Moyamoya disease: is a nonatheroscleroticprogressive steno-occlusive arteriopathy that mostfrequently affects the intracranial ICAs and proximalsegments of the MCAs and ACAs. It may also involvethe posterior circulation.Spontaneous occlusion of the major intracranialarteries is typically accompanied by the appearance of atuft of fine collateral vessels at the base of the brain.Moyamoya is a Japanese word meaning puff ofsmoke, or ambiguous, because of not only the tiny tuftof collaterals but also for obscure etiology.Definition
The term moyamoya disease is reserved for thosecases in which the intracranial vascular changes areprimary and truly idiopathic.Moyamoya syndrome ( secondary moyamoya,moyamoya phenomenon, syndromic moyamoya, quasi-moyamoya, or moyamoya-like vascular changes) isused with the intracranial vascular changes that occurin association with another condition, such aspostcranial radiation or neurofibromatosis type 1.Moyamoya disease was first described in Japan in1957 (Suzuki)Definition
circle of willis
Etiology• unknown.• A genetic mode of inheritance is considered possiblebecause of the higher incidence of the disease inJapan and Korea.• wide spread use of MRI and &MRA have been usedin detecting the disease in asymptomatic familialcases( 10%).• Familial MMD has been linked to ch 3, 6, 8, 12and17.• Secondary: such as postcranial radiation,neurofibromatosis type 1 or Epstein-Barr virusinfection .
1. when at least one first-degree relative is affected.2. 10% are familial.3. Earlier age of onset (10 & 40 IN SPORADIC)4. Greater female>male (1:5 or 1:3 in sporadic).5. AD with incomplete penetrance.6. Familial MMD has been linked to ch 3, 6, 8, 12and 17.7. Familial moyamoya disease is associated with(a) SLE. (b) Basilar tip aneurysms.8. Screening with MRA has been recommended forfamily members of patients with MMD (30 fold )Familial moyamoya disease
More common in Japan, china and South Korea .1. Japan:(a) Prevalence rate of 3.16 and annual incidence of 0.35per 100,000.About 100 new cases are identified each year.(c) Male to female ratio: 1:1.8.(d) Peak ages are 10–14 years(50%) and 40s.Incidence per 100,000 is highest among AsianAmericans:– Asian Americans: 0.28– African Americans 0.13Epidemiology
The primary lesion in moyamoya disease isprogressive fibrocellular thickening of the intimaconsisting of fibrocellular materials, but without lipidsor calcification as is seen in atherosclerosis.The internal elastic lamina becoming infolded,tortuous, redundant, and fragmented.The media is thinned, with a diminished number ofsmooth muscle cells.No inflammatory changes are seen.superficial temporal arteries may affected.The secondary lesions in moyamoya syndrome aredilated, tortuous thalamostriate and lenticulostriatearteries at the base of the brain.Pathophysiology
Factors involved in pathogenesis1)Role of angiogenic factors.• Basic Fibroblast growth factor: mediator of the neovascularresponse.• Transforming growth beta factor 1 (TGF beta 1), a factorinvolved in angiogenesis• Hepatocyte growth factor, an angiogenic factor2) Excess prostaglandin.3) Infection : Epstein-Barr virus infection. This was based on theincreased presence of EBV DNA and antibody in patients withmoyamoya.4) Alteration in metaloproteinase gene expression (remodeling).5) Primary defect in smooth muscle cells repair response.This suggests that there be a derangement in the vessel wallrepair mechanism that leads to long-term proliferation of cellsand progressive occlusion of the vessel lumen.
The classic description of moyamoya disease separates:1- juvenile form 2- adult form.Clinical features of moyamoya diseaseTransient ischemic attack (TIA), Ischemic stroke, Hemorrhagicstroke and EpilepsyIn children, symptomatic episodes of ischemia may be triggeredby exercise, crying, coughing, straining, fever or hyperventilationIn adults: ICH is the presenting event in >60% of cases.Bleeding may arise from the following:– Abnormal vascular networks– Intracranial aneurysmsAbout 1/3 of patients recurrentIV hemorrhage is the most common 69%.Mortality in the acute phase is 2.4% with infarction and 16.4%with hemorrhage.
Clinical featuresIschemic events more frequent in children.Hemorrhagic strokeEpilepsy.choreaIn children: 77%-ischemic events59%-TIA5%-ICHIn adults: 69%-ICH(IVH)27%-TIA +ischemic strokeEpilepsy: 25%- children , 5% -adults.Asymptomatic moyamoya disease
Unilateral disease ( probable moyamoya disease):(a) Progression to bilateral disease:–75% of patients with mild or equivocal contralateralfindings progressed,only 10% of patients with no initial contralateralfindings progressed.(b) Unilateral disease common adults >children.(c) Familial occurrence is less common in patients withunilateral disease,d) CSF levels of bFGF are lower in patients withunilateral disease compared with patients with definitemoyamoya disease.Unilateral disease MMD
NEUROIMAGING1-CT scan.2- MRI and MRA3-CTA4-DSA5-Cerebral blood flow studies
1-CT scanCT scan: infarction may involve cortical and subcorticalregions. In the patients with parenchymal hemorrhageCT usually show a high density area indicating blood inthe basal ganglia, thalamus and/or ventricular system
1. MRI has been used extensively in Japan for screeningpurposes(a) Signal voids in the basal ganglia.(b) Marked leptomeningeal enhancement onpostcontrast images(c) Evidence of infarction, atrophy, andventriculomegaly(d) Hemorrhage2. Ivy sign: Marked diffuse leptomeningealenhancement on postcontrast T1-weighted and FLAIRimages. Considered to represent the fine vascularnetwork over the pial surface. vivid contrast enhancement and high signal on FLAIR dueto slow flow.2-MRI
Signal voids in the basal gangliaSignal voids in thebasal gangliaMoyamoya vesselsare visualized asmultiple small roundor tortuous lowintensity areasextending from thesuprasellar cisternsto the basal ganglia
Bilateral moyamoya disease(a) Transverse postcontrast T1-weightedMR image showsdiffuse leptomeningealenhancement, with someenhancement of perforatingarteries (arrowheads) in basalganglia. Areas supplied by theposterior cerebral artery arerelatively spared.b) Transverse unenhancedFLAIR MR image shows subtlehigh signal intensities(arrowheads) alongleptomeninges in bilateralfrontal regions and wasinterpreted as equivocal.Ivy signT1cFLAIR
(a) Transverse: postcontrast T1-weighted MR image shows diffuseenhancement alongleptomeningeal surfaces (arrow-heads), predominantly in righthemisphere. (b) Transverse unenhancedFLAIR MR image reveals multipleareas of high signal intensity(arrowheads) in leptomeningesBoth a and b were interpretedas depicting the leptomeningeal i(c) Transverse gadolinium-enhanced FLAIR MR imageshows high signal intensities(arrowheads) in leptomeninges ofleft frontal and right frontoparietalregions, which are less apparentthan those inb. Unenhanced FLAIR imagingis better for depicting theleptomeningeal: ivy sign.enhanced FLAIR
absence of the middle and anteriorcerebral arteries bilaterally (A).Janda P H et al. J Am Osteopath Assoc 2009;109:547-553hypertrophy lenticulostriate arteries
Lateral MRA proximal occlusion of the MCAs &ACAs
3- CTA & DSA1-Cerebral angiography should demonstrate the following findings:(a) Stenosis or occlusion at the terminal portion of the ICA and/orthe proximal portion of the ACA and/or MCA.(b) Abnormal vascular networks in the vicinity of the occlusive orstenotic lesions.(c) These findings should be present bilaterally.2. When MRI and MRA clearly demonstrate all of the findingslisted later, catheter angiography is not mandatory.(a) Stenosis or occlusion at the terminal portion of the ICA and atthe proximal portion of the ACA and MCA.(b) An abnormal vascular network in the basal ganglia on MRA.An abnormal vascular network can be diagnosed on MRI when >2apparent flow voids are seen in one side of the BG.c) (1) and (2) are seen bilaterally.
