Photograph by Grant Delin
Scott Fischell, CFO and COO of NeuraLieve, tests a prototype of the company’s portable transcranial magnetic stimulator. The device sends magnetic pulses into the nerves of the head and cerebral cortex, stopping migraines cold.
Neil Hughes knows the sensation all too well. Everything goes blurry, and sunlight seems to reach his eyes bent every which way, as though he has suddenly slipped underwater. As the light grows brighter at the periphery of his field of vision, he raises his hands to cover his eyes, like the blinders on a horse. But the gesture is futile: An electrical firestorm, which medical researchers call an aura, is already raging inside his head.
Auras are neural disturbances that signal the onset of migraine headaches. They manifest themselves in numerous ways, including multichromatic showers of shooting stars, flashing lights, zigzagging lines, images broken up into herringbone or cubist patterns, loss of vision, weakness, tingling, or confusion. Sometimes the hallucinations mysteriously come and go and are a minor annoyance. More often, what follows is a nightmare: a seemingly interminable bout with throbbing head pain, nausea, and diarrhea.
For most of his adult life, Hughes, now 53, got migraines up to six times a month that rendered him violently ill, often with frightening spasms. “I would lose several days of my life lying in bed, not even knowing what time it was,” he says. He tried one remedy after another, to no avail. Doctors, he discovered, barely had a clue about what causes migraines and couldn’t offer him much relief. But now, after taking part in a clinical trial of a new device designed to quell the electrical storms in his brain, Hughes hopes he may never be laid low by a migraine again.
For the 40 million or so North Americans who suffer from chronic migraines, the condition has proved maddeningly resistant to treatment—or even explanation. Migraine researchers once focused most of their attention on the constriction and sudden dilation of blood vessels that serve the brain. They knew that stimuli such as bright lights, stress, chocolate, and other foods could trigger changes in cranial circulation. And they found that, in turn, hormonelike substances called prostaglandins were secreted along with other substances that, combined with the dilation of scalp arteries, stimulate the brain’s pain receptors. But that did little to explain what made one person rather than another a migraineur—someone who is prone to migraines.
In the early 1960s, researchers found that migraineurs produce low levels of serotonin, which inhibits pain and helps constrict blood vessels. This discovery led to the development of a class of drugs called triptans—most notably sumatriptan—that mimic the effect of serotonin. Triptans are still widely used and relieve active migraines 60 to 70 percent of the time. But they can also have dangerous side effects. When Hughes tried sumatriptan in the early 1990s, the injections set his heart racing and made him feel like his blood was on fire—“that’s how you knew it was working,” he says. He was willing to put up with the drug at first because it was so good at stopping migraines. Then he suffered two minor heart attacks. “My cardiologist said the drug could now kill me,” Hughes says. “So there I was, back to square one, living with Anacin.”
It wasn’t until the late 1990s that neuroscientists discovered a deeper source of migraines and their auras—and with it the potential for a cure. Migraineurs, they found, have a hypersensitive occipital cortex, which covers the back of the brain. By stimulating the cortical area responsible for vision, some researchers were able to trigger auralike hallucinations much more easily in migraineurs than in other subjects. The same sensitivity may make migraineurs more susceptible to bright lights, noise, and other triggers. Neuroimaging studies showed that such triggers set off an electrical wave of firing neurons that spread over the occipital cortex at a rate of several millimeters per minute. Known as a cortical spreading depression, this phenomenon had been hypothesized as far back as 1941 by the neuropsychologist and migraineur Karl Lashley. The unusual neuronal activity, in turn, seemed to foment the vessel dilation and release of prostaglandins and other substances first noted by migraine researchers.
Cortical spreading depression has also been observed in epileptics just prior to seizures, and this insight eventually led to the new migraine treatment Hughes has tested. Adrian Upton, a neurologist at McMaster University Medical Centre in Ontario, first suggested the idea in 2000. Upton had previously worked with the company NeuroPace—founded by the inventor Robert Fischell and his sons David, a physicist, Tim, a cardiologist, and Scott, an M.B.A.—to develop an implantable brain defibrillator for epileptics. By making neurons fire ahead of the cortical spreading depression, as if setting off a prescribed burn in the path of a forest fire, they found they could stop the wave of neurons from spreading, and thereby prevent seizures. “Why wouldn’t the same principle work on migraines?” they wondered.