Meghana Srinivas, MD

Prabhakaran S, Liebeskind DS, Cotsonis G, Nizam A, Feldmann E, Sangha RS, Campo-Bustillo I, Romano JG, and on behalf of the MYRIAD Investigators. Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease. Stroke. 2021;52:1961–1966.

Intracranial atherosclerotic disease (ICAD) is a progressive pathological process of the cerebral vasculature which can lead to symptomatic stenosis of the blood vessels, causing occurrence and/or recurrence of strokes. Intracranial stenosis accounts for 10% of ischemic strokes in the United States with 12 to 20% experiencing recurrent strokes within one year of index stroke.

Shyam Prabhakaran et al. performed a post hoc analysis of the MYRIAD study (Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease) of ICAD patients with recent (less than 21 days) stroke/transient ischemic attack, 50-99% stenosis and those who had 6–8 weeks MRI Brain per protocol.  The study reported the risk of clinical stroke recurrence in the territory of the symptomatic artery at 1 year was 8.8%, with nearly 25% of patients having recurrent infarcts on 6- to 8-week brain magnetic resonance imaging (MRI). 

In this post hoc analysis of the MYRIAD study of biomarkers for recurrent strokes, multiple DWI lesion patterns at baseline were independently associated with recurrent infarcts at 6-8 weeks. New infarcts on 6- to 8-week MRI was associated with younger age (57.7 versus 66.0 years; P<0.01) and diabetes (32.6% versus 14.6%, P=0.05). Those with index ischemic stroke were more likely to have recurrent infarcts than those with TIA (31.3% versus 4.6%, P=0.01). Other factors with strong association for recurrent ischemic strokes include the presence of prior infarcts in patients with ICAD and baseline infarct patterns such as multiple infarcts, and borderzone infarct patterns have been associated with greater risk of stroke recurrence. Despite intensive medical management with antithrombotics and high dose statins, occurrence of very early recurrent infarct can be explained by early hemodynamic factors (with borderzone infarcts) and artery-to-artery embolism as unstable plaques can be friable and embolize atherothombotic material distally, especially in the first few days after index stroke or TIA.

It becomes pertinent in clinical practice to identify biomarkers predicting recurrence of ischemic strokes given the disease burden can be subclinical/silent. It is prudent to look for diagnostic biomarkers at the time of index event, such as hypoperfusion detected by QMRA and PET imaging, which have shown to predict stroke risk in patients with symptomatic vertebrobasilarand extracranial and intracranial atherosclerotic disease, Transcranial Doppler for micro emboli signal detection and study of plaque vulnerability especially if obtained during an earlier time window of index stroke.

Although the post hoc analysis has limitations, as not adjusting for multiple comparisons with the results being only hypothesis-generating overall, it did highlight important factors which can be used to design future studies.