Hyperglycemia on hospital admission is a common phenomenon in acute ischemic stroke patients and represents an independent predictor of poor clinical outcome with or without acute recanalization ...therapies (systemic thrombolysis or mechanical thrombectomy). Effective restoration of normoglycemia is considered to be beneficial, but conclusive evidence from randomized controlled clinical trials and specific recommendations are lacking. In addition, aggressive glucose control can be complicated by hypoglycemia leading to early neurological deterioration. We conducted a systematic literature review with the aim of addressing several questions: timing of glucose control, target range, type of insulin delivery, duration and practicability of glucose-lowering protocols. Special issues regarding mechanical thrombectomy and glycemic variability can then be investigated in future trials which are also being considered.
Lacunar stroke (LS) and intracerebral hemorrhage (ICH) are 2 diverse manifestations of small vessel disease. What predisposes some patients to ischemic stroke and others to hemorrhage is not well ...understood.
We performed a nested case-control study within the FHS (Framingham Heart Study) comparing people with incident ICH and lacunar ischemic stroke, to age- and sex-matched controls for baseline prevalence and levels of cardiovascular risk factors.
We identified 118 LS (mean age 74 years, 51% male) and 108 ICH (75 years, 46% male) events. Hypertension, diabetes mellitus, smoking, and obesity were strongly associated with LS. Hypertension, but not diabetes mellitus, smoking, or cholesterol levels increased the odds of ICH. Contrary to LS, ICH cases had lower body mass index (BMI) than their controls (26 versus 27); BMI <20 was associated with 4-fold higher odds for ICH. In direct comparison, LS cases had higher BMI (28 versus 26) and obesity prevalence (odds ratio, 3.1); BMI <20 was associated with significantly lower odds of LS (odds ratio, 0.1).
LS and ICH share hypertension, but not diabetes mellitus, as a common risk factor. ICH cases had lower BMI compared with not only LS but their controls as well; this finding is unexplained and merits further exploration.
Hyperglycemia in the acute phase of intracerebral hemorrhage (ICH) has been associated with poor functional outcomes, however all interventions to lower glucose have yielded neutral or negative ...results. We attempt an explanation of the causal role of hyperglycemia in ΙCH outcome using generalized structural equation modeling.
Consecutive primary ICH patients admitted to an academic hospital between 2007 and 2018 were identified. Patients with missing baseline or follow up CT scans and without 90 day follow up status were excluded. We constructed a causal model accounting for pre-defined markers of ICH severity to evaluate the association between mean 72 h glucose and 90 day functional outcome measured by modified Rankin Scale, dichotomized as favorable ≤2 or unfavorable >2.
Primary analyses included 410 patients (70.4 ± 13.8years, 43 % female). Mean 72 h glucose was 137.5 ± 33.4mg/dl and 102 (25 %) patients were diabetic. On univariable analysis, higher glucose levels were negatively correlated with favorable outcome (p < 0.0001). However in the structural equation model, this relationship was significantly attenuated (p = 0.06) after accounting for the causal effect of diabetes (p < 0.0001), hematoma volume (p < 0.0001), intraventricular extension (p = 0.01) and Glasgow coma scale (p = 0.001) on glucose levels. On secondary analyses stratifying by diagnosis of diabetes, higher glucose levels were negatively correlated with favorable outcome in patients without diabetes (p = 0.04), but not in patients with diabetes (p = 0.35).
Hyperglycemia may be a downstream effect of other markers of ICH severity, particularly among patients without diabetes, suggesting a possible explanation for the limited evidence of glucose lowering interventions in outcome.
Background
Perihematomal edema (PHE) has been proposed as a radiological marker of secondary injury and therapeutic target in intracerebral hemorrhage (ICH). We conducted a systematic review and ...meta-analysis to assess the prognostic impact of PHE on functional outcome and mortality in patients with ICH.
Methods
We searched major databases through December 2020 using predefined keywords. Any study using logistic regression to examine the association between PHE or its growth and functional outcome was included. We examined the overall pooled effect and conducted secondary analyses to explore the impact of individual PHE measures on various outcomes separately. Study quality was assessed by three independent raters using the Newcastle–Ottawa Scale. Odds ratios (per 1-unit increase in PHE) and their confidence intervals (CIs) were log transformed and entered into a DerSimonian-Laird random-effects meta-analysis to obtain pooled estimates of the effect.
Results
Twenty studies (
n
= 6633 patients) were included in the analysis. The pooled effect size for overall outcome was 1.05 (95% CI 1.02–1.08;
p
< 0.00). For the following secondary analyses, the effect size was weak: mortality (1.01; 95% CI 0.90–1.14), functional outcome (1.04; 95% CI 1.02–1.07), both 90-day (1.06; 95% CI 1.02–1.11), and in-hospital assessments (1.04; 95% CI 1.00–1.08). The effect sizes for PHE volume and PHE growth were 1.04 (95% CI 1.01–1.07) and 1.14 (95% CI 1.04–1.25), respectively. Heterogeneity across studies was substantial except for PHE growth.
Conclusions
This meta-analysis demonstrates that PHE volume within the first 72 h after ictus has a weak effect on functional outcome and mortality after ICH, whereas PHE growth might have a slightly larger impact during this time frame. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.
The etiology and significance of diffusion-weighted imaging (DWI) lesions in patients with acute intracerebral hemorrhage (ICH) remain unclear.
To evaluate which factors are associated with DWI ...lesions, whether associated factors differ by ICH location, and whether DWI lesions are associated with functional outcomes.
This analysis pooled individual patient data from 3 randomized clinical trials (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial, Antihypertensive Treatment of Acute Cerebral Hemorrhage trial, and Intracerebral Hemorrhage Deferoxamine phase 2 trial) and 1 multicenter prospective study (Ethnic/Racial Variations of Intracerebral Hemorrhage). Patients were enrolled from August 1, 2010, to September 30, 2018. Of the 4782 patients, 1788 who underwent magnetic resonance imaging scans of the brain were included. Data were analyzed from July 1 to December 31, 2019.
The primary outcome consisted of factors associated with DWI lesions. Secondary outcomes were poor functional outcome, defined as a modified Rankin score (mRS) of 4 to 6, and mortality, both assessed at 3 months. Mixed-effects logistic regression was used to evaluate the association between exposures and outcomes. Subgroup analyses stratified by hematoma location were performed.
After exclusion of 36 patients with missing data on DWI lesions, 1752 patients were included in the analysis (1019 men 58.2%; mean SD age, 60.8 13.3 years). Diffusion-weighted imaging lesions occurred in 549 patients (31.3%). In mixed-effects regression models, factors associated with DWI lesions included younger age (odds ratio OR per year, 0.98; 95% CI, 0.97-0.99), black race (OR, 1.64; 95% CI, 1.17-2.30), admission systolic blood pressure (OR per 10-mm Hg increase, 1.13; 95% CI, 1.08-1.18), baseline hematoma volume (OR per 10-mL increase, 1.12; 95% CI, 1.02-1.22), cerebral microbleeds (OR, 1.85; 95% CI, 1.39-2.46), and leukoaraiosis (OR, 1.59; 95% CI, 1.67-2.17). Diffusion-weighted imaging lesions were independently associated with poor mRS (OR, 1.50; 95% CI, 1.13-2.00), but not with mortality (OR, 1.11; 95% CI, 0.72-1.71). In subgroup analyses, similar factors were associated with DWI lesions in lobar and deep ICH. Diffusion-weighted imaging lesions were associated with poor mRS in deep but not lobar ICH.
In a large, heterogeneous cohort of prospectively identified patients with ICH, results were consistent with the hypothesis that DWI lesions represent acute sequelae of chronic cerebral small vessel disease, particularly hypertensive vasculopathy. Diffusion-weighted imaging lesions portend a worse prognosis after ICH, mainly deep hemorrhages.
IntroductionPatients with stroke-like symptoms may be underutilising emergency medical services and avoiding hospitalisation during the COVID-19 pandemic. We investigated a decline in admissions for ...stroke and transient ischaemic attack (TIA) and emergency department (ED) stroke alert activations.MethodsWe retrospectively compiled total weekly hospital admissions for stroke and TIA between 31 December 2018 and 21 April 2019 versus 30 December 2019 and 19 April 2020 at five US tertiary academic comprehensive stroke centres in cities with early COVID-19 outbreaks in Boston, New York City, Providence and Seattle. We collected available data on ED stroke alerts, stroke severity using the National Institutes of Health Stroke Scale (NIHSS) and time from symptom onset to hospital arrival.ResultsCompared with 31 December 2018 to 21 April 2019, a decline in stroke/TIA admissions and ED stroke alerts occurred during 30 December 2019 to 19 April 2020 (p trend <0.001 for each). The declines coincided with state stay-at-home recommendations in late March. The greatest decline in hospital admissions was observed between 23 March and 19 April 2020, with a 31% decline compared with the corresponding weeks in 2019. Three of the five centres with 2019 and 2020 stroke alert data had a 46% decline in ED stroke alerts in late March and April 2020, compared with 2019. Median baseline NIHSS during these 4 weeks was 10 in 2020 and 7 in 2019. There was no difference in time from symptom onset to hospital arrival.ConclusionAt these five large academic US hospitals, admissions for stroke and TIA declined during the COVID-19 pandemic. There was a trend for fewer ED stroke alerts at three of the five centres with available 2019 and 2020 data. Acute stroke therapies are time-sensitive, so decreased healthcare access or utilisation may lead to more disabling or fatal strokes, or more severe non-neurological complications related to stroke. Our findings underscore the indirect effects of this pandemic. Public health officials, hospital systems and healthcare providers must continue to encourage patients with stroke to seek acute care during this crisis.
Hypertension is the most potent stroke risk factor and is also related to cerebral small vessel disease. We studied the relation between mid-to-late-life hypertension trends and cerebral white matter ...injury in community-dwelling individuals from the FHS (Framingham Heart Study).
FHS Offspring cohort participants with available mid-life and late-life blood pressure measurements and brain magnetic resonance imaging were included. Multiple regression analyses were used to relate hypertension trends (normotension-normotension reference, normotension-hypertension, and hypertension-hypertension) to white matter injury metrics on diffusion tensor imaging (free water, fractional anisotropy, and peak skeletonized mean diffusivity) and Fluid Attenuated Inversion Recovery (white matter hyperintensity volume) by different blood pressure cutoffs (130/80, 140/90, and 150/90 mm Hg).
We included 1018 participants (mean age 47.3±7.4 years at mid-life and 73.2±7.3 at late-life). At the 140/90 mm Hg cutoff, the hypertension-hypertension trend was associated with higher free water (β, 0.16 95% CI, 0.03-0.30;
=0.021) and peak skeletonized mean diffusivity (β, 0.15 95% CI, 0.01-0.29;
=0.033). At a 130/80 mm Hg cutoff, the hypertension-hypertension trend had significantly higher free water (β, 0.16 95% CI, 0.01-0.30;
=0.035); and the normotension-hypertension (β, 0.24 95% CI, 0.03-0.44;
=0.027) and hypertension-hypertension (β, 0.22 95% CI, 0.04-0.41;
=0.022) trends had significantly increased white matter hyperintensity volume. Exploratory stratified analysis showed effect modifications by
allele and age.
Mid-to-late-life hypertension exposure is significantly associated with microstructural and to a lesser extent, visible white matter injury; the effects are observed at both conventional and lower blood pressure cutoffs and are associated with longer duration of hypertension.
Objective
To examine the effect of individual cerebral small vessel disease (CSVD) markers and cumulative CSVD burden on functional independence, ambulation and hematoma expansion in spontaneous ...intracerebral hemorrhage (ICH).
Methods
Retrospective analysis of prospectively collected data from an observational study of consecutive patients with spontaneous ICH, brain MRI within 1 month from ictus, premorbid modified Rankin Scale (mRS) score ≤ 2, available imaging data and 90-day functional status in a tertiary academic center. Functional outcomes included 90-day functional independence (mRS ≤ 2) and independent ambulation; radiographic outcome was hematoma expansion (> 12.5 ml absolute or > 33% relative increase in ICH volume). We identified the presence and burden of individual CSVD markers (cerebral microbleeds (CMBs), enlarged perivascular spaces, lacunes, white matter hyperintensities) and composite CSVD burden score and explored their association with outcomes of interest in multivariable models adjusting for well-established confounders.
Results
111 patients were included, 65% lobar ICH, with a median volume 20.8 ml. 43 (38.7%) achieved functional independence and 71 (64%) independent ambulation. In multivariable adjusted models, there was higher total CSVD burden (OR 0.61, 95% CI 0.37–0.96,
p
= 0.03) and CMBs presence (OR 0.32, 95% CI 0.1–0.88,
p
= 0.04) remained independently inversely associated with functional independence. Individual CSVD markers or total CSVD score had no significant relation with ambulation and ICH expansion. Larger ICH volume and deep ICH location were the major determinants of lack of independent ambulation.
Conclusions
Our findings suggest that in ICH patients without previous functional dependence, total CSVD burden and particularly presence of CMBs significantly affect functional recovery. The latter is a novel finding and merits further exploration.
Introduction:
Glycemic variability (GV) has been associated with worse prognosis in critically ill patients. We sought to evaluate the potential association between GV indices and clinical outcomes ...in acute stroke patients.
Methods:
Consecutive diabetic and nondiabetic, acute ischemic or hemorrhagic stroke patients underwent regular, standard-of-care finger-prick measurements and continuous glucose monitoring (CGM) for up to 96 h. Thirteen GV indices were obtained from CGM data. Clinical outcomes during hospitalization and follow-up period (90 days) were recorded. Hypoglycemic episodes disclosed by CGM but missed by finger-prick measurements were also documented.
Results:
A total of 62 acute stroke patients 48 ischemic and 14 hemorrhagic, median NIHSS score: 9 (IQR: 3–16) points, mean age: 65 ± 10 years, women: 47%, nondiabetic: 79% were enrolled. GV expressed by higher mean absolute glucose (MAG) values was associated with a lower likelihood of neurological improvement during hospitalization before and after adjusting for potential confounders (OR: 0.135, 95% CI: 0.024–0.751, p = 0.022). There was no association of GV indices with 3-month clinical outcomes. During CGM recording, 32 hypoglycemic episodes were detected in 17 nondiabetic patients. None of these episodes were identified by the periodic blood glucose measurements and therefore they were not treated.
Conclusions:
Greater GV of acute stroke patients may be related to lower odds of neurological improvement during hospitalization. No association was disclosed between GV indices and 3-month clinical outcomes.