Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Nonconvulsive status epilepticus in adults — insights into the invisible

Subjects

Key Points

  • Nonconvulsive status epilepticus (NCSE) is defined as a continuous state of seizures without convulsions, or multiple nonconvulsive seizures for more than 30 min without interictal full recovery

  • The variable and subtle clinical features of NCSE make diagnosis and treatment challenging, as they can arise from other pathological conditions

  • The introduction of continuous electroencephalography and the characterization of electrographic criteria have delineated several NCSE types that are associated with different prognoses in various clinical settings

  • The classification of NCSE should mainly be based on aetiology, as the outcomes of NCSE are driven largely by the underlying pathology

  • Treatment of NCSE encompasses general intensive care, rapid administration of antiepilepic drugs, and treatment of the underlying or concomitant diseases

Abstract

Nonconvulsive status epilepticus (NCSE) is a state of continuous or repetitive seizures without convulsions. Owing to the nonspecific symptoms and considerable morbidity and mortality associated with NCSE, clinical research has focused on early diagnosis, risk stratification and seizure termination. The subtle symptoms and the necessity for electroencephalographic confirmation of seizures result in under-diagnosis with deleterious consequences. The introduction of continuous EEG to clinical practice, and the characterization of electrographic criteria have delineated a number of NCSE types that are associated with different prognoses in several clinical settings. Epidemiological studies have uncovered risk factors for NCSE; knowledge of these factors, together with particular clinical characteristics and EEG observations, enables tailored treatment. Despite these advances, NCSE can be refractory to antiepileptic drugs, necessitating further escalation of treatment. The presumptive escalation to anaesthetics, however, has recently been questioned owing to an association with increased mortality. This Review compiles epidemiological, clinical and diagnostic aspects of NCSE, and considers current treatment options and prognosis.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Major symptoms of nonconvulsive status epilepticus.
Figure 2: Recommendations for the use of continuous electroencephalography (cEEG) monitoring in critical illnesses.
Figure 3: Recommendations for the treatment of nonconvulsive status epilepticus (NCSE) in the intensive care unit (ICU).

References

  1. Brophy, G. M. et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit. Care 17, 3–23 (2012).

    Article  PubMed  Google Scholar 

  2. Trinka, E. et al. A definition and classification of status epilepticus — report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 56, 1515–1523 (2015).

    Article  PubMed  Google Scholar 

  3. Fagan, K. J. & Lee, S. I. Prolonged confusion following convulsions due to generalized nonconvulsive status epilepticus. Neurology 40, 1689–1694 (1990).

    CAS  Article  PubMed  Google Scholar 

  4. Sutter, R. & Kaplan, P. W. Electroencephalographic criteria for nonconvulsive status epilepticus: synopsis and comprehensive survey. Epilepsia 53 (Suppl. 3), 1–51 (2012).

    Article  PubMed  Google Scholar 

  5. 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).

    Article  PubMed  Google Scholar 

  6. 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).

    Article  PubMed  Google Scholar 

  7. Sutter, R., Marsch, S., Fuhr, P., Kaplan, P. W. & Rüegg, S. Anesthetic drugs in status epilepticus: risk or rescue? A 6-year cohort study. Neurology 82, 656–664 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Marchi, N. A. et al. Status epilepticus: impact of therapeutic coma on outcome. Crit. Care Med. 43, 1003–1009 (2015).

    Article  PubMed  Google Scholar 

  9. Sutter, R. Conflicting clinical implications of therapeutic coma for status epilepticus. Crit. Care Med. 43, 1144–1145 (2015).

    Article  PubMed  Google Scholar 

  10. DeLorenzo, R. J., Pellock, J. M., Towne, A. R. & Boggs, J. G. Epidemiology of status epilepticus. J. Clin. Neurophysiol. 12, 316–325 (1995).

    CAS  Article  PubMed  Google Scholar 

  11. Rosenow, F., Hamer, H. M. & Knake, S. The epidemiology of convulsive and nonconvulsive status epilepticus. Epilepsia 48 (Suppl. 8), 82–84 (2007).

    Article  PubMed  Google Scholar 

  12. Dunne, J. W., Summers, Q. A. & Stewart-Wynne, E. G. Non-convulsive status epilepticus: a prospective study in an adult general hospital. Q. J. Med. 62, 117–126 (1987).

    CAS  PubMed  Google Scholar 

  13. 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).

    Article  PubMed  Google Scholar 

  14. Laccheo, I. et al. Non-convulsive status epilepticus and non-convulsive seizures in neurological ICU patients. Neurocrit. Care 22, 202–211 (2015).

    Article  PubMed  Google Scholar 

  15. Privitera, M. D. & Strawsburg, R. H. Electroencephalographic monitoring in the emergency department. Emerg. Med. Clin. North Am. 12, 1089–1100 (1994).

    CAS  PubMed  Google Scholar 

  16. Towne, A. R. et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology 54, 340–345 (2000).

    CAS  Article  PubMed  Google Scholar 

  17. Rüegg, S., Hunziker, P., Marsch, S. & Schindler, C. Association of environmental factors with the onset of status epilepticus. Epilepsy Behav. 12, 66–73 (2008).

    Article  PubMed  Google Scholar 

  18. Bauer, G. & Trinka, E. Nonconvulsive status epilepticus and coma. Epilepsia 51, 177–190 (2010).

    Article  PubMed  Google Scholar 

  19. Fernández-Torre, J. L., Rebollo, M., Gutiérrez, A., López-Espadas, F. & Hernández-Hernández, M. A. Nonconvulsive status epilepticus in adults: electroclinical differences between proper and comatose forms. Clin. Neurophysiol. 123, 244–251 (2012).

    Article  PubMed  Google Scholar 

  20. Rittenberger, J. C., Popescu, A., Brenner, R. P., Guyette, F. X. & Callaway, C. W. Frequency and timing of nonconvulsive status epilepticus in comatose post-cardiac arrest subjects treated with hypothermia. Neurocrit. Care 16, 114–122 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Marcuse, L. V., Lancman, G., Demopoulos, A. & Fields, M. Nonconvulsive status epilepticus in patients with brain tumors. Seizure 23, 542–547 (2014).

    Article  PubMed  Google Scholar 

  22. Thabet, F., Al Maghrabi, M., Al Barraq, A. & Tabarki, B. Cefepime-induced nonconvulsive status epilepticus: case report and review. Neurocrit. Care 10, 347–351 (2009).

    Article  PubMed  Google Scholar 

  23. Shneker, B. F. & Fountain, N. B. Assessment of acute morbidity and mortality in nonconvulsive status epilepticus. Neurology 61, 1066–1073 (2003).

    Article  PubMed  Google Scholar 

  24. Knake, S. et al. Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia 42, 714–718 (2001).

    CAS  Article  PubMed  Google Scholar 

  25. Koutroumanidis, M. in Nonconvulsive Status Epilepticus: Epilepsy Research Foundation Workshop Reports. Epileptic Disord. 7, 279–282 (2005).

    Google Scholar 

  26. Dziewas, R., Kellinghaus, C. & Ludemann, P. Nonconvulsion status epilepticus in patients with juvenile myoclonic epilepsy: types and frequencies. Seizure 11, 335–339 (2002).

    Article  PubMed  Google Scholar 

  27. Agathonikou, A., Panayiotopoulos, C. P., Giannakodimos, S. & Koutroumanidis, M. Typical absence status in adults: diagnostic and syndromic considerations. Epilepsia 39, 1265–1276 (1998).

    CAS  Article  PubMed  Google Scholar 

  28. Kaplan, P. W. Nonconvulsive status epilepticus. Semin. Neurol. 16, 33–40 (1996).

    CAS  Article  PubMed  Google Scholar 

  29. Patsalos, P. N., Fröscher, W., Pisani, F. & van Rijn, C. M. The importance of drug interactions in epilepsy therapy. Epilepsia 43, 365–385 (2002).

    CAS  Article  PubMed  Google Scholar 

  30. Jordan, K. G. Nonconvulsive status epilepticus in acute brain injury. J. Clin. Neurophysiol. 16, 332–340 (1999).

    CAS  Article  PubMed  Google Scholar 

  31. Young, G. B., Jordan, K. G. & Doig, G. S. An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: an investigation of variables associated with mortality. Neurology 47, 83–89 (1996).

