Endovascular treatment of CCSVI really works: the benefits of treating venous brain congestion can be documented Ivo Petrov, MD, PhD Sofia City Clinic Cardiology and angiology department

x I do not have any potential conflict of interest related to this presentation Ivo Petrov, MD

The eyes only see and believe what the brain can understand!

In testimonials after CCSVI endovascular treatment many patients say they have improvement in: Brain fogue Chronic feeling of fatigue Blurriness of vision Walking balance control Is it possible these conditions to be measured (quantified) and expressed numerically? NO But these kind of neurologic disturbances are real and life changing for the MS patients Malagoni AM, Galeotti R, Zamboni P .Int Angiol. Is chronic fatigue… 2010 Apr;29(2):176-82.

CCSVI cascade:. Brain venous obstruction. Venous congestion CCSVI cascade: Brain venous obstruction Venous congestion Microextravasations Blood-brain barrier damage: -autoimmune activation -demielinization -neurodegeneration Normal CCSVI

Tokuda hospital experience in CCSVI (February 2010-February 2012) Up to date CCSVI endovascular treament 1311 patients, 2998 veins (2.3 lesions per patient) MS: 1303 patients; Migraine: 5 patients; LAS: 2 patients; Left sided amaurosis: 1 patient.

Substudy of the Bulgarian CCSVI registry Results of Comparative blood gas analysis in jugular and femoral veins in patients with multiple sclerosis and chronic cerebrospinal venous insufficiency before and after endovascular treatment. Ivo Petrov, MD, PhD L. Grozdinski, MD, PhD Tokuda Hospital Sofia Cardiology and angiology department Substudy of the Bulgarian CCSVI registry

Background After the provided endovascular treatment in CCSVI and MS positive patients- 852 patients (1975 treated veins) from February 2010 to March 2011, we have often observed immediate functional neurologic improvements even on the angiographic table. That gave us the reason to search for objective and measurable surrogate markers that can explain the immediate changes we have observed in the patient ‘s functional condition.

Background 1. Chronic inhalation of air with elevated concentration of CO2 and low concentration of O2 or in altitude sickness lead to symptoms very similar to the chronic symptoms in MS: dizziness, fatigue, impaired and double vision, disarthria, sensitivity disturbances 2. Chronic hypoxia-hypercapnia influences cognitive function in chronic obstructive pulmonary disease. 3. Neuronal death during combined intermittent hypoxia/hypercapnia is due to mitochondrial dysfunction

Background We assumed that chronic venous stasis leads to impaired perfusion and gas exchange impairment and that restoration of normal circulation leads to almost immediate gas exchange normalization at brain level and subsequently to fast neurologic improvement

Blood gas analysis substudy Our research included total of 228 patients 178 patients with CCSVI and MS /average age 44.86/, with different degree of jugular vein stenosis /53 patients with 50- 80% stenosis, 125 patients with above 80% stenosis/ 50 healthy control group /average age 54.6/ Samples were taken under standard conditions during an invasive or interventional procedure from the femoral introducer and from the distal part of jugular and azygous veins At ambience temperature 20o C 2 ml of blood in a heparinized syringe after initial aspiration of 5 ml through the same catheter in order to remove remainings of contrast media, saline or blood from other regions

Results. Comparative blood gas analysis in jugular vein between MS patients and control group

Bloog-gaz analysis in Jugular vein in patients with MS before and after treatment. Immediate improvement:

The most probable reason for this immediate truncular veins blood gaz analysis improvement is the immediate improvement in microcirculation (both perfusion and run off) and more efficient gaz exchange on microcirculatory level. Here is the the direct prove: On a group of patients(9) with evidence of CCSVI submitted to balloon angioplasty or stenting we performed SPECT- 99mTc- HMPAO dynamic brain scintigraphy before and after the endovascular procedure and showed: - improvement of the brain perfusion in the treated hemisphere - improvement of the wash-out timing of the involved zone - reduced perfusion brain asymmetry after the procedure

Total occlusion of the innominate vein

Generally underperfused brain Spots with totally missing perfusion L to R asymetria (left hemisphere missing perfusion)

Vessel recanalization using Coronary CTO technique (Asahi Miracle wires and OTW RyuJin low profile balloons)

Stepwise balloon predilation

Partial recanalization after ballooning. Collaterals still persisting

Full recanalization and flow restoration after stent implanation. Collaterals disappeared.

