A Survey of Surrogates and Health Care Professionals Indicates Support of Cognitive Motor Dissociation-Assisted Prognostication.

BACKGROUND: Prognostication of patients with acute disorders of consciousness is imprecise but more accurate technology-supported predictions, such as cognitive motor dissociation (CMD), are emerging. CMD refers to the detection of willful brain activation following motor commands using functional magnetic resonance imaging or machine learning-supported analysis of the electroencephalogram in clinically unresponsive patients. CMD is associated with long-term recovery, but acceptance by surrogates and health care professionals is uncertain. The objective of this study was to determine receptiveness for CMD to inform goals of care (GoC) decisions and research participation among health care professionals and surrogates of behaviorally unresponsive patients. METHODS: This was a two-center study of surrogates of and health care professionals caring for unconscious patients with severe neurological injury who were enrolled in two prospective US-based studies. Participants completed a 13-item survey to assess demographics, religiosity, minimal acceptable level of recovery, enthusiasm for research participation, and receptiveness for CMD to support GoC decisions. RESULTS: Completed surveys were obtained from 196 participants (133 health care professionals and 63 surrogates). Across all respondents, 93% indicated that they would want their loved one or the patient they cared for to participate in a research study that supports recovery of consciousness if CMD were detected, compared to 58% if CMD were not detected. Health care professionals were more likely than surrogates to change GoC with a positive (78% vs. 59%, p = 0.005) or negative (83% vs. 59%, p = 0.0002) CMD result. Participants who reported religion was the most important part of their life were least likely to change GoC with or without CMD. Participants who identified as Black (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.04-0.36) or Hispanic/Latino (OR 0.39, 95% CI 0.2-0.75) and those for whom religion was the most important part of their life (OR 0.18, 95% CI 0.05-0.64) were more likely to accept a lower minimum level of recovery. CONCLUSIONS: Technology-supported prognostication and enthusiasm for clinical trial participation was supported across a diverse spectrum of health care professionals and surrogate decision-makers. Education for surrogates and health care professionals should accompany integration of technology-supported prognostication.

Low hemoglobin causes hematoma expansion and poor intracerebral hemorrhage outcomes.

Objectives: 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 (HE) risk and poor outcomes using human observational data and assessed causal relationships using a translational murine model of anemia and ICH. Methods: ICH patients with baseline hemoglobin measurements and serial CT neuroimaging enrolled between 2010-2016 to a multicenter, prospective observational cohort study were studied. Patients with systemic evidence of coagulopathy were excluded. Separate regression models assessed relationships of baseline hemoglobin with HE (≥33% and/or ≥6mL growth) and poor long-term neurological outcomes (modified Rankin Scale 4-6) after adjusting for relevant covariates. Using a murine collagenase ICH model with serial neuroimaging in anemic vs. non-anemic C57/BL6 mice, intergroup differences in ICH lesion volume, ICH volume changes, and early mortality were assessed. Results: Among 1190 ICH patients analyzed, lower baseline hemoglobin levels associated with increased odds of HE (adjusted OR per -1g/dL hemoglobin decrement: 1.10 [1.02-1.19]) and poor 3-month clinical outcomes (adjusted OR per -1g/dL hemoglobin decrement: 1.11 [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, final lesion volumes, and greater mortality, as compared to non-anemic mice. Conclusions: These results, in a human cohort and a mouse model, provide novel evidence suggesting that anemia has causal roles in HE and poor ICH outcomes. Additional studies are required to clarify whether correcting anemia can improve these outcomes.

Relationships of hematocrit concentration with dementia from a multiethnic population-based study.

