Current Neurology and Neuroscience Reports

, Volume 2, Issue 4, pp 345–356

The current state of treatment of status epilepticus

  • Lawrence J. Hirsch
  • Jan Claassen
Article
  • 93 Downloads

Abstract

There have been many important developments in the diagnosis and treatment of status epilepticus in the recent past. Earlier treatment, including at home by caregivers and in the field by paramedics, has been shown to be safe and effective. Rapid-acting anesthetic agents, such as midazolam and propofol, are being used more often for refractory status epilepticus, though clinical trials are lacking. Nonconvulsive status epilepticus is being considered and recognized more often, including in ambulatory patients with a confusional state, after convulsive status epilepticus, and in critically ill patients. Modern technology and continuous digital electroencephalogram (EEG) recordings have taught us many things, but have raised at least as many questions. Much work needs to be done regarding the significance of certain EEG patterns (particularly periodic discharges) and when and how to treat them. This article reviews these issues, concentrating on recent advances and practical issues related to the clinical care of patients with status epilepticus.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Working Group on Status Epilepticus: Treatment of convulsive status epilepticus: recommendations of the Epilepsy Foundation of America’s Working Group on Status Epilepticus. JAMA 1993, 270:854–859.CrossRefGoogle Scholar
  2. 2.
    Treiman DM, Meyers PD, Walton NY, et al.: A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med 1998, 339:792–798.PubMedCrossRefGoogle Scholar
  3. 3.
    Lowenstein DH: Status Epilepticus: an overview over the clinical problem. Epilepsia 1999, 40(suppl 1):S3-S8.PubMedCrossRefGoogle Scholar
  4. 4.
    Lowenstein DH, Bleck T, Macdonald RL: It’s time to revise the definition of status epilepticus. Epilepsia 1999, 40:120–122.PubMedCrossRefGoogle Scholar
  5. 5.
    Niedermeyer E, Ribeiro M: Considerations of nonconvulsive status epilepticus. Clin Electroencephalography 2000, 31:192–195.Google Scholar
  6. 6.
    Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA: Time trends in incidence, mortality, and case-fatality after first episode of status epilepticus. Epilepsia 2001, 42:1031–1035.PubMedCrossRefGoogle Scholar
  7. 7.
    Claassen J, Lokin JK, Fitzsimmons BF, Mendelsohn FA, Mayer SA: Predictors of functional disability and mortality after status epilepticus. Neurology 2002, 58:139–142.PubMedGoogle Scholar
  8. 8.
    Towne AR, Pellock JM, Ko D, DeLorenzo RJ: Determinants of mortality in status epilepticus. Epilepsia 1994, 35:27–34.PubMedCrossRefGoogle Scholar
  9. 9.
    Waterhouse EJ, Garnett LK, Towne AR, et al.: Prospective population-based study of intermittent and continuous convulsive status epilepticus in Richmond, Virginia. Epilepsia 1999, 40:752–758.PubMedCrossRefGoogle Scholar
  10. 10.
    DeLorenzo RJ, Hauser WA, Towne AR, et al.: A prospective, population-based epidemiological study of status epilepticus in Richmond, Virginia. Neurology 1996, 46:1029–1035.PubMedGoogle Scholar
  11. 11.
    Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA: Incidence of status epilepticus in Rochester, Minnesota, 1965–1984. Neurology 1998, 50:735–741.PubMedGoogle Scholar
  12. 12.
    Lowenstein DH, Alldredge BK: Status epilepticus at an urban public hospital in the 1980s. Neurology 1993, 43:483–488.PubMedGoogle Scholar
  13. 13.
    DeLorenzo RJ, Pellock JM, Towne AR, Boggs JG: Epidemiology of status epilepticus. J Clin Neurophysiol 1995, 12:316–325.PubMedGoogle Scholar
