Migraine Prophylaxis in Patients with

Patent Foramen Ovale:

PFO Closure vs. Traditional Preventative

Measures

By: Samantha HowellSubmitted 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

Study Headache Type

Cured Improved Cured or Improved

No Change or Worsened

Wilmshurst (2000)

Migraine (of any type)

10/21 (48%) 8/21 (38%) 18/21 (86%) 3/21 (14%)

Migraine with Aura

7/16 (44%) 8/16 (50%) 15/16 (94%) 1/16 (6%)

Migraine Without Aura

3/5 (60%) 0/5 (0%) 3/5 (60%) 2/5 (40%)

Giardini (2006)

Migraine (of any type)

11/13 (85%) 1/13 (8%) 12/13 (92%) 1/13 (8%)

Migraine with Aura

NA NA NA NA

Migraine Without Aura

NA NA NA NA

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 ComparisonTable 2-Reduction of migraine activity by PFO closure vs.

Traditional Migraine Prophylaxis

Source Prophylactic Daily Dosage % Reduction in Migraine Activity

Buchanan 2006 Gabapentin (anti-epileptic) 1.8-2.4 g 36%

Botox 25 International Units 45%

Vitamin B2-Riboflavin 400 mg 56%

Coenzyme 10 300 mg microparticles 48%

Silberstein 2004 Topiramate (anti-epileptic) 100 mg/d 54%

Silberstein 2002 Propanolol (beta-blocker) 120-240 mg 44%

Magnesium 600 mg 41.6%

Aspirin (NSAID) 650 mg 20-30%

Schrader 2001 Lisinopril (ACE Inhibitor) 20 mg 30%

Wilmshurst 2000 PFO Closure N/A 86%

Giardini 2006 PFO Closure N/A 92%

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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