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Written in Frustration and The Story of a Remarkable Medicine


Head Injuries and Surgery

Hoff and Hoff, Monatsschrift Psychiatrie and Neurologie (1947),2599 reported a controlled study of the effectiveness of PHT in the prevention of post-traumatic seizures. One hundred World War 11 veterans with head injuries were randomized into two groups of fifty. One group received 200 mg PFff daily, while the other group, serving as controls, received no treatment unless seizures developed. During the first four years, only two patients (4%) from the PHT-treated group developed seizures, (one after he had become a heavy drinker), while seventeen (38%) developed seizures in the control group. Four years later, BIRKMAYER, Wiener Kliniscbe Wocbenscbrift (1951),2340 reported additional results of this study. Six percent of the patients in the PHT-treated group had seizures compared to 51% in the control group. The author concludes that small doses of PHT are sufficient to protect against post-traumatic epilepsy.

2599. Hoff, H., Hoff, H., Advances in the treatment of epilepsy, Monatsschr. Psychiatr. Neurol., 114: 105-18, 1947.
2340. Birkmayer, W., Die behandlung der traumatischen epilepsie, Wein. Klin. Wochenschr., 63: 606-9, 1951.

The Czechoslovakia Health Ministry, Medical World News (1968),70 issued a directive requiring doctors to give PHT and phenobarbital to every trauma victim who remains unconscious for more than three hours. After six months, if no signs of epilepsy have appeared, the drugs are phased out over the next nine to eighteen months. This directive was based upon work by DR. KAREL POPEK, chief neurologist at the Neurological Clinic of the University Medical Faculty in Brno, Czechoslovakia. Dr. Popek conducted a controlled clinical study of PHT and phenobarbital in patients with cerebral concussion or other serious head injuries. He considered the results of the study persuasive enough to warrant routine use of the drugs as preventive therapy. (See also SERVIT AND MUSIL, Ref. 2256.)

70. Popek, K., Czechs make anticonvulsants a must for coma victims, Med. World News, 33, March 8, 1968.

2256. Servitz, Z. and Muzil, F., Prophylactic treatment of post-traumatic epilepsy: results of a long-term follow-up in Czechoslovakia, Epilepsia, 22: 315-20, 1981.

Wohns and Wyler, Journal of Neurosurgery (1979),2122 reported on sixty-two patients whose head injuries were sufficiently severe to cause high probability of post-traumatic seizures. Of fifty patients treated with PHT, 10% developed late onset seizures. Twelve patients not treated with PHT, but who had head injuries of equal magnitude, had a 50% incidence of seizures.

2122. Wohns, R. N. W. and Wyler, A. R., Prophylactic phenytoin in severe head injuries, J. Neurosurg., 51: 507-8, 1979.

Young, Rapp, Brooks, Madauss and Norton, Epilepsia (1979),2134 in a study involving eighty-four patients with head injuries, reported the beneficial use of PHT for post-traumatic seizure prophylaxis. With PHT only five of eighty-four individuals had seizures within a year after severe head injury, and only one of these patients had more than one seizure. The authors concluded that the greatly reduced incidence of post-traumatic seizures in these patients demonstrates the prophylactic effect of PHT.

2134. Young, B., Rapp, R., Brooks, W. H., Madauss, W. and Norton, J. A., Posttraumatic epilepsy prophylaxis, Epilepsia, 20: 671-81,1979.

Servit and Musil, Epilepsia (1981),2256 report the results of a long-term study of prophylactic treatment of post-traumatic epilepsy performed in Czechoslovakia during the years 1963 through 1980. The prophylactically treated group of 144 patients with severe brain injuries was compared with a control group of twenty-four equally damaged cases without prophylactic treatment. Prophylactic treatment consisted of PHT (160-240 mg/day) and phenobarbital (30-60 mg/day) administered for periods of two years in the majority of cases. The incidence of late post-traumatic epilepsy was 25% in the control, compared with 2.1% in the prophylactically treated group.

2256. Servitz, Z. and Muzil, F., Prophylactic treatment of post-traumatic epilepsy: results of a long-term follow-up in Czechoslovakia, Epilepsia, 22: 315-20, 1981.

White, Penry, Bracket, Lisco, Art, Nemore, Mann, Mumaw and Whitley, NINCDS (1982),3068 in a double-blind study of forty-nine severely head-injured patients, compared the combination of PHT and phenobarbitat to placebo in preventing post-traumatic seizures. Groups were matched for severity of injury. PHT levels were maintained at 10-20 mg/ml and phenobarbital levels at 20-30 mg/ml. Patients treated with PHT and phenobarbital had a significantly lower incidence of post-traumatic epilepsy than the placebo group.

