Idiopathic Primary Generalized Epilepsies: Benign?

Child being tested for epilepsy.

For many years the general teaching on idiopathic primary generalized epilepsies has been that they tend to be fairly benign syndromes. These syndromes (which include juvenile myoclonic epilepsy, juvenile or childhood absence epilepsy, benign neonatal convulsions, and generalized seizures on awakening) all can have generalized spike and wave discharges with an otherwise normal background EEG and “normal” imaging. Patients usually respond well to anti-epileptics (as long as the right drug is chosen –- usually valproate or lamotrigine) and cognitive development is thought to be normal.

However, some previous studies have showed that patients with juvenile myoclonic epilepsy (JME) have significant evidence of network dysfunction and poorer than expected cognitive function as adults. What has been unclear is whether this was an intrinsic feature of the syndrome or caused by the social and medical consequences of epilepsy and anti-epileptic medications during brain maturation. Now, a new study in the Annals of Neurology calls this starkly into question and demonstrates that there are likely intrinsic aspects of JME that cause defects in brain maturation and function.¹

The authors followed a cohort of well characterized JME patients for 2 years following initial diagnosis; they report on the outcomes and details of imaging results. The group consisted of 19 patients with newly diagnosed JME who were compared with 57 matched controls. The authors did a careful 2-year followup of cognitive trajectory and volumetric MRI analysis. They found that the cognitive abilities of JME patients were a little worse at diagnosis and that this trajectory continued over the following 2 years. They also found frontoparietal-temporal volumetric abnormalities in associated areas.

The import of this study is pretty clear. JME patients appear to have modest cognitive defects and imaging abnormalities-- even from early in the course of their disease-- that are really not likely to be due to treatment with anti-epileptics. This is a pretty clear departure from the traditional teaching on this subject and begs the question as to whether similar results would be found in the other “benign” childhood and juvenile epilepsy syndromes with spike and wave.

References:

1. Lin JJ, Dabbs K, Riley JD, et al. Neurodevelopment in new-onset juvenile myoclonic epilepsy over the first 2 years. Ann Neurol. 2014;76(5):660-668.