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Research Letters |

Cerebral and Cervical Venous Outflow Abnormalities Are Dynamic FREE

Ellen Marder, MD; Pramod Gupta, MD; Michael Ragland, ARDMS; Olaf Stüve, MD, PhD
[+] Author Affiliations

Author Affiliations: Neurology Section (Drs Marder and Stüve), Division of Radiology (Dr Gupta and Mr Ragland), Dallas VA Medical Center, VA North Texas Health Care System; Department of Neurology, University of Texas Southwestern Medical Center (Drs Marder and Stüve), Dallas, Texas; and Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Germany (Drs Gupta and Stüve).


Arch Neurol. 2012;69(10):1380-1381. doi:10.1001/archneurol.2012.1938.
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Published online

It was recently proposed that inflammation associated with multiple sclerosis (MS) is caused by chronic cerebrospinal venous insufficiency (CCSVI) owing to chronically elevated cerebral venous pressure that leads to disruption of the blood-brain barrier and entry of inflammatory mediators into the central nervous system.1 The results of the original studies1 that reported CCSVI in 100% of patients with MS (as demonstrated by specific venous ultrasonography abnormalities) have not consistently been replicated using sonography,26 magnetic resonance venography,7,8 or selective venography.4 Intracranial pressure measurements in patients with MS are no different from control subjects.9 In a 2011 study of US veterans with MS, we failed to show any association between cerebral venous ultrasonography abnormalities and MS.10 There was no significant difference between the number of ultrasonography abnormalities found in patients with MS compared with control subjects. In addition, none of the study subjects fulfilled criteria of CCSVI, defined as 2 or more ultrasonography abnormalities by proponents of the controversial CCSVI theory.1 Overall, currently there appears to be no scientific evidence to support CCSVI as an etiologic factor in MS. Nevertheless, both patients and practitioners continue to promote it and treat it as if it were.

One possible reason to explain conflicting results from different research studies is the potentially low reliability and reproducibility of venous ultrasonography assessments owing to the plasticity of these vessels. We hypothesized that repeat studies would show intrapersonal variations with regard to venous diameter and blood flow. Therefore, all 8 study subjects of our original investigation10 with any abnormal ultrasonography results within the cervical or cerebral veins—including patients with a clinically isolated syndrome, relapsing-remitting MS, secondary progressive MS, or primary progressive MS—and healthy control subjects were reevaluated to determine whether the original findings could be replicated. Both the ultrasonography technician and interpreter were blinded to the subjects' diagnosis. The ultrasonography technician did not have access to original study results, which were available to the ultrasonography interpreter. All repeat ultrasonography studies were normal (Table).

Table Graphic Jump LocationTable. Results of Repeat Ultrasonography in Individuals Positive for CCSVI Criteriaa

These observations indicate that cerebral and cervical venous abnormalities as detected by ultrasonography may not always be persistent structural abnormalities and may further weaken the association of singular abnormal imaging findings and MS.

Correspondence: Dr Stüve, Neurology Section, VA North Texas Health Care System, Dallas VA Medical Center, 4500 S Lancaster Rd, Dallas, TX 75216 (olaf.stuve@utsouthwestern.edu).

Author Contributions:Study concept and design: Marder, Gupta, and Stüve. Acquisition of data: Marder, Gupta, Ragland, and Stüve. Analysis and interpretation of data: Marder and Stüve. Drafting of the manuscript: Marder, Ragland, and Stüve. Critical revision of the manuscript for important intellectual content: Gupta and Stüve. Statistical analysis: Marder and Stüve. Administrative, technical, and material support: Marder, Gupta, Ragland, and Stüve. Study supervision: Gupta and Stüve.

Financial Disclosure: None reported.

Zamboni P, Galeotti R, Menegatti E,  et al.  Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis.  J Neurol Neurosurg Psychiatry. 2009;80(4):392-399
PubMed   |  Link to Article
Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ. No cerebrocervical venous congestion in patients with multiple sclerosis.  Ann Neurol. 2010;68(2):173-183
PubMed
Baracchini C, Perini P, Calabrese M, Causin F, Rinaldi F, Gallo P. No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset.  Ann Neurol. 2011;69(1):90-99
PubMed   |  Link to Article
Zivadinov R, Marr K, Butter G,  et al.  Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS.  Neurology. 2011;77(2):138-144
PubMed   |  Link to Article
Mayer CA, Pfeilschifter W, Lorenz MW,  et al.  The perfect crime? CCSVI not leaving a trace in MS.  J Neurol Neurosurg Psychiatry. 2011;82(4):436-440
PubMed   |  Link to Article
Tsvigoulis G, Mantatzis M, Bogiatzi C,  et al.  Extracranial venous hemodynamics in multiple sclerosis: a case-control study.  Neurology. 2011;77(13):1241-1245
PubMed   |  Link to Article
Hojnacki D, Zamboni P, Lopez-Soriano A,  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.  Int Angiol. 2010;29(2):127-139
PubMed
Wattjes MP, van Oosten BW, de Graaf WL,  et al.  No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study.  J Neurol Neurosurg Psychiatry. 2011;82(4):429-435
PubMed   |  Link to Article
Meyer-Schwickerath R, Haug C, Hacker A,  et al.  Intracranial venous pressure is normal in patients with multiple sclerosis.  Mult Scler. 2011;17(5):637-638
PubMed   |  Link to Article
Marder E, Gupta P, Greenberg B,  et al.  No cerebral or cervical venous insufficiency in US veterans with multiple sclerosis.  Arch Neurol. 2011;68(12):1521-1525
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable. Results of Repeat Ultrasonography in Individuals Positive for CCSVI Criteriaa

References

Zamboni P, Galeotti R, Menegatti E,  et al.  Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis.  J Neurol Neurosurg Psychiatry. 2009;80(4):392-399
PubMed   |  Link to Article
Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ. No cerebrocervical venous congestion in patients with multiple sclerosis.  Ann Neurol. 2010;68(2):173-183
PubMed
Baracchini C, Perini P, Calabrese M, Causin F, Rinaldi F, Gallo P. No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset.  Ann Neurol. 2011;69(1):90-99
PubMed   |  Link to Article
Zivadinov R, Marr K, Butter G,  et al.  Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS.  Neurology. 2011;77(2):138-144
PubMed   |  Link to Article
Mayer CA, Pfeilschifter W, Lorenz MW,  et al.  The perfect crime? CCSVI not leaving a trace in MS.  J Neurol Neurosurg Psychiatry. 2011;82(4):436-440
PubMed   |  Link to Article
Tsvigoulis G, Mantatzis M, Bogiatzi C,  et al.  Extracranial venous hemodynamics in multiple sclerosis: a case-control study.  Neurology. 2011;77(13):1241-1245
PubMed   |  Link to Article
Hojnacki D, Zamboni P, Lopez-Soriano A,  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.  Int Angiol. 2010;29(2):127-139
PubMed
Wattjes MP, van Oosten BW, de Graaf WL,  et al.  No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study.  J Neurol Neurosurg Psychiatry. 2011;82(4):429-435
PubMed   |  Link to Article
Meyer-Schwickerath R, Haug C, Hacker A,  et al.  Intracranial venous pressure is normal in patients with multiple sclerosis.  Mult Scler. 2011;17(5):637-638
PubMed   |  Link to Article
Marder E, Gupta P, Greenberg B,  et al.  No cerebral or cervical venous insufficiency in US veterans with multiple sclerosis.  Arch Neurol. 2011;68(12):1521-1525
PubMed   |  Link to Article

Correspondence

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