, Volume 59, Issue 5, pp 1091–1099 | Cite as

Pharmacological Prophylaxis of Post-Traumatic Epilepsy

Review Article


Early and late epileptic seizures are a frequent complication of severe head traumas. The administration of anticonvulsant drugs immediately after head injury is commonly implemented as a prophylactic measure; however, there is a lack of consensus on the usefulness of prophylaxis with anticonvulsants for the prevention of late post-traumatic epilepsy (PTE). The inconsistent evidence accumulated so far from clinical studies, most nonrandomised and uncontrolled in design, and the limited knowledge of the processes underlying post-traumatic epileptogenesis, do not warrant empirical pharmacological prophylaxis with long term administration of conventional anticonvulsants. Phenytoin and phenobarbital (phenobarbitone) are used to a large extent in this indication. As a general rule, a benefit/risk analysis in individual patients should drive prophylactic drug prescription in PTE as it can have potential detrimental effects on a patient’s recovery. New compounds, such as free-radical scavengers and antiperoxidants, show encouraging experimental results, but their clinical use is still very limited.


Valproic Acid Vigabatrin Audiogenic Seizure Pharmacological Prophylaxis Severe Head Trauma 


  1. 1.
    Jensen RL, Stone JL. Benjamin Winslow Dudley and early American trephination for post-traumatic epilepsy. Neurosurgery 1997; 41: 263–8PubMedCrossRefGoogle Scholar
  2. 2.
    Walker AE, Blumer D. The fate of World War II veterans with posttraumatic seizures. Arch Neurol 1989; 46: 23–6PubMedCrossRefGoogle Scholar
  3. 3.
    Hoff H, Hoff H. Fortschritte in der Behandlung der Epilepsie. Monatsschr Psychiat Neurol 1947; 114: 105–18CrossRefGoogle Scholar
  4. 4.
    Birkmayer W. Die Behandlung der traumatischen epilepsie. Wien Klin Wochenschr 1951; 63: 606–9PubMedGoogle Scholar
  5. 5.
    Servit Z. Prophylactic treatment of posttraumatic epilepsy. Nature 1960; 188: 669–70PubMedCrossRefGoogle Scholar
  6. 6.
    Jennett WB, Levin WS. Traumatic epilepsy after closed head injuries. J Neurol Neurosurg Psychiatry 1960; 23: 295–301PubMedCrossRefGoogle Scholar
  7. 7.
    Popek K, Musil F. Clinical trial to prevent posttraumatic epilepsy after severe brain injuries in adult [in Czechoslovakian]. Cas Lek Cesk 1969; 108: 133–47PubMedGoogle Scholar
  8. 8.
    Adeloye A, Odeku EL. Epilepsy after missile wounds of the head. J Neurol Neurosurg Psychiatry 1971; 34: 98–103PubMedCrossRefGoogle Scholar
  9. 9.
    Jennett WB. Epilepsy after non-missile head injuries. London: Heinemann Medical Books, 1975Google Scholar
  10. 10.
    Young B, Rapp RP, Brooks WH, et al. Posttraumatic epilepsy prophylaxis. Epilepsia 1979; 20: 671–81PubMedCrossRefGoogle Scholar
  11. 11.
    Murri L, Parenti G, Bonuccelli U, et al. Phénobarbital prophylaxis of posttraumatic epilepsy. Ital J Neurol Sci 1980; 1: 225–30PubMedGoogle Scholar
  12. 12.
    Zajac J, Kowalczyk K, Fabian F, et al. Epilepsy and complication after craniocerebral traumas. Monogr Neural Sci 1980; 5: 285–9PubMedGoogle Scholar
  13. 13.
    Servit Z, Musil F. Prophylactic treatment of posttraumatic epilepsy: results of a long-term follow-up in Czechoslovakia. Epilepsia 1981; 22: 315–20PubMedCrossRefGoogle Scholar
  14. 14.
    Pechadre M, Lauxerois M, Colnet G, et al. Prevention of late post-traumatic epilepsy by phenytoin in severe brain injuries: 2 years’ follow-up. Presse Med 1991; 20: 841–5PubMedGoogle Scholar
  15. 15.
    Penry JK, White BG, Brackett CE. A controlled prospective study of the pharmacological prophylaxis of posttraumatic epilepsy. Neurology 1979; 29: 600–1CrossRefGoogle Scholar
  16. 16.
