Skip to main content
SpringerLink
Log in

Cellular Damage and the Neuropathology of Status Epilepticus

  • Chapter
Status Epilepticus

Part of the book series: Current Clinical Neurology ((CCNEU))

Abstract

The neuropathology of status epilepticus (SE) is well established. This chapter will review the histopathology and pathophysiology of cellular damage associated with SE based on observations from human cases and experimentally induced SE. The mechanisms of hyperexcitability leading to excitotoxic cell death will be discussed. This chapter concentrates on human generalized convulsive status epilepticus (GCSE) because it is most relevant, but the complementary nature of experimental findings from animal research will be emphasized.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Dodrill CB, Wilensky AJ. Intellectual impairment as an outcome of status epilepticus. Neurology 1990;40(suppl 2):23–27.

    PubMed  CAS  Google Scholar 

  2. Aicardi J, Chevrie JJ. Convulsive status epilepticus in infants and children. A study of 239 cases. Epilepsia 1970;11:187–197.

    PubMed  CAS  Google Scholar 

  3. Lothman EW, Bertram EH. Epileptogenic effects of status epilepticus. Epilepsia 1993;34(suppl 1):S59–70.

    PubMed  Google Scholar 

  4. Kapur J. Status epilepticus in epileptogenesis. Curr Opin Neurol 1999;12:191–195.

    Article  PubMed  CAS  Google Scholar 

  5. Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA. Incidence of status epilepticus in Rochester, Minnesota, 1965–1984. Neurology 1998;50:735–741.

    PubMed  CAS  Google Scholar 

  6. Eriksson KJ, Koivikko MJ. Status epilepticus in children: aetiology, treatment, and outcome. Dev Med Child Neurol 1997;39:652–658.

    Article  PubMed  CAS  Google Scholar 

  7. Epps S, Schwaner C, Waldman W, Fountain NB. Status epilepticus as the first seizure in epilepsy. Epilepsia 2002;43(suppl 7):282.

    Google Scholar 

  8. Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA. Risk of unprovoked seizure after acute symptomatic seizure: effect of status epilepticus. Ann Neurol 1998;44:908–912.

    Article  PubMed  CAS  Google Scholar 

  9. Kramer RE, Luders H, Lesser RP, Weinstein MR, Dinner DS, Morris HH, Wyllie E. Transient focal abnormalities of neuroimaging studies during focal status epilepticus. Epilepsia 1987;28:528–532.

    PubMed  CAS  Google Scholar 

  10. Nohria V, Lee N, Tien RD, Heinz ER, Smith JS, DeLong GR, Skeen MB, Resnick TJ, Crain B, Lewis DV. Magnetic resonance imaging evidence of hippocampal sclerosis in progression: a case report. Epilepsia 1994;35:1332–1336.

    Article  PubMed  CAS  Google Scholar 

  11. Tien RD, Felsberg GJ. The hippocampus in status epilepticus: demonstration of signal intensity and morphologic changes with sequential fast spin-echo MR imaging. Radiology 1995;194:249–256.

    PubMed  CAS  Google Scholar 

  12. Wieshmann UC, Woermann FG, Lemieux L, Free SL, Bartlett PA, Smith SJ, Duncan JS, Stevens JM, Shorvon SD. Development of hippocampal atrophy: a serial magnetic resonance imaging study in a patient who developed epilepsy after generalized status epilepticus. Epilepsia 1997;38:1238–1241.

    Article  PubMed  CAS  Google Scholar 

  13. Riela AR, Sires BP, Penry JK. Transient magnetic resonance imaging abnormalities during partial status epilepticus. J Child Neurol 1991;6:143–145.

    PubMed  CAS  Google Scholar 

  14. Salmenpera T, Kalviainen R, Partanen K, Mervaala E, Pitkanen A. MRI volumetry of the hippocampus, amygdala, entorhinal cortex, and perirhinal cortex after status epilepticus. Epilepsy Res 2000;40:155–170.

    Article  PubMed  CAS  Google Scholar 

  15. Henry TR, Drury I, Brunberg JA, Pennell PB, McKeever PE, Beydoun A. Focal cerebral magnetic resonance changes associated with partial status epilepticus. Epilepsia 1994;35:35–41.

    Article  PubMed  CAS  Google Scholar 

  16. DeGiorgio CM, Gott PS, Rabinowicz AL, Heck CN, Smith T, Correale J. Neuron-specific enolase, a marker of acute neuronal injury, is increased in complex partial status epilepticus. Epilepsia 1996;37:606–609.

    Article  PubMed  CAS  Google Scholar 

  17. DeGiorgio CM, Heck CN, Rabinowicz AL, Gott PS, Smith T, Correale J. Serum neuron-specific enolase in the major subtypes of status epilepticus. Neurology 1999;52;746–749.

