Abstract
In adult patients with status epilepticus (SE)—a life-threatening state of ongoing or repetitive seizures—the current evidence regarding outcome prediction is based on clinical, biochemical and EEG determinants. These predictors of outcome involve clinical features such as age, history of prior seizures or epilepsy, SE aetiology, level of consciousness, and seizure type at SE onset. The clinical risk–benefit calculation between the danger of undertreated persistent seizure activity and, conversely, the potential damage from unwarranted aggressive treatments remains a constant challenge. Improved knowledge of outcome determinants, as well as increased availability of reliable outcome prediction models early in the course of SE, is paramount for optimization of treatment of patients who develop this disorder. In this Review, we discuss the major prognostic determinants of outcome in SE. Through consideration of studies that provide measures of association between predictors of SE outcome and death, we propose a detailed—but as yet unvalidated—paradigm for assessment of these predictors during the course of SE. Such an algorithm could guide the organization of results from existing trials and provide direction with regard to the parameters that should be monitored in future studies of SE.
Key Points
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The most reliable clinical determinants for early prediction of outcome in status epilepticus (SE) are age, prior seizures or epilepsy, SE aetiology, level of consciousness, and seizure type at onset
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These variables have been integrated and validated in a clinical scoring system (the Status Epilepticus Outcome Score) for rapid outcome prognostication at SE onset
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The current outcome score for SE does not encompass the totality of aetiological, biochemical and EEG characteristics—factors that interact in a complex manner and show promise for outcome prognostication
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On the basis of the available data, we propose a detailed—but as yet unvalidated—paradigm for the assessment of outcome predictors during the course of SE
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References
Lowenstein, D. H., Bleck, T. & Macdonald, R. L. It's time to revise the definition of status epilepticus. Epilepsia 40, 120–122 (1999).
Knake, S. et al. Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia 42, 714–718 (2001).
DeLorenzo, R. J. in Seizures and Epilepsy in the Elderly (eds Rowan, A. J. & Ramsay, R. E.) 191–205 (Butterworth-Heinemann, 1997).
Chin, R. F., Neville, B. G. & Scott, R. C. A systematic review of the epidemiology of status epilepticus. Eur. J. Neurol. 11, 800–810 (2004).
DeLorenzo, R. J. et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 46, 1029–1035 (1996).
Logroscino, G., Hesdorffer, D. C., Cascino, G., Annegers, J. F. & Hauser, W. A. Short-term mortality after a first episode of status epilepticus. Epilepsia 38, 1344–1349 (1997).
Novy, J., Logroscino, G. & Rossetti, A. O. Refractory status epilepticus: a prospective observational study. Epilepsia 51, 251–256 (2010).
Hesdorffer, D. C., Logroscino, G., Cascino, G., Annegers, J. F. & Hauser, W. A. Incidence of status epilepticus in Rochester, Minnesota, 1965–1984. Neurology 50, 735–741 (1998).
Wu, Y. W., Shek, D. W., Garcia, P. A., Zhao, S. & Johnston, S. C. Incidence and mortality of generalized convulsive status epilepticus in California. Neurology 58, 1070–1076 (2002).
Coeytaux, A., Jallon, P., Galobardes, B. & Morabia, A. Incidence of status epilepticus in French-speaking Switzerland: (EPISTAR). Neurology 55, 693–697 (2000).
Hauser, W. A., Annegers, J. F. & Elveback, L. R. Mortality in patients with epilepsy. Epilepsia 21, 399–412 (1980).
Logroscino, G. et al. Long-term mortality after a first episode of status epilepticus. Neurology 58, 537–541 (2002).
Waterhouse, E. J. et al. Prospective population-based study of intermittent and continuous convulsive status epilepticus in Richmond, Virginia. Epilepsia 40, 752–758 (1999).
Rossetti, A. O., Hurwitz, S., Logroscino, G. & Bromfield, E. B. Prognosis of status epilepticus: role of aetiology, age, and consciousness impairment at presentation. J. Neurol. Neurosurg. Psychiatry 77, 611–615 (2006).
Claassen, J., Lokin, J. K., Fitzsimmons, B. F. Mendelsohn, F. A. & Mayer, S. A. Predictors of functional disability and mortality after status epilepticus. Neurology 58, 139–142 (2002).
Logroscino, G., Hesdorffer, D. C., Cascino, G. & Hauser, W. A. Status epilepticus without an underlying cause and risk of death: a population-based study. Arch. Neurol. 65, 221–224 (2008).
Sagduyu, A., Tarlaci, S. & Sirin, H. Generalized tonic–clonic status epilepticus: causes, treatment, complications and predictors of case fatality. J. Neurol. 245, 640–646 (1998).
Koubeissi, M. & Alshekhlee, A. In-hospital mortality of generalized convulsive status epilepticus: a large US sample. Neurology 69, 886–893 (2007).
Celesia, G. G., Messert, B. & Murphy, M. J. Status epilepticus of late adult onset. Neurology 22, 1047–1055 (1972).
Sung, C. Y. & Chu, N. S. Status epilepticus in the elderly: etiology, seizure type and outcome. Acta Neurol. Scand. 80, 51–56 (1989).
DeLorenzo, R. J., Towne, A. R., Pellock, J. M. & Ko, D. Status epilepticus in children, adults, and the elderly. Epilepsia 33 (Suppl. 4), 15–25 (1992).
Legriel, S. et al. Outcomes in 140 critically ill patients with status epilepticus. Intensive Care Med. 34, 476–480 (2007).
Towne, A. R., Pellock, J. M., Ko, D. & DeLorenzo, R. J. Determinants of mortality in status epilepticus. Epilepsia 35, 27–34 (1994).
Rossetti, A. O. et al. Status Epilepticus Severity Score (STESS): a tool to orient early treatment strategy. J. Neurol. 255, 1561–1566 (2008).
Rudin, D. et al. High prevalence of nonconvulsive and subtle status epilepticus in an ICU of a tertiary care center: a three-year observational cohort study. Epilepsy Res. 96, 140–150 (2011).
Holtkamp, M. et al. A “malignant” variant of status epilepticus. Arch. Neurol. 62, 1428–1431 (2005).
Delanty, N., French, J. A., Labar, D. R., Pedley, T. A. & Rowan, A. J. Status epilepticus arising de novo in hospitalized patients: an analysis of 41 patients. Seizure 10, 116–119 (2001).
[No authors listed] Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis of the International League Against Epilepsy. Epilepsia 34, 592–596 (1993).
[No authors listed] Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 22, 489–501 (1981).
[No authors listed] Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 30, 389–399 (1989).
Berg, A. T. et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 51, 676–685 (2010).
Aminoff, M. J. & Simon, R. P. Status epilepticus: causes, clinical features and consequences in 98 patients. Am. J. Med. 69, 657–666 (1980).
Rossetti, A. O. et al. Status epilepticus: an independent outcome predictor after cerebral anoxia. Neurology 69, 255–260 (2007).
Hui, A. C., Cheng, C., Lam, A., Mok, V. & Joynt, G. M. Prognosis following postanoxic myoclonus status epilepticus. Eur. Neurol. 54, 10–13 (2005).
Rundgren, M., Westhall, E., Cronberg, T., Rosén, I. & Friberg, H. Continuous amplitude-integrated electroencephalogram predicts outcome in hypothermia-treated cardiac arrest patients. Crit. Care Med. 38, 1838–1844 (2010).
Zandbergen, E. G., Koelman, J. H., de Haan, R. J. & Hijdra, A. SSEPs and prognosis in postanoxic coma: only short or also long latency responses? Neurology 67, 583–586 (2006).
Rossetti, A. O., Urbano, L. A., Delodder, F., Kaplan, P. W. & Oddo, M. Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest. Crit. Care 14, R173 (2010).
Fugate, J. E. et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann. Neurol. 68, 907–914 (2010).
Sutter, R., Marsch, S., Fuhr, P. & Rüegg, S. Mortality and recovery from refractory status epilepticus in the ICU: a 7-year observational study. Epilepsia 54, 502–511 (2013).
