COVID-19 Related Acute Hemorrhagic Necrotizing Encephalitis: A Report of Two Cases and Literature Review.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, has proven neurotropism and causes a multitude of neurologic manifestations. Acute hemorrhagic necrotizing encephalitis (AHNE), though rare, can be seen in patients with severe infection and is associated with devastating neurologic outcomes. The true prevalence of this syndrome is unknown due to underrecognition, difficulty in timely acquisition of neuroimaging, and high mortality in this subset of patients escaping detection. It is a distinct clinicoradiological syndrome, with patients suffering from rapidly worsening encephalopathy and coma within the first two weeks of severe illness and hemorrhagic necrotizing parenchymal changes on neuroimaging. The pathophysiology of this syndrome is unclear but hypothesized to occur due to cytokine storm, blood-brain-barrier dysfunction, and direct viral-mediated endotheliopathy. Diagnosis requires a high index of suspicion in patients who have unexplained persistent severe encephalopathy associated with COVID-19 infection. Most patients have elevated systemic inflammatory markers and severe lung disease with hypoxic respiratory failure requiring mechanical ventilation. MRI is the imaging modality of choice, with a distinct neuroimaging pattern. CSF (cerebrospinal fluid) studies have a low yield for viral particle detection with currently available testing. While long-term outcomes are unclear, early immunomodulatory treatment with intravenous immunoglobulin, plasma exchange, and steroids may portend a favorable outcome. We discuss two cases of COVID-19 related AHNE and also include a pertinent literature search of similar cases in PubMed to consolidate the AHNE clinical syndrome, neuroimaging characteristics, management strategies, and reported short-term prognosis.

A Triage Model for Interhospital Transfers of Low Risk Intracerebral Hemorrhage Patients.

OBJECTIVES: Intracerebral hemorrhage comprises a large proportion of inter-hospital transfers to comprehensive stroke centers from centers without comprehensive stroke center resources despite lack of mortality benefit and low comprehensive stroke center resource utilization. The subset of patients who derive the most benefit from inter-hospital transfers is unclear. Here, we create a triage model to identify patients who can safely avoid transfer to a comprehensive stroke center. MATERIALS AND METHODS: A retrospective cohort of spontaneous intracerebral hemorrhage patients transferred to our comprehensive stroke center from surrounding centers was used. Patients with early discharge from the Neuroscience Intensive Care Unit without use of comprehensive stroke center resources were identified as low risk, non-utilizers. Variables associated with this designation were used to develop and validate a triage model. RESULTS: The development and replication cohorts comprised 358 and 99 patients respectively, of whom 78 (22%) and 26 (26%) were low risk, non-utilizers. Initial Glasgow Coma Scale and baseline hemorrhage volume were associated with low risk, non-utilizers in multivariate analysis. Initial Glasgow Coma Scale >13, intracerebral hemorrhage volume <15ml, absence of intraventricular hemorrhage, and supratentorial location had an area under curve, specificity, and sensitivity of 0.72, 91.4%, 52.6%, respectively, for identifying low risk, non-utilizers, and 0.75, 84.9%, 65.4%, respectively, in the replication cohort. CONCLUSIONS: Spontaneous intracerebral hemorrhage patients with Glasgow Coma Scale >13, intracerebral hemorrhage volume <15 ml, absence of intraventricular hemorrhage, and supratentorial location might safely avoid inter-hospital transfer to a comprehensive stroke center. Validation in a prospective, multicenter cohort is warranted.

Combination of Intra-Hematomal Hypodensity on CT and BRAIN Scoring Improves Prediction of Hemorrhage Expansion in ICH.

BACKGROUND: Hematoma expansion (HE) occurs in 1/3 of ICH patients and is associated with poor outcome. Intra-hematomal hypodensity (IHH) on CT has been reported to predict HE, as has the "BRAIN" score. We sought to assess the predictive value of these markers alone and in combination. METHODS: We performed a retrospective single-center study of ICH patients with CT < 6 h from onset. Two blinded neurologists assessed IHH on initial CT. Two HE definitions were examined: > 6 ml and > 6 ml or > 33%. Multivariable logistic regression was used to determine the relationship between IHH and HE. Predictive value of the BRAIN score alone and integrated with IHH was assessed. RESULTS: In 122 included patients, median ICH volume was 13 ml, median time to CT 2.0 h; HE > 6 ml occurred in 31% and > 6 ml/> 33% in 43% of subjects. IHH were identified in 61% of patients with moderate inter-rater agreement (κ = 0.59). In multivariable analysis, IHH was associated with HE using > 6 ml definition (OR 8.3, 95% CI, 2.6-32.8, P < 0.001) but not using the > 6 ml/> 33% definition (OR 1.9, 95% CI 0.84-4.3, P = 0.12). Rate of HE (> 6 ml) increased across increasing BRAIN score quartiles (Q1:11%, Q2:23%, Q3:43%, Q4:57%, P for trend < 0.001). Rate of HE > 6 ml in patients with BRAIN score ≥ 10 and IHH was 55%, with either alone was 33%, and with neither was 3%. CONCLUSIONS: Combining IHH on non-contrast CT and a simple clinical BRAIN score is a potentially powerful way to predict those patients at very high and very low risk of HE.

Normonatremic osmotic demyelination in the setting of acquired immune deficiency syndrome and malnutrition: case report and literature review.

In this report, we present the case of a 43-year-old woman with AIDS, disseminated aspergillosis, and malnutrition who developed osmotic demyelination syndrome. AIDS-related osmotic demyelination has only been documented in a handful of cases to date, and it appears independent of the classic mechanism of rapid correction of hyponatremia. In this manuscript, we review the six prior cases of osmotic demyelination in AIDS patients and compare their circumstances to that of our own patient. It appears that complications of malnutrition, possibly related to depletion of organic osmolytes in the central nervous system, may place AIDS patients at greater risk of osmotic demyelination. These, and other proposed mechanisms, deserve further inquiry.

Diagnosis and Management of Coagulopathy-Related Intracerebral Hemorrhage.

Coagulopathy, defined as impaired clot formation, is common in intensive care units (ICUs). Many physiological derangements lead to dysfunctional hemostasis in the ICU; most of these are acquired rather than congenital. Coagulopathies in the ICU are often related to systemic diseases, autoimmune dysfunction, acute infection, organ dysfunction, therapeutic medications, and/or other medical treatments. A significant complication of coagulopathy in the critically ill is major bleeding, defined as fatal hemorrhage, hemodynamic instability, transfusion requirement, or intracranial hematomas. Coagulopathy in the ICU often poses complex management dilemmas, especially when coagulopathy coexists with a thrombotic state. Coagulopathy associated with intracerebral hemorrhage (ICH) bears directly on neurologic prognosis and functional outcome. There is a paucity of high-quality evidence for the management of coagulopathies in neurocritical care; however, data derived from studies of patients with ICH may inform treatment decisions. This article focuses on acquired conditions such as pharmacological therapies, organ failure, and platelet dysfunction that are often associated with defective clot formation in the ICU that result in or exacerbate ICH.