Addressing the Association Between Stress and Seizure Frequency

Stress is known to be associated with health conditions such as hypertension, heart disease, and gastrointestinal disorders. Less well-known is its connection to another medical problem: seizures.

“Stress is the most common self-reported trigger for seizures in patients with epilepsy,” Jamie Maguire, PhD, a professor of neuroscience at Tufts University School of Medicine, told Neurology Advisor. “Stress hormone levels are elevated in patients with epilepsy, and are further elevated following seizures.” 

Despite the strong link, experts do not fully understand the mechanisms behind it, though recent findings offer some clues. Research published in December 2014 in Epilepsy & Behavior suggests anxiety may have a role in some cases of stress-precipitated seizures.¹ Of 266 patients at a tertiary epilepsy clinic, 219 reported stress as a seizure trigger: 85% of these patients cited chronic stress as the cause, while 68% indicated that acute stress precipitated their seizures. Patients who reported stress-triggered seizures had significantly higher scores on the Generalized Anxiety Disorder 7-item (GAD–7) scale.

“Our research so far suggests that anxiety level somehow interacts to make people more susceptible to stress as a seizure trigger,” study researcher Michael Privitera, MD, a professor and director of the Epilepsy Center at the University of Cincinnati Neuroscience Institute, told Neurology Advisor. “It’s not clear whether anxiety — and to a lesser extent, depression — interact with stress in the brains of these susceptible people to trigger seizures, or whether it’s actually anxiety they are experiencing when they report stress.” He and his colleagues are currently investigating these questions in a randomized controlled trial.

Mediating Stress Response

Rodent studies conducted by Maguire and colleagues at Tufts University provide insight into potential neurochemical mechanisms involved in the relationship between stress and seizures.^2,3

“Research on the association between stress and epilepsy has focused on the stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, which mediates the body’s physiological response to stress,” said Maguire. “Our lab has demonstrated a novel mechanism through which stress activates the HPA axis,” leading to “changes in the hippocampus, resulting in compromised GABAergic inhibition. The hippocampus is particularly vulnerable to stress, and we propose that these changes may be associated with the impact of stress on neuronal excitability in the hippocampus, which may play a role in the impact of stress on seizure susceptibility.”

Their findings also indicate that seizures directly activate the HPA axis, thereby increasing stress hormone levels, which have been shown to be proconvulsant and may increase seizure susceptibility independently of stress. “We propose that seizure-induced activation of the HPA axis may be one mechanism whereby seizures beget seizures or contribute to seizure clustering in patients with epilepsy,” said Maguire.

A study published in July 2014 in Epilepsy & Behavior found support for the role of the HPA axis in the stress-seizure connection in human subjects.⁴ Researchers used functional Magnetic Resonance Imaging (fMRI) to compare brain differences between patients with epilepsy and healthy controls in response to a psychosocial stressor. Compared to controls, the patients demonstrated altered cortisol response and decreased activation in multiple areas of the brain. Additionally, patients whose epilepsy was poorly controlled “showed negative association between seizure frequency and activation in the bilateral subgenual anterior cingulate,”⁴ which is associated with activity of the HPA-axis.

In the future, Privitera and colleagues “hope to identify which patients may best respond to stress reduction, identify which stress reduction methods work best for seizures, and to better understand the mechanism behind this relationship in order to develop future treatments.”

Addressing Stress in Patients

Meanwhile, there are practical steps clinicians can take to improve outcomes for their patients with stress-precipitated seizures. “First, any patient that reports stress as a seizure trigger should be screened for treatable anxiety or depression,” said Privitera, and they should be encouraged to adopt stress-reduction practices. Since most physicians don’t recognize stress as a trigger for seizures, they generally don’t make such recommendations.

However, many patients seem to have learned firsthand that stress reduction methods can decrease the frequency of their seizures. In Privitera’s study, 57% of patients reporting stress-induced seizures had tried stress-reduction approaches (meditation, yoga, and other types of exercise were the most common), and 88% of these patients reported that these techniques led to improvement in their seizures. Even among the patients who did not cite stress as a trigger for seizures, 25% had tried stress reduction methods, and 71% of this group reported subsequent improvement.

“It was very surprising that so many had tried these and that so many patients reported that their seizures had improved. This is not something that many patients report spontaneously in the office,” said Privitera.

In addition to the lifestyle approaches to help manage stress, other recent research suggests that skin-conductance biofeedback could help reduce stress-triggered seizures in patients with drug-resistant temporal lobe epilepsy. In findings reported in Epilepsy & Behavior, 12 sessions of biofeedback training led to a 49% decrease in the frequency of seizures in 11 patients.

“Since most stress reduction methods would not interfere with ongoing treatment, clinicians should be recommending stress reduction methods to all patients as an adjunctive or integrative treatment,” said Privitera.

References

1. Privitera M, Walters M, Lee I, et al. Characteristics of people with self-reported stress-precipitated seizures. Epilepsy & Behavior. 2014; 41:74-7.
2. MacKenzie G, Maguire J. Chronic stress shifts the GABA reversal potential in the hippocampus and increases seizure susceptibility. Epilepsy Research. 2015; 109:13-27.
3. O’Toole KK, Hooper A, Wakefield S, Maguire J. Seizure-induced disinhibition of the HPA axis increases seizure susceptibility. Epilepsy Research. 2014; 108(1):29-43.
4. Allendorfer JB, Heyse H, Mendoza L, et al. Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy — A pilot cross-sectional fMRI study. Epilepsy & Behavior. 2014; 36:115-23.
5. Micoulaud-Franchi JA, Kotwas I, Lanteaume L, et al. Skin conductance biofeedback training in adults with drug-resistant temporal lobe epilepsy and stress-triggered seizures: A proof-of-concept study. Epilepsy & Behavior. 2014; 41:244-50.