Systemic Complications of Status Epilepticus.

Early prediction of long-term mortality in status epilepticus is important given the high fatality rate in the years after diagnosis. To improve prognostication of long-term mortality after status epilepticus diagnosis. This retrospective, multicenter, multinational cohort study analyzed adult patients who were diagnosed with and treated for status epilepticus at university hospitals in Odense, Denmark, between January 1, 2008, and December 31, 2017, as well as in Oslo, Norway; Marburg, Germany; and Frankfurt, Germany. They were aged 18 years or older and had first-time, nonanoxic status epilepticus. A new scoring system, called the ACD score, for predicting 2-year (long-term) mortality after hospital discharge for status epilepticus was developed in the Danish cohort and validated in the German and Norwegian cohorts. The ACD score represents age at onset, level of consciousness at admission, and duration of status epilepticus. Data analysis was performed between September 1, 2019, and March 31, 2020. Long-term follow-up using data from national and local civil registries in Denmark, Norway, and Germany. The predefined end point was 2-year survival for all patients and for a subgroup of patients with status epilepticus causes that were not damaging or were less damaging to the brain. Neurological deficits before and after onset, demographic characteristics, etiological categories of status epilepticus, comorbidities, survival, time points, treatments, and prognostic scores for different measures were assessed. A total of 261 patients (mean [SD] age, 67.2 [14.8] years; 132 women [50.6%]) were included, of whom 145 patients (mean [SD] age, 66.3 [15.0] years; 78 women [53.8%]) had status epilepticus causes that were not damaging or were less damaging to the brain. The validation cohort comprised patients from Norway (n = 139) and Germany (n = 906). At hospital discharge, 29.8% of patients (n = 64 of 215) had new moderate to severe neurological deficits compared with baseline. New neurological deficits were a major predictor of 2-year survival after hospital discharge (odds ratio, 5.1; 95% CI, 2.2-11.8); this association was independent of etiological category. Nonconvulsive status epilepticus in coma and duration of status epilepticus were associated with development of new neurological deficits, and a simple 3-factor score (ACD score) combining these 2 risk factors with age at onset was developed to estimate survival after status epilepticus diagnosis. The ACD score had a linear correlation with 2-year survival (Pearson r2 = 0.848), especially in the subset of patients with a low likelihood of brain damage. This study found that age, long duration, and nonconvulsive type of status epilepticus in coma were associated with the development of new neurological deficits, which were predictors of long-term mortality. Accounting for risk factors for new neurological deficits using the ACD score is a reliable method of prediction of long-term outcome in patients with status epilepticus causes that were not damaging or were less damaging to the brain.

Epilepsy in Angelman syndrome

Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit.

Background: Status epilepticus (SE) is one of the most common neurological emergencies in childhood. However, the clinical features and prognosis are poorly characterized in China. Objectives: To summarize the clinical features and outcomes among Chinese children. Methods: Children aged from 29 days to 18 years with SE were included in Children’s Hospital of Fudan University. The demography, etiology, seizure types, treatment and outcome were analysed. The statistics were conducted by SPSS19. Results: There were 247 SE patients (F:M=1.25:1). The mean age was 2.4 years. Most of them had acute symptomatic SE (53.06%) including viral encephalitis (48.46%). Most of them had convulsive status epilepticus (83.4%), others had non-convulsive status epilepticus (16.6%). Most of them had combination therapy (74.89%). Lengths of follow-up ranged from 1 month to 3 years after onset of SE. Most of cases were bad outcome (73.80%). Etiology and neurological image were significant risk predictors by multiple logistic regression analysis. Mortality rate was 16.95%. Recurrence rate was 20.76%. Most of cases died within 1 month after onset of SE (65.0%). Most of cases also recurred within 1 month (81.63%). Duration of SE and mechanical ventilation were related to death by multiple logistic regression analysis. The number of antiepileptic drugs (AED) and anaesthetic treatment were related to recurrence of SE by Cox survival analysis. Conclusion: The proportion of SE was highest in children younger less than 1 year. The most common etiology of SE in children was acute symptomatic, especially viral encephalitis. The clinical features between CSE and NCSE were different. Risk factors between recurrence and death were different. The death rate was higher in cases with duration of SE ≥ 3 hours and mechanical ventilation. Maintenance treatment ≥ 3 AEDs and anaesthetic treatment were related to higher recurrence rate. These results suggested we can improve the prognosis by terminating seizure in time