    PubMed  CAS  Google Scholar 

  18. Correale J, Rabinowicz AL, Heck CN, Smith TD, Loskota WJ, DeGiorgio CM. Status epilepticus increases CSF levels of neuron-specific enolase and alters the blood-brain barrier. Neurology 1998;50:1388–1391.

    PubMed  CAS  Google Scholar 

  19. Rabinowicz AL, Correale J, Bracht KA, Smith, TD, DeGiorgio CM. Neuron-specific enolase is increased after nonconvulsive status epilepticus. Epilepsia 1995;36:475–479.

    Article  PubMed  CAS  Google Scholar 

  20. Meyer Z, Beck E, Shepherd M. Unusually severe lesions in the brain following status epilepticus. J Neurol Neurosurg Psychiatry 1955;18:24–33.

    PubMed  CAS  Google Scholar 

  21. Norman RM. The neuropathology of status epilepticus. Med Sci Law 1964;4:46–51.

    PubMed  CAS  Google Scholar 

  22. Corsellis JAN, Bruton CJ. Neuropathology of status epilepticus in humans. In: Delgado-Escueta AV, Wasterlain CG, Treiman DM, Porter RJ, eds. Status Epilepticus. (Advances in Neurology; vol. 34.) New York: Raven Press; 1983:129–140.

    Google Scholar 

  23. Nixon J, Bateman D, Moss T. An MRI and neuropathological study of a case of fatal status epilepticus. Seizure 2001;10:588–591.

    Article  PubMed  CAS  Google Scholar 

  24. Albala BJ, Moshe SL, Okada R. Kainic acid-induced seizures: a developmental study. Dev Brain Res 1990;13:139–148.

    Article  Google Scholar 

  25. Stafstrom CE, Thompson JL, Holmes GL. Kainic acid in the developing brain: status epilepticus and spontaneous recurrent seizures. Dev Brain Res 1992;65:227–236.

    Article  CAS  Google Scholar 

  26. Cilio MR, Sogawa Y, Cha BH, Liu X, Huang LT, Holmes GL. Long-term effects of status epilepticus in the immature brain are specific for age and model. Epilepsia 2003;44:518–528.

    Article  PubMed  Google Scholar 

  27. Fujikawa DG, Itabashi HH, Wu A, Shinmei SS. Status epilepticus-induced neuronal loss in humans without systemic complications or epilepsy. Epilepsia 2000;41:981–991.

    Article  PubMed  CAS  Google Scholar 

  28. DeGiorgio CM, Tomiyasu U, Gott PS, Treiman DM. Hippocampal pyramidal cell loss in human status epilepticus. Epilepsia. 1992;33:23–27.

    Article  PubMed  CAS  Google Scholar 

  29. Knopman D, Margolis G, Reeves AG. Prolonged focal epilepsy and hypoxemia as a cause of focal brain damage: a case study. Ann Neurol 1977;1:195–198.

    Article  PubMed  CAS  Google Scholar 

  30. Soffer D, Melamed E, Assaf Y, Cotev S. Hemispheric brain damage in unilateral status epilepticus. Ann Neurol 1986;20:737–740.

    Article  PubMed  CAS  Google Scholar 

  31. Kaplan PW. Nonconvulsive status epilepticus: to lump or to split? Epilepsia 1994;35(suppl 8):9(abstract).

    Google Scholar 

  32. Fountain NB, Lothman EW. Pathophysiology of status epilepticus. J Clin Neurophysiol 1995;12:326–342.

    PubMed  CAS  Google Scholar 

  33. Shneker B, Fountain NB. Epilepsy as chronic sequelae following nonconvulsive status epilepticus. Epilepsia 2001;42(suppl 7):147(abstract).

    Google Scholar 

  34. Scholtes FB, Reiner WO, Meinardi H. Nonconvulsive status epilepticus: causes, treatment and outcome in 65 patients. J Neurol Neurosurg Psychiatry 1996;61:93–95.

    Article  PubMed  CAS  Google Scholar 

  35. Shneker BF, Fountain NB. Assessment of acute morbidity and mortality in nonconvulsive status epilepticus. Neurology 2003;61:1066–1073.

    PubMed  Google Scholar 

  36. Lothman EW, Bertram EH, Bekenstein JW, Perlin JB. Self-sustaining limbic status epilepticus induced by “continuous” hippocampal stimulation: electrographic and behavioral characteristics. Epilepsy Res 1989;3:107–119

    Article  PubMed  CAS  Google Scholar 

  37. Turski WA, Cavalheiro EA, Bortolotto ZA, Mello LM, Schwarz M, Turski L. Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. Brain Res 1984;321:237–253.

