So, you’re working in the ED when a new stroke code is activated. You walk over and see a young gentleman with the complaint of left facial tingling, right arm and leg weakness with some tingling. Overall though, a relatively well looking person with mild deficits. Neurology gets there, the patient is whisked off to CT, and imaging shows nothing abnormal on CT or CTA. Intrepid resident that you are, you immediately know that his NIHSS is 4.

What next? Do you push TPA? Do you observe?

Today I want to bring to your attention the PRISMS trial. It looked at Alteplase (TPA) vs Aspirin for Mild Stroke (here defined as a NIHSS <5). The brief points you should know: It was a randomized, double-blind, double-placebo controlled trial which looked at neurologic outcome at 90d. Patients were either given IV TPA with oral placebo, or IV placebo with oral Aspirin. Patients were >18 years old, with stroke symptoms at 3hours of less. Exclusion criteria were your normal TPA exclusion criteria, ICH, or patients that presented with significant disability (for example, isolated dysarthria and aphasia could have a low score but would be considered significantly disabling).

So what were the results? 313 patients with a mean NIHSS of 2 were assessed, and the main conclusion was: ”Among patients with minor nondisabling acute ischemic stroke, treatment with alteplase vs aspirin did not increase the likelihood of favorable functional outcome at 90 days. However, the very early study termination precludes any definitive conclusions, and additional research may be warranted.” Futhermore, 3.3% of patients receiving alteplase had symptomatic ICH (vs 0% in the aspirin group), and 13% of all patients were later found to have a stroke mimic as the underlying etiology for their initial presentation.

It’s interesting (read: very important) to know why the study was cut short. The study was sponsored by the manufacturer of alteplase, and subsequently the study was stopped short due to “slow enrollment”. This should raise significant suspicions on the readers part, as nearly 800,000 people have a stroke in the US every year. To say that only 300-some patients could be recruited seems at best a little difficult to believe.

Take home message: The benefit for TPA in minor stroke is questionable, and may be harmful.

It is important to note that the current AHA and ACEP guidelines for IV TPA, however, do not take into account the severity. The standard of care is to give TPA to any suspected stroke (without any contraindication to TPA). ACEP policy states that: “When feasible, shared decision-making between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke.” Here at Sinai, there is no policy regarding written vs verbal consent for TPA. However, this not a benign medication and caries significant risk; it is not something to be given without at least a discussion with the patient/family.



  1. Khatri P et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits. The PRISMS randomized clinical trial. JAMA 2018; 320(2): 156-66. PMID: 29998337


May 2024