1. Marian Simka, MD PhD Katowice, Poland
Chronic cerebrospinal venous insufficiency: State of the art and research challenges
Marian Simka, MD PhD Katowice, Poland

2. Disclosures: received publication fees from Servier International
received speaker fees from American Access Care
is employed in the hospital, where the treatments for CCSVI are patient-paid

3. Multiple sclerosis is chronic and debilitating neurological disease that is commonly regarded as an autoimmune disorder
However, a unifying hypothesis of such an autoimmunity has yet to be identified

4. The discovery of occlusions in the extracranial veins that drain the central nervous system, so called chronic cerebrospinal venous insufficiency CCSVI sheds a new light on this problem

5. Atrophy of small intracerebral veins in MS patients
healthy control early MS advanced MS

6. Since CCSVI comprises the blood outflow from a vital organ, for many doctors it seems reasonable to unblock such an obstruction

7. Others, however, argue that such interventions should be accepted as a valid treatment option for MS only on condition that: ∎ an impact of venous insufficiency on MS was demonstrated ∎ the procedures to alleviate these vascular pathologies were proven technically feasible and safe ∎ the treatments were proven to result in clinical benefit

8. Rationale for the treatment for CCSVI
At the moment no pharmacological agent for MS is effective in a long run
Even if only a subgroup of MS patients would benefit from the treatments for CCSVI, such procedures could be a breakthrough in the MS management

9. Three main questions regarding hypothetical venous insufficiency in the cerebral and spinal territory should primarily be answered:
Does chronic cerebrospinal venous insufficiency exist?
If it does, is it exclusively associated with multiple sclerosis?
If associated, does such a connection have an impact on neurological pathology?

10. Does chronic cerebrospinal venous insufficiency exist?
Problems with definition of CCSVI:
definition using ultrasonographic parameters
definition using angiographic (phlebographic) parameters
small but relevant differences between protocols and interpretations of the findings

11. normal abnormal

12. normal ?? abnormal ???

13. Published evidence: 13 different angiographic studies have shown % prevalence of venous lesions in MS patients

14. Does chronic cerebrospinal venous insufficiency exist?
Yes
at least, in terms of angiographic findings in MS patients

15. If CCSVI exists, is it exclusively associated with multiple sclerosis?
CCSVI seems to be a clinical entity distinct from multiple sclerosis
The majority of, but not all, MS patients, can demonstrate venous lesions
Such vascular abnormalities can also be found in non-multiple sclerosis individuals, and also in healthy controls

16. CCSVI and Parkinson disease
Atypical MRI outflow pattern found in >50% of Parkinson patients Haacke M et al.

17. If CCSVI exists, is it exclusively associated with multiple sclerosis?
Sonographic signs of CCSVI commonly found in the patients suffering from:
other neurodegenerative pathologies
Parkinson disease
migraine
non-neurological autoimmune disorders

18. If CCSVI is associated with MS, does such a connection have an impact on neurological pathology?
It is unlikely that CCSVI is secondary to pathological processes of nervous tissue
CCSVI lesions are preferentially found in the left IJV (congenital deffect?)

19. If CCSVI is associated with MS, does such a connection have an impact on neurological pathology?
It is unlikely that CCSVI is secondary to pathological processes of nervous tissue
CCSVI lesions are free from inflammation in histological exams
CONTROL MS

20. If CCSVI is associated with MS, does such a connection have an impact on neurological pathology?
Hubbard et al. Normalization of fMRI BOLD after angioplasty in CCSVI patients

21. ”Venous undershoot” in fMRI BOLD black - control red – MS patients before PTA blue – patients after PTA
Hubbard et al. Normalization of fMRI BOLD after angioplasty in CCSVI patient

22. Hypothetical mechanisms by which venous insufficiency could influence MS-associated processes
proinflammatory and toxic role for iron
chronic brain hypoxia resulting from blockage of venous outflow
disintegration of the blood-brain barrier caused by stagnant and refluxing flow pattern in cerebral venules

23. If CCSVI is associated with MS, does such a connection have an impact on neurological pathology?
It has recently been suggested that CCSVI may change benign infection caused by hypothetical infections agent of MS into clinically overt neurological disease

24. Safety and feasibility of endovascular treatment for CCSVI

25. Papers on safety of endovascular procedures for CCSVI: (12 articles)
Zamboni (Italy) J Vasc Surg pts
Ludyga (Poland) Phlebology 2010 – 344 pts
Mandato (USA) J Vasc Interv Radiol – 231 pts
Petrov (Bulgaria) J Endovasc Ther pts
Kostecki (Poland) Neuroendocrinol Lett 2011 – 36 pts
Kipshidze (Georgia) Georg MedNews pts
Lugli (Italy) Phlebology 2012 – 167 pts
Beelen (Belgium) Phlebology 2012 – 67 pts
Hubbard (USA) - J Vasc Interv Radiol 2012 – 259 pts
Zamboni (Italy) - Eur J Vasc Endovasc Surg - 15 pts
Simka (Poland)- Vasc Dis Manag 2012 – 340 pts
Eisele (Argentina) – Fleb Linfol pts
Total: 2004 pts
No mortality, very low incidence of major complications (1-2%)

26. Safety of the treatment for CCSVI (a meta-analysis)
The procedures are very safe if no stents are implanted
The use of stents is associated with increased rate of complications (still, rarely serious)
However, there is a high rate of restenosis after endovascular treatment (inadequate technique? elastic recoil? thrombosis/scarring? progression of CCSVI?)

27. compression of jugular vein by aberrant omohyoid muscle

28. Clinical efficacy of endovascular treatment for CCSVI

29. Clinical benefit from the treatment for CCSVI
10 open-label trials published, 1440 patients
Zamboni ; J Vasc Surg pts , 18 months follow-up – clinical improvement in relapsing-remitting patients, stop of progression in progressive MS
Ludyga ; Przeg Flebol pts , 6 months follow-up – clinical improvement in majority of clinical domains, irrespective of clinical status before the treatment
Kostecki ; Neuroendocrinol Lett 2011 – 36 pts, 6 months follow-up , temporary improvement, not statistically significant
Lugli; Phlebology 2012 – 167 pts, 1 month follow-up , clinical improvement in 69% of patients
Beelen; Phlebology 2012 – 67 pts, 3, 6, 12 months follow-up, temporary improvement, not statistically significant
Hubbard - J Vasc Interv Radiol 2012 – 259 pts, 6 months follow-up – clinical improvement in majority of clinical domains, irrespective of clinical status before the treatment
Simka; Vasc Dis Manag 2012 – 340 pts, 6 months follow-up –improvement of chronic fatigue
Milic D; J Vasc Surg 2012 – 205 pts, 6 and 12 months follow-up, temporary improvement, not statistically significant
Eisele G; Flebol Linfol 2012 – 15 pts, 1, 3 and 6 months follow-up, clinical improvement in majority of clinical domains except for EDSS
Sekhar K; J Vasc Interv Radiol 2012 – 192 pts, 3 months follow-up, clinical improvement in majority of clinical domains, better results in relapsing-remitting patients

30. Clinical efficacy of the treatment for CCSVI (a meta-analysis)
Chronic fatigue improves after the treatment in majority of MS patients
Other symptoms that may improve include: headache, bladder control, balance problems, paresthesiae, cold extremities
Impaired walking, weak legs, usually do not improve
Some patients (10-20%) may deteriorate after the treatment for CCSVI

31. MRI efficacy of endovascular treatment for CCSVI
Zamboni et al. Eur J Vasc Endovasc Surg pts, a crossover study statistically significant improvement in terms of plaque load during 6 months follow-up

32. Clinical efficacy of endovascular treatment for CCSVI
Randomized Control Trials with sham-surgery arm ongoing:
USA (2 trials)
Italy
Australia
planned:
United Kingdom
Canada

33. 3rd Annual ISNVD Meeting
23-25 February 2013 Kraków, Poland  

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