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Immediate-use steam sterilization (IUSS) shortens the time of sterilization but may increase the risk of surgical site infection (SSI). Among 23,919 procedures with 416 (1.7%) procedures resulting in SSI, IUSS was associated with a 1.52 (95% CI, 1.10-2.11) times higher risk of SSI. IUSS should be minimized., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2024.)

Objective: Prior studies evaluating the impact of discontinuation of contact precautions (DcCP) on methicillin-resistant Staphylococcus aureus (MRSA) outcomes have characterized all healthcare-associated infections (HAIs) rather than those likely preventable by contact precautions. We aimed to analyze the impact of DcCP on the rate of MRSA HAI including transmission events identified through whole genome sequencing (WGS) surveillance., Design: Quasi experimental interrupted time series., Setting: Acute care medical center., Participants: Inpatients., Methods: The effect of DcCP (use of gowns and gloves) for encounters among patients with MRSA carriage was evaluated using time series analysis of MRSA HAI rates from January 2019 through December 2022, compared to WGS-defined attributable transmission events before and after DcCP in December 2020., Results: The MRSA HAI rate was 4.22/10,000 patient days before and 2.98/10,000 patient days after DcCP (incidence rate ratio [IRR] 0.71 [95% confidence interval 0.56-0.89]) with a significant immediate decrease ( P = .001). There were 7 WGS-defined attributable transmission events before and 11 events after DcCP (incident rate ratio 0.90 [95% confidence interval 0.30-2.55])., Conclusions: DcCP did not result in an increase in MRSA HAI or, in WGS-defined attributable transmission events. Comprehensive analyses of the effect of transmission prevention measures should include outcomes specifically measuring transmission-associated HAI., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2024.)

We estimated the extent of respiratory virus transmission over three pre-COVID-19 seasons. Of 16,273 assays, 22.9% (3,726) detected ≥1 respiratory virus. The frequency of putatively hospital-acquired infection ranged from 6.9% (influenza A/B) to 24.7% (adenovirus). The 176 clusters were most commonly associated with rhinovirus/enterovirus (70) and influenza A/B (62).

Objectives: New Delhi metallo-β-lactamase (NDM) is an emergent mechanism of carbapenem resistance associated with high mortality and limited treatment options. Because the bla NDM resistance gene is often carried on plasmids, traditional infection prevention and control (IP&C) surveillance methods and reactive whole genome sequencing (WGS) may not detect plasmid transfer in multispecies outbreaks., Methods: Initial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance performed weekly. To resolve NDM-encoding plasmids, we performed long-read sequencing and constructed hybrid assemblies. WGS data for suspected outbreaks was shared with the IP&C team for assessment and intervention., Results: We observed a multispecies outbreak of NDM-5-producing Enterobacterales isolated from 15 patients between February 2021 and February 2023. The 19 clinical and surveillance isolates sequenced included 7 bacterial species encoding the same NDM-5 plasmid. WGS surveillance and epidemiologic investigation characterized 10 horizontal plasmid transfer events and 6 bacterial transmission events between patients in varying hospital units., Conclusions: Our investigation revealed a complex, multispecies outbreak of NDM involving multiple plasmid transfer and bacterial transmission events. We highlight the utility of combining traditional IP&C and prospective genomic methods in identifying and containing plasmid-associated outbreaks., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We describe 2 cases of extensively drug-resistant Pseudomonas aeruginosa infection caused by a strain of public health concern, as it was recently associated with a nationwide outbreak of contaminated artificial tears. Both cases were detected through database review of genomes in the Enhanced Detection System for Hospital-Associated Transmission (EDS-HAT), a routine genome sequencing-based surveillance program. We generated a high-quality reference genome for the outbreak strain from an isolate from our center and examined the mobile elements encoding blaVIM-80 and bla-GES-9 carbapenemases. We used publicly available Pseudomonas aeruginosa genomes to explore the genetic relatedness and antimicrobial resistance genes of the outbreak strain., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To describe a novel attribution metric estimating the causal source location of healthcare-associated Clostridioides difficile and compare it with the current US National Healthcare Safety Network (NHSN) surveillance reporting standard., Design: Quality improvement study., Setting: Two acute care facilities., Methods: A novel attribution metric assigned days of attribution to locations where patients were located for 14 days before and the day of their C. difficile diagnosis. We correlated the NHSN-assigned unit attribution with the novel attribution measure and compared the proportion of attribution assigned to inpatient units., Results: During a 30-month period, there were 727 NHSN C. difficile healthcare-associated infections (HAIs) and 409 non-HAIs; the novel metric attributed 17,034 days. The correlation coefficients for NHSN and novel attributions among non-ICU units were 0.79 (95% CI, 0.76-0.82) and 0.74 (95% CI, 0.70-0.78) and among ICU units were 0.70 (95% CI, 0.63-0.76) and 0.69 (95% CI, 0.60-0.77) at facilities A and B, respectively. The distribution of difference in percent attribution showed higher inpatient unit attribution using NHSN measure than the novel attribution metric: 38% of ICU units and 15% of non-ICU units in facility A, and 20% of ICU units and 25% of non-ICU units in facility B had a median difference >0; no inpatient units showed a greater attribution using the novel attribution metric., Conclusion: The novel attribution metric shifts attribution from inpatient units to other settings and correlates modestly with NHSN methodology of attribution. If validated, the attribution metric may more accurately target C. difficile reduction efforts., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2023.)

Objective: To assess the impact of a 24-hour autocancellation of uncollected Clostridioides difficile samples in reducing reported healthcare-associated infections (HAIs)., Design: Quality-improvement, before-and-after implementation study., Setting: The study was conducted in 17 hospitals in Pennsylvania., Interventions: Clostridioides difficile tests that are not collected within 24 hours are automatically canceled ("autocancel") through the electronic health record. The intervention took place at 2 facilities (intervention period November 2021-July 2022) and subsequently at 15 additional facilities (April 2022-July 2022). Quality measures included percentage of orders canceled, C. difficile HAI rate, percent positivity of completed tests, and potential adverse outcomes of canceled or delayed testing., Results: Of 6,101 orders, 1,090 (17.9%) were automatically canceled after not being collected for 24 hours during the intervention periods. The reported C. difficile HAI rates per 10,000 patient days did not significantly change. These rates were 8.07 in the 6-month preintervention period and 8.77 in the intervention period for facilities A and B combined (incidence rate ratio [IRR], 1.09; 95% CI, 0.88-1.34; P = .43), and were 5.23 HAIs per 10,000 patient days in the 6-month preintervention period and 5.33 in the intervention period for facilities C-Q combined (IRR, 1.02; 95% CI, 0.79-1.32; P = .87). From the preintervention to the intervention periods, the percent positivity rates of completed C. difficile tests increased by 1.1% for facilities A and B and by 1.4% for facilities C-Q. No adverse outcomes were observed., Conclusions: The 24-hour autocancellation of uncollected C. difficile orders reduced testing but did not result in reported HAI reduction.

