomics-based kinetic modeling to evaluate changes in metabolic capacities. We compared our findings regarding acute metabolic adaptation to published proteomic and transcriptomic data from chronic epilepsy patients. Epileptic tissue acutely responded to uninterrupted SLEs by upregulating ATP production capacity. This was achieved by a coordinated increase in the abundance of proteins from the respiratory chain and oxidative phosphorylation system. In contrast, chronic epileptic tissue shows a 25-40% decrease in ATP production capacity. In summary, our study reveals that epilepsy leads to dynamic metabolic changes. Acute epileptic activity boosts ATP production, while chronic epilepsy reduces it significantly.

The pharmacologic management of status epilepticus in pregnant patients: a scoping review

AbstractBackgroundStatus epilepticus (SE) is defined as 5 min or more of seizure activity or two recurrent seizures without a return to baseline. Healthcare providers encounter a challenge when a patient with SE is pregnant. SE is not only detrimental to the mother but can also put the baby at risk of severe harm. SE must be treated rapidly and therefore healthcare providers have very little time to thoroughly review the risk and benefits of available antiseizure medication in this population.AimTo evaluate the current available evidence related to the management of SE in pregnancy.DesignA literature search of PubMed, CINAHL, ProQuest Nursing & Allied Health Source, and Web of Science databases was conducted (2012–2022) using the following search terms: ‘pregnancy’, ‘pregnant women’ OR ‘gestation’ AND ‘status epilepticus’, ‘generalized status epilepticus’, ‘generalized convulsive status epilepticus’, ‘non convulsive status epilepticus’ OR ‘non‐convulsive status epilepticus’. Full‐text randomised controlled trials, clinical trials, observational studies, and case reports published in English were included. Data were extracted and the quality of the studies was evaluated using the Mixed Methods Appraisal Tool.ResultsThe literature described 29 pregnancies and 30 total foetuses. Intravenous benzodiazepine use for emergent control was reported in 45% of patients. Phenytoin and levetiracetam were primarily utilised for urgent control, with a variety of agents used for refractory SE. Ninety‐seven percent of maternal outcomes were reported as positive. The most common outcome was the birth of a healthy term infant. There were seven cases of pregnancy loss.ConclusionPublications pertaining to the treatment of SE in pregnancy are limited to case reports and small observational studies. Use of a benzodiazepine followed by levetiracetam or phenytoin is appropriate, whereas valproic acid should be utilised only when necessary due to the risk of major congenital malformation.

Enhanced Fyn-tau and NR2B-PSD95 interactions in epileptic foci in experimental models and human epilepsy.

Epilepsy and Alzheimer's disease share some common pathologies such as neurodegeneration, seizures and impaired cognition. However, the molecular mechanisms of these changes are still largely unknown. Fyn, a Src-family non-receptor tyrosine kinase (SFK), and its interaction with tau in mediating brain pathology in epilepsy and Alzheimer's disease can be a potential therapeutic target for disease modification. Although Fyn and tau pathology occurs in both Alzheimer's disease and epilepsy, the dynamics of Fyn-tau and PSD95-NR2B interactions affected by seizures and their impact on brain pathology in epilepsy have not been investigated. In this study, we demonstrate a significant increase of Fyn-tau interactions following seizure induction by kainate in both acute and chronic rodent models and in human epilepsy. In the early phase of epileptogenesis, we show increased Fyn/tau/NR2B/PSD95/neuronal nitric oxide synthase complexes after status epilepticus and a postsynaptic increase of phosphorylated tau (pY18 and AT8), Fyn (pSFK-Y416), NMDAR (pNR2B-Y1472) and neuronal nitric oxide synthase. Hippocampal proximity ligation assay and co-immunoprecipitation revealed a sustained increase of Fyn-tau and NR2B-PSD95 complexes/binding in rat chronic epilepsy at 3 months post-status epilepticus. Enhanced Fyn-tau complexes strongly correlated with the frequency of spontaneously recurring convulsive seizures and epileptiform spikes in the chronic epilepsy model. In human epileptic brains, we also identified increased Fyn-tau and NR2B-PSD95 complexes, tau phosphorylation (pY18 and AT8) and Fyn activation (pSFK-Y416), implying the translational and therapeutic potential of these molecular interactions. In tau knockout mice and in rats treated with a Fyn/SFK inhibitor saracatinib, we found a significant reduction of phosphorylated Fyn, tau (AT8 in saracatinib-treated), NR2B and neuronal nitric oxide synthase and their interactions (Fyn-tau and NR2B-PSD95 in saracatinib-treated group; NR2B-PSD95 in tau knockout group). The reduction of Fyn-tau and NR2B-PSD95 interactions in the saracatinib-treated group, in contrast to the vehicle-treated group, correlated with the modification in seizure progression in the rat chronic epilepsy model. These findings from animal models and human epilepsy provide evidence for the role of Fyn-tau and NR2B-PSD95 interactions in seizure-induced brain pathology and suggest that blocking such interactions could modify the progression of epilepsy.