Swisher, C. B., Doreswamy, M., Gingrich, K. J., Vredenburgh, J. J. & Kolls, B. J. Phenytoin, levetiracetam, and pregabalin in the acute management of refractory status epilepticus in patients with brain tumors. Neurocrit. Care 16, 109–113 (2012).
Ding, D. et al. Premature mortality risk in people with convulsive epilepsy: long follow-up of a cohort in rural China. Epilepsia 54, 512–517 (2012).
Shneker, B. F. & Fountain, N. B. Assessment of acute morbidity and mortality in nonconvulsive status epilepticus. Neurology 61, 1066–1073 (2003).
Cockerell, O. C., Walker, M. C., Sander, J. W. & Shorvon, S. D. Complex partial status epilepticus: a recurrent problem. J. Neurol. Neurosurg. Psychiatry 57, 835–837 (1994).
Dodrill, C. B. & Wilensky, A. J. Intellectual impairment as an outcome of status epilepticus. Neurology 40, 23–27 (1990).
Parviainen, I., Kälviäinen, R. & Ruokonen, E. Propofol and barbiturates for the anesthesia of refractory convulsive status epilepticus: pros and cons. Neurol. Res. 29, 667–671 (2007).
Prabhakar, H., Bindra, A., Singh, G. P. & Kalaivani, M. Propofol versus thiopental sodium for the treatment of refractory status epilepticus. Cochrane Database of Systematic Reviews Issue 8. Art. No.:CD009202. http://dx.doi.org/10.1002/14651858.CD009202.pub2.
Claassen, J., Hirsch, L. J., Emerson, R. G. & Mayer, S. A. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 43, 146–153 (2002).
Sutter, R. et al. Associations between infections and clinical outcome parameters in status epilepticus: a retrospective 5-year cohort study. Epilepsia 53, 1489–1497 (2012).
Rossetti, A. O., Logroscino, G. & Bromfield, E. B. A clinical score for prognosis of status epilepticus in adults. Neurology 66, 1736–1738 (2006).
Corsellis, J. A. & Bruton, C. J. Neuropathology of status epilepticus in humans. Adv. Neurol. 34, 129–139 (1983).
Salmenperä, T., Kälviäinen, R., Partanen, K., Mervaala, E. & Pitkänen, A. MRI volumetry of the hippocampus, amygdala, entorhinal cortex, and perirhinal cortex after status epilepticus. Epilepsy Res. 40, 155–170 (2000).
Drislane, F. W., Blum, A. S., Lopez, M. R., Gautam, S. & Schomer, D. L. Duration of refractory status epilepticus and outcome: loss of prognostic utility after several hours. Epilepsia 50, 1566–1571 (2009).
Towne, A. R. Epidemiology and outcomes of status epilepticus in the elderly. Int. Rev. Neurobiol. 81, 111–127 (2007).
Bausell, R., Svoronos, A., Lennihan, L. & Hirsch, L. J. Recovery after severe refractory status epilepticus and 4 months of coma. Neurology 77, 1494–1495 (2011).
Fernández-Torre, J. L. et al. Ambulatory non-convulsive status epilepticus evolving into a malignant form. Epileptic Disord. 14, 41–50 (2012).
Sutter, R., Fuhr, P., Grize, L., Marsch, S. & Rüegg, S. Continuous video-EEG monitoring increases detection rate of nonconvulsive status epilepticus in the ICU. Epilepsia 52, 453–457 (2011).
Nei, M., Lee, J. M., Shanker, V. L. & Sperling, M. R. The EEG and prognosis in status epilepticus. Epilepsia 40, 157–163 (1999).
Jaitly, R., Sgro, J. A., Towne, A. R., Ko, D. & DeLorenzo, R. J. Prognostic value of EEG monitoring after status epilepticus: a prospective adult study. J. Clin. Neurophysiol. 14, 326–334 (1997).
Mayer, S. A. et al. Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch. Neurol. 59, 205–210 (2002).
Kalita, J., Misra, U. K. & Patel, R. Initial EEG in status epilepticus is helpful in predicting seizure recurrence. Electromyogr. Clin. Neurophysiol. 46, 139–144 (2006).
Foreman, B. et al. Generalized periodic discharges in the critically ill: a case-control study of 200 patients. Neurology 79, 1951–1960 (2012).
Garzon, E., Fernandes, R. M. & Sakamoto, A. C. Serial EEG during human status epilepticus: evidence for PLED as an ictal pattern. Neurology 57, 1175–1183 (2001).
Royds, J. A., Timperley, W. R. & Taylor, C. B. Levels of enolase and other enzymes in the cerebrospinal fluid as indices of pathological change. J. Neurol. Neurosurg. Psychiatry 44, 1129–1135 (1981).
Steinberg, R. et al. Experimental brain ischemia: neuron-specific enolase level in cerebrospinal fluid as an index of neuronal damage. J. Neurochem. 43, 19–24 (1984).
Hatfield, R. H. & McKernan, R. M. CSF neuron-specific enolase as a quantitative marker of neuronal damage in a rat stroke model. Brain Res. 577, 249–252 (1992).
Zandbergen, E. G. J. et al. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology 66, 62–68 (2006).
Almaraz, A. C., Bobrow, B. J., Wingerchuk, D. M., Wellik, K. E. & Demaerschalk, B. M. Serum neuron specific enolase to predict neurological outcome after cardiopulmonary resuscitation. Neurologist 15, 44–48 (2009).
Olivecrona, M., Rodling-Wahlström, M., Naredi, S. & Koskinen, L. O. S-100B and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy. J. Neurol. Neurosurg. Psychiatry 80, 1241–1247 (2009).
Steffen, I. G. et al. Mild therapeutic hypothermia alters neuron specific enolase as an outcome predictor after resuscitation: 97 prospective hypothermia patients compared to 133 historical non-hypothermia patients. Crit. Care 14, R69 (2010).
Zandbergen, E. G., de Haan, R. J. & Hijdra, A. Systematic review of prediction of poor outcome in anoxic-ischaemic coma with biochemical markers of brain damage. Intensive Care Med. 27, 1661–1667 (2001).
Cronberg, T. et al. Neuron-specific enolase correlates with other prognostic markers after cardiac arrest. Neurology 77, 623–630 (2011).
Rabinowicz, A. L., Correale, J. D., Bracht, K. A., Smith, T. D. & DeGiorgio, C. M. Neuron-specific enolase is increased after nonconvulsive status epilepticus. Epilepsia 36, 475–479 (1995).
DeGiorgio, C. M. et al. Serum neuron-specific enolase in human status epilepticus. Neurology 45, 1134–1137 (1995).
DeGiorgio, C. M. et al. Neuron-specific enolase, a marker of acute neuronal injury, is increased in complex partial status epilepticus. Epilepsia 37, 606–609 (1996).
DeGiorgio, C. M. et al. Serum neuron-specific enolase in the major subtypes of status epilepticus. Neurology 52, 746–749 (1999).
Peltola, J. et al. Indicators of inflammation after recent tonic-clonic epileptic seizures correlate with plasma interleukin-6 levels. Seizure 11, 44–46 (2002).
Bauer, S. et al. NK and CD4+ T cell changes in blood after seizures in temporal lobe epilepsy. Exp. Neurol. 211, 370–377 (2008).
Librizzi, L., Noe, F., Vezzani, A., de Curtis, M. & Ravizza, T. Seizure-induced brain-borne inflammation sustains seizure recurrence and blood–brain barrier damage. Ann. Neurol. 72, 82–90 (2012).
Li, G. et al. Cytokines and epilepsy. Seizure 20, 249–256 (2011).
Sutter, R., Grize, L., Fuhr, P., Rüegg, S. & Marsch, S. Acute phase proteins and mortality in status epilepticus: a five-year observational cohort study. Crit. Care Med. 41, 1526–1533 (2013).
Alapirtti, T. et al. C-reactive protein and seizures in focal epilepsy: a video-electroencephalographic study. Epilepsia 53, 790–796 (2012).
Scholtes, F. B., Renier, W. O. & Meinardi, H. Generalized convulsive status epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia 35, 1104–1112 (1994).
Brophy, G. M. et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit. Care 17, 3–23 (2012).
