1. Moyamoya syndrome in adults: a pictorial review.
Z Hutchinson, S Clifford, A Carroll, N Tubridy, S O'Riordan, J Kinsella, C McGuigan, RP Killeen. Department of Radiology, St. Vincent’s University Hospital, Elmpark, Dublin 4, Ireland.
Control Number: 1547
Poster Number: eP20

2. Purpose
To provide a clear understanding of the background, presentation, prognosis and treatment of adult onset moyamoya syndrome.
To illustrate the characteristic findings of the syndrome using computed tomography angiography (CTA), magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) images.
To compare the imaging findings of unilateral versus bilateral, and untreated versus treated moyamoya syndrome.
None of the authors listed have affiliations with or involvement in any organization or entity with any financial interest, or non-financial in the subject matter or materials discussed in this manuscript. We would like to acknowledge the contributions of the radiology department in St. Vincent’s University Hospital.

3. Background
Moyamoya disease was first referenced in the literature in 1957 as a vascular phenomenon caused by “hypoplasia of the internal carotid arteries”(1). In 1969, Suzuki described a condition involving “stenosis or an occlusion” of “the terminal part of the internal carotid artery” with the nearby anterior middle cerebral artery (ACA) or middle cerebral artery (MCA) sometimes involved along with the development of a “net-like” system of collateral vessels(2).
The characteristic angiographic appearance of the collateral circulation gives rise to this condition’s distinctive name ‘moyamoya’ which is Japanese for “something hazy, like a puff of cigarette smoke”(2).
This pictorial review aims to focus on moyamoya syndrome as distinct from moyamoya disease. The pathology is the same in both entities, and is caused by stenosis or occlusion of the distal portion of the intracranial internal carotid artery and/or proximal portion of the middle cerebral artery or anterior cerebral artery with a nearby abnormal collateral vascular network(2).

4. Moyamoya disease versus syndrome
The technical difference between the two conditions is defined by the presence or absence of an associated underlying condition(3).
If no condition is present, then moyamoya disease is diagnosed.
Moyamoya syndrome is diagnosed when moyamoya disease occurs with another disease entity such as atherosclerosis, neurofibromatosis type 1 (von Recklinghausen disease), sickle cell disease, Down’s Syndrome, hyperthyroidism or in the setting of prior radiotherapy to the head or neck(4). The syndrome can also be unilateral or bilateral(4).
In the literature, moyamoya syndrome is also referred to as ‘quasi moyamoya disease’, ‘akin-moyamoya disease’ or ‘secondary moyamoya disease’(4).
In practice, the distinction between moyamoya disease and moyamoya syndrome is blurred and remains to yet be fully clarified(3). More importantly, the distinction is not essential, as the treatment of the two conditions is the same(3). Moyamoya vasculopathy or moyamoya phenomenon are terms now used to encompass both conditions(3).

5.  Pathology   
Moyamoya is a result of progressive carotid artery occlusion. Occlusion of the arteries is attributed to a combination of luminal hyperplasia and thrombosis(7).
As occlusion occurs, collaterals develop at the base of the brain(4) from a combination of dilated preexisting, and newly formed, arterioles; these are seen as flow voids on T1 and T2-weighted MRI sequences (Figure 1).
Leptomeningeal vessels can also dilate and contribute to the collateral network. Their appearance on FLAIR or T1 post-contrast imaging produces the characteristic “ivy sign”(8) (Figure 2).
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Purpose,
Materials and methods,
Results
Conclusion-
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6. Figure 1 A a A AW
MRI Axial T2
54 year old female presented with migraine. Diagnosed with moyamoya syndrome, with a right-sided MCA abnormality. This image demonstrates an abnormal flow void of the right internal carotid artery (A) and smaller flow voids more laterally due to the presence of collateral vessels (a).

7. Figure 2
AS.
Axial FLAIR
18 year old female with moyamoya syndrome, with a left sided “ivy sign” of leptomeningeal enhancement.

8. Epidemiology
The incidence of moyamoya disease is per 100,0007 in Asia and Japan and 0.09 per 100,000 in the United States(6). The incidence of moyamoya syndrome is less well documented but can occur in any race(4).
Moyamoya disease is almost twice as common in females as males.
It has a bimodal peak of occurrence, normally presenting in children at approximately five years of age, and in adulthood during the mid-forties(9). No similar data is available for moyamoya syndrome.
The underlying aetiology of moyamoya is currently unknown. A genetic cause has been suggested in approximately 10% of cases(5). Figure 3 demonstrates multiple small collateral vessels in the region of the right MCA, in right sided moyamoya. This patient had a small right carotid canal, suggesting the right sided MCA stenosis is chronic in nature.
For those cases not thought to be due to a genetic cause, high levels of human growth factors and transcription factors are considered to involved(6). Other factors such as trauma may be involved in the pathology of moyamoya. Figure 4 shows a patient who developed moyamoya, possibly as a result of trauma.

