Percutaneous Patent Foramen Ovale Closure Impact on Migraine
Percutaneous Patent Foramen Ovale Closure Impact on Migraine
If one accepts that a PFO plays a pivotal role in the course of a migraine attack, the following scenarios are possible: given that the concept of migraine is based on an increased neuronal excitability and the presence of migraine triggers, a PFO can either allow solid or metabolic migraine triggers to avoid pulmonary clearance and then hit sensitive regions of the cortex, and thereby initiate a migraine attack. Alternatively, a PFO can act as a sensitizer of neurons to respond to any trigger with the initiation of a cortical spreading depression wave. Chronic shunting may repetitively expose occipital neurons to microemboli or vasoactive peptides, thereby lowering their 'neuronal threshold' (Figure 2). Of all these theories, the possibility of microemboli as triggers of migraine attacks is probably the most likely as it is supported by the majority of current literature. Box 1 summarizes the current arguments favoring the embolic hypothesis.
(Enlarge Image)
Figure 2.
Hypothesis of how a patent foramen ovale interacts with migraine.
Metabolic right-to-left shunting has been proposed as an alternative trigger of migraine attacks. Serotonin, usually metabolized by the pulmonary monoamine oxidase, can partially escape pulmonary clearance in the presence of a right-to-left shunt. The exact role of serotonin in migraine is not clear, but drugs designed to specifically antagonize a subgroup of serotonin receptors (i.e., triptans) can abort migraine attacks. Serotonin may either activate platelets to aggregate more easily and hence lead to cerebral infarction, or may by itself initiate cortical spreading depression by binding to specific receptors.
All theories imply that it is not the PFO per se, but rather the right-to-left shunt that accounts for migraine. The fact that closure of pulmonary fistulae is also associated with migraine improvement underscores the concept that not the anatomy, but the functional impact of right-to-left shunts is associated with migraine.
How May PFO Closure Affect Migraine?
If one accepts that a PFO plays a pivotal role in the course of a migraine attack, the following scenarios are possible: given that the concept of migraine is based on an increased neuronal excitability and the presence of migraine triggers, a PFO can either allow solid or metabolic migraine triggers to avoid pulmonary clearance and then hit sensitive regions of the cortex, and thereby initiate a migraine attack. Alternatively, a PFO can act as a sensitizer of neurons to respond to any trigger with the initiation of a cortical spreading depression wave. Chronic shunting may repetitively expose occipital neurons to microemboli or vasoactive peptides, thereby lowering their 'neuronal threshold' (Figure 2). Of all these theories, the possibility of microemboli as triggers of migraine attacks is probably the most likely as it is supported by the majority of current literature. Box 1 summarizes the current arguments favoring the embolic hypothesis.
(Enlarge Image)
Figure 2.
Hypothesis of how a patent foramen ovale interacts with migraine.
Metabolic right-to-left shunting has been proposed as an alternative trigger of migraine attacks. Serotonin, usually metabolized by the pulmonary monoamine oxidase, can partially escape pulmonary clearance in the presence of a right-to-left shunt. The exact role of serotonin in migraine is not clear, but drugs designed to specifically antagonize a subgroup of serotonin receptors (i.e., triptans) can abort migraine attacks. Serotonin may either activate platelets to aggregate more easily and hence lead to cerebral infarction, or may by itself initiate cortical spreading depression by binding to specific receptors.
All theories imply that it is not the PFO per se, but rather the right-to-left shunt that accounts for migraine. The fact that closure of pulmonary fistulae is also associated with migraine improvement underscores the concept that not the anatomy, but the functional impact of right-to-left shunts is associated with migraine.