Skip to main content

Advertisement

SpringerLink
Log in

Predicting and Treating Post-traumatic Epilepsy

  • Critical Care Neurology (H Hinson, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Abstract

Purpose of Review

This is a narrative review of the literature pertaining to early post-traumatic seizures (PTS) and post-traumatic epilepsy (PTE; late, unprovoked seizures), with particular emphasis on current identified biomarkers. We will present the reader current management strategies and society guidelines for the management of PTS. We also indicate potential targets for further investigation to identify patients at high risk for PTE and clinical intervention to prevent PTE.

Recent Findings

A recent large cohort study again demonstrated that intracranial hemorrhage—including subarachnoid, subdural, and epidural—and severity of head injury were significant risk factors for development of PTS. While several prior studies have shown the efficacy of antiseizure medications in preventing early PTS in adults, a number of recent retrospective and randomized trials have demonstrated the efficacy of antiseizure medications in preventing early PTS in children. This has prompted new society guidelines for antiseizure medication (ASMs) prophylaxis in pediatric TBI. Recent investigations redemonstrated that early PTS, intracranial hemorrhage, and severity of TBI are major risk factors for PTE.

Summary

Brief (1–2 weeks) use of prophylactic ASMs—particularly levetiracetam or phenytoin—is effective for the prevention of early PTS in patients with moderate to severe TBI, but prophylactic ASMs for the prevention of PTE are ineffective and not recommended. Continued research into potential biomarkers is needed to identify patients at the highest risk of developing PTE as well as to identify effective therapies for preventing the development of PTE in at-risk patients.

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

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Maas AIR, Menon DK, David Adelson PD, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16(12):987–1048. https://doi.org/10.1016/S1474-4422(17)30371-X.

    Article  PubMed  Google Scholar 

  2. Dewan MC, Rattani A, Gupta S, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2019;130(4):1080–97. https://doi.org/10.3171/2017.10.JNS17352.

    Article  Google Scholar 

  3. WHO. Neurological Disorders: Public Health Challenges. Published 2006. https://www.who.int/publications/i/item/9789241563369. Accessed 12 Feb 2022.

  4. Frey LC. Epidemiology of posttraumatic epilepsy: a critical review. Epilepsia. 2003;44(SUPPL. 10):11–7. https://doi.org/10.1046/j.1528-1157.44.s10.4.x.

    Article  PubMed  Google Scholar 

  5. Asikainen I, Kaste M, Sarna S. Early and late posttraumatic seizures in traumatic brain injury rehabilitation patients: brain injury factors causing late seizures and influence of seizures on long-term outcome. Epilepsia. 1999;40(5):584–9. https://doi.org/10.1111/J.1528-1157.1999.TB05560.X.

    Article  CAS  PubMed  Google Scholar 

  6. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475–82. https://doi.org/10.1111/EPI.12550.

    Article  PubMed  Google Scholar 

  7. Emanuelson I, Uvebrant P. Occurrence of epilepsy during the first 10 years after traumatic brain injury acquired in childhood up to the age of 18 years in the south western Swedish population-based series. Brain Inj. 2009;23(7–8):612–6. https://doi.org/10.1080/02699050902973913.

    Article  CAS  PubMed  Google Scholar 

  8. Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injury. N Engl J Med. 1998;338(1):20–24.

  9. Englander J, Bushnik T, Duong TT, et al. Analyzing risk factors for late posttraumatic seizures: a prospective, multicenter investigation. Arch Phys Med Rehabil. 2003;84(3 SUPPL. 1):365–73. https://doi.org/10.1053/apmr.2003.50022.

    Article  PubMed  Google Scholar 

  10. Ritter AC, Wagner AK, Fabio A, et al. Incidence and risk factors of posttraumatic seizures following traumatic brain injury: a traumatic brain injury model systems study. Epilepsia. 2016;57(12):1968–1977. https://doi.org/10.1111/epi.13582.

