Transcript Moyamoya Disease

Moyamoya Disease: Largely Unknown
Pathogenesis, Diagnosis and Treatment
Lian Duan
Department of Neurosurgery, 307 Hospital, PLA
The Center for Cerebrovascular Disease, PLA
Moyamoya
Normal
Macroscopical and microscopical findings at autopsy.
A：malformation of the vascular network around the proximal MCA；
B: fine vascular network；C: SAH in the right parieto-temporal area；
D: SAH in right parietal lobe.
Lin R, Clinical and immunopathological features of moyamoya disease. PLoS One 2012
Photomicrographs of brain vessels in MMD patients.
Lin R, Clinical and immunopathological features of moyamoya disease. PLoS One 2012
Immunohistochemical study of intracranial arteries.
A,D:immunoreactivity indicating that a-SMA is detected in the
thickened intima of MCA. B,D:S100A4 protein is detected in the
thickened intima and media smooth muscle cells
Lin R, Clinical and immunopathological features of moyamoya disease. PLoS One 2012
VEGF, bFGF，MMP1-3， MMP9， MMP12， PDGF-BB ，
TGF-β1，TNF-α IL-1β, IL-6, IL-8...
Up-regulated spots that were significantly and consistently changed in
human sera of moyamoya patients compared to normal controls.
Koh EJ: Comparative analysis of serum proteomes of MMD. J Korean Neurosurg Soc 2010
Down-regulated spots that were significantly and consistently changed in
human sera of moyamoya patients compared to normal controls.
Koh EJ: Comparative analysis of serum proteomes of MMD. J Korean Neurosurg Soc 2010
Mechanism of neovascularzation
Increased levels of circulating CD34+ cells in patients with
angiographic evidence of moyamoya-like vessels.
Yoshihara T: Increase in circulating CD34+ cells in patients with angiographic evidence of
moyamoya-like vessels. J Cereb Blood Flow Metab 2008.
Increased Levels of Circulating Endothelial Progenitor Cells in
Patients With Moyamoya Disease
Rafat N: Increased levels of circulating endothelial progenitor cells in patients with MMD. Stroke 2009.
The EPC-CFU numbers from MMD patients.
Formation of EPC-CFUs at 7 days after plating the MNCs of MMD patients
at different disease stages. Advanced stage MMD patients had lower CFU
numbers than early stage MMD patients or controls (D).
Jung KH: Circulating EPC as a pathogenetic marker of MMD. J Cereb Blood Flow Metab 2008.
Kim JH: Decreased level and defective function of EPC in children with MMD. J Neurosci Res 2010.
Genetic Analyses: Current Concepts and Future Directions
Prevalence
(per 100000)
Incidence
Japan
6.03
0.54
Hokkaido
10.5
0.94
Nanjing
3.92
0.43
US
-----
0.086
Kraemer: Analysis of HLA genes in caucasian patients with idiopathic MMA. Acta Neurochir(wien) 2012.
Unified multipoint linkage analysis between familial MMD and
markers on chromosome 17q24-25.
Yamauchi T: Linkage of familial MMD to chromosome 17q25. Stroke 2000.
The vascular injury repair model.
Kang HS: Single nucleotide polymorphisms of tissue inhibitor of metalloproteinase genes in
familial MMD. Neurosurgery 2006.
Kamada: A genome-wide association study identifies rnf213 as the first MMD gene. J Hum Genet 2011.
Association analysis of 63 non-familial MMD cases and 45 control
subjects and the structure of the RNF213 protein.
Kamada F: A genome-wide association study identifies rnf213 as the first MMD gene. J Hum Genet 2011.
Kamada F: A genome-wide association study identifies rnf213 as the first MMD gene. J Hum Genet 2011.
Kamada F: A genome-wide association study identifies rnf213 as the first MMD gene. J Hum Genet 2011.
Further investigations are needed to identify
the underlying cause of moyamoya disease.
Data from proteomics, progenitor cell
research and genetic investigations in
moyamoya disease will not only be important
for the development of novel therapies
specific to moyamoya disease but will also
have the potential to enhance treatment
options for a wide variety of disorders of the
CNS, including stroke, hemorrhage, vascular
malformations, and CNS tumors.
Diagnosis
Increased Thyroid Function and Elevated Thyroid Autoantibodies in
Pediatric
Patients With MMD
Patients
(N=114)
Controls
(N=114)
Elevated thyroid
autoantibodies
13.2
3.5
TPOAb-positive
11.4
1.8
TGAb-positive
12.3
3.5
LICA
RICA
F, 5y, weakness of right extremities for 2 year.
M, 46y, numbness and weakness in his right extremities for 1 year
MMD
Coexistence of MMD and aneurysm
The correlation between
moyamoya disease and arteriosclerosis
M, 45y, paralysis of right limb and speech disorders for 9 month,
hypertension disease history for 7 years.
DSA also show stenosis of bilateral vertebral arteries
The portion of vasculopathy
Angiograph of LICA
Angiograph of LVA
Challenge to diagnosis criteria
• Moyamoya disease or moyamoya
syndrom?
• PCA involvement
Treatment
F,39y,first ventricular hemorrhage in 27th May,2007
LICA
RICA
LVA
Angiogram after bilateral EDAS in 19th Aug,2009
Left
Right
Second hemorrhage in 24th May,2012 after
bilateral EDAS
Third hemorrhage the second day after EDAS using left
occipital artery in 25th June,2012
• In some cases, successful surgery can not
prevent disease progress (infarct and
hemorrhage), making us go back to the study
of pathogenesis of MMD.