Skip to main content

Advertisement

SpringerLink
Log in

Status Epilepticus: an Overview for Neuroscientists

  • Neuropharmacology (G Aston-Jones, Section Editor)
  • Published:
Current Pharmacology Reports Aims and scope Submit manuscript

Abstract

Recent Findings

Evidences suggest the pathophysiological role of GABA, glutamate, inflammatory cascade, hypoxia, etc. in the development of status epilepticus (SE). But the exact understanding of SE seizure is still unknown.

Purpose of Review

SE is a lethal neurological disorder that is associated with elevated rates of mortality and morbidity. SE is demarcated by recurring seizures caused by a failure of mechanisms responsible for the termination of seizures or from the initiation of mechanisms, which lead to abnormally, persistent seizures after time point (t1). Long-term consequences are spotted in this condition after time point (t2), together with the death of neurons, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. Clinically first-line treatment with benzodiazepines is given for seizure inhibition. But in severe cases, these drugs are not efficient for treatment. The unavailability of viable medications to halt the onset and progression of the condition could be due to a lack of understanding of the pathophysiological mechanism. Due to the complexity of the brain, it is very difficult to understand exact pathways; thorough understanding of pathophysiology would be beneficial in designing new drug regimen for patients.

Summary

This review paper emphasizes on pathophysiology, etiology, diagnostic parameters, and drugs used in the secession of seizures promptly, which would be helpful for the development of effective therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

SE:

Status epilepticus

CSE:

Convulsive SE

ESE:

Established SE

RSE:

Refractory SE

FSE:

Focal SE

SRSE:

Super RSE

GCSE:

Generalized CSE

GABA:

Gamma-aminobutyric acid

NMDA:

N-methyl-D-aspartate

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

NKCC:

Na-K-Cl cotransporter

CNS:

Central nervous system

AEDs:

Antiepileptic drugs

CT:

Computed tomography

cEEG:

Continuous electroencephalogram

NCSE:

Non-CSE

IVAD:

Implantable ventricular assist device

qEEG:

Quantitative EEG

NRSE:

Non-RSE

ICU:

Intensive care unit

MRI:

Magnetic resonance imaging

References

  1. Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon S, Lowenstein DH. A definition and classification of status epilepticus–report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56(10):1515–23. https://doi.org/10.1111/epi.13121.

    Article  PubMed  Google Scholar 

  2. Guterman EL, Burke JF, Sporer KA. Prehospital treatment of status epilepticus in the United States. JAMA. 2021;326(19):1970–1.

    Article  CAS  Google Scholar 

  3. Lee SK. Diagnosis and treatment of status epilepticus. J Epilepsy Res. 2020;10(2):45–54.

    Article  Google Scholar 

  4. Johnson EL, Kaplan PW. Status epilepticus: definition, classification, pathophysiology, and epidemiology. Semin Neurol. 2020;40:647–51. https://doi.org/10.1055/s-0040-1718722.

    Article  PubMed  Google Scholar 

  5. Rossetti AO, Alvarez V. Update on the management of status epilepticus. Curr Opin Neurol. 2021;34(2):172–81. https://doi.org/10.1097/WCO.0000000000000899.

    Article  PubMed  Google Scholar 

  6. Claassen J, Goldstein JN. Emergency neurological life support: status epilepticus. Neurocrit Care. 2017;27(1):152–8. https://doi.org/10.1007/s12028-017-0460-1.

    Article  PubMed  Google Scholar 

  7. Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, Bare M, Bleck T, Dodson WE, Garrity L, Jagoda A. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48–61. https://doi.org/10.5698/1535-7597-16.1.48.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hirsch LJ, Gaspard N, van Baalen A, Nabbout R, Demeret S, Loddenkemper T, Navarro V, Specchio N, Lagae L, Rossetti AO, Hocker S. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia. 2018;59(4):739–44. https://doi.org/10.1111/epi.14016.

    Article  PubMed  Google Scholar 

  9. DeLorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy L, Garnett L, Fortner CA, Ko D. A prospective, population-based epidemiologic study of status epilepticus in Richmond,Virginia. Neurology. 1996;46(4):1029–35. https://doi.org/10.1212/WNL.46.4.1029.

    Article  CAS  PubMed  Google Scholar 

  10. Lv RJ, Wang Q, Cui T, Zhu F, Shao XQ. Status epilepticus-related etiology, incidence and mortality: a meta-analysis. Epilepsy Res. 2017;136:12–7. https://doi.org/10.1016/j.eplepsyres.2017.07.006.

    Article  PubMed  Google Scholar 

  11. Tiamkao S, Pranbul S, Sawanyawisuth K, Thepsuthammarat K. Integrated Epilepsy Research Group. A national database of incidence and treatment outcomes of status epilepticus in Thailand. Int J Neurosci. 2014;124(6):416–20. https://doi.org/10.3109/00207454.2013.850084.

    Article  PubMed  Google Scholar 

  12. Al-Sofyani KA. An insight into the current understanding of status epilepticus: from concept to management. Neurol Res Int. 2021. https://doi.org/10.1155/2021/9976754.

  13. Paris M, Reddy U. Update on the management of status epilepticus. Anaesth Intensive Care Med. 2018;19(3):83–6. https://doi.org/10.1016/j.mpaic.2017.12.008.

    Article  Google Scholar 

  14. Cock HR. Drug-induced status epilepticus. Epilepsy Behav. 2015;49:76–82. https://doi.org/10.1016/j.yebeh.2015.04.034.

    Article  PubMed  Google Scholar 

  15. Goodkin HP, Yeh JL, Kapur J. Status epilepticus increases the intracellular accumulation of GABAA receptors. J Neurosci. 2005;25(23):5511–20. https://doi.org/10.1523/JNEUROSCI.0900-05.2005.

    Article  CAS  PubMed  Google Scholar 

  16. Naylor DE, Liu H, Wasterlain CG. Trafficking of GABAA receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci. 2005;25(34):7724–33. https://doi.org/10.1523/JNEUROSCI.4944-04.2005.

    Article  CAS  PubMed  Google Scholar 

  17. Naylor DE, Liu H, Niquet J, Wasterlain CG. Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus. Neurobiol Dis. 2013;54:225–38. https://doi.org/10.1016/j.nbd.2012.12.015.

    Article  CAS  PubMed  Google Scholar 

  18. Naylor DE. Glutamate and GABA in the balance: convergent pathways sustain seizures during status epilepticus. Epilepsia. 2010;51:106–9. https://doi.org/10.1111/j.1528-1167.2010.02622.x.

    Article  CAS  PubMed  Google Scholar 

  19. Brooks-Kayal AR, Pritchett DB. Developmental changes in human γ-aminobutyric acida receptor subunit composition. Ann Neurol. 1993;34(5):687–93. https://doi.org/10.1002/ana.410340511.

    Article  CAS  PubMed  Google Scholar 

  20. Kumar SS, Bacci A, Kharazia V, Huguenard JR. A developmental switch of AMPA receptor subunits in neocortical pyramidal neurons. J Neurosci. 2002;22(8):3005–15. https://doi.org/10.1523/JNEUROSCI.22-08-03005.2002.

    Article  CAS  PubMed  Google Scholar 

  21. Crino PB, Duhaime AC, Baltuch G, White R. Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical dysplasia. Neurology. 2001;56(7):906–13. https://doi.org/10.1212/WNL.56.7.906.

    Article  CAS  PubMed  Google Scholar 

  22. Loddenkemper T, Talos DM, Cleary RT, Joseph A, Fernández IS, Alexopoulos A, Kotagal P, Najm I, Jensen FE. Subunit composition of glutamate and gamma-aminobutyric acid receptors in status epilepticus. Epilepsy Res. 2014;108(4):605–15. https://doi.org/10.1016/j.eplepsyres.2014.01.015.

    Article  CAS  PubMed  Google Scholar 

  23. Dzhala VI, Talos DM, Sdrulla DA, Brumback AC, Mathews GC, Benke TA, Delpire E, Jensen FE, Staley KJ. NKCC1 transporter facilitates seizures in the developing brain. Nat Med. 2005;11(11):1205–13. https://doi.org/10.1038/nm1301.

