Moyamoya Disease and Syndrome - mc.vanderbilt.edu · Discussion • Epidemiology • Presentaon •...

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Moyamoya Disease and Syndrome

Robert J. Singer, M.D.

Department of Neurosurgery

Neurovascular Therapeu?cs (Adult and Pediatric)

Vanderbilt University Medical Center

Nashville, TN

robert.singer@vanderbilt .edu

Sco$ M, Smith E. N Eng J Med 360;12 NEJM March 19, 2009

Discussion

• Epidemiology

• Presenta?on

• Pathophysiological features

• Natural history and prognosis

• Diagnosis

• Screening

• Treatment

Defini?ons

• Moyamoya Syndrome – “something hazy”

– PredisposiDon to stroke– Usually progressive stenosis of the intracranial internal caroDds and their proximal branches (posterior circulaDon involvement rare)

– Compensatory neovascularizaDon involving surrounding circulaDon (external caroDds, dural branches, corDcal branches…

Moyamoya Syndrome

Moyamoya Disease

• Pa?ents with no known associated risk factors…

• 40% with unilateral disease on ini?al presenta?on develop contralateral findings

Moyamoya “paQern”

Epidemiology

• Most common pediatric cerebrovascular disease in Japan ( 3 per 100,000)

• Reported worldwide

• Peak incidence: 5 and 40

• Female: male… 2:1

Epidemiology (U.S.)

• .086 per 100,000– 4.6 for Asian Americans

– 2.2 for African Americans

– 0.5 for Hispanics

Ucnino K et al. Neurology 2005;65:956-‐8

Presenta?on

20.0% v. 2.8% in children

Japan 42%

Symptoms at Presenta?on

• Ischemic – Hemiparesis, dysarthria, aphasia, cogniDve impairment

– Seizures, visual deficits, syncope, personality changes

–May be transient or fixed• ProvocaDon by hypervenDlaDon, exerDon or dehydraDon

Tagawa T et al. Stroke 1987;18:906-‐10

PresentaDon (Hemorrhagic)

• Loca?on: intraventricular, intraparenchymal (basal ganglia common), or subarachnoid

Courtesy: Michael Ayad, MD, PhD

PresentaDon

• Headache

–Meningeal/leptomeningeal dilata?on

•May s?mulate dural nocioceptors

• Persists in 63% (despite therapy)• Can regress post op…

Seol H et al. J Neurosurg 2005;103:Suppl:439-‐42

Presenta?on

• Choreiform movements – DilataDon of collateral vessels in the basal ganglia– 8/10 showed symptomaDc improvement a`er revascularizaDon…

Sco$ RM et al. J Neurosurg 2004;100:Suppl:142-‐9

Presenta?on

• Morning glory disk abnormality (MGDA)– Enlargement and funneling of the opDc disk with reDnovascular anomalies (neovascularizaDon)

Taylor D. Eye 2005;21:1271-‐84

Pathophysiological features

• Research targets:– Pathological analysis of affected Dssue– GeneDc linkage studies– Role of angiogenesis and extracellular matrix-‐related pepDdes in disease development and progression

Vasculogenesis/Angiogenesis...

Neurolation around 18-‐24 days

metabolic needs met by diffusion of amniotic fluid(ends around day 26 when neural tube closes)

neural tube surrounded by meninx primitiva (dural progenitor) which has a vascular plexus

Vasculogenesis/Angiogenesis...

meninx primitiva contains hemangioblastic cells (splanchnopleuric mesoderm)

hemangioblastic cells condense (vasculogenesis) into blood islands and

differentiate into stem cells and angioblasts...

congenital vascular malformations develop in this period of differentiation and coalescence...

(no later than the 8th week of development)

Growth factors in vasculo/angiogenesis

VEGF Angiopoietin Ephrins

(mediated by endothelial cell tyrosine kinases)

Genes Dev. 1999 13: 1055-1066

-‐Smooth muscle cell hyperplasia and luminal thrombosis

-‐AQenua?on of the media with irregular elas?c lamina-‐Caspase-‐dependent apoptosis implicated as a contributory mechanismin arterial wall degreda?on

-‐Collaterals demonstrate fragmented elas?c lamina, thinned media and microaneurysms (likely cause of hemorrhage) 2˚ hemodynamic shear stress

• Gene?cs (polygenic or AD with incomplete penetrance)– 6-‐10% proporDon of first degree relaDves with moyamoya