Scrub Typhus Meningoencephalitis Presenting as Generalized Convulsive Status Epilepticus with Basal Ganglia and Extra-limbic Cortical Involvement, Complicated by Cortical Multifocal Myoclonus

Background Scrub typhus is an acute febrile infectious disease highly prevalent in the Asia Pacific region, often referred to as the “tsutsugamushi triangle.” This mite-borne rickettsial zoonosis is caused by Orientia tsutsugamushi, an intracellular Gram-negative organism that primarily targets endothelial cells. The resulting vasculitis leads to multisystem involvement. In terms of neurological manifestations, meningoencephalitis is the most common presentation of scrub typhus. Other frequent neurological manifestations include cranial nerve paresis, transverse myelitis, and polyneuropathy. Status epilepticus, while reported, is a rare presenting feature of this infection. Although scrub typhus has been documented to present as limbic encephalitis, there have been no previous descriptions in the literature of neuroradiological patterns affecting the basal ganglia or extra-limbic cortices in this condition. Case Report We report a case of a 23-year-old previously healthy woman who presented with scrub typhus meningoencephalitis. The condition manifested as encephalitis with involvement of the basal ganglia and extra-limbic cortices. She presented with generalized convulsive status epilepticus, which was complicated by cortical multifocal myoclonus. Discussion Scrub typhus can be a significant diagnostic challenge, potentially presenting with generalized convulsive status epilepticus and mimicking both clinical and radiological features of arboviral encephalitides, such as those caused by West Nile and Japanese encephalitis viruses. Furthermore, as demonstrated in this case, its radiological presentation can resemble that of autoimmune encephalitis. Given that scrub typhus is amenable to treatment with antibiotics, such as doxycycline and azithromycin, which do not increase seizure risk, it should be considered in the differential diagnosis for patients presenting with seizures or encephalitis, especially in endemic areas.

Calsyntenin-1 expression and function in brain tissue of lithium-pilocarpine rat seizure models.

To present the expression of calsyntenin-1 (Clstn1) in the brain and investigate the potential mechanism of Clstn1 in lithium-pilocarpine rat seizure models. Thirty-five male SD adult rats were induced to have seizures by intraperitoneal injection of lithium chloride pilocarpine. Rats exhibiting spontaneous seizures were divided into the epilepsy (EP) group (n=15), whereas those without seizures were divided into the control group (n=14). Evaluate the expression of Clstn1 in the temporal lobe of two groups using Western blotting, immunohistochemistry, and immunofluorescence. Additionally, 55 male SD rats were subjected to status epilepticus (SE) using the same induction method. Rats experiencing seizures exceeding Racine's level 4 (n=48) were randomly divided into three groups: SE, SE+control lentivirus (lentiviral vector expressing green fluorescent protein [LV-GFP]), and SE+Clstn1-targeted RNA interference lentivirus (LV-Clstn1-RNAi). The LV-GFP group served as a control for the lentiviral vector, whereas the LV-Clstn1-RNAi group received a lentivirus designed to silence Clstn1 expression. These lentiviral treatments were administered via hippocampal stereotactic injection 2 days after SE induction. Seven days after SE, Western blot analysis was performed to evaluate the expression of Clstn1 in the hippocampus and temporal lobe. Meanwhile, we observed the latency of spontaneous seizures and the frequency of spontaneous seizures within 8 weeks among the three groups. The expression of Clstn1 in the cortex and hippocampus of the EP group was significantly increased compared to the control group (p<.05). Immunohistochemistry and immunofluorescence showed that Clstn1 was widely distributed in the cerebral cortex and hippocampus of rats, and colocalization analysis revealed that it was mainly co expressed with neurons in the cytoplasm. Compared with the SE group (11.80±2.17 days) and the SE+GFP group (12.40±1.67 days), there was a statistically significant difference (p<.05) in the latency period of spontaneous seizures (15.14±2.41 days) in the SE+Clstn1+RNAi group rats. Compared with the SE group (4.60±1.67 times) and the SE+GFP group (4.80±2.05 times), the SE+Clstn1+RNAi group (2.0±.89 times) showed a significant reduction in the frequency of spontaneous seizures within 2 weeks of chronic phase in rats (p<.05). Elevated Clstn1 expression in EP group suggests its role in EP onset. Targeting Clstn1 may be a potential therapeutic approach for EP management.

