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In vivo demonstration of blood-brain barrier impairment in Moyamoya disease

  • Original Article - Vascular Neurosurgery - Ischemia
  • Published:
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Abstract

Background

Moyamoya disease (MMD) is a cerebrovascular disorder characterized by fragile vascular system. Previous studies suggested that the blood-brain barrier (BBB) destabilizing cytokine angiopoietin-2 plays a critical role in increasing vascular plasticity and endothelial disintegration in MMD. The aim of this study was to assess cerebrovascular integrity in vivo in patients affected by MMD.

Methods

We retrospectively analyzed 11 patients that underwent bypass for MMD (MMD group), 11 patients that underwent bypass for atherosclerotic cerebrovascular disease (ACVD—control group I), and 5 patients that underwent clipping for unruptured aneurysms (non-ischemic—control group II). Sodium fluorescein (NaFL) extravasation was evaluated during videoangiography when checking for bypass patency. A grading system (0, +, ++, +++) was used to define the extent of extravasation. Frequency and intensity of leakage was compared among different groups.

Results

NaFL extravasation appeared in 10/11 (91%) patients with MMD and in 8/11 (73%) patients with ACVD during bypass procedures. Extravasation was observed in none of the patients undergoing clipping for unruptured aneurysms. Although both chronic ischemic patient groups showed a comparably high incidence of NaFL extravasation, the MMD group was characterized by a much greater intensity of NaFL extravasation (grade +++ in 82%) than the ACVD group (grade +++ in 27%, p < 0.05).

Conclusions

We demonstrate blood-brain barrier impairment in MMD patients for the first time in vivo. This may be due to mechanisms intrinsic to the unique pathology of MMD, probably explaining the higher association with hemorrhage and post-operative hyperperfusion.

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References

  1. Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7(1):41–53

    CAS  Google Scholar 

  2. Acerbi F, Cavallo C, Broggi M, Cordella R, Anghileri E, Eoli M, Schiariti M, Broggi G, Ferroli P (2014) Fluorescein-guided surgery for malignant gliomas: a review. Neurosurg Rev 37(4):547–557

    Article  Google Scholar 

  3. Acerbi F, Broggi M, Schebesch K-M et al (2017) Fluorescein-guided surgery for resection of high-grade gliomas: a multicentric prospective phase II study (FLUOGLIO). Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-17-1184

  4. Ballabh P, Braun A, Nedergaard M (2004) The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16(1):1–13

    Article  CAS  Google Scholar 

  5. Baltsavias G, Khan N, Valavanis A (2015) The collateral circulation in pediatric moyamoya disease. Childs Nerv Syst 31(3):389–398

    Article  Google Scholar 

  6. Blecharz KG, Frey D, Schenkel T et al (2017) Autocrine release of angiopoietin-2 mediates cerebrovascular disintegration in Moyamoya disease. J Cereb Blood Flow Metab 37(4):1527–1539

    Article  CAS  Google Scholar 

  7. Czabanka M, Peña-Tapia P, Schubert GA, Woitzik J, Vajkoczy P, Schmiedek P (2008) Characterization of cortical microvascularization in adult moyamoya disease. Stroke 39(6):1703–1709

    Article  Google Scholar 

  8. De Reuck J, Crevits L, De Coster W, Sieben G, vander Eecken H (1980) Pathogenesis of Binswanger chronic progressive subcortical encephalopathy. Neurology 30(9):920–928

    Article  Google Scholar 

  9. Ergin A, Wang M, Zhang JY, Bruce JN, Fine RL, Bigio IJ, Joshi S (2012) The feasibility of real-time in vivo optical detection of blood-brain barrier disruption with indocyanine green. J Neuro-Oncol 106(3):551–560

    Article  CAS  Google Scholar 

  10. Ewing JR, Knight RA, Nagaraja TN, Yee JS, Nagesh V, Whitton PA, Li L, Fenstermacher JD (2003) Patlak plots of Gd-DTPA MRI data yield blood-brain transfer constants concordant with those of 14C-sucrose in areas of blood-brain opening. Magn Reson Med 50(2):283–292

    Article  Google Scholar 

  11. Fujimura M, Watanabe M, Narisawa A, Shimizu H, Tominaga T (2009) Increased expression of serum Matrix Metalloproteinase-9 in patients with moyamoya disease. Surg Neurol 72(5):476–480 discussion 480

    Article  Google Scholar 

  12. Fujimura M, Shimizu H, Inoue T, Mugikura S, Saito A, Tominaga T (2011) Significance of focal cerebral hyperperfusion as a cause of transient neurologic deterioration after extracranial-intracranial bypass for moyamoya disease: comparative study with non-moyamoya patients using N-isopropyl-p-[(123)I]iodoamphetamine single-photon emission computed tomography. Neurosurgery 68(4):957–964 discussion 964-965

    Article  Google Scholar 

  13. Fukui M (1997) Guidelines for the diagnosis and treatment of spontaneous occlusion of the circle of Willis (“moyamoya” disease). Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare, Japan. Clin Neurol Neurosurg 99(Suppl 2):S238–S240

    Article  Google Scholar 

  14. Hoffman HJ, Olszewski J (1961) Spread of sodium fluorescein in normal brain tissue. A study of the mechanism of the blood-brain barrier. Neurology 11:1081–1085

    Article  CAS  Google Scholar 

  15. Kaku Y, Iihara K, Nakajima N, Kataoka H, Fukuda K, Masuoka J, Fukushima K, Iida H, Hashimoto N (2012) Cerebral blood flow and metabolism of hyperperfusion after cerebral revascularization in patients with moyamoya disease. J Cereb Blood Flow Metab 32(11):2066–2075

    Article  CAS  Google Scholar 

  16. Kakucs C, Florian I-A, Ungureanu G, Florian I-S (2017) Fluorescein angiography in intracranial aneurysm surgery: a helpful method to evaluate the security of clipping and observe blood flow. World Neurosurg 105:406–411

    Article  Google Scholar 

  17. Kawaguchi S, Sakaki T, Morimoto T, Kakizaki T, Kamada K (1996) Characteristics of intracranial aneurysms associated with moyamoya disease. A review of 111 cases. Acta Neurochir 138(11):1287–1294

    Article  CAS  Google Scholar 

  18. Kim D-E, Schellingerhout D, Jaffer FA, Weissleder R, Tung C-H (2005) Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis. J Cereb Blood Flow Metab 25(2):226–233

    Article  Google Scholar 

  19. Kozler P, Pokorný J (2003) Altered blood-brain barrier permeability and its effect on the distribution of Evans blue and sodium fluorescein in the rat brain applied by intracarotid injection. Physiol Res 52(5):607–614

    CAS  PubMed  Google Scholar 

  20. Kuroda K, Kinouchi H, Kanemaru K, Nishiyama Y, Ogiwara M, Yoshioka H, Horikoshi T (2013) Intra-arterial injection fluorescein videoangiography in aneurysm surgery. Neurosurgery 72(2 Suppl Operative):ons141–ons150 discussion ons150

    PubMed  Google Scholar 

  21. Lane BC, Cohen-Gadol AA (2014) A prospective study of microscope-integrated intraoperative fluorescein videoangiography during arteriovenous malformation surgery: preliminary results. Neurosurg Focus 36(2):E15

    Article  Google Scholar 

  22. Lane B, Bohnstedt BN, Cohen-Gadol AA (2015) A prospective comparative study of microscope-integrated intraoperative fluorescein and indocyanine videoangiography for clip ligation of complex cerebral aneurysms. J Neurosurg 122(3):618–626

    Article  Google Scholar 

  23. Li Y, Rey-Dios R, Roberts DW, Valdés PA, Cohen-Gadol AA (2014) Intraoperative fluorescence-guided resection of high-grade gliomas: a comparison of the present techniques and evolution of future strategies. World Neurosurg 82(1–2):175–185

    Article  Google Scholar 

  24. Malmgren LT, Olsson Y (1980) Differences between the peripheral and the central nervous system in permeability to sodium fluorescein. J Comp Neurol 191(1):103–107

    Article  CAS  Google Scholar 

  25. Matano F, Mizunari T, Murai Y, Kubota A, Fujiki Y, Kobayashi S, Morita A (2017) Quantitative comparison of the intraoperative utility of indocyanine green and fluorescein videoangiographies in cerebrovascular surgery. Oper Neurosurg Hagerstown Md 13(3):361–366

    Article  Google Scholar 

  26. Misra BK, Samantray SK, Churi ON (2017) Application of fluorescein sodium videoangiography in surgery for spinal arteriovenous malformation. J Clin Neurosci 38:59–62

    Article  Google Scholar 

  27. Miyamoto S, Yoshimoto T, Hashimoto N, Okada Y, Tsuji I, Tominaga T, Nakagawara J, Takahashi JC, Trial Investigators JAM (2014) Effects of extracranial-intracranial bypass for patients with hemorrhagic moyamoya disease: results of the Japan Adult Moyamoya trial. Stroke 45(5):1415–1421

    Article  Google Scholar 

  28. Nakaji K, Ihara M, Takahashi C, Itohara S, Noda M, Takahashi R, Tomimoto H (2006) Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents. Stroke 37(11):2816–2823

    Article  CAS  Google Scholar 

  29. Narducci A, Onken J, Czabanka M, Hecht N, Vajkoczy P (2018) Fluorescein videoangiography during extracranial-to-intracranial bypass surgery: preliminary results. Acta Neurochir. https://doi.org/10.1007/s00701-017-3453-0

  30. Nishimura Y, Yata K, Nomoto T et al (2013) Identification of a novel indoline derivative for in vivo fluorescent imaging of blood-brain barrier disruption in animal models. ACS Chem Neurosci 4(8):1183–1193

    Article  CAS  Google Scholar 

  31. Peña-Tapia PG, Kemmling A, Czabanka M, Vajkoczy P, Schmiedek P (2008) Identification of the optimal cortical target point for extracranial-intracranial bypass surgery in patients with hemodynamic cerebrovascular insufficiency. J Neurosurg 108(4):655–661

    Article  Google Scholar 

  32. Rosenberg GA (2012) Neurological diseases in relation to the blood-brain barrier. J Cereb Blood Flow Metab 32(7):1139–1151

    Article  CAS  Google Scholar 

  33. Shaik IH, Miah MK, Bickel U, Mehvar R (2013) Effects of short-term portacaval anastomosis on the peripheral and brain disposition of the blood-brain barrier permeability marker sodium fluorescein in rats. Brain Res 1531:84–93

    Article  CAS  Google Scholar 

  34. Skoog I, Wallin A, Fredman P, Hesse C, Aevarsson O, Karlsson I, Gottfries CG, Blennow K (1998) A population study on blood-brain barrier function in 85-year-olds: relation to Alzheimer’s disease and vascular dementia. Neurology 50(4):966–971

    Article  CAS  Google Scholar 

  35. Suzuki J, Takaku A (1969) Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol 20(3):288–299

    Article  CAS  Google Scholar 

  36. Uchino H, Kazumata K, Ito M, Nakayama N, Kuroda S, Houkin K (2014) Intraoperative assessment of cortical perfusion by indocyanine green videoangiography in surgical revascularization for moyamoya disease. Acta Neurochir 156(9):1753–1760

    Article  Google Scholar 

  37. Yoshioka H, Kinouchi H, Nishiyama Y, Kanemaru K, Yagi T, Hanihara M, Horikoshi T (2014) Advantage of microscope integrated for both indocyanine green and fluorescein videoangiography on aneurysmal surgery: case report. Neurol Med Chir (Tokyo) 54(3):192–195

    Article  Google Scholar 

Download references

Funding

The study was supported by grants from Deutsche Forschungsgemeinschaft (DFG: VA 244/10-1) FOR 2325 NVI and European Stroke Research Network (EUSTROKE HEALTH-F2-2008-202213).

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Authors and Affiliations

  1. Department of Neurosurgery, Charitè-Universitätsmedizin Berlin, Berlin, Germany

    Alessandro Narducci, Kaku Yasuyuki, Julia Onken, Kinga Blecharz & Peter Vajkoczy

  2. Klinik für Neurochirurgie mit Arbeitsbereich Pädiatrische Neurochirurgie, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Peter Vajkoczy

Authors
  1. Alessandro Narducci
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  2. Kaku Yasuyuki
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  3. Julia Onken
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  4. Kinga Blecharz
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  5. Peter Vajkoczy
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Corresponding author

Correspondence to Peter Vajkoczy.

Ethics declarations

The study was approved by the local Ethics Committee (EA4/121/17). The paper is reported following the STROBE statement. All patients signed an informed consent form prior to the surgical procedure. A specific consent form was not required for study enrollment, because of its retrospective nature.

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The authors declare that they have no conflict of interest.

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This article is part of the Topical Collection on Vascular Neurosurgery - Ischemia

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Narducci, A., Yasuyuki, K., Onken, J. et al. In vivo demonstration of blood-brain barrier impairment in Moyamoya disease. Acta Neurochir 161, 371–378 (2019). https://doi.org/10.1007/s00701-019-03811-w

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  • DOI: https://doi.org/10.1007/s00701-019-03811-w

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