Infections in status epilepticus: A retrospective 5-year cohort study

PurposeStatus epilepticus (SE) has attracted renewed interest lately, and efforts are made to optimize every treatment stage. For refractory SE, optimal supporting care involves mechanical ventilation and intensive care unit (ICU) admission. Infections often complicate SE and recently a single-centre observational study demonstrated an association between infections and poor short-term outcome of SE in a cohort of severely ill patients. We have here attempted to replicate those findings in a different cohort.MethodWe performed a retrospective observational study and included all patients with a diagnosis of SE during 2008–2012 at a Swedish tertiary referral centre.ResultsThe cohort consisted of 103 patients (53% female, 47% male, median age 62 years, range 19–87 years). In house mortality was less than 2 and 70% of the patients’ were discharged home. The most common aetiologies of SE were uncontrolled epilepsy (37%) and brain tumours (16%). A total of 39 patients suffered infections during their stay. Presence of infection was associated with mechanical ventilation (OR 3.344, 95% CI 1.44–7.79) as well as not being discharged home (OR2.705, 95% CI 1.14–6.44), and duration of SE was significantly longer in patients with infection (median 1 day vs. 2.5 days, p < 0.001).ConclusionWe conclude that the previously described association between infections, a longer SE duration, and an unfavourable outcome of SE seems valid also in SE of less severe aetiology.     

Lidocaine in refractory status epilepticus: confirmation of efficacy with continuous EEG monitoring.

Lidocaine was efficacious in 2 patients with refractory status epilepticus (RSE) unresponsive to several antiepileptic drugs (AEDs), including high-dose barbiturates. We confirmed the efficacy of lidocaine with, for the first time in adults, continuous EEG monitoring. Lidocaine, when properly used, may be a treatment option in RSE.     

Treatments with midazolam and lidocaine for status epilepticus in neonates

Status epilepticus (SE) occurs in children of all ages. Recent epidemiologic investigations of SE show heightened morbidity and mortality in newborns and young infants. However, the existing definition of SE in newborns is not precise and not easily applied in clinical investigations or in clinical practice. To evaluate the underlying conditions, clinical features and treatment of SE in neonates in Japan, a retrospective multi-center study was performed. In the initial investigation, questionnaires were sent to pediatric neurologists in 194 neonatal intensive care units of university hospitals, children's hospitals, and general hospitals throughout in Japan. The questionnaires sought information on the background of each case, types of seizures, etiology of SE, treatments, results and adverse effects of treatment for patients less than 1 week old who had prolonged or frequently repeated seizures lasting more than 15 min and who are refractory to treatment with conventional anticonvulsants, such as diazepam (DZP), phenobarbital (PB) or phenytoin (PHT). As a secondary investigation, 65 cases from nine institutes, which completely fulfilled these criteria and were treated with midazolam (MDL) or lidocaine (Lid) to stop seizures were examined more fully. Subtle seizure and generalized tonic-clonic seizure were the most frequent seizure types. Neonatal SE was most frequently associated with hypoxic-ischemic encephalopathy, followed by intraventricular hemorrhage, central nervous system infections, and cerebral infarction. The final treatment outcome was available for 72.7% and 81.3% of MDL- and Lid-treated patients, respectively. Adverse effects of MDL and Lid were identified in 7.3% and 6.3% of patients, respectively. To reveal electroclinical seizures, clinical seizures without ictal discharge or other non-epileptic movements in neonates was important for appropriate treatment. MDL and Lid were useful drugs for the treatment of neonatal SE.     

