Neurosurgery notes/Vascular/Occlusive disease/Moyamoya disease

Moyamoya disease

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Occlusive disease
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Definition

  • Progressive spontaneous occlusion of one or usually both ICAs (usually at the level of the carotid siphon) and their major branches, with secondary formation of an anastomotic collateral capillary network at the base of the brain which has been termed “moyamoya,”
    • With progression, can involve
      • Proximal MCAs
      • Proximal ACAs
      • Vertebrobasilar system (rare).
    • Associated aneurysms (see below) and rarely AVMs can be seen.
    • Eventually the dilated capillary (moyamoya) vessels disappear with the development of collaterals from the ECA
      • Meningeal collaterals are called “rete mirabile”
  • Moyamoya: Japanese word for something hazy like a “puff of cigarette smoke” (resembles on angiography).

Numbers

  • Incidence in Japan is higher (0.35/100,000/yr) than in North America.
  • Prevalence of 10.5 patients per 100,000
  • Age
    • Two peaks (may not be same disease):
      • Juvenile (highest peak): age < 10 yrs (mean 3)
      • Adult: 3rd & 4th decade.
  • Sex
    • Slight female predominance (1.8:1).
  • Genetics:
    • Some evidence for familial tendency (some Asian families have an incidence as high as 7%),
    • Genetics appears autosomal dominant with low penetrance.
    • Associated with some HLA antigens (B40 in juvenile form; B54(20) in adult) and anti-double-stranded DNA antibody.

Risk factors

  • PMHx of inflammation head & neck inflammation

Pathophysiology

Primary moyamoya disease
  • Idiopathic stenosis of the proximal anterior and middle cerebral arteries that is neither atherosclerotic nor inflammatory in origin.
  • Most common
  • Studies show elevated basic fibroblast growth factor in the dura and scalp arteries in patients with moyamoya.
  • The internal elastic lamina of affected vessels may be thinned or duplicated.
  • Might be a systemic vascular disease as similar vascular changes may also occur in the heart, kidney, and other organs
  • Genome-wide association study identified the RNF213 gene in the 17q25 region as a susceptibility gene for moyamoya disease among East Asians.
Secondary moyamoya disease (AKA “quasi-moyamoya disease” or “moyamoya syndrome.”)
  • Angiographic findings of moyamoya associated with:
    • Graves’ disease/thyrotoxicosis
    • History of cerebral inflammatory disease, including meningitis (especially tubercular (TB) meningitis and leptospirosis)
    • Retinitis pigmentosa
    • Vascular disorders:
      • Atherosclerosis, fibromuscular dysplasia, pseudoxanthoma elasticum
    • Congenital disorders:
      • Down syndrome, Marfan syndrome, Turner syndrome, NF1, tuberous sclerosis, Apert syndrome
    • Hematologic disorders:
      • Fanconi anaemia,
      • Sickle cell disease
        • Most common cause of Moyamoya in the UK
        • (In the U.S. one of the more common associations) and sickle cell trait)
    • Following radiation therapy for skull base glioma in children
    • Head trauma
    • Systemic lupus erythematosus (SLE)

Associated aneurysms

  • Intracranial aneurysms are frequently associated with moyamoya disease (MMD).
  • Due to
    • Increased flow through dilated collaterals, or
    • Congenital defect in the arterial wall that predisposes them to aneurysms.
  • 3 types:
    • Usual sites of aneurysms in the Circle of Willis,
    • In peripheral portions of cerebral arteries, e.g. posterior/anterior choroidal, Heubner’s, and
    • Within moyamoya vessels.
  • The frequency of aneurysms in the vertebrobasilar system is ≈ 62%
    • Which is much higher than in the general population.
  • Aneurysmal SAH may be the actual cause of some haemorrhages that were erroneously attributed to moyamoya vessels.

Natural history

  • Incidence of disease progression in one study was 20% in adult patients with MMD.
  • Female patients had a higher risk of disease progression than males.
  • Prognosis of untreated MMD is poor,
    • 73% rate of major deficit or death within 2 years of diagnosis in children
    • Similarly poor outlook in adults.

