The Effect of 30-Day Adequate Transitions of Acute Stroke Care on 90-Day Readmission or Death.

OBJECTIVES: We explore patient-reported behaviors and activities within 30-days post-stroke hospitalization and their role in reducing death or readmissions within 90-days post-stroke. METHODS: We constructed the adequate transitions of care (ATOC) composite score, measuring patient-reported participation in eligible behaviors and activities (diet modification, weekly exercise, follow-up medical appointment attendance, medication adherence, therapy use, and toxic habit cessation) within 30 days post-stroke hospital discharge. We analyzed ATOC scores in ischemic and intracerebral hemorrhage stroke patients discharged from the hospital to home or rehabilitation facilities and enrolled in the NIH-funded Transitions of Care Stroke Disparities Study (TCSD-S). We utilized Cox regression analysis, with the progressive adjustment for sociodemographic variables, social determinants of health, and stroke risk factors, to determine the associations between ATOC score within 30-days and death or readmission within 90-days post-stroke. RESULTS: In our sample of 1239 stroke patients (mean age 64+/-14, 58% male, 22% Hispanic, 22% Black, 52% White, 76% discharged home), 13% experienced a readmission or death within 90 days (3 deaths, 160 readmissions, 3 readmissions with subsequent death). Seventy percent of participants accomplished a ≥75% ATOC score. A 25% increase in ATOC was associated with a respective 20% (95% CI 3%-33%) reduced risk of death or readmission within 90-days. CONCLUSION: ATOC represents modifiable behaviors and activities within 30-days post-stroke that are associated with reduced risk of death or readmission within 90-days post-stroke. The ATOC score should be validated in other populations, but it can serve as a tool for improving transitions of stroke care initiatives and interventions.

Factors and Behaviors Related to Successful Transition of Care After Hospitalization for Ischemic Stroke.

BACKGROUND: Our objective is to describe adoption of the posthospitalization behaviors associated with successful transition of care and related baseline characteristics. METHODS: This study includes 550 participants in the Transition of Care Stroke Disparities Study, a prospective observational cohort derived from the Florida Stroke Registry. Participants had an ischemic stroke (2018-2021), discharged home or to rehabilitation, with modified Rankin Scale score=0-3 (44% women, 24% Black, 48% White, 26% Hispanic, 35% foreign-born). We collected baseline sociodemographic and clinical characteristics. A structured telephone interview at 30-day postdischarge evaluated outcomes including medication adherence, medical appointment attendance, outpatient therapy, exercise, diet modification, toxic habit cessation, and a calculated composite adequate transition of care measure. Multivariable analyses assessed the association of baseline characteristics with 30-day behaviors. RESULTS: At 30 days, medication adherence was achieved by 89%, medical appointments by 82%, outpatient therapy by 76%, exercise by 71%, diet modification by 68%, toxic habit cessation by 35%, and adequate transition of care measure by 67%. Successful adequate transition of care participants were more likely to be used full-time (42% versus 31%, P=0.02), live with a spouse (60% versus 47%, P=0.01), feel close to ≥3 individuals (84% versus 71%, P<0.01), have history of dyslipidemia (45 versus 34%, P=0.02), have thrombectomy (15% versus 8%, P=0.02), but less likely to have a history of smoking (17% versus 32%, P<0.001), coronary artery disease (14% versus 21%, P=0.04), and heart failure (3% versus 11%, P<0.01). Multivariable logistic regression analyses revealed that multiple socio-economic factors and prestroke comorbid diseases predicted fulfillment of transition of care measures. There was no difference in outcomes during the Covid-19 pandemic (2020-2021) compared with prepandemic years (2018-2019). CONCLUSIONS: One in 3 patients did not attain adequate 30-day transition of care behaviors. Their achievement varied substantially among different measures and was influenced by multiple socioeconomic and clinical factors. Interventions aimed at facilitating transition of care from hospital after stroke are needed. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT03452813.

Disparities in transitions of acute stroke care: The transitions of care stroke disparities study methodological report.

OBJECTIVE: The Transitions of Stroke Care Disparities Study (TCSD-S) is an observational study designed to determine race-ethnic and sex disparities in post-hospital discharge transitions of stroke care and stroke outcomes and to develop hospital-level initiatives to reduce these disparities to improve stroke outcomes. MATERIALS AND METHODS: Here, we present the study rationale, describe the methodology, report preliminary outcomes, and discuss a critical need for the development, implementation, and dissemination of interventions for successful post-hospital transition of stroke care. The preliminary outcomes describe the demographic, stroke risk factor, socioeconomic, and acute care characteristics of eligible participants by race-ethnicity and sex. We also report on all-cause and vascular-related death, readmissions, and hospital/emergency room representations at 30- and 90-days after hospital discharge. RESULTS: The preliminary sample included data from 1048 ischemic stroke and intracerebral hemorrhage discharged from 10 comprehensive stroke centers across the state of Florida. The overall sample was 45% female, 22% Non-Hispanic Black and 21% Hispanic participants, with an average age of 64 ± 14 years. All cause death, readmissions, or hospital/emergency room representations are 10% and 19% at 30 and 90 days, respectively. One in 5 outcomes was vascular-related. CONCLUSIONS: This study highlights the transition from stroke hospitalization as an area in need for considerable improvement in systems of care for stroke patients discharged from hospital. Results from our preliminary analysis highlight the importance of investigating race-ethnic and sex differences in post-stroke outcomes.

Frequency and Prognostic Significance of Clinical Fluctuations Before Hospital Arrival in Stroke.

BACKGROUND AND PURPOSE: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized. METHODS: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0-5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines-Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes. RESULTS: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations. CONCLUSIONS: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02072681.

Accuracy of transcranial Doppler in detecting intracranial stenosis in patients with sickle cell anemia when compared to magnetic resonance angiography.

BACKGROUND: Stroke, the most devastating consequence of sickle cell anemia (SCA), is associated with endothelial damage and intracranial artery stenosis. We aimed to assess transcranial Doppler (TCD) ultrasound accuracy in detecting intracranial stenosis when compared to magnetic resonance angiography (MRA). METHODS: Children with SCA and at least one TCD and MRA within 1 month were identified from a retrospectively collected database. Sensitivity and specificity were obtained to assess the overall accuracy of TCD mean flow velocity (mFV) ≥200 cm/s in detecting vessel stenosis of ≥50%. Multivariate analysis identified independent factors associated with MRA stenosis. RESULTS: Among 157 patients in the database, 64 had a TCD and MRA within 1 month (age 11.8 ± 5.3 years, 56% female, 20% with cerebral infarcts on MRI, 8 or 13% had mFV ≥200 cm/s and 20% or 21%, had intracranial stenosis ≥50% on MRA). TCD mFV ≥200 cm/s had a high specificity (95%) but low sensitivity (29%) to detecting intracranial stenosis. As a continuous variable, TCD mFV of 137.5 cm/s had maximal specificity (77%) and sensitivity (72%). After adjustment for age, hemoglobin level, transfusion status, hydroxyurea treatment, and vessel, for every increase in cm/sec on TCD, there was a 2% increase in the odds of ≥50% stenosis on MRA (p < 0.001). CONCLUSION: Our study reports TCD mFV is a positive predictor of MRA stenosis in SCA, independent of patient characteristics, including hemoglobin. A mFV ≥200 cm/s is highly specific but less sensitive in detecting stenosis ≥50%. Lower mFV cut points may be needed for the early detection of intracranial stenosis.

Lipid Levels and Short-Term Risk of Recurrent Brain Infarcts in Symptomatic Intracranial Stenosis.

OBJECTIVES: Hyperlipidemia is a strong risk factor for intracranial atherosclerotic disease (ICAD) and clinical stroke recurrence. We explored the effect of serum lipid levels on subclinical infarct recurrence in the Mechanisms of earlY Recurrence in Intracranial Atherosclerotic Disease (MYRIAD) study. MATERIALS AND METHODS: We included enrolled MYRIAD patients with lipid measurements and brain MRI at baseline and brain MRI at 6-8 weeks. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6-8 weeks compared to baseline brain MRI. We assessed the association between baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and recurrent infarct at 6-8 weeks using multivariable logistic regression. RESULTS: Among 74 patients (mean age 64.2±12.9 years, 59.5% were white, 60.8% men), 20 (27.0%) had new or recurrent infarcts. Mean HDL-C (37.2 vs. 43.9 mg/dL, P=0.037) was lower and TG (113.5 vs. 91.3 mg/dL, P=0.008) was higher while TC (199.8 vs. 174.3 mg/dL, P=0.061) and LDL-C (124.3 vs. 101.2 mg/dL, P=0.053) were nominally higher among those with recurrent infarcts than those without. LDL-C (adj. OR 1.022, 95% CI 1.004-1.040, P=0.015) and TG (adj. OR 1.009, 95% CI 1.001-1.016, P=0.021) were predictors of recurrent infarct at 6-8 weeks adjusting for other clinical and imaging factors. CONCLUSIONS: Baseline cholesterol markers can predict early infarct recurrence in patients with symptomatic ICAD. More intensive and rapid lipid lowering drugs may be required to reduce risk of early recurrence.

Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND AND PURPOSE: While prior studies identified risk factors for recurrent stroke in patients with symptomatic intracranial atherosclerotic disease, few have assessed risk factors for early infarct recurrence. METHODS: We performed a post hoc analysis of the MYRIAD study (Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease) of intracranial atherosclerotic disease patients with recent (<21 days) stroke/transient ischemic attack, 50% to 99% stenosis and who underwent 6- to 8-week magnetic resonance imaging (MRI) per protocol. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6 to 8 weeks compared to index brain MRI. Qualifying events and clinical and imaging outcomes were centrally ascertained by 2 independent reviewers. We assessed the association between baseline clinical and imaging variables and recurrent infarct in bivariate models and multivariable logistic regression to identify independent predictors of infarct recurrence. RESULTS: Of 105 enrolled patients in MYRIAD, 89 (84.8%) were included in this analysis (mean age, 64±12 years, 54 [60.7%] were male, and 53 [59.6%] were White). The median time from qualifying event to MRI was 51+16 days, on which 22 (24.7%) patients had new or recurrent infarcts. Younger age (57.7 versus 66.0 years; P<0.01), diabetes (32.6% versus 14.6%, P=0.05), index stroke (31.3% versus 4.6%, P=0.01), anterior circulation location of stenosis (29.7% versus 12.0%, P=0.08), number of diffusion-weighted imaging lesions (>1: 40.0%, 1: 26.9% versus 0: 4.4%, P<0.01), and borderzone infarct pattern (63.6% versus 25.0%, P=0.01) on baseline MRI were associated with new or recurrent infarcts. Age (adjusted odds ratio, 0.93 [95% CI, 0.89-0.98], P<0.01) and number of diffusion-weighted imaging lesions (adjusted odds ratio, 3.24 [95% CI, 1.36-7.71], P<0.01) were independently associated with recurrent infarct adjusting for hypertension, diabetes, and stenosis location (anterior versus posterior circulation). CONCLUSIONS: An index multi-infarct pattern is associated with early recurrent infarcts, a finding that might be explained by plaque instability and artery-to-artery embolism. Further investigation of plaque vulnerability in intracranial atherosclerotic disease is needed. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02121028.

Thrombolysis in Mild Stroke: A Comparative Analysis of the PRISMS and MaRISS Studies.

Background and Purpose: Mild ischemic stroke patients enrolled in randomized controlled trials of thrombolysis may have a different symptom severity distribution than those treated in routine clinical practice. Methods: We compared the distribution of the National Institutes of Health Stroke Scale (NIHSS) scores, neurological symptoms/severity among patients enrolled in the PRISMS (Potential of r-tPA for Ischemic Strokes With Mild Symptoms) randomized controlled trial to those with NIHSS score ≤5 enrolled in the prospective MaRISS (Mild and Rapidly Improving Stroke Study) registry using global P values from χ2 analyses. Results: Among 1736 participants in MaRISS, 972 (56%) were treated with alteplase and 764 (44%) were not. These participants were compared with 313 patients randomized in PRISMS. The median NIHSS scores were 3 (2­4) in MaRISS alteplase-treated, 1 (1­3) in MaRISS non­alteplase-treated, and 2 (1­3) in PRISMS. The percentage with an NIHSS score of 0 to 2 was 36.3%, 73.3%, and 65.2% in the 3 groups, respectively (P<0.0001). The proportion of patients with a dominant neurological syndrome (≥1 NIHSS item score of ≥2) was higher in MaRISS alteplase-treated (32%) compared with MaRISS nonalteplase-treated (13.8%) and PRISMS (8.6%; P<0.0001). Conclusions: Patients randomized in PRISMS had comparable deficit and syndromic severity to patients not treated with alteplase in the MaRISS registry and lesser severity than patients treated with alteplase in MaRISS. The PRISMS trial cohort is representative of mild patients who do not receive alteplase in current broad clinical practice.

Predictors of Outcomes in Patients With Mild Ischemic Stroke Symptoms: MaRISS.

Background and Purpose: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3­5. Few symptomatic intracerebral hemorrhages were recorded (<1%). Conclusions: A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3­5 subgroup. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02072681.

Risk Factors Control and Early Recurrent Cerebral Infarction in Patients with Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND: The risk of early recurrent cerebral infarction (RCI) is high in patients with symptomatic intracranial atherosclerotic disease (IAD). We sought to determine the relationship between risk factor control and early RCI risk among patients with symptomatic IAD. METHODS: We analyzed participants with symptomatic IAD in the multi-center prospective observational MYRIAD study. Risk factor control was assessed at 6-8-week follow-up. Optimal risk factor control was defined by target systolic blood pressure, being non-smoker, target physical activity, and antiplatelet and antilipidemic therapy compliance. Age-adjusted associations were calculated between risk factor control and RCI determined by MRI-evident new infarcts in the territory of the stenotic vessel at 6-8 weeks from the index event. RESULTS: Among 82 participants with clinical and brain MRI information available 6-8 weeks after the index event (mean age 63.5 ±12.5 years, 62.2% men), RCI occurred in 21 (25.6%) cases. At 6-8-week follow-up, 37.8% had target systolic blood pressure, 92.7% were non-smokers, 51.2% had target physical activity, and 98.8% and 86.6% were compliant with antiplatelet and antilipidemic therapy, respectively. Optimal risk factor control increased from 4.9% at baseline to 19.5% at 6-8-week follow-up (p=0.01). None of the participants with optimal risk factor control at follow-up had RCI (0% vs. 31.8%, p<0.01). CONCLUSIONS: Only one-fifth of MYRIAD participants had optimal risk factor control during early follow-up. Approximately half and two-thirds had physical inactivity and uncontrolled systolic blood pressure, respectively. These risk factors may represent important therapeutic targets to prevent early RCI in patients with symptomatic IAD.

Infarct Recurrence in Intracranial Atherosclerosis: Results from the MyRIAD Study.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism. METHODS: This prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks. RESULTS: Amongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes. CONCLUSIONS: Despite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02121028.

Mechanisms of early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD): Rationale and design.

RATIONALE: Intracranial atherosclerotic disease (ICAD) is the most common cause of ischemic stroke with the highest rate of recurrence, despite aggressive medical management. Diverse mechanisms may be responsible for ICAD-related cerebral ischemia, with potential therapeutic implications. Here we present the rationale, design and methods of the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study. The aim of MyRIAD is to determine the mechanisms of stroke in ICAD through physiologic imaging biomarkers that evaluate impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, artery to artery embolism, and their interaction. METHODS AND DESIGN: This is a prospective observational study of patients with recently symptomatic (<21 days) ICAD with 50-99% stenosis treated medically and monitored for up to 1 year. An estimated 110 participants are recruited at 10 sites to identify the association between the presence of each mechanism of ischemia and recurrent stroke. The primary outcome is ischemic stroke in the territory of the symptomatic artery. Secondary outcomes include new cerebral infarction on MRI at 6-8 weeks and recurrent TIA in the territory of the symptomatic artery. DISCUSSION: MyRIAD is positioned to define the role of specific mechanisms of recurrent ischemia in patients with symptomatic ICAD. This knowledge will allow the development and implementation of effective and specific treatments for this condition.

Distinct Short-Term Outcomes in Patients With Mild Versus Rapidly Improving Stroke Not Treated With Thrombolytics.

BACKGROUND AND PURPOSE: Mild stroke (MS) and rapidly improving stroke (RIS) symptoms are common stroke presentations. Our objective is to describe the short-term outcomes in this population. METHODS: A retrospective analysis of patients with ischemic stroke in the Get With The Guidelines-Stroke registry who arrived ≤4.5 hours from symptom onset not treated with thrombolytics because of MS and RIS. Outcomes included in-hospital death, home discharge, independent ambulation at discharge, and length of stay; these were analyzed for the categories of MS, RIS, and MS+RIS. Multivariable models evaluated the associations of individual and hospital covariates with outcomes. RESULTS: Among 42 394 patients with MS and RIS not treated with thrombolytics, 27% were not discharged directly home, 27.2% did not ambulate independently, and 61.1% had length of stay ≥3 days, despite a low in-hospital mortality of 0.8%. Adjusted outcomes were better for MS+RIS compared with MS; RIS also had better independent ambulation and home discharge compared with MS. Among those with a documented National Institutes of Health Stroke Scale, 25% of those with National Institutes of Health Stroke Scale 0 to 5 and half of those with National Institutes of Health Stroke Scale >5 could not be discharged directly to home or ambulate independently. Older individuals, women, blacks, transport by ambulance, delayed arrival, greater severity and greater burden of vascular risk factors, except for dyslipidemia, had worse adjusted outcomes for home discharge and independent ambulation. CONCLUSIONS: A significant proportion of patients with MS and RIS not treated with thrombolytics have suboptimal discharge outcomes. We found significant differences between MS, RIS, and MS+RIS and identified factors associated with worse outcomes.

Transcranial Doppler detection of cerebral fat emboli and relation to paradoxical embolism: a pilot study.

BACKGROUND: The fat embolism syndrome is clinically characterized by dyspnea, skin petechiae, and neurological dysfunction. It is associated mainly with long bone fracture and bone marrow fat passage to the systemic circulation. An intracardiac right-to-left shunt (RLS) could allow larger fat particles to reach the systemic circulation. Transcranial Doppler can be a useful tool to detect both RLS and the fat particles reaching the brain. METHODS AND RESULTS: We prospectively studied patients with femur shaft fracture with RLS evaluation, daily transcranial Doppler with embolus detection studies, and neurological examinations to evaluate the relation of RLS and microembolic signals to the development of fat embolism syndrome. Forty-two patients were included; 14 had an RLS detected. Seven patients developed neurological symptoms; all of them had a positive RLS (P=<0.001). The patients with an RLS showed higher counts and higher intensities of microembolic signals (P=<0.05 and P=<0.01, respectively) compared with those who did not have an RLS identified. The presence of high microembolic signal counts and intensities in patients with RLS was strongly predictive of the occurrence of neurological symptoms (odds ratio, 204; 95% confidence interval, 11 to 3724; P<0.001) with a positive predictive value of 86% and negative predictive value of 97%. CONCLUSIONS: In patients with long bone fractures, the presence of an RLS is associated with larger and more frequent microembolic signals to the brain detected by transcranial Doppler study and can predict the development of neurological symptoms.

Moderate correlation between breath-holding and CO(2) inhalation/hyperventilation methods for transcranial doppler evaluation of cerebral vasoreactivity.

BACKGROUND: Both CO(2) inhalation followed by hyperventilation and breath-holding have been utilized to measure cerebral vasomotor reactivity (VMR) but their correlation has been poorly studied and understood. METHODS: A retrospective study was conducted in 143 subjects (62.6 ± 15.8 years old, 64% men) with transcranial Doppler ultrasonography measurement of mean flow velocity (MFV) at baseline, after 30 seconds of breath-holding, and after CO(2) inhalation followed by hyperventilation, in the left and right middle cerebral artery. Breath-holding index (BHI) was calculated as the percentage of MFV increase from baseline per second of apnea. CO(2) inhalation/hyperventilation index (CO(2) /HV) was calculated as the percentage of MFV difference between CO(2) inhalation and hyperventilation. RESULTS: There were 75 carotid arteries with >70% stenosis or occlusion, and 18 middle cerebral arteries with >50% stenosis or occlusion. The mean BHI was 0.93 ± 0.7 and 0.89 ± 0.6, whereas the mean CO(2) /HV was 61 ± 26% and 60 ± 26%, respectively, on the right and left sides. The correlation between BHI and CO(2) /HV was moderate on the right (r = 0.33; p < 0.01) and left sides (r = 0.38; p < 0.01). Multivariate linear regression analysis indicated that age (p = 0.01) and history of stroke (p = 0.007) were associated independently with an impaired VMR on the right as measured by CO(2) /HV. No predictors for impaired VMR by CO(2) /HV on the left and by BHI on either side were found. CONCLUSIONS: CO(2) /HV and BHI are only moderately correlated. Further studies are necessary to determine which method more accurately predicts clinical morbidity. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound 2012; Published online in Wiley Online Library.

High-dose atorvastatin enhances impaired cerebral vasomotor reactivity.

