Cerebrovascular Complication and Valve Surgery in Infective Endocarditis.

Infective endocarditis (IE) with neurologic complications is common in patients with active IE. The most common and feared neurological complication of left-sided IE is cerebrovascular, from septic emboli causing ischemic stroke, intracranial hemorrhage (ICH), or an infectious intracranial aneurysm with or without rupture. In patients with cerebrovascular complications, valve replacement surgery is often delayed for concern of further neurological worsening. However, in circumstances when an indication for valve surgery to treat IE is present, the benefits of early surgical treatment may outweigh the potential neurologic deterioration. Furthermore, valve surgery has been associated with lower in-hospital mortality than medical therapy with intravenous antibiotics alone. Early valve surgery can be performed within 7 days of transient ischemic attack or asymptomatic stroke when medically indicated. Timing of valve surgery for IE after symptomatic medium or large symptomatic ischemic stroke or ICH remains challenging, and current data in the literature are conflicting about the risks and benefits. A delay of 2 to 4 weeks from the time of the cerebrovascular event is often recommended, balancing the risks and benefits of surgery. The range of timing of valve surgery varies depending on the clinical scenario, and is best determined by a multidisciplinary decision between cardiothoracic surgeons, cardiologists, infectious disease experts, and vascular neurologists in an experienced referral center.

Pre-Hospital Diagnosis in Mobile Stroke Unit.

OBJECTIVES: Mobile stroke unit (MSU) has been shown to rapidly provide pre-hospital thrombolysis in acute ischemic stroke (AIS). MSU encounters neurological disorders other than AIS that require emergent treatment. METHODS/MATERIALS: We obtained pre-hospital diagnosis and treatment data from the prospectively collected dataset on 221 consecutive MSU encounters. Based on initial clinical evaluation and neuroimaging obtained on MSU, the diagnosis of AIS (definite, probable, and possible AIS, transient ischemic attack), intracranial hemorrhage, and likely stroke mimics was made. RESULTS: From July 2014 to April 2015, 221 patients were treated on MSU. 78 (35%) patients had initial clinical diagnosis of definite/probable AIS or TIA, 69 (31%) were diagnosed as possible AIS or TIA, 15 (7%) had intracranial hemorrhage while 59 patients (27%) were diagnosed as likely stroke mimics. Stroke mimics encountered included 13 (6%) metabolic encephalopathy, 11 (5%) seizures, 9 (4%) migraines, 3 (1%) substance abuse, 2 (1%) CNS tumor, 3 (1%) infectious etiology and 3 (1%) hypoglycemia. Fifty-four (24%) patients received non-thrombolytic treatments on MSU CONCLUSION: About one third of MSU encounters were not AIS initially, including intracranial hemorrhage and stroke mimics. MSU can be utilized to provide pre-hospital treatments in emergent neurological conditions other than AIS.

Infectious causes of stroke.

PURPOSE OF REVIEW: Stroke continues to be a leading cause of debility in the world. Infections have been associated with stroke, but are not considered as directly causal, and so they are not often included in the traditional stroke workup and management. They are especially important in patients with stroke of undetermined etiology, and in certain patient populations, such as young patients without traditional risk factors, and immunocompromised patients. RECENT FINDINGS: There has been strong evidence for infectious conditions, such as endocarditis, and pathogens, such as varicella zoster in stroke causation, and more supportive evidence is surfacing in recent years of several organisms increasing the stroke risk or being directly causal in stroke. The evidence also seems to be pointing to the role of inflammation in increasing the risk of stroke via accelerated atherosclerosis, vasculitis and vasculopathy. SUMMARY: Infectious causes should be considered in the differential and work up of stroke in certain patient populations and appropriate treatments need to be initiated to minimize adverse stroke-related outcomes.

MRI Presentation of Infectious Intracranial Aneurysms in Infective Endocarditis.