Background: Mobile ultraviolet (UV) disinfection uses UV-C light to render microorganisms nonviable and reduce environmental transmission of pathogens in hospital settings. Optimal strategies for deployment must consider the cost, physical layout, and staffing resources. The aim of this quality improvement study was to increase UV disinfection utilization by developing novel deployment strategies without adding resources., Methods: A novel deployment strategy and tools were developed by a multidisciplinary group that included infection prevention, environmental services, and nursing unit staff. Utilization was tracked via a manufacturer-supported database. The infection prevention team analyzed the weekly UV disinfection minutes, cycles, and proportions of cycles completed in defined areas across 4 periods: baseline, pilot, baseline 2, and intervention., Results: The median (range) disinfection cycle times per week during a geographically confined pilot (4,985 minutes [3,476-6,551] minutes) and the intervention period (1,454 [512-3,085] minutes) were lower than either baseline period (5,394 [3,953-6,987] and 6,641 [2,830-7,276] minutes, respectively). Cycles per week were lower in the intervention period than in the preceding 3 periods., Conclusions: Use of UV disinfection in acute care settings should be guided by multidisciplinary groups balancing resources against efficacy and using tailored tools to promote efficiency., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate variables that affect risk of contamination for endoscopic retrograde cholangiopancreatography and endoscopic ultrasound endoscopes., Design: Observational, quality improvement study., Setting: University medical center with a gastrointestinal endoscopy service performing ∼1,000 endoscopic retrograde cholangiopancreatography and ∼1,000 endoscopic ultrasound endoscope procedures annually., Methods: Duodenoscope and linear echoendoscope sampling (from the elevator mechanism and instrument channel) was performed from June 2020 through September 2021. Operational changes during this period included standard reprocessing with high-level disinfection with ethylene oxide gas sterilization (HLD-ETO) was switched to double high-level disinfection (dHLD) (June 16, 2020-July 15, 2020), and duodenoscopes changed to disposable tip model (March 2021). The frequency of contamination for the co-primary outcomes were characterized by calculated risk ratios., Results: The overall pathogenic contamination rate was 4.72% (6 of 127). Compared to duodenoscopes, linear echoendoscopes had a contamination risk ratio of 3.64 (95% confidence interval [CI], 0.69-19.1). Reprocessing using HLD-ETO was associated with a contamination risk ratio of 0.29 (95% CI, 0.06-1.54). Linear echoendoscopes undergoing dHLD had the highest risk of contamination (2 of 18, 11.1%), and duodenoscopes undergoing HLD-ETO and the lowest risk of contamination (0 of 53, 0%). Duodenoscopes with a disposable tip had a 0% contamination rate (0 of 27)., Conclusions: We did not detect a significant reduction in endoscope contamination using HLD-ETO versus dHLD reprocessing. Linear echoendoscopes have a risk of contamination similar to that of duodenoscopes. Disposable tips may reduce the risk of duodenoscope contamination.

Objective: To evaluate the impact of a diagnostic stewardship intervention on Clostridioides difficile healthcare-associated infections (HAI)., Design: Quality improvement study., Setting: Two urban acute care hospitals., Interventions: All inpatient stool testing for C. difficile required review and approval prior to specimen processing in the laboratory. An infection preventionist reviewed all orders daily through chart review and conversations with nursing; orders meeting clinical criteria for testing were approved, orders not meeting clinical criteria were discussed with the ordering provider. The proportion of completed tests meeting clinical criteria for testing and the primary outcome of C. difficile HAI were compared before and after the intervention., Results: The frequency of completed C. difficile orders not meeting criteria was lower [146 (7.5%) of 1,958] in the intervention period (January 10, 2022-October 14, 2022) than in the sampled 3-month preintervention period [26 (21.0%) of 124; P < .001]. C. difficile HAI rates were 8.80 per 10,000 patient days prior to the intervention (March 1, 2021-January 9, 2022) and 7.69 per 10,000 patient days during the intervention period (incidence rate ratio, 0.87; 95% confidence interval, 0.73-1.05; P = .13)., Conclusions: A stringent order-approval process reduced clinically nonindicated testing for C. difficile but did not significantly decrease HAIs., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2023.)

Background: Most hospitals use traditional infection prevention (IP) methods for outbreak detection. We developed the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), which combines whole-genome sequencing (WGS) surveillance and machine learning (ML) of the electronic health record (EHR) to identify undetected outbreaks and the responsible transmission routes, respectively., Methods: We performed WGS surveillance of healthcare-associated bacterial pathogens from November 2016 to November 2018. EHR ML was used to identify the transmission routes for WGS-detected outbreaks, which were investigated by an IP expert. Potential infections prevented were estimated and compared with traditional IP practice during the same period., Results: Of 3165 isolates, there were 2752 unique patient isolates in 99 clusters involving 297 (10.8%) patient isolates identified by WGS; clusters ranged from 2-14 patients. At least 1 transmission route was detected for 65.7% of clusters. During the same time, traditional IP investigation prompted WGS for 15 suspected outbreaks involving 133 patients, for which transmission events were identified for 5 (3.8%). If EDS-HAT had been running in real time, 25-63 transmissions could have been prevented. EDS-HAT was found to be cost-saving and more effective than traditional IP practice, with overall savings of $192 408-$692 532., Conclusions: EDS-HAT detected multiple outbreaks not identified using traditional IP methods, correctly identified the transmission routes for most outbreaks, and would save the hospital substantial costs. Traditional IP practice misidentified outbreaks for which transmission did not occur. WGS surveillance combined with EHR ML has the potential to save costs and enhance patient safety., Competing Interests: Potential conflicts of interest. V. S. C. reports serving on the Board of Directors, American Society of Microbiology, and reports being a co-founder, equity stakeholder of Microbial Genome Sequencing, LLC. G. M. S. reports serving as a scientific advisor, Infectious Diseases Connect (received personal payments as advisor on issues related to infection prevention and control) and Chair, Publications Committee, Society for Healthcare Epidemiology of America (volunteer). D. V. T. reports being a paid consultant for Century Therapeutics. L. H. H. reports receiving consulting fees from Infectious Diseases Connect for a presentation about the present work at a scientific advisory board meeting. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Reconstruction of distal wounds in lower extremities can be challenging due to the lack of tissue to perform local flaps. Fasciocutaneous and muscular flaps are some options for coverage, such as the reverse-flow fasciocutaneous sural flap., Objective: To present an 18-month experience on ankle, calcaneus, and foot reconstruction using the reverse-flow sural flap, performed by the Complex Wounds Group of the Plastic Surgery Department of the University of São Paulo Medical School., Methods: An observational, retrospective and descriptive study was performed through data survey on medical records of all patients treated between November 2018 and June 2020., Results: Nine reverse-flow fasciocutaneous sural flaps were performed. All patients were men. The mean age was 38 years old. Five patients had acute wounds for traffic collision, one electrical trauma and three chronic post-traumatic injuries. The ankle was the most common injury site (6), followed by foot (2) and calcaneus (1). Four patients had complications, three of which were partial necrosis and one distal epitheliosis. No case of total necrosis was recorded. The average hospital stay was 30.1 days., Conclusion: The reverse-flow fasciocutaneous sural flap proved to be a viable, reproducible, and reliable option for distal lower limb reconstruction. Level of Evidence IV, Case Series., Competing Interests: All authors declare no potential conflict of interest related to this article.

