Predicting hematoma expansion using machine learning: An exploratory analysis of the ATACH 2 trial.

INTRODUCTION: Hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) is a key predictor of poor prognosis and potentially amenable to treatment. This study aimed to build a classification model to predict HE in patients with ICH using deep learning algorithms without using advanced radiological features. METHODS: Data from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) was utilized. Variables included in the models were chosen as per literature consensus on salient variables associated with HE. HE was defined as increase in either >33% or 6 mL in hematoma volume in the first 24 h. Multiple machine learning algorithms were employed using iterative feature selection and outcome balancing methods. 70% of patients were used for training and 30% for internal validation. We compared the ML models to a logistic regression model and calculated AUC, accuracy, sensitivity and specificity for the internal validation models respective models. RESULTS: Among 1000 patients included in the ATACH-2 trial, 924 had the complete parameters which were included in the analytical cohort. The median [interquartile range (IQR)] initial hematoma volume was 9.93.mm3 [5.03-18.17] and 25.2% had HE. The best performing model across all feature selection groups and sampling cohorts was using an artificial neural network (ANN) for HE in the testing cohort with AUC 0.702 [95% CI, 0.631-0.774] with 8 hidden layer nodes The traditional logistic regression yielded AUC 0.658 [95% CI, 0.641-0.675]. All other models performed with less accuracy and lower AUC. Initial hematoma volume, time to initial CT head, and initial SBP emerged as most relevant variables across all best performing models. CONCLUSION: We developed multiple ML algorithms to predict HE with the ANN classifying the best without advanced radiographic features, although the AUC was only modestly better than other models. A larger, more heterogenous dataset is needed to further build and better generalize the models.

Association of Neighborhood Socioeconomic Status With Withdrawal of Life-Sustaining Therapies After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Mortality after intracerebral hemorrhage (ICH) is common. Neighborhood socioeconomic status (nSES) is an important social determinant of health (SDoH) that can affect clinical outcome. We hypothesize that SDoH, including nSES, contribute to differences in withdrawal of life-sustaining therapies (WLSTs) and mortality in patients with ICH. METHODS: We performed a retrospective study of patients with ICH at 3 tertiary care hospitals between January 2017 and December 2022 identified through the Get with the Guidelines Database. We collected data on age, clinical severity, race/ethnicity, median household income, insurance, marital status, religion, mortality before discharge, and WLST from the electronic medical record. We assessed for associations between SDoH and WLST, mortality, and poor discharge mRS using Mann-Whitney U tests and χ2 tests. We performed multivariable analysis using backward stepwise logistic regression. RESULTS: We identified 868 patients (median age 67 [interquartile range (IQR) 55-78] years; 43% female) with ICH. Of them, 16% were Black non-Hispanic, 17% were Asian, and 15% were of Hispanic ethnicity; 50% were on Medicare and 22% on Medicaid, and the median (IQR) household income was $81,857 ($58,669-$122,078). Mortality occurred in 17% of patients, and of them, 84% of patients had WLST. Patients from zip codes with higher median household incomes had higher incidence of WLST and mortality (p < 0.01). Black non-Hispanic race was associated with lower WLST and discharge mortality (p ≤ 0.01 for both). In multivariable analysis adjusting for age and clinical severity scores, patients who lived in zip codes with high-income levels were more likely to have WLST (adjusted odds ratio [aOR] 1.88; 95% CI 1.29-2.74) and mortality before discharge (aOR 1.5; 95% CI 1.06-2.13). DISCUSSION: SDoH, including nSES, are associated with WLST after ICH. This has important implications for the care and management of patients with ICH.

Poor Accuracy of Manually Derived Head Computed Tomography Parameters in Predicting Intracranial Hypertension After Nontraumatic Intracranial Hemorrhage.

BACKGROUND: The utility of head computed tomography (CT) in predicting elevated intracranial pressure (ICP) is known to be limited in traumatic brain injury; however, few data exist in patients with spontaneous intracranial hemorrhage. METHODS: We conducted a retrospective review of prospectively collected data in patients with nontraumatic intracranial hemorrhage (subarachnoid hemorrhage [SAH] or intraparenchymal hemorrhage [IPH]) who underwent external ventricular drain (EVD) placement. Head CT scans performed immediately prior to EVD placement were quantitatively reviewed for features suggestive of elevated ICP, including temporal horn diameter, bicaudate index, basal cistern effacement, midline shift, and global cerebral edema. The modified Fisher score (mFS), intraventricular hemorrhage score, and IPH volume were also measured, as applicable. We calculated the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of these radiographic features for the coprimary outcomes of elevated ICP (> 20 mm Hg) at the time of EVD placement and at any time during the hospital stay. Multivariable backward stepwise logistic regression analysis was performed to identify significant radiographic factors associated with elevated ICP. RESULTS: Of 608 patients with intracranial hemorrhages enrolled during the study time frame, 243 (40%) received an EVD and 165 (n = 107 SAH, n = 58 IPH) had a preplacement head CT scan available for rating. Elevated opening pressure and elevated ICP during hospitalization were recorded in 48 of 152 (29%) and 103 of 165 (62%), respectively. The presence of ≥ 1 radiographic feature had only 32% accuracy for identifying elevated opening pressure (PPV 30%, NPV 58%, area under the curve [AUC] 0.537, 95% asymptotic confidence interval [CI] 0.436-0.637, P = 0.466) and 59% accuracy for predicting elevated ICP during hospitalization (PPV 63%, NPV 40%, AUC 0.514, 95% asymptotic CI 0.391-0.638, P = 0.820). There was no significant association between the number of radiographic features and ICP elevation. Head CT scans without any features suggestive of elevated ICP occurred in 25 of 165 (15%) patients. However, 10 of 25 (40%) of these patients had elevated opening pressure, and 15 of 25 (60%) had elevated ICP during their hospital stay. In multivariable models, mFS (adjusted odds ratio [aOR] 1.36, 95% CI 1.10-1.68) and global cerebral edema (aOR 2.93, 95% CI 1.27-6.75) were significantly associated with elevated ICP; however, their accuracies were only 69% and 60%, respectively. All other individual radiographic features had accuracies between 38 and 58% for identifying intracranial hypertension. CONCLUSIONS: More than 50% of patients with spontaneous intracranial hemorrhage without radiographic features suggestive of elevated ICP actually had ICP > 20 mm Hg during EVD placement or their hospital stay. Morphological head CT findings were only 32% and 59% accurate in identifying elevated opening pressure and ICP elevation during hospitalization, respectively.

Markers of infection and inflammation are associated with post-thrombectomy mortality in acute stroke.

OBJECTIVE: We explored the relationship between markers of infection and inflammation and mortality in patients with acute ischemic stroke who underwent thrombectomy. METHODS: We performed retrospective chart review of stroke patients who underwent thrombectomy at two tertiary academic centers between December 2018 and November 2020. Associations between discharge mortality, WBC count, neutrophil percentage, fever, culture data, and antibiotic treatment were analyzed using the Wilcoxon rank sum test, Student's t-test, and Fisher's exact test. Independent predictors of mortality were identified with multivariable analysis. Analyses were repeated excluding COVID-positive patients. RESULTS: Of 248 patients who underwent thrombectomy, 41 (17 %) died prior to discharge. Mortality was associated with admission WBC count (11 [8-14] vs. 9 [7-12], p = 0.0093), admission neutrophil percentage (78 % ± 11 vs. 71 % ± 14, p = 0.0003), peak WBC count (17 [13-22] vs. 12 [9-15], p < 0.0001), fever (71 % vs. 27 %, p < 0.0001), positive culture (44 % vs. 15 %, p < 0.0001), and days treated with antibiotics (3 [1-7] vs. 1 [0-4], p < 0.0001). After controlling for age, admission NIHSS and post-thrombectomy ASPECTS score, mortality was associated with admission WBC count (OR 13, CI 1.32-142, p = 0.027), neutrophil percentage (OR 1.03, CI 1.0-1.07, p = 0.045), peak WBC count (OR 301, CI 24-5008, p < 0.0001), fever (OR 24.2, CI 1.77-332, p < 0.0001), and positive cultures (OR 4.24, CI 1.87-9.62, p = 0.0006). After excluding COVID-positive patients (n = 14), peak WBC count, fever and positive culture remained independent predictors of mortality. CONCLUSION: Markers of infection and inflammation are associated with discharge mortality after thrombectomy. Further study is warranted to investigate the causal relationship of these markers with clinical outcome.

Pre-admission antithrombotic use is associated with 3-month mRS score after thrombectomy for acute ischemic stroke.

In patients who undergo thrombectomy for acute ischemic stroke, the relationship between pre-admission antithrombotic (anticoagulation or antiplatelet) use and both radiographic and functional outcome is not well understood. We sought to explore the relationship between pre-admission antithrombotic use in patients who underwent thrombectomy for acute ischemic stroke at two medical centers in New York City between December 2018 and November 2020. Analyses were performed using analysis of variance and Pearson's chi-squared tests. Of 234 patients in the analysis cohort, 65 (28%) were on anticoagulation, 64 (27%) were on antiplatelet, and 105 (45%) with no antithrombotic use pre-admission. 3-month Modified Rankin Scale (mRS) score of 3-6 was associated with pre-admission antithrombotic use (71% anticoagulation vs. 77% antiplatelet vs. 56% no antithrombotic, p = 0.04). There was no relationship between pre-admission antithrombotic use and Thrombolysis in Cerebral Iinfarction (TICI) score, post-procedure Alberta Stroke Program Early CT Score (ASPECTS) score, rate of hemorrhagic conversion, length of hospital admission, discharge NIH Stroke Scale (NIHSS), discharge mRS score, or mortality. When initial NIHSS score, post-procedure ASPECTS score, and age at admission were included in multivariate analysis, pre-admission antithrombotic use was still significantly associated with a 3-month mRS score of 3-6 (OR 2.36, 95% CI 1.03-5.54, p = 0.04). In this cohort of patients with acute ischemic stroke who underwent thrombectomy, pre-admission antithrombotic use was associated with 3-month mRS score, but no other measures of radiographic or functional outcome. Further research is needed on the relationship between use of specific anticoagulation or antiplatelet agents and outcome after acute ischemic stroke, but moreover, improve stroke prevention.

Tachycardia is associated with mortality and functional outcome after thrombectomy for acute ischemic stroke.

BACKGROUND: The relationship between cardiac function and mortality after thrombectomy for acute ischemic stroke is not well elucidated. METHODS: We analyzed the relationship between cardiac function and mortality prior to discharge in a cohort of patients who underwent thrombectomy for acute ischemic stroke at two large medical centers in New York City between December 2018 and November 2020. All analyses were performed using Welch's two sample t-test and logistic regression accounting for age, initial NIHSS and post-procedure ASPECTS score, where OR is for each unit increase in the respective variables. RESULTS: Of 248 patients, 41 (16.5%) died prior to discharge. Mortality was significantly associated with higher initial heart rate (HR; 89 ± 19 bpm vs 80 ± 18 bpm, p = 0.004) and higher maximum HR over entire admission (137 ± 26 bpm vs 114 ± 25 bpm, p < 0.001). Mortality was also associated with presence of NSTEMI/STEMI (63% vs 29%, p < 0.001). When age, initial NIHSS score, and post-procedure ASPECTS score were included in multivariate analysis, there was still a significant relationship between mortality and initial HR (OR 1.03, 95% CI 1.01- 1.05, p = 0.02), highest HR over the entire admission (OR 1.03, 95% CI 1.02-1.05, p < 0.001), and presence of NSTEMI/STEMI (OR 3.76, 95% CI 1.66-8.87, p = 0.002). CONCLUSIONS: Tachycardia is associated with mortality in patients who undergo thrombectomy. Further investigation is needed to determine whether this risk is modifiable.

Stroke epidemiology and outcomes in the modern era of left ventricular assist devices.

The care for the patients with end-stage heart failure has been revolutionized by the introduction of durable left ventricular assist devices, providing a substantial improvement in patient survival and quality of life and an alternative to heart transplantation. The newest devices have lower instances of mechanical dysfunction and associated pump thrombosis. Despite these improvements in complications, the use of continuous flow assist devices is still associated with high rates of thrombotic and hemorrhagic complications, most notably stroke in approximately 10% of continuous flow assist devices patients per year. With the newest HeartMate 3 devices, there have been lower observed rates of stroke, which has in part been achieved by both improvements in pump technology and knowledge of the risk factors for stroke and neurological complications. The therapeutic options available to clinicians to reduce the risk of stroke, including management of hypertension and antithrombotics, will be reviewed in this manuscript.