Status epilepticus (SE) is an important emergency situation associated with high morbidity and mortality. The goal of pharmacological therapy-rapid seizure termination-is only achieved in just over half of patients with first-line anti-epileptic drug (AED) therapy and many patients require second and higher lines of AEDs to achieve seizure termination; therefore, there is a clear need for more effective treatment options. Lacosamide is a relatively new AED and the intravenous formulation has shown promise for treatment of SE. The aim of the current study was to compare electroencephalographic (EEG) response and seizure termination with intravenous lacosamide (±other AEDs) in patients with convulsive versus non-convulsive SE, in a Spanish intensive care setting. In this prospective, observational study, patients with convulsive or non-convulsive SE who received intravenous lacosamide 400 mg/day for 8 days were compared in terms of EEG response and seizure termination. Adverse events were not specifically assessed. Fifty-three patients (69.8 % male; mean age 55.2 years) were treated with lacosamide (mean dose 390.6 mg) as first- (20.8 %), second- (34 %), third (22.6 %) or fourth-line (22.6 %) treatment for convulsive (n = 23, 43.4 %) or non-convulsive (n = 30, 56.6 %) SE. The majority of patients (73.6 %) had a comorbid condition, predominantly hypertension (35.8 %), and most (79.2 %) received at least one concomitant AED, including midazolam (54.7 %), valproic acid (52.8 %), and levetiracetam (30.2 %). Patient characteristics and treatment received did not differ significantly between the convulsive and non-convulsive SE groups. EEG recordings following lacosamide treatment demonstrated the elimination of paroxysmal activity (disappearance and/or attenuation of epileptiform activity in >60 % of recording time) in 56.6 % of patients; 69.6 % of convulsive and 46.7 % of non-convulsive SE groups. Among all patients, 90.6 % showed some EEG improvement (disappearance of epileptiform activity in <30 % total recording time or disappearance and/or attenuation of epileptiform activity in 30-60 % total recording time); and there was no significant between-group difference for achievement of seizure termination (90.0 vs. 91.3 % for non-convulsive vs. convulsive SE). Intravenous lacosamide (±other AEDs) was similarly effective in patients with convulsive or non-convulsive SE. Further investigation into the use of lacosamide in the treatment of SE is warranted.

PurposeTo document the 2-year mortality and seizure recurrence rate of a prospective cohort of patients identified with status epilepticus (SE). MethodsPatients presenting to any hospital in the Auckland region between April 6 2015, and April 5 2016, with a seizure lasting 10 min or longer were identified. Follow up was at 2 years post index SE episode via telephone calls and detailed review of clinical notes. ResultsWe identified 367 patients with SE over the course of one year. 335/367 (91.3 %) were successfully followed up at the 2-year mark. Two-year all-cause mortality was 50/335 (14.9 %), and 49/267 (18.4 %) when febrile SE was excluded. Two-year seizure recurrence was 197/335 (58.8 %). On univariate analyses, children (preschoolers 2 to < 5 years and children 5 to < 15 years), Asian ethnicity, SE duration <30 mins and acute (febrile) aetiology were associated with lower mortality, while older age >60 and progressive causes were associated with higher mortality on both univariate and multivariate analyses. Age < 2 years and acute aetiology were associated with lower seizure recurrence, while non convulsive status epilepticus (NCSE) with coma and a history of epilepsy were associated with higher seizure recurrence. On multivariate analyses, a history of epilepsy, as well as having both acute and remote causes were associated with higher seizure recurrence. ConclusionsAll-cause mortality in both the paediatric and adult populations at 2 years was lower than most previous reports. Older age, SE duration ≥30 mins and progressive aetiologies were associated with the highest 2-year mortality, while febrile SE had the lowest mortality. A history of epilepsy, NCSE with coma, and having both acute and remote causes were associated with higher seizure recurrence at 2 years. Future studies should focus on functional measures of outcome and long-term quality of life.

Does semiology of status epilepticus have an impact on treatment response and outcome?

