A New Marker for Migraine?

Investigators may have discovered a new biomarker for episodic migraine, according to new research.

“Our study suggests that sphingolipids may participate in migraine pathophysiology and that, upon further validation, it is possible a panel of these sphingolipids could be utilized to identify the presence or absence of migraine,” says lead study author B. Lee Peterlin, DO, associate professor of neurology and Director of Headache Research at the Johns Hopkins University School of Medicine in Baltimore.

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“The study suggests that these lipids are somehow modified or altered in those with migraine as compared to those who do not have headache, including migraine,” Peterlin says. “It also opens a new path of research to finding a novel migraine drug target.”

Peterlin and his colleagues analyzed data from 52 women with episodic migraine and 36 women who did not have any headaches. Those with migraine had an average of 5.6 headache days per month. All participants underwent neurological testing, had body mass index measured, and provided blood samples.

Investigators then tested the blood samples for a group of lipids that participate in energy homeostasis and help to regulate inflammation in the brain. They looked at several different lipids collectively known as sphingolipids—specifically, they measured levels of ceramides and sphingomyelin.

The team used an analysis approach called machine learning that incorporates ceramide and sphingomyelin data with clinical information to develop a computer-based system to diagnose migraine. Using this computer-based system, they tested the blood of a random small sampling of 14 study participants and were able to correctly identify all those who had migraine and those who did not based on the blood lipid levels.

“Biomarkers can be used to diagnose medical disorders based on a blood test and to help guide identification of the best treatments for patients,” he says.

Total levels of ceramides were decreased in women with episodic migraine as compared to those women without any headache disorders. The migraine group had approximately 6,000 ng/ml of total ceramides in their blood, while the control group only had about 10,500 ng/ml.

Every standard deviation increase in total ceramide levels was associated with more than a 92% lower risk of having migraine. In contrast, every standard deviation increase in levels of sphingomyelin was associated with a 2.5 times greater risk of migraine.

“As with the start of all research with the long-term goal of identification of a new biomarker or novel drug target for any disease state, this study was the first step on the path,” Peterlin says. “Many more will be needed to know for sure if these lipids can be an operational biomarker for migraine.”

But Peterlin believes their findings suggest further research is warranted with regard to whether these sphingolipids could be targeted to develop migraine treatment. He and his colleagues are planning to conduct additional studies using larger and new patient cohorts.

Colleen Mullarkey


Peterlin BL, Mielke MM, Dickens AM, Chatterjee S, Dash P, Alexander G, et al. Interictal, circulating sphingolipids in women with episodic migraine: A case-control study. Neurology. 2015 Sep 9. [Epub ahead of print].