不同类型小儿癫痫持续状态的临床及脑电图分析

目的 分析不同类型儿童癫痫持续状态（ＳＥ）的临床和脑电图（ＥＥＧ）特征,以期对ＳＥ作出早期诊断及处理。方法 用录像脑电图监测的方法对１９９６年３月至１９９９年３月北京医科大学第一医院儿科（２４例）和香港大学儿科部（３例）收治的２７例癫饿按发作类型进行分类,分析不同为临床发作特征及年龄、病因、脑发育水平、诱发因素和药物反应等对ＳＥＲ 影响。结果 本组２７例ＳＥ患儿强直＝阵挛性ＳＥ１例,强直性ＳＥ２例     

An epidemiological study of children with status epilepticus in Okayama, Japan

BACKGROUND: The incidence of status epilepticus (SE) in Asian children, including Japanese, has not been reported. METHODS: In 2003, we performed an epidemiological study of SE on Japanese children (31 days or older to <15 years of age) in Okayama City by ascertaining all lifetime first episodes of SE. RESULTS: Thirty-seven patients (22 males and 15 females) were identified. The annual incidence of SE was 38.8 per 100,000 population (95% CI: 24.5-49.5). Febrile SE in the absence of CNS infection accounted for 17. Acute symptomatic etiologies other than febrile SE were observed in eight patients, including three cases of influenza encephalitis/encephalopathy. Five were classified as remote symptomatic and the remaining seven as cryptogenic. The highest incidence (155.1/100,000) was seen in the age range of 31 days or older to <1 year, followed by 101.5/100,000 in the age range of one year, and the incidence decreased after eight years. In 26 of the 37 patients, SE was their first seizure. As for seizure types, 32 had convulsive SE, including tonic status in one. Five others showed nonconvulsive SE, including complex partial SE in four and absence status in one. No one died of SE. Two patients who brought on SE because of influenza encephalitis/encephalopathy suffered from motor disturbance with or without mental disturbance after SE. CONCLUSIONS: The incidence of SE tended to be higher in Japanese children than reported in Caucasians. The Japanese had an age-specific incidence pattern similar to that of Caucasians.     

Underlying neurologic disorders and recurrence rates of status epilepticus in childhood

Background: The underlying neurologic disorders of status epilepticus (SE) in childhood remain poorly characterized. Methods: We reviewed 249 consecutive patients with SE, aged 1 month to 18 years, who were referred to Tottori University Hospital from 1984 to 2002. After exclusion of SE patients with acute symptomatic etiology and progressive encephalopathy, such as acute encephalitis/encephalopathy, meningitis, head trauma, or metabolic disorders, we analyzed 112 patients, aged 3 months to 14 years, and focused on the epilepsy classification and perinatal brain damage in these patients. Results: Major underlying neurologic disorders were non-symptomatic epilepsy (41 patients, 36.6%), perinatal brain damage (15 patients, 13.4%), non-syndromic mental retardation (17 patients, 15.2%), and congenital disorders including chromosomal abnormalities (13 patients, 11.6%). In non-symptomatic epilepsy, childhood epilepsy with occipital paroxysms (Panayiotopoulos syndrome, 11 patients) and severe myoclonic epilepsy in infancy (SMEI, 6 patients) were common and had high recurrence rates (81.8% and 66.7%, respectively). In patients with a history of perinatal brain damage, preterm birth, neonatal seizure, asphyxia, and neonatal hypoglycemia were frequent. Neonatal hypoglycemia and neonatal seizure were related to the recurrence of SE (100% and 87.5%, respectively). They were mostly diagnosed as symptomatic occipital lobe epilepsy. Parieto-occipital paroxysms were associated with a high recurrence rate of SE (80.6%). Conclusions: Although the underlying neurologic disorders of SE are heterogeneous, three specific epileptic syndromes (Panayiotopoulos syndrome, SMEI, and symptomatic occipital lobe epilepsy secondary to neonatal hypoglycemia and neonatal seizure) were the most common causes of SE and were associated with higher recurrence rates.     

Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus

Purpose: To evaluate the feasibility and safety of intravenous (iv) levetiracetam (LEV) added to the standard therapeutic regimen in adults with status epilepticus (SE), and as secondary objective to assess a population pharmacokinetic (PK) model for ivLEV in patients with SE. Methods: In 12 adults presenting with SE, 2,500 mg ivLEV was added as soon as possible to standardized protocol, consisting of iv clonazepam and/or rectal diazepam, as needed followed by phenytoin or valproic acid. ivLEV was administered over approximately 5 min, in general after administration of clonazepam, regardless the need for further treatment. During 24‐h follow‐up, patients were observed for any clinically relevant side‐effects. Blood samples for PK analysis were available in 10 patients. A population PK model was developed by iterative two‐stage Bayesian analysis and compared to PK data of healthy volunteers. Results: Eleven patients with a median age of 60 years were included in the per protocol analysis. Five were diagnosed as generalized‐convulsive SE, five as partial‐convulsive SE, and one as a nonconvulsive SE. The median time from hospital admission to ivLEV was 36 min. No serious side effects could be related directly to the administration of ivLEV. During PK analysis, four patients showed a clear distribution phase, lacking in the others. The PK of the population was best described by a two‐compartment population model. Mean (standard deviation, SD) population parameters included volume of distribution of central compartment: 0.45 (0.084) L/kg; total body clearance: 0.0476 (0.0147) L/h/kg; distribution rate constants, central to peripheral compartment (k₁₂): 0.24 (0.12)/h, and peripheral to central (k₂₁): 0.70 (0.22)/h. Mean maximal plasma concentration was 85 (19) mg/L. Discussion: The addition of ivLEV to the standard regimen for controlling SE seems feasible and safe. PK data of ivLEV in patients with SE correspond to earlier values derived from healthy volunteers, confirming a two‐compartment population model.     

Convulsive status epilepticus: clinical profile in a developing country

PURPOSE: In developing countries optimal care of status epilepticus (SE) is associated with major barriers, particularly transportation. METHODS: A prospective study of SE was performed between 1994 and 1996 to determine the clinical profile, response to treatment and outcome, Glasgow Outcome Scale (GOS). RESULTS: Of the 85 patients admitted, the mean age was 33 years (8-75 years), 16% <16 years of age. The mean duration of SE before admission was 18.02 h (1-72 h). Only 23 (28%) patients, all locals, presented within <3 h of onset. Etiology included acute symptomatic (54%), remote symptomatic (7%), cryptogenic (19%), and established epilepsy (20%). Central nervous system infections accounted for 24 (28%) of the etiologies. Seventy-five (88%) patients responded to first-line drugs and 10 (12%) required second-line drugs. The mean duration of SE was significantly long in nonresponders (Mean +/- SD: 32.6 +/- 20.11 vs. 15.2 +/- 18.32, p < 0.006). Duration (p < 0.01; OR 1.04, 95% CI 1.01-1.07) and acute symptomatic etiology (p < 0.038; OR 10.38, 95% CI 1.13-95.09) were the independent predictors of no-response to first-line drugs. Of the nine deaths (10.5%), eight were in acute symptomatic group. Predictors of mortality included female sex (p < 0.017, OR 13.41, 95% CI 1.59-115.38) and lack of response to first-line drugs (p < 0.0001, OR 230.27, 95% CI 8.78-6037.19). Longer duration was associated with poor GOS 1-4 (p = 0.001). Of the 37 patients with <6 h, 81% had GOC5 outcome. CONCLUSION: This study suggests that longer duration of SE and acute symptomatic etiology are independent predictors of lack of response to first-line drugs. Failure to respond to first-line drugs and duration predict the outcome.     

Insights into the sequence of structural consequences of convulsive status epilepticus: a longitudinal MRI study

While acute hippocampal magnetic resonance imaging (MRI) changes have been demonstrated, the long-term structural consequence of status epilepticus remains unclear. Also the timing of previously reported fornix abnormalities in patients with mesial temporal sclerosis (MTS) is unknown. We report longitudinal volumetic MRI and diffusion tensor imaging (DTI) findings of the hippocampus and fornix in a patient following status epilepticus. Left hippocampal atrophy demonstrated progression beyond 6 months poststatus epilepticus while the right hippocampus and bilateral fornices demonstrated stable volumetric and diffusion abnormalities throughout the study. Our findings provide evidence that status epilepticus can induce permanent hippocampal damage with the delayed timing of the structural changes being consistent with programmed cell death.     

Status epilepticus in children with epilepsy: Dutch study of epilepsy in childhood

PURPOSE: To study course and outcome of epilepsy in children having had a status epilepticus (SE) as the presenting sign or after the diagnosis. METHODS: A total of 494 children with newly diagnosed epilepsy, aged 1 month through 15 years, were followed prospectively for 5 years. RESULTS: A total of 47 Children had SE. Forty-one of them had SE when epilepsy was diagnosed. For 32 (78%), SE was the first seizure. SE recurred in 13 out of 41 (32%). Terminal remission at 5 years (TR5) was not significantly worse for these 41 children: 31.7% had a TR5 <1 year versus 21.2% of 447 children without SE. They were not more often intractable. Five out of six children with first SE after diagnosis had a TR5 <1 year. Mortality was not significantly increased for children with SE. Independent factors associated with SE at presentation were remote symptomatic and cryptogenic etiology, and a history of febrile convulsions. Children with first SE after inclusion more often had symptomatic etiology. CONCLUSIONS: Although we find a trend for shorter TR5 in children with SE at presentation, outcome and mortality are not significantly worse. Etiology is an important factor for prognosis. Children with SE during the course of their epilepsy have a worse prognosis and a high recurrence rate of SE. This outcome is not due to the SE itself, but related to the etiology and type of epilepsy. The occurrence of SE is just an indicator of the severity of the disease.     

Continuous infusion of midazolam in the treatment of refractory generalized convulsive status epilepticus

We studied the efficacy and safety of midazolam given as a continuous infusion in the treatment of refractory generalized convulsive status epilepticus (RGCSE). We carried out a prospective, open study, in 19 patients (11 men) with RGCSE in the intensive care unit at Firat Medical Center in Elazig. When intravenous administration of 0.3 mg/kg diazepam (three times at 5-min intervals), 20 mg/kg phenytoin, and 20 mg/kg phenobarbital failed to bring the episode under control, patients were administered an intravenous bolus of midazolam (200 μg/kg) followed by a continuous infusion at 1 μg/kg min. The dose was increased by 1 μg/kg min every 15 min until the episode of seizure was brought under control. The time from beginning of treatment to control of seizures, infusion rate, and side-effects were monitored. The mean age of the patients was 40.4 years (range 16–87 years). The clinical etiology of RGCSE was idiopathic epilepsy (6 cases), anoxicischemic cerebral insult due to cardiac arrest (3), viral encephalitis (2), intrahemispheric hematoma due to hemorrhagic stroke (1), cerebral infarct due to ischemic stroke (1), pituitary adenoma (1), post-traumatic epilepsy (1), renal failure (1), tuberculous meningitis (1), and unknown (2). In eighteen (94.7%) patients, seizures were completely controlled in a mean time of 45 min (range, 5–120 min) at a mean infusion rate of 8 μg/kg min (range, 3–21 μg/kg min). In one patient seizures did not stop. Midazolam administration did not cause any significant change in blood pressure, heart rate, oxygen saturation, or respiratory status. The mean time to full consciousness for patients after stopping the infusion was 1.6 hours (range, 2.0–8.5 hours). The mean infusion duration of midazolam was 14.5 hours (range, 12–25 hours). Midazolam is an effective and safe drug to control RGCSE, and may represent a substantial improvement over current therapeutic approaches such as pentobarbital anesthesia. Received: 15 December 2001 / Accepted in revised form: 10 July 2002 Correspondence to B. Müngen     

成人顽固性癫痫持续状态的临床分析

目的 探讨成人顽固性癫痫持续状态（RSE）的危险因素、临床特点、治疗及预后。方法 54例癫痫持续状态（SE）．58次发作事件，分为RSE组和非顽固性癫痫持续状态（NRSE）组．对病因、诱因、临床表现、辅助检查、预后等进行对比分析。结果 RSE占SE的43．1％，病毒性脑炎是RSE最主要的病因（P=0．001），相反，既往癫痫发作在NRSE中更常见（P=0．000），相应地药物治疗的改变引起的SE多为NRSE（P=-0．003）；RSE组GCS评分及预后较NRSE组均差（均P=0．000）。结论 SE经一、二线抗癫痫药治疗后仍有很大一部分难以控制，病毒性脑炎是导致RSE的一个重要病因，其预后较差．目前对RSE的治疗还缺乏十分合理的方案。     

Status epilepticus severity score as a predictor for the length of stay at hospital for acute-phase treatment in convulsive status epilepticus

To date, hospital length of stay (LOS) determinants for convulsive status epilepticus’s (CSE) acute-phase treatment have not been sufficiently investigated, as opposed to those for status epilepticus’s (SE) outcome predictors, such as status epilepticus severity score (STESS). Here, we aimed at assessing the significance of STESS in the LOS in patients with CSE. We retrospectively reviewed consecutive adult patients with CSE who were transported to the emergency department of our urban tertiary care hospital in Tokyo, Japan. The study period was from August 2010 to September 2015. The primary endpoint was the LOS of patients with CSE who were directly discharged after acute-phase treatment, and survival analysis for LOS until discharge was conducted. As a result, among 132 eligible patients with CSE admitted to our hospital, 96 (72.7%) were directly discharged with a median LOS of 10 days (IQR: 4–19 days). CSE patients with severe seizures, represented by higher STESS (≥3), had a significantly longer LOS after adjustments with multiple covariates (p = 0.016, in restricted mean survival time analysis). Additionally, prediction for the binomial longer/shorter LOS achieved better performance when STESS was incorporated into the prediction model. Our findings indicate that STESS can also be used as a rough predictor of longer LOS at index admission of patients with CSE.     

Long-term survival in patients with status epilepticus: A tertiary referral center study

Purpose:   To determine long-term survival in patients with status epilepticus (SE).
Methods:   We prospectively followed patients admitted for the first (69.6%) or recursive episode of SE between January 1, 1989 and December 31, 1997 at the Institute of Neurology, Belgrade, Serbia, until death or study termination (December 31, 2006). Data were obtained for cause of death; etiology of SE—acute symptomatic (AS), progressive symptomatic (PS), remote symptomatic (RS), and idiopathic/cryptogenic (I/C); presence of epilepsy; and reoccurrence of SE. Standardized mortality rate (SMR), survival, and regression analysis were used.
Results:   A total of 120 of 750 patients with an episode of SE (15.9%) died in the 30-day period following SE. Data for 207 of 630 (32.8%) surviving patients (35.7% with initial SE) were available at the end of follow-up [median 12 years; 95% confidence interval (CI) 11.1–12.8]. SMR was significantly increased (SMR = 1.81; 95% CI 1.32–2.41). There were 46 deaths (22.2%): 15 of 65 in the AS, 20 of 29 in the PS, 6 of 29 in the RS, and 5 of 75 in the I/C groups. Five-year survival rate was lowest in the PS (45%) compared to AS (91%), RS (87%), and I/C (99%) groups. The following characteristics increased long-term risk for mortality: older age [Exp(B) 1.05, 95% CI 1.029–1.072], PS and AS etiology [Exp(B) 15.6, 95% CI 5.8–41.6; 3.3, 95% CI 1.2–9.1], presence of epilepsy [Exp(B) 2.3, 95% CI 1.2–4.3], and initial SE [Exp(B) 2.4, 95% CI 1.4–4.4].
Discussion:   Approximately one of five patients die within 12 years after an episode of SE. Symptomatic SE (PS and AS), initial SE, age, and presence of epilepsy are associated with long-term increased risk of death.     

