An observational electro-clinical study of status epilepticus: from management to outcome

Status epilepticus (SE) is a neurological emergency associated with a high morbidity and mortality. A prospective 3-year study was conducted in our hospital on 56 consecutive inpatients with SE. Demographic and clinical data were collected. EEG and clinical SE features were considered for the SE classification, both separately and together. The etiology of SE was determined. Patients were treated according to international standardized protocols of guidelines for the management of epilepsy. Response to treatment was evaluated clinically and electrophysiologically. Outcome at 30 days was considered as good, poor or death. Convulsive SE (CSE) was observed in 35 patients and non-convulsive SE (NCSE) in 21. Patients with CSE, in particular focal-CSE, were older than those with NCSE. As regards etiology, patients with SE secondary to cerebral lesions were the oldest, followed by patients with anoxic SE and those with toxic dysmetabolic SE. A first-line treatment was usually sufficient to control seizure activity in lesional and epileptic SE, while more aggressive treatment was necessary in all anoxic SE patients. Outcome was good in 35 patients, poor in 12, while 9 died. A prompt neurophysiological EEG evaluation, combined with the clinical evaluation, helps to make a rapid prognosis and take therapeutic management decisions. First-line treatments may be sufficient to control electro-clinical status in lesional and epileptic SE, while intensive care unit management, a more aggressive therapeutic approach and continuous EEG monitoring are recommended for refractory SE.     

Pediatric status epilepticus: a perspective from Saudi Arabia

The purpose of this study was to assess risk factors and management of status epilepticus and non–status epilepticus seizures at a community hospital in Saudi Arabia. The research design was a prevalence study of a convenience sample of pediatric seizure episodes admitted to a 350-bed hospital from 1992 to 1997. The mean age at presentation was 2 years, 10 months, 43% of patients had no history of seizures, and 17% were transferred from other hospitals. Fifty-nine (28%) of 212 seizure episodes were status epilepticus (SE). These SE episodes were significantly more likely than non–SE episodes to be associated with a history of seizures, prior antiepileptic drug (AED) therapy, the presence of an acute etiology, and prolonged duration of seizures before hospitalization. SE episodes were also significantly more likely than non–SE episodes to receive an inappropriate AED, to require intensive care unit admission, to suffer morbidity, and to have SE recurrence at follow-up; however, the difference in mortality was not significant. In conclusion, children with SE were more likely than those with non–SE seizures to have a history of seizures and acute brain insults, prolonged seizure duration before hospitalization, and less optimal management and outcomes. Management of SE in this referral population can be improved by more rapid access to appropriate medical care.     

Treatment of status epilepticus]

Status epilepticus (SE) is a condition requiring emergency care. There are convulsive SE, non-convulsive SE including complex partial status and absence status, non-convulsive electric SE and pseudostatus epilepticus, although convulsive SE is the most common. Diagnosis of status epilepticus of complex partial seizures (CPS) and absence seizures was significantly delayed because delays in seeking medical attention were common. The seizures were generalized convulsive SE in 84% and CPS status in 16%, and the overall mortality rate was 15% in 41 SE patients of our study. EEG monitoring is important to make or exclude the diagnosis of SE. Diazepam is the first choice medication and effective in the management of SE, and lately, lorazepam, midazolam, propofol and pentobarbital etc as emergency therapy. Phenytoin is also considered first-line agent in the emergency management of SE. Repetitive transcranial magnetic stimulation (rTMS) led to a prolonged latency for seizure induction after an intraperitoneal injection of pentylenetetrazol (PTZ) and effectively prevented the development of status epilepticus of PTZ-induced convulsions in the rats. Our data suggest that rTMS has suppressive effects on the neuronal excitability in rats. These effects are anticonvulsive and suggest the possibility of therapeutic use of rTMS in the patients with refractory seizures.     

Treatment of Status Epilepticus in Adults: Guidelines of the Italian League Against Epilepsy

Summary:  Status epilepticus (SE) is a medical emergency which can lead to significant morbidity and mortality and requires prompt diagnosis and treatment. SE is differentiated into generalized or partial SE on the basis of its electro-clinical manifestations. The guidelines for the management of SE produced by the Italian League against Epilepsy also distinguish three different stages of SE (initial, established and refractory), based on time elapsed since the onset of the condition and responsiveness to previously administered drugs. Treatment should be started as soon as possible, particularly in generalized convulsive SE, and should include general support measures, drugs to suppress epileptic activity and, whenever possible, treatments aimed at relieving the underlying (causative) condition. Benzodiazepines are the first line antiepileptic agents, and i.v. lorazepam is generally preferred because it is associated with a lower risk of early relapses. If benzodiazepines fail to control seizures, i.v. phenytoin is usually indicated, though i.v. phenobarbital or i.v. valproate may also be considered. Refractory SE requires admission to an intensive care unit (ICU) to allow adequate monitoring and support of respiratory, metabolic and hemodynamic functions and cerebral electrical activity. In refractory SE, general anesthesia may be required. Propofol and thiopental represent first line agents in this setting, after careful assessment of potential risks and benefits.     