  11. Vespa PM, Nuwer MR, Nenov V, et al. Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continous electroencephalographic monitoring. J Neurosurg. 1999;91(5):750–60. https://doi.org/10.3171/jns.1999.91.5.0750.Increased.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Arndt DH, Lerner JT, Matsumoto JH, et al. Subclinical early posttraumatic seizures detected by continuous EEG monitoring in a consecutive pediatric cohort. Epilepsia. 2013;54(10):1780–8. https://doi.org/10.1111/EPI.12369.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Vespa P, Miller C, McArthur D, et al. Nonconvulsive electrographic seizures after trumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic. Crit Care Med. 2007;35(12):2830–6. https://doi.org/10.1002/aur.1474.Replication.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hahn Y, Fuchs S, Flannery A, Bartherl M, McLone D. Factors influencing posttraumatic seizures in children - PubMed. Neurosurgery. 1988;May(22):864–867. https://pubmed.ncbi.nlm.nih.gov/3380275/. Accessed 3 Mar 2022.

  15. Kortbeek JB, Al Turki SA, Ali J, et al. Advanced trauma life support, 8th edition, the evidence for change. J Trauma - Inj Infect Crit Care. 2008;64(6):1638–1650. https://doi.org/10.1097/TA.0B013E3181744B03.

  16. Agrawal A, Timothy J, Pandit L, Manju M. Post-traumatic epilepsy: an overview. Clin Neurol Neurosurg. 2006;108(5):433–9. https://doi.org/10.1016/j.clineuro.2005.09.001.

    Article  PubMed  Google Scholar 

  17. •• Laing J, Gabbe B, Chen Z, Perucca P, Kwan P, O’Brien T. Risk factors and prognosis of early posttraumatic seizures in moderate-severe traumatic brain injury: a population-based study. JAMA Neurol. 2022:1-8. https://doi.org/10.1001/jamaneurol.2021.5420. A critical study that demonstrated risk factors of post-traumatic seizures but most importantly showed that patients with post-traumatic seizures had poorer outcomes compared with patients without post-traumatic seizures.

  18. Arango JI, Deibert CP, Brown D, Bell M, Dvorchik I, Adelson PD. Posttraumatic seizures in children with severe traumatic brain injury. https://doi.org/10.1007/s00381-012-1863-0.

  19. Gupta P, Sayed N, Ding K, et al. Subtypes of post-traumatic epilepsy: clinical, electrophysiological, and imagin findings. J Neurotrauma. 2014;31:1439–43.

    Article  Google Scholar 

  20. Hudak AM, Trivedi K, Harper CR, et al. Evaluation of seizure-like episodes in survivors of moderate and severe traumatic brain injury. J Head Trauma Rehabil. 2004;19(4):290–5. https://doi.org/10.1097/00001199-200407000-00003.

    Article  PubMed  Google Scholar 

  21. Temkin NR. Risk factors for posttraumatic seizures in adults. Epilepsia. 2003;44(SUPPL. 10):18–20. https://doi.org/10.1046/J.1528-1157.44.S10.6.X.

    Article  PubMed  Google Scholar 

  22. Sheikh ZB, Stretz C, Maciel CB, et al. Deep versus lobar intraparenchymal hemorrhage: seizures, hyperexcitable patterns, and clinical outcomes. Crit Care Med. 2020:E505–E513. https://doi.org/10.1097/CCM.0000000000004317.

  23. Gilmore E, Choi HA, Hirsch LJ, Claassen J. Seizures and CNS hemorrhage: spontaneous intracerebral and aneurysmal subarachnoid hemorrhage. Neurologist. 2010;16(3):165–75. https://doi.org/10.1097/NRL.0B013E3181C7CD0B.

    Article  PubMed  Google Scholar 

  24. Angeleri F, Majkowski J, Cacchiò G, et al. Posttraumatic epilepsy risk factors: one-year prospective study after head injury. Epilepsia. 1999;40(9):1222–30. https://doi.org/10.1111/J.1528-1157.1999.TB00850.X.

    Article  CAS  PubMed  Google Scholar 

  25. •• Burke J, Gugger J, Ding K, et al. Association of posttraumatic epilepsy with 1-year outcomes after traumatic brain injury. JAMA Netw Open. 2021;4(12):1–14. https://doi.org/10.1001/jamanetworkopen.2021.40191. An important study showing that post-traumatic epilepsy is a significant sequela of traumatic brain injury and is associated with unfavorable outcomes.

  26. Herman ST. Epilepsy after brain insult. Neurology. 2002;59(9 suppl 5):S21–6. https://doi.org/10.1212/WNL.59.9_SUPPL_5.S21.

    Article  PubMed  Google Scholar 

  27. Kim JA, Boyle EJ, Wu AC, et al. Epileptiform activity in traumatic brain injury predicts post-traumatic epilepsy. Ann Neurol. 2018;83(4):858–62. https://doi.org/10.1002/ana.25211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Jasper HH, Kershman J, Elvidge A. Electroenc6phalography in head injury. Res Publ Ass nerv ment Dis. 1945;24:388–420.

    Google Scholar 

  29. Williams D. The electro-encephalogram in acute head injuries. J Neurol Psychiatry. 1941;4(2):107–30. https://doi.org/10.1136/JNNP.4.2.107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jennett B, van de Sande J. EEG prediction of post-traumatic epilepsy. Epilepsia. 1975;16(2):251–6. https://doi.org/10.1111/J.1528-1157.1975.TB06055.X.

    Article  CAS  PubMed  Google Scholar 

  31. Punia V, Fitzgerald Z, Zhang X, et al. Electroencephalographic biomarkers of epilepsy development in patients with acute brain injury: a matched, parallel cohort study. Ann Clin Transl Neurol. 2019;6(11):2230–9. https://doi.org/10.1002/acn3.50925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Vespa P, Tubi M, Claassen J, et al. Metabolic crisis occurs with seizures and periodic discharges after brain trauma. Ann Neurol. 2016;79(4):579–90.

    Article  Google Scholar 

  33. Komoltsev IG, Sinkin MV, Volkova AA, et al. A translational study on acute traumatic brain injury: high incidence of epileptiform activity on human and rat electrocorticograms and histological correlates in rats. Brain Sci. 2020;10(9):1–20. https://doi.org/10.3390/brainsci10090570.

    Article  CAS  Google Scholar 

  34. Bragin A, Li L, Almajano J, et al. Pathologic electrographic changes after experimental traumatic brain injury. Epilepsia. 2016;57(5):735–45. https://doi.org/10.1111/EPI.13359.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Fan Y, Dong L, Liu X, Wang H, Liu Y. Recent advances in the noninvasive detection of high-frequency oscillations in the human brain. Rev Neurosci. 2020;32(3):305–21. https://doi.org/10.1515/REVNEURO-2020-0073.

    Article  PubMed  Google Scholar 

  36. Klotz KA, Sag Y, Schönberger J, Jacobs J. Scalp ripples can predict development of epilepsy after first unprovoked seizure in childhood. Ann Neurol. 2021;89(1):134–42. https://doi.org/10.1002/ANA.25939.

    Article  PubMed  Google Scholar 

  37. D’Alessandro R, Tinuper P, Ferrara R, et al. CT scan prediction of late post-traumatic epilepsy. J Neurol Neurosurg Psychiatry. 1982;45(12):1153–5. https://doi.org/10.1136/JNNP.45.12.1153.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kumar R, Gupta RK, Husain M, et al. Magnetization transfer MR imaging in patients with posttraumatic epilepsy. Am J Neuroradiol. 2003;24(2):218–24.

    PubMed  PubMed Central  Google Scholar 

  39. Messori A, Polonara G, Carle F, Gesuita R, Salvolini U. Predicting posttraumatic epilepsy with MRI: prospective longitudinal morphologic study in adults. Epilepsia. 2005;46(9):1472–81. https://doi.org/10.1111/j.1528-1167.2005.34004.x.

    Article  PubMed  Google Scholar 

  40. •• Lutkenhoff ES, Shrestha V, Ruiz Tejeda J, et al. Early brain biomarkers of post-traumatic seizures: initial report of the multicentre epilepsy bioinformatics study for antiepileptogenic therapy (EpiBioS4Rx) prospective study. J Neurol Neurosurg Psychiatry. 2020;91(11):1154–7. https://doi.org/10.1136/JNNP-2020-322780. Cohort of moderate-severe TBI patients demonstrating that cortical thinning, particularly over left frontal and temporal lobes, can serve as a highly accurate neuroimaging biomarker for PTS.

  41. • Feldman RE, Rutland JW, Fields MC, et al. Quantification of perivascular spaces at 7T: A potential MRI biomarker for epilepsy. Seizure. 2018;54:11–8. https://doi.org/10.1016/J.SEIZURE.2017.11.004. Innovative article demonstrating multimodal quantitative neuroimaging and EEG analyses to further identify PTE biomarkers.

  42. Duncan D, Barisano G, Cabeen R, et al. Analytic tools for post-traumatic epileptogenesis biomarker search in multimodal dataset of an animal model and human patients. Front Neuroinform. 2018;12:86. https://doi.org/10.3389/FNINF.2018.00086.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Dadas A, Janigro D. Breakdown of blood brain barrier as a mechanism of post-traumatic epilepsy. 2019;123. https://doi.org/10.1016/j.nbd.2018.06.022.

  44. Tomkins O, Shelef I, Kaizerman I, et al. Blood–brain barrier disruption in post-traumatic epilepsy. J Neurol Neurosurg Psychiatry. 2008;79(7):774–7. https://doi.org/10.1136/JNNP.2007.126425.

    Article  CAS  PubMed  Google Scholar 

  45. Tomkins O, Feintuch A, Benifla M, Cohen A, Friedman A, Shelef I. Blood-brain barrier breakdown following traumatic brain injury: a possible role in posttraumatic epilepsy. Cardiovasc Psychiatry Neurol. 2011;2011. https://doi.org/10.1155/2011/765923.

  46. Sierra A, Laitinen T, Gröhn O, Pitkänen A. Diffusion tensor imaging of hippocampal network plasticity. Brain Struct Funct. 2015;220(2):781–801. https://doi.org/10.1007/S00429-013-0683-7.

    Article  PubMed  Google Scholar 

  47. Bendlin BB, Ries ML, Lazar M, et al. Longitudinal changes in patients with traumatic brain injury assessed with diffusion-tensor and volumetric imaging. Neuroimage. 2008;42(2):503–14. https://doi.org/10.1016/J.NEUROIMAGE.2008.04.254.

    Article  PubMed  Google Scholar 

  48. Sidaros A, Engberg AW, Sidaros K, et al. Diffusion tensor imaging during recovery from severe traumatic brain injury and relation to clinical outcome: a longitudinal study. Brain. 2008;131(Pt 2):559–72. https://doi.org/10.1093/BRAIN/AWM294.

    Article  PubMed  Google Scholar 

  49. Gupta RK, Saksena S, Agarwal A, et al. Diffusion tensor imaging in late posttraumatic epilepsy. Epilepsia. 2005;46(9):1465–71. https://doi.org/10.1111/J.1528-1167.2005.01205.X.

    Article  PubMed  Google Scholar 

  50. Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol. 2011;7(1):31–40. https://doi.org/10.1038/NRNEUROL.2010.178.

    Article  CAS  PubMed  Google Scholar 

  51. Terrone G, Frigerio F, Balosso S, Ravizza T, Vezzani A. Inflammation and reactive oxygen species in status epilepticus: biomarkers and implications for therapy. Epilepsy Behav. 2019;101(Pt B). https://doi.org/10.1016/J.YEBEH.2019.04.028.

  52. Zhu G, Okada M, Yoshida S, et al. Effects of interleukin-1beta on hippocampal glutamate and GABA releases associated with Ca2+-induced Ca2+ releasing systems. Epilepsy Res. 2006;71(2–3):107–16. https://doi.org/10.1016/J.EPLEPSYRES.2006.05.017.

