Non-Vitamin K Antagonist Oral Anticoagulants for the Treatment of Cerebral Venous Sinus Thrombosis: a Retrospective, Matched Cohort Analysis.

BACKGROUND: The management of cerebral venous sinus thrombosis (CVT) is a common problem facing vascular neurologists. American Heart Association/American Stroke Association guidelines suggest the use of heparin followed by vitamin K antagonists (VKAs) for anticoagulation in CVT. In recent years, the evidence base has solidified for the use of non-vitamin K antagonist oral anticoagulants (NOACs) in lower extremity deep vein thrombosis. Because data supporting their use in CVT are limited, with the strongest evidence comprising one randomized controlled trial of dabigatran, we sought to review our experience with NOACs in the treatment of CVT at a tertiary care center to address efficacy and safety. METHODS: We retrospectively reviewed charts of all patients with CVT treated with an NOAC at our tertiary care facility in the years 2011-2019. We collected data on demographics, risk factors for CVT, clinical features at presentation, imaging results, anticoagulation regimen, bleeding complications, and disability at follow-up. We compared disability at follow-up and major hemorrhagic events with age-matched and sex-matched controls treated with VKAs over the same time period and with historical controls. RESULTS: We identified 29 patients with CVT treated with an NOAC, 27 of whom had follow-up within our system. NOACs that were used for treatment included apixaban (20 patients), rivaroxaban (6 patients) and dabigatran (1 patient). NOAC use was associated with stabilization of a clot or partial recanalization in 55.6% of patients and complete recanalization in 14.8% at a median follow-up time of 6 months. The median modified Rankin Score (mRS) at follow-up was 0, with one death. Three patients (11.1%) had major bleeding complications, including two with symptomatic worsening of intracranial hemorrhage. Comparisons of 27 age-matched and sex-matched controls treated with VKAs showed no significant differences in terms of partial recanalization (55.6% vs. 63.0%, p = 0.29), complete recanalization (14.8% vs. 25.9%, p = 0.73), mRS at follow-up (median 0 vs. 0, p = 0.23), or major bleeding (11.1% vs. 11.1%, p > 0.99). Comparisons with the historical International Study on Cerebral Vein and Dural Sinus Thrombosis cohort showed similar functional outcomes: 92.6% of patients treated with NOACs and 88.9% of patients treated with VKAs at the Washington University School of Medicine in St. Louis, as well as 86.2% of patients treated with VKAs in the historical study cohort, had mRS of 0-2 at follow-up (p = 0.60). Rates of major bleeding compared with this cohort were also similar (11.1% vs. 11.1% vs. 14.5%, p = 0.80). CONCLUSIONS: The safety and efficacy results of NOAC use for CVT were similar to those for age-matched and sex-matched controls treated with VKAs, as well as historical published controls. Assessment of NOAC efficacy and safety in CVT in multicenter cohort studies and randomized controlled trials is warranted.

Management of Patients on Non-Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association.

Non-vitamin K oral anticoagulants (NOACs) are now widely used as alternatives to warfarin for stroke prevention in atrial fibrillation and management of venous thromboembolism. In clinical practice, there is still widespread uncertainty on how to manage patients on NOACs who bleed or who are at risk for bleeding. Clinical trial data related to NOAC reversal for bleeding and perioperative management are sparse, and recommendations are largely derived from expert opinion. Knowledge of time of last ingestion of the NOAC and renal function is critical to managing these patients given that laboratory measurement is challenging because of the lack of commercially available assays in the United States. Idarucizumab is available as an antidote to rapidly reverse the effects of dabigatran. At present, there is no specific antidote available in the United States for the oral factor Xa inhibitors. Prothrombin concentrate may be considered in life-threatening bleeding. Healthcare institutions should adopt a NOAC reversal and perioperative management protocol developed with multidisciplinary input.

Cerebrovascular Events After Continuous-Flow Left Ventricular Assist Devices.

