For some period of time, folks have debated the utility of thrombolysis in lacunar infarcts. The underlying concern is with regard to their underlying suspected pathology relating to non-thrombotic occlusion of small perforating arteries, in contrast to the process seen in small- or large-vessel stroke. This little subgroup analysis of WAKE-UP – the MRI-driven tissue-based trial of alteplase for ischemic stroke – tries to shed further light on this specific concern.
Of the 503 patients included in WAKE-UP (out of 1,362 patients screened), 108 had imaging-defined lacunar infarcts. The median NIHSS of these patients was 4 to 5, and about half were randomized to alteplase and half to placebo. Overall, this subgroup – underpowered for any definitive conclusion – demonstrated similar outcomes as those whose stroke subtype was not lacunar.
The issue is not so much the finding observed here, but the effort in the Discussion and accompanying editorial to generalize WAKE-UP to all strokes. There is only a loose association between DWI and FLAIR findings and predicting time of stroke onset in their cited reference. A little fewer than 2/3rds of strokes of ≤4.5h age seem to have positive DWI and negative FLAIR, and this study enrolled only a tiny fraction of patients with potential lacunar infarcts.
Long story short, a treatment effect observed in this tissue-based enrollment cohort cannot reliably predict treatment response for lacunar strokes screened and treated based on routine non-contrast imaging. Most patients screened for WAKE-UP were excluded based on not meeting imaging criteria, potentially around half of whom were otherwise within 4.5 hour stroke onset (based on their citation above). Thrombolysis does benefit the patients in WAKE-UP, overall, but this almost certainly represents the ceiling for a positive effect size – and in routine practice, effectiveness is likely much lower.
Related aside: when we start routinely screening strokes with MRI in that happy future time, do we exclude DWI+/FLAIR+ from thrombolysis, even if within the “treatment window”? I would think so.
“Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts in the WAKE-UP Trial”
https://jamanetwork.com/journals/jamaneurology/fullarticle/2729091