    CAS  Article  PubMed  Google Scholar 

  32. Kondziella, D. et al. Continuous EEG monitoring in aneurysmal subarachnoid hemorrhage: a systematic review. Neurocrit. Care 22, 450–461 (2015).

    CAS  Article  PubMed  Google Scholar 

  33. Walker, M. C. Status epilepticus on the intensive care unit. J. Neurol. 250, 401–406 (2003).

    Article  PubMed  Google Scholar 

  34. Yablon, S. A. Posttraumatic seizures. Arch. Phys. Med. Rehabil. 74, 983–1001 (1993).

    CAS  PubMed  Google Scholar 

  35. Vespa, P. M. et al. Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring. J. Neurosurg. 91, 750–760 (1999).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. Ronne-Engstrom, E. & Winkler, T. Continuous EEG monitoring in patients with traumatic brain injury reveals a high incidence of epileptiform activity. Acta Neurol. Scand. 114, 47–53 (2006).

    CAS  Article  PubMed  Google Scholar 

  37. Vespa, P. M. et al. Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis. Crit. Care Med. 35, 2830–2836 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Thapa, A. et al. Post-traumatic seizures — a prospective study from a tertiary level trauma center in a developing country. Seizure 19, 211–216 (2010).

    Article  PubMed  Google Scholar 

  39. Vespa, P. M. et al. Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy. Neurology 75, 792–798 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. Velioglu, S. K., Ozmenoglu, M., Boz, C. & Alioglu, Z. Status epilepticus after stroke. Stroke 32, 1169–1172 (2001).

    CAS  Article  PubMed  Google Scholar 

  41. Labovitz, D. L., Hauser, W. A. & Sacco, R. L. Prevalence and predictors of early seizure and status epilepticus after first stroke. Neurology 57, 200–206 (2001).

    CAS  Article  PubMed  Google Scholar 

  42. Waterhouse, E. J. et al. Synergistic effect of status epilepticus and ischemic brain injury on mortality. Epilepsy Res. 29, 175–183 (1998).

    CAS  Article  PubMed  Google Scholar 

  43. Claassen, J. et al. Electrographic seizures and periodic discharges after intracerebral hemorrhage. Neurology 69, 1356–1365 (2007).

    CAS  Article  PubMed  Google Scholar 

  44. De Herdt, V. et al. Early seizures in intracerebral hemorrhage: incidence, associated factors, and outcome. Neurology 77, 1794–1800 (2011).

    CAS  Article  PubMed  Google Scholar 

  45. Dennis, L. J. et al. Nonconvulsive status epilepticus after subarachnoid hemorrhage. Neurosurgery 51, 1136–1143 (2002).

    Article  PubMed  Google Scholar 

  46. Claassen, J. et al. Prognostic significance of continuous EEG monitoring in patients with poor-grade subarachnoid hemorrhage. Neurocrit. Care 4, 103–112 (2006).

    Article  PubMed  Google Scholar 

  47. Hart, Y. et al. Epilepsy after subarachnoid hemorrhage: the frequency of seizures after clip occlusion or coil embolization of a ruptured cerebral aneurysm. J. Neurosurg. 115, 1159–1168 (2011).

    Article  PubMed  Google Scholar 

  48. Little, A. S. et al. Nonconvulsive status epilepticus in patients suffering spontaneous subarachnoid hemorrhage. J. Neurosurg. 106, 805–811 (2007).

    Article  PubMed  Google Scholar 

  49. Rosengart, A. J. et al. Outcome in patients with subarachnoid hemorrhage treated with antiepileptic drugs. J. Neurosurg. 107, 253–260 (2007).

    Article  PubMed  Google Scholar 

  50. Lanzino, G. & Kassell, N. F. Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part II. A cooperative study in North America. J. Neurosurg. 90, 1018–1024 (1999).

    CAS  Article  PubMed  Google Scholar 

  51. Lanzino, G. et al. Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part I. A cooperative study in Europe, Australia, New Zealand, and South Africa. J. Neurosurg. 90, 1011–1017 (1999).

    CAS  Article  PubMed  Google Scholar 

  52. Haley, E. C. et al. A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in North America. J. Neurosurg. 86, 467–474 (1997).

    CAS  Article  PubMed  Google Scholar 

  53. Kassell, N. F., Haley, E. C. Jr, Apperson-Hansen, C. & Alves, W. M. Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand. J. Neurosurg. 84, 221–228 (1996).

    CAS  Article  PubMed  Google Scholar 

  54. Schmitt, S. E. et al. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 79, 1094–1100 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Gaspard, N. et al. New-onset refractory status epilepticus: etiology, clinical features, and outcome. Neurology 85, 1604–1613 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Thakur, K. T. et al. Predictors of outcome in acute encephalitis. Neurology 81, 793–800 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Claassen, J., Mayer, S. A., Kowalski, R. G., Emerson, R. G. & Hirsch, L. J. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 62, 1743–1748 (2004).

    CAS  Article  PubMed  Google Scholar 

  58. Rossetti, A. O., Oddo, M., Liaudet, L. & Kaplan, P. W. Predictors of awakening from postanoxic status epilepticus after therapeutic hypothermia. Neurology 72, 744–749 (2009).

    Article  PubMed  Google Scholar 

  59. Crepeau, A. Z. et al. Value analysis of continuous EEG in patients during therapeutic hypothermia after cardiac arrest. Resuscitation 5, 785–789 (2014).

    Article  Google Scholar 

  60. Fukuda, T., Matsubara, T., Doi, K., Fukuda-Ohashi, N. & Yahagi, N. Predictors of favorable and poor prognosis in unwitnessed out-of-hospital cardiac arrest with a non-shockable initial rhythm. Int. J. Cardiol. 176, 910–915 (2014).

    Article  PubMed  Google Scholar 

  61. Greer, D. et al. Clinical examination for outcome prediction in nontraumatic coma. Crit. Care Med. 40, 1150–1156 (2012).

    Article  PubMed  Google Scholar 

  62. Tsetsou, S., Oddo, M. & Rossetti, A. O. Clinical outcome after a reactive hypothermic EEG following cardiac arrest. Neurocrit. Care 19, 283–286 (2013).

    Article  PubMed  Google Scholar 

  63. 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).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Rossetti, A. O., Oddo, M., Logroscino, G. & Kaplan, P. W. Prognostication after cardiac arrest and hypothermia: a prospective study. Ann. Neurol. 67, 301–307 (2010).

    PubMed  Google Scholar 

  65. Claassen, J. et al. Recommendations on the use of EEG monitoring in critically ill patients: consensus statement from the neurointensive care section of the ESICM. Intensive Care Med. 39, 1337–1351 (2013).

    CAS  Article  PubMed  Google Scholar 

  66. Sutter, R., Rüegg, S. & Tschudin-Sutter, S. Seizures as adverse events of antibiotic drugs: a systematic review. Neurology 85, 1332–1341 (2015).

    CAS  Article  PubMed  Google Scholar 

  67. American Academy of Neurology. Clinical practice guideline process manual. [online], (2011).

  68. Kilickap, S. et al. Nonconvulsive status epilepticus due to ifosfamide. Ann. Pharmacother. 40, 332–335 (2006).

    CAS  Article  PubMed  Google Scholar 

  69. Patterson, D. M. et al. Nonconvulsive status epilepticus and leucoencephalopathy after high-dose methotrexate. J. Clin. Oncol. 29, e459–e461 (2011).

    Article  PubMed  Google Scholar 

  70. Bottaro, F. J., Martinez, O. A., Pardal, M. M., Bruetman, J. E. & Reisin, R. C. Nonconvulsive status epilepticus in the elderly: a case-control study. Epilepsia 48, 966–972 (2007).

    CAS  Article  PubMed  Google Scholar 

  71. Zak, R., Solomon, G., Petito, F. & Labar, D. Baclofen-induced generalized nonconvulsive status epilepticus. Ann. Neurol. 36, 113–114 (1994).

