Patterns of cortical hyperexcitability in adolescent/adult-onset generalized epilepsies.

Purpose: To investigate whether using transcranial magnetic stimulation (TMS) to derive if measures of cortical excitability changes can distinguish between various adolescent/adult-onset generalized epilepsy syndromes at different phases of the disorder.

Methods: One hundred thirty-seven patients with adolescent/adult-onset generalized epilepsy divided into juvenile myoclonic epilepsy, juvenile absence epilepsy, and generalized epilepsy with tonic-clonic seizures only were studied. The cohorts were further divided into drug naive-new onset, refractory, and seizure-free groups. Motor threshold (MT) and paired pulse TMS at short (2, 5, 10, 15 msec) and long (100-300 msec) interstimulus intervals (ISIs) were measured. Results were compared to those of 20 controls.

Key Findings: In the drug-naive cohorts MT was reduced (p < 0.05) and cortical excitability increased at 2 and 5 msec and 150, 250, and 300 msec ISIs (p < 0.01) in juvenile myoclonic epilepsy compared to other generalized epilepsy groups and controls. Cortical excitability increased to a lesser degree in other generalized epilepsy syndromes compared to controls, but those two syndromes were not distinguishable from one another. The changes in paired pulse TMS were more prominent in the groups with refractory seizures and very small in the groups who were seizure free.

Significance: There are syndrome specific changes in cortical excitability associated with generalized epilepsy. These changes are also dependent on seizure control with medication. Juvenile myoclonic epilepsy has a higher cortical excitability profile compared to other adolescent/adult-onset generalized epilepsy syndromes and can be clearly distinguished from them during all phases.