    Article  CAS  PubMed  Google Scholar 

  24. Rakhade SN, Jensen FE. Epileptogenesis in the immature brain: emerging mechanisms. Nat Rev Neurol. 2009;5(7):380. https://doi.org/10.1038/nrneurol.2009.80.

    Article  CAS  PubMed  Google Scholar 

  25. Rakhade SN, Zhou C, Aujla PK, Fishman R, Sucher NJ, Jensen FE. Early alterations of AMPA receptors mediate synaptic potentiation induced by neonatal seizures. J Neurosci. 2008;28(32):7979–90. https://doi.org/10.1523/JNEUROSCI.1734-08.2008.

    Article  CAS  PubMed  Google Scholar 

  26. Van Vliet EA, da Costa AS, Redeker S, Van Schaik R, Aronica E, Gorter JA. Blood–brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain. 2007;130(2):521–34. https://doi.org/10.1093/brain/awl318.

    Article  PubMed  Google Scholar 

  27. Han H, Mann A, Ekstein D, Eyal S. Breaking bad: the structure and function of the blood-brain barrier in epilepsy. AAPS J. 2017;19(4):973–88. https://doi.org/10.1208/s12248-017-0096-2.

    Article  CAS  PubMed  Google Scholar 

  28. Nadal A, Fuentes E, McNaughton PA. Glial cell responses to lipids bound to albumin in serum and plasma. Prog Brain Res. 2001;132:367–74. https://doi.org/10.1016/S0079-6123(01)32088-5.

    Article  CAS  PubMed  Google Scholar 

  29. Ranaivo HR, Wainwright MS. Albumin activates astrocytes and microglia through mitogen-activated protein kinase pathways. Brain Res. 2010;1313:222–31. https://doi.org/10.1016/j.brainres.2009.11.063.

    Article  CAS  Google Scholar 

  30. Cacheaux LP, Ivens S, David Y, Lakhter AJ, Bar-Klein G, Shapira M, Heinemann U, Friedman A, Kaufer D. Transcriptome profiling reveals TGF-β signaling involvement in epileptogenesis. J Neurosci. 2009;29(28):8927–35. https://doi.org/10.1523/JNEUROSCI.0430-09.2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Vezzani A, Friedman A, Dingledine RJ. The role of inflammation in epileptogenesis. Neuropharmacology. 2013;69:16–24. https://doi.org/10.1016/j.neuropharm.2012.04.004.

    Article  CAS  PubMed  Google Scholar 

  32. Van Vliet EA, Aronica E, Vezzani A, Ravizza T. Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies. Neuropathol Appl Neurobiol. 2018;44(1):91–111. https://doi.org/10.1111/nan.12444.

    Article  PubMed  Google Scholar 

  33. Dey A, Kang X, Qiu J, Du Y, Jiang J. Anti-inflammatory small molecules to treat seizures and epilepsy: from bench to bedside. Trends Pharmacol Sci. 2016;37(6):463–84. https://doi.org/10.1016/j.tips.2016.03.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bankstahl JP, Löscher W. Resistance to antiepileptic drugs and expression of P-glycoprotein in two rat models of status epilepticus. Epilepsy Res. 2008;82(1):70–85. https://doi.org/10.1016/j.eplepsyres.2008.07.007.

    Article  CAS  PubMed  Google Scholar 

  35. Amengual-Gual M, Fernández IS, Wainwright MS. Novel drugs and early polypharmacotherapy in status epilepticus. Seizure. 2019;68:79–88. https://doi.org/10.1016/j.seizure.2018.08.004.

    Article  PubMed  Google Scholar 

  36. Al-Mufti F, Claassen J. Neurocritical care: status epilepticus review. Crit Care Clin. 2014;30(4):751–64. https://doi.org/10.1016/j.ccc.2014.06.006.

    Article  PubMed  Google Scholar 

  37. Marawar R, Basha M, Mahulikar A, Desai A, Suchdev K, Shah A. Updates in refractory status epilepticus. Crit Care Res Pract. 2018;2018:9768949. https://doi.org/10.1155/2018/9768949.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, LaRoche SM, Riviello JJ, Shutter L, Sperling MR, Treiman DM. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3–23. https://doi.org/10.1007/s12028-012-9695-z.

