BlueCross and BlueShield of Montana Medical Policy/Codes
Diagnosis and Treatment of Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis
Chapter: Medicine: Treatments
Current Effective Date: August 27, 2013
Original Effective Date: August 27, 2013
Publish Date: May 27, 2013
Description

Questions are being asked about the possible role of chronic cerebrospinal venous insufficiency (CCSVI) in the pathogenesis of multiple sclerosis (MS), and correction of CCSVI is being evaluated as a possible treatment for MS.  Correction of CCSVI may be referred to as the “Liberation Procedure.”

Multiple sclerosis (MS) is generally considered a chronic inflammatory demyelinating disease of the central nervous system (brain, spinal cord, optic nerve) felt to be triggered by an autoimmune response to myelin.

However, in part due to the periventricular predilection of the lesions of multiple sclerosis, vascular etiologies (CCSVI) have also been considered.  An animal model for MS was developed by injecting obstructing agents into the venous sinuses.  This etiology and treatment approach for MS had not been actively pursued for many years; recent reports by a European researcher have renewed interest in this topic.

The core foundation of this vascular theory is that there is abnormal venous drainage from the brain due to outflow obstruction in the draining jugular vein and/or azygos veins.  This abnormal venous drainage, which is characterized by special ultrasound criteria is said to cause intracerebral flow disturbance or outflow problems that lead to periventricular deposits.  In the CCSVI theory, these deposits have a similarity to the iron deposits seen around the veins in the legs in patients with chronic deep vein thrombosis.  Those studying this theory have promoted balloon dilatation, with or without stenting, to treat the outflow problems, thereby curing CCSVI and by the same token alleviating MS complaints.

Policy

Investigational

Blue Cross and Blue Shield of Montana (BCBSMT) considers the identification and subsequent treatment of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis experimental, investigational and unproven.

Federal Mandate

Federal mandate prohibits denial of any drug, device, or biological product fully approved by the FDA as investigational for the Federal Employee Program (FEP). In these instances coverage of these FDA-approved technologies are reviewed on the basis of medical necessity alone. Call the BCBSMT FEP Customer Service Department at 1-800-634-3569 for benefit information.

Rationale for Benefit Administration

This medical policy was developed through consideration of peer reviewed medical literature, FDA approval status, accepted standards of medical practice in Montana, Technology Evaluation Center evaluations, and the concept of medical necessity. BCBSMT reserves the right to make exceptions to policy that benefit the member when advances in technology or new medical information become available.

The purpose of medical policy is to guide coverage decisions and is not intended to influence treatment decisions. Providers are expected to make treatment decisions based on their medical judgment. BCBSMT recognizes the rapidly changing nature of technological development and welcomes provider feedback on all medical policies.

When using this policy to determine whether a service, supply or device will be covered, please note that member contract language will take precedence over medical policy when there is a conflict.

Rationale

Recent interest in the role of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) followed reports from a European vascular surgeon, Zamboni.  He used ultrasound and catheter-based venography to describe venous insufficiency in the internal jugular veins, vertebral veins, and deep cerebral veins of MS patients and described the finding as CCSVI.  Using five ultrasound criteria, Zamboni and colleagues reported both sensitivity and specificity of 100% in separating MS patients from controls; clinical improvement was reported in MS patients in a nonblinded trial with CCSVI following catheter-based venoplasty.  In this study, 65 consecutive patients with CCSVI, subdivided by MS clinical course into 35 with relapsing remitting (RR), 20 with secondary progressive (SP), and 10 with primary progressive (PP) MS, underwent percutaneous transluminal angioplasty (PTA).  Mean follow-up was 18 months.  In this study, outpatient endovascular treatment of CCSVI was noted to be feasible, with a minor complication rate.  Postoperative venous pressure was significantly lower.  The risk of restenosis was higher in the internal jugular vein.  The endovascular treatment was noted to improve MS clinical outcome measures, especially in the RR group: the rate of relapse-free patients changed from 27% to 50% postoperatively (p<0.001).  The Multiple Sclerosis Functional Composite at one year improved significantly in RR patients (p<0.008) but not in PP or SP.  Physical quality of life (QOL) improved significantly in RR (p<0.01) and in PP patients (p<0.03), with a positive trend in SP (p<0.08).  The authors concluded that PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR disease, the clinical course was positively influenced by treatment.  The authors also indicated these results were from a pilot study and that a subsequent randomized controlled study is warranted.

In a study by other investigators, Doepp and colleagues evaluated 56 patients with MS and 20 controls and found that none met the criteria for CCSVI using ultrasound.  In a small study from Germany, Mayer and colleagues evaluated 20 MS patients (mean age 42.2 yrs; median Extended Disability Status Scale 3.0, range 0-6.5) and 20 healthy controls.  Extra- and intracranial venous flow direction was assessed by color-coded duplex sonography, and extracranial venous cross-sectional area (VCSA) of the internal jugular and vertebral veins (IJV/VV) was measured in B-mode to assess the five previously proposed CCSVI criteria.  IJV-VCSA 0.3 cm2 or less indicated 'stenosis,' and IJV-VCSA decrease from supine to upright position 'reverted postural control.'  The sonographer, data analyzer, and statistician were blinded to the patient and/or control status of the participants.  In this study, no participant showed retrograde flow of cervical or intracranial veins.  IJV-VCSA of 0.3 cm2 or less was found in 13 MS patients and 16 controls (p=0.48).  A decrease in IJV-VCSA from supine to upright position was observed in all participants, but this denotes a physiological finding.  No MS patient and one control had undetectable IJV flow despite deep inspiration (p=0.49).  Only one healthy control and no MS patients fulfilled at least two criteria for CCSVI.  The authors of this triple-blinded extra- and transcranial duplex sonographic assessment of cervical and cerebral veins concluded their study does not provide supportive evidence for the presence of CCSVI in MS patients.