NLRP3 Inflammasome Inhibition After Pilocarpine-Induced Status Epilepticus Attenuates Chronic Inflammation in Epileptic Mice.

To investigate the effects of inhibiting the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome on neuronal damage and chronic pro-inflammatory responses during epileptogenesis in a mouse model of pilocarpine-induced status epilepticus (SE). Mice were randomly allocated into three groups: control, SE, and SE + MCC 950. The expression patterns of M1 and M2 microglial biomarkers in the hippocampus were quantified using Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunofluorescence staining. Additionally, seizure susceptibility, video-electroencephalography recording, Morris water maze test, and brain immunofluorescence staining were performed to evaluate the epileptic brain 4 weeks post-SE. Within 72 hours post-SE, hippocampal microglia demonstrated a preferential polarization towards the M1 phenotype, a trend that was mitigated by NLRP3 inflammasome inhibition. During epileptogenesis, SE mice treated with NLRP3 inflammasome inhibition exhibited reduced neuronal damage, improved cognitive function, decreased seizure susceptibility, and attenuated chronic pro-inflammatory responses. Inhibition of NLRP3 inflammasome post-SE effectively ameliorates neuronal loss, seizure susceptibility, and cognitive dysfunction during epileptogenesis. This neuroprotective effect may be mediated through the mitigation of chronic pro-inflammatory responses within the epileptic brain.

Use Of Ketamine In Refractory Status Epilepticus With Hemodynamic Instability

The use of benzodiazepines, such as midazolam, as a last-resort treatment for refractory status epilepticus is widely practiced, particularly in patients who are hemodynamically stable. However, as the dosage of this antiepileptic agent is increased, it potentiates γ-aminobutyric acid (GABA) activity, which can lead to hypotension and subsequently necessitate the administration of vasopressor agents, especially in cases involving hemodynamic instability, as illustrated by this case where a young man who arrived at the emergency department with complaints of epileptic seizures and was already on regular anti-epileptic medications. During a seizure episode in the department, he was administered intravenous Lorazepam according to standard protocol to stop the seizure, and then placed on an IV infusion of Midazolam. However, his hemodynamics became unstable due to the side effects of the benzodiazepines administered. To address this instability, the decision was made to initiate an infusion of Ketamine along with a low dose of Midazolam. This combination successfully terminated the epileptic activity and stabilized his hemodynamics. In these instances, either concurrent or standalone administration of N-methyl-D-aspartate (NMDA) receptor antagonists might prove beneficial for managing refractory status epilepticus. For example, ketamine infusion can inhibit the reuptake of catecholamines into the systemic circulation, thereby aiding in the maintenance of blood pressure in hemodynamically unstable patients. The initial application of a combined third-line therapy, which involves blocking NMDA receptors while simultaneously enhancing GABAergic activity, appears promising for the management of refractory status epilepticus

ERK1/2 Regulates Epileptic Seizures by Modulating the DRP1-Mediated Mitochondrial Dynamic.

