Acute ischemic lesions seen on brain magnetic resonance imaging (MRI) are associated with poor intracerebral hemorrhage (ICH) outcomes, but drivers for these lesions are unknown. Rapid hemoglobin decrements occur in the initial days after ICH and may impair brain oxygen delivery. We investigated whether acute hemoglobin decrements after ICH are associated with MRI ischemic lesions and poor long-term ICH outcomes. Consecutive patients with acute spontaneous ICH enrolled into a single-center prospective cohort study were assessed. Change in hemoglobin levels from admission to brain MRI was defined as the exposure variable. The presence of MRI ischemic lesions on diffusion-weighted imaging was the primary radiographic outcome. Poor 6-month modified Rankin Scale score (4–6) was assessed as our clinical outcome. Separate regression models assessed relationships between exposure and outcomes adjusting for relevant confounders. These relationships were also assessed in a separate prospective single-center cohort of patients with ICH receiving minimally invasive hematoma evacuation. Of 190 patients analyzed in our primary cohort, the mean age was 66.7 years, the baseline hemoglobin level was 13.4 g/dL, and 32

Cerebral ischemia is frequently detected after intracerebral hemorrhage (ICH) on diffusion-weighted imaging (DWI) and is associated with worse outcomes. Although the mechanism is uncertain, cerebral autoregulation impairment due to severe hypertension has been suggested from prior studies. We tested the hypothesis that more severe left ventricular hypertrophy (LVH), a marker of chronic hypertension-mediated organ damage, is associated with DWI lesions after ICH. Using a single-center observational cohort study, we included all patients with spontaneous ICH between 2009 and 2019 with available magnetic resonance imaging (MRI) who underwent transthoracic echocardiography (TTE) during the index hospitalization. LVH was primarily categorized as none/mild or moderate/severe based on the TTE report and was secondarily defined using calculated left ventricular mass index (LVMI) measurement. The primary outcome measure was acute DWI lesion presence on brain MRI. The number of DWI lesions was assessed as a secondary outcome. A total of 187 patients (mean [SD] age 66.4 [14.5] years, 50.8

Electroencephalography (EEG) has emerged as a powerful tool in the diagnosis, characterization, and prognostication of patients with disorders of consciousness (DoC). EEG is a well-established monitoring tool for the treatment of specific patient populations with impaired consciousness, such as those with status epilepticus and cardiac arrest. The interrogation of neuronal circuitry using evoked and event-related potentials adds prognostic information in comatose individuals. Novel paradigms integrating transcranial magnetic stimulation may provide insights into the underpinnings of arousal and awareness. Covert consciousness, or willful brain activation to motor commands in behaviorally unresponsive patients, may be diagnosed using EEG recordings and has been linked to better outcomes. These advanced EEG methods are increasingly being explored and integrated into the management of DoC patients.

BACKGROUND:Major ABO-incompatible platelet transfusions are associated with poor intracerebral hemorrhage (ICH) outcomes, yet drivers for this relationship remain unclear. Brain magnetic resonance imaging (MRI) ischemic lesions after ICH are neuroimaging biomarkers of secondary brain injury and are associated with poor outcomes. Given that ABO-incompatible platelet transfusions can induce immune complex formation, thrombo-inflammation, and endothelial barrier disruption, factors that could exacerbate cerebral ischemia, we explored whether major ABO-incompatible platelet transfusions are risk factors for ischemic lesions on brain MRI after ICH. METHODS:Adult patients admitted to a tertiary-care academic center between 2009 and 2016 who received a single-platelet transfusion within 24 hours of admission after an ICH, had available donor/recipient ABO data, and brain MRI during the hospitalization were analyzed. Adjusted regression models evaluated relationships between major ABO-incompatible platelet units and MRI ischemic lesions. RESULTS:A total of 40 patients were included in the study. The mean age was 67.1 (SD, 14.1), and 37.5% were female. Twenty percent of patients received a major ABO-incompatible platelet unit. Major ABO-incompatible platelet transfusions were associated with increased odds of MRI ischemic lesions after adjusting for ICH severity (adjusted odds ratio, 9.2 [95% CI, 1.3-62.7]). CONCLUSIONS:Our exploratory findings suggest that major ABO-incompatible platelet transfusions may contribute to secondary brain injury after ICH. Further work is needed to assess whether avoiding major ABO-incompatible platelet transfusions can prevent secondary brain injury burden and improve ICH outcomes.