BACKGROUND: Cerebrovascular events (CVE) are among the most common and serious complications after implantation of continuous-flow left ventricular assist devices (CF-LVAD). We studied the incidence, subtypes, anatomical distribution, and pre- and post-implantation risk factors of CVEs as well as the effect of CVEs on outcomes after CF-LVAD implantation at our institution. METHODS: Retrospective analysis of clinical and neuroimaging data of 372 patients with CF-LVAD between May 2005 and December 2013 using standard statistical methods. RESULTS: CVEs occurred in 71 patients (19%), consisting of 35 ischemic (49%), 26 hemorrhagic (37%), and 10 ischemic+hemorrhagic (14%) events. History of coronary artery disease and female gender was associated with higher odds of ischemic CVE (OR 2.84 and 2.5, respectively), and diabetes mellitus was associated with higher odds of hemorrhagic CVE (OR 3.12). While we found a higher rate of ischemic CVEs in patients not taking any antithrombotic medications, no difference was found between patients with ischemic and hemorrhagic CVEs. Occurrence of CVEs was associated with increased mortality (HR 1.62). Heart transplantation was associated with improved survival (HR 0.02). In patients without heart transplantation, occurrence of CVE was associated with decreased survival. CONCLUSIONS: LVADs are associated with high rates of CVE, increased mortality, and lower rates of heart transplantation. Further investigations to identify the optimal primary and secondary stroke prevention measures in post-LVAD patients are warranted.

Baseline Hemodynamic Impairment and Future Stroke Risk in Adult Idiopathic Moyamoya Phenomenon: Results of a Prospective Natural History Study.

BACKGROUND AND PURPOSE: The purpose was to test the hypothesis that increased oxygen extraction fraction (OEF), a marker of severe hemodynamic impairment measured by positron emission tomography, is an independent risk factor for subsequent ischemic stroke in this population. METHODS: Adults with idiopathic moyamoya phenomena were recruited between 2005 and 2012 for a prospective, multicenter, blindly adjudicated, longitudinal cohort study. Measurements of OEF were obtained on enrollment. Subjects were followed up for the occurrence of ipsilateral ischemic stroke at 6-month intervals. Patients were censored at the time of surgical revascularization or at last follow-up. The primary analysis was time to ischemic stroke in the territory of the occlusive vasculopathy. RESULTS: Forty-nine subjects were followed up during a median of 3.7 years. One of 16 patients with increased OEF on enrollment had an ischemic stroke and another had an intraparenchymal hemorrhage. Three of 33 patients with normal OEF had an ischemic stroke. On a per-hemisphere basis, 21 of 79 hemispheres with moyamoya vasculopathy had increased OEF at baseline. No ischemic strokes and one hemorrhage occurred in a hemisphere with increased OEF (n=21). Sixteen patients (20 hemispheres), including 5 with increased OEF at enrollment, were censored at a mean of 5.3 months after enrollment for revascularization surgery. CONCLUSIONS: The risk of new or recurrent stroke was lower than expected. The low event rate, low prevalence of increased OEF, and potential selection bias introduced by revascularization surgery limit strong conclusions about the association of increased OEF and future stroke risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00629915.

RBC Transfusion Improves Cerebral Oxygen Delivery in Subarachnoid Hemorrhage.

