Evaluation of Extracranial and Intracranial Venous Structures with Doppler Sonography, Cranial MR Venography and Selective Venography in Relapsing-Remitting Multiple Sclerosis Patients and Their Comparisons with Healthy Controls

Abstract

Chronic cerebrospinal venous insufficiency (CCSVI), defined as impaired drainage at internal juguler vein (IJV) and/or azygos veins, has been accused of as an etiological factor in multiple sclerosis (MS) recently. This theory has initiated serious discussions due to negation of the autoimmune theory in MS. With this theory, MS etiopathogenesis has attracted attention due to its different perspectives and many studies have been started. A lot of studies are being conducted at many centers and conflicting results have been reported recently. We aimed to evaluate extracranial and intracranial venous structures by Doppler sonography (DS), cranial MR venography(MRV), and selective venography(SV) for the presence of CCSVI in MS patients and compare the results with healthy subjects. DS, SV and cranial MRV were performed in 25 relapsing-remitting MS patients´whereas cranial MRV and DS were performed in 20 healthy subjects. We found significantly more reflux in MS by DS than the control group (p<0.05, p=0.001). There was no significant difference in the intracranial veins by cranial MRV between two groups. Presence of 50% or more stenosis, detected by selective venography, in right IJV, left IJV, and azygos vein was in 72%, 76%, and 16% of MS patients, respectively. Presence of seventy five or more- stenosis in right IJV, and left IJV was detected in 60% and 48% of MS patients, respectively. There was azygos vein anomaly in 44% of MS patients. The CCSVI rate in our study was 76 % in MS patients. The high rate of collateral circulation that we detected may be an indication of the reflux we detected in patients. Presence of stenosis supporting the CCSVI theory was shown in our study with a limited number of MS patients. Further studies with more patients should be carried out to verify the results. It is not possible to say whether CSSVR is a pathology specific to the MS patient or if there is a physiological variation that may occur in everyone. In order to decide this, we think that more studies are needed in a larger number of patients to further the investigations and to determine the relationship between MS and CSR and / or its effects on MS symptoms.

Keywords

• multiple sclerosis
• cerebral veins
• intra-extracranial veins

Relapsing Remitting Multipl Skleroz Hastalarında Ekstrakraniyal ve İntrakraniyal Venöz Yapıların Doopler Sonografi, Kraniyal MR Venografi ve Selektif Venografi ile Değerlendirilmesi ve Sağlıklı Kontroller ile Karşılaştırılması

Abstract

Son yıllarda Multipl skleroz (MS) etyolojisinde, internal juguler ven (IJV) ve/veya azigos venlerde venöz drenaj bozukluğu olarak tanımlanan kronik serebrospinal venöz yetmezliğin (KSSVY) etkili olduğu ileri sürülmektedir. Bu teori, MS etyopatogenezinde etkili olduğu düşünülen otoimmün teoriyi toptan yadsıması nedeni ile ciddi tartışmalar başlatmıştır. Bu teori ile, MS etyopatogenezine farklı açılardan bakılması nedeniyle ilgi çekmiş ve bununla ilgili birçok çalışma başlatılmıştır. Çalışmamızda Doppler sonografi (DS), kranial MR venografi (MRV) ve selektif venografi (SV) ile MS hastalarında KSSVY’nin varlığının tespiti, ekstrakraniyal-intrakraniyal venöz yapıların yapısal- fonksiyonel açıdan incelenmesi, sağlıklı kişilerle karşılaştırılması amaçlanmıştır. 25 Relapsing Remitting MS hastasına DS, SV ve kraniyal MRV yapılırken, 20 sağlıklı kişiye kraniyal MR venografi ve Doppler sonografi yapıldı. Hastalarda DS’ de reflü varlığı açısından kontrol grubuna göre istatistiksel olarak anlamlı idi (p<0,05 P=0,001) . Kraniyal MRV’ de intrakraniyal venlerde morfolojik açıdan hasta ve sağlıklı grup arasında istatistiksel olarak anlamlı fark yoktu. Selektif venografide hastaların %72’sinde sağ IJV’de, %76’sında sol IJV’de, %12’sinde azigos vende %50 ve üzeri darlık saptanırken; hastaların %60 da sağ IJV de, %48 inde sol IJV de ve %16 sında ise azigos vende %75 ve üzeri darlık izlendi. Hastaların %44’ünde azigos vende anomali izlendi. Çalışmamızdaki MS hastalarında KSSVY görülme oranı %76 idi. Saptamış olduğumuz yüksek orandaki kolateral dolaşım varlığı, hastalarda saptadığımız reflünün bir göstergesi olabilir. Kontrol grubuna etik kurul selekktif selektif venografiye izin vermediği için normalde nasıl olduğunu bilmiyoruz. Bu çalışmada sınırlı sayıda hasta grubunda bu teoriyi destekleyecek darlık bazı hastalarda gösterilmiştir. KSSVY ‘liğin MS hastasına özgü bir patoloji mi yoksa herkeste olabilecek fizyolojik bir varyasyon olup olmadığını söylemek mümkün değildir. Buna karar vermek için incelemeleri ilerletmek MS ve KSSVY arasındaki ilişkiyi ve/veya bunun MS belirtileri üzerindeki etkilerini saptamak için daha çok sayıda hastada yapılacak geniş çalışmalara ihtiyaç olduğu düşüncesindeyiz. Bu konuda daha ileri çalışmalara ihtiyaç vardır.

