Treatment Of Nonconvulsive Status Epilepticus Research Articles

Sustained effort network for treatment of status epilepticus/European academy of neurology registry on adult refractory status epilepticus (SENSE-II/AROUSE)

BackgroundStatus Epilepticus (SE) is a common neurological emergency associated with a high rate of functional decline and mortality. Large randomized trials have addressed the early phases of treatment for convulsive SE. However, evidence regarding third-line anesthetic treatment and the treatment of nonconvulsive status epilepticus (NCSE) is scarce. One trial addressing management of refractory SE with deep general anesthesia was terminated early due to insufficient recruitment. Multicenter prospective registries, including the Sustained Effort Network for treatment of Status Epilepticus (SENSE), have shed some light on these questions, but many answers are still lacking, such as the influence exerted by distinct EEG patterns in NCSE on the outcome. We therefore initiated a new prospective multicenter observational registry to collect clinical and EEG data that combined may further help in clinical decision-making and defining SE.MethodsSustained effort network for treatment of status epilepticus/European Academy of Neurology Registry on refractory Status Epilepticus (SENSE-II/AROUSE) is a prospective, multicenter registry for patients treated for SE. The primary objectives are to document patient and SE characteristics, treatment modalities, EEG, neuroimaging data, and outcome of consecutive adults admitted for SE treatment in each of the participating centers and to identify factors associated with outcome and refractoriness. To reach sufficient statistical power for multivariate analysis, a cohort size of 3000 patients is targeted.DiscussionThe data collected for the registry will provide both valuable EEG data and information about specific treatment steps in different patient groups with SE. Eventually, the data will support clinical decision-making and may further guide the planning of clinical trials. Finally, it could help to redefine NCSE and its management.Trial registrationNCT number: NCT05839418.

Non-convulsive seizures and non-convulsive status epilepticus in neuro-intensive care unit.

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.

Power spectrum analysis and outcomes of non-convulsive status epilepticus: a single-center study.

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 60s 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 ± 19.1years (range, 12-72years), including 24 males (50%) and 24 females (50%). When the spectral power of 60s equaled to 11.30 μV2 for predicting impairment of consciousness, (sensitivity, specificity) = (0.979, 0.625). When the spectral power of 60s equaled to 52.70 μV2 for predicting myoclonic jerks, (sensitivity, specificity) = (0.783, 0.756). There were 27 patients (56.3%) followed up with a duration over 12months. Nineteen patients (70.4%) continued to have seizures. Eleven (40.7%) resisted to at least two kinds of appropriate anti-seizure medication at maximum tolerated levels. Five patients with prolonged NCSE suffered from loss of brain parenchymal volume on follow-up MRI scans. Spectral 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.

Hippocampal injury and learning deficits following non-convulsive status epilepticus in periadolescent rats

The effects of non-convulsive status epilepticus (NCSE) on the developing brain remain largely elusive. Here we investigated potential hippocampal injury and learning deficits following one or two episodes of NCSE in periadolescent rats. Non-convulsive status epilepticus was induced with subconvulsive doses of intrahippocampal kainic acid (KA) under continuous EEG monitoring in postnatal day 43 (P43) rats. The RKA group (repeated KA) received intrahippocampal KA at P43 and P44, the SKA group (single KA injection) received KA at P43 and an intrahippocampal saline injection at P44. Controls were sham-treated with saline. The modified two-way active avoidance (MAAV) test was conducted between P45 and P52 to assess learning of context-cued and tone-signaled electrical foot-shock avoidance. Histological analyses were performed at P52 to assess hippocampal neuronal densities, as well as potential reactive astrocytosis and synaptic dysfunction with GFAP (glial fibrillary acidic protein) and synaptophysin (Syp) staining, respectively. Kainic acid injections resulted in electroclinical seizures characterized by behavioral arrest, oromotor automatisms and salivation, without tonic-clonic activity. Compared to controls, both the SKA and RKA groups had lower rates of tone-signaled shock avoidance (p < 0.05). In contextual testing, SKA rats were comparable to controls (p > 0.05), but the RKA group had learning deficits (p < 0.05). Hippocampal neuronal densities were comparable in all groups. Compared to controls, both the SKA and RKA groups had higher hippocampal GFAP levels (p < 0.05). The RKA group also had lower hippocampal Syp levels compared to the SKA and control groups (p < 0.05), which were comparable (p > 0.05). We show that hippocampal NCSE in periadolescent rats results in a seizure burden-dependent hippocampal injury accompanied by cognitive deficits. Our data suggest that the diagnosis and treatment of NCSE should be prompt.

