Anatomical Variability, Sex-Based Differences, and Age-Specific Therapies in Stroke

Stroke remains a leading cause of death and disability worldwide, but outcomes are far from uniform across patient populations. Traditional stroke research has predominantly centered on generalized mechanisms and treatment strategies. However, mounting evidence highlights that anatomical heterogeneity, sex-linked biological differences, and age-dependent physiological variations critically influence stroke onset, severity, therapeutic responsiveness, and recovery. Recent advances in neuroimaging, molecular biology, and precision medicine now allow us to disentangle these dimensions with greater clarity. For instance, structural vascular variability can alter collateral flow and infarct progression; hormonal influences and chromosomal differences underlie divergent stroke phenotypes between men and women; and age shapes neurovascular resilience, neuroplasticity, and responses to pharmacological or interventional therapies. A systematic exploration of these factors is urgently needed to improve risk stratification, optimize individualized treatment, and design more inclusive clinical trials. This special thematic issue aims to unify current knowledge, stimulate debate, and foster translational approaches that acknowledge patient diversity in stroke care.

We invite submissions that span the spectrum of basic, translational, and clinical research, with emphasis on how anatomical, sex-based, and age-specific factors intersect to shape stroke pathophysiology and therapy. Contributions may include original research, reviews, meta-analyses, clinical trial reports, technical advances, and perspective articles.

Key themes include:

1. Anatomical Variability in Stroke
 Cerebral vascular variants (circle of Willis morphology, collateral pathways, vascular tortuosity) and their impact on ischemic vulnerability
 Neuroimaging biomarkers capturing individual variability in perfusion and tissue viability. Implications of vascular anatomy for endovascular procedures and surgical outcomes.

2. Sex-Based Differences
 Hormonal modulation of stroke risk, progression, and recovery.
 Sex-specific inflammatory and immune responses following ischemia or hemorrhage.
 Gender disparities in clinical trial representation and therapeutic efficacy.

3. Age-Specific Therapies
 Pediatric versus adult stroke: differing mechanisms and management priorities.
 Stroke in the elderly: frailty, comorbidities, and challenges in reperfusion therapies.
 Neuroplasticity, rehabilitation, and cognitive outcomes across age groups.

4. Translational and Therapeutic Perspectives
 Precision medicine and patient-tailored therapeutic approaches.
 Incorporation of anatomical and demographic variability into predictive models and trial designs.
 Future directions for personalized rehabilitation and secondary prevention.

This Research Topic will serve as a multidimensional platform highlighting how intrinsic variability among patients influences both disease course and therapeutic strategies in stroke. By integrating perspectives across neuroanatomy, endocrinology, geriatrics, imaging, and clinical practice, the collection aims to:

 Advance understanding of heterogeneity in stroke pathophysiology.
 Promote equity by addressing sex and age as determinants of care.
 Inspire more inclusive and representative clinical research.
 Translate individualized insights into improved patient outcomes.

This collection will be of interest to neurologists, neurosurgeons, neuroradiologists, stroke physicians, rehabilitation specialists, and basic scientists working on neurovascular biology. By attracting multidisciplinary contributions, it will foster a more nuanced understanding of diversity in stroke and accelerate the transition toward precision stroke medicine.