MRI findings in aphasic status epilepticus

Ictal-MRI studies including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and MR-angiography (MRA) in patients with aphasic status epilepticus (ASE) are lacking. In this report, we aim to describe the consequences of the ASE on DWIs and its impact on cerebral circulation. We retrospectively studied eight patients with ASE confirmed by ictal-EEG, who underwent ictal-MRI shortly after well-documented onset (mean time delay 3 h). ASE consisted in fluctuating aphasia, mostly associated with other subtle contralateral neurological signs such as hemiparesia, hemianopia, or slight clonic jerks. In MRI, six patients showed cortical temporoparietal hyperintensity in DWI and four of them had also ipsilateral pulvinar lesions. Five patients showed close spatial hyperperfusion areas matching the DWI lesions and an enhanced blow flow in the middle cerebral artery. Parenchymal lesions and hemodynamic abnormalities were not associated with seizure duration or severity in any case. The resolution of DWI lesions at follow-up MRI depended on the length of the MRIs interval. In patients with ASE, lesions on DWI in the temporo-parietal cortex and pulvinar nucleus combined with local hyperperfusion can be observed, even when they appear distant from the epileptic focus or the language areas.     

Isoflurane for 7 days in refractory status epilepticus

There is limited experience with continuous (>3 days) isoflurane anesthesia for status epilepticus (SE). We present a case with prolonged SE, probably due to thallium intoxication, in which isoflurane successfully suppressed seizure activity over 7 days without adverse effects. When isoflurane was discontinued, seizures returned despite high doses of barbiturates, and the patient died several months later. Early isoflurane anesthesia is an effective alternative therapy in prolonged convulsive SE resistant to common therapy and intravenous general anesthesia. However, its continuous application for several days requires familiarity with anesthesiologic principles, and scavenging of expiratory air.     

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.     

Intravenous midazolam in convulsive status epilepticus in children with pharmacoresistant epilepsy

Although the efficacy of midazolam in refractory status epilepticus and as a first-line agent in children with established status epilepticus has been reported, differences in starting doses, continuation method, timing of efficacy assessment, and discontinuation pose limitations in deriving a specific protocol for midazolam use. An audit of clinical experience with a protocol of midazolam as first-line agent for impending status epilepticus (defined as a continuous, generalized, convulsive seizure lasting >5 minutes) in 76 episodes of unprovoked convulsive status epilepticus in children 1–15 years old with treatment-refractory epilepsy demonstrated that: (1) repeated bolus midazolam 0.1 mg/kg (every 5 minutes, maximum 5) controlled 91% of events; (2) three bolus doses controlled 89% of the episodes, with minimal chance of response beyond that; (3) treating impending status resulted in lower doses (mean 0.17 mg/kg) than reported and infrequent utilization of additional anticonvulsants (9%); and (4) adverse events were infrequent (respiratory depression 13%, assisted ventilation 3%).     

Predictors of refractoriness in a Turkish status epilepticus data bank

Refractory status epilepticus (RSE) is known to constitute approximately 10–50% of all cases of status epilepticus (SE) and is associated with significant morbidity and mortality. In the present study, data from a prospectively collected SE database were analyzed. Patients with RSE (defined as a SE episode requiring a second line of intravenous treatment following intravenous phenytoin) were compared with patients with nonrefractory SE (NRSE); 290 episodes of SE were identified, of which 108 (38%) were defined as RSE. Univariate analysis revealed that age, female gender, SE type, SE duration, and acute etiology were associated with refractoriness, whereas electroencephalographic patterns were not. Nonconvulsive SE, which is probably associated with delays in treatment initiation, was a predictor of RSE, although it was not retained as a predictor in multivariate analysis. In the latter analysis, female gender (odds ratio: 1.815, 95% CI: 1.053–3.126) and acute etiology (odds ratio: 0.619, 95% CI: 0.429–0.894) were shown to be the only significant independent predictors of refractoriness.