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.     

Treatment of Refractory Status Epilepticus in Childhood

Refractory status epilepticus (RSE) is characterized by a prolonged seizure that persists despite adequate initial management. RSE accounts for almost one quarter of all status epilepticus and carries significant risk for morbidity and mortality. Treatment varies widely between institutions regarding medication choice, dose, and monitoring. Several agents including nonanesthetic antiepileptic drugs (AEDs), anesthetic AEDs, enteral AEDs, and other therapies have been used in RSE. We review the current treatment strategies for RSE, focusing on patient selection, monitoring, optimal dosing and administration of medications, efficacy, adverse effects, and treatment duration.     

Nonconvulsive Status Epilepticus in Childhood Localization-Related Epilepsy

PURPOSE: To report on three children with localization-related epilepsy who exhibited minor seizures (atypical absences, brief atonic, and myoclonic) and nonconvulsive status epilepticus (NCSE) consisting of these minor seizures, and to elucidate their significance. METHODS: We studied the electroclinical characteristics of these children. Ictal electroencephalograms (EEGs) of NCSE were evaluated by using simultaneous video-EEG-electromyogram (EMG) polygraphic recordings. RESULTS: All patients began to have partial seizures between the ages of 6 months and 2 years 7 months, with minor seizures appearing later, between the ages of 1 year 11 months and 6 years 6 months. These minor seizures evolved into NCSE. Complex partial seizures remained after suppression of the minor seizures. Interictal EEGs taken when the minor seizures appeared showed excessive diffuse epileptic discharges in addition to multifocal spike-waves. Before and after suppression of the minor seizures, focal epileptic discharges predominated on the EEGs. On ictal EEGs of brief atonic and myoclonic seizures, diffuse spike-wave and polyspike-wave bursts were detected. Ictal EEGs of the atypical absences revealed diffuse spike-wave bursts mixed with irregular high-voltage slow waves, often interspersed with brief atonic and myoclonic seizures. When atypical absences lasted for a long time, patients manifested NCSE. Polytherapy might be related to the occurrence of minor seizures and NCSE, because all patients were treated with polytherapy at their appearance, and simplification of antiepileptic drug (AED) therapy seemed to be effective. CONCLUSIONS: We concluded that this NCSE is a type of atypical absence status which is an age-dependent, transient, electroclinical condition. The mechanism of occurrence of these minor seizures might be related to secondary bilateral synchrony.     

Electrical Status Epilepticus in Sleep: Clinical Presentation and Pathophysiology

Electrical status epilepticus in sleep involves an electroencephalographic pattern where interictal epileptiform activity is potentiated in the transition from wakefulness to sleep. Near-continuous spikes and waves that occupy a significant proportion of nonrapid eye movement sleep appear as a result of sleep-potentiated epileptiform activity. This electroencephalographic pattern appears in different electroclinical syndromes that present three common characteristics with different degrees of severity: seizures, sleep-potentiated epileptiform activity, and neuropsychologic regression. Continuous spikes and waves during sleep comprise the severest epileptic encephalopathy in the electroclinical spectrum. Landau-Kleffner syndrome presents with intermediate severity. Some “benign” pediatric focal epileptic syndromes represent the mildest end of this continuum. Based on published data, we provide a framework for clinical and electrical events. The underlying mechanisms leading to sleep potentiation of epileptiform activity in electrical status epilepticus in sleep are incompletely understood. A genetic basis or acquired early developmental insult may disrupt the normal maturation of neuronal networks. These factors may dynamically alter normal processes of brain development, leading to an age-related pattern of electroclinical expression of electrical status epilepticus in sleep.     

Status Epilepticus in Childhood: A Retrospective Study of Intitial Convulsive Status and Subsequent Epilepsies

A retrospective study was carried out on 261 patients with various epilepsies who had undergone convulsive status epilepticus prior to the subsequent onset of epileptic seizures. 1. Convulsive status epilepticus was found more in partial epilepsy and secondary generalized epilepsy at about the same rate, and evidently less in primary generalized epilepsy. On the average, three-fourths commenced their convulsive disorders with initial status epilepticus. 2. There were free intervals of years following intial status and preceding subsequent epilepsy. The interval was evidently shorter, less than two years, in a majority of patients with secondary generalized epilepsy, whereas the interval was mostly longer, more than six years, in patients with partial epilepsy. 3. The permanent deficient sequelae resulting from initial status were most closely associated with secondary generalized epilepsy. This was also exemplified by the higher rate of atrophic change on CCT. On the contrary, such permanent sequelae were less marked in partial epilepsy especially of complex seizure. 4. It was concluded that secondary generalized epilepsy resulted in cases with more severe brain damage within a relatively shorter interval, whereas complex partial seizure resulted from less severe damage with an obviously longer interval following convulsive status epilepticus.     

