How to face an ICAD?

Intracranial atherosclerotic disease (ICAD) is a dynamic disease characterized by the development, progression, and complication of atherosclerotic plaques affecting major intracranial arteries. ICAD prevalence varies within population with high spread in Asian, Hispanic and African ethnicities and relatively rare manifestation among Caucasians (up to 10% of ischemic stroke) although, nevertheless, it is more common in autopsy studies[1] Therefore, considering the distribution of the world’s population, ICAD may represent a major cause of stroke and vascular cognitive impairment globally[2].

Step-by-step technique and expert’s recommendation: 

1. In patients with large vessel occlusion (LVO) the diagnosis of ICAD may be very challenging. There are however some clinical and imaging clues increasing its probability such as absence of a known major cardiac embolic source, preceding transitory symptoms that can be explained by ischemia in the same arterial territory, absence of CT arterial hyperdense sign or MRI susceptibility sign, watershed-type infarction suggesting hemodynamic compromise caused by a pre-existing stenotic lesion[2].
2. In case of LVO without high suspicion of ICAD, start with first-line approach: large bore catheter aspiration or combine technique with aspiration and stent-retriever. This will clean up the lesion and probably reveal the presence of the underlying disease. 
3. Perform a quick run to increase the chance of visualizing the stenosis before thrombus re-formation occurs.
4. Based on DSA findings, you may find some features suggestive of ICAD: a truncal-type occlusion, suboptimal arterial opening with residual stenosis. Another typical feature is early worsening of arterial caliber after thrombectomy, that can lead to arterial re-occlusion.
5. Whenever the diagnosis of ICAD is confirmed or highly probable, start with i.v antiaggregation and wait carefully. You may use inhibitors of GpIIb/IIIa (Tirofiban, Eptifibatide, Abciximab) or inhibitor of P2Y12 (Cangrelor). Below you can find advantages and disadvantages of both:
   1. Inhibitors of GpIIb/IIIa (Tirofiban, Eptifibatide): 
      • advantages: the ability of cutting the bindings of fibrinogen so it is more effective when there is already a pre-existing thrombus
      • disadvantages: longer drug action time (15-30 minutes), longer half-life (2h-2.5h), irreversible
   2. Inhibitor of P2Y12 (Cangrelor): 
      • advantages: short drug action time (2 minutes), shorter half-life (30 minutes), reversible which makes it safer in case of larger established infarcted zone and potential hemorrhagic complications
      • disadvantages: it only blocs activity of the platelets so is less effective in already existing clot.
6. While waiting, you may give to the patient vasodilators i.a (Nimodypine) to exclude eventuality of a vasospasm as an underlying problem.
7. Whenever you observe aggravation of the stenosis, hemodynamic compromise or re-occlusion go with the angioplasty and/or stenting. Below you will find some options of the strategy with a brief overview:
   1. Angioplasty: it may be a first line strategy but when performed solely, there is higher risk of re-occlusion because of re-thrombosis or dissection within the ruptured atherosclerotic plaque. 

Can be used especially as a pre-stenting strategy: 

• with balloon-expandable stents – when there is no flow by the stenosis  
• with self-expanding stents – to prepare and dilate the lesion

1. Balloon expandable-stent implantation: considered as a best choice to stabilize the lesion whenever it is technically possible. Balloon expandable-stents have better radial force compared to laser-cut stents, but are more difficult to navigate because of their rigidity.

Can be used when:      

• diameter is bigger than 2 mm
• segment of the artery is not curved
• there is no mismatch in diameter of the proximal and distal part of the artery
  1. Laser-cut stent implantation (f.ex. Solitaire AB or Enterprise) you may use them whenever it is technically impossible to place balloon-expandable stents or when there are some anatomical inconveniences listed above. Laser-cut stents are easier to navigate but have worse radial force so you need to pre-dilatate the lesion first. 

Technical concerns:

• POT – proximal optimization of the stent – the technique used in cardiology with balloon-expandable stenting when there is a difference of the diameter between arteries.

Description of the technique: size of the chosen stent should be that one of a distal part of the vessel. After the stent placement, the angioplasty with the bigger balloon in proximal part of the stent is performed. The result is two different diameters within the stent.

Its usage in intracranial arteries is limited due to potential danger with balloon overdilatation.

• Stenosis adjustment – it is not mandatory to dilatate the lesion to regular size of the artery, sometimes undersizing may be sufficient and effective in terms of hyperperfusion prevention.
• Early stent re-occlusion – it is important to distinguish mechanism of the re-occlusion: antiaggregation insufficiency vs. mechanical impediment: if the proximal part of the stent is patent – it is probably not a fault of platelet’s aggregation within the stent, but more a mechanical impediment due to insufficient opening of the stent. 
• Distal navigation under iv. antiaggregation – should be performed carefully because the risk of bleeding complication is increased compare to regular thrombectomy. 

ICAD can be the underlying cause of large vessel occlusion in stroke patients undergoing mechanical thrombectomy and its diagnosis can be very challenging. Proper antiaggregation is crucial but whenever insufficient, you should consider stabilize the lesion with angioplasty and/or stent placement.

Literature:

1. Sacco RL, Kargman DE, Gu Q, et al. Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The nNorthern Manhattan Stroke Study. Stroke 1995; 26: 14–20.
2. Psychogios, Marios, et al. "European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease." European stroke journal 7.3 (2022): III-IV.