    CAS  Article  PubMed  Google Scholar 

  72. Kaplan, P. W. & Birbeck, G. Lithium-induced confusional states: nonconvulsive status epilepticus or triphasic encephalopathy? Epilepsia 47, 2071–2074 (2006).

    CAS  Article  PubMed  Google Scholar 

  73. Bertran, F., Denise, P. & Letellier, P. Nonconvulsive status epilepticus: the role of morphine and its antagonist. Neurophysiol. Clin. 30, 109–112 (2000).

    CAS  Article  PubMed  Google Scholar 

  74. Olnes, M. J., Golding, A. & Kaplan, P. W. Nonconvulsive status epilepticus resulting from benzodiazepine withdrawal. Ann. Intern. Med. 139, 956–958 (2003).

    Article  PubMed  Google Scholar 

  75. Emre, M., Walser, H. & Baumgartner, G. Non-convulsive status epilepticus after abrupt withdrawal of hypnotic-sedative drugs. Eur. Arch. Psychiatry Neurol. Sci. 235, 21–25 (1985).

    CAS  Article  PubMed  Google Scholar 

  76. Sutter, R., Rüegg, S. & Kaplan, P. W. Epidemiology, diagnosis, and management of nonconvulsive status epilepticus — opening Pandora's box. Neurol. Clin. Pract. 2, 275–286 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Walker, M. et al. Nonconvulsive status epilepticus: Epilepsy Research Foundation workshop reports. Epileptic Disord. 7, 253–296 (2005).

    PubMed  Google Scholar 

  78. Oddo, M. & Rossetti, A. O. Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia. Crit. Care Med. 42, 1340–1347 (2014).

    Article  PubMed  Google Scholar 

  79. Krumholz, A., Stern, B. J. & Weiss, H. D. Outcome from coma after cardiopulmonary resuscitation: relation to seizures and myoclonus. Neurology 38, 401–405 (1988).

    CAS  Article  PubMed  Google Scholar 

  80. Levy, D. E. et al. Predicting outcome from hypoxic–ischemic coma. JAMA 253, 1420–1426 (1985).

    CAS  Article  PubMed  Google Scholar 

  81. Snyder, B. D. et al. Neurologic prognosis after cardiopulmonary arrest: III. Seizure activity. Neurology 30, 1292–1297 (1980).

    CAS  Article  PubMed  Google Scholar 

  82. Zandbergen, E. G. et al. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology 66, 62–68 (2006).

    CAS  Article  PubMed  Google Scholar 

  83. Chen, R., Bolton, C. F. & Young, B. Prediction of outcome in patients with anoxic coma: a clinical and electrophysiologic study. Crit. Care Med. 24, 672–678 (1996).

    CAS  Article  PubMed  Google Scholar 

  84. Geocadin, R. G. et al. Neurologic prognosis and withdrawal of life support after resuscitation from cardiac arrest. Neurology 67, 105–108 (2006).

    CAS  Article  PubMed  Google Scholar 

  85. Bouwes, A. et al. Predictive value of neurological examination for early cortical responses to somatosensory evoked potentials in patients with postanoxic coma. J. Neurol. 259, 537–541 (2012).

    Article  PubMed  Google Scholar 

  86. Sutter, R. et al. Electroencephalography for diagnosis and prognosis of acute encephalitis. Clin. Neurophysiol. 126, 1524–1531 (2015).

    Article  PubMed  Google Scholar 

  87. Claassen, J. How I treat patients with EEG patterns on the ictal-interictal continuum in the neuro ICU. Neurocrit. Care 11, 437–444 (2009).

    Article  PubMed  Google Scholar 

  88. Koren, J. P. et al. Rhythmic and periodic EEG patterns of 'ictal–interictal uncertainty' in critically ill neurological patients. Clin. Neurophysiol. 127, 1176–1181 (2015).

