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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.00154

Ongoing Secondary Degeneration of the Limbic System in Patients with Ischemic Stroke: A Longitudinal MRI Study

 Muhammad E. Haque1*,  Refaat E. Gabr1,  Khader M. Hasan1, Sarah D. George1,  Octavio D. Arevalo1, Alicia M. Zha1,  Susan Alderman1, Jerome Jeevarajan1, Manuel F. Mas1, Xu Zhang1,  Nikunj Satani1, Elliott R. Friedman1, Clark W. Sitton1 and Sean I. Savitz1
  • 1Institute for Stroke and Cerebrovascular Diseases, University of Texas Health Science Center at Houston, United States


Purpose: Ongoing post-stroke structural degeneration and neuronal loss preceding neuropsychological symptoms such as cognitive decline and depression are poorly understood. Various substructures of the limbic system have been linked to cognitive impairment. In this longitudinal study, we investigated the post-stroke macro- and micro-structural integrity of the limbic system using structural and diffusion tensor magnetic resonance imaging.

Materials and Methods: Nineteen ischemic stroke patients (11 men, 8 women, average age 53.4±12.3, range 18 -75 years), with lesions remote from the limbic system, were serially imaged three times over one year. Structural and diffusion-tensor images (DTI) were obtained on a 3.0T MRI system. The cortical thickness, subcortical volume, mean diffusivity (MD), and fractional anisotropy (FA) were measured in eight different regions of the limbic system. The National Institutes of Health Stroke Scale (NIHSS) was used for clinical assessment. A mixed model for multiple factors was used for statistical analysis, and p-values < 0.05 was considered significant.

Results: All patients demonstrated improved NIHSS values over time. The ipsilesional subcortical volumes of the thalamus, hippocampus, and amygdala significantly decreased (p <0.05) and MD significantly increased (p <0.05). The ipsilesional cortical thickness of the entorhinal and perirhinal cortices was significantly smaller than the contralesional hemisphere at 12 months (p <0.05). The cortical thickness of the cingulate gyrus at 12 months was significantly decreased at the caudal and isthmus regions as compared to the one month assessment (p <0.05). The cingulum fibers had elevated MD at the ipsilesional caudal-anterior and posterior regions compared to the corresponding contralesional regions.

Conclusion: Despite the decreasing NIHSS scores, we found ongoing unilateral neuronal loss/secondary degeneration in the limbic system, irrespective of the lesion location. These results suggest a possible anatomical basis for post stroke psychiatric complications.

Keywords: Limbic System Atrophy, Secondary degeneration, Chronic Loss of Gray Matter, Longitudinal Neuroimaging Study, ischemic stroke

Received: 05 Nov 2018; Accepted: 06 Feb 2019.

Edited by:

Rick Dijkhuizen, University Medical Center Utrecht, Netherlands

Reviewed by:

Nishant K. Mishra, MD, PhD, FESO, Icahn School of Medicine at Mount Sinai, United States
Stefan Greisenegger, Medical University of Vienna, Austria  

Copyright: © 2019 Haque, Gabr, Hasan, George, Arevalo, Zha, Alderman, Jeevarajan, Mas, Zhang, Satani, Friedman, Sitton and Savitz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Muhammad E. Haque, University of Texas Health Science Center at Houston, Institute for Stroke and Cerebrovascular Diseases, Houston, United States,