Presentation (Burke 2009)

  • 4 types of presentation
    • Ischemic 63.4%,
      • Predominates in childhood
        • Making up 69% of cases in patients under 10 years old
        • Ischaemic symptoms are often provoked by straining or by hyperventilation (e.g. during crying or blowing a wind instrument),
          • Which is thought to produce hypocapnia with reactive vasoconstriction.
        • Symptoms may present repetitively and can result in motor aphasia, cortical blindness, mental retardation, and low IQ over the long term.
        • The Progression of occlusion is more common in children than adults.
      • Headache
        • Most common presenting symptom,
    • Haemorrhagic 21.6%
      • 66% of adult cases exhibit haemorrhages with a higher occurrence in females.
      • 70–80% of haemorrhages.
        • Due to rupture of the fragile moyamoya vessels
          • Produces bleeding in the basal ganglia (BG), thalamus, or ventricles (from the ventricular wall)
        • SAH
          • Due to rupture of associated aneurysms
      • Risk of haemorrhage is increased in stages 5 & 6 of MMD.
    • Epileptic 7.6%,
    • “Other” 7.5%.

Diagnostic criteria

  • Bilateral symmetrical stenosis OR occlusion of the terminal portion of the ICAs AND
    • If unilateral, the diagnosis is considered questionable, and these cases may progress to bilateral involvement)
  • Presence of dilated collateral vessels at the base of the brain.
  • Other characteristic findings include:
    • Stenosis/occlusion starting at termination of ICA and at origins of ACA and MCA
    • Abnormal vascular network in region of BG (intraparenchymal anastomosis)
    • Transdural anastomosis (rete mirabile), AKA “vault moyamoya.”
      • Contributing arteries:
        • Anterior falcial
        • Middle meningeal
        • Ethmoidal
        • Occipital
        • Tentorial
        • STA
    • Moyamoya collaterals may also form from internal maxillary artery via ethmoid sinus to forebrain in frontobasal region

Investigation

CT
  • Up to 40% of ischemic cases have normal CT.
  • Low density areas (LDAs) may be seen,
    • Usually confined to cortical and subcortical areas (unlike atherosclerotic disease or acute infantile hemiplegia which tend to have LDAs in basal ganglia as well).
    • LDAs tend to be multiple and bilateral,
      • Especially in the PCA distribution (poor collaterals),
      • More common in children.
MRI and MRA
  • MRA usually discloses the stenosis or occlusion of the ICA.
  • Moyamoya vessels appear as flow voids on MRI (especially in basal ganglia) and a fine network of vessels on MRA,
  • Are demonstrated better in children than adults.
  • Parenchymal ischemic changes are commonly shown, usually in watershed areas.
  • Ivy sign on Flair imaging (sulcal hyperintensity)
    • Prognostic biomarker
  • MRI and MRA cannot diagnose Moyamoya if it is just unilateral disease.
Angiography
  • Aim
    • Establish the diagnosis
    • Identifies suitable vessels for revascularization procedures
    • Unearths associated aneurysms.
  • Show
    • Stenosis or occlusion at the terminal portion of the ICA and/or at the proximal portion of the ACAs and/or the MCAs
    • Abnormal vascular networks in the vicinity of the occlusive or stenotic lesions in the arterial phase.
  • Cerebral angiography is not mandatory when MR imaging and MR angiography clearly demonstrate:
    • Bilateral stenosis or occlusion at the terminal portion of the ICA and at the proximal portion of the ACAs and MCAs on MR angiography,
    • Bilateral abnormal vascular network in the basal ganglia on MR angiography (> 2 apparent flow voids are observed in 1 side of the basal ganglia on MR imaging).
  • The angiography-related complication rate is higher than with atherosclerotic occlusive disease.
  • Avoid dehydration prior to and hypotension during the procedure.
  • Six angiographic stages of MMD (Suzuki staging)
    • Tend to progress up until adolescence and stabilize by age 20
        • Stage
        Angiographic Findings
        I
        Narrowing of the carotid fork (i.e. ICA bifurcation)
        II
        Initiation of the moyamoya: continued narrowing of the ICA; dilation of the ACA and MCA; initial moyamoya blush
        III
        Intensification of the moyamoya: loss of proximal ACA and MCA; leptomeningeal collateralization from the PCA; increase in moyamoya blush
        IV
        Minimization of the moyamoya: progressive occlusion of ICA reaching origin of PCA; reduction in moyamoya blush
        V
        Reduction of the moyamoya: complete loss of ICA, ACA, and MCA; increased collateral supply from ECA; further reduction in moyamoya blush
        VI
        Disappearance of the moyamoya: disappearance of blood supply from ICA; blood supply exclusively from ECA; disappearance of moyamoya vessels
        ACA: anterior cerebral artery;
        ECA: external carotid artery;
        ICA, internal carotid artery;
        MCA, middle cerebral artery;
        PCA, posterior cerebral artery.
         