Outcome for patients with status epilepticus (SE) depends strongly on etiology. Duration of SE is also predictive, at least in the first 2 h, but beyond this it is unclear that duration of SE influences outcome significantly. We sought to determine the influence of duration of SE on outcome in patients with prolonged SE, and to compare this influence with that of other factors. We reviewed the clinical course and outcome of 119 patients with SE, diagnosed by both clinical manifestations and electroencephalography (EEG) evidence. Using univariate and multivariate analyses, we sought predictors of outcome (survival vs. death or vegetative state) among age, etiology (epilepsy, anoxia or severe hypoxia, or other), presence of earlier epilepsy, multiple medical problems, presentation in coma, and type of SE (focal or generalized). Median duration of SE was 48 h. Survival was greater with a shorter duration, especially when <10 h (69% vs. 31% for longer duration; p < 0.05). Epilepsy as the etiology, and an earlier diagnosis of epilepsy offered a favorable prognosis (p < 0.01), but only the former on multivariate analysis. Coma and SE caused by anoxia/hypoxia were unfavorable factors. Once corrected for etiology, presentation in coma, and type of SE (focal or generalized), duration of SE did not have a significant effect on outcome. Overall mortality was high, 65%, but 10 patients survived SE lasting over 3.5 days. A duration of <10 h was associated with better outcome in SE, but this was not significant once etiology, presentation in coma, and type of SE were accounted for. Etiology of SE is still the primary determinant of outcome. Unless it follows anoxia, prolonged SE should not be considered a hopeless condition.

Nonconvulsive status epilepticus (SE) is not uncommon and comprises at least one-third of all cases of SE. However, nonconvulsive SE consists of very different syndromes, a common feature being the difficulty in making the diagnosis. In this review, nonconvulsive SE is divided into typical absence SE, complex partial SE, nonconvulsive SE in patients with learning difficulties (including electrical SE during sleep, atypical absence SE and tonic SE), and nonconvulsive SE in coma. These conditions have different prognoses and treatments. The diagnosis of these conditions is critically dependent on EEG. When the EEG demonstrates typical ictal patterns, the diagnosis is usually straightforward. However, in many circumstances the EEG has to be differentiated from encephalopathic patterns, and this differentiation can prove troublesome, although the clinical and electrographic response to treatment can prove helpful. Nonconvulsive SE in patients with learning difficulties possibly provides the greatest diagnostic difficulty; the clinical presentation can be subtle resulting in the diagnosis being frequently missed. Whether the neuronal damage that occurs in convulsive SE and in animal models of limbic SE also occurs in nonconvulsive SE in humans is still a matter of debate. There are critical differences between the animal models and the human condition. Indeed, the prognosis of nonconvulsive SE is usually dependent on the underlying aetiology rather than the persistence of electrographic discharges. Because of these doubts, a more conservative approach to the treatment of particular types of nonconvulsive SE (those with a better prognosis) has been taken in this article. Thus, in most instances, oral benzodiazepines for the treatment of typical absence SE and complex partial SE are recommended. In some circumstances intravenous medication is necessary, but in neither condition is anaesthetic coma recommended. This contrasts with nonconvulsive SE in coma in which a more aggressive approach is suggested. Until there are more relevant animal models, and controlled trials of conservative versus more aggressive treatment, treatment regimens for nonconvulsive SE will remain largely speculative.

THE AIM OF THIS ARTICLE: To review the causes, clinical signs, pathophysiology, consequences, and treatment of seizures and status epilepticus in critically ill patients. Only 25% of people, who have seizures and status epilepticus, have epilepsy as well. In the intensive care settings, seizures and status epilepticus are a common neurologic complication, which is attributable to primary neurologic pathology (stroke, hemorrhage, tumor, central nervous system infection, head trauma) or secondary to critical illness (anoxic brain damage, intoxications, metabolic abnormalities) and clinical management. There are three main subtypes of status epilepticus in intensive care units: generalized convulsive status epilepticus, focal motor status epilepticus, and nonconvulsive status epilepticus. A seizure is a consequence of electrical neurological derangement because of sudden imbalance between the inhibitory and excitatory forces within the network of cortical neurons. The main inhibiting neurotransmitter in the brain is gamma-aminobutyric acid (GABA), which binds to GABA-A and GABA-B receptors. The main excitatory neurotransmitter is glutamate, which binds to N-methyl-D-aspartate receptors. Different ions (Cl(-), K(+), Na(+), Ca(2+)) also play a role in the pathophysiology of seizures. Prolonged status epilepticus may lead to different systemic and neurologic consequences. Generalized convulsive status epilepticus is one of the most common emergencies encountered in clinical practice, which requires immediate treatment. The first-line drugs are benzodiazepines (lorazepam, diazepam), the second-line ones - phenytoin and fosphenytoin. For the treatment of refractory status epilepticus, barbiturates (phenobarbital, pentobarbital, thiopental), valproate, midazolam, propofol, and isoflurane are used. The dosage of drugs and parameters to monitor are referred in the article. The mortality from generalized convulsive status epilepticus is 15-50%; the main factors, influencing prognosis, are the cause and the duration of status epilepticus and age of a patient.

P87. Does semiology of status epilepticus have an impact on refractoriness and outcome?

Human status epilepticus (SE) is consistently associated with cognitive problems, and with widespread neuronal necrosis in hippocampus and other brain regions. In animal models, convulsive SE causes extensive neuronal necrosis. Nonconvulsive SE in adult animals also leads to widespread neuronal necrosis in vulnerable regions, although lesions develop more slowly than they would in the presence of convulsions or anoxia. In very young rats, nonconvulsive normoxic SE spares hippocampal pyramidal cells, but other types of neurons may not show the same resistance, and inhibition of brain growth, DNA and protein synthesis, and of myelin formation and of synaptogenesis may lead to altered brain development. Lesions induced by SE may be epileptogenic by leading to misdirected regeneration. In SE, glutamate, aspartate, and acetylcholine play major roles as excitatory neurotransmitters, and GABA is the dominant inhibitory neurotransmitter. GABA metabolism in substantia nigra (SN) plays a key role in seizure arrest. When seizures stop, a major increase in GABA synthesis is seen in SN postictally. GABA synthesis in SN may fail in SE. Extrasynaptic factors may also play an important role in seizure spread and in maintaining SE. Glial immaturity, increased electronic coupling, and SN immaturity facilitate SE development in the immature brain. Major increases in cerebral blood flow (CBF) protect the brain in early SE, but CBF falls in late SE as blood pressure falters. At the same time, large increases in cerebral metabolic rate for glucose and oxygen continue throughout SE. Adenosine triphosphate (ATP) depletion and lactate accumulation are associated with hypermetabolic neuronal necrosis. Excitotoxic mechanisms mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors open ionic channels permeable to calcium and play a major role in neuronal injury from SE. Hypoxia, systemic lactic acidosis, CO2 narcosis, hyperkalemia, hypoglycemia, shock, cardiac arrhythmias, pulmonary edema, acute renal tubular necrosis, high output failure, aspiration pneumonia, hyperpyrexia, blood leukocytosis and CSF pleocytosis are common and potentially serious complications of SE. Our improved understanding of the pathophysiology of brain damage in SE should lead to further improvement in treatment and outcome.

Prognosis of status epilepticus in patients requiring intravenous anesthetic drugs (a single center experience)

Previous work suggested that there is a lower mortality for convulsive status epilepticus (SE) with intermittent seizures (intermittent SE) as opposed to SE with continuous seizure activity (continuous SE). A plausible hypothesis to explain this difference is that the shorter ictal time in intermittent SE is responsible for the lower mortality in this group. This study investigates the relative contributions of total ictal time and SE duration to the differing mortalities of intermittent and continuous SE. Six hundred forty-five cases of prospectively identified convulsive SE were examined. Nonparametric statistical methods were used to compare continuous SE and intermittent SE variables. Multivariate logistic regression analyses were used to determine which factors were most highly associated with mortality. Intermittent SE cases were analyzed to evaluate the relative contributions of ictal time versus SE duration to mortality. Intermittent SE had a significantly lower mortality than continuous SE (19.6 vs. 31.4%; p < 0.001) in adults but not in children. Intermittent and continuous SE durations did not significantly differ in adult cases but did differ in pediatric cases. Ictal time was significantly shorter than SE duration for intermittent SE in both adults and children. After adjusting for age, etiology, and SE duration, SE type (continuous SE vs. intermittent SE) was shown to have an independent effect on mortality in adults. The relative risk of mortality for continuous SE was 1.79 times that of intermittent SE (p = 0.04). After controlling for SE duration, ictal time did not significantly affect mortality in adults. Intermittent and continuous convulsive SE were common in both pediatric and adult populations. Intermittent SE had a significantly lower mortality than did continuous SE. This difference in mortality was not completely explained by differences in SE duration, total ictal time, etiology, or age. Further research is needed to identify the factor(s) contributing to the significant difference in mortality between intermittent SE and continuous SE.

Status epilepticus in epileptic patients: Related syndromes, precipitating factors, treatment and outcome in a video-EEG population-based study