Rabinstein, Alejandro A.

Angioinvasive fungal infections of the cerebral vasculature often lead to significant morbidity and mortality. High clinical suspicion and early antifungal therapy could improve outcomes. We describe the fatal case of a patient with a rapidly enlarging cavernous carotid aneurysm due to angioinvasive fungus. This case highlights the challenges in diagnosis and management of this condition.

Background: Cerebral microbleeds (CMBs) are a common vascular pathology associated with future intracerebral hemorrhage. Plasma biomarkers of amyloid, tau, and neurodegeneration may provide a screening avenue to identify those with CMBs, but evidence is conflicting. Objective: To determine the association between plasma biomarkers (Aβ40, Aβ42, t-tau, p-tau181, p-tau217, neurofilament light chain (NfL)) and CMBs in a population-based study of aging and whether these biomarkers predict higher signal on Aβ-PET imaging in patients with multiple CMBs. Methods: 712 participants from the Mayo Clinic Study of Aging with T2* GRE MRI and plasma biomarkers were included. Biomarkers were analyzed utilizing Simoa (Aβ40, Aβ42, t-tau, NfL) or Meso Scale Discovery (p-tau181, p-tau217) platforms. Cross-sectional associations between CMBs, plasma biomarkers and Aβ-PET were evaluated using hurdle models and multivariable regression models. Results: Among the 188 (26%) individuals with≥1 CMB, a lower plasma Aβ42/Aβ40 ratio was associated with more CMBs after adjusting for covariables (IRR 568.5 95% CI 2.8–116,127). No other biomarkers were associated with risk or number CMBs. In 81 individuals with≥2 CMBs, higher plasma t-tau, p-tau181, and p-tau217 all were associated with higher Aβ-PET signal, with plasma p-tau217 having the strongest predictive value (r2 0.603, AIC –53.0). Conclusion: Lower plasma Aβ42/Aβ40 ratio and higher plasma p-tau217 were associated with brain amyloidosis in individuals with CMBs from the general population. Our results suggest that in individuals with multiple CMBs and/or lobar intracranial hemorrhage that a lower plasma Aβ42/Aβ40 ratio or elevated p-tau217 may indicate underlying cerebral amyloid angiopathy.

Background Intracranial aneurysms are reported in 6%–10% of patients with bicuspid aortic valve (BAV), and routine intracranial aneurysm surveillance has been advocated by some. We assessed the prevalence and features of the most important patient‐outcome: aneurysmal sub‐arachnoid hemorrhage (aSAH), as compared with controls without aSAH, and tricuspid aortic valve (TAV) with aSAH. Methods and Results Adult patients with accurate diagnosis of aSAH and at least one echocardiogram between 2000 and 2019 were identified from a consecutive prospectively maintained registry of aSAH admissions. Controls without a diagnosis of SAH were age‐ and sex‐matched. BAV prevalence was confirmed echocardiographically. Severity of aSAH was categorized using modified Fisher and World Federation of Neurological Scale. Neurologic outcome was assessed using modified Rankin score. A total 488 aSAH cases and 990 controls were identified and BAV status was confirmed. Prevalence of BAV in patients with aSAH was 1.2% (6/488) versus 3.5% (35/990) in controls, P =0.01. BAV+aSAH were noted to be younger than TAV+aSAH (56±11 versus 68±14; P =0.03) with smaller aneurysms (5±2 versus 7±4; P =0.31). The severity of aSAH was lesser in BAV+aSAH than TAV (modified Fisher grade>2 50% versus 74%; P =0.19, World Federation of Neurological Scale grade>3 17% versus 36%; P =0.43). BAV+aSAH had less severe neurologic disability (modified Rankin score 3%–6 33% versus 49% in TAV; P =0.44) and comparable in‐hospital mortality rates ( P =0.93). BAV had lower odds for aSAH on multivariate analysis (odds ratio 0.23[CI 0.08–0.65]; P =0.01). Conclusions Prevalence of BAV was 3 times lower in the aSAH registry than in controls without aSAH. BAV+aSAH had clinically smaller aneurysms, clinically smaller bleeds, and better neurologic outcome as compared with TAV+aSAH, which needs to be confirmed in larger studies. These findings argue against routine surveillance for intracranial aneurysms in patients with BAV without aortic coarctation.