        Schematic diagram of the six stages of MMD according to the Suzuki staging system (the red vessel represents the internal carotid artery system and the gray vessel represents the meningeal branches from the extracranial artery). a Stage 1: narrowing begins at the fork of the carotid artery (the narrowed part is pointed by the hollow arrow). b Stage 2: initiation of moyamoya collaterals (the red triangle shows the narrow parts of intracranial arteries, the small red arrow shows the moyamoya collaterals around the narrowed vessels and the hollow red arrow shows the distal branch dilatation of the middle cerebral artery and anterior cerebral artery). c Stage 3: aggravation of moyamoya collaterals around the narrowed vessels. d Stage 4: exacerbation of the narrowed vessels, and the moyamoya collaterals begin to fade. e Stage 5: large vessels occlusion and more obvious reduction of surrounding moyamoya changes. f Stage 6: disappearance of moyamoya collaterals and internal carotid artery system vessels, instead, the territories of the internal carotid artery are supplied from the external carotid artery (the black arrow shows the collaterals from the extracranial artery)
        Schematic diagram of the six stages of MMD according to the Suzuki staging system (the red vessel represents the internal carotid artery system and the gray vessel represents the meningeal branches from the extracranial artery).
        a Stage 1: narrowing begins at the fork of the carotid artery (the narrowed part is pointed by the hollow arrow).
        b Stage 2: initiation of moyamoya collaterals (the red triangle shows the narrow parts of intracranial arteries, the small red arrow shows the moyamoya collaterals around the narrowed vessels and the hollow red arrow shows the distal branch dilatation of the middle cerebral artery and anterior cerebral artery).
        c Stage 3: aggravation of moyamoya collaterals around the narrowed vessels.
        d Stage 4: exacerbation of the narrowed vessels, and the moyamoya collaterals begin to fade.
        e Stage 5: large vessels occlusion and more obvious reduction of surrounding moyamoya changes.
        f Stage 6: disappearance of moyamoya collaterals and internal carotid artery system vessels, instead, the territories of the internal carotid artery are supplied from the external carotid artery (the black arrow shows the collaterals from the extracranial artery)
        DSA images with lateral views of patients with MMD of ICA (I–V) and ECA (VI). (I) Suzuki’s Stage I: narrowing of carotid fork. (II) Suzuki’s Stage II: initiation of basal moyamoya, ACA and ACM are dilated. (III) Suzuki’s Stage III: intensification of moyamoya, remarkable moyamoya vessels at the base of the brain, MCA and ACA can be occluded. (IV) Suzuki’s Stage IV: minimization of basal moyamoya, more and more transdural anastomoses occur, next to MCA and ACA the PCA can be affected. (V) Suzuki’s Stage V: even more reduction of basal moyamoya vessels, intracerebral anastomoses between ACP and ACM occur prominent. (VI) Suzuki’s Stage VI: vascularisation of ACA and MCA exclusively through transdural anastomosis of ACE and basilar/vertebral arteries
        DSA images with lateral views of patients with MMD of ICA (I–V) and ECA (VI).
        (I) Suzuki’s Stage I: narrowing of carotid fork.
        (II) Suzuki’s Stage II: initiation of basal moyamoya, ACA and ACM are dilated.
        (III) Suzuki’s Stage III: intensification of moyamoya, remarkable moyamoya vessels at the base of the brain, MCA and ACA can be occluded.
        (IV) Suzuki’s Stage IV: minimization of basal moyamoya, more and more transdural anastomoses occur, next to MCA and ACA the PCA can be affected.
        (V) Suzuki’s Stage V: even more reduction of basal moyamoya vessels, intracerebral anastomoses between ACP and ACM occur prominent.
        (VI) Suzuki’s Stage VI: vascularisation of ACA and MCA exclusively through transdural anastomosis of ACE and basilar/vertebral arteries
        • Used for diagnosis, surgical planning, and monitoring progression.
        • More applicable to children as many adults remain within the same stage.
        • Most cases belong to stages 3-5.
        • Stages not strongly related to clinical symptoms.
         
      • At 4 ECA start coming in to supply brain
        • Stage
        Combined
        ICA
        ACA/MCA
        PCA
        Moyamoya
        ECA supply
        1
        ICA start stenosis, No blush
        Start of stenosis
        Normal
        Normal
        No blush
        Nil
        2
        ICA continue stenosis
        Start blush
        Continued stenosis
        Dilatation
        Normal
        Start blush
        Nil
        3
        ICA occlusion Max blush
        Occluded
        Occluded
        Normal
        Greatest blush
        Nil
        4
        PCA occlusion Reduce blush
        Occlusion
        Occluded
        Occluded
        Reduced blush
        Nil
        5
        Start ECA Reduced blush
        Occluded
        Occluded
        Occluded
        Reduced blush
        Start
        6
        Entire ECA, No blush
        Occluded
        Occluded
        Occluded
        No blush
        Entire brain
EEG
  • Non-specific in the adult.
  • Juvenile cases:
    • High-voltage slow waves may be seen at rest, predominantly in the occipital and frontal lobes.
    • Hyperventilation produces a normal buildup of monophasic slow waves (delta-bursts) that return to normal 20–60 seconds after hyperventilation.
    • In >50% of cases, after or sometimes continuous with buildup is a second phase of slow waves (this characteristic finding is called “rebuildup”), which are more irregular and slower than the earlier waves, and usually normalize in ≤ 10 minutes.
Cerebral blood flow (CBF) studies
  • CBF is decreased in children with MMD,
    • But relatively normal in adults.
  • There is a shift of CBF from the frontal to the occipital lobes
    • Reflecting the increasing dependency of CBF on the posterior circulation.
  • Children with MMD have impaired autoregulation of CBF to blood pressure and CO2
    • With more impairment of vasodilatation in response to hypercapnia or hypotension than vasoconstriction in response to hypocapnia or hypertension.
  • Xenon (Xe-133) CT can identify areas of low perfusion.
  • Repeating the study after an acetazolamide challenge (which causes vasodilatation) evaluates reserve capacity of CBF and can identify areas of “steal” which are at high risk of future infarction.
    • As the vessels are maximally vasodilated and therefore cannot dilate anymore to lower resistance to gain more blow flow to the region

