Article Text

VALPROIC ACID IS EFFECTIVE IN DIFFERENT TYPES OF HEADACHE AND CONVULSIVE DISORDERS PROBABLY BECAUSE IT INHIBITS REPLICATION OF T. GONDII
  1. J Prandota1
  1. 1Department Of Social Pediatrics, Faculty Of Public Health, University Medical School, Wroclaw, Poland

Abstract

Background Valproic acid (VA) is effective in treatment of migraine with and without aura, drug-resistant migraine, tension-type headache, and/or chronic daily headache, as well as in epilepsy. The aim of this study was therefore to focus on the pathomechanisms that may be responsible for these clinical effects.

Methods Literature data were selected to illustrate that latent CNS T. gondii infection/inflammation intensity and/or host defense mechanisms may be affected by changes in the mechanisms mediated by an IFN-γ responsive gene family, production of NO, cytokines, tryptophan degradation by indoleamine 2,3-dioxygenase, limiting the availability of intracellular iron to T. gondii, production of reactive oxygen/nitrogen species (ROS), and finally cause of different types of headache or epilepsy.

Results VA was found to induce generation of ROS and NO, as well as decreased IFN-γ, IL-6 and TNF-α production. These irregularities could markedly improve host defense mechanisms important for immune control of the parasite, because an in vitro study showed that VA inhibited replication of T. gondii tachyzoites at median concentration of 4.1 mg/ml, similar to that of trimethoprim (5.3 mg/ml), which displayed a synergistic effect with VA. It is likely that most treated patients with different types of headache or epilepsy attain therapeutic levels of VA within the brain necessary for the inhibition of T. gondii since the level of VA in the CNS of treated individuals is approximately 20% of the serum levels (20–100 mg/ml).

Conclusion Subjects with different types of headache or epilepsy should have test(s) for T. gondii infection performed obligatorily.

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