Status Epilepticus and Refractory Status Epilepticus Management

Status epilepticus (SE) describes persistent or recurring seizures without a return to baseline mental status and is a common neurologic emergency. SE can occur in the context of epilepsy or may be symptomatic of a wide range of underlying etiologies. The clinician׳s aim is to rapidly institute care that simultaneously stabilizes the patient medically, identifies and manages any precipitant conditions, and terminates seizures. Seizure management involves “emergent” treatment with benzodiazepines followed by “urgent” therapy with other antiseizure medications. If seizures persist, then refractory SE is diagnosed and management options include additional antiseizure medications or infusions of midazolam or pentobarbital. This article reviews the management of pediatric SE and refractory SE.     

Électroencéphalographie dans les états de mal épileptiques : glossaire, protocole et interprétation

Electroencephalography is a useful tool in the diagnosis and management of status epilepticus (SE) and it can also give prognostic information. It can help to confirm that an episode of SE has ended. It can identify the patients who have unsuspected subclinical seizures. There is a wide range of presentations of SE. Nearly all types of seizures have the potential of occurring in a repeated or continuous form. The polymorphic EEG patterns in SE reflect this wide variety. But controversial patterns also exist in the form of periodic epileptiform discharges. While some authors considered these patterns to be interictal or postictal, others postulate that these patterns are ictal. In these cases, clinical features are very important in order to conclude. Generalized convulsive SE is a medical emergency and the EEG is not necessary to make a diagnosis. Convulsive generalized SE requires immediate treatment and in this case, EEG is used in guiding treatment especially in refractory SE that may evolve into subtle SE. In non-convulsive SE, diagnosis is not obvious on the basis of clinical signs and symptoms alone and the diagnosis must be confirmed by urgent EEG. EEG can also be used to distinguish SE from psychogenic seizures, movement disorders and in patients who have causes of persistent loss of consciousness (metabolic encephalopathy, postanoxic encephalopathy). This article proposes a protocol for the use of the EEG in SE, guidelines and simple vocabulary for a good interpretation and comprehension of the EEG.     

Treatment of seizure emergencies: convulsive and non-convulsive status epilepticus

Status epilepticus (SE), defined as recurrent epileptic seizures without complete recovery between seizures, is one of the most serious manifestations of epilepsy. Generalized convulsive status epilepticus (GCSE) is the most common and most life-threatening form of SE, and aging increases the mortality risk. In a recent study of treatment of GCSE, 226 of 518 evaluable patients (43.6%) were of age 65 or older. In the 157 elderly patients with overt GCSE, phenobarbital was successful as first-line treatment in 71.4%, lorazepam in 63%, diazepam and phenytoin in 53.3%, and phenytoin alone in 41.5%. Phenobarbital and lorazepam were more successful than phenytoin alone. In the 69 elderly patients with subtle GCSE, success as the first treatment was 30.8% for phenobarbital, 14.3% for lorazepam, 11.8% for phenytoin, and 7.7% for diazepam and phenytoin. Overall, the results were similar to those reported for the entire study. Lorazepam, because of ease of use, is probably the best drug for the initial treatment of overt GCSE in the elderly; phenobarbital may be the best drug for subtle GCSE in this group, but more data are needed. The term "nonconvulsive SE" has been used to include complex partial SE and absence SE - both of which present as an "epileptic twilight state" - and SE in comatose patients. The diagnosis can be challenging, particularly in the elderly, as overlapping clinical features and electroencephalogram patterns can be seen in SE and in a variety of encephalopathic conditions. There is a suggestion that aggressive treatment of elderly patients with nonconvulsive SE may worsen prognosis. Clearly, there is a need for more data to better understand management of elderly patients with both convulsive and nonconvulsive SE.     

Place de l’électroencéphalogramme dans l’état de mal épileptique

Recordings of the electroencephalogram (EEG) play a major role in the management of patients with status epilepticus (SE). The EEG contributes to the diagnosis of SE, can be used to identify differential and syndromic diagnoses, and sometimes provides the etiologic diagnosis. EEG is helpful in monitoring therapeutic management and is an essential component of the follow up. The interpretation of the EEG in a patient with refractory SE is difficult, requiring clinical experience in this domain. We discuss the different modalities of EEG recording and their indications in emergency situations.     

Estatus epiléptico focal: revisión del tratamiento farmacológico

IntroductionStatus epilepticus (SE) is a neurological emergency associated with high morbidity and mortality. One prognostic factor is the type of SE. The purpose of this review is to analyse the most recent recommendations of different scientific societies and expert groups on the treatment of SE, and the latest studies, to assess the literature on the management of focal SE.MethodsWe searched PubMed for studies published between 1 August 2008 and 1 August 2018 on the pharmacological treatment of focal SE and its different types in adults.ResultsWe identified 29 publications among reviews, treatment guidelines, meta-analyses, clinical trials, and case series on the treatment of SE. Only 3 of them accounted for whether SE was focal or generalised; 4 focused exclusively on focal SE, and 7 differentiated between convulsive and non-convulsive SE and also record the presence of focal seizures. Treatment recommendations for focal SE do not differ from those of generalised SE in stages I and II: initially intravenous lorazepam or diazepam, if the intravenous route is available, and otherwise intramuscular midazolam, followed by intravenous phenytoin, valproate, levetiracetam, or lacosamide if seizures persist. Use of anaesthetic drugs should be delayed for as long as possible in patients with refractory focal SE.ConclusionsThe available scientific evidence is insufficient to claim that pharmacological treatment of focal SE should be different from treatment for generalised SE. More studies with a greater number of patients are needed.     

Epidemiology of status epilepticus in a rural area of northern Italy: a 2-year population-based study

We performed a 2-year population-based study on status epilepticus (SE) in adults in the rural area of Lugo di Romagna, northern Italy, to verify whether an area of low-level urbanization has a lower risk of occurrence of SE (as recently suggested), different clinical features and short-term prognosis than areas of high-level urbanization. We found crude and age- and sex-adjusted annual incidence rates of SE of 16.5/100 000 and 11.6/100 000, respectively. In patients under 60 years crude incidence was 2.9/100 000 and in the elderly (>/=60 years) 38.6/100 000. Acute symptomatic SE accounted for 30% and a cerebrovascular pathology was the most frequently associated etiologic condition (60%). A history of seizures was reported in 41% of patients. The first therapeutic intervention was mainly benzodiazepines (lorazepam 46%; diazepam 33%). The 30-day case fatality was 7%. We observed that the adult population of an area with a low level of urbanization has the same risk for SE, clinical features and short-term prognosis as European urban areas. The only contrasting result is the 30-day case fatality of 7% against the 39% found in the other Italian study (Bologna), despite the similarity of the SE features in these two areas of the same region. We infer that the short-term prognosis of SE could also be considerably influenced by differences in health service organization (and hence management) possibly due to different levels of urbanization.     

Autonomic status epilepticus in Panayiotopoulos syndrome and other childhood and adult epilepsies: a consensus view

PURPOSE: To discuss and propose a definition of autonomic status epilepticus (SE), describe its clinical and EEG features, and review what is known about its epidemiology, pathophysiology, differential diagnosis, and management. METHODS: An international consortium of established researchers in the field was identified from their published work, agreed the purpose of the project, searched the literature, and, by use of e-mail communication, agreed the consensus document. RESULTS: Autonomic SE is a condition lasting at least 30 min and characterized by epileptic activity causing altered autonomic function of any type at seizure onset or in which manifestations consistent with altered autonomic function are prominent (quantitatively dominant or clinically important) even if not present at seizure onset. It is best described, and probably most commonly encountered in children, with Panayiotopoulos syndrome. However, it also occurs in children with symptomatic epilepsies and, exceptionally, in adults. Its pathogenesis and most appropriate management are poorly understood. CONCLUSIONS: It is hoped that this document will help clinical recognition of Autonomic SE, reduce misdiagnosis, and promote further interest and studies into what has been a relatively neglected area.     

Google search behavior for status epilepticus

BackgroundMillions of people surf the Internet every day as a source of health-care information looking for materials about symptoms, diagnosis, treatments and their possible adverse effects, or diagnostic procedures. Google is the most popular search engine and is used by patients and physicians to search for online health-related information. This study aimed to evaluate changes in Google search behavior occurring in English-speaking countries over time for the term “status epilepticus” (SE).MethodsUsing Google Trends, data on global search queries for the term SE between the 1st of January 2004 and 31st of December 2014 were analyzed. Search volume numbers over time (downloaded as CSV datasets) were analyzed by applying the “health” category filter.ResultsThe research trends for the term SE remained fairly constant over time. The greatest search volume for the term SE was reported in the United States, followed by India, Australia, the United Kingdom, Canada, the Netherlands, Thailand, and Germany. Most terms associated with the search queries were related to SE definition, symptoms, subtypes, and treatment. The volume of searches for some queries (nonconvulsive, focal, and refractory SE; SE definition; SE guidelines; SE symptoms; SE management; SE treatment) was enormously increased over time (search popularity has exceeded a 5000% growth since 2004).ConclusionsMost people use search engines to look for the term SE to obtain information on its definition, subtypes, and management. The greatest search volume occurred not only in developed countries but also in developing countries where raising awareness about SE still remains a challenging task and where there is reduced public knowledge of epilepsy.Health information seeking (the extent to which people search for health information online) reflects the health-related information needs of Internet users for a specific disease. Google Trends shows that Internet users have a great demand for information concerning some aspects of SE (definition, subtypes, symptoms, treatment, and guidelines). Policy makers and neurological scientific societies have the responsibility to try to meet these information needs and to better target public information campaigns on SE to the general population.This article is part of a Special Issue entitled “Status Epilepticus”.     

Gaps and opportunities in refractory status epilepticus research in children: A multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG)

PurposeStatus epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the ‘pediatric Status Epilepticus Research Group’ (pSERG).MethodsA literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network.ResultsThe care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome.ConclusionThe care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE.     

Levetiracetam versus lorazepam in status epilepticus: a randomized,open labeled pilot study

For the management of status epilepticus (SE), lorazepam (LOR) is recommended as the first and phenytoin or fosphenytoin as the second choice. Both these drugs have significant toxicity. Intravenous levetiracetam (LEV) has become available, but its efficacy and safety has not been reported in comparison to LOR. We report a randomized, open labeled pilot study comparing the efficacy and safety of LEV and LOR in SE. Consecutive patients with convulsive or subtle convulsive SE were randomized to LEV 20 mg/kg IV over 15 min or LOR 0.1 mg/kg over 2–4 min. Failure to control SE within 10 min of administration of one study drug was treated by the other study drug. The primary endpoint was clinical seizure cessation and secondary endpoints were 24 h freedom from seizure, hospital mortality, and adverse events. Our results are based on 79 patients. Both LEV and LOR were equally effective. In the first instance, the SE was controlled by LEV in 76.3% (29/38) and by LOR in 75.6% (31/41) of patients. In those resistant to the above regimen, LEV controlled SE in 70.0% (7/10) and LOR in 88.9% (8/9) patients. The 24-h freedom from seizure was also comparable: by LEV in 79.3% (23/29) and LOR in 67.7% (21/31). LOR was associated with significantly higher need of artificial ventilation and insignificantly higher frequency of hypotension. For the treatment of SE, LEV is an alternative to LOR and may be preferred in patients with respiratory compromise and hypotension.     

The EEG of status epilepticus.

SUMMARY: Gastaut noted that there are as many forms of status epilepticus (SE) as there are seizure types. The pleomorphic EEG patterns reflect this wide variety of clinical types. The different electroclinical types of status epilepticus share EEG characteristics including rhythmic activity, epileptiform discharges, and often a waxing and waning evolution. Gray zones of interpretation exist in the form of runs of epileptiform periodic discharges, typically of lower frequency, and lesser temporal variability. In diagnosing SE, clinical correlation and response to parenteral anti-epileptic drugs (AEDs) are of particular importance. Accurate diagnosis of electroclinical SE type is essential, because it determines prognosis and dictates the intensity of therapeutic management. Some patients with benign forms of SE may benefit from nonparenteral treatment, and be followed up clinically and by spot EEGs. Conversely, intensive care unit management with anesthesia and continuous monitoring, and parenteral AEDs may be required for refractory convulsive SE.     

Mortality after a First Episode of Status Epilepticus in the United States and Europe

Summary:  Objective: In the last decade several studies have been published on incidence, etiology, and prognosis of status epilepticus (SE) with population-based data from the United States and Europe. The aim of this review is to summarize the available information on the epidemiology of SE and to outline the sources of the variability in reported mortality after SE.
Methods: Comparison of mortality studies in SE from the United States and Europe.
Results: The incidence of SE is lower in Europe (9.9–15.8/10,000) than in the United States (18.3–41/100,000). The overall mortality after SE is similar in the two U.S. studies: the case fatality is 21% in Rochester, and 22% in Richmond. All European studies excluded SE after anoxic encephalopathy following cardiac arrest. This exclusion may partly explain the lower case fatality (around 10%) found in two of the European studies. The study from Bologna showed the highest case fatality (33%) even after exclusion of anoxic encephalopathy. The mortality in acute symptomatic SE was higher than for other forms of SE across all studies.
Conclusions: Short-term mortality after SE occurs mainly in the acute symptomatic group. Based on published data, it is not clear if differences in early management and medical treatment have any impact on prognosis or whether the differences can be attributed only to differences in distribution of the underlying causes in acute symptomatic SE. Future studies should address this issue.     

