ISCHEMIC STROKE / VASCULITIS
Takayasu arteritis
Created 24/05/2023, last revision 27/05/2023
Etiology
- Takayasu arteritis is an inflammatory disease affecting the aorta and its branches
- predominantly occurs in young oriental women (female to male ratio is 8:1)
- etiology is unknown
- cell-mediated immune mechanisms are involved; histology shows similar findings to temporal (giant cell) arteritis
- inflammation starts with adventitial mononuclear infiltration
- later, mononuclear inflammation of the media may occur, accompanied by granulomatous changes
- onset usually in the first 3 decades of life
- inflammation causes irregular thickening of the affected artery, and the following may occur:
- concentric stenosis or occlusion (initially granulomatous changes of the media and adventitia, later intimal hyperplasia)
- thrombosis
- aneurysm (∼ 30% of patients)
Clinical presentation
Systemic symptoms
- most commonly in the initial phase
- fatigue, fever, weight loss, night sweats, myalgia, and/or arthralgia
- many patients present only with focal symptoms caused by hypoperfusion of the affected organ or limb
CNS involvement
- symptoms of decreased cerebral perfusion
- dizziness and syncopes (> 50%), subclavian steal syndrome
- ischemic stroke
- visual disturbances (visual field defects, amaurosis, retinal hemorrhages)
- intracerebral hemorrhage (most commonly due to aneurysm rupture)
Involvement of the heart and other arteries
- secondary renovascular hypertension
- limb arteries involvement
- the diagnostic sign is the weakness of the pulse (“pulseless disease“); most patients have an absent pulse in at least one limb
- reduced blood pressure in one or both arms
- blood pressure difference > 20mm Hg between the left and right arm or between the arm and leg on the same side
- bruits are often audible over the subclavian arteries (in the supraclavicular fossa), brachial arteries, carotid arteries, abdominal aorta, or femoral arteries
- limb claudication
- Takayasu arteritis is a chronic disease where collateral circulation usually develops – ischemic ulcerations or gangrenes are rare
- signs of aortic coarctation (e.g., hypertension, headache, leg claudication)
- cardiac symptoms
- angina pectoris / myocardial infarction (due to the narrowing of the coronary artery orifice)
- heart failure due to aortic regurgitation
- angina pectoris / myocardial infarction (due to the narrowing of the coronary artery orifice)
- pulmonary hypertension, pulmonary infarcts
Diagnostic evaluation
The diagnosis of Takayasu arteritis is based on:
- typical symptoms and signs (see above)
- typical imaging
- evidence of inflammation detected by blood tests
Imaging methods
- characteristic findings in the aorta and its branches (always examine the descending aorta and renal arteries):
- segmental concentric stenoses/occlusions
- poststenotic dilation
- collateral arteries
- aneurysms
- carotid ultrasound – a direct visualization of wall thickening, may assess the flow in distal segments and collaterals
- magnetic resonance imaging
- MRA
- T1C+ dark(black) blood sequence helps to detect inflammatory changes in the vessel wall
- MRA
- CTA
- DSA
- FDG PET/CT
- demonstration of inflammatory arterial involvement
[Chrapko, 2015] - hypometabolism in some brain regions [Berlit, 2010]
- demonstration of inflammatory arterial involvement
- Takayasu arteritis can progress silently even if clinical status and laboratory studies suggest remission ⇒ periodic vascular imaging is required
Blood tests
- tests are nonspecific
- ↑CRP (C-reactive protein), ESR (erythrocyte sedimentation rate) > 40mm (but normal values do not exclude active disease)
- anemia of chronic disease (usually mild)
- leukocytosis
- elevated platelet levels
- ↑ metalloproteinases MMP-2, MMP-3 and MMP-9
Blood pressure measurement
- BP should be measured in all extremities
- accurate measurement can be difficult
- if both subclavian arteries are affected, systemic BP can be measured only in the unaffected legs
- if both subclavian arteries are affected, and the patient has coarctation of the descending aorta and/or involvement of both iliac/femoral arteries, accurate noninvasive BP measurement is not possible ⇒ central arterial pressure may be measured via angiography to detect occult hypertension
- other signs of occult hypertension are:
- hypertensive retinopathy
- echocardiographic evidence of concentric left ventricular hypertrophy
- severe hypertension may cause complications that may be confused with symptoms of vasculitis
Diagnostic criteria and classification
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Diagnostic criteria of Takayasu arteritis
( American College of Rheumatology, 2022) |
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Absolute requirements
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Additional clinical criteria
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Additional imaging criteria
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| A score of ≥ 5 points is needed to classify as Takayasu arteritis |
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Diagnostic crieteria of Takayasu arteritis
( American College of Rheumatology, 1990) |
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Typical clinical complaints lasting > 1 month
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major |
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minor |
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minor minor minor |
Proof of arterial involvement
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major
major
minor
minor minor
minor
minor
minor
minor
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High probability of Takayasu arteritis
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Differential diagnosis
- atherosclerosis
- age > 40 years
- more common in men
- lesions in typical locations
- fibromuscular dysplasia (FMD)
- rarely affects the subclavian artery; practically never the aorta
- temporal arteritis (does not affect CCA and subclavian artery)
- vascular infections
- syphilitic aortitis (typical aortic calcifications)
- tuberculous, fungal aortitis
- neurofibromatosis type I
- idiopathic inflammatory conditions (e.g., ankylosing spondylitis with aortitis, Behçet syndrome, sarcoidosis)
Stroke prevention
- antiplatelet therapy [Souza, 2010]
- treatment of hypertension (problem with BP assessment with subclavian arteries stenoses/occlusions)
- low sodium diet
- stenting or bypass surgery in cervical arteries
- procedures performed during remission have better results
Immunosuppressive therapy
- start with PREDNISONE 1 mg/kg, gradually taper over several weeks; the target dose is individualized (based on inflammatory markers and clinical status)
- after achieving remission (decrease in ESR and CRP, correction of anemia), maintain a dose of 5-10 mg/day for 1-2 years
- rapid tapering may lead to relapse
- prevention of osteoporosis is necessary during long-term corticosteroid treatment – e.g., Caltrate PLUS 1-0-1 or Kombi-Kalz 1000/880 1-0-0
- combine corticosteroids with immunosuppressants or immunomodulators whenever possible
Immunosuppressants – cytostatics
- approximately 50-70% of patients require additional treatment with immunosuppressive drugs
- for less aggressive forms use:
- azathioprine (IMURAN) 1-2 mg/kg/day
- mycophenolate (CELLCEPT)
- for aggressive forms:
- methotrexate 0.15-3 mg/kg/day
- cyclophosphamide (ENDOXAN) 2 mg/kg/day
New immunosuppressive agents [Mekinian, 2015]
- biological-targeted treatments
- monoclonal antibody against IL 6 receptor – tocilizumab (ROACTEMRA)
- TNF alpha blocker – for resistant conditions
Reconstructive procedures
- vascular procedures for organ-threatening ischemia, such as stenting or bypass surgery (besides cervical arteries, limb, mesenteric and renal arteries are also treated)
Follow up
Laboratory tests
- CRP unreliable
- ESR – decline during remission present in ∼ 60% of cases ⇒ unreliable marker [Matsuyama,2003]
- metalloproteinases [Matsuyama,2003]
- MMP-2 diagnostic > 800 ng/mL
- relapse – MMP-3 > 100 ng/mL and MMP-9 > 75 ng/mL
Imaging methods
- vascular lesions may progress even when clinical and laboratory studies suggest remission
- repeated vascular imaging to assess stenosis grade and wall width/enhancement is essential
- MRI of the neck (incl. black blood sequences) + MRA
- neurosonology
- CT angiography
Prognosis
- the course is usually relapsing and remitting or chronic/progressive
- despite therapy, the prognosis is uncertain, and the disease often progresses
- restenosis of the intervened arterial segments often occurs despite combined immunosuppressive therapy
