Intramuscular atenolol and levetiracetam reduce mortality in a rat model of paraoxon-induced status epilepticus.
Ontology highlight
ABSTRACT:
SUBMITTER: Deshpande LS
PROVIDER: S-EPMC7708441 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundStatus epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line treatment but fails to control SE in about one-third of patients. Levetiracetam may be used for SE that is refractory to benzodiazepine therapy.ObjectiveTo examine, by means of a systematic review, the role of IV levetiracetam for the treatment of SE in adults.Data sourcesMEDLINE, Embase, CENTRAL, and CINAHL databases were searched, from inception to August 18, 2020.Study selection and data extractionIncluded in this review were prospective randomized controlled trials comparing levetiracetam with another antiepileptic drug, given with or after a benzodiazepine, in adult patients with SE. The primary outcome was cessation of SE. Quality of evidence was assessed with the Cochrane risk-of-bias tool. Characteristics of the included studies were reported using descriptive statistics.Data synthesisFive studies compared IV levetiracetam with valproic acid, phenytoin (or its prodrug fosphenytoin), or both. All 5 studies found no statistically significant differences in efficacy or safety end points. There were numerically more cases of hypotension and respiratory failure with phenytoin, and more cases of psychiatric adverse effects (e.g., post-ictal psychosis) with levetiracetam.ConclusionsAvailable evidence suggests that levetiracetam is as effective as valproic acid or phenytoin for the cessation of SE in adults. Other factors should therefore dictate the choice of antiepileptic drug for patients with SE, such as adverse effect profile, logistics of administration, drug cost, inclusion on hospital formularies, and drug availability.
| S-EPMC8677000 | biostudies-literature
Project description:Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.This double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics. Subjects whose convulsions had persisted for more than 5 minutes and who were still convulsing after paramedics arrived were given the study medication by either intramuscular autoinjector or intravenous infusion. The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy. Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures. This trial tested the hypothesis that intramuscular midazolam was noninferior to intravenous lorazepam by a margin of 10 percentage points.At the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the intramuscular-midazolam group and in 282 of 445 (63.4%) in the intravenous-lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0 to 16.1; P<0.001 for both noninferiority and superiority). The two treatment groups were similar with respect to need for endotracheal intubation (14.1% of subjects with intramuscular midazolam and 14.4% with intravenous lorazepam) and recurrence of seizures (11.4% and 10.6%, respectively). Among subjects whose seizures ceased before arrival in the emergency department, the median times to active treatment were 1.2 minutes in the intramuscular-midazolam group and 4.8 minutes in the intravenous-lorazepam group, with corresponding median times from active treatment to cessation of convulsions of 3.3 minutes and 1.6 minutes. Adverse-event rates were similar in the two groups.For subjects in status epilepticus, intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation. (Funded by the National Institute of Neurological Disorders and Stroke and others; ClinicalTrials.gov number, ClinicalTrials.gov NCT00809146.).
| S-EPMC3307101 | biostudies-literature
Project description:ObjectiveIn vivo studies of epilepsy typically use prolonged status epilepticus to generate recurrent seizures. However, reports on variable status duration have found discrete differences in injury after 40-50 min of seizures, suggesting a pathophysiologic sensitivity to seizure duration. In this report we take a multivariate cluster analysis to study a short duration status epilepticus model using in vivo 7T magnetic resonance spectroscopy (MRS) and histologic evaluation.MethodsThe Hellier Dudek model was applied with 45 min of status epilepticus after which the animals were imaged twice, at 3 days and 3 weeks post-status epilepticus. Single voxel point resolved spectroscopy (PRESS) MRS was used to acquire data from the dentate gyrus and CA3 region of the hippocampus, assessing metabolite ratios to total creatine (tCr). In a subset of animals after the second imaging study, brains were analyzed histologically by Nissl staining.ResultsA hierarchical cluster analysis performed on the 3-day data from 21 kainate-treated animals (dentate gyrus voxel) segregated into two clusters, denoted by KM (more injured, n = 6) and KL (less injured, n = 15). Although there was no difference in kainate dosing or seizure count between them, the metabolic pattern of injury was different. The KM group displayed the largest significant changes in neuronal and glial parameters; the KL group displayed milder but significant changes. At 3 weeks, the KL group returned to normal compared to controls, whereas the KM group persisted with depressed N-acetyl aspartate (NAA)/tCr, glutamate/tCr, and increased inositol/tCr and glutamine/tCr. The classification was also consistent with subsequent histologic patterns at 3 weeks.SignificanceAlthough a short status period might be expected to generate a continuous distribution of metabolic injury, these data show that the short Hellier Dudek model appears to generate two levels of injury. The changes seen in segregated groups persisted into 3 weeks, and can be interpreted according to neuronal and glial biomarkers consistent with histology results.
| S-EPMC5215597 | biostudies-literature
Project description:Levetiracetam (LEV) suppresses the upregulation of proinflammatory molecules that occurs during epileptogenesis after status epilepticus (SE). Based on previous studies, LEV likely helps prevent the onset of epilepsy after insults to the brain, unlike other conventional anti-epileptic drugs. Recently, we discovered that the increase in Fosl1 expression that occurs after lipopolysaccharide (LPS) stimulation is suppressed by LEV and that Fosl1 inhibition suppresses inflammation in BV-2 microglial cells. These data indicate that Fosl1 is an important target of LEV and a key factor in preventing epilepsy onset. In this study, we examined the effects of LEV on Fosl1 expression and neuroinflammation in vivo. During epileptogenesis, the post-SE upregulation of hippocampal levels of Fosl1 and many inflammatory factors were suppressed by LEV. Fosl1 expression showed a characteristic pattern different from that of the expression of Fos, an immediate-early gene belonging to the same Fos family. At 2 days after SE, Fosl1 was predominantly expressed in astrocytes but was rarely detected in microglia, whereas Fos expression was distributed in various brain cell types. The expression of A2 astrocyte markers was similar to that of Fosl1 and was significantly suppressed by LEV. These results suggest that LEV may regulate astrocyte reactivity through regulation of Fosl1.
| S-EPMC9317701 | biostudies-literature
Project description:To clarify the different regional brain electroencephalogram (EEG) activities and biochemical responses in seizure and epilepsy models, we assessed the EEG and c-Fos immunolabeling characteristics in a lithium-pilocarpine-induced status epilepticus (SE) model and pentylenetetrazol (PTZ)-induced seizure model. The regional brain activities were evaluated by EEG and c-Fos immunolabeling. ZnT3 immunostaining was performed to observe hippocampal mossy fiber sprouting (MFS) within 7 days after the induction of SE in the lithium-pilocarpine model. The EEG recordings showed distinctive features of activation in different brain areas. With the aggravation of the behavioral manifestations of the seizures, the frequency and amplitude of the discharges on EEG gradually increased. SE was eventually induced and sustained. The labeling of c-Fos was enhanced in the cortex and hippocampal CA1, CA3, and dentate gyrus (DG); however, compared to the PTZ-induced seizure model, c-Fos staining could only be observed in the striatum and thalamus in the lithium-pilocarpine-induced epilepsy model. In each brain region, prominent c-Fos labeling was observed 2 h and 4 h after the induction of SE or seizures and diminished at 24 h. During the lithium-pilocarpine-induced chronic epilepsy phase after SE induction, MFS was observed 7 days after SE and was accompanied by the dynamic evolution of epileptic EEG activities. These findings validated the lithium-pilocarpine-induced SE model as an epilepsy model with a specific spatial-temporal profile of neural activation. The EEG characteristics and c-Fos expression patterns differ from those presented in a previous study using a PTZ-induced seizure model. Hippocampal mossy fiber spouting might be associated with spontaneous seizures during the chronic phase and can be detected at least within 1 week by ZnT3 staining after stimulation.
| S-EPMC6974466 | biostudies-literature
Project description:Status Epilepticus (SE) is common in neonates and infants, and is associated with neuronal injury and adverse developmental outcomes. However, the role of SE in this injury is uncertain. Until now, we have lacked an animal model in which seizures result in neuronal injury in rodent models at ages below postnatal day 12 (P12) unless seizures are combined with inflammatory stressors.We induced SE with high-dose lithium and pilocarpine in P7 rats, which are developmentally close to human neonates. Several EEG measures and O2 saturation were recorded during the 6h following initiation of SE. We assessed neuronal injury at 6 and 24h post-SE onset using Fluoro-Jade B staining (FJB) and caspase-3a immunoreactivity (IR).EEGs showed continuous polyspikes activity for 54.3 ± 6.7 min, while O2 saturation showed no significant hypoxemia. By 24h after SE onset, significant neuronal injury was observed in CA1/subiculum, CA3, dentate gyrus, thalamus, neocortex, amygdala, piriform cortex, lateral entorhinal cortex, hypothalamus, caudate putamen, globus pallidus, ventral pallidum, and nucleus accumbens. At 24h post-SE, caspase-3a IR was significantly increased in CA1/subiculum, thalamus, and neocortex compared to sham, and caspase-3a IR neurons had fragmented nuclei, suggesting that SE triggered an irreversible form of cell injury.In conclusion, we have developed a model of cholinergic SE in P7 rat pups, which combines high survival (69.9% survival at 24h) and widespread brain injury. These studies suggest that the immature brain is vulnerable to severe forms of SE.
| S-EPMC4740206 | biostudies-literature
Project description:LEV is known to be involved in neuroprotection via anti-angiogenesis and anti-inflammatory activities against blood-brain barrier dysfunction in the acute phase of epileptogenesis after SE, but the mechanism remains unclear. The purpose of this study is to comprehensively examine the gene expression in hippocampus of LEV-treated and untreated pilocarpine induced (PILO-) SE mouse in order to understand the whole process of early epileptogenesis.
2022-06-09 | GSE205373 | GEO
Project description:Levetiracetam can be used for seizure control alone or in combination with other antiepileptic medications. A previous study achieved the minimum targeted serum drug concentration after rectal administration of levetiracetam in healthy dogs. The purpose of the present study was to determine the pharmacokinetics of rectal LEV in dogs presented for cluster seizures or status epilepticus and potentially in treatment with other anti-epileptic drugs. Furthermore, preliminary information on response to this treatment as add-on to the standard treatment protocol is reported.Eight client-owned dogs were enrolled. Plasma levetiracetam concentrations (measured at 0, 30, 60, 90, 120, 180, 240, 360, 720, and 1440 min after drug administration) reached the minimum target concentration (5 ?g/ml) at 30 min in all but one patient. At T1 (30 min) the mean concentration was 28.2?±?15.5 ?g/ml. Plasma concentrations remained above the targeted minimum concentration in all patients until 240 min and in 7/8 until 360 min. Six out of eight patients experienced no seizures in the 24-h period after hospitalization and were classified as "responders".Minimum plasma levetiracetam concentration can be reached after rectal administration of 40 mg/kg in dogs affected by cluster seizures and status epilepticus and concurrently receiving other antiepileptic drugs. These preliminary results may encourage the evaluation of rectal levetiracetam as an additional treatment option for cluster seizures and status epilepticus in a larger number of dogs.
| S-EPMC6006693 | biostudies-other
Project description:PurposeThe immature rat brain is highly susceptible to seizures, but has a resistance to pathological changes induced by seizures as compared to adult rats. However, prolonged seizures during early-life enhance cellular injury and hyperexcitability induced by convulsive insults later in adulthood. The mechanisms underlying these phenomena are not understood. In adult models, the CA1 axons reorganize their projections to subiculum. Seizure induced plasticity in this pathway has not been investigated in immature seizure models, and may contribute to the vulnerability to later seizures.MethodsOn postnatal day 15, rats experienced convulsive status epilepticus with kainic acid (KA). Seizure induced plasticity was examined with Timm histochemistry and iontophoretic injections of sodium selenite, a retrograde tracer. Cellular injury was evaluated with Fluoro-Jade B histochemistry.ResultsRetrograde tracing experiments determined a 67% larger dorsoventral extent of retrograde labeling in the CA1 pyramidal region after tracer injections in subiculum. The synaptic reorganization of the CA1 projection to subiculum was noted in the absence of overt neuronal injury in subiculum or CA1. In contrast, mossy fiber sprouting was detected into the stratum oriens of CA3 with limited neuronal injury to CA3 pyramidal neurons. No mossy fiber sprouting into the inner molecular layer of the dentate gyrus, or CA1 sprouting into the stratum moleculare of CA1 were noted.ConclusionsThe results indicate that the developing brain has distinct mechanisms of seizure induced reorganization as compared to the adult brain. Our experiments show that the concept of "resistance of the immature brain to excitotoxicity" is considerably more complicated than generally believed. Morphological plasticity in the immature brain appears more extensive in distal, but not proximal, projections of hippocampal pathways, and across hippocampal lamellae. The abnormal connectivity between hippocampal lamellae might play a role in the increased susceptibility to injury and hyperexcitability associated with later convulsive insults.
| S-EPMC1876715 | biostudies-literature
Project description:Objective: Status epilepticus is a major emergency condition. The choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial, including levetiracetam vs. fosphenytoin. We compare the safety of intravenous levetiracetam and fosphenytoin as a second-line treatment in patients with status epilepticus using a nationwide database. Methods: An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from March 1, 2011 to March 31, 2018. Patients who received intravenous levetiracetam on the day of admission were defined as the levetiracetam group and those who received intravenous fosphenytoin on the day of admission were defined as the fosphenytoin group. Propensity score matching was performed to compare outcomes obtained for the levetiracetam and fosphenytoin groups. Results: The analysis examined data of 5,667 patients. Overall, 1,403 (25%) patients received levetiracetam; 4,264 (75%) received fosphenytoin. One-to-one propensity score matching created 1,363 matched pairs. No significant difference was found in in-hospital mortality (5.2 vs. 5.1%; odds ratio, 1.03; 95% confidence interval, 0.73-1.46). The proportion of vasopressor use on the day of admission was significantly lower for the levetiracetam group than for the fosphenytoin group (3.2 vs. 4.9%; odds ratio, 0.63; 95% confidence interval, 0.43-0.92). No significant difference was found in other secondary outcomes including total hospitalization cost. Conclusion: Levetiracetam was related to significantly reduced vasopressor use on the day of admission than that found for fosphenytoin, in adult status epilepticus.
| S-EPMC7348044 | biostudies-literature