Social Determinants of Health Attenuate the Relationship Between Race and Ethnicity and White Matter Hyperintensity Severity but not Microbleed Presence in Patients with Intracerebral Hemorrhage.

BACKGROUND: The association between race and ethnicity and microvascular disease in patients with intracerebral hemorrhage (ICH) is unclear. We hypothesized that social determinants of health (SDOHs) mediate the relationship between race and ethnicity and severity of white matter hyperintensities (WMHs) and microbleeds in patients with ICH. METHODS: We performed a retrospective observational cohort study of patients with ICH at two tertiary care hospitals between 2013 and 2020 who underwent magnetic resonance imaging of the brain. Magnetic resonance imaging scans were evaluated for the presence of microbleeds and WMH severity (defined by the Fazekas scale; moderate to severe WMH defined as Fazekas scores 3-6). We assessed for associations between sex, race and ethnicity, employment status, median household income, education level, insurance status, and imaging biomarkers of microvascular disease. A mediation analysis was used to investigate the influence of SDOHs on the associations between race and imaging features. We assessed the relationship of all variables with discharge outcomes. RESULTS: We identified 233 patients (mean age 62 [SD 16]; 48% female) with ICH. Of these, 19% were Black non-Hispanic, 32% had a high school education or less, 21% required an interpreter, 11% were unemployed, and 6% were uninsured. Moderate to severe WMH, identified in 114 (50%) patients, was associated with age, Black non-Hispanic race and ethnicity, highest level of education, insurance status, and history of hypertension, hyperlipidemia, or diabetes (p < 0.05). In the mediation analysis, the proportion of the association between Black non-Hispanic race and ethnicity and the Fazekas score that was mediated by highest level of education was 65%. Microbleeds, present in 130 (57%) patients, was associated with age, highest level of education, and history of diabetes or hypertension (p < 0.05). Age, highest level of education, insurance status, and employment status were associated with discharge modified Rankin Scale scores of 3-6, but race and ethnicity was not. CONCLUSIONS: The association between Black non-Hispanic race and ethnicity and moderate to severe WMH lost significance after we adjusted for highest level of education, suggesting that SDOHs may mediate the association between race and ethnicity and microvascular disease.

Systemic Inflammatory Response Syndrome is Associated with Hematoma Expansion in Intracerebral Hemorrhage.

OBJECTIVES: Systemic inflammatory response syndrome (SIRS) and hematoma expansion are independently associated with worse outcomes after intracerebral hemorrhage (ICH), but the relationship between SIRS and hematoma expansion remains unclear. MATERIALS AND METHODS: We performed a retrospective review of patients admitted to our hospital from 2013 to 2020 with primary spontaneous ICH with at least two head CTs within the first 24 hours. The relationship between SIRS and hematoma expansion, defined as ≥6 mL or ≥33% growth between the first and second scan, was assessed using univariable and multivariable regression analysis. We assessed the relationship of hematoma expansion and SIRS on discharge mRS using mediation analysis. RESULTS: Of 149 patients with ICH, 83 (56%; mean age 67±16; 41% female) met inclusion criteria. Of those, 44 (53%) had SIRS. Admission systolic blood pressure (SBP), temperature, antiplatelet use, platelet count, initial hematoma volume and rates of infection did not differ between groups (all p>0.05). Hematoma expansion occurred in 15/83 (18%) patients, 12 (80%) of whom also had SIRS. SIRS was significantly associated with hematoma expansion (OR 4.5, 95% CI 1.16 - 17.39, p= 0.02) on univariable analysis. The association remained statistically significant after adjusting for admission SBP and initial hematoma volume (OR 5.72, 95% CI 1.40 - 23.41, p= 0.02). There was a significant indirect effect of SIRS on discharge mRS through hematoma expansion. A significantly greater percentage of patients with SIRS had mRS 4-6 at discharge (59 vs 33%, p=0.02). CONCLUSION: SIRS is associated with hematoma expansion of ICH within the first 24 hours, and hematoma expansion mediates the effect of SIRS on poor outcome.

Cerebrospinal fluid from COVID-19 patients with olfactory/gustatory dysfunction: A review.