Rossetti, A. O., Alvarez, V., Januel, J. M. & Burnand, B. Treatment deviating from guidelines does not influence status epilepticus prognosis. J. Neurol. 260, 421–428 (2013).
Lowenstein, D. H. & Alldredge, B. K. Status epilepticus at an urban public hospital in the 1980s. Neurology 43, 483–488 (1993).
Alldredge, B. K. et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N. Engl. J. Med. 345, 631–637 (2001).
Treiman, D. M. et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N. Engl. J. Med. 339, 792–798 (1998).
Silbergleit, R. et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N. Engl. J. Med. 366, 591–600 (2012).
Hocker, S. E., Britton, J. W., Mandrekar, J. N., Wijdicks, E. F. & Rabinstein, A. A. Predictors of outcome in refractory status epilepticus. JAMA Neurol. 70, 72–77 (2013).
Roberts, R. J. et al. Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study. Crit. Care 13, R169 (2009).
Kowalski, R. G. et al. Third-line antiepileptic therapy and outcome in status epilepticus: the impact of vasopressor use and prolonged mechanical ventilation. Crit. Care Med. 40, 2677–2684 (2012).
Ala-Kokko, T. I. et al. Incidence of infections in patients with status epilepticus requiring intensive care and effect on resource utilization. Anaesth. Intensive Care 34, 639–644 (2006).
Privitera, M., Hoffman, M., Moore, J. L. & Jester, D. EEG detection of nontonic–clonic status epilepticus in patients with altered consciousness. Epilepsy Res. 18, 155–166 (1994).
Manno, E. M., Pfeifer, E. A., Cascino, G. D., Noe, K. H. & Wijdicks, E. F. Cardiac pathology in status epilepticus. Ann. Neurol. 58, 954–957 (2005).
Etsten, B. & Li, T. H. Hemodynamic changes during thiopental anesthesia in humans: cardiac output, stroke volume, total peripheral resistance, and intrathoracic blood volume. J. Clin. Invest. 34, 500–510 (1955).
Iyer, V. N., Hoel, R. & Rabinstein, A. A. Propofol infusion syndrome in patients with refractory status epilepticus: an 11-year clinical experience. Crit. Care Med. 37, 3024–3030 (2009).
Hocker, S., Prasad, A. & Rabinstein, A. A. Cardiac injury in refractory status epilepticus. Epilepsia 54, 518–522 (2012).
Spencer, R. G., Cox, T. S. & Kaplan, P. W. Global T-wave inversion associated with nonconvulsive status epilepticus. Ann. Intern. Med. 129, 163–164 (1998).
Sutter, R., Kaplan, P. W. & Rüegg, S. Independent external validation of the Status Epilepticus Severity Score. Crit. Care Med. (in press).
Prasad, A., Worrall, B. B., Bertram, E. H. & Bleck, T. P. Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia 42, 380–386 (2001).
Acknowledgements
R. Sutter is supported by the Research Funds of the University of Basel, the Scientific Society Basel, and the Gottfried and Julia Bangerter-Rhyner Foundation. P. W. Kaplan receives funding from the Qatar Research Foundation for continuous EEG monitoring in status epilepticus.
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R. Sutter wrote the article. All authors researched data for the article, and provided substantial contribution to discussions of content, and to the review and/or editing of the manuscript before submission.
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S. Rüegg has received unconditional research grants from UCB; honoraria for serving on the scientific advisory boards of Eisai and UCB; travel grants from GlaxoSmithKline, Janssen-Cilag and UCB; and speaker fees from UCB; and has served as a consultant for Eisai, GlaxoSmithKline, Janssen-Cilag, Pfizer, Novartis and UCB. The other authors declare no competing interests.
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Evidence for important determinants of outcome in adults with status epilepticus (DOC 78 kb)
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Sutter, R., Kaplan, P. & Rüegg, S. Outcome predictors for status epilepticus—what really counts. Nat Rev Neurol 9, 525–534 (2013). https://doi.org/10.1038/nrneurol.2013.154
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DOI: https://doi.org/10.1038/nrneurol.2013.154
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