MicroRNAs (miRNAs) are small non-coding RNA that are powerful regulators of gene expression and can affect the expression of hundreds of genes. miRNAs can be packed in small extracellular vesicles (SEV) and released into the extracellular space by neurons and microglia to act locally as well as pass through the blood-brain barrier and act systemically. We sought to understand the differences in neuronal SEV miRNA expression between frontotemporal dementia (FTD), Alzheimer's disease (AD), and healthy aging. Plasma was obtained from FTD, AD, and healthy aging participants that were matched based on age, sex, and race/ ethnicity. Additionally, a subset of participants also provided paired cerebrospinal fluid samples to compare neuronal SEV miRNAs in plasma and cerebrospinal fluid. Neuronal SEV were isolated using differential ultracentrifugation and antibody conjugated Dynabeads® for the neuronal surface marker, L1CAM. RNA sequencing was performed. 12 FTD, 11 with AD, and 10 healthy aging participants were enrolled in the study. In FTD, SEV miRNA-181c was downregulated compared to healthy controls. In AD, miRNA-122 and miRNA-3591 were downregulated compared to those in healthy controls and FTD. Using an FDR <0.2, only miRNA-21-5p was found to have increased expression in the cerebrospinal fluid compared to plasma in a group of AD and FTD participants. SEV miRNA-181c is significantly downregulated in FTD compared to healthy controls and may mediate its effects through microglial-directed neuroinflammation and interaction with TAR DNA-binding protein 43 (TDP-43) based on pathway analysis. Additionally, the FOXO and Hippo pathways may be important mediators of FTD, based on pathway analysis. Lastly, because only one SEV miRNA was differentially expressed between the plasma and cerebrospinal fluid in paired samples, plasma represents an appropriate biofluid for studying neuronal SEV miRNA.

Background Despite recent advancements in the treatment of acute ischemic stroke (AIS) with large vessel occlusion (LVO), infarct progression over time and functional outcomes remain variable. This variation in outcomes may be partially attributed to an underlying state of chronic cerebral hypoperfusion and ischemia affecting small cerebral perforating arterioles, venules, and capillaries of the brain; broadly termed cerebral small vessel disease (CSVD). We investigated the association between CSVD burden and the degree of disability following successful recanalization with endovascular thrombectomy (EVT) in patients with AIS presenting with LVO. Methodology We conducted a single center retrospective analysis of all patients presenting with AIS LVO between May 2016 and May 2019. Patients who were premorbidly independent and presented within six hours from the last known well (LKW) with a proximal anterior circulation occlusion confirmed on computed tomography (CT) angiography of the head or neck were treated with EVT. Patients presenting after six hours and up to 24 hours from LKW with a target ischemic core to perfusion mismatch profile on CT or magnetic resonance (MR) perfusion, or a clinical imaging mismatch on MR diffusion-weighted imaging, were also treated. Patients with successful revascularization, defined as a thrombolysis in cerebral infarction score 2b or 3, were included and evaluated for CSVD burden. The presence of CSVD was quantified using the Fazekas scale (0-3). All patients were further evaluated for disability at 90 days using the modified Rankin Scale (mRS, range 0-6). An mRS score of ≤2 was defined as a good functional outcome. Results Of the 190 patients evaluated, absent (Fazekas grade 0), mild (Fazekas grade 1), moderate (Fazekas grade 2), and severe (Fazekas grade 3) CSVD was present in 33 (17.4%), 84 (44.2%), 35 (18.4%), and 38 (20.0%) patients, respectively. Patients with severe CSVD (Fazekas grade 3) were found to be older, had a higher presenting National Institute of Health Stroke Scale (NIHSS), and had greater proportions of preexisting atrial fibrillation and dementia compared to patients with no CSVD (Fazekas grade 0). Using a multivariate ordinal logistic regression model to adjust for age, presenting NIHSS, thrombus location, LKW to groin puncture time, use of tissue plasminogen activator, ischemic infarct volume, development of a symptomatic intracerebral hemorrhage, and treatment with hemicraniectomy, patients with Fazekas grade 3 were significantly more likely to have poor 90-day functional outcomes compared to patients with Fazekas grade 0 (odds ratio 10.25, 95% confidence interval [3.3-31.84]). Conclusions Based on our analytical cohort of AIS LVO patients treated with EVT, we found that patients with severe CSVD burden had worse functional outcomes at 90 days and increased mortality. These results provide evidence that the burden of CSVD may be considered an independent risk factor of poor c...

Mechanical thrombectomy 6–24 h after the last time where a patient was known to be without signs or symptoms of a stroke is the standard of care for patients with a stroke due to large vessel occlusion. This is referred to as thrombectomy within an extended time window. There have been very few studies looking at patients who had seizures within the first week (early post-stroke seizures) following mechanical thrombectomy in this extended time window. Our study suggests that this group of patients does not have a higher incidence of early post stroke seizures. Our findings do reveal however, that patients who do have early post-stroke seizures may have a less favorable functional outcome at 90 days than those who did not develop early seizures. Hence, rapid identification and subsequent treatment of seizures in these patients is important.

BACKGROUND: Hemoglobin concentration and diffusion-weighted imaging (DWI) ischemic lesions are separately known to be associated with poor intracerebral hemorrhage (ICH) outcomes. While hemoglobin concentrations have known relationships with ischemic stroke, it is unclear whether hemoglobin concentration is associated with DWI ischemic lesions after ICH. We sought to investigate the hypothesis that hemoglobin concentrations would associate with DWI lesions after ICH and further investigated their relationships with clinical outcomes. METHODS: Supratentorial ICH patients enrolled between 2010 and 2016 to a prospective, multicenter, observational cohort study (ERICH study [Ethnic/Racial Variations of Intracerebral Hemorrhage]) were assessed. Patients from this study with baseline, admission hemoglobin, and hospitalization magnetic resonance imaging were analyzed. Hemoglobin was examined as the primary exposure variable defined as a continuous variable (g/dL). Magnetic resonance imaging DWI ischemic lesion presence was assessed as the primary radiographic outcome. Primary analyses assessed relationships of hemoglobin with DWI lesions. Secondary analyses assessed relationships of DWI lesions with poor 3-month outcomes (modified Rankin Scale score, 4–6). These analyses were performed using separate multivariable logistic regression models adjusting for relevant covariates. RESULTS: Of 917 patients with ICH analyzed, mean baseline hemoglobin was 13.8 g/dL (±1.9), 60% were deep ICH, and DWI lesions were identified in 27% of the cohort. In our primary analyses, increased hemoglobin, defined as a continuous variable, was associated with DWI lesions (adjusted odds ratio, 1.21 per 1 g/dL change in hemoglobin [95% CI, 1.07–1.37]) after adjusting for sex, race, ICH severity, time to magnetic resonance imaging, and acute blood pressure change. In secondary analyses, DWI lesions were associated with poor 3-month outcomes (adjusted odds ratio, 1.83 [95% CI, 1.24–2.69]) after adjusting for similar covariates. CONCLUSIONS: We identified novel relationships between higher baseline hemoglobin concentrations and DWI ischemic lesions in patients with ICH. Further studies are required to clarify the role of hemoglobin concentration on both cerebral small vessel disease pathophysiology and ICH outcomes.