OBJECTIVES: Impaired oxygen delivery due to reduced cerebral blood flow is the hallmark of delayed cerebral ischemia following subarachnoid hemorrhage. Since anemia reduces arterial oxygen content, it further threatens oxygen delivery increasing the risk of cerebral infarction. Thus, subarachnoid hemorrhage may constitute an important exception to current restrictive transfusion practices, wherein raising hemoglobin could reduce the risk of ischemia in a critically hypoperfused organ. In this physiologic proof-of-principle study, we determined whether transfusion could augment cerebral oxygen delivery, particularly in vulnerable brain regions, across a broad range of hemoglobin values. DESIGN: Prospective study measuring cerebral blood flow and oxygen extraction fraction using O-PET. Vulnerable brain regions were defined as those with baseline oxygen delivery less than 4.5 mL/100 g/min. SETTING: PET facility located within the Neurology/Neurosurgery ICU. PATIENTS: Fifty-two patients at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage with hemoglobin 7-13 g/dL. INTERVENTIONS: Transfusion of one unit of RBCs over 1 hour. MEASUREMENTS AND MAIN RESULTS: Baseline hemoglobin was 9.7 g/dL (range, 6.9-12.9), and cerebral blood flow was 43 ± 11 mL/100 g/min. After transfusion, hemoglobin rose from 9.6 ± 1.4 to 10.8 ± 1.4 g/dL (12%; p < 0.001) and oxygen delivery from 5.0 (interquartile range, 4.4-6.6) to 5.5 mL/100 g/min (interquartile range, 4.8-7.0) (10%; p = 0.001); the response was comparable across the range of hemoglobin values. In vulnerable brain regions, transfusion resulted in a greater (16%) rise in oxygen delivery associated with reduction in oxygen extraction fraction, independent of Hgb level (p = 0.002 vs normal regions). CONCLUSIONS: This study demonstrates that RBC transfusion improves cerebral oxygen delivery globally and particularly to vulnerable regions in subarachnoid hemorrhage patients at risk for delayed cerebral ischemia across a wide range of hemoglobin values and suggests that restrictive transfusion practices may not be appropriate in this population. Large prospective trials are necessary to determine if these physiologic benefits translate into clinical improvement and outweigh the risk of transfusion.

Aneurysmal Subarachnoid Hemorrhage: Strategies for Preventing Vasospasm in the Intensive Care Unit.

This article addresses the intensive care unit (ICU) management of patients with aneurysmal subarachnoid hemorrhage (SAH), with an emphasis on the prevention of cerebral vasospasm and delayed cerebral ischemia (DCI), which are major contributors to morbidity and mortality. Interventions addressing various steps in the development of vasospasm have been attempted, with variable success. Enteral nimodipine remains the only approved measure to potentially prevent DCI. Since oral and intravenous administrations are limited by hypotension, direct administration via sustained-release pellets and intraventricular administration of sustained-release microparticles are being investigated. Studies of other calcium channel blockers have been disappointing. Efforts to remove blood from the subarachnoid space via cisternal irrigation, cisternal or ventricular thrombolysis, and lumbar cerebrospinal fluid drainage have met with limited and variable success, and they remain an area of active investigation. Several interventions that had early promise have failed to show benefit when studied in large trials; these include tirilazad, magnesium, statins, clazosentan, transluminal angioplasty, and hypervolemia.

Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage.

BACKGROUND: Statins may promote vasodilation following subarachnoid hemorrhage (SAH) and improve the response to blood pressure elevation. We sought to determine whether simvastatin increases cerebral blood flow (CBF) and alters the response to induced hypertension after SAH. METHODS: Statin-naïve patients admitted <72 h after WFNS ≥2 aneurysmal SAH were randomly assigned to 80 mg simvastatin/day or placebo for 21 days. Regional CBF was measured with quantitative (15)O PET on SAH day 7-10 before and after raising mean arterial pressure (MAP) 20-25 %. Autoregulatory index (AI) was calculated as the ratio of % change in resistance (MAP/CBF) to % change in MAP. Angiography was performed within 24 h of PET. Results are presented as simvastatin vs. placebo. RESULTS: Thirteen patients received simvastatin and 12 placebo. Clinical characteristics were similar. Moderate or severe angiographic vasospasm occurred in 42 vs. 45 % and delayed cerebral ischemia in 14 vs. 55 % (p = 0.074). During PET studies, MAP (110 ± 10 vs. 111 ± 12), global CBF (41 ± 12 vs. 43 ± 13), and CVR (2.95 ± 1.0 vs. 2.81 ± 1.0) did not differ at baseline. When MAP was raised to 135 ± 7 mm Hg vs. 137 ± 15, global CBF did not change. Global AI did not differ (107 ± 59 vs. 0. 89 ± 52 %, p = 0.68). CBF did not change in regions with low baseline flow or in regions supplied by vessels with angiographic vasospasm in either group. Six-month modified Rankin Scale scores did not differ. CONCLUSIONS: Our data indicate that initiation of therapy with high-dose simvastatin does not alter baseline CBF or response to induced hypertension.

Faculty and medical student attitudes about preclinical classroom attendance.