OBJECTIVE: Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship. METHODS: A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003-2008. Participants received baseline hematocrit testing, MRI neuroimaging, and cognitive assessments at baseline and long-term follow-up. Associations of baseline hematocrit as a categorical variable (low, normal [reference], and high based on laboratory reference levels) with incident dementia were assessed using Cox models adjusting for relevant covariates. Separate analyses investigated whether MRI CSVD mediated these relationships. RESULTS: We studied 1207 NOMAS participants (mean age 71±9 years, 60% female, 66% Hispanic). Mean hematocrit was 41.2% (±3.8) with 16% of participants developing incident dementia. Lower hematocrit associated with increased dementia risk (adjusted hazard ratio 1.81 [1.01-3.23]) after adjusting for age, sex, race/ethnicity, education, APOE status, and comorbidities. High hematocrit was not associated with dementia risk. No interactions by sex or race/ethnicity were seen and baseline CSVD did not mediate relationships between hematocrit and dementia. CONCLUSIONS: Low hematocrit associated with dementia risk in our diverse population cohort. Further work is needed to assess mechanisms behind anemia's relationship with dementia to assess whether this can serve as a trackable, preventable/treatable risk factor for dementia.

Impact of Aphasia on Brain Activation to Motor Commands in Patients with Acute Intracerebral Hemorrhage.

BACKGROUND: Brain activation to motor commands is seen in 15% of clinically unresponsive patients with acute brain injury. This state called cognitive motor dissociation (CMD) is detectable by electroencephalogram (EEG) or functional magnetic resonance imaging, predicts long-term recovery, and is recommended by recent guidelines to support prognostication. However, false negative CMD results are a particular concern, and occult aphasia in clinically unresponsive patients may be a major factor. This study aimed to quantify the impact of aphasia on CMD testing. METHODS: We prospectively studied 61 intensive care unit patients admitted with acute primary intracerebral hemorrhage (ICH) who had behavioral evidence of command following or were able to mimic motor commands. All patients underwent an EEG-based motor command paradigm used to detect CMD and comprehensive aphasia assessments. Logistic regression was used to identify predictors of brain activation, including aphasia types and associations with recovery of independence (Glasgow Outcome Scale-Extended score ≥ 4). RESULTS: Of 61 patients, 50 completed aphasia and the EEG-based motor command paradigm. A total of 72% (n = 36) were diagnosed with aphasia. Patients with impaired comprehension (i.e., receptive or global aphasia) were less likely to show brain activation than those with intact comprehension (odds ratio [OR] 0.23 [95% confidence interval 0.05-0.89], p = 0.04). Brain activation was independently associated with Glasgow Outcome Scale-Extended ≥ 4 by 12 months (OR 2.4 [95% confidence interval 1.2-5.0], p = 0.01) accounting for the Functional Outcome in Patients with Primary ICH score (OR1.3 [95% confidence interval 1.0-1.8], p = 0.01). CONCLUSIONS: Brain activation to motor commands is four times less likely for patients with primary ICH with impaired comprehension. False negative results due to occult receptive aphasia need to be considered when interpreting CMD testing. Early detection of brain activation may help predict long-term recovery in conscious patients with ICH.

Anemia From Inflammation After Intracerebral Hemorrhage and Relationships With Outcome.

BACKGROUND: Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes. METHODS AND RESULTS: Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High-Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long-term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90-day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: -0.27 [95% CI, -0.37 to -0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62-0.93]) independent to inflammation and ICH severity. CONCLUSIONS: We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes. REGISTRATION: https://www.clinicaltrials.gov Unique identifier: NCT01662895.

Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes.

BACKGROUND: Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. METHODS: Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. RESULTS: Of 44 patients analyzed, the mean age was 64 years, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. CONCLUSIONS: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.

Premorbid Blood Pressure Control Modifies Risk of DWI Lesions With Acute Blood Pressure Reduction in Intracerebral Hemorrhage.

