Relationship between chronic cerebro-spinal venous insufficiency CCSVI and MS L.Grozdinski and I.Petrov, M.Iloska,M.Pavlova Clinic of Angiology and Phlebology Tokuda Hospital Sofia, Bulgaria

Multiple sclerosis (MS) This is an inflammatory, neurodegenerative, disease of the central neurological system (brain, spine); It was first discovered by Charcot, 1868

Frequency and occurance Two million people suffer from MS in the world Highest frequency have North America and North Europe up to 80/100 000

Specifics and prognosis MS affects young people between 25 – 35 years; Patients with MS live 5-10 years less than the rest of the people; After 25 years over 50% of the patients become dissabled.

Axon – myelin affection Autoimmune theory for development of MS Infection causing BBB breakdown, myelin affection - autoimmune reaction and MS Genetic factors Infections BBB Breakdown Virus Attack Causing Axon – myelin affection T-kyller lymphocytes Autoimmune reaction Demyelination Neuron MS Lymphocytes

Unsolved questions The ethiological and pathogenetic mechanism stil stay uncleared; There′s no explanation why the BBB is breaking down; There′s no explanation why the inflamatory reaction is around the cerebral vein;

2009 P.Zamboni discovers CCSVI in patients with MS CCSVI is congenital venous malformation – stenoses of internal jugular and azygous veins and insufficient cerebrospinal venous drainage.

Zambony`s theory of CCSVI- MS Disturbed venous drainage Venous hypertention Disturbed of BBB Migration of blood cells Er – precipitation of iron Irons causes neurodegeneration CCSVI causes:

US – Color Doppler Study of Jugular vein Total tesded – 550 patients Control group – 50 p without MS; Group A – 500 p with MS Results: Control group – 46 p without date for CCSVI and 4 p (8%) suspected for CCSVI Group A (MS) – 461 p – 92,2% comfermed for CCSVI and 39 p – 7,8% without proven date for CCSVI

Bozev (MS)– Stenosis of Jugular vein – US screening

Zarev(MS) – Stenosis of IJV – US screening

K.G.( MS ). Valve stenosis of RIJV US - screening I.P

A.R.(MS) Valve stenosis and insuff. of IJV US screening

Study with venography Exzamined - 461 p with CCSVI – MS found with US Patients were from: Bulgaria, Canada, UK, Irland,USA, Holand, Italy, France, Slovenia, Hungary, Greece, Suisse, Norwey,Litva, Macedonia, Croatia,Malta,Rumenia,Kipar,Harvatia

Forms of MS and clinical stage Relapsing Remitting – 278 p – 55.6% Primary progressive – 177 p – 35,4% Secondary progressive – 38 p – 7,6% Clinicaly isolated syndrom – 7 p – 1,4 % EDSS – average – 5.2 stage Continuance of MS – 9 years

Color Doppler screening of IJV Total 550 p. Control gr.О–50p. mean,SD, n , % Gr.A– MS 500 p. Gr.А1-461 p. CCSVI Gr.А2- 39 p. Мах.D IJV в мм. 8.2 +-2.8 8.6 +-3.2 8.7 +-3.1 8.5 +- 2.9 Min.D IJV в мм. 4.5+-1.7 1.8+-3.7* 1.7+-3.5* 3.1 +- 3.2* min.d/max.d% 54% 20%* 19%* 36% Stenosis in ІJV 5% 92%* 100%* 5 % Reflux in IJV 7% 67 %* 70 %* 12 % Reduction of flow in IJV 6 % 50 %* 73%* 12% -ΔCSA в IJV 2% 63%* 66%* 0 % 8 % 92 %* CCSVI 4 10 % 123 89.1%* 123 100%* 0 0 %

Venography In 461 patients with CCSVI –MS found by US , venography confirmed CCSVI in 100%; Jugular vein stenoses – 461 p. – 100% Jugular vein + Azygos stenoses – 339 p – 73,5% Independetly jugular vein stenoses – 122 p, 26,4% Stenoses were over 60% to 99%.

Venography - IJV -МS

Comparison - Color Doppler and venography CCSVI - MS CCSVI 461 p. 1383 vein ColorDoppler total 922 IJV Venography 1383 n.,% Vein stenosis – n vein 793 86 % 1112 80.4% Vein stenosis - patient 461 100% Stenosis IJV – vein 86% 773 83.8% Stenosis IJV – p. Stenosis v.azygos - 339 73.5%

CCSVI -US Doppler diagnostic/Venography comparison CCSVI diagnostic US sensitivity – 98%; Concurrence – 91,6%

Stenosis IJV before and after endovascular treatment

Stenosis vena azygos – before and after endovascular treatment

Clinical improvement after endovascular treatment Early improvement up to one week – 81%; Improvment up to 6 months – 60%

Venous theory of MS VT CCSVI - CVI Valve stenosis/ Stenosis insufficiency Stenosis v. Jugularis/ Azygos Reflux VBP venous drainage Er (Fe) fibrin ED Destruction of BBB Insufficiency T-Lymp infiltration perivascular edema disturbed microcirculation CO2 O2 progressive neurodegenerative disease autoimmune process Neurodegenerative disease - MS

Conclusion In patients suffering from MS a high frequency of CCSVI is established (using US and Venography) This proves relationship between MS and CCSVI. MS simptoms improve after the endovascular treatment