Abstract Body: Introduction: Oral carriage of Streptococcus mutans (the main pathogen of dental caries), positive for cnm that encodes the collagen-binding protein Cnm, is associated with the development of hypertensive intracerebral hemorrhage and increase of cerebral microbleeds (CMBs) in our retrospective observational studies. Herein, we prospectively investigated a relationship between Cnm-expressing S. mutans and increase in CMBs in a longitudinal multicenter cohort study.
Methods: We initiated a multicenter, prospective cohort study (RAMESSES: Risk assessment of Cnm-positive S. mutans in stroke survivors; UMIN Clinical Trials Registry: UMIN000045559) in November 2018 with 14 domestic institutions. We included patients who experienced stroke or transient ischemic attack that developed within the past year, and had deep intracerebral hemorrhage or at least one deep CMBs on T2* weighted brain magnetic resonance imaging. The observation period was 2 years. The primary outcome was the number of newly developed deep CMBs between patients with Cnm-positive S. mutans and those without. The newly developed CMBs were compared by Mann-Whitney U test, and the frequency of patients who newly developed CMBs was compared by chi-square test.
Results: Out of 227 patients (138 patients with ischemic stroke, 60 patients with hemorrhagic stroke, 23 patients with ischemic and hemorrhagic stroke, 7 patients with TIA, and 2 patients with hemorrhagic stroke and TIA during the past year), the median age was 70 (interquartile range [IQR]: 62–79) years, and the number of women was 63 (27.8%). The number of patients with Cnm-positive S. mutans was 34 (15.0%), and that without was 133 (85.0%). Patients with Cnm-positive S. mutans had significantly larger number of newly developed deep CMBs over 2 years than those without (0 [IQR, 0–1] vs. 0 [0–0]; p = 0.030), and the frequency of patients who had newly developed deep CMBs tended to be higher in patients with Cnm-positive S. mutans than in those without (13 [41.9%] vs. 41 [24.7%]; p = 0.079). Regarding lobar CMBs, the number (p = 0.22) and frequency (p = 0.22) were comparable between the two groups.
Discussion: The 2-year longitudinal prospective cohort study unveiled that Cnm-positive S. mutans was significantly associated with increase in CMBs, which validated our previous retrospective studies. These findings may provide guidance for novel prophylactic strategies against Cnm-positive S. mutans-induced CMBs and intracerebral hemorrhage.