9. B b Coronal MIP CTA Figure 3 B CND
Coronal MIP CTA
42 year old male presented with vertigo and headache. Diagnosed with moyamoya syndrome with involvement of the right internal carotid artery and MCA. Supra-clinoid stenosis is seen in this image (B) along with small collateral vessels (b).

10. Figure 4
LM– demonstrates interval moyamoya occurring following trauma.
CTA
38 year old male, who had a previously normal MRI brain and then presented 2 years later with right sided MCA occlusion, consistent with moyamoya, as demonstrated on CTA. Of note, the patient reported trauma in the interval between the two scans.

11. Results
Presentation
Moyamoya can present at any age, usually in the form of epilepsy or headache(4).
The majority of children, regardless of age, tend to present with the sequelae of ischaemia, such as a transient ischaemic attack (TIA) or stroke(12, 13). These outcomes are commonly precipitated by hyperventilation, in the form of crying, laughing or sneezing episodes(14).
The patient in figure 7initially presented with laughter induced syncope and was given a diagnosis of moyamoya.
In the adult population, Asian adults are more likely to suffer from an intracranial hemorrhage than Caucasians(2, 14). In the United States, adults most commonly suffer from ischaemic symptoms but are more likely than children to suffer a haemorrhagic stroke(12, 13).
Moyamoya may also be asymptomatic(10, 11).

12. C c Axial MIP CTA Figure 5 C
RW--- associated basilar artery aneurysm.
Axial MIP CTA
54 year old male presented with acute onset dizziness and vomiting. Diagnosed with moyamoya with bilateral involvement of the internal carotid arteries and MCAs on a background of a basilar artery aneurysm (c). “Puff of smoke” collaterals are seen in this image (C).

13. Diagnosis
The gold standard for diagnosing moyamoya disease uses formal angiography to demonstrate:
1. Stenosis or occlusion of the terminal portion of the intracranial internal carotid artery or stenosis of the proximal portion of the anterior and/or middle cerebral artery on both sides.
2. Presence of networks of abnormal collateral vessels adjacent to the stenosis on both sides(4).
Formal angiography is not required if the same findings are demonstrated using MRI or MRA(4). MRI, MRA or CTA may be preferred over formal angiography.
Cerebral blood flow (CBF) can be assessed using single photon emission computed tomography (SPECT) studies. In the setting of moyamoya, this investigation can be used both in diagnosis and assessment of severity(4). SPECT uses radiotracers to evaluate CBF both at rest and under stress. At rest, the study is generally normal but becomes markedly abnormal with the introduction of the vasodilatory agent acetazolamide. (4). Figure 6 demonstrates a normal SPECT in a patient with known moyamoya.

14. Figure 6 AW
SPECT
54 year old female, who is the same patient as figure 1. Normal perfusion scan, demonstrating compensation, despite known right-sided moyamoya.

15. Prognosis
The prognosis of patients with moyamoya syndrome depends on the underlying cause(4).
Moyamoya disease progresses in the majority of patients(2).
Recent research suggests that progression occurs in 20% of those who are not treated and about half of this cohort will have a TIA, haemorrhage or infarct(15).
The recurrence of symptoms is higher in those who are not treated and is associated with a worse prognosis(13, 14). Survival and functional outcome is worse in those who have had a haemorrhagic stroke(14).
Outcome also depends on the patient’s neurological status when treatment commences(12).

16. Axial MIP CTA Axial CTA Figure 7 Image A Image B
ND- small right carotid canal, may be cause of right sided moyamoya.
Axial MIP CTA
Axial CTA
42 year old male, the same patient as figure 3. This image demonstrates multiple small collateral vessels in the region of the right MCA . This patient was noted to have a very small right carotid canal (Image B).

17. Treatment Medical treatment
There is no curative treatment for moyamoya.
Treatment is preventative and aims to reduce the risk of stroke and to reduce the symptoms that occur due to the abnormal moyamoya vasculature(7).
Treatment options include medical and surgical approaches.
Medical treatment
Medical treatment is sub-divided into two treatment periods: acute stroke and stroke prevention.
In the acute ischaemic stroke period, the use of anti-coagulants, including heparin, aspirin, argatroban or ozagrel are recommended, along with endaravone for cerebroprotection(4).

