Saturday, 27 July 2013

CCSVI July..Its CCSVI super saturday...

#MSResearch #MSblog CCVSI is not causal in MS

Dolic K, Siddiqui AH, Karmon Y, Marr K, Zivadinov R. The role of noninvasive and invasive diagnostic imaging techniques for detection of extra-cranial venous system anomalies and developmental variants. BMC Med. 2013 Jun 27;11(1):155. [Epub ahead of print]

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 haemodynamic consequences for the intra-cranial venous drainage in MS patients and other neurologic disorders, and in aging, remains unproven.

Was this paper written before or after the clinical study done by this group? The use of "further research is needed" should be banned from abstracts or maybe people need to do the further work before publishing as it says this work does not say much concrete.

Luo J, Yablonskiy DA, Hildebolt CF, Lancia S, Cross AH. Gradient echo magnetic resonance imaging correlates with clinical measures and allows visualization of veins within multiple sclerosis lesions.

Mult Scler. 2013 Jul 8. [Epub ahead of print]

BACKGROUND:Conventional magnetic resonance imaging (MRI) methods do not quantify the severity of multiple sclerosis (MS) white matter lesions or measure pathology within normal-appearing white matter (NAWM).

OBJECTIVE: Gradient Echo Plural Contrast Imaging (GEPCI), a fast MRI technique producing inherently co-registered images for qualitative and quantitative assessment of MS, was used to 1) correlate with disability; 2) distinguish clinical MS subtypes; 3) determine prevalence of veins co-localized within lesions in WM.

METHODS:Thirty subjects representing relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS) subtypes were scanned with clinical and GEPCI protocols. Standard measures of physical disability and cognition were correlated with magnetic resonance metrics. Lesions with central veins were counted for RRMS subjects.

RESULTS:Tissue damage load (TDL-GEPCI) and lesion load (LL-GEPCI) derived with GEPCI correlated better with MS functional composite (MSFC) measures and most other neurologic measures than lesion load derived with FLAIR (LL-FLAIR). GEPCI correctly classified clinical subtypes in 70% subjects. A central vein could be identified in 76% of WM lesions in RRMS subjects on GEPCI T2*-SWI images.

CONCLUSION: GEPCI lesion metrics correlated better with neurologic disability than lesion load derived using FLAIR imaging, and showed promise in classifying clinical subtypes of MS. These improvements are likely attributable to the ability of GEPCI to quantify tissue damage.

So white matter lesions centre around veins. I guess we knew this

Fankhauser GT, Stone WM, Fu R, Money SR. Spiral vein graft for internal jugular bypass in a patient with multiple sclerosis and suspected chronic cerebrospinal venous insufficiency. Ann Vasc Surg. 2013;27(5):673.e5-8.
Chronic cerebrospinal venous insufficiency (CCSVI) has been implicated as a contributing factor to multiple sclerosis (MS). This theory is strongly debated within the neurology and radiology communities. This report presents the case of a 45-year-old man with known MS and suspected CCSVI who had undergone previous internal jugular angioplasty and stenting. The patient reported dramatic improvement of symptoms after intervention. The stent thrombosed despite anti-thrombotic medication, and several endovascular interventions failed to restore long-term patency. Open venous reconstruction of the internal jugular vein was performed with a spiral graft from the saphenous vein. The patient's symptoms improved for several weeks until the venous reconstruction occluded. This case is the first reported open venous reconstruction for suspected CCSVI.

It had to happen, obviously once people realise that the effect of CCSVI wears off then it has to be repeated to unblock the vein so more money for the scammers. They may put in a stent but the obvious next stage of the scam is to by-pass the vein. The sapenous vein is used by surgeons in by-pass surgery. Why not let dodgy surgeons in on the act.

In this case it was a failure be warned. There is no class I evidence that these procedures provides benefit.  You should not do this unless being part of a clinical trial so it canbe really assessed whether benefit is being seen.

I see it now.....the Canadian government shelling out another $8,000,000 for a trial

I wonder how many people have had this procedure done?. 

Diehn FE, Schwartz KM, Hunt CH, Eckel LJ, Campeau NG, Carter RE, Allred JB, Kallmes DF. Prevalence of Incidental Narrowing of the Superior Segment of the Internal Jugular Vein in Patients Without Multiple Sclerosis. Clin Neuroradiol. 2013 Jul 2. [Epub ahead of print]

PURPOSE:Internal jugular vein (IJV) narrowing superiorly is likely relatively frequent. IJV narrowing has been proposed as a potential pathophysiologic component for multiple sclerosis (MS). Our purpose was to investigate the prevalence of incidental superior IJV narrowing in patients imaged with neck computed tomography angiography (CTA) for reasons unrelated to IJV pathology or MS.

METHODS:We retrospectively identified 164 consecutive adult patients who had undergone neck CTA in which at least one IJV superior segment was opacified (158 right, 155 left IJVs). At the narrowest point of the upper IJV, each IJV was assessed for dominance, graded (shape and narrowing), measured (diameter and area), and located (axially and craniocaudally). Associations were analyzed using Spearman rank correlations (p < 0.05 significant). Medical records were reviewed for MS.

RESULTS: Among 164 patients, at least one IJV was: absent/pinpoint in 15 % (25/164), occluded/nearly occluded in 26 % (43/164). Shape, narrowing, and the three measurements all correlated with each other (all p < 0.01). Lateral location with respect to C1 transverse foramen correlated with subjectively and objectively smaller IJVs (p < 0.01). The most common craniocaudal location was at the C1 transverse process (79 % (125/158) of right and 81 % (126/155) of left IJVs). No patient had a diagnosis of MS.

CONCLUSIONS: The appearance of the superior IJV is variable, with an occlusive/near-occlusive appearance present in approximately one-quarter of patients without known MS undergoing CTA. Radiologists should be aware of and cautious to report or ascribe clinical significance to this frequent anatomic variant.

Yet more evidence that a causal link of narrowing veins to MS is lacking

Brod SA, Kramer LA, Cohen AM, Barreto AD, Bui TT, Jemelka JR, Ton K, Lindsey JW, Nelson F, Narayana PA, Wolinsky JS. Chronic cerebrospinal venous insufficiency: masked multimodal imaging assessment. Mult Scler. 2013 Jul. [Epub ahead of print]

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) was implicated in the pathophysiology of multiple sclerosis (MS).

OBJECTIVE: We evaluated neurosonography (NS), magnetic resonance venography (MRV), and transluminal venography (TLV) in subsets of MS patients drawn from a single-center, prospective, case-control study of 206 MS and 70 non-MS volunteers.

METHODS: As previously reported, findings on high-resolution B-mode NS imaging with color and spectral Doppler of the extracranial and intracranial venous drainage consistent with CCSVI were similar among MS and non-MS volunteers (3.88% vs 7.14%; p = 0.266). Ninety-nine MS participants consented to intravascular contrast-enhanced 3D MRV to assess their major systemic and intracranial venous circulation, and 40 advanced to TLV that included pressure measurements of the superior vena cava, internal jugular, brachiocephalic, and azygous veins.

RESULTS: NS findings and MRV patterns were discrepant for 26/98 evaluable subjects, including four with abnormal findings on NS that had normal venous anatomy by MRV. In no instance were TLV pressure gradients indicative of clinically significant functional stenosis encountered. The three imaging approaches provided generally consistent data with discrepancies referable to inherent technique properties.

CONCLUSIONS: Our findings lend no support for altered venous outflow dynamics as common among MS patients, nor do they likely contribute to the disease process.

Somebody gloated "there is no evidence that EAE and MS are the same right"...I guess the response is "There is no compelling evidence for  a venous abnormality as a causal link of MS  right!"

Simka M, Ludyga T, Latacz P, Kazibudzki M, Majewski E, Zaniewski M Chronic cerebrospinal venous insufficiency is unlikely to be a direct trigger of multiple sclerosisMultiple Sclerosis and Related Disorders Volume 2, Issue 4 , Pages 334-339, 

Background Chronic cerebrospinal venous insufficiency, a vascular pathology affecting the veins draining the central nervous system can accompany multiple sclerosis and is suspected to be involved in its pathogenesis.
Objective.This study was aimed at exploring a potential role for chronic cerebrospinal venous insufficiency in triggering multiple sclerosis. If it were venous abnormalities responsible for neurological pathology, one should expect negative correlation, i.e. more severe vascular lesions in the patients with early onset of multiple sclerosis.
Methods Localization and degree of venous blockages in 350 multiple sclerosis patients were assessed using catheter venography. Statistical analysis comprised evaluation of the correlations between severity of venous lesions and patients' age at onset of the disease.
Results We found weak, yet statistically significant positive correlations between patients' age at onset of multiple sclerosis and accumulated and maximal scores of venous lesions. The patients, also those with duration of multiple sclerosis not longer than 5 years, who had their first attack of the disease at younger age, presented with less severe vascular lesions.
Positive correlation suggests that venous lesions are not directly triggering multiple sclerosis. There should be another factor that initiates pathological processes in the central nervous system.

Somebody gloated "there is no evidence that EAE and MS are the same right"...I guess the response is "There is no compelling evidence for  a venous abnormality as a causal link of MS  right!"
Am I just repeating myself? Well we have heard this over and over again, the weight of evidence I think is overwhelming.