3068. White, B. C., Penry, J. K., Bracket, C. F., Lisco, M., Art, D., Nemore, J., Mann, T., Mumaw, L., Whitley, L., Study on pharmacological prophylaxis of posttraumatic epilepsy in severely head injured patients utilizing therapeutic serum levels of antiepileptic drugs. NINCDS, Bethesda, Md. & Kansas Univ. Med, Center, Ka., 1982.

North, Penhall, Hanieh, Frewin and Taylor, Journal of Neurosurgery (1983),2833 reported a double-blind study of PHT versus placebo as prophylaxis against post-craniotomy seizures in 281 patients. One hundred forty patients received PHT and 141, placebo. Patients were followed for one year. PHT significantly reduced the incidence of post-craniotomy seizures in comparison to placebo. For the entire group of PHT-treated patients, this reduction was greatest within the first three months, when the risk of seizures was greatest. In certain high-risk patients (following operations for aneurysm, head injury and meningioma) there was a significantly lower incidence of seizures at both one month and approximately one year.

2833. North, J. B., Penhall, R. K., Hanieh, A., Frewin, D. B., Taylor, W. B., Phenytoin and postoperative epilepsy-a double-blind study, J. Neurosurg., 58: 672-7, 1983.

El-Zayat, Journal of Neurological and Orthopaedic Medicine and Surgery (1988), 3404 treated fifty patients, all military personnel casualties of Iraq-Iran War, suffering solitary extra-cerebral head injuries by shells. For their post-concussion symptoms, 25 patients were treated with phenytoin (100 mg tid) while a similar control group was treated with placebo for one month. After one month both groups were analyzed.

In the phenytoin-treated group, there was relief for 17 of 20 patients who suffered headaches; 16 of 18 who were insomniacs; 11 of 15 who experienced tiredness; and 8 of 12 had memory improvement. In the control group, there was improvement for 12 of 22 who suffered with headache; 5 of 16 slept better: 4 of 12 no longer experienced tiredness; and 1 of 8 had memory improvement. The author found phenytoin to be effective in treating his patients for symptoms related to post-concussion syndrome.

3404. El-Zayat, S.G., Role of phenytoin in the post-convulsion syndrome following missile head injury, J. Neurol. Orthop. Med. Surg., 9(3): 253, 1988.

Lewis, Yee, Inkelis and Gilmore, Annals of Emergency Medicine (1993), 3405 conducted a retrospective study of the medical records of 194 head trauma pediatric patients, ranging in age from 3 months to 15 years. The authors' goal was to determine the clinical characteristics associated with early post-traumatic seizures in children with head trauma. Based on their recorded Glasgow Coma Scale (GCS) score, the patients were divided into two groups: one with scores of 3 to 8 and the other 9 to 15. In the group having the GCS score of 3 to 8 (high risk group), there were 17 patients receiving no anticonvulsive medication. Nine of these suffered post-traumatic seizures (53%). Only 2 of 13 patients (15%) receiving prophylactic phenytoin suffered post-traumatic seizures. This difference attained one-tailed statistical significance. The results of their study suggest, to the authors, that prophylactic phenytoin is beneficial in preventing early post-traumatic seizures in children as well as adults. In their discussion, the authors cite that prophylactic phenytoin to prevent early post-traumatic seizures potentially is important because approximately one half of patients with severe head trauma and GCS scores of 3 to 8 have increased intracranial pressure. Any process that increases intracranial pressure or increases the imbalance between cerebral oxygen supply and demand may have a negative effect on a patient's long-term prognosis. Seizures cause both an increase in intracranial pressure and an increase in cerebral oxygen demand, and measures taken to decrease their likelihood might be beneficial to the patient. Because cerebral edema and associated increased intracranial pressure begin early after the injury, the prevention of early post-traumatic seizures is most important.

3405. Lewis, R.J., Yee, L., Inkelis, S.H., and Gilmore, D., Clinical predictors of post-traumatic seizures in children with head trauma,, Ann. Emerg. Med., 22(7):1114-1118, 1993.

See also Ref.

3406. Haltiner, A.M., Newell, D.W., Temkin, N.R., Dikmen, S.S., and Winn, H.R., Side effects and mortality associated with the use of phenytoin for early posttraumatic seizure prophylaxis, J. Neurosurg., 91:588-592, 1999.

3407. Dikmen, S.S., Temkin, N.R., Miller, B., Machamer, J., Winn, H.R., Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures, JAMA, 265(10): 1271-7, 1991.

3408. Beenen, L.F., Lindeboom, J., Kasteleijn-Nolst Trenite D.G., Heimans, J.J., Snoek, F.J., Touw, D.J., Ader, H.J., and Van Alphen, H.A., Comparative double-blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: Efficacy, tolerability, and cognitive effects, J. Neurol.Neurosurg. Psychiatry, 67:474-480, 1999.

3409. Aldrete, J.A., Romo-Salas, F., and Castillo, R.A., Methods in treating acute cerebral ischemia, Rev. Esp. Anesthesiol. Reanim., 33(3): 193-6, 1986.

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