50 Years Ago in The Journal of Pediatrics:

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Smith, AG and Ramsay, AB. J Pediatr 1960;57:585-8

In 1960, the choice of anti-seizure medications was rather limited: phenytoin and phenobarbital were the mainstays of treatment. Ethosuximide was newly available for children with absence (“petit mal”) epilepsy. Bromide salts and the ketogenic diet were alternatives. It would be another 14 and 18 years until carbamazepine and valproic acid became available. Phenytoin remains an effective and inexpensive anti-seizure medication; it is the most commonly prescribed anti-seizure medication in the world.

We are fortunate in 2010 to have some 2 dozen medications we can prescribe for epilepsy; however the advantages over older medications have little to do with greater efficacy and everything to do with apparent reduction in the risk of adverse effects and the convenience of simpler dosing regimens.

Fifty years ago in The Journal, Smith and Ramsay described the effectiveness of adding phenobarbital (on a 4-times per day dosing regimen) to phenytoin (3-times per day) in a child with uncontrolled seizures caused by Sturge-Weber syndrome. The authors note the then recently described efficacy of hemipsherectomy for intractable epilepsy in children with Sturge-Weber syndrome.¹

In 2010, with so many once-a-day and twice-a-day anti-seizure medications at our disposal, we sympathize with the parents trying to adhere (in the modern parlance) to the 2 drug/3-times-a-day/4-times-a-day regimen. But a closer reading reveals the authors' advocacy of solid principles we rely on today for treating children with intractable epilepsy: (1) Maximizing the first medication is advisable before adding a second drug; (2) Slow titration is often well tolerated when using a potentially sedating medication like phenobarbital; (3) Control of epilepsy may be transient, and consideration of intervention with epilepsy surgery should be considered when reasonable medications have failed; and (4) Behavior and cognitive symptoms are not entirely attributable to the medications and the underlying epilepsy. Parents' anxiety has a cost, and wise counseling by the pediatrician (and neurologist) to “avoid overprotection and to permit the patient to lead as normal a life as possible” is indispensable.

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Reference 

1. Krynauw RA. Infantile hemiplegia treated by removing one cerebral hemisphere. J Neurol Neurosurg Psychiatry. 1950;13:243–267
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