    Article  PubMed  Google Scholar 

  39. Basha MM, Alqallaf A, Shah AK. Drug-induced EEG pattern predicts effectiveness of ketamine in treating refractory status epilepticus. Epilepsia. 2015;56(4):e44–8. https://doi.org/10.1111/epi.1294.

    Article  CAS  PubMed  Google Scholar 

  40. Haider HA, Esteller R, Hahn CD, Westover MB, Halford JJ, Lee JW, Shafi MM, Gaspard N, Herman ST, Gerard EE, Hirsch LJ. Sensitivity of quantitative EEG for seizure identification in the intensive care unit. Neurology. 2016;87(9):935–44. https://doi.org/10.1212/WNL.0000000000003034.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Stewart CP, Otsubo H, Ochi A, Sharma R, Hutchison JS, Hahn CD. Seizure identification in the ICU using quantitative EEG displays. Neurology. 2010;75(17):1501–8. https://doi.org/10.1212/WNL.0b013e3181f9619e.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nair PP, Kalita J, Misra UK. Role of cranial imaging in epileptic status. Eur J Radiol. 2009;70(3):475–80. https://doi.org/10.1016/j.ejrad.2008.02.007.

    Article  PubMed  Google Scholar 

  43. Legriel S, Bruneel F, Dalle L, Appere-de-Vecchi C, Georges JL, Abbosh N, Henry-Lagarrigue M, D’Allonnes LR, Mokhtar HB, Audibert J, Guezennec P. Recurrent takotsubo cardiomyopathy triggered by convulsive status epilepticus. Neurocrit Care. 2008;9(1):118–21. https://doi.org/10.1007/s12028-008-9107-6.

    Article  PubMed  Google Scholar 

  44. Bleck TP. Convulsive disorders: status epilepticus. Clin Neuropharmacol. 1991;14(3):191–8. https://doi.org/10.1097/00002826-199106000-00001.

    Article  CAS  PubMed  Google Scholar 

  45. Legriel S, Mourvillier B, Bele N, Amaro J, Fouet P, Manet P, Hilpert F. Outcomes in 140 critically ill patients with status epilepticus. Intensive Care Med. 2008;34(3):476–80. https://doi.org/10.1007/s00134-007-0915-5.

    Article  PubMed  Google Scholar 

  46. Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determinants of mortality in status epilepticus. Epilepsia. 1994;35(1):27–34. https://doi.org/10.1111/j.1528-1157.1994.tb02908.x.

    Article  CAS  PubMed  Google Scholar 

  47. Giovannini G, Monti G, Polisi MM, Mirandola L, Marudi A, Pinelli G, Valzania F, Girardis M, Nichelli PF, Meletti S. A one-year prospective study of refractory status epilepticus in Modena. Italy Epilepsy Behav. 2015;49:141–5. https://doi.org/10.1016/j.yebeh.2015.05.022.

    Article  PubMed  Google Scholar 

  48. Biton V, Rosenfeld WE, Whitesides J, Fountain NB, Vaiciene N, Rudd GD. Intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures. Epilepsia. 2008;49(3):418–24. https://doi.org/10.1111/j.1528-1167.2007.01317.x.

    Article  CAS  PubMed  Google Scholar 

  49. Rowland AG, Gill AM, Stewart AB, Appleton RE, Al Kharusi A, Cramp C, Yeung LK. Review of the efficacy of rectal paraldehyde in the management of acute and prolonged tonic–clonic convulsions. Arch Dis Child. 2009;94(9):720–3. https://doi.org/10.1136/adc.2009.157636.

    Article  CAS  PubMed  Google Scholar 

  50. Kobayashi O, Iwasaki Y, Yamanouchi H, Sugai K. A case of refractory status epilepticus associated with aberrant intracranial shunt tube: efficacy of lidocaine in the determination of the epileptic focus. Brain Dev. 1994;26(4):329–34.

