Percutaneous patent foramen ovale closure in refractory migraine with aura: A case report with literature review and pathophysiological insights

Abstract

Patent foramen ovale (PFO), present in 20 - 30% of the population, is often asymptomatic but may allow right-to-left blood shunting that bypasses pulmonary filtration. This phenomenon has been implicated in cryptogenic stroke and migraine with aura, where microemboli or vasoactive substances may trigger cortical spreading depression. This work, through a clinical case, evaluates the role of percutaneous PFO closure in managing refractory migraine with aura by reviewing current evidence and pathophysiological mechanisms. Initially used for stroke prevention, PFO closure has been proposed as a compassionate treatment for refractory migraines. Although observational studies reported reductions in migraine frequency and severity, randomized trials have been inconsistent. Meta-analyses suggest benefits in specific subgroups, such as patients with aura, but heterogeneity limits conclusions. This case report presents the case of a 22-year-old patient with refractory migraine and a confirmed PFO who underwent successful percutaneous closure, achieving complete migraine remission, improved quality of life, and no evidence of residual shunting. Larger trials are needed to refine patient selection and validate guidelines.

Keywords

Migraine / Patent foramen ovale / Percutaneous closure

Acknowledgments

None.

Funding

None.

Conflict of interest

Paolo Scacciatella is the Guest Editor of this special issue, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

Author contributions

Conceptualization: Paolo Scacciatella

Formal analysis: Paolo Scacciatella

Investigation: Paolo Scacciatella

Methodology: Paolo Scacciatella, Stefano Albani

Writing - original draft: Giulia Marchisio

Writing - review & editing: All authors

Ethics approval and consent to participate

This study was approved by the ethics committee of Valle d’Aosta. Written permission was obtained from each of the subjects to participate in the study.

Consent for publication

Written permission was obtained from each of the subjects to publish their data and/or images.

Availability of data

Data used in this work is available from the corresponding author upon reasonable request.

Further disclosure

Part of the set of findings has been presented at the congress “Heart, Brain, and Vessels” that took place in Aosta, Italy, on June 13 - 14, 2024.

References

[1] Pristipino C, Sievert H, D’Ascenzo F, et al. European position paper on the management of patients with patent foramen ovale: General approach and left circulation thromboembolism. Eur Heart J. 2019; 40(38):3182-3195. doi: 10.1093/eurheartj/ehy649

[2] Pristipino C, Germonpré P, Toni D, et al. European position paper on the management of patients with patent foramen ovale: Part II - decompression sickness, migraine, arterial deoxygenation syndromes and select high‐risk clinical conditions. Eur Heart J. 2021; 42:1545-1553. doi: 10.1093/eurheartj/ehaa1070

[3] Mattle HP, Evers S, Hildick-Smith D, et al. Percutaneous closure of patent foramen ovale in migraine with aura, a randomized controlled trial. Eur Heart J. 2016; 37:2029-2036. doi: 10.1093/eurheartj/ehw027

[4] Tobis JM, Charles A, Silberstein SD, et al. Percutaneous closure of patent foramen ovale in patients with migraine: The PREMIUM Trial. J Am Coll Cardiol. 2017; 70:2766-2774. doi: 10.1016/j.jacc.2017.09.1105

[5] Dowson A, Mullen MJ, Peatfield R, et al. Migraine intervention with STARFlex technology (MIST) trial: A prospective, multicenter, double‐blind, sham‐controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. Circulation. 2008; 117(11):1397-1404. doi: 10.1161/CIRCULATIONAHA.107.727271

[6] Elbadawi A, Barssoum K, Abuzaid AS, Rezq A, Biniwale N, Alotaki E, et al. Meta‐analysis of randomized trials on percutaneous patent foramenovale closure for prevention of migraine. Acta Cardiol. 2018; 74(2):124-129. doi: 10.1080/00015385.2018.1475027

[7] Shi YJ, Lv J, Han XT, Luo GG. Migraine and percutaneous patent foramen ovale closure: A systematic review and meta‐analysis. BMC Cardiovasc Disord. 2017; 17(1):203. doi: 10.1186/s12872-017-0644-9

[8] Butera G, Biondi-Zoccai GGL, Carminati M, et al. Systematic review and meta‐analysis of currently available clinical evidence on migraine and patent foramen ovale percutaneous closure: Much ado about nothing? Catheter Cardiovasc Interv. 2010; 75(4):494-504. doi: 10.1002/ccd.22232

[9] Vigna C, Marchese N, Inchingolo V, et al. Improvement of migraine after patent foramen ovale percutaneous closure in patients with subclinical brain lesions: A case‐control study. JACC Cardiovasc Interv. 2009; 2(2):107-113. doi: 10.1016/j.jcin.2008.10.011

[10] Morandi E, Anzola G, Angeli S, Melzi G, Onorato E. Transcatheter closure of patent foramen ovale: A new migraine treatment? J Interv Cardiol. 2003; 16:39-42. doi: 10.1046/J.1540-8183.2003.08001.x

[11] Dubiel M, Bruch L, Schmehl I, et al. Migraine headache relief after percutaneous transcatheter closure of interatrial communications. J Interv Cardiol. 2008; 21:32-37. doi: 10.1111/J.1540-8183.2007.00316.X

[12] Butera G, Agostoni E, Biondi-Zoccai G, et al. Migraine, stroke and patent foramen ovale: A dangerous trio? J Cardiovasc Med (Hagerstown). 2008; 9:233-238. doi: 10.2459/JCM.0b013e3282058912

[13] Schwedt TJ, Demaerschalk BM, Dodick DW. Patent foramen ovale and migraine: A quantitative systematic review. Cephalalgia. 2008; 28:531-540. doi: 10.1111/j.14682982.2008.01554.x

[14] Luermans J, Post M, Temmerman F, et al. Closure of a patent foramen ovale is associated with a decrease in prevalence of migraine. Acta Cardiol. 2004; 62:1439-1440. doi: 10.2143/AC.63.5.2033223

[15] Trabattoni D, Fabbiocchi F, Montorsi P, et al. Sustained long‐term benefit of patent foramen ovale closure on migraine. Catheter Cardiovasc Interv. 2011; 77:570-574. doi: 10.1002/ccd.22826

[16] Zhang Q, Lu J, Yan M, et al. The efficacy of percutaneous patent foramen ovale closure on migraine: A meta‐analysis of randomized controlled trials and observational studies. BioMed Res Int. 2021; 2021:6643266. doi: 10.1155/2021/6643266

[17] Silalahi T, Hariyanto T. Efficacy and safety of patent foramen ovale closure for mitigating migraine: A systematic review and meta‐analysis of randomized trials and observational studies. Ther Adv Neurol Disord. 2024; 17:1-14. doi: 10.1177/17562864241271033

[18] Rigatelli G, Dell’Avvocata F, Ronco F, et al. Primary transcatheter patent foramen ovale closure is effective in improving migraine in patients with high‐risk anatomic and functional characteristics for paradoxical embolism. JACC Cardiovasc Interv. 2010; 3:282-287. doi: 10.1016/j.jcin.2009.11.019

[19] Wahl A, Praz F, Tai T, et al. Improvement of migraine headaches after percutaneous closure of patent foramen ovale for secondary prevention of paradoxical embolism. Heart. 2010; 96:967-973. doi: 10.1136/hrt.2009.181156

[20] Milev I, Zafirovska P, Zimbakov Z, et al. Transcatheter closure of patent foramen ovale: A single center experience. Open Access Maced J Med Sci. 2016; 4:613-618. doi: 10.3889/oamjms.2016.113

[21] Saver JL, Carroll JD, Thaler DE, et al. Long‐term outcomes of patent foramen ovale closure or medical therapy after stroke (Respect Trial). N Engl J Med. 2017; 376:1022-1032. doi: 10.1056/NEJMoa1610057

[22] Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017; 377(11):1011-1021. doi: 10.1056/NEJMoa1705915

[23] Søndergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017; 377:1033-1042. doi: 10.1056/NEJMoa1707404

[24] Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline from the American Heart Association/American Stroke Association. Stroke. 2014; 45(7):2160-2236. doi: 10.1161/STR.0000000000000024

[25] Spies C, Schräder R. Transcatheter closure of patent foramen ovale in patients with migraine headache. J Interv Cardiol. 2006; 19:552-557. doi: 10.1111/J.1540-8183.2006.00210.X

[26] Spies C, Kavinsky CJ, Schräder R. Patent foramen ovale in patients with migraine headache: Should it be closed? Minerva Med. 2007; 98:25-36.

[27] Wang YL, Wang FZ, Zhang Y, et al. Association of migraine with patent foramen ovale closure: A systematic review and meta‐analysis. Int J Cardiol Heart Vasc. 2022; 39:100992. doi: 10.1016/j.ijcha.2022.100992

[28] Zhang Y, Wang H, Liu LL. Patent foramen ovale closure for treating migraine: A meta‐analysis. J Interv Cardiol. 2022; 2022:6456272. doi: 10.1155/2022/6456272

[29] Davis D, Gregson J, Willeit P, Stephan B, Al-Shahi Salman R, Brayne C. Patent foramen ovale, ischemic stroke and migraine: Systematic review and stratified meta‐analysis of association studies. Neuroepidemiology. 2012; 40:56-67. doi: 10.1159/000341924

[30] Chessa M, Colombo C, Butera G, et al. Is it too early to recommend patent foramen ovale closure for all patients who suffer from migraine? A single-centre study. J Cardiovasc Med. 2009; 10(5):401-405. doi: 10.2459/JCM.0b013e328329caf5

[31] Centro Cardiologico Monzino.Migraine With Aura and Causal or Incidental Patent Foramen Ovale (PFO): Identification of Biomarker(s) to Select Patients Who Would Most Benefit From PFO Closure (MANET); 2023. Available from:

[32] Sommer RJ, Robbins BT. Migraine headache and patent foramen ovale: Observational studies, the randomized clinical trials, and the GORE RELIEF clinical study. Cardiol Clin. 2024; 42(4):497-507. doi: 10.1016/j.ccl.2024.01.007

[33] Li Z, Dong J, Yan Y, et al. Study design and rationale of COMPETE: Comparison of the effect of medication therapy in alleviating migraine with patent foramen ovale. Am Heart J. 2024; 269:1-7. doi: 10.1016/j.ahj.2023.12.011

[34] Trabattoni D, Brambilla M, Canzano P, et al. Migraine in patients undergoing PFO closure: Characterization of a platelet‐associated pathophysiological mechanism: The LEARNER study. JACC Basic Transl Sci. 2022; 7(6):525-540. doi: 10.1016/j.jacbts.2022.02.002

[35] Liu K, Wang BZ, Hao Y, Song S, Pan M. The correlation between migraine and patent foramen ovale. Front Neurol. 2020; 11:543485. doi: 10.3389/fneur.2020.543485

[36] Snijder J, Luermans J, De Heij AH, et al. Patent foramen ovale with atrial septal aneurysm is strongly associated with migraine with aura: A large observational study. J Am Heart Assoc. 2016; 5:e003771. doi: 10.1161/JAHA.116.003771