epilepsyUSA, Issue 5, 2010

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Epilepsy as a Spectrum Disorder

Gordy Slack, special to epilepsyUSA

Maria’s first 8 years were overshadowed by her seizures. Her days were sometimes interrupted by complex partial seizures and every month or two she would have generalized seizures, which would leave her cranky and exhausted for several hours. So, when her seizures were finally controlled with adjustments to her medications, both Maria, who was then 8, and her parents had high hopes that life would finally become normal.

Things were not that simple, says child and adolescent psychiatrist Tatiana Falcone, M.D., at the Cleveland Clinic’s Pediatric Epilepsy Center. In fact, when Maria’s seizures finally ceased, her quality of life took a turn for the worse. Once happy to practice her violin daily and to play with friends, she lost interest both in her instrument and other people. She was melancholic, tired and irritable. Her parents couldn’t figure it out; after years of struggle, they had finally succeeded in controlling her seizures. How could she be unhappy when things were finally looking up? That’s when Maria was referred to Falcone’s clinic, and that’s when she was diagnosed with depression.

Temporal lobe epilepsy (TLE) patients are 50-percent more likely even than other people with epilepsy to be depressed, says Falcone, whose study of depression among epilepsy patients was presented at the American Epilepsy Society meeting in Boston last December. “It’s very common for TLE patients to remain or to become depressed after their seizures are controlled,” Falcone says. An association between different diagnoses, such as epilepsy and depression, is known to doctors as a comorbidity. And while depression and epilepsy have long been recognized as comorbid, the mechanisms that link them are only now emerging. And as the mechanisms that underlie other psychiatric and neurological problems are plumbed, a consensus is now emerging that epilepsy is better viewed, and treated, not simply as a disorder defined by seizures, but as something more complex and nuanced, more explicitly interrelated with other illnesses. A growing cadre of specialists suggest that epilepsy be described as a spectrum disorder.

Disabling and striking as they can be, “seizures are often only the tip of the epilepsy iceberg,” says Frances Jensen, M.D., professor of neurology at Harvard Medical School and director of epilepsy research at Children’s Hospital in Boston. “We’re beginning to pay attention to what’s down below. Often that includes other serious problems, too.”

“We want to learn more about the molecular underpinnings, about what is really going on in the epileptic brain, beyond the seizures,” says Jensen. “Maybe epilepsy is tapping into the same processes as other diseases; they may be connected, down deep.”

Some of those problems manifest medically and others more socially: “Even kids who’ve not had seizures for 15 years may have higher rates of academic and social problems,” says Jensen, who also points to strong associations between epilepsy and attention deficit hyperactivity disorder (ADHD), autism, migraine headaches, Alzheimer’s disease, language and memory disorders and depression.

“There is good evidence of genetic links between epilepsy and migraine,” says Orrin Devinsky, M.D., Director of the Comprehensive Epilepsy Center at New York University’s Langone Medical Center. “That explains why many of the same drugs are often effective for epilepsy and migraine and depression. They probably have similar genetic mechanisms or patho-physiological or biological causes that result in the symptoms. They probably are linked at a fundamental level.”

Recurrent seizures can impair the function of serotonin neurons and a serotonin deficit can cause depression, says Devinsky. And there is also a higher incidence of epilepsy in the depressed population suggesting that not having enough serotonin might also cause seizures.

“The overlap is fascinating,” says Devinsky. “If we pay attention, we have a lot to learn about the shared or overlapping mechanisms.”

But most physicians still over-focus on their epileptic patients’ seizures, says Jensen. “Typically, the doctor will ask: How many seizures have you had? How long were they? How far apart? But they often ignore other elements,” she says. “Separate, parallel disease processes may have been caused by the seizures. Or the dysfunction that caused the seizures may still be causing other problems that were overlooked by doctors focusing only on seizures.”

“We think of epilepsy as recurrent seizures,” says Devinsky. “And seizures are big problems. But if you record with electrodes from the brain, you’ll often record abnormal physiology in the brain 24 hours a day seven days a week. Epilepsy may not just be hitting patients twice a month for 2 minutes each; it may be hitting them 24/7, just in ways that aren’t causing seizures.” “The goal should be to treat the person, not the seizures, says Stanford University’s Robert Fisher. “So you must also address comorbid conditions; mood changes, ADD and all of the associated medical conditions you can identify,” says Fisher, a professor of neurology and neurological sciences.

Jensen, a leading advocate for “pulling epilepsy out of the shadows” by focusing resources and attention on its underlying causes, expects that with the combination of new imaging techniques and the emerging power to crunch huge amounts of data, we will, in the not too distant future, be able to diagnose and begin to treat epilepsy even before the patient’s first seizure occurs. But until then, it is important that patients with epilepsy and the doctors who treat them, look beyond their seizures and keep an eye out for other, “deeply-related” problems. Many of these, such as depression, often go undiagnosed—and some completely untreated— for years, at great expense to families, society and, especially, patients.

Recognizing the connection between epilepsy and its underlying causes and its comorbidities will not only have scientific and medical ramifications for the future, it also has important clinical ones today.

The pediatric epilepsy group at Cleveland Clinic, where Falcone practices, now screens every patient with epilepsy for depression and other psychological, social and neurological problems that might also be affecting quality of life. When 8-year-old Maria appeared in her office, Falcone recognized her depression and prescribed an anti-depressant and cognitive behavioral therapy. Three months later, Maria was back to her old self: happy, social and playing her violin. This time, though, she was also seizure-free.