1h AFTER BEFORE Generally underperfused brain Spots with totally missing perfusion L to R assimetria 1h AFTER Good general perfusion No spots with missing perfusion L to R equalization

MULTIPLE SCLEROSIS LESIONS: FLAIR and Perfusion Weighted Imaging (PWI can be used to study the hemodynamics of the brain) Perfusion weighted MRI shows all MS lesions have the same vascular characteristics Anatomic evidence of lesions from FLAIR imaging

Conclusions: Jugular veins blood gas analysis in CCSVI is remarkable with hyperkapnia, hypoxemia and desaturation with statistically significant difference compared to the control group The interventional treatment leads to mild immediate improvement of the gas exchange disturbances The successful endovascular treatment and restoration of the extracranial blood flow leads to immediate improvement in the brain perfusion

ASSOCIATION OF CCSVI AND MS S o u r c e Multiple sclerosis and CCSVI: a population-based case control study. A higher frequency of CCSVI has been found in MS patients; it was more evident in patients with advanced MS, suggesting that CCSVI could be related to MS disability. Department DANA GF Ingrassia, Section of Neurosciences, University of Catania, Catania, Italy. PMID: 22870210 [PubMed - in process] PMCID: PMC3411668

ASSOCIATION OF CCSVI AND MS Chronic cerebrospinal venous insufficiency is not more prevalent in patients with mild multiple sclerosis: a sonographer-blinded, case-control ultrasound study. Our findings indicate that CCSVI, as defined by the Zamboni ultrasound criteria, is not present in CIS and mild RRMS (EDSS ≤2), providing further evidence that CCSVI does not have a causal role in MS; however, we found an apparent increase in IJV variation in patients with CIS or mild MS that would warrant further investigation. Department of Neurology, Austin Health, Heidelberg, Australia.

ASSOCIATION OF CCSVI AND MS Disability caused by multiple sclerosis is associated with the number of extra cranial venous stenoses: possible improvement by venous angioplasty. Results of a prospective study. The number of venous narrowings is higher in more disabled patients. A significant improvement in clinical disability in the relapsing-remitting group was observed. Phlebology. 2012 Nov 30. Denislic M, Milosevic Z, Zorc M, Ravnik IZ, Mendiz O.

Methods Assessment of jugular endovascular malformations in chronic cerebrospinal venous insufficiency: colour-Doppler scanning and catheter venography compared with intravascular ultrasound. CV was significantly inferior to CD sonography and IVUS in detecting JEM. Differences between IVUS and CD sonography in detecting JEM and in quantifying jugular diameters were not significant. The IJV CSA was underestimated by CD sonography compared with IVUS. CD sonography was proven to be important in the anatomical characterization of CCSVI, providing useful information for correct intravascular treatment. Phlebology. 2012 Nov 15 Scalise F, Farina M, Manfredi M, Auguadro C, Novelli E.

CRITICISM OS CCSVI DIAGNOSTIC CRITERIA The European Society of Neurosonology and Cerebral Hemodynamics (ESNCH) has considerable concerns regarding the accuracy of the proposed criteria for CCSVI in MS. Therefore, any potentially harmful interventional treatment such as transluminal angioplasty and/or stenting should be strongly discouraged. J Neurol. 2012 Dec;259(12):2585-9. doi: 10.1007/s00415-012-6541-3. Epub 2012 May 31.

RESULTS OF ENDOVASCULAR TREATMENT Venous angioplasty in multiple sclerosis: neurological outcome at two years in a cohort of relapsing-remitting patients. Endovascular treatment of concurrent CCSVI seems to be safe and repeatable and may reduce annual relapse rates and cumulative disability in patients with relapsing-remitting MS. Randomized controlled studies are needed to further assess the clinical effects of endovascular treatment of CCSVI in MS. Funct Neurol. 2012 Jan-Mar;27(1):55-9.

RESULTS OF ENDOVASCULAR TREATMENT An endovascular treatment of Chronic Cerebro- Spinal Venous Insufficiency in multiple sclerosis patients - 6 month follow-up results. The endovascular treatment in patients with MS and concomitant CCSVI did not have an influence on the patient's neurological condition; however, in the mid-term follow-up, an improvement in some quality-of-life parameters was observed. Department of Surgery, Medical University of Silesia, District Specialist Hospital, Tychy, Poland. Kostecki J, Zaniewski M, Ziaja K, Urbanek T, Kuczmik W, Krzystanek E, Ziaja D, Korzeniowski T, Majewski E, Hartel M, Swiat M, Sioma-Markowska U.

RESULTS OF ENDOVASCULAR TREATMENT Safety of endovascular treatment of chronic cerebrospinal venous insufficiency: a report of 240 patients with multiple sclerosis. Endovascular treatment of CCSVI is a safe procedure; there is a 1.6% risk of major complications. Cardiac monitoring is essential to detect intraprocedural arrhythmias. Ultrasonography after the procedure is recommended to confirm venous patency and to identify patients experiencing acute venous thrombosis. J Vasc Interv Radiol. 2012 Jan;23(1):55-9. Epub 2011 Nov 15.

Thank you for the attention!