Chronic cerebrospinal venous insufficiency and the doubtful promise of an endovascular treatment for multiple sclerosis Howard Dorne, 1 Osama O Zaidat, 2 David Fiorella, 3 Joshua Hirsch, 4 Charles Prestigiacomo, 5 Felipe Albuquerque, 6 Robert W Tarr 7 INTRODUCTION Recently, a radically different concept regarding the pathogenesis of multiple sclerosis (MS) has been proposed. Termed chronic cerebrospinal venous insufficiency (CCSVI), it suggests that macro occlusive abnormalities of the extracranial venous drainage pathways of the brain and spinal cord can cause or contribute to MS. As a consequence of this theory, it has been suggested that angioplasty and possibly stenting of the internal jugular and/or azygos veins can improve the signs and symptoms of MS. These interventions have been performed sporadically across the globe in an open label fashion and never in the context of a well designed, controlled, randomized and blinded clin- ical trial. Despite this, the procedure has been labeled by some as ‘liberation proce- dure’ and caused a firestorm of interest in the medical and MS communities, both for and against its utilization. The argu- ments on all sides are passionate, ranging from the belief that venous intervention is a miracle cure that must not be withheld from patients, to the feeling that the procedure is ineffective and unwarranted at best and dangerous at worst. The various camps commonly protest that those with differing views are not acting in the best interest of their patients. As neurointerventionalists interested in interventional treatment of neurological disorders, it is time to take a thorough and objective look at CCSVI. This commen- tary will examine the origin of the CCSVI theory and discuss the data supporting and refuting its existence. An attempt will be made to critically analyze the available data and provide constructive recommen- dations about whether or not endovas- cular therapy represents a reasonable option at this point in time for patients with MS. BRIEF REVIEW OF MULTIPLE SCLEROSIS MS is a fearful and unpredictable disease that brings an enormous physical, emotional and financial burden on patients, family, relatives, friends and society in general. It is the most common cause of physical disability, with esti- mated 250 000e350 000 individual diag- nosed with MS in the USA. The peak age at onset is 20e40 years. It affects women more so than men and is more common among Caucasians. MS can present with just about any neurological symptom in any part of the nervous system, sensory, motor, cranial nerves, visual, autonomic, coordination and myelopathic on different occasions with cumulative disability. 1 Diagnosis is based on clinical and imaging criteria (McDonald criteria) to establish the dissemination in place (different CNS sites) and time (at least 30 days between clinical relapses and 90 days for new MRI lesion without clinical relapse). The clin- ical course of MS is most commonly relapsing remitting, with return to base- line after each relapse, followed by secondary progressive starting as relapsing remitting, then primary progressive MS. 1 The most prevalent hypothesis regarding the pathophysiological basis for MS is that it is an autoimmune inflammatory disease triggered by environmental factors (toxic and infectious triggers) with genetic predisposition leading to myelin and axonal destruction in the brain and spinal cord by the immune system. 1 To date, MS management has been limited to the indefinite administration of ‘disease modifying’ medications and immune modulating agents which may reduce the number and severity of relapses. 1 These agents are not only costly but are associ- ated with a wide spectrum of side effects ranging from mild to severe. THE CCSVI THEORY AND SUPPORTIVE DATA In 2006, Zamboni, an Italian vascular surgeon, in an article titled ‘ The big idea: iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis’ suggested that there were simi- larities between chronic venous disease of the extremities and MS. 2 He raised the possibility that venous reflux or obstruc- tion in cerebral and spinal veins might have a relationship to MS. 2 Several years later, Zamboni et al reported on blinded transcranial and extracranial color Doppler sonographic findings in patients with MS and matched healthy controls and those with other neurological disorders. 3 They focused on five findings: (1) reflux in the internal jugular vein (IJV) or vertebral veins >0.88 s; (2) reflux propagated in at least one out of the three deep cerebral veins >0.55 s; (3) high resolution B mode evidence of proximal IJV stenosis; (4) flow not Doppler detectable in the IJV or vertebral veins despite deep inspirations; and (5) negative difference of the cross sectional area of the IJV comparing the value obtained in the supine versus the sitting position. The authors concluded that detection of two or more of these findings constitutes the diagnosis of CCSVI. They found CCSVI in all MS patients and in none of the controls. The sensitivity, specificity, positive predictive value and negative predictive value of the test were all 100%. They concluded that there was CCSVI in MS patients. 3 In a second paper, Zamboni et al published that catheter venography in patients who met CCSVI Doppler criteria showed stenosis in the azygos vein 86% of the time and one or both IJV were affected in 91%. In this study, the venographer was not blinded to the patients’ diagnosis. 4 The study proposed four venographic patterns: (A) large IJV with one IJV or proximal azygous vein stenosis; (B) both 1 St Joseph Hospital Health System, Orange, California, USA; 2 Department of Neurology, Neurosurgery and Radiology, Froedtert Hospital/Medical College of Wisconsin, Milwaukee, Wisconsin, USA; 3 Stony Brook University Medical Center, Stony Brook, New York, USA; 4 Massachusetts General Hospital, Boston, Massachusetts, USA; 5 New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA; 6 Barrow Neurological Institute, Phoenix, Arizona, USA; 7 University Hospitals Case Medical Center, Cleveland, Ohio, USA Correspondence to Dr R W Tarr, University Hospitals Case Medical Center, Cleveland, OH 44102, USA; robert.tarr@uhhospitals.org J NeuroIntervent Surg December 2010 Vol 2 No 4 309 Editorial commentary on September 25, 2021 by guest. Protected by copyright. http://jnis.bmj.com/ J NeuroIntervent Surg: first published as 10.1136/jnis.2010.003947 on 23 October 2010. Downloaded from on September 25, 2021 by guest. Protected by copyright. http://jnis.bmj.com/ J NeuroIntervent Surg: first published as 10.1136/jnis.2010.003947 on 23 October 2010. Downloaded from on September 25, 2021 by guest. Protected by copyright. http://jnis.bmj.com/ J NeuroIntervent Surg: first published as 10.1136/jnis.2010.003947 on 23 October 2010. Downloaded from