ISCHEMIC STROKE / CLASSIFICATION AND ETIOLOGY

Moyamoya disease

Created 11/05/2023, last revision 19/05/2023

  • progressive stenoocclusive disorder affecting the terminal segment of the internal carotid artery (ICA) and proximal segments of the arteries forming the circle of Willis (ACA, MCA, PCA)
  • an abnormal network of fine collateral arteries (lenticulostriate arteries, thalamic perforators, and pial arteries) is formed near stenotic vessels, resembling smoke puffs (moya-moya)
  • the process is usually bilateral, but unilateral manifestation does not exclude the diagnosis
Moyamoya

Etiology

  • moyamoya angiopathy (moyamoya pattern) may be caused by a variety of congenital and acquired diseases (see table)
  • proliferation and thickening of the intima of the terminal ICA segment and proximal MCA segment predominate;  the proliferating intima may contain lipid deposits, but there is no evidence of inflammation  [Bang, 2015]
  • thrombi may be present
  • associated neovascularization occurs as a compensatory mechanism (collateral circulation)
  • in practice, moyamoya should be considered more as a radiologic entity that can be associated with several diseases
  • acquired (e.g., moyamoya syndrome in vasculitis) – see table
  • congenital – sporadic and familial forms (10% are reported, but the number is probably higher)
    • AD transmission with low penetrance has been demonstrated in familial cases of MMD with linkage to chromosomes 3,6,8,12 and 17 (e.g., 17q25.3 Raptor); Ring finger 213 (RNF213) appears to be an important gene, its exact function is unknown  [Bang, 2015]
    • the moyamoya pattern may be caused  by other inherited vasculopathies (Grange syndrome, ACTA2 mutations, etc.)

→ more about etiology can be found here

Enlarged intima (black arrow) and intraluminal thrombus (blue arrow) in moyamoya [Scott, 2009]
 Moyamoya disease
  • idiopathic with possible inherited abnormality (several mutations already described)
  • known inherited disorders associated with moyamoya angiopathy (e.g., Grange syndrome, ACTA2 mutations, etc.)
 Moyamoya syndrome – acquired disorders

Epidemiology

  • predominantly in Asians, with the highest prevalence in Japan (3.16 cases/100,000 inhabitants)
  • rarely affects Caucasians, African Americans, and Hispanics
  • peak incidence around age 4 (2/3) and then at age 30-40 (1/3)
  • approx. 10% of cases are familial (inherited)

Clinical presentation

  • onset of symptoms in a wide age range (4 months to 67 years), with a peak in the 1st and 3-4th decade of life
  • the clinical course is variable, ranging from asymptomatic forms to TIAs or strokes with permanent neurological deficit
  • mono- or hemiparesis, sensory disturbances, involuntary movements, headache, cognitive impairment, and epileptic seizures are common in children;  intracerebral hemorrhage is relatively rare
  • in adults, intraventricular, subarachnoid, or intraparenchymal bleeding is more common (in up to 30% of cases)
    • hematomas most commonly result from ruptured collaterals  [Kim, 2017]
  • watershed infarcts are common
  • clinical presentation (especially the incidence of bleeding) is influenced by race (higher incidence of bleeding in Asians than in Caucasians)

Diagnostic evaluation

Diagnostic criteria

Radiological and histological diagnostic criteria for MMD
 Angiographic findings suggesting the diagnosis of moyamoya
  • stenosis or occlusion of the terminal ICA (TICA) and proximal segments of the MCA and ACA
  • abnormal vascular network near occlusions, seen in the arterial phase
  • the finding is usually bilateral
 Histopathologic findings suggesting the diagnosis of moyamoya
  • thickening of the intima leading to stenosis or occlusion of the artery, typically found in the terminal segment of the ACI and the origin of MCA and ACA
  • stenosis or occlusion of the arteries of the circle of Willis with intimal thickening
  • multiple arterioles occurring in the vicinity of the Circle of Willis
Moyamoya disease staging    [Suzuki 1969]
Stage 1 – narrowing of the carotid bifurcation
Stage 2 – formation of collaterals (“moyamoya arteries”), stenosis of the terminal ICA, dilatation of the MCA and ACA
Stage 3 – intensive formation of moyamoya arteries, progression of stenoses of ICA, MCA, and ACA
Stage 4 – gradual disappearance of moyamoya arteries, the disappearance of PCA, further narrowing of ICA, MCA, and ACA
Stage 5 – a further reduction of moyamoya arteries with occlusion of ICA, ACA, and MCA
Stage 6 – ICA essentially disappears; the brain is supplied by the ECA
  • the staging system was first described by Suzuki and Takaku in 1969 and is still used
  • staging refers to findings on DSA, although the similar system may be applied to MRA or CTA
  • progression is more rapid in children than in adolescents or adults

Imaging modalities

  • digital subtraction angiography (DSA) – the gold standard, practically replaced by MRA/CTA
  • MR+MRA / CT+CTA
    • parenchymal lesions
      • typically watershed or territorial infarcts
      • hemorrhages or asymptomatic microbleeds (GRE/SWI sequences)
      • atrophy
    • evidence of stenoses in typical localizations (distal ICA, M1 ev. ACP) + typical collateral network
      • unilateral findings in up to 18%
    • imaging of the vessel wall can help in DDx (atherosclerosis, inflammation)
      • concentric stenosis
      • no or minimal enhancement
      • homogeneous T2 signal
      • absence of atherosclerosis
    • detection of collaterals
      • perforator network (puff of smoke) is seen mainly on DSA (less frequently and to a lesser extent on CTA and MRA)
      • Ivy sign – increased signal on MR FLAIR and T1C+ in the leptomeninges and perivascular spaces – indicates slow or retrograde flow in the leptomeningeal and cortical arteries  Moyamoya - evidence of leptomeningeal collaterals (Ivy sign)  [Ohta, 1995]  [Tharayil, 2019]
  • neurosonology
    • the flow in the affected and distal segments can be monitored + monitoring of VMR ⇒ may help to indicate surgical treatment
  • genetic testing
    • RNF213 gene on 17q25 (in Asians) → see here
    • “moyamoya panel” (incl. ACTA2, Grange sy, etc.)

Moyamoya disease

Moyamoya with multiple collaterals on DSA and multi-infarct involvement on MRI
Moyamoya - evidence of leptomeningeal collaterals (ivy sign)

Differential diagnosis

  • moyamoya syndrome (see the table above) must be distinguished

Management

Surgery

  • always consider the risk-benefit ratio
    • surgical treatment is mainly indicated in patients with a progressive, symptomatic course
    • EC-IC bypass may be considered in patients with stroke/TIA  (AHA/ASA 2021 2a/C-LD)
  • moya-moya syndrome with possible causal treatment (e.g., vasculitis) should be excluded before surgery   [Fujimura, 2015]
  • procedures:
    • direct anastomosis between the superficial temporal artery (STA) and middle cerebral artery (STA-MCA)  [Golby, 1999]

      • vessel-to-vessel anastomosis, immediate revascularization (convenient when symptoms progress)
      • required recipient vessel size > 1-1.5 mm
      • problematic in children
    • indirect anastomosis (flow improvement can be expected within weeks because a new capillary network is built; it can be performed in children)
      • encephalo-duro-arterio-synangiosis (EDAS)
      • encephalo-duro-arterio-myo-synangiosis (EDAMS)
      • pial synangiosis
    • direct + indirect anastomosis
  • the aim is to improve flow and prevent further formation of fragile collaterals
  • a clinical study comparing the effect of conservative and surgical treatment is not available
    • JAM trial showed marginal benefit in preventing rebleeding
    • several smaller studies have shown conflicting results
  • according to a meta-analysis, better outcomes can be expected with direct and combined anastomosis compared to indirect anastomosis alone  (Nguyen, 2022)
  • the situation in asymptomatic forms is unclear
STA-MCA bypass
Moyamoya disease - STA-MCA bypass

Conservative therapy

  • there is no specific drug therapy to alter the course of the disease
  • standard treatment is used for ischemic and hemorrhagic strokes
    • efficacy and safety of thrombolysis is unclear;  increased risk of bleeding from fragile collaterals need to be considered
  • in secondary stroke prevention, antiplatelet therapy is used
    • not an evidence-based practice; should be individualized based on the type and severity of the stroke, angiographic findings, and after weighing the risks and benefits of therapy
    • increased risk of ICH should be taken into account
    • antiplatelet therapy is also accepted by the AHA/ASA Guidelines 2021 (2b/C-LD)
    • bleeding is common in Asians, making the situation with antithrombotics problematic
  • role of antiplatelet therapy in primary stroke prevention is unclear

Prognosis

  • prognostic factors
    • rate and extent of vascular occlusions
    • the patient’s ability to establish a functional collateral circulation
    • age
    • neurologic deficit
    • extent of infarct
  • some patients are stable without surgical intervention, sometimes after severe cerebral infarct or hemorrhage with a permanent disability
  • approx. 50-60% of affected patients have cognitive impairment due to multiinfarct dementia
  • mortality is ~10% in adults and ~4-5% in children
    • the most common cause of death is intracranial hemorrhage
Send this to a friend
Hi,
you may find this topic useful:

Moyamoya disease
link: https://www.stroke-manual.com/moyamoya-disease/