Harboring Cnm-Expressing Streptococcus Mutans In The Oral Cavity Relates To Both Deep and Lobar Cerebral Microbleeds

Streptococcus mutans, a major cariogenic bacterium, expressing the collagen-binding protein Cnm induces cerebrovascular inflammation, resulting in the impairment of blood brain barrier integrity followed by cerebral bleeding. We here examined the association of Cnm-positive S. mutans with cerebral microbleeds (CMBs) in acute stroke patients selected from a single-center registry database. Of 428 patients who received oral bacterial examinations among 3154 stroke patients, 326 patients who harbored S. mutans were identified. After excluding four patients without imaging data, we compared 72 patients with Cnm-positive S. mutans and 250 with Cnm-negative S. mutans. Deep, lobar and infratentorial CMBs were observed in 46 (63.9%), 36 (50.0%), 25 (34.7%) patients with Cnm-positive S. mutans and 144 (57.6%), 114 (45.6%), 101 (40.4%) with Cnm-negative S. mutans. Possession of Cnm-positive S. mutans was related to higher numbers of both deep and lobar, but not infratentorial, CMBs (risk ratios 1.57 [1.07‒2.30], deep; 5.44 [2.50‒11.85], lobar). Statistical significance persisted after adjusting for age, sex, hypertension, stroke type, National Institutes of Health Stroke Scale score, and cerebral amyloid angiopathy (risk ratios 1.61 [1.14‒2.27], deep; 5.14 [2.78‒9.51], lobar). Our study indicated that reduction of Cnm-positive S. mutans may serve as a therapeutic approach for improving the prognosis of stroke patients.

Cerebral Microbleeds and Acute Hematoma Characteristics in the ATACH-2 and MISTIE III Trials

Background and Objectives:To study the relationship between the presence of cerebral microbleeds (CMBs) and acute hematoma characteristics among patients with primary intracerebral hemorrhage (ICH).Methods:We pooled individual patient data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-2) trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial (MISTIE III). We included subjects with a brain magnetic resonance imaging (MRI) scan. Exposure was the presence of a CMB. The co-primary outcomes were admission ICH volume and hematoma expansion. Mixed-effects linear and logistic regression models were used, with demographics and comorbidities considered fixed effects, and the study cohort treated as a random effect. Additional analyses assessed the relationship between CMB topography and number, and hematoma characteristics.Results:Of the 1,499 ICH patients enrolled in the parent trials, 466 (31.1%) were included in this analysis, and 231 (49.6%) patients had CMBs. In adjusted models, presence of CMBs was associated with smaller ICH volume (Beta, -0.26; 95% CI, -0.44 to -0.08), and lower odds of hematoma expansion (OR, 0.65; 95% CI 0.40-0.95; P=0.04). The strength of association between CMBs and hematoma characteristics increased with increasing number of CMBs. The location of the CMBs and the severity of leukoaraiosis did not modify these results.Discussion:In a pooled cohort of ICH patients, our results are consistent with the hypothesis that more severe underlying small vessel disease, as represented by CMBs, leads to smaller baseline hematoma volumes and reduced hematoma expansion. Underlying cerebral small vessel disease may be of prognostic significance after ICH.Classification of Evidence:This study provides Class II evidence that the presence of microbleeds on MRI is associated with a smaller ICH volume at presentation and a lower rate of hematoma expansion on follow-up imaging.

A pilot study of the association between leukoaraiosis and cerebral atherosclerosis using synthetic magnetic resonance imaging

Background Leukoaraiosis is a type of lesion characterized by tissue rarefaction or myelin pallor resulting from axons loss and gliosis. Synthetic magnetic resonance imaging (MRI) could yield quantitative T1, T2, proton density (PD) values of leukoaraiosis in addition to information on the volume of the lesion. Purpose To investigate the feasibility of quantifying leukoaraiosis using synthetic MRI and to explore the association between leukoaraiosis and cerebral small vascular diseases and cerebral atherosclerosis. Material and Methods Patients with acute ischemic stroke were enrolled in this study. All participants underwent a conventional T2-weighted image, brain volume, CUBE fluid attenuated inversion recovery, and synthetic MRI acquisition using a 3.0-T MR system. A time-of-flight magnetic resonance angiography was also obtained. We evaluated the T1, T2, PD values and leukoaraiosis volume. Results Analysis of the leukoaraiosis volume ratios demonstrated a positive association with T2 values, a negative association with T1 values, and no association with PD values. Leukoaraiosis volume ratios were independently correlated with age ( P < 0.001), lacunes ( P = 0.022), and cerebral microbleeds ( P = 0.010). A statistical association was found between both age ( P < 0.001) and lacunes ( P = 0.047) and leukoaraiosis T2 values. Conclusion Synthetic MRI may enhance the evaluation of leukoaraiosis, in addition to providing information on its volume. Leukoaraiosis may represent a type of cerebral small vascular disease rather than cerebral atherosclerosis and may share the same pathological mechanism as lacunes and cerebral microbleeds.