    McQueen JK, Blackwood DHR, Harris P, et al. Low risk of late post-traumatic seizures following severe head injury: implications for clinical trials of prophylaxis. J Neurol Neurosurg Psychiatry 1983; 46: 899–904PubMedCrossRefGoogle Scholar
  17. 17.
    Young B, Rapp RP, Norton JA, et al. Failure of prophylactically administered phenytoin to prevent late posttraumatic seizures. J Neurosurg 1983; 58: 236–41PubMedCrossRefGoogle Scholar
  18. 18.
    Young B, Rapp RP, Norton JA, et al. Failure of prophylactically administered phenytoin to prevent posttraumatic seizures in children. Childs Brain 1983; 10: 185–92PubMedGoogle Scholar
  19. 19.
    Temkin NR, Dikmen SS, Wilensky AJ, et al. A randomized double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med 1990; 323: 497–502PubMedCrossRefGoogle Scholar
  20. 20.
    Paillas JE, Paillas N, Bureau M. Posttraumatic epilepsy.Introduction and clinical observations. Epilepsia 1970; 11: 5–15PubMedCrossRefGoogle Scholar
  21. 21.
    Rapport RL, Penry JK. A survey of attitudes towards the pharmacological prophylaxis of posttraumatic epilepsy. J Neurosurg 1973; 38: 159–66PubMedCrossRefGoogle Scholar
  22. 22.
    Johnson AL, Harris P, McQueen JK, et al. Phenytoin prophylaxis for posttraumatic seizures. J Neurosurg 1983; 59: 727–8PubMedGoogle Scholar
  23. 23.
    Deutschmann CS, Haines SJ. Anticonvulsant prophylaxis in neurological surgery. Neurosurgery 1985; 17: 510–7CrossRefGoogle Scholar
  24. 24.
    Loiseau P, Marchai C. Epilepsie post-traumatique. Epilepsies 1990; 2: 199–202Google Scholar
  25. 25.
    Majkowski J. Posttraumatic epilepsy. In: Dam M, Gram L, editors. Comprehensive epileptology. New York (NY): Raven Press, 1990: 281–8Google Scholar
  26. 26.
    Murri L, Parenti G, Annegers JF. Pharmacological prophylaxis for posttraumatic epilepsy. Pisa: Pacini, 1991Google Scholar
  27. 27.
    Temkin NR, Dikmen SS, Winn HR. Management of head injury.Posttraumatic seizures. Neurosurg Clin N Am 1991; 2: 425–35PubMedGoogle Scholar
  28. 28.
    Willmore LJ. Post-traumatic epilepsy — mechanisms and prevention. In: Pedley TA, Meldrum BS, editors. Recent advances in epilepsy. London: Churchill Livingstone, 1992: 107–17Google Scholar
  29. 29.
    Yablon SA. Posttraumatic seizures. Arch Phys Med Rehabil 1993; 74: 983–1001PubMedGoogle Scholar
  30. 30.
    Dugan EM, Howell JM. Posttraumatic seizures. Emerg Med Clin North Am 1994; 12: 1081–7PubMedGoogle Scholar
  31. 31.
    Janz D. Risk and drug prevention of epileptic seizures after cerebral lesions. Zentralbl Neurochir 1994; 55: 1–8PubMedGoogle Scholar
  32. 32.
    Schierhout G, Roberts I. Prophylactic antiepileptic agents after head injury: a systematic review. J Neurol Neurosurg Psychiatry 1998; 64: 108–12PubMedCrossRefGoogle Scholar
  33. 33.
    de la Pena P, Porta-Etessam J. Post-traumatic epilepsy. Rev Neurol 1998; 26; 256–61PubMedGoogle Scholar
  34. 34.
    Dunn LT, Foy PM. Anticonvulsant and antibiotic prophylaxis in head injury. Ann R Coll Surg Engl 1994; 76: 147–9PubMedGoogle Scholar
  35. 35.
    Lee ST, Lui TN, Wong CW, et al. Early seizures after moderate closed head injury. Acta Neurochir (Wien) 1995; 137: 151–4CrossRefGoogle Scholar
  36. 36.