 Rahman MT, Sethi SK, Utriainen DT, Hewett JJ, Haacke EM. A comparative study of magnetic resonance venography techniques for the evaluation of the internal jugular veins in multiple sclerosis patients. Magn Reson Imaging. 2013 Jul 11. doi:pii: S0730-725X(13)00211-7

BACKGROUND AND PURPOSE: The use of magnetic resonance imaging (MRI) to assess the vascular nature of diseases such as multiple sclerosis (MS) is a growing field of research. This work reports on the application of MR angiographic (MRA) and venographic (MRV) techniques in assessing the extracranial vasculature in MS patients. 
MATERIALS AND METHODS: A standardized MRI protocol containing 2D TOF-MRV and dynamic 3D contrast-enhanced (CE) MRAV was run for 170 MS patients and 40 healthy controls (HC). The cross-sectional area (CSA) of the internal jugular veins (IJVs) was measured at three neck levels in all subjects for both MRV techniques to determine the presence of venous stenoses. All data were analyzed retrospectively. 
RESULTS: For the values where both methods showed signal, the 3D method showed larger CSA measurement values compared to 2D methods in both IJVs, in both MS and HC subjects which was confirmed with student paired t-tests. Of the 170 MS patients, 93 (55%) in CE-MRAV and 103 (61%) in TOF-MRV showed stenosis in at least one IJV. The corresponding numbers for the 40 HC subjects were 2 (5%) and 4 (10%), respectively. Carotid ectasias with IJV stenosis were seen in 26 cases (15%) with 3D CE-MRAV and were not observable with 2D TOF-MRV. Carotid ectasias were not seen in the HC group. In the 2D TOF-MRV data, banding of the IJVs related to slow flow was seen in 58 (34%) MS cases and in no HC cases. MS patients showed lower average CSAs than the HC subjects. 
CONCLUSION: The 3D CE MRAV depicted the vascular anatomy more completely than the 2D TOF-MRV. However, the 3D CE MRAV does not provide any information about the flow characteristics which are indirectly available in the 2D TOF-MRV in those cases where there is slow flow.

Not much to say here, stenois in controls and more MSers...sound familiar ......nothing causal.

Juenemann M, Yeniguen M, Stolz E, Berghoff M. No evidence for CCVSI in relapsing-remitting multiple sclerosis patients with moderate disability. J Neurol. 2013 Jul 14. [Epub ahead of print]

Didn't get to read this one, but the title is rather damming

Benedict RH, Weinstock-Guttmam B, Marr K, Valnarov V, Kennedy C, Carl E, Brooks C, Hojnacki D, Zivadinov R.Chronic cerebrospinal venous insufficiency is not associated with cognitive impairment in multiple sclerosis. BMC Med. 2013 Jul 18;11(1):167. [Epub ahead of print]
BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has been reported in multiple sclerosis (MS) yet its significance in relation to cognitive function is undetermined.This study measured the association between the presence and severity of CCSVI and cognitive impairment in patients with MS.
METHODS: CCSVI was assessed using extra-cranial and trans-cranial Doppler sonography in 109 MS patients (79 with relapsing-remitting, 23 with secondary-progressive and 7 with primary-progressive disease subtype). A subject was considered CCSVI-positive if >=2 venous haemodynamic criteria were fulfilled. The Minimal Assessment of Cognitive Function in MS (MACFIMS) battery was administered assessing the full spectrum of cognitive domains known to be affected by MS. Depression was quantified using the Beck Depression Inventory Fast Screen (BDIFS). Partial correlations, analysis of variance (or covariance) and linear regression were used to examine the hypothesis that CCSVI status is related to cognition or depression after controlling for education and gender.
RESULTS: There were 64 (58.7%) patients who were considered CCSVI-positive. The regression models predicting venous haemodynamic insufficiency severity score were not statistically significant for any of the MACFIMS predictor variables. The analysis of variance tests showed a significant effect of CCSVI-positive diagnosis on cognitive ability in only one of the 10 MACFIMS outcomes, and that one was in the opposite direction of the tested hypothesis. There was no correspondence between CCSVI diagnosis and depression, as measured by the BDIFS.
CONCLUSIONS: We find no evidence of an association between the presence and severity of CCSVI with cognitive impairment and depression in patients with MS.

There is no correlation between CCSVI and cognitive impairment. some, not me, may say why would you expect correlations with something that does not exist....

In MS, I would say that MRI does show correlations with cognitive impairments......I would not say MRI causes MS, would you?

However something that MRI detects is involved in/the consequence of the problem

Krsmanovi E, Ivkovi M, Lepi T, Stankovi A, Rai Evi R, Din I E. Small internal jugular veins with restricted outflow are associated with severe multiple sclerosis: a sonographer-blinded, case--control ultrasound study. BMC Neurol. 2013 ;13(1):90. [Epub ahead of print]
BACKGROUND: Recent evidence has indicated an association between chronic cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis. Small internal jugular veins (IJVs) (with a cross-sectional area of less than 0.4 cm2) have been previously described as difficult to catheterize, and their presence may potentially affect cerebrospinal venous drainage. In this blinded extracranial color-Doppler study we had two principal aims: first, to assess prevalence of CCSVI among Serbian MS patients compared to healthy controls; and second, to assess prevalence of small IJVs (with a CSA <= 0.4 cm2) among MS patients and controls.
METHODS: The sixty seven unrelated patients with clinical isolated syndrome (CIS), relapsing-remitting (RR), secondary progressive (SP) and primary progressive (PP) multiple sclerosis and 21 healthy controls were examined by high-resolution color-Doppler.
RESULTS: The ultrasonographic criteria of CCSVI (according to Zamboni) were positive in 11.9% of the patients and in none of the control subjects. The CCSVI-positive patients had significantly longer disease durations and were significantly more disabled (measured by their Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) scores), but after adjustment for gender and disease duration, CCSVI was not an independent risk factor for multiple sclerosis severity. The small IJVs were found in 28.4% of the patients and 28.6% of the controls. The patients with small IJVs were associated with decreased venous outflow from the brain and presented with longer disease durations and significantly higher EDSS and MSSS scores compared to patients without small IJVs. Analysis adjusted for gender and disease duration showed that small IJV is an independent factor associated with multiple sclerosis severity (EDSS >=6) (adjusted OR = 8.9, 95% CI: 1.8-45.6, p = 0.007). Among patients with small IJVs the 36.84% were also CCSVI positive.
CONCLUSIONS: Both, CCSVI and small IJVs seem to influence or follow MS severity, but only small IJVs turned out to be an independent factor in this study. Thus, small IJVs with restricted outflow, which might be aspects of CCSVI different from the criteria originally described by Zamboni, emerge as a cofactor in the multifactorial pathophysiology of multiple sclerosis.

Canada, Italy and Serbia have been CCSVI hotspots. This study from Serbia reports yet another study showing CCSVI is not causal to MS. The answer to this in pretty clear the original Zamboni concept is not correct...100% Msers with CCSVI and 0% controls. 

Laughlin S, Macgowan CK, Traubici J, Chan K, Khan S, Arnold DL, Marrie RA, Banwell B.

No Evidence for Impairment of Venous Hemodynamics in Children or Young Adults with Pediatric-Onset Multiple Sclerosis. AJNR Am J Neuroradiol. 2013 Jul. [Epub ahead of print]

BACKGROUND AND PURPOSE:Chronic cerebrospinal venous insufficiency is a postulated etiologic factor for multiple sclerosis, but the higher frequency with longer disease duration and progressive disability suggests that chronic cerebrospinal venous insufficiency is secondary to chronic disease. We evaluated the presence of chronic cerebrospinal venous insufficiency in pediatric-onset MS.
MATERIALS AND METHODS:Twenty-six pediatric patients with MS (18 years of age or younger), 26 age-matched healthy controls, and 13 young adults with pediatric-onset MS underwent sonography of the internal jugular, vertebral, and deep cerebral veins. Five venous hemodynamic criteria were assessed, with 2 criteria required for chronic cerebrospinal venous insufficiency. MR imaging studies, performed in the pediatric patients with MS and healthy control groups, included intracranial 2D time-of-flight MR venography and velocity-sensitive phase-contrast sequences. Contrast-enhanced brain MR images were obtained in pediatric patients with MS to further evaluate venous patency. We used paired t tests, Wilcoxon matched pairs, McNemar tests, and exact conditional logistic regression to estimate the association of chronic cerebrospinal venous insufficiency with MS.
RESULTS:Fifty participants (73.5%) had normal ultrasound findings, 15 (23.1%) met 1 venous hemodynamic criterion, and 2 pediatric patients with MS and 1 young adult with pediatric-onset MS met chronic cerebrospinal venous insufficiency criteria. Chronic cerebrospinal venous insufficiency was not associated with MS (odds ratio, 2.41; 95% CI, 0.19-infinity). Demographic and disease characteristics did not differ between the patients with MS meeting chronic cerebrospinal venous insufficiency criteria (n = 3) and those who did not (n = 36; all, P > .05). The mean (SD) MR imaging measures of intracerebral flow did not differ between the 2 pediatric patients with MS meeting chronic cerebrospinal venous insufficiency criteria (0.85 ± 0.11) and healthy controls (0.87 ± 0.16, P = .50); no child demonstrated venous obstruction.
CONCLUSIONS:Chronic cerebrospinal venous insufficiency is rarely observed in children or young adults with pediatric-onset MS. Venous anatomy and flow rates indicate that venous outflow is intact in pediatric patients with MS. Our findings argue against chronic cerebrospinal venous insufficiency as a component of MS aetiology.
Enough already many times do you want to hear the same thing, CCSVI is not causal to MS!, if is not observed in early MS so if present is an secondary age/disease-related event.

CCSVI also continues its downward trend.

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