    Article  CAS  PubMed  Google Scholar 

  53. Diamond ML, Ritter AC, Failla MD, et al. IL-1β associations with posttraumatic epilepsy development: a genetics and biomarker cohort study. Epilepsia. 2014;55(7):1109–19. https://doi.org/10.1111/EPI.12628/SUPINFO.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Balosso S, Liu J, Bianchi ME, Vezzani A. Disulfide-containing high mobility group box-1 promotes N-methyl-D-aspartate receptor function and excitotoxicity by activating Toll-like receptor 4-dependent signaling in hippocampal neurons. Antioxid Redox Signal. 2014;21(12):1726–40. https://doi.org/10.1089/ARS.2013.5349.

    Article  CAS  PubMed  Google Scholar 

  55. Wang KY, Yu GF, Zhang ZY, Huang Q, Dong XQ. Plasma high-mobility group box 1 levels and prediction of outcome in patients with traumatic brain injury. Clin Chim Acta. 2012;413(21–22):1737–41. https://doi.org/10.1016/J.CCA.2012.07.002.

    Article  CAS  PubMed  Google Scholar 

  56. Wang N, Liu H, Ma B, et al. CSF high-mobility group box 1 is associated with drug-resistance and symptomatic etiology in adult patients with epilepsy. Epilepsy Res. 2021;177. https://doi.org/10.1016/J.EPLEPSYRES.2021.106767.

  57. Walker LE, Sills GJ, Jorgensen A, et al. High-mobility group box 1 as a predictive biomarker for drug-resistant epilepsy: a proof-of-concept study. Epilepsia. 2022;63(1):e1–6. https://doi.org/10.1111/EPI.17116.

    Article  CAS  PubMed  Google Scholar 

  58. Treiman DM. GABAergic mechanisms in epilepsy. Epilepsia. 2001;42(SUPPL. 3):8–12. https://doi.org/10.1046/J.1528-1157.2001.042SUPPL.3008.X.

    Article  PubMed  Google Scholar 

  59. Darrah SD, Miller MA, Ren D, et al. Genetic variability in glutamic acid decarboxylase genes: associations with post-traumatic seizures after severe TBI. Epilepsy Res. 2013;103(2–3):180–94. https://doi.org/10.1016/J.EPLEPSYRES.2012.07.006.

    Article  CAS  PubMed  Google Scholar 

  60. Ritter AC, Kammerer CM, Brooks MM, Conley YP, Wagner AK. Genetic variation in neuronal glutamate transport genes and associations with posttraumatic seizure. Epilepsia. 2016;57(6):984–93. https://doi.org/10.1111/EPI.13397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kumar RG, Breslin KB, Ritter AC, Conley YP, Wagner AK. Variability with astroglial glutamate transport genetics is associated with increased risk for post-traumatic seizures. J Neurotrauma. 2019;36(2):230–8. https://doi.org/10.1089/NEU.2018.5632/ASSET/IMAGES/LARGE/FIGURE3.JPEG.

    Article  PubMed  Google Scholar 

  62. Wagner AK, Miller MA, Scanlon J, Ren D, Kochanek PM, Conley YP. Adenosine A1 receptor gene variants associated with post-traumatic seizures after severe TBI. Epilepsy Res. 2010;90(3):259–72. https://doi.org/10.1016/J.EPLEPSYRES.2010.06.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Deckert J, Jorgensen MB. Evidence for pre- and postsynaptic localization of adenosine A1 receptors in the CA1 region of rat hippocampus: a quantitative autoradiographic study. Brain Res. 1988;446(1):161–4. https://doi.org/10.1016/0006-8993(88)91308-X.

    Article  CAS  PubMed  Google Scholar 

  64. Mareš P, Haugvicová R, Kubová H. Interaction of excitatory amino acid agonists with cortical afterdischarges in developing rats. Epilepsia. 2002;43(SUPPL. 5):61–7. https://doi.org/10.1046/J.1528-1157.43.S.5.21.X.

    Article  PubMed  Google Scholar 

  65. Diaz-Arrastia R. Homocysteine and neurologic disease. Arch Neurol. 2000;57(10):1422–7. https://doi.org/10.1001/ARCHNEUR.57.10.1422.