Keywords

• Kronik serebrospinal venöz yetmezlik
• multipl skleroz
• serebral ven

References

1. 1. Lassmann H, Brück W and Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol 2007;17:210-8.
2. 2. Türk Börü U, Alp R, Sur H. and Gül L. Prevalence of multiple sclerosis door-to-door survey in Maltepe, Istanbul, Türkey. Neuroepidemiology, 2006;27:17-21.
3. 3. Kabat EA, Glusman M and Knaub V. Immunochemical estimation of albumin and gamma globulin in normal and pathological cerebrospinal fluid. Fed Proc 1948;7:306.
4. 4. Zamboni P, Menegatti E, Bartolomei I, et al. Intracranial venous haemodynamics in multiple sclerosis. Current Neuro vasc. Research 2007;4: 252–8
5. 5. Zamboni P. The big idea: iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis. J R Soc Med. 2006;99:589-93
6. 6. Zamboni P, Lanzara S, Mascoli F, Caggiati A, Liboni A. Inflammation in venous disease. Int Angiol 2008;27:361-93
7. 7. Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009;80:392–99
8. 8. Hojnacki D, Zamboni P, Lopez-Soriano A, et al. Use of neck magnetic resonance venography, Doppler sonography and selective venography for diagnosis of chronic cerebrospinal venous insufficiency: a pilot study in multiple sclerosis patients and healthy controls. Int Angiol 2010;29:127-39.

9. 9. Dolic K, Marr K, Valnarov V, et al. Sensitivity and specificity for screening of chronic cerebrospinal venous insufficiency using a multimodal non-invasive imaging approach in patients with multiple sclerosis. Funct Neurol. 2011;26:205-14
10. 10. Doepp F, Würfel JT, Pfueller CF, et al. Venous drainage in multiple sclerosis: a combined MRI and ultrasound study. Neurology. 2011;77:1745-51.
11. 11. Traboulsee AL et all. Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study. Lancet. 2014 Jan 11;383(9912):138-45
12. 12. Zamboni P, Menegatti E, Galeotti R, et al. The value of cerebral Doppler venous haemodynamics in the assessment of multiple sclerosis. J Neurol Sci 2009;282:21–7.
13. 13. Al-Omari MH, Rousan LA. Internal jugular vein morphology and hemodynamics in patients with multiple sclerosis. Int Anjiol 2010 ;29:115-20
14. 14. Baracchini C, Perini P, Calabrese M, et al. No evidence of al.chronic cerebrospinal venous insufficiency in clinically isolated syndrome suggestive of MS. