Status epilepticus (SE) is an important neurological emergency. Early diagnosis could improve outcomes. Traditionally, SE is defined as seizures lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness. Some specialists argued that the duration of seizures qualifying as SE should be shorter and the operational definition of SE was suggested. It is unclear whether physicians follow the operational definition. The objective of this study was to investigate whether the incidence of SE was underestimated and to investigate the underestimate rate.

Objective: Status epilepticus (SE) is one of the most critical symptoms of encephalitis. Studies on early predictions of progression to super-refractory status epilepticus (SRSE) and poor outcome in SE due to acute encephalitis are scarce. We aimed to investigate the values of neuroimaging and continuous electroencephalogram (EEG) in the multimodal prediction. Methods: Consecutive patients with convulsive SE due to acute encephalitis were included in this study. Demographics, clinical features, neuro-imaging characteristics, medical interventions, and anti-epileptic treatment responses were collected. All the patients had EEG monitoring for at least 24 h. We determined the early predictors of SRSE and prognostic factors of 3-month outcome using multivariate logistic regression analyses. Results: From March 2008 to February 2018, 570 patients with acute encephalitis were admitted to neurological intensive care unit (N-ICU) of Xijing hospital. Among them, a total of 94 patients with SE were included in this study. The percentage of non-SRSE and SRSE were 76.6 and 23.4%. Cortical or hippocampal abnormality on neuroimaging (p = 0.002, OR 20.55, 95% CI 3.16-133.46) and END-IT score (p < 0.001, OR 4.07, 95% CI 1.91-8.67) were independent predictors of the progression to SRSE. At 3 months after N-ICU discharge, 56 (59.6%) patients attained good outcomes, and 38 (40.4%) patients had poor outcomes. The recurrence of clinical or EEG seizures within 2 h after the infusion rate of a single anesthetic drug >50% proposed maximal dose (p = 0.044, OR 4.52, 95% CI 1.04-19.68), tracheal intubation (p = 0.011, OR 4.99, 95% CI 1.37-11.69) and emergency resuscitation (p = 0.040, OR 9.80, 95% 1.11-86.47) predicted poor functional outcome. Interpretation: Initial neuro-imaging findings assist early identification of the progression to SRSE. Continuous EEG monitoring contributes to outcome prediction in SE due to acute encephalitis.

We discuss a case of a 64-year-old male with a history of liver failure presenting with altered mental status, initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus (NCSE) by electroencephalogram (EEG). NCSE is a difficult diagnosis to make, given no clear consensus on diagnostic criteria. Especially in the intensive care unit setting of persistent altered mental status with no clear etiology, NCSE must be considered in the differential diagnosis, as the consequences of delayed diagnosis and treatment can be substantial. EEG can be useful in the evaluation of patients with hepatic encephalopathy who have persistently altered levels of consciousness despite optimal medical management.

Temporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults; it often starts in infancy or early childhood. Although TLE is primarily considered to be a grey matter pathology, a growing body of evidence links this disease with white matter abnormalities. In this study, we explore the impact of TLE onset and progression in the immature brain on white matter integrity and development utilising the rat model of Li-pilocarpine-induced TLE at the 12th postnatal day (P). Diffusion tensor imaging (DTI) and Black-Gold II histology uncovered disruptions in major white matter tracks (corpus callosum, internal and external capsules, and deep cerebral white matter) spreading through the whole brain at P28. These abnormalities were mostly not present any longer at three months after TLE induction, with only limited abnormalities detectable in the external capsule and deep cerebral white matter. Relaxation Along a Fictitious Field in the rotating frame of rank 4 indicated that white matter changes observed at both timepoints, P28 and P72, are consistent with decreased myelin content. The animals affected by TLE-induced white matter abnormalities exhibited increased functional connectivity between the thalamus and medial prefrontal and somatosensory cortex in adulthood. Furthermore, histological analyses of additional animal groups at P15 and P18 showed only mild changes in white matter integrity, suggesting a gradual age-dependent impact of TLE progression. Taken together, TLE progression in the immature brain distorts white matter development with a peak around postnatal day 28, followed by substantial recovery in adulthood. This developmental delay might give rise to cognitive and behavioural comorbidities typical for early-onset TLE.

Background. Our goal was to perform a systematic review on the use of repetitive transcranial magnetic stimulation (rTMS) in the treatment of status epilepticus (SE) and refractory status epilepticus (RSE). Methods. MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to August 2015), and gray literature were searched. The strength of evidence was adjudicated using Oxford and GRADE methodology. Results. We identified 11 original articles. Twenty-one patients were described, with 13 adult and 8 pediatric. All studies were retrospective. Seizure reduction/control with rTMS occurred in 15 of the 21 patients (71.4%), with 5 (23.8%) and 10 (47.6%) displaying partial and complete responses, respectively. Seizures recurred after rTMS in 73.3% of the patients who had initially responded. All studies were an Oxford level 4, GRADE D level of evidence. Conclusions. Oxford level 4, GRADE D evidence exists to suggest a potential impact on seizure control with the use of rTMS for FSE and FRSE, though durability of the therapy is short-lived. Routine use of rTMS in this context cannot be recommended at this time. Further prospective study of this intervention is warranted.

Status epilepticus (SE) is defined as a continuous clinical and/or electrographic seizure activity lasting five minutes or more or recurrent seizure activity without return to baseline. There is a paucity of epidemiological studies of SE, as most research is derived from small population studies. The overall incidence of SE is 9.9 to 41 per 100,000/year, with peaks in children and the elderly and with febrile seizures and strokes as its main etiologies. The etiology is the major determinant of mortality. Governments and the academic community should predominantly focus on the primary prevention of etiologies linked to SE, as these are the most important risk factors for its development. This review describes the incidence, prevalence, etiology, risk factors, outcomes and costs of SE and aims to identify future research and public health needs.

The aim of this systematic review was to describe particularities in epidemiology, outcome, and management modalities in the older adult population with status epilepticus. There is a higher incidence of status epilepticus in the older adult population, and it commonly has a nonconvulsive presentation. Diagnosis in this population may be difficult and requires an unrestricted use of EEG. Short and long term associated-mortality are high, and age over 60 years is an independent factor associated with poor outcome. Stroke (acute or remote symptomatic), miscellaneous metabolic causes, dementia, infections hypoxemia, and brain injury are among the main causes of status epilepticus occurrence in this age category. The use of anticonvulsive agents can be problematic as well. Thus, it is important to take into account the specific aspects related to the pharmacokinetic and pharmacodynamic changes in older critically-ill adults. Beyond these precautions, the management may be identical to that of the younger adult, including prompt initiation of symptomatic and anticonvulsant therapies, and a broad and thorough etiological investigation. Such management strategies may improve the vital and functional prognosis of these patients, while maintaining a high overall quality of care.

Status epilepticus (SE) is an acute event, characterized by repeated or continuous seizures, which alters neuronal properties of the brain and can promote the epileptic disorder. Experimental observations indicate that SE becomes progressively less responsive to anti-epileptic drugs, suggesting changes in the underlying physiology. To assess the effect of SE on neuronal dynamics as it progresses, we measured changes in neuronal activity from CA3 hippocampus, ipsilateral and contralateral to a focal intrahippocampal injection of kainic acid during the full course of SE, 24 h post-SE, and one week post-SE. The progressively intensifying behavioral response during SE was accompanied by changes in intrinsic firing properties of single neurons, LFP oscillations and interaction between single neurons and the oscillations. These results show important changes in neuronal and network activity underlying the progression of SE.

Status epilepticus (SE) induces rapid hyper-activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. HPA axis hyperactivity results in excess exposure to high levels of circulating glucocorticoids, which are associated with neurotoxicity and depression-like behavior. These observations have led to the hypothesis that HPA axis dysfunction may exacerbate SE-induced brain injury. To test this hypothesis, we used the mouse pilocarpine model of epilepsy to determine whether use of the glucocorticoid receptor antagonist RU486 can attenuate hippocampal pathology following SE. Excess glucocorticoid secretion was evident 1 day after SE in the mice, preceding the development of spontaneous seizures (which can take weeks to develop). RU486 treatment blocked the SE-associated elevation of glucocorticoid levels in pilocarpine-treated mice. RU486 treatment also mitigated the development of hippocampal pathologies induced by SE, reducing loss of hilar mossy cells and limiting pathological cell proliferation in the dentate hilus. Mossy cell loss and accumulation of ectopic hilar cells are positively correlated with epilepsy severity, suggesting that early treatment with glucocorticoid antagonists could have anti-epileptogenic effects.

Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats.

Status epilepticus (SE) is a life-threatening medical emergency with significant morbidity and mortality. SE is associated with a robust and sustained increase in serum glucocorticoids, reaching concentrations sufficient to activate the dense population of glucocorticoid receptors (GRs) expressed among hippocampal excitatory neurons. Glucocorticoid exposure can increase hippocampal neuron excitability; however, whether activation of hippocampal GRs during SE exacerbates seizure severity remains unknown. To test this, a viral strategy was used to delete GRs from a subset of hippocampal excitatory neurons in adult male and female mice, producing hippocampal GR knockdown mice. Two weeks after GR knockdown, mice were challenged with the convulsant drug pilocarpine to induce SE. GR knockdown had opposing effects on early vs late seizure behaviors, with sex influencing responses. For both male and female mice, the onset of mild behavioral seizures was accelerated by GR knockdown. In contrast, GR knockdown delayed the onset of more severe convulsive seizures and death in male mice. Concordantly, GR knockdown also blunted the SE-induced rise in serum corticosterone in male mice. GR knockdown did not alter survival times or serum corticosterone in females. To assess whether loss of GR affected susceptibility to SE-induced cell death, within-animal analyses were conducted comparing local GR knockdown rates to local cell loss. GR knockdown did not affect the degree of localized neuronal loss, suggesting cell-intrinsic GR signaling neither protects nor sensitizes neurons to acute SE-induced death. Overall, the findings reveal that hippocampal GRs exert an anti-convulsant role in both males and females in the early stages of SE, followed by a switch to a pro-convulsive role for males only. Findings reveal an unexpected complexity in the interaction between hippocampal GR activation and the progression of SE.

Acute complications from cocaine abuse are commonly treated in the emergency department (ED); one of the most consequential is status epilepticus. The incidence of this complication is not clearly defined in the prior literature on cocaine-associated sequelae. We evaluated the incidence of status epilepticus in patients with seizures secondary to suspected cocaine use.

Acute injuries or insults to the cortex, such as trauma, subarachnoid hemorrhage, lobar hemorrhage, can cause seizures or status epilepticus(SE). Neocortical SE is associated with coma, worse prognosis, delayed recovery, and the development of epilepsy. The anatomical structures progressively recruited during neocortical-onset status epilepticus (SE) is unknown. Therefore, we constructed large-scale maps of brain regions active during neocortical SE.

Prolonged seizures are associated with injury to vulnerable neurons, particularly in the hippocampus. Identification of compounds that attenuate injury after prolonged seizures could be of value in the management of refractory status epilepticus. We hypothesized that topiramate, an anticonvulsant with multiple mechanisms of action, would attenuate hippocampal neuronal injury when given after experimental status epilepticus. Limbic status epilepticus was induced in adult male Wistar rats for 140 min by unilateral hippocampal electrical stimulation. Rats then received intraperitoneal injections of either vehicle (n=6) or topiramate at 20 mg/kg (n=6), 40 mg/kg (n=7) or 80 mg/kg (n=7). Three days later, hippocampal sections were processed for neuronal degeneration using a silver impregnation stain. Seizure-induced damage was assessed by measuring the density of silver staining in hippocampal regions CA1, CA3 and dentate hilus. Administration of topiramate at each dose was associated with a significant reduction in staining density bilaterally in area CA1 and the dentate hilus. Reduction in staining density in area CA3 was seen contralateral to the side of stimulation at the two higher topiramate doses only. The results indicate that administration of topiramate after experimental status epilepticus can attenuate seizure-induced hippocampal neuronal injury.

Super-refractory status epilepticus (SRSE) presents management challenges due to the absence of randomized controlled trials and a plethora of potential medical therapies. The literature on treatment options for SRSE reports variable success and quality of evidence. This review is a sequel to the 2020 American Epilepsy Society (AES) comprehensive review of the treatment of convulsive refractory status epilepticus (RSE).

Both variegate and acute intermittent porphyria can manifest with various neurological symptoms. Although acute symptomatic seizures have been previously described, they are typically tonic-clonic and focal impaired awareness seizures. Convulsive status epilepticus and epilepsia partialis continua are rare and have been described on a case report basis. To our knowledge, there are no previously reported cases describing non-convulsive status epilepticus (NCSE) with electroencephalogram (EEG) documentation in the setting of acute porphyria crisis. We report a unique presentation of NCSE, which resolved after administering levetiracetam in a patient with variegate porphyria, without a known seizure disorder.

Status epilepticus (SE) is a prevalent disorder associated with significant morbidity, including the development of epilepsy and mortality. Cardiac arrhythmias (i.e. inappropriate sinus tachycardia and bradycardia, asystole, and atrioventricular blocks) are observed in patients following SE. We characterized ictal (during a seizure) and interictal (between seizure) cardiac arrhythmogenesis following SE using continuous electrocardiography and video electroencephalography (vEEG) recordings throughout a 14-day monitoring period in an intrahippocampal chemoconvulsant mouse model that develops epilepsy. We quantified heart rhythm abnormalities and examined whether the frequency of cardiac events correlated with epileptiform activity, circadian (light/dark) cycle, the presence of seizures, and survival during this period of early epileptogenesis (the development of epilepsy) following SE. Shortly following SE, mice developed an increased interictal heart rate and heart rhythm abnormalities (i.e. sinus pause and sinus arrhythmias) when compared to control mice. Heart rhythm abnormalities were more frequent during the light cycle and were not correlated with increased epileptiform activity or seizure frequency. Finally, SE animals had early mortality, and a death event captured during vEEG recording demonstrated severe bradycardia prior to death. These cardiac changes occurred within 14 days after SE and may represent an early risk factor for sudden death following SE.

In March 2020, the World Health Organization declared the SARS-CoV-2 infection-related coronavirus Disease (COVID-19) a pandemic. During the first and second waves of the pandemic spread, there have been several reports of COVID-19-associated neurological manifestations, including acute seizures and status epilepticus (SE). In this systematic review, we summarized the available data on clinical features, diagnosis, and therapy of COVID-19-related SE.

Hippocampal damage caused by status epilepticus (SE) can bring about cognitive decline and emotional disorders, which are common clinical comorbidities in patients with epilepsy. It is therefore imperative to develop a novel therapeutic strategy for protecting hippocampal damage after SE. Mitochondrial dysfunction is one of contributing factors in epilepsy. Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria, we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE.

Status epilepticus (SE) is a life-threatening neurologic emergency. Despite advances in management, in-hospital mortality remains unchanged. This is partly due to the pharmacoresistance which develops the longer that seizures persist. Therefore, rapid antiseizure medication (ASM) administration may represent a beneficial treatment option. The purpose of this study was to determine: 1) whether in-hospital mortality is reduced with shorter latencies to initial treatment of SE with an ASM (LTSE); and 2) the critical time frame during which LTSE is associated with reduced in-hospital mortality.