BACKGROUND: The radiographic appearance of infectious intracranial aneurysms (IIAs) of infective endocarditis (IE) on magnetic resonance imaging (MRI) of brain is varied. We aimed to describe the IIA-specific MRI features in a series of patients with IIAs. METHODS: Records of patients with active IE who had digital subtraction angiography (DSA) at a tertiary medical center from January 2011 to December 2016 were reviewed. MRIs performed prior to IIA treatment were reviewed for findings on susceptibility-weighted imaging (SWI), diffusion-weighted imaging, and T1 with and without contrast. RESULTS: Of the 732 patients with IE, 53 (7%) had IIAs. Of these, 28 patients had an evaluable pre-treatment MRI, in whom 33 IIAs were imaged. MRI to DSA median time was 1 day (interquartile range = 1-5). On MRI, 12 (36%) IIAs had SWI lesion with contrast enhancement, 7 (21%) had cerebral microbleeds, 3 (11%) had sulcal SWI lesion, 2 (6%) IIAs had abscesses, 3 (9%) had intraparenchymal hemorrhage, 3 (9%) had subarachnoid hemorrhage, and 6 (18%) had ischemic stroke at the anatomical locations of IIAs. Four IIAs (12%) had no correlating MRI findings, though those patients had MRI without contrast. CONCLUSION: The MRI features such as SWI lesion and contrast enhancement were the commonest MRI presentations associated with the presence of IIA.

Acute Ischemic Stroke Therapy in Infective Endocarditis: Case Series and Systematic Review.

OBJECTIVES: To evaluate the safety of acute ischemic stroke (AIS) therapy in patients with infective endocarditis (IE) with intravenous thrombolysis (IVT) or endovascular therapy (EVT) such as mechanical thrombectomy. METHODS: We conducted a retrospective study of patients who underwent AIS therapy with IVT or EVT at a tertiary referral center from 2013 to 2017, that were later diagnosed with acute IE as the causative mechanism. We then performed a systematic review of reports of acute ischemic reperfusion therapy in IE since 1995 for their success rates in terms of neurological outcome, and mortality, and their risk of hemorrhagic complication. RESULTS: In the retrospective portion, 8 participants met criteria, of whom 4 received IVT and 4 received EVT. Through systematic review, 24 publications of 32 participants met criteria. Combined, a total of 40 participants were analyzed: 18 received IVT alone, 1 received combined IVT plus EVT, and 21 received EVT alone. IVT compared to EVT were similar in rates of good neurologic outcomes (58% versus 76%, P= .22) and mortality (21% versus 19%, P= .87), but had higher post-therapy intracranial hemorrhage (63% versus 18% [P= .006]). CONCLUSION: IV thrombolysis has a higher rate of post-therapy intracranial hemorrhage compared to EVT. EVT should be considered as first-line AIS therapy for patients with known, or suspected, IE who present with a large vessel occlusion.

Magnetic Resonance Imaging Susceptibility-Weighted Imaging Lesion and Contrast Enhancement May Represent Infectious Intracranial Aneurysm in Infective Endocarditis.

BACKGROUND: Infectious intracranial aneurysm (IIA) can complicate infective endocarditis (IE). We aimed to describe the magnetic resonance imaging (MRI) characteristics of IIA. METHODS: We reviewed IIAs among 116 consecutive patients with active IE by conducting a neurological evaluation at a single tertiary referral center from January 2015 to July 2016. MRIs and digital cerebral angiograms (DSA) were reviewed to identify MRI characteristics of IIAs. MRI susceptibility weighted imaging (SWI) was performed to collect data on cerebral microbleeds (CMBs) and sulcal SWI lesions. RESULTS: Out of 116 persons, 74 (63.8%) underwent DSA. IIAs were identified in 13 (17.6% of DSA, 11.2% of entire cohort) and 10 patients with aneurysms underwent MRI with SWI sequence. Nine (90%) out of 10 persons with IIAs had CMB >5 mm or sulcal lesions in SWI (9 in sulci, 6 in parenchyma, and 5 in both). Five out of 8 persons who underwent MRI brain with contrast had enhancement within the SWI lesions. In a multivariate logistic regression analysis, both sulcal SWI lesions (p < 0.001, OR 69, 95% CI 7.8-610) and contrast enhancement (p = 0.007, OR 16.5, 95% CI 2.3-121) were found to be significant predictors of the presence of IIAs. CONCLUSIONS: In the individuals with IE who underwent DSA and MRI, we found that neuroimaging characteristics, such as sulcal SWI lesion with or without contrast enhancement, are associated with the presence of IIA.

Nurses Are as Specific and Are Earlier in Calling In-Hospital Stroke Alerts Compared to Physicians.

INTRODUCTION: In-hospital stroke alerts are typically activated by nurses or physicians when a patient's neurological status acutely changes from baseline. It is unclear if knowledge of stroke symptoms translates to accurate activation of the acute stroke team. We hypothesized that nurses who activate the stroke alert system would correctly identify as great a proportion of acute strokes as physicians. We also investigated the time to activation of these in-hospital stroke alerts. METHODS: We retrospectively reviewed consecutive inpatient stroke team calls over a 12-month period at a single, tertiary care center. Calls and exact times were identified from the acute stroke pager log. The type of provider who called the stroke alert, patient characteristics, last known well time, and acute stroke symptoms was prospectively collected and retrospectively verified through electronic medical record review. Patients with definite stroke then were retrospectively identified by World Health Organization Monitoring of Trends and Determinants in Cardiovascular Disease (WHO MONICA) criterion. RESULTS: A total of 93 calls were analyzed. Nurses and physicians/midlevel providers activated the in-hospital stroke alert with a similar percentage of correct stroke diagnosis (62.7% versus 58.8%, P = .82). Nurses activated stroke alerts significantly earlier than physicians/midlevel providers (median 2 hours [IQR .5-6 hours] versus 4.9 hours [IQR 1.3-21.3 hours], P = .0096) from last known well time. CONCLUSIONS: Nurses identify in-hospital ischemic events with a similar percentage as physicians, and they activate the stroke alerts significantly earlier. The median nursing activation time fell within a 3-hour window for potential systemic thrombolytic or early endovascular therapy. An intensive, focused, collaborative education of nursing staff may further improve inpatient stroke outcomes.

Predictors of infarct growth after endovascular therapy for acute ischemic stroke.

BACKGROUND: Intra-arterial (IA) thrombectomy for acute ischemic stroke has an excellent recanalization rate but variable outcomes. The core infarct also grows at a variable rate despite recanalization. We aim to study the factors that are associated with infarct growth after IA therapy. METHODS: We reviewed the hyperacute ischemic stroke imaging database at Cleveland Clinic for those undergoing endovascular thrombectomy of anterior circulation from 2009 to 2012. Patients with both pretreatment and follow-up magnetic resonance imaging were included. Seventy-six patients were stratified into quartiles by infarct volume growth from initial to follow-up diffusion-weighted imaging (DWI) measure by a region of interest demarcation. RESULTS: The median infarct growth of each quartile was .6 cm(3) (no-growth group), 13.8, 37, and 160.2 cm(3) (large-growth group). Pretreatment stroke severity was comparable among groups. Compared with the no-growth group, the large-growth group had larger initial infarct defined by computed tomography (CT) Alberta Stroke Program Early CT score (median 10 versus 8, P = .032) and DWI volume (mean 13.8 versus 29.2 cm(3), P = .034), lack of full collateral vessels on CT angiography (36.8% versus 0%, P = .003), and a lower recanalization rate (thrombolysis in cerebral infarction ≥2b, P = .044). The increase in infarct growth is associated with decrease in favorable outcomes defined by a modified Rankin Scale score of 0-2 at 30 days: 57.9%, 42.1%, 21.1%, and 5.3%, respectively (P < .001). DWI reversal was observed in 11 of 76 patients, translating to 82% favorable outcome. CONCLUSIONS: Infarct evolution after endovascular thrombectomy is associated with an outcome. DWI reversal or no growth translated to a favorable outcome. Small initial ischemic core, good collateral support, and better recanalization grades predict the smaller infarct growth and favorable outcome after endovascular thrombectomy.