[Pharmacotherapy and intensive care aspects of status epilepticus: update 2020/2021].

Die gezielte Therapie epileptischer Ereignisse und im Speziellen des Status epilepticus (SE) setzt das sichere Erkennen der Krankheitsbilder voraus, wofür gerade bei Formen mit vorwiegend nichtmotorischen Symptomen klinische und elektroenzephalographische Expertise notwendig ist. Die im Jahr 2020 erfolgte Fortschreibung der deutschen Leitlinie zur Behandlung des SE hält an der streng stufengerechten Therapie fest, die eskalierend die Anwendung von Benzodiazepinen, spezifischen Antiepileptika und Anästhetika vorsieht. Bisher ist die Eingrenzung eines in den allermeisten Fällen wirksamen sowie zugleich sicheren und interaktionsfreien Antiepileptikums nicht gelungen. Individuelle Vorerkrankungen und aktuelle Begleitumstände gehen daher genauso wie Erfahrungen des Behandlerteams in die differenzierte Behandlung des SE ein. Insbesondere bei therapierefraktären Formen des SE erweist sich die Therapie als durchaus kompliziert und hat regelhaft intensivmedizinische Implikationen. Mithin ergeben sich im Zuge der modernen SE-Behandlung zahlreiche interdisziplinäre Schnittstellen. Zukünftige wissenschaftliche Fragstellungen werden sich u. a. mit der optimalen Therapie des nonkonvulsiven SE und hier v. a. dem Ausmaß und dem Zeitpunkt von adäquaten Therapieschritten sowie mit assoziierten ethischen Fragen einer Therapieeskalation beschäftigen.

Levetiracetam and Lacosamide in the treatment of Non-Convulsive Status Epilepticus (1347)

Levetiracetam and Lacosamide in the treatment of Non-Convulsive Status Epilepticus (1347)

Diagnosis and Treatment of Status Epilepticus.

The definition of status epilepticus (SE) was revised recently in accordance with the various evidences of neuronal injury and changes in clinical settings. Currently, the most acceptable duration of continuous seizure activity is 5 minutes. In 2015, the International League Against Epilepsy Task Force, which was convened to develop a definition and classification of SE, presented a new classification based on four axes: 1) semiology, 2) etiology, 3) electroencephalogram (EEG) correlates, and 4) age. The essential element of nonconvulsive SE (NCSE) is the presence of neurological abnormalities induced by a prolonged epileptic process. The definition of refractory SE involves either clinical or electrographic seizures that persist after adequate doses of an initial benzodiazepine and acceptable second-line antiseizure drugs. The use of EEG is critical in the diagnosis and treatment of NCSE. However, there are a wide range of EEG abnormalities in NCSE. Both the Neurocritical Care Society and the American Epilepsy Society have suggested a paradigm for treating convulsive SE (CSE). The first-line treatment of CSE with benzodiazepine is well-established. The second-line treatment comprises intravenous (IV) doses of fosphenytoin (phenytoin), valproate, phenobarbital, levetiracetam, or midazolam. Although fosphenytoin (phenytoin) and valproate are commonly used in NCSE, the effectiveness of antiepileptic drugs (AEDs) on NCSE has not been well studied. New AEDs such as IV levetiracetam and lacosamide can also be used to treat NCSE with fewer side effects and drug-drug interactions. For refractory SE, general anesthesia with IV midazolam, propofol, pentobarbital, or thiopental could be applied. Use of ketamine, megadose phenobarbital therapy, and multiple combinations of various AEDs including high doses of oral AEDs can also be considered. New-onset refractory status epilepticus (NORSE) and its subcategory, febrile infection-related epilepsy syndrome, involve autoimmune processes. AEDs alone are poorly effective in the treatment of SE in autoimmune encephalitis. Immunotherapy such as steroids, immunoglobulin, rituximab, or tocilizumab can be effective.

