Immunological Aspects of Moyamoya Disease

  • Ji Hoon Phi
  • Seung-Ki Kim
  • Kyu-Chang Wang
  • Byung-Kyu Cho


Immunological phenomena have pervasive effects on the human body. Many physiological and pathological processes involve the immune system. Because of this pervasiveness, it is often difficult to know whether an observed immunological reaction truly underlies a process or whether it is simply an epiphenomenon. The role of the immune system in moyamoya disease is a controversial issue. The etiology of moyamoya disease is currently unknown. Various etiologies, genetic and environmental, have been proposed; however, none have been definitively proven. There is a lot of evidence for immunological abnormalities in patients with moyamoya disease. However, much of the evidence is indirect and lacks a solid causal relationship. Nonetheless, it is strongly believed that immunological processes play an important role at least in the progression of moyamoya disease. In this chapter, the pathological and epidemiological evidence that supports the immunological origin of moyamoya disease is discussed.


Down Syndrome Hepatocyte Growth Factor Kawasaki Disease Takayasu Arteritis Moyamoya Disease 


  1. 1.
    Galkina E, Ley K (2009) Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol 27:165–197PubMedCrossRefGoogle Scholar
  2. 2.
    Ridker PM, Hennekens CH, Buring JE et al (2000) C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342(12):836–843PubMedCrossRefGoogle Scholar
  3. 3.
    Andersson J, Johansson L, Ladenvall P et al (2009) C-reactive protein is a determinant of first-ever stroke: prospective nested case-referent study. Cerebrovasc Dis 27(6):544–551PubMedCrossRefGoogle Scholar
  4. 4.
    Mach F, Schonbeck U, Sukhova GK et al (1998) Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 394(6689):200–203PubMedCrossRefGoogle Scholar
  5. 5.
    Saha P, Modarai B, Humphries J et al (2009) The monocyte/macrophage as a therapeutic target in atherosclerosis. Curr Opin Pharmacol 9(2):109–118PubMedCrossRefGoogle Scholar
  6. 6.
    Takebayashi S, Matsuo K, Kaneko M (1984) Ultrastructural studies of cerebral arteries and collateral vessels in moyamoya disease. Stroke 15(4):728–732PubMedCrossRefGoogle Scholar
  7. 7.
    Takekawa Y, Umezawa T, Ueno Y et al (2004) Pathological and immunohistochemical findings of an autopsy case of adult moyamoya disease. Neuropathology 24(3):236–242PubMedCrossRefGoogle Scholar
  8. 8.
    Masuda J, Ogata J, Yutani C (1993) Smooth muscle cell proliferation and localization of macrophages and T cells in the occlusive intracranial major arteries in moyamoya disease. Stroke 24(12):1960–1967PubMedCrossRefGoogle Scholar
  9. 9.
    Houkin K, Yoshimoto T, Abe H et al (1998) Role of basic fibroblast growth factor in the pathogenesis of moyamoya disease. Neurosurg Focus 5(5):e2PubMedCrossRefGoogle Scholar
  10. 10.
    Soriano SG, Cowan DB, Proctor MR et al (2002) Levels of soluble adhesion molecules are elevated in the cerebrospinal fluid of children with moyamoya syndrome. Neurosurgery 50(3):544–549PubMedGoogle Scholar
  11. 11.
    Nanba R, Kuroda S, Ishikawa T et al (2004) Increased expression of hepatocyte growth factor in cerebrospinal fluid and intracranial artery in moyamoya disease. Stroke 35(12):2837–2842PubMedCrossRefGoogle Scholar
  12. 12.
    Kim SK, Yoo JI, Cho BK et al (2003) Elevation of CRABP-I in the cerebrospinal fluid of patients with Moyamoya disease. Stroke 34(12):2835–2841PubMedCrossRefGoogle Scholar
  13. 13.
    Sasaki T, Nogawa S, Amano T (2006) Co-morbidity of moyamoya disease with Graves' disease. report of three cases and a review of the literature. Intern Med 45(9):649–653PubMedCrossRefGoogle Scholar
  14. 14.
    Im SH, Oh CW, Kwon OK et al (2005) Moyamoya disease associated with Graves disease: special considerations regarding clinical significance and management. J Neurosurg 102(6):1013–1017PubMedCrossRefGoogle Scholar
  15. 15.
    Tendler BE, Shoukri K, Malchoff C et al (1997) Concurrence of Graves' disease and dysplastic cerebral blood vessels of the moyamoya variety. Thyroid 7(4):625–629PubMedCrossRefGoogle Scholar