Addition of hyperacute MRI AIDS in patient selection, decreasing the use of endovascular stroke therapy.

BACKGROUND AND PURPOSE: The failure of recent trials to show the effectiveness of acute endovascular stroke therapy (EST) may be because of inadequate patient selection. We implemented a protocol to perform pretreatment MRI on patients with large-vessel occlusion eligible for EST to aid in patient selection. METHODS: We retrospectively identified patients with large-vessel occlusion considered for EST from January 2008 to August 2012. Patients before April 30, 2010, were selected based on computed tomography/computed tomography angiography (prehyperacute protocol), whereas patients on or after April 30, 2010, were selected based on computed tomography/computed tomography angiography and MRI (hyperacute MRI protocol). Demographic, clinical features, and outcomes were collected. Univariate and multivariate analyses were performed. RESULTS: We identified 267 patients: 88 patients in prehyperacute MRI period and 179 in hyperacute MRI period. Fewer patients evaluated in the hyperacute MRI period received EST (85 of 88, 96.6% versus 92 of 179, 51.7%; P<0.05). The hyperacute-MRI group had a more favorable outcome of a modified Rankin scale 0 to 2 at 30 days as a group (6 of 66, 9.1% versus 33 of 140, 23.6%; P=0.01), and when taken for EST (6 of 63, 9.5% versus 17 of 71, 23.9%; P=0.03). On adjusted multivariate analysis, the EST in the hyperacute MRI period was associated with a more favorable outcome (odds ratio, 3.4; 95% confidence interval, 1.1-10.6; P=0.03) and reduced mortality rate (odds ratio, 0.16; 95% confidence interval, 0.03-0.37; P<0.001). CONCLUSIONS: Implementation of hyperacute MRI protocol decreases the number of endovascular stroke interventions by half. Further investigation of MRI use for patient selection is warranted.

Intra-arterial therapy for acute ischemic stroke under general anesthesia versus monitored anesthesia care.

BACKGROUND: Recent studies have shown that intra-arterial recanalization therapy (IAT) for acute ischemic stroke (AIS) is associated with worse clinical outcomes when performed under general anesthesia (GA) compared to local anesthesia, with or without conscious sedation. The reasons for this association have not been systematically studied. METHODS: We retrospectively reviewed 190 patients who underwent IAT for anterior circulation AIS from January 2008 to December 2012 at our institution. Baseline demographics, vessels involved, acute stroke treatment including intravenous tissue type plasminogen activator (tPA) use, use of GA vs. monitored anesthesia care (MAC), location of thrombus, recanalization grade, radiologic post-procedural intracerebral hemorrhage, and 30-day outcomes were collected. Relevant clinical time points were recorded. Detailed intra-procedural hemodynamics including maximum/minimum heart rate, systolic blood pressure (BP), diastolic BP, mean BP, use of pressors and episodes of hypotension were collected. Our study's outcomes were as follows: in-hospital mortality, 30-day good outcome (mRS ≤2), successful recanalization and radiologic post-procedural intracerebral hemorrhage. RESULTS: Ninety-one patients received GA and 99 patients received MAC. There was no significant difference in the NIHSS score between the two groups but the GA group had a higher number of ICA occlusions (31.9 vs. 18.2%, p = 0.043). The time from the start of anesthesia to incision (23.0 ± 12.5 min vs. 18.7 ± 11.3 min, p = 0.020) and the time from the start of anesthesia to recanalization (110 ± 57.2 vs. 92.3 ± 43.0, p = 0.045) was longer in the GA group. The time from incision to recanalization was not significantly different between the two groups. mRS 0-2 was achieved in 22.8% of patients in the MAC group compared to 14.9% in GA (p = 0.293). Higher mortality was seen in the GA group (25.8 vs. 13.3%, p = 0.040). Successful recanalization (TICI 2b-3) was similar between the GA and MAC (57.8 vs. 48.5%, p = 0.182) groups, but GA had a higher number of parenchymal hematomas (26.3 vs. 10.1%, p = 0.003). There was no difference in the intra-procedural hemodynamic variables between the GA and MAC groups. Anesthesia type was an independent predictor for mortality (along with age and initial NIHSS), and the only independent predictor for parenchymal hematomas, with MAC being protective for both. CONCLUSION: Our study has confirmed previous findings of GA being associated with poorer outcomes and higher mortality in patients undergoing IAT for AIS. Detailed analysis of intra-procedural hemodynamics did not reveal any significant difference between the two groups. Parenchymal hematoma was the major driver of the difference in outcomes.

Posttreatment variables improve outcome prediction after intra-arterial therapy for acute ischemic stroke.

BACKGROUND: There are multiple clinical and radiographic factors that influence outcomes after endovascular reperfusion therapy (ERT) in acute ischemic stroke (AIS). We sought to derive and validate an outcome prediction score for AIS patients undergoing ERT based on readily available pretreatment and posttreatment factors. METHODS: The derivation cohort included 511 patients with anterior circulation AIS treated with ERT at 10 centers between September 2009 and July 2011. The prospective validation cohort included 223 patients with anterior circulation AIS treated in the North American Solitaire Acute Stroke registry. Multivariable logistic regression identified predictors of good outcome (modified Rankin score ≤2 at 3 months) in the derivation cohort; model ß coefficients were used to assign points and calculate a risk score. Discrimination was tested using C statistics with 95% confidence intervals (CIs) in the derivation and validation cohorts. Calibration was assessed using the Hosmer-Lemeshow test and plots of observed to expected outcomes. We assessed the net reclassification improvement for the derived score compared to the Totaled Health Risks in Vascular Events (THRIVE) score. Subgroup analysis in patients with pretreatment Alberta Stroke Program Early CT Score (ASPECTS) and posttreatment final infarct volume measurements was also performed to identify whether these radiographic predictors improved the model compared to simpler models. RESULTS: Good outcome was noted in 186 (36.4%) and 100 patients (44.8%) in the derivation and validation cohorts, respectively. Combining readily available pretreatment and posttreatment variables, we created a score (acronym: SNARL) based on the following parameters: symptomatic hemorrhage [2 points: none, hemorrhagic infarction (HI)1-2 or parenchymal hematoma (PH) type 1; 0 points: PH2], baseline National Institutes of Health Stroke Scale score (3 points: 0-10; 1 point: 11-20; 0 points: >20), age (2 points: <60 years; 1 point: 60-79 years; 0 points: >79 years), reperfusion (3 points: Thrombolysis In Cerebral Ischemia score 2b or 3) and location of clot (1 point: M2; 0 points: M1 or internal carotid artery). The SNARL score demonstrated good discrimination in the derivation (C statistic 0.79, 95% CI 0.75-0.83) and validation cohorts (C statistic 0.74, 95% CI 0.68-0.81) and was superior to the THRIVE score (derivation cohort: C statistic 0.65, 95% CI 0.60-0.70; validation cohort: C-statistic 0.59, 95% CI 0.52-0.67; p < 0.01 in both cohorts) but was inferior to a score that included age, ASPECTS, reperfusion status and final infarct volume (C statistic 0.86, 95% CI 0.82-0.91; p = 0.04). Compared with the THRIVE score, the SNARL score resulted in a net reclassification improvement of 34.8%. CONCLUSIONS: Among AIS patients treated with ERT, pretreatment scores such as the THRIVE score provide only fair prognostic information. Inclusion of posttreatment variables such as reperfusion and symptomatic hemorrhage greatly influences outcome and results in improved outcome prediction.

Patient-Reported Outcomes Predict Future Emergency Department Visits and Hospital Admissions in Patients With Stroke.

Background Identification of stroke patients at increased risk of emergency department (ED) visits or hospital admissions allows implementation of mitigation strategies. We evaluated the ability of the Patient-Reported Outcomes Information Measurement System (PROMIS) patient-reported outcomes (PROs) collected as part of routine care to predict 1-year emergency department (ED) visits and admissions when added to other readily available clinical variables. Methods and Results This was a cohort study of 1696 patients with ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, or transient ischemic attack seen in a cerebrovascular clinic from February 17, 2015, to June 11, 2018, who completed the following PROs at the visit: Patient Health Questionnaire-9, Quality of Life in Neurological Disorders cognitive function, PROMIS Global Health, sleep disturbance, fatigue, anxiety, social role satisfaction, physical function, and pain interference. A series of logistic regression models was constructed to determine the ability of models that include PRO scores to predict 1-year ED visits and all-cause and unplanned admissions. In the 1 year following the PRO encounter date, 1046 ED visits occurred in 548 patients; 751 admissions occurred in 453 patients. All PROs were significantly associated with future ED visits and admissions except PROMIS sleep. Models predicting unplanned admissions had highest optimism-corrected area under the curve (range, 0.684-0.724), followed by ED visits (range, 0.674-0.691) and then all-cause admissions (range, 0.628-0.671). PROs measuring domains of mental health had stronger associations with ED visits; PROs measuring domains of physical health had stronger associations with admissions. Conclusions PROMIS scales improve the ability to predict ED visits and admissions in patients with stroke. The differences in model performance and the most influential PROs in the prediction models suggest differences in factors influencing future hospital admissions and ED visits.

IV tPA given in the golden hour for emergent large vessel occlusion stroke improves recanalization rates and clinical outcomes.

BACKGROUND: Early thrombolysis for acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) is associated with better clinical outcome. This is thought to be due to greater tissue salvage with earlier recanalization. We explored whether ultra-early administration of intravenous tissue plasminogen activator (IV tPA) within 60 min (Golden Hour) of symptom onset for AIS due to ELVO is associated with a higher rate of recanalization. METHODS: We performed a retrospective analysis of recanalization rates and clinical outcomes in patients with AIS due to ELVO treated with IV tPA, comparing patients who received IV tPA within 60 min of stroke symptom onset with those treated beyond 60 min. RESULTS: Between January 2013 and December 2016, 158 patients with AIS due to ELVO were treated with IV tPA. Of these, 25 (15.8%) patients received IV tPA within 60 min of stroke symptom onset, while the remaining 133 (84.2%) patients received IV tPA beyond 60 min. The ultra-early treatment group was found to have a higher rate of complete recanalization (28.0% vs 6.8%, 95% CI 1.78-16.63), better chance of early neurological improvement (76.0% vs 50.4%, 95% CI 1.16-8.65), favorable clinical outcomes (mRS ≤ 2 or return to premorbid mRS) (65.0% vs 36.8%, 95% CI 1.42-9.34), and lower mortality (5% vs 31.1%, 95% CI 0.01-0.74) at 90-day follow-up compared to the later treatment group. CONCLUSION: Our data suggest that ultra-early administration of IV tPA significantly improves recanalization rates and clinical outcomes in patients with AIS due to ELVO.

Recycling endosomes of polarized epithelial cells actively sort apical and basolateral cargos into separate subdomains.

The plasma membranes of epithelial cells plasma membranes contain distinct apical and basolateral domains that are critical for their polarized functions. However, both domains are continuously internalized, with proteins and lipids from each intermixing in supranuclear recycling endosomes (REs). To maintain polarity, REs must faithfully recycle membrane proteins back to the correct plasma membrane domains. We examined sorting within REs and found that apical and basolateral proteins were laterally segregated into subdomains of individual REs. Subdomains were absent in unpolarized cells and developed along with polarization. Subdomains were formed by an active sorting process within REs, which precedes the formation of AP-1B-dependent basolateral transport vesicles. Both the formation of subdomains and the fidelity of basolateral trafficking were dependent on PI3 kinase activity. This suggests that subdomain and transport vesicle formation occur as separate sorting steps and that both processes may contribute to sorting fidelity.

Left atrial appendage closure device implantation in patients at very high risk for stroke.

BACKGROUND: Little is known about the role of left atrial appendage closure using the Watchman device (Boston Scientific) in patients who are at very high risk for stroke. OBJECTIVE: The purpose of this study was to assess the role of Watchman in patients with CHA2DS2-VASc ≥5. METHODS: All patients undergoing procedures for Watchman implant at our institution were enrolled in a prospective registry. All 104 consecutive recipients with CHA2DS2-VASc ≥5 were included. RESULTS: Median patient age was 78.5 ± 6.4 years, 56% were male, mean CHA2DS2-VASc was 5.7 ± 0.9, and mean HASBLED was 4.0 ± 1.0. Indications for implantation were significant prior bleeding (73%), unacceptable bleeding risk (21%), and unacceptable stroke and bleeding risk (6%). Watchman implantation was successful in all patients. All but 2 patients completed 45 days of postprocedural anticoagulation; 56% used warfarin and 44% used a novel oral anticoagulant. Transesophageal echocardiogram at 45 days revealed no significant peridevice leak. One patient was found to have a small mobile, filamentous echodensity attached on the medial aspect of the Watchman device. This resolved with longer anticoagulation with dabigatran and did not result in adverse outcome. At 1-year follow up, ischemic stroke had occurred in 3 patients (2.8%) at 96, 119, and 276 days after the procedure. CONCLUSION: In a population of patients with mean CHA2DS2-VASc of 5.7, Watchman implantation seemed to be safe and efficacious, with a residual annual ischemic stroke risk of 2.8%. In an atrial fibrillation population with a similar CHA2DS2-VASc score, the estimated annual risk of stroke is ≈12% off anticoagulation and >4% on warfarin.

Uncovering multiple axonal targeting pathways in hippocampal neurons.

Neuronal polarity is, at least in part, mediated by the differential sorting of membrane proteins to distinct domains, such as axons and somata/dendrites. We investigated the pathways underlying the subcellular targeting of NgCAM, a cell adhesion molecule residing on the axonal plasma membrane. Following transport of NgCAM kinetically, surprisingly we observed a transient appearance of NgCAM on the somatodendritic plasma membrane. Down-regulation of endocytosis resulted in loss of axonal accumulation of NgCAM, indicating that the axonal localization of NgCAM was dependent on endocytosis. Our data suggest the existence of a dendrite-to-axon transcytotic pathway to achieve axonal accumulation. NgCAM mutants with a point mutation in a crucial cytoplasmic tail motif (YRSL) are unable to access the transcytotic route. Instead, they were found to travel to the axon on a direct route. Therefore, our results suggest that multiple distinct pathways operate in hippocampal neurons to achieve axonal accumulation of membrane proteins.

Clinical course of infectious intracranial aneurysm undergoing antibiotic treatment.

INTRODUCTION: Infectious intracranial aneurysm (IIA, or mycotic aneurysm) is a cerebrovascular complication of infective endocarditis. We aimed to describe the clinical course of IIAs during antibiotic treatment. METHODS: We reviewed medical records of persons with infective endocarditis who underwent cerebral angiography at a single tertiary referral center from 2011 to 2016. Aneurysms were followed with subsequent angiography for unfavorable outcome (growth, rupture, no change, or new IIA formation) or favorable outcome (regression or resolution) until endovascular therapy, aneurysm resolution, or end of observation. RESULTS: Of 618 patients included, 40 (6.5%) had 43 IIAs. Eighteen (42%) aneurysms underwent initial endovascular treatment. Twenty-five unruptured aneurysms were followed for a median 18 antibiotic days after IIA discovery (interquartile range [IQR] 4-32). Eleven (44%) aneurysms had unfavorable outcome (1 rupture, 2 new IIA formation, 6 enlargement, and 2 no change) at median 21 days (IQR 5-32). Favorable angiographic outcome was seen in 7 (28%) patients (6 resolution, 1 regression) at median 36 days (IQR 24-41). Seven aneurysms had no angiographic reevaluations but showed no evidence of rupture during clinical follow-up for median 4 days (IQR 3-12) until hospital discharge. Saccular morphology was associated with unfavorable aneurysmal outcome (p = 0.013). Longer duration of antibiotic exposure prior to IIA discovery was associated with favorable aneurysmal outcome (p = 0.046). CONCLUSION: IIAs represent a dynamic disease. Only a quarter of IIAs resolve with antibiotics alone. Saccular aneurysmal morphology might predict unfavorable aneurysmal outcome. IIA found after longer antibiotic therapy has higher likelihood of resolution or regression on antibiotic treatment.