Diagnostic Procedure and Therapeutic Approaches in Nonconvulsive Status Epilepticus (NCSE)

Nonconvulsive epileptic seizures are major type of seizures of all patients with predominantly focal epilepsy. However, this problem is still insufficiently studied, the literature presents a few data on the diagnosis and treatment of nonconvulsive status epilepticus (NCSE). NCSE is a prolonged seizure, not accompanied by severe motor presentation. Such attacks occur much more often than previously thought. NCSE is divided into focal NCSE (complex partial status epilepticus), and generalized NCSE, often referred as absence status. The absence status divides into a typical absence status (presents with suppression of consciousness of various depths, myoclonic twitching of the eyelids, impoverishment of speech production and hallucinations), atypical absence status (presents with retardation of mental processes and eyelid myoclonus) and late absence status (long-term disorientation accompanied by cognitive deficiency and presents mainly in elderly patients). According to the available sources, more than 30% of patients in the intensive care units with impaired consciousness of unclear genesis are patients with NCSE. Use of antiepileptic drugs for intravenous administration opens better opportunities in the treatment of patients with status epilepticus and NCSE.

EEG efficiency of detecting sub-clinical seizures in critical ill patients: Retrospective study

Introduction Continuous electroencephalography (cEEG) monitoring in the critical care setting demonstrates a linear increase in seizure incidence with declining mental status. Delayed diagnosis and treatment of non-convulsive status epilepticus (NCSE) may lead to increased mortality. No clinical or paraclinical parameter can reliably distinguish elderly patients with delirium with or without patterns compatible with NCSE in the absence of cEEG monitoring. EEG may be over-utilized in our hospital ICUs & usually ordered for most of the patient with altered mental status. We aimed to evaluate the efficiency of EEG to detect subclinical seizures in patients with altered level of consciousness. Methods Single-center retrospective study comprised 24 patients who were hospitalized in King Fahad Specialist Hospital in Dammam between January2017-December2018 due to change of their level of consciousness. Descriptive analysis was used to study the factors involved in the patient findings. Findings/prognosis Only 1 of the 4 patients with subclinical seizures had periodic lateralizing epileptogenic discharges. Only one of the patients with the subclinical seizures was known to have seizure. Last 2 patients were post cardiac arrest & one had brain metastasis. 2 of the patients with the subclinical seizure died few days later because of the seizure or drug side effects. Conclusion Patient with decrease level of consciousness after clinical seizure increase suspicion of subclinical seizure, therefore, early diagnosis of the subclinical seizure allows early management and most likely better outcome. However, there was an over utilization of EEG found in through the study.

非惊厥性癫痫持续状态诊断治疗方面的研究进展

非惊厥性癫痫持续状态诊断治疗方面的研究进展

Nonconvulsive seizures and nonconvulsive status epilepticus in the neuro ICU should or should not be treated aggressively: A debate

This article presents a “debate” about the appropriate level of aggressiveness of treatment for nonconvulsive status epilepticus (NCSE), held at the International Congress of Clinical Neurophysiology in Washington D.C. on 4 May 2018. The proposition for discussion was “Nonconvulsive seizures and status epilepticus in the intensive care unit should be treated aggressively.” Dr. Andrea O. Rossetti from Lausanne, Switzerland, spoke in support of the proposition and Dr. Lawrence J. Hirsch from New Haven, Connecticut, discussed reasons for rejecting the proposal. Dr. Frank W. Drislane from Boston, Massachusetts, was asked by the conference organizers to add comments and perspective.

F87 EEG cap placement for expedited identification of non-convulsive status epilepticus

Introduction The objective of this study is to compare the accuracy and time to diagnose of an EEG cap compared to a standard EEG in the setting of suspected non-convulsive status epilepticus (NCSE). NCSE is diagnosed exclusively by EEG and becomes more resistant to treatment one hour after continued seizure activity (Meierkord et al., 2007; Young et al., 1996). At night in many institutions standard EEGs experience significant latency periods that may delay diagnosis and treatment. In contrast EEG caps are quicker to place than standard electrodes and can be placed by residents who are already in the hospital and don’t need to commute, potentially decreasing time to diagnose and treat. Methods For patients with suspected NCSE, residents directly place an EEG cap after ordering a stat EEG by standard hospital protocol. Both EEG cap recordings and standard EEG recordings were analyzed in a blinded manner by an epileptologist. Timing, accuracy of interpretation, and cost were compared. Currently 13 patients have been enrolled, with goal of 20 total patients. Results EEG cap placement reduced the time to obtain EEG recording by over one hour compared to standard EEG. Preliminary data if the first 10 subjects showed no differences in diagnosis of status. Conclusion Use of EEG caps allows for more rapid identification and treatment of NCSE. EEG caps are useful in guiding clinical decision making in suspected NCSE.

Diazepam for Outpatient Treatment of Nonconvulsive Status Epilepticus in Pediatric Patients with Angelman Syndrome (P4.274)

Diazepam for Outpatient Treatment of Nonconvulsive Status Epilepticus in Pediatric Patients with Angelman Syndrome (P4.274)

Diazepam for outpatient treatment of nonconvulsive status epilepticus in pediatric patients with Angelman syndrome

Nonconvulsive status epilepticus (NCSE) is present in multiple pediatric neurogenetic syndromes with epileptic encephalopathies. While intravenous (IV) medications are used inpatient for treatment of critical illness-related NCSE, there is no consensus on treatment of ambulatory NCSE. Up to 50% of patients with Angelman syndrome (AS) have NCSE with myoclonic or atypical absence status. Here we report our experience in pediatric patients with AS and NCSE treated outpatient with a tapering course of oral diazepam. We conducted a chart review of 104 patients seen in the Angelman Syndrome Clinic at Massachusetts General Hospital from January 2008 to March 2017, who met the criteria. Response to treatment was defined as cessation of NCSE symptoms with electroencephalogram (EEG) confirmation when possible. Twenty-one patients with NCSE were identified, and 13 patients (9 male) with 25 episodes of NCSE were included. Mean age at NCSE episode was 5years 4months (15months–12years). Six patients had one episode of NCSE, and 7 patients had recurrent episodes (mean: 2.7; range: 2–4). Median diazepam treatment was 6days (4–12days), with a mean dose of 0.32mg/kg/day divided over 2–3 administrations, decreased every 2days. Nine episodes required multiple courses; however, oral diazepam alone was ultimately successful in 80% (20/25) of NCSE episodes. Oral diazepam was well-tolerated with no major side effects. A short course of oral diazepam is well-tolerated and effective in patients with AS who have ambulatory NCSE. It may be considered prior to escalating to inpatient care in AS and possibly other epilepsy syndromes.

Transition from intravenous to enteral ketamine for treatment of nonconvulsive status epilepticus

