ISCHEMIC STROKE / CLASSIFICATION AND ETIOLOGY

Arterial dissection

Created 05/05/2023, last revision 07/11/2023

ESO guidelines for the management of extracranial and intracranial artery dissection (2021)

Definition and pathophysiology

arterial dissection is characterized by a tear in the inner layer of the arterial wall
blood enters the tear and separates the wall layers – a false lumen is formed in addition to the true lumen
the false lumen is often thrombosed and leads to stenosis or occlusion of the artery (in the case of occlusion, the diagnosis of dissection is more difficult).
thrombus growth and/or arterio-arterial embolization may occur (more common in extracranial arteries)
dissecting aneurysm may also develop
rupture through the adventitia leads to bleeding (causing SAH in intracranial lesion)

Epidemiology

dissection mainly affects younger and middle-aged individuals
- accounts for ∼ 5% of strokes in the age group < 45 years
- rare cause of stroke in the elderly population
- incidence is increasing due to better imaging
carotid arteries are most commonly involved (∼ 80% of cases; typically, the lesion is located below the skull base), while vertebral arteries are involved in ∼ 20% of cases (at level C1-2 – atlas loop)
- more than one vessel is affected in ∼ 25% of cases
intracranial dissection is relatively rare
dissection poses the highest risk of stroke within the first 14 days (absolute risk increase is ~1.25%, decreasing to 0.18% in weeks 3-4) [Morris, 2017]

Etiology

spontaneous x traumatic (trauma or C-spine manipulation)
- in both cases, the arterial wall or some of its layers is presumed to be defective
abrupt hyperextension/rotation of the head causes tension of the carotid artery over the transverse processes of C2, C3 or the lateral process of the atlas with subsequent tearing of the intima, or, conversely, the carotid artery is wedged between the mandible and C1 after extensive and rapid flexion
similarly, the vertebral artery is usually bruised over the edges of the transverse foramina or the atlas arch
if spontaneous dissection is suspected, renal artery imaging (in addition to cerebral artery imaging) is recommended to exclude Fibromuscular dysplasia

Some conditions associated with arterial dissection
Fibromuscular dysplasia (FMD) Syphilitic angiopathy Proliferative inflammation in some forms of arteritis Moya-moya Connective tissue disorders (Marfan syndrome, Ehlers-Danlos syndrome)

Clinical presentation

Extracranial dissection

Carotid dissection

unilateral neck, head, or orbital pain
Horner’s syndrome (caused by damage to the adventitial sympathetic plexus)
Harlequin sign (hyperhidrosis and flush of the contralateral half of the face during physical exertion) [Drexler, 2014]
lesion of cranial nerves IX-XII (compressed by the dissecting aneurysm) [Kasravi, 2010]
- may imitatate brainstem lesion
stroke symptoms in ~ 2/3 of cases
pulsatile tinnitus (DDx of CCF or dural fistula)
symptoms of carotid dissection can range from asymptomatic carotid stenosis/occlusion to extensive territorial stroke

Vertebral artery dissection

ipsilateral neck pain
a combination of extra- and intracranial involvement is common
symptoms depend on the extent of dissection (particularly whether the basilar artery or spinal arteries are involved) and the status of the collaterals
- dissection without concomitant distal embolization might remain asymptomatic if the contralateral VA is fully functional
- spinal cord ischemia results from the occlusion or hypoperfusion of spinal arteries

Aortic arch dissection → see separate chapter

dissection may be a source of emboli or lead to stenosis/occlusion of the aortic branches (most commonly CCA and ICA)
presents with:
- sudden onset of severe chest pain that radiates between the shoulder blades (often initially mistaken for a coronary event).
- hypotension, sometimes with transient loss of consciousness
- asymmetrical or very weak pulses in the neck and upper limbs
- cardiac tamponade may occur ⇒ urgent surgery is needed

Intracranial dissection

intracranial dissections are rare in the absence of systemic connective tissue disease
predominantly occurring in the vertebrobasilar territory and the supraclinoid portion of the ICA
headache typically occurs at the onset, almost always followed by the development of a neurological deficit
- in extracranial dissections, the development of a neurological deficit is gradual, often occurring several days after the initial headache; asymptomatic lesions are not uncommon
the main mechanism is hemodynamic failure behind the occlusion or stenosis (including occlusion of perforators); hemodynamically induced fluctuation of the neurological deficit is frequent
- distal embolization predominates in extracranial dissections
intracranial dissection may also lead to subarachnoid hemorrhage
diagnosis is difficult; angiographic findings are often nonspecific (occlusion or stenosis); typical features (string sign, double lumen) can usually not be seen
intracranial dissection may be confused with vasculitis
- involvement of the ICA may be suggestive of giant cell arteritis, which predominantly affects the petrous and cavernous segments
intracranial dissection usually has a worse prognosis than extracranial dissection (due to limited potential for collateral circulation)

Diagnostic evaluation

atypical history of head/neck pain after C-spine injury or manipulation, followed by development of neurologic deficit
vascular imaging (neurosonology, CTA/MRA/DSA) is essential; these findings are typical:
- a smooth, convex, elongated enlargement of the vessel wall causing luminal narrowing (string sign), stenosis may terminate relatively abruptly at the distal end
- a double lumen (pathognomonic finding)
- a dissecting aneurysm
diagnosis of intracranial dissection is problematic because:
- finding of nonspecific segmental stenosis or occlusion is common – may be confused with partially recanalized thrombus, thrombotic occlusion, or vasculitis
- typical string sign is often absent
- MR detection of evident intramural hematoma on the transverse section is less probable
- artery fenestration must be differentiated

Neurosonology

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CT angiography

string sign
double lumen
dissecting aneurysm (pseudoaneurysm)

The left ICA dissection with distinct "string sign"

Digital subtraction angiography

DSA is considered the gold standard for the diagnosis of dissection
not suitable for monitoring (in contrast to neurosonology)
typical findings:
- string sign
- dissecting aneurysm
- presence of double lumen

Internal carotid artery dissection on DSA

Magnetic resonance imaging (MRI)

the image changes over time (through acute, subacute, and chronic phases) – it is necessary to evaluate fat- and blood-suppressed T1, T2, and TOF simultaneously [Habs, 2011]
in the subacute phase, the T1 sequence shows a thrombus in the false lumen (T1 hyperintense ring)
MRA shows a luminal narrowing and possibly a thrombus in the false lumen

Different stages of an ICA dissection on MRI [Habs, 2011]

The right ICA dissection localized under the skull base ( T1 and CTA)

Management

treatment strategy for dissection-related stroke should be individualized
treatment options include:
- thrombolysis
- endovascular treatment
- anticoagulant/antiplatelet therapy (SAPT or DAPT)

Thrombolysis in dissection-related acute stroke

dissection was not listed as a contraindication in the NINDS or ECASS II trials, but the number of enrolled patients is unknown
according to published series of patients treated with IVT and IAT, efficacy and safety appear to be similar to those with other stroke etiologies [Biller, 2014] [Nedeltchev, 2002] [Georgiadis, 2006]
it remains uncertain whether thrombolysis (as well as anticoagulation) might contribute to the progression of intramural hematoma
IVT may be considered for isolated cervical dissection (ESO guidelines 2021)
IVT should rather not be used for intracranial dissection (ESO 2021 – expert consensus)
IVT is absolutely contraindicated for aortic dissection

→ intravenous thrombolysis

Endovascular therapy

stenting may be indicated in patients who experience a recurrent stroke despite medical therapy (AHA/ASA 2021 2b/C-LD) [Biller, 2014]
in the acute phase, the endovascular procedure may be performed in:
- patients with a tandem lesion (ICA dissection + intracranial occlusion – the procedure appears to be safe [Marnat, 2020]
- patients with extracranial ICA dissection, particularly if a tight stenosis or occlusion causes symptomatic hypoperfusion (demonstrated by TCD/TCCD or CTP)
- patients with intracranial dissection resulting in hypoperfusion (e.g., due to a progressive stenosis)
dual antiplatelet therapy (ASA+CLP) is required prior to stenting and should be continued for 3 months
self-expanding stents are preferred
- multiple stents may be necessary; start distally and ensure that stents partially overlap
thromboembolic complications can be treated mechanically, with IAT or IIb/IIIa inhibitors
progressive pseudoaneurysms can be managed with a stent or stent graft

Stenting for dissection of the carotid artery

Antithrombotics

anticoagulant or antiplatelet therapy should be continued for at least 3 months (AHA/ASA 2021 1/C-EO)
- although the primary mechanism involves arterial wall bleeding, the predominant mechanism of stroke is distal thrombotic embolization
studies comparing the effects of antiplatelet and anticoagulant therapy have shown no difference in efficacy in preventing recurrent stroke
- CADISS (Cervical Artery Dissection In Stroke) remains the only randomized trial [Hugh, 2019]
  - n=250, 124 (anticoagulation) vs 126 (antiplatelet), stroke + death/3 months: 1% vs 2% (p=0.63)
- non-randomized trial following 298 patients with carotid dissection showed similar results for aspirin and anticoagulants [Georgiadis, 2009]
- TREAT-CAD study is ongoing; it should demonstrate the noninferiority of ASA versus warfarin
intracranial dissections carry a higher risk of SAH due to the specific wall configuration (narrow media, absence of lamina externa), which tends to favor antiplatelet therapy
anticoagulation is not appropriate in patients with larger infarcts (↑ bleeding risk)
comparison between monotherapy (SAPT) and dual antiplatelet therapy (DAPT) is not available

Anticoagulants

for 3 months, then switch to ASA
some authors recommend repeating the vascular imaging in 2-3 months and adjusting the duration of anticoagulation based on the results
- complete recanalization allows an earlier switch to ASA
- persistent stenosis and luminal irregularities may warrant continued anticoagulation for up to 6 months

Antiplatelets

aspirin 75-100mg daily is most commonly used
short-term dual antiplatelet therapy (ASA+CLP) may be considered
antiplatelet therapy should be continued for at least 3 months
it is unclear whether long-term antithrombotic therapy should be continued in patients without connective tissue disease.
- probably not; studies are not available
likely/possible indications for long-term antiplatelet therapy: [Biller, 2014] :
- residual stenosis or persistent occlusion (evidence of benefit is lacking)
- patients with connective tissue disease and recurrent dissections
- pseudoaneurysm sac thrombosis

Other measures

standard treatment of vascular risk factors (especially maintaining normal blood pressure)
oral contraception is not recommended
avoid statins unless indicated for another reason