Migraine associated with patent foramen ovale may be caused by reactivation of cerebral toxoplasmosis triggered by arterial blood oxygen desaturation.

Approximately two billion people worldwide are chronically infected with T. gondii and yet with largely unknown consequences. On the other hand, several authors reported an association between migraine and patent foramen ovale (PFO), and different types of headaches, including migraine, may be precipitated by various diseased states or medications associated with marked immune irregularities, which sometimes cause reactivation of latent cerebral toxoplasmosis (CT). Recently, in a group of 104 subjects with migraine, 46 individuals (44.2%) were found to be seropositive for T. gondii. PFO, atrial septal defects, as well as pulmonary right-to-left shunts are usually associated with a various degree of arterial blood oxygen desaturation. Hypoxia is associated with an increase in the generation of several proinflammatory cytokines and other inflammation mediators, such as TNF-alpha, IL-1-beta, IL-6, IL-8, chemokines (monocyte chemoattractant protein-1, CC-chemokine receptor 2, macrophage inflammatory protein-1alpha, intercellular adhesion molecule-1), acute-phase protein gene expressions, COX-2 gene transcription, induction of iNOS, and reactive oxygen species. Moreover, hypoxia markedly decreased T-lymphocyte IL-2 mRNA, a key cytokine responsible for B-cell proliferation and immunoglobulin secretion, and ischemic tissues demonstrated intravascular neutrophil accumulation, vascular damage, and increased vascular wall permeability. Interestingly, T. gondii activates hypoxia-inducible factor 1 already at physiologically relevant oxygen levels and requires HIF1 for growth and survival. These abnormalities may cause imbalance in the host/T. gondii immune system, which finally results in the reactivation of CT. In addition, hypoxia may participate in paradoxical microembolism because arterial oxygen desaturation enhances expression of plasminogen activator inhibitor-1, an important factor which suppresses fibrinolysis, and this effect may be further amplified by a decreased expression of plasminogen activators, finally causing blood hypercoagulability and paradoxical microembolism. In summary, further studies are required to verify the above-presented pathomechanisms probably responsible for the association between PFO and the development of migraine. It is possible that some migraineurs with PFO may benefit from evaluation and treatment of toxoplasmosis in the future once more information is known.