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Resumen La arteriopatia autosomica dominante cerebral con infartos subcorticales y leucoencefalopatia es una enfermedad autosomica dominante de pequenos vasos causada por mutaciones del gen NOTCH3. Tipicamente se presenta con migrana, eventos isquemicos cerebrales recurrentes y trastornos cognitivos. Las crisis epilepticas son inusuales como manifestacion inicial, pero aun mas infrecuente es su presentacion como status epilepticus no convulsivo 1 . Se presenta una serie familiar de 3 casos con esta arteriopatia, entre los cuales 2 de ellos tuvieron status epilepticus como manifestacion de la enfermedad.

To summarize and evaluate clinical experiences with refractory status epilepticus in which cannabidiol (CBD) was utilized for cessation of seizure activity.A comprehensive literature review was performed on PubMED, MEDLINE, Scopus, and CINAHL between May - June 2022 with the assistance of a medical reference librarian using the following search terms: "Cannabidiol" [MAJR], "Status Epilepticus" [MAJR], "New-Onset Refractory Status Epilepticus", and "cannabidiol." Reports that provided dosing regimens and patient outcomes were included.Thirty-two articles were screened. Five articles were selected for inclusion in this review and detailed the clinical courses of 11 patients. Five of the 11 patients received CBD during the chronic epilepsy stage, while the remaining 6 received it during a period of acute status epilepticus. Patients were trialed on an average of 9 anti-epileptic drugs prior to CBD administration, after which 9 of the 11 patients experienced a reduction of seizure activity. Dosing of CBD ranged between 5-25 mg/kg/day and was titrated based on patient response to therapy. Adverse effects were relatively benign and were generally limited to gastrointestinal discomfort, reported after seizure cessation.CBD may provide a potentially efficacious and safe management strategy in refractory status epilepticus, including patients with new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome. A potential for drug-drug interactions between CBD and anti-epileptic drugs warrants judicious monitoring. Additional research is necessary to determine a definitive dosing strategy for this agent.

This study aimed to determine the mortality, causes of death and factors affecting the outcome of convulsive status epilepticus (CSE) at 10 years.This retrospective study consisted of 62 consecutive adult patients diagnosed with CSE at the Helsinki University Hospital (HUS) emergency department during 2002-2003. Patients were followed for up to 10 years or up to the time of death. Data on patient demographics, CSE characteristics, treatment, complications, and outcome from the time of CSE were collected. The Official Statistics of Finland provided the information on mortality and causes of death. Survival analysis was conducted using Cox proportional hazards regression analysis.In-hospital mortality was 8.1%, and mortality was 25.8% at one year, 51.6% at five years and 64.5% at 10 years. Estimated standardized mortality ratio (SMR) was 5.3 and the deceased patients lost 20.9 potential years of life, on average. The leading causes of death were disorders of the brain or the circulatory system, epilepsy-related conditions or intracranial tumours. The univariable survival analysis demonstrated that age ≥65 (HR=2.8, p=0.001), Charlson Comorbidity Index (CCI)0 (CCI=1-3: HR=3.0, p=0.009; CCI3: HR=8.4, p0.001), Status Epilepticus Severity Score (STESS)4 (HR=5.3, p0.001) and Epidemiology-Based Mortality Score (EMSE-EAC)15 (HR=2.2, p=0.036) were risk factors and a Glasgow outcome scale (GOS) of 5 at discharge (HR=0.14, p=0.025) was a protective factor for survival. The multivariable analysis established STESS4 (HR=5.0, p=0.002) and CCI0 (CCI=1-3: HR=2.9, p=0.015;CCI3: HR=6.3, p=0.006) as independent risk factors and GOS3 (time-dependent) (GOS=4: HR=0.33, p=0.048;GOS=5: HR=0.13, p=0.019) as a protective factor for survival.The rate of long-term mortality and number of potential years of life lost were high. Factors demonstrative of the overall situation of the patients, such as comorbidities, functional state after CSE and age, were significant predictors for long-term outcome.

Determine the prevalence of seizure clusters (two or more seizures in six hours), use of rescue medications, and adverse outcomes associated with seizure clusters in pediatric patients with a range of epilepsy severities, and identify risk factors predictive of seizure clusters.Prospective observational two-center study, including phone call and seizure diary follow-up for 12 months in patients with epilepsy aged one month to 18 years. We classified patients into three risk groups based on seizures within the prior year: high, seizure cluster (two or more seizures within one day); intermediate, at least one seizure but no days with two or more seizures; low, no seizures.One-third (32.3%; high risk, 72.4%; intermediate risk, 30.4%; low risk, 3.1%) of 297 patients had a seizure cluster during the study, including half (46.2%) of the patients with active seizures at baseline (intermediate- and high-risk groups combined). Emergency room visits or injuries were no more likely due to a seizure cluster than an isolated seizure. Rescue medications were utilized in 15.8% of patients in the high-risk group and 19.2% in the intermediate-risk group. History of status epilepticus (adjusted odds ratio [aOR], 2.13; confidence interval [CI], 1.09 to 4.16]), seizure frequency greater than four per month (aOR, 4.27; CI, 1.92 to 9.50), and high-risk group status (aOR, 6.42; CI, 2.97 to 13.87) were associated with greater odds of seizure cluster.Seizure clusters are common in pediatric patients with epilepsy. High seizure frequency was the strongest predictor of clusters. Rescue medications were underutilized. Future studies should evaluate the applicability and effectiveness of these medications for optimization of pediatric seizure cluster treatment and reduction of seizure-related emergency department visits, injuries, and mortality.

Treatment of seizure clusters endeavors to prevent additional seizures and avoid progression to conditions such as prolonged seizures and status epilepticus. Rescue therapies are key components of seizure action plans (SAPs) for individuals with seizure clusters. Three rescue therapies are approved in the United States for the treatment of seizure clusters: diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. Diazepam rectal gel is an effective rescue therapy for seizure clusters, though adults and adolescents may have social reservations regarding its administration. Intranasal delivery of midazolam or diazepam is a promising alternative to rectal administration because these formulations offer easy, socially acceptable administration exhibit a rapid onset, and allow for the possibility of self-administration. Off-label benzodiazepines, such as orally disintegrating lorazepam and intranasal use of an intravenous (IV) formulation of midazolam via nasal atomizer, are less well characterized regarding bioavailability and tolerability compared with approved agents.

Purpose Seizures pose a significant burden in patients with primary and secondary brain tumors during the end-of-life period. A wide range of 6 to 56% of clinically observed epileptic seizures at the end of life has been reported. We aimed to analyse the incidence of epileptic seizures at the end of life in brain tumor patients more accurately using not only clinical but also electrophysiological findings. Methods This retrospective, single center study included brain tumor patients who died during the stay on the ward or within 7 days after discharge between 01/2015 and 08/2020. Clinical observation of seizures derived from the original medical records and EEG findings (within 45 days prior to death) were analyzed to determine the incidence of seizures in that period. Results Of the 68 eligible patients, 50 patients (73.5%) suffered from seizures within 45 days prior to death, of which n = 24 had a status epilepticus. The diagnosis of seizures/ status epilepticus was determined either by the presentation of clinical signs in 45 patients and if not, by the detection of a (possible) non-convulsive status epilepticus in the EEG of five patients. Conclusion In the presence of neurologically trained staff and with the frequent use of routine EEG, we were able to identify seizures and to distinguish status epilepticus from encephalopathy/ hypoactive delirium. We detected a higher incidence of seizures and status epilepticus at the end of life in neurooncological patients than previously reported.

Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available evidence and provide estimates of comparative effectiveness and ranking of treatment effects.All randomized controlled trials studying patients (1 month of age) with benzodiazepine-resistant SE were included. Outcomes including seizure cessation within 60 min, seizure freedom for 24 h, death, respiratory depression warranting intubation and cardiovascular instability were studied. Conventional and network meta-analyses (NMA) were done.Seventeen studies were included (16 in NMA). Phenobarbital and high-dose levetiracetam were significantly superior to phenytoin with respect to seizure cessation within 60 min. Network ranking demonstrated that phenobarbital had the highest probability of being the best among the studied interventions followed by high-dose levetiracetam and high-dose valproate. Network meta-analysis was limited by predominant indirect evidence and high heterogeneity.On pairwise comparisons, phenobarbital was found to be associated with a higher risk of need for intubation and cardiovascular instability. Levetiracetam had a better safety profile than fosphenytoin.Based on low quality evidence, phenobarbital appears to be the most effective agent for seizure cessation within 60 min of administration in patients with benzodiazepine resistant status epilepticus. High-dose levetiracetam, high-dose valproate and fosphenytoin are probably equally effective. Choice of medication may be guided by effectiveness, safety concerns, availability, cost and systemic co-morbidities.

Functional status (FSt) describes the phenomenon of prolonged non-epileptic attacks that may be misidentified as Status Epilepticus (SE). The early differentiation between epileptic and functional status is crucial in order to avoid unnecessarily invasive and costly medical escalation in the latter group, including the hazards of overmedication, intubation and intensive care admission. The authors conducted a literature review of available studies describing cases of functional status to extract the common aspects of FSt seizure semiology, investigations used to differentiate from SE, and guidance for managing FSt. A search was carried out using Medline, Embase and PsychInfo databases and 3909 papers were extracted for review. 30 papers were found relevant for inclusion, describing 260 cases of FSt. FSt was found to occur more commonly in younger, female patients with a family history of epilepsy, co-morbid psychiatric diagnosis and following a recent traumatic event. Common clinical features of FSt during and after, the events were identified. While video-EEG remains the gold standard investigation for differentiating FSt from SE, many of the included studies considered the utility of other investigation modalities including serum markers and neuroimaging. One key shortcoming identified within the literature reviewed was a lack of well-defined guidance on the acute management of FSt. We offer an A-F step management plan for the immediate and longer term assessment and treatment of FSt.

Most seizures in critical ill patients are non-convulsive, and some patients may develop non-convulsive status epilepticus (NCSE), a state of continuous or repetitive seizures without convulsions. With the growing use of continuous electroencephalogram (EEG) monitoring in neuro-intensive care units, non-convulsive seizure (NCS) and NCSE are increasingly diagnosed in patients with impaired consciousness, and progress has been made in identifying various EEG characteristics of NCS/NCSE. Epidemiological studies have contributed to a better understanding of etiologies and risk factors for NCS and NCSE. However, sufficient clinical trials about the treatment of NCS and NCSE are still lacking. The appropriate level of aggressiveness in the treatment of NCSE is still debated, particularly with regard to the use of anesthetics in patients with refractory NCSE. In this review, we summarize the EEG, clinical, epidemiological, diagnostic and therapeutic knowledge of NCS and NCSE in the neuro-intensive care setting in detail.

To investigate and analyze the etiology and prognosis of patients with new-onset status epilepticus (NOSE).We conducted a retrospective analysis of all adult patients (≧16 years old) who were admitted to Sichuan Provincial People's Hospital between January 2018 and December 2020 with status epilepticus (SE) and no prior epilepsy history.We collected data from 85 patients, aged from 16 to 90 years, of whom 49 were male and 36 were female. Fifty-five of these cases (64.7%) were younger than 60 years of age. Acute symptomatic SE was mostly seen in the NOSE (53.9%), followed by unknown SE (25.9%), progressive SE (11.8%), and remote SE (9.4%). The differences in the etiology of NOSE between age groups were statistically significant (P .05). For the young, the main etiology remained unknown (36.3%), followed by autoimmune-related SE (16.4%); in the elderly, the primary etiology was central nervous system (CNS) infection (23.3%), followed by cerebrovascular disease (20%), and intracranial tumors (20%). Normal imaging was mostly seen in young people with NOSE (P .001). Regarding outcome parameters and risk factors in patients with NOSE, adverse outcome was associated with age (OR = 3.5, 95% CI = 0.108-0.758, P = .012), co-infection (OR = 4.5, 95% CI = 0.083-0.599, P = .003), and tracheal intubation (OR = 6.318, 95% CI = 0.060-0.204, P = .011).In our cohort, intracranial tumors, CNS infections, and cerebrovascular disease were the predominant causes of NOSE in the elderly, while autoimmune encephalitis was the largest recognized cause of NOSE in young patients. In addition, imaging varies with age. According to the data, preventing infections may enhance patient prognosis because greater infection rates are connected with less favorable results. Meanwhile, age and mechanical ventilation are related to the prognosis of NOSE.

Diagnosis of non-convulsive status epilepticus (NCSE) is challenging and outcomes during follow-up are not clear. This study aimed to conduct power spectrum analysis in NCSE and measure outcomes of patients.We searched continuous EEG monitoring (cEEG) recordings to identify patients of NCSE. An artifact-free cEEG epoch of continuous 60 s was chosen for spectral power analysis. We also collected electronic medical records of the patients for extracting clinical information. Patients recruited were followed up at least every half a year.There were 48 patients with 64 independent NCSE episodes during different course of disease recruited in the study, with a mean age of 40.3 ± 19.1 years (range, 12-72 years), including 24 males (50%) and 24 females (50%). When the spectral power of 60 s equaled to 11.30 μVSpectral power analysis can be used to detect mental status and limb jerks. Early diagnosis and treatment of NCSE are important, which can influence outcomes of the patients during follow-up.

In patients with status epilepticus (SE), the clinical significance of ictal changes on magnetic resonance imaging (MRI) is insufficiently understood. We here studied whether the presence of ictal MRI changes was associated with neurological deterioration at discharge.The retrospective cohort comprised all identifiable patients treated at Odense University Hospital in the period 2008-2017. All amenable MRIs were systemically screened for ictal changes. Patient demographics, electroencephalography, seizure characteristics, treatment, and SE duration were assessed. Neurological status was estimated before and after SE. The predefined endpoint was the association of neurological deterioration and ictal MRI changes.Of 261 eligible patients, 101 received at least one MRI during SE or within 7 days after cessation; 43.6% (44/101) had SE due to non- or less brain-damaging etiologies. Patients who received MRI had a longer duration of SE, less frequently had a history of epilepsy, and were more likely to have SE due to unknown causes. Basic characteristics (including electroencephalographic features defined by the Salzburg criteria) did not differ between patients with (n = 20) and without (n = 81) ictal MRI changes. Timing of MRI was important; postictal changes were rare within the first 24 h and hardly seen5 days after cessation of SE. Ictal MRI changes were associated with a higher risk of neurological deterioration at discharge irrespective of etiology. Furthermore, they were associated with a longer duration of SE and higher long-term mortality that reached statistical significance in patients with non- or less brain-damaging etiologies.In this retrospective cohort, ictal changes on MRI were associated with a higher risk of neurological deterioration at discharge and, possibly, with a longer duration of SE and poorer survival.

We performed virological analysis of resected brain tissues from a patient with temporal lobe epilepsy associated with mesial temporal sclerosis after febrile status epilepticus caused by human herpesvirus 6 infection. The patient had febrile status epilepticus at 9 months of age associated with human herpesvirus 6 infection. Magnetic resonance imaging revealed reduced water diffusion in the right temporal lobe and hippocampus. Polymerase chain reaction analysis detected 1.6 × 10

Status epilepticus (SE) is an acute, life-threatening medical condition that requires immediate, effective therapy. Therefore, the acute care of prolonged seizures and SE is a constant challenge for healthcare professionals, in both the pre-hospital and the in-hospital settings. Benzodiazepines (BZDs) are the first-line treatment for SE worldwide due to their efficacy, tolerability, and rapid onset of action. Although all BZDs act as allosteric modulators at the inhibitory gamma-aminobutyric acid (GABA)subA/subreceptor, the individual agents have different efficacy profiles and pharmacokinetic and pharmacodynamic properties, some of which differ significantly. The conventional BZDs clonazepam, diazepam, lorazepam and midazolam differ mainly in their durations of action and available routes of administration. In addition to the common intravenous, intramuscular and rectal administrations that have long been established in the acute treatment of SE, other administration routes for BZDs-such as intranasal administration-have been developed in recent years, with some preparations already commercially available. Most recently, the intrapulmonary administration of BZDs via an inhaler has been investigated. This narrative review provides an overview of the current knowledge on the efficacy and tolerability of different BZDs, with a focus on different routes of administration and therapeutic specificities for different patient groups, and offers an outlook on potential future drug developments for the treatment of prolonged seizures and SE.

Temporal lobe epilepsy is the most common drug-resistant epilepsy. To cure epilepsy, drugs must target the mechanisms at the origin of seizures. Thus, the present investigation aimed to evaluate the antiepileptic- and anti-amnesic-like effects of an aqueous extract of Syzygium cumini against kainate-induced status epilepticus in mice, and possible mechanisms of action. Mice were divided into 7 groups and treated as follows: normal group or kainate group received po distilled water (10 mL/kg), four test groups received Syzygium cumini (28.8, 72, 144, and 288 mg/kg, po), and the positive control group treated intraperitoneally (ip) with sodium valproate (300 mg/kg). An extra group of normal mice was treated with piracetam (200 mg/kg, po). Treatments were administered 60 min before the induction of status epilepticus with kainate (15 mg/kg, ip), and continued daily throughout behavioral testing. Twenty-four hours after the induction, T-maze and Morris water maze tasks were successively performed. The animals were then sacrificed and some markers of oxidative stress and neuroinflammation were estimated in the hippocampus. The extract significantly prevented status epilepticus and mortality. In the T-maze, the aqueous extract markedly increased the time spent and the number of entries in the discriminated arm. In the Morris water maze, the extract significantly increased the time spent in the target quadrant during the retention phase. Furthermore, the aqueous extract induced a significant reduction of oxidative stress and neuroinflammation. These results suggest that the aqueous extract of Syzygium cumini has antiepileptic- and anti-amnesic-like effects, likely mediated in part by antioxidant and anti-inflammatory activities.

Nonconvulsive status epilepticus (NCSE) is misdiagnosed in50% of cases in the emergency department. Computed tomographic perfusion (CTP) has been implemented in the hyperacute setting to detect seizure-induced hyperperfusion. However, the diagnostic value of CTP is limited by the lack of thresholds for hyperperfusion and high interrater variability. This pilot case-control study aims at identifying the diagnostic value of reverse Tmax (rTmax) in differentiating NCSE from acute ischemic stroke in the hyperacute setting.We enrolled patients with NCSE (Salzburg criteria-based diagnosis) and stroke cases 1:1 matched for clinical features and time of presentation. CTP standard maps (mean transit time [MTT]-cerebral blood volume-cerebral blood flow [CBF]) and rTmax maps were elaborated and rated by two experts in CTP blinded to the final diagnosis. Hyperperfusion was adjudicated for standard CTP maps as an increase in CBF and a decrease in MTT, and for rTmax as the presence of a black area on 3-, 2-, and 1-s threshold maps. Cronbach alpha was used for interrater agreement; receiver operating curve analysis was run to measure accuracy with area under the curve.Overall, 34 patients were included (17 NCSE, 17 stroke; time from onset to imaging = 2 h for both groups). People with NCSE were older and more frequently had a history of epilepsy. NCSE patients had hyperperfusion on rTmax maps in 11 of 17 cases versus zero of 17 in stroke. Intra- and interrater reliability was higher for rTmax than for standard CTP maps (κ = 1 vs. κ = .6). rTmax was 82% (95%CI = 67-97%) accurate in predicting NCSE versus stroke in the hyperacute setting. Agreement between neuroimaging and electroencephalography (EEG) was limited at a hemispheric level for standard CTP maps, whereas rTMax had agreement with EEG largely reaching the sublobar level.rTmax mapping might represent a reliable tool to spot NCSE-induced hyperperfusion with a threshold-based reproducible approach. Further studies are needed for validation and implementation in the differential diagnosis of focal neurological deficit in the hyperacute setting.

The aim of this study was to compare the function of the glymphatic system in patients with status epilepticus (SE) with that in healthy controls by diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. We also investigated the association between glymphatic system function and the clinical characteristics of SE.We retrospectively enrolled 28 patients with SE and 31 healthy controls matched for age and sex. All study participants underwent diffusion tensor imaging using the same 3-T MRI scanner, and the DTI-ALPS index was calculated. We compared the DTI-ALPS index between the SE group and the control group. We also evaluated the associations of the DTI-ALPS index with etiology and type of SE, age, putative duration of seizure, time interval until MRI, seizure-related changes on diffusion-weighted imaging, and any previous structural lesions.The DTI-ALPS index was significantly lower in the SE group than in the control group (1.462 ± 0.297 vs. 1.632 ± 0.270, p = 0.026) and was negatively correlated with age (r = - 0.280, p = 0.032) in the SE group. However, there were no significant between-group differences in the DTI-ALPS index according to other clinical factors.The finding of a significantly lower DTI-ALPS index in the SE group suggests that the glymphatic system is impaired in patients with SE. DTI-ALPS is a useful tool for evaluation of the function of the glymphatic system in these patients.

Background and ObjectivesThe outcome of status epilepticus (SE) largely varies depending on clinical characteristics. Risk stratification is necessary for tailoring the aggressiveness of treatment and predicting outcomes of individual patients with SE. In this study, we assessed differences in mortality, neurologic disability, and prognostic factors associated with SE across sociodemographic and clinical characteristics.MethodsWe conducted a nationwide population-based retrospective cohort study using the National Health Insurance Service (NHIS) database linked with the national death and disability registries. SE was identified from admission or emergency department visits using a diagnostic code of G41 from the International Classification of Diseases, 10th Revision. Individuals with new-onset SE that occurred from January 1, 2010, to December 31, 2018, were included. Active epilepsy, refractoriness of SE, potential etiology, and comorbidities were ascertained by diagnostic codes and/or prescription records from the NHIS database as potential prognostic factors. Outcomes included 30-day and 1-year mortality and neurologic disabilities after SE. Prognostic factors for mortality were assessed by the Cox regression hazard model. We performed a subgroup analysis according to age: pediatric SE (age ResultsA total of 33,814 patients with new-onset SE were included (6,818 children/adolescents and 26,996 adults). The 30-day mortality was 8.5% (1.8% in pediatric SE and 10.2% in adult SE), and the 1-year mortality was 25.1% (4.6% in pediatric SE and 30.3% in adult SE). Overall, 10.7% of patients newly acquired neurologic disabilities after SE, with the highest incidence in children aged 5–9 years (21.3%). Intractable epilepsy developed in 0.8% of entire SE. Old age, presence of acute etiology, and refractoriness were poor prognostic factors for mortality in both pediatric and adult SE. Male sex, low economic status, no active epilepsy, and comorbidities were additional factors for a poor prognosis in adults.DiscussionNew-onset SE was associated with substantial mortality and disability. Although SE-related mortality was higher in adults, disabilities developed more commonly in children and adolescents. The major determinants of mortality differed between pediatric and adult SE.

Patients with refractory status epilepticus (RSE) have failed treatment with benzodiazepines and ≥1 second-line intravenous (IV) antiseizure medication (ASM). Guidelines recommend IV anesthesia when second-line ASMs have failed, but potential harms can outweigh the benefits. Novel treatments are needed to stop and durably control RSE without escalation to IV anesthetics. Ganaxolone is an investigational neuroactive steroid in development for RSE treatment. This study's objective was to determine the appropriate dosing for IV ganaxolone in RSE and obtain a preliminary assessment of efficacy and safety.This was an open-label, phase 2 trial conducted from February 19, 2018 to September 18, 2019, at three sites in the United States. Patients were aged ≥12 years, had convulsive or nonconvulsive SE, and failed to respond to ≥1 second-line IV ASM. Twenty-one patients were screened; 17 were enrolled. Patients received IV ganaxolone added to standard-of-care ASMs. Ganaxolone infusion was initiated as an IV bolus (over 3 min) with continuous infusion of decreasing infusion rates for 48-96 h followed by an 18-h taper. There were three ganaxolone dosing cohorts: low, 500 mg/day; medium, 650 mg/day; and high, 713 mg/day. The primary end point was the number of patients not requiring escalation to IV anesthetic treatment within 24 h of ganaxolone initiation.Most of the 17 enrolled patients (65%) had nonconvulsive SE, and had failed a median of three prior ASMs, including first-line benzodiazepine and second-line IV ASM therapy. Median time to SE cessation following ganaxolone initiation was 5 min. No patient required escalation to third-line IV anesthetics during the 24-h period following ganaxolone initiation. Two treatment-related serious adverse events (sedation) were reported. Of the three deaths, none was considered related to ganaxolone; all occurred 9-22 days after completing ganaxolone.IV ganaxolone achieved rapid and durable seizure control in patients with RSE, and showed acceptable safety and tolerability.

Background The “coronavirus disease 2019” (COVID-19) pandemic, caused by the “severe-acute-respiratory-syndrome-coronavirus 2” (SARS-CoV-2), challenges healthcare systems worldwide and impacts not only COVID-19 patients but also other emergencies. To date, data are scarce on the extent to which the COVID-19 pandemic impacted status epilepticus (SE) and its treatment. Objective To assess the influence of the COVID-19 pandemic on the incidence, management and outcome of SE patients. Study design This is a retrospective, multicentre trial, approved by the University of Cologne (21-1443-retro). Methods All SE patients from the urban area of Cologne transmitted to all acute neurological departments in Cologne between 03/2019 and 02/2021 were retrospectively analysed and assessed for patient characteristics, SE characteristics, management, and outcome in the first pandemic year compared to the last pre-pandemic year. Results 157 pre-pandemic (03/2019–02/2020) and 171 pandemic (from 03/2020 to 02/2021) SE patients were included in the analyses. Acute SARS-CoV-2 infections were rarely detected. Patient characteristics, management, and outcome did not reveal significant groupwise differences. In contrast, regarding prehospital management, a prolonged patient transfer to the hospital and variations in SE aetiologies compared to the last pre-pandemic year were observed with less chronic vascular and more cryptogenic and anoxic SE cases. No infections with SARS-CoV-2 occurred during inpatient stays. Conclusions SARS-CoV-2 infections did not directly affect SE patients, but the transfer of SE patients to emergency departments was delayed. Interestingly, SE aetiology rates shifted, which warrants further exploration. Fears of contracting an in-hospital SARS-CoV-2-infection were unfounded due to consequent containment measures.

Although the treatment of epilepsy primarily focuses on prevention, recurrent seizures are unfortunately an ongoing reality, particularly in people with epilepsy who live with chronic refractory seizures. Rescue medications are agents which can be administered in urgent/emergent seizure episodes such as seizure clusters or prolonged seizures with the goal of terminating seizure activity, preventing morbidity, and decreasing the risk of further seizures.This review first discusses clinical opportunities for rescue medications, with particular attention focused on seizure clusters and prolonged seizures, including their epidemiology, risk factors, and associated morbidity. Current rescue medications, their indications, efficacy, and adverse effects are discussed. We then discuss rescue medications and formulations which are currently under development, concentrating on practical aspects relevant for clinical care.Rescue medications should be considered for all people with epilepsy with ongoing seizures. Recent rescue medications including intranasal formulations provide considerable advantages. New rescue medications are being developed which may expand opportunities for effective treatment. In the future, combining rescue medications with seizure detection and seizure prediction technologies should further expand opportunities for use and should reduce the morbidity of seizures and provide increased comfort, control, and quality of life for people living with epilepsy.

Objective We describe the clinical, electroencephalograph^ and neuroimaging findings of older patients with typical absence status epilepticus (ASE). Methods This investigation was a retrospective analysis of prospectively collected consecutive patients between January 2011 and October 2021. All patients ≥60 years with impairment of awareness and continuous generalized, rhythmic, synchronous and symmetric epileptiform discharges and normal background on video-electroencephalogram (vEEG) were included. Results Six patients were identified with a diagnosis of typical ASE. The mean age was 67 years. Five could be classified as idiopathic generalized epilepsy (IGE) though two had been erroneously categorized as cryptogenic focal epilepsy (FE). In one, the episode of ASE was thought to represent the beginning of late-onset IGE (de novo late-onset typical ASE). In all cases, ASE was controlled within the first 24 hours. Significance Typical ASE is a rare cause of confusion in the elderly population requiring urgent vEEG evaluation. It most frequently represents reactivation of a previous IGE, in effect related to patients with epilepsy with onset in childhood or adolescence, not previously diagnosed or treated, representing rather the debut of (de novo) late-onset IGE.

Panayiotopoulos syndrome (PS) is a common benign epilepsy in childhood, characterized by predominantly autonomic symptoms such as emesis, pallor, and seizures, which are often prolonged. In an emergency room (ER), particularly when unconsciousness is prolonged, differentiating PS from acute encephalopathy is challenging. In this study, we aimed to elucidate the differences in clinical features of patients with PS and acute encephalopathy who visited our ER.We retrospectively reviewed 18 patients who were transferred to our ER because of status epilepticus later diagnosed as PS, and 30 patients with acute encephalopathy, between July 2012 and July 2017. We compared patient demographics, clinical characteristics, and treatment.Most patients (90%) with acute encephalopathy had convulsive seizures of greater than or equal to 15 min, whereas only three patients (17%) with PS had convulsive seizures of greater than or equal to 15 min (P 0.001). In addition, seizures were treatable in all patients with PS with a small dose of midazolam (0.1 mg/kg), but all patients with acute encephalopathy required midazolam at 0.3 mg/kg or more (P 0.001). More patients with PS had autonomic symptoms compared to those with acute encephalopathy (e.g., vomiting [78% vs. 3%, P 0.001]). Non-convulsive status epilepticus was observed in 22% of PS patients, but not in any acute encephalopathy patients. In contrast, fever was observed in all patients with acute encephalopathy (100%), but less frequently in those with PS (11%, P 0.001).PS was characterized by 1) convulsive seizures shorter than 15 min, 2) seizures treatable with small doses of midazolam, and 3) autonomic symptoms. PS could be differentiated from acute encephalopathy in the early stages of the syndrome.

To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death.This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2 years. Patients were randomized to slow withdrawal (160 days) or rapid withdrawal (60 days) and were followed for 12 months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12 months. A non-inferiority analysis was performed with non-inferiority margin of - 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal.The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9 months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI - 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population.Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering.

The neurosteroid allopregnanolone (ALLO) is under investigation as a treatment for benzodiazepine-refractory status epilepticus (SE). Here, we assess the cardiopulmonary safety of intravenous ALLO by itself and after a clinically recommended dose of midazolam (MDZ) in two healthy adult beagles. Each dog received ALLO (1 mg/kg, IV), and after a washout period of 2 weeks, each dog was dosed with MDZ (0.2 mg/kg, IV) followed 10 minutes later by ALLO. Behavioral state, vital signs, arterial blood gases, blood chemistries, and plasma ALLO concentrations were monitored for up to 6 hours after dosing. The dogs appeared sleepy but were fully responsive after both treatments. No depression of mean arterial pressure or respiratory rate was noted. Blood gas measurements failed to show evidence of drug-induced acute respiratory acidosis. Estimated maximum plasma ALLO concentrations were in the range of 1500 to 3000 ng/ml. The results indicate that intravenous ALLO can be used safely to treat benzodiazepine-refractory SE, even when administered shortly after a benzodiazepine.

A new onset of status epilepticus in a previously healthy adult preceded by a recent minor febrile infection represents a diagnostic and therapeutic challenge in clinical practice. Considering the broad spectrum of epileptic encephalopathies caused by autoimmune mechanisms, differential diagnosis for new-onset refractory status epilepticus (NORSE) should include febrile infection-related epilepsy syndrome (FIRES), in order to not underestimate the underlying etiological condition triggering epilepsy in non-epileptic patients (Hon et al. in Recent Pat Inflamm Allergy Drug Discov 12:128-135, 2018). We report a case of acute encephalopathy with refractory seizures after a febrile illness (FIRES) in a young adult with complete remission of symptoms as well as dramatic improvement of EEG abnormalities following intravenous immunoglobulin and proper antiepileptic medications. We conducted an extensive workup including lumbar puncture, blood tests, EEG serial monitoring, MRI brain, total body CT scan, and PET brain with FDG to shed light on the etiology of the disease.

Vaccination against the SARS-CoV-2 virus is a primary tool to combat the COVID-19 pandemic. However, vaccination is a common seizure trigger in individuals with Dravet syndrome (DS). Information surrounding COVID-19 vaccine side effects in patients with DS would aid caregivers and providers in decisions for and management of COVID-19 vaccination.A survey was emailed to the Dravet Syndrome Foundation's Family Network and posted to the Dravet ParentCaregiver Support Group on Facebook between May and August 2021. Deidentified information obtained included demographics and vaccination status for individuals with DS. Vaccine type, side effects, preventative measures, and changes in seizure activity following COVID-19 vaccination were recorded. For unvaccinated individuals, caregivers were asked about intent to vaccinate and reasons for their decision.Of 278 survey responses, 120 represented vaccinated individuals with DS (median age = 19.5 years), with 50% reporting no side effects from COVID-19 vaccination. Increased seizures following COVID-19 vaccination were reported in 16 individuals, but none had status epilepticus. Of the 158 individuals who had not received a COVID-19 vaccination, 37 were older than 12 years (i.e., eligible at time of study), and only six of these caregivers indicated intent to seek vaccination. The remaining 121 responses were caregivers to children younger than 12 years, 60 of whom indicated they would not seek COVID-19 vaccination when their child with DS became eligible. Reasons for vaccine hesitancy were fear of increased seizure activity and concerns about vaccine safety.These results indicate COVID-19 vaccination is well tolerated by individuals with DS. One main reason for vaccine hesitancy was fear of increased seizure activity, which occurred in only 13% of vaccinated individuals, and none had status epilepticus. This study provides critical and reassuring insights for caregivers and health care providers making decisions about the safety of COVID-19 vaccinations for individuals with DS.

To investigate the effect of Coronavirus disease 2019 (COVID-19) measures on the hospitalization of patients with epilepsy and status epilepticus (SE).This interrupted time series design included data from the Thai Universal Coverage Scheme electronic database between January 2017 and September 2020. The monthly hospitalization rate of epilepsy and SE was calculated by the number of hospitalizations divided by the midyear population. Segmented regression fitted by ordinary least squares (OLS) was used to detect the immediate and overtime effects of COVID-19 measures on the hospitalization rate.During January 2017 and September 2020, the numbers of epilepsy and SE patients admitted to the hospital were 129 402 and 15 547 episodes, respectively. The monthly trend of the hospitalization rate in epilepsy decreased immediately after the COVID-19 measure (0.739 per 100 000 population [95% CI: 0.219 to 1.260]). In particular, the number of children declined to 1.178 per 100 000 population, and the number of elderly individuals dropped to 0.467 per 100 000 population, while there was a nonstatistically significant change in SE.COVID-19 measures reduced the hospital rate in epilepsy, particularly in children and adults. However, there was no change in SE patients.

Introduction: Status epilepticus (SE) in pregnancy represents a life-threatening medical emergency for both mother and fetus. Pregnancy-related pharmacokinetic modifications and the risks for fetus associated with the use of antiseizure medications (ASMs) and anesthetic drugs complicate SE management. No standardized treatment protocol for SE in pregnancy is available to date. Areas covered: In this review, we provide an overview of the current literature on the management of SE in pregnancy and we propose a multidisciplinary-based protocol approach. Expert opinion: Literature data are scarce (mainly anecdotal case reports or small case series). Prompt treatment of SE during pregnancy is paramount and a multidisciplinary team is needed. Benzodiazepines are the drugs of choice for SE in pregnancy. Levetiracetam and phenytoin represent the most suitable second-line agents. Valproic acid should be administered only if other ASMs failed and preferably avoided in the first trimester of pregnancy. For refractory SE, anesthetic drugs are needed, with propofol and midazolam as preferred drugs. Magnesium sulfate is the first-line treatment for SE in eclampsia. Termination of pregnancy, via delivery or abortion, is recommended in case of failure of general anesthetics. Further studies are needed to identify the safest and most effective treatment protocol.

Status epilepticus is a serious condition caused by disorders and diseases that affect the central nervous system. In status epilepticus, hypersynchronous epileptic activity lasts longer than the usual duration of isolated self-limited seizures (time t1), which causes neuronal damage or alteration of neuronal networks at a certain time point (time t2), depending on the type of and duration of status epilepticus. The successful management of status epilepticus includes both the early termination of seizure activity and the earliest possible identification of a causative etiology, which may require independent acute treatment. In nonconvulsive status epilepticus, patients present only with subtle clinical signs or even without any visible clinical manifestations. In these cases, EEG allows for the assessment of cerebral function and identification of patterns in need of urgent treatment.In 2015, the International League Against Epilepsy proposed a new definition and classification of status epilepticus, encompassing four axes: symptomatology, etiology, EEG, and age. Various validation studies determined the practical usefulness of EEG criteria to identify nonconvulsive status epilepticus. The American Clinical Neurophysiology Society has incorporated these criteria into their most recent critical care EEG terminology in 2021. Etiology, age, symptomatology, and the metabolic demand associated with an increasing duration of status epilepticus are the most important determinants of prognosis. The consequences of status epilepticus can be visualized in vivo by MRI studies.The current knowledge about status epilepticus allows for a more reliable diagnosis, earlier treatment, and improved cerebral imaging of its consequences. Outcome prediction is a soft tool for estimating the need for intensive care resources.

To provide data on inpatient costs and cost-driving factors in children and adolescents due to non-refractory (NSE), refractory (RSE), and super-refractory status epilepticus (SRSE).All children and adolescents treated for status epilepticus (SE) between 2011 and 2018 at the Frankfurt University Hospital were analyzed for health care utilization.We evaluated 223 admissions in 174 patients (6.8 ± 5.1 years, median 5.5 years, range 0.1-17.5 years, 109 males [62.6%]) treated for SE. Mean costs of hospital treatment were €5,711 (median €2,330, range = €654-€102,414) per patient per admission, with a mean length of stay (LOS) of 9.2 days (median 5.0, range = 1-101), resulting in mean costs of €621 per SE treatment day. Course of SE had a significant impact on the mean costs, which were €3,386 in NSE (median €2,139, range €654-€38,236, €529 per treatment day; 37% of total inpatient costs due to SE), €7,409 in RSE (median €2,772, range €700-€38,236; €612 per treatment day, 38% of total inpatient costs due to SE) and €17,436 in SRSE (median €6,911, range €2,138-102,414; €842 per treatment day, 25% of total inpatient costs due to SE). Independent cost-driving factors were three or more treatment steps, acute-symptomatic etiology, and unfavorable modified Rankin Scale score at admission. Increased LOS was predicted by three or more treatment steps and unfavorable modified Rankin Scale score at admission. Overall mortality at discharge was 1.3% (three patients).Acute treatment of SE, and particularly RSE and SRSE, is associated with high hospital costs and prolonged LOS. Patients with disabilities are at risk for an unfavorable course of SE, resulting in prolonged LOS. In general, mortality associated with SE is low in children and adolescents, however three or more treatment steps are associated with high treatment costs.

Febrile status epilepticus evolves from a febrile seizure (FS) in 5% of cases. Its prompt recognition is challenging, especially when motor manifestations are absent or subtle. We describe the ictal electroclinical features of non-convulsive febrile status epilepticus (NCFSE) following an apparently concluded FS, initially misinterpreted as postictal obtundation and in some way mimicking the described "non-epileptic twilight state". We present an electroclinical study of 18 children, collected in our unit, who presented with NCFSE after an apparently resolved FS, longitudinally followed for one year to seven years and nine months (mean: four years and three months). The age at first NCFSE ranged between one year and two months and five years and eight months (mean: two years and six months). Patients were examined after spontaneous or rectal diazepam-induced resolution of a FS, while showing persisting impairment of awareness. A lack of responsiveness to painful stimulation, abnormal posturing and aphasia were present in all cases, variably associated with perioral cyanosis, hypersalivation, automatisms, gaze deviation and other lateralizing signs; eyes were open. The EEG recording started 20 to 140 minutes after the apparent resolution of the FS and was invariably characterized by delta or theta-delta pseudorhythmic activity, mainly involving the fronto-temporal regions, with hemispheric predominance in two thirds of the cases. The electroclinical condition, lasting 25 to 210 minutes, quickly recovered after intravenous diazepam. Follow-up revealed normal neurodevelopment and EEG in almost all patients (learning disability emerged in three). In five subjects, NCSE relapsed (twice in two). None presented afebrile seizures. Our series highlights the electroclinical features of focal NCFSE. Distinctive elements are a lack of reactivity, cyanosis, lateralizing clinical and EEG signs, and resolution clearly tied to intravenous benzodiazepine administration.

Background and ObjectivesEyelid myoclonia (EM) with absences (EMA) is a generalized epilepsy syndrome with a prognosis and clinical characteristics that are still partially undefined. We investigated electroclinical endophenotypes and long-term seizure outcome in a large cohort of patients with EMA.MethodsIn this multicenter retrospective study, patients with EMA with ≥5 years of follow-up were included. We investigated prognostic patterns and sustained terminal remission (STR), along with their prognostic factors. Moreover, a 2-step cluster analysis was used to investigate the presence of distinct EMA endophenotypes.ResultsWe included 172 patients with a median age at onset of 7 years (interquartile range [IQR] 5–10 years) and a median follow-up duration of 14 years (IQR 8.25–23.75 years). Sixty-six patients (38.4%) displayed a nonremission pattern, whereas remission and relapse patterns were encountered in 56 (32.6%) and 50 (29.1%) participants. Early epilepsy onset, history of febrile seizures (FS), and EM status epilepticus significantly predicted a nonremission pattern according to multinomial logistic regression analysis. STR was achieved by 68 (39.5%) patients with a mean latency of 14.05 years (SD ±12.47 years). Early epilepsy onset, psychiatric comorbid conditions, and a history of FS and generalized tonic-clonic seizures were associated with a lower probability of achieving STR according to a Cox regression proportional hazards model. Antiseizure medication (ASM) withdrawal was attempted in 62 of 172 patients, and seizures recurred in 74.2%. Cluster analysis revealed 2 distinct clusters with 86 patients each. Cluster 2, which we defined as EMA-plus, was characterized by an earlier age at epilepsy onset, higher rate of intellectual disability, EM status epilepticus, generalized paroxysmal fast activity, self-induced seizures, FS, and poor ASM response, whereas cluster 1, the EMA-only cluster, was characterized by a higher rate of seizure remission and more favorable neuropsychiatric outcome.DiscussionEarly epilepsy onset was the most relevant prognostic factor for poor treatment response. A long latency between epilepsy onset and ASM response was observed, suggesting the effect of age-related brain changes in EMA remission. Last, our cluster analysis showed a clear-cut distinction of patients with EMA into an EMA-plus insidious subphenotype and an EMA-only benign cluster that strongly differed in terms of remission rates and cognitive outcomes.

Status epilepticus (SE) persisting despite two anti-seizures medications (ASM) and anesthetics is labeled super refractory (SRSE), correlating with important morbidity and mortality. Its treatment relies on expert opinions. Due to its pharmacological properties, ketamine (KET) has received increasing attention, but data are essentially retrospective.To describe an unselected cohort of adults receiving KET for SRSE.Analysis of a prospective registry of consecutive SE episodes, identifying SRSE patients receiving ketamine (KET). Comparison with recent adult series including more than 10 patients.Eleven patients received KET after a median of 4 days (range: 2-20); median dose was 5 mg/kg/h (range: 2.5-15). KET provided permanent SE control in three (27%). Previous series, using KET administration delays and doses similar to our cohort, report KET efficacy in 28-96% of cases.We found a lower SE control rate than existing literature, whose data are, however, often retrospective, potentially selecting patients with less severe SE forms or responding to KET. This might explain outcome differences, as KET administration modalities were comparable with our cohort. Since randomized controlled studies are lacking on this subject, the analysis of this prospective, unselected cohort, if confirmed, suggests a current overestimation of KET efficacy in SRSE.

Background To assess the frequency and clinical characteristics of seizures in adult critically ill patients, to identify predictors of recurrent seizures not transforming into status epilepticus and to characterize their effects on course and outcome. Methods ICU patients at a Swiss academic medical center with seizures not transforming into status epilepticus from 2015 to 2020 were included. Recurrent seizures and associated clinical characteristics were primary, death, and return to premorbid neurologic function were secondary outcomes. Results Two hundred of 26,370 patients (0.8%) with a median age of 65 years had seizures during ICU stay. Seizure semiology was described in 82% (49% generalized; 33% focal) with impaired consciousness during seizures in 80% and motor symptoms in 62%. Recurrent seizures were reported in 71% (36% on EEG) and associated with longer mechanical ventilation (p = 0.031), higher consultation rate by neurologists (p p Conclusions Seizures in ICU patients are infrequent, but mostly recurrent, and associated with higher resource utilization. Whenever seizures are observed, clinicians should be vigilant about the increased risk of seizures recurrence and the need for antiseizure treatment must be carefully discussed. While known epilepsy seems to promote recurrent seizures, our results suggest that both acidosis and previous emergency surgery seem to have protective/antiseizure effects. Trial registration Clinicaltrials.gov (No. NCT03860467).

Biomarkers predicting poor outcomes of status-epilepticus-associated-with-fever (SEF) at an early stage may contribute to treatment guidance. However, none have been reported thus far. We investigated the dynamics of serum growth and differentiation factor (GDF)-15 after seizure onset in patients with SEF and determined whether GDF-15 can predict poor outcomes, particularly in the first 6 h after seizure onset.We enrolled 37 pediatric patients with SEF and eight patients with simple febrile seizures (SFS) and collected their blood samples within 24 h of seizure onset and eight febrile control patients between March 1, 2017 and September 30, 2020. All patients were aged ≤15 years.In the SEF group, the median post-seizure serum GDF-15 values were 1,065 (6h), 2,720 (6-12 h), and 2,411 (12-24 h) pg/mL. The median serum GDF-15 in the first 6 h was measured in patients with SEF without a significant past medical history (n = 21) and was found to be statistically significantly higher (1,587 pg/mL) than in the febrile control (551 pg/mL) and SFS (411 pg/mL) groups. The median serum GDF-15 was statistically significantly higher in patients with SEF with sequelae (n = 5) and patients with acute encephalopathy with biphasic seizures/reduced diffusion/hemorrhagic shock and encephalopathy syndrome (n = 6) than in patients with SEF without sequelae (n = 16) (15,898 vs 756 pg/mL) and patients with prolonged FS (n = 15) (9,448 vs 796 pg/mL).This study demonstrates the dynamics of serum GDF-15 in patients with SEF and indicates the potential of GDF-15 as an early predictor of poor outcomes.

Super-refractory status epilepticus (SRSE) is associated with significant morbidity and mortality in children. We explored the clinical spectrum, specific characteristics, and outcome in SRSE patients admitted in a pediatric intensive care unit (PICU) and investigated how well current diagnostic or treatment modalities perform compared to Status Epilepticus (SE) and Refractory SE (RSE) patients.Retrospective analysis of PICU patients admitted with convulsive SE during 2009-2019. Eighty-six patients were classified as SE, RSE, and SRSE. New-onset RSE (NORSE) and febrile infection-related epilepsy syndrome (FIRES) were also identified. Functional outcome was evaluated by the modified Rankin scale.Patients with SRSE (n = 20) had longer weaning off anesthetics (p = 0.014), length of stay, mechanical ventilation duration, higher illness severity scores, and poorer outcome compared to SE (n = 13) or RSE (n = 53) patients (all p 0.001). Diagnosis, mainly expressed by high prevalence of NORSE (n = 13) and FIRES (n = 9), was independently associated with SRSE (p = 0.024). Abnormal MRI findings (p = 0.005), and epilepsy-related pathogenic variants identified by whole-exome sequencing (WES) were mostly found in SRSE patients. Compared to intravenous immunoglobulins and steroid pulses, plasmapheresis and ketogenic diet, more often used in SRSE (p 0.01), contributed better to seizure control. Only SRSE (AUROC0.80, 95% CI = 0.68-0.94, p 0.001) and diagnosis (AUROC0.70, 95% CI = 0.55-0.83, p = 0.02) could predict a poor outcome.The majority of SRSE patients are characterized by considerable functional decline and morbidity. WES analysis may reveal epilepsy-related pathogenic variants while early aggressive immunotherapy and/or ketogenic diet might prove beneficial. Multicenter studies for prediction models of outcome are needed.

To evaluate factors associated with progression of convulsive refractory status epilepticus(RSE) to super refractory status epilepticus(SRSE) and long term outcome in children.In this open cohort study, data of children admitted with convulsive RSE from 2010 to 2018 was retrospectively analyzed. The outcome at two years was graded according to the Glasgow outcome scale(GOS).Fifty six children formed study population, 24 progressed to SRSE. The mean age of the study population was 9.38 ± 4.28(2-16) years. There was no significant difference for age between SRSE and RSE children (9.53 ± 4.50 years vs. 9.17 ± 4.06 years; p = 0.756). Acute symptomatic aetiology was the most common aetiology for RSE (57.1%) and SRSE (54.2%). There were no differences for aetiology between children who progressed to SRSE and those who did not. Mean length of stay in the NICU was 13.54 ± 17.53 days and children who progressed to SRSE had a longer length of stay in NICU (4.78 ± 3.03 days vs. 25.21 ± 21.77 days; p 0.001). The mortality was 14.2%. Acidosis was more common in children who died (27.1% vs. 87.5%;p 0.001). There was no significant difference in the mortality between RSE and SRSE (9.4% vs. 20.8%; p = 0.268). At latest follow up 34 (60.7%) children had good outcome. Poor outcome was more common in children who progressed to SRSE(29.4% vs. 63.6%;p 0.015).Acute symptomatic etiology is more frequent in children with RSE and SRSE. Progression to SRSE did not significantly increase mortality but associated with poor GOS outcome. Encouragingly, 60% of children had good outcome.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common type of acute encephalopathy in Japan; the condition is clinically characterized by prolonged seizures as the initial neurological symptom, followed by late seizures 4-6 days later. It is difficult to differentiate AESD from prolonged febrile seizures (PFSs). Here, we explored the use of electroencephalography to differentiate AESD from PFSs.We studied the electroencephalograms (EEGs) of children6 years of age diagnosed with AESD or PFSs; all EEGs were recorded within 48 h of seizure onset (i.e., before the late seizures of AESD). Two pediatric neurologists evaluated all EEGs, focusing on the basic rhythm, slowing during wakefulness/arousal by stimuli, spindles, fast waves, and slowing during sleep.The EEGs of 14 children with AESD and 31 children with PFSs were evaluated. Spindles were more commonly reduced or absent in children with AESD than in those with PFSs (71% vs. 31%, p = 0.021). Fast waves were also more commonly reduced or absent in children with AESD (21% vs. 0%, p = 0.030). The rates of all types of slowing did not differ between children with AESD and those with PFSs, but continuous or frequent slowing during sleep was more common in the former (50% vs. 17%, p = 0.035).EEG findings may usefully differentiate AESD from PFSs. Reduced or absent spindles/fast waves and continuous or frequent slowing during sleep are suggestive of AESD in children with prolonged seizures associated with fever.

Status epilepticus (SE) is a life-threatening prolonged epileptic seizure. A rapid diagnosis is fundamental to initiate antiepileptic treatment and to prevent the development of neurological sequels. Several serum and cerebrospinal fluid biomarkers have been proposed to help in the diagnosis of SE. Nevertheless, previous studies were conducted on too small patient cohorts, precluding the utilization of interesting biomarkers for the SE diagnosis. Here, we aimed to assess the ability of Neuron Specific Enolase (NSE), S100-beta protein (S100B) and progranulin to help in the diagnosis of SE in a large cohort of patients (36 control patients, 56 patients with pharmacoresistant epilepsy and 82 SE patients). Blood NSE, S100B and progranulin levels were higher in SE patients when compared with control patients or patients with pharmacoresistant epilepsy. Both NSE and progranulin levels were higher in cerebrospinal fluid from SE patients when compared with control patients. The receiver-operating characteristics curves revealed good accuracy at detecting SE for serum S100B (AUC 0.748) and plasma progranulin (AUC 0.756). The performances were lower for serum NSE (AUC 0.624). Eighty-four percent of patients with serum S100B levels above 0.09 ng/mL presented with a SE, whereas 90% of patients without SE had serum S100B levels lower than 0.09 ng/mL. Serum S100B levels were not significantly different according to SE etiology, SE semiology or SE refractoriness. Our results confirm that NSE, S100B and progranulin levels are increased after SE. We suggest that serum S100B levels might be added to clinical evaluation and electroencephalogram to identify difficult-to-diagnose form of SE.

Diagnosis of epileptic seizures, particularly regarding status epilepticus (SE), may be challenging in an emergency room setting. The aim of the study was to study the diagnostic yield of perfusion computed tomography (pCT) in patients with single epileptic seizures and SE. We retrospectively reviewed the records of patients who followed an acute ischemic stroke pathway during a 9-month period and who were finally diagnosed with a single epileptic seizure or SE. Perfusion maps were visually analyzed for the presence of hyperperfusion and hypoperfusion. Clinical data, EEG patterns, and neuroimaging findings were compared. We included 47 patients: 20 (42.5%) with SE and 27 (57.5%) with single epileptic seizure. Of 18 patients who showed hyperperfusion on pCT, 12 were ultimately diagnosed with SE and eight had EEG findings compatible with an SE pattern. Focal hyperperfusion on pCT had a sensitivity of 60% (95% CI 36.4-80.2) and a specificity of 77.8% (95% CI 57.2-90.6) for predicting a final diagnosis of SE. The presence of cerebral cortical and thalamic hyperperfusion had a high specificity for predicting SE presence. Of note, 96% of patients without hyperperfusion on pCT did not show an SE pattern on early EEG. In acute settings, detection by visual analysis of focal cerebral cortical hyperperfusion on pCT in patients with epileptic seizures, especially if accompanied by the highly specific feature of thalamic hyperperfusion, is suggestive of a diagnosis of SE and requires clinical and EEG confirmation. The absence of focal hyperperfusion makes a diagnosis of SE unlikely

De novo aphasic status epilepticus (ASE) in patients without a previous history of epilepsy and without cerebral lesions (aphasic NOSE) is rare. The aim of the study is to describe its clinical characteristics, etiologies, and outcome.Single-center study including consecutive patients presenting to the emergency department between 2011 and 2019 with acute aphasia, which was finally diagnosed as aphasic NOSE. Subsequent episodes of aphasia (5 min) were recorded and divided into confirmed ASE and postictal aphasic episodes (non-ASE). Clinical characteristics of the two types of episodes were compared.Nineteen patients were included, suffering fifty episodes of epileptic aphasia, episodes per patient 2.6 (range 1-7). Fifteen patients (71.4%) were women, mean age at ASE onset was 66.05 years old (SD 6.3). Nine (47%) patients died, 6 of them (66.7%) during the aphasic episode. Ictal EEG was available in 37 episodes, confirming the diagnosis of ASE in 12 episodes; in 8 episodes, the EEG fulfilled the criteria of possible ASE. The most frequent etiologies were inflammatory and vascular. Comparing ASE with non-ASE episodes, ASE was longer than non-ASE (225 vs 65 h, p .024) and was treated more frequently with BZD (76 vs 24%, p .001) but with a longer delay (22.2 vs 1.5 h, p .06).ASE is a treatable, highly relapsing emergency, with the subsequent relapses ASE or postictal aphasia. EEG is diagnostic in half of the patients, while in others imaging techniques are also useful. Benzodiazepines should be administered. Persistent aphasia, of more than 65 hours' duration, is highly suggestive of ASE.

