Homeostatic effects of plasma valproate levels on corticospinal excitability changes induced by 1Hz rTMS in patients with juvenile myoclonic epilepsy

Clin Neurophysiol. 2006 Jun;117(6):1217-27. doi: 10.1016/j.clinph.2006.02.015. Epub 2006 Apr 27.


Objective: The preliminary results of noninvasive brain stimulation for epilepsy treatment have been encouraging, but mixed. Two important factors may contribute to this heterogeneity: the altered brain physiology of patients with epilepsy and the variable presence of antiepileptic drugs. Therefore, we aimed to study the effects of 1 Hz rTMS on corticospinal excitability in patients with juvenile myoclonic epilepsy (JME) in two different conditions: low- or high-plasma valproate levels.

Methods: Fifteen patients with JME and 12 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS was assessed in JME patients with low- and high-plasma valproate levels; and these results were compared with those in healthy subjects.

Results: In patients with chronic use of valproate and low-plasma concentrations, 1 Hz rTMS had a similar significant inhibitory effect on corticospinal excitability as in healthy subjects. However, in the same patients when the serum valproate concentration was high, 1 Hz rTMS increased the corticospinal excitability significantly. In addition, there was a significant positive correlation between plasma valproate levels and the motor threshold changes after 1 Hz rTMS.

Conclusions: Our findings can be accounted for by mechanisms of homeostatic plasticity and illustrate the dependency of the modulatory effects of rTMS on the physiologic state of the targeted brain cortex.

Significance: The therapeutic use of rTMS in epilepsy should take into consideration the interaction between rTMS and drugs that change cortical excitability.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / blood*
  • Combined Modality Therapy
  • Homeostasis / drug effects
  • Humans
  • Myoclonic Epilepsy, Juvenile / drug therapy*
  • Myoclonic Epilepsy, Juvenile / physiopathology
  • Pyramidal Tracts / drug effects*
  • Pyramidal Tracts / physiopathology
  • Transcranial Magnetic Stimulation*
  • Treatment Outcome
  • Valproic Acid / administration & dosage
  • Valproic Acid / blood*


  • Anticonvulsants
  • Valproic Acid