Migraine is a common, chronic neurovascular disorder characterized by attacks of severe headache, autonomic nervous system dysfunction and, in some patients, aura, and disabling neurological symptoms. Worldwide, migraine prevalence is as high as 18% in the general population. Increased frequency of patent foramen ovale (PFO) in migraineurs was first reported in 1998 in a case-control study. Since then, others have described a 60% prevalence of PFO in patients suffering from migraine with aura. The presence of a right-to-left shunt (RLS) is thought to be a potent trigger of migraine attacks, although the mechanism is unknown. Moreover, PFO closure has correlated with improved migraine symptoms in several retrospective uncontrolled studies. The aim of this single-center, prospective study is to assess the impact of PFO closure on migraine attacks over time together with evaluation of potential predictive risk factors.
The Study will evaluate the results of approximately 100 subjects from a single center study registered in this trial. Subjects who experienced transient ischemic attack (TIA) or stroke with a clinical indication to PFO closure and symptomatic for migraine with/o aura are considered for a migraine score analysis at baseline before PFO closure and during the subsequent follow-up (FU) at 6 and 12-months, together with lab evaluation for platelet reactivity tests (P selectin, Thromboxane B2), Prostaglandin E1 and 2 (PGE1, PGE2), serotonin, cytokines and prostaglandin PGE1 urinary metabolite run under aspirin therapy. The research questions are as follows: Does the presence of a large PFO have any impact on migraine with aura? Do migraineurs with aura and PFO have higher biomarkers of platelet activation than control patients? and are they at higher risk of stroke and TIA recurrences based on high on clopidogrel platelet reactivity? What is the effect of PFO severity on monthly migraine frequency and aura frequency? What is the result of PFO closure in migraineur patients with PFO? Do Migraine with aura patients with large PFO have higher platelet activation and better migraine resolution after PFO closure?
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
Pts undergoing PFO closure will receive 2-months of DAPT and 6 months of aspirin after patent foramen ovale (PFO) closure; they will be compared to healthy subjects on aspirin treatment
Centro Cardiologico Monzino, IRCCS
Milan, MI, Italy
Change in Migraine Characteristics
The evaluation in absolute numbers of patients fully responders, non-responders or with a moderate benefit on migraine symptoms after PFO Closure was performed
Time frame: The outcome data were evaluated at 6-months and 12-months after PFO closure and compared to baseline
Migraine Assessment by Anzola's Score
The change in migraine severity, incidence and duration with or without aura as measured by the Anzola's score (The score is the expression of the sum of each corresponding value referring to migraine duration, frequency and the presence or absence of aura). The minimum value was 2 and the maximum 9; the higher the value, worse is the migraine classification. Anzola's score: Duration 0=No pain 1=\<6 hours 2=6-12 hours 3=\>12 hours Frequency 0=No pain 1=1-4/month 2=5-9/month 3=\>10/month Aura 0=No aura 1=Aura in ≥1 attack
Time frame: Baseline, 6 months and 12-months after PFO closure
Platelet Activation (I)
Platelet Thrombin generation potential in migraineurs and healthy subjects
Time frame: baseline and 6 months after PFO closure
Platelet Activation (II)
Platelet Thrombin generation Potential in Migraneurs and Healthy subjects
Time frame: Baseline and 6 months after PFO closure
Platelet Activation (III)
Platelets' endogenous thrombin generation potential in Migraneurs and Healthy subjects
Time frame: baseline and six months after PFO closure
Platelet Activation (IV)
Platelets' functional activity measured as the amount of thrombin generation
Time frame: Baseline and six-months after PFO closure
Platelet Aggregation (I)
Platelet aggregation was measured on PAP-8 aggregometer (BioData). Briefly, PRP aliquots (250µL) were pipetted into a siliconized glass cuvette, stirred at 1200 rpm at 37°C and stimulated with arachidonic acid (1mM), collagen (2µg/ml), ADP (5µM), TRAP-6 (5µM). Light transmission was recorded for 5 min after stimuli addition and platelet aggregation was reported as maximal percentage of light transmission. Aspirin-treated patients were considered drug responders when platelet aggregation was less than 20% after arachidonic acid (1mM) stimulation.
Time frame: baseline and 6 months after PFO Closure
Clinical Outcomes
Absence of TIA and stroke recurrences after PFO closure and during the follow-up
Time frame: In hospital, six and 12 months follow-up
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