    Barry E, Bergey GK, Krumholz A, et al. Posttraumatic seizure types vary with the interval after head injury. Epilepsia 1997; 38 Suppl. 8: 49S-50SGoogle Scholar
  37. 37.
    McCrory PR, Berkovic SF. Concussive convulsions.Incidence in sport and treatment recommendations. Sports Med 1998; 25: 131–6PubMedCrossRefGoogle Scholar
  38. 38.
    Wohlrab G, Schmitt B, Boltshauser E. Benign focal epilepti-form discharges in children after severe head trauma: prognostic value and clinical course. Epilepsia 1997; 38: 275–8PubMedCrossRefGoogle Scholar
  39. 39.
    Pohlmann-Eden B, Bruchmeir J. Predictors and dynamics of posttraumatic epilepsy. Acta Neurol Scand 1997; 95: 257–62PubMedCrossRefGoogle Scholar
  40. 40.
    Lee ST, Lui TN, Wong CW, et al. Early seizures after severe closed head injury. Can J Neurol Sci 1997; 24: 40–3PubMedGoogle Scholar
  41. 41.
    Rish BL, Caveness WE Relation of prophylactic medication to the occurrence of early seizures following craniocerebral trauma.J Neurosurg 1973; 38: 155–8PubMedCrossRefGoogle Scholar
  42. 42.
    Wohns RNW, Wyler AR. Prophylactic phenytoin in severe head injuries. J Neurosurg 1979; 51: 507–9PubMedCrossRefGoogle Scholar
  43. 43.
    Young B, Rapp RP, Norton JA, et al. Failure of prophylactically administered phenytoin to prevent early posttraumatic seizures. J Neurosurg 1983; 58: 231–5PubMedCrossRefGoogle Scholar
  44. 44.
    Temkin NR, Haglund MM, Winn HR. Causes, prevention, and treatment of post-traumatic epilepsy. New Horiz 1995; 3: 518–22PubMedGoogle Scholar
  45. 45.
    Haitiner AM, Newell DW, Temkin NR, et al. Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis. J Neurosurg 1999; 91: 588–92CrossRefGoogle Scholar
  46. 46.
    Glötzner FL, Haubitz I, Miltner F, et al. Scizure prevention using carbamazepine following severe brain injuries. Neurochirurgia (Stuttg) 1983; 26: 66–79Google Scholar
  47. 47.
    Anderson GD, Gidal BE, Hendryx RJ, et al. Decreased plasma protein binding of valproate in patients with acute head trauma. Br J Clin Pharmacol 1994; 37: 559–62PubMedCrossRefGoogle Scholar
  48. 48.
    Griebel ML. Phenytoin protein binding in pediatric patients with acute traumatic injury. Crit Care Med 1990; 18: 385–91PubMedCrossRefGoogle Scholar
  49. 49.
    Rivey MP, Allington DR, Stone JD, et al. Alteration of carbamazepine pharmacokinetics in patients with traumatic brain injury. Brain Inj 1995; 9: 41–7PubMedCrossRefGoogle Scholar
  50. 50.
    Annegers JF, Grabow JD, Groover RV, et al. Scizures after head trauma: a population study. Neurology 1980; 30: 683–9PubMedCrossRefGoogle Scholar
  51. 51.
    Meirowsky AM. Notes on posttraumatic epilepsy in missile wounds of the brain. Mil Med 1982; 147: 632–4PubMedGoogle Scholar
  52. 52.
    Credner L. Klinische und sociale Auswirkungen von Hirn-schadigungen. Z Gesamte Neurol Psychiat 1930; 126: 721–57CrossRefGoogle Scholar
  53. 53.
    Salazar AM, Jabbari B, Vance SC, et al. Epilepsy after penetrating head injury.I. Clinical correlates: a report of the Vietnam Head Injury Study. Neurology 1985; 35: 1406–14PubMedCrossRefGoogle Scholar
  54. 54.
    Lockard JS, Congdon WC, Ducharme LL, et al. Prophylaxis with diphenylhydantoin and phenobarbital in alumina-gel monkey model.I. Twelve months of treatment: seizure, EEG, blood, and behavioral data. Epilepsia 1976; 17: 37–47PubMedCrossRefGoogle Scholar
  55. 55.
    Lockard JS, Ducharme LL, Congdon WC, et al. Prophylaxis with diphenylhydantoin and phenobarbital in alumina-gel monkey model. II. Fourth-month follow-up period: seizure, EEG, blood and behavioral data. Epilepsia 1976; 17: 49–57PubMedCrossRefGoogle Scholar
  56. 56.
    Rapport 2nd RL, Ojemann GA. Prophylactically administered phenytoin. Effects of the development of chronic cobalt-induced epilepsy in the cat. Arch Neurol 1975; 32: 539–48PubMedCrossRefGoogle Scholar
  57. 57.
    Willmore LJ, Triggs WJ. Effect of phenytoin and cortico-steroids on seizures and lipid peroxidation in experimental post-traumatic epilepsy. J Neurosurg 1984; 60: 467–72PubMedCrossRefGoogle Scholar
  58. 58.
    Payan H, Toga M, Berard-Badier M. The pathology of posttraumatic epilepsies. Epilepsia 1970; 11: 81–94PubMedCrossRefGoogle Scholar
  59. 59.
    McKinney RA, Debanne D, Gahwiler BH, et al. Lesion-induced axonal sprouting and hyperexcitability in the hippo-campus in vitro: implications for the genesis of posttraumatic epilepsy. Nat Med 1997; 3: 990–6PubMedCrossRefGoogle Scholar
  60. 60.
    Bush PC, Prince DA, Miller KD. Increased pyramidal excitability and NMDA conductance can exlain posttraumatic epileptogenesis without disinhibition: a model. J Neurophysiol 1999; 82: 1748–58PubMedGoogle Scholar
  61. 61.
    Angeleri F, Majkowski J, Cacchiò G, et al. Posttraumatic epilepsy risk factors: one-year prospective study after head injury. Epilepsia 1999; 40: 1222–30PubMedCrossRefGoogle Scholar
  62. 62.
    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: 584–9PubMedCrossRefGoogle Scholar
  63. 63.
    Schultze M, Dauch WA, Guttinger M, et al. Risk factors for posttraumatic fits and epilepsy. Zentralbl Neurochir 1999; 60: 163–7Google Scholar
  64. 64.
    Caveness WF. Epilepsy, a product of trauma in our time. Epilepsia 1976; 17: 207–15PubMedCrossRefGoogle Scholar
  65. 65.
    Weiss GH, Feeney DM, Caveness WF, et al. Prognostic factors for the occurrence of posttraumatic epilepsy. Arch Neurol 1983; 40: 7–10PubMedCrossRefGoogle Scholar
  66. 66.
    Weiss GH, Salazar AM, Vance SC, et al. Predicting posttraumatic epilepsy in penetrating head injury. Arch Neurol 1986; 43: 771–3PubMedCrossRefGoogle Scholar
  67. 67.
    Gruber R, Bubl R, Fruttiger V. Anticonvulsive prophylaxis after juvenile craniocerebral injuries: a retrospective evaluation. Z Kinderchir 1985; 40: 199–202PubMedGoogle Scholar
  68. 68.
    Wang EC, Geyer JR, Berger MS. Incidence of postoperative epilepsy in children following subfrontal craniotomy for tumor. Pediatr Neurosurg 1994; 21: 165–73PubMedCrossRefGoogle Scholar
  69. 69.
    North JB, Penhall RK, Hanieh A, et al. Phenytoin and postoperative epilepsy: a double-blind study. J Neurosurg 1983; 58: 672–7PubMedCrossRefGoogle Scholar
  70. 70.
    Kuijlen JM, Teernstra OP, Kessels AG, et al. Effectiveness of antiepileptic prophylaxis used with supratentorial craniotomies: a meta-analysis. Scizure 1996; 5: 291–8Google Scholar
  71. 71.
    Caveness WF, Meirowsky AM, Rish BL, et al. The nature of posttraumatic epilepsy. J Neurosurg 1979; 50: 545–53PubMedCrossRefGoogle Scholar
  72. 72.
    Weiss GH, Salazar AM, Vance SC, et al. Predicting phenytoin in severe head injuries. J Neurosurg 1979; 51: 507–9CrossRefGoogle Scholar
  73. 73.
    Jennett WB. Posttraumatic epilepsy: phenytoin prophylaxis [letter]. J Neurosurg 1980; 52: 291PubMedGoogle Scholar
  74. 74.
    Hauser WA. Prevention of post-traumatic epilepsy. N Engl J Med 1990; 323: 540–2PubMedCrossRefGoogle Scholar
  75. 75.
    Bauer G, Luef G, Marosi M, et al. Phenytoin for the prevention of post-traumatic seizures [letter]. N Engl J Med 1991; 324: 341PubMedGoogle Scholar
  76. 76.
    Massagli TL. Prophylaxis and treatment of posttraumatic epilepsy with phenytoin. West J Med 1992; 157: 663–4PubMedGoogle Scholar
  77. 77.
    Murri L, Arrigo A, Bonuccelli U, et al. Phenobarbital in the prophylaxis of late posttraumatic seizures. Ital J Neurol Sci 1992; 13: 755–60PubMedCrossRefGoogle Scholar
  78. 78.
    Manaka S. Cooperative prospective study on posttraumatic epilepsy: risk factors and the effect of prophylactic anticonvulsant. Jpn J Psychiatry Neurol 1992; 46: 311–5PubMedGoogle Scholar
  79. 79.
    Price DJ. The efficiency of sodium valproate as the only anti-convulsant administered to neurosurgical patients. In: Parsonage MF, Caldwell ADS, editors. The place of sodium valproate in the treatment of epilepsy. London: Academic Press, 1980: 23–30Google Scholar
  80. 80.
    Temkin NR, Dikmen SS, Anderson GD, et al. Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg 1999; 91: 593–600PubMedCrossRefGoogle Scholar
  81. 81.
    Glötzner FL. Epilepsy prophylaxis with carbamazepine in severe head injuries. In: Murri L, Parenti G, Annegers JF, editors. Pharmacological prophylaxis for posttraumatic epilepsy. Pisa: Pacini, 1991: 59–72Google Scholar
  82. 82.
    Shin C, Rigsbee LC, McNamara JO. Anti-seizure and anti-epileptogenic effect of gamma-vinyl gamma-aminobutyric acid in amygdaloid kindling. Brain Res 1986; 398: 370–4PubMedCrossRefGoogle Scholar
  83. 83.
    Rubin JJ, Willmore LJ. Prevention of iron-induced epileptiform discharges in rats by treatment with antiperoxidants. Exp Neurol 1980; 67: 472–80PubMedCrossRefGoogle Scholar
  84. 84.
    Kabuto H, Yokoi I, Habu H, et al. Reduction in nitric oxide synthase activity with development of an epileptogenic focus induced by ferric chloride in the rat brain. Epilepsy Res 1996; 25: 65–8PubMedCrossRefGoogle Scholar
  85. 85.
    Yokoi I, Toma J, Liu J, et al. Adenosines scavenged hydroxy radicals and prevented posttraumatic epilepsy. Free Radic Biol Med 1995; 19: 473–9PubMedCrossRefGoogle Scholar
  86. 86.
    Schubert P, Kreutzberg GW. Cerebral protection by adenosine. Acta Neurochir (Wien) 1993; 57: 80–8Google Scholar
  87. 87.
    Willmore LJ, Triggs WJ, Gray JD. The role of iron-induced hippocampal peroxidation in acute epileptogenesis. Brain Res 1986; 382: 422–6PubMedCrossRefGoogle Scholar
  88. 88.
    Demopoulos HB, Flamm ES, Seligman ML, et al. Antioxidant effects of barbiturates in model membranes undergoing free radical damage. Acta Neurol Scand 1977; 7: 12–3Google Scholar
  89. 89.
    Kontos HA, Wei EP. Superoxide production in experimental brain injury. J Neurosurg 1986; 64: 803–7PubMedCrossRefGoogle Scholar
  90. 90.
    Hall ED, Yonkers PA, McCall JM, et al. Effects of the 21-aminosteroid U74006F on experimental head injury in mice. J Neurosurg 1988; 68: 456–61PubMedCrossRefGoogle Scholar
  91. 91.
    Muizelaar JP, Marmarou A, Young HF, et al. Improving the outcome of severe head injury with the oxygen radical scavenger polyethylene glycol-conjugated Superoxide dismutase: a phase II trial. J Neurosurg 1993; 78: 375–82PubMedCrossRefGoogle Scholar
  92. 92.
