Cerebrovascular Disease: Natural History, Diagnostic Evaluation, Plaque, and Medical Therapy

29.1Definition and presentation

Cerebrovascular disease presents as either an incidental asymptomatic plaque or a symptomatic syndrome requiring urgent evaluation. Symptomatic disease involves a recent neurological event corresponding to the affected arterial territory.

Presenting features of symptomatic carotid disease include:

• Hemispheric motor or language deficits.
• Ipsilateral retinal ischemic events (amaurosis fugax).
• Non-disabling minor stroke or transient ischemic attack (TIA).

The primary risk in symptomatic disease is early recurrent stroke, which clusters heavily within the first 90 days after the index event Amarenco TIA Registry · 2016. Under contemporary urgent-evaluation pathways, the 1-year stroke risk is approximately 5%. Urgent assessment and immediate secondary prevention reduce the 90-day recurrent stroke rate from approximately 10.3% under standard care to 2.1% with an early-access pathway, achieving a hazard ratio near 0.20 EXPRESS · 2007.

29.2Diagnosis and imaging classification

Diagnostic evaluation determines symptom attribution, stenosis severity, and the underlying stroke mechanism.

• Neurological history establishes symptom laterality, territory (retinal, anterior, or posterior circulation), and time elapsed since onset.
• Brain imaging defines the infarct burden and differentiates large-artery atherosclerosis from cardioembolic, small-vessel, or cryptogenic stroke mechanisms AHA/ASA 2021.
• Carotid duplex ultrasound is the initial vascular imaging modality. On Society of Radiologists in Ultrasound criteria, a peak systolic velocity (PSV) below 125 cm/s indicates less than 50% stenosis, 125 to 230 cm/s indicates 50 to 69%, and above 230 cm/s indicates 70 to 99%; an end-diastolic velocity above 100 cm/s and an ICA/CCA PSV ratio above 4 support 70% or greater SRU 2003.
• Confirmatory cross-sectional imaging (computed tomography angiography or magnetic resonance angiography) is mandated for any non-trivial duplex abnormality considered for intervention. This resolves duplex ambiguity and characterises the aortic arch, common carotid origin, and distal internal carotid artery ESVS 2023 · SVS 2022. Modality selection is dictated by renal function, contrast allergy, and implanted devices.

Stenosis severity classification depends on the measurement method. The NASCET method compares the minimal residual lumen to the normal distal cervical internal carotid artery, defining moderate stenosis as 50 to 69% and severe stenosis as 70 to 99% Rothwell (2004) · NASCET · 1991. Measurements generated by the ECST method are numerically distinct and not interchangeable with NASCET grades ECST · 1998.

29.3Baseline medical therapy

Medical management is the foundation of cerebrovascular care, acting as both primary treatment and the baseline against which intervention is evaluated.

• Antiplatelet therapy: Single antiplatelet therapy is the standard maintenance regimen. Short-course dual antiplatelet therapy is used early after minor stroke or high-risk TIA. A 21-day course of clopidogrel and aspirin reduces 90-day recurrent stroke CHANCE · 2013. A 90-day course of clopidogrel and aspirin reduces ischemic events but increases major hemorrhage POINT · 2018. A 30-day course of ticagrelor and aspirin reduces the composite of stroke or death at the expense of more severe bleeding THALES · 2020. Indefinite dual therapy is contraindicated; 18 months of clopidogrel and aspirin increases life-threatening bleeding to 2.6% compared with 1.3% for clopidogrel alone, with no recurrent stroke benefit MATCH · 2004.
• Lipid-lowering therapy: High-intensity statin therapy reduces long-term recurrence. Atorvastatin 80 mg daily reduces 5-year recurrent stroke rates to 11.2% versus 13.1% on placebo, accompanied by a small hemorrhagic stroke signal SPARCL · 2006. The treatment target is an LDL-C below 70 mg/dL (1.8 mmol/L), achieved with a high-intensity statin and add-on ezetimibe or a PCSK9 inhibitor when the target is not met AHA/ASA 2021.
• Blood-pressure control, glycemic management, and lifestyle modification (including smoking cessation) are universally required components of primary and secondary stroke prevention SVS 2022 · AHA/ASA 2021 · AHA Primary Prevention (2014).