  14. 14.
    Cole AJ: Is epilepsy a progressive disease? The neurobiological consequences of epilepsy. Epilepsia 2000, 41(suppl 2):S13–22.PubMedCrossRefGoogle Scholar
  15. 15.
    Shorvon S: Prognosis and outcome of status epilepticus. In Status Epilepticus: Its Clinical Features and Treatment in Children and Adults. Edited by Shorvon S. Cambridge: Cambridge University Press; 1999:293–312.Google Scholar
  16. 16.
    Shorvon S: Emergency treatment of epilepsy: acute seizures, serial seizure clusters and status epilepticus. In Handbook of Epilepsy Treatment. Edited by Shorvon S. Oxford: Blackwell Science; 2000:173–194.Google Scholar
  17. 17.
    Wasterlain CG, Fujikawa DG, Penix L, Sankar R: Pathophysiologic mechanisms of brain damage from status epilepticus. Epilepsia 1993, 34(suppl 1):S37–53.PubMedGoogle Scholar
  18. 18.
    Mazarati AM, Baldwin RA, Sankar R, Wasterlain CG: Timedependent decrease in the effectiveness of antiepileptic drugs during the course of self-sustaining status epilepticus. Brain Res 1998, 814:179–185.PubMedCrossRefGoogle Scholar
  19. 19.
    Alldredge BK, Gelb AM, Isaacs SM, et al.: A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001, 345:631–637. This important study demonstrated that benzodiazepines were safe and effective when administered by paramedics for out-of-hospital status epilepticus in adults. It found that 59% of patients with status epilepticus treated with intravenous lorazepam in the field were no longer seizing by arrival at the emergency department (compared with 43% treated with intravenous diazepam and 21% treated with placebo).PubMedCrossRefGoogle Scholar
  20. 20.
    Lowenstein DH, Alldredge BK: Status epilepticus. N Engl J Med 1998, 338:970–976.PubMedCrossRefGoogle Scholar
  21. 21.
    Scott RC, Besag FM, Neville BG: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Lancet 1999, 353:623–626. This group studied seizures lasting greater than 5 minutes in a group of children with severe epilepsy, and found that outpatient treatment with buccal midazolam was slightly more effective than rectal diazepam (75% vs 59%; P=0.16). Buccal or intranasal medication is easier to administer and more socially acceptable, and should receive further attention in the near future.PubMedCrossRefGoogle Scholar
  22. 22.
    Camfield PR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial [commentary]. J Pediatr 1999, 135:398–399.PubMedGoogle Scholar
  23. 23.
    Scheepers M, Scheepers B, Clarke M, Comish S, Ibitoye M: Is intranasal midazolam an effective rescue medication in adolescents and adults with severe epilepsy? Seizure 2000, 9:417–422.PubMedCrossRefGoogle Scholar
  24. 24.
    Jeannet PY, Roulet E, Maeder-Ingvar M, et al.: Home and hospital treatment of acute seizures in children with nasal midazolam. Eur J Paediatr Neurol 1999, 3:73–77.PubMedCrossRefGoogle Scholar
  25. 25.
    Towne AR, DeLorenzo RJ: Use of intramuscular midazolam for status epilepticus. J Emerg Med 1999, 17:323–328.PubMedCrossRefGoogle Scholar
  26. 26.
    Chamberlain JM, Altieri MA, Futterman C, et al.: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatr Emerg Care 1997, 13:92–94.PubMedCrossRefGoogle Scholar
  27. 27.
    Dreifuss FE, Rosman NP, Cloyd JC, et al.: A comparison of rectal diazepam gel and placebo for acute repetitive seizures. N Engl J Med 1998, 338:1869–1875.PubMedCrossRefGoogle Scholar
  28. 28.
    Cereghino JJ, Mitchell WG, Murphy J, et al.: Treating repetitive seizures with a rectal diazepam formulation: a randomized study. The North American Diastat Study Group. Neurology 1998, 51:1274–1282.PubMedGoogle Scholar
