Association Between Glycemic Gap and In-hospital Outcomes in Aneurysmal Subarachnoid Hemorrhage.

Introduction: Glycemic gap (GG), as determined by the difference between glucose and the hemoglobin A1c (HbA1c)-derived estimated average glucose (eAG), is associated with poor outcomes in various clinical settings. There is a paucity of data describing GG and outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Our main objectives were to evaluate the association of admission glycemic gap (aGG) with in-hospital mortality and with poor composite outcome and to compare aGG's predictive value to admission serum glucose. Secondary outcomes were the associations between aGG and neurologic complications including vasospasm and delayed cerebral ischemia following aSAH. Methods: We retrospectively reviewed 119 adult patients with aSAH admitted to a single tertiary care neuroscience ICU. Spearman method was used for correlation for non-normality of data. Area under the curve (AUC) for Receiver Operating Characteristic (ROC) curve was used to estimate prediction accuracy of aGG and admission glucose on outcome measures. Multivariable analyses were conducted to assess the value of aGG in predicting in-hospital poor composite outcome and death. Results: Elevated aGG at or above 30 mg/dL was identified in 79 (66.4%) of patients. Vasospasm was not associated with the elevated aGG. Admission GG correlated with admission serum glucose (r = 0.94, p < 0.01), lactate (r = 0.41, p < 0.01), procalcitonin (r = 0.38, p < 0.01), and Hunt and Hess score (r = 0.51, p < 0.01), but not with HbA1c (r = 0.02, p = 0.82). Compared to admission glucose, aGG had a statistically significantly improved accuracy in predicting inpatient mortality (AUC mean ± SEM: 0.77 ± 0.05 vs. 0.72 ± 0.06, p = 0.03) and trended toward statistically improved accuracy in predicting poor composite outcome (AUC: 0.69 ± 0.05 vs. 0.66 ± 0.05, p = 0.07). When controlling for aSAH severity, aGG was not independently associated with delayed cerebral ischemia, poor composite outcome, and in-hospital mortality. Conclusion: Admission GG was not independently associated with in-hospital mortality or poor outcome in a population of aSAH. An aGG ≥30 mg/dL was common in our population, and further study is needed to fully understand the clinical importance of this biomarker.

Admission glycemic gap in the assessment of patients with intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is the most common type of hemorrhagic stroke. Glycemic gap, determined by the difference between glucose and the HbA1c-derived average glucose, predicts poor outcomes in various clinical settings. Our main objective was to evaluate association of some admission factors and outcomes in relation to admission glycemic gap (AGG) in patients with ICH. METHODS: We retrospectively analyzed 506 adult patients with ICH between 2014 and 2019. AGG was defined as A1c-derived average glucose (28.7×HbA1c-46.7) subtracted from admission glucose. Admission factors and hospital outcomes indicative of poor outcome (i.e. death, gastrostomy tube, tracheostomy, and discharge status) were compared between patients with elevated (greater than 80 mg/dL) vs. non-elevated (less than or equal-to 80 mg/dL) AGG. Pearson chi-square test was used for independence, and multivariate analysis was used for association. SPSS and excel were used for all data analysis. RESULTS: We found that 67 of 506 (13%) ICH patients had elevated AGG with a mean of 137.3 mg/dL compared to 439 (87%) non-elevated AGG with a mean of 12.6 mg/dL. While mean and standard deviation values for age, weight,and body mass index were comparable between groups, the elevated AGG group had significantly higher admission glucose (286.1 ± 84.3 vs. 140.1 ± 42.5, p < 0.001), higher lactic acid (3.26 ± 2.04 mmol/L vs. 1.99 ± 1.33 mmol/L, p < 0.001), lower Glasgow Coma Scale (GCS) scores (7.70 ± 4.28 vs. 11.24 ± 4.14, p < 0.001), and higher ICH score (median 3, IQR 2-4 vs. median 1, IQR 0-3, p < 0.001). Higher AGG was associated with an increased likelihood of mechanical ventilation, and in-hospital mortality (74.6% vs. 38.3% and 47.8% vs. 15.0% respectively, p < 0.001). Placements of tracheostomy and gastrostomy were similar between the two groups (13.4% vs. 11.8%, p = 0.69% and 1.5% and 4.6%, p = 0.34 respectively). The higher AGG group had a more common poor discharge outcome to either long-term acute care, skilled nursing facility, and/or hospice (65.7% vs. 42.6%, p < 0.001). Hospital cost and length of hospitalization did not differ significantly. Although AGG was not an independent predictor of poor outcome, multivariate analysis showed it was significantly associated with poor outcome while admission glucose was not (p < 0.001 vs. p = 0.167). CONCLUSION: Elevated AGG was associated with worse GCS and ICH scores on admission, as well as need for mechanical ventilation, in hospital mortality and poor discharge status. Elevated AGG has value in prediction of outcome, but existing understanding is limited.

Unusual Pattern of Arterial Macrothrombosis Causing Stroke in a Young Adult Recovered from COVID-19.

Coronavirus disease-19 (COVID-19) pandemic continues to grow all over the world. Neurological manifestations related to COVID-19, including acute ischemic Stroke (AIS), have been reported in recent studies. In most of these, the patients are older, have multiple co-morbidities as risk factors for AIS and have developed a severe respiratory illness. Herein, we report a 36-year-old man with no significant past medical history who recently recovered from a mild COVID-19 infection and presented with unusual pattern of arterial macrothrombosis causing AIS. When the AIS happened, he had no COVID-19 related symptoms, had two negative screening tests for the infection and his chest CT was unremarkable.

Older Age Is Not Associated with Worse Outcomes Following Decompressive Hemicraniectomy for Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Decompressive hemicraniectomy (DHC) is commonly offered after large spontaneous intracerebral hemorrhage (ICH) as a life-saving measure. Based on limited available evidence, surgery is sometimes avoided in the elderly. The association between age and outcomes following DHC in spontaneous ICH remains largely understudied. OBJECTIVE: The goal of this study is to investigate the influence of older age on outcomes of patients who undergo DHC for spontaneous ICH. METHODS: In this retrospective cohort study, inpatient data were obtained from the United States Nationwide Inpatient Sample from 2000 to 2011. Using International Classification of Diseases, ninth revision designations, patients with a primary diagnosis of nontraumatic ICH who underwent DHC were identified. The primary outcome of interest was the association of age to inpatient mortality and poor outcome. Subjects were grouped by age: 18-50, 51-60, 61-70, and more than 70 years. Sample characteristics were compared across age groups using χ2 testing, and univariate and multivariate Poisson Regression was performed using a generalized equation to estimate rate ratios for primary and secondary outcomes. RESULTS: One thousand one hundred and forty four patient cases were isolated. Death occurred in an estimated 28.9% and poor outcome in 86.4%. In multivariate Poisson regression models, there was no difference in hospital mortality or poor outcome by age group. Although younger patients were more likely to be diagnosed with herniation, total complication rate was similar between age groups. CONCLUSIONS: Our study results do not provide evidence that age independently predicts in-hospital mortality or poor outcomes. The true influence of age on outcomes is unclear, and further study is needed to determine which factors may be best in selecting candidates for DHC following spontaneous ICH.

Serum Lactic Acid Following Aneurysmal Subarachnoid Hemorrhage Is a Marker of Disease Severity but Is Not Associated With Hospital Outcomes.

Background: Following aneurysmal subarachnoid hemorrhage, peripherally-drawn lactic acid has been associated with poor outcomes; however, its clinical significance is unknown. We investigated admission factors and patient outcomes associated with serum lactic acid in this population. Methods: This was a retrospective observational study of 105 consecutive patients with serum lactate collected within 24 h of admission. Primary objectives were to determine the incidence of admission lactic acidemia, and factors positively and negatively associated with lactate levels. We also sought to determine if admission lactic acidemia was associated with patient outcomes, including vasospasm, delayed cerebral ischemia, mortality, and discharge disposition. Results: Admission serum lactic acid was elevated in 56 patients (53% of the cohort). Levels were positively associated with Hunt & Hess and modified Fisher grade, glucose, troponin I and white blood cell counts, and negatively associated with GCS and ventilator-free days. Admission lactate was not associated with the development of vasospasm or delayed cerebral ischemia. Patients with elevated lactic acid more often died during hospitalization, and less often were discharged home. After adjusting for other predictors of poor outcome, the adjusted odds of inpatient mortality (OR 0.97, 95% CI 0.79-1.20; p = 0.80) and discharge to home (OR 1.00, 95% CI 0.80-1.26; p = 0.97) was not associated with admission lactic acid. Conclusions: Early serum lactic acid elevation is common following aneurysmal subarachnoid hemorrhage and is associated with the clinical and radiographic grade of hemorrhage. Levels did not independently predict short-term outcomes when adjusted for established predictors of poor outcome. Further study is needed to determine the clinical significance of peripherally-drawn lactic acid in aneurysmal subarachnoid hemorrhage.