Background: Traditional methods of outbreak investigations utilize reactive whole genome sequencing (WGS) to confirm or refute the outbreak. We have implemented WGS surveillance and a machine learning (ML) algorithm for the electronic health record (EHR) to retrospectively detect previously unidentified outbreaks and to determine the responsible transmission routes., Methods: We performed WGS surveillance to identify and characterize clusters of genetically-related Pseudomonas aeruginosa infections during a 24-month period. ML of the EHR was used to identify potential transmission routes. A manual review of the EHR was performed by an infection preventionist to determine the most likely route and results were compared to the ML algorithm., Results: We identified a cluster of 6 genetically related P. aeruginosa cases that occurred during a 7-month period. The ML algorithm identified gastroscopy as a potential transmission route for 4 of the 6 patients. Manual EHR review confirmed gastroscopy as the most likely route for 5 patients. This transmission route was confirmed by identification of a genetically-related P. aeruginosa incidentally cultured from a gastroscope used on 4of the 5 patients. Three infections, 2 of which were blood stream infections, could have been prevented if the ML algorithm had been running in real-time., Conclusions: WGS surveillance combined with a ML algorithm of the EHR identified a previously undetected outbreak of gastroscope-associated P. aeruginosa infections. These results underscore the value of WGS surveillance and ML of the EHR for enhancing outbreak detection in hospitals and preventing serious infections., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Vancomycin-resistant enterococci (VRE) are a major cause of hospital-acquired infections. The risk of infection from interventional radiology (IR) procedures is not well documented. Whole-genome sequencing (WGS) surveillance of clinical bacterial isolates among hospitalized patients can identify previously unrecognized outbreaks., Methods: We analyzed WGS surveillance data from November 2016 to November 2017 for evidence of VRE transmission. A previously unrecognized cluster of 10 genetically related VRE (Enterococcus faecium) infections was discovered. Electronic health record review identified IR procedures as a potential source. An outbreak investigation was conducted., Results: Of the 10 outbreak patients, 9 had undergone an IR procedure with intravenous (IV) contrast ≤22 days before infection. In a matched case-control study, preceding IR procedure and IR procedure with contrast were associated with VRE infection (matched odds ratio [MOR], 16.72; 95% confidence interval [CI], 2.01 to 138.73; P = .009 and MOR, 39.35; 95% CI, 7.85 to infinity; P < .001, respectively). Investigation of IR practices and review of the manufacturer's training video revealed sterility breaches in contrast preparation. Our investigation also supported possible transmission from an IR technician. Infection prevention interventions were implemented, and no further IR-associated VRE transmissions have been observed., Conclusions: A prolonged outbreak of VRE infections related to IR procedures with IV contrast resulted from nonsterile preparation of injectable contrast. The fact that our VRE outbreak was discovered through WGS surveillance and the manufacturer's training video that demonstrated nonsterile technique raise the possibility that infections following invasive IR procedures may be more common than previously recognized., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains belonging to sequence type 258 (ST258) are frequent causes of hospital-associated outbreaks and are a major contributor to the spread of carbapenemases. This genetic lineage emerged several decades ago and remains a major global health care challenge. In this study, genomic epidemiology was used to investigate the emergence, evolution, and persistence of ST258 carbapenem-resistant K. pneumoniae outbreak-causing lineages at a large tertiary care hospital over 8 years. A time-based phylogenetic analysis of 136 ST258 isolates demonstrated the succession of multiple genetically distinct ST258 sublineages over the 8-year period. Ongoing genomic surveillance identified the emergence and persistence of several distinct clonal ST258 populations. Patterns of multidrug resistance determinants and plasmid replicons were consistent with continued evolution and persistence of these populations. Five ST258 outbreaks were documented, including three that were caused by the same clonal lineage. Mutations in genes encoding effectors of biofilm production and iron acquisition were identified among persistent clones. Two emergent lineages bearing K. pneumoniae integrative conjugative element 10 (ICE Kp10 ) and harboring yersiniabactin and colibactin virulence factors were identified. The results show how distinct ST258 subpopulations have evolved and persisted within the same hospital over nearly a decade. IMPORTANCE The carbapenem class of antibiotics is invaluable for the treatment of selected multidrug-resistant Gram-negative pathogens. The continued transmission of carbapenem-resistant bacteria such as ST258 K. pneumoniae is of serious global public health concern, as treatment options for these infections are limited. This genomic epidemiologic investigation traced the natural history of ST258 K. pneumoniae in a single health care setting over nearly a decade. We found that distinct ST258 subpopulations have caused both device-associated and ward-associated outbreaks, and some of these populations remain endemic within our hospital to the present day. The finding of virulence determinants among emergent ST258 clones supports the idea of convergent evolution of drug-resistant and virulent CRKP strains and highlights the need for continued surveillance, prevention, and control efforts to address emergent and evolving ST258 populations in the health care setting., (Copyright © 2019 Marsh et al.)

Objective: Recovery of multidrug-resistant (MDR) Pseudomonas aeruginosa and Klebsiella pneumoniae from a cluster of patients in the medical intensive care unit (MICU) prompted an epidemiologic investigation for a common exposure., Methods: Clinical and microbiologic data from MICU patients were retrospectively reviewed, MICU bronchoscopes underwent culturing and borescopy, and bronchoscope reprocessing procedures were reviewed. Bronchoscope and clinical MDR isolates epidemiologically linked to the cluster underwent molecular typing using pulsed-field gel electrophoresis (PFGE) followed by whole-genome sequencing., Results: Of the 33 case patients, 23 (70%) were exposed to a common bronchoscope (B1). Both MDR P. aeruginosa and K. pneumonia were recovered from the bronchoscope's lumen, and borescopy revealed a luminal defect. Molecular testing demonstrated genetic relatedness among case patient and B1 isolates, providing strong evidence for horizontal bacterial transmission. MDR organism (MDRO) recovery in 19 patients was ultimately linked to B1 exposure, and 10 of 19 patients were classified as belonging to an MDRO pseudo-outbreak., Conclusions: Surveillance of bronchoscope-derived clinical culture data was important for early detection of this outbreak, and whole-genome sequencing was important for the confirmation of findings. Visualization of bronchoscope lumens to confirm integrity should be a critical component of device reprocessing.

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., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To clarify whether recurrence risk for intracerebral hemorrhage (ICH) is higher among black and Hispanic individuals and whether this disparity is attributable to differences in blood pressure (BP) measurements and their variability., Methods: We analyzed data from survivors of primary ICH enrolled in 2 separate studies: (1) the longitudinal study conducted at Massachusetts General Hospital (n = 759), and (2) the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study (n = 1,532). Participants underwent structured interview at enrollment (including self-report of race/ethnicity) and were followed longitudinally via phone calls and review of medical records. We captured systolic BP (SBP) and diastolic BP measurements, and quantified variability as SBP and diastolic BP variation coefficients. We used multivariable (Cox regression) survival analysis to identify risk factors for ICH recurrence., Results: We followed 2,291 ICH survivors (1,121 white, 529 black, 605 Hispanic, and 36 of other race/ethnicity). Both black and Hispanic patients displayed higher SBP during follow-up ( p < 0.05). Black participants also displayed greater SBP variability during follow-up ( p = 0.032). In univariable analyses, black and Hispanic patients were at higher ICH recurrence risk ( p < 0.05). After adjusting for BP measurements and their variability, both Hispanic (hazard ratio = 1.51, 95% confidence interval 1.14-2.00, p = 0.004) and black (hazard ratio = 1.98, 95% confidence interval 1.36-2.86, p < 0.001) patients remained at higher risk of ICH recurrence., Conclusion: Black and Hispanic patients are at higher risk of ICH recurrence; hypertension severity (average BP and its variability) does not fully account for this finding. Additional studies will be required to further elucidate determinants for this health disparity., (© 2018 American Academy of Neurology.)

Background and Purpose: Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemorrhage (ICH). We performed a genome-wide association study (GWAS) of hematoma volume with the aim of identifying novel biological pathways involved in the pathophysiology of primary brain injury in ICH., Methods: We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admission head computed tomography to calculate hematoma volume via semiautomated computer-assisted technique. After quality control and imputation, 7 million genetic variants were available for association testing with ICH volume, which was performed separately in lobar and nonlobar ICH cases using linear regression. Signals with P <5×10 - 8 were pursued in replication and tested for association with admission Glasgow coma scale and 3-month post-ICH dichotomized (0-2 versus 3-6) modified Rankin Scale using ordinal and logistic regression, respectively., Results: The discovery phase included 394 ICH cases (228 lobar and 166 nonlobar) and identified 2 susceptibility loci: a genomic region on 22q13 encompassing PARVB (top single-nucleotide polymorphism rs9614326: β, 1.84; SE, 0.32; P =4.4×10 -8 ) for lobar ICH volume and an intergenic region overlying numerous copy number variants on 17p12 (top single-nucleotide polymorphism rs11655160: β, 0.95; SE, 0.17; P =4.3×10 -8 ) for nonlobar ICH volume. The replication included 240 ICH cases (71 lobar and 169 nonlobar) and corroborated the association for 17p12 ( P =0.04; meta-analysis P =2.5×10 -9 ; heterogeneity, P =0.16) but not for 22q13 ( P =0.49). In multivariable analysis, rs11655160 was also associated with lower admission Glasgow coma scale (odds ratio, 0.17; P =0.004) and increased risk of poor 3-month modified Rankin Scale (odds ratio, 1.94; P =0.045)., Conclusions: We identified 17p12 as a novel susceptibility risk locus for hematoma volume, clinical severity, and functional outcome in nonlobar ICH. Replication in other ethnicities and follow-up translational studies are needed to elucidate the mechanism mediating the observed association., (© 2018 American Heart Association, Inc.)

