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Sex-specific differences in white matter microvascular integrity after ischaemic stroke
  1. Mark R Etherton1,
  2. Ona Wu1,2,3,
  3. Pedro Cougo1,4,
  4. Svetlana Lorenzano1,5,
  5. Hua Li3,
  6. Lisa Cloonan1,
  7. Mark J R J Bouts1,2,6,
  8. Arne Lauer1,7,
  9. Ken Arai3,
  10. Eng H Lo1,3,
  11. Steve K Feske8,
  12. Karen L Furie9,
  13. Natalia S Rost1
  1. 1Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  2. 2Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States
  3. 3Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
  4. 4Medical School of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
  5. 5Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy
  6. 6Institute of Psychology, Leiden University, Leiden, Netherlands
  7. 7Department of Neuroradiology, Goethe-Universitat Frankfurt am Main, Frankfurt, Germany
  8. 8Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
  9. 9Department of Neurology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
  1. Correspondence to Dr Mark R Etherton; metherton{at}partners.org

Abstract

Background and purpose Functional outcomes after ischaemic stroke are worse in women, despite adjusting for differences in comorbidities and treatment approaches. White matter microvascular integrity represents one risk factor for poor long-term functional outcomes after ischaemic stroke. The aim of the study is to characterise sex-specific differences in microvascular integrity in individuals with acute ischaemic stroke.

Methods A retrospective analysis of subjects with acute ischaemic stroke and brain MRI with diffusion-weighted (DWI) and dynamic-susceptibility contrast-enhanced (DSC) perfusion-weighted imaging obtained within 9 hours of last known well was performed. In the hemisphere contralateral to the acute infarct, normal-appearing white matter (NAWM) microvascular integrity was measured using the K2 coefficient and apparent diffusion coefficient (ADC) values. Regression analyses for predictors of K2 coefficient, DWI volume and good outcome (90-day modified Rankin scale (mRS) score <2) were performed.

Results 105 men and 79 women met inclusion criteria for analysis. Despite no difference in age, women had increased NAWM K2 coefficient (1027.4 vs 692.7×10–6/s; p=0.006). In women, atrial fibrillation (β=583.6; p=0.04) and increasing NAWM ADC (β=4.4; p=0.02) were associated with increased NAWM K2 coefficient. In multivariable regression analysis, the K2 coefficient was an independent predictor of DWI volume in women (β=0.007; p=0.01) but not men.

Conclusions In women with acute ischaemic stroke, increased NAWM K2 coefficient is associated with increased infarct volume and chronic white matter structural integrity. Prospective studies investigating sex-specific differences in white matter microvascular integrity are needed.

  • stroke
  • leukoaraiosis
  • MRI

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Footnotes

  • Contributors MRE: designed and conceptualised study; analysed the data; data acquisition; drafted the manuscript for intellectual content. OW: designed and conceptualised study; analysed the data; data acquisition; revised the manuscript for intellectual content. PC, SL, HL, LC, MJRJB, AL, KA and EHL: data acquisition; revised manuscript for intellectual content. SKF and KLF: designed and conceptualised study; revised manuscript for intellectual content. NSR: designed and conceptualised study; analysed data; revised manuscript for intellectual content.

  • Funding This work was supported by the National Institutes of Health NINDS Specialized Program of Transitional Research in Acute Stroke grant P50-NS051343; R01NS082285; R01NS086905; R01NS059775. Mark Etherton is supported in part by AHA – 17CPOST33680102. Ona Wu is supported in part by NIH-NINDS P50NS051343, R01NS059775, R01NS063925, R01NS082285 and R01NS086905. Pedro Cougo, Svetlana Lorenzano, Hua Li, Steven Feske, and Karen Furie were supported by NIH 5P50NS051343. Natalia S. Rost is supported in part by NIH-NINDS R01NS082285 and R01NS086905.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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