Skip to main content
Top
Published in: BMC Medicine 1/2011

Open Access 01-12-2011 | Research article

Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report

Authors: Paolo Zamboni, Erica Menegatti, Bianca Weinstock-Guttman, Michael G Dwyer, Claudiu V Schirda, Anna M Malagoni, David Hojnacki, Cheryl Kennedy, Ellen Carl, Niels Bergsland, Christopher Magnano, Ilaria Bartolomei, Fabrizio Salvi, Robert Zivadinov

Published in: BMC Medicine | Issue 1/2011

Login to get access

Abstract

Background

Several studies have reported hypoperfusion of the brain parenchyma in multiple sclerosis (MS) patients. We hypothesized a possible relationship between abnormal perfusion in MS and hampered venous outflow at the extracranial level, a condition possibly associated with MS and known as chronic cerebrospinal venous insufficiency (CCSVI).

Methods

We investigated the relationship between CCSVI and cerebral perfusion in 16 CCSVI MS patients and 8 age- and sex-matched healthy controls. Subjects were scanned in a 3-T scanner using dynamic susceptibility, contrast-enhanced, perfusion-weighted imaging. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM) and the subcortical GM (SGM). The severity of CCSVI was assessed according to the venous hemodynamic insufficiency severity score (VHISS) on the basis of the number of venous segments exhibiting flow abnormalities.

Results

There was a significant association between increased VHISS and decreased CBF in the majority of examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for GM and WM (r = -0.70 to -0.71, P < 0.002 and P corrected = 0.022), and for the putamen, thalamus, pulvinar nucleus of thalamus, globus pallidus and hippocampus (r = -0.59 to -0.71, P < 0.01 and P corrected < 0.05). No results for correlation between VHISS and CBV or MTT survived multiple comparison correction.

Conclusions

This pilot study is the first to report a significant relationship between the severity of CCSVI and hypoperfusion in the brain parenchyma. These preliminary findings should be confirmed in a larger cohort of MS patients to ensure that they generalize to the MS population as a whole. Reduced perfusion could contribute to the known mechanisms of virtual hypoxia in degenerated axons.
Appendix
Available only for authorised users
Literature
1.
go back to reference Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Gianesini S, Bartolomei I, Mascoli F, Salvi F: A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg. 2009, 50: 1348-1358. 10.1016/j.jvs.2009.07.096. e1-e3CrossRefPubMed Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Gianesini S, Bartolomei I, Mascoli F, Salvi F: A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg. 2009, 50: 1348-1358. 10.1016/j.jvs.2009.07.096. e1-e3CrossRefPubMed
2.
go back to reference Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Tacconi G, Dall'ara S, Bartolomei I, Salvi F: Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009, 80: 392-399. 10.1136/jnnp.2008.157164.CrossRefPubMed Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Tacconi G, Dall'ara S, Bartolomei I, Salvi F: Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009, 80: 392-399. 10.1136/jnnp.2008.157164.CrossRefPubMed
3.
go back to reference De Keyser J, Steen C, Mostert JP, Koch MW: Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance. J Cereb Blood Flow Metab. 2008, 28: 1645-1651. 10.1038/jcbfm.2008.72.CrossRefPubMed De Keyser J, Steen C, Mostert JP, Koch MW: Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance. J Cereb Blood Flow Metab. 2008, 28: 1645-1651. 10.1038/jcbfm.2008.72.CrossRefPubMed
4.
go back to reference Varga AW, Johnson G, Babb JS, Herbert J, Grossman RI, Inglese M: White matter hemodynamic abnormalities precede sub-cortical gray matter changes in multiple sclerosis. J Neurol Sci. 2009, 282: 28-33. 10.1016/j.jns.2008.12.036.CrossRefPubMedPubMedCentral Varga AW, Johnson G, Babb JS, Herbert J, Grossman RI, Inglese M: White matter hemodynamic abnormalities precede sub-cortical gray matter changes in multiple sclerosis. J Neurol Sci. 2009, 282: 28-33. 10.1016/j.jns.2008.12.036.CrossRefPubMedPubMedCentral
5.
go back to reference Trapp BD, Stys PK: Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol. 2009, 8: 280-291. 10.1016/S1474-4422(09)70043-2.CrossRefPubMed Trapp BD, Stys PK: Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol. 2009, 8: 280-291. 10.1016/S1474-4422(09)70043-2.CrossRefPubMed
6.
go back to reference Zamboni P, Menegatti E, Weinstock-Guttman B, Schirda C, Cox JL, Malagoni AM, Hojanacki D, Kennedy C, Carl E, Dwyer MG, Bergsland N, Galeotti R, Hussein S, Bartolomei I, Salvi F, Zivadinov R: The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics. Funct Neurol. 2009, 24: 133-138.PubMed Zamboni P, Menegatti E, Weinstock-Guttman B, Schirda C, Cox JL, Malagoni AM, Hojanacki D, Kennedy C, Carl E, Dwyer MG, Bergsland N, Galeotti R, Hussein S, Bartolomei I, Salvi F, Zivadinov R: The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics. Funct Neurol. 2009, 24: 133-138.PubMed
7.
go back to reference Zivadinov R, Weinstock-Guttman B, Benedict R, Tamano-Blanco M, Hussein S, Abdelrahman N, Durfee J, Ramanathan M: Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor. Hum Mol Genet. 2007, 16: 2659-2668. 10.1093/hmg/ddm189.CrossRefPubMed Zivadinov R, Weinstock-Guttman B, Benedict R, Tamano-Blanco M, Hussein S, Abdelrahman N, Durfee J, Ramanathan M: Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor. Hum Mol Genet. 2007, 16: 2659-2668. 10.1093/hmg/ddm189.CrossRefPubMed
8.
go back to reference Dwyer MG, Bergsland N, Saluste E, Sharma J, Jaisani Z, Durfee J, Abdelrahman N, Minagar A, Hoque R, Munschauer FE, Zivadinov R: Application of hidden Markov random field approach for quantification of perfusion/diffusion mismatch in acute ischemic stroke. Neurol Res. 2008, 30: 827-834. 10.1179/174313208X340987.CrossRefPubMed Dwyer MG, Bergsland N, Saluste E, Sharma J, Jaisani Z, Durfee J, Abdelrahman N, Minagar A, Hoque R, Munschauer FE, Zivadinov R: Application of hidden Markov random field approach for quantification of perfusion/diffusion mismatch in acute ischemic stroke. Neurol Res. 2008, 30: 827-834. 10.1179/174313208X340987.CrossRefPubMed
9.
go back to reference Ostergaard L, Weisskoff RM, Chesler DA, Gyldensted C, Rosen BR: High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis. Magn Reson Med. 1996, 36: 715-725. 10.1002/mrm.1910360510.CrossRefPubMed Ostergaard L, Weisskoff RM, Chesler DA, Gyldensted C, Rosen BR: High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis. Magn Reson Med. 1996, 36: 715-725. 10.1002/mrm.1910360510.CrossRefPubMed