Treatment

General information
  • No medical or surgical treatment has been proven effective in reducing the rate of hemorrhage in the adult with MMD.
    • However, multiple large case series have supported the efficacy of cerebral revascularization for reducing the incidence of ischemic strokes and TIAs.
  • The paediatric population is typically treated with indirect revascularization because
    • The likelihood of angiogenesis is higher in children than in adults
    • Direct bypass is technically challenging and more prone to thrombosis in children.
      • Children vessels are smaller
  • General lifestyle advice for pre- or post-bypass moyamoya patients includes:
    • Avoid oral contraceptives or hormone replacement therapy
      • Due to the risk of cerebral thrombosis (especially through bypass graft)
    • Lifelong aspirin
    • Ensure headgear/helmets do not constrict blood supply to the bypass,
    • Avoid donating blood
      • Due to risk of TIA/stroke from loss of intravascular volume
Asymptomatic moyamoya disease
  • No guidelines yet.
  • Subtle findings of cerebral infarction and disturbed cerebral hemodynamic were detected in 20% and 40% of the involved hemispheres, respectively.
  • Angiographic stage was more advanced in elderly patients.
  • Of 34 medically-treated patients, 7 experienced TIA, ischemic stroke or haemorrhage during a mean follow-up period of 43.7 months.
  • Cerebral infarction or haemorrhage did not occur in the 6 patients who underwent surgical revascularization.
Medical treatment
  • Not proven of benefit
    • Platelet inhibitors
    • Anticoagulants
    • Calcium channel blockers
    • Steroids
    • Mannitol
    • Low-molecular-weight dextran
    • Antibiotics
  • Steroids
    • May be considered for involuntary movements and acutely during recurrent TIAs.
Surgical treatment
  • General information
    • Patients with mass effect from clot may be candidates for urgent decompression. Revascularization procedures, however, should be performed when the patient is stable under nonemergent conditions.
  • Indication
    • History of infarct/ hemorrhage/progressive disease
  • Aims
    • Augment blood flow
    • Improvement in CBF
    • Reduction in further ischemic events
    • Reduction in hemorrhagic events
  • Revascularization regions
    • MCA territory:
      • EDAS,EDAMS, STA- MCA bypass multiple burr holes
    • ACA territory:
      • Bypass vascularized dural flap
  • Perioperative management
    • Avoid hyperventilation: due to increased sensitivity of collaterals, keep PaCO2 40–50mmHg to avoid ischemic infarction
    • Avoid hypotension: maintain BP at normotensive levels
    • Avoid alpha-adrenergic agents because of vasoconstrictive effects
    • Cerebral protection: mild hypothermia (32–34 °C) and barbiturates are routinely used
    • Papaverine helps prevent vascular spasm
  • Postoperatively (following STA-MAC bypass procedures):
    • Extubate on table
    • Avoid hypertension:
      • May cause
        • Bleeding at anastomotic site and
        • In areas of increased perfusion within the brain
    • Avoid hypotension:
      • May result in graft occlusion
    • Aspirin is started on the post-op day #1
    • Watch for evidence of CSF leak
    • Monitor coag studies and correct abnormalities
    • Cerebral arteriogram is recommended 2–6 months post-op
  • Suggested criteria for revascularization procedures
    • Patients presenting with infarction or haemorrhage but are in good neurologic condition
    • Infarction<2cm maximal diameter on CT, and all previous haemorrhages have completely resolved
    • Angiographic stage is II-IV
    • Timing of operation: ≥ 2 months after most recent attack
  • Neurological complications
    • Include
      • Perioperative cerebral infarction
        • Ischemia mechanisms involve the "watershed shift phenomenon" and thrombo-embolic complications.
        • Mech
          • Retrograde blood supply from STA-MCA bypass may interfere with the anterograde blood flow from the proximal MCA, and thus result in the temporary decrease in CBF at the cortex supplied by the adjacent branch of MCA
            • Particularly in paediatric moyamoya disease.
          • Thrombo-embolic complications at the anastomosed site
          • Mechanical compression by swollen temporal muscle flap could also cause cerebral ischemia in the acute stage.
      • Cerebral hyperperfusion syndrome.
        • May occur in nearly 40% of adult patients 2-6 days after STA-MCA bypass.
        • Rapid focal increase in CBF (hyperemia) at the site of the anastomosis could result in vasogenic edema and/or hemorrhagic conversion in moyamoya disease.
        • Focal cerebral hyperperfusion
          • Causes temporary focal neurological deficit such as aphasia, hemiparesis, and dysarthria in a blood pressure dependent manner.
    • Preventive measures include good perioperative hydration, haemoglobin control, and the use of anti-platelet agents.