Anterior thalamic deep brain stimulation is an effective therapeutic option for patients with drug-refractory focal epilepsy who are poor surgical candidates. Although the precise mechanism of action of thalamic neurostimulation is unknown, studies demonstrating increased efficacy over time have raised the possibility that therapeutic benefits are mediated by stimulation-related long-term neuroplastic changes. Adverse effects related to hardware malfunction have been previously described, and most commonly include local infection, sensory disturbances, and migration of leads. However, the withdrawal effect of sudden deep brain stimulation malfunction on seizure control is unclear. We present the case of a 21-year-old patient with intractable focal epilepsy who developed status epilepticus concurrently with unexpected deep brain stimulator battery failure, 21 months post implantation. This case demonstrates an unfamiliar possible adverse effect of anterior thalamic stimulation withdrawal and emphasizes the importance of stimulator hardware assessment in patients presenting with seizure worsening.

This retrospective observational study was conducted to examine the temporal relationship between increased cell count, lactate concentration in cerebrospinal fluid (CSF) and blood-CSF barrier dysfunction and the onset of a seizure event.Patients with a seizure event who underwent lumbar puncture for CSF analysis during diagnostic work-up (interindividual analysis) and those with at least one follow-up CSF analysis (intraindividual analysis) were studied. Pathologically altered parameters, such as cell count, lactate concentration, and blood-CSF barrier dysfunction as indicated by the albumin quotient (QAn increased CSF cell count (4/µl) was shown in 3% of our patients, whereas pathological lactate concentrations were found in 24% after single seizures and 28% after status epilepticus (SE)/recurring seizures. However, lactate levels showed a marked decrease with increasing time after an isolated seizure (p0.0001) but not after SE/recurring seizures. Lactate levels were most frequently and significantly elevated within the first six hours after a single seizure (p0.0001). Blood-CSF barrier dysfunction was detected in 34% after isolated seizures and in 47% after SE/recurrent seizures. Blood-CSF barrier dysfunction showed no association with latency between seizure onset and time of CSF collection.Changes in lactate and CSF protein concentrations are common after epileptic seizures. In contrast, CSF pleocytosis is uncommon and should prompt careful investigation for the presence of intrathecal infection or autoimmune CNS disease. Elevated lactate levels more than 6 h after the seizure event may indicate ongoing epileptic activity.

This study aimed to evaluate the differences in hippocampal structural volumes and intra-hippocampal networks between patients with status epilepticus (SE) and healthy controls.We enrolled 45 patients with SE and 35 age- and sex-matched healthy controls. We excluded patients with active structural lesions, which could be a direct cause of SE, but included patients with co-existing lesions. Co-existing lesions were defined as any lesions possibly related to the occurrence of SE, including encephalomalacia, cavernous malformation, dural arteriovenous fistula, and normal pressure hydrocephalus, etc. We divided 45 patients into those with co-existing lesions (n = 21) and those without co-existing lesions (n = 24). We conducted a volumetric analysis using FreeSurfer (version 7), and the intra-hippocampal structural co-variance network was analyzed with a graph theoretical analysis based on the structural volumes of the hippocampal subfields.The structural volumes and intra-hippocampal structural co-variance networks were not different between patients with and without co-existing lesions. However, both structural volumes and intra-hippocampal structural co-variance networks were significantly different in patients with SE compared to healthy controls, and the ratio of the volume difference: [(volume of controls-volume of patients)/volume of controls] was highest in the left hippocampus (0.195), left amygdala (0.143), left thalamus (0.126), and right cortex (0.084). In addition, the global connectivity measurements including radius, diameter, eccentricity, and assortativity were significantly increased, and the small-worldness index was significantly decreased in patients with SE. Notably, structural volumes were negatively related to age but not to the duration of SE.Our study revealed significant alterations in structural volumes and intra-hippocampal structural co-variance networks in patients with SE compared to healthy controls, even though hippocampal atrophy was not evident on visual analysis; this is likely due to the direct effect of SE itself.

Dynamin-1-like (DNM1L) is a gene located on chromosome 12p11.21 that encodes for dynamin-related protein (DRP1), a GTPase involved in mitochondrial and peroxisomal fusion, which plays a pivotal role in brain development. The missense variant, p.Arg403Cys, is clinically associated with childhood-onset super-refractory status epilepticus, with either subsequent poor neurological outcome or death (described in 13 patients). We present a 20-year-old girl carrying this mutation with a history of two episodes of super-refractory focal myoclonic status epilepticus which manifested as epilepsia partialis continua (EPC) with a 13-year interval, during which she displayed moderate intellectual disability, social and school reintegration, without complete control of myoclonic manifestations. The first status, which occurred at the age of six, was associated with transient left side thalamic involvement and the second episode with right side transient basal ganglia hyperintensity on MRI. After the second status, a persistent vegetative state with both drug-resistant epilepsia partialis continua and reticular myoclonus endured; the MRI showed progressive brain atrophy. In contrast to previous published cases, this new case of childhood-onset DNM1L encephalopathy demonstrated biphasic clinical progression. The main features of our patient were EPC, super-refractory status epilepticus, and transient and migrating subcortical thalamic hyperintensity on MRI at onset. The unusual clinical course is also noticeable, indicating possible epigenetic and/or protective factors, without underestimating the progressive and genetic basis of this encephalopathy. Precise characterization of seizures and whole-exome sequencing are crucial in order to establish early diagnosis.

Mutations in the ATP1A3 gene (which encodes the main α subunit in neuronal Na+/K+-ATPases) cause various neurological syndromes including alternating hemiplegia of childhood. This rare disorder is characterized by paroxysmal episodes of hemiplegia, dystonia, oculomotor abnormalities, and occasionally developmental regression. Approximately 50% of alternating hemiplegia of childhood patients also have epilepsy, which is either focal or generalized. Seizures are often drug resistant. We report a 10-year-old girl with the D801N ATP1A3 mutation and alternating hemiplegia of childhood who manifested with drug-resistant focal seizures as an infant and throughout childhood. At the age of about10.5 years, her epilepsy evolved into electrical status epilepticus in sleep with generalized discharges. These changes coincided with developmental regression consistent with epileptic encephalopathy. Additionally, MRI and MR spectroscopy showed new cortical atrophy and markedly depressed N-acetyl aspartate peaks compared to previous normal studies. Electrical status epilepticus in sleep resolved after medication adjustments. She, now, only four months after her diagnosis of electrical status epilepticus in sleep, has regained most of the skills that were lost only a few months earlier. Our observations document that alternating hemiplegia of childhood can result in the above-described unique features; particularly, progression of focal epilepsy to electrical status epilepticus in sleep with generalized features and reversible epileptic encephalopathy.

Background Convulsive status epilepticus is the most severe form of epilepsy and requires urgent treatment. We synthesised the current evidence on first-line treatments for controlling seizures in adults with convulsive status epilepticus before, or at, arrival at hospital. Methods We conducted a systematic review of randomised controlled trials (RCTs) assessing antiepileptic drugs offered to adults as first-line treatments. Major electronic databases were searched. Results Four RCTs (1234 adults) were included. None were conducted in the UK and none assessed the use of buccal or intranasal midazolam. Both intravenous lorazepam and intravenous diazepam administered by paramedics were more effective than placebo and, notably, intramuscular midazolam was non-inferior to intravenous lorazepam. Overall, median time to seizure cessation from drug administration varied from 2 to 15 min. Rates of respiratory depression among participants receiving active treatments ranged from 6.4 to 10.6%. Mortality ranged from 2 to 7.6% in active treatment groups and 6.2 to 15.5% in control groups. Conclusions Intravenous and intramuscular benzodiazepines are safe and effective in this clinical context. Further research is needed to establish the most clinically and cost-effective first-line treatment and preferable mode of administration. Head-to-head trials comparing buccal versus intranasal midazolam versus rectal diazepam would provide useful information to inform the management of the first stage of convulsive status epilepticus in adults, especially when intravenous or intramuscular access is not feasible. Approaches to improve adherence to clinical guidelines on the use of currently available benzodiazepines for the first-line treatment of convulsive status epilepticus should also be considered.