0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Contribution |

A “Malignant” Variant of Status Epilepticus FREE

Martin Holtkamp, MD; Jalal Othman, MD; Katharina Buchheim, MD; Florian Masuhr, MD; Eva Schielke, MD; Hartmut Meierkord, MD
[+] Author Affiliations

Author Affiliations: Department of Neurology, Charité–Universitätsmedizin Berlin (Drs Holtkamp, Othman, Buchheim, Masuhr, and Meierkord), and Department of Neurology, Auguste-Viktoria-Krankenhaus Berlin (Dr Schielke), Berlin, Germany.


Arch Neurol. 2005;62(9):1428-1431. doi:10.1001/archneur.62.9.1428.
Text Size: A A A
Published online

Background  Status epilepticus (SE) frequently does not respond to common first-line anticonvulsants. In a substantial portion of patients, administration of anticonvulsant anesthetics is inevitable. Even this aggressive approach fails to terminate SE in an undefined number of cases. We have coined the term malignant SE for this most severe variant of SE.

Objective  To assess frequency, risk factors, and in-hospital outcome of malignant SE.

Design  Retrospective cohort study.

Setting  Neurologic intensive care unit of a large university hospital.

Patients  Sample of 35 episodes of SE not responding to first-line anticonvulsants in 34 patients.

Main Outcome Measures  Predictive and prognostic features of episodes of malignant SE with persistent epileptic activity after high-dose anesthetics compared with features of the remainder of cases with refractory SE and persistent epileptic activity after failure of first-line anticonvulsants.

Results  Status epilepticus that could not be controlled by first-line anticonvulsants resulted in malignant SE in 20% of cases. Patients with malignant SE were significantly younger than patients with refractory SE (P = .03). Encephalitis was identified as an independent risk factor for malignant SE (P = .008). Outcome in malignant SE was poor, with significantly longer duration of seizure activity (P<.001), longer stay in the neurologic intensive care unit (P<.001) and in the hospital (P = .007), and more patients with functional dependency at discharge from the hospital (P = .04).

Conclusions  Malignant SE is not rare after failure of first-line anticonvulsants. The patient at risk is typically young and suffers from encephalitis. Such patients should be treated aggressively early in the course of SE to prevent malignant SE.

Figures in this Article

Status epilepticus (SE) may occur with various degrees of severity. In many cases, the condition can be terminated by first-line anticonvulsants, but about 30% to 50% of cases are refractory.1,2 There are no standardized treatment guidelines for refractory SE (RSE). In current practice, anticonvulsant anesthetics are applied after failure of first-line drugs in almost all patients with generalized convulsive SE and in most patients with complex partial SE.3 However, even anesthetics may fail to terminate SE,412 a condition for which we suggest the term malignant SE (MSE). Malignant SE cannot be terminated by any substance and continues for weeks or months. In some of the reported cases, the condition has been suggested to represent a distinct disease entity, but a cause could not be determined.11

While RSE has been characterized as to frequency, risk factors, and outcome,2 similar data on MSE are lacking. In the current study, we compared predictive, therapeutic, and prognostic features of MSE with those of the remainder of cases of SE not responding to first-line anticonvulsants. The identification of patients at risk may help to prevent the development of MSE by the use of aggressive therapeutic interventions early in the course of SE.

DEFINITION AND CLASSIFICATION

Malignant SE was defined as persistent clinical and/or electrophysiologic epileptic activity immediately recurring within 5 days after tapering of the maximal dose of intravenous anesthetic anticonvulsants required to achieve an electroencephalographic (EEG) burst suppression pattern previously. This time gap was chosen to ascertain that the suppressive effect of high-dose anesthetics on the EEG, which may last hours to days,13,14 had ceased.

Refractory SE was defined as all forms of continuous clinical and/or electrophysiologic epileptic activity not responding to first-line anticonvulsants regardless of the delay from seizure onset, and excluding patients with MSE. First-line anticonvulsant drugs had to be applied in adequate form and dose. A treatment regimen was considered adequate if it included intravenous administration of at least 10 mg of diazepam, 1 mg of clonazepam, 6 mg of lorazepam, or 5 mg of midazolam hydrochloride followed by phenytoin in a minimum dose of 10 mg/kg.2 Status epilepticus not treated with phenytoin was considered refractory with continuing epileptic activity after a double dose of benzodiazepines.

