CCSVI October

Macgowan CK, Chan KY, Laughlin S, Marrie RA, Banwell B. Cerebral arterial and venous blood flow in adolescent multiple sclerosis patients and age-matched controls using phase contrast MRI. J Magn Reson Imaging. 2013 Sep 30. doi: 10.1002/jmri.24388. [Epub ahead of print]

PURPOSE:Altered cerebrovascular blood flow has been proposed as a mechanism for multiple sclerosis (MS). The primary objective of this study was to measure arterial and venous blood flow in adolescent MS patients and healthy controls (HC), in whom confounding factors such as age and lifestyle are less influential.
MATERIALS AND METHODS:Phase-contrast magnetic resonance imaging (MRI) was used to measure flow in 26 MS patients and 26 controls aged 17.7 ± 1.8 and 17.8 ± 2.1 years, respectively. Flow was measured in the left and right internal carotid arteries (ICA), vertebral arteries (VA), internal jugular veins (IJV), and epidural veins (EV). Eighteen MS patients returned for a second MRI examination after 6 months. In all participants, ultrasound criteria for chronic cerebrospinal venous insufficiency (CCSVI) were also evaluated.
RESULTS:Flows (mL/min) in the MS group versus HC group were as follows: right ICA = 262 ± 57 vs. 263 ± 32, left ICA = 260 ± 67 vs. 270 ± 36, right VA = 96 ± 50 vs. 103 ± 30, left VA = 104 ± 37 vs. 118 ± 41, right IJV = 342 ± 180 vs. 345 ± 195, left IJV = 190 ± 131 vs. 250 ± 148, right EV = 33 ± 29 vs. 48 ± 43, and left EV = 36 ± 35 vs. 44 ± 28 (P > 0.17 for all comparisons). In MS participants, a non-significant trend to lower flow in the left IJV was observed, and the flow pulsatility index in the epidural veins was higher. Two MS participants met ultrasound criteria for CCSVI, but no significant difference in flow was detected.
CONCLUSION: No population difference in flow rate was detected in adolescent MS participants relative to age-matched controls.

If venous abnormalities were causal in MS, then they would be seen in young MSers, this adds further weight to the fact that they are age related events and therefore unlikely to be causal

Traboulsee AL, Knox KB, Machan L, Zhao Y, Yee I, Rauscher A, Klass D, Szkup P, Otani R, Kopriva D, Lala S, Li DK, Sadovnick D.Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study. Lancet. 2013 Oct . doi:pii: S0140-6736(13)61747-X. 

Chronic cerebrospinal venous insufficiency has been proposed as a unique combination of extracranial venous blockages and haemodynamic flow abnormalities that occurs only in patients with multiple sclerosis and not in healthy people. Initial reports indicated that all patients with multiple sclerosis had chronic cerebrospinal venous insufficiency. We aimed to establish the prevalence of venous narrowing in people with multiple sclerosis, unaffected full siblings, and unrelated healthy volunteers.

METHODS: We did an assessor-blinded, case-control, multicentre study of people with multiple sclerosis, unaffected siblings, and unrelated healthy volunteers. We enrolled the study participants between January, 2011 and March, 2012, and they comprised 177 adults: 79 with multiple sclerosis, 55 siblings, and 43 unrelated controls, from three centres in Canada. We assessed narrowing of the internal jugular and azygous veins with catheter venography and ultrasound criteria for chronic cerebrospinal venous insufficiency proposed by Zamboni and colleagues. Catheter venography data were available for 149 participants and ultrasound data for 171 participants.
FINDINGS: Catheter venography criteria for chronic cerebrospinal venous insufficiency were positive for one of 65 (2%) people with multiple sclerosis, one of 46 (2%) siblings, and one of 32 (3%) unrelated controls (p=1·0 for all comparisons). Greater than 50% narrowing of any major vein was present in 48 of 65 (74%) people with multiple sclerosis, 31 of 47 (66%) siblings (p=0·41 for comparison with patients with multiple sclerosis), and 26 of 37 (70%) unrelated controls (p=0·82). The ultrasound criteria for chronic cerebrospinal venous insufficiency were fulfilled in 35 of 79 (44%) participants with multiple sclerosis, 17 of 54 (31%) siblings (p=0·15 for comparison with patients with multiple sclerosis) and 17 of 38 (45%) unrelated controls (p=0·98). The sensitivity of the ultrasound criteria for detection of greater than 50% narrowing on catheter venography was 0·406 (95% CI 0·311-0·508), and specificity was 0·643 (0·480-0·780).
INTERPRETATION: This study shows that chronic cerebrospinal venous insufficiency occurs rarely in both patients with multiple sclerosis and in healthy people. Extracranial venous narrowing of greater than 50% is a frequent finding in patients with multiple sclerosis, unaffected siblings, and unrelated controls. The ultrasound criteria are neither sensitive nor specific for narrowing on catheter venography. The significance of venous narrowing to multiple sclerosis symptomatology remains unknown.

Some say this should be the final curtain for CCSVI. How much more evidence is needed? This backs up the Italian MS Society study

Zivadinov R, Karmon Y, Dolic K, Hagemeier J, Marr K, Valnarov V, Kennedy CL, Hojnacki D, Carl EM, Hopkins LN, Levy EI, Weinstock-Guttman B, Siddiqui AH.Multimodal noninvasive and invasive imaging of extracranial venous abnormalities indicative of CCSVI: results of the PREMiSe pilot study. 
BMC Neurol. 2013 Oct 20;13(1):151. [Epub ahead of print]

BACKGROUND: There is no established noninvasive or invasive diagnostic imaging modality at present that can serve as a ‘gold standard’ or “benchmark” for the detection of the venous anomalies, indicative of chronic cerebrospinal venous insufficiency (CCSVI). We investigated the sensitivity and specificity of 2 invasive vs. 2 non-invasive imaging techniques for the detection of extracranial venous anomalies in the internal jugular veins (IJVs) and azygos vein/vertebral veins (VVs) in patients with multiple sclerosis (MS).

METHODS: The data for this multimodal imaging comparison pilot study was collected in phase 2 of the “Prospective Randomized Endovascular therapy in Multiple Sclerosis” (PREMiSe) study using standardized imaging techniques. Thirty MS subjects were screened initially with Doppler sonography (DS), out of which 10 did not fulfill non-invasive screening procedure requirements on DS that consisted of >=2 venous haemodynamic extracranial criteria. Accordingly, 20 MS patients with relapsing MS were enrolled into the multimodal diagnostic imaging study. For magnetic resonance venography (MRV), IJVs abnormal findings were considered absent or pinpoint flow, whereas abnormal VVs flow was classified as absent. Abnormalities of the VVs were determined only using non-invasive testing. Catheter venography (CV) was considered abnormal when >=50% lumen restriction was detected, while intravascular ultrasound (IVUS) was considered abnormal when >=50% restriction of the lumen or intra-luminal defects or reduced pulsatility was found. Non-invasive and invasive imaging modality comparisons between left, right and total IJVs and between the VVs and azygos vein were performed. Because there is no reliable way of non-invasively assessing the azygos vein, the VVs abnormalities detected by the non-invasive testing were compared to the azygos abnormalities detected by the invasive testing. All image modalities were analyzed in a blinded manner by more than one viewer, upon which consensus was reached. The sensitivity and specificity were calculated using contingency tables denoting the presence or absence of vein-specific abnormality findings between all imaging modalities used individually as the benchmark.
RESULTS: The sensitivity of CV + IVUS was 68.4% for the right and 90% for the left IJV and 85.7% for the azygos vein/VVs, compared to venous anomalies detected on DS. Compared to the venous anomalies detected on MRV, the sensitivity of CV + IVUS was 71.4% in right and 100% in left IJVs and 100% in the azygos vein/VVs; however, the specificity was 38.5%, 38.9% and 11.8%, respectively. The sensitivity between the two invasive imaging techniques, used as benchmarks, ranged from 72.7% for the right IJV to 90% for the azygos vein but the IVUS showed a higher rate of venous anomalies than the CV. There was excellent correspondence between identifying collateral veins on MRV and CV.
CONCLUSIONS: Non-invasive DS screening for the detection of venous anomalies indicative of CCSVI may be a reliable approach for identifying patients eligible for further multimodal invasive imaging testing of the IJVs. However, the non-invasive screening methods were inadequate to depict the total amount of azygos vein/VVs anomalies identified with invasive testing. This pilot study, with limited sample size, shows that both a non-invasive and invasive multimodal imaging diagnostic approach should be recommended to depict a range of extracranial venous anomalies indicative of CCSVI. However, lack of invasive testing on the study subjects whose results were negative on the DS screening and of healthy controls, limits further generalizibility of our findings. In addition, the findings from the 2 invasive techniques confirmed the existence of severe extracranial venous anomalies that significantly impaired normal blood outflow from the brain in this group of MS patients.

