Cervical artery dissection (CAD)

• Accounts for 1-2% of all ischemic strokes but in younger people 10-20% of all ischemic strokes.
• Annual incidence of 2.6-5 per 100,000 people, occuring at a mean age of 44-47 years. Dissection is rare after age 65.
• Trauma, migraine, pregnancy, postpartum, hypertension, strangulation, infection, connective tissue inflammation, SCUBA diving, and chiropractic manipulation have been reported as predisposing factors.
• Associated with connective tissue disorders like Ehlers-Danlos, osteogenesis imperfecta and Marfan syndrome.
• Probably multifactorial but genetic predispositon is likely.
  • Familial cases without any known connective tissue disease represent up to 5% of hostpital-based cohorts.
  • Concomitant arterial abnormalities are often observed, such as fibromuscular dysplasia, hyperdistensibility of the arterial wall, aortic root dilatation, endothelial dysfunction, and there might be an association with intracranial aneurysms.
  • Clinical signs of connective tissue disease such as skeletal, ocular or skin abnormalities are frequently associations.
• Paradoxically, many risk factors for ischemic stroke such as hypercholesterolemia and obesity are inversely associated with CAD
• An estimated 40% of “spontaneous” dissections are caused by mild trauma. Truly atraumatic dissection is thought to be secondary to vessel anomaly, either underlying arteriopathy, inflammatory process or structural instability of the affected artery.
• Iatrogenic CAD may occur as a complication of cerebral angiography.
• Internal carotid dissection (ICAD) is more common than vertebral artery dissection (VCAD).
• Extracranial ICAD dissections are more common than intracranial and the majority occur 2-3 cm distal to the common carotid bifurcation.

Pathophysiology

1. Intimal tear allows blood to enter in the tunica media of the vessel wall under pressure.
2. Blood dissects through the vessel wall, separating the layers as a wall hematoma is formed.
3. Might be entry-only dissection or entry-exit. In the latter, a distal intimal tear allows re-entry of blood in the vessel lumen as a false lumen is formed.
4. If the hematoma expands under the tunica adventitia it may cause a subadventitial dissection and pseudoaneurysm formation.
5. Wall hematoma reduces the true lumen’s diameter and may cause significant stenosis or occlusion.
6. Ischemic stroke may be caused by:
   1. Embolism of thrombotic material from the hematoma in the vessel wall.
   2. Embolism secondary to high-grade luminal stenosis.
   3. Reduced blood flow due to luminal obstruction.
7. As the wall hematoma expands, the mass effect may affect adjacent structures and cause secondary symptoms (e.g damage to sympathetic plexus around ICA -> Horner’s syndrome)
8. In time the hematoma becomes organised or resolves and a false lumen may or may not persist.

Clinical presentation

• Headache and/or neck pain, usually but not always ipsilateral to the dissected vessel, is the most common symptom occuring in up to 80% of cases.
• Headache is more common in ICAD and neck pain is more common in VAD.
• Painful tinnitus, facial pain, painful Horner’s syndrome (partial Horner, without anhidrosis), painful cranial nerve XI palsy, and signs of cerebral or retinal ischemia are other presentations.
• Vertigo is a common symptom in VAD.
• TIA is equally as common in ICAD as in VCAD but stroke is more common in VCAD.
• The average time from dissection onset to symptoms is 2-3 days but may be as long as 1 month.
• CAD may mimic a benign primary headache.

Imaging of CAD

Nonenhanced CT

• May demonstrate high attenuation crescent (as seen in axial plane) wall thickening at the site of the dissection, corresponding to the wall hematoma.
• May show signs of parenchymal ischemia.

CT angiography

• Eccentric enlargement of the affected portion of the artery.
• Abnormal vessel contour.
• The typical appearance is a narrowed, eccentric lumen surounded by a crescent-shaped mural hematoma that may display thin annular enhancement.
• Intimal flap (seen in <10% of all dissections).
• Dissecting pseudoaneurysm.

MRI

• Fat-saturated, non-enhanced T1-weighted and T2-weighted sequences: High signal crescent eccentric enlargement in vessel wall (hematoma in acute phase).
• SWI: blooming intramural hematoma.
• TOF-MRA: Absent flow-void or abnormal vessel contour.
• Early after onset (<24h), hematoma may be isointense on T1/T2, SWI might not show any blooming artifact and the dissection may be missed.