In comatose patients with no or only subtle motor phenomena, SE was defined by the presence of repetitive generalized or focal epileptiform discharges (spikes, sharp waves, and spike waves) excluding periodic lateralized epileptiform discharges, generalized periodic epileptiform discharges, and stimulus-induced rhythmic, periodic, or ictal discharges. Termination of SE was defined in patients treated with anesthetics by cessation of seizure activity and absence of a burst suppression pattern or flat line on the EEG. Patients who did not receive anesthetics were regarded as successfully treated if seizure activity ceased clinically. Two or more unprovoked epileptic seizures that had occurred more than 4 weeks before the onset of SE defined preexisting epilepsy.

Encephalitis was defined as encephalopathy (depressed or altered level of consciousness lasting 24 hours or longer, lethargy, or change in personality) and 1 or more of the following symptoms: fever, focal neurologic findings, cerebrospinal fluid (CSF) pleocytosis, and EEG or neuroimaging findings consistent with encephalitis,15 after exclusion of systemic infections. Encephalitis was infectious, noninfectious, or of unknown etiology.

PATIENT SAMPLE

All episodes of SE not responding to first-line anticonvulsants in patients aged 18 years or older admitted between January 1, 1993, and December 31, 2002, to the Neurological Intensive Care Unit, Charité–Universitätsmedizin Berlin, Germany, were analyzed retrospectively. The study had the approval of the institutional review board. In a first step, the computer-assisted patient files were searched by using the keywords status epilepticus, seizure clustering, and prolonged epileptic seizures. By these criteria, 138 episodes in 129 patients suitable for a diagnosis of SE were identified. We then excluded all episodes of SE that responded to adequate application of first-line anticonvulsants. We also excluded all episodes of nonepileptic origin (psychogenic seizure, prolonged convulsive syncope, transient ischemic attack, etc) that had initially been regarded as SE. The records of 5 patients with 6 episodes could not be retrieved in the archives. Thus, 35 episodes in 34 patients fulfilled our definition of SE refractory to first-line anticonvulsants and were included in the present analysis.

CLINICAL DATA

We used a structured data collection grid completed by 2 independent reviewers to analyze the clinical variables. For each episode of SE, patients’ demographic data (age, sex) and history of epilepsy were documented. Furthermore, data concerning cause, symptoms, and treatment course were evaluated. Finally, duration of SE, treatment duration in the neurologic intensive care unit, length of in-hospital stay, in-hospital mortality, and functional outcome at hospital discharge using the Glasgow Outcome Scale16 were analyzed.

STATISTICAL ANALYSIS

Data were collected with the database program Access 2000 (Microsoft, Redmond, Wash). Statistical calculations were performed with SPSS version 11.0 software (SPSS Inc, Chicago, Ill). Frequency distributions of predictive, therapeutic, and prognostic features were compared between patients with MSE and RSE to identify characteristics of MSE, and were calculated by the χ2 test. For analysis of continuous data with normal distribution, the unpaired, 2-tailed t test was used, and for data with nonnormal distribution, the Mann-Whitney test was used. Predictors associated with MSE (P<.20) were entered into a backward stepwise logistic regression analysis to identify independent risk factors. Differences were considered significant if P<.05.

STUDY POPULATION

A total of 35 episodes in 34 patients fulfilled the diagnostic criteria for SE not responding to first-line anticonvulsants. The mean ± SD age was 52.1 ± 18.4 years (range, 18-88 years). Seven episodes (20%) were compatible with our definition of MSE. Six patients (86%) with MSE were female, but sex distribution was not significantly different from that of patients with RSE (16 [57%] female; P = .17). The mean ± SD age of patients with MSE (38.7 ± 13 years) was significantly lower than that of patients with RSE (55.4 ± 18.2 years; P = .03).

