Treatment of refractory status epilepticus with hemispherectomy

A 7-year-old boy with left hemiparesis secondary to right hemispheric cortical dysplasia was admitted to the hospital with increasing numbers of seizures. Magnetic resonance imaging showed a small dysplastic right hemisphere with abnormally thickened gyri and an apparently normal left hemisphere. Previous video-electroencephalogram (EEG) monitoring showed bilateral independent spikes and generalized slow spike-and-wave episodes on EEG and [18F]fluorodeoxyglucose (FDG) positron emission tomography scan demonstrated scattered areas of regional hypometabolism bilaterally; therefore hemispherectomy was not undertaken at that time. During this hospital stay, nonconvulsive status epilepticus developed and was refractory to multiple medical therapies including pentobarbital (PTB) coma. Burst-suppression pattern during PTB coma appeared to be generalized spike and wave, but when EEG was reviewed with increased time resolution spikes suggested a right hemisphere origin. The patient underwent bilateral intracarotid amobarbital spike-suppression test that showed only minimal suppression of epileptiform discharges with injection of the left carotid, but complete suppression of spike activity after right-sided carotid injection. A right hemispherectomy was performed with complete cessation of status epilepticus. Postoperative EEG showed no epileptiform discharges. Patient follow-up was limited to 12 months after surgery. The patient had regained the ability to walk unaided and was seizure free with a single antiepileptic medication. This case illustrates a potentially life-saving procedure for refractory status epilepticus and several techniques including a spike-suppression test to aid in prediction of cessation of seizures after hemispherectomy.     

Palliative functional hemispherectomy for treatment of refractory status epilepticus associated with Alpers' disease

Purpose  

Palliative epilepsy surgery is considered for patients that would benefit from surgical therapy for intractable epilepsy but are not candidates for curative procedures. In many cases, the goals of therapy focus on improved quality of life more than seizure freedom. We discuss the use of epilepsy surgery for refractory status epilepticus, as well as the rationale and ethical considerations for employing a palliative procedure in otherwise fatal diseases.     

Treatment of pediatric refractory status epilepticus with topiramate

Objective

We evaluated a topiramate (TPM) regimen for treating refractory status epilepticus in the largest pediatric series, reported to date.

Methods

Fourteen patients received TPM via the nasogastric route. Initially, all patients received TPM as a 5?mg/kg loading dose followed by 5?mg/kg/day in two doses as maintenance. Thereafter, patients were divided into three groups based on the response to TPM therapy and seizure cessation time (full responder, partial responder, and nonresponder). Four patients received only thiopental, two received thiopental, and high-dose midazolam, one received thiopental, high-dose midazolam, and propofol, two received only propofol, one received propofol, and high-dose midazolam and four patients were on a high-dose midazolam infusion.

Results

The median time to seizure cessation was 5.5?h (range 2?C48?h). Nine patients were full responders, three were partial responders, and two were nonresponders At follow-up, six patients were weaned successfully from thiopental, two patients from high-dose midazolam and three patients from propofol. Three patients developed mild metabolic acidosis during TPM theraphy.

Conclusions

Most of the patients responded to this treatment which was well tolerated. So we recommended its use for terminating refractory status epilepticus in children.     

Treatment of refractory complex-partial status epilepticus with propofol: case report

PURPOSE: We report a case of a 65-year-old woman who had a subarachnoid and intraventricular hemorrhage secondary to rupture of an anterior communicating artery aneurysm and developed nonconvulsive status epilepticus of the complex-partial type, refractory to phenytoin (PHT), phenobarbital (PB), valproate (VPA), and lorazepam (LZP). METHODS: Three weeks after diagnosis of nonconvulsive status epilepticus, general anesthesia was induced with propofol and titrated to burst suppression on the electroencephalogram (EEG). RESULTS: During propofol infusion, the serum VPA level declined markedly, and despite >3 g daily doses, did not return to the therapeutic range, until several days after propofol was discontinued. Continuous propofol infusion was stopped after 7 days, and the patient recovered consciousness. Despite further complications, she gradually regained normal function and was discharged home 4 months after surgery. CONCLUSIONS: This is the first case of nonconvulsive status epilepticus successfully treated with propofol.     

