“What is so exciting about the epileptic encephalopathy model is that while something causes the epilepsy, we think it is the epilepsy that directly contributes to the outcomes in autism and mental retardation,” said Dr. Berg. “If that hypothesis is true, then if we can do something about the epilepsy, maybe we can help rescue development. There is supporting evidence to suggest that—basically, that early, effective interventions may spare developmental function.”
Children with newly diagnosed epilepsy have also been linked to higher rates of ADHD. “Put another way, children with ADHD are at increased risk of developing epilepsy,” said Dr. Berg. The same study also found that adults with epilepsy were more likely than controls to have experienced significant symptoms of depression and to have attempted suicide. “I showed you first that people with epilepsy were more likely to attempt suicide, and now I’m showing you that people who are depressed, who have attempted suicide, are more likely to develop epilepsy. It goes both ways. This has led many of us to consider the hypothesis—which I have dubbed the central comorbidity hypothesis—that the disruptions in function that cause an apparently normal brain to have seizures may produce other effects as well. And these may precede or even outlast the active phase of epilepsy. It’s basically a common-cause model. But now the cause isn’t a lesion of the brain exactly, but it’s a neurophysiologic and neurochemical mechanism.”
The Clinical Picture
“This is not a disorder that is just about seizures,” emphasized Dr. Berg. “From a practical standpoint, when you are in your office with a patient with epilepsy, realize that this is someone who may be suffering, has suffered, or who will suffer from psychiatric complications, including depression.
“There are cognitive concerns that occur in these people,” she continued. “They may be subtle, but they are very important…. Mortality is an issue that is very much tied into depression and epilepsy. And let’s not forget the behavioral concerns that we see. These and several other disorders form a spectrum of epilepsy-associated disorders that are linked by mechanisms that we are just now starting to understand.”
Patients with epilepsy are more likely to describe themselves as sad, nervous, and worthless, they have more sleep problems and recurring pain, and they have lower rates of academic achievement, employment, and marriage. Between a fifth and a quarter of children with epilepsy have intellectual disability consistent with mental retardation, and higher rates of autism have been reported in this population. Furthermore, standardized mortality rates are two to four times higher among people with epilepsy, and even higher among children with epilepsy. In particular, having epilepsy increases the risk of suicide early on by a factor of fivefold and doubles that risk later in life.
“This is a highly stigmatized disorder,” Dr. Berg commented at the 63rd Annual Meeting of the American Epilepsy Society. “It is highly disruptive in one’s life.”
Determining potential underlying causes of these cognitive and behavioral comorbidities associated with epilepsy is a major focus of Dr. Berg’s research. She grouped the impact of epilepsy and seizure activity into three categories—episodic and transient effects; chronic, progressive effects; and developmental and encephalopathic effects.