OBJECTIVE: We reviewed the literature on cerebrospinal fluid (CSF) testing in patients with altered olfactory/gustatory function due to COVID-19 for evidence of viral neuroinvasion. METHODS: We performed a systematic review of Medline and Embase to identify publications that described at least one patient with COVID-19 who had altered olfactory/gustatory function and had CSF testing performed. The search ranged from December 1, 2019 to November 18, 2020. RESULTS: We identified 51 publications that described 70 patients who met inclusion criteria. Of 51 patients who had CSF SARS-CoV-2 PCR testing, 3 (6%) patients had positive results and 1 (2%) patient had indeterminate results. Cycle threshold (Ct; the number of amplification cycles required for the target gene to exceed the threshold, which is inversely related to viral load) was not provided for the patients with a positive PCR. The patient with indeterminate results had a Ct of 37 initially, then no evidence of SARS-CoV-2 RNA on repeat testing. Of 6 patients who had CSF SARS-CoV-2 antibody testing, 3 (50%) were positive. Testing to distinguish intrathecal antibody synthesis from transudation of antibodies to the CSF via breakdown of the blood-brain barrier was performed in 1/3 (33%) patients; this demonstrated antibody transmission to the CSF via transudation. CONCLUSION: Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare in patients with altered olfactory/gustatory function. While pathology studies are needed, our review suggests it is unlikely that these symptoms are related to viral neuroinvasion.

COVID-19 associated brain/spinal cord lesions and leptomeningeal enhancement: A meta-analysis of the relationship to CSF SARS-CoV-2.

BACKGROUND AND PURPOSE: We reviewed the literature to evaluate cerebrospinal fluid (CSF) results from patients with coronavirus disease 2019 (COVID-19) who had neurological symptoms and had an MRI that showed (1) central nervous system (CNS) hyperintense lesions not attributed to ischemia and/or (2) leptomeningeal enhancement. We sought to determine if these findings were associated with a positive CSF severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR). METHODS: We performed a systematic review of Medline and Embase from December 1, 2019 to November 18, 2020. CSF results were evaluated based on the presence/absence of (1) ≥ 1 CNS hyperintense lesion and (2) leptomeningeal enhancement. RESULTS: In 117 publications, we identified 193 patients with COVID-19 who had an MRI of the CNS and CSF testing. There were 125 (65%) patients with CNS hyperintense lesions. Patients with CNS hyperintense lesions were significantly more likely to have a positive CSF SARS-CoV-2 PCR (10% [9/87] vs. 0% [0/43], p = 0.029). Of 75 patients who had a contrast MRI, there were 20 (27%) patients who had leptomeningeal enhancement. Patients with leptomeningeal enhancement were significantly more likely to have a positive CSF SARS-CoV-2 PCR (25% [4/16] vs. 5% [2/42], p = 0.024). CONCLUSION: The presence of CNS hyperintense lesions or leptomeningeal enhancement on neuroimaging from patients with COVID-19 is associated with increased likelihood of a positive CSF SARS-CoV-2 PCR. However, a positive CSF SARS-CoV-2 PCR is uncommon in patients with these neuroimaging findings, suggesting they are often related to other etiologies, such as inflammation, hypoxia, or ischemia.

Cerebrospinal fluid findings in patients with seizure in the setting of COVID-19: A review of the literature.

We reviewed the literature on cerebrospinal fluid (CSF) studies in patients who had a seizure in the setting of COVID-19 infection to evaluate for evidence of viral neuroinvasion. We performed a systematic review of Medline and Embase to identify publications that reported one or more patients with COVID-19 who had a seizure and had CSF testing preformed. The search ranged from December 1st 2019 to November 18th 2020. We identified 56 publications which described 69 unique patients who met our inclusion criteria. Of the 54 patients whose past medical history was provided, 2 (4%) had epilepsy and 1 (2%) had a prior seizure in the setting of hyperglycemia, but the remaining 51 (94%) had no history of seizures. Seizure was the initial symptom of COVID-19 for 15 (22%) patients. There were 26 (40%) patients who developed status epilepticus. SARS-CoV-2 PCR testing was performed in the CSF for 45 patients; 6 (13%) had a positive CSF SARS-CoV-2 PCR, only 1 (17%) of whom had status epilepticus. The cycle thresholds were not reported. Evaluation for CSF SARS-CoV-2 antibodies (directly or indirectly, via testing for CSF oligoclonal bands or immunoglobulins) was performed in 26 patients, only 2 (8%) of whom had evidence of intrathecal antibody synthesis. Of the 11 patients who had CSF autoimmune antibody panels tested, 1 had NMDA antibodies and 1 had Caspr-2 antibodies. Detection of SARS-CoV-2 in the CSF of patients with seizures who have COVID-19 is uncommon. Our review suggests that seizures in this patient population are not likely due to direct viral invasion of the brain.