Treatment of refractory status epilepticus: literature review and a proposed protocol

Refractory status epilepticus describes continuing seizures despite adequate initial pharmacologic treatment. This situation is common in children, but few data are available to guide management. We review the literature related to the pharmacologic treatment and overall management of refractory status epilepticus, including midazolam, pentobarbital, phenobarbital, propofol, inhaled anesthetics, ketamine, valproic acid, topiramate, levetiracetam, pyridoxine, corticosteroids, the ketogenic diet, and electroconvulsive therapy. Based on the available data, we present a sample treatment algorithm that emphasizes the need for rapid therapeutic intervention, employs consecutive medications with different mechanisms of action, and attempts to minimize the risk of hypotension. The initial steps suggest using benzodiazepines and phenytoin. Second steps suggest using levetiracetam or valproic acid, which exert few hemodynamic adverse effects and have multiple mechanisms of action. Additional management strategies that could be employed in tertiary-care settings, such as coma induction guided by continuous electroencephalogram monitoring and surgical options, are also discussed.     

Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review

BACKGROUND: New continuous infusion antiepileptic drugs (cIV-AEDs) offer alternatives to pentobarbital for the treatment of refractory status epilepticus (RSE). However, no prospective randomized studies have evaluated the treatment of RSE. This systematic review compares the efficacy of midazolam (MDL), propofol (PRO), and pentobarbital (PTB) for terminating seizures and improving outcome in RSE patients. METHODS: We performed a literature search of studies describing the use of MDL, PRO, or PTB for the treatment of RSE published between January 1970 and September 2001, by using MEDLINE, OVID, and manually searched bibliographies. We included peer-reviewed studies of adult patients with SE refractory to at least two standard AEDs. Main outcome measures were the frequency of immediate treatment failure (clinical or electrographic seizures occurring 1 to 6 h after starting cIV-AED therapy) and mortality according to choice of agent and titration goal (cIV-AED titration to "seizure suppression" versus "EEG background suppression"). RESULTS: Twenty-eight studies describing a total of 193 patients fulfilled our selection criteria: MDL (n = 54), PRO (n = 33), and PTB (n = 106). Forty-eight percent of patients died, and mortality was not significantly associated with the choice of agent or titration goal. PTB was usually titrated to EEG background suppression by using intermittent EEG monitoring, whereas MDL and PRO were more often titrated to seizure suppression with continuous EEG monitoring. Compared with treatment with MDL or PRO, PTB treatment was associated with a lower frequency of short-term treatment failure (8 vs. 23%; p < 0.01), breakthrough seizures (12 vs. 42%; p < 0.001), and changes to a different cIV-AED (3 vs. 21%; p < 0.001), and a higher frequency of hypotension (systolic blood pressure <100 mm Hg; 77 vs. 34%; p < 0.001). Compared with seizure suppression (n = 59), titration of treatment to EEG background suppression (n = 87) was associated with a lower frequency of breakthrough seizures (4 vs. 53%; p < 0.001) and a higher frequency of hypotension (76 vs. 29%; p < 0.001). CONCLUSIONS: Despite the inherent limitations of a systematic review, our results suggest that treatment with PTB, or any cIV-AED infusion to attain EEG background suppression, may be more effective than other strategies for treating RSE. However, these interventions also were associated with an increased frequency of hypotension, and no effect on mortality was seen. A prospective randomized trial comparing different agents and titration goals for RSE with obligatory continuous EEG monitoring is needed.     

Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane

BACKGROUND: Refractory status epilepticus (RSE) is defined as continued seizures after 2 or 3 antiepileptic drugs have failed. Several intravenous agents have been used for RSE; however, problems occur with their toxicity and/or effectiveness. OBJECTIVE: To report our experience with inhalational anesthesia (IA) in patients who were refractory to other antiepileptic drugs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review during a 4-year period of patients with RSE treated with isoflurane and/or desflurane. MAIN OUTCOME MEASURE: Efficacy of IA on therapy in terminating RSE. RESULTS: Seven patients (4 male) aged 17 to 71 years received 7 to 15 (mean, 10) antiepileptic drugs in addition to IAs. The IAs were initiated after 1 to 103 (mean, 19) days of RSE and were used for a mean +/- SD 11 +/- 8.9 days. All patients received isoflurane, and 1 patient in addition received desflurane anesthesia 21 days after the onset of RSE for a total of 19 days. Regardless of seizure type, isoflurane and desflurane consistently stopped epileptic discharges with adequate, sustained electroencephalographic burst suppression within minutes of initiating IA therapy. Four patients had good outcomes, 3 died (1 of acute hemorrhagic leukoencephalitis, 1 of bowel infarction, and 1 of toxic encephalopathy, who remained in a persistent vegetative state until death 5.5 months after the onset of seizures). Complications during IA therapy included hypotension (7/7), atelectasis (7/7), infections (5/7), paralytic ileus (3/7), and deep venous thrombosis (2/7). No patient developed renal or hepatic dysfunction. CONCLUSIONS: Isoflurane and desflurane adequately suppressed RSE in all cases. Complications were common, but mortality and long-term morbidity were related to the underlying disease and duration of RSE. Prolonged use of isoflurane and desflurane is well tolerated.     

Treatment of refractory partial status epilepticus with multiple subpial transection: case report.

Status epilepticus (SE) represents a medical emergency that annually affects 60,000--150,000 individuals in the United States. Selective neuronal loss in vulnerable areas has been pathologically demonstrated following convulsive SE primarily affecting the limbic system, thalamus and cerebellum. Morbidity in those cases that follow refractory SE (RSE) is poorly documented. There have been anecdotal reports of surgical treatment for this condition, especially secondary to brain lesions. We report a 6-year-old patient who was in RSE for 60 days, without a brain lesion documented by MRI. The patient underwent multiple subpial transection (MST) of the sensorimotor cortex, which by ictal EEG and ictal SPECT proved to be the epileptogenic zone. We conclude that MST should be considered as an alternative treatment for refractory partial SE.     

Levetiracetam in children with refractory status epilepticus

The objective of this study was to investigate the utility of levetiracetam (LEV) in children with refractory status epilepticus (RSE). Records of children with RSE who received LEV as adjunctive therapy were reviewed. Over a 7-year period, 11 children had received LEV for RSE. Age ranged from 2 days to 9 years (median = 2.5 months). Prior to administration of LEV, the number of anticonvulsants used to treat RSE ranged from 2 to 7 (median = 3). Starting doses of LEV ranged from 15 to 70 mg/kg (median = 30 mg/kg). LEV was felt to be of benefit in 45% (5/11) of cases, resulting in either resolution of RSE or successful weaning of patients off continuous infusions of other anticonvulsants. In 27% (3/11), response to LEV was unclear as other medications were either added or increased concomitantly with LEV use. The median latency to cessation of RSE following LEV initiation was 1.5 days (range = 1-8 days). All responding patients were on LEV doses >or= 30 mg/kg/day (median 40 mg/kg/day). No significant adverse effects of LEV were reported. LEV may be an effective and safe adjuvant therapy in children with RSE.     

Pentobarbital treatment of refractory status epilepticus

We studied nine patients with status epilepticus refractory to standard therapy. In all patients so treated, IV pentobarbital terminated seizure activity. Mortality was high (77%) in those treated, but was attributed to underlying pathology and possibly to duration of status epilepticus. Pentobarbital therapy should be initiated within 0 to 2 hours after onset of seizures, with continuous EEG monitoring in an intensive care unit.     