    Article  PubMed  Google Scholar 

  89. Gaspard, N. et al. Interrater agreement for Critical Care EEG Terminology. Epilepsia 55, 1366–1373 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Stewart, C. P. et al. Seizure identification in the ICU using quantitative EEG displays. Neurology 75, 1501–1508 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  91. Sackellares, J. C., Shiau, D. S., Halford, J. J., LaRoche, S. M. & Kelly, K. M. Quantitative EEG analysis for automated detection of nonconvulsive seizures in intensive care units. Epilepsy Behav. 22 (Suppl. 1), S69–S73 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Herman, S. T. et al. Consensus statement on continuous EEG in critically ill adults and children, part I: indications. J. Clin. Neurophysiol. 32, 87–95 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Herman, S. T. et al. Consensus statement on continuous EEG in critically ill adults and children, part II: personnel, technical specifications, and clinical practice. J. Clin. Neurophysiol. 32, 96–108 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Burneo, J. G., Fang, J. & Saposnik, G. Impact of seizures on morbidity and mortality after stroke: a Canadian multi-centre cohort study. Eur. J. Neurol. 17, 52–58 (2010).

    CAS  Article  PubMed  Google Scholar 

  95. Bladin, C. F. et al. Seizures after stroke: a prospective multicenter study. Arch. Neurol. 57, 1617–1622 (2000).

    CAS  Article  PubMed  Google Scholar 

  96. Lason, W., Dudra-Jastrzebska, M., Rejdak, K. & Czuczwar, S. J. Basic mechanisms of antiepileptic drugs and their pharmacokinetic/pharmacodynamic interactions: an update. Pharmacol. Rep. 63, 271–292 (2011).

    CAS  Article  PubMed  Google Scholar 

  97. Treiman, D. M. et al. A comparison of four treatments for generalized convulsive status epilepticus. N. Engl. J. Med. 339, 792–798 (1998).

    CAS  Article  PubMed  Google Scholar 

  98. Prasad, M., Krishnan, P. R., Sequeira, R. & Al-Roomi, K. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst. Rev. 9, CD003723 (2014).

    Google Scholar 

  99. Meierkord, H. et al. EFNS guideline on the management of status epilepticus in adults. Eur. J. Neurol. 17, 348–355 (2010).

    CAS  Article  PubMed  Google Scholar 

  100. Thomas, P. et al. Nonconvulsive status epilepticus of frontal origin. Neurology 52, 1174–1183 (1999).

    CAS  Article  PubMed  Google Scholar 

  101. Scholtes, F. B., Renier, W. O. & Meinardi, H. Simple partial status epilepticus: causes, treatment, and outcome in 47 patients. J. Neurol. Neurosurg. Psychiatry 61, 90–92 (1996).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  102. Schwartz, M. S. & Scott, D. F. Isolated petit-mal status presenting de novo in middle age. Lancet 2, 1399–1401 (1971).

    CAS  Article  PubMed  Google Scholar 

  103. Tomson, T., Svanborg, E. & Wedlund, J. E. Nonconvulsive status epilepticus: high incidence of complex partial status. Epilepsia 27, 276–285 (1986).

    CAS  Article  PubMed  Google Scholar 

  104. Espay, A. J., Andrade, D. M., Wennberg, R. A. & Lang, A. E. Atypical absences and recurrent absence status in an adult with Angelman syndrome due to the UBE3A mutation. Epileptic Disord. 7, 227–230 (2005).

    PubMed  Google Scholar 

  105. Garmel, G. M., Jacobs, A. K. & Eilers, M. A. Tonic status epilepticus: an unusual presentation of unresponsiveness. Ann. Emerg. Med. 21, 223–227 (1992).

    CAS  Article  PubMed  Google Scholar 

  106. Shorvon, S. The management of status epilepticus. J. Neurol. Neurosurg. Psychiatry 70 (Suppl. 2), ii22–ii27 (2001).

    PubMed  PubMed Central  Google Scholar 

  107. Ostrow, L. W. & Kaplan, P. W. Tonic status and electrodecremental paroxysms in an adult without epilepsy. Epileptic Disord. 13, 99–101 (2011).

