PFO Prevalence in Children with Migraine Plus Aura Matches That of Adults

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Children who suffer from migraine with aura have a significantly higher prevalence of patent foramen ovale (PFO) than those with aura-free migraines or the general population. The findings, according to an observational single-center study published online March 31, 2011, ahead of print in the Journal of Pediatrics, suggest that PFO may play a causal role in migraine with aura.

Rachel T. McCandless, MD, and colleagues from the Primary Children’s Medical Center (Salt Lake City, UT), enrolled 109 children ages 6 to 18 years who were diagnosed with migraine by pediatric neurologists at the hospital from February 2008 to September 2009. Patients were evaluated for PFO and right-to-left shunting with transthoracic echocardiography (TTE) as well as color-flow and contrast transcranial Doppler scanning.

Within the migraine group, 38 patients (35%) had aura and 71 (65%) did not. Overall PFO prevalence was 35% in pediatric migraine patients according to TTE measurements. This frequency matched PFO prevalence in the general population, which the researchers estimated to be 25% based on previously published data on older children and adults (P = 0.13).

The difference reached statistical significance when aura was added into the equation. PFO were found in 50% of subjects who had migraine plus aura (P = 0.0004 vs. the general population) but in only 27% of those without aura (P = 0.73 vs. the general population).

The distribution of PFO prevalence in pediatric migraine patients with aura mirrors that of adults with migraine and aura, the paper reports, suggesting that spontaneous PFO closure is unlikely after 6 years of age.

Contrast transcranial Doppler showed a trend toward larger right-to-left shunting and likelihood of aura, but the study was underpowered. “We estimate that a sample size of nearly 500 is needed to detect a significant difference in the degree of atrial shunting between pediatric patients with migraine with and without aura,” the authors note.

Prevalence ‘Not Just a Coincidence’

In an e-mail communication, Dr. McCandless told TCTMD that the study touches on a common conundrum. “Pediatric medicine has long been plagued by the question of how much we can generalize results from studies in adult patients to our pediatric population. We have often found that what is true in adults is not necessarily so in children, which underlines the importance of pediatric research,” she said. “I was surprised that our results showing a significantly higher prevalence of PFO in children with migraine with aura so closely mirror that of studies in adults.”

Robert J. Sommer, MD, of Columbia University Medical Center (New York, NY), pointed out that the PFO prevalence in pediatric migraine patients without aura also matched that found in adults with migraine but without aura.

Although these associations have been known for several years in adult migraine patients, he said, “[w]hat’s interesting is now that we’re looking at this in children, since the numbers are literally identical, it just goes to prove that there really is a relationship there. It’s not just a coincidence that we [observed this in] the adult population, because it’s the same pathophysiology in children.”

Therapeutic Implications Unclear

“One of the questions that’s going to come up, of course, as a result of this is [whether there are] therapies for children,” Dr. Sommer said. These include the possibility of PFO closure and antiplatelet therapy, which he noted seems to be beneficial in some adult patients. “And so while this is just an observational study, it opens the door to the same kind of therapeutic queries in the pediatric world that we’re already having on the adult side.”

Dr. McCandless cautioned, however, that despite the study’s intriguing results, “it is still unclear whether a causal relationship truly exists.

“I do not currently recommend closure of PFO in children with migraines given the lack of rigorous scientific data,” she continued. “Hopefully, as some of the ongoing randomized trials are published on PFO closure for treatment of migraines, this question will be answered for the thousands of adult and pediatric migraine sufferers.”

Dr. McCandless reported that the cardiology department at her institution was seeing increasing numbers of pediatric patients with migraines being referred “for the question of PFO, often because someone else in the family has undergone PFO closure with good results.”

Pediatric patients tend to be less aggressively treated for migraines than their adult counterparts, added Dr. Sommer, because migraine therapies can be somewhat toxic. In terms of PFO closure for headache relief, there is limited experience in children, “just like there’s not a ton of experience in the adult world,” he said, noting that pediatrics is only lagging behind by a few years. “But there are definitely patients who have PFOs who have had stroke in childhood then had their PFOs closed.”

The Specter of MIST

Both Drs. Sommer and McCandless were undeterred by the negative results of the MIST (Migraine Intervention with the STARFlex Technology) study, which failed to show PFO closure resulted in migraine relief for adult patients.

“While this study is important, it has been widely criticized due to concerns regarding the effectiveness of the device chosen, as well as study design issues,” Dr. McCandless noted, adding that “it is difficult to generalize the results of this study to the general population of migraine sufferers.”

According to Dr. Sommer, “MIST was one of the great fiascos of our era. I think the jury is still out.”

“The critical question in the whole PFO saga, whether stroke or migraine [prevention], remains patient selection. How do we know in the migraine group which patients are going to respond to therapy? Right now we don’t really have any good tests,” Dr. Sommer said. The one exception has been patients who previously experienced stroke, he added, reporting that studies have shown up to 70% of such patients see improvements in headache with PFO closure.

 

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Source:
McCandless RT, Arrington CB, Nielsen DC, et al. Patent foramen ovale in children with migraine headaches. J Pediatr. 2011;Epub ahead of print.

 

 

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