BACKGROUND: Hypoperfusion due to blood pressure (BP) reduction is a potential mechanism of cerebral ischemia after intracerebral hemorrhage. However, prior evaluations of the relationship between BP reduction and ischemia have been conflicting. Untreated chronic hypertension is common in intracerebral hemorrhage and alters cerebral autoregulation. We hypothesized that the risk of diffusion-weighted imaging (DWI) hyperintensities from acute BP reduction is modified by premorbid BP control. METHODS: Individuals enrolled in the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage) from 2010 to 2015 were categorized as untreated, treated, or nonhypertensive based on preintracerebral hemorrhage diagnosis and antihypertensive medication use. The percent reduction of systolic BP (SBP) was calculated between presentation and 24 hours from admission. The primary outcome was the presence of DWI lesions. Using logistic regression, we tested the association between chronic hypertension status, SBP reduction, and their interaction with DWI lesion presence. RESULTS: From 3000 participants, 877 with available magnetic resonance imaging met inclusion (mean age, 60.5±13.3 years; 42.5% women). DWI lesions were detected in 25.9%. Untreated, treated, and no hypertension accounted for 32.6%, 47.9%, and 19.5% of cases, respectively. SBP reduction was not directly associated with DWI lesions; however, an interaction effect was observed between SBP reduction and chronic hypertension status (P=0.036). Nonhypertensive subjects demonstrated a linear risk of DWI lesion presence with greater SBP reduction, whereas untreated hypertension demonstrated a stable risk across a wide range of SBP reduction (P=0.023). CONCLUSIONS: Premorbid BP control, especially untreated hypertension, may influence the relationship between DWI lesions and acute BP reduction after intracerebral hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01202864.

Admission viscoelastic hemostatic assay parameters predict poor long-term intracerebral hemorrhage outcomes.

Background: Viscoelastic hemostatic assays (VHA) provide more comprehensive assessments of coagulation compared to conventional coagulation assays. While VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. Methods: Spontaneous ICH patients enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with prior anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Results: Of 44 patients analyzed, mean age was 64, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64%. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted OR for every second increase in clot formation time: 1.04, 95% CI: 1.00-1.09, p = 0.04) and weaker clot strength (adjusted OR for every millimeter increase of maximum clot firmness: 0.84, 95% CI: 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. Conclusions: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA guided treatments should be incorporated into ICH care.

Primary and Secondary Intracerebral Hemorrhage in Pregnant and Nonpregnant Young Adults by SMASH-UP Criteria.

BACKGROUND: Intracerebral hemorrhage (ICH) is a major cause of maternal morbidity, but its pathophysiology is poorly characterized. We investigated characteristics of pregnancy-associated ICH (P-ICH), compared with ICH in similar aged nonpregnant adults of both sexes. METHODS AND RESULTS: We performed a retrospective analysis of 134 adults aged 18 to 44 years admitted to our center with nontraumatic ICH from January 1, 2012, to December 31, 2021. We compared ICH characteristics among 3 groups: those with P-ICH (pregnant or within 12 months of end of pregnancy); nonpregnant women; and men. We categorized ICH pathogenesis according to a modified scheme, SMASH-UP (structural, medications, amyloid angiopathy, systemic, hypertension, undetermined, posterior reversible encephalopathy syndrome/reversible cerebral vasoconstriction syndrome), and calculated odds ratios and 95% CIs for primary (spontaneous small-vessel) ICH versus secondary ICH (structural lesions or coagulopathy related), using nonpregnant women as the reference. We also compared specific ICH pathogenesis by SMASH-UP criteria and functional outcomes between groups. Of 134 young adults with nontraumatic ICH, 25 (19%) had P-ICH, of which 60% occurred postpartum. Those with P-ICH had higher odds of primary ICH compared with nonpregnant women (adjusted odds ratio, 4.5 [95% CI, 1.4-14.7]). The odds of primary ICH did not differ between men and nonpregnant women. SMASH-UP pathogenesis for ICH differed significantly between groups (P<0.001). While the in-hospital mortality rate was lowest in the P-ICH group (4%) compared with nonpregnant women (13%) and men (24%), 1 in 4 patients with P-ICH were bedbound and dependent at the time of discharge. CONCLUSIONS: In our cohort of young adults with ICH, 1 in 5 was pregnancy related. P-ICH differed in pathogenesis compared with non-pregnancy-related ICH in young adults, suggesting unique pathophysiology.