DSA

• Irregular lumen.
• String sign (thin contrast flow distal to a stenotic segment) or “string and pearl sign” - focal narrowing and a distal focal dilatation.
• Pseudoaneurysm.
• Intimal flap or double lumen (rarely seen).

Angiographic differentials:

• Atherosclerosis - ulcerated plaque may look like an intimal flap.
• Fibromuscular dysplasia - often bilateral, “string of beads” appearance.
• Carotid web (carotid intimal variant fibromuscular dysplasia).
• Traumatic pseudoaneurysm may be indistinguishable from a dissecting pseudoaneurysm.
• Congenital ICA malformations/dysgenesis.

Due to the small caliber of vertebral arteries and their proximity to bony structures, CT might be superior to MRI in detecting VCAD. No method is superior to the other in detecting ICAD.

Because MRI can directly visualise the intramural hematoma it is also useful in distinguishing an acute/subacute from an older dissection.

Reported sensitivity and specificity varies widely for both CTA and MRA and most are probably underastimates, based on older studies.

The American Stroke Association (ASA), and the International Headache Society recommend MRI with fat suppression as the best initial screening test. CTA is recommended if the dissection is in early stage or if the MRI is equivocal.

Management

There is a paucity of randomised placebo-controlled studies on the specific treatment of CAD. Current recommendations are based on the best available data and for the most part remain empiric. The goal of treatment is to prevent ischemic stroke.

• If the patient presents with ischemic stroke and meets the criteria for thrombolysis, thrombolysis (either intravenous or intraarterial) should be considered.
  • There is a risk that the intramural thrombus may be destabilised, leading to more intramural bleeding and expanding dissection.
  • The safety of both IV and IA thrombolysis is comparable to non-dissection stroke, but its efficacy is questionable.
• In the majority of patients the lumen will heal by itself at a mean time of 3 months.
• The 2011 AHA/ASA guidelines recommend treatment with either an anticoagulant or an antiplatelet for at least 3 to 6 months.
• None of the existing (mostly non-randomized) studies have shown superior efficacy or safety of one treatment to the other.
• Some authorities prefer anticoagulation if the dissection causes a significant stenosis of the true lumen of the vessel.
• Dual antiplatelet treatment should be considered at least in the acute phase in patients at high-risk for ischemic events such as high grade stenosis or occlusion, those presenting with TIA or minor stroke, patients with significant coexisting risk factors for stroke or previous stroke. The higher bleeding risk demands careful consideration of the risk/benefit ratio on an case-by-case basis.
• Surgical or endovascular treatment should be considered in patients that suffer recurrent ischemic events despite appropriate medical therapy, and in patients with significantly compromised cerebral blood flow.

References

• Cervical artery dissections: A review J Emerg Med. 2016 Nov;51(5):508-518. doi: 10.1016/j.jemermed.2015.10.044
• ESO guideline for the management of extracranial and intracranial artery dissection Eur Stroke J. 2021 Oct 13;6(3):XXXIX–LXXXVIII. doi: 10.1177/23969873211046475
• Greenberg M Handbook of Neurosurgery 8th edition, Thieme
• Osborn A Osborn’s Brain 2th edition, Lippincott Williams & Wilkins 2018
• Antiplatelet Therapy vs Anticoagulation Therapy in Cervical Artery Dissection The Cervical Artery Dissection in Stroke Study (CADISS) Randomized Clinical Trial Final Results JAMA Neurol. 2019;76(6):657-664. doi: 10.1001/jamaneurol.2019.0072
• Cervical Artery Dissection Continuum (Minneap Minn). 2023 Apr 1;29(2):540-565. doi: 10.1212/CON.0000000000001233
• Spontaneous Cervical Artery Dissection: The Borgess Classification Front Neurol. 2013 Sep 17;4:133. doi: 10.3389/fneur.2013.00133
• Angioplasty and stenting in carotid dissection with or without associated pseudoaneurysm AJNR Am J Neuroradiol. 2005 Oct;26(9):2328-35