1. Update of
Moyamoya Disease
Dr/AYMAN ALMALT

2. Moyamoya Disease
1.Definition
2.Etiology
3.Epidemiology
4.Pathophysiology
5.Clinical presentation
6.Neuroimaging
7.Diagnosis
8.Treatment
9.Prognosis

3. Moyamoya disease: is a nonatherosclerotic
progressive steno-occlusive arteriopathy that most
frequently affects the intracranial ICAs and proximal
segments of the MCAs and ACAs. It may also involve
the posterior circulation.
Spontaneous occlusion of the major intracranial
arteries is typically accompanied by the appearance of a
tuft of fine collateral vessels at the base of the brain.
Moyamoya is a Japanese word meaning puff of
smoke, or ambiguous, because of not only the tiny tuft
of collaterals but also for obscure etiology.
Definition

4. The term moyamoya disease is reserved for those
cases in which the intracranial vascular changes are
primary and truly idiopathic.
Moyamoya syndrome ( secondary moyamoya,
moyamoya phenomenon, syndromic moyamoya, quasi-
moyamoya, or moyamoya-like vascular changes) is
used with the intracranial vascular changes that occur
in association with another condition, such as
postcranial radiation or neurofibromatosis type 1.
Moyamoya disease was first described in Japan in
1957 (Suzuki)
Definition

5. circle of willis

6. Etiology
• unknown.
• A genetic mode of inheritance is considered possible
because of the higher incidence of the disease in
Japan and Korea.
• wide spread use of MRI and &MRA have been used
in detecting the disease in asymptomatic familial
cases( 10%).
• Familial MMD has been linked to ch 3, 6, 8, 12and
17.
• Secondary: such as postcranial radiation,
neurofibromatosis type 1 or Epstein-Barr virus
infection .

7. 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 for
family members of patients with MMD (30 fold )
Familial moyamoya disease

8. 1. cranial radiotherapy
2. Atherosclerosis
3. phakomatoses
neurofibromatosis type 1(NF1)
tuberous sclerosis (TS)
4. infection
tuberculous meningitis
bacterial leptomeningitis, post-varicella vasculitis
5. connective tissue disorders
systemic lupus erythematosus (SLE)
6. haematological disorders
sickle cell disease, anti phospholipid syndrome
Moyamoya syndrome

9. More common in Japan, china and South Korea .
1. Japan:
(a) Prevalence rate of 3.16 and annual incidence of 0.35
per 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 Asian
Americans:
– Asian Americans: 0.28
– African Americans 0.13
Epidemiology

10. The primary lesion in moyamoya disease is
progressive fibrocellular thickening of the intima
consisting of fibrocellular materials, but without lipids
or calcification as is seen in atherosclerosis.
The internal elastic lamina becoming infolded,
tortuous, redundant, and fragmented.
The media is thinned, with a diminished number of
smooth muscle cells.
No inflammatory changes are seen.
superficial temporal arteries may affected.
The secondary lesions in moyamoya syndrome are
dilated, tortuous thalamostriate and lenticulostriate
arteries at the base of the brain.
Pathophysiology

11. Factors involved in pathogenesis
1)Role of angiogenic factors.
• Basic Fibroblast growth factor: mediator of the neovascular
response.
• Transforming growth beta factor 1 (TGF beta 1), a factor
involved in angiogenesis
• Hepatocyte growth factor, an angiogenic factor
2) Excess prostaglandin.
3) Infection : Epstein-Barr virus infection. This was based on the
increased presence of EBV DNA and antibody in patients with
moyamoya.
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 wall
repair mechanism that leads to long-term proliferation of cells
and progressive occlusion of the vessel lumen.

12. The classic description of moyamoya disease separates:
1- juvenile form 2- adult form.
Clinical features of moyamoya disease
Transient ischemic attack (TIA), Ischemic stroke, Hemorrhagic
stroke and Epilepsy
In children, symptomatic episodes of ischemia may be triggered
by exercise, crying, coughing, straining, fever or hyperventilation
In adults: ICH is the presenting event in >60% of cases.
Bleeding may arise from the following:
– Abnormal vascular networks
– Intracranial aneurysms
About 1/3 of patients recurrent
IV hemorrhage is the most common 69%.
Mortality in the acute phase is 2.4% with infarction and 16.4%
with hemorrhage.

13. Clinical features
Ischemic events more frequent in children.
Hemorrhagic stroke
Epilepsy.
chorea
In children: 77%-ischemic events
59%-TIA
5%-ICH
In adults: 69%-ICH(IVH)
27%-TIA +ischemic stroke
Epilepsy: 25%- children , 5% -adults.
Asymptomatic moyamoya disease

14. Unilateral disease ( probable moyamoya disease):
(a) Progression to bilateral disease:
–75% of patients with mild or equivocal contralateral
findings progressed,
only 10% of patients with no initial contralateral
findings progressed.
(b) Unilateral disease common adults >children.
(c) Familial occurrence is less common in patients with
unilateral disease,
d) CSF levels of bFGF are lower in patients with
unilateral disease compared with patients with definite
moyamoya disease.
Unilateral disease MMD

15. NEUROIMAGING
1-CT scan.
2- MRI and MRA
3-CTA
4-DSA
5-Cerebral blood flow studies

16. 1-CT scan
CT scan: infarction may involve cortical and subcortical
regions. In the patients with parenchymal hemorrhage
CT usually show a high density area indicating blood in
the basal ganglia, thalamus and/or ventricular system

17. 1. MRI has been used extensively in Japan for screening
purposes
(a) Signal voids in the basal ganglia.
(b) Marked leptomeningeal enhancement on
postcontrast images
(c) Evidence of infarction, atrophy, and
ventriculomegaly
(d) Hemorrhage
2. Ivy sign: Marked diffuse leptomeningeal
enhancement on postcontrast T1-weighted and FLAIR
images. Considered to represent the fine vascular
network over the pial surface.
 vivid contrast enhancement and high signal on FLAIR due
to slow flow.
2-MRI

18. Signal voids in the basal ganglia
Signal voids in the
basal ganglia
Moyamoya vessels
are visualized as
multiple small round
or tortuous low
intensity areas
extending from the
suprasellar cisterns
to the basal ganglia

19. Bilateral moyamoya disease
(a) Transverse postcontrast T1-
weightedMR image shows
diffuse leptomeningeal
enhancement, with some
enhancement of perforating
arteries (arrowheads) in basal
ganglia. Areas supplied by the
posterior cerebral artery are
relatively spared.
b) Transverse unenhanced
FLAIR MR image shows subtle
high signal intensities
(arrowheads) along
leptomeninges in bilateral
frontal regions and was
interpreted as equivocal.
Ivy sign
T1c
FLAIR

20. RT>LT
Ivy signT1c

21. (a) Transverse: postcontrast T1-
weighted MR image shows diffuse
enhancement along
leptomeningeal surfaces (arrow-
heads), predominantly in right
hemisphere
. (b) Transverse unenhanced
FLAIR MR image reveals multiple
areas of high signal intensity
(arrowheads) in leptomeninges
Both a and b were interpreted
as depicting the leptomeningeal i
(c) Transverse gadolinium-
enhanced FLAIR MR image
shows high signal intensities
(arrowheads) in leptomeninges of
left frontal and right frontoparietal
regions, which are less apparent
than those in
b. Unenhanced FLAIR imaging
is better for depicting the
leptomeningeal: ivy sign.
enhanced FLAIR

22. MRI flair
MRA
Rt MCA &ACA
RT leptomeningeal colateral
Ivy sign

23. supraclinoid portion
A1
Lt ICA

24. absence of the middle and anterior
cerebral arteries bilaterally (A).
Janda P H et al. J Am Osteopath Assoc 2009;109:547-553
hypertrophy lenticulostriate arteries

25. Lateral MRA proximal occlusion of the MCAs &ACAs

26. 3- CTA & DSA
1-Cerebral angiography should demonstrate the following findings:
(a) Stenosis or occlusion at the terminal portion of the ICA and/or
the proximal portion of the ACA and/or MCA.
(b) Abnormal vascular networks in the vicinity of the occlusive or
stenotic lesions.
(c) These findings should be present bilaterally.
2. When MRI and MRA clearly demonstrate all of the findings
listed later, catheter angiography is not mandatory.
(a) Stenosis or occlusion at the terminal portion of the ICA and at
the 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 >2
apparent flow voids are seen in one side of the BG.
c) (1) and (2) are seen bilaterally.

27. Puff of smoke
DSA
LT MCA&ACA

28. hazy cloud

29. Stenosis
No ACA

30. moyamoya.
(front view)
Angiogram of the
right carotid artery
showing occlusion of
the intracranial
carotid bifurcation
with collateral blood
flow originating
from the external
carotid artery (blue
arrows), and basal
arteries (red arrow),
creating the
characteristic "puff
of smoke" (circled
area)

31. Right IC arteriogram in
lateral projection shows the
right ICA (curved arrow) is
occluded, and thus the
anterior cerebral and middle
cerebral arteries are
occluded.
There are marked
moyamoya vessels. Through
the persistent primitive
trigeminal artery (straight
arrow), the BA and its
branches are opacified, but
both PCAs are occluded in
their proximal portions
(arrowheads).

32. CBF imaging techniques for moyamoya patients
include PET, xenon CT and SPECT.
 Regional CBF in patients with moyamoya is
characteristically diminished in the frontal and
temporal lobes and and in central brain structures
that are involved with basal moyamoya vessels but
elevated in the posterior circulation territory
(cerebellum and occipital lobes).
 The degree of hemodynamic stress in patients with
moyamoya disease varies greatly between patients.
 CBF studies can help predict the risk of stroke and
the success of revascularization surgery.
4-Cerebral blood flow studies

34. DIAGNOSIS
• The diagnosis of MM.D is based upon the
characteristic angiographic appearance of
bilateral stenoses affecting the distal
internal carotid arteries & proximal circle
of willis vessels, along with the presence of
prominent basal collateral vessels

35. Medical treatment with vasodilators, corticosteroids,
antiplatelet agents etc. has been tried with doubtful
efficacy
 Patients are often put on aspirin, even though there
is no evidence that it stops or reverses arterial
occlusion.
Treatment

36. 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 as
superficial temporal-middle cerebral artery bypass .
• indirect revascularization is preferred in treatment
of children.
• The decision is based on angiography and cerebral
blood flow studies.
• TlAs reduce in frequency and patients do not
develop new strokes in successful cases.

37. Prognosis
The natural history tends to be progressive with
extensive intracranial large artery occlusion and
collateral circulation.
The natural history may be more benign in US
compared to Asian population.
Moyamoya D. is one of the D.D. of stroke in children
and young adults.

39. Cerebral blood flow and
metabolism in moyamoya
• The morbidity of moyamoya is directly related to cerebral blood flow.
• This was demonstrated in earlier studies using Xenon-133 inhalation. The
cerebral blood flow was decreased most in the frontal region with relatively
normal flow in the temporal and occipital region. After hyperventilation the
blood flow was reduced in all regions.
• Positron emission tomographic studies have shown an increase in total blood
volume, especially in the striatum and increased transit time. The
cerebrovascular response to hypercapnia was shown to be impaired. These
changes were reversed after reperfusion surgery.
• PET studies have also demonstrated the vasodilatation in normal areas after
the termination of hyperventilation. This may cause a steal response increasing
hypoperfusion.
• These studies may help to understand the effects of chronic cerebral occlusive
disease. Xenon computed tomography has been used for pre and post surgical
evaluation.
• These studies were found to correlate with angiographic studies and have been
claimed to be superior in the study of basal ganglia and posterior circulation.
• Diffusion weighted imaging and perfusion magnetic resonance imagine using
contrast have been used in the study of ischemic episodes.
• Serial studies have also shown the decrease in cerebral blood flow with
advancing age

40. Angiographic features of moyamoya
• The development of the moyamoya network may be seen
at different sites
• The formation of network of vessels at the frontal base with
blood supply from the branches of the ophthalmic artery is
known as ethmoidal moyamoya.
• Dilatation of the basilar artery and formation of moyamoya
network by perforating branches of the posterior cerebral
artery is known as posterior basal moyamoya.
• Vault moyamoya is due to development of extra and
intracranial transdural leptomeningeal collaterals between pial
vessel and branches of the external carotid artery.
• A well-developed posterior callosal artery is seen. The large
and proliferating irregular vessels and transdiploic collaterals
of the external carotid artery that supplies the ischemic regions
of the brain essentially cause the moyamoya network.