BACKGROUND: Technological advances have diminished reliance on classroom attendance for mastering preclinical medical school course content, but nonattendance may have unintended consequence on the learning environment. Perceptions among educators and students regarding the value of attendance and implications of nonattendance have not been systematically studied. PURPOSES: The purpose of this study was to investigate differences in medical student and faculty attitudes regarding preclinical classroom attendance and the impact of nonattendance on educators and the learning environment. METHODS: Using Internet-based surveys, we assessed attitudes about preclinical classroom attendance among medical students and teaching faculty at Washington University School of Medicine. Our primary hypothesis was that students would be less likely than faculty to place societal value on attendance and relate it to professionalism. RESULTS: A total of 382 (79%) of 484 eligible students and 248 (64%) of 387 eligible faculty completed the survey. Both groups recognized a negative impact of poor attendance on faculty enthusiasm for teaching (students 83%, faculty 75%), but faculty were significantly more likely to endorse a negative impact on effectiveness of lectures (75% vs. 42%, p<.0001) and small-groups (92% vs. 76%, p<.0001) and a relationship between attendance and professionalism (88% vs. 68%, p<.0001). Students were significantly more likely to support free choice among learning opportunities (90% vs. 41%, p<.0001) including regularly missing class for research and community service activities (70% vs. 14%, p<.0001) and to consider lecture videos an adequate substitute for attendance (70% vs. 15%, p<.0001). Free-text responses suggested that students tended to view class-going primarily as a tool for learning factual material, whereas many faculty viewed it as serving important functions in the professional socialization process. CONCLUSIONS: In this single-center cohort, medical student and teaching faculty attitudes differed regarding the importance of classroom attendance and its relationship to professionalism, findings that were at least partially explained by differing expectations of the purpose of the preclinical classroom experience.

Relationship between angiographic vasospasm and regional hypoperfusion in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Angiographic vasospasm frequently complicates subarachnoid hemorrhage and has been implicated in the development of delayed cerebral ischemia. Whether large-vessel narrowing adequately accounts for the critical reductions in regional cerebral blood flow underlying ischemia is unclear. We sought to clarify the relationship between angiographic vasospasm and regional hypoperfusion. METHODS: Twenty-five patients with aneurysmal subarachnoid hemorrhage underwent cerebral catheter angiography and 15O-positron emission tomographic imaging within 1 day of each other (median of 7 days after subarachnoid hemorrhage). Severity of vasospasm was assessed in each intracranial artery, whereas cerebral blood flow and oxygen extraction fraction were measured in 28 brain regions distributed across these vascular territories. We analyzed the association between vasospasm and perfusion and compared frequency of hypoperfusion (cerebral blood flow<25 mL/100 g/min) and oligemia (low oxygen delivery with oxygen extraction fraction≥0.5) in territories with versus without significant vasospasm. RESULTS: Twenty-four percent of 652 brain regions were supplied by vessels with significant vasospasm. Cerebral blood flow was lower in such regions (38.6±12 versus 48.7±16 mL/100 g/min), whereas oxygen extraction fraction was higher (0.48±0.19 versus 0.37±0.14, both P<0.001). Hypoperfusion was seen in 46 regions (7%), but 66% of these were supplied by vessels with no significant vasospasm; 24% occurred in patients without angiographic vasospasm. Similarly, oligemia occurred more frequently outside territories with vasospasm. CONCLUSIONS: Angiographic vasospasm is associated with reductions in cerebral perfusion. However, regional hypoperfusion and oligemia frequently occurred in territories and patients without vasospasm. Other factors in addition to large-vessel narrowing must contribute to critical reductions in perfusion.

Developing a Video-Based Learning Module to Teach Decision-Making for Cubital Tunnel Surgery.

BACKGROUND: Although intraoperative educational videos have become increasingly popular, comparatively few videos teach clinical reasoning for surgical procedures. The objectives of this study were to develop an engaging online video-based module to teach decision-making for cubital tunnel surgery, including supercharge nerve transfer, using a multimedia learning framework; and evaluate its effectiveness and use for continuing professional development. METHODS: The educational module consisted of a prelecture knowledge assessment, choice of two self-guided video lectures (7 minutes and 28 minutes), and a postlecture knowledge assessment. An additional assessment examined knowledge retention 3 months after module completion. Surgeon surveys were administered after each knowledge assessment. RESULTS: A total of 279 surgeons participated in the educational module (75 percent practicing surgeons, 25 percent trainees), 112 surgeons completed the postlecture assessment, and 71 surgeons completed the knowledge retention assessment. Median score on the prelecture assessment was five out of 10 (interquartile range, four to seven). Scores improved by three points (10-point scale; p < 0.0001) in the postlecture assessment. Median score on the knowledge retention assessment was eight out of 10 (interquartile range, six to nine), with participants maintaining a two-point increase from their prelecture score ( p = 0.0002). Among surgeons completing this assessment, 68 percent reported that the module had changed their management of cubital tunnel syndrome. CONCLUSIONS: This study introduces a framework for the development of online multimedia modules for surgical education. It also underscores a demand among surgeons for easily accessible, reusable educational resources. Similar video-based modules may be developed to address this demand to facilitate continuing professional development in surgery.

Poor correlation between perihematomal MRI hyperintensity and brain swelling after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The perihematomal hyperintensity (PHH) is commonly interpreted to represent cerebral edema following intracerebral hemorrhage (ICH), but the accuracy of this interpretation is unknown. We therefore investigated the relationship between the changes in PHH and the changes in hemispheric brain volume as a measure of edema during the first week after ICH. METHODS: Fifteen individuals aged 66 ± 13 with baseline hematoma size of 13.1 ml (range 3-43) were prospectively studied with sequential MRI 1.0 ± 0.5, 2.6 ± 0.9, and 6.5 ± 1.0 days after spontaneous supratentorial ICH. Changes in hemispheric brain volume were assessed on MPRAGE using the Brain-Boundary Shift Integral (BBSI). Hematoma and PHH volumes were measured on T2-weighted images. RESULTS: Brain volume increased a small but statistically significant amount (6.3 ± 8.0 ml, 0.6 ± 0.7%) between the first and second scans relative to 10 normal controls (-0.9 ± 4.1 ml, P = 0.02) and returned toward baseline at the third scan (1.5 ± 9.5 ml vs. controls 0.9 ± 4.0 ml, P = 0.85). There were no significant differences in the volume changes between the two hemispheres at scan 2 or scan 3. At both scan 2 (P = 0.04) and scan 3 (P = 0.004), the change in PHH was significantly greater than and poorly correlated with the change in ipsilateral hemispheric volume. There were no significant correlations between the change in NIH Stroke Scale (NIHSS) and the change in PHH, ipsilateral, or total brain volume at scan 2 or scan 3 (all P > 0.05). CONCLUSIONS: In patients with small-to-moderate-sized hematomas, change in PHH was a poor measure of brain edema in the first week following ICH. A small degree of bihemispheric brain swelling occurred, but was of little clinical significance.

Cerebral hemodynamic and metabolic effects of equi-osmolar doses mannitol and 23.4% saline in patients with edema following large ischemic stroke.

INTRODUCTION: Cerebral edema after ischemic stroke is frequently treated with mannitol and hypertonic saline (HS); however, their relative cerebrovascular and metabolic effects are incompletely understood, and may operate independent of their ability to lower intracranial pressure. METHODS: We compared the effects of 20% mannitol and 23.4% saline on cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF), and oxygen metabolism (CMRO(2)), in nine ischemic stroke patients who deteriorated and had >2 mm midline shift on imaging. (15)O-PET was performed before and 1 h after administration of randomly assigned equi-osmolar doses of mannitol (1.0 g/kg) or 23.4% saline (0.686 mL/kg). RESULTS: Baseline CBF values (ml/100g/min) in the infarct core, periinfarct region, remaining ipsilateral hemisphere, and contralateral hemisphere in the mannitol group were 5.0 ± 3.9, 25.6 ± 4.4, 35.6 ± 8.6, and 45.5 ± 2.2, respectively, and in the HS group were 8.3 ± 9.8, 35.3 ± 10.9, 38.2 ± 15.1, and 35.2 ± 12.4, respectively. There was a trend for CBF to rise in the contralateral hemisphere after mannitol from 45.5 ± 12.2 to 57.6 ± 21.7, P = 0.098, but not HS. CBV, OEF, and CMRO(2) did not change after administration of either agent. Change in CBF in the contralateral hemisphere after osmotic therapy was strongly correlated with baseline blood pressure (R (2)= 0.879, P = 0.002). CONCLUSIONS: We conclude that at higher perfusion pressures, osmotic agents may raise CBF in non-ischemic tissue. We conclude that at higher perfusion pressures, osmotic agents may raise CBF in non-ischemic tissue.

Executive dysfunction and depressive symptoms associated with reduced participation of people with severe congestive heart failure.

OBJECTIVE: We investigated participation levels and relationships among cognition, depression, and participation for people with severe congestive heart failure (CHF). METHOD: People with severe CHF (New York Heart Association Class III or IV) awaiting heart transplantation (N = 27) completed standardized tests of cognition and self-report measures of executive dysfunction, depressive symptoms, and participation. RESULTS: Possible depression (64%) and cognitive impairment (15%-59%) were prevalent. Participants reported significant reductions in participation across all activity domains since CHF diagnosis (ps < .001). Worse executive dysfunction and depressive symptoms were associated with reduced participation and together accounted for 35%-46% of the variance in participation (ps < .01). CONCLUSION: Participation restrictions associated with CHF are not limited to physically demanding activities and are significantly associated with executive dysfunction and depression. Cardiac rehabilitation should address cognitive and psychological functioning in the context of all life situations instead of focusing solely on physical function and disability.

Lack of association between acute stroke, post-stroke dementia, race, and ß-amyloid status.

INTRODUCTION: Stroke and Alzheimer disease share risk factors and often co-occur, and both have been reported to have a higher prevalence in African Americans as compared to non-Hispanic whites. However, their interaction has not been established. The objective of this study was to determine if preclinical Alzheimer disease is a risk factor for stroke and post-stroke dementia and whether racial differences moderate this relationship. METHODS: This case-control study was analyzed in 2019 using retrospective data from 2007 to 2013. Participants were adults age 65 and older with and without acute ischemic stroke. Recruitment included word of mouth and referrals in Saint Louis, MO, with stroke participants recruited from acutely hospitalized patients and non-stroke participants from community living older adults who were research volunteers. Our assessment included radiologic reads of infarcts, microbleeds, and white matter hyperintensitites (WMH); a Pittsburgh Compound B PET measure of cortical ß-amyloid binding; quantitative measures of hippocampal and WMH volume; longitudinal Mini Mental State Examination (MMSE) scores; and Clinical Dementia Rating (CDR) 1 year post-stroke. RESULTS: A total of 243 participants were enrolled, 81 of which had a recent ischemic stroke. Participants had a mean age of 75, 57% were women, and 52% were African American. Cortical amyloid did not differ significantly by race, stroke status, or CDR post-stroke. There were racial differences in MMSE scores at baseline (mean 26.8 for African Americans, 27.9 for non-Hispanic whites, p = 0.03), but not longitudinally. African Americans were more likely to have microbleeds (32.8% vs 22.6%, p = 0.04), and within the acute stroke group, African Americans were more likely to have small infarcts (75.6% vs 56.8%, p = 0.049). CONCLUSION: Preclinical Alzheimer disease did not show evidence of being a risk factor for stroke nor predictive of post-stroke dementia. We did not observe racial differences in ß-amyloid levels. However, even after controlling for several vascular risk factors, African Americans with clinical stroke presentations had greater levels of vascular pathology on MRI.

Transient focal increase in perihematomal glucose metabolism after acute human intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Progressive perihematomal cell death over 3 to 4 days has been described after experimental intracerebral hemorrhage (ICH). We investigated whether progressive perihematomal damage occurs in human subjects by measuring relative changes in regional cerebral glucose metabolism with (18)F-fluorordeoxyglucose (FDG) positron emission tomography at multiple time points during the first week after ICH. METHODS: Thirteen subjects with a median hematoma volume of 22 cm(3) were studied 1.0+/-0.3, 2.9+/-0.8, and 6.7+/-1.6 days after ICH. Normalized mean counts in 5 concentric annular 2-mm-thick perihematomal volumes-of-interest (VOIs) were compared to the initial study. Next, automated searches with 0.5 to 5.0 mL spherical VOIs identified maximum focal changes in normalized counts compared to the initial study. RESULTS: No annular or focal decrease in perihematomal FDG uptake developed. Instead, FDG uptake significantly increased at session #2 in the first 3 2-mm annular VOIs (9.2%+/-14.2, 7.8%+/-11.3, 5.9%+/-9.0), returning to baseline at session #3. The VOI search identified focal regions of increased perihematomal FDG uptake relative to the contralateral control hemispheres in 6 subjects, which accounted for the annular increase. CONCLUSIONS: Perihematomal glucose metabolism increased transiently in a subset of patients 2 to 4 days after acute ICH. These transient focal increases in glucose metabolism occurring in the brain after acute ICH demonstrate that there are ongoing processes in response to injury that last for days. Although further studies are needed to elucidate their pathophysiology, these processes may be indicative of a prolonged window for intervention to improve neurological outcome.

Red blood cell transfusion increases cerebral oxygen delivery in anemic patients with subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Anemia is common after subarachnoid hemorrhage and may exacerbate the reduction in oxygen delivery (DO(2)) underlying delayed cerebral ischemia. The association between lower hemoglobin and worse outcome, including more cerebral infarcts, supports a role for red blood cell transfusion to correct anemia. However, the cerebral response to transfusion remains uncertain, because higher hemoglobin may increase viscosity and further impair cerebral blood flow (CBF) in the setting of vasospasm. METHODS: Eight patients with aneurysmal subarachnoid hemorrhage and hemoglobin <10 g/dL were studied with (15)O-positron emission tomography before and after transfusion of 1 U red blood cells. Paired t tests were used to analyze the change in global and regional CBF, oxygen extraction fraction, and oxygen metabolism after transfusion. DO(2) was calculated from CBF and arterial oxygen content. CBF, oxygen metabolism, and DO(2) are reported in mL/100 g/min. RESULTS: Transfusion resulted in a 15% rise in hemoglobin (8.7+/-0.8 to 10.0+/-1.0 g/dL) and arterial oxygen content (11.8+/-1.0 to 13.6+/-1.1 mL/dL; both P<0.001). Global CBF remained stable (40.5+/-8.1 to 41.6+/-9.9), resulting in an 18% rise in DO(2) from 4.8+/-1.1 to 5.7+/-1.4 (P=0.017). This was associated with a fall in oxygen extraction fraction from 0.49+/-0.11 to 0.41+/-0.11 (P=0.11) and stable oxygen metabolism. Rise in DO(2) was greater (28%) in regions with oligemia (low DO(2) and oxygen extraction fraction > or =0.5) at baseline but was attenuated (10%) within territories exhibiting angiographic vasospasm, where CBF fell 7%. CONCLUSIONS: Transfusion of red blood cells to anemic patients with subarachnoid hemorrhage resulted in a significant rise in cerebral DO(2) without lowering global CBF. This was associated with reduced oxygen extraction fraction, which may improve tolerance of vulnerable brain regions to further impairments of CBF. Further studies are needed to confirm the benefit of transfusion on delayed cerebral ischemia and balance this against potential systemic and cerebral risks.