  29. 29.
    Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M: Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. BMJ 2000, 321:83–86. This randomized study of prolonged febrile seizures found that seizures were terminated more quickly with intranasal midazolam than with intravenous diazepam, primarily due to more rapid administration. This treatment (nasal or buccal midazolam) may prove useful out of the hospital or in patients without intravenous access.PubMedCrossRefGoogle Scholar
  30. 30.
    DeLorenzo RJ, Waterhouse EJ, Towne AR, et al.: Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia 1998, 39:833–840.PubMedCrossRefGoogle Scholar
  31. 31.
    Towne AR, Waterhouse EJ, Boggs JG, et al.: Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology 2000, 54:340–345. The researchers found that among 236 comatose patients that had no current or past evidence of seizures, 8% showed electrographic seizures. Thus, any patient with unexplained coma should receive an electroencephalogram.PubMedGoogle Scholar
  32. 32.
    Shaner DM, McCurdy SA, Herring MO, Gabor AJ: Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Neurology 1988, 38:202–207.PubMedGoogle Scholar
  33. 33.
    Leppik IE, Derivan AT, Homan RW, et al.: Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 1983, 249:1452–1454.PubMedCrossRefGoogle Scholar
  34. 34.
    Karceski S, Morrell MJ: The expert consensus guideline series. Treatment of epilepsy. Epilepsy Behav 2001, 2:A1-A50.CrossRefGoogle Scholar
  35. 35.
    Treiman DM, Walton NY, Collins JF, Point P: Treatment of status epilepticus if first drug fails [abstract]. Epilepsia 1999, 40:243.Google Scholar
  36. 36.
    Mayer SA, Claassen J, Lokin J, Fitzsimmons BF, Mendehlson F: Predictors of refractory status epilepticus Arch Neurol 2002, in press.Google Scholar
  37. 37.
    Bleck TP: Advances in the management of refractory status epilepticus. Crit Care Med 1993, 21:955–957.PubMedCrossRefGoogle Scholar
  38. 38.
    Claassen J, Hirsch LJ, Emerson RG, et al.: Continuous EEG monitoring and midazolam infusion for nonconvulsive refractory status epilepticus. Neurology 2001, 57:1036–1042. A large, single-center study of 33 patients with refractory status epilepticus treated with midazolam and receiving prolonged, continuous electroencephalogram (EEG) monitoring. Although very effective at stopping seizures, breakthrough and withdrawal seizures were quite common; most of these were subclinical, stressing the importance of continuous EEG monitoring in these patients.PubMedGoogle Scholar
  39. 39.
    Claassen J, Hirsch LJ, Emerson RG, Mayer SA: Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 2002, in press. An exhaustive, systematic review of the world’s literature on this topic. Pentobarbital titrated to suppression-burst appeared more effective, but more toxic, when compared with midazolam and propofol titrated to seizure suppression. Half the patients died in all three groups. This leaves plenty of uncertainty, and plenty of room for "clinical judgment" when choosing one of these treatments.Google Scholar
  40. 40.
    Prasad A, Worrall BB, Bertram EH, Bleck TP: Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia 2001, 42:380–386.PubMedCrossRefGoogle Scholar
  41. 41.
    Naritoku DK, Sinha S: Prolongation of midazolam half-life after sustained infusion for status epilepticus. Neurology 2000, 54:1366–1368.PubMedGoogle Scholar
  42. 42.
    Stecker MM, Kramer TH, Raps EC, et al.: Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings. Epilepsia 1998, 39:18–26.PubMedCrossRefGoogle Scholar