Neuroprotective strategies following intraparenchymal hemorrhage.

Intracerebral hemorrhage and, more specifically, intraparenchymal hemorrhage, are devastating disease processes with poor clinical outcomes. Primary injury to the brain results from initial hematoma expansion while secondary hemorrhagic injury occurs from blood-derived products such as hemoglobin, heme, iron, and coagulation factors that overwhelm the brains natural defenses. Novel neuroprotective treatments have emerged that target primary and secondary mechanisms of injury. Nonetheless, translational application of neuroprotectants from preclinical to clinical studies has yet to show beneficial clinical outcomes. This review summarizes therapeutic agents and neuroprotectants in ongoing clinical trials aimed at targeting primary and secondary mechanisms of injury after intraparenchymal hemorrhage.

Matrix metalloproteinase-9: dual role and temporal profile in intracerebral hemorrhage.

BACKGROUND: Clinical outcome after intracerebral hemorrhage (ICH) remains poor. Recent trials in ICH, focusing on hematoma reduction, have not yielded significant clinical improvement. The modulation of matrix metalloproteinase (MMP)-9 may represent a potential therapeutic target for reducing perihematomal edema (PHE) and improving clinical outcome. METHODS: We searched Cochrane Library, Ovid/Medline, and PubMed databases using combinations of the following MeSH search terms: "intracerebral hemorrhage," "matrix metalloproteinase," "minocycline," "inhibition," and "neuroprotection". RESULTS: MMP-9 levels in animal models have largely shown detrimental correlations with mortality, clinical outcome, hematoma volume, and PHE. Animal models and clinical studies have established a timeline for MMP-9 expression and corresponding PHE that include an initial peak on days 1-3 and a secondary peak on day 7. Clinical studies evaluating MMP-9 levels in the acute phase (days 1-3) and subacute phase (day 7) of ICH suggest that MMP-9 may be detrimental in the acute phase through destruction of basal lamina, activation of vascular endothelial growth factor, and activation of apoptosis but assist in recovery in the subacute phase through angiogenesis. CONCLUSIONS: MMP-9 inhibition represents a potentially effective target for neuroprotection in ICH. However, as a ubiquitous protein, the inhibition of pathologic processes must be balanced against the preservation of neuroprotective angiogenesis. As the opposing roles of MMP-9 may have similar mechanisms, the most important factor may be the timing of MMP-9 inhibition. Further studies are necessary to delineate these mechanisms and their temporal relationship.

Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury.

Intracerebral hemorrhage (ICH) is associated with a higher degree of morbidity and mortality than other stroke subtypes. Despite this burden, currently approved treatments have demonstrated limited efficacy. To date, therapeutic strategies have principally targeted hematoma expansion and resultant mass effect. However, secondary mechanisms of brain injury are believed to be critical effectors of cell death and neurological outcome following ICH. This article reviews the pathophysiology of secondary brain injury relevant to ICH, examines pertinent experimental models, and highlights emerging therapeutic strategies. Treatment paradigms discussed include thrombin inhibitors, deferoxamine, minocycline, statins, granulocyte-colony stimulating factors, and therapeutic hypothermia. Despite promising experimental and preliminary human data, further studies are warranted prior to effective clinical translation.

Therapeutic hypothermia in acute ischemic stroke.

Induced hypothermia has been used for neuroprotection in cardiac and neurovascular procedures. Experimental and translational studies provide evidence for its utility in the treatment of ischemic cerebrovascular disease. Over the past decade, these principles have been applied to the clinical management of acute stroke. Varying induction methods, time windows, clinical indications, and adjuvant therapies have been studied. In this article the authors review the mechanisms and techniques for achieving therapeutic hypothermia in the setting of acute stroke, and they outline pertinent side effects and complications. The manuscript summarizes and examines the relevant clinical trials to date. Despite a reasonable amount of existing data, this review suggests that additional trials are warranted to define the optimal time window, temperature regimen, and precise clinical indications for induction of therapeutic hypothermia in the setting of acute stroke.