ISCHEMIC STROKE
Smooth Muscle Alpha-Actin (ACTA2) angiopathy
David Goldemund M.D.
Updated on 14/01/2024, published on 05/12/2022
- ACTA2 angiopathy is a vascular disease resulting from either occluded or enlarged arteries and can be caused by mutations in a single gene
- the vascular smooth muscle cell-specific isoform of α-actin (ACTA2) is a significant component of the contractile apparatus throughout the arterial system (Guo, 2009)
- heterozygous ACTA2 mutations can cause the inappropriate proliferation of SMCs ⇒ this may represent another pathogenetic pathway contributing to occlusive vascular disease
- most cases are diagnosed in childhood and present with:
- familial thoracic aortic aneurysms and dissections (TAAD)
- premature onset of coronary artery disease (CAD)
- premature ischemic strokes (including moyamoya angiopathy)
- in addition to the recommended routine imaging of the aorta for aneurysms, ACTA2-mutation carriers should also be monitored for CAD and cerebrovascular occlusive disease
Etiopathology
- SMCs and myofibroblasts from affected individuals proliferate more rapidly in culture than control cells ⇒ increased SMCs proliferation leads to steno-occlusive disease
- not all regions are affected; it is hypothesized that SMC proliferation depends on the presence of the mutation and an additional factor (vascular injury or increased biomechanical stress)
Clinical presentation
- aortic disease
- thoracic aortic aneurysm and dissection in childhood and young adulthood
- patent ductus arteriosus
- cerebrovascular disease
- ischemic strokes/TIA
- seizures
- pulmonary arterial hypertension
- peripheral arterial aneurysms
- GI abnormalities
- intestinal malrotation
- gastroesophageal reflux (GER)
- constipation
Diagnostic evaluation
Brain imaging (CT/MRI)
- periventricular white matter lesions
- border zone or territorial infarcts
Vascular imaging (CTA/MRA, neurosonology)
- medium to large vessels stenosis or occlusion, proximal ICA segment dilation
- intracranial multisegmental angiopathy (usually intracranial ICA)
- thoracic aortic aneurysm or dissection
Genetic testing
- mostly de novo mutations
- in familiar forms, inheritance is autosomal dominant
Differential diagnosis
- large vessel atherosclerosis
- vasculitis
- other genetic vascular diseases (e.g., Grange syndrome)
- connective tissue disorders
- sickle cell disease
Management
Acute stroke therapy
- standard acute stroke treatment → Recanalization therapy
- exclude aortic dissection before administration of a thrombolytic agent!
Prevention of cerebrovascular disease
- standard medical therapy
- antithrombotic drugs
- in elderly patients, initiate aggressive treatment of vascular risk factors
- address modifiable risk factors like hypertension, diabetes, smoking, and dyslipidemia to minimize the likelihood of cerebrovascular events
- avoid hypotension in moyamoya angiopathy or severe large vessel stenosis
- consider reconstructive procedures like PTA or bypass surgery in patients with severe symptomatic stenosis or moyamoya