So 50% of MSers tested did not have doppler ultrasound evidence of CCSVI but more invasive techniques found venous abnormalities which low specificity.

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  • How much money has been spent to expose this ludicrous theory? Unfortunately there will always be a subset of the ms population that is easily manipulated.

    • Keep in mind that this subset exists in just about every chronically ill patient population (cancer, ALS, etc.). And yes, it's truly tragic. The best action a chronically ill patient population can do is minimize the influence of the subset so that they do not have a negative impact on research.

      Does anyone know of the actual extent of the damage the CCSVIers have caused to MS research and the goal of finding a cure?

    • I think it is pretty clear what the Zamboni Cult has done to MSers and the patient doctor relation ship. It is no secret that they have promoted the notion that there is a conspiracy between "Big Pharma" and neurologists to the point that some patient have a distrust of their doctors.

      Unfortunately, as we know time is brain and the longer you wait to get treatment the more damage is being done, not to mention the fact that people who start treatment late have a poor outcome.

      MS is a neurdegenerative disease and you need to stop damage before it transitions to this state. This even hold true for primary progressive MSers:

      People who have transitioned to a progressive state may promote this notion since there really is nothing that can be done for them, so they echo the sentiment that none of the therapies work. But in reality, it is going to be very hard to repair the damage done once you reach a progressive state. This would be akin to saying that science has not made any advances in lung cancer after one smokes for their entire life. But in fact, lung cancer can be dramatically reduced if you don't smoke in the first place.

      So, the Zamboni Cult will continue to believe what they want even though the evidence shows the opposite. But hopefully MSers who are newly diagnosed do not fall prey to their propoganda.

    • Now the comments are being moderated,we have not turned the comments off and if insuting will not see the light of day and so we will not be tempted to respond.

  • Dr. Robert Fox of the Cleveland Clinic had very useful data come out of his small cadaver study: venous narrowing was the same in MSers vs nonMSers but intraluminal abnormalities were concentrated in the MSer group. Studies looking just at venous wall narrowing would be expected to find no difference, as Dr. Fox did. It would be nice to have a large scale cadaver study. There is an offshoot theory looking at CCSVI not as an insufficiency but as a hypertension. Intraluminal abnormalities are abrupt blockages that are more likely to transmit pressure upstream than gradual narrowings of the venous wall which absorb that pressure. There is more to be explored.

    • I can see your point, Maren. There may be an answer in there somewhere. But who should fund that exploration? How likely is it to be fruitful, compared to other theories out there? How should we prioritize? I care about this not only because I have MS, but because my 90-year-old father sends money to the National MS Society on my behalf. Because my sister-in-law raises money for the cause in bike races wearing my name. Because my sister excitedly sends me articles inevitably titled "New Hope for Multiple Sclerosis Sufferers" featuring this year's version of bee sting therapy.

      I want a cure for MS. But I also want to know the people who love me aren't being scammed just because they love me. I want to know their efforts and intentions are invested where they matter.

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