Takotsubo Syndrome Associated With Structural Brain Alterations of the Limbic System

Hiestand, Thierry; Hänggi, Jürgen; Klein, Carina; Topka, Marlene Sofie; Jaguszewski, Miłosz; Ghadri, Jelena R.; Lüscher, Thomas F.; Jäncke, Lutz; Templin, Christian

doi:10.1016/j.jacc.2017.12.022

Cited by 87 publications

(74 citation statements)

References 5 publications

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“…There were both volumetric and functional differences in the right insula in TTS patients during the acute phase. Our study confirms previously found reduced GM volume in the amygdala and the right insular cortex [11], as well as volumetric changes in the right paracingulate cortex. These regions form the central autonomic network (CAN) which regulates the cardiovascular system [4].…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, the lower functional connectivity in TTS patients in temporal regions was previously noted also in the chronic phase, where decrease in functional [10] and structural [11] connectivity was found in a network that involved these regions as part of the parasympathetic network, as well as decrease in cingulate as part of the sympathetic and limbic networks.…”

Section: Discussionsupporting

confidence: 56%

“…Furthermore, there was decreased cortical thickness in the antero-ventral insulae. In the same study cohort, structural connectivity analysis showed reduction mainly within the limbic system, whereas the subnetwork analysis of autonomic nervous system showed decrease in the left amygdala, both hippocampi, left parahippocampus and right putamen [11].…”

Section: Introductionmentioning

confidence: 82%

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

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 82%

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

et al. 2020

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“…In 2018, Hiestand et al used magnetic resonance imaging to reveal structural and connective differences in the limbic networks of TTS patients and healthy subjects. Specifically, patients with TTS had a cortex over the limbic region and significantly reduced connectivity in the autonomic nervous system, including the left amygdala, both hippocampi, the left superior temporal pole, and right putamen [47]. Moreover, a recently published study similarly reported reduced functional connectivity in the limbic systems of patients with TTS patients relative to healthy individuals [48].…”

Section: Brain-heart Connection In Takotsubo Syndromementioning

confidence: 93%

The Brain-Heart Connection in Takotsubo Syndrome: The Central Nervous System, Sympathetic Nervous System, and Catecholamine Overload

Wang

Pei

2020

Cardiology Research and Practice

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Takotsubo syndrome (TTS), also known as stress cardiomyopathy, is a type of acute heart failure syndrome triggered by intense psychological or physiological stress. TTS typically manifests as acute chest pain, dyspnea or syncope that mimics an acute myocardial infarction but does not involve coronary artery obstruction. e current understanding of the pathogenesis of TTS suggests that sympathetic nervous system (SNS) activation plays a central role. Specifically, stress can activate the SNS and lead to the over-release of catecholamine, which have toxic effects on myocardial tissue when present at excessive levels. However, the brain changes associated with TTS and the connection between the brain and the heart in patients with this disease remain unclear. In recent years, several published reports have revealed the role of this brain-heart connection in the pathogenesis of TTS.is review summarizes recent studies regarding SNS activation, catecholamine overload, and the brain-heart connection in patients with TTS from both pathophysiological and mechanistic aspects.

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“…An argument against the insular cortex being the trigger of TTS is the recent finding from a study by Klein et al By multivariate pattern analysis using machine learning with multimodal MRI data the authors found consistent structural and functional alterations in TTS patients compared to controls with a prediction accuracy of 82%, particularly in brain regions constituting the emotional‐autonomic control system (right/left parahippocampal gyrus, right/left paracentral lobe, left amygdala, left hippocampus, right/left supplementary motor area, right/left precentral gyrus, left fusiform gyrus) . In a study applying surface‐based morphometry (SBM) and voxel‐based morphometry (VBM) to T1‐weighted MRI scans, Hiestand et al demonstrated substantial anatomical differences between TTS patients and healthy controls in the limbic network comprising the insula, amygdala, cingulate cortex, and hippocampus, which are all strongly involved in the control of emotional processing, cognition, and the autonomic nervous system …”

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confidence: 99%

Insular cortex lesions are not the only culprit in Takotsubo syndrome

Finsterer

2018

Clinical Cardiology

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Insular cortex lesions are not the only culprit in Takotsubo syndromeWith interest we read the considerations of Marafioti et al about the association of Takotsubo syndrome (TTS) and the insular cortex (insula of Reil). 1 We have the following comments and concerns.Currently, the pathogenesis of TTS, of which the in-hospital mortality is 1.2%, 2 is unknown. 3 However, several speculations have been raised to explain etiology and pathogenesis of TTS. The most widely accepted pathophysiological explanation for TTS is that there is overactivity of sympathetic neurons leading to an increased release of noradrenaline from nerve endings of sympathetic neurons. 4 The strongest argument for this hypothesis is that TTS frequently occurs after an event with endogenous or exogenous stress. However, there are patients in whom TTS is not related to a previous stressful event. 5 Another argument against the stress hypothesis of TTS is that catecholamines may not be elevated in each patient with TTS. Assuming that the insular cortex is linked to central sympathetic projections and responsible for QTc-prolongation, ventricular arrhythmias should be a frequent complication of ischemic stroke in the median cerebral artery territory, which supplies the insular cortex. However, this is not the case and the cerebral autonomic outflow is not only associated with the insular cortex but also with for example, the thickness of the frontal cortex. 10 QTc-prolongation is generally associated with a higher risk of cardiovascular re-hospitalization at follow-up. 11In summary, considerations about the pathogenesis of TTS remain speculative. There are arguments for and against the various speculations. Not only a single mechanism may explain the occurrence of TTS but the phenomenon may be multicausal. For example, we should not neglect the hypothalamic-pituitary-adrenergic axis and the limbic system network. Overall, the stress hypothesis remains the most appealing explanation for the phenomenon so far.

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Takotsubo Syndrome Associated With Structural Brain Alterations of the Limbic System

Cited by 87 publications

References 5 publications

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

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

The Brain-Heart Connection in Takotsubo Syndrome: The Central Nervous System, Sympathetic Nervous System, and Catecholamine Overload

Insular cortex lesions are not the only culprit in Takotsubo syndrome

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