title: The effect of valproate on silent period and corticomotor excitability.
abstract: OBJECTIVE
  To investigate, by transcranial magnetic stimulation, the effects of valproate on silent period and corticomotor excitability.
  
  
  METHODS
  thirty patients with generalized epilepsy were studied at baseline, and re-examined 4 (S1) and 25 (S2) weeks after the administration of valproate (mean dose: 1040 +/- 284 mg). Transcranial magnetic stimulation was performed with a figure of eight coil (recording, first dorsal interosseous). Threshold was measured at 1% steps. Silent period was measured using a recently described protocol. Briefly, silent periods were elicited at 5% increments from 0 to 100% maximum stimulus intensity. At each stimulus intensity, 4 silent periods were obtained and the average value of silent period duration was used to construct a stimulus/response curve of stimulus intensity versus silent period. The resulting curves were then fitted to a Boltzman function and were statistically compared. The motor-evoked potential recruitment curve was constructed under active conditions and analyzed in a similar way.
  
  
  RESULTS
  Valproate increased threshold from 36.5 +/- 5.99% at baseline to 41.02 +/- 7.84% at S1 (p < 0.0001, paired t-test). The maximum value of the silent period curve decreased from 257.5 +/- 3.9 ms at baseline to 230.3 +/- 3.9 ms at S1 (p < 0.0001, F-test and AIC) while the other best-fit values (V(50), slope, threshold) were not significantly affected. Regarding the motor-evoked potential recruitment curve, the maximum value decreased significantly post-drug (from 0.449 +/- 0.007 to 0.392 +/- 0.009, p < 0.01, F-test and AIC test), whereas the rest of the best-fit values remained unaffected.
  
  
  CONCLUSIONS
  In patients with idiopathic generalized epilepsy, valproate increases threshold and reduces the maximum values of the silent period curve and the motor-evoked potential recruitment curve. These findings probably reflect valproate's effects on voltage-dependent Na(+) channels, as well as an activation of GABA(A) receptors.
authors.affiliation: Department of Neurology III, "G. Papanikolaou" Hospital, Aristotle University of Thessaloniki, Greece.
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Kazis
authors.forename: Vasilios K
authors.initials: VK
authors.lastname: Kimiskidis
authors.forename: Sotirios
authors.initials: S
authors.lastname: Papagiannopoulos
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Sotirakoglou
authors.forename: Daniel
authors.initials: D
authors.lastname: Divanoglou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Vlaikidis
authors.forename: Kerry R
authors.initials: KR
authors.lastname: Mills
authors.forename: Aristeidis
authors.initials: A
authors.lastname: Kazis
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004829:Epilepsy, Generalized / Q000188:drug therapy / Q000503:physiopathology*; D019054:Evoked Potentials, Motor / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid