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Brain & Heart Updates on the treatment of PFO

3.4. Migraine

The 2021 European position paper included an original
meta-analysis of both observational and randomized
studies evaluating the effectiveness of PFO closure
on migraine recurrence. 10 Observational studies
demonstrated a statistically significant improvement in
migraine symptoms following PFO closure, and meta-
analyses of secondary endpoints in randomized studies
showed a significant reduction in the frequency and
duration of migraine attacks. Nonetheless, the analysis
concluded that current evidence is insufficient to draw
definitive conclusions due to significant methodological Figure 2. Complexity of the network of a patent foramen ovale-related
limitations, including heterogeneous outcome definitions syndrome1. Copyright © 2019 Europa Group. Reprinted with permission
.
across studies. of Europa Group.
In addition, recent studies have provided mechanistic 11
evidence demonstrating a causal relationship between a clearly identified primary cause. The consensus
PFO and some forms of migraine with aura. promoted a multidimensional risk assessment framework,
encouraging consideration of all potential risk factors and
These findings support that the indication for PFO comorbidities rather than focusing on a presumed single
closure in migraine remains limited. At present, closure cause. This approach aims to integrate individual risk
is recommended only within clinical trials or under profiles to optimize secondary prevention strategies.
compassionate use in patients suffering from migraine
with aura who experience severely reduced quality of life Key to this strategy is the use of personalized
despite maximal medical therapy. Ongoing randomized diagnostic algorithms that incorporate patient-specific
5,11
studies are expected to provide further clarity and refine characteristics – such as age, comorbidities, biomarkers,
these recommendations. and validated risk scores. These algorithms, combined with
advanced imaging techniques, facilitate a more comprehensive
4. New perspectives in the classification, evaluation of thromboembolic risk and associated conditions.
approach, and selection of high-risk In clinical practice, this multidimensional approach
patients not only aids in identifying the most probable cause of

The collective guidance documents on the treatment of stroke but also signals a shift toward recognizing distinct
PFO in its associated syndromes has consistently faced phenotypes within syndromes traditionally viewed as
challenges due to the significant heterogeneity of the singular entities. Furthermore, it introduces a probabilistic
studied populations. Consequently, deriving universally framework, acknowledging that managing multiple
applicable conclusions has proven difficult. As graphically potential causes may become necessary when definitive
summarized in Figure 2, this variability stems from causality cannot be determined.
disparate mechanisms resulting in diverse phenotypes, The landscape of stroke prevention and management
often indistinguishable with current diagnostic techniques, is evolving rapidly, fueled by innovative diagnostics,
even among patients classified within the same clinical individualized treatments, and novel therapeutic
syndrome. paradigms. These advances promise a transformative era in

Indeed, in both observational and randomized understanding and treating PFO-related conditions, paving
studies – as well as meta-analyses – this phenotypic the way for improved patient outcomes. Technologies such
diversity results in variable effects, wide confidence as big data and advanced information systems offer the
intervals, and high numbers - needed-to-treat, creating potential to better characterize and manage these complex,
barriers to substantial improvements in treatment efficacy. dynamic phenotypes, promising improved precision in care.
Addressing these limitations demands a paradigm shift
toward a reclassification with personalized, phenotype- 5. Conclusion
driven treatment approaches. Evidence increasingly supports a causal role of PFO in
A significant step in this direction was the 2014 various medical conditions, with percutaneous closure for
European Consensus on ESUS, which described strokes high-risk patients gaining prominence in guidelines. These
with multiple potential causes, including PFO, without documents aim to assist clinicians in making evidence-

Volume 3 Issue 3 (2025) 5 doi: 10.36922/bh.8133