Introduction: The selection of acute ischemic stroke patients relies on the interpretation of radiological studies, commonly including noncontrast CT (ASPECTS score), CTA, and in some circumstances, CT perfusion (CTP) scans. Hypothesis: The interrater reliability between readers of noncontrast head CT will be moderate and not as good as that between readers of CT perfusion scans. Methods: Retrospective study of consecutive ischemic stroke patients who were considered for endovascular stroke therapy at an academic medical center from April 2010 - November 2014. All patients underwent CT, CTA, and CTP. Images were independently reviewed by four readers (A, B, C, D) in total (2 experienced neuroradiologists, one experienced neurointensivist, and one neuroradiology fellow). Each rated half of the cohort. All readers performed online training in ASPECTS. Moderate-to-good collateral circulation was defined as filling of 50% or more of the middle cerebral artery pial arterial territory on CTA, as in ESCAPE trial. An “acceptable core” on CTP was defined as in EXTEND-IA trial with core volume < 70 mL, mismatch ratio >1.2, and absolute mismatch volume >10 mL but was qualitatively estimated. Interrater agreement was assessed for total ASPECTS, dichotomized ASPECTS (≥6 vs <6), evaluation of collaterals, and evaluation of core. Agreement was assessed using kappa statistic, which was weighted for the total ASPECTS analysis. Results: Our cohort included 119 patients with acute stroke and large vessel occlusion. Interrater agreement for total ASPECTS was very good between readers C and D (' 0.70) and good between A and B (' 0.55). For dichotomized ASPECTS, agreement was fair-to-good (' 0.30 for C/D; ' 0.41 for A/B). Agreement for grading collaterals on CTA was good to very good (' 0.64 for C /D; ' 0.54 for A/B). Agreement for rating core on CTP was very good (' 0.78 for C/D; ' 0.62 for A/D). Conclusions: Interrater reliability is good to very good for total ASPECTS score, dichotomous grading of collaterals on CTA, and subjective estimation of core size on CTP. Agreement is only fair to good for dichotomized ASPECTS.

Objectives: Limited information is available on the prevalence of cardiorespiratory arrest (CA) and its predisposing factors in patients with acute ischemic stroke. We analyzed/evaluated clinical characteristics, risk factors, access to care, and survival in stroke patients who developed a cardiac arrest. Methods: This is a multicenter cohort study including consecutive patients with acute ischemic stroke admitted to regional stroke centers participating in the Registry of the Canadian Stroke Network from July 2003 to March 2008. Patients with DNR order on admission were excluded. CA was defined as cardiac or respiratory arrest within 30 days of admission documented by a physician and identified from resuscitation records. The main outcome measures were the 30-day and 1-year survival among patients with CA vs. no CA. We also assessed the association between medical complications during hospitalization and CA. Results: Overall, 9,019 patients with acute ischemic stroke were included. Cardiac arrest was observed in 352 patients (3.9%). In patients with CA, 30-day survival (17.9% vs. 90.7%, P<0.001) and 1-year survival (4.5% vs. 80.1, p<0.001) were significantly lower. Less than 1% of stroke patients with CA were discharged home (vs. 47.3%; p<0.0001). Other outcome measures are summarized in Table 1. On multivariable analyses, older age, more severe stroke, previous history of myocardial infarction, congestive heart failure, atrial fibrillation, and diabetes were associated with CA. Conclusions: Cardiac arrest affects less than 5% of patients admitted with an acute ischemic stroke and is associated with poor outcomes. Less than 1% of patients were independent or discharged home.

Background: Current guidelines recommend that initial management of patients with an intracerebral hemorrhage (ICH) occur in a neuroscience intensive care unit (ICU). However, some patients can be safely managed without ICU care. We evaluated factors that may predict the need for ICU level of care. Methods: We reviewed the medical records of all adult patients with supratentorial ICH presenting within 72 hours of symptom onset seen from 2009-2012. Patients admitted for palliative care or ICH due to a known structural lesion were excluded. Criteria defining need for ICU level of care were: need for intubation/mechanical ventilation, hyperosmolar therapy, neurosurgical procedure, prolonged ICU admission, or significant clinical deterioration. A univariate and multivariable logistic regression analysis was performed on patient demographics, medical comorbidities, time to presentation, vital signs, GCS/FOUR score, medications, laboratory studies, and imaging to identify independent predictors of the need for ICU admission. Results: 229 patients met inclusion criteria. Based on our triage criteria, 128 patients (56%) required ICU level of care. Multivariable analysis identified five factors that best predicted the need for ICU admission: younger age, shorter time to presentation, lower FOUR score, larger hemorrhage volume, and use of anticoagulants at presentation (table). Intraventricular hemorrhage and GCS score were not significant predictors on the multivariable analysis. Conclusion: Age, time to presentation, FOUR score, hemorrhage volume, and use of anticoagulants predict the need for ICU care after ICH. These variables will be used to develop a formula to aid clinicians in appropriate initial triage of patients with ICH.