Puff of smokeDSALT MCA&ACA
moyamoya.(front view)Angiogram of theright carotid arteryshowing occlusion ofthe intracranialcarotid bifurcationwith collateral bloodflow originatingfrom the externalcarotid artery (bluearrows), and basalarteries (red arrow),creating thecharacteristic "puffof smoke" (circledarea)
Right IC arteriogram inlateral projection shows theright ICA (curved arrow) isoccluded, and thus theanterior cerebral and middlecerebral arteries areoccluded.There are markedmoyamoya vessels. Throughthe persistent primitivetrigeminal artery (straightarrow), the BA and itsbranches are opacified, butboth PCAs are occluded intheir proximal portions(arrowheads).
CBF imaging techniques for moyamoya patientsinclude PET, xenon CT and SPECT. Regional CBF in patients with moyamoya ischaracteristically diminished in the frontal andtemporal lobes and and in central brain structuresthat are involved with basal moyamoya vessels butelevated in the posterior circulation territory(cerebellum and occipital lobes). The degree of hemodynamic stress in patients withmoyamoya disease varies greatly between patients. CBF studies can help predict the risk of stroke andthe success of revascularization surgery.4-Cerebral blood flow studies
DIAGNOSIS• The diagnosis of MM.D is based upon thecharacteristic angiographic appearance ofbilateral stenoses affecting the distalinternal carotid arteries & proximal circleof willis vessels, along with the presence ofprominent basal collateral vessels
Medical treatment with vasodilators, corticosteroids,antiplatelet agents etc. has been tried with doubtfulefficacy Patients are often put on aspirin, even though thereis no evidence that it stops or reverses arterialocclusion.Treatment
Surgery for moyamoya• create collateralization on the brain surface.• Indirect revascularization procedures such as EDAS(encephaloduroarterio synangiosis), pial synangiosis,indirect revasularization using muscle flaps etc.• Direct revascularization procedures such assuperficial temporal-middle cerebral artery bypass .• indirect revascularization is preferred in treatmentof children.• The decision is based on angiography and cerebralblood flow studies.• TlAs reduce in frequency and patients do notdevelop new strokes in successful cases.
PrognosisThe natural history tends to be progressive withextensive intracranial large artery occlusion andcollateral circulation.The natural history may be more benign in UScompared to Asian population.Moyamoya D. is one of the D.D. of stroke in childrenand young adults.
Cerebral blood flow andmetabolism in moyamoya• The morbidity of moyamoya is directly related to cerebral blood flow.• This was demonstrated in earlier studies using Xenon-133 inhalation. Thecerebral blood flow was decreased most in the frontal region with relativelynormal flow in the temporal and occipital region. After hyperventilation theblood flow was reduced in all regions.• Positron emission tomographic studies have shown an increase in total bloodvolume, especially in the striatum and increased transit time. Thecerebrovascular response to hypercapnia was shown to be impaired. Thesechanges were reversed after reperfusion surgery.• PET studies have also demonstrated the vasodilatation in normal areas afterthe termination of hyperventilation. This may cause a steal response increasinghypoperfusion.• These studies may help to understand the effects of chronic cerebral occlusivedisease. Xenon computed tomography has been used for pre and post surgicalevaluation.• These studies were found to correlate with angiographic studies and have beenclaimed to be superior in the study of basal ganglia and posterior circulation.• Diffusion weighted imaging and perfusion magnetic resonance imagine usingcontrast have been used in the study of ischemic episodes.• Serial studies have also shown the decrease in cerebral blood flow withadvancing age
Angiographic features of moyamoya• The development of the moyamoya network may be seenat different sites• The formation of network of vessels at the frontal base withblood supply from the branches of the ophthalmic artery isknown as ethmoidal moyamoya.• Dilatation of the basilar artery and formation of moyamoyanetwork by perforating branches of the posterior cerebralartery is known as posterior basal moyamoya.• Vault moyamoya is due to development of extra andintracranial transdural leptomeningeal collaterals between pialvessel and branches of the external carotid artery.• A well-developed posterior callosal artery is seen. The largeand proliferating irregular vessels and transdiploic collateralsof the external carotid artery that supplies the ischemic regionsof the brain essentially cause the moyamoya network.