ABO blood type and thromboembolic complications after intracerebral hemorrhage: An exploratory analysis.

BACKGROUND AND PURPOSE: Non-O blood types are known to be associated with thromboembolic complications (TECs) in population-based studies. TECs are known drivers of morbidity and mortality in intracerebral hemorrhage (ICH) patients, yet the relationships of blood type on TECs in this patient population are unknown. We sought to explore the relationships between ABO blood type and TECs in ICH patients. METHODS: Consecutive adult ICH patients enrolled into a prospective observational cohort study with available ABO blood type data were analyzed. Patients with cancer history, prior thromboembolism, and baseline laboratory evidence of coagulopathy were excluded. The primary exposure variable was blood type (non-O versus O). The primary outcome was composite TEC, defined as pulmonary embolism, deep venous thrombosis, ischemic stroke or myocardial infarction, during the hospital stay. Relationships between blood type, TECs and clinical outcomes were separately assessed using logistic regression models after adjusting for sex, ethnicity and ICH score. RESULTS: Of 301 ICH patients included for analysis, 44% were non-O blood type. Non-O blood type was associated with higher admission GCS and lower ICH score on baseline comparisons. We identified TECs in 11.6% of our overall patient cohort. . Although TECs were identified in 9.9% of non-O blood type patients compared to 13.0% in O blood type patients, we did not identify a significant relationship of non-O blood type with TECs (adjusted OR=0.776, 95%CI: 0.348-1.733, p=0.537). The prevalence of specific TECs were also comparable in unadjusted and adjusted analyses between the two cohorts. In additional analyses, we identified that TECs were associated with poor 90-day mRS (adjusted OR=3.452, 95% CI: 1.001-11.903, p=0.050). We did not identify relationships between ABO blood type and poor 90-day mRS (adjusted OR=0.994, 95% CI:0.465-2.128, p=0.988). CONCLUSIONS: We identified that TECs were associated with worse ICH outcomes. However, we did not identify relationships in ABO blood type and TECs. Further work is required to assess best diagnostic and prophylactic and treatment strategies for TECs to improve ICH outcomes.

Relationships of Hematocrit With Chronic Covert and Acute Symptomatic Lacunar Ischemic Lesions.

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) concentrations are known to associate with ischemic stroke. It is unclear whether RBC concentrations associate specifically with small vessel disease lacunar infarcts. We investigated the hypothesis that RBC concentrations associate with both chronic covert and acute symptomatic brain MRI lacunar infarcts. METHODS: A cross-sectional observational analysis was performed across 2 cohorts with available hematocrit (as the assessment of RBC concentration exposure) and MRI outcome data. The primary setting was a population-based cohort of stroke-free, older adult (>50 years) participants from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2009. A second replication sample consisted of patients admitted with acute stroke and enrolled into the Columbia Stroke Registry (CSR) between 2005 and 2020. Associations of hematocrit with (1) chronic, covert lacunar infarcts and (2) symptomatic (i.e., acute) lacunar strokes were separately assessed from the NOMAS and CSR cohorts, respectively, using general additive models after adjusting for relevant covariates. RESULTS: Of 1,218 NOMAS participants analyzed, 6% had chronic, covert lacunar infarcts. The association between hematocrit and these covert lacunar infarcts was U-shaped (χ2 = 9.21 for nonlinear associations; p = 0.03), with people with hematocrit extremes being more likely to have covert lacunar infarcts. Of the 1,489 CSR patients analyzed, 23% had acute lacunar strokes. In this sample, only the relationships of increased hematocrit concentrations and lacunar strokes were replicated (adjusted coefficient ß = 0.020; SE = 0.009; p = 0.03). DISCUSSION: We identified relationships of hematocrit with MRI lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. The relationship between increased hematocrit concentrations with lacunar infarcts was replicated in both cohorts. Further studies are required to clarify the mechanisms behind the relationships of hematocrit with ischemic cerebral small vessel disease.

