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Late Post-traumatic Epilepsy in Children and Young Adults: Impropriety of Long-Term Antiepileptic Prophylaxis and Risks in Tapering

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Abstract

Background

After traumatic brain injury, epilepsy affects up to 20 % of children. It is a risk factor, for both clinical recovery and cognitive performance; therefore pharmacological therapy is advisable. Current guidelines recommend prophylaxis to be initiated as soon as possible and tapered 1 week after trauma. However, no guideline exists for paediatric patients and the clinical practice is heterogeneous.

Objective

In our institute, prophylaxis was routinely tapered 6 months after trauma. Therefore we investigated whether this prophylaxis or its tapering influenced the development of post-traumatic epilepsy, together with several clinical-demographic factors.

Methods

The study population comprised all patients with post-traumatic brain injury referred to this institute between 2002 and 2009 who consented to participate. Clinical, epileptological and pharmacological data were collected. The role of prophylaxis and several other predictors on occurrence of post-traumatic epilepsy was analysed through logistic regressions.

Results

Two hundred and three patients (145 paediatric) were followed for 57 months on average. Risk factors for epilepsy were past neurosurgery [odds ratio (OR) = 2.61, 95 % confidence interval (CI) 1.15–5.96], presence of epileptiform anomalies (OR = 6.92, 95 % CI 3.02–15.86) and the presence of prophylaxis (OR = 2.49, 95 % CI 1.12–5.52), while higher intelligence quotient (IQ) was protective (OR = 0.96, 95 % CI 0.95–0.98). While evaluating possible different effects within and after 6 months (tapering, for those under prophylaxis), we found that epileptiform anomalies (OR = 7.61, 95 % CI 2.33–24.93, and OR = 8.21, 95 % CI 3.00–22.44) and IQ (OR = 0.96, 95 % CI 0.94–0.98, and OR = 0.97, 95 % CI 0.95–0.98) were always significant predictors of epilepsy, while neurosurgery (OR = 4.38, 95 % CI 1.10–17.45) was significant only within 6 months from trauma, and prophylaxis (OR = 3.98, 95 % CI 1.62–9.75) only afterwards.

Conclusions

These results suggest that prophylaxis was irrelevant when present; furthermore its tapering increased the risk of epilepsy. Since the presence of epileptiform anomalies was the main predictor of post-traumatic epilepsy, such anomalies may be useful to better direct the choice of prophylaxis.

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References

  1. Dikmen SS, Machamer JE, Powell JM, et al. Outcome 3 to 5 years after moderate severe traumatic brain injury, associated mortality and risk factor. Arch Phys Med Rehabil. 2003;84:1449–57.

    Article  PubMed  Google Scholar 

  2. Agrawal A, Timothy J, Pandit L, et al. Post-traumatic epilepsy: an overview. Clin Neurol Neurosurg. 2006;108:433–9.

    Article  PubMed  Google Scholar 

  3. Yeh CC, Chen TL, Hu CJ, et al. Risk of epilepsy after traumatic brain injury: a retrospective population-based cohort study. J Neurol Neurosurg Psychiatry. 2013;84:441–5.

    Article  PubMed  Google Scholar 

  4. Appleton RE, Demellweek C. Posttraumatic epilepsy in children, requiring inpatient rehabilitation following head injury. J Neurol Neurosurg Psychiatry. 2002;72:669–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Barlow KM, Spowart JJ, Minns RA. Early posttraumatic seizures in nonaccidental head injury: relation to outcome. Dev Med Child Neurol. 2000;42:591–4.

    Article  CAS  PubMed  Google Scholar 

  6. Annegers JF, Grabow RV, Groover RV, et al. Seizure after head trauma: a population study. Neurology. 1980;30:683–9.

    Article  CAS  PubMed  Google Scholar 

  7. Lowenstein DH. Epilepsy after head injury: an overview. Epilepsia. 2009;50:4–9.

    Article  PubMed  Google Scholar 

  8. Frey LC. Epidemiology of posttraumatic epilepsy: a critical review. Epilepsia. 2003;44:11–7.

    Article  PubMed  Google Scholar 

  9. Colorado Division of Workers’ Compensation. Traumatic brain injury medical treatment guidelines. Denver (CO): Colorado Division of Workers’ Compensation; 2012 Nov 26, p 119. Available at: https://www.guideline.gov/content.aspx?id=43752.

  10. Adelson PD, Bratton SL, Carney NA, et al. Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 19. The role of anti-seizure prophylaxis following severe pediatric traumatic brain injury. Pediatr Crit Care Med. 2003;4:S72–5.

    Article  PubMed  Google Scholar 

  11. Chang BS, Lowenstein DH. Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2003;14:10–6.

    Article  Google Scholar 

  12. Bratton SL, Chestnut RM, Ghajar J, et al. Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS; Guidelines for the management of severe traumatic brain injury. XIII. Antiseizure prophylaxis. J Neurotrauma. 2007;24:S83–6.

    PubMed  Google Scholar 

  13. Schierhout G, Roberts I. Prophylactic antiepileptic agents after head injury: a systematic review. J Neurol Neurosurg Psychiatry. 1998;64:108–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Iudice A, Murri L. Pharmacological prophylaxis of post-traumatic epilepsy. Drugs. 2000;59:1091–9.

    Article  CAS  PubMed  Google Scholar 

  15. Torbic H, Forni AA, Anger KE, et al. Use of antiepileptics for seizure prophylaxis after traumatic brain injury. Am J Health Syst Pharm. 2013;70:759–66.

    Article  CAS  PubMed  Google Scholar 

  16. Szaflarski JP, Nazzal Y, Dreer LE. Post-traumatic epilepsy: current and emerging treatment options. Neuropsychiatr Dis Treat. 2014;10:1469–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Weston J, Greenhalgh J, Marson AG. Antiepileptic drugs as prophylaxis for post-craniotomy seizures. Cochrane Database Syst Rev. 2015;3:CD007286.

    PubMed  Google Scholar 

  18. Thompson K, Pohlmann-Eden B, Campbell LA, et al. Pharmacological treatments for preventing epilepsy following traumatic head injury. Cochrane Database Syst Rev. 2015;8:CD009900.

    PubMed  Google Scholar 

  19. Mazzini L, Cossa FM, Angelino E, et al. Posttraumatic epilepsy: neuroradiologic and neuropsychological assessment of long-term outcome. Epilepsia. 2003;44:569–74.

    Article  PubMed  Google Scholar 

  20. Grisar T, Bottin P, De Borchgrave D’Altena V, et al. Prophylaxis of the epilepsies: should anti-epileptic drugs be used for preventing seizures after acute brain injury? Acta Neurol Belg. 2005;105:5–13.

    CAS  PubMed  Google Scholar 

  21. Young B, Rapp RP, Norton JA, et al. Failure of prophylactically administered phenytoin to prevent post-traumatic seizures in children. Childs Brain. 1983;10:185–92.

    CAS  PubMed  Google Scholar 

  22. Janz D. Prognosis and prophylaxis of post-traumatic epilepsy. Boll Lega It Epil. 1982;39:37–41.

    Google Scholar 

  23. Dichter MA. Posttraumatic epilepsy: the challenge of translating discoveries in the laboratory to pathways to a cure. Epilepsia. 2009;50:41–5.

    Article  PubMed  Google Scholar 

  24. Temkin NR. Preventing and treating posttraumatic seizures: the human experience. Epilepsia. 2009;50:10–3.

    Article  PubMed  Google Scholar 

  25. Beghi E. Overview of studies to prevent posttraumatic epilepsy. Epilepsia. 2003;44:21–6.

    Article  CAS  PubMed  Google Scholar 

  26. Zhang LL, Zeng LN, Li YP. Side effects of phenobarbital in epilepsy: a systematic review. Epileptic Disord. 2011;13:349–65.

    PubMed  Google Scholar 

  27. Brodie MJ, Kwan P. Current position of phenobarbital in epilepsy and its future. Epilepsia. 2012;53:40–6.

    Article  CAS  PubMed  Google Scholar 

  28. Ijff DM, Aldenkamp AP. Cognitive side-effects of antiepileptic drugs in children. Handb Clin Neurol. 2013;111:707–18.

    Article  PubMed  Google Scholar 

  29. Englander J, Bushnik T, Duong TT, et al. Analyzing risk factors for late posttraumatic seizures: a prospective, multicenter investigation. Arch Phys Med Rehabil. 2003;84:365–73.

    Article  PubMed  Google Scholar 

  30. Statler KD. Pediatric posttraumatic seizures: epidemiology, putative mechanisms of epileptogenesis and promising investigational progress. Dev Neurosci. 2006;28:354–63.

    Article  CAS  PubMed  Google Scholar 

  31. Jensen FE. Introduction. Posttraumatic epilepsy: treatable epileptogenesis. Epilepsia. 2009;50:1–3.

    PubMed Central  Google Scholar 

  32. Muñoz-Sánchez MA, Murillo-Cabezas F, Cayuela A, et al. The significance of skull fracture in mild head trauma differs between children and adults. Childs Nerv Syst. 2005;21:128–32.

    Article  PubMed  Google Scholar 

  33. Asikainen I, Kaste M, Sarna S. Early and late posttraumatic seizures in traumatic brain injury rehabilitation patients: brain injury factors causing late seizures influence of seizures on long- term outcome. Epilepsia. 1998;40:584–9.

    Article  Google Scholar 

  34. Hunt RF, Boychuk JA, Smith BN. Neural circuit mechanisms of post-traumatic epilepsy. Front Cell Neurosci. 2013;7:89.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Formisano R, Barba C, Buzzi MG, et al. The impact of prophylactic treatment on post-traumatic epilepsy after severe traumatic brain injury. Brain Inj. 2007;21:499–504.

    Article  CAS  PubMed  Google Scholar 

  36. Verellen RM, Cavazos JE. Post-traumatic epilepsy: an overview. Therapy. 2010;7:527–31.

    Article  PubMed  PubMed Central  Google Scholar 

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Author notes

    Authors and Affiliations

    1. Scientific Institute IRCCS Eugenio Medea, 23842, Bosisio Parini, Lecco, Italy

      Sandra Strazzer, Marco Pozzi, Paolo Avantaggiato, Nicoletta Zanotta, Roberta Epifanio, Elena Beretta, Francesca Formica, Federica Locatelli, Sara Galbiati, Emilio Clementi & Claudio Zucca

    2. Unit of Clinical Pharmacology, CNR Institute of Neuroscience, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy

      Emilio Clementi

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    1. Sandra Strazzer
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    Correspondence to Emilio Clementi.

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    Funding

    This work was supported by Agenzia Italiana del Farmaco and the Italian Ministry of Health (Ricerca Corrente 2016, to S.S. and E.C. and C.Z.). The funding public institutions had no role in any part of the work.

    Conflict of interest

    Sandra Strazzer reports no conflicts of interest, Marco Pozzi reports no conflicts of interest, Paolo Avantaggiato reports no conflicts of interest, Nicoletta Zanotta reports no conflicts of interest, Roberta Epifanio reports no conflicts of interest, Elena Beretta reports no conflicts of interest, Francesca Formica reports no conflicts of interest, Federica Locatelli reports no conflicts of interest, Sara Galbiati reports no conflicts of interest, Emilio Clementi reports no conflicts of interest, and Claudio Zucca reports no conflicts of interest.

    Ethical approval

    All procedures involving human participants were performed in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. When clinical data were collected, informed consent to anonymise them and use them for research purposes was obtained from all individual participants included in the study. For this type of retrospective study, formal approval from the institutional committee is not required; only a notification of usage of anonymised data is needed.

    Additional information

    S. Strazzer and M. Pozzi contributed equally to the work.

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    Strazzer, S., Pozzi, M., Avantaggiato, P. et al. Late Post-traumatic Epilepsy in Children and Young Adults: Impropriety of Long-Term Antiepileptic Prophylaxis and Risks in Tapering. Pediatr Drugs 18, 235–242 (2016). https://doi.org/10.1007/s40272-016-0167-3

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