Age, Sex, and Cerebral Microbleeds Affect White Matter Integrity Across Adulthood After Mild Traumatic Brain Injury

The contributions of age, sex, and cerebral microbleeds (CMBs) to WM changes after mild traumatic brain injury (mTBI) have not been studied. We used diffusion tensor imaging (DTI) to map WM fractional anisotropy (FA) changes across the first ~6 months post-mTBI in 109 subjects aged 18-77 (46 females; age µ: 40 y, σ: 17 y) imaged within ~1 week post-injury and ~6 months later. After partialing out age, sex, and CMB counts, significant mean FA decreases were found in the anterior body, posterior body, and splenium of the corpus callosum (CC; p = 0.003, 0.009 and 0.015, respectively), left superficial frontal fasciculus (p = 0.008), and left branch of the corticospinal tract (CST; p = 0.007). Age contributed to mean FAs measured acutely in the CC body (p = 0.04), and chronically in the CC genu (p &lt; 0.001), CC body (p = 0.01), and middle longitudinal fasciculi (p = 0.04), older adults exhibiting larger decreases. CMB counts were positively associated with mean FA decreases in the CC body (p = 0.04) and middle longitudinal fasciculi (p = 0.04). Significant age-by-sex and CMB count-by-age interactions mediated FA decreases in the CC genu (p = 0.02 and p = 0.03, respectively), older males exhibiting larger decreases. Thus, the CC, longitudinal fasciculi, superficial frontal WM and CST are particularly vulnerable to post-traumatic neurodegeneration moderated by age, sex and CMB count, men and older adults being at highest risk for adverse effects. Future research should investigate our findings relative to cognitive function.

White Matter Hyperintensities and Cerebral Microbleeds in Ataxia-Telangiectasia

Background and ObjectivesTo systematically assess the occurrence of cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs) in the largest published cohort of adults with ataxia-telangiectasia (AT).MethodsWe assessed 38 adults with AT (age range 18–55 years) including 15 classic and 23 variant AT, evaluated by two independent assessors. WMHs were quantified on T2-fluid attenuated inversion recovery images using the semiquantitative modified Scheltens and Fazekas scales and CMB on susceptibility-weighted imaging and T2*-weighted gradient echo sequences using the Brain Observer MicroBleed Scale.ResultsCMBs were more frequently found in classic AT compared with variant AT (66.7% vs 5.9%) predominantly in cortical and subcortical regions. WMHs were seen in 25 (73.5%) probands and CMBs in 9 (31.0%). The burden of WMHs increased with age, and WMHs were focused in periventricular and deep white matter regions. WMHs were more frequently seen in variant than classic AT.DiscussionThis cohort study confirms that WMHs and CMBs are a frequent finding in AT. Further longitudinal studies are required to understand how WMHs and CMBs relate to the neurodegeneration that occurs in AT and the predisposition to cerebral hemorrhage.

Disrupted White Matter Integrity and Cognitive Functions in Amyloid-β Positive Alzheimer’s Disease with Concomitant Lobar Cerebral Microbleeds

Background: Lobar cerebral microbleeds (CMBs), which can impair white matter (WM), are often concomitant with definite Alzheimer’s disease (AD). Objective: To explore the features of cognitive impairments and WM disruptions due to lobar CMBs in patients with AD. Methods: There were 310 participants who underwent Florbetapir F18 (AV45) amyloid PET and susceptibility-weighted imaging. Participants with cognitive impairment and amyloid-β positive (ADCI) were included into three groups: ADCI without CMBs, with strictly lobar CMBs (SL-CMBs), and with mixed CMBs (M-CMBs). Tract-based spatial statistics were performed to detect the group differences in WM integrity. Results: There were 82 patients and 29 healthy controls finally included. A decreasing tendency in memory and executive performance can be found among HCs > no CMBs (n = 16) >SL-CMBs (n = 41) >M-CMBs (n = 25) group. Compared to no CMBs, M-CMBs group had significantly decreased fractional anisotropy in left anterior thalamic radiation (ATR), forceps major, forceps minor and inferior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus (IFOF), and superior longitudinal fasciculus. M-CMBs group also had lower fractional anisotropy in left ATR, IFOF, uncinate fasciculus, and forceps minor compared with SL-CMBs. Furthermore, analysis of Pearson correlation indicated damages in discrepant WMs were positively associated with impairment of memory, executive function, and attention. Conclusion: This study showed lobar CMBs had intensively aggravated cognitive impairments associated with extensive WM damages in definite AD. These findings highlight that lobar CMBs play an important role in AD progression and need to be taken into consideration for the early detection of AD.