Migraines have baffled humankind at least as far back as the ancient Egyptians, who blamed the excruciating headaches, and their often-accompanying visual auras and nausea, on the supernatural.

Now, in a development doctors are calling revolutionary, an international group of neurologists has deciphered the mystery of why people get migraines and, in doing so, has determined how to greatly reduce their frequency and severity.

The discovery “has revolutionized our treatment of migraine,” said Dr. P. Christopher H. Gottschalk, a neurologist at Yale Medicine and a professor of neurology at the Yale School of Medicine.

“I’m witnessing a change in the landscape,” said Dr. Sandhya Mehla, a headache specialist and vascular neurologist with Hartford HealthCare Medical Group. “I would say this is a milestone.”

Melanie Stengel Photo.

For years, Linda Kelley-Dodd suffered with all the hallmarks of migraine, including auras, nausea, smell and light sensitivities. Monoclonal antibody therapy has changed her life.

The discovery, the fruit of 40 years of research, won four scientists in Sweden, Denmark and the United States the 2021 Brain Prize, the world’s most prestigious award in neurology.

It’s already leading to treatments that can significantly reduce migraine attacks as well as minimize any breakthrough headaches. The new class of drugs has the potential to change the lives of the 1 billion migraine sufferers around the globe.

Linda Kelley-Dodd’s life has already been transformed. The Bristol resident started having headaches as a teenager, although, she said, “It wasn’t until I was in my 20s that I really noticed, this is a problem for me, this is really, truly a problem.”

Before becoming one of Gottschalk’s patients, Kelley-Dodd, 49, who’s the costume project coordinator at the David Geffen School of Drama at Yale, experienced all the hallmarks of migraine. In addition to headaches, she had auras, nausea, smell sensitivity and, especially, light sensitivity, which forced her to wear sunglasses when she drove home at night because the headlights of oncoming cars were so painful.

Her headaches varied. “Sometimes they would range from just a low-grade headache to a full-on I-can’t-deal-with-the-world-please-just-somebody-make-it-go-away.”

She carried an arsenal to help “at least just tamp down the pain so I could semi-function” and “plowed through Excedrin Migraine” for days at a time, “jacking” herself up on Coca-Cola, aspirin and ibuprofen.

A year and a half ago, however, Kelley-Dodd started monoclonal antibody therapy, injecting herself once a month with a drug called Emgality.

“I can’t talk about how amazing this drug is,” she said. “It has completely changed my life.”

Cause of Migraine

Migraine, the scientists found, is the result of an interaction between the largest nerve in the head, called the trigeminal, and the meninges, the thin membrane surrounding the brain that senses pain.

When fibers in the trigeminal nerve are activated, they emit powerful chemical signals that dilate blood vessels in the meninges. The meninges then becomes inflamed, triggering a migraine.

What activates the trigeminal fibers is highly individualistic. In her essay, “In Bed,” Joan Didion, a lifelong migraineur, wrote:

“Almost anything can trigger a specific attack of migraine: stress, allergy, fatigue, an abrupt change in barometric pressure, a contretemps over a parking ticket. A flashing light. A fire drill.”

The researchers found that blocking those chemical signals, which they named calcitonin gene-related peptides (CGRP), can abort a migraine. This is what monoclonal antibodies, or CGRP antagonists, do.

Mehla of the Hartford HealthCare Medical Group called the discovery “a milestone” because it led to “the first medications that were specifically designed and tested only for migraine.” In the past, she said, doctors have had to treat their patients with medications that were developed for other medical conditions.

“Migraine is in our genes, so it really cannot be cured,” she said. But these new medications can greatly reduce their frequency.

Another huge benefit, said Gottschalk, is that their side effects “have been practically zero.”

The ‘Migraine Personality’

Like tuberculosis, migraine has often been linked to personality. In the 1930s, New York neurologist Harold Wolff asserted that the condition was especially prominent among perfectionists, those driven by ambition, a theory that remained popular until the 1980s.

And because one in three migraineurs are women, the disease has long been dismissed, or at least minimized, as just another psychosomatic condition of neurotic women.

“It’s distressing. It was not that long ago, 50 years ago, that doctors who were specialists in headache were writing [that] clearly the migraine personality includes sexual frustration in women. Unbelievable!”

— Dr. P. Christopher H. Gottschalk

For a disease that has been part of the human condition for as long as migraines have, it may be surprising that it took so long to understand it. Gottschalk blames that not only on its association with women’s supposed neuroses but also because migraine is one of those “invisible diseases.”

“It’s not like diabetes, where your sugar’s way high,” he said. “It’s not like high blood pressure where you can do a thing on your arm and show that there’s a number that’s higher than it should be. It’s somehow … mysterious or unsettling that there’s not a clear source of the problem that people can identify.”

Insurance Coverage

The CGRP receptor antagonists are, predictably, expensive—about $500 a month—but Mehla and Gottschalk are optimistic about their cost to patients in the longer term.

“I have to say it’s not as bleak as I was afraid it would be in the beginning,” Gottschalk said, “but it’s also not as good as it should be. The fact that [the medication is] FDA-approved specifically for migraine means that pretty much every commercial insurance has to approve at least one of these antibodies, and usually it’s more than one.”

Patients seeking monoclonal antibody treatment had to have tried several drugs in the past before an insurer approves the new regimen.

“Most of the patients that we see in the headache clinic are the ones who have tried something before,” Mehla said. “So, our patients usually meet the criteria if we are prescribing it. But [given the robust response], we can foresee that these medications will be covered much faster.”

— Dr. Sandhya Mehla

Her Long Road

Kelley-Dodd’s road to controlling her headaches may have been a bit atypical in that she was referred to Gottschalk for another ailment. And that it wasn’t until she started getting treatment for the other ailment that she started getting treatment for her migraines.

“I went for years without proper treatment,” she said, “not knowing that there was even treatment.”

Today, Kelley-Dodd admits, it’s a little hard for her to remember everything she went through in her 20s and 30s. She laughs as she remembers thinking, “This isn’t actually the way a human should live, where I would just power through these headaches. You just have to power through.”

“I think, truly, there isn’t enough information out there for humans to understand that this truly is a disability,” she said, “and that it truly affects people’s lives.”