Objective: Using the Nationwide Inpatient Sample (NIS), we determined morbidity, mortality and trends in ischemic and hemorrhagic stroke complications in patients receiving Extracorporeal Membranous Oxygenation (ECMO). Materials and Methods: Using the NIS from 2001-2011, patients receiving ECMO were identified. We analyzed their ischemic and hemorrhagic stroke complication rates and compared discharge status between these patients and those without cerebrovascular complications. Morbidity was defined as discharge to a long-term facility. Ischemic and hemorrhagic stroke rates were compared between two time periods (2001-2006 and 2007-2011). Continuous variables were compared with a student’s t-test and categorical variables were compared with the chi-squared test. Results: A total of 23,950 ECMO patients were included in this study of which 22108 patients (92.3%) had no cerebrovascular complications, 980 patients (4.1%) had ischemic stroke and 862 patients (3.6%) had hemorrhagic stroke. Of those without cerebrovascular complications there was a 49.9% mortality rate and a 6.8% morbidity rate. Patients with ischemic stroke had a mortality rate of 44.3% (P=0.0006) and a morbidity rate of 14.6% (P<0.0001). Patients with hemorrhagic stroke had a mortality rate of 59.7% (P<0.0001) and a morbidity rate of 9.5% (P=0.002). The proportion of patients with ischemic stroke increased from 2.8% in 2001-2006 to 5.1% in 2007-2011 (P<0.0001) and patients with hemorrhagic stroke increased from 2.4% in 2001-2006 to 4.5% in 2007-2011(P<0.0001). Conclusion: ECMO patients complicated with ischemic and hemorrhagic stroke had higher morbidity than those with no cerebrovascular complications. Patients with hemorrhagic stroke had a 10% worsened mortality rate than those with no cerebrovascular complications. The proportion of ECMO patients with cerebrovascular complications has nearly doubled between 2001-2011.

Background and Purpose: Strict maintenance of normovolemia is standard of care in treatment of aneurysmal subarachnoid hemorrhage (aSAH) and induced hypervolemia is used to treat delayed cerebral ischemia (DCI) from vasospasm. Fluid-related complications are not uncommon. We tested the hypothesis that fluid balance affected clinical outcomes in aSAH. Methods: We reviewed 307 patients with aSAH admitted to the Neuroscience Intensive Care Unit (NICU) from October 2001 to June 2011. We collected data on fluid balance during NICU stay, clinical and radiographic evidence of vasospasm, cardiopulmonary complications, and functional outcomes by modified Rankin scale (mRS) upon follow-up (mean 8 ± 8 months). Poor functional outcome was defined as mRS 3-6. Associations of variables of interest with outcome were assessed using univariable and multivariable logistic regression. Propensity scores were estimated to account for imbalances between patients with positive versus negative fluid balance and were included in multivariable models. Results: Average net fluid balance was 1153 ± 5586 mL. Results of univariate analysis are shown on the Table. On multivariate analysis, WFNS grade at nadir (p<0.001, OR=3.09, 95%CI 2.38-4.02) and positive fluid balance per liter increase (p=0.0005, OR=1.12, 95%CI 1.05-1.20) were associated with poor functional outcome. For every liter increase in positive net fluid balance, there was a 12% increased risk of a poor functional outcome on adjusted analysis (Area under ROC Curve 0.868). The association between positive net fluid balance and poor functional outcomes was confirmed using propensity score analysis to control for multiple confounding variables. Conclusions: Greater positive net fluid balance is independently associated with poorer functional outcome in patients with aSAH. This association does not appear to be solely explained by an excess of cardiopulmonary complications.