    CAS  Google Scholar 

  51. Franco V, Iudice A, Grillo E, Citraro R, De Sarro G, Russo E. Perspective on the use of perampanel and intravenous carbamazepine for generalized seizures. Expert Opin Pharmacother. 2014;15(5):637–44. https://doi.org/10.1517/14656566.2014.879572.

    Article  CAS  PubMed  Google Scholar 

  52. Miller P, Kovar I. Chlormethiazole in the treatment of neonatal status epilepticus. Postgrad Med. 1983;59(698):801–2. https://doi.org/10.1136/pgmj.59.698.801.

    Article  CAS  Google Scholar 

  53. Derivan AT, Homan RW, Walker J, Ramsay RE, Patrick B. Double-blind study of lorazepam and diazepam in status epilepticus. Jama. 1983;249(11):1452–4. https://doi.org/10.1001/jama.1983.03330350028021.

    Article  PubMed  Google Scholar 

  54. Trinka E Benzodiazepines used primarily for emergency treatment (diazepam, lorazepam and midazolam). The treatment of epilepsy. 2009 431-46. https://doi.org/10.1002/9781444316667.ch34.

  55. Congdon PJ, Forsythe WI. Intravenous clonazepam in the treatment of status epilepticus in children. Epilepsia. 1980;21(1):97–102. https://doi.org/10.1111/j.1528-1157.1980.tb04049.x.

    Article  CAS  PubMed  Google Scholar 

  56. Burneo JG, Anandan JV, Barkley GL. A prospective study of the incidence of the purple glove syndrome. Epilepsia. 2001;42(9):1156–9. https://doi.org/10.1046/j.1528-1157.2001.12901.x.

    Article  CAS  PubMed  Google Scholar 

  57. Perucca E. Pharmacological and therapeutic properties of valproate. CNS Drugs. 2002;16(10):695–714. https://doi.org/10.2165/00023210-200216100-00004.

    Article  CAS  PubMed  Google Scholar 

  58. Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, Handforth A, Faught E, Calabrese VP, Uthman BM, Ramsay RE. A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med. 1998;339(12):792–8. https://doi.org/10.1056/NEJM199809173391202.

    Article  CAS  PubMed  Google Scholar 

  59. Singhi S, Murthy A, Singhi P, Jayashree M. Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus. J Child Neurol. 2002;17(2):106–10. https://doi.org/10.1177/088307380201700203.

    Article  PubMed  Google Scholar 

  60. Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639–49. https://doi.org/10.2174/1381612043382846.

    Article  CAS  PubMed  Google Scholar 

  61. Rossetti AO, Milligan TA, Vulliémoz S, Michaelides C, Bertschi M, Lee JW. A randomized trial for the treatment of refractory status epilepticus. Neurocrit Care. 2011;14(1):4–10. https://doi.org/10.1007/s12028-010-9445-z.

    Article  CAS  PubMed  Google Scholar 

  62. Rossetti AO. Novel anesthetics and other treatment strategies for refractory status epilepticus. Epilepsia. 2009;50(Suppl 12):51–3. https://doi.org/10.1111/j.1528-1167.2009.02369.x.

    Article  PubMed  Google Scholar 

  63. Mirsattari SM, Sharpe MD, Young GB. Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane. Arch Neurol. 2004;61(8):1254–9. https://doi.org/10.1001/archneur.61.8.1254.

    Article  PubMed  Google Scholar 

  64. Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011;134(10):2802–18. https://doi.org/10.1093/brain/awr215.

    Article  PubMed  Google Scholar 

  65. Borris DJ, Bertram EH, Kapur J. Ketamine controls prolonged status epilepticus. Epilepsy Res. 2000;42(2-3):117–22. https://doi.org/10.1016/S0920-1211(00)00175-3.

    Article  CAS  PubMed  Google Scholar 

  66. Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000;41:3–9. https://doi.org/10.1111/j.1528-1157.2000.tb02163.x.

    Article  CAS  PubMed  Google Scholar 

  67. Gaspard N, Foreman B, Judd LM, Brenton JN, Nathan BR, McCoy BM, Al-Otaibi A, Kilbride R, Fernández IS, Mendoza L, Samuel S. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study. Epilepsia. 2013;54(8):1498–503. https://doi.org/10.1111/epi.12247.