PREEXISTING EPILEPSY, CAUSE, AND SYMPTOMS

Only 1 of the 7 patients with MSE had preexisting epilepsy, compared with 8 (29%) of those with RSE. Encephalitis was the only single cause significantly more frequently seen in MSE (5 [71%]) than RSE (3 [11%]; P = .003). All 8 patients with encephalitis (5 with MSE, 3 with RSE) had had fever and symptoms of encephalopathy for at least 24 hours before the onset of seizure activity. In 6 of the patients, CSF pleocytosis (median white blood cell count, 52/μL; range, 16-256/μL) with predominantly mononuclear cells was found. Oligoclonal bands were found in the CSF of 3 patients, and in 2 of the 8 patients a causative agent was proven (herpes simplex virus and cytomegalovirus). In a multivariate analysis, only encephalitis was an independent risk factor for MSE (odds ratio, 31.5; 95% confidence interval, 2.5-396; P = .008). Further individual causes are listed in the Table. The most common clinical presentation was complex partial SE in both groups, found in 5 (71%) of MSE episodes and 12 (43%) of RSE episodes. No symptomatology of SE was seen significantly more often in 1 of the 2 study groups. Focal onset of seizure activity occurred in 5 (71%) of cases of MSE and thus had an incidence not significantly different from that in RSE (22 [79%]).

Table Graphic Jump LocationTable. Causes of Malignant and Refractory Status Epilepticus
TREATMENT

Titration of anesthetic anticonvulsants to a burst suppression pattern was performed by definition in all cases of MSE. An anesthetic was administered in 10 cases of RSE (36%) (P = .003), and in 4 (40%) of those cases the anesthetic was titrated to a burst suppression pattern (P = .02) (Figure). Duration of anesthetic therapy was significantly longer in MSE (median, 15 days) than RSE (median, 3 days; P = .03). Anesthetics of first choice in MSE were thiopental sodium (n = 5), midazolam (n = 1), and propofol (n = 1). Anesthetics of first choice in RSE were propofol (n = 6), midazolam (n = 2), and thiopental (n = 2). Propofol was used significantly more often in RSE than MSE (P = .04).

Place holder to copy figure label and caption
Figure.

Flowchart indicating the treatment response in 35 episodes of status epilepticus refractory to first-line anticonvulsants.

Graphic Jump Location
OUTCOME MEASURES

Seizure duration was significantly longer in MSE (median, 17 days) than RSE (median, 2 days; P<.001). The median length of stay in the neurologic intensive care unit was significantly longer in MSE (53 days) than RSE (10 days; P<.001). Median in-hospital stay was also significantly longer in MSE (100 days) than RSE (25 days; P = .007). In-hospital mortality was similar in MSE (1 [14%]) and RSE (5 [18%]). One patient with MSE and 2 patients with RSE died during persistent seizures. The other patients died of medical complications. Five of 6 surviving patients with MSE and 4 of 23 surviving patients with RSE were discharged from the hospital with a reduction of 2 points or more on the Glasgow Outcome Scale compared with admission values, indicating marked functional dependency (P = .04).

In the present study, the frequency of MSE amounted to 20% of all patients with SE refractory to first-line anticonvulsants. In a systematic review including almost 200 patients, the efficacy of RSE treatment with anesthetic anticonvulsants was assessed. Epileptic activity recurred between 60 minutes and 6 hours after the initial loading dose in 8% to 20% of cases and after 6 hours of intravenous treatment in 12% to 51% of cases, depending on the drug used.17 However, these figures indicate treatment failure with anesthetics and do not represent the frequency of malignant or other difficult-to-treat forms of SE. Thus, our study provides the first data, to our knowledge, about the frequency of MSE in a large series of patients with SE not responding to first-line anticonvulsants.

In this study, encephalitis was identified as an independent predictor of MSE. An infectious agent was identified in a quarter of our patients, which is in line with studies on encephalitis reporting specific microbiological agents only in a minority of cases.15 Therefore, encephalitis frequently has to be diagnosed on the basis of clinical, CSF, EEG, and magnetic resonance imaging findings15; in the present study, symptoms of encephalopathy and fever before seizure onset, as well as mononuclear CSF pleocytosis, were regarded as sufficient.

