Functional neuroimaging in the acute phase of Takotsubo syndrome: volumetric and functional changes of the right insular cortex

Abstract

Background A brain-heart interaction has been proposed in Takotsubo syndrome (TTS). Structural changes in the limbic system and hypoconnectivity between certain brain areas in the chronic phase of the disease have been reported, but little is known concerning functional neuroimaging in the acute phase. We hypothesized anatomical and functional changes in the central nervous system and investigated whole-brain volumetric and functional connectivity alterations in the acute phase TTS patients compared to controls. Methods Anatomical and resting-state functional magnetic resonance imaging were performed in postmenopausal females: thirteen in the acute TTS phase and thirteen healthy controls without evidence of coronary artery disease. Voxel-based morphometry and graph theoretical analysis were applied to identify anatomical and functional differences between patients and controls. Results Significantly lower gray matter volumes were found in TTS patients in the right middle frontal gyrus (p = 0.004) and right subcallosal cortex (p = 0.009) compared to healthy controls. When lower threshold was applied, volumetric changes were noted in the right insular cortex (p = 0.0113), the right paracingulate cortex (p = 0.012), left amygdala (p = 0.018), left central opercular cortex (p = 0.017), right (p = 0.013) and left thalamus (p = 0.017), and left cerebral cortex (p = 0.017). Graph analysis revealed significantly (p < 0.01) lower functional connectivity in TTS patients compared to healthy controls, particularly in the connections originating from the right insular cortex, temporal lobes, and precuneus. Conclusion In the acute phase of TTS volumetric changes in frontal regions and the central autonomic network (i.e. insula, anterior cingulate cortex, and amygdala) were noted. In particular, the right insula, associated with sympathetic autonomic tone, had both volumetric and functional changes.

Case report: takotsubo syndrome in infectious endocarditis

“…Nevertheless, there is another plausible and interesting mechanism possibly inducing TTS in IE patients. As previously stated, TTS has been associated with central nervous system disorders involving regions responsible for emotional processing [ 2 – 5 ]. Thus, it is noteworthy to mention that in the patients who received cerebral imaging cerebral embolisms were detected, amongst others affecting the temporal lobe [ 12 , 13 ].…”

“…TTS with concomitant IE is a rare phenomenon and the effect of TTS on the course of IE as well as their mechanistic relationship is currently not understood. While it is recognized that emotional and physical stress can lead to TTS the exact pathomechanism is unknown, but recently, the brain–heart interaction is getting more and more into the spotlight [ 2 – 5 ]. Here, we report the first case of TTS in prosthetic aortic valve endocarditis.…”

“…Therefore, it is conceivable that cerebral embolisms caused by IE might precede TTS development. This supports the theory that the central nervous system, and especially, the parts involved in generation and processing of emotions are of utmost importance for TTS development [ 2 – 5 ].…”

Takotsubo Syndrome: Uncovering Myths and Misconceptions

“…Intriguingly, the prevalence of (acute or past) neurologic disorders is 2 times higher in TTS patients compared to age- and sex-matched controls with ACS [ 6 ]. More recently, functional magnetic resonance imaging studies demonstrated alterations of brain regions (central autonomic network), further highlighting the importance of the brain-heart axis in the development of TTS [ 48 – 50 ]. Thus, the association between neurologic disorders and TTS is not only for the cardiologists but also for all clinicians to recognize.…”

Long-term management of Takotsubo syndrome: a not-so-benign condition

“…Specifically, stress can activate the sympathetic nervous system and lead to a complex pathophysiologic cascade including catecholamine toxicity, abnormal myocardial perfusion, myocardial stunning, and endothelial dysfunction [1]. Several neuroimaging studies demonstrated structural and functional alterations in stress-related brain networks of TTS patients during the acute phase [140], during follow-up [141][142][143] and even before the acute event [144]. These findings suggest long-lasting psychological stress in TTS patients which increases the risk of recurrence.…”