18. Thrombolysis is not recommended(4). If the stroke is haemorrhagic, adequate blood pressure control is required, and vitamin K and frozen blood products can also be considered(4).
Stroke prevention is in the form of aspirin and/or clopidogrel(4). Treatment of known risk factors, including high cholesterol or hypertension, and lifestyle modifications should also be undertaken including regular exercise, low fat diet and smoking cessation(4).
While medical treatment is recommended there is little data available to demonstrate the efficacy of its use(4). There is some evidence to suggest that surgery is a better long term option. In a large review of patients treated with anti-platelet agents, 38% went on to have subsequent surgical intervention(16, 17).

19. Surgical treatment
Surgery may be considered prior to medical management in patients who are suffering from ischaemic symptoms or are asymptomatic(4). Options include direct or indirect approaches to revascularization(7).
Direct revascularization restores flow by directly anastomosing a branch of the external carotid artery, usually the superficial temporal artery, to the affected cerebral artery at a point distal to the diseased segment(7). This method is very effective in adults suffering from ischaemic symptoms(18).
Figure 8 demonstrates a direct surgical revascularization procedure anastomosing the left superficial temporal artery to the middle cerebral artery.
Indirect revascularization uses different parts of the cranial anatomy supplied by the external carotid artery branches as conduits for new cerebral supply. Structures such as the temporalis muscle (encephalo-myo-synangiosis) or the dura (encephalo-duro-synagngiosis) are placed in direct contact with the pia, and over a period of weeks develop new vessels that permeate the brain tissue and provide arterial supply(4).
Direct and indirect revascularization procedures can be performed either independently or in combination with one another(4).

20. D E D Axial MIP CTA Figure 7
The same 18 year old female following a direct surgical revascularization procedure anastomosing the left superficial temporal artery (E) to the middle cerebral artery (D). The patient is now 3 months post-procedure and the laughter-induced syncope has not recurred since the surgery. D E D AS
18 year old female with a background of Neurofibromatosis Type 1 presented with laughter-induced syncope. Diagnosed with moyamoya with left-sided involvement of the left internal carotid artery and MCA (D).
Axial MIP CTA

21. Conclusion
The reader of this pictorial review should now be informed regarding the presentation, diagnosis and prognosis of moyamoya in adults.
They should be able to identify the classical findings, on the variety of imaging modalities, and have a knowledge of the treatment options.
Thank you.

22. References
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2. Suzuki J TA. Cerebrovascular "moyamoya" disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969;20:
3. Miki FujiMura TT. Diagnosis of moyamoya disease: international standard and regional differences Neurol Med Chir (Tokyo) : 189–93.
4. Research Committee on the Pathology and Treatment of Spontaneous Occlusion of the Circle of Willis; Health Labour Sciences Research Grant for Research on Measures for Infractable Diseases. Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion of the circle of Willis. Neurol Med Chir (Tokyo). 2012;52(5):
5. Mineharu Y TK, Yamakawa H, Inoue K, Ikeda H, Kikuta KI, Takagi Y, Nozaki K, Hashimoto N, Koizumi A. Inheritance pattern of familial moyamoya disease: autosomal dominant mode and genomic imprinting. J Neurol Neurosurg Psychiatry. 2006;77:
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7. Scott RM SE. Moyamoya disease and moyamoya syndrome. N Engl J Med 2009;360:
8. Fujiwara H MS, Kuribayashi S. . Leptomeningeal high signal intensity (ivy sign) on fluid-attenuated inversion-recovery (FLAIR) MR images in moyamoya disease. Eur J Radiol 2005(55):
9. Baba T HK, Kuroda S. Novel epidemiological features of moyamoya disease J Neurol Neurosurg Psychiatry. 2008;79:900-4.

23. References Continued
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12. Scott RM SJ, Robertson RL, Madsen JR, Soriano SG, Rockoff MA. Long-term outcome in children with moyamoya syndrome after cranial revascularization by pial synangiosis. J Neurosurg ;100(Suppl):142-9.
13. Hallemeier CL RK, Grubb RL Jr, Chicoine MR, Moran CJ, Cross DT 3rd, Sipfel GJ, Dacey RG Jr, Derdeyn CP. Clinical features and outcome in North American adults with moyamoya phenomenon. Stroke. 2006;37:
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