Brain Regions Associated With Unfavorable Outcomes in Post-Stroke Patients

Abdullah Hashmi, MD

July 07, 2022

The study covered in this summary was published in as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Rich-club areas of ischemic stroke are predefined highly interconnected brain regions. They were shown to be associated with increased odds of unfavorable outcomes among patients after ischemic stroke.

  • The rich-club lesions were spatially specific in their relevance for long-term stroke outcomes. Effects on long-term outcomes were smaller for the majority of random combinations of six regions.

  • Rich-club areas were more important with respect to long-term outcomes among women than among men.

Why This Matters

  • The study aimed to enhance the understanding of factors underlying unfavorable outcomes for patients with ischemic stroke. The investigators sought to enhance understanding of physiologic brain organization and network structure.

  • The findings suggest that lesions to rich-club regions should be taken into consideratioin when deciding patient-centered, individualized acute stroke treatments.

  • The findings will allow greater understanding of long-term outcomes after stroke.

  • The findings support the notion of intimate links between rich-club region malfunction and neuropsychiatric diseases and can possibly explain cerebral sex differences beyond ischemic stroke.

Study Design

  • Among patients with acute ischemic stroke who were enrolled in the multisite MRI-GENIE study, MRI data recorded at the time of the index stroke, and 3-month Modified Rankin Scale (mRS) data were analyzed.

  • Structural stroke lesions were parcellated into 108 atlas-defined bilateral subcortical brain regions. Individual brain regions were captured as two compound effects, one for six bilateral rich-club regions, and the other for all non–rich-club regions.

  • A probabilistic lesion-symptom mapping framework was designed, and permutation analysis was used to probe the rich-club constellation against 1000 random constellations of brain regions.

  • Sex-specific analyses involved comparison of male- and female-specific rich-club-region effects.

Key Results

  • Analysis included data from a total of 822 patients; 27.7% had mRS scores >2, and 39% were women.

  • The rich-club model outperformed the baseline model (weights of model comparison: rich-club model: 0.96; baseline: 0.04). Rich-club regions were relevant in explaining unfavorable functional outcomes (area under the curve: 0.8).

  • The rich-club combination had a higher relevance than 98.4% of random constellations (15/1000 random constellations with higher mean posterior values). Among the 15 constellations with higher mean values, the most frequently selected regions were the inferior temporal gyrus, the putamen, the cingulate gyrus, and the superior parietal lobule.

  • Rich-club regions were substantially more important in explaining long-term outcome in women than in men (mean of the difference distribution: -0.107, 90%; highest probability density intervals: -0.193 to -0.0124).


  • Although the researchers utilized a large stroke database, overall, patients' lesions were fairly small, and the patients were relatively mildly affected by their strokes (73% had favorable outcomes).

  • Information on acute treatment or the prestroke level of stroke was not readily available for the entire cohort.

  • The definition of rich-club regions was focused on white matter. Alternative definitions that were gray matter–focused or definitions involving functional resting state fMRI data-defined measures were not used.

  • The study relied on six rich-club regions that had been established in prior research. Future work could evaluate different numbers of rich-club regions.


  • The study received no commercial funding.

  • The original article contains a listing of the authors' relevant financial relationships.

This is a summary of a preprint research study, "The Relevance of Rich Club Regions for Functional Outcome Post-stroke Is Enhanced in Women," written by researchers at Harvard Medical School, Massachusetts General Hospital, the J. Philip Kistler Stroke Research Center, Boston, Massachusetts, Lund University, Skane University Hospital, Department of Neurology, Lund, Sweden, the University of Technology, Sydney, Sydney, Australia, and the MRI-GENIE and GISCOME Investigators and the International Stroke Genetics Consortium. It was published on medRxiv and was provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on


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