29.4Revascularization and treatment choice

Procedural intervention provides incremental stroke prevention when anatomic and clinical features indicate a risk that outweighs the perioperative hazard. Carotid endarterectomy (CEA) is the standard revascularization modality, while carotid artery stenting (CAS) is reserved for selected candidates. Intervention is performed only when institutional 30-day stroke or death rates remain <= 6% for symptomatic disease and <= 3% for asymptomatic disease ESVS 2023.

Decision logic for revascularization:

1. Determine symptom status and timing. Symptomatic severe disease receives the highest benefit from expedited surgery. NASCET demonstrated an absolute risk reduction of 17 percentage points at 2 years for 70 to 99% stenosis (26% stroke risk on medical therapy versus 9% with CEA) NASCET · 1991. Benefit peaks within 14 days of the qualifying event ESVS 2023 · Rothwell (2004). The number-needed-to-treat (NNT) is approximately 5 when performed within 2 weeks, rising to approximately 125 if delayed beyond 12 weeks.
2. Stratify symptomatic moderate stenosis by sex. Benefit in 50 to 69% stenosis is smaller and subgroup-dependent, yielding an approximate 5-year NNT of 9 for men compared with 36 for women Rothwell (2004).
3. Evaluate asymptomatic disease against baseline risk. Prophylactic intervention relies on surviving the initial procedural hazard to accrue long-term benefit. ACAS reported a 5-year aggregate stroke risk of 11.0% with trial-era medical therapy versus 5.1% after CEA for >= 60% asymptomatic stenosis ACAS · 1995. In ACST-1, 10-year stroke rates were 10.8% after immediate CEA versus 16.9% with deferred intervention ACST-1 (2010).
4. Apply morphology modifiers. In contemporary practice, asymptomatic intervention decisions integrate stenosis severity with imaging-defined plaque morphology, patient life expectancy, and stroke risk despite optimal medical therapy ESVS 2023 · ESO 2021. High-risk plaque features that shift an asymptomatic patient toward intervention include echolucent or predominantly hypoechoic plaque (Gray-Weale/Geroulakos type 1 to 2), a juxtaluminal black area greater than 8 mm2 on ultrasound, plaque ulceration, intraplaque haemorrhage on MRI, clinically silent ipsilateral infarction on CT or MRI, spontaneous embolisation (microembolic signals) on transcranial Doppler, stenosis progression, and impaired cerebrovascular reserve.
5. Transition to definitive medical therapy. Patients with a prohibitive operative risk (unable to meet the 3% or 6% caps), limited life expectancy, uncertain symptom attribution, or competing non-atherosclerotic stroke mechanisms are maintained exclusively on secondary medical prevention.

29.5Surveillance

Surveillance targets patients managed medically who may cross an intervention threshold, and tracks the durability of completed procedural care.

• Routine follow-up relies on actionable imaging to identify progressive stenosis or the emergence of high-risk plaque morphology that triggers reconsideration of surgery.
• Clinical evaluation verifies adherence to the baseline medical strategy, specifically statin dose intensity, blood-pressure target attainment, and smoking cessation.
• Surveillance is discontinued when the patient is no longer a candidate for future intervention due to limited life expectancy or severe competing medical risks SVS 2022.

29.6Areas of controversy

The magnitude of benefit for prophylactic revascularization in asymptomatic severe carotid stenosis is actively debated. Historical trials demonstrating an advantage for CEA were conducted before high-intensity statins and modern antithrombotic regimens lowered the baseline stroke risk ACAS · 1995 · ACST-1 (2010). The CREST-2 program directly tests intensive medical management alone against revascularization (stenting or endarterectomy) plus intensive medical therapy for >= 70% asymptomatic stenosis. Early 4-year CREST-2 reports show primary outcome rates of 6.0% in the stenting medical-management group versus 2.8% in the stenting group, and 5.3% in the endarterectomy medical-management group, with the surgical comparison not showing a statistically significant reduction CREST-2 (2026) · CREST-2 Protocol (2017). The precise criteria for embedding plaque morphology into asymptomatic thresholds also remain non-uniform across major society guidelines.