Neurology -- Correspondence for Schwerzmann et al., 62 (8) 1399-1401

Correspondence published:

Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks: Vinod K. Gupta (8 June 2004)

Reply to Gupta: Markus Schwerzmann, Stephan Windecker (8 June 2004)

Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks 8 June 2004

Vinod K. Gupta,
Dubai Police Medical Services, Dubai, United Arab Emirates
P.O. Box 12005, Dubai, United Arab Emirates
Send Correspondence to journal:
Re: Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks

docgupta{at}emirates.net.ae Vinod K. Gupta

Schwerzmann et al [1] found that closure of patent foramen ovale (PFO) reduced the frequency of attacks by >50% in migraine patients with aura (MA+) and without aura (MA-). These authors suggest PFO closure for prophylaxis of migraine and recommend a prospective trial.
The incidence of migraine headache in patients in the year prior to PFO closure was twice the expected prevalence. [1] Stress is one of the most common precipitants of migraine attacks. [2] The cerebral and peripheral events associated with PFO in these patients [1] are significant medical occurrences correctable only by invasive intervention. To exclude event-related stress, the incidence of migraine attacks prior to the event, diagnosis of PFO, or both, must be determined.
Secondly, the >50% reduction of migraine attacks following PFO closure [1] is statistically significant but biologically debatable. The placebo responsiveness of patients with migraine is increased. Inclusion of migraine patients with as few as two attacks per month in the analysis [1] could represent an important confounding variable; the probability of comparable replication of low-frequency attacks during the pre-trial, run- in and trial periods is low. Migraine patients with less than four headache attacks per month for at least three prospective pre-trial months should not be considered suitable for trials of prophylaxis. Moreover, inclusion of a post-PFO closure period of six-months of antiplatelet therapy into a composite 12-month post-procedure headache frequency analysis, [1] increases the confounding effect.
The reason that a higher prevalence of right-to-left shunt (RLS) should prevail in migraine patients with PFO is unclear. Periodic RLS in PFO occurs only when the right atrial pressure or pulmonary circulation afterload intermittently exceeds that of the systemic circulation. Is the systemic circulation in migraine patients a relatively low-resistance system that permits intermittent RLS? This is important because propranolol lowers systemic blood pressure and afterload. Also, whereas the clinico-pharmacological similarities of MA+ and MA- outweigh their phenomenological differences, [3] in one study no therapeutic benefit of PFO closure was found in of MA- patients. [4] Thirdly, MA+ has been associated with both RLS and correction of left-to-right shunt in atrial septal defect. [5]
Fourthly, it is difficult to accept that paradoxical emboli are being repeatedly directed over months or years to the same cerebral site to produce consistently lateralizing headache. The importance of lateralization of headache cannot be overemphasized. [3]
Finally, the neuroprotective effect of CSD in cerebral ischemia is well known.
References
1. Schwerzmann M, Wiher S, Nedeltchev K, et al. Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks. Neurology 2004;62:1399-1401.
2. Blau JN, Thavapalan M. Preventing migraine: a study of precipitating factors. Headache 1988;28:481-483.
3. Gupta VK. Classification of primary headaches: pathophysiology versus nosology? Published electronic response to: Peatfield R. A revised classification of headache disorders. Available at: http://bmj.com/cgi/content/full/328/7432/119?etoc (22 January 2004).
4. Sztajzel R, Genoud D, Roth S, et al. Patent foramen ovale, a possible cause of symptomatic migraine: a study of 74 patients with acute ischemic stroke. Cerebrovasc Dis 2002;13:102-106.
5. Gupta VK. Closure of atrial septal defect and migraine. Headache 2004;44:291-292.

Reply to Gupta 8 June 2004

Markus Schwerzmann,
Cardiology, University Hospital Bern, Bern, Switzerland
see article,
Stephan Windecker
Send Correspondence to journal:
Re: Reply to Gupta

markus.schwerzmann{at}uhn.on.ca Markus Schwerzmann, et al.

We appreciate Dr. Gupta�s interest in the association of patent foramen ovale (PFO) with migraine. The methodological pitfalls of the retrospective analysis of our study have been addressed in the manuscript.[1] Drawbacks include the risk of ignoring potential confounders, e.g. emotional and physical stress imposed by the index ischemic event. The average time between the index embolic event and percutaneous PFO closure in our study was a mean of 6 months (range 3 days to 3 years). However, migraine attack frequency did not differ between patients undergoing percutaneous PFO closure within 3 months or after 9 months since the index event. Accordingly, emotional or physical stress related to the ischemic index event did not appear to substantially influence headache attack frequency. The retrospective nature of our work has the advantage of eliminating a placebo effect of percutaneous PFO closure itself on migraine frequency, since patients under analysis were unaware of a potential benefit of the intervention on migraine outcome.
The median attack frequency in unselected migraine patients is 1.5 headache attacks per month,[2] which corresponds closely to the median attack frequency in our patient groups. Due to the retrospective nature of our analysis, restricting outcome measurements on selected patient groups (e.g. patients with weekly migraine) would be arbitrary and a matter of debate. The beneficial effect of percutaneous PFO closure on migraine attack frequency in those with only few monthly headache attacks appears beneficial for a wide spectrum of patients suffering from migraine.
While our study confirms an association between PFO and migraine headache, the pathophysiological mechanism underlying improvement in migraine after percutaneous PFO closure remains unclear. Reduction of transient cerebral ischemia provoked by PFO mediated paradoxical embolism has been suggested as potential mechanism and is supported by an increasing number of clinical reports describing a therapeutic effect exerted by antithrombotic therapy.[3] PFO mediated paradoxical embolism depends on pressure differences between right and left atria. This pressure difference is less influenced by systemic afterload and its pharmacological manipulation, than by changes in pulmonary artery pressure and right ventricular function as determinants of intermittent right-to-left shunt.
The present study does not answer all the questions raised by Dr. Gupta. But we hope that the work of Post et al [4] and ourselves [1] will promote further research in this field provide further insight into the association between PFO and migraine.
References
1. Schwerzmann M, Wiher S, Nedeltchev K, et al. Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks. Neurology 2004;62: 1399-1401.
2. Ferrari MD. Migraine. Lancet 1998;351:1043-51.
3. Wammes-van der Heijden EA, Tijssen CC, van't Hoff AR, Egberts ACG. A Thromboembolic Predisposition and the Effect of Anticoagulants on Migraine. Headache: The Journal of Head and Face Pain. 2004:44;399-402.
4. Post MC, Thijs V, Herroelen L, Budts WIHL. Closure of a patent foramen ovale is associated with a decrease in prevalence of migraine. Neurology 2004:62;1439-1440.