ORLANDO—Many patients with seizures, especially those with temporal lobe epilepsy, experience symptoms of anxiety and panic. Paradoxically, these symptoms may decline as seizure activity increases, suggesting a possible link between patient mood and inhibitory brain mechanisms, according to a study presented at the 53rd Annual Meeting of the American Epilepsy Society.

The social and physical consequences of epilepsy provide a firm basis for patients' emotional distress. Although seizures typically occupy only minutes a month for people with uncontrolled epilepsy, the unpredictability of these events can significantly impair quality of life. A seizure may strike at any time, often without warning; embarrassment, physical injuries, loss of driving privileges, or dismissal from a job can result.

To characterize the relationship between anxiety and seizure frequency, investigators from Weill Medical College of Cornell University, New York, examined 80 adults with epilepsy, most of whom had partial seizures. Subjects had a mean age of 38 (range, 20 to 79) and 69% were female. The average number of seizures in the month prior to assessment was eight, with a range of zero to 90; one in five subjects had 10 or more seizures per month. To assess anxiety levels, researchers administered two neuropsychological inventories, the investigator-rated Hamilton Anxiety Rating Scale (HAM-A) and the subject-rated State-Trait Anxiety Index (STAI).

The results revealed a statistically significant negative correlation (r = -0.23) between seizure frequency and HAM-A scores. Patients with fewer than 10 seizures per month had a mean HAM-A score of 11.5, while those with 10 or more seizures per month had a mean score of only 6.5. Findings from the STAI were similar but fell short of statistical significance. The researchers concluded that patients with high seizure rates had lower anxiety levels than those with infrequent seizures.

PRIMARY EFFECT OR ADAPTIVE RESPONSE?

"I [expected] to find the exact opposite of what we found," acknowledged study coauthor Cynthia Harden, MD, Associate Professor of Neurology and Neuroscience and an epileptologist at Weill Medical College. The findings, she noted, are open to at least two interpretations. One possibility is that the low levels of anxiety in patients with frequent seizures is an adaptive psychological response "related to learned helplessness. People who are used to having seizures get used to having them; they've learned not to have an emotional reaction because they feel helpless about not being able to prevent seizures."

However, an alternative explanation is that the reduction in anxiety is a primary effect of epilepsy itself. If that is the case, said lead author Martin Andrew Goldstein, MD, Senior Resident in Neurology at New York Hospital, "it is hard not to invoke the amygdala as a component [of the process]." Numerous studies have linked the amygdala to the pathophysiology of anxiety/panic symptoms; the structure integrates signals from interoceptive and exteroceptive stimuli and distributes processed afferent data to other regions of the brain, including the basal ganglia, brainstem, cerebral cortex, hypothalamus, and limbic system. These regions, in turn, generate affective, autonomic, and cognitive components of the anxiety/panic response. However, since seizures "disrupt the homeostasis of the brain," it is possible that frequent episodes alter function of the amygdala, thereby reducing anxiety, Dr. Goldstein said.

Interestingly, in patients who have relative few seizures, the correlation between seizure frequency and anxiety was slightly positive. This suggests that "there exists some seizure frequency threshold at which the circuit underlying anxiety generation becomes refractory to further input," according to Dr. Goldstein and colleagues.

Future studies should explore which hypothesis best explains the relationship between seizure frequency and anxiety, Dr. Harden said. If possible, such studies should utilize "a more objective marker of anxiety in epilepsy patients, perhaps incorporating neuroimaging." She added that "we are continuing to look at mood and anxiety in epilepsy patients and maybe we'll try to incorporate seizure parameters such as foci and lateralization, as well as comorbid psychiatric problems."

In the meantime, Dr. Goldstein suggested, "epileptologists need to be more sensitive to anxiety and depression" in their patients. Clinicians should not only address seizure control, he said, but encourage their epilepsy patients to discuss symptoms of anxiety.

NR

—Andrew Wilner, MD
Contributing Writer

Suggested Reading
Goddard AW, Charney DS. Toward an integrated neurobiology of panic disorder. J Clin Psychiatry. 1997;58(suppl 2):4-11.
Malmgren K, Sullivan M, Ekstedt G, et al. Health-related quality of life after epilepsy surgery: a Swedish multicenter study. Epilepsia. 1997;38:830-838.

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