Left atrial appendage closure device implantation in patients with prior intracranial hemorrhage.

BACKGROUND: The Watchman device (Boston Scientific), used for left atrial appendage closure (LAAC), was approved for stroke prevention in patients with atrial fibrillation (AF) and an appropriate rationale to avoid long-term oral anticoagulation. Patients with AF and prior intracranial hemorrhage (ICH) were excluded from clinical trials because of perceived risks of perioperative anticoagulation. OBJECTIVE: The purpose of this study was to study the efficacy and safety of LAAC using Watchman in patients with AF and prior ICH. METHODS: In a multidisciplinary AF/stroke prevention clinic, 38 consecutive patients with AF and prior ICH underwent Watchman implantation. Patients were enrolled in a prospectively maintained data registry. RESULTS: Patients' mean CHA2DS2-VASc score was 5.0 ± 1.3 and HAS-BLED score 4.2 ± 1.0. Prior ICH events were intraparenchymal (60%), subdural (24%), or subarachnoid bleeds (16%). The median event-to-implantation time was 637 days (minimum 60). Watchman was implanted in all patients with no procedural complications. All patients completed 45 days of anticoagulation with warfarin (55%), apixaban (37%), or dabigatran (8%). Transesophageal echocardiograms at 45 days showed no peridevice leak, and 1 patient had a small filamentous echodensity on device that resolved with anticoagulation. While undergoing anticoagulation, none of the patients developed recurrent ICH. Minor bleeding occurred in 1 patient (trauma-related lower extremity hematoma at 19 days postimplantation). At 13.4 months (quartiles 8-19) of follow-up, there were no strokes, ICH, or deaths. CONCLUSION: AF patients with prior ICH tolerated short-term anticoagulation for the purpose of Watchman implantation. LAAC with attendant short-term anticoagulation seems to be both safe and effective in this patient population.

ASPECTS discrepancies between CT and MR imaging: analysis and implications for triage protocols in acute ischemic stroke.

BACKGROUND: Optimal imaging triage for intervention for large vessel occlusions remains unclear. MR-based imaging provides ischemic core volumes at the cost of increased imaging time. CT Alberta Stroke Program Early CT Score (ASPECTS) estimates are faster, but may be less sensitive. OBJECTIVE: To assesses the rate at which MRI changed management in comparison with CT imaging alone. METHODS: Retrospective analysis of patients with acute ischemic stroke undergoing imaging triage for endovascular therapy was performed between 2008 and 2013. Univariate and multivariate analyses were performed. Multivariate logistic regression was used to evaluate the effect of time on disagreement in MRI and CT ASPECTS scores. RESULTS: A total of 241 patients underwent both diffusion-weighted imaging (DWI) and CT. Six patients with DWI ASPECTS ≥6 and CT ASPECTS <6 were omitted, leaving 235 patients. For 47 patients, disagreement between the two modalities resulted in different treatment recommendations. The estimated probability of disagreement was 20.0% (95% CI 15.4% to 25.6%). In a multivariate logistic regression, CT ASPECTS >7 (p=0.004) and admission National Institutes of Health Stroke Scale (NIHSS) score <16 (p=0.008) were simultaneously significant predictors of agreement in ASPECTS. The time between modalities was a marginally significant predictor (p=0.080). CONCLUSIONS: The study suggests that patients with NIHSS scores at admission of <16 and patients with CT ASPECTS >7 have a higher likelihood of agreement between CT and DWI based on an ASPECTS cut-off value of 6. Additional MRI for triage in patients with NIHSS at admission of >16, and ASPECTS of 6 or 7 may be more likely to change management. Unsurprisingly, patients with low CT ASPECTS had good correlation with MRI ASPECTS.