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

Abstract P4: Predictors of Outcomes in Patients With Mild Ischemic Stroke Symptoms: Results From the Mild and Rapidly Improving Stroke Study (mariss)

Background: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective 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 TIA presenting with stroke symptoms and a baseline NIHSS 0-5 within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale (mRS) 0-1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16 (SIS-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 (GWTG)-Stroke participating hospitals (age 65 + 14, 42% women, final diagnosis ischemic stroke 90%, TIA 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, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, arm and leg weakness. Similar outcomes were noted for the alteplase-treated and the untreated groups. Alteplase treated patients were younger (64 + 13 vs. 67 + 1.4) with a higher NIHSS (2.9 + 1.4 vs. 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 effect on SIS-16 in the restricted sample of baseline NIHSS 3-5. Very few symptomatic hemorrhages were recorded (3/999). Conclusions: A large proportion of stroke patients presenting with a 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 an indication of efficacy was noted in the NIHSS 3-5 subgroup

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 \u3e1 at 30 days and mRS 0-1 at 90 days OR mRS \u3e2 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

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

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

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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 3–5. 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 3–5 subgroup. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02072681