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Abstract

Objectives:

A chronic state of impaired cerebral and cervical venous drainage, termed chronic cerebrospinal venous insufficiency (CCSVI), has recently been implicated in the pathogenesis of multiple sclerosis (MS). We performed a color-coded Doppler sonography case-control study to externally validate the CCSVI criteria.

Methods:

We prospectively evaluated consecutive patients with clinically definite MS and healthy volunteers using extracranial and transcranial color-coded Doppler sonography. The recently developed neurosonology criteria for CCSVI detection were used for interpretation of ultrasound assessments. The presence of venous reflux in cervical veins was assessed both in the sitting and upright position during a short period of apnea and after Valsalva maneuver.

Results:

We recruited 42 patients with MS (mean age 39 ± 11 years, 17 men) and 43 control individuals (mean age 38 ± 12 years, 16 men). Very good/excellent intrarater and interrater agreement (κ values 0.82–1.00) was documented in 3 out of 5 CCSVI criteria. There was no evidence of stenosis or nondetectable Doppler flow in cervical veins in patients and controls. Reflux in internal jugular vein (IJV) was documented in 1 patient (2%) and 1 control subject (2%), both in sitting and supine posture during apnea. After performing Valsalva maneuver, we documented the presence of IJV valve incompetence in 3 patients with MS (7%) and 4 healthy volunteers (9%; p > 0.999).

Conclusions:

With established reproducibility of venous ultrasound testing, our data argue against CCSVI as the underlying mechanism of MS. Without further independent validation of CCSVI, potentially dangerous endovascular procedures, proposed as novel therapy for MS, should not be performed outside controlled clinical trials.

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Information & Authors

Information

Published In

Neurology®
Volume 77Number 13September 27, 2011
Pages: 1241-1245
PubMed: 21849653

Publication History

Received: January 17, 2011
Accepted: March 10, 2011
Published online: August 17, 2011
Published in print: September 27, 2011

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Authors

Affiliations & Disclosures

G. Tsivgoulis, MD, RVT, FESO
From the Departments of Neurology (G.T., C.B., K.V., C.P., I.H.) and Radiology (M.M., P.P.), Democritus University of Thrace, School of Medicine, Alexandroupolis; and Second Department of Neurology (K.V.), University of Athens, School of Medicine, Attikon Hospital, Athens, Greece.
M. Mantatzis, MD
From the Departments of Neurology (G.T., C.B., K.V., C.P., I.H.) and Radiology (M.M., P.P.), Democritus University of Thrace, School of Medicine, Alexandroupolis; and Second Department of Neurology (K.V.), University of Athens, School of Medicine, Attikon Hospital, Athens, Greece.
C. Bogiatzi, MD
From the Departments of Neurology (G.T., C.B., K.V., C.P., I.H.) and Radiology (M.M., P.P.), Democritus University of Thrace, School of Medicine, Alexandroupolis; and Second Department of Neurology (K.V.), University of Athens, School of Medicine, Attikon Hospital, Athens, Greece.
K. Vadikolias, MD
From the Departments of Neurology (G.T., C.B., K.V., C.P., I.H.) and Radiology (M.M., P.P.), Democritus University of Thrace, School of Medicine, Alexandroupolis; and Second Department of Neurology (K.V.), University of Athens, School of Medicine, Attikon Hospital, Athens, Greece.
K. Voumvourakis, MD
From the Departments of Neurology (G.T., C.B., K.V., C.P., I.H.) and Radiology (M.M., P.P.), Democritus University of Thrace, School of Medicine, Alexandroupolis; and Second Department of Neurology (K.V.), University of Athens, School of Medicine, Attikon Hospital, Athens, Greece.
P. Prassopoulos, MD
From the Departments of Neurology (G.T., C.B., K.V., C.P., I.H.) and Radiology (M.M., P.P.), Democritus University of Thrace, School of Medicine, Alexandroupolis; and Second Department of Neurology (K.V.), University of Athens, School of Medicine, Attikon Hospital, Athens, Greece.
C. Piperidou, MD
From the Departments of Neurology (G.T., C.B., K.V., C.P., I.H.) and Radiology (M.M., P.P.), Democritus University of Thrace, School of Medicine, Alexandroupolis; and Second Department of Neurology (K.V.), University of Athens, School of Medicine, Attikon Hospital, Athens, Greece.
I. Heliopoulos, MD
From the Departments of Neurology (G.T., C.B., K.V., C.P., I.H.) and Radiology (M.M., P.P.), Democritus University of Thrace, School of Medicine, Alexandroupolis; and Second Department of Neurology (K.V.), University of Athens, School of Medicine, Attikon Hospital, Athens, Greece.

Notes

Address correspondence and reprint requests to Dr. Georgios Tsivgoulis, Kapodistriou 3, Nea Chili, Alexandroupolis, Greece, 68100 [email protected]

Author Contributions

Dr. Tsivgoulis: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, study supervision. Dr. Mantatzis: drafting/revising the manuscript, contribution of vital reagents/tools/patients. Dr. Bogiatzi: analysis or interpretation of data, acquisition of data. Dr. Vadikolias: drafting/revising the manuscript, study concept or design. Dr. Voumvourakis: drafting/revising the manuscript, acquisition of data. Dr. Prassopoulos: drafting/revising the manuscript. Dr. Piperidou: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, acquisition of data, statistical analysis. Dr. Heliopoulos: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, acquisition of data, statistical analysis.

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  2. Percutaneous transluminal angioplasty for treatment of chronic cerebrospinal venous insufficiency (CCSVI) in people with multiple sclerosis, Cochrane Database of Systematic Reviews, 2019, 7, (2019).https://doi.org/10.1002/14651858.CD009903.pub3
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  3. Four-dimensional flow magnetic resonance imaging and ultrasound assessment of cerebrospinal venous flow in multiple sclerosis patients and controls, Journal of Cerebral Blood Flow & Metabolism, 37, 4, (1483-1493), (2016).https://doi.org/10.1177/0271678X16657345
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  5. Brain Hyperechogenicities are not Associated with Venous Insufficiency in Multiple Sclerosis: A Pilot Neurosonology Study, Journal of Neuroimaging, 26, 1, (150-155), (2015).https://doi.org/10.1111/jon.12248
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  6. Evaluation of Hemodynamic Properties of Cerebral Venous Drainage in Patients with Multiple Sclerosis: A Case-Control Study, Polish Journal of Radiology, 79, (323-327), (2014).https://doi.org/10.12659/PJR.890690
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  9. 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, Journal of Vascular and Interventional Radiology, 25, 11, (1785-1794.e17), (2014).https://doi.org/10.1016/j.jvir.2014.07.024
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