    Toulmond S, Serrano A, Benavides J, et al. Prevention by eliprodil (SL 82.0715) of traumatic brain damage in the rat. Existence of a large (18h) therapeutic window. Brain Res 1993; 620: 32–41PubMedCrossRefGoogle Scholar
  93. 93.
    Greenberg RS, Helfaer MA, Kirsh JR, et al. Nitric oxide synthase inhibition with NG-mono-methyl-L-arginine reversibly decreases cerebral blood flow in piglets. Crit Care Med 1994; 22: 384–92PubMedCrossRefGoogle Scholar
  94. 94.
    Musleh W, Bruce A, Malfroy B, et al. Effects of EUK-8, a synthetic catalytic Superoxide scavenger, on hypoxia- and acidosis-induced damage in hippocampal slices. Neuropharmacology 1994; 33: 929–34PubMedCrossRefGoogle Scholar
  95. 95.
    Bullock R. Strategies for neuroprotection with glutamate antagonists. Extrapolating from evidence taken from the first stroke and head injury studies. Ann N Y Acad Sci 1995; 765: 272–8PubMedCrossRefGoogle Scholar
  96. 96.
    Smith DH, Gennarelli TA, Mclntosh TK. The potential of 21 aminosteroids (lazaroids) as neuroprotective therapies in CNS injury. CNS Drugs 1995; 3: 159–63CrossRefGoogle Scholar
  97. 97.
    Tsuchida E, Bullock R. The effect of the glycine site-specific N-methyl-D-aspartate antagonist ACEA1021 on ischemic brain damage caused by acute subdural hematoma in the rat. J Neurotrauma 1995; 12: 279–88PubMedCrossRefGoogle Scholar
  98. 98.
    Komatsu M, Hiramatsu M, Yokoyama H, et al. Effect of TJ-960 (a japanese herbal medicine) on free radical changes within an iron-induced focal epileptogenic region in rat brain measured by in vivo L-band electron spin resonance. Neurosci Lett 1996; 205: 189–92PubMedCrossRefGoogle Scholar
  99. 99.
    Petty MA, Poulet P, Haas A, et al. Reduction of traumatic brain injury-induced cerebral oedema by a free radical scavenger. Eur J Pharmacol 1996; 307: 149–55PubMedCrossRefGoogle Scholar
  100. 100.
    Tsuchida E, Harms JF, Woodward JJ, et al. A use-dependent sodium channel antagonist, 619C89, in reduction of ischemic brain damage and glutamate release after acute subdural hematoma in the rat. J Neurosurg 1996; 85: 104–11PubMedCrossRefGoogle Scholar
  101. 101.
    Young B, Runge JW, Waxman KS, et al. Effects of pegorgotein on neurologic outcome of patients with severe head injury. A multicenter, randomized controlled trial. JAMA 1996; 276: 538–43PubMedCrossRefGoogle Scholar
  102. 102.
    Bordi F, Pietra C, Ziviani L, et al. The glycine antagonist GV150526 protects somatosensory evoked potentials and reduces the infarct area in the MCAo model of focal ischemia in the rat. Exp Neurol 1997; 145: 425–33PubMedCrossRefGoogle Scholar
  103. 103.
    Dewitt DS, Prough DS, Uchida T, et al. Effects of nalmefene, CG3703, tirilazad, or dopamine on cerebral blood flow, oxygen delivery, and electroencephalographic activity after traumatic brain injury and hemorrhage. J Neurotrauma 1997; 14: 931–41PubMedCrossRefGoogle Scholar
  104. 104.
    Kawamata T, Katayama Y, Maeda T, et al. Antioxidant, OPC-14117, attenuates edema formation and behavioral deficits following cortical contusion in rats. Acta Neurochir (Wien) 1997; 70 Suppl.: 191–3Google Scholar
  105. 105.
    Lees KR. Cerestat and other NMDA antagonists in ischemic stroke. Neurology 1997; 49 Suppl. 4: 66S-9SCrossRefGoogle Scholar
  106. 106.
    Maiese K, TenBroeke M, Kue I. Neuroprotection of lubeluzole is mediated through the signal transduction pathways of nitric oxide. J Neurochem 1997; 68: 710–4PubMedCrossRefGoogle Scholar
  107. 107.
    Baker K, Marcus CB, Huffman K, et al. Synthetic combined Superoxide dismutase/catalase mimetics are protective as a delayed treatment in a rat stroke model: a key role for reactive oxygen species in ischemic brain injury. J Pharmacol Exp Ther 1998; 284: 215–21PubMedGoogle Scholar
  108. 108.
    Kabuto H, Yokoi I, Ogawa N. Melatonin inhibits iron-induced epileptic discharges in rats by suppressing peroxidation. Epilepsia 1998; 39: 237–43PubMedCrossRefGoogle Scholar
  109. 109.
    Kucukkaya B, Aker R, Yuksel M, et al. Low dose MK-801 protects against iron-induced oxidative changes in a rat model of focal epilepsy. Brain Res 1998; 788: 133–6PubMedCrossRefGoogle Scholar
  110. 110.
    Rauhala P, Lin AM, Chiueh CC. Neuroprotection by S-nitrosoglutathione of brain dopamine neurons from oxidative stress. FASEB J 1998; 12: 165–73PubMedGoogle Scholar
  111. 111.
    Braakman R. The European Study Group on Nimodipine in severe head injury. A multicenter trial of the efficacy of nimodipine on outcome after head injury. J Neurosurg 1994; 80: 797–804CrossRefGoogle Scholar
  112. 112.
    Hans P, Triffaux M, Bonhomme V, et al. Control of drug-resistant epilepsy after head injury with intravenous nimodipine. Acta Anaesthesiol Belg 1994; 45: 175–8PubMedGoogle Scholar
  113. 113.
    Cunitz G. Early management of head injury. Acta Anaesthesiol Scand 1997; 111: 46–7Google Scholar
  114. 114.
    Graber KD, Prince DA. Tetrodotoxin prevents posttraumatic epileptogenesis in rats. Ann Neurol 1999; 46: 234–42PubMedCrossRefGoogle Scholar
  115. 115.
    Deymeer F, Leviton A. Posttraumatic seizures: an assessment of the epidemiologic literature. Cent Nerv Syst Trauma 1985; 2: 33–43PubMedGoogle Scholar
  116. 116.
    Annegers JF. The incidence of epilepsy after head trauma. In: Murri L, Parenti G, Annegers JF, editors. Pharmacological prophylaxis of posttraumatic epilepsy. Pisa: Pacini, 1991: 7–16Google Scholar
  117. 117.
    American Association of Neurological Surgeons. Guidelines for the management of severe head injuries. Neurol Alert 1997; 5: 35–6Google Scholar
  118. 118.
    Brain Injury Special Interest Group of the American Academy of Physical Medicine and Rehabilitation. Practice parameter: antiepileptic drug treatment of posttraumatic seizures. Arch Phys Med Rehabil 1998; 79: 594–7CrossRefGoogle Scholar
  119. 119.
    Dauch WA, Schütze M, Güttinger M, et al. Post-traumatic seizure prevention-results of a survey of 127 neurosurgery clinics. Zentralbl Neurochir 1996; 57: 190–5PubMedGoogle Scholar
  120. 120.
    Hernandez TD. Preventing post-traumatic epilepsy after brain injury: weighing the costs and benefits of anticonvulsant prophylaxis. Trends Pharmacol Sci 1997; 18: 59–62PubMedCrossRefGoogle Scholar
  121. 121.
    Hernandez TD, Naritoku DK. Scizures, epilepsy, and functional recovery after traumatic brain injury: a reappraisal. Neurology 1997; 48: 803–6PubMedCrossRefGoogle Scholar
  122. 122.
    Dikmen SS, Temkin NR, Miller B, et al. Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures. JAMA 1991; 265: 1271–7PubMedCrossRefGoogle Scholar
  123. 123.
    Massagli TL. Neurobehavioral effects of phenytoin, carbamazepine, and valproic acid: implications for use in traumatic brain injury. Arch Phys Med Rehabil 1991; 72: 219–26PubMedGoogle Scholar
  124. 124.
    Haitiner AM, Temkin NR, Winn HR, et al. The impact of post-traumatic seizures on 1-year neuropsychological and psychological outcome of head injury. J Int Neuropsychol Soc 1996; 2: 494–504CrossRefGoogle Scholar

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© Adis International Limited 2000

Authors and Affiliations

  1. 1.Department of Neurosciences, Section of NeurologyUniversity of PisaPisaItaly

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