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


CONCLUSIONS
The therapeutic use of rTMS in epilepsy should take into consideration the interaction between rTMS and drugs that change cortical excitability.
Fregni
Felipe
F
Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., KS 452, Boston, MA 02215, USA. ffregni@bidmc.harvard.edu
Boggio
Paulo S
PS
Valle
Angela C
AC
Otachi
Patricia
P
Thut
Gregor
G
Rigonatti
Sergio P
SP
Marcolin
Marco A
MA
Fecteau
Shirley
S
Pascual-Leone
Alvaro
A
Fiore
Lia
L
Valente
Kette
K
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood*; D003131:Combined Modality Therapy; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D020190:Myoclonic Epilepsy, Juvenile / Q000188:drug therapy* / Q000503:physiopathology; D011712:Pyramidal Tracts / Q000187:drug effects* / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood*
D000927:Anticonvulsants; D014635:Valproic Acid