Higher White Blood Cell Count In The First Week After Stroke Predicts Worse Cognitive Outcomes In A Population With Smaller Ischemic Strokes

Introduction: Infection after stroke is more common with large strokes and thus peripheral markers of inflammation are not well defined in stroke survivors with smaller strokes. We sought here to define the prevalence of infection, low grade fever (T≥38°C), and white blood cell count over 11x10 3 /mL (WBC>11) in the first week after stroke in subjects with smaller stroke sizes, and to ask how inflammation in the acute period affects cognitive outcomes in this population. Methods: We performed systematic chart review of hospitalization after ischemic stroke (up to 7 days) in 65 subjects enrolled in the StrokeCog study who returned for testing 5-13 months later (median stroke volume 6 mL, [IQR 0.5, 16.6]). We assessed infection (CDC consensus criteria), highest WBC, and presence of T≥38°C. Mann-Whitney U test and general linear models were used to assess whether WBC in the first week predicted outcomes at follow-up: MoCA, Stroke Impact Scale Depression (SIS3), a global cognitive score, and composite scores of memory, motor functioning, processing speed, language, and spatial ability. Models were adjusted when appropriate for age, sex, and stroke size or NIHSS at admission. Results: Infection and T≥38°C were each present in 8%, and WBC>11 in 18% of participants within 7 days of stroke. Since only high WBC was present in a substantial proportion of subjects, we compared outcomes in high (>11) vs. normal (≤11) WBC. Subjects with high WBC had larger strokes (13cc [6.6, 38.6] vs. 3.2[0.4, 10.6], p= 0.027) and worse admission NIHSS (10[4,13)] vs 2[1,5], p =0.003). In addition, WBC>11 in the first week was associated with worse mood and lower scores in memory, language, and global cognition months later. After adjustment, WBC remained significantly predictive of mood ( p =.039) and global cognition ( p =0.003); language remained significant if adjusted for stroke size ( p =0.010) but not NIHSS ( p =0.19). Conclusions: Infection and T≥38°C are uncommon during acute hospitalization of ischemic stroke survivors who can return to complete comprehensive testing batteries 5-13 months later. WBC>11 within the first week after stroke may be a marker of later inflammation and predicts more chronic depression and worse cognitive outcomes in this population.