Cerebrospinal fluid in COVID-19: A systematic review of the literature.

OBJECTIVE: We sought to review the literature on cerebrospinal fluid (CSF) testing in patients with COVID-19 for evidence of viral neuroinvasion by SARS-CoV-2. METHODS: We performed a systematic review of Medline and Embase between December 1, 2019 and November 18, 2020 to identify case reports or series of patients who had COVID-19 diagnosed based on positive SARS-CoV-2 polymerase chain reaction (PCR) or serologic testing and had CSF testing due to a neurologic symptom. RESULTS: We identified 242 relevant documents which included 430 patients with COVID-19 who had acute neurological symptoms prompting CSF testing. Of those, 321 (75%) patients had symptoms that localized to the central nervous system (CNS). Of 304 patients whose CSF was tested for SARS-CoV-2 PCR, there were 17 (6%) whose test was positive, all of whom had symptoms that localized to the central nervous system (CNS). The majority (13/17, 76%) of these patients were admitted to the hospital because of neurological symptoms. Of 58 patients whose CSF was tested for SARS-CoV-2 antibody, 7 (12%) had positive antibodies with evidence of intrathecal synthesis, all of whom had symptoms that localized to the CNS. Of 132 patients who had oligoclonal bands evaluated, 3 (2%) had evidence of intrathecal antibody synthesis. Of 77 patients tested for autoimmune antibodies in the CSF, 4 (5%) had positive findings. CONCLUSION: Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare. Most neurological complications associated with SARS- CoV-2 are unlikely to be related to direct viral neuroinvasion.

Respiratory and Blood Stream Infections are Associated with Subsequent Venous Thromboembolism After Primary Intracerebral Hemorrhage.

BACKGROUND: Infection and venous thromboembolism (VTE) are associated with worse outcomes after intracerebral hemorrhage (ICH). The relationship between infection and VTE in ICH patients is unclear. We hypothesized that infection would be associated with subsequent VTE after ICH. METHODS: We retrospectively studied consecutively admitted spontaneous primary ICH patients from 2009 to 2018 surviving beyond 24 h. The primary predictor variable was infection, diagnosed prior to VTE. The primary outcome was VTE. We used multivariable logistic regression models to estimate the odds ratios and 95% confidence intervals (OR, 95% CI) for VTE risk after infection of any type, after adjusting for ICH score, length of stay and days to deep venous thrombosis (DVT) prophylaxis. Similar analysis was done to estimate the association of infection subtypes, including respiratory and urinary and blood stream infections (BSI) with VTE. RESULTS: There were 414 patients (mean age 65 years, 47% female) that met were analyzed. Infection was diagnosed in 181 (44%) patients. Incident VTE was diagnosed in 36 (9%) patients, largely comprised of DVT (n = 32; 89%). Infection overall was associated with increased risk of subsequent VTE (adjusted OR 4.5, 95% CI 1.6-12.6). Respiratory (adjusted OR 5.7, 95% CI 2.8-11.7) and BSI (adjusted OR 4.0, 95% CI 1.3-11.0) were associated with future VTE. Urinary and other infections were not associated with subsequent VTE. CONCLUSIONS: Infections are associated with subsequent risk of VTE among patients with ICH. Further investigation is required to elucidate mechanisms behind this association and to improve VTE prevention after ICH.

Risk factors for intracerebral hemorrhage in patients with COVID-19.

Intracerebral hemorrhage (ICH) can be a devastating complication of coronavirus disease (COVID-19). We aimed to assess risk factors associated with ICH in this population. We performed a retrospective cohort study of adult patients admitted to NYU Langone Health system between March 1 and April 27 2020 with a positive nasopharyngeal swab polymerase chain reaction test result and presence of primary nontraumatic intracranial hemorrhage or hemorrhagic conversion of ischemic stroke on neuroimaging. Patients with intracranial procedures, malignancy, or vascular malformation were excluded. We used regression models to estimate odds ratios and 95% confidence intervals (OR, 95% CI) of the association between ICH and covariates. We also used regression models to determine association between ICH and mortality. Among 3824 patients admitted with COVID-19, 755 patients had neuroimaging and 416 patients were identified after exclusion criteria were applied. The mean (standard deviation) age was 69.3 (16.2), 35.8% were women, and 34.9% were on therapeutic anticoagulation. ICH occurred in 33 (7.9%) patients. Older age, non-Caucasian race, respiratory failure requiring mechanical ventilation, and therapeutic anticoagulation were associated with ICH on univariate analysis (p < 0.01 for each variable). In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33-12.24, p < 0.001). ICH was associated with increased mortality (adjusted OR 2.6, 95 % CI 1.2-5.9). Anticoagulation use is associated with increased risk of ICH in patients with COVID-19. Further investigation is required to elucidate underlying mechanisms and prevention strategies in this population.

Clinical Impact of Hematoma Expansion in Left Ventricular Assist Device Patients.

BACKGROUND: Hematoma expansion (HE) is associated with poor outcome in patients with intracerebral hemorrhage (ICH), but the impact on patients with an left ventricular assist device (LVAD) is unknown. We aimed to define the occurrence of HE in the LVAD population and to determine the association between HE and mortality. METHODS: We performed a retrospective cohort study of LVAD patients and intentionally matched anticoagulated controls without LVAD admitted to Columbia University Irving Medical Center with ICH between 2008 and 2019. We compared HE occurrence between patients with an LVAD and those without an LVAD using regression modeling, adjusting for factors known to influence HE. We evaluated pump thrombosis following anticoagulation reversal. We examined the association between HE and hospital mortality using Poisson regression modeling adjusting for factors associated with poor outcome. RESULTS: Among 605 patients with an LVAD, we identified 28 patients with ICH meeting the study's inclusion criteria. Our LVAD ICH cohort was predominantly male (71%), with a mean age of 56 ± 10 years. The median baseline hematoma size was 20.1 mL3 (interquartile range [IQR], 8.6-46.9 mL3), and the median ICH score was 1 (IQR, 1-2). There was no significant difference in occurrence of HE in LVAD patients and matched non-LVAD patients (adjusted odds ratio [OR], 1.3; 95% confidence interval [CI], 0.4-4.2). There was an association between HE and in-hospital mortality in LVAD patients (adjusted OR, 4.8; 95% CI, 1.4-6.2). CONCLUSIONS: HE occurrence appears to be similar in LVAD and non-LVAD patients. HE has a significant impact on LVAD ICH mortality, underscoring the importance of adequate coagulopathy reversal and blood pressure management in these patients.

Assessing Cerebrovascular Hemodynamics Using Transcranial Doppler in Patients with Mechanical Circulatory Support Devices.

BACKGROUND AND PURPOSE: Mechanical circulatory support (MCS) devices are commonly used in heart failure patients. These devices carry risk for presumably embolic and additionally hemorrhagic stroke. Alterations in blood flow play a key role in stroke pathophysiology, and we aimed to learn more about hemodynamic compromise. In this study, we used transcranial Doppler (TCD) ultrasound to define hemodynamics of commonly used nonpulsatile MCS devices, as well as pulsatile devices, with special attention to the total artificial heart (TAH). METHODS: From 2/2013 through 12/2016, we prospectively enrolled patients with MCS who underwent TCD imaging. We analyzed TCD parameters, including peak systolic velocity, end-diastolic velocity, pulsatility indices (PIs), and number of high-intensity transient signals. Waveform morphologies were compared between various MCS devices. RESULTS: We performed 132 TCD studies in 86 MCS patients. Waveforms in patients supported by venoarterial-extracorporeal membrane oxygenation demonstrated continuous flow without clear systolic peaks with an average (±SD) PI of .43 (±.2). PIs were low in patients with continuous-flow left ventricular assist devices with a mean PI of .32 (±.13). Impella patients had morphologically distinct pulsatile waveforms and a higher mean PI of .65 (±.24). In intra-arterial balloon pump patients, mean PI was 1.01 (±.16) and diastolic upstrokes were pronounced. In TAH patients, mean middle cerebral artery velocity of 79.69 (±32.33) cm/seconds and PI of .74 (±.14) approached normal values. CONCLUSION: TCD can detect characteristic waveforms in patients supported by various MCS devices. These device-specific TCD patterns are recognizable and reproducible.