Medical Management With Diazepam for Electrical Status Epilepticus During Slow Wave Sleep in Children

ObjectiveOral diazepam, administered in varying doses, is among the few proposed treatment options for electrical status epilepticus during slow wave sleep in children. We sought to retrospectively evaluate the long-term efficacy of high-dose oral diazepam in reducing electrographic and clinical evidence of electrical status epilepticus during slow wave sleep in children. Additionally, we surveyed caregivers to assess safety and behavioral outcomes related to ongoing therapy.MethodsWe collected demographic and clinical data on children treated for electrical status epilepticus during slow wave sleep between October 2010 and March 2013. We sought to identify the number of patients who achieved at least a 50% reduction in spike wave index on electroencephalograph after receiving high-dose oral diazepam. We also administered a questionnaire to caregivers to assess for behavioral problems and side effects.ResultsWe identified 42 evaluable patients who received high-dose diazepam (range 0.23-2.02 mg/kg per day) to treat electrical status epilepticus during slow wave sleep. Twenty-six patients had spike reduction data and 18/26 (69.2%) children achieved a greater than 50% reduction in spike wave count from an average of 15.54 to 5.05 (P = 0.001). We received 28 responses to the questionnaire. Some patients experienced new onset of difficulties with problem-solving and speech and writing development. Sleep disturbances (50%) and irritability (57.1%) were the most frequent side effects reported. There did not appear to be a dose-related effect with electroencephalograph changes, behavioral effects, or side effects.ConclusionsHigh-dose oral diazepam significantly reduces the spike wave count on electroencephalograph in children with electrical status epilepticus during slow wave sleep. Although this therapy improves electroencephalograph-related findings, it can be associated with concerning neurological and behavioral side effects in some individuals, so further study is warranted.     

The Management of Refractory Status Epilepticus: An Update

Summary:  Refractory status epilepticus (RSE) is an important and serious clinical problem that typically requires prolonged and high-level intensive care, and is often associated with poor outcome. This review addresses some of the current issues concerning the management of RSE, including recent definitions used for clinical studies, epidemiology, clinical course, and outcome. Current approaches to treatment, including the now relatively standard use of intravenous anesthetic agents, as well as emerging therapies utilizing drugs such as valproate and topiramate, are discussed as well.     

Ketamine Prevents Learning Impairment When Administered Immediately after Status Epilepticus Onset

Permanent cognitive impairment is common following status epilepticus (SE) in both humans and animals. We examined the effect of the NMDA antagonist ketamine administered after SE onset on two forms of associative learning in the rat: conditioned taste aversion and fear-conditioned analgesia. Following the onset of lithium/pilocarpine-induced SE, rats were administered either ketamine (100 mg/kg) or acepromazine (25 mg/kg). Acepromazine-treated animals show marked deficits in both learning measures at 1 month after SE. In contrast, ketamine-treated and nonepileptic control animals did not differ in performance for either task. Although studies have shown that ketamine is ineffective at controlling electrographic seizures early in SE, these results are consistent with previous studies showing that ketamine can preserve learning proficiency if administered shortly after seizure onset. As a clinically available drug, ketamine may prove useful in the treatment of SE when combined with conventional antiepileptic strategies.     

Practice Variations in the Management of Status Epilepticus

Background

Numerous anticonvulsant agents are now available for treating status epilepticus (SE). However, a paucity of data is available to guide clinicians in the initial treatment of seizures or SE. This study describes the current strategies being employed to treat SE in the USA.

Methods

Fifteen American academic medical centers completed a retrospective, multicenter, observational study by reviewing 10?C20 of the most recent cases of SE at their institution prior to December 31, 2009. A multivariate analysis was performed to determine factors associated with cessation of seizures.

Results

A total of 150 patients were included. Most patients with SE had a seizure disorder (58?%). SE patients required a median of 3 AEDs for treatment. Three quarters of patients received a benzodiazepine as first-line therapy (74.7?%). Phenytoin (33.3?%) and levetiracetam (10?%) were commonly used as the second AED. Continuous infusions of propofol, barbiturate, or benzodiazepine were used in 36?% of patients. Median time to resolution of SE was 1?day and was positively associated with presence of a complex partial seizure, AED non-compliance prior to admission, and lorazepam plus another AED as initial therapy. Prolonged ICU length of stay and topiramate therapy prior to admission were negatively associated with SE resolution. Mortality was higher in patients without a history of seizure (22.2?vs 6.9?%, p?=?0.006).

Conclusions

The use of a benzodiazepine followed by an AED, such as phenytoin or levetiracetam, is common as first and second-line therapy for SE and appears to be associated with a shorter time to SE resolution. AED selection thereafter is highly variable. Patients without a history of seizure who develop SE had a higher mortality rate.     

Therapeutic Plasma Exchange for Malignant Refractory Status Epilepticus: A Case Report

BackgroundRefractory status epilepticus is a prolongation of status epilepticus despite anticonvulsant therapy with two or three medications in proper doses; it is defined as malignant status epilepticus if it takes weeks or months. Intravenous immunoglobulin, high-dose steroids, magnesium infusion, pyridoxine, hypothermia, ketogenic diet, electroconvulsive therapy, and surgical therapy are the other treatment options for status epilepticus.PatientOur 5-year-old male patient was hospitalized at our pediatric intensive care unit because of status epilepticus secondary to meningoencephalitis. No response could be obtained with many medical and nonmedical therapies in our patient, who developed malignant status epilepticus with unknown etiology. Therapeutic plasma exchange was applied as convulsions continued.ResultOurs is the first child for whom therapeutic plasma exchange was successfully applied because of malignant refractory status epilepticus secondary to meningoencephalitis.ConclusionTherapeutic plasma exchange may be a treatment option for children with refractory status epilepticus following presumed meningoencephalitis.