Previous studies found encephalitis to be a primary cause of SE refractory to anesthetic anticonvulsants as well,5,12 but in most reported cases the cause remained unknown.4,79,11 Van Lierde et al11 reported a series of 6 young patients with refractory multifocal febrile SE, most of whom required long-lasting general anesthesia. A cause could not be established in a single case, and the existence of a distinct RSE syndrome was discussed. Interestingly, mild mononuclear CSF pleocytosis has been described in many patients but has been attributed to SE rather than to CNS infection.4,8,11 Some studies have focused on SE-induced pleocytosis, describing increased white blood cell counts in the CSF up to 71/μL in 10% to 20% of patients with SE lacking concomitant infectious diseases.18,19 In a clinical landmark study by Aminoff and Simon,19 a polymorphonuclear CSF pleocytosis was reported in the vast majority of SE cases. However, the typical CSF feature of viral encephalitis is mononuclear pleocytosis, as seen in the current patients and in most previously described patients with malignant or otherwise-termed forms of long-lasting SE.4,8,11 Thus, at least some of the reported cases of SE refractory to anesthetics with unknown cause may have been caused by encephalitis. The present findings indicate that a malignant course of SE depends on the underlying cause. This argues against the hypothesis that MSE or similar forms of difficult-to-treat SE display a distinct clinical entity.

In the present study, some cases were regarded to be refractory to first-line anticonvulsants after administration of a double dose of benzodiazepines without subsequent phenytoin.20 The rationale of this approach is based on the preliminary finding that the addition of second- and third-line medications rarely controls seizures.21 Treatment failure with anesthetics did not depend on the drug used, but barbiturates, midazolam, and propofol share similar mechanisms of action, since all exert γ-aminobutyric acid (GABA)–ergic properties. In continuing SE, a progressive erosion of efficacy of GABAergic drugs is well known in patients21 and animal models,22 and the administration of non-GABAergic drugs such as ketamine hydrochloride has been encouraged in RSE.23 Although experimental studies on ketamine in prolonged SE have been promising,24 clinical evidence is anecdotal.25 Further studies focusing on alternatives to or endorsement of GABAergic drugs are urgently needed in RSE and MSE.

The small number of patients, the retrospective design, and the lack of long-term prognostic data do not allow firm conclusions about the possible impact of MSE on clinical outcome. However, it should be noted that more patients in the MSE group than in the RSE group were severely disabled at hospital discharge. Thus, MSE not only prolongs the in-hospital stay but also is associated with adverse effects on the clinical outcome.

In summary, the present study indicates that the typical patient at risk to develop a malignant course of SE is young and has encephalitis. Early aggressive treatment strategies seem to be reasonable in these patients. To further investigate predictors, clinical features, and outcome of patients with MSE, the establishment of a prospective multicenter database appears to be appropriate.

Correspondence: Martin Holtkamp, MD, Department of Neurology, Charité–Universitätsmedizin Berlin, Schumannstr 20/21, 10117 Berlin, Germany (martin.holtkamp@charite.de).

Accepted for Publication: December 7, 2004.

Author Contributions:Study concept and design: Holtkamp, Othman, Buchheim, and Meierkord. Acquisition of data: Holtkamp, Othman, Buchheim, and Schielke. Analysis and interpretation of data: Holtkamp, Othman, Buchheim, Masuhr, and Schielke. Drafting of the manuscript: Holtkamp, Othman, Buchheim, Masuhr, and Meierkord. Critical revision of the manuscript for important intellectual content: Holtkamp, Othman, Buchheim, Schielke, and Meierkord. Statistical analysis: Holtkamp, Othman, and Buchheim. Administrative, technical, and material support: Holtkamp and Meierkord. Study supervision: Masuhr and Meierkord.

Acknowledgment: We thank Brigitte Wegner, MD, Institute of Medical Biometry, Charité–Universitätsmedizin Berlin, for statistical advice.