    PubMed  Google Scholar 

  108. Lee, S. I. Nonconvulsive status epilepticus. Ictal confusion in later life. Arch. Neurol. 42, 778–781 (1985).

    CAS  Article  PubMed  Google Scholar 

  109. Kutluay, E., Pakoz, B., Yuksel, A. & Beydoun, A. Nonconvulsive status epilepticus manifesting as pure alexia (alexia without agraphia). Epilepsy Behav. 10, 626–628 (2007).

    Article  PubMed  Google Scholar 

  110. Eue, S., Grumbt, M., Müller, M. & Schulze, A. Two years of experience in the treatment of status epilepticus with intravenous levetiracetam. Epilepsy Behav. 15, 467–469 (2009).

    CAS  Article  PubMed  Google Scholar 

  111. Rupprecht, S., Franke, K., Fitzek, S., Witte, O. W. & Hagemann, G. Levetiracetam as a treatment option in non-convulsive status epilepticus. Epilepsy Res. 73, 238–244 (2007).

    CAS  Article  PubMed  Google Scholar 

  112. Navarro, V. et al. Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial. Lancet Neurol. 15, 47–55 (2016).

    CAS  Article  PubMed  Google Scholar 

  113. Bleck, T. P. Refractory status epilepticus. Curr. Opin. Crit. Care 11, 117–120 (2005).

    Article  PubMed  Google Scholar 

  114. 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).

    CAS  Article  PubMed  Google Scholar 

  115. Rossetti, A. O., Logroscino, G. & Bromfield, E. B. Refractory status epilepticus: effect of treatment aggressiveness on prognosis. Arch. Neurol. 62, 1698–1702 (2005).

    Article  PubMed  Google Scholar 

  116. 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).

    CAS  Article  PubMed  Google Scholar 

  117. Guitton, C. et al. Propofol infusion syndrome during refractory status epilepticus in a young adult: successful ECMO resuscitation. Neurocrit. Care 15, 139–145 (2011).

    CAS  Article  PubMed  Google Scholar 

  118. Wong, J. M. Propofol infusion syndrome. Am. J. Ther. 17, 487–491 (2010).

    Article  PubMed  Google Scholar 

  119. Roberts, R. J. et al. Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study. Crit. Care 13, R169 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Krishnamurthy, K. B. & Drislane, F. W. Relapse and survival after barbiturate anesthetic treatment of refractory status epilepticus. Epilepsia 37, 863–867 (1996).

    CAS  Article  PubMed  Google Scholar 

  121. Stecker, M. M. et al. Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings. Epilepsia 39, 18–26 (1998).

    CAS  Article  PubMed  Google Scholar 

  122. Claassen, J. et al. Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology 57, 1036–1042 (2001).

    CAS  Article  PubMed  Google Scholar 

  123. Marchi, N. A. et al. Status epilepticus: impact of therapeutic coma on outcome. Crit. Care Med. 43, 1003–1009 (2015).

    Article  PubMed  Google Scholar 

  124. Rossetti, A. O. et al. Status Epilepticus Severity Score (STESS): a tool to orient early treatment strategy. J. Neurol. 255, 1561–1566 (2008).

    Article  PubMed  Google Scholar 

  125. Albers, J. M. et al. Intravenous lacosamide — an effective add-on treatment of refractory status epilepticus. Seizure 20, 428–430 (2011).

    Article  PubMed  Google Scholar 

  126. Sutter, R., Marsch, S. & Rüegg, S. Safety and efficacy of intravenous lacosamide for adjunctive treatment of refractory status epilepticus: a comparative cohort study. CNS Drugs 27, 321–329 (2013).

    CAS  Article  PubMed  Google Scholar 

  127. Hottinger, A., Sutter, R., Marsch, S. & Rüegg, S. Topiramate as an adjunctive treatment in patients with refractory status epilepticus: an observational cohort study. CNS Drugs 26, 761–772 (2012).

    CAS  Article  PubMed  Google Scholar 

  128. Kramer, A. H. Early ketamine to treat refractory status epilepticus. Neurocrit. Care 16, 299–305 (2012).

    Article  PubMed  Google Scholar 

  129. Synowiec, A. S. et al. Ketamine use in the treatment of refractory status epilepticus. Epilepsy Res. 105, 183–188 (2013).

    CAS  Article  PubMed  Google Scholar 

  130. Gaspard, N. et al. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study. Epilepsia 54, 1498–1503 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  131. Zeiler, F. A. Early use of the NMDA receptor antagonist ketamine in refractory and superrefractory status epilepticus. Crit. Care Res. Pract. 2015, 831260 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Fernandez, A. & Claassen, J. Refractory status epilepticus. Curr. Opin. Crit. Care 18, 127–131 (2012).

    Article  PubMed  Google Scholar 

  133. Thakur, K. T. et al. Ketogenic diet for adults in super-refractory status epilepticus. Neurology 82, 665–670 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  134. Sutter, R., Kaplan, P. W. & Rüegg, S. Outcome predictors for status epilepticus — what really counts. Nat. Rev. Neurol. 9, 525–534 (2013).

    Article  PubMed  Google Scholar 

  135. Wasterlain, C. G., Fujikawa, D. G., Penix, L. & Sankar, R. Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia 34 (Suppl. 1), S37–S53 (1993).

    Article  PubMed  Google Scholar 

  136. Fujikawa, D. G., Itabashi, H. H., Wu, A. & Shinmei, S. S. Status epilepticus-induced neuronal loss in humans without systemic complications or epilepsy. Epilepsia 41, 981–991 (2000).

    CAS  Article  PubMed  Google Scholar 

  137. Fernández-Torre, J. L. et al. Necrotizing leukoencephalopathy associated with nonconvulsive status epilepticus and periodic short-interval diffuse discharges: a clinicopathological study. Clin. EEG Neurosci. 37, 50–53 (2006).

    Article  PubMed  Google Scholar 

  138. 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).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  139. Kaplan, P. W. Assessing the outcomes in patients with nonconvulsive status epilepticus: nonconvulsive status epilepticus is underdiagnosed, potentially overtreated, and confounded by comorbidity. J. Clin. Neurophysiol. 16, 341–352 (1999).

    CAS  Article  PubMed  Google Scholar 

  140. Rossetti, A. O. et al. Status epilepticus: an independent outcome predictor after cerebral anoxia. Neurology 69, 255–260 (2007).

    CAS  Article  PubMed  Google Scholar 

  141. 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).

    CAS  Article  PubMed  Google Scholar 

  142. 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).

    CAS  Article  PubMed  Google Scholar 

  143. DeGiorgio, C. M. et al. Serum neuron-specific enolase in human status epilepticus. Neurology 45, 1134–1137 (1995).

    CAS  Article  PubMed  Google Scholar 

  144. 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).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  145. DeGiorgio, C. M. et al. Serum neuron-specific enolase in the major subtypes of status epilepticus. Neurology 52, 746–749 (1999).

    CAS  Article  PubMed  Google Scholar 

  146. Schmitt, B. & Bandtlow, C. Serum NSE in status epilepticus. Neurology 46, 1780–1781 (1996).

    CAS  Article  PubMed  Google Scholar 

  147. Kaplan, P. W. EEG criteria for nonconvulsive status epilepticus. Epilepsia 48 (Suppl. 8), 39–41 (2007).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

R.S. is supported by the Scientific Society Basel, the Gottfried and Julia Bangerter-Rhyner Foundation, and the Foundation of the University of Basel for promotion of science and young investigators, all in Switzerland. P.W.K. is funded by a Qatar Research Foundation grant to investigate continuous EEG monitoring in status epilepticus.

Author information

Authors and Affiliations

Authors

Contributions

R.S. and S.S. developed the concept of the Review, performed the literature search, and developed the tables and figures. All authors analyzed the data and wrote the manuscript. P.W.K. revised the manuscript before submission.

Corresponding author

Correspondence to Raoul Sutter.

Ethics declarations

Competing interests

R.S has received travel grants from UCB Pharma and holds shares in Roche and Novartis. S.S. and P.W.K. declare no competing interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sutter, R., Semmlack, S. & Kaplan, P. Nonconvulsive status epilepticus in adults — insights into the invisible. Nat Rev Neurol 12, 281–293 (2016). https://doi.org/10.1038/nrneurol.2016.45

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2016.45

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing