Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Original Paper

Brain Microvasculature Involvement in ANCA Positive Vasculitis

González-Suárez I.a · Arpa J.a · Ríos-Blanco J.J.b

Author affiliations

aNeurology Department, Hospital of Clínico San Carlos, C/Professor Martin Lagos, and bInternal Medicine Department, Hospital Universitario La Paz, Madrid, Spain

Related Articles for ""

Cerebrovasc Dis 2016;41:313-321

Do you have an account?

Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.
Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00


Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 20, 2015
Accepted: December 30, 2015
Published online: February 18, 2016
Issue release date: April 2016

Number of Print Pages: 9
Number of Figures: 0
Number of Tables: 6

ISSN: 1015-9770 (Print)
eISSN: 1421-9786 (Online)

For additional information: https://www.karger.com/CED

Abstract

Objective: Endothelial dysfunction is associated with arterial stiffness, a factor that is increasingly recognised as an important determinant of cardiovascular risk. High-flow organs such as the brain and kidneys are particularly sensitive to excessive pressure and flow pulsatility. High, local blood flow is associated with low microvascular impedance, which facilitates the penetration of excessive pulsatile energy into the microvascular bed leading to tissue damage. Systemic endothelial dysfunction and arterial stiffness have been demonstrated in peripheral vessels in associated vasculitis (AAV). Although, the brain involvement is not infrequent in AAV, it has not been evaluated previously. Our aim is to evaluate the involvement of the brain microvasculature in AAV. Methods: Twenty-three patients with inactive AAV were studied. Brain blood flow was assessed by transcranial Doppler (TCD) and single-photon positron emission tomography (SPECT), structural brain involvement by brain MRI and cognitive scores by Montreal Cognitive Assessment (MoCA) test. Results: Lower mean flow velocity (MFV) was associated to altered SPECT perfusion, higher white matter changes (WMC), lower MoCA scores and younger age (p < 0.05). Middle cerebral artery pulsatility index (MCA-PI) was related to hypertension, diabetes, lower scores on MoCA, increased vasculitis damage index (VDI) and perfusion impairment in SPECT (p < 0.05). These data were reproduced for all intracranial arteries. Up to 88.9% of patients had WMC on MRI. A higher lesion load was associated with age, decreased MoCA and fewer MFV with higher PI. The multivariable linear regression analysis showed that the greater the lesion loads, greater the bifrontal atrophy, MCA-PI and lower MoCA scores. Up to 60.9% of patients presented a decreased MoCA score (p = 0.012). It appeared to be related to VDI (p = 0.04), WMC (p = 0.004) and altered SPECT (p = 0.05). Conclusions: The alterations in brain perfusion SPECT, the presence of white matter lesions on MRI, as well as increased PI and RI with lower MFV of the cerebral vessels in TCD suggest the presence of microangiopathy in asymptomatic AAV that could lead to cognitive impairment.

© 2016 S. Karger AG, Basel


References

  1. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al: 2012 revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013;65:1-11.
  2. Zhang W, Zhou G, Shi Q, Zhang X, Zeng XF, Zhang FC: Clinical analysis of nervous system involvement in ANCA-associated systemic vasculitides. Clin Exp Rheumatol 2009;27(1 suppl 52):S65-S69.
  3. Nishino H, Rubino FA, DeRemee RA, Swanson JW, Parisi JE: Neurological involvement in Wegener's granulomatosis: an analysis of 324 consecutive patients at the Mayo clinic. Ann Neurol 1993;33:4-9.
  4. Guillevin L, Lhote F, Gayraud M, Cohen P, Jarrousse B, Lortholary O, et al: Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients. Medicine (Baltimore) 1996;75:17-28.
  5. Sierra C, de la Sierra A, Chamorro A, Larrousse M, Domenech M, Coca A: Cerebral hemodynamics and silent cerebral white matter lesions in middleaged essential hypertensive patients. Blood Press 2004;13:304-309.
  6. Lee KY, Sohn YH, Baik JS, Kim GW, Kim JS: Arterial pulsatility as an index of cerebral microangiopathy in diabetes. Stroke 2000;31:1111-1115.
  7. Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, et al: The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum 1990;33:1101-1107.
  8. Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, et al: The American college of rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990;33:1094-1100.
  9. Hellmich B, Flossmann O, Gross WL, Bacon P, Cohen-Tervaert JW, Guillevin L, et al: EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 2007;66:605-617.
  10. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al: The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695-699.
  11. Alexandrov AV, Sloan MA, Wong LK, Douville C, Razumovsky AY, Koroshetz WJ, et al: Practice standards for transcranial Doppler ultrasound: part I - test performance. J Neuroimaging 2007;17:11-18.
  12. Ringelstein EB, Kahlscheuer B, Niggemeyer E, Otis SM: Transcranial Doppler sonography: anatomical landmarks and normal velocity values. Ultrasound Med Biol 1990;16:745-761.
  13. Irimia P, Segura T, Serena J, Moltó JM: Sociedad Española de Neurosonología SONES. Neurosonología, 2011. Aplicaciones diagnósticas para la práctica clínica. Madrid, Panamericana, 2011, p 99.
  14. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, et al: Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis 2012;34:290-296.
  15. Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, et al: National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006;37:2220-2241.
  16. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA: MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol 1987;149:351-356.
  17. Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjögren M, et al; European task force on age-related white matter changes: a new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001;32:1318-1322.
  18. Booth AD, Jayne DR, Kharbanda RK, McEniery CM, Mackenzie IS, Brown J, et al: Infliximab improves endothelial dysfunction in systemic vasculitis: a model of vascular inflammation. Circulation 2004;109:1718-1723.
  19. Filer AD, Gardner-Medwin JM, Thambyrajah J, Raza K, Carruthers DM, Stevens RJ, et al: Diffuse endothelial dysfunction is common to ANCA associated systemic vasculitis and polyarteritis nodosa. Ann Rheum Dis 2003;62:162-167.
  20. Raza K, Thambyrajah J, Townend JN, Exley AR, Hortas C, Filer A, et al: Suppression of inflammation in primary systemic vasculitis restores vascular endothelial function: lessons for atherosclerotic disease. Circulation 2000;102:1470-1472.
  21. Wang P, Ba ZF, Chaudry IH: Administration of tumor necrosis factor-alpha in vivo depresses endothelium-dependent relaxation. Am J Physiol 1994;266(6 pt 2):H2535-H2541.
  22. de Groot JC, de Leeuw FE, Breteler MM: Cognitive correlates of cerebral white matter changes. J Neural Transm Suppl 1998;53:41-67.
  23. Aldasoro M, Martínez C, Vila JM, Medina P, Lluch S: Influence of endothelial nitric oxide on adrenergic contractile responses of human cerebral arteries. J Cereb Blood Flow Metab 1996;16:623-628.
  24. Toda N: Mediation by nitric oxide of neurally-induced human cerebral artery relaxation. Experientia 1993;49:51-53.
  25. White RP, Deane C, Vallance P, Markus HS: Nitric oxide synthase inhibition in humans reduces cerebral blood flow but not the hyperemic response to hypercapnia. Stroke 1998;29:467-472.
  26. White RP, Vallance P, Markus HS: Effect of inhibition of nitric oxide synthase on dynamic cerebral autoregulation in humans. Clin Sci (Lond) 2000;99:555-560.
  27. Vane JR, Anggård EE, Botting RM: Regulatory functions of the vascular endothelium. N Engl J Med 1990;323:27-36.
  28. Lüscher TF, Vanhoutte PM: The Endothelium: Modulator of Cardiovascular Function. Boca Raton, CRC Press, 1990.
  29. Quyyumi AA: Endothelial function in health and disease: new insights into the genesis of cardiovascular disease. Am J Med 1998;105:32S-39S.
  30. Vanhoutte PM, Shimokawa H, Tang EH, Feletou M: Endothelial dysfunction and vascular disease. Acta Physiol (Oxf) 2009;196:193-222.
  31. Lok J, Gupta P, Guo S, Kim WJ, Whalen MJ, van Leyen K, et al: Cell-cell signalling in the neurovascular unit. Neurochem Res 2007;32:2032-2045.
  32. Iadecola C: Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci 2004;5:347-360.
  33. Hawkins BT, Davis TP: The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005;57:173-185.
  34. Booth AD, Wallace S, McEniery CM, Yasmin, Brown J, Jayne DR, et al: Inflammation and arterial stiffness in systemic vasculitis: a model of vascular inflammation. Arthritis Rheum 2004;50:581-588.
  35. Savage CO, Pottinger BE, Gaskin G, Pusey CD, Pearson JD: Autoantibodies developing to myeloperoxidase and proteinase 3 in systemic vasculitis stimulate neutrophil cytotoxicity toward cultured endothelial cells. Am J Pathol 1992;41:335-342.
  36. Morel DW, Hessler JR, Chisolm GM: Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid. J Lipid Res 1983;24:1070-1076.
  37. Bakker SL, de Leeuw FE, den Heijer T, Koudstaal PJ, Hofman A, Breteler MM: Cerebral haemodynamics in the elderly: the Rotterdam study. Neuroepidemiology 2004;23:178-184.
  38. Sun ZW, Zhu YX, Liu HY, Liu J, Zhu XQ, Zhou JN, et al: Decreased cerebral blood flow velocity in apolipoprotein E epsilon4 allele carriers with mild cognitive impairment. Eur J Neurol 2007;14:150-155.
  39. Sabayan B, Jansen S, Oleksik AM, van Osch MJ, van Buchem MA, van Vliet P, et al: Cerebrovascular hemodynamics in Alzheimer's disease and vascular dementia: a meta-analysis of transcranial Doppler studies. Ageing Res Rev 2012;11:271-277.
  40. Bude RO, Rubin JM: Relationship between the resistivity index and vascular compliance and resistance. Radiology 1999;114:411-417.
  41. Titianova EB, Velcheva IV, Mateev PS: Effects of aging and hematocrit on cerebral blood flow velocity in patients with unilateral cerebral infarctions: a Doppler ultrasound evaluation. Angiology 1993;44:100-106.
  42. Ackerstaff RG, Keunen RW, van Pelt W, Montauban van Swijndregt AD, Stijnen T: Influence of biological factors on changes in mean cerebral blood flow velocity in normal ageing: a transcranial Doppler study. Neurol Res 1990;12:187-191.
  43. Cho SJ, Sohn YH, Kim GW, Kim JS: Blood flow velocity changes in the middle cerebral artery as an index of the chronicity of hypertension. J Neurol Sci 1997;150:77-80.
  44. Foerstl H, Biedert S, Hewer W: Multiinfarct and Alzheimer-type dementia investigated by transcranial Doppler sonography. Biol Psychiatry 1989;26:590-594.
  45. Sharma VK, Tsivgoulis G, Lao AY, Malkoff MD, Alexandrov AV: Noninvasive detection of diffuse intracranial disease. Stroke 2007;38:3175-3181.
  46. Heliopoulos I, et al: Association of ultrasonographic parameters with subclinical white-matter hyperintensities in hypertensive patients. Cardiovasc Psychiatry Neurol 2012;2012:616572.
  47. Kidwell CS, el-Saden S, Livshits Z, Martin NA, Glenn TC, Saver JL: Transcranial Doppler pulsatility indices as a measure of diffuse small-vessel disease. J Neuroimaging 2001;11:229-235.
  48. Halpern EJ, Merton DA, Forsberg F: Effect of distal resistance on Doppler US flow patterns. Radiology 1998;67:761-767.
  49. Mäntylä R, Aronen HJ, Salonen O, Pohjasvaara T, Korpelainen M, Peltonen T, et al: Magnetic resonance imaging white matter hyperintensities and mechanism of ischemic stroke. Stroke 1999;30:2053-2058.
  50. Kwa VI, Stam J, Blok LM, Verbeeten B Jr: T2-weighted hyperintense MRI lesions in the pons in patients with atherosclerosis. Stroke 1997;28:1357-1360.
  51. Ostrow PT, Miller LL: Pathology of small artery disease. Adv Neurol 1993;62:93-123.
  52. Pullicino P, Ostrow P, Miller L, Snyder W, Munschauer F: Pontine ischemic rarefaction. Ann Neurol 1995;37:460-466.
  53. Scarpelli M, Salvolini U, Diamanti L, Montironi R, Chiaromoni L, Maricotti M: MRI and pathological examination of post-mortem brains: the problem of white matter high signal areas. Neuroradiology 1994;36:393-398.
  54. Breteler MM, van Amerongen NM, van Swieten JC, Claus JJ, Grobbee DE, van Gijn J, et al: Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam study. Stroke 1994;25:1109-1115.
  55. van Swieten JC, Staal S, Kappelle LJ, Derix MM, van Gijn J: Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts? J Neurol 1996;243:196-200.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 20, 2015
Accepted: December 30, 2015
Published online: February 18, 2016
Issue release date: April 2016

Number of Print Pages: 9
Number of Figures: 0
Number of Tables: 6

ISSN: 1015-9770 (Print)
eISSN: 1421-9786 (Online)

For additional information: https://www.karger.com/CED


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.