Treiman  DMMeyers  PDWalton  NY  et al. Veterans Affairs Status Epilepticus Cooperative Study Group, A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med 1998;339792- 798
PubMed Link to Article
Mayer  SAClaassen  JLokin  JMendelsohn  FDennis  LJFitzsimmons  BF Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 2002;59205- 210
PubMed Link to Article
Holtkamp  MMasuhr  FHarms  LEinhaupl  KMMeierkord  HBuchheim  K The management of refractory generalised convulsive and complex partial status epilepticus in three European countries: a survey among epileptologists and critical care neurologists. J Neurol Neurosurg Psychiatry 2003;741095- 1099
PubMed Link to Article
Pohlmann-Eden  BGass  APeters  CNWennberg  RBluemcke  I Evolution of MRI changes and development of bilateral hippocampal sclerosis during long lasting generalised status epilepticus. J Neurol Neurosurg Psychiatry 2004;75898- 900
PubMed Link to Article
Skaff  PTLabiner  DM Status epilepticus due to human parvovirus B19 encephalitis in an immunocompetent adult. Neurology 2001;571336- 1337
PubMed Link to Article
Lousa  MSanchez-Alonso  SRodriguez-Diaz  RDalmau  J Status epilepticus with neuron-reactive serum antibodies: response to plasma exchange. Neurology 2000;542163- 2165
PubMed Link to Article
Nixon  JBateman  DMoss  T An MRI and neuropathological study of a case of fatal status epilepticus. Seizure 2001;10588- 591
PubMed Link to Article
Chee  MWLo  NK Asymmetric hippocampal atrophy and extra-hippocampal epilepsy following refractory status epilepticus in an adult. J Neurol Sci 1997;147203- 204
PubMed Link to Article
Yamashita  MYamamoto  T Amygdalo-subicular degeneration in a young adult with status epilepticus and choreoathetoid movements of acute onset. Clin Neuropathol 1999;1845- 50
PubMed
Prasad  AWorrall  BBBertram  EHBleck  TP Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia 2001;42380- 386
PubMed Link to Article
Van Lierde  IVan Paesschen  WDupont  PMaes  ASciot  R De novo cryptogenic refractory multifocal febrile status epilepticus in the young adult: a review of six cases. Acta Neurol Belg 2003;10388- 94
PubMed
Yaffe  KLowenstein  DH Prognostic factors of pentobarbital therapy for refractory generalized status epilepticus. Neurology 1993;43895- 900
PubMed Link to Article
Parviainen  IUusaro  AKalviainen  RKaukanen  EMervaala  ERuokonen  E High-dose thiopental in the treatment of refractory status epilepticus in intensive care unit. Neurology 2002;591249- 1251
PubMed Link to Article
Stover  JFLenzlinger  PMStocker  R  et al.  Thiopental in CSF and serum correlates with prolonged loss of cortical activity. Eur Neurol 1998;39223- 228
PubMed Link to Article
Glaser  CAGilliam  SSchnurr  D  et al.  In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998-2000. Clin Infect Dis 2003;36731- 742
PubMed Link to Article
Jennett  BBond  M Assessment of outcome after severe brain damage. Lancet 1975;1480- 484
PubMed Link to Article
Claassen  JHirsch  LJEmerson  RGMayer  SA Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 2002;43146- 153
PubMed Link to Article
Barry  EHauser  WA Pleocytosis after status epilepticus. Arch Neurol 1994;51190- 193
PubMed Link to Article
Aminoff  MJSimon  RP Status epilepticus: causes, clinical features and consequences in 98 patients. Am J Med 1980;69657- 666
PubMed Link to Article
Manno  EM New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003;78508- 518
PubMed Link to Article
Lowenstein  DHAlldredge  BK Status epilepticus at an urban public hospital in the 1980s. Neurology 1993;43483- 488
PubMed Link to Article
Kapur  JMacdonald  RL Rapid seizure-induced reduction of benzodiazepine and Zn2+ sensitivity of hippocampal dentate granule cell GABAA receptors. J Neurosci 1997;177532- 7540
PubMed
Bleck  TP Refractory status epilepticus in 2001. Arch Neurol 2002;59188- 189
PubMed Link to Article
Borris  DJBertram  EHKapur  J Ketamine controls prolonged status epilepticus. Epilepsy Res 2000;42117- 122
PubMed Link to Article
Sheth  RDGidal  BE Refractory status epilepticus: response to ketamine. Neurology 1998;511765- 1766
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Flowchart indicating the treatment response in 35 episodes of status epilepticus refractory to first-line anticonvulsants.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable. Causes of Malignant and Refractory Status Epilepticus

