Sunday, 16 September 2012

Research: CCSVI papers back after the Summer holiday

After 2 months of essentially nothing in terms of papers published nothing, now the periodical "Neurological Research" gives the journal over to CCSVI topics
Morovic S, Zamboni P. CCSVI is associated with multiple sclerosis. Neurol Res. 2012;34(8):770-9.

BACKGROUND: To analyze all the arguments against chronic cerebrospinal venous insufficiency (CCSVI) as a medical entity, and its association with multiple sclerosis (MS) and to revise all the findings suggesting a possible connection between these two entities.

METHODS: We revised the methodology and results of all fourteen published studies on prevalence of CCSVI in MS patients. Furthermore, we take into consideration other work dealing with possible causes and explanations of venous, as well as vascular dysfunctions linked with MS.

RESULTS: Studies of prevalence show a great variability in prevalence of CCSVI in MS patients. However, a recent meta-analysis assessed an over 13 times increased prevalence in MS. Global hypoperfusion of the brain, and reduced cerebral spinal fluid dynamics in MS was shown to be related to CCSVI. Post-mortem studies show a higher prevalence of intraluminal defects in the main extracranial vein in MS patients in respect to controls.

DISCUSSION: Taking into account the current epidemiological data, the autoptic findings, and the relationship between CCSVI and both hypoperfusion and cerebrospinal fluid flow, CCSVI can be inserted in the list of multiple factors involved in MS pathogenesis. Our careful data analysis may conclude that great variability in prevalence of CCSVI in MS patients can be a result of different methodologies used in venous ultrasound assessment. Finally, it has been proven that CCSVI share the three main risk factors with MS. On the other hand, smoking is the most important risk factor for endothelial cell damage, vitamin D has a protective role and Epstein-Barr virus passes the blood-brain barrier by invading the endothelial cells, therefore, epidemiologically, linking the imbalance of these three factors to MS through autoimmunity.

This gives us no new insight from the Bard of CCSVI. As ever it is claimed that there are methodological differences, with on the whole more vascular abnormalities in MSers. But maybe some aetiology

Karmon Y, Ramanathan M, Minagar A, Zivadinov R, Weinstock-Guttman B Arterial, venous and other vascular risk factors in multiple sclerosis. Neurol Res. 2012;34:754-60.

Utriainen D, Trifan G, Sethi S, Elias S, Hewett J, Feng W, Haacke EM.Magnetic resonance imaging signatures of vascular pathology in multiple sclerosis.Neurol Res. 2012 Oct;34(8):780-92.

The above two are reviews which again go over things endlessly discussed on the BLOG and elsewhere

Feng W, Utriainen D, Trifan G, Elias S, Sethi S, Hewett J, Haacke EM. Characteristics of flow through the internal jugular veins at cervical C2/C3 and C5/C6 levels for multiple sclerosis patients using MR phase contrast imaging.Neurol Res. 2012 Oct;34(8):802-9

OBJECTIVES: To study blood flow characteristics through the internal jugular veins (IJVs) at the cervical levels C2/C3 and C5/C6 in the neck of multiple sclerosis (MS) patients.
METHODS: Magnetic resonance imaging at 3T was performed on 323 MS patients. Phase contrast imaging was used to quantify blood flow at both the C2/C3 and C5/C6 levels. Total IJV flow (tIJF) was normalized by total arterial flow (tAF). Contrast-enhanced time-resolved 3D MR arteriovenography and 2D time-of-flight MR venography were performed to assess IJV anatomy. Based on this assessment, the MS population was divided into non-stenotic (NST) and stenotic (ST) subjects.
RESULTS: Of all the patients, 100 (31%) belonged to the NST group and 223 (69%) belonged to the ST group. At the C2/C3 and C5/C6 levels, the normalized tIJF of the ST group was 56±26% and 51±23%, respectively. This was significantly lower than that of the NST group, 85±13% and 73±12% (P<0·001). Zero percent and 5% of the NST group had a normalized tIJF of less than 50% at the C2/C3 and C5/C6 levels, compared to 37% and 47% for the ST group. The tAF was smaller for the secondary and primary progressive MS patients than the relapsing remitting MS patients (P = 0·02 and 0·01, respectively), while the tIJF was similar among all MS types.

CONCLUSION: Total blood flow through the IJVs at both the C2/C3 and C5/C6 levels was reduced in the Stenotic group compared to the non-stenotic group.

If there was a stenosis (narrowing) of the vessels then flow surely would have to lower, which is what was found. Would this occur in healthy people too? However there were plenty of people with apparent narrowing so there will be no shortage of people for the trials.

Diaconu CI, Staugaitis SM, Fox RJ, Rae-Grant A, Schwanger C, McBride JM. A technical approach to dissecting and assessing cadaveric veins pertinent to chronic cerebrospinal venous insufficiency in multiple sclerosis. Neurol Res. 2012;34(8):810-8.
OBJECTIVE: To establish a detailed technical procedure for studying the anatomical correlates of chronic cerebrospinal venous insufficiency in cadavers of multiple sclerosis and control subjects, and to present our findings of the normal anatomic venous structures, with reference to previous descriptions from the literature.
METHODS: This study examined the internal jugular veins (IJVs), the brachiocephalic veins, and the azygos vein from 20 cadavers (10 control and 10 multiple sclerosis). These veins were exposed, isolated by clamps from the rest of the venous system, flushed with water, and then injected with fluid silicone from the superior ends of both IJVs. After the silicone cured to its solid state, the venous tree was removed en bloc and dissected longitudinally to expose the luminal surface. All vein segments were analyzed for anatomic variation. Anatomical analysis for this manuscript focused on normal vein architecture and its variants.
RESULTS: Thirty-seven of 40 IJVs contained valves: 29 bicuspid, 6 tricuspid, and 2 unicuspid. The average circumferences of the right and left IJVs were 2·2 and 1·8 cm, respectively. Thirteen of 20 azygos veins contained a valve, located on average 3·6 cm away from the superior vena cava junction. Nine of the 13 azygos valves were bicuspid; four were tricuspid. Only one of the 40 brachiocephalic veins contained a valve.
DISCUSSION: We detailed a technical approach for harvesting cadaveric neck and thoracic veins with relevance to chronic cerebrospinal venous insufficiency. The anatomy of the venous system has significant variability, including differing number of valves in different regions and variable characteristics of the valves. Average vein circumference was less than that typically reported in imaging studies of live patients.

So this study is warming us up for their next study which is pathology of CCSVI which will tell us there is variability and some differences but...lets wait and see. Hope the flushing does not clean the blocking.

Therefore a number of reviews that tell us very little new, surely it is response to venoplasty (so called liberation therapy) that we are all waiting to hear about .

However it will be CCSVI central at ECTRIMS in the up and coming weeks 

Comi G et al. Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and global venous haemodynamics in multiple sclerosis: the CoSMo study- This was funded by the Italian Multiple Sclerosis Foundation but Dr. Zamboni from the scientific committee because of failure of the commitee to comply with his diagnostic protocol. This is an Observational Study of the Prevalence of CCSVI in Multiple Sclerosis and in Other Neurodegenerative Diseases (COSMO). I think we know what this one will be saying......because of Interim Analysis.