  16. 16.
    Utku U, Asil T, Celik Y et al (2004) Reversible MR angiographic findings in a patient with autoimmune Graves disease. Am J Neuroradiol 25(9):1541–1543PubMedGoogle Scholar
  17. 17.
    Booth F, Yanofsky R, Ross IB et al (1999) Primary antiphospholipid syndrome with moyamoya-like vascular changes. Pediatr Neurosurg 31(1):45–48PubMedCrossRefGoogle Scholar
  18. 18.
    Bakdash T, Cohen AR, Hempel JM, Hoagland J, Newman AJ (2002) Moyamoya, dystonia during hyperventilation, and antiphospholipid antibodies. Pediatr Neurol 26(2):157–160PubMedCrossRefGoogle Scholar
  19. 19.
    Bonduel M, Hepner M, Sciuccati G et al (2001) Prothrombotic disorders in children with moyamoya syndrome. Stroke 32(8):1786–1792PubMedCrossRefGoogle Scholar
  20. 20.
    Jea A, Smith ER, Robertson R et al (2005) Moyamoya syndrome associated with Down syndrome: outcome after surgical revascularization. Pediatrics 116(5):e694–701PubMedCrossRefGoogle Scholar
  21. 21.
    Kusters MA, Verstegen RH, Gemen EF et al (2009) Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol 156(2):189–193PubMedCrossRefGoogle Scholar
  22. 22.
    Goldacre MJ, Wotton CJ, Seagroatt V et al (2004) Cancers and immune related diseases associated with Down's syndrome: a record linkage study. Arch Dis Child 89(11):1014–1017PubMedCrossRefGoogle Scholar
  23. 23.
    Leno C, Mateo I, Cid C et al (1998) Autoimmunity in Down's syndrome: another possible mechanism of moyamoya disease. Stroke 29(4):868–869PubMedCrossRefGoogle Scholar
  24. 24.
    Yamada H, Deguchi K, Tanigawara T et al (1997) The relationship between moyamoya disease and bacterial infection. Clin Neurol Neurosurg 99(Suppl 2):S221–224PubMedGoogle Scholar
  25. 25.
    Tanigawara T, Yamada H, Sakai N et al (1997) Studies on cytomegalovirus and Epstein-Barr virus infection in moyamoya disease. Clin Neurol Neurosurg 99(Suppl 2):S225–228PubMedGoogle Scholar
  26. 26.
    Visudhiphan P, Chiemchanya S, Sirinavin S (1992) Internal carotid artery occlusion associated with Mycoplasma pneumoniae infection. Pediatr Neurol 8(3):237–239PubMedCrossRefGoogle Scholar
  27. 27.
    Leonardi S, Pavone P, Rotolo N et al (2005) Stroke in two children with Mycoplasma pneumoniae infection. A causal or casual relationship? Pediatr Infect Dis J 24(9):843–845PubMedCrossRefGoogle Scholar
  28. 28.
    Fu M, Wong KS, Lam WW et al (1998) Middle cerebral artery occlusion after recent Mycoplasma pneumoniae infection. J Neurol Sci 157(1):113–115PubMedCrossRefGoogle Scholar
  29. 29.
    Tanir G, Aydemir C, Yilmaz D et al (2006) Internal carotid artery occlusion associated with Mycoplasma pneumoniae infection in a child. Turk J Pediatr 48(2):166–171PubMedGoogle Scholar
  30. 30.
    Greco F, Castellano Chiodo D, Sorge A et al (2006) Multiple arterial ischemic strokes in a child with moyamoya disease and Mycoplasma pneumoniae infection. Minerva Pediatr 58(1):63–68PubMedGoogle Scholar
  31. 31.
    Eleftheriou D, Dillon MJ, Brogan PA (2009) Advances in childhood vasculitis. Curr Opin Rheumatol 21(4):411–418PubMedCrossRefGoogle Scholar
  32. 32.
    Pinna GS, Kafetzis DA, Tselkas OI et al (2008) Kawasaki disease: an overview. Curr Opin Infect Dis 21(3):263–270PubMedCrossRefGoogle Scholar
  33. 33.
    Tann OR, Tulloh RM, Hamilton MC (2008) Takayasu's disease: a review. Cardiol Young 18(3):250–259PubMedCrossRefGoogle Scholar
  34. 34.
    Togao O, Mihara F, Yoshiura T et al (2004) Prevalence of stenoocclusive lesions in the renal and abdominal arteries in moyamoya disease. Am J Roentgenol 183(1):119–122Google Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  • Ji Hoon Phi
    • 1
  • Seung-Ki Kim
    • 2
  • Kyu-Chang Wang
    • 1
  • Byung-Kyu Cho
    • 1
  1. 1.Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's HospitalSeoul National University College of MedicineJongno-guRepublic of Korea
  2. 2.Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Research Center for Rare DiseaseSeoul National University College of MedicineJongno-guRepublic of Korea

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