Little is known about what factors predict intractable epilepsy at the
time of initial diagnosis. We performed a case-control study to ident
ify early predictors of medically intractable epilepsy in children. Ca
ses were children who had an average of one seizure or more a month ov
er a 2-year period and who, during that time, had failed trials of at
least three different antiepileptic drugs (AEDs). Controls were childr
en who had epilepsy, who had been seizure-free for greater than or equ
al to 2 years, and who had never, before becoming seizure-free, met th
e definition for intractable epilepsy. Strong univariate associations
were noted between intractability and several factors: infantile spasm
s (IS) remote symptomatic epilepsy, a history of status epilepticus (S
E) before the diagnosis of epilepsy, neonatal seizures, and microcepha
ly. Cases were significantly younger than controls at onset (1.8 vs. 5
.8 years); this was not due solely to cases with onset during the firs
t year of life but was an association apparent throughout the age rang
e studied, With multiple logistic regression, independent predictors o
f intractability were IS, odds ratio(OR) = 10.32, p = 0.03; age at ons
et with a decreasing risk with increasing age, OR = 0.77 per year, p <
0.0001; remote symptomatic epilepsy, OR = 2.24, p = 0.04; and SE, OR
= 3.30, p = 0.04. These findings complement those of recent cohort stu
dies of remission of epilepsy and provide useful leads for future pros
pective studies of intractable epilepsy.