Suboptimal Cerebral Perfusion is Associated with Ischemia After Intracerebral Hemorrhage.

BACKGROUND: Remote ischemic lesions on diffusion-weighted imaging (DWI) occur in one third of patients with intracerebral hemorrhage (ICH) and are associated with worse outcomes. The etiology is unclear and not solely due to blood pressure reduction. We hypothesized that impaired cerebrovascular autoregulation and hypoperfusion below individualized lower limits of autoregulation are associated with the presence of DWI lesions. METHODS: This was a retrospective, single-center study of all primary ICH with intraparenchymal pressure monitoring within 10 days from onset and subsequent magnetic resonance imaging. Pressure reactivity index was calculated as the correlation coefficient between mean arterial pressure and intracranial pressure. Optimal cerebral perfusion pressure (CPPopt) is the cerebral perfusion pressure (CPP) with the lowest corresponding pressure reactivity index. The difference between CPP and CPPopt, time spent below the lower limit of autoregulation (LLA), and time spent above the upper limit of autoregulation (ULA) were calculated by using mean hourly physiologic data. Univariate associations between physiologic parameters and DWI lesions were analyzed by using binary logistic regression. RESULTS: A total of 505 h of artifact-free data from seven patients without DWI lesions and 479 h from six patients with DWI lesions were analyzed. Patients with DWI lesions had higher intracranial pressure (17.50 vs. 10.92 mm Hg; odds ratio 1.14, confidence interval 1.01-1.29) but no difference in mean arterial pressure or CPP compared with patients without DWI lesions. The presence of DWI lesions was significantly associated with a greater percentage of time spent below the LLA (49.85% vs. 14.70%, odds ratio 5.77, confidence interval 1.88-17.75). No significant association was demonstrated between CPPopt, the difference between CPP and CPPopt, ULA, LLA, or time spent above the ULA between groups. CONCLUSIONS: Blood pressure reduction below the LLA is associated with ischemia after acute ICH. Individualized, autoregulation-informed targets for blood pressure reduction may provide a novel paradigm in acute management of ICH and require further study.

ABO Blood Type and Thromboembolic Complications after Intracerebral Hemorrhage: an exploratory analysis.

Background and Purpose: Non-O blood types are known to be associated with thromboembolic complications (TECs) in population-based studies. TECs are known drivers of morbidity and mortality in intracerebral hemorrhage (ICH) patients, yet the relationships of blood type on TECs in this patient population are unknown. We sought to explore the relationships between ABO blood type and TECs in ICH patients. Methods: Consecutive adult ICH patients enrolled into a prospective observational cohort study with available ABO blood type data were analyzed. Patients with cancer history, prior thromboembolism, and baseline laboratory evidence of coagulopathy were excluded. The primary exposure variable was blood type (non-O versus O). The primary outcome was composite TEC, defined as pulmonary embolism, deep venous thrombosis, ischemic stroke or myocardial infarction, during the hospital stay. Relationships between blood type, TECs and clinical outcomes were separately assessed using logistic regression models after adjusting for sex, ethnicity and ICH score. Results: Of 301 ICH patients included for analysis, 44% were non-O blood type. Non-O blood type was associated with higher admission GCS and lower ICH score on baseline comparisons. We identified TECs in 11.6% of our overall patient cohort. Although TECs were identified in 9.9% of non-O blood type patients compared to 13.0% in O blood type patients, we did not identify a significant relationship of non-O blood type with TECs (adjusted OR = 0.776, 95%CI: 0.348-1.733, p = 0.537). The prevalence of specific TECs were also comparable in unadjusted and adjusted analyses between the two cohorts. In additional analyses, we identified that TECs were associated with poor 90-day mRS (adjusted OR = 3.452, 95% CI: 1.001-11.903, p = 0.050). We did not identify relationships between ABO blood type and poor 90-day mRS (adjusted OR = 0.994, 95% CI:0.465-2.128, p = 0.988). Conclusions: We identified that TECs were associated with worse ICH outcomes. However, we did not identify relationships in ABO blood type and TECs. Further work is required to assess best diagnostic and prophylactic and treatment strategies for TECs to improve ICH outcomes.