  43. 43.
    Yaffe K, Lowenstein DH: Prognostic factors of pentobarbital therapy for refractory generalized status epilepticus. Neurology 1993, 43:895–900.PubMedGoogle Scholar
  44. 44.
    Brown LA, Levin GM: Role of propofol in refractory status epilepticus. Ann Pharmacother 1998, 32:1053–1059.PubMedCrossRefGoogle Scholar
  45. 45.
    Limdi NA, Faught E: The safety of rapid valproic acid infusion. Epilepsia 2000, 41:1342–1345.PubMedGoogle Scholar
  46. 46.
    Sinha S, Naritoku DK: Intravenous valproate is well tolerated in unstable patients with status epilepticus. Neurology 2000, 55:722–724.PubMedGoogle Scholar
  47. 47.
    Naritoku DK, Mueed S: Intravenous loading of valproate for epilepsy. Clin Neuropharmacol 1999, 22:102–106.PubMedCrossRefGoogle Scholar
  48. 48.
    Venkataraman V, Wheless JW: Safety of rapid intravenous infusion of valproate loading doses in epilepsy patients. Epilepsy Res 1999, 35:147–153.PubMedCrossRefGoogle Scholar
  49. 49.
    White JR, Santos CS: Intravenous valproate associated with significant hypotension in the treatment of status epilepticus. J Child Neurol 1999, 14:822–823.PubMedGoogle Scholar
  50. 50.
    Hanna JP, Ramundo ML: Rhabdomyolysis and hypoxia associated with prolonged propofol infusion in children. Neurology 1998, 50:301–303.PubMedGoogle Scholar
  51. 51.
    Lisanby SH, Bazil CW, Resor SR, et al.: ECT in the treatment of status epilepticus. J ECT 2001, 17:210–215.PubMedCrossRefGoogle Scholar
  52. 52.
    Griesemer DA, Kellner CH, Beale MD, Smith GM: Electroconvulsive therapy for treatment of intractable seizures. Initial findings in two children. Neurology 1997, 49:1389–1392.PubMedGoogle Scholar
  53. 53.
    Ma X, Liporace J, O’Connor MJ, Sperling MR: Neurosurgical treatment of medically intractable status epilepticus. Epilepsy Res 2001, 46:33–38.PubMedCrossRefGoogle Scholar
  54. 54.
    Niebauer M, Gruenthal M: Topiramate reduces neuronal injury after experimental status epilepticus. Brain Res 1999, 837:263–269.PubMedCrossRefGoogle Scholar
  55. 55.
    Klitgaard H: Levetiracetam: the preclinical profile of a new class of antiepileptic drugs? Epilepsia 2001, 42(suppl 4):13–18.PubMedGoogle Scholar
  56. 56.
    Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA: Short-term mortality after a first episode of status epilepticus. Epilepsia 1997, 38:1344–1349.PubMedCrossRefGoogle Scholar
  57. 57.
    Young GB: An assessment of nonconvulsive seizures in the ICU using continuous EEG monitoring: an investigation of variables associated with mortality. Neurology 1996, 47:83–89.PubMedGoogle Scholar
  58. 58.
    Oxbury JM, Whitty CW: Causes and consequences of status epilepticus in adults. A study of 86 cases. Brain 1971, 94:733–744.PubMedCrossRefGoogle Scholar
  59. 59.
    Aminoff MJ, Simon RP: Status epilepticus: causes, clinical features and consequences in 98 patients. Am J Med 1980, 69:657–666.PubMedCrossRefGoogle Scholar
  60. 60.
    Jaitly R, Sgro JA, Towne AR, Ko D, DeLorenzo RJ: Prognostic value of EEG monitoring after status epilepticus: a prospective adult study. J Clin Neurophys 1997, 14:326–334.CrossRefGoogle Scholar
  61. 61.
    Nei M, Lee JM, Shanker VL, Sperling MR: The EEG and prognosis in status epilepticus. Epilepsia 1999, 40:157–163.PubMedCrossRefGoogle Scholar
  62. 62.
    Kaplan PW: Nonconvulsive status epilepticus in the emergency room. Epilepsia 1996, 37:643–650.PubMedCrossRefGoogle Scholar
  63. 63.
    Krumholz A, Sung GY, Fisher RS, et al.: Complex partial status epilepticus accompanied by serious morbidity and mortality. Neurology 1995, 45:1499–1504.PubMedGoogle Scholar
  64. 64.
    Shneker BF, Fountain NB: Epilepsy as chronic sequel of nonconvulsive status epilepticus [abstract]. Epilepsia 2001, 42:147.Google Scholar
  65. 65.
    Treiman DM: Electroclinical features of status epilepticus. J Clin Neurophys 1995, 12:343–362.CrossRefGoogle Scholar
  66. 66.
    Garzon E, Fernandes RM, Sakamoto AC: Serial EEG during human status epilepticus: evidence for PLED as an ictal pattern. Neurology 2001, 57:1175–1183.PubMedGoogle Scholar
  67. 67.
    Pohlmann-Eden B, Hoch DB, Cochius JI, Chiappa KH: Periodic lateralized epileptiform discharges—a critical review. J Clin Neurophysiol 1996, 13:519–530.PubMedCrossRefGoogle Scholar
  68. 68.
    Husain AM, Mebust KA, Radtke RA: Generalized periodic epileptiform discharges: etiologies, relationship to status epilepticus, and prognosis. J Clin Neurophysiol 1999, 16:51–58.PubMedCrossRefGoogle Scholar
  69. 69.
    Treiman DM, Walton NY, Kendrick C: A progressive sequence of electroencephalographic changes during generalized convulsive status epilepticus. Epilepsy Res 1990, 5:49–60.PubMedCrossRefGoogle Scholar
  70. 70.
    Assal F, Papazyan JP, Slosman DO, Jallon P, Goerres GW: SPECT in periodic lateralized epileptiform discharges (PLEDs): a form of partial status epilepticus? Seizure 2001, 10:260–265.PubMedCrossRefGoogle Scholar
  71. 71.
    Handforth A, Cheng JT, Mandelkern MA, Treiman DM: Markedly increased mesiotemporal lobe metabolism in a case with PLEDs: further evidence that PLEDs are a manifestation of partial status epilepticus. Epilepsia 1994, 35:876–881.PubMedCrossRefGoogle Scholar
  72. 72.
    Kaplan PW: Assessing the outcomes in patients with nonconvulsive status epilepticus: NCSE is underdiagnosed, potentially overtreated, and confounded by comorbidity. J Clin Neurophysiol 1999, 16:341–352. Excellent review.PubMedCrossRefGoogle Scholar
  73. 73.
    Reiher J, Rivest J, Grand’Maison F, Leduc CP: Periodic lateralized epileptiform discharges with transitional rhythmic discharges: association with seizures. Electroencephalogr Clin Neurophysiol 1991, 78:12–17.PubMedCrossRefGoogle Scholar
  74. 74.
    Grand’Maison F, Reiher J, Leduc CP: Retrospective inventory of EEG abnormalities in partial status epilepticus. Electroencephalogr Clin Neurophysiol 1991, 79:264–270.PubMedCrossRefGoogle Scholar
  75. 75.
    Litt B, Wityk RJ, Hertz SH: Nonconvulsive status epilepticus in the critically ill elderly. Epilepsia 1998, 39:1194–1202.PubMedCrossRefGoogle Scholar
  76. 76.
    Van Cott AC, Blatt I, Brenner RP: Stimulus-sensitive seizures in postanoxic coma. Epilepsia 1996, 37:868–874.PubMedCrossRefGoogle Scholar
  77. 77.
    Young GB, Campbell VC: EEG monitoring in the intensive care unit: pitfalls and caveats. J Clin Neurophysiol 1999, 16:40–45.PubMedCrossRefGoogle Scholar
  78. 78.
    Jordan KG: Continuous EEG and evoked potential monitoring in the neuroscience intensive care unit. J Clin Neurophysiol 1993, 10:445–475.PubMedCrossRefGoogle Scholar
  79. 79.
    Jordan K: Continuous EEG monitoring in the Neuroscience ICU and ED. J Clin Neurophysiol 1999, 16:14–39. Excellent review.PubMedCrossRefGoogle Scholar
  80. 80.
    Vespa PM, Nuwer MR, Nenov V, et al.: Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring. J Neurosurg 1999, 91:750–760.PubMedGoogle Scholar

Copyright information

© Current Science Inc. 2002

Authors and Affiliations

  • Lawrence J. Hirsch
    • 1
  • Jan Claassen
    • 1
  1. 1.Comprehensive Epilepsy Center, Columbia University Neurological InstituteNew YorkUSA

Personalised recommendations