10.
go back to reference Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 1995, 57: 289-300. Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 1995, 57: 289-300.
11.
go back to reference Adhya S, Johnson G, Herbert J, Jaggi H, Babb JS, Grossman RI, Inglese M: Pattern of hemodynamic impairment in multiple sclerosis: dynamic susceptibility contrast perfusion MR imaging at 3.0 T. Neuroimage. 2006, 33: 1029-1035. 10.1016/j.neuroimage.2006.08.008.CrossRefPubMedPubMedCentral Adhya S, Johnson G, Herbert J, Jaggi H, Babb JS, Grossman RI, Inglese M: Pattern of hemodynamic impairment in multiple sclerosis: dynamic susceptibility contrast perfusion MR imaging at 3.0 T. Neuroimage. 2006, 33: 1029-1035. 10.1016/j.neuroimage.2006.08.008.CrossRefPubMedPubMedCentral
12.
go back to reference Ge Y, Law M, Johnson G, Herbert J, Babb JS, Mannon LJ, Grossman RI: Dynamic susceptibility contrast perfusion MR imaging of multiple sclerosis lesions: characterizing hemodynamic impairment and inflammatory activity. AJNR Am J Neuroradiol. 2005, 26: 1539-1547.PubMed Ge Y, Law M, Johnson G, Herbert J, Babb JS, Mannon LJ, Grossman RI: Dynamic susceptibility contrast perfusion MR imaging of multiple sclerosis lesions: characterizing hemodynamic impairment and inflammatory activity. AJNR Am J Neuroradiol. 2005, 26: 1539-1547.PubMed
13.
go back to reference Inglese M, Park SJ, Johnson G, Babb JS, Miles L, Jaggi H, Herbert J, Grossman RI: Deep gray matter perfusion in multiple sclerosis: dynamic susceptibility contrast perfusion magnetic resonance imaging at 3 T. Arch Neurol. 2007, 64: 196-202. 10.1001/archneur.64.2.196.CrossRefPubMed Inglese M, Park SJ, Johnson G, Babb JS, Miles L, Jaggi H, Herbert J, Grossman RI: Deep gray matter perfusion in multiple sclerosis: dynamic susceptibility contrast perfusion magnetic resonance imaging at 3 T. Arch Neurol. 2007, 64: 196-202. 10.1001/archneur.64.2.196.CrossRefPubMed
14.
go back to reference Law M, Saindane AM, Ge Y, Babb JS, Johnson G, Mannon LJ, Herbert J, Grossman RI: Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology. 2004, 231: 645-652. 10.1148/radiol.2313030996.CrossRefPubMed Law M, Saindane AM, Ge Y, Babb JS, Johnson G, Mannon LJ, Herbert J, Grossman RI: Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology. 2004, 231: 645-652. 10.1148/radiol.2313030996.CrossRefPubMed
15.
go back to reference Wuerfel J, Paul F, Zipp F: Cerebral blood perfusion changes in multiple sclerosis. J Neurol Sci. 2007, 259: 16-20. 10.1016/j.jns.2007.02.011.CrossRefPubMed Wuerfel J, Paul F, Zipp F: Cerebral blood perfusion changes in multiple sclerosis. J Neurol Sci. 2007, 259: 16-20. 10.1016/j.jns.2007.02.011.CrossRefPubMed
16.
go back to reference Rizzi A, Quaglio D, Vasquez G, Mascoli F, Amadesi S, Calò G, Regoli D, Zamboni P: Effects of vasoactive agents in healthy and diseased human saphenous veins. J Vasc Surg. 1998, 28: 855-861. 10.1016/S0741-5214(98)70061-8.CrossRefPubMed Rizzi A, Quaglio D, Vasquez G, Mascoli F, Amadesi S, Calò G, Regoli D, Zamboni P: Effects of vasoactive agents in healthy and diseased human saphenous veins. J Vasc Surg. 1998, 28: 855-861. 10.1016/S0741-5214(98)70061-8.CrossRefPubMed
17.
go back to reference Wuerfel J, Bellmann-Strobl J, Brunecker P, Aktas O, McFarland H, Villringer A, Zipp F: Changes in cerebral perfusion precede plaque formation in multiple sclerosis: a longitudinal perfusion MRI study. Brain. 2004, 127: 111-119. 10.1093/brain/awh007.CrossRefPubMed Wuerfel J, Bellmann-Strobl J, Brunecker P, Aktas O, McFarland H, Villringer A, Zipp F: Changes in cerebral perfusion precede plaque formation in multiple sclerosis: a longitudinal perfusion MRI study. Brain. 2004, 127: 111-119. 10.1093/brain/awh007.CrossRefPubMed
18.
go back to reference Lee BB, Bergan J, Gloviczki P, Laredo J, Loose DA, Mattassi R, Parsi K, Villavicencio JL, Zamboni P, International Union of Phlebology (IUP): Diagnosis and treatment of venous malformations: Consensus Document of the International Union of Phlebology (IUP)-2009. Int Angiol. 2009, 28: 434-451.PubMed Lee BB, Bergan J, Gloviczki P, Laredo J, Loose DA, Mattassi R, Parsi K, Villavicencio JL, Zamboni P, International Union of Phlebology (IUP): Diagnosis and treatment of venous malformations: Consensus Document of the International Union of Phlebology (IUP)-2009. Int Angiol. 2009, 28: 434-451.PubMed
19.
go back to reference Lee BB: Regarding "A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency.". J Vasc Surg. 2010, 52: 533-10.1016/j.jvs.2010.03.030.CrossRefPubMed Lee BB: Regarding "A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency.". J Vasc Surg. 2010, 52: 533-10.1016/j.jvs.2010.03.030.CrossRefPubMed
20.
go back to reference Bergan JJ, Schmid-Schonbein GW, Smith PD, Nicolaides AN, Boisseau MR, Eklof B: Chronic venous disease. N Engl J Med. 2006, 355: 488-498. 10.1056/NEJMra055289.CrossRefPubMed Bergan JJ, Schmid-Schonbein GW, Smith PD, Nicolaides AN, Boisseau MR, Eklof B: Chronic venous disease. N Engl J Med. 2006, 355: 488-498. 10.1056/NEJMra055289.CrossRefPubMed
21.
go back to reference Fujita A, Nakamura M, Tamaki N, Kohmura E: Haemodynamic assessment in patients with dural arteriovenous fistulae: dynamic susceptibility contrast-enhanced MRI. Neuroradiology. 2002, 44: 806-811. 10.1007/s00234-002-0843-6.CrossRefPubMed Fujita A, Nakamura M, Tamaki N, Kohmura E: Haemodynamic assessment in patients with dural arteriovenous fistulae: dynamic susceptibility contrast-enhanced MRI. Neuroradiology. 2002, 44: 806-811. 10.1007/s00234-002-0843-6.CrossRefPubMed
22.
go back to reference Noguchi K, Kubo M, Kuwayama N, Kamisaki Y, Tomizawa G, Kameda K, Kawabe H, Ogawa S, Watanabe N, Endo S, Seto H: Intracranial dural arteriovenous fistulas with retrograde cortical venous drainage: assessment with CBV by dynamic susceptibility contrast magnetic resonance imaging. AJNR Am J Neuroradiol. 2006, 27: 1252-1256.PubMed Noguchi K, Kubo M, Kuwayama N, Kamisaki Y, Tomizawa G, Kameda K, Kawabe H, Ogawa S, Watanabe N, Endo S, Seto H: Intracranial dural arteriovenous fistulas with retrograde cortical venous drainage: assessment with CBV by dynamic susceptibility contrast magnetic resonance imaging. AJNR Am J Neuroradiol. 2006, 27: 1252-1256.PubMed
23.
go back to reference Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ: No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol. 2010, 68: 173-183.CrossRefPubMed Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ: No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol. 2010, 68: 173-183.CrossRefPubMed
24.
go back to reference Krogias C, Schröder A, Wiendl H, Hohlfeld R, Gold R: ["Chronic cerebrospinal venous insufficiency" and multiple sclerosis: critical analysis and first observation in an unselected cohort of MS patients] [in German]. Nervenarzt. 2010, 81: 740-746. 10.1007/s00115-010-2972-1.CrossRefPubMed Krogias C, Schröder A, Wiendl H, Hohlfeld R, Gold R: ["Chronic cerebrospinal venous insufficiency" and multiple sclerosis: critical analysis and first observation in an unselected cohort of MS patients] [in German]. Nervenarzt. 2010, 81: 740-746. 10.1007/s00115-010-2972-1.CrossRefPubMed
25.
go back to reference Sundstrom P, Wahlin A, Ambarki K, Birgander R, Eklund A, Malm J: Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control study. Ann Neurol. 2010, 68: 255-259. 10.1002/ana.22132.CrossRefPubMed Sundstrom P, Wahlin A, Ambarki K, Birgander R, Eklund A, Malm J: Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control study. Ann Neurol. 2010, 68: 255-259. 10.1002/ana.22132.CrossRefPubMed
26.
go back to reference Zamboni P: Regarding "No cerebrocervical venous congestion in patients with multiple sclerosis: intraluminal jugular septation.". Ann Neurol. 2010, 68: 969-970. 10.1002/ana.22152.CrossRefPubMed Zamboni P: Regarding "No cerebrocervical venous congestion in patients with multiple sclerosis: intraluminal jugular septation.". Ann Neurol. 2010, 68: 969-970. 10.1002/ana.22152.CrossRefPubMed
27.
go back to reference Trapp BD, Nave K-A: Multiple sclerosis: an immune or neurodegenerative disorder?. Annu Rev Neurosci. 2008, 31: 247-69. 10.1146/annurev.neuro.30.051606.094313.CrossRefPubMed Trapp BD, Nave K-A: Multiple sclerosis: an immune or neurodegenerative disorder?. Annu Rev Neurosci. 2008, 31: 247-69. 10.1146/annurev.neuro.30.051606.094313.CrossRefPubMed
28.
go back to reference Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L: Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998, 338: 278-85. 10.1056/NEJM199801293380502.CrossRefPubMed Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L: Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998, 338: 278-85. 10.1056/NEJM199801293380502.CrossRefPubMed
29.
go back to reference Trapp BD, Stys PK: Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol. 2009, 8: 280-91. 10.1016/S1474-4422(09)70043-2.CrossRefPubMed Trapp BD, Stys PK: Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol. 2009, 8: 280-91. 10.1016/S1474-4422(09)70043-2.CrossRefPubMed
Metadata
Title
Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report
Authors
Paolo Zamboni
Erica Menegatti
Bianca Weinstock-Guttman
Michael G Dwyer
Claudiu V Schirda
Anna M Malagoni
David Hojnacki
Cheryl Kennedy
Ellen Carl
Niels Bergsland
Christopher Magnano
Ilaria Bartolomei
Fabrizio Salvi
Robert Zivadinov
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2011
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-9-22

Other articles of this Issue 1/2011

BMC Medicine 1/2011 Go to the issue