    Article  PubMed  CAS  Google Scholar 

  38. Jope RS, Morrisett RA, Snead OC. Characterization of lithium potentiation of pilocarpine-induced status epilepticus in rats. Exp Neurol 1986;91:471–480.

    Article  PubMed  CAS  Google Scholar 

  39. Meldrum BS, Brierley JB. Prolonged epileptic seizures in primates. Arch Neurol 1973;28:10–17.

    PubMed  CAS  Google Scholar 

  40. Meldrum BS, Horton RW. Physiology of status epilepticus in primates. Arch Neurol 1973;28:1–9.

    PubMed  CAS  Google Scholar 

  41. Meldrum BS, Vigouroux RA, Brierley JB. Systemic factors and epileptic brain damage. Arch Neurol 1973;29:82–87.

    PubMed  CAS  Google Scholar 

  42. Lowenstein DH, Simon RP, Sharp FR. The pattern of 72-kDa heat shock protein-like immunoreactivity in the rat brain following flurothyl-induced status epilepticus. Brain Res 1990;531:173–182.

    Article  PubMed  CAS  Google Scholar 

  43. Thomas J, Yang YC. Allylglycine-induced seizures in male and female rats. Physiol Behav 1991;49:1181–1183.

    Article  PubMed  CAS  Google Scholar 

  44. Walton NY, Treiman DM. Experimental secondarily generalized convulsive status epilepticus induced by D,L-homocysteine thiolactone. Epilepsy Res 1988;2:79–86.

    Article  PubMed  CAS  Google Scholar 

  45. Terndrup TE, Paskanik AM, Fordyce WE, Kanter RK. Development of a piglet model of status epilepticus: preliminary results. Ann Emerg Med 1993;22:164–170.

    Article  PubMed  CAS  Google Scholar 

  46. Raines A, Henderson TR, Swinyard EA, Dretchen KL. Comparison of midazolam and diazepam by the intramuscular route for the control of seizures in a mouse model of status epilepticus. Epilepsia 1990;31:313–317.

    PubMed  CAS  Google Scholar 

  47. Tomlinson FH, Anderson RE, Meyer FB. Effect of arterial blood pressure and serum glucose on brain intracellular pH, cerebral and cortical blood flow during status epilepticus in the white New Zealand rabbit. Epilepsy Res 1993;14:123–137.

    Article  PubMed  CAS  Google Scholar 

  48. Bayne LL, Simon RP. Systemic and pulmonary vascular pressures during generalized seizures in sheep. Ann Neurol 1981;10:566–569.

    Article  PubMed  CAS  Google Scholar 

  49. Collins RC, Olney JW. Focal cortical seizures cause distant thalamic lesions. Science 1982;218:177–179.

    Article  PubMed  CAS  Google Scholar 

  50. Lothman EW, Collins RC. Kainic acid induced limbic seizures: metabolic, behavioral, electroencephalographic and neuropathological correlates. Brain Res 1981;218:299–318.

    Article  PubMed  CAS  Google Scholar 

  51. Mathis C, Ungerer A. Comparative analysis of seizures induced by intracerebroventricular administration of NMDA, kainate and quisqualate in mice. Exp Brain Res 1992;88:277–282.

    Article  PubMed  CAS  Google Scholar 

  52. Dakshinamurti K, Sharma SK, Sundaram M. Domoic acid induced seizure activity in rats. Neurosci Lett 1991;127:193–197.

    Article  PubMed  CAS  Google Scholar 

  53. Sutherland GR, Ross BD, Lesiuk H, Peeling J, Pillay N, Pinsky C. Phosphate energy metabolism during domoic acid-induced seizures. Epilepsia 1993;34:996–1002.

    Article  PubMed  CAS  Google Scholar 

  54. McIntyre DC, Nathanson D, Edson N. A new model of partial status epilepticus based on kindling. Brain Res 1982;250:53–63.

    Article  PubMed  CAS  Google Scholar 

  55. Handforth A, Ackermann RF. Electrogenic status epilepticus induced from numerous limbic sites. Epilepsy Res 1993;15:21–26.

    Article  PubMed  CAS  Google Scholar 

  56. Bertram EH, Lenn NJ, Lothman EW. The hippocampus in experimental chronic epilepsy: a morphometric analysis. Ann Neurol 1990;27:38–43.

    Article  Google Scholar 

  57. Du F, Whetsell WO, Abu-Khalil B, Blumenkopf B, Lothman EW, Schwarcz R. Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy. Epilepsy Res 1993;16:223–233.

    Article  PubMed  CAS  Google Scholar 

  58. Schwob JE, Fuller T, Price JL, Olney JW. Widespread patterns of neuronal damage following systemic or intracerebral injections of kainic acid: a histological study. Neuroscience 1980;5:991–1014.