References

Treiman  DMMeyers  PDWalton  NY  et al. Veterans Affairs Status Epilepticus Cooperative Study Group, A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med 1998;339792- 798
PubMed Link to Article
Mayer  SAClaassen  JLokin  JMendelsohn  FDennis  LJFitzsimmons  BF Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 2002;59205- 210
PubMed Link to Article
Holtkamp  MMasuhr  FHarms  LEinhaupl  KMMeierkord  HBuchheim  K The management of refractory generalised convulsive and complex partial status epilepticus in three European countries: a survey among epileptologists and critical care neurologists. J Neurol Neurosurg Psychiatry 2003;741095- 1099
PubMed Link to Article
Pohlmann-Eden  BGass  APeters  CNWennberg  RBluemcke  I Evolution of MRI changes and development of bilateral hippocampal sclerosis during long lasting generalised status epilepticus. J Neurol Neurosurg Psychiatry 2004;75898- 900
PubMed Link to Article
Skaff  PTLabiner  DM Status epilepticus due to human parvovirus B19 encephalitis in an immunocompetent adult. Neurology 2001;571336- 1337
PubMed Link to Article
Lousa  MSanchez-Alonso  SRodriguez-Diaz  RDalmau  J Status epilepticus with neuron-reactive serum antibodies: response to plasma exchange. Neurology 2000;542163- 2165
PubMed Link to Article
Nixon  JBateman  DMoss  T An MRI and neuropathological study of a case of fatal status epilepticus. Seizure 2001;10588- 591
PubMed Link to Article
Chee  MWLo  NK Asymmetric hippocampal atrophy and extra-hippocampal epilepsy following refractory status epilepticus in an adult. J Neurol Sci 1997;147203- 204
PubMed Link to Article
Yamashita  MYamamoto  T Amygdalo-subicular degeneration in a young adult with status epilepticus and choreoathetoid movements of acute onset. Clin Neuropathol 1999;1845- 50
PubMed
Prasad  AWorrall  BBBertram  EHBleck  TP Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia 2001;42380- 386
PubMed Link to Article
Van Lierde  IVan Paesschen  WDupont  PMaes  ASciot  R De novo cryptogenic refractory multifocal febrile status epilepticus in the young adult: a review of six cases. Acta Neurol Belg 2003;10388- 94
PubMed
Yaffe  KLowenstein  DH Prognostic factors of pentobarbital therapy for refractory generalized status epilepticus. Neurology 1993;43895- 900
PubMed Link to Article
Parviainen  IUusaro  AKalviainen  RKaukanen  EMervaala  ERuokonen  E High-dose thiopental in the treatment of refractory status epilepticus in intensive care unit. Neurology 2002;591249- 1251
PubMed Link to Article
Stover  JFLenzlinger  PMStocker  R  et al.  Thiopental in CSF and serum correlates with prolonged loss of cortical activity. Eur Neurol 1998;39223- 228
PubMed Link to Article
Glaser  CAGilliam  SSchnurr  D  et al.  In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998-2000. Clin Infect Dis 2003;36731- 742
PubMed Link to Article
Jennett  BBond  M Assessment of outcome after severe brain damage. Lancet 1975;1480- 484
PubMed Link to Article
Claassen  JHirsch  LJEmerson  RGMayer  SA Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 2002;43146- 153
PubMed Link to Article
Barry  EHauser  WA Pleocytosis after status epilepticus. Arch Neurol 1994;51190- 193
PubMed Link to Article
Aminoff  MJSimon  RP Status epilepticus: causes, clinical features and consequences in 98 patients. Am J Med 1980;69657- 666
PubMed Link to Article
Manno  EM New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003;78508- 518
PubMed Link to Article
Lowenstein  DHAlldredge  BK Status epilepticus at an urban public hospital in the 1980s. Neurology 1993;43483- 488
PubMed Link to Article
Kapur  JMacdonald  RL Rapid seizure-induced reduction of benzodiazepine and Zn2+ sensitivity of hippocampal dentate granule cell GABAA receptors. J Neurosci 1997;177532- 7540
PubMed
Bleck  TP Refractory status epilepticus in 2001. Arch Neurol 2002;59188- 189
PubMed Link to Article
Borris  DJBertram  EHKapur  J Ketamine controls prolonged status epilepticus. Epilepsy Res 2000;42117- 122
PubMed Link to Article
Sheth  RDGidal  BE Refractory status epilepticus: response to ketamine. Neurology 1998;511765- 1766
PubMed Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 58

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Pediatric status epilepticus management. Curr Opin Pediatr 2014;26(6):668-74.