Fugate, Jennifer E.

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.

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.

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.

Background: Whether a significant proportion of cryptogenic stroke (CS) is caused by under-detected paroxysmal atrial fibrillation (PAF) is not known. Prolonged ambulatory cardiac monitoring may detect episodes of PAF in patients with stroke of unknown cause (cryptogenic stroke, CS). However, it is unclear whether PAF is more common in patients wtih CS compared with patients with stroke of known cause (SKC). We performed a case control study to compare the rates of detection of PAF in CS vs SKC using prolonged ambulatory cardiac rhythm monitoring. Methods and Results: We prospectively enrolled 132 patients within 3 months of a stroke (66 with CS and 66 with SKC) to undergo 3-week ambulatory cardiac rhythm monitoring using the CardioNet MCOT system. Stroke group was assigned by consensus between two vascular neurologists upon enrollment based on the Causative Classification of Stroke system. Primary endpoint was detection of PAF of any duration independently confirmed by two cardiologists blinded to the stroke group. The groups were well balanced except that patients with CS tended to be older and to have less hypertension and diabetes. Four patients (2 in each group) were excluded because of insufficient stroke evaluation or early discontinuation of monitoring. Episodes of PAF were detected in 16/64 (25%) patients with CS and 9/64 (14%) patients with SKC (p=0.12). Only 5 patients had episodes of PAF lasting > 30 seconds (3 with CS and 2 with SKC). Six of the 9 patients from the SKC group with PAF had small subcortical infarctions; the other 3 had cortical strokes ascribed to artery-to-artery embolism (2 with complex aortic plaques, 1 with severe vertebrobasilar stenosis). In patients under age 65, episodes of PAF were more common in the CS group (22% vs 3; p=0.07) while in patients age 65 or older the rates of detection were very similar (29% in CS vs 28% in SKC; p=0.9). Conclusions: Very short episodes of PAF are relatively common in patients with CS and with SKC, and their pathogenic significance is unclear. However, considering only patients under 65, a greater proportion of cryptogenic stroke patients had PAF, suggesting it might be pathogenic.

Introduction: Long-term cardiac monitoring studies have unveiled low-burden, occult atrial fibrillation (AF) in some patients with otherwise cryptogenic stroke (CS). But occult AF is also found in some normal individuals and patients with stroke of known cause (KS). Clinical management would be aided by estimates of how often occult AF in a patient with CS is causal versus incidental. Methods: Through systematic search, we identified all case-control and cohort studies applying identical long-term monitoring techniques to both CS and KS patients. We performed a random-effects meta-analyses across these studies to determine the best estimate of the differential frequency of occult AF in CS and KS among all patients, and across age subgroups. We then applied Bayes’ theorem (method of Alsheikh-Ali et al, Stroke 2009) to determine the probability that occult AF is causal or incidental. Results: The systematic search identified 3 case-control and cohort studies enrolling 575 patients (337 CS, 238 KS). Methods of long-term monitoring were implantable loop recorder in 191 (33.2%), extended mobile external cardiac monitor in 277 (48.2%), and patch/event/Holter monitoring in 107 (18.6%). In formal meta-analysis, the summary odds ratio for occult AF in CS vs KS in all patients was 1.72 (95%CI 0.91-3.25) (Figure). With application of Bayes theorem, the corresponding probabilities indicated that, when present, occult AF in CS patients is causal in 44.4% and incidental in 55.6%. Only one study reported age-specific subgroup data: these suggested occult AF in CS patients was causal in 93% of patients <65y vs 5.6% of patients ≥65y, but estimates had limited precision. Conclusions: In patients with cryptogenic stroke, when occult AF is found, it is likely causal in about 44% of patients, who may benefit from anticoagulation, and likely incidental in about 56% of patients, who may not benefit from anticoagulation. Figure

Introduction: Five randomized trials proving the efficacy and safety of mechanical embolectomy for ischemic stroke patients used differing radiological methods to select patients for treatment. Hypothesis: The percentage of patients evaluated in a non-clinical trial setting that would meet radiological criteria to be included in the five trials will differ substantially. Methods: Retrospective study of consecutive ischemic stroke patients who were considered for endovascular stroke therapy based on confirmed intracranial large vessel occlusion (M1, M2, or carotid terminus) at an academic medical center from April 2010 - November 2014. All patients underwent CT perfusion and CT angiogram. Results: The table shows baseline characteristics of 119 patients. Median age was 69 years (IQR 57-79) and median NIHSS 18 (IQR 14-21). Most patients had ASPECTS score ≥ 6 (n=105, 88.2%). The M1 segment of MCA was the most common vessel occluded (n=81, 68%). All 119 patients (100%) met radiological criteria for MR CLEAN while 105 (88.2%) met criteria for SWIFT-PRIME, 96 (80.7%) for REVASCAT, 80/116 (69.0%) for EXTEND IA, and 74 (62.2%) for ESCAPE. IV TPA was given to 58 patients (48.7%) and acute endovascular stroke therapy attempted in 66 (55.5%). Any intracranial hemorrhage was more common in the patients treated with endovascular therapy than in those who were not (36% vs. 17%, p=0.025). The frequency of symptomatic ICH did not significantly differ between these two groups (6.1% vs 3.8%, p=0.691). Conclusions: The percentage of patients with acute stroke and large vessel occlusion that would qualify for endovascular stroke trials based on radiological criteria varies considerably (62%-100%) in a non-clinical trial cohort from an academic comprehensive stroke center. Additional individual patient characteristics influence treatment decisions in non-clinical trial settings.