Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a systematic review and meta-analysis

Objectives Numerous studies have indicated that chronic cerebrospinal venous insufficiency is a potential factor in causing multiple sclerosis in recent years, but this conclusion remains unconfirmed. This meta-analysis examined the correlation between multiple sclerosis and chronic cerebrospinal venous insufficiency. Methods We searched Embase and Medline (Ovid) for publications published from 1 January 2006 to 1 May 2022. The meta-analysis was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Eligible studies (n=20) included 3069 participants from seven countries. Pooled analysis indicated that chronic cerebrospinal venous insufficiency was more frequent in patients with multiple sclerosis than in healthy controls (OR 3.36; 95% CI 1.92 to 5.85; p<0.001) with remarkable heterogeneity among studies (I2=79%). Results were more strongly correlated in subsequent sensitivity analyses, but heterogeneity was also more substantial. We removed studies that initially proposed a chronic cerebrospinal venous insufficiency team as well as studies by authors involved in or advocating endovascular therapies. Conclusions Chronic cerebrospinal venous insufficiency is significantly associated with multiple sclerosis and it is more prevalent in patients with multiple sclerosis than in healthy individuals, but considerable heterogeneity of results is still observed.

[1]  E. Mayo-Wilson,et al.  The PRISMA 2020 statement: an updated guideline for reporting systematic reviews , 2021, Systematic Reviews.

[2]  R. Zivadinov,et al.  No association between variations in extracranial venous anatomy and clinical outcomes in multiple sclerosis patients over 5 years , 2019, BMC Neurology.

[3]  Judith Ter Schure,et al.  Accumulation Bias in meta-analysis: the need to consider time in error control , 2019, F1000Research.

[4]  J. Illes,et al.  Safety and efficacy of venoplasty in MS , 2018, Neurology.

[5]  Clare Baecher-Allan,et al.  Multiple Sclerosis: Mechanisms and Immunotherapy , 2018, Neuron.

[6]  L. Tesio,et al.  Efficacy and Safety of Extracranial Vein Angioplasty in Multiple Sclerosis , 2017, JAMA neurology.

[7]  R. Zivadinov,et al.  Centralized and Local Color Doppler Ultrasound Reading Agreement for Diagnosis of the Chronic Cerebrospinal Venous Insufficiency in Patients with Multiple Sclerosis , 2017, Current neurovascular research.

[8]  P. Calabresi,et al.  Extracranial Venous Drainage Pattern in Multiple Sclerosis and Healthy Controls: Application of the 2011 Diagnostic Criteria for Chronic Cerebrospinal Venous Insufficiency , 2016, European Neurology.

[9]  A. Vestri,et al.  Prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: a blinded sonographic evaluation , 2015, Phlebology.

[10]  R. Gold,et al.  “Liberation treatment” for chronic cerebrospinal venous insufficiency in multiple sclerosis: the truth will set you free , 2014, Brain and behavior.

[11]  M. Dake,et al.  Recommendations for multimodal noninvasive and invasive screening for detection of extracranial venous abnormalities indicative of chronic cerebrospinal venous insufficiency: a position statement of the International Society for Neurovascular Disease. , 2014, Journal of vascular and interventional radiology : JVIR.

[12]  R. Frayne,et al.  Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis , 2014, Canadian Medical Association Journal.

[13]  M. Ramanathan,et al.  Prospective randomized trial of venous angioplasty in MS (PREMiSe) , 2014, Neurology.

[14]  M. Simka.  Chronic cerebrospinal venous insufficiency: current perspectives , 2014 .

[15]  T. Psaltopoulou,et al.  Chronic cerebrospinal venous insufficiency and multiple sclerosis: a comprehensive meta-analysis of case–control studies , 2014, Therapeutic advances in neurological disorders.

[16]  E. Novelli,et al.  Cross-sectional area variations of internal jugular veins during supine head rotation in multiple sclerosis patients with chronic cerebrospinal venous insufficiency: a prospective diagnostic controlled study with duplex ultrasound investigation , 2013, BMC Neurology.

[17]  R. Fox,et al.  Hydration status substantially affects chronic cerebrospinal venous insufficiency assessments , 2013, Neurology. Clinical practice.

[18]  M. Simka,et al.  Diagnostic accuracy of current sonographic criteria for the detection of outflow abnormalities in the internal jugular veins , 2013, Phlebology.

[19]  D. Imperiale,et al.  Chronic cerebrospinal venous insufficiency in multiple sclerosis: A sonographer-blinded case-control study , 2013, Clinical Neurology and Neurosurgery.

[20]  Clive B Beggs,et al.  Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis , 2013, BMC Medicine.

[21]  L. Visser,et al.  Occurrence of CCSVI in patients with MS and its relationship with iron metabolism and varicose veins , 2013, European journal of neurology.

[22]  W. Liboni,et al.  Chronic Cerebrospinal Venous Insufficiency Is Not Associated with Multiple Sclerosis and Its Severity: A Blind-Verified Study , 2013, PloS one.

[23]  H. Siebner,et al.  Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis , 2012, Acta neurologica Scandinavica.

[24]  G. Quattrocchi,et al.  Multiple Sclerosis and CCSVI: A Population-Based Case Control Study , 2012, PloS one.

[25]  S. Saip,et al.  Chronic cerebrospinal venous insufficiency: does ultrasound really distinguish multiple sclerosis subjects from healthy controls? , 2012, European Radiology.

[26]  M. Amato,et al.  No association between chronic cerebrospinal venous insufficiency and pediatric-onset multiple sclerosis , 2012, Multiple sclerosis.

[27]  A. Brunetti,et al.  Multiple sclerosis: cerebral circulation time. , 2012, Radiology.

[28]  Angelo Taibi,et al.  Does thoracic pump influence the cerebral venous return? , 2012, Journal of applied physiology.

[29]  E. Frohman,et al.  No cerebral or cervical venous insufficiency in US veterans with multiple sclerosis. , 2011, Archives of neurology.

[30]  F. Kantarcı,et al.  Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS , 2011, Neurology.

[31]  M. Dake,et al.  Chronic cerebrospinal venous insufficiency in multiple sclerosis: a historical perspective. , 2011, Functional neurology.

[32]  M. Calabrese,et al.  Progressive multiple sclerosis is not associated with chronic cerebrospinal venous insufficiency , 2011, Neurology.

[33]  D. Centonze,et al.  Proposed chronic cerebrospinal venous insufficiency criteria do not predict multiple sclerosis risk or severity , 2011, Annals of neurology.

[34]  Arthur S Slutsky,et al.  The rise of people power , 2011, Nature.

[35]  H. Steinmetz,et al.  The perfect crime? CCSVI not leaving a trace in MS , 2011, Journal of Neurology, Neurosurgery & Psychiatry.

[36]  M. Calabrese,et al.  No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset , 2011, Annals of neurology.

[37]  F. Barkhof,et al.  Cardiovascular and Interventional Radiological Society of Europe Commentary on the Treatment of Chronic Cerebrospinal Venous Insufficiency , 2010, CardioVascular and Interventional Radiology.

[38]  Frederik Barkhof,et al.  No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[39]  Michele Tarsilla.  Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[40]  F. Salvi,et al.  The reproducibility of colour Doppler in chronic cerebrospinal venous insufficiency associated with multiple sclerosis. , 2010, International angiology : a journal of the International Union of Angiology.

[41]  F. Salvi,et al.  Use of neck magnetic resonance venography, Doppler sonography and selective venography for diagnosis of chronic cerebrospinal venous insufficiency: a pilot study in multiple sclerosis patients and healthy controls. , 2010, International angiology : a journal of the International Union of Angiology.

[42]  F. Salvi,et al.  A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. , 2009, Journal of vascular surgery.

[43]  F. Carinci,et al.  Venous collateral circulation of the extracranial cerebrospinal outflow routes. , 2009, Current neurovascular research.

[44]  Paolo Zamboni,et al.  The value of cerebral Doppler venous haemodynamics in the assessment of multiple sclerosis , 2009, Journal of the Neurological Sciences.

[45]  F. Salvi,et al.  The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics. , 2009, Functional neurology.

[46]  F. Salvi,et al.  Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[47]  P. Zamboni.  The Big Idea: Iron-Dependent Inflammation in Venous Disease and Proposed Parallels in Multiple Sclerosis , 2006, Journal of the Royal Society of Medicine.

[48]  R. Müri,et al.  Transtemporal power- and frequency-based color-coded duplex sonography of cerebral veins and sinuses. , 1997, AJNR. American journal of neuroradiology.

[49]  A. Nirkko,et al.  Transoccipital power-based color-coded duplex sonography of cerebral sinuses and veins. , 1997, Stroke.

[50]  D. Caramella,et al.  Percutaneous Venous Angioplasty in Patients With Multiple Sclerosis And Chronic Cerebrospinal Venous Insufficiency: A Randomized Wait List Control Study. , 2020, Annals of vascular surgery.

[51]  P. Tugwell,et al.  The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses , 2014 .