Anticipatory anxiety of seizures is associated with ictal emotional distress and amygdala onset seizures

Abstract

Objective Anxiety disorders are a frequent psychiatric condition in patients with epilepsy. Anticipatory anxiety of seizures (AAS) is described as a daily persistent fear or excessive worry of having a seizure. AAS seems to be related to “subjective ictal anxiety” reported by patients. The current study aimed to assess the association between objective ictal features and the presence of AAS. Methods Ninety‐one patients with drug‐resistant focal epilepsy underwent a standardized psychiatric assessment, specific for epilepsy, and presurgical long‐term video‐electroencephalography (EEG) or stereo‐EEG (SEEG). We compared seizure semiology and epilepsy features of patients with AAS (n = 41) to those of patients without AAS (n = 50). We analyzed emotional and motor behavior ictal signs as well as ictal consciousness. We further assessed amygdala ictal involvement in seizures recorded with SEEG (n = 28). Results AAS was significantly associated with the presence of ictal emotional distress; negative emotional behavior (p < .01) and negative emotion were explicitly reported to the examiner during recording (p = .015), regardless of the ictal level of consciousness. Among the patients recorded with SEEG, we found a significant involvement of amygdala within the seizure onset zone (p < .01) for patients with AAS. Significance Higher risk of developing AAS is associated with seizures expressing negative emotional symptoms, independently of ictal consciousness level. Persistent interictal fear of seizures might be viewed as the consequence of a reinforcement of the emotional networks secondary to amygdala involvement in seizures of temporal origin. Physicians should screen for AAS not only to assess the impact of epilepsy on daily life, but also as an interictal biomarker of ictal semiology and emotional network involvement at seizure onset.

Epilepsy-Specific Anxiety: A Potential Clue to the Seizure Onset Zone

“…In response, Tarrada and colleagues evaluate the relation between anticipatory anxiety of seizures and multiple dimensions of ictal phenomena: subjective ictal anxiety reported by participants retrospectively in the interictal period, objective ictal features observed on video, and location of seizure onset among 3 specific areas of interest investigated via stereo-EEG. 7 The findings build on the group’s prior work demonstrating an association between subjective experience of anxiety during seizures and AAS 8 to now demonstrate independent association of AAS with subjective ictal anxiety and objective negative emotional behavior on ictal video recording. Interictal generalized anxiety, measured by the Generalized Anxiety Disorder-7 (GAD-7), and shorter duration of epilepsy were also independently associated with presence of AAS.…”

“…There were no statistically significant associations with regard to insula or orbitofrontal involvement, though only 11/28 participants with stereo-EEG data available had orbitofrontal electrode coverage. 7 While these findings are interesting and may suggest a role for anxiety symptoms as not only a comorbidity, but also a seizure localizing feature, this work is limited by the small, single center sample and bias in electrode sampling locations based on temporal lobe hypotheses for the seizure onset zone. Likewise, the assessment of AAS was done using a single question developed by the authors of this study, as there are currently no established diagnostic criteria for AAS.…”

“…Screening for AAS could be accomplished using the question employed in the Tarrada et al study: "In your everyday life, are you afraid of having an epileptic seizure?" 7 Finally, the work by Tarrada et al suggests that presence of AAS may have specific localizing value for seizure onset, further supporting the importance of identifying AAS in people with epilepsy, not only to treat a comorbidity, but to potentially benefit management of the epilepsy itself. This may be especially important among those with drug-resistant epilepsy, in which specific localization is essential for pursuing highly effective surgical epilepsy therapies.…”

“…Interictal generalized anxiety, measured by the Generalized Anxiety Disorder-7 (GAD-7), and shorter duration of epilepsy were also independently associated with presence of AAS. 7 Among 28 individuals who had stereo-EEG data available, considering the 3 regions of interest determined a priori (amydgala, insula, and orbitofrontal gyri), all 11 individuals with anticipatory anxiety of seizures had amygdala involvement in seizures, and 91% of these had seizure onset in the amygdala, compared to 41% in the non-AAS group. This finding was statistically significant, with a strong effect size.…”

“…Interictal generalized anxiety, measured by the Generalized Anxiety Disorder-7 (GAD-7), and shorter duration of epilepsy were also independently associated with presence of AAS. 7 …”