Flow volume measurement of arterial venous and cerebrospinal fluid in patients with multiple sclerosis

 

 Permissions and Reprints

Abstract

Background Multiple sclerosis (MS) is usually described as an autoimmune disease, although the exact mechanism of the disease remains unknown. There have been studies reporting that venous flow abnormalities may be involved in the pathogenesis of MS or many of the associated clinical manifestations.

Objective The aim of this study was to evaluate flow volumes of the middle cerebral artery (MCA), transverse sinus (TS), and cerebral aqueduct using phase contrast magnetic resonance imaging (PC-MRI) in relapsing-remitting MS patients and a control group.

Methods We included 34 patients diagnosed by the McDonald criteria, revised in 2017, as well as 15 healthy controls matched by age and sex. The MRI scans were performed using a 1.5-T superconducting scanner. Axial T1-weighted, T2-weighted, and PC-MRI sequences were performed for the quantitative investigation of flow volume measurements. Quantitative analyses of flows were performed using flow analyses program PC-MRI angiography software. A circular region of interest was placed manually into the cerebral aqueduct, bilateral MCA, and TS.

Results Flow volumes of the cerebral aqueduct and MCA were not statistically significant between the MS and control groups. The flow volumes of the TS for the patient group were lower than those of the control group, and this difference was statistically significant.

Conclusions A reduced TS flow volume in MS patients was noted in the present study when compared with the control group, suggesting a relation between venous pathologies and MS. Further studies are needed to understand whether this relation is causal or epiphenomenal.

Resumo

Antecedentes A esclerose múltipla (EM) é comumente descrita como uma doença autoimune, embora seu mecanismo exato permaneça desconhecido. Há estudos que afirmam que anormalidades no fluxo venoso podem estar relacionadas à patogênese da EM ou a muitas das manifestações clínicas associadas.

Objetivo O objetivo deste estudo é avaliar os volumes de fluxo da artéria cerebral média (ACM), do seio transverso (ST) e do aqueduto cerebral usando ressonância magnética com contraste de fase (PC-MRI) em com EM recorrente-remitente.

Métodos Incluímos 34 pacientes diagnosticados pelos critérios de McDonald, revisados em 2017, além de 15 controles saudáveis pareados por idade e gênero. A ressonância magnética foi realizada usando um scanner supercondutor de 1,5 T. As sequências de PC-RM axiais, ponderadas em T1 e ponderadas em T2 foram realizadas para investigação quantitativa das medidas de volume de fluxo. As análises quantitativas de fluxo foram realizadas usando o software de angiografia PC-MRI do programa de análise de fluxo. Uma região circular de interesse foi localizada manualmente no aqueduto cerebral, ACM bilateral e ST.

Resultados Os volumes de fluxo do aqueduto cerebral e da ACM não foram estatisticamente significantes entre o grupo de pacientes e os controles. Os volumes ST do grupo de pacientes foram menores que os do grupo controle, e essa diferença foi estatisticamente significante.

Conclusões No presente estudo, um menor volume de fluxo ST foi registrado em pacientes com EM em comparação ao grupo controle, sugerindo uma relação entre patologias venosas e EM; Mais estudos são necessários para entender se essa relação é causal ou um fenômeno secundário.

Authors' Contributions

SA: planning and design of the study, the analysis of the data, and the writing of the article; MG: responsible for the selection of patients in accordance with the inclusion criteria.