    Article  CAS  PubMed  Google Scholar 

  66. Bigal ME, Lipton RB, Cohen J, Silberstein SD. Epilepsy and migraine. Epilepsy Behav. 2003;4(SUPPL. 2):13–24. https://doi.org/10.1016/J.YEBEH.2003.07.003.

    Article  Google Scholar 

  67. Scher AI, Wu H, Tsao JW, et al. MTHFR C677T genotype as a risk factor for epilepsy including post-traumatic epilepsy in a representative military cohort. J Neurotrauma. 2011;28(9):1739–45. https://doi.org/10.1089/NEU.2011.1982/SUPPL_FILE/SUPP_DATA.PDF.

    Article  PubMed  Google Scholar 

  68. Schierhout G, Roberts I. Prophylactic antiepileptic agents after head injury: a systematicreview. J Neurol Neurosurg Psychiatry. 1998;64(1):108. https://doi.org/10.1136/JNNP.64.1.108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Temkin NR. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials. Epilepsia. 2001;42(4):515–24. https://doi.org/10.1046/J.1528-1157.2001.28900.X.

    Article  CAS  PubMed  Google Scholar 

  70. Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, Winn HR. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med. 1990;323(8):497–502. https://doi.org/10.1056/NEJM199008233230801.

    Article  CAS  PubMed  Google Scholar 

  71. Young B, Rapp RP, Norton JA, Haack D, Tibbs PA, Bean JR. Failure of prophylactically administered phenytoin to prevent early posttraumatic seizures. J Neurosurg. 1983;58(2):231–5. https://doi.org/10.3171/JNS.1983.58.2.0231.

    Article  CAS  PubMed  Google Scholar 

  72. Pechadre J, Lauxerois M, Colnet G, et al. Prevention of late post-traumatic epilepsy by phenytoin in severe brain injuries. 2 years’ follow-up. Press Med. 1991;11(20 (18)):841–845. https://pubmed.ncbi.nlm.nih.gov/1829177/. Accessed 18 Feb 2022.

  73. Mcqueen JK, Blackwood DHR, Harris P, Kalbag RM, Johnson AL. Low risk of late post-traumatic seizures following severe head injury: implications for clinical trials of prophylaxis. J Neurol Neurosurg Psychiatry. 1983;46(10):899–904. https://doi.org/10.1136/JNNP.46.10.899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the Management of Severe TraumaticBrain Injury, Fourth Edition. Neurosurgery. 2016. https://doi.org/10.1227/NEU.0000000000001432.

  75. Chang BS, Lowenstein DH. Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2003;60(1):10–6. https://doi.org/10.1212/01.WNL.0000031432.05543.14.

    Article  PubMed  Google Scholar 

  76. Rowe AS, Goodwin H, Brophy GM, et al. Seizure prophylaxis in neurocritical care: a review of evidence-based support. Pharmacother J Hum Pharmacol Drug Ther. 2014;34(4):396–409. https://doi.org/10.1002/PHAR.1374.

    Article  Google Scholar 

  77. Szaflarski JP, Meckler JM, Szaflarski M, Shutter LA, Privitera MD, Yates SL. Levetiracetam use in critically ill patients. Neurocrit Care. 2007;7(2):140–7. https://doi.org/10.1007/S12028-007-0042-8.

    Article  PubMed  Google Scholar 

  78. Klein P, Herr D, Pearl PL, et al. Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy. Arch Neurol. 2012;69(10):1290–5. https://doi.org/10.1001/ARCHNEUROL.2012.445.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Xu JC, Shen J, Shao WZ, et al. The safety and efficacy of levetiracetam versus phenytoin for seizure prophylaxis after traumatic brain injury: a systematic review and meta-analysis. 2016;30(9):1054–1061. https://doi.org/10.3109/02699052.2016.1170882.