Injury patterns associated with cognitive motor dissociation.

In unconscious appearing patients with acute brain injury, wilful brain activation to motor commands without behavioural signs of command following, known as cognitive motor dissociation (CMD), is associated with functional recovery. CMD can be detected by applying machine learning to EEG recorded during motor command presentation in behaviourally unresponsive patients. Identifying patients with CMD carries clinical implications for patient interactions, communication with families, and guidance of therapeutic decisions but underlying mechanisms of CMD remain unknown. By analysing structural lesion patterns and network level dysfunction we tested the hypothesis that, in cases with preserved arousal and command comprehension, a failure to integrate comprehended motor commands with motor outputs underlies CMD. Manual segmentation of T2-fluid attenuated inversion recovery and diffusion weighted imaging sequences quantifying structural injury was performed in consecutive unresponsive patients with acute brain injury (n = 107) who underwent EEG-based CMD assessments and MRI. Lesion pattern analysis was applied to identify lesion patterns common among patients with (n = 21) and without CMD (n = 86). Thalamocortical and cortico-cortical network connectivity were assessed applying ABCD classification of power spectral density plots and weighted pairwise phase consistency (WPPC) to resting EEG, respectively. Two distinct structural lesion patterns were identified on MRI for CMD and three for non-CMD patients. In non-CMD patients, injury to brainstem arousal pathways including the midbrain were seen, while no CMD patients had midbrain lesions. A group of non-CMD patients was identified with injury to the left thalamus, implicating possible language comprehension difficulties. Shared lesion patterns of globus pallidus and putamen were seen for a group of CMD patients, which have been implicated as part of the anterior forebrain mesocircuit in patients with reversible disorders of consciousness. Thalamocortical network dysfunction was less common in CMD patients [ABCD-index 2.3 (interquartile range, IQR 2.1-3.0) versus 1.4 (IQR 1.0-2.0), P < 0.0001; presence of D 36% versus 3%, P = 0.0006], but WPPC was not different. Bilateral cortical lesions were seen in patients with and without CMD. Thalamocortical disruption did not differ for those with CMD, but long-range WPPC was decreased in 1-4 Hz [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.7-0.9] and increased in 14-30 Hz frequency ranges (OR 1.2; 95% CI 1.0-1.5). These structural and functional data implicate a failure of motor command integration at the anterior forebrain mesocircuit level with preserved thalamocortical network function for CMD patients with subcortical lesions. Amongst patients with bilateral cortical lesions preserved cortico-cortical network function is associated with CMD detection. These data may allow screening for CMD based on widely available structural MRI and resting EEG.

Concordance Between Active Partial Thromboplastin Time and Anti-Factor Xa Assays in Neurocritically Ill Patients Receiving Subcutaneous Heparin Prophylaxis.

