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Cause Mostly Unknown
Epidemiologist Hauser Traces Roots of Epilepsy

By Rich McManus

On the Front Page...

Occurring within the cloaked realm of the human cranium, epilepsy — a firestorm in the brain that can incapacitate a victim for seconds to hours — is a neurological disease whose cause, in about two-thirds of all cases, is unknown. Because it occurs in such an inviolate sanctum, epilepsy is most easily examined from without. Therefore medicine deploys its least invasive weapon — epidemiology — to probe the phenomenon from its margins, detailing whom it hits, and when, and in association with a great number of factors including age, prior medical history, habits (including drinking and drug use) and genetic legacy.


On hand in Lipsett Amphitheater June 18 to shed light on the issue was Dr. W. Allen Hauser of Columbia University's College of Physicians and Surgeons, whom host Dr. William Theodore, chief of the clinical epilepsy section, NINDS, called "clearly the leading world expert on the epidemiology of epilepsy."

"Most people find epidemiology sort of boring," Hauser began, because it deals in probabilities, large and ungraspable numbers, and such statistical arcana as confidence intervals. "Even the Epilepsy Foundation has no idea where its numbers (on the incidence of epilepsy in the population) come from...The fact is, two-thirds of the time or more, we can't answer why convulsive disorders occur," he said.

In an attempt to establish the cause of epilepsy, science has looked for a triggering event, such as a febrile seizure (a convulsion associated with fever), then examined whether the disease developed down the line. But you can do chicken-and-egg thinking, too: Did some unknown factor lead to the febrile seizure, and then subsequent epilepsy? Various causal directions are hypothesized, and Hauser focused on pathways of association taking the form of some exposing event — say stroke, or head injury, or central nervous system infection — which is then followed by epilepsy. His research has shown that those three precursors each result in a 20-fold increase in risk of the disease. Other risk-elevators for epilepsy include Alzheimer's or any other progressive neurological disease, and brain tumor. And a classic Vietnam War-era study showed that a bullet through the head inflates epilepsy risk 600-fold.

Employing data from Iceland, where whole-population information is accessible, Hauser said unprovoked seizures occur in approximately 55 of every 100,000 people. The ratio is 57/100K in males and 53/100K in females. Worldwide, the ratio appears to be about 43 cases in every 100,000, with males having a slightly higher risk globally. "That leads us to wonder, is there something about being female that's protective?" Hauser asked.

Age is also a risk factor for epilepsy. "The risk is high in the first year of life," Hauser said, "and falls dramatically at midlife, then increases dramatically to its highest incidence in the oldest age group." A study in Harlem showed that age alone is associated with a 30 percent elevation in risk of epilepsy for every decade past age 20, he reported.

Around 6 percent of epilepsy cases can be tied to alcohol abuse (heavy drinking is the equivalent of severe head injury, Hauser noted), and nearly 9 percent of cases follow head trauma.

Epilepsy is not uncommon following a stroke, and the risk endures even decades after the stroke has occurred. In those who suffer a seizure after a first stroke, 20 percent develop epilepsy within 5 years, "and the risk goes up after that. Even 20 years later, the risk is elevated 3-fold...The risk is substantial — it's greater than many people think," Hauser said. "And it's long-term." While stroke results in elevated epilepsy risk, a TIA (transient ischemic attack), interestingly enough, results in no increased susceptibility, provided there is no permanent damage, he said.

A person who suffers a seizure in the first week after a stroke has a 30 percent higher risk of developing epilepsy later on, he said. "The first seizure may beget later seizures, but it is more likely that this event is a marker for severity or location of stroke."

A ruptured cerebral aneurysm also elevates epilepsy risk; within 5 years of such an event, almost 30 percent of survivors develop the disease.

Central nervous system infections cause epilepsy, he continued. "They set up the milieu for it," observed Hauser, showing evidence that encephalitis results in a 15-fold increase in risk.

The litany he recited had a common theme: if something bad happens to the brain, epilepsy often results eventually. This was true for cases of brain injury: "There is a 15 percent increase in risk in the first few years following mild injury," Hauser stated. "For moderate trauma (resulting in unconsciousness for a half-hour to 24 hours), the risk is 3-fold, and for severe trauma, the risk is 20-fold." Even 10 years after a head injury of any severity, the epilepsy risk is elevated, he said. "Whatever it is that's happening is not short-term." (Playing tackle football is not associated with any increase in epilepsy, he observed, nor does boxing lead to the disease.)

Alzheimer's disease, too, elevates risk: "There is a 6- to 10-fold increased risk, compared to age-matched normal controls," Hauser said. "[AD is] a potent predictor of the disease."

Other ailments associated with epilepsy include depression, hypertension and migraine. Those who suffer major depression have a 6-fold increase in epilepsy risk. In a study population of those over age 50 with hypertension associated with left ventricular hypertrophy, there was a 9-fold increase in epilepsy risk, though a therapy of diuretics appears to reverse that risk, and may be an important adjunctive therapy, Hauser said. And in a study of adults and children, migraine headache appears associated with a 4-fold risk, and if it occurs with an aura in children, risk goes up to 10-fold (adults with aura have a 3-fold risk).

Of the two kinds of epilepsy — partial and generalized — a specific gene has been found only for the latter type, Hauser reported.

Alcohol, he said, is clearly a risk factor. "Abstainers have a slightly increased risk. Those who consume two drinks a day seem to be okay with respect to risk. But at 3-4 drinks a day and up, the risk increases."

Other elevators of risk include: a history of attention deficit hyperactivity disorder (3-fold, but 4-fold if ADD only); mental retardation (9-fold); cerebral palsy (12-fold); a combination of retardation and CP (50-fold).

Hauser ended his talk by pointing out that pre- and perinatal health dangers (including seizures during infancy) are not risk factors for epilepsy, and noted that marijuana use appears, in his studies, to have a somewhat protective effect against epilepsy.

"We're hoping we can whittle down that 62 percent (of epilepsy cases) for which the cause is not known," Hauser concluded.

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