  80. Yang Y, Zheng F, Xu X, Wang X. Levetiracetam versus phenytoin for seizure prophylaxis following traumatic brain injury: a systematic review and meta-analysis. CNS Drugs. 2016;30(8):677–88. https://doi.org/10.1007/S40263-016-0365-0.

    Article  PubMed  Google Scholar 

  81. Temkin NR, Dikmen SS, Anderson GD, et al. Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg. 1999;91(4):593–600. https://doi.org/10.3171/JNS.1999.91.4.0593.

    Article  CAS  PubMed  Google Scholar 

  82. Glotzner FL, Haubitz I, Miltner F, Kapp G, Pflughaupt KW. Seizure prevention using carbamazepine following severe brain injuries. Neurochirurgia (Stuttg). 1983;26(3):66–79. https://doi.org/10.1055/S-2008-1053615.

    Article  CAS  Google Scholar 

  83. Rish BL, Caveness WF. Relation of prophylactic medication to the occurrence of early seizures following craniocerebral trauma. J Neurosurg. 1973;38(2):155–8. https://doi.org/10.3171/JNS.1973.38.2.0155.

    Article  CAS  PubMed  Google Scholar 

  84. Manaka S. Cooperative prospective study on posttraumatic epilepsy: risk factors and the effect of prophylactic anticonvulsant. Jpn J Psychiatry Neurol. 1992;46(2):311–5. https://doi.org/10.1111/J.1440-1819.1992.TB00865.X.

    Article  CAS  PubMed  Google Scholar 

  85. Lewis RJ, Yee L, Inkelis SH, Gilmore D. Clinical predictors of post-traumatic seizures in children with head trauma. Ann Emerg Med. 1993;22(7):1114–8. https://doi.org/10.1016/S0196-0644(05)80974-6.

    Article  CAS  PubMed  Google Scholar 

  86. Liesemer K, Bratton SL, Zebrack CM, Brockmeyer D, Statler KD. Early post-traumatic seizures in moderate to severe pediatric traumatic brain injury: Rates, risk factors, and clinical features. J Neurotrauma. 2011;28(5):755–62. https://doi.org/10.1089/NEU.2010.1518/ASSET/IMAGES/LARGE/FIGURE1.JPEG.

    Article  PubMed  Google Scholar 

  87. •• Kolf MJ, McPherson CC, Kniska KS, Luecke CM, Lahart MA, Pineda JA. Early post-traumatic seizure occurrence in pediatric patients receiving levetiracetam prophylaxis with severe traumatic brain injury. J Pediatr Pharmacol Ther. 2020;25(3):241–5. https://doi.org/10.5863/1551-6776-25.3.241. Innovative article demonstrating multimodal quantitative neuroimaging and EEG analyses to further identify PTE biomarkers.

  88. •• Chong S-L, Qian S, Hui S, et al. Early posttraumatic seizures in pediatric traumatic brain injury: a multicenter analysis. J Neurosurg Pediatr. 2021;29(2):225–31. https://doi.org/10.3171/2021.8.PEDS21281. One of the largest (multicenter) cohort studies investigating outcomes of PTS in pediatric patients with moderate to severe TBI.

  89. Pearl PL, McCarter R, McGavin CL, et al. Results of phase II levetiracetam trial following acute head injury in children at risk for post traumatic epilepsy. Epilepsia. 2013;54(9): e135. https://doi.org/10.1111/EPI.12326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Chung MG, O’Brien NF. Prevalence of early posttraumatic seizures in children with moderate to severe traumatic brain injury despite levetiracetam prophylaxis. Pediatr Crit Care Med. 2016;17(2):150–6. https://doi.org/10.1097/PCC.0000000000000588.

    Article  PubMed  Google Scholar 

  91. • Kochanek PM, Tasker RC, Carney N, et al. Guidelines for the management of pediatric severe traumatic brain injury, third edition: update of the Brain Trauma Foundation guidelines, executive summary. Neurosurgery. 2019;84(6):1169-1178. https://doi.org/10.1093/NEUROS/NYZ051. Most recent pediatric’s Brain Trauma Foundation guidelines.

  92. Surtees TL, Kumar I, Garton HJL, et al. Levetiracetam prophylaxis for children admitted with traumatic brain injury. Pediatr Neurol. 2022;126:114–9. https://doi.org/10.1016/J.PEDIATRNEUROL.2021.10.009.

    Article  PubMed  Google Scholar 

  93. Punia V, Garcia CG, Hantus S. Incidence of recurrent seizures following hospital discharge in patients with LPDs (PLEDs) and nonconvulsive seizures recorded on continuous EEG in the critical care setting. Epilepsy Behav. 2015;49:250–4. https://doi.org/10.1016/j.yebeh.2015.06.026.

    Article  PubMed  Google Scholar 

  94. •• Dikmen SS, Temkin NR, Miller B, Machamer J, Winn HR. Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures. JAMA. 1991;265(10):1271–7. https://doi.org/10.1001/JAMA.1991.03460100073027. Cohort study demonstrating that long-term ASM use may worsen functional outcomes, particularly in the absence of PTE.

  95. Pingue V, Mele C, Nardone A. Post-traumatic seizures and antiepileptic therapy as predictors of the functional outcome in patients with traumatic brain injury. Sci Rep. 2021;11(1):1–12. https://doi.org/10.1038/s41598-021-84203-y.

    Article  CAS  Google Scholar 

  96. Punia V, Chandan P, Fesler J, Newey CR, Hantus S. Post-acute symptomatic seizure (PASS) clinic: a continuity of care model for patients impacted by continuous EEG monitoring. Epilepsia Open. 2020;5(2):255–62. https://doi.org/10.1002/EPI4.12393.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Turovsky EA, Zinchenko VP, Gaidin SG, Turovskaya MV. Calcium-binding proteins protect GABAergic neurons of the hippocampus from hypoxia and ischemia in vitro. Biochem (Moscow), Suppl Ser A Membr Cell Biol. 2018;12(1):74–84. https://doi.org/10.1134/S1990747818010105.

  98. Chen T, Dai SH, Jiang ZQ, et al. The AMPAR antagonist perampanel attenuates traumatic brain injury through anti-oxidative and anti-inflammatory activity. Cell Mol Neurobiol. 2017;37(1):43–52. https://doi.org/10.1007/S10571-016-0341-8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge the editorial assistance of the NC Translational and Clinical Sciences (NC TraCS) Institute and I2B2 software, which was used in conducting the study; both are supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR002489. We would also like to thank the University of North Carolina in Chapel Hill for providing access to the literature required to complete this review.

Funding

CR receives funding from the Physician in training Program, University of North Carolina School of Medicine. Dr. Hirsch has received consultation fees for advising from Accure, Aquestive, Ceribell, Eisai, Marinus, Medtronic, Neurelis, Neuropace, and UCB; royalties from Wolters-Kluwer for authoring chapters for UpToDate-Neurology, and from Wiley for co-authoring the book “Atlas of EEG in Critical Care,” by Hirsch and Brenner; and honoraria for speaking from Neuropace, Natus, and UCB.

Author information

Authors and Affiliations

  1. Department of Neurology, University of North Carolina, 170 Manning Drive, Physician Office, CB 7025, Chapel Hill, NC, 27599-7025, USA

    Clio Rubinos MD MSCR & Brandon Waters MD

  2. Department of Neurology, Yale University School of Medicine, New Haven, CT, USA

    Lawrence J. Hirsch MD

Authors
  1. Clio Rubinos MD MSCR
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brandon Waters MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lawrence J. Hirsch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clio Rubinos MD MSCR.

Ethics declarations

Conflict of Interest

Clio Rubinos declares that she has no conflict of interest. Brandon Waters declares that he has no conflict of interest. Lawrence J. Hirsch declares that he has no conflict of interest.

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 Critical Care Neurology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rubinos, C., Waters, B. & Hirsch, L.J. Predicting and Treating Post-traumatic Epilepsy. Curr Treat Options Neurol 24, 365–381 (2022). https://doi.org/10.1007/s11940-022-00727-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-022-00727-2

Keywords

Search

Navigation