Stroke researchers map sex-related differences in stroke severity, outcomes

BOSTON – Acute ischemic strokes are devastating events caused by blockage of blood circulation in the brain, which can be fatal or lead to severe lifelong disabilities such as paralysis and speech impairment.

It is frequently reported that stroke affects men and women differently. For example, more women than men experience a stroke each year, women are more likely to exhibit signs of stroke such as fatigue and mental confusion rather than classic signs of stroke such as paralysis, and women tend to have more severe strokes than men.

“We frequently take care of stroke patients whose outcomes we cannot explain – and when I say outcomes I mean disability as a result of stroke. Many times we can’t predict which patients will do well and why, and this is further complicated by the differences in outcomes between men and women,” says Natalia S. Rost, MD, MPH, FAAN, FAHA, chief of the Stroke Division in the Massachusetts General Hospital (MGH) Department of Neurology and professor of Neurology at Harvard Medical School.

But as Rost and colleagues report in a study published in Nature Communications, outcomes after acute ischemic strokes are linked to sex-specific patterns in how and where brain lesions –areas of damaged tissue – occur.

“In our study we had the opportunity to link specific lesions to stroke severity in men and women, and we could actually show that lesions in the left posterior [back] part of the brain lead to higher stroke severity in women than in men,” says lead author Anna Katharina Bonkhoff, MD, a stroke research fellow at MGH.

As part of an international collaboration, Rost, Bonkhoff and colleagues collected and studied 1,058 brain imaging scans of patients who had suffered from acute ischemic strokes, and used the images to conduct a sex-specific lesion-symptom analysis that is designed to link specific brain lesions to specific symptoms such as partial paralysis or speech difficulties (aphasia).

Their goal was to more clearly identify the sex-specific effects of lesion patterns affecting similar regions of the brain in both men and women, and to create a map of lesion “constellations” or clusters that may account for the higher severity of stroke in females.

Specifically, they found that higher stroke severity in women but not in men is associated with lesions occurring in the left hemisphere of the brain, in the vicinity of blood vessels at or near the back of the brain.

Their research has the potential to both identify sex-specific areas resulting in certain functional deficits after acute ischemic stroke, and to encourage clinicians to develop more “sex aware” treatments for patients with acute stroke. For example, women with stroke affecting the vulnerable areas might derive greater benefit than men from a surgical procedure to remove a blood clot (thrombectomy), they speculate.

“Such a sex-informed acute stroke care has the potential to alleviate the burden of disease on an individual patient level, as well as broader and socioeconomically relevant levels,” the investigators write.

The study was supported in part by grants from the National Institutes of Health and by health agencies and foundations in co-authors’ nations. Rost is also a Samana Cay MGH Research Scholar 2019-2024.

Rost discloses compensation as a scientific advisory consultant for Omniox, Sanofi Genzyme, and AbbVie Inc. Bonkhoff reports no competing interests.

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 August 2020, Mass General was named #6 in the U.S. News & World Report list of "America’s Best Hospitals."