1. POLISH EXPERIENCE IN CCSVI TREATMENT Marian Simka EuroMedic Department of Vascular & Endovascular Surgery Katowice Poland

2. Multiple sclerosis is a chronic and debilitating neurologic disease of as yet unknown etiology. Although it is commonly regarded as an autoimmune disorder, many findings are difficult to explain on the basis of autoimmunity. An efficient therapy that can protect a patient from progression of the disease does not currently exist.

3. 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

4. How could we define CCSVI ? CCSVI is a functional and/or structural abnormality of the veins draining the central nervous system

5. CCSVI comprises clinically significant stenoses or occlusions in the main venous pathways draining the brain and spinal cord internal jugular veins

6. azygous vein

7. brachiocephalic vein

8. Perhaps, lesions in the intracranial veins also play a role

9. CCSVI

10. Prevalence of CCSVI in MS patients: - most of research based on Doppler sonography (highly operator-dependent) - prevalence according to catheter venography assessment: 96% of MS patients (Simka M. Funct. Neurol. 2011) Prevalence of CCSVI in healthy controls: - according to Doppler sonography findings: 0-30% - according to catheter venography – not known

11. Is CCSVI related to multiple sclerosis ? - Higher prevalence of retinal pathology in MS patients with unilateral stenosis of internal jugular veins (phenomenon poorly understandable within autoimmune paradigm of MS)

12. Optical coherence tomography of the eye – average ganglion cell complex thickeness ***

13. Is the treatment for CCSVI safe ?  Zamboni ; J Vasc Surg. 2009 - 65 patients  Ludyga ; Phlebology 2010 – 344 patients  Petrov ; J Endovasc Ther. 2011 - 461 patients  Kostecki ; Neuroendocrinol Lett. 2011 – 36 pts  Mandato ; J Vasc Interv Radiol.2011 – 257patients TOTAL: 1163 pts No major complications, except for early thrombotic occlusions of treated veins (1-2%)

14. Does the treatment for CCSVI result in improvement of MS ?  Zamboni ; J Vasc Surg. 2009 - 65 patients  Ludyga ; Przeg Flebol. - 94 patients  Kostecki ; Neuroendocrinol Lett. 2011 – 36 pts  TOTAL: 195 patients - Improvement in some domains, especially regarding quality of life - No significant improvement in terms of EDSS

15. MSIS-29 ― 6 months after endovascular treatment improvement worsening

16. Change of fatigue severity 6 months after endovascular treatment depending on pre-procedural FSS scores

17. CCSVI can be diagnosed by means of: color doppler sonography

18. Diagnostic accuracy of Doppler sonography (catheter venography as the reference test)

19. Still, current knowledge about CCSVI is very limited

20. MRI efficacy of endovascular treatment for CCSVI Zamboni ; Eur J Vasc Endovasc Surg 2011 – 15pts, a crossover study, statistically significant improvement in terms of plaque load during 6 months follow-up

21. What we do not know: Is CCSVI the causal factor for MS, a co-factor or an epiphenomenon By which mechanism does CCSVI drive MS: - initiation of autoimmune reaction ? - toxic role for iron ? - chronic ischemia and hypoperfusion of nervous tissue ? - pathologic interplay between neurons and glia ?

22. What we do not know: How high is prevalence of CCSVI in “healthy” population ? How high is such a prevalence in the patients with other neurologic diseases ?

23. Is CCSVI is a congenital pathology ? Congenital only in some MS patients? What we do not know:

24. How to diagnose CCSVI ? - which is the best method? - Doppler sonography, MR venography, catheter venography ? a combination of the tests? What should be regarded as a pathology – and what as an anatomic variant ? What we do not know:

25. Are treatments for CCSVI efficient in a long- term perspective ? Which subgroups of the patients can benefit and which cannot ? Are we under-treating or over-treating the patients ? What we do not know:

26. Should endovascular or surgical treatment for CCSVI be accompanied by pharmacological treatment ? If yes, which drugs should be used ? What we do not know:

27.  which lesions should not be treated?  which patients should not be treated? DO NOT KNOW more research is needed

28. Two Randomized Control Trials with sham surgery arm are being done USA Italy The results should be known the next year (American study) and in 2013 (Italian study) Clinical efficacy of endovascular treatment for CCSVI