Enlighten-Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label phase 3 trial with blinded endpoint

Background and Purpose-Despite the abundance of emerging multimodal imaging techniques in the field of stroke, there is a paucity of data demonstrating a strong correlation between imaging findings and clinical outcome. This study explored how proximal arterial occlusions alter flow in collateral vessels and whether occlusion or extent of collaterals correlates with prehospital symptoms of fluctuation and worsening since onset or predict in-hospital worsening. Methods-Among 741 patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke, 134 cases with proximal middle cerebral artery occlusion and 235 control subjects with no occlusions were identified. CT angiography was used to identify occlusions and grade the extent of collateral vessels in the sylvian fissure and leptomeningeal convexity. History of symptom fluctuation or progressive worsening was obtained on admission. Results-Prehospital

Purpose Admission infarct core lesion size is an important determinant of management and outcome in acute (<9 hrs) stroke. Our purpose was to: (1) determine the optimal CT perfusion (CTP) parameter to define infarct core using various post-processing platforms, and (2) establish the degree of variability in threshold values between these different platforms. Methods We evaluated 48 consecutive cases with vessel occlusion and admission CTP and DWI within 3 hours of each other. CTP was acquired with a “second-generation” 66-second biphasic cine protocol, and post-processed using “standard” (from two vendors, “A-std” and “B-std”) and “delay-corrected” (from one vendor, “A-dc”) commercial software. ROC curve analysis was performed comparing each CTP parameter - both absolute and normalized to the contralateral uninvolved hemisphere - between infarcted and non-infarcted regions, as defined by co-registered DWI. Results Cerebral blood flow (CBF) had the highest accuracy (ROC “area under curve”, AUC), for all three platforms (p<0.01). The maximal AUC's for each parameter were: absolute CBF 0.88, CBV 0.81, and MTT 0.82, and relative CBF 0.88, CBV 0.83, and MTT 0.82. Optimal ROC operating point thresholds varied significantly between different platforms (Friedman test, p<0.01). Conclusion Admission absolute and normalized “second-generation” cine acquired CT-CBF lesion volumes correlate more closely with DWI defined infarct core than do those of CT-CBV or MTT. Although limited availability of DWI for some patients creates impetus to develop alternative methods of estimating core, the marked variability in quantification amongst different post-processing software limits generalizability of parameter map thresholds between platforms.

Background Decreased diffusion (DD) consistent with acute ischemia may be detected on MRI after acute intracerebral hemorrhage (ICH), but its risk factors and impact on functional outcomes are not well defined. We tested the hypotheses that DD after ICH is related to acute blood pressure (BP) reduction and lower hemoglobin (HGB) and presages worse functional outcomes. Methods Patients who underwent MRI were prospectively evaluated for DD by certified neuroradiologists blinded to outcomes. HGB and BP data were obtained via electronic queries. Outcomes were obtained at 14 days and 3 months with the modified Rankin Scale (mRS), a functional scale scored from 0 (no symptoms) to 6 (dead). We used logistic regression for dependence or death (mRS 4 to 6). Results DD distinct from the hematoma was found on MRI in 36 of 95 patients (38%). DD was associated with greater BP reductions from baseline, and a higher risk of dependence or death at 3 months (OR 4.8, 95% CI 1.7 – 13.9, P=0.004) after correction for ICH Score (1.8 per point, 95%CI 1.2–3.1, P=0.01). Lower HGB was associated with worse ICH score, larger hematoma volume and worse outcomes, but not DD. Conclusions DD is common after ICH, associated with greater acute BP reductions, and associated with disability and death at 3 months in multivariate analysis. The potential benefits of acute BP reduction to reduce hematoma growth may be limited by DD. The prevention and treatment of cerebral ischemia manifested as DD is a potential method to improve outcomes.

Purpose To study the relationship between OSA and risk of COVID-19 infection and disease severity, identified by the need for hospitalization and progression to respiratory failure. Methods We queried the electronic medical record system for an integrated health system of 10 hospitals in the Chicago metropolitan area to identify cases of COVID-19. Comorbidities and outcomes were ascertained by ICD-10-CM coding and medical record data. We evaluated the risk for COVID-19 diagnosis, hospitalization, and respiratory failure associated with OSA by univariate tests and logistic regression, adjusting for diabetes, hypertension, and BMI to account for potential confounding in the association between OSA, COVID-19 hospitalization, and progression to respiratory failure. Results We identified 9405 COVID-19 infections, among which 3185 (34%) were hospitalized and 1779 (19%) were diagnosed with respiratory failure. OSA was more prevalent among patients requiring hospitalization than those who did not (15.3% versus 3.4%, p < 0.0001; OR 5.20, 95% CI (4.43, 6.12)), and among those who progressed to respiratory failure (19.4% versus 4.5%, p < 0.0001; OR 5.16, 95% CI (4.41, 6.03)). After adjustment for diabetes, hypertension, and BMI, OSA was associated with increased risk for hospitalization (OR 1.65; 95% CI (1.36, 2.02)) and respiratory failure (OR 1.98; 95% CI (1.65, 2.37)). Conclusions Patients with OSA experienced approximately 8-fold greater risk for COVID-19 infection compared to a similar age population receiving care in a large, racially, and socioeconomically diverse healthcare system. Among patients with COVID-19 infection, OSA was associated with increased risk of hospitalization and approximately double the risk of developing respiratory failure.

Training neurosurgeons in ChinaIn their Correspondence, Norton and colleagues 1 remarked that neurosurgery should be an attractive option for the best medical students, regardless of gender, ethnicity, or socioeconomic status. However, this might not be the case in China. Because of the skills and knowledge that neurosurgical depart ments demand, recruitment of students is not easy. For example, in some institutions, neurosurgery students had a lower admission score than those in other clinical specialties, such as orthopaedics and cardiology. 2,

Background and Purpose-Multimodal imaging is gaining an important role in acute stroke. The benefit of obtaining additional clinically relevant information must be weighed against the detriment of increased cost, delaying time to treatment, and adverse events such as contrast-induced nephropathy. Use of National Institutes of Health Stroke Scale (NIHSS) score to predict a proximal arterial occlusion (PO) is suggested by several case series as a viable method of selecting cases appropriate for multimodal imaging. Methods-Six hundred ninety-nine patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke were dichotomized according to the presence of a PO, including a subgroup of 177 subjects with middle cerebral artery M1 occlusion. Results-The median NIHSS score of patients found to have a PO was higher than the overall median (9 versus 5, PϽ0.0001). The median NIHSS score of patients with middle cerebral artery M1 occlusion was 14. NIHSS score Ն10 had 81% positive predictive value for PO but only 48% sensitivity with the majority of subjects with PO presenting with lower NIHSS scores. All patients with NIHSS score Ն2 would need to undergo angiographic imaging to detect 90% of PO. Conclusions-High NIHSS score correlates with the presence of a proximal arterial occlusion in patients presenting with acute cerebral ischemia. No NIHSS score threshold can be applied to select a subgroup of patients for angiographic imaging without failing to capture the majority of cases with clinically important occlusive lesions. The finding of minimal clinical deficits should not deter urgent angiographic imaging in otherwise appropriate patients suspected of acute stroke.

Rationale: The prognostic significance of delirium symptoms in intensive care unit (ICU) patients with focal neurologic injury is unclear. Objectives: To determine the relationship between delirium symptoms and subsequent functional outcomes and quality of life (QOL) after intracerebral hemorrhage. Methods: We prospectively enrolled 114 patients. Delirium symptoms were routinely assessed twice daily using the Confusion Assessment Method for the ICU by trained nurses. Functional outcomes were recorded with modified Rankin Scale (scored from 0 [no symptoms] to 6 [dead]), and QOL outcomes with Neuro-QOL at 28 days, 3 months, and 12 months. Measurements and Main Results: Thirty-one (27%) patients had delirium symptoms ("ever delirious"), 67 (59%) were never delirious, and the remainder (14%) had persistent coma. Delirium symptoms were nearly always hypoactive, were detected mean 6 days after intracerebral hemorrhage presentation, and were associated with longer ICU length of stay (mean 3.5 d longer in ever vs. never delirious patients; 95% confidence interval, 1.5-8.3; P ¼ 0.004) after correction for age, admit National Institutes of Health (NIH) Stroke Scale, and any benzodiazepine exposure. Delirium symptoms were associated with increased odds of poor outcome at 28 days (odds ratio, 8.7; 95% confidence interval, 1.4-52.5; P ¼ 0.018) after correction for admission NIH Stroke Scale and age, and with worse QOL in the domains of applied cognition-executive function and fatigue after correcting for the NIH Stroke Scale, age, benzodiazepine exposure, and time of follow-up. Conclusions: After focal neurologic injury, delirium symptoms were common despite low rates of infection and sedation exposure, and were predictive of subsequent worse functional outcomes and lower QOL. Keywords: delirium; outcomes; quality of lifeThe symptoms of delirium, a potential consequence of multiple clinical disease states and physiologic aberrations, include a shift in baseline mental status, inattention, and disorganized thinking or altered level of consciousness. Although nonspecific, this syndrome is an independent predictor of higher mortality (1), longer length of stay (LOS), higher cost of care, and worse long-term cognitive outcomes in medical, surgical, burn, and trauma intensive care unit (ICU) patients (2). There are few such data, however, in ICU patients with focal neurologic injury without systemic illness.Risk factors for delirium symptoms are typically global (infection [3] and intravenous sedation, particularly benzodiazepines [BZDs]) (4, 5) as opposed to focal lesions (e.g., hematoma). Most mechanically ventilated patients are delirious during hospitalization (1), potentially because of the sedation regimen (e.g., BZD infusion), but sedation is typically minimized in neurologically injured patients to permit repeated neurologic assessment that may lead to an acute intervention (6).Screening tests for delirium have been recently validated in neurologically ill patients (7-9), including ischemic stroke (7, 10) and intracerebra...