Chronic cerebrospinal venous insufficiency as a cause of multiple sclerosis: controversy and reality.

Cleveland Clinic, Mellen Center for Multiple Sclerosis Treatment and Research, 9500 Euclid Avenue, U10, Cleveland, OH, 44195, USA.
Current Treatment Options in Cardiovascular Medicine 02/2012; 14(2):203-14. DOI: 10.1007/s11936-012-0168-7
Source: PubMed

ABSTRACT OPINION STATEMENT: Multiple sclerosis (MS) is a relapsing and progressive disorder of the central nervous system. It is characterized most commonly by episodes of clinical worsening, followed by clinical improvement. Pathologically, MS is associated with focal areas of myelin destruction, inflammation, and axonal transection ("demyelinating plaques") in the brain and spinal cord. Traditionally, MS has been considered an autoimmune disorder, with the primary pathophysiology arising from an errant immune system. Recent work has raised the possibility that MS is not caused primarily by an immune abnormality but may instead arise from venous anomalies affecting the jugular and/or azygos venous systems. This condition has been called chronic cerebrospinal venous insufficiency (CCSVI). It has been proposed that CCSVI may be pathogenic in MS, causing venous back pressure and iron deposition, with a secondary immune response. Some investigators have proceeded to unblinded nonrandomized angioplasty and stenting procedures in patients with CCSVI, with anecdotal reports of symptom improvement. Because of conflicting data on the presence of CCSVI and the absence of controlled trials of CCSVI intervention, the current standard of clinical care is neither to evaluate multiple sclerosis (MS) patients for CCSVI anomalies, nor to intervene with procedures to alter such anomalies. There is intense interest and ongoing work to evaluate the presence of venous anomalies in MS patients as well as in normal controls and patients with other neurologic conditions; to characterize such anomalies, if present; and to further understand whether the concept of a "backpressure" pathology is borne out by the evidence. If CCSVI is indeed a pathogenic mechanism for some subset of the MS population, this would dramatically change the focus of attention for therapeutic endeavors and monitoring for this population and would bring MS therapeutics firmly into the area of vascular intervention. On the other hand, the history of MS research contains many novel and potentially paradigm-shifting ideas that were later disproved by other investigators.

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    ABSTRACT: The extra-cranial venous system is complex and not well studied in comparison to the peripheral venous system. A newly proposed vascular condition, named chronic cerebrospinal venous insufficiency (CCSVI), described initially in patients with multiple sclerosis (MS) has triggered intense interest in better understanding of the role of extra-cranial venous anomalies and developmental variants. So far, there is no established diagnostic imaging modality, non-invasive or invasive, that can serve as the "gold standard" for detection of these venous anomalies. However, consensus guidelines and standardized imaging protocols are emerging. Most likely, a multimodal imaging approach will ultimately be the most comprehensive means for screening, diagnostic and monitoring purposes. Further research is needed to determine the spectrum of extra-cranial venous pathology and to compare the imaging findings with pathological examinations. The ability to define and reliably detect noninvasively these anomalies is an essential step toward establishing their incidence and prevalence. The role for these anomalies in causing significant hemodynamic consequences for the intra-cranial venous drainage in MS patients and other neurologic disorders, and in aging, remains unproven.
    BMC Medicine 06/2013; 11(1):155. DOI:10.1186/1741-7015-11-155 · 7.28 Impact Factor
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    ABSTRACT: To analyze the presence of chronic cerebrospinal venous insufficiency parameter and vascular abnormalities, in the internal jugular veins (IJVs) and/or vertebral veins in sitting and supine posture, in patients with Meniere's disease compared to healthy general population. A prospective study on 32 patients affected by definite Ménière was performed from February 2012 to January 2013. All subjects underwent an echo-color Doppler examination of the cerebrospinal venous flow. 21 of the 32 Menieric patients showed a statistically significant reflux in the intracranial veins versus healthy (65.6 vs 25%; P < 0.001). A high prevalence of IJVs stenosis with hemodynamic changes (increased velocity or absence of flow) was observed (66.7 vs 33.3%; P < 0.05). The other parameters considered did not show statistically significant differences among the two groups. The results obtained showed a vascular pattern of cerebrospinal venous system present in patients affected by definite Meniere. This vascular impairment significantly affects the vascular areas more directly involved in the venous drainage of the inner ear. Thus venous stasis may be considered a further pathogenetic mechanism for development of Meniere's disease.
    Archives of Oto-Rhino-Laryngology 12/2013; 272(1). DOI:10.1007/s00405-013-2841-1 · 1.61 Impact Factor
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    ABSTRACT: OBJECTIVES: Chronic cerebrospinal venous insufficiency (CCSVI) is a malformative condition characterized by several anomalies of the azygos and/or internal jugular veins (IJVs). Recommended diagnosis of CCSVI is performed with colour-Doppler (CD) sonography. Though catheter venography (CV) is considered as the gold standard for determining vascular anatomy, its uniplanar point of view does not allow an overall evaluation of endoluminal structures. This limit could be addressed by intravascular ultrasound (IVUS). The aim of this report is to evaluate, in patients with multiple sclerosis (MS), the accuracy of CD sonography and CV versus IVUS in estimating the diameter and the cross-sectional area (CSA) of the IJVs and in detecting jugular endoluminal malformations (JEM). METHOD: Forty-five MS patients with CCSVI, diagnosed by CD sonography, were submitted to CV during IJVs angioplasty. Twenty-five subjects were also examined with IVUS. The IJVs maximum diameter (MAXD) and CSA were estimated. CD and CV data were compared with IVUS data with the Bland-Altman method. RESULTS: The mean difference in IJV MAXD recorded by CD and IVUS was -0.5 mm. The mean difference in IJV MAXD recorded by CV and IVUS was 3.36 mm. The mean difference in IJV CSA recorded by CD and IVUS was -11.2 mm(2). JEM recorded by IVUS were detected by CD sonography and CV with 88% and 32% accuracy, respectively. CONCLUSIONS: CV was significantly inferior to CD sonography and IVUS in detecting JEM. Differences between IVUS and CD sonography in detecting JEM and in quantifying jugular diameters were not significant. The IJV CSA was underestimated by CD sonography compared with IVUS. CD sonography was proven to be important in the anatomical characterization of CCSVI, providing useful information for correct intravascular treatment.
    Phlebology 11/2012; DOI:10.1258/phleb.2012.012079 · 1.92 Impact Factor