Clinician scientist Ivan Osorio considers seizure prediction the “holy grail of neuroscience.”
Although the best medicines can’t control seizures in nearly 25 percent of cases, epilepsy is as inspiring to Osorio—who received an Epilepsy Research Foundation New Therapy Grant in 2006—as it is intractable to his patients.

“Among the neurological disorders, it is the one where you can make the most difference,” said Osorio, who is a professor of neurology at the University of Kansas Medical Center in Kansas City, Mo.

In between seizures, the epileptic brain is, for the most part, normal. Seizures come in like a lion and go out like a lamb. But how to tame the lion?

Relaxation events
The idea that something is terribly but only temporarily amiss in the epileptic brain persuaded Osorio to look at similar phenomena. Back in the mid 1980’s, when he started his quest, “epileptology was ignoring quantitative approaches,” that involve mathematical or physical analysis, he said. “I realized that we might have to use tools outside of medicine.”

Beyond the medical establishment, Osorio found other grail seekers trying to understand something as terrible— and as temporary—as a seizure. In this group of physicists and seismologists seeking to predict earthquakes, Osorio realized he’d found kindred spirits—and a kindred phenomenon.

“Earthquakes and seizures are both relaxation events,” he explained. “Energy accumulates over a long period of time, and then discharges quickly to relax the system.”

It might be decades or centuries before a 30-second “Big One” takes out a city to “relax” the Earth’s crust. Similarly, days, weeks or months might pass before a 30-second seizure “relaxes” an epileptic brain. On that singular intuition, Osorio built a case. With geophysicist Didier Sornette—formerly of UCLA who now studies financial bubbles, crashes, risk and natural disasters at the Swiss Federal Institute of Technology in Zurich— computational neuroscientist John Milton of the Claremont Colleges in Claremont, Calif., and Lawrence, Kansas-based mathematician Mark Frei, Osorio rallied the tools of seismology and the language of numbers to describe what he calls “quakes of the brain.”

Comparing a catalog of 16,032 seizures detected in 60 human subjects with drug-resistant epilepsies against a catalog of 307,019 earthquakes in the Southern California Seismic Network —81,977 of two or greater magnitude on the Richter scale—Osorio and his team made a discovery he says “startled” them.

The same well-tested mathematical laws that apply to seismic events also apply, with some minor conditions, to the untested frontier of epileptic seizures.

Earthquake laws
Seismologists know these laws well. Among them, the Omori Law says that “earthquakes, regardless of their size, beget more earthquakes.” And the power law says “the longer it has been since the last earthquake—or seizure—the longer it will be until the next one.”

Epileptic seizures share similar properties and combined, the earthquake laws suggest a predictive strategy to Osorio and his team.

According to the Omori Law, short, imperceptible seismic bursts (mini-earthquakes less than 2.0 on the Richter scale) can trigger and therefore precede bigger earthquakes. Seismologists pick up these short bursts on a seismograph, but we don’t feel them.

Likewise, an EEG—which Osorio calls “a neurological seismograph”—can pick up short bursts of abnormal but unperceived brain electrical activity. If the Omori Law holds, this sub-clinical “noise” may trigger seizures, large or small.

When Osorio announced his team’s discovery last year, the response was immediate and worldwide. The New York Times, New Scientist, The Scientist, Discover Magazine—even the Guardian newspaper of London—broadcast the unusual correlations.

“The idea that earthquakes and seizures represent essentially the same phenomena is very intriguing,” said Carl Bazil, an associate professor of clinical neurology and epilepsy specialist at the Columbia University College of Physicians and Surgeons in New York City. The comparison Osorio and his colleagues offer “looks correct,” Bazil explained after reviewing a paper about their results. “Earthquakes and seizures do appear to represent the same type of energy oscillation.”

But Bazil stops short at the idea earthquake mathematics could make seizures predictable. “Many of epilepsy’s devastating consequences could be mitigated if accurate predictions were available,” Bazil said. But no effort to predict either earthquakes or seizures “has ever been successful in the least.”

Prevailing canon
As creator and host of Coping With Epilepsy, a 3,200- member online forum based in Friendswood, Texas, Bernard Ertl said Osorio’s research won’t make much difference to the average person with epilepsy “unless some enterprising company makes a personal/home EEG system that people can wear and use all the time.”

Even so, Ertl, whose wife has epilepsy, sees some immediate benefits.

“This research may ultimately provide greater validation for EEG neuro-feedback as a long-term treatment option for epilepsy,” he said. “And it does hold promise as a new diagnostic paradigm.”

Indeed, Osorio said his work challenges the prevailing diagnostic canon, which maintains that “only the big clinical seizures are the important ones.

“Seismology recently lived through a kind of revolution by finally realizing that numerous small earthquakes are probably the most important triggers of large earthquakes,” he said. Continuing the analogy, Osorio seeks a similar revolution in epileptology, “based on the hypothesis that subclinical seizures and other minor EEG events are clues for predicting large seizures. Just as no seismologist would ignore an earthquake only a seismograph can detect, no neurologist should ignore aberrant electrical activity only an EEG can detect.” But they do, Osorio said, creating an “incomplete clinical picture” that mistakenly characterizes an epileptic seizure according to “typical” intensity and duration.

Neither sacred nor divine
Osorio’s quest recalls a time twenty-four hundred years ago, when the Greek physician Hippocrates cast aside two thousand years of myth and legend during which epilepsy was known as “the Sacred Disease,” and the person with epilepsy either a demon incarnate or an angel on Earth.

“It is neither more divine nor more sacred than other diseases,” Hippocrates wrote. “It has a natural cause.”

But finding that cause has eluded neurology, partly because epilepsy “isn’t so much understood as it is catalogued, according to highly subjective and arbitrary definitions,” said Osorio.

He reminds that seismologists long ago learned that such classification systems—which seek to define the typical rather than to understand the diverse—are doomed to fail.

“There’s no such thing as a typical seizure,” Osorio said. “Just like there’s no such thing as a typical earthquake.”