Magnetic stimulation of the brain in generalized epilepsy: Reversal of cortical hyperexcitability by anticonvulsants

Abstract

Observations on experimental models suggest that diffuse cortical hyperexcitability is an important abnormality in the generalized epilepsies. We used the threshold for transcranial magnetic stimulation as an index of motor cortical excitability in 89 neurologically normal control subjects and 56 patients with idiopathic generalized epilepsy (20 untreated and 36 chronically treated with anticonvulsants). Magnetic stimulation was repeated in 10 patients after valproate monotherapy had been commenced and in 23 control subjects. The threshold intensity was significantly lower in the untreated patients (46 +/- 5% [mean +/- 95% confidence interval]) than in the control subjects (56 +/- 2%). Treated patients had significantly higher thresholds (64 +/- 4%) than did untreated patients and control subjects. A significant increase in threshold intensity (8 +/- 2%) occurred in patients retested after starting valproate; there was no significant change in retested control subjects (-1 +/- 2%). Threshold intensity was positively correlated with plasma valproate levels (rs = 0.37). The findings suggest that cortical excitability is increased in idiopathic generalized epilepsy and is reduced following anticonvulsant treatment. Transcranial magnetic stimulation is of use in examining the pathophysiology of generalized epilepsy. Furthermore, changes in threshold intensity in response to anticonvulsant treatment may prove useful in guiding therapy.