Publication History

Received: 27 August 2021

Accepted: 31 October 2021

Article published online:
29 September 2022

© 2022. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

• References

• 1 Compston A, Coles A. Multiple sclerosis. Lancet 2008; 372 (9648): 1502-1517
  CrossrefPubMedGoogle Scholar
• 2 Ramagopalan SV, Dobson R, Meier UC, Giovannoni G. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol 2010; 9 (07) 727-739
  CrossrefPubMedGoogle Scholar
• 3 Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47 (06) 707-717
  CrossrefPubMedGoogle Scholar
• 4 Zamboni P, Galeotti R, Menegatti E. et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009; 80 (04) 392-399
  CrossrefPubMedGoogle Scholar
• 5 Gorucu Y, Albayram S, Balci B. et al. Cerebrospinal fluid flow dynamics in patients with multiple sclerosis: a phase contrast magnetic resonance study. Funct Neurol 2011; 26 (04) 215-222
  PubMedGoogle Scholar
• 6 Blinkenberg M, Akeson P, Sillesen H. et al. Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis. Acta Neurol Scand 2012; 126 (06) 421-427
  CrossrefPubMedGoogle Scholar
• 7 Zivadinov R, Marr K, Cutter G. et al. Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology 2011; 77 (02) 138-144 DOI: 10.1212/WNL.0b013e318212a901.
  CrossrefPubMedGoogle Scholar
• 8 Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ. No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 2010; 68 (02) 173-183
  CrossrefPubMedGoogle Scholar
• 9 Mayer CA, Pfeilschifter W, Lorenz MW. et al. The perfect crime? CCSVI not leaving a trace in MS. J Neurol Neurosurg Psychiatry 2011; 82 (04) 436-440
  CrossrefPubMedGoogle Scholar
• 10 Zamboni P, Menegatti E, Galeotti R. et al. The value of cerebral Doppler venous haemodynamics in the assessment of multiple sclerosis. J Neurol Sci 2009; 282 (1-2) 21-27
  CrossrefPubMedGoogle Scholar
• 11 Alvarez JI, Cayrol R, Prat A. Disruption of central nervous system barriers in multiple sclerosis. Biochim Biophys Acta 2011; 1812 (02) 252-264
  CrossrefPubMedGoogle Scholar
• 12 Magliozzi R, Howell OW, Reeves C. et al. A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 2010; 68 (04) 477-493
  CrossrefPubMedGoogle Scholar
• 13 Hochmeister S, Grundtner R, Bauer J. et al. Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis. J Neuropathol Exp Neurol 2006; 65 (09) 855-865
  CrossrefPubMedGoogle Scholar
• 14 Haacke EM, Ge Y, Sethi SK, Buch S, Zamboni P. An Overview of Venous Abnormalities Related to the Development of Lesions in Multiple Sclerosis. Front Neurol 2021; 12: 561458
  CrossrefPubMedGoogle Scholar
• 15 Simka M, Ludyga T, Latacz P, Kazibudzki M, Majewski E, Zaniewski M. Chronic cerebrospinal venous insufficiency is unlikely to be a direct trigger of multiple sclerosis. Mult Scler Relat Disord 2013; 2 (04) 334-339 DOI: 10.1016/j.msard.2013.02.004.
  CrossrefPubMedGoogle Scholar
• 16 Amato MP, Saia V, Hakiki B. et al. No association between chronic cerebrospinal venous insufficiency and pediatric-onset multiple sclerosis. Mult Scler 2012; 18 (12) 1791-1796 DOI: 10.1177/1352458512445943.
  CrossrefPubMedGoogle Scholar
• 17 Atkinson W, Forghani R, Wojtkiewicz GR. et al. Ligation of the jugular veins does not result in brain inflammation or demyelination in mice. PLoS One 2012; 7 (03) e33671 DOI: 10.1371/journal.pone.0033671.
  CrossrefPubMedGoogle Scholar
• 18 Laupacis A, Lillie E, Dueck A. et al. Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a meta-analysis. CMAJ 2011; 183 (16) E1203-E1212 DOI: 10.1503/cmaj.111074.
  CrossrefPubMedGoogle Scholar
• 19 Reekers J. A swan song for CCSVI. Cardiovasc Intervent Radiol 2014; 37 (02) 287-288 DOI: 10.1007/s00270-013-0833-6.
  CrossrefPubMedGoogle Scholar
• 20 Traboulsee AL, Knox KB, Machan L. et al. Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study. Lancet 2014; 383 (9912): 138-145 DOI: 10.1016/S0140-6736(13)61747-X.
  CrossrefPubMedGoogle Scholar
• 21 Srichai MB, Lim RP, Wong S, Lee VS. Cardiovascular applications of phase-contrast MRI. AJR Am J Roentgenol 2009; 192 (03) 662-675