– Associated loci on chromosomes 3, 6, 8 and 17(q25) mutaDon affecDng TIMP-‐2 (Dssue inhibitor of matrix metalloproteinase type 2)

– HLA haplotypes have been described

Mineharu Y. Neurology 2008;70:2357-‐63

• Angiogenesis and extracellular matrix related pep?des – Increased BFGF, TGFB-‐1, HGF, VEGF, HIF1-‐a, MMP, and intracellular adhesion molecules

–Mechanisms of interacDon are not well described

Yoshimoto T et al. Stroke 1996;27:2160-‐5

Natural History and Prognosis

• Rate of progression is high

• 2/3 have symptoma?c progression over a 5 year periodπ

• Outcome poor without treatment

• Rate of progression ader surgery: 2.6%•

• Neurologic status at the ?me of treatment predicts long-‐term outcome (early diagnosis is important…)

πChoi J et al. ClinNeurolNeurosurg 1997;99:Suppl2:S11-‐18

•Fung L et al. Childs NervSyst 2005;21:358-‐64

Diagnosis

• Pursue in the seeng of unexplained symptoms referable to cerebral ischemia (par?cularly in children)

• Several imaging modali?es are used…

Diagnosis (CT)

Ischemic Hemorrhagic

Diagnosis (CTA)

Diagnosis (MRI/A)

“ivy” sign on FLAIR images suggests poor corDcal flow

Diagnosis (Angiography)

Grade 1 Grade 4

Suzuki J et al. Arch Neurol 1969;20:288-‐99

Diagnosis

• EEG-‐ “rebuild-‐up” phenomenon, occurs ader hyperven?la?on (monophasic slow waves), indicates diminished cerebral perfusion

• Transcranial Doppler (TCD)

• Perfusion studies to assess flow… – CTP, Xenon CT, Acetazolamide SPECT

Diagnosis (Diamox SPECT)

Treatment

• Does not reverse primary disease process

• Protects against further strokes by improving hemispheric blood flow

• Medical therapy– AnDplatelet agents for microthrombi

– Calcium channel blockers for headache

Treatment

• Surgery– External caroDd is spared by the disease and used for revascularizaDon • Direct and Indirect approaches

– direct: superficial temporal artery (STA) to middle cerebral artery (MCA)

» can be difficult in children due to small caliber of vessels

» benefit over indirect methods is debated

Treatment• STA-‐MCA bypass (direct)

Courtesy; Gary Steinberg, Stanford University Medical Center

Treatment

• STA-‐MCA bypass (direct)

Courtesy; Gary Steinberg, Stanford University Medical Center

-‐AnDplatelet agents post-‐op

Treatment

• Indirect techniques– Omental transplant (1978)

• STA-‐gastroepiploic arteries– MulDple burr holes

• +/-‐ dural opening– Encephaloduroarteriosynangiosis

• STA-‐dura mater

– Encephalomyoarteriosynangiosis• STA/temporalis muscle to pial surface

– Pialsynangiosis• STA-‐pial surface

Reis CV et al. Neurosurgical Focus 2006

Treatment • Indirect – Pialsynangiosis

PialSynangiosis

Treatment• Indirect

Pialsynangiosis

Burr hole revascularizaDon

Treatment

• PerioperaDve/IntraoperaDve– AddiDonal risk of CVA/ischemia

• Crying, hypervenDlaDon can potenDate hypocarbia• Pain control is essenDal• Normotension/normothermia/hypervolemia

• Supplemental O2

• Postop– Volume maintanence (1.25-‐1.50 Dmes normal maintenance for 48-‐72h)

– Aspirin (325 mg for adults, 81mg for preteen)

Nomura S et al. Childs NervSyst 2001;17:270-‐4

Treatment

• Results:– Stroke reducDon is significant postop… roughly 70% will have CVA prior to treatment

– PostoperaDve stroke risk drops to around 4%...

– 87% derived symptomaDc benefit with direct/indirect and combined techniques showing equal effecDveness

Fung LW et al. Childs NervSyst 2005;21:358-‐64

Future…

• Precondi?oning

• Angiogenic triggers

• Treatment for chronic ischemia

• Thanks!

Giant PICA aneurysm with bypass

Moyamoya Disease and Syndrome - mc.vanderbilt.edu · Discussion • Epidemiology • Presentaon •...

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