Age-Dependent Consequences of Status Epilepticus: Animal Models

Summary:  Status epilepticus (SE) is a significant neurological emergency that occurs most commonly in children. Although SE has been associated with an elevated risk of brain injury, it is unclear from clinical studies in whom and under what circumstances brain injury will occur. The purpose of this review is to evaluate the effects of age on the consequences of SE. In this review, we focus mainly on the animal data that describe the consequences of a single episode of SE induced in the adult and immature rat brain. The experimental data suggest that the risk of developing SE-induced brain damage, subsequent epilepsy and cognitive deficits in large part depends on the age in which the SE occurs. Younger rats are more resistant to seizure-induced brain damage than older rats; however, when SE occurs in immature rats with abnormal brains, there is an increase in the severity of seizure-induced brain injury. Better understanding of the pathophysiologic mechanisms underlying the age-specific alterations to the brain induced by SE will lead to the development of novel and effective strategies to improve the deleterious consequences.     

Generalized convulsive status epilepticus management in adults: A cohort study with evaluation of professional practice

Purpose: Generalized convulsive status epilepticus (GCSE) needs immediate management. Despite guidelines, adherence to management protocols is often poor, this contributing to poor outcome. We aimed to evaluate the usefulness of a management protocol in GCSE. Methods: This is a prospective population‐based study of consecutive adults with GCSE in Haute‐Garonne district, France. Demographics and treatment procedures were documented. Factors associated with seizure termination and refractoriness were analyzed using logistic regression. Results: One hundred eighteen episodes in 111 adults (mean age 55 years) between October 2006 and February 2008 were included. SE was convulsive in 101 episodes. Incidence was 6.6 per 100,000 and case fatality was 9%. Adequate initial treatment according to protocol was observed in 38%; 64% were treated out‐of‐hospital, and SE was refractory in 27% [no response after two antiepileptic drugs (AED)]. Patients who received adequate first‐line treatment were 6.8 times [95% confidence interval (CI) 2.8–16.9] more likely to have seizure termination, with 74% versus 29% efficacy rate (p < 0.0001). Inadequate initial management was 4.7 times (1.9–11.1) more likely to need several benzodiazepine doses (p = 0.0004) and 9.1 times (3.7–20) more likely to require a long‐acting AED as next treatment (p < 0.0001). Seizure termination after initial treatment was associated with decreased intensive care unit stay [1 (1–2) versus 2 (1–5.5) days, p < 0.0001] and hospital stay [3 (2–11) versus 7 (3–18) days, p = 0.009]. Discussion: GCSE termination and outcome seem clearly associated with adherence to treatment protocol. Results add to the debate on appropriate allocation of resources for out‐of‐hospital treatment, licensed drugs, and achievement of guideline implementation to improve SE outcome.     

Nonfatal pulmonary embolus associated with clozapine treatment: a case series

Clozapine is a tricyclic dibenzodiazepine efficacious in the management of treatment-resistant chronic schizophrenia. Although case reports of arrhythmias and cardiomyositis have been reported with clozapine use, severe acute cardiovascular side effects (SE) tend to be rare in clozapine treatment. The author reports on a case series of three patients treated with clozapine on a long-term inpatient unit that developed nonfatal pulmonary emboli (PE) and deep venous thrombosis (DVT). While not a contraindication, potential increased PE risk should be discussed with initiation of clozapine treatment.     

Treatment of status epilepticus with electroconvulsive therapy

OBJECTIVE: To describe a case in which electroconvulsive therapy (ECT) was used successfully to treat refractory status epilepticus (SE) after all pharmacological therapies were exhausted. METHODS: A 39-year-old man with no seizure history presented in SE secondary to presumed viral encephalitis. His seizures remained refractory to medical management, and he was placed in a pentobarbital-induced coma. Multiple attempts to wean pentobarbital over the next several months failed due to SE relapses. With all standard pharmacological therapies exhausted, the patient underwent a series of 3 ECT sessions per day for 3 consecutive days. Electroencephalogram improvements were noted immediately with diffusely slow activity and with a delayed response over time in the patient's neurological examination. Twelve months post-ECT, the patient is awake, alert, and being managed on antiepileptic medications as outpatient. DISCUSSION: This case further illustrates the role of ECT in the treatment of refractory SE.