Thread by @ShadiYaghi2

#ICAD Tweetorial: Intracranial atherosclerotic disease is the most common cause of stroke worldwide accounting for nearly 10% of ischemic strokes in the United States and up to 50% of ischemic strokes in China.

SAMMPRIS showed that the risk of recurrent events in medically treated ICAD patients was 6.6% at 3 months and 12.2% at 1 year but post-SAMMPRIS studies using real world data demonstrated a rate as high as 25% at 90-days (Stroke. 2017 Aug; 48(8): 2158–2163) @ShyamSprabhak

In #ICAD, rupture of intracraial atherosclerotic plaque leads to thrombus formation. Smaller thrombi can therefore break loose and embolize distally causing distal infarcts. Also, the unstable plaque can extend to occlude perforating branches leading to deep perforator infarcts.

Furthermore, plaque rupture can cause/worsen luminal narrowing impeding blood flow/perfusion and thus causing infarcts related to reduced distal blood flow/perfusion. The infarct pattern may often provide clues on the implicated mechanism.

This Figure provides examples (A) Internal border‐zone infarct. (B) Core infarct. (C) Perforator infarct. (D) Cortical border‐zone infarct. The magenta color signifies the area of infarction and the green color signifies brain tissue with Tmax delay threshold of 6 seconds or more

The SAMMPRIS trial showed superiority of medical treatment in all patients with symptomatic ICAD. But why are we still seeing a relatively high recurrent rate of stroke in #ICAD? It is likely that medical treatment does not work for all!

Why is this the case? Medical treatment can help stabilize atherosclerotic plaques & reduce the risk of embolization, but is unlikely to acutely improve blood flow/perfusion in the affected territory & may not be effective in preventing recurrent stroke when the flow is impaired

SAMMPRIS showed that anterior circulation borderzone infarcts were associated with increased risk of stroke (Stroke. 2019;50:143–147). Also VERITAS showed an associated between impaired blood flow and recurrence risk in posterior circulation ICAD (JAMA Neurol. 2016;73(2):178-185)

Also, this study showed that distal hypoperfusion in acutely symptomatic ICAD with 50-99% stenosis is associated with stroke recurrence and could be used to enrich future trials of secondary stroke prevention in ICAD patients. onlinelibrary.wiley.com/doi/abs/10.111…

Thus patients with ICAD and impaired distal blood flow or perfusion may benefit from testing perfusion strategies beyond aggressive medical management alone. Analysis of SAMMPRIS showed fewer events with stenting in those with borderzone infarcts. ahajournals.org/doi/full/10.11…

What biomarker should we use to identify these patients? According to several studies & VERITAS, in patients with posterior circulation ICAD, impaired distal blood flow may be best measured by quantitative MRA. But what should we use in patients with anterior circulation ICAD?

One may argue to use borderzone infarct pattern. But often areas beyond the borderzone territory may be subject to hypoperfusion and in some the borderzone territory may be infarcted without any further territory at risk. Therefore known the perfusion status is crucial.

Here is an example of a patient with symptomatic severe left M1 stenosis with deterioration despite aggressive medical treatment. The infarct pattern appears to be atheroembolic but the perfusion showed a moderate size territory at-risk. So getting perfusion was helpful.

Therefore, symptomatic ICAD has a high risk of early recurrence. Impaired distal perfusion/flow portends a high recurrence risk despite optimal medical treatment. Studies validating optimal biomarkers and thresholds & testing early reperfusion in those at higher risk, are needed.

The PERFUSE-ICAS study, if funded, will investigate perfusion thresholds in patients with anterior circulation #ICAD to help select patients for trials testing reperfusion therapies. @ShyamSprabhak @dliebesk @UCLAStroke @BrownNeurology @UCStrokeTeam @PoojaKhatriMD @vagal01