Migraine Prophylaxis in Patients with Patent Foramen Ovale:

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

2. 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)

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. Results Table 1-Effect of PFO closure on migraine headaches

10. 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%

11. 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

12. For Comparison Table 2-Reduction of migraine activity by PFO closure vs. Traditional Migraine Prophylaxis

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

14. 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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