Distinct clinical and inflammatory signatures in anterior vs. posterior circulation strokes

Background: While clinical differences between anterior (AC) and posterior (PC) circulation strokes are recognized, the underlying biological distinctions remain poorly defined, limiting the development of personalized therapies. This study aimed to delineate the unique clinical profiles and identify the distinct inflammatory signatures of AC versus PC ischemic strokes, thereby providing a biological basis for their classification as separate pathophysiological entities. Methods: This retrospective cohort study analyzed 499 ischemic stroke patients (434 AC, 65 PC) admitted to a tertiary neurological center. Stroke subtype was confirmed by neuroimaging. A comprehensive comparative analysis was conducted on demographic characteristics, vascular risk factors, clinical severity via National Institutes of Health Stroke Scale (NIHSS) scores, and key laboratory parameters upon admission, with a focus on inflammatory markers (C-reactive protein and white blood cell count). Results: The core innovation of this study is the discovery of a novel, divergent inflammatory signature: AC strokes were characterized by a systemic, C-reactive protein (CRP)-dominant response (14.97 vs. 8.65 mg/L, p < 0.001), whereas PC strokes exhibited a distinct, leukocyte-dominant profile (WBC count 10.80 vs. 9.36 × 10⁹/L, p < 0.001). This biological divergence was mirrored by a notable clinical dissociation, where PC strokes presented with significantly lower baseline NIHSS scores (8.31 vs. 13.47, p < 0.001), highlighting the insensitivity of standard severity scales to posterior-specific deficits. Furthermore, PC strokes were associated with older age and a higher rate of previous stroke, while AC strokes were more frequently linked to atrial fibrillation. Conclusion: Our findings establish that AC and PC strokes are not merely anatomical variants but distinct pathophysiological entities, each possessing a unique biological fingerprint. The discovery of opposing inflammatory profiles, coupled with the clear dissociation from standard clinical severity scores, provides a compelling rationale to move beyond a “one-size-fits-all” approach in stroke care. This evidence lays a critical foundation for developing subtype-specific diagnostic biomarkers and targeted immunomodulatory strategies, representing a key translational step toward advancing precision medicine for stroke patients.