Intracerebral Hemorrhagic Expansion Occurs in Patients Using Non-Vitamin K Antagonist Oral Anticoagulants Comparable with Patients Using Warfarin.

BACKGROUND: Non-vitamin K antagonist oral anticoagulant (NOAC) use has significantly reduced intracerebral hemorrhagic (ICH) risk compared with standard anticoagulant treatment. Hematoma expansion (HE) is a known predictor of mortality in warfarin-associated ICH. Little is known about HE in patients using NOACs. METHODS: We conducted a retrospective chart review of patients with ICH admitted to Cedars-Sinai Medical Center from October 2010 to June 2016. We identified patients with concomitant administration of an oral anticoagulant and collected data including evidence of HE on imaging and modified Rankin Scale (mRS) at discharge. We defined HE as relative (≥33% increase) or absolute expansion (≥12 mL). We compared outcomes of patients with and without HE. RESULTS: Out of 814 patients with ICH who were admitted, we identified 9 patients with recent NOAC use and 18 intentionally matched controls on warfarin. We found no significant differences in National Institutes of Health Stroke Scale or ICH score on presentation (median [interquartile range] 15 [5,21] versus 7 [1.25,19.5] [P = .41] and 2 [1,4] versus 1 [1,3] [P = .33]) between patients on NOACs and those on warfarin. Four out of the 9 patients on NOAC and 5 of the 18 patients on warfarin demonstrated HE, with no significant difference (P = .42). There were no significant differences in mRS on discharge between groups (P = .52). CONCLUSIONS: In our coagulopathic NOAC patient population, HE occurs within 6 hours in 44% of patients. This case series did not have sufficient statistical power to detect significant differences between the groups. To our knowledge, this is one of the largest case series reporting on HE with concomitant NOAC use.

Meta-Analysis of Pre-Clinical Trials of Therapeutic Hypothermia for Intracerebral Hemorrhage.

Therapeutic hypothermia (TH) is a potent neuroprotectant for experimental ischemic stroke, but studies of TH for intracerebral hemorrhage (ICH) are emerging. We systematically reviewed the experimental literature to assess TH efficacy for ICH. We found 18 suitable papers; quality scores were moderately good. Compared with normothermia, TH reduced measures of edema (mean effect size (95% CI) -1.6873 (-2.3640, -1.0106), p < 0.0001) or blood-brain barrier leakage (p < 0.0001) and improved behavioral outcomes (p < 0.0001). There was no evidence of publication bias. In this meta-analysis of available preclinical studies of ICH, TH is potently effective for reducing perihematomal edema and for improving behavioral outcomes.

Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function.

We have identified a lethal phenotype characterized by sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males [Online Mendelian Inheritance in Man (OMIM) accession no. 608800]. Twenty-one affected individuals with this autosomal recessive syndrome were ascertained in nine separate sibships among the Old Order Amish. High-density single-nucleotide polymorphism (SNP) genotyping arrays containing 11,555 single-nucleotide polymorphisms evenly distributed across the human genome were used to map the disease locus. A genome-wide autozygosity scan localized the disease gene to a 3.6-Mb interval on chromosome 6q22.1-q22.31. This interval contained 27 genes, including two testis-specific Y-like genes (TSPYL and TSPYL4) of unknown function. Sequence analysis of the TSPYL gene in affected individuals identified a homozygous frameshift mutation (457_458insG) at codon 153, resulting in truncation of translation at codon 169. Truncation leads to loss of a peptide domain with strong homology to the nucleosome assembly protein family. GFP-fusion expression constructs were constructed and illustrated loss of nuclear localization of truncated TSPYL, suggesting loss of a nuclear localization patch in addition to loss of the nucleosome assembly domain. These results shed light on the pathogenesis of a disorder of sexual differentiation and brainstem-mediated sudden death, as well as give insight into a mechanism of transcriptional regulation.