Standard clinical and imaging-based small vessel disease parameters associated with mild stroke versus non-mild stroke.

Background: Mild stroke has variable outcomes, and there is an ongoing debate regarding whether the administration of thrombolytics improves outcomes in this subgroup of stroke patients. Having a better understanding of the features of mild stroke may help identify patients who are at risk of poor outcomes. Objective: The objective of this study is to evaluate the association of clinical and imaging-based small vessel disease features (white matter hyperintensities and cerebral microbleeds) with stroke severity and clinical outcomes in patients with mild stroke. Methods: In this retrospective study, mild stroke was defined as a National Institute of Health stroke scale (NIHSS) score <5. Clinical, laboratory and imaging data were compared between patients with mild stroke versus non-mild stroke (NIHSS≥5). Multivariate logistic regression analysis was performed to identify predictors of mild stroke and poor discharge outcome. Results: Among 296 patients included in the study, 131 patients (44%) had mild stroke. On multivariate analysis, patients with mild stroke were three times more likely to have sensory symptoms [odds ratio (OR) = 2.9; 95% confidence interval (CI) = (1.2-6.8)] and four times more likely to have stroke due to small vessel disease (OR = 3.7; 95%CI = 1.4-9.9). Among patients with mild stroke, higher age (OR = 1.1; 95%CI = 1.02-1.1), presence of cerebral microbleed (OR = 4.5; 95%CI = 1.5-13.8), vertigo (OR = 7.3; 95%CI = 1.2-45.1) and weakness (OR = 5.0; 95%CI = 1.2-20.3) as presenting symptoms were more likely to have poor discharge outcome. Conclusion: Sensory symptoms and stroke due to small vessel disease are more common in mild stroke than non-mild stroke. Among patients with mild stroke, presence of cerebral microbleeds on imaging and symptoms of muscle weakness are associated with poor discharge outcome. Larger studies are needed to assess the impact of cerebral microbleed on mild stroke outcomes and risk stratify the benefit of thrombolytics in this group.

Kidney impairment and outcomes in acute ischaemic stroke.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of stroke and mortality. AIMS: To evaluate the clinical and imaging features and outcomes of patients with and without kidney impairment among t admitted for acute ischaemic stroke (AIS). METHODS: AIS patients with brain magnetic resonance imaging (MRI) were included in the study. Kidney impairment was defined by an admission estimated glomerular filtration rate < 60 mL/min/1.73 m2 . Cerebral microbleeds (CMB) and white matter hyperintensities (WMH) were evaluated using the Microbleed Anatomical Rating Scale and Fazekas scales, respectively. Primary outcomes were defined by modified Rankin Scale (mRS) and discharge disposition. Multivariate logistic regression analysis was performed to evaluate factors associated with the presence of kidney impairment and poor discharge outcomes. RESULTS: Of the 285 patients with AIS, 80 had kidney impairment on admission. Patients with kidney impairment were older (mean age ± standard deviation: 74.7 ± 12.9 vs 64.4 ± 13.8 years, P < 0.0001) and had more neurological deficits on National Institutes of Health Stroke Scale (NIHSS) score (median 8.5 vs 5, P = 0.02). In unadjusted analysis, patients with kidney impairment were less likely to have a good functional outcome (mRS 0-2: 36% vs 57%, P = 0.002) and good discharge outcome (home or inpatient rehabilitation: 68% vs 82%, P = 0.008). On multivariate analysis, kidney impairment was associated with higher NIHSS score (odds ratio (OR) = 1.04; 95% confidence interval (CI) = 1.002-1.08) and severe WMH (OR = 1.99; 95% CI = 1.06-3.77) suggestive of small vessel disease, but kidney impairment was not associated with poor discharge outcome (OR = 1.62; 95% CI = 0.75-3.53). CONCLUSION: Presence of kidney impairment at the time of stroke presentation, regardless of previous renal function, is associated with more neurological deficits and severe WMH on MRI.

Neurological deterioration and computed tomography perfusion changes with increased time to peak in lacunar stroke.

OBJECTIVES: Lacunar strokes can have fluctuations and progression in the acute period leading to poor outcomes. Our study sought to evaluate if, in lacunar strokes, neurological deterioration (ND) was associated with blood pressure (BP) variations, stroke size, or increased time to peak (TTP) on admission computed tomography perfusion (CTP). METHODS: Patients with lacunar stroke who had magnetic resonance imaging and CTP performed were enrolled in the study. ND was defined as ≥1-point worsening on a modified National Institutes of Health Stroke Scale (NIHSS) score or the Medical Research Council scale compared to baseline assessment. The difference in BP between the day of admission and the day of ND was calculated. Multivariate logistic regression analysis, adjusted for pertinent clinical and imaging covariates, was performed to determine predictors of ND. RESULTS: Among 409 patients screened, 49 were eligible for the study. There was no difference in age, gender, race, medical history, admission BP, and the modified NIHSS score between patients with and without ND. In unadjusted analysis, patients with ND tended to have increased TTP in the stroke area compared to the control (12 [63%] vs. 11 [37%], P = 0.07). On multivariate analysis adjusted for covariates, presence of an increased TTP on CTP was a predictor of ND (odds ratio [95% confidence interval] = 4.80 [1.15-20.10], P = 0.03). CONCLUSION: The presence of an increased TTP on CTP corresponding to the stroke lesion on diffusion-weighted imaging is a predictor of ND in patients with lacunar stroke. Larger studies are needed to confirm our findings.

Clinical and Imaging Features Associated with the Utilization of Comfort Measures Only in Acute Ischemic Stroke.

Objectives: Up to 10% of acute ischemic stroke (AIS) patients can die in the first 30 days. Older age and a higher National Institutes of Health Stroke Scale (NIHSS) score are associated with transition to comfort measures only (CMO) in AIS. There are insufficient data on specific stroke etiology, infarct location, or vascular territory for the association of AIS with the use of CMO. We therefore evaluated the clinical and imaging factors associated with utilization of CMO and their outcomes. Methods: AIS patients seen in an academic comprehensive stroke center in the United States between July 1, 2015, and June 30, 2016, were subgrouped based on the use of CMO orders (CMO vs. non-CMO) during hospitalization. Clinical, laboratory, and imaging data were analyzed. Multivariable logistic regression analysis was performed, adjusting for pertinent covariates. Results: The study consisted of 296 patients, 27 (9%) patients were transitioned to CMO. Compared with non-CMO patients, those with CMO were older (mean ± standard deviation: 66 ± 15 vs. 75 ± 11 years, p = 0.002). Hemorrhagic transformation of AIS was more likely in CMO (17% vs. 41%, p = 0.0030) compared with non-CMO patients. On multivariate analysis, severe stroke measured by the NIHSS score (odds ratio [OR] = 1.2; 95% confidence interval [CI] = 1.1-1.4), infarction of the insular cortex (OR = 12.9; 95% CI = 1.4-118.4), and presence of cerebral edema with herniation (OR = 9.4; 95% CI = 2.5-35.5) were associated with transition to CMO. Conclusions: The presence of severe stroke, infarction of the insular cortex, and cerebral edema with herniation were associated with utilization of CMO in AIS. Impairment of multiple neurological functions served by the insular cortex could play a role in transition to CMO.

Association of deep white matter hyperintensity with left ventricular hypertrophy in acute ischemic stroke.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are associated with the presence of left ventricular hypertrophy (LVH). It is unclear if periventricular WMH (PV-WMH) and or deep WMH (D-WMH) are associated with LVH. We evaluated the association of PV-WMH and D-WMH with common transthoracic echocardiogram abnormalities, including LVH in acute ischemic stroke. METHODS: PV-WMH and D-WMH were graded on a 0-3 score based on the Fazekas scale. Patients were categorized into clinically significant PV-WMH and D-WMH (score 2-3) and controls (score 0-1). Multivariate logistic regression analysis was performed to determine abnormalities on echocardiogram associated with PV-WMH and D-WMH. RESULTS: Among 272 patients, 137 patients had PV-WMH and 93 patients had D-WMH with a score of 2-3 on Fazekas scale. Compared to controls, patients with PV-WMH (mean age±standard deviation: 60.8±14.4 vs. 73.8±11.2 years) and D-WMH (63.4±14.4 vs. 75.0±11.1 years) were older. Compared to controls, PV-WMH was associated with history of stroke (22 [16%] vs. 37 [27%], p = .03) and valvular calcification (33 [24%] vs. 61 [45%], p = .0005); D-WMH was associated with history of atrial fibrillation (25 [14%] vs. 22 [24%], p = .04), valvular calcification (50 [28%] vs. 44 [47%], p = .001), and LVH (30 [17%] vs. 25 [27%], p = .049). In multivariate analysis, PV-WMH was associated with age (odds ratio [OR] = 1.09; 95% confidence interval [CI] = 1.06-1.12) and stroke history (OR = 2.1; 95% CI = 1.1-4.1), and D-WMH was associated with age (OR = 1.07; 95% CI = 1.05-1.10) and LVH (OR = 2.0; 95% CI = 1.0-4.0). CONCLUSION: LVH is associated with D-WMH but not with PV-WMH. Although valvular calcification is common, it is likely age related than due to WMH.

Dystonia as a Presenting Feature of Acute Ischemic Stroke: A Case Report and Literature Review.

Hypokinetic and hyperkinetic movement disorders can occur post-stroke. Of these, dystonia is known to occur in the chronic stage of stroke. Rarely, acute dystonia can present as a symptom of acute ischemic stroke or develop during hospitalization for ischemic stroke. In this article, we present a case of acute focal dystonia as a presenting symptom of acute ischemic stroke, review the literature to summarize previous reports, and provide more insight into the pathophysiologic mechanisms related to this presentation.

Adapting Clinical Practice of Thrombolysis for Acute Ischemic Stroke Beyond 4.5 Hours: A Review of the Literature.

Several clinical trials have demonstrated that advanced neuroimaging can select patients for recanalization therapy in an extended time window. The favorable functional outcomes and safety profile of these studies have led to the incorporation of neuroimaging in endovascular treatment guidelines, and most recently, also extended to decision making on thrombolysis. Two randomized clinical trials have demonstrated that patients who are not amenable to endovascular thrombectomy within 4.5 hours from symptoms discovery or beyond 4.5 hours from the last-known-well time may also be safely treated with intravenous thrombolysis and have a clinical benefit above the risk of safety concerns. With the growing aging population, increased stroke incidence in the young, and the impact of evolving medical practice, healthcare and stroke systems of care need to adapt continuously to provide evidence-based care efficiently. Therefore, understanding and incorporating appropriate screening strategies is critical for the prompt recognition of potentially eligible patients for extended-window intravenous thrombolysis. Here we review the clinical trial evidence for thrombolysis for acute ischemic stroke in the extended time window and provide a review of new enrolling clinical trials that include thrombolysis intervention beyond the 4.5 hour window.

Factors associated with the presence of cerebral microbleeds and its influence on outcomes of stroke not treated with alteplase.

OBJECTIVES: Cerebral microbleeds (CMB) are associated with increased risk of hemorrhagic transformation (HT) of ischemic stroke with alteplase. Whether the presence of CMB influences the risk of HT and discharge outcomes of stroke patients not receiving alteplase is unclear. We evaluated the factors associated with the presence of CMB, and if the rates of HT and discharge outcomes were modified by the presence of CMB among stroke patients not treated with alteplase. METHODS: Ischemic stroke patients who had MRI and did not receive alteplase were included in the study. CMB, HT and white matter hyperintensity (WMH) were evaluated using Microbleed Anatomical Rating Scale, Heidelberg bleeding classification, and Fazekas scales, respectively. Multivariate regression analysis was performed to evaluate factors associated with the presence of CMB. RESULTS: Among 196 patients in the study, 58 (30%) patients had CMB. Nine patients had ≥ 10 CMBs. Median National Institutes of Health stroke scale score was 4. In multivariate analysis, age (OR=1.07;95%CI=1.01-1.12), history of stroke (OR=3.10;95%CI=1.08-8.92), congestive heart failure (OR=7.26;95%CI=1.58-33.42), admission diastolic blood pressure (OR=1.03;95%CI=1.003-1.06) and severe WMH defined as Fazekas score 4-6 (OR=4.69;95%CI=1.80-12.23) were significantly associated with the presence of CMB. There was no difference in HT (10% vs 12%, p = 0.80) or discharge outcomes (modified Rankin Scale 0-2: 53% vs 57%, p = 0.62) of patients with CMB compared to those without CMB. CONCLUSION: CMB are associated with severe WMH and higher diastolic blood pressure. CMB are not associated with the HT occurrence or discharge outcome of mild ischemic stroke in the absence of alteplase.

Factors that Influence Door-to-Needle Administration for Acute Stroke Patients in the Emergency Department.

ABSTRACT: BACKGROUND: There is growing importance on discovering factors that delay time to intervention for acute ischemic stroke (AIS) patients, as rapid intervention is essential for better patient outcomes. The management of these patients involves a multidisciplinary effort and quality improvement initiatives to safely increase treatment with intravenous (IV) thrombolytic. The objective of this pilot study is to evaluate factors of acute stroke care in the emergency department (ED) and their impact on IV alteplase administration. METHODS: A sample of 89 AIS patients who received IV alteplase from a single academic medical institution was selected for retrospective analysis. System characteristics (presence of a stroke nurse and time of day) and patient characteristics (mode of arrival and National Institutes of Health Stroke Scale score on arrival) were analyzed using descriptive statistics and multiple regression to address the study question. RESULTS: The mean door-to-needle time is 53.74 (38.06) minutes, with 74.2% of patients arriving to the ED via emergency medical services and 25.8% having a stroke nurse present during IV alteplase administration. Mode of arrival (P = .001) and having a stroke nurse present (P = .022) are significant predictors of door-to-needle time in the ED. CONCLUSION: Although many factors can influence door-to-needle times in the ED, we did not find National Institutes of Health Stroke Scale score on arrival and time of day to be significant factors. Patients arriving to the ED by personal vehicle will have a significant delay in IV alteplase administration, therefore emphasizing the importance of using emergency medical services. Perhaps more importantly, collaborative efforts including the addition of a specialized stroke nurse significantly decreased time to IV alteplase administration for AIS patients. With this dedicated role, accelerated triage and more effective management of AIS patients is accomplished, leading to decreased intervention times and improving patient outcomes.

Effective fiber hypertrophy in satellite cell-depleted skeletal muscle.

An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca(2+) sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells.