Background:

Goal of ischemic stroke management: to save brain tissue that is hypo perfused but viable
surrounding the ischemic core

Current therapies:
Evidence for intravenous thrombolytics
Evidence for mechanical thrombectomy
Current guideline is not to withhold thrombolytic therapy

The No Reflow phenomenon and recanalization

-failure of blood to reperfuse an ischemic area after physical obstruction is removed or bypassed
-Postulated to be due to microvascular obstruction/thrombosis
- from neutrophils clogging circulation
-oxidative stress in pericytes

Concept/hypothesis: Mechanical embolectomy recanalizes larger arteries but does not translate
to reperfusion of ischemic tissue through distal capillaries which cannot be seen in angiography

Can intra-arterial alteplase AFTER mechanical thrombectomy improve brain reperfusion.

Previous studies have had the intervention employed prior to MT, doing it after may allow better
access of the thrombolytic to the capillary bed

1. Clean up of smaller thrombi

2.

Trial design:
Multicenter, double-blind, placebo-controlled trial in 7 endovascular stroke centers in Catalonia,
Spain

Inclusion criteria:
Patient with symptomatic large vessel occlusion in anterior distribution who have been treated
with MT  mTICI score 2b/3 OR mTICI on diagnostic angio before MT

Time to intra-arterial rt-PA <24hrs from last seen well

Modified rankin scale 0-1: no pre-stroke function disability

Imaging:
1. NCCT or brain MRI on admission to rule out blood and ASPECTS score >6 if symptoms
have lasts <4.5 hrs
2. At the same time CT perfusion or DWI-MRI, if symptoms >4.5 hrs

Exclusion criteria:
NIHSS score >25
C/I to IV tPA (except time to therapy)
Platelets <50k; INR >1.7
Hemorrhage on CT/MRI
Complete clinical recovery in angio suite during procedure (evaluated by neurologist if
unanesthetized)

Imaging scoring to discuss:

ASPECTS score: 10-point score used for anterior circulation strokes: looking at two cuts
1. Level of thalamus and basal ganglia
2. Rostral to basal ganglia
Start at 10 and deduct one point from initial score for every region involved

https://radiopaedia.org/cases/mca-alberta-stroke-program-early-ct-score-aspects-illustration?
lang=us

subcortical structures: caudate, internal capsule, lentiform nucleus

mTICI score
Primary outcomes:

Wide confidence intervals

Strongly indicative of clean-up lytics
Alteplase iA up to ¼ of IV, will have higher concentration

Pre-thrombectomy era: in 90s pure iA lytics, didn’t work great, then MT came about

Only applies to subset with successful MT

Imbalances in early time to treatment, could have residual confounding
Need more heterogenous population

Limitation:
Low recruitment d/t recruitment issues with COVID and inability to obtain placebo 
overestimation of treatment effects, wide confidence intervals, premature stopping/underdosing
of IV tPA before starting MT

Next step: MVO because devices are smaller!