BackgroundNonconvulsive status epilepticus (NCSE) is a diagnosis that is often challenging and one that may progress to refractory NCSE. Ketamine is a noncompetitive N-methyl-d-aspartate antagonist that increasingly has been used to treat refractory status epilepticus. Current Neurocritical Care Society guidelines recommend intravenous (IV) ketamine infusion as an alternative treatment for refractory status epilepticus in adults. On the other hand, enteral ketamine use in NCSE has been reported in only 6 cases (1 adult and 5 pediatric) in the literature to date.Case presentationA 33-year-old woman with a history of poorly controlled epilepsy presented with generalized tonic-clonic seizures, followed by recurrent focal seizures that evolved into NCSE. This immediately recurred within 24 h of a prior episode of NCSE that was treated with IV ketamine. Considering her previous response, she was started again on an IV ketamine infusion, which successfully terminated NCSE. This time, enteral ketamine was gradually introduced while weaning off the IV formulation. Treatment with enteral ketamine was continued for 6 months and then tapered off. There was no recurrence of NCSE or seizures and no adverse events noted during the course of treatment.ConclusionThis case supports the use of enteral ketamine as a potential adjunct to IV ketamine in the treatment of NCSE, especially in cases without coma. Introduction of enteral ketamine may reduce seizure recurrence, duration of stay in ICU, and morbidity associated with intubation.

Diagnosis and treatment of nonconvulsive status epilepticus in children

The Neurocritical Care Society′s Guidelines for the Evaluation and Management of Status Epilepti-cus defines status epilepticus as the epilepsy lasts for 5 minutes or longer, with continuous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery (returning to baseline) between seizures.Nonconvulsive status epilepticus (NCSE) can be classified into with or without coma/stupor types.The diagnosis of NCSE needs continuous video electroencephalogram monitoring and the indications include: (1) altered mental status appear after seizures, acute brain injury or other unknown causes; (2)efficacy evaluation of seizure therapy is performed to confirm whether nonconvulsive seizures or NCSE is controlled monitoring for 24 to 48 hours; (3)identification of cerebral ischemia.Modified Salzburg consensus criteria for NCSE suggests that the diagnosis of NCSE needs the combination of clinical features and electroencephalograms.Suspected clinical features and signs of NCSE should last at least 10 minutes, and altered EEG of suspected NCSE should last at least 10 seconds.Benzodiazepines is the first choice of treatment in NCSE and antiepileptic drugs are selected if necessary.If the NCSE lasts longer than 60 minutes, anesthetics or other therapies may be administered. Key words: Nonconvulsive status epilepticus; Continuous electroencephaography; Consensus; Diagnosis; Treatment

[Can treatment with anesthetic anticonvulsive drugs worsen outcome in status epilepticus?]

Nowadays, there is an ongoing discussion about the risks and benefits of anesthetic treatment concerning outcome in status epilepticus (SE). Therefore, we performed aretrospective database analysis to examine the influence of treatment with anesthetic drugs and narcosis in SE on mortality and disability. All treatment episodes of SE at the Department of Neurology of the University of Rostock between 01January 2000 and 31December 2009 were evaluated. SE severity before treatment, mortality, and disability at discharge were taken into account. Of 167 treatment episodes of SE,34 included treatment with anesthetic anticonvulsive drugs and narcosis. In the treatment episodes with use of anesthetic anticonvulsive drugs and narcosis, there was amore than twofold increased risk for death compared to the other treatment episodes. However, due to sample size this difference was not significant (p= 0.09). Cardiopulmonary complications were the cause of death in 4 of 5patients dying during treatment episodes with anesthetic anticonvulsive drugs and narcosis. At discharge, disability as measured with the Modified Rankin Scale was higher in patients treated with anesthetic anticonvulsive drugs and narcosis than in the others (p= 0.03). A subgroup analysis revealed that especially in patients with nonconvulsive SE with impaired consciousness treatment with narcosis was associated with ahigher rate of new deficits or mortality (p= 0.012). Especially when considering narcosis for treatment of nonconvulsive SE, risks and benefits should be carefully weighed. When treating SE with anesthetic drugs and narcosis, everything has to be done to avoid cardiopulmonary complications.

Intravenous anesthesia in treatment of nonconvulsive status epilepticus: Characteristics and outcomes

ObjectiveTo determine factors associated with continuous anesthetic drug (IVAD) use in nonconvulsive status epilepticus (NCSE). MethodsRetrospective cohort study of patients who met clinical and EEG criteria of NCSE from 2009 to 2014 at a tertiary academic medical center. Patients were categorized according to IVAD use. Outcome variables were response to treatment and in-hospital death. We used descriptive analyses for baseline characteristics and outcome variable differences among patients who did and did not receive IVAD. ResultsForty-three patients had a total of 45 NCSE episodes. IVAD was used in 69% of the episodes. Patients treated with IVAD were younger (53.1±14.1 vs 64.1±13.3, p=0.019). The episodes treated with IVAD occurred more frequently in patients with an acute neurologic pathology (58% vs 21%, p=0.024) and those presenting in a coma (39% vs 7%, p=0.030). NCSE resolved in 74% of the patients who received IVAD. Duration of NCSE did not differ significantly by treatment group. There were total 13 in-hospital deaths: ten in IVAD users vs three in the no-IVAD group (p>0.05). Only one in-hospital death appeared to be a direct consequence of IVAD use. Mortality was more common among episodes that were not treated according to the published status epilepticus treatment guidelines compared to the episodes where guidelines were followed. ConclusionOur findings showed that factors such as younger age, acute neurologic pathology and coma at presentation were associated with IVAD use in patients with NCSE. These factors should be controlled in the future outcome and effectiveness studies to determine the effect of IVAD use on outcome of NCSE.

Diagnosis, Etiology, and Treatment of Nonconvulsive Status Epilepticus, a Semiological Oriented Review.

Nonconvulsive status epilepticus (NCSE) defines a prolonged electrographic seizure activity resulting in nonconvulsive symptoms. Semiology is a crucial element in diagnosis, etiological evaluation, and treatment plan of NCSE. It includes mostly generalized myoclonic status (GMS), focal simple motor status (FSMS), and dyscognitive status (DS). This review aims to guide clinicians in diagnosis, etiological evaluation, and treatment of patients with NCSE based on semiological presentation. Diagnosis of GMS and FSMS is based mainly on semiology, whereas DS often requires EEG for differential diagnosis with nonepileptic events. GMS and FSMS etiological investigation may be readily prioritized based on semiological type, whereas DS requires EEG for further classification in psychomotor status and absence status. Choice of appropriate treatment is dictated by the semiological presentation, EEG findings, and etiology. Surgery and other interventions including electroconvulsive therapy and vagal nerve stimulation should be considered in patients refractory to medical treatment.

34.: Non-convulsive status epilepticus in the elderly: A review

Altered mental state (AMS) is a common presentation in the elderly to the emergency department. It has been determined that about 16% of patients aged 60 or older with confusion of unknown origin had non-convulsive status epilepticus (NCSE). The diagnosis of NCSE is difficult in the elderly because possible etiologies of confusion could present with the same clinical picture. NCSE in the elderly carries major morbidity and mortality, attributable primarily to the etiology. Treatment of NCSE in the elderly is complex, involving treatment of the etiology and concomitant medical illnesses, whilst balancing the side effects and drug interactions of antiepileptic drugs. A review of the recent literature had been undertaken to look at the studies done on elderly patients with confusion of unknown origin or altered mental states that used an electroencephalogram (EEG) in the workup of these patients, and considered the differential diagnosis of NCSE. At this point, there are many unanswered questions. There needs to be a prospective study to determine the prevalence of NCSE specifically in the elderly patients who present with AMS consecutively. There probably is a need to look at the prevalence of NCSE due to specific etiologies in the elderly. There is a need to identify clinical features in these elderly patients which would predict NCSE with adequate sensitivity and specificity. There is also a need to develop management guidelines on timing, duration and cost effectiveness of emergency EEG in the context of investigating these elderly patients who present with AMS. In an ideal scenario, elderly patients with AMS could have an array of investigations done routinely in the emergency department without delay. NCSE could be picked up on the initial emergent EEG, and together with other neuro-imaging and biochemistry investigations, work out the etiology of the NCSE, and then decide on the appropriate treatment. The treatment plan could be analyzed for risk and benefits with the aid of a decision analysis tool.