Background: Laboratory monitoring is not recommended when subcutaneous unfractionated heparin (SQ-UFH) is administered at prophylactic doses. However, aPTT prolongation and associated hemorrhage has been reported in the neurocritically ill. At our institution, Neuroscience Intensive Care Unit (Neuro-ICU) patients with prolonged aPTT are further evaluated with a follow up aPTT and anti-factor Xa. Purpose: The purpose of this study was to describe concordance between aPTT and anti-factor Xa in neurocritically ill patients receiving prophylactic SQ-UFH with evidence of aPTT prolongation. Methods: A retrospective chart review of adult patients admitted to the Neuro-ICU from June 2017 to June 2019 was performed. Patients were included if they received SQ-UFH with aPTT levels and at least one anti-factor Xa level drawn within one hour of each other. Concordance between paired aPTT and anti-factor Xa was evaluated using Cohen's weighted kappa. Results: Forty two patients with 56 paired aPTT and anti-factor Xa levels were included. The most prescribed SQ-UFH regimen was 5000 units every 8 hours (60.7%) and anti-factor Xa levels were drawn a median (IQR) of 5.7 (3.1-10.7) hours after the SQ-UFH dose. Only 16 (28.6%) pairs were in concordance. The analysis showed a weighted kappa of .09; 95% CI [-.05 to .22] indicating poor agreement. Conclusions: In neurocritically ill patients receiving prophylactic SQ-UFH with aPTT prolongation, there was poor concordance between aPTT and anti-factor Xa. This suggests that aPTT prolongation may not be solely driven by heparin activity and further evaluation of mechanistic drivers for coagulopathy in this population is necessary.

Automatic identification of intracranial pressure waveform during external ventricular drainage clamping: segmentation via wavelet analysis.

Objective. The objective of this study is to develop and validate a method for automatically identifying segments of intracranial pressure (ICP) waveform data from external ventricular drainage (EVD) recordings during intermittent drainage and closure.Methods. The proposed method uses time-frequency analysis through wavelets to distinguish periods of ICP waveform in EVD data. By comparing the frequency compositions of the ICP signals (when the EVD system is clamped) and the artifacts (when the system is open), the algorithm can detect short, uninterrupted segments of ICP waveform from the longer periods of non-measurement data. The method involves applying a wavelet transform, calculating the absolute power in a specific range, using Otsu thresholding to automatically identify a threshold, and performing a morphological operation to remove small segments. Two investigators manually graded the same randomly selected one-hour segments of the resulting processed data. Performance metrics were calculated as a percentage.Results. The study analyzed data from 229 patients who had EVD placed following subarachnoid hemorrhage between June 2006 and December 2012. Of these, 155 (67.7%) were female and 62 (27%) developed delayed cerebral ischemia. A total of 45 150 h of data were segmented. 2044 one-hour segments were randomly selected and evaluated by two investigators (MM and DN). Of those, the evaluators agreed on the classification of 1556 one-hour segments. The algorithm was able to correctly identify 86% (1338 h) of ICP waveform data. 8.2% (128 h) of the time the algorithm either partially or fully failed to segment the ICP waveform. 5.4% (84 h) of data, artifacts were mistakenly identified as ICP waveforms (false positives).Conclusion. The proposed algorithm automates the identification of valid ICP waveform segments of waveform in EVD data and thus enables the inclusion in real-time data analysis for decision support. It also standardizes and makes research data management more efficient.

Red Blood Cell Transfusions Are Not Associated With Incident Complications or Poor Outcomes in Patients With Intracerebral Hemorrhage.

Background Anemia is associated with poor intracerebral hemorrhage (ICH) outcomes, yet the relationship of red blood cell (RBC) transfusions to ICH complications and functional outcomes remains unclear. We investigated the impact of RBC transfusion on hospital thromboembolic and infectious complications and outcomes in patients with ICH. Methods and Results Consecutive patients with spontaneous ICH enrolled in a single-center, prospective cohort study from 2009 to 2018 were assessed. Primary analyses assessed relationships of RBC transfusions on incident thromboembolic and infectious complications occurring after the transfusion. Secondary analyses assessed relationships of RBC transfusions with mortality and poor discharge modified Rankin Scale score 4 to 6. Multivariable logistic regression models adjusted for baseline demographics and medical disease severity (Acute Physiology and Chronic Health Evaluation II), and ICH severity (ICH score).Of 587 patients with ICH analyzed, 88 (15%) received at least one RBC transfusion. Patients receiving RBC transfusions had worse medical and ICH severity. Though patients receiving RBC transfusions had more complications at any point during the hospitalization (64.8% versus 35.9%), we found no association between RBC transfusion and incident complications in our regression models (adjusted odds ratio [aOR], 0.71 [95% CI, 0.42-1.20]). After adjusting for disease severity and other relevant covariates, we found no significant association between RBC transfusion and mortality (aOR, 0.87 [95% CI, 0.45-1.66]) or poor discharge modified Rankin Scale score (aOR, 2.45 [95% CI, 0.80-7.61]). Conclusions In our cohort with ICH, RBC transfusions were expectedly given to patients with higher medical and ICH severity. Taking disease severity and timing of transfusions into account, RBC transfusion was not associated with incident hospital complications or poor clinical ICH outcomes.

A Deep Learning Framework for Deriving Noninvasive Intracranial Pressure Waveforms from Transcranial Doppler.

Increased intracranial pressure (ICP) causes disability and mortality in the neurointensive care population. Current methods for monitoring ICP are invasive. We designed a deep learning framework using a domain adversarial neural network to estimate noninvasive ICP, from blood pressure, electrocardiogram, and cerebral blood flow velocity. Our model had a mean of median absolute error of 3.88 ± 3.26 mmHg for the domain adversarial neural network, and 3.94 ± 1.71 mmHg for the domain adversarial transformers. Compared with nonlinear approaches, such as support vector regression, this was 26.7% and 25.7% lower. Our proposed framework provides more accurate noninvasive ICP estimates than currently available. ANN NEUROL 2023;94:196-202.

Association Between Soluble Intercellular Adhesion Molecule-1 and Intracerebral Hemorrhage Outcomes in the FAST Trial.

BACKGROUND: Neutrophil-mediated inflammation in the acute phase of intracerebral hemorrhage (ICH) worsens outcome in preclinical studies. sICAM-1 (soluble intercellular adhesion molecule-1), an inducible ligand for integrins and cell-cell adhesion molecules, is critical for neutrophil extravasation. We aimed to determine whether serum levels of sICAM-1 are associated with worse outcomes after ICH. METHODS: We conducted a post hoc secondary analysis of an observational cohort using data from the FAST trial (Factor-VII for Acute Hemorrhagic Stroke Treatment). The study exposure was the admission serum level of sICAM-1. The coprimary outcomes were mortality and poor outcome (modified Rankin Scale score 4-6) at 90 days. Secondary radiological outcomes were hematoma expansion at 24 hours and perihematomal edema expansion at 72 hours. We used multiple linear and logistic regression analyses to test for associations between sICAM-1 and outcomes, after adjustment for demographics, ICH severity characteristics, change in the systolic blood pressure in the first 24 hours, treatment randomization arm, and the time from symptom onset to study drug administration. RESULTS: Of 841 patients, we included 507 (60%) with complete data. Hematoma expansion occurred in 169 (33%), while 242 (48%) had a poor outcome. In multivariable analyses, sICAM-1 was associated with mortality (odds ratio, 1.53 per SD increase [95% CI, 1.15-2.03]) and poor outcome (odds ratio, 1.34 per SD increase [CI, 1.06-1.69]). In multivariable analyses of secondary outcomes, sICAM-1 was associated with hematoma expansion (odds ratio, 1.35 per SD increase [CI, 1.11-1.66]), but was not associated with log-transformed perihematomal edema expansion at 72 hours. In additional analyses stratified by treatment assignment, similar results were noted in the recombinant activated factor-VII arm, but not in the placebo arm. CONCLUSIONS: Admission serum levels of sICAM-1 were associated with mortality, poor outcome, and hematoma expansion. Given the possibility of a biological interaction between recombinant activated factor-VII and sICAM-1, these findings highlight the need to further explore the role of sICAM-1 as a potential marker of poor ICH outcomes.