Follow-up ASPECTS improves prediction of potentially lethal malignant edema in patients with large middle cerebral artery stroke.

BACKGROUND: Recent studies have shown that follow-up head CT is a strong predictor of functional outcomes in patients with middle cerebral artery stroke and mechanical thrombectomy. We sought to determine whether total and/or regional follow-up Alberta Stroke Program Early CT Score (ASPECTSfu) are associated with important clinical outcomes during hospitalization and improve the performance of clinical prediction models of potentially lethal malignant edema (PLME). METHODS: We conducted a retrospective study of patients at three medical centers in a major North American metropolitan area with baseline and follow-up head CTs after large middle cerebral artery stroke between 2006 and 2022. We used multivariable logistic regression to test the association of total and regional ASPECTSfu with PLME (cerebral edema related death or surgery), adjusting for total baseline ASPECTS, age, sex, admission glucose, tissue plasminogen activator, and mechanical thrombectomy. We compared existing clinical risk models with and without total or regional ASPECTSfu using area under the curve. RESULTS: In our 560 patient cohort, lower total ASPECTSfu was significantly associated with higher odds of PLME when adjusting for confounders (OR 1.69, 95% CI 1.49 to 2.0), and improved model discrimination compared with existing models and models using baseline ASPECTS. Deep territory involvement (OR 2.46, 95% CI 1.53 to 4.01) and anterior territory involvement (OR 3.23, 95% CI 1.88 to 5.71) were significantly associated with PLME. CONCLUSIONS: Lower ASPECTSfu and certain locations on regional ASPECTSfu, including deep and anterior areas, were significantly associated with PLME. Including ASPECTSfu information improved discrimination of established edema prediction models and could be used immediately to help facilitate clinical management decisions and prognostication.

Do Neuroprognostic Studies Account for Self-Fulfilling Prophecy Bias in Their Methodology? The SPIN Protocol for a Systematic Review.

Self-fulfilling prophecy bias occurs when a perceived prognosis leads to treatment decisions that inherently modify outcomes of a patient, and thus, overinflate the prediction performance of prognostic methods. The goal of this series of systematic reviews is to characterize the extent to which neuroprognostic studies account for the potential impact of self-fulfilling prophecy bias in their methodology by assessing their adequacy of disclosing factors relevant to this bias. Methods: Studies evaluating the prediction performance of neuroprognostic tools in cardiac arrest, malignant ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and spontaneous intracerebral hemorrhage will be identified through PubMed, Cochrane, and Embase database searches. Two reviewers blinded to each other's assessment will perform screening and data extraction of included studies using Distiller SR and following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will abstract data pertinent to the methodology of the studies relevant to self-fulfilling prophecy bias. Results: We will conduct a descriptive analysis of the data. We will summarize the reporting of mortality according to timing and mode of death, rates of exposure to withdrawal of life-sustaining therapy, reasoning behind limitations of supportive care, systematic use of standardized neuroprognostication algorithms and whether the tool being investigated is part of such assessments, and blinding of treatment team to results of neuroprognostic test being evaluated. CONCLUSIONS: We will identify if neuroprognostic studies have been transparent in their methodology to factors that affect the self-fulfilling prophecy bias. Our results will serve as the foundation for standardization of neuroprognostic study methodologies by refining the quality of the data derived from such studies.

Validation of a Crisis Standards of Care Model for Prioritization of Limited Resources During the Coronavirus Disease 2019 Crisis in an Urban, Safety-Net, Academic Medical Center.

OBJECTIVES: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital. DESIGN: We applied our hospital-adopted guidelines, which defined severe and major chronic conditions as those associated with a greater than 50% likelihood of 1- and 5-year mortality, respectively, to a critically ill patient population. We investigated mortality for the same intervals. SETTING: An urban safety-net hospital ICU. PATIENTS: All adults hospitalized during April of 2015 and April 2019 identified through a clinical database search. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 365 admitted patients, 15.89% had one or more defined chronic life-limiting conditions. These patients had higher 1-year (46.55% vs 13.68%; p < 0.01) and 5-year (50.00% vs 17.22%; p < 0.01) mortality rates than those without underlying conditions. Irrespective of classification of disease severity, patients with metastatic cancer, congestive heart failure, end-stage renal disease, and neurodegenerative disease had greater than 50% 1-year mortality, whereas patients with chronic lung disease and cirrhosis had less than 50% 1-year mortality. Observed 1- and 5-year mortality for cirrhosis, heart failure, and metastatic cancer were more variable when subdivided into severe and major categories. CONCLUSIONS: Patients with major and severe chronic medical conditions overall had 46.55% and 50.00% mortality at 1 and 5 years, respectively. However, mortality varied between conditions. Our findings appear to support a crisis standards protocol which focuses on acute illness severity and only considers underlying conditions carrying a greater than 50% predicted likelihood of 1-year mortality. Modifications to the chronic lung disease, congestive heart failure, and cirrhosis criteria should be refined if they are to be included in future models.

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage.

Macrophages are a source of both proinflammatory and restorative functions in damaged tissue through complex dynamic phenotypic changes. Here, we sought to determine whether monocyte-derived macrophages (MDMs) contribute to recovery after acute sterile brain injury. By profiling the transcriptional dynamics of MDMs in the murine brain after experimental intracerebral hemorrhage (ICH), we found robust phenotypic changes in the infiltrating MDMs over time and demonstrated that MDMs are essential for optimal hematoma clearance and neurological recovery. Next, we identified the mechanism by which the engulfment of erythrocytes with exposed phosphatidylserine directly modulated the phenotype of both murine and human MDMs. In mice, loss of receptor tyrosine kinases AXL and MERTK reduced efferocytosis of eryptotic erythrocytes and hematoma clearance, worsened neurological recovery, exacerbated iron deposition, and decreased alternative activation of macrophages after ICH. Patients with higher circulating soluble AXL had poor 1-year outcomes after ICH onset, suggesting that therapeutically augmenting efferocytosis may improve functional outcomes by both reducing tissue injury and promoting the development of reparative macrophage responses. Thus, our results identify the efferocytosis of eryptotic erythrocytes through AXL/MERTK as a critical mechanism modulating macrophage phenotype and contributing to recovery from ICH.

Recommendations for the management of cerebral and cerebellar infarction with swelling: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

BACKGROUND AND PURPOSE: There are uncertainties surrounding the optimal management of patients with brain swelling after an ischemic stroke. Guidelines are needed on how to manage this major complication, how to provide the best comprehensive neurological and medical care, and how to best inform families facing complex decisions on surgical intervention in deteriorating patients. This scientific statement addresses the early approach to the patient with a swollen ischemic stroke in a cerebral or cerebellar hemisphere. METHODS: The writing group used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge. The panel reviewed the most relevant articles on adults through computerized searches of the medical literature using MEDLINE, EMBASE, and Web of Science through March 2013. The evidence is organized within the context of the American Heart Association framework and is classified according to the joint American Heart Association/American College of Cardiology Foundation and supplementary American Heart Association Stroke Council methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive American Heart Association internal peer review. RESULTS: Clinical criteria are available for hemispheric (involving the entire middle cerebral artery territory or more) and cerebellar (involving the posterior inferior cerebellar artery or superior cerebellar artery) swelling caused by ischemic infarction. Clinical signs that signify deterioration in swollen supratentorial hemispheric ischemic stroke include new or further impairment of consciousness, cerebral ptosis, and changes in pupillary size. In swollen cerebellar infarction, a decrease in level of consciousness occurs as a result of brainstem compression and therefore may include early loss of corneal reflexes and the development of miosis. Standardized definitions should be established to facilitate multicenter and population-based studies of incidence, prevalence, risk factors, and outcomes. Identification of patients at high risk for brain swelling should include clinical and neuroimaging data. If a full resuscitative status is warranted in a patient with a large territorial stroke, admission to a unit with neurological monitoring capabilities is needed. These patients are best admitted to intensive care or stroke units attended by skilled and experienced physicians such as neurointensivists or vascular neurologists. Complex medical care includes airway management and mechanical ventilation, blood pressure control, fluid management, and glucose and temperature control. In swollen supratentorial hemispheric ischemic stroke, routine intracranial pressure monitoring or cerebrospinal fluid diversion is not indicated, but decompressive craniectomy with dural expansion should be considered in patients who continue to deteriorate neurologically. There is uncertainty about the efficacy of decompressive craniectomy in patients ≥60 years of age. In swollen cerebellar stroke, suboccipital craniectomy with dural expansion should be performed in patients who deteriorate neurologically. Ventriculostomy to relieve obstructive hydrocephalus after a cerebellar infarct should be accompanied by decompressive suboccipital craniectomy to avoid deterioration from upward cerebellar displacement. In swollen hemispheric supratentorial infarcts, outcome can be satisfactory, but one should anticipate that one third of patients will be severely disabled and fully dependent on care even after decompressive craniectomy. Surgery after a cerebellar infarct leads to acceptable functional outcome in most patients. CONCLUSIONS: Swollen cerebral and cerebellar infarcts are critical conditions that warrant immediate, specialized neurointensive care and often neurosurgical intervention. Decompressive craniectomy is a necessary option in many patients. Selected patients may benefit greatly from such an approach, and although disabled, they may be functionally independent.

Plantar flexion with noxious dorsal foot stimulation in brain death.

BACKGROUND: Plantar flexion with plantar stimulation has been well described in brain death, and is compatible with brain death. However, plantar flexion with stimulation to the dorsal surface of the foot has not been reported previously in brain dead patients. METHODS: Case report with Technetium-99 m hexamethylpropyleneamine oxime brain scan and video. RESULTS: A 46-year-old woman suffered severe anoxic brain injury following massive pulmonary embolism 5 days after arthroscopic knee surgery. Neurologic examination was consistent with brain death, with the exception of plantar flexion when noxious stimulation was applied to the dorsal surface of the great toe on each side. Ancillary testing with a technetium-99 m nuclear scan demonstrated absence of cerebral perfusion, supporting the diagnosis of brain death. CONCLUSIONS: Noxious stimulation to the dorsal surface of the foot may trigger spinally mediated plantar flexion in patients with brain death.