  CrossrefPubMedGoogle Scholar
• 22 Tsuruda JS, Shimakawa A, Pelc NJ, Saloner D. Dural sinus occlusion: evaluation with phase-sensitive gradient-echo MR imaging. AJNR Am J Neuroradiol 1991; 12 (03) 481-488
  PubMedGoogle Scholar
• 23 Saloner D. The AAPM/RSNA physics tutorial for residents. An introduction to MR angiography. Radiographics 1995; 15 (02) 453-465
  CrossrefPubMedGoogle Scholar
• 24 Nayler GL, Firmin DN, Longmore DB. Blood flow imaging by cine magnetic resonance. J Comput Assist Tomogr 1986; 10 (05) 715-722
  CrossrefPubMedGoogle Scholar
• 25 Tanaka R, Iwasaki Y, Koprowski H. Ultrastructural studies of perivascular cuffing cells in multiple sclerosis brain. Am J Pathol 1975; 81 (03) 467-478
  PubMedGoogle Scholar
• 26 Ge Y, Law M, Johnson G. et al. Dynamic susceptibility contrast perfusion MR imaging of multiple sclerosis lesions: characterizing hemodynamic impairment and inflammatory activity. AJNR Am J Neuroradiol 2005; 26 (06) 1539-1547
  PubMedGoogle Scholar
• 27 Segal MB, Pollay M. The secretion of cerebrospinal fluid. Exp Eye Res 1977; 25 (Suppl): 127-148
  CrossrefPubMedGoogle Scholar
• 28 Gray H. Anatomy of the Human Body. Lewis WH. editor. 20th edn. Lea & Febiger; Philadelphia: 1918. 2000. Bartleby.Com. 7 Aug. 2010
• 29 Connor SE, O'Gorman R, Summers P. et al. SPAMM, cine phase contrast imaging and fast spin-echo T2-weighted imaging in the study of intracranial cerebrospinal fluid (CSF) flow. Clin Radiol 2001; 56 (09) 763-772
  CrossrefPubMedGoogle Scholar
• 30 Barkhof F, Kouwenhoven M, Scheltens P, Sprenger M, Algra P, Valk J. Phase-contrast cine MR imaging of normal aqueductal CSF flow. Effect of aging and relation to CSF void on modulus MR. Acta Radiol 1994; 35 (02) 123-130
  CrossrefPubMedGoogle Scholar
• 31 Brinkmann G, Harlandt O, Muhle C, Brossmann J, Heller M. [Quantification of fluid flow in magnetic resonance tomography: an experimental study of a flow model and liquid flow measurements in the cerebral aqueduct in volunteers]. Röfo Fortschr Geb Röntgenstr Nuklearmed 2000; 172 (12) 1043-1051
  PubMedGoogle Scholar
• 32 Zamboni P, Menegatti E, Weinstock-Guttman B. et al. The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics. Funct Neurol 2009; 24 (03) 133-138
  PubMedGoogle Scholar
• 33 Sundström P, Wåhlin 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 (02) 255-259
  CrossrefPubMedGoogle Scholar
• 34 Beggs CB, Magnano C, Shepherd SJ. et al. Aqueductal cerebrospinal fluid pulsatility in healthy individuals is affected by impaired cerebral venous outflow. J Magn Reson Imaging 2014; 40 (05) 1215-1222
  CrossrefPubMedGoogle Scholar
• 35 Putnam TJ. Studies in multiple sclerosis: IV: “encephalitis” and sclerotic plaques produced by venular obstruction. Arch Neurol Psychiatry 1935; 33: 929-940
  CrossrefGoogle Scholar
• 36 Tracy J, Putnam MD, Ludwig V, Chiavacci MD, Hans Hoff MD, Hyman G. et al Results of treatment of multiple sclerosis with dicoumarin. Arch Neurol Psychiatry 1947; 57 (01) 1-13
  CrossrefPubMedGoogle Scholar
• 37 Jurkiewicz E, Kotulska K, Nowak K. et al. MR venography in children and adolescents with multiple sclerosis does not show increased prevalence of extracranial veins anomalies. Eur J Paediatr Neurol 2014; 18 (02) 218-222
  CrossrefPubMedGoogle Scholar
• 38 McTaggart RA, Fischbein NJ, Elkins CJ. et al. Extracranial venous drainage patterns in patients with multiple sclerosis and healthy controls. AJNR Am J Neuroradiol 2012; 33 (08) 1615-1620
  CrossrefPubMedGoogle Scholar
• 39 Marchione P, Morreale M, Giacomini P. et al. Ultrasonographic evaluation of cerebral arterial and venous haemodynamics in multiple sclerosis: a case-control study. PLoS One 2014; 9 (10) e111486 DOI: 10.1371/journal.pone.0111486.
  CrossrefPubMedGoogle Scholar
• 40 Bastianello S, Romani A, Viselner G. et al. Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study. BMC Neurol 2011; 11: 132 DOI: 10.1186/1471-2377-11-132.
  CrossrefPubMedGoogle Scholar