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Hakan Ay, MD, a stroke physician and an investigator in the department of Radiology is the senior author of a recently published paper in Annals of Neurology, Stroke-Related Visceral Alterations: A Voxel-Based Neuroanatomic Localization Study

What was the question you set out to answer with this study?

It is currently not fully known what parts of the human brain predispose to cardiac and systemic abnormalities (CSAs) when injured.

In this study, our team set to investigate whether there are specific parts of the brain, which when injured, are associated with CSA observed after acute stroke.

What Methods or Approach Did You Use?

Consecutive patients with acute ischemic stroke were prospectively recruited into the Heart-Brain Interactions Study at the Massachusetts General Hospital.

Using a mapping technique that considers the brain as a whole rather than focusing on a particular region of interest, our team created detailed maps of brain infarcts that were linked to factors like elevated plasma troponin T (cTnT), prolonged QTc intervals on electrocardiograms (ECG), in-hospital infections, and acute stress hyperglycemia (ASH).

We examined the relationship between infarct location and CSA using a permutation-based approach and identified clusters of contiguous voxels associated with a p-value <0.05.

What Did You Find?

We identified significant, spatially segregated regions (clusters of voxels) in the brain for each CSA. Clusters encompassed both insular and non-insular regions.

 The clusters for troponin elevation and QTc prolongation mapped to the right hemisphere. There were three clusters for acute stress hyperglycemia, the largest of which was in the left hemisphere.

We found two clusters for post-stroke infection, one associated with pneumonia in the left and one with urinary tract infection in the right hemisphere. The relationship between infarct location and CSA persisted after adjusting for infarct volume.

What are the Implications?

We demonstrate that there are discrete regions of brain infarcts associated with CSAs that the patient can later develop using a mapping approach that is free from the bias of an a priori hypothesis as to any specific location. Demonstration of the existence of such regions is a step towards better understanding of the link between the brain and internal organ system dysfunction.

What are the Next Steps?

The existence of brain regions could be used to bootstrap towards new markers for better differentiation between neurogenic and organ-level mechanisms for CSA in the future. Differentiation between the neurogenic and non-neurogenic mechanisms will likely have an important impact in the management of patients with acute stroke. For example, with elevated cardiac enzymes and ECG changes occurring concomitantly with acute ischemic stroke, diagnosis of acute myocardial infarction would require a different evaluation and management than if the diagnosis had been acute stroke with secondary EGG changes.

Location information could be used to identify patients at risk of developing CSA as well. Timely identification of such at-risk population could trigger development of new therapeutic strategies and hence, improved clinical outcomes in the future.

Future studies in larger datasets and the use of alternative mapping methods such as lesion network mapping could allow for generation of more refined risk maps and better understanding of the causality between the brain damage and subsequent CSA.

Paper cited:

Arsava, E. M., Chang, K., Tawakol, A., Loggia, M. L., Goldstein, J. N., Brown, J., Park, K. Y., Singhal, A. B., Kalpathy-Cramer, J., Sorensen, A. G., Rosen, B. R., Samuels, M. A., & Ay, H. (2023). Stroke-Related Visceral Alterations: A Voxel-Based Neuroanatomic Localization Study. Annals of neurology, 10.1002/ana.26785. Advance online publication. https://doi.org/10.1002/ana.26785

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.