After seizures, the hyperactivation of extracellular signal-regulated kinases (ERK1/2) causes mitochondrial dysfunction. Through the guidance of dynamin-related protein 1 (DRP1), ERK1/2 plays a role in the pathogenesis of several illnesses. Herein, we speculate that ERK1/2 affects mitochondrial division and participates in the pathogenesis of epilepsy by regulating the activity of DRP1. LiCl-Pilocarpine was injected intraperitoneally to establish a rat model of status epilepticus (SE) for this study. Before SE induction, PD98059 and Mdivi-1 were injected intraperitoneally. The number of seizures and the latency period before the onset of the first seizure were then monitored. The analysis of Western blot was also used to measure the phosphorylated and total ERK1/2 and DRP1 protein expression levels in the rat hippocampus. In addition, immunohistochemistry revealed the distribution of ERK1/2 and DRP1 in neurons of hippocampal CA1 and CA3. Both PD98059 and Mdivi-1 reduced the susceptibility of rats to epileptic seizures, according to behavioral findings. By inhibiting ERK1/2 phosphorylation, the Western blot revealed that PD98059 indirectly reduced the phosphorylation of DRP1 at Ser616 (p-DRP1-Ser616). Eventually, the ERK1/2 and DRP1 were distributed in the cytoplasm of neurons by immunohistochemistry. Inhibition of ERK1/2 signaling pathways downregulates p-DRP1-Ser616 expression, which could inhibit DRP1-mediated excessive mitochondrial fission and then regulate the pathogenesis of epilepsy.

A Simulation-Based Assessment of Levetiracetam Concentrations Following Fixed and Weight-Based Loading Doses: A Meta-Regression and Pharmacokinetic Modeling Analysis.

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

Clinical Value of lncRNA MALAT1 and miR-154-5p in the Severity and Prognosis of Convulsive Status Epilepticus

Clinical Value of lncRNA MALAT1 and miR-154-5p in the Severity and Prognosis of Convulsive Status Epilepticus

Neuroprotective effects of pink lotus oil in kainic acid-induced epilepsy

Excitotoxicity-induced oxidative stress results in neuronal cell death. Pink lotus essential oil (PLO) is a concentrated volatile oil from lotus blossoms widely used in traditional medicine. This study aimed to explore the possible therapeutic effects of PLO and its underlying mechanisms on kainic acid (KA)-induced oxidative stress and hippocampal cell death in a mouse model of epilepsy. Mice were treated with 100 mg/kg or 200 mg/kg PLO to ameliorate neurodegeneration and seizure-induced behavior induced by KA injection. Pre- and post-treatment of PLO increased antioxidant activities, reduced the seizure score, prevented oxidative stress by increasing GSH and CAT levels, and reduced MDA (malondialdehyde) levels after KA-induced status epilepticus. KA injection created neuronal cell death in the pyramidal layers of CA1 and CA3 subfields of the hippocampus, and affected interneurons in the hilus of the dentate gyrus. PLO treatment notably diminished KA-induced neuronal cell death in these areas through activation of the Akt signaling pathway, increasing reactive astrogliosis, and up-regulation of GDNF expression. Moreover, caspase-3 expression, and microglia activation were significantly decreased in PLO treatments. Taken together, these results suggest that PLO possesses antiepileptic, anti-apoptosic, and neuroprotective effects on KA-induced epileptogenesis indicating that PLO may serve as a dietary supplement option in the treatment of epilepsy or of other neurodegenerative disorders.

Long-term Effect of Multichannel tDCS Protocol in Patients with Central Cortex Epilepsies Associated with Epilepsia Partialis Continua.

Epilepsia partialis continua (EPC) is a rare type of focal motor status epilepticus that causes continuous muscle jerking in a specific part of the body. Experiencing this type of seizure, along with other seizure types, such as focal motor seizures and focal to bilateral tonic-clonic seizures, can result in a disabling situation. Non-invasive brain stimulation methods like transcranial direct current stimulation (tDCS) show promise in reducing seizure frequency (SF) when medications are ineffective. However, research on tDCS for EPC and related seizures is limited. We evaluated personalized multichannel tDCS in drug-resistant EPC of diverse etiologies for long-term clinical efficacy We report three EPC patients undergoing a long-term protocol of multichannel tDCS. The patients received several cycles (11, 9, and 3) of five consecutive days of stimulation at 2mA for 2 × 20min, targeting the epileptogenic zone (EZ), including the central motor cortex with cathodal electrodes. The primary measurement was SF changes. In three cases, EPC was due to Rasmussen's Encephalitis (case 1), focal cortical dysplasia (case 2), or remained unknown (case 3). tDCS cycles were administered over 6 to 22 months. The outcomes comprised a reduction of at least 75% in seizure frequency for two patients, and in one case, a complete cessation of severe motor seizures. However, tDCS had no substantial impact on the continuous myoclonus characterizing EPC. No serious side effects were reported. Long-term application of tDCS cycles is well tolerated and can lead to a considerable reduction in disabling seizures in patients with various forms of epilepsy with EPC.