The influence of statin therapy on cerebral vasomotor function has not been fully characterized. We report the effects of high-dose atorvastatin therapy on cerebral vasomotor reactivity (VMR) in patients with controlled hypertension and dyslipidemia. We prospectively enrolled 36 patients with controlled hypertension and a low-density lipoprotein (LDL) cholesterol concentration >100 mg/dL. Atorvastatin 80 mg was given daily for 6 months and then discontinued. VMR was assessed by hypercapnic and hypocapnic transcranial Doppler challenge in both the right and left middle cerebral artery (MCA) at baseline, and after 3 and 6 months of therapy. Forty-five days after statin cessation, a repeat VMR was performed. VMR impairment was defined as ≤70%. Blood pressure, lipid levels, liver function, and creatine kinase level were monitored. Mean patient age was 60 years, 16 were men, and 13 had a previous history of subcortical infarction. Mean LDL cholesterol level before treatment was 154 ± 30 mg/dL. Atorvastatin lowered LDL by 53% at 3 months and by 46% at 6 months. Baseline VMR was 71% ± 21% in the right MCA and 70% ± 19% in the left MCA. No significant effect of atorvastatin on VMR was seen at 3 months and 6 months in the study population as a whole. In the subgroup of patients with baseline VMR impairment, atorvastatin therapy was associated with significantly improved VMR at both 3 and 6 months. This effect persisted for at least 45 days after discontinuation of therapy. Our findings indicate that high-dose atorvastatin therapy can significantly improve impaired cerebral VMR, and that the effects of atorvastatin on VMR persist for 1.5 months after discontinuation of therapy. We found no benefit of atorvastatin therapy in patients with preserved baseline vasoreactivity.

Functional status at 30 and 90 days after mild ischaemic stroke.

BACKGROUND/OBJECTIVE: This study compares the global disability status of patients who had a mild ischaemic stroke at 30 and 90 days poststroke, as measured by the modified Rankin Scale (mRS), and identifies predictors of change in disability status between 30 and 90 days. METHODS: The study population included 1339 patients who had a ischaemic stroke enrolled in the Mild and Rapidly Improving Stroke Study with National Institutes of Health (NIH) stroke score 0-5 and mRS measurements at 30 and 90 days. Outcomes were (1) Improvement defined as having mRS >1 at 30 days and mRS 0-1 at 90 days OR mRS >2 at 30 days and mRS 0-2 at 90 days and (2) Worsening defined as an increase of ≥2 points or a worsening from mRS of 1 at 30 days to 2 at 90 days. Demographic and clinical characteristics at hospital arrival were abstracted from medical records, and regression models were used to identify predictors of functional improvement and decline from 30 to 90 days post-stroke. Significant predictors were mutually adjusted in multivariable models that also included age and stroke severity. RESULTS: Fifty-seven per cent of study participants had no change in mRS value from 30 to 90 days. Overall, there was moderate agreement in mRS between the two time points (weighted kappa=0.59 (95% CI 0.56 to 0.62)). However, worsening on the mRS was observed in 7.54% of the study population from 30 to 90 days, and 17.33% improved. Participants of older age (per year OR 1.02, 95% CI 1.00 to 1.03), greater stroke severity (per NIH Stroke Scale (NIHSS) point at admission OR 1.17, 95% CI 1.03 to 1.34), and those with no alteplase treatment (OR 1.72, 95% CI 1.11 to 2.69) were more likely to show functional decline after mutual adjustment. DISCUSSION: A quarter of all mild ischaemic stroke participants exhibited functional changes between 30 and 90 days, suggesting that the 30-day outcome may insufficiently represent long-term recovery in mild stroke and longer follow-up may be clinically necessary. TRIAL REGISTRATION NUMBER: NCT02072681.

Intracranial dolichoectasia in patients with symptomatic intracranial atherosclerotic disease: Results from the MYRIAD study.

BACKGROUND AND PURPOSE: It is unknown whether intracranial atherosclerotic disease (ICAD), in addition to causing stenosis, also associates with abnormal arterial enlargement, a condition known as intracranial dolichoectasia (IDE). Across symptomatic ICAD patients, we aim to determine IDE prevalence and IDE impact on cerebral hemodynamics and recurrent cerebral ischemia. METHODS: We analyzed 98 participants (mean age 63.8 ± 11.9 years, 56.1% men) of the prospective observational study MYRIAD. Participants were enrolled within 21 days of an ischemic stroke or transient ischemic attack caused by moderate-to-severe ICAD. Semi-automatic vessel segmentation was used to determine diameters, length, and tortuosity-index of proximal intracranial arteries. Either ectasia (increased diameter) or dolichosis (increased length or TI) defined IDE. We assessed IDE association with new infarcts during 12-month follow-up, and IDE correlation with cerebral hemodynamics determined by quantitative MR-angiography (QMRA), MR-perfusion weighted-imaging, and transcranial Doppler breath-holding index. RESULTS: IDE was present in 35.7% of patients and 10.2% of symptomatic arteries. Basilar stenosis was associated with higher IDE prevalence (27.8% vs. 8.8%, p = 0.04), whereas other symptomatic arteries showed no association with IDE. Symptomatic arteries with IDE had lower hypoperfusion prevalence on MR-PWI (11.1% vs. 28.4%, p = 0.03). Increased diameter (r = 0.33, p<0.01) and tortuosity-index (r = 0.29, p = 0.01) showed positive correlation with QMRA flow rate. IDE was not associated with new infarcts during follow-up. CONCLUSIONS: IDE was common among symptomatic ICAD patients. IDE was not associated with stroke recurrence. Instead, increased diameter and tortuosity correlated with improved blood flow across the stenotic artery, suggesting that IDE may originate as an adaptive mechanism in ICAD.

Imaging Patterns of Recurrent Infarction in the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) Study.

Introduction: While much is known about recurrent clinical events in patients with intracranial atherosclerotic disease (ICAD), there is limited data on characteristics of recurrent infarcts. Methods: The NIH-funded MyRIAD prospective, observational study was designed to identify mechanisms of ischemia and predictors of recurrence in ICAD. Recurrent infarction was assessed on MRI at 6-8 weeks. We reviewed the DWI/ADC and FLAIR sequences in patients with recurrent stroke and characterized the number of infarcts, infarct location, size, and patterns based on whether they were borderzone (BZ), perforator (SC/P), cortical or territorial (C/T), and mixed. Temporal characteristics were delineated by ADC/FLAIR correlation. Results: Of the 89 patients with 6-8 weeks MRI, 22 (24.7%) had recurrent infarcts in the territory of the symptomatic artery. Recurrent infarcts were evident on DWI in 63.6% and single infarcts in 54.5%. The median recurrent infarct volume was 2.0 cm3 compared to median index infarct volumes of 2.5 cm3. A mixed infarct pattern was most common (40.9%), followed by borderzone (22.7%), cortical or territorial (27.3%), while only 9.1% were in a perforator artery distribution. Amongst those with a mixed pattern, 8/9 had a borderzone distribution infarct as part of their mixed infarct pattern. Conclusion: These findings provide novel data on the characteristics of early recurrent infarcts in patients with symptomatic ICAD.

The Mild and Rapidly Improving Stroke Study (MaRISS): Rationale and design.

RATIONALE: Although mild and rapidly improving stroke symptoms are the most common first stroke presentation, this group has been understudied in acute stroke trials. Observational and retrospective studies suggest residual disability in one third of patients. AIMS: To elucidate long-term outcomes of patients with mild and rapidly improving stroke, evaluate the predictors of outcome, and examine the association with alteplase treatment. SAMPLE SIZE: The initial estimate of 2650 participants to detect a 9% difference in non-disabled 90-day outcomes between alteplase-treated and untreated participants was revised to 2000 after a pre-planned re-estimation based on actual treatment rates. METHODS AND DESIGN: Prospective observational study of patients with mild ischemic stroke (NIHSS ≤ 5) or rapidly improving stroke symptoms evaluated within 4.5 h from onset. OUTCOMES: The primary outcome is the proportion of patients with modified Rankin Scale (mRS) ≥ 2 at 90 days; the primary safety outcome is symptomatic hemorrhagic transformation within 36 h among those treated with alteplase. Secondary outcomes include the 90-day Barthel Index, Stroke Impact Scale 16, European Quality of Life scale, mRS at 30 days, and 30- and 90-day mortality. DISCUSSION: MaRISS will define outcomes and their predictors and clarify the effects of alteplase in patients with mild and rapidly improving stroke symptoms, providing clinicians with important information to manage this population.