    Article  PubMed  CAS  Google Scholar 

  59. Simon RP, Aminoff MJ, Benowitz NL. Changes in plasma catecholamines after tonic-clonic seizures. Neurology 1984;34:255–257.

    PubMed  CAS  Google Scholar 

  60. Lothman EW. The biochemical basis and pathophysiology of status epilepticus. Neurology 1990;40(suppl 2):13–23.

    PubMed  CAS  Google Scholar 

  61. Wasterlain CG, Fujikawa DG, Penix L, Sankar R. Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia 1993;34(suppl 1):S37–53.

    PubMed  Google Scholar 

  62. Siesjo BK, Ingvar M, Folbergrova J, Chapman AG. Local cerebral circulation and metabolism in bicuculline-induced status epilepticus: Relevance for development of cell damage. In: Delgado-Escueta AV, Wasterlain CG, Treiman DM, Porter RJ, eds. Status Epilepticus. (Advances in Neurology, vol. 34.). New York: Raven Press; 1983:217–230.

    Google Scholar 

  63. Meldrum BS, Nilsson B. Cerebral blood flow and metabolic rate early and late in prolonged epileptic seizures induced in rats by bicuculline. Brain 1976;99:523–542.

    Article  PubMed  CAS  Google Scholar 

  64. Blennow G, Brierley JB, Meldrum BS, Siesjo BK. Epileptic brain damage. The role of systemic factors that modify cerebral energy metabolism. Brain 1978;101:687–700.

    Article  PubMed  CAS  Google Scholar 

  65. Perl TM, Bedard L, Kosatsky T, Hockin JC, Todd EC, Remis RS. An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. N Engl J Med 1990;322:1775–1780.

    Article  PubMed  CAS  Google Scholar 

  66. Teitelbaum JS, Zatorre RJ, Carpenter S, Gendron D, Evans AC, Gjedde A, Cashman NR. Neurologic sequelae of domoic acid intoxication due to ingestion of contaminated mussels. N Engl J Med 1990;322:1781–1787.

    Article  PubMed  CAS  Google Scholar 

  67. Cendes F, Andermann F, Carpenter S, Zatorre RJ, Cashman NR. Temporal lobe epilepsy caused by domoic acid intoxication: evidence for glutamate receptor-mediated excitotoxicity in humans. Ann Neurol 1995;37:123–126.

    Article  PubMed  CAS  Google Scholar 

  68. Meldrum BS. Concept of activity-induced cell death in epilepsy: historical and contemporary perspectives. Prog Brain Res 2002;135:3–11.

    Article  PubMed  CAS  Google Scholar 

  69. Fountain NB. Status epilepticus: risk factors and complications. Epilepsia 2000;41(suppl 2):S23–30.

    Article  PubMed  Google Scholar 

  70. Jope RS, Johnson GVW, Baird MS. Seizure-induced protein tyrosine phosphorylation in rat brain regions. Epilepsia 1991;32:755–760.

    PubMed  CAS  Google Scholar 

  71. Pollard H, Cantagrel S, Charriaut-Marlangue C, Moreau J, Ben Ari Y. Apoptosis associated DNA fragmentation in epileptic brain damage. Neuroreport 1994;5:1053–1055.

    Article  PubMed  CAS  Google Scholar 

  72. Fujikawa DG, Shinmei SS, Cai B. Kainic acid-induced seizures produce necrotic, not apoptotic, neurons with internucleosomal DNA cleavage: implications for programmed cell death mechanisms. Neuroscience 2000;98:41–53.

    Article  PubMed  CAS  Google Scholar 

  73. Monaghan DT, Cotman CW. Distribution of N-methyl-D-aspartate-sensitive L-(3H)glutamate-binding sites in rat brain. J Neurosci 1985;5:2909–2918.

    PubMed  CAS  Google Scholar 

  74. Ozawa S, Kamiya H, Tsuzuki K. Glutamate receptors in the mammalian central nervous system. Prog Neurobiol 1998;54:581–618.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Comprehensive Epilepsy Program, Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA

    Nathan B. Fountain MD

Authors
  1. Nathan B. Fountain MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Harvard Medical School, Comprehensive Epilepsy Program, Beth Israel Deaconess Medical Center, Boston, Massachusetts

    Frank W. Drislane MD (Associate Professor of Neurology) (Associate Professor of Neurology)

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Fountain, N.B. (2005). Cellular Damage and the Neuropathology of Status Epilepticus. In: Drislane, F.W. (eds) Status Epilepticus. Current Clinical Neurology. Humana Press. https://doi.org/10.1385/1-59259-945-1:181

Download citation

  • DOI: https://doi.org/10.1385/1-59259-945-1:181

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-355-8

  • Online ISBN: 978-1-59259-945-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation