Migraine Prophylaxis in Patients with Patent Foramen Ovale: PFO Closure vs. Traditional Preventative Measures By: Samantha Howell Submitted to: Dr. Gurwell

Migraines 28 million Americans each year Characterized by: pulsing or throbbing pain, unilateral pain commonly, interferes with daily activities, worsened by physical activity Has to be accompanied by one of the following: N/V, photophobia, or phonophobia 2 types: Migraine with aura (20%) Migraine without aura (80%) Aura-a sensory disturbance (visual typical)

Pathophysiology Poorly understood Excitation wave theory Cerebral ischemia Lungs may play a role -if bypassed allow microemboli and substances like serotonin and ADP to get to the brain via circulation -one possibility is PFO or ASD Neurovascular cause

Patent Foramen Ovale Failure of foramen ovale to close at birth Right-to-left shunt of blood PFO may be present in 40-60% of migraine with aura sufferers Closing this defect may be a future treatment for migraine

Traditional Migraine Prophylaxis Avoidance of Triggers Stress Management Pharmacological Prophylactic Treatments used if MHA occurs more than 2x a month, not controlled with acute tx, or the patient takes abortive tx more than 2x a week Anti-epileptics (Topiramate, Gabapentin) NSAIDS (Ibuprofen) Antidepressants Beta blockers (Atenolol) Calcium channel blockers (Verapamil) ACEi (Lisinopril) Magnesium Botox Other Vitamins/Minerals

Clinical Question In patients with migraine with aura who have a known patent foramen ovale (PFO), is there a quality-of-life benefit to PFO closure surgery or would migraine symptoms be equally controlled with pharmacological prophylactic treatment? Methods: Three PubMed Database searches were performed to attempt to answer this question

Wilmshurst, 2000 Retrospective study looking at effects of PFO closure on migraine headaches (n=21) Surgery was performed to treat decompression illness Treated with aspirin for 6 mos. post-op Patients were interviewed about migraine after the surgery (had to recall symptoms before and after procedure)-IHS guidelines used to determine if patients had migraines 9-32 month follow-up

Giardini, 2006 Prospective study looking at long-term efficacy of PFO closure on migraine in stroke patients (n=13) Surgery was performed due to previous stroke Treated with aspirin for 12 months following the surgery Patients were interviewed about migraine and the condition severity was assessed using MIDAS questionnaire 4.9 ± 1.4 years follow-up

Results Table 1-Effect of PFO closure on migraine headaches

Silberstein, 2004 Randomized, double-blind, placebo-controlled trial (n=284) 26 week treatment period using 50, 100, or 200 mg/d of Topiramate and matching amounts of placebo Patients kept diaries recording periods with migraine headache Success of the drug was based on change from baseline Percentage of patients with decreased frequency and severity in each group: 100 mg/d Topiramate = 54% 200 mg/d Top. = 52.3% 50 mg/d Top. = 35.9% Placebo = 22.6%

Schrader, 2001 Randomized, placebo controlled, crossover study (n=60) 30 pts. took 10 mg Lisinopril once daily for 1 wk and then two 10 mg tablets once daily for 11 wks followed by 2 wk washout period-then one placebo pill daily for one wk and then two placebo pills once daily for 11 wks. Another 30 pts. took the placebo pills during the first 12 wks and lisinopril during the next 12 wks Patients also recorded symptoms in a diary Results: -For days with migraine, a reduction by at least 50% was seen in 30% of participants -32% of participants saw at least a 50% reduction in headache severity compared to placebo period

For Comparison Table 2-Reduction of migraine activity by PFO closure vs. Traditional Migraine Prophylaxis SourceProphylacticDaily Dosage % Reduction in Migraine Activity Buchanan 2006 Gabapentin (anti-epileptic) g36% Botox25 International Units45% Vitamin B2-Riboflavin 400 mg56% Coenzyme mg microparticles48% Silberstein 2004 Topiramate (anti-epileptic) 100 mg/d54% Silberstein 2002 Propanolol (beta-blocker) mg44% Magnesium600 mg41.6% Aspirin (NSAID)650 mg20-30% Schrader 2001 Lisinopril (ACE Inhibitor) 20 mg30% Wilmshurst 2000PFO ClosureN/A86% Giardini 2006PFO ClosureN/A92%

Study Strengths and Limitations Strengths (PFO) MIDAS IHS Follow-up 5 yrs Strengths (Meds) Randomized, placebo- controlled Large number of subjects Quantitative measures Limitations (PFO) Sample size Retrospective (Wilmshurst, 2000) Participant Recall error Limitations (All) All data gathered was somewhat subjective (participant diaries, etc.)

Conclusions PFO closure looks promising-higher percentage of patients in the PFO closure trials had reduced frequency and severity of migraines PFO closure is invasive and there is not enough research Additionally, not everyone who has migraines has the heart wall defect The surgical procedure should only be recommended at this time for individuals with multiple conditions related to PFO Our patients with PFO and migraines should simply be placed on traditional prophylactic meds or use acute treatment until more research is done

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