• intracranial stenosis is a major factor that increases the risk of stroke [Bos, 2014]
  • it is the cause of ~10% of strokes
  • the annual risk of recurrent stroke in symptomatic IC stenosis is  4-18%
  • modern imaging modalities (TCD/TCCD, CTA, and MRA) allow non-invasive and easy diagnosis of intracranial stenosis [Degnan, 2011]


Mechanisms of stroke in IC stenosis
  • hypoperfusion in high-grade stenosis
    • CBF decreases distally up to > 75% by XeCT
  • occlusion of the artery at the site of the stenosis
    • thrombus, intraplaque hemorrhage, plaque rupture
  • distal embolization
    • microembolic signals (MES) are present on TCD in 36% of patients with recent symptomatic IC stenosis
    • in the chronic stage, the number of MES is minimal, and in asymptomatic stenoses, they are usually not detected at all  [Segura, 2001]
  • occlusion of the perforator by growing plaque
The most common causes of intracranial stenosis
  • progression of stenosis can occur for the following reasons:
    • growth of atherosclerotic plaque
    • thrombosis
    • plaque rupture with intraplaque hemorrhage

Diagnostic evaluation

Examples of intracranial stenoses detected on TCCD, CTA, MRA and DSA


CT/MR angiography

  • the optimal imaging method is CTA
  • non-contrast intracranial MRA may overestimate the stenosis grade
MCA stenosis on CTA

Stenosis of M1 section of MCA on CTA
MCA stenosis on MRA (M1 segment)

Digital subtractive angiography

  • currently replaced by CTA in most cases


  • enables to determine the cerebral blood flow (CBF)

Intravascular sonography (IVUS) [Zacharatos, 2010]

  • used in cardiology, now being tested in carotid and intracranial territories  IVUS
  • clarifies the morphology of the stenosis (atherosclerotic plaque vs. inflammation, etc.)

Optic coherent tomography (OCT)  Optical coherence tomography imaging demonstrated the atherosclerotic plaque (white arrowheads) with calcifications) (Yang, 2021)

  • OCT uses near-infrared light to image the arterial anatomy with much higher resolution than IVUS (10 vs. 100 μm)
  • used in cardiology, also tested in vascular neurology
    • assessment of plaque structure   (Yang, 2021)
    • assessment of stent position after the procedure and at follow-up
    • potential for use during the stenting procedure is investigated
  • outperforms IVUS in determining plaque morphology (presence of thrombus, hemorrhage, fibrous cap rupture, etc.) and in differentiating other causes of stenosis


Asymptomatic stenosis
  • antiplatelet therapy + aggressive treatment of vascular risk factors (see below)
  • endovascular intervention is not indicated
Symptomatic stenosis
  • the risk of recurrent stroke/TIA or vascular death in patients with IC stenosis is 10-12%/year [Chimowitz,2005]
    • older studies reported a risk of up to 22%/year with conservative treatment; despite that, the risk is ~2 times higher than in patients with extracranial stenosis
  • the mainstay of treatment of intracranial and extracranial stenoses is aggressive treatment of vascular risk factors

Aggressive treatment of vascular risk factors

  • target BP < 120/80 mm Hg (if possible with respect to comorbidities)  AHA/ASA 2021 1/B-NR)
    • careful with lower values, hypoperfusion behind severe stenosis may be provoked
    • in therapy, prefer ACE-I or sartans
  • intensive lipid-lowering therapy with target LDL < 1.4 mmol/l (after stroke/TIA) → target lipid values
    • SPARCL trial showed a reduction in the recurrence risk in patients with recent stroke/TIA
  • tight glycemic control
    • achieve target glycosylated hemoglobin + manage insulin resistance
    • patients with diabetes < 6% (60 mmol/mol)
    • patients without diabetes < 4.5% (45 mmol/mol)
  • lifestyle interventions:
    • smoking cessation → see here
    • obesity control
      • according to some recommendations, the target BMI <20-24!
      • waist circumference female/ male <80/<94 cm
    • healthy diet (e.g., Med-Diet)
    • appropriate and regular physical activity
      • 150 min/wk of moderate aerobic activity or 75 min/wk of vigorous aerobic activity

Anticoagulant vs. antiplatelet therapy

  • the mainstay of medical treatment is antiplatelet therapy (AHA/ASA 2021 I/B-R)
    • WASID trial did not show the superiority of anticoagulants over antiplatelet therapy
    • start ASA 100-325 mg/d
    • efficacy of clopidogrel, cilostazol, or ticagrelor in monotherapy is unknown  (AHA/ASA 2021 2b/C-EO)
  • in patients with recent stroke/TIA (<30 days) and stenosis >70%, DAPT (ASA+CLP 75mg) for up to 90 days may be considered – SAMMPRIS (AHA/ASA 2021 2a/B-NR)
  • in patients with recent minor stroke/TIA (< 24h) and intracranial stenosis > 30%, DAPT with ASA + ticagrelor 2x 90mg for 30 days may be considered (AHA/ASA 2021 2a/B-NR)
  • DAPT ASA/CLP + cilostazol 200 mg/d may be considered in patients with recent stroke/TIA (< 24h) and intracranial stenosis > 50% (AHA/ASA 2021 2b/B-NR)
  • anticoagulation may be considered when antiplatelet therapy is ineffective or in cases of stenoses with extensive thrombosis

Percutaneous transluminal angioplasty with stenting (PTAS)

  • due to the small diameter of the intracranial arteries, the risk of complications during the endovascular procedures is higher than for procedures on the extracranial arteries
    • significant risk of vasospasm, dissection, and arterial rupture with high mortality and morbidity
    • stenting may be difficult if there is extracranial kinking
  • on the other hand, even mild dilatation of an intracranial stenosis may be beneficial as it leads to a significant improvement in blood flow
    • hemodynamic failure is an important mechanism for the development of ischemia in intracranial stenoses (as opposed to extracranial stenoses where distal embolization prevails)
  • the SSYLVIA and ASS1T-1 trials have demonstrated the technical feasibility of intracranial angioplasty
    • successful stent deployment was achieved in 95-97.5% of cases, with restenosis >50% in up to 30% of patients/year
  • however, the SAMMPRIS and VISSIT (Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) trials failed to show the benefit of stenting over medical therapy
  • for symptomatic stenoses of 50-69%, the procedure is associated with high mortality and morbidity compared to medical therapy (AHA/ASA 2021 3/B-NR)
  • for symptomatic stenoses of 70-99%, angioplasty should not be the first-line therapy, even in patients already on monotherapy (AHA/ASA 2021 3/A) (⇒ switching to DAPT is preferred)
  • angioplasty may be considered as the last option when aggressive medical therapy fails in stenoses of 70-99% – however, the benefit is unknown (AHA/ASA 2021 2b/C-LD)
    • stenosis > 70% + failure of maximal medical therapy
  • the SAMMPRIS trial  evaluated the efficacy and safety of percutaneous transluminal angioplasty and stenting (PTAS) with the Wingspan system in symptomatic severe atherosclerotic intracranial stenosis (70-99%) compared to aggressive medical therapy alone
    • 30-day stroke/death 14.7% vs 5.8% (conservative treatment)
    • primary endpoint at 1 year: 12% (aggressive conservative treatment) vs. 20% (PTAS)
    • patients did not benefit from endovascular therapy because of a high risk of periprocedural complications and a low risk of stroke recurrence with aggressive conservative treatment
    • the high efficacy of aggressive conservative treatment supports the fact that in SAMMPRIS, patients treated conservatively were less likely to have a recurrent stroke than in the WASID trial
    • the superiority of conservative management persisted at 2-4 year follow-up (14.1% vs. 20.6% at 2 years (P = 0.07) and 14.9% vs. 23.9% at 3 years (P =0 .0193) (Derdeyn, 2013)
  • negative results were also reported in the VISSIT trial (Vitesse Intracranial Stent Study for Ischemic Stroke Therapy)  [Zaidat, 2015]
    • using a balloon-expandable stent compared with medical therapy alone led to a higher risk of stroke/TIA in the same territory after 12 months and a higher risk of any stroke or TIA within 30 days

Surgery (EDAS – Encephalo-Duro-Arterio-Synangiosis)

  • positive results of the phase 2a ERSIAS trial (annual risk of recurrence 9.6% vs. 21.2%; randomized trial is planned)

EC-IC bypass

  • not recommended for intracranial stenoses/occlusions  (AHA/ASA 2021 3/B-R)

Intracranial angioplasty procedure

  • continue dual antiplatelet therapy (aspirin 100 mg + clopidogrel 75 mg) after the procedure
  • duration of DAPT depends on the type of stent
    • coated stents:  6-12 months (such as Taxus or Pharos)
    • standard stent (such as Wingspan): ≥ 4 weeks
  • after the required duration of DAPT, switch to long-term single antiplatelet therapy (SAPT)
  • evaluation of procedural success:
    • technical success – achievement of residual stenosis < 30% by PTA or stent deployment
    • m/m at 30 days (periprocedural); reported in the range of 5-30%
  • factors that may reduce the chance of procedural success include:
    • inability to place the guiding catheter below the skull base
    • significant tortuosity of the proximal arteries
    • stenosis length > 10mm
    • multiple stenoses or tortuous segments
  • equipment:
    • stents:
      • Pharos, Taxus, etc. (drug-eluting stents)
      • Wingspan (standard stent)
    • balloons: Gateway, Maverick, etc.
  • before the procedure, angiographically verify the appearance and etiology of the stenosis (AS plaque, dissection?)
  • treatment of stenosis caused by dissection:
    • do not use drug-eluting stents
    • in the acute stage, self-expandable stent insertion is recommended instead of PTA
    • in the chronic phase, concomitant PTA is often required
  • the incidence of periprocedural morbidity/mortality is reported varies widely (6-20%) depending on the methodology and patient selection
    • in the SAMMPRIS trial, the 30-day incidence of stroke/death was 14.7%
  • distal protection is not available for intracranial procedures
  • an additional stent can be used with hemodynamically significant intracranial dissection
  • in case of severe vasospasm, the microwire should be withdrawn
    • vasospasm should resolve in 5-10 minutes
    • if vasospasm persists, try local vasodilators

→ overview of complications of endovascular procedures

  • monitoring:
  • variable incidence reported
  • classification according to localization to the stent
    • peri-stent restenosis
    • intra-stent restenosis
  • most restenoses occur within 6 months
  • the clinical significance of restenosis is unclear
  • there is no significant difference in the incidence of restenosis between angioplasty and stenting

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Management of intracranial stenosis
link: https://www.stroke-manual.com/management-intracranial-stenosis/