Burden of cerebral hypoperfusion in patients with delayed cerebral ischemia after subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) may result in focal neurological deficits and cerebral infarction, believed to result from critical regional rather than global impairments in cerebral blood flow (CBF). However, the burden of such regional hypoperfusion has not been evaluated by gold-standard voxel-by-voxel CBF measurements. Specifically, the authors sought to determine whether the proportion of brain affected by hypoperfusion was greater in patients with DCI than in SAH controls without DCI and whether the symptomatic hemisphere (in those with lateralizing deficits) exhibited a greater cerebral hypoperfusion burden. METHODS: Sixty-one patients with aneurysmal SAH underwent 15O PET to measure regional CBF during the period of risk for DCI (median 8 days after SAH, IQR 7-10 days). Regions of visibly abnormal brain on head CT studies, including areas of hemorrhage and infarction, were excluded. Burden of hypoperfusion was defined as the proportion of PET voxels in normal-appearing brain with CBF < 25 ml/100 g/min. Global CBF and hypoperfusion burden were compared between patients with and those without DCI at the time of PET. For patients with focal impairments from DCI, the authors also compared average CBF and hypoperfusion burden in symptomatic versus asymptomatic hemispheres. RESULTS: Twenty-three patients (38%) had clinical DCI at the time of PET. Those with DCI had higher mean arterial pressure (MAP; 126 ± 14 vs 106 ± 12 mm Hg, p < 0.001) and 18 (78%) were on vasopressor therapy at the time of PET study. While global CBF was not significantly lower in patients with DCI (mean 39.4 ± 11.2 vs 43.0 ± 8.3 ml/100 g/min, p = 0.16), the burden of hypoperfusion was greater (20%, IQR 12%-23%, vs 12%, 9%-16%, p = 0.006). Burden of hypoperfusion performed better than global CBF as a predictor of DCI (area under the curve 0.71 vs 0.65, p = 0.044). Neither global CBF nor hypoperfusion burden differed in patients who responded to therapy compared to those who had not improved by the time of PET. Although hemispheric CBF was not lower in the symptomatic versus contralateral hemisphere in the 13 patients with focal deficits, there was a trend toward greater burden of hypoperfusion in the symptomatic hemisphere (21% vs 18%, p = 0.049). CONCLUSIONS: The burden of hypoperfusion was greater in patients with DCI, despite hemodynamic therapies, higher MAP, and equivalent global CBF. Similarly, hypoperfusion burden was greater in the symptomatic hemisphere of DCI patients with focal deficits even though the average CBF was similar to that in the contralateral hemisphere. Evaluating the proportion of the brain with critical hypoperfusion after SAH may better capture the extent of DCI than averaging CBF across heterogenous brain regions.

Education Research: Physician identification and patient satisfaction on an academic neurology inpatient service.

OBJECTIVE: To determine the relationship between neurology inpatient satisfaction and (1) number of physicians involved in the patient's care and (2) patients' ability to identify their physicians. METHODS: A 10-item questionnaire addressing patient satisfaction and identification of physicians on the care team was administered to patients admitted to an academic, tertiary care, inpatient neurology service from May 1 to October 31, 2012. We hypothesized higher satisfaction among patients having fewer physicians on the care team and among patients able to identify their physicians. RESULTS: A total of 652 patients were enrolled. An average of 3.9 (range 3-8) physicians were involved in each patient's care. Patients were able to correctly identify on average 2.4 (60.7%) physicians involved in their care. Patients who were very satisfied correctly identified a larger percentage of physicians involved in their care (63.8% vs 50.7%, p < 0.001), were more likely to identify a physician who knew them best (94.3% vs 43.6%, p < 0.001) and who was "in charge" of their care (94.1% vs 57.6%, p < 0.001), and were more likely to have private insurance (82.8% vs 70.5%, p < 0.001) and fewer physicians involved in their care (3.84 vs 4.06, p = 0.02). CONCLUSIONS: Neurology inpatients' ability to identify physicians involved in their care is associated with patient satisfaction. Strategies to enhance patient satisfaction might target improving physician identification, reducing actual or perceived disparities in care based on payer status, and reducing handoffs or conducting handoffs at the bedside.

Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography. METHODS: In a systematic review of OVID MEDLINE-with additional hand-searching of relevant studies' bibliographies- from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5-24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known. FINDINGS: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56-76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36-0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46-11·60; p<0·0001), antiplatelet use (1·68, 1·06-2·66; p=0·026), and anticoagulant use (3·48, 1·96-6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75-0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95-6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03-0·07). INTERPRETATION: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials. FUNDING: UK Medical Research Council and British Heart Foundation.