Importance: Response to intensive blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH) might vary with the degree of underlying cerebral small vessel disease., Objectives: To characterize cerebral microbleeds (CMBs) in acute ICH and to assess the potential for interaction between underlying small vessel disease (as indicated by CMB number and location) and assignment to acute intensive BP targeting for functional outcomes and hematoma expansion., Design, Setting, and Participants: Preplanned subgroup analyses in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial were performed. The ATACH-2 was an open-label international randomized clinical trial that investigated optimal acute BP lowering in 1000 patients with acute ICH. Analyses followed the intent-to-treat paradigm. Participants were enrolled between May 2011 and September 2015 and followed up for 3 months. Eligible participants were aged at least 18 years with ICH volumes less than 60 mL on computed tomography (CT) and a Glasgow Coma Scale score of at least 5 on initial assessment, in whom study drug could be initiated within 4.5 hours of symptom onset. Eight hundred thirty-three participants were excluded, leaving 167 who had an interpretable axial T2*-weighted gradient-recalled echo sequence on magnetic resonance imaging to assess CMBs for inclusion in these subgroup analyses., Main Outcomes and Measures: The primary outcome of interest was death or disability (modified Ranking Scale score, 4-6) at 3 months. The secondary outcome of interest was hematoma volume expansion of at least 33% on a CT scan obtained 24 hours after randomization compared with the entry scan., Results: A total of 167 patients were included; their mean (SD) age was 61.9 (13.2) years, and 98 (58.7%) were male. Cerebral microbleeds were present in 120 patients. Forty-six of 157 (29.3%) patients had poor outcome (modified Ranking Scale score, ≥4), and hematoma expansion was observed in 29 of 144 (20.1%) patients. Risk of poor outcome was similar for those assigned to intensive vs standard acute BP lowering among patients with CMBs (relative risk, 1.19; 95% CI, 0.61-2.33; P = .61) and those without CMBs (relative risk, 1.42; 95% CI, 0.43-4.70; P = .57), and no significant interaction was observed (interaction coefficient, 0.18; 95% CI, -1.20 to 1.55; P = .80). Risk of hematoma expansion was also similar, and no significant interaction between treatment and CMBs was observed (interaction coefficient, 0.62; 95% CI, -1.08 to 2.31; P = .48)., Conclusions and Relevance: Cerebral microbleeds are highly prevalent among patients with ICH but do not seem to influence response to acute intensive BP treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT01176565.

Rapid reversal of coagulopathy is recommended in warfarin-associated intracerebral hemorrhage (WAICH). However, rapid correction of the INR has not yet been proven to improve clinical outcomes, and the rate of correction with fresh-frozen plasma (FFP) can be variable. We sought to determine whether faster INR reversal with FFP is associated with decreased hematoma expansion and improved outcome. We performed a retrospective analysis of a prospectively collected cohort of consecutive patients with WAICH presenting to an urban tertiary care hospital from 2000 to 2013. Patients with baseline INR > 1.4 treated with FFP and vitamin K were included. The primary outcomes are occurrence of hematoma expansion, discharge modified Rankin Scale (mRS), and 30-day mortality. The association between timing of INR reversal, ICH expansion, and outcome was investigated with logistic regression analysis. 120 subjects met inclusion criteria (mean age 76.9, 57.5% males). Median presenting INR was 2.8 (IQR 2.3-3.4). Hematoma expansion is not associated with slower INR reversal [median time to INR reversal 9 (IQR 5-14) h vs. 10 (IQR 7-16) h, p = 0.61]. Patients with ultimately poor outcome received more rapid INR reversal than those with favorable outcome [9 (IQR 6-14) h vs. 12 (8-19) h, p = 0.064). We find no evidence of an association between faster INR reversal and either reduced hematoma expansion or better outcome.

Introduction: Acute non-traumatic convexity subarachnoid haemorrhage (cSAH) is increasingly recognised in cerebral amyloid angiopathy (CAA). We investigated: (a) the overlap between acute cSAH and cortical superficial siderosis-a new CAA haemorrhagic imaging signature and (b) whether acute cSAH presents with particular clinical symptoms in patients with probable CAA without lobar intracerebral haemorrhage., Methods: MRI scans of 130 consecutive patients meeting modified Boston criteria for probable CAA were analysed for cortical superficial siderosis (focal, ≤3 sulci; disseminated, ≥4 sulci), and key small vessel disease markers. We compared clinical, imaging and cortical superficial siderosis topographical mapping data between subjects with versus without acute cSAH, using multivariable logistic regression., Results: We included 33 patients with probable CAA presenting with acute cSAH and 97 without cSAH at presentation. Patients with acute cSAH were more commonly presenting with transient focal neurological episodes (76% vs 34%; p<0.0001) compared with patients with CAA without cSAH. Patients with acute cSAH were also more often clinically presenting with transient focal neurological episodes compared with cortical superficial siderosis-positive, but cSAH-negative subjects with CAA (76% vs 30%; p<0.0001). Cortical superficial siderosis prevalence (but no other CAA severity markers) was higher among patients with cSAH versus those without, especially disseminated cortical superficial siderosis (49% vs 19%; p<0.0001). In multivariable logistic regression, cortical superficial siderosis burden (OR 5.53; 95% CI 2.82 to 10.8, p<0.0001) and transient focal neurological episodes (OR 11.7; 95% CI 2.70 to 50.6, p=0.001) were independently associated with acute cSAH., Conclusions: This probable CAA cohort provides additional evidence for distinct disease phenotypes, determined by the presence of cSAH and cortical superficial siderosis., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Purpose: Spontaneous cerebellar intracerebral hemorrhage (ICH) has been reported to be mainly associated with vascular changes secondary to hypertension. However, a subgroup of cerebellar ICH seems related to vascular amyloid deposition (cerebral amyloid angiopathy). We sought to determine whether location of hematoma in the cerebellum (deep and superficial regions) was suggestive of a particular hemorrhage-prone small-vessel disease pathology (cerebral amyloid angiopathy or hypertensive vasculopathy)., Methods: Consecutive patients with cerebellar ICH from a single tertiary care medical center were recruited. Based on data from pathological reports, patients were divided according to the location of the primary cerebellar hematoma (deep versus superficial). Location of cerebral microbleeds (CMBs; strictly lobar, strictly deep, and mixed CMB) was evaluated on magnetic resonance imaging., Results: One-hundred and eight patients (84%) had a deep cerebellar hematoma, and 20 (16%) a superficial cerebellar hematoma. Hypertension was more prevalent in deep than in patients with superficial cerebellar ICH (89% versus 65%, respectively; P <0.05). Among patients who underwent magnetic resonance imaging, those with superficial cerebellar ICH had higher prevalence of strictly lobar CMB (43%) and lower prevalence of strictly deep or mixed CMB (0%) compared with those with deep superficial cerebellar ICH (6%, 17%, and 38%, respectively). In a multivariable model, presence of strictly lobar CMB was associated with superficial cerebellar ICH (odds ratio, 3.8; 95% confidence interval, 1.5-8.5; P =0.004)., Conclusions: Our study showed that superficial cerebellar ICH is related to the presence of strictly lobar CMB-a pathologically proven marker of cerebral amyloid angiopathy. Cerebellar hematoma location may thus help to identify those patients likely to have cerebral amyloid angiopathy pathology., (© 2017 American Heart Association, Inc.)

Objective: Oral anticoagulation treatment (OAT) resumption is a therapeutic dilemma in intracerebral hemorrhage (ICH) care, particularly for lobar hemorrhages related to amyloid angiopathy. We sought to determine whether OAT resumption after ICH is associated with long-term outcome, accounting for ICH location (ie, lobar vs nonlobar)., Methods: We meta-analyzed individual patient data from: (1) the multicenter RETRACE study (n = 542), (2) a U.S.-based single-center ICH study (n = 261), and (3) the Ethnic/Racial Variations of Intracerebral Hemorrhage study (n = 209). We determined whether, within 1 year from ICH, OAT resumption was associated with: (1) mortality, (2) favorable functional outcome (modified Rankin Scale = 0-3), and (3) stroke incidence. We separately analyzed nonlobar and lobar ICH cases using propensity score matching and Cox regression models., Results: We included 1,012 OAT-related ICH survivors (633 nonlobar and 379 lobar). Among nonlobar ICH survivors, 178/633 (28%) resumed OAT, whereas 86/379 (23%) lobar ICH survivors did. In multivariate analyses, OAT resumption after nonlobar ICH was associated with decreased mortality (hazard ratio [HR] = 0.25, 95% confidence interval [CI] = 0.14-0.44, p < 0.0001) and improved functional outcome (HR = 4.22, 95% CI = 2.57-6.94, p < 0.0001). OAT resumption after lobar ICH was also associated with decreased mortality (HR = 0.29, 95% CI = 0.17-0.45, p < 0.0001) and favorable functional outcome (HR = 4.08, 95% CI = 2.48-6.72, p < 0.0001). Furthermore, OAT resumption was associated with decreased all-cause stroke incidence in both lobar and nonlobar ICH (both p < 0.01)., Interpretation: These results suggest novel evidence of an association between OAT resumption and outcome following ICH, regardless of hematoma location. These findings support conducting randomized trials to explore risks and benefits of OAT resumption after ICH. Ann Neurol 2017;82:755-765., (© 2017 American Neurological Association.)

To better understand factors influencing spiritual care during critical illness, we examined the use of spiritual care in patients hospitalized with intracerebral hemorrhage (ICH), a frequently disabling and fatal disease. Specifically, the study was designed to examine which demographic and clinical characteristics were associated with chaplain visits to critically ill patients. The charts of consecutive adults (>18) with spontaneous ICH presenting to a single academic medical center between January 2014 and September 2015 were reviewed. Chaplains visited 86 (32%) of the 266 patients. Family requests initiated the majority of visits (57%). Visits were disproportionately to Catholic patients and those with more severe injury. Even among Catholics, 28% of those who died had no chaplaincy visit. Standardized chaplaincy screening methods and note templates may help maximize access to spiritual care and delineate the religious and spiritual preferences of patients and families.

Primary intracerebral haemorrhage and lacunar ischaemic stroke are acute manifestations of progressive cerebral microvascular disease. Current paradigms suggest atherosclerosis is a chronic, dynamic, inflammatory condition precipitated in response to endothelial injury from various environmental challenges. Myeloperoxidase plays a central role in initiation and progression of vascular inflammation, but prior studies linking myeloperoxidase with stroke risk have been inconclusive. We hypothesized that genetic determinants of myeloperoxidase levels influence the development of vascular instability, leading to increased primary intracerebral haemorrhage and lacunar stroke risk. We used a discovery cohort of 1409 primary intracerebral haemorrhage cases and 1624 controls from three studies, an extension cohort of 12 577 ischaemic stroke cases and 25 643 controls from NINDS-SiGN, and a validation cohort of 10 307 ischaemic stroke cases and 29 326 controls from METASTROKE Consortium with genome-wide genotyping to test this hypothesis. A genetic risk score reflecting elevated myeloperoxidase levels was constructed from 15 common single nucleotide polymorphisms identified from prior genome-wide studies of circulating myeloperoxidase levels (P < 5 × 10-6). This genetic risk score was used as the independent variable in multivariable regression models for association with primary intracerebral haemorrhage and ischaemic stroke subtypes. We used fixed effects meta-analyses to pool estimates across studies. We also used Cox regression models in a prospective cohort of 174 primary intracerebral haemorrhage survivors for association with intracerebral haemorrhage recurrence. We present effects of myeloperoxidase elevating single nucleotide polymorphisms on stroke risk per risk allele, corresponding to a one allele increase in the myeloperoxidase increasing genetic risk score. Genetic determinants of elevated circulating myeloperoxidase levels were associated with both primary intracerebral haemorrhage risk (odds ratio, 1.07, P = 0.04) and recurrent intracerebral haemorrhage risk (hazards ratio, 1.45, P = 0.006). In analysis of ischaemic stroke subtypes, the myeloperoxidase increasing genetic risk score was strongly associated with lacunar subtype only (odds ratio, 1.05, P = 0.0012). These results, demonstrating that common genetic variants that increase myeloperoxidase levels increase risk of primary intracerebral haemorrhage and lacunar stroke, directly implicate the myeloperoxidase pathway in the pathogenesis of cerebral small vessel disease. Because genetic variants are not influenced by environmental exposures, these results provide new support for a causal rather than bystander role for myeloperoxidase in the progression of cerebrovascular disease. Furthermore, these results support a rationale for chronic inflammation as a potential modifiable stroke risk mechanism, and suggest that immune-targeted therapies could be useful for treatment and prevention of cerebrovascular disease., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background and Objective: Due to conflicting results in multiple studies, uncertainty remains regarding sex differences in severity and mortality after intracerebral hemorrhage (ICH). We investigated the impact of sex on ICH severity, expansion, and mortality., Methods: We analyzed prospectively collected ICH patients and assessed clinical variables and mortality rate. Mediation analyses were used to examine associations between sex and mortality and sex and hematoma expansion., Results: 2212 patients were investigated, 53.5% male. Men with ICH were younger (72 vs. 77years), had greater smoking and alcohol use, and were more likely to have hypertension, diabetes, hypercholesterolemia and coronary artery disease (all p<0.05). Lobar hemorrhages were more frequent in women (47.6% vs 38.4%, p<0.001). Male sex was a risk factor for hematoma expansion (Odd Ratio (OR) 1.7, 95% confidence interval (CI) 1.15-2.50, p=0.007). Multivariable analysis found that male sex was independently associated with 90-day mortality (OR 2.15 (95% CI 1.46-3.19), p<0.001), and one-year mortality (Hazard Ratio 1.28 (95% CI: 1.09-1.50), p=0.003). Early hematoma expansion mediated a portion of the association between sex and mortality (mediation p=0.02)., Conclusions: Men with ICH experience a higher risk of both expansion and early and late mortality, even after controlling for known risk factors. Further research is needed to explore the biological mechanisms underlying these observed differences., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Low levels of serum albumin may increase the risk of infections and mortality in critically ill patients. We tested the hypothesis that admission hypoalbuminemia predicted infectious complications and poor outcome in subjects with acute intracerebral hemorrhage (ICH). We analyzed a single center cohort of ICH patients collected between 1994 and 2015. Pneumonia, urinary tract infection and sepsis were retrospectively identified, according to validated criteria. Serum albumin was measured on admission and hypoalbuminemia was defined as total albumin ≤3.5 g/dL. The association between albumin levels, infections, and mortality at 90 days was tested with multivariable logistic regression analyses. A total of 2010 patients were included (median age 74 years, 54.5% males) of whom 444 (22.1%) had hypoalbuminemia on admission and 763 (38%) died within 90 days. The frequency of pneumonia, urinary tract infection, and sepsis was 19.9, 15.1, and 2.7%, respectively. Hypoalbuminemic patients had lower admission Glasgow coma scale, higher frequency of intraventricular hemorrhage and were more likely to have a history of chronic kidney or liver disease. After adjustment for potential confounders, hypoalbuminemia was an independent predictor of pneumonia [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.34-2.33, p < 0.001] and sepsis (OR 2.29, 95% CI 1.22-4.30, p = 0.010). Low levels of albumin were also independently associated with higher mortality at 90 days (OR 1.78, 95% CI 1.30-2.44, p < 0.001). In conclusion, early hypoalbuminemia is common and predicts poor outcome in ICH patients. Increased susceptibility to pneumonia and sepsis may be the pathophysiological mechanism underlying this association.

Background: Lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH)., Methods: We retrospectively analyzed a prospectively collected cohort of ICH patients ascertained between 1994 and 2015. We identified subjects with lymphocyte count obtained within 24 h from onset, and AL was defined as lymphocyte count <1000/μL. Infectious complications were assessed through retrospective chart review. Association between AL, infections, and mortality was investigated using multivariable logistic regression., Results: Of the 2014 patients meeting inclusion criteria, 548 (27.2%) had AL and 605 (30.0%) developed an infectious complication. Case-fatality at 90 days was 36.9%. Patients with AL had larger hematoma volumes, higher frequency of intraventricular hemorrhage, and lower Glasgow Coma Scale score on presentation (all p < 0.001). AL was independently associated with increased risk of pneumonia [odds ratio (OR) 1.97, 95% confidence interval (CI) 1.50-2.58, p < 0.001] and multiple infections (OR 1.84, 95% CI 1.24-2.71, p = 0.003). AL was also an independent predictor of 90-day mortality (OR 1.55, 95% CI 1.18-2.04, p = 0.002) after adjusting for confounders., Conclusions: AL is common in ICH patients and independently associated with increased risk of infectious complications and poor outcome. Further studies will be needed to determine whether prophylactic antibiotics in ICH patients with AL can improve outcome.

Importance: Hematoma expansion is an important determinant of outcome in spontaneous intracerebral hemorrhage (ICH) due to small vessel disease (SVD), but the association between the severity of the underlying SVD and the extent of bleeding at the acute phase is unknown to date., Objective: To investigate the association between key magnetic resonance imaging (MRI) markers of SVD (as per the Standards for Reporting Vascular Changes on Neuroimaging [STRIVE] guidelines) and hematoma volume and expansion in patients with lobar or deep ICH., Design, Setting, and Participants: Analysis of data collected from 418 consecutive patients admitted with primary lobar or deep ICH to a single tertiary care medical center between January 1, 2000, and October 1, 2012. Data were analyzed on March 4, 2016. Participants were consecutive patients with computed tomographic images allowing ICH volume calculation and MRI allowing imaging markers of SVD assessment., Main Outcomes and Measures: The ICH volumes at baseline and within 48 hours after symptom onset were measured in 418 patients with spontaneous ICH without anticoagulant therapy, and hematoma expansion was calculated. Cerebral microbleeds, cortical superficial siderosis, and white matter hyperintensity volume were assessed on MRI. The associations between these SVD markers and ICH volume, as well as hematoma expansion, were investigated using multivariable models., Results: This study analyzed 254 patients with lobar ICH (mean [SD] age, 75 [11] years and 140 [55.1%] female) and 164 patients with deep ICH (mean [SD] age 67 [14] years and 71 [43.3%] female). The presence of cortical superficial siderosis was an independent variable associated with larger ICH volume in the lobar ICH group (odds ratio per quintile increase in final ICH volume, 1.49; 95% CI, 1.14-1.94; P = .004). In multivariable models, the absence of cerebral microbleeds was associated with larger ICH volume for both the lobar and deep ICH groups (odds ratios per quintile increase in final ICH volume, 1.41; 95% CI, 1.11-1.81; P = .006 and 1.43; 95% CI, 1.04-1.99; P = .03; respectively) and with hematoma expansion in the lobar ICH group (odds ratio, 1.70; 95% CI, 1.07-2.92; P = .04). The white matter hyperintensity volumes were not associated with either hematoma volume or expansion., Conclusions and Relevance: In patients admitted with primary lobar or deep ICH to a single tertiary care medical center, the presence of cortical superficial siderosis was an independent variable associated with larger lobar ICH volume, and the absence of cerebral microbleeds was associated with larger lobar and deep ICHs. The absence of cerebral microbleeds was independently associated with more frequent hematoma expansion in patients with lobar ICH. We provide an analytical framework for future studies aimed at limiting hematoma expansion.

Importance: Calcium is a key cofactor of the coagulation cascade and may play a role in the pathophysiology of intracerebral hemorrhage (ICH)., Objective: To investigate whether a low serum calcium level is associated with an increase in the extent of bleeding in patients with ICH as measured by baseline hematoma volume and risk of hematoma expansion., Design, Setting, and Participants: Prospective cohort study of 2103 consecutive patients with primary ICH ascertained during the period between 1994 and 2015 at an academic medical center. The statistical analysis was performed in January 2016., Main Outcomes and Measures: Total calcium level was measured on admission, and hypocalcemia was defined as a serum calcium level of less than 8.4 mg/dL. Baseline and follow-up hematoma volumes, detected by noncontrast computed tomography, were measured using a computer-assisted semiautomatic analysis. Hematoma expansion was defined as an increase of more than 30% or 6 mL from baseline ICH volume. Associations between serum calcium level and baseline hematoma volume and between serum calcium level and ICH expansion were investigated in multivariable linear and logistic regression models, respectively., Results: A total of 2123 patients with primary ICH were screened, and 2103 patients met the inclusion criteria (mean [SD] age, 72.7 [12.5] years; 54.3% male patients), of whom 229 (10.9%) had hypocalcemia on admission. Hypocalcemic patients had a higher median baseline hematoma volume than did normocalcemic patients (37 mL [IQR, 15-72 mL] vs 16 mL [IQR, 6-44 mL]; P < .001). Low calcium levels were independently associated with higher baseline ICH volume (β = -0.13, SE = .03, P < .001). A total of 1393 patients underwent follow-up noncontrast computed tomography and were included in the ICH expansion analysis. In this subgroup, a higher serum calcium level was associated with reduced risk of ICH expansion (odds ratio, 0.55 [95% CI, 0.35-0.86]; P = .01), after adjusting for other confounders., Conclusions and Relevance: Hypocalcemia correlates with the extent of bleeding in patients with ICH. A low calcium level may be associated with a subtle coagulopathy predisposing to increased bleeding and might therefore be a promising therapeutic target for acute ICH treatment trials., Competing Interests: Disclosures: Dr Goldstein reports having received research and consulting fees from CSL Behring and consulting fees from Bristol-Myers Squibb. No other disclosures are reported.

Objective: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH., Methods: We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk., Results: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10 -4 ) with no heterogeneity across studies (I 2  = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10 -6 )., Interpretation: Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740., (© 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Objective: To determine whether hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), a monogenetic disease model for the sporadic variant of amyloid angiopathy (sCAA), has a comparable recurrent intracerebral hemorrhage (ICH) risk and mortality after a first symptomatic ICH., Methods: We included patients with HCHWA-D from the Leiden University Medical Center and patients with sCAA from the Massachusetts General Hospital in a cohort study. Baseline characteristics, hemorrhage recurrence, and short- and long-term mortality were compared. Hazard ratios (HRs) adjusted for age and sex were calculated with Cox regression analyses., Results: We included 58 patients with HCHWA-D and 316 patients with sCAA. Patients with HCHWA-D had fewer cardiovascular risk factors (≥1 risk factor 24% vs 70% in sCAA) and were younger at the time of presenting hemorrhage (mean age 54 vs 72 years in sCAA). Eight patients (14%) with HCHWA-D and 46 patients (15%) with sCAA died before 90 days. During a mean follow-up time of 5 ± 4 years (total 1,550 person-years), the incidence rate of recurrent ICH in patients with HCHWA-D was 20.9 vs 8.9 per 100 person-years in sCAA. Patients with HCHWA-D had a long-term mortality of 8.2 vs 8.4 per 100 person-years in patients with sCAA. After adjustments, patients with HCHWA-D had a higher risk of recurrent ICH (HR 2.8; 95% confidence interval 1.6-4.9; p < 0.001) and a higher long-term mortality (HR 2.8; 95% confidence interval 1.5-5.2; p = 0.001)., Conclusions: Patients with HCHWA-D have worse long-term prognosis after a first ICH than patients with sCAA. The absence of cardiovascular risk factors in most patients with HCHWA-D suggests that vascular amyloid is responsible for the recurrent hemorrhages. HCHWA-D is therefore a pure form of cerebral amyloid angiopathy with an accelerated clinical course and provides a good model to study the pathophysiology and future therapeutic interventions of amyloid-related hemorrhages., (© 2016 American Academy of Neurology.)

Background and Purpose: We recently showed that cerebral amyloid angiopathy (CAA) is associated with functionally relevant brain network impairments, in particular affecting posterior white matter connections. Here we examined how these brain network impairments progress over time., Methods: Thirty-three patients with probable CAA underwent multimodal brain magnetic resonance imaging at 2 time points (mean follow-up time: 1.3±0.4 years). Brain networks of the hemisphere free of intracerebral hemorrhages were reconstructed using fiber tractography and graph theory. The global efficiency of the network and mean fractional anisotropies of posterior-posterior, frontal-frontal, and posterior-frontal network connections were calculated. Patients with moderate versus severe CAA were defined based on microbleed count, dichotomized at the median (median=35)., Results: Global efficiency of the intracerebral hemorrhage-free hemispheric network declined from baseline to follow-up (-0.008±0.003; P=0.029). The decline in global efficiency was most pronounced for patients with severe CAA (group×time interaction P=0.03). The decline in global network efficiency was associated with worse executive functioning (β=0.46; P=0.03). Examination of subgroups of network connections revealed a decline in fractional anisotropies of posterior-posterior connections at both levels of CAA severity (-0.006±0.002; P=0.017; group×time interaction P=0.16). The fractional anisotropies of posterior-frontal and frontal-frontal connections declined in patients with severe but not moderate CAA (group×time interaction P=0.007 and P=0.005). Associations were independent of change in white matter hyperintensity volume., Conclusions: Brain network impairment in patients with CAA worsens measurably over just 1.3-year follow-up and seem to progress from posterior to frontal connections with increasing disease severity., (© 2016 American Heart Association, Inc.)

Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ε2/ε4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5-1.2%). Factors associated with delayed seizures included cortical involvement on index haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P = 0.008) and presence of ≥ 1 APOE ε4 copies (hazard ratio 1.95, P = 0.020). Delayed seizures were associated with worse long-term functional outcome (hazard ratio 1.83, P = 0.005), but the association was removed by adjusting for neuroimaging and genetic markers of cerebral small vessel disease. Delayed seizures after intracerebral haemorrhage are associated with different risk factors, when compared to recurrent seizures. They are also associated with worse functional outcome, but this finding appears to be related to underlying small vessel disease. Further investigations into the connections between small vessel disease and delayed seizures are warranted., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background and Purpose: The computed tomography angiography (CTA) spot sign is a validated predictor of hematoma expansion and poor outcome in supratentorial intracerebral hemorrhage (ICH), but patients with brainstem ICH have typically been excluded from the analyses. We investigated the frequency of spot sign and its relationship with hematoma expansion and outcome in patients with primary pontine hemorrhage (PPH)., Methods: We performed a retrospective analysis of PPH cases obtained from a prospectively collected cohort of consecutive ICH patients who underwent CTA. CTA first-pass readings for spot sign presence were analyzed by two trained readers. Baseline and follow-up hematoma volumes on non-contrast CT scans were assessed by semi-automated computer-assisted volumetric analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratio, and accuracy of spot sign for prediction of in-hospital mortality were calculated., Results: 49 subjects met the inclusion criteria of whom 11 (22.4 %) showed a spot sign. In-hospital mortality was higher in spot sign-positive versus spot sign-negative subjects (90.9 vs 47.4 %, p = 0.020). Spot sign showed excellent specificity (95 %) and PPV (91 %) in predicting in-hospital mortality. Absolute hematoma growth, defined as parenchymal and intraventricular hematoma expansion of any amount, was significantly higher in spot sign-positive versus spot sign-negative subjects (13.72 ± 20.93 vs 3.76 ± 8.55 mL, p = 0.045)., Conclusions: As with supratentorial ICH, the CTA spot sign is a common finding and is associated with higher risk of hematoma expansion and mortality in PPH. This marker may assist clinicians in prognostic stratification.

Importance: Patients who have experienced intracerebral hemorrhage (ICH) appear to develop cognitive impairment at high rates, both early after ICH and over the long term., Objective: To identify and compare risk factors for early and delayed dementia after ICH., Design, Setting, and Participants: A longitudinal study enrolled patients who had experienced ICH from January 1, 2006, to December 31, 2013. A total of 738 participants 18 years or older, without pre-ICH dementia, who presented to a tertiary care academic institution with primary ICH were included in the analyses of early post-ICH dementia (EPID). After accounting for incident dementia and mortality at 6 months, 435 participants were included in the analyses of delayed post-ICH dementia (DPID)., Exposures: Intracerebral hemorrhage., Main Outcomes and Measures: Cognitive performance was captured using the modified Telephone Interview for Cognitive Status test. Outcomes included EPID, diagnosed within 6 months after ICH, and DPID, diagnosed beyond 6 months after ICH., Results: Among 738 patients who had experienced ICH (mean [SD] age, 74.3 [12.1] years; 384 men [52.0%]), 140 (19.0%) developed dementia within 6 months. A total of 435 patients without dementia at 6 months were followed up longitudinally (median follow-up, 47.4 months; interquartile range, 43.4-52.1 months), with an estimated yearly incidence of dementia of 5.8% (95% CI, 5.1%-7.0%). Larger hematoma size (hazard ratio [HR], 1.47 per 10-mL increase; 95% CI, 1.09-1.97; P < .001 for heterogeneity) and lobar location of ICH (HR, 2.04; 95% CI, 1.06-3.91; P = .02 for heterogeneity) were associated with EPID but not with DPID. Educational level (HR, 0.60; 95% CI, 0.40-0.89; P < .001 for heterogeneity), incident mood symptoms (HR, 1.29; 95% CI, 1.02-1.63; P = .01 for heterogeneity), and white matter disease as defined via computed tomography (HR, 1.70; 95% CI, 1.07-2.71; P = .04 for heterogeneity) were associated with DPID but not EPID., Conclusions and Relevance: Incident dementia early after ICH is strongly associated with hematoma size and location. Delayed incident dementia is frequent among patients who have experienced ICH and is not prominently associated with acute characteristics of ICH. These findings suggest the existence of heterogeneous biological mechanisms accounting for early vs delayed cognitive decline among patients who have experienced ICH.

Objective: We sought to determine whether APOE genotype influences a previously observed decline in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels preceding primary intracerebral hemorrhage (ICH), as a potential demonstration of nonamyloid mechanisms of APOE in ICH risk., Methods: We performed a single-center retrospective longitudinal analysis using patients with known APOE genotype drawn from an ongoing cohort study of ICH. Serum lipid measurements for TC, triglycerides (TGs), LDL, and high-density lipoprotein (HDL) collected within 2 years before and after index ICH were extracted from electronic medical records. Piecewise linear mixed-effects models were used to compare APOE allele-specific effects on temporal serum lipid trends in ICH. Demographics, medical history, medications, and health maintenance data were included as fixed effects. Inter- and intraindividual variations in lipid levels were modeled as random effects., Results: A total of 124 ICH cases were analyzed. APOE ε4 carriers had greater rates of decline in serum TC and LDL within 6 months preceding ICH (TC: -7.30 mg/dL/mo, p = 0.0035; LDL: -8.44 mg/dL/mo, p = 0.0001). Conversely, serum TC and LDL levels in APOE ε2 carriers were unchanged within the same time period. APOE genotype had no associations with serum HDL or TG trends., Conclusions: APOE allele status predicts serum TC and LDL changes preceding acute ICH. Our results have implications for ongoing efforts in dissecting the role of dyslipidemia in cerebrovascular disease risk. APOE genotype-specific influence on lipid trends provides a clue for one mechanism by which APOE may influence risk of ICH. Further characterization of the metabolic roles of APOE is needed to improve the understanding of APOE biology in cerebrovascular disease risk.

Background and Purpose: Acute leukocytosis is a well-established response to intracerebral hemorrhage (ICH). Leukocytes, because of their interaction with platelets and coagulation factors, may in turn play a role in hemostasis. We investigated whether admission leukocytosis was associated with reduced bleeding after acute ICH., Methods: Consecutive patients with primary ICH were prospectively collected from 1994 to 2015 and retrospectively analyzed. We included subjects with a follow-up computed tomographic scan available and automated complete white blood cell count performed within 48 hours from onset. Baseline and follow-up hematoma volumes were calculated with semiautomated software, and hematoma expansion was defined as volume increase >30% or 6 mL. The association between white blood cell count and ICH expansion was investigated with multivariate logistic regression., Results: A total of 1302 subjects met eligibility criteria (median age, 75 years; 55.8% men), of whom 207 (15.9%) experienced hematoma expansion. Higher leukocyte count on admission was associated with reduced risk of hematoma expansion (odds ratio for 1000 cells increase, 0.91; 95% confidence interval, 0.86-0.96; P=0.001). The risk of hematoma expansion was inversely associated with neutrophil count (odds ratio, 0.90; 95% confidence interval, 0.85-0.96; P=0.001) and directly associated with monocyte count (odds ratio, 2.71; 95% confidence interval, 1.08-6.83; P=0.034). There was no association between lymphocyte count and ICH expansion (odds ratio, 0.96; 95% confidence interval, 0.79-1.17; P=0.718)., Conclusions: Higher admission white blood cell count is associated with lower risk of hematoma expansion. This highlights a potential role of the inflammatory response in modulating the coagulation cascade after acute ICH., (© 2016 American Heart Association, Inc.)

Objective: We aimed to describe the temporal variation in circulating lipid levels among patients with intracerebral hemorrhage (ICH) and investigate their association with ICH risk., Methods: This was a single-center, retrospective, longitudinal, case-control analysis using cases drawn from an ongoing cohort study of primary ICH and controls drawn from a hospital-based clinical data registry. Piecewise linear mixed-effect random coefficient models were used to determine the significance of changes in serum lipid trends on ICH risk., Results: Two hundred twelve ICH cases and 301 control individuals were analyzed. Overall trends in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels differed between ICH cases and non-ICH controls (p = 0.00001 and p = 0.0092, respectively). Patients with ICH experience accelerated decline in serum TC and LDL levels during 6 months immediately preceding ICH, compared with levels between 6 and 24 months pre-ICH (TC: -29.25 mg/dL, p = 0.001; LDL: -21.48 mg/dL, p = 0.0038), which was not observed in non-ICH controls. Subgroup analysis confirmed that this phenomenon cannot be attributed to statin or alcohol exposure. Serum triglycerides and high-density lipoprotein trends did not differ between groups., Conclusions: Longitudinal lipid levels differ between ICH cases and non-ICH controls, most notably for a decline in serum TC and LDL levels within 6 months preceding primary ICH, independent of statin or alcohol use. These changes in serum TC and LDL trends suggest a biological pathway that precipitates ICH occurrence. Further studies are needed to replicate these results and characterize rate of change in serum lipids as a potential biomarker of impending acute cerebral injury., (© 2016 American Academy of Neurology.)

Objectives: Intracerebral hemorrhage is a devastating disorder with no current treatment. Whether perihematomal edema is an independent predictor of neurologic outcome is controversial. We sought to determine whether perihematomal edema expansion rate predicts outcome after intracerebral hemorrhage., Design: Retrospective cohort study., Setting: Tertiary medical center., Patients: One hundred thirty-nine consecutive supratentorial spontaneous intracerebral hemorrhage patients 18 years or older admitted between 2000 and 2013., Interventions: None., Measurements and Main Results: Intracerebral hemorrhage, intraventricular hemorrhage, and perihematomal edema volumes were measured from CT scans obtained at presentation, 24-hours, and 72-hours postintracerebral hemorrhage. Perihematomal edema expansion rate was the difference between initial and follow-up perihematomal edema volumes divided by the time interval. Logistic regression was performed to evaluate the relationship between 1) perihematomal edema expansion rate at 24 hours and 90-day mortality and 2) perihematomal edema expansion rate at 24 hours and 90-day modified Rankin Scale score. Perihematomal edema expansion rate between admission and 24-hours postintracerebral hemorrhage was a significant predictor of 90-day mortality (odds ratio, 2.97; 95% CI, 1.48-5.99; p = 0.002). This association persisted after adjusting for all components of the intracerebral hemorrhage score (odds ratio, 2.21; 95% CI, 1.05-4.64; p = 0.04). Similarly, higher 24-hour perihematomal edema expansion rate was associated with poorer modified Rankin Scale score in an ordinal shift analysis (odds ratio, 2.40; 95% CI, 1.37-4.21; p = 0.002). The association persisted after adjustment for all intracerebral hemorrhage score components (odds ratio, 2.07; 95% CI, 1.12-3.83; p = 0.02)., Conclusions: Faster perihematomal edema expansion rate 24-hours postintracerebral hemorrhage is associated with worse outcome. Perihematomal edema may represent an attractive translational target for secondary injury after intracerebral hemorrhage.

Background: Cerebral amyloid angiopathy (CAA) is increasingly recognized as a cause of cognitive impairment in the elderly, but the cognitive profile in patients with the disease has not been well characterized., Objective: To characterize the neuropsychological profile of CAA patients without dementia and to determine the association between cognitive performance in different domains and neuroimaging lesions characteristic of CAA., Methods: Fifty-eight non-demented CAA patients were compared to 138 cognitively normal subjects using a standard neuropsychological test battery. Total brain volume (TBV), white matter hyperintensities, number of lobar cerebral microbleeds, hippocampal volume, and cortical superficial siderosis in all CAA patients were assessed. The association between these neuroimaging markers and neuropsychological performance in different cognitive domains in the CAA group were analyzed., Results: Patients with CAA had significantly worse performance on all individual neuropsychological domains tested, when compared to the cognitive normal group. The cognitive decline of CAA patients was most noticeable in tests for processing speed with a Z score of -1.92±1.56 (mean±SD), then followed by executive function (-0.93±1.01), episodic memory (-0.87±1.29), semantic fluency (-0.73±1.06), and attention (-0.42±0.98). TBV of the CAA patients was correlated with processing speed (β= 0.335, p = 0.03) and executive function (β= 0.394, p = 0.01)., Conclusions: Non-demented patients with CAA had cognitive deficits in multiple areas. Lower TBV was related to slower processing speed and worse executive function.

Unlabelled: ESSENTIALS: Fresh frozen plasma (FFP) may be associated with a dose-based risk of pulmonary complications. Patients received FFP for warfarin reversal at a large academic hospital over a 3-year period. Almost 20% developed pulmonary complications, and the risk was highest after > 3 units of FFP. The risk of pulmonary complications remained significant in multivariable analysis., Background: Fresh frozen plasma (FFP) is often administered to reverse warfarin anticoagulation. Administration has been associated with pulmonary complications, but it is unclear whether this risk is dose-related. Aims We sought to characterize the incidence and dose relationship of pulmonary complications, including transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI), after FFP administration for warfarin reversal., Methods: We performed a structured retrospective review of patients who received FFP for warfarin reversal in the emergency department (ED) of an academic tertiary-care hospital over a 3-year period. Logistic regression was used to explore the relationship between FFP dose and risk of pulmonary events., Results: Two hundred and fifty-one patients met the inclusion criteria. Overall, 49 patients (20%) developed pulmonary complications, including 30 (12%) with TACO, two (1%) with TRALI, and 17 (7%) with pulmonary edema not meeting the criteria for TACO. Pulmonary complications were significantly more frequent in those who received > 3 units of FFP (34.0% versus 15.6%, 95% confidence interval for risk difference 7.9%-8.9%). After stratification by subtype of complication, only the risk of TACO was statistically significant (28.3% versus 7.6%, 95% confidence interval for risk difference 8.2%-16.6%). In multivariable analysis controlling for age, sex, initial systolic blood pressure, and intravenous fluids given in the ED, > 3 units of FFP remained a significant risk factor for pulmonary complications (odds ratio 2.49, 95% confidence interval 1.21-5.13)., Conclusions: Almost 20% of patients who received FFP for warfarin reversal developed pulmonary complications, primarily TACO, and this risk increased with > 3 units of FFP. Clinicians should be aware of and prepared to manage these complications., (© 2015 International Society on Thrombosis and Haemostasis.)

Importance: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an important diagnosis to reach in clinical practice because many patients with the disease respond to immunosuppressive therapy. Reliable noninvasive diagnostic criteria for CAA-ri would allow some patients to avoid the risk of brain biopsy., Objective: To test the sensitivity and specificity of clinical and neuroimaging-based criteria for CAA-ri., Design, Setting, and Participants: We modified the previously proposed clinicoradiological criteria and retrospectively analyzed clinical medical records and magnetic resonance imaging fluid-attenuated inversion recovery and gradient-echo scans obtained from individuals with CAA-ri and noninflammatory CAA. At 2 referral centers between October 1, 1995, and May 31, 2013, and between January 1, 2009, and December 31, 2011, participants included 17 individuals with pathologically confirmed CAA-ri and 37 control group members with pathologically confirmed noninflammatory CAA. The control group was further divided into those with past lobar intracerebral hemorrhage (ICH) (n = 21) and those with cerebral microbleeds only and no history of ICH (n = 16). The dates of our analysis were September 1, 2012, to August 31, 2015., Main Outcomes and Measures: The sensitivity and specificity of prespecified criteria for probable CAA-ri (requiring asymmetric white matter hyperintensities extending to the subcortical white matter) and possible CAA-ri (not requiring the white matter hyperintensities to be asymmetric)., Results: The 17 patients in the CAA-ri group were a mean (SD) of 68 (8) years and 8 (47%) were women. In the CAA-ri group, 14 of 17 (82%) met the criteria for both probable and possible CAA-ri. In the control group having noninflammatory CAA with lobar ICH, 1 of 21 (5%) met the criteria for possible CAA-ri, and none met the criteria for probable CAA-ri. In the control group having noninflammatory CAA with no ICH, 11 of 16 (69%) met the criteria for possible CAA-ri, and 1 of 16 (6%) met the criteria for probable CAA-ri. These findings yielded a sensitivity and specificity of 82% and 97%, respectively, for the probable criteria and a sensitivity and specificity of 82% and 68%, respectively, for the possible criteria., Conclusions and Relevance: Our data suggest that a reliable diagnosis of CAA-ri can be reached from basic clinical and magnetic resonance imaging information alone, with good sensitivity and excellent specificity.