ICAD Management - Ep.1/2: Post MT early reocclusion - SLICE Worldwide 2023

Endovascular Treatments for Acute Large Vessel Occlusion (LVO) Stroke associated with Intracranial Atherosclerotic Disease (ICAD)

Intracranial atherosclerotic disease (ICAD) is a considerable etiology of acute ischemic stroke (AIS), among which acute large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT) is challenging in terms of early diagnosis and appropriate endovascular treatment (EVT) strategy. 

Clues to ICAD-LVO

Despite that ICAD-LVO can hardly be fully diagnosed and distinguished from other intracranial vessel occlusion mimics, especially arterial dissection or hard clot before thrombectomy, suspicion of ICAD as an underlying etiology of LVO based on clinical and imaging indicators could be extremely helpful for EVT strategy.

Clinical predictors can be categorized as demographics, vascular risk factors and clinical manifestations as follows. ICAD is highly prevalent in certain ethnic groups-Asian, Hispanic and African populations. The reported LVO with underlying ICAD was up to 29% of anterior circulation and 51% of posterior circulation in Asian population. Presence of atherosclerotic risk factors, such as hypertension, diabetes mellitus, hyperlipidemia and smoking history, and absence of major cardiac embolic sources, i.e., atrial fibrillation, increase probability of ICAD-LVO. Patients with ICAD-LVO tend to have hemodynamic compromise triggers, lower baseline NIHSS, recurrent or fluctuating symptoms within the same culprit territory and slow progressing clinical course compared with embolic stroke.

Baseline imaging integrates with multidimensional information to predict ICAD-LVO. Contrast CT derived imaging shows occlusion site and morphology, clot burden scores (CBS) and collateral compensation (truncal-type occlusion and good pial collaterals for ICAD). Common locations for ICAD include proximal M1, proximal and middle basilar artery, siphon of ICA and V4 segment. Watershed or scattered deep brain infarct patterns together with non-acute ischemic lesions within the same culprit cerebral artery have great predictive value for ICAD-LVO. Hyperacute ischemic core volume tends to be lower measured on CTP or DWI imaging. Signs suggesting in-situ erythrocyte-rich thrombus, such as hyperdense cerebral artery sign (HCAS) on noncontrast CT and susceptibility vessel sign (SVS) on SWI, would be less prevalent. Presence of intracranial calcification and other intracranial atherosclerotic stenosis might also be clues.[1, 2]

Two predictive models of ICAD-LVO are available for practical reference:

1) ABC2D: distinguish intracranial atherosclerotic stenosis-related occlusion (ICAS-O) from embolism-related occlusion (EMB-O); (absence of) atrial fibrillation-3, blood pressure-1; clinical neurological deficit (NIHSS<7)-1; (absence of) computed tomography hyperdense sign-1, diabetes mellitus-1; cutoff≥4 (0-7)[3]

2) DIRECT-MT derived: ICAS-LVO vs non LCAS-LVO; atrial fibrillation history, hypertension and smoking, occlusion located at the proximal M1 and M2, hyperdense artery sign, and clot burden score (CTA)[4]

EVT for ICAD-LVO: step-by-step techniques and experts’ recommendations

Before MT, signs on the initial DSA, including robust collateral circulation, the tapering sign, jet-like appearance, and truncal-type occlusion, highly suggest underlying ICAD for LVO. 

Combined technique or stent retriever as the first-pass might be preferred to more effectively debulk surrounding thrombus and visualize underlying residual stenosis during the stent opening. A quick run should be performed for diagnosis purpose immediately after a thrombectomy pass in case of early arterial caliber or flow worsening or re-occlusion, which also indicate ICAD-LVO[5]. Intravenous bolus or loading dose of antiplatelets might be started while waiting for control angiography. 

Bail-out strategy could be performed so long as MT alone doesn’t achieve sustainable  revascularization. The patient should be under proper sedation for intracranial angioplasty. Balloon-mounted stents are technically feasible providing with better radial force for proximal ICAD lesions, typically proximal M1, ophthalmic and intra-petrosal segments of ICA. Balloon angioplasty alone might be first choice for lesions not amenable to balloon-mounted stent, such as distal or bifurcation locations, different diameter in proximal and distal landing zone, arteries smaller than 2mm, or high-grade Mori lesions (long segment or tightly angled)[6]; oversized laser-cut stents could be used for rescue stenting after angioplasty under circumstance of severe dissection or residual stenosis, or whenever the artery starts to close down during waiting period. Some self-expanding stents could be deployed through balloon dilation catheter to avoid long exchange. Keep access to the true lumen once achieved. 

Antiplatelet Therapy for ICAD-LVO

Considering relatively high rate of early reocclusion after MT and possible necessity of bailout angioplasty, parenteral antiplatelets should be started as early as underlying ICAD is highly suspected, especially for patients who are not on dual antiplatelet therapy (DAPT) within one week prior to the stroke onset. Cone beam/dyna-CT could be used to rule out intracranial hemorrhage before intravenous antiplatelets. Either inhibitors of GpIIb/IIIa (Tirofiban, Eptifibatide, Abciximab) or P2Y12 (Cangrelor) could be given intravenously. Subgroup analyses of RESCUE BT trial suggested an efficacy trend and safety of intravenous tirofiban in patients with large artery atherosclerosis-related LVO undergoing EVT, and dose of tirofiban was 10mcg/kg bolus and then 0.15mcg/kg/min maintenance for up to 24 hours[7], which acts in 15~30 minutes with a half-life of 2~2.5h. Suggestive dose of intravenous cangrelor is 30mcg/kg bolus and then 4mcg/kg/min maintenance, which acts in 2 minutes with a shorter half-life of 30 minutes. Subsequent DAPT should be overlapped with 4~6h for tirofiban and 1h for cangrelor before discontinuing intravenous infusion. CYP2C19 genetic testing or platelet aggregometry is practicable to rule out potential clopidogrel nonresponders and substitute the new-generation antiplatelet agents, such as ticagrelor. 

Technical concerns:

·Strong support system

Either Wingspan or balloon-mounted stents could be difficult to navigate due to rigidity especially in torturous vasculature; thus a strong support system, typically long sheaths and intermediate catheters, can be placed high enough for support catheters to kiss the stenosis. Stiff micro-guidewire provides extra support particularly during long exchange. Lengths of devices should be compatible, otherwise short valve for flushing could be a backup.  

·Sub-optimal angioplasty

The snow plowing effect from the angioplasty procedure is a major concern for worsening perforator stroke risk. In target lesions close to perforators (<2mm), typically M1 segment with the lenticulostriate perforators or upper-middle segment of the basilar artery with the pontine perforators, submaximal angioplasty could be achieved by undersizing the balloon and/or balloon-mounted stent to approximately 80% of true luminal diameter and inflating the balloon gradually. Short balloon-mounted stents (9~13mm) are easier to navigate with less perforator coverage. Residual stenosis up to 30% is acceptable to avoid post-stenting angioplasty.   

Conclusion

LVO due to underlying ICAD can be indicated according to demographic characteristics, atherosclerotic risk factors, clinical history, non-invasive imaging and DSA features; and should be differentiated with other intracranial arterial stenotic etiologies. At least one pass of MT is suggested to debulk surrounding thrombus followed by a quick run to show underlying stenosis. Bailout angioplasty with balloon and/or stent might be optional for selective patients and lesions but still lacks RCT evidence; future studies regarding timing and strategy of rescue are warranted. Nevertheless, effective fast-acting antiplatelet therapy is crucial to prevent reocclusion and prepare patients for emergency angioplasty.     

Literature:

1.Huo, X., et al., Endovascular Treatment for Acute Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Disease. Semin Neurol, 2023. 43(3): p. 337-344.

2.de Havenon, A., et al., Large Vessel Occlusion Stroke due to Intracranial Atherosclerotic Disease: Identification, Medical and Interventional Treatment, and Outcomes. Stroke, 2023. 54(6): p. 1695-1705.

3.Liao, G., et al., A simple score to predict atherosclerotic or embolic intracranial large-vessel occlusion stroke before endovascular treatment. J Neurosurg, 2022: p. 1-8.

4.Li, H., et al., Early diagnosis of intracranial atherosclerotic large vascular occlusion: A prediction model based on DIRECT-MT data. Front Neurol, 2022. 13: p. 1026815.

5.Psychogios, M., et al., European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease. Eur Stroke J, 2022. 7(3): p. Iii-iv.

6.Alexander, M.J. and W. Yu, Intracranial atherosclerosis update for neurointerventionalists. J Neurointerv Surg, 2023.

7.Qiu, Z., et al., Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial. Jama, 2022. 328(6): p. 543-553.