The genetic and acquired hypotheses of etiology of hippocampal sclerosis (HS) were studied at the University of Melbourne, Australia, using quantitative MRI in three monozygous (MZ) twin pairs, only the index twin having temporal lobe epilepsy and HS. The MZ twin pairs (mean age, 29 years) were compared with 30 age-matched control subjects having no neurologic disorder. All affected twins had HS and a history of prolonged seizures with fever in early childhood. Temporal lobe epilepsy began at 2 to 6 months after the febrile seizure, at ages 7 mos to 3.5 years. Intracranial volume ipsilateral to the HS was relatively small in 2 of 3 affected twins, when compared to the unaffected twin. HS was not caused by perinatal abnormalities and was unrelated to birth order. The absence of HS in the unaffected twin is evidence against a genetic basis for HS. An acquired lesion secondary to prolonged febrile seizures is the more likely mechanism. 
COMMENT. Monozygotic twin studies support an acquired basis for the hippocampal sclerosis associated with temporal lobe epilepsy, secondary to prolonged febrile seizures in early childhood. All three MZ pairs for which the proband had temporal lobe epilepsy (TLE) and HS were discordant for the clinical diagnosis of TLE. Definitive dysplastic changes were not uncovered by MR, but subtle changes could not be ruled out.