In a study from the U.S., Zivadinov and colleagues used ultrasound to evaluate CCSVI in 499 subjects.  A subject was considered CCSVI-positive if two or more venous hemodynamic (VH) criteria were fulfilled.  The authors’ studies of transcranial and extracranial echo-colored Doppler (ECD) were carried out in 499 enrolled subjects: 289 with MS, 163 health controls (HC), 26 other neurologic disease (OND), 21 clinically isolated syndrome (CIS).  Prevalence rates for CCSVI were calculated in three ways: first, using only the subjects for whom diagnosis was certain (i.e., borderline subjects were excluded); secondly, including the borderline subjects in the "no CCSVI" group; and finally, taking into account subjects who presented any of the VH criteria.  CCSVI prevalence with borderline cases included in the "no CCSVI" group was 56.1% in MS, 42.3% in OND, 38.1% in CIS, and 22.7% in HC (p<0.001).  The CCSVI prevalence figures were 62.5% for MS, 45.8% for OND, 42.1% for CIS, and 25.5% for HC when borderline cases were excluded (p<0.001).  The prevalence of one or more positive VH criteria was the highest in MS (81.3%), followed by CIS (76.2%), OND (65.4%), and HC (55.2%) (p<0.001).  CCSVI prevalence was higher in patients with progressive than in nonprogressive MS (p=0.004).  The authors concluded that their findings were consistent with an increased prevalence of CCSVI in MS but with modest sensitivity and specificity.  They also noted that their findings point against CCSVI having a primary causative role in the development of MS.

In an editorial on CCSVI, Fox and Rae-Grant also note that CCSVI does not explain the genetic, ethnic, or geographic occurrence of MS but also noted that CCSVI has not been studied in relation to these factors.

Given the minimal, and conflicting data available to date on CCSVI in MS, a number of studies are underway.  These research studies are evaluating not only the diagnostic approach to CCSVI, but also evaluating potential treatment of CCSVI in randomized, blinded comparative studies.  The editorial above (Fox et al.) indicated that with the uncertainties of the relationship between CCSVI and MS and the potential risks of intervention, CCSVI interventions, such as balloon venoplasty, should be restricted to blinded controlled trials that have carefully chosen clinical endpoints and appropriate safety oversight.

Summary

Since the relationship between CCSVI and MS is not certain and because the impact of treating CCSVI on outcomes of MS is not known, the evaluation of MS patients for CCSVI and the treatment of CCSVI in patients with MS is experimental, investigational and unproven.

Practice Guidelines and Position Statements

The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) commentary on the treatment of chronic cerebrospinal venous insufficiency notes that “Thus far, no trial data are available, and there is currently no randomized controlled trial (RCT) in progress.  Therefore, the basis for this new treatment rests on anecdotal evidence and successful testimonies by patients on the Internet.  CIRSE believes that this is not a sound basis on which to offer a new treatment, which could have possible procedure-related complications, to an often desperate patient population.”

Coding

Disclaimer for coding information on Medical Policies           

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy.  They may not be all-inclusive.          

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers.  Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

ICD-9 Codes

00.01, 00.40, 00.41, 00.42, 00.43, 39.50, 340, 437.1, 459.81

ICD-10 Codes

G35, I67.8, I87.2, I87.9

Procedural Codes: 35460, 35476, 75978
References
  1. Zamboni P, Galeotti R, Menegatti E et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009; 80(4):392-9.
  2. Zamboni P, Galeotti R, Menegatti E et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg 2009; 50(6):1348-58.
  3. Doepp F, Paul F, Valdueza JM et al. No cerebrospinal venous congestion in patients with multiple sclerosis. Ann Neurol 2010; 68(2):155-9.
  4. 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):436-40.
  5. Zivadinov R, Marr K, Cutter G et al. Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology 2011 Apr 13 [Epub ahead of print].
  6. Fox RJ, Rae-Grant A. Chronic cerebrospinal venous insufficiency: have we found the cause and cure of MS? Neurology 2011 Apr 13 [Epub ahead of print].
  7. Reekers JA, Lee MJ, Belli AM et al. Cardiovascular and Interventional Radiological Society of Europe commentary on the treatment of chronic cerebrospinal venous insufficiency. Cardiovasc Intervent Radiol 2011; 34(1):1-2.
  8. Diagnosis and Treatment of Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2011 June) Surgery 8.01.56.
History
May 2013  New 2013 BCBSMT medical policy.  The identification and subsequent treatment of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis is considered experimental, investigational and unproven. 
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Diagnosis and Treatment of Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis