Cervical and Intracranial Artery Dissection

Arterial dissection is a leading cause of stroke in young and middle-aged adults, accounting for approximately 10-25% of strokes in patients under 45 years. Dissection occurs when a tear in the arterial intima allows blood to enter the vessel wall, creating an intramural hematoma that can cause luminal stenosis, occlusion, or aneurysmal dilation. The clinical consequences range from local symptoms (pain, Horner syndrome) to devastating stroke from thromboembolism or hemodynamic compromise.

Management of dissection spans acute reperfusion decisions, secondary prevention strategies, and long-term follow-up. Recent trials including CADISS, TREAT-CAD, and STOP-CAD have shaped our understanding of antithrombotic therapy, though important questions remain about optimal treatment selection.

Pathophysiology

Dissection begins with a tear in the intimal layer, allowing blood to track into the arterial wall and form an intramural hematoma. This hematoma can expand subintimally (causing stenosis or occlusion) or subadventitially (causing aneurysmal dilation). A critical anatomical distinction exists between extracranial and intracranial dissections:

• Extracranial (cervical) dissection: The internal carotid and vertebral arteries have a well-developed adventitia that contains the dissection within the vessel wall. Stroke occurs primarily through artery-to-artery thromboembolism from the injured segment.
• Intracranial dissection: Intracranial arteries have a thinner media and lack an external elastic lamina, making them more prone to rupture through the adventitia and subarachnoid hemorrhage (SAH). The risk of SAH fundamentally changes the management approach.

Common Locations

Acute Management: Thrombolysis

The key question in the hyperacute setting is whether thrombolysis is safe in the presence of an arterial dissection. The theoretical concern is that tPA could extend the intramural hematoma, worsen stenosis, or promote vessel rupture. However, the dominant mechanism of stroke in dissection is thromboembolism, which is directly addressed by thrombolysis.

Extracranial (Cervical) Dissection

Multiple observational studies and registry analyses have demonstrated that IV thrombolysis is safe and effective in patients with cervical artery dissection presenting with acute ischemic stroke:

• AHA/ASA Guidelines (2019, 2024): IVT is reasonably safe and probably recommended (Class IIa, Level C-LD)
• ESO Guidelines (2021): Recommend IVT for extracranial dissection if standard inclusion/exclusion criteria are met

STOP-CAD tPA (2024) analyzed 1,653 patients with spontaneous cervical dissection presenting within 1 day of stroke symptoms. Compared to no IVT, thrombolysis was associated with:

• Better 90-day functional outcomes: aOR 1.67 (95% CI 1.23-2.28, p=0.001)
• No significant increase in symptomatic ICH: aOR 1.52 (95% CI 0.79-2.92, p=0.215)
• Benefit most evident in patients with NIHSS >5 and no intracranial extension

Intracranial Dissection

Intracranial dissection presents a more complex scenario. The absence of an external elastic lamina and thin adventitia create a real risk of rupture and subarachnoid hemorrhage with thrombolysis.

• ESO Guidelines (2021): IVT should be avoided in intracranial dissection (expert consensus)
• AHA/ASA: No specific recommendation due to lack of evidence

Acute Management: Thrombectomy

Mechanical thrombectomy is reasonable in patients with large vessel occlusion (LVO) in the setting of cervical artery dissection. Key considerations:

• ESO Guidelines (2021): Suggest thrombectomy for acute ischemic stroke with extracranial dissection and LVO of the anterior circulation
• AHA/ASA (2024): Thrombectomy is reasonable in otherwise eligible patients with LVO and cervical dissection
• Intracranial dissection: ESO makes no recommendation due to insufficient evidence

Procedural considerations include:

• Obtain CTA to identify the dissection site and plan approach
• Careful catheter navigation to avoid worsening dissection
• Stent retriever or aspiration techniques both feasible
• Decision about acute cervical stenting is individualized (see below)

Emergent Stenting in Dissection

Acute stenting of a dissected segment is generally avoided due to risks including:

• Worsening dissection or vessel perforation
• Need for aggressive antiplatelet therapy in acute stroke setting
• Most dissections will recanalize spontaneously with medical therapy

However, emergent stenting may be considered in select situations:

Secondary Prevention: Antiplatelet vs Anticoagulation

The optimal antithrombotic strategy for secondary prevention after cervical artery dissection has been debated for decades. Three major trials have addressed this question, with somewhat conflicting results.

CADISS (2015/2019)

CADISS was the first randomized trial comparing antiplatelet therapy to anticoagulation in 250 patients with symptomatic cervical artery dissection. Patients were randomized within 7 days of symptom onset:

• Stroke at 3 months: 2% (antiplatelet) vs 1% (anticoagulation) — no significant difference (p=0.63)
• Combined stroke and death: 2.5% in both groups
• Recanalization at 3 months: 35% complete, 35% persistent irregularity, 16% dissecting aneurysm, 25% remained occluded

Interpretation: CADISS found no difference between strategies, but was underpowered with low event rates. The trial established that both approaches are reasonable.

TREAT-CAD (2021)

TREAT-CAD randomized 194 patients with MRI-confirmed symptomatic cervical dissection to aspirin 300 mg daily versus vitamin K antagonists (VKA). The trial used a composite endpoint including clinical events and MRI findings:

• Primary composite (stroke, hemorrhage, death, or new MRI lesion): 23% (aspirin) vs 15% (VKA)
• Clinical stroke: 8% (aspirin) vs 0% (VKA)
• Subclinical MRI lesions: 15% vs 13%
• Major extracranial hemorrhage: 0% vs 1%

Interpretation: TREAT-CAD failed to establish non-inferiority of aspirin to VKA. All clinical strokes occurred in the aspirin arm. While not powered to show superiority, the results raised concern about aspirin monotherapy.

TREAT-CAD 6-Month Follow-Up (2025)

TREAT-CAD 6-months evaluated outcomes from 3 to 6 months in 122 participants continuing aspirin (n=93) or VKA (n=29):

• New events (3-6 months): 3.2% (aspirin) vs 3.4% (VKA) — no difference
• All events were hemorrhagic — no ischemic strokes or deaths in either group
• Absolute risk difference: 0.2% (95% CI −8.0% to 7.5%)

Interpretation: After the initial 3-month high-risk period, recurrent events are rare in both groups. All late events were hemorrhagic, raising questions about the benefit of continued antithrombotic therapy beyond 3 months.

STOP-CAD (2024)

STOP-CAD was a large multicenter observational study of 3,636 patients with cervical dissection comparing exclusive antiplatelet (n=2,453) versus exclusive anticoagulation (n=402) therapy:

• Ischemic stroke by 180 days: 3.3% (antiplatelet) vs 1.5% (anticoagulation) — trend favoring anticoagulation (HR 0.80, p=0.67 overall)
• Major hemorrhage by 180 days: 0.5% (antiplatelet) vs 0.7% (anticoagulation) — higher with anticoagulation (HR 5.56, p=0.009)
• 87% of strokes occurred within the first 30 days

Key subgroup finding: In patients with occlusive dissection, anticoagulation was associated with significantly lower ischemic stroke risk: HR 0.40 (95% CI 0.18-0.88, p=0.009). This interaction was not seen in non-occlusive dissection.

Trial Comparison: Secondary Prevention

Role of Dual Antiplatelet Therapy

The evidence for DAPT in cervical artery dissection is limited, but extrapolation from minor stroke/TIA trials (CHANCE, POINT) suggests potential benefit:

• AHA (2024): When considered safe, a short DAPT course (with loading dose, followed by single agent) may be preferred over monotherapy, especially in patients who would have been eligible for DAPT trials
• Rationale: The early high-risk period (first 2-4 weeks) aligns with the time window where DAPT has shown benefit in minor stroke/TIA
• Typical approach: Aspirin + clopidogrel for 21-30 days, then transition to aspirin or clopidogrel monotherapy

DOACs in Cervical Dissection

Direct oral anticoagulants are increasingly used in dissection, though trial data specifically comparing DOACs to VKA is limited:

• In STOP-CAD, 46% of anticoagulated patients received DOACs
• Practical advantages: No INR monitoring, fewer drug interactions, rapid onset
• Most commonly used: Apixaban 5 mg BID, rivaroxaban 20 mg daily
• No head-to-head trial vs warfarin in dissection; extrapolation from AF and VTE data

Duration of Therapy and Follow-Up

The recurrence risk in cervical dissection is front-loaded, with most strokes occurring within the first 2 weeks:

• STOP-CAD: 87% of strokes occurred within 30 days
• TREAT-CAD 6-months: No ischemic strokes between 3-6 months in either group

Recommended Approach

• Minimum duration: 3 months (AHA/ASA Class I, Level C-EO)
• Typical duration: 3-6 months
• Follow-up imaging: CTA or MRA at 3-6 months to assess recanalization, stenosis, and aneurysm formation
• Recanalization rates: ~60-80% by 3-6 months; treatment type does not appear to affect recanalization

Dissecting Aneurysms

Dissecting aneurysms (pseudoaneurysms) form in ~15-20% of cervical dissections. Management is generally conservative:

• Most do not enlarge, become symptomatic, or require intervention
• Follow-up imaging at 3-6 months and 12 months is reasonable
• Intervention (endovascular or surgical) reserved for enlarging aneurysms, mass effect, or recurrent embolic events despite medical therapy

Special Considerations

Intracranial Dissection

• Higher risk of SAH — favors antiplatelet over anticoagulation
• Avoid thrombolysis if intracranial dissection is confirmed before IVT decision
• Consider neurosurgical/neurointerventional consultation for dissecting aneurysms

Intracranial Extension of Extracranial Dissection

• Common scenario: ICA dissection extending into petrous or cavernous segment
• The primary lesion remains extracranial; thrombolysis is reasonable if otherwise indicated
• Distinguish from primary intracranial dissection

Bilateral or Multiple Dissections

• Occur in ~15-25% of cases
• Consider evaluation for connective tissue disorders
• Higher stroke risk; more aggressive antithrombotic approach may be warranted

Summary: Treatment Algorithm

References

1. Markus HS, et al. Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial. Lancet Neurol. 2015;14(4):361-367.
2. Engelter ST, et al. Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial. Lancet Neurol. 2021;20(5):341-350.
3. Engelter ST, et al. The 6-months follow-up of the TREAT-CAD trial. Eur Stroke J. 2025.
4. Yaghi S, et al. Antithrombotic treatment for stroke prevention in cervical artery dissection (STOP-CAD). Stroke. 2024;55:908-918.
5. Yaghi S, et al. Intravenous thrombolysis in cervical artery dissection (STOP-CAD tPA). Stroke. 2024.
6. Debette S, et al. ESO guideline for the management of extracranial and intracranial artery dissection. Eur Stroke J. 2021;6(3):XXXIX-LXXXVIII.
7. Yaghi S, et al. Treatment and outcomes of cervical artery dissection in adults: A scientific statement from the AHA. Stroke. 2024;55:e91-e106.
8. Powers WJ, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update. Stroke. 2019;50:e344-e418.