    Article  CAS  PubMed  Google Scholar 

  68. Reddy DS. Neurosteroids: endogenous role in the human brain and therapeutic potentials. Prog Brain Res. 2010;186:113–37. https://doi.org/10.1016/B978-0-444-53630-3.00008-7.

    Article  CAS  PubMed  Google Scholar 

  69. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia. 1993;34(3):453–8. https://doi.org/10.1111/j.1528-1157.1993.tb02586.x.

    Article  CAS  PubMed  Google Scholar 

  70. McHugh JC, Delanty N. Epidemiology and classification of epilepsy: gender comparisons. Int Rev Neurobiol. 2008;83:11–26. https://doi.org/10.1016/S0074-7742(08)00002-0.

    Article  PubMed  Google Scholar 

  71. Frye CA. Hormonal influences on seizures: basic neurobiology. Int Rev Neurobiol. 2008;83:27–77. https://doi.org/10.1016/S0074-7742(08)00003-2.

    Article  PubMed  Google Scholar 

  72. Herzog AG. Catamenial epilepsy: update on prevalence, pathophysiology and treatment from the findings of the NIH Progesterone Treatment Trial. Seizure. 2015;28:18–25. https://doi.org/10.1016/j.seizure.2015.02.024.

    Article  PubMed  Google Scholar 

  73. Reddy DS, Estes WA. Clinical potential of neurosteroids for CNS disorders. Trends Pharmacol Sci. 2016;37(7):543–61. https://doi.org/10.1016/j.tips.2016.04.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Reddy D. Role of hormones and neurosteroids in epileptogenesis. Front Cell Neurosci. 2013;7:115. https://doi.org/10.3389/fncel.2013.00115.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Lévesque M, Herrington R, Leclerc L, Rogawski MA, Avoli M. Allopregnanolone decreases interictal spiking and fast ripples in an animal model of mesial temporal lobe epilepsy. Neuropharmacology. 2017;121:12–9. https://doi.org/10.1016/j.neuropharm.2017.04.020.

    Article  CAS  PubMed  Google Scholar 

  76. Dhir A, Chopra K. On the anticonvulsant effect of allopregnanolone (a neurosteroid) in neonatal rats. Life Sci. 2015;143:202–8. https://doi.org/10.1016/j.lfs.2015.09.008.

    Article  CAS  PubMed  Google Scholar 

  77. Lonsdale D, Burnham WM. The anticonvulsant effects of allopregnanolone against amygdala-kindled seizures in female rats. Neurosci Lett. 2007;411(2):147–51. https://doi.org/10.1016/j.neulet.2006.10.023.

    Article  CAS  PubMed  Google Scholar 

  78. Broomall E, Natale JE, Grimason M, Goldstein J, Smith CM, Chang C, Kanes S, Rogawski MA, Wainwright MS. Pediatric super-refractory status epilepticus treated with allopregnanolone. Ann Neurol. 2014;76(6):911–5. https://doi.org/10.1002/ana.24295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Reddy K, Reife R, Cole AJ. SGE-102: a novel therapy for refractory status epilepticus. Epilepsia. 2013;54:81–3. https://doi.org/10.1111/epi.12286.

    Article  CAS  PubMed  Google Scholar 

  80. Meletti S, Lucchi C, Monti G, Giovannini G, Bedin R, Trenti T, Rustichelli C, Biagini G. Decreased allopregnanolone levels in cerebrospinal fluid obtained during status epilepticus. Epilepsia. 2017;58(2):e16–20. https://doi.org/10.1111/epi.13625.

    Article  CAS  PubMed  Google Scholar 

  81. Rosenthal ES, Claassen J, Wainwright MS, Husain AM, Vaitkevicius H, Raines S, Hoffmann E, Colquhoun H, Doherty JJ, Kanes SJ. Brexanolone as adjunctive therapy in super-refractory status epilepticus. Ann Neurol. 2017;82(3):342–52. https://doi.org/10.1002/ana.25008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Dorandeu F. Ketamine for the treatment of (super) refractory status epilepticus? Not quite yet. Expert Rev Neurother. 2017;17:419–21. https://doi.org/10.1080/14737175.2017.1288099.

    Article  CAS  PubMed  Google Scholar 

  83. Dorandeu F, Dhote F, Barbier L, Baccus B, Testylier G. Treatment of status epilepticus with ketamine, are we there yet? CNS Neurosci Ther. 2013;19(6):411–27. https://doi.org/10.1111/cns.12096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Knake S, Rochon J, Fleischer S, Katsarou N, Back T, Vescovi M, Oertel WH, Reis J, Hamer HM, Rosenow F. Status epilepticus after stroke is associated with increased long-term case fatality. Epilepsia. 2006;47(12):2020–6. https://doi.org/10.1111/j.1528-1167.2006.00845.x.

    Article  PubMed  Google Scholar 

  85. Sutter R, Marsch S, Fuhr P, Rüegg S. Mortality and recovery from refractory status epilepticus in the intensive care unit: a 7-year observational study. Epilepsia. 2013;54(3):502–11. https://doi.org/10.1111/epi.12064.

    Article  PubMed  Google Scholar 

  86. Hocker SE, Britton JW, Mandrekar JN, Wijdicks EF, Rabinstein AA. Predictors of outcome in refractory status epilepticus. JAMA Neurol. 2013;70(1):72–7. https://doi.org/10.1001/jamaneurol.2013.578.

    Article  PubMed  Google Scholar 

  87. Bausell R, Svoronos A, Lennihan L, Hirsch LJ. Recovery after severe refractory status epilepticus and 4 months of coma. Neurology. 2011;77(15):1494–5. https://doi.org/10.1212/WNL.0b013e318232abc0.

    Article  PubMed  Google Scholar 

  88. Mayer SA, Claassen J, Lokin J, Mendelsohn F, Dennis LJ, Fitzsimmons BF. Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol. 2002;59(2):205–10. https://doi.org/10.1001/archneur.59.2.205.

    Article  PubMed  Google Scholar 

  89. Sutter R, Grize L, Fuhr P, Rüegg S, Marsch S. Acute-phase proteins and mortality in status epilepticus: a 5-year observational cohort study. Crit Care Med. 2013;41(6):1526–33. https://doi.org/10.1097/CCM.0b013e318287f2ac.

    Article  PubMed  Google Scholar 

  90. Holtkamp M, Othman J, Buchheim K, Meierkord H. Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit. J Neurol Neurosur Ps. 2005;76(4):534–9. https://doi.org/10.1136/jnnp.2004.041947.

    Article  CAS  Google Scholar 

  91. Neligan A, Shorvon SD. Frequency and prognosis of convulsive status epilepticus of different causes: a systematic review. Arch Neurol. 2010;67(8):931–40. https://doi.org/10.1001/archneurol.2010.169.

    Article  PubMed  Google Scholar 

  92. Yoon J, Kim K. Detecting signals of new technological opportunities using semantic patent analysis and outlier detection. Scientometrics. 2012;90(2):445–61. https://doi.org/10.1007/s11192-011-0543-2.

    Article  Google Scholar 

  93. Baraban SC. Compounds and methods for treating an epileptic disorder. University of California. US10695325B2. 2020-06-30.

  94. McNamara JO, Liu G, Gu B, He XP, Krishnamurthy K, Huang Y, Mook R. Methods for the prevention or treatment of epilepsy. Duke University. US20190269752A1. 2019-09-05.

  95. von Moltke LL, Weiden PJ, Hard ML. Aripiprazole dosing strategy. Alkermes Pharma Ireland Ltd. US20190298716A1. 2019-10-03.

  96. Irazoqui P, Budde RB, Pederson D. Prevention of reflux induced laryngospasm. Purdue Research Foundation. US20190336758A1. 2019-11-07.

  97. Galer BS, Faingold CL, Martin P. Compositions and methods for treating respiratory depression with fenfluramine. Zogenix International Ltd. US20190380979A1. 2019-12-31.

  98. Bekenstein U, Soreq H, Greenberg D. Methods for controlling seizures by manipulating the levels of microRNA-211 (miR-211) in the brain. Uriah Bekenstein. US20200102559A1. 2020-04-02.

  99. Osorio I. Contingent cardio-protection for epilepsy patients. Flint Hills Scientific LLC. US20200206508A1. 2020-07-02.

  100. Rogawski MA, Pessah IS, Cao Z, Lein PJ. Mitigation of epileptic seizures by combination therapy using benzodiazepines and neurosteroids. University of California. US20200215078A1. 2020-07-09.

  101. Salituro FG, Blanc-Pillado MJ, Morningstar M, Harrison BL. 9(11)-unsaturated neuroactive steroids and their methods of use. Sage Therapeutics, Inc. WO2020082065A1. 2020-04-23.

  102. Blanc-Pillado MJ, Salituro FG. 3.alpha.-hydroxy-17.beta.-amide neuroactive steroids and compositions thereof. Sage Therapeutics, Inc. WO2020132504A1. 2020-06-25.

  103. Umscheid CA, Margolis DJ, Grossman CE. Key concepts of clinical trials: a narrative review. Postgrad Med. 2011;123(5):194–204.

    Article  Google Scholar 

  104. Seizure Rescue Medication: Caregiver Education in a Simulation Setting. (ClinicalTrials.gov Identifier: NCT03562351). https://clinicaltrials.gov/ct2/ show/NCT03562351?cond=NCT03562351. BostonChildren'sHospital. 2020.

  105. EEG Cap for Identification of Non-Convulsive Status Epilepticus. (ClinicalTrials.gov Identifier: NCT03138876). https://clinicaltrials.gov/ct2/show/NCT03138876 ?cond=NCT03138876. MayoClinic. 2019.

  106. Efficacy of Ketamine Infusion Compared With Traditional Anti-epileptic Agents in Refractory Status Epilepticus. (ClinicalTrials.gov Identifier: NCT03115489). https://clinicaltrials.gov/ct2/show/NCT03115489?cond=NCT03115489.UniversityofAlabamaatBirmingham. 2020.

  107. Established Status Epilepticus Treatment Trial (ESETT). (ClinicalTrials.gov Identifier: NCT01960075). https://clinicaltrials.gov/ct2/show/NCT01960075?cond=NCT01960075.UniversityofVirginia. 2020.

  108. Study to Evaluate SAGE-547 Injection as Adjunctive Therapy for the Treatment of Super-Refractory Status Epilepticus (SRSE). (ClinicalTrials.gov Identifier: NCT02052739). https://clinicaltrials.gov/ct2/show/NCT02052739?cond=NCT020 52739. SageTherapeutics. 2020.

  109. A Study With SAGE-547 for Super-Refractory Status Epilepticus. (ClinicalTrials.gov Identifier: NCT02477618). https://clinicaltrials.gov/ct2/show/NCT02477618 ?cond=NCT02477618. ] SageTherapeutics. 2019.

Download references

Acknowledgements

The authors are very thankful to Radhika Pandita for proofreading and editing the manuscript.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences & Research University, Pushp Vihar, Sec 3, M.B Road, New Delhi, 110017, India

    Neha Raina, Radha Rani, Brijesh Ojha & Madhu Gupta

  2. Department of Pharmacy, School of Medical & Allied Sciences, GD Goenka University, Gurgaon, 122103, India

    Monu Yadav

  3. Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India

    Bigul Yogeshver Bhardwaj

Authors
  1. Neha Raina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Monu Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Radha Rani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Brijesh Ojha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bigul Yogeshver Bhardwaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Madhu Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Madhu Gupta.

Ethics declarations

Conflict of Interest

The authors revealed that there is no conflict of interest regarding the publication of this paper.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Neuropharmacology.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raina, N., Yadav, M., Rani, R. et al. Status Epilepticus: an Overview for Neuroscientists. Curr Pharmacol Rep 8, 36–47 (2022). https://doi.org/10.1007/s40495-021-00272-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40495-021-00272-7

Keywords

Search

Navigation