BACKGROUND:Although lower hemoglobin levels associate with worse intracerebral hemorrhage (ICH) outcomes, causal drivers for this relationship remain unclear. We investigated the hypothesis that lower hemoglobin relates to increased hematoma expansion risk and poor outcomes using human observational data and assessed causal relationships using a translational murine model of anemia and ICH. METHODS:A multicenter, prospective observational cohort study of 2997 patients with ICH enrolled between 2010 and 2016 was assessed. Patients with baseline hemoglobin measurements and serial computed tomography neuroimaging were included for analyses. Patients with systemic evidence of coagulopathy were excluded. Separate regression models assessed relationships of baseline hemoglobin with hematoma expansion (≥33% and/or ≥6 mL growth) and poor long-term neurological outcomes (modified Rankin Scale score of 4-6) after adjusting for relevant covariates. Using a murine collagenase ICH model with serial neuroimaging in anemic versus nonanemic C57/BL6 mice, intergroup differences in ICH lesion volume, lesion volume changes, and early mortality were assessed. RESULTS:Among 1190 ICH patients analyzed, the mean age was 61 years old, and 62% of the cohort were males. Lower baseline hemoglobin levels are associated with increased odds of hematoma expansion (adjusted odds ratio per -1 g/dL hemoglobin decrement, 1.10 [95% CI, 1.02-1.19]) and poor 3-month clinical outcomes (adjusted odds ratio per -1 g/dL hemoglobin decrement, 1.11 [95% CI, 1.03-1.21]). Similar relationships were seen with poor 6- and 12-month outcomes. In our animal model, anemic mice had significantly greater ICH lesion expansion, 24-hour lesion volumes, and greater mortality, as compared with nonanemic mice. CONCLUSIONS:These results, in a human cohort and a mouse model, provide novel evidence suggesting that anemia has causal roles in hematoma expansion and poor ICH outcomes. Additional studies are required to clarify whether correcting anemia can improve these outcomes.

Background: Anemia is a risk factor for worse intracerebral hemorrhage (ICH) outcomes, yet the underlying drivers remain unclear. Though anemia and inflammation are interrelated, it is unknown whether anemia influences inflammatory responses to ICH. We investigated the impact of anemia on inflammatory cell phenotypes seen in murine brains with and without ICH. Methods: Two different models of anemia were generated from 8-week-old, female C57/BL6 mice. The separate cohorts included: 1) chronic anemia model via iron-deficient chow compared to iron replete control diet, and 2) acute anemia model via red blood cell hemolysis using anti-TER119 injection compared to IgG control injection. After confirmation of anemia vs control via modified Drabkin assays, ICH was induced via collagenase injection into the right striatum, and brains and peripheral blood harvested 24 hours after ICH. Separate single cell suspensions were prepared from ICH and non-ICH hemispheres as well as peripheral blood and cells were stained for immunophenotyping using flow cytometry. Similar procedures were performed in mice without ICH. Two-tailed Student's t-tests were performed to compare immune cell populations between anemic vs non-anemic mice. Results: We identified a robust cerebral immune response to ICH in all groups. In the chronic anemia model, infiltrating macrophages and lymphocytes, particularly T cells, were elevated, while helper and gamma-delta T cells were lower in the ICH hemisphere in iron deficient anemic mice compared to iron replete controls (p<0.05). However, in the acute anemia model, only non-parenchymal intracranial macrophages were significantly elevated in the ICH hemisphere in anemic anti-TER119 injected mice compared to IgG injected controls (p<0.05). Notably, we observed a significant increase in infiltrating lymphocytes in the contralateral hemispheres in both acute and chronic models of anemia, compared to non-anemic controls. These findings in the brain were distinct from peripheral blood, where no major differences in immune cell populations were noted. Finally, in anemic mice without ICH, we did not identify a differential cerebral immune response compared to non-anemic controls. Conclusions: Anemia can differentially impact the inflammatory response to ICH in the central nervous system, based on its etiology and chronicity. Further work is required to assess whether anemia modification can abrogate pathologic immune pathways and improve ICH outcomes.

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution. We identify cell-specific targets and previously unrecognized roles for microglial and ependymal subtypes. Ependymal-4 was a hub of neuroinflammatory signaling. A distinct microglial lineage shared features with disease-associated microglia at 24 h, with persistent gene-expression changes in microglia-4 even 6 months after contusional TBI, contrasting all other cell types that mostly returned to naive levels. Regional and sexual dimorphism were noted. CEREBRI, our searchable atlas (https://shiny.crc.pitt.edu/cerebri/), identifies previously unrecognized cell subtypes/molecular targets and is a leverageable platform for future efforts in TBI and other diseases with overlapping pathophysiology.