Cardiac injury in refractory status epilepticus

Purpose: We sought to describe the spectrum of cardiac injury in refractory status epilepticus (RSE). Methods: We reviewed all patients with RSE between 1999 and 2011 at Mayo Clinic. RSE was defined as generalized convulsive or nonconvulsive status epilepticus (SE) that continued despite initial therapies. Exclusion criteria were age <18 years, anoxic SE, psychogenic SE, simple partial SE, absence SE, and repeat RSE. Patients were divided into those with (transient left ventricular [LV] dysfunction; electrocardiography [ECG] abnormality—new T‐wave inversion, ST elevation or ST depression, or QTc prolongation; and/or elevated blood troponin T levels) versus those without evidence of cardiac injury. Key Findings: We identified 59 consecutive patients with RSE. In 24 patients no cardiac‐specific diagnostic studies were obtained. Twenty‐two of the remaining 35 patients demonstrated markers of cardiac injury. General anesthesia was necessary for control of seizures in 31 of 35 patients for 10.5 ± 17.4 days. Twenty‐three patients had troponin levels drawn at onset of SE, of which nine were abnormal. ECG findings at onset of SE included ST elevation (11.4%), ST depression (5.7%), new T‐wave inversion (37.1%), and nonspecific ST changes (37.1%). Cardiac arrhythmias included ventricular tachycardia/fibrillation (11.4%), atrioventricular block (2.9%), atrial fibrillation/flutter (20.0%), sinus bradycardia (48.6%), and sinus tachycardia (65.7%). Intervention was required for cardiac arrhythmias in 42.9%. QTc was prolonged in 22.9% of patients. One patient met criteria for non–ST‐elevation myocardial infarction (NSTEMI). Three of 14 patients evaluated with ECG during SE demonstrated reversible systolic dysfunction. In‐hospital mortality was 34.3%. Outcome was worse in the group with markers of cardiac injury but the difference was not statistically significant (p = 0.14). Significance: Markers of cardiac injury are common in RSE and may be underrecognized in this population. These disturbances may require specific treatment and are often reversible. Routine performance of ECG and troponin followed by an echocardiography in those with repolarization abnormalities is probably justified. This was a biased sample of patients with severe RSE who had cardiac studies performed. The prevalence of findings in this study refers to this subgroup only.     

Efficacy of topiramate in children with refractory status epilepticus

PURPOSE: Status epilepticus (SE) is a life-threatening medical condition associated with significant morbidity and mortality that requires urgent medical intervention. Although several agents are available to treat SE, they occasionally fail to abort seizure activity. Topiramate (TPM) was anecdotally reported to be effective in adult patients with refractory SE. In this study, we evaluated the efficacy of TPM administered to children with this condition. METHODS: We retrospectively reviewed the pediatric SE database at the University of Michigan Medical Center and identified three children with refractory SE who were treated with TPM. Those children failed to respond to treatment with benzodiazepines, phenytoin, phenobarbital, midazolam, or pentobarbital. Additional treatment with TPM was administered by nasogastric tube. All patients were continuously monitored by 21-channel digital EEG machines, and the diagnosis of SE was made by a board-certified neurophysiologist. RESULTS: The ages of the three children were 4.5 months, 34 months, and 11 years. TPM was initiated at 2 mg/kg/day in two children and at 3 mg/kg/day in the third. The status was terminated in all three children within 24 h of maintenance therapy with TPM at 5-6 mg/kg/day. CONCLUSIONS: These results support the potential efficacy of TPM for children with refractory SE. Larger prospective series are needed to confirm those results.     

Prolonged treatment of refractory status epilepticus in a child

Barbiturate anesthesia, which is commonly used for refractory status epilepticus, is an effective treatment, but with many significant complications. The relationship between the duration of this extreme therapy and the ultimate outcome of refractory status epilepticus has not been well studied. We report a 7-year-old girl who presented with refractory status epilepticus secondary to presumed encephalitis with a focal lesion on cranial magnetic resonance imaging. She was treated for 70 days with high-dose antiepileptic drugs and recovered with a residual seizure disorder. This case suggests that, if the status epilepticus is due to a reversible cause such as encephalitis, neurologic recovery may occur despite this very prolonged course of extreme therapy.     

Prolonged coma from refractory status epilepticus

Objective

Status epilepticus is a life-threatening medical condition. In its most severe form, refractory status epilepticus (RSE) seizures may not respond to first and second-line anti-epileptic drugs. RSE is associated with a high mortality and significant medical complications in survivors with prolonged hospitalizations.

Methods

We describe the clinical course of RSE in the setting of new onset lupus in a 31-year-old male who required prolonged barbiturate coma.

Results

Seizure stopped on day 64 of treatment. Prior to the resolution of seizures, discussion around withdrawal of care took place between the physicians and patient's family. Medical care was continued because of the patient's age, normal serial MRI studies, and the patient's reversible medical condition.

Conclusion

Few evidence-based data exist to guide management of RSE. Our case emphasizes the need for continuous aggressive therapy when neuroimaging remains normal.     

Aborted and refractory status epilepticus in children: a comparative analysis

PURPOSE: The aims of this retrospective study were: (1) to compare the demographics, clinical characteristics, etiology, and EEG findings of status epilepticus aborted with medication (ASE) and refractory status epilepticus (RSE), (2) to describe the treatment response of status epilepticus (SE), and (3) to determine predictors of long-term outcome in children with SE. METHODS: Medical records and EEG lab logs with ICD-9 diagnostic codes related to SE were reviewed. Patients younger than 18 years of age, hospitalized in 1994-2004 at the Mayo Clinic, Rochester, were included. RESULTS: One hundred fifty-four children had SE; 94 (61%) had ASE, and 60 (39.0%) had RSE. Family history of seizures, higher seizure frequency score, higher number of maintenance antiepileptic drugs (AEDs), nonconvulsive SE, and focal or electrographic seizures on initial EEG were associated with RSE by univariate analysis. In-hospital mortality was significantly higher in RSE (13.3%) than in ASE (2.1%). In the long term, survivors with RSE developed more new neurological deficits (p < 0.001) and more epilepsy (p < 0.004) than children with ASE. Children treated in a more aggressive fashion appeared to have better treatment responses (p < 0.001) and outcomes (p = 0.03). Predictors of poor outcome were long seizure duration (p < 0.001), acute symptomatic etiology (p = 0.04), nonconvulsive SE (NCSE) (p = 0.01), and age at admission <5 years (p = 0.05). DISCUSSION: Several patient and clinical characteristics are associated with development of RSE and poor outcome. Prospective, randomized trials that assess different treatment protocols in children with SE are needed to determine the optimal sequence and timing of medications.     

Efficacy of perampanel in refractory nonconvulsive status epilepticus and simple partial status epilepticus

We provide some evidence concerning the efficacy of perampanel (PER) in refractory status epilepticus (SE). We retroactively identified patients with SE treated in our department by searching for the term “status epilepticus” in the electronic archive of medical records. We present and analyze in this paper the subset of data of the patients treated with PER. We analyzed ten episodes of SE in nine patients. At the first administration, PER was given in a dosage of 6 mg to most of our patients (7 of 10). On average, PER was administered as the 6th antiepileptic drug (AED) (range: 2–10). Depending on the criterion for efficacy, PER appears effective for the termination of SE in 2 to 6 (of 10) episodes. Unfortunately, safety data for the administration of PER with loading doses needed for the treatment of SE are lacking. Because of this, PER should be used very carefully in refractory SE and only after first-line treatment options have failed.