Dixon Yang, MD

Romano JG, Gardner H, Campo-Bustillo I, Khan Y, Tai S, Riley N, Smith EE, Sacco RL, Khatri P, Alger HM, et al, on behalf of the MaRISS Investigators. Predictors of Outcomes in Patients With Mild Ischemic Stroke Symptoms: MaRISS. Stroke. 2021;52:1995–2004.

Acute ischemic stroke commonly presents with mild or improving symptoms,1 often defined as minor stroke with NIHSS ≤ 5. Many of these patients are not treated with acute thrombolytic therapy due to exclusion from the landmark NINDS recombinant tissue-type plasminogen activator efficacy trials.2 Despite perceived minor symptoms, many of those hospitalized may be unable to walk independently or return directly to home at discharge.3 Effects of thrombolysis and long-term outcomes in minor stroke are still not well understood. Thus, Romano and colleagues sought to describe multidimensional long-term outcomes in patients with mild ischemic stroke symptoms from MaRISS (Mild and Rapidly Improving Stroke Study).

This prospective observational study recruited sites who participated in Get With The Guidelines-Stroke, had more than 300 annual stroke discharges, and reflected regional and national representation of hospital centers. Eligible MaRISS participants presented within 4.5 hours from stroke symptoms onset, had a brain CT excluding non-ischemic causes, and initial NIHSS of 0-5. Those with pre-morbid disability of mRS ≥2 or with complete resolution of symptoms on initial evaluation were excluded. The primary outcome was an mRS score of 0-1 at 90 days post-event. Secondary outcomes included Barthel Index 95-100 versus <95, Stroke Impact Scale-16 (SIS-16) ≥88.2 versus <88.2, and European Quality of Life 5D-5L 1 versus <1 and its visual analogue scale ≥90 versus <90.

A total of 1765 participants were included, of which 57% received alteplase, 90% had final diagnosis of ischemic stroke, and 10% had final diagnosis of transient ischemic attack. At 90 days, over a third of patients had an mRS ≥ 2, and a quarter were not independent. Those who were older, women, non-Hispanic Black and Hispanic individuals, Medicaid recipients, smokers, and with pre-morbid diabetes, atrial fibrillation and prior stroke had worse outcomes. Acute stroke characteristics of higher initial NIHSS, visual field deficits, and extremity weaknesses had worse outcomes. Outcomes did not differ between alteplase-treated and non-treated groups. In adjusted models, alteplase was only associated with improved outcomes measured by SIS-16 in a subsample of those with initial NIHSS 3-5.

The authors concluded that a large proportion of these minor stroke patients have a disabled outcome and that alteplase was not overall associated with improved outcomes, except potentially in those with NIHSS 3-5. The study may have been limited by potential selection bias. Those with clearly disabling symptoms on presentation may have been more likely included in the treatment group. Further, information on high-risk recurrent stroke or neurologic deterioration mechanisms were not available. Regardless, the study highlights the limitations of NIHSS in capturing disabling symptoms. Importantly, the authors found a low rate of alteplase-related symptomatic intracerebral hemorrhage (1.8%), though this may have been confounded by bias from the enrollment window of 24 hours post-symptom onset. The findings also raise interesting implications that certain scores may better discriminate functional differences in the minor stroke cohort, such as SIS-16. Future studies may seek to take this multidimensional scoring approach in the minor stroke population and further examine effect of acute thrombolysis in subgroups of minor stroke, including high-risk patient characteristics and NIHSS 3-5.


  1. Smith EE, Fonarow GC, Reeves MJ, Cox M, Olson DM, Hernandez AF, et al. Outcomes in mild or rapidly improving stroke not treated with intravenous recombinant tissue-type plasminogen activator: findings from Get With The Guidelines-Stroke. Stroke. 2011;42:3110–3115.
  2. Khatri P, Kleindorfer DO, Yeatts SD, Saver JL, Levine SR, Lyden P, et al. Strokes with minor symptoms: an exploratory analysis of the NINDS rt-PA trials. Stroke. 2010;41:2581-2586.
  3. Romano JG, Smith EE, Liang L, Gardener H, Campo-Bustillo I, Khatri P, et al. Distinct short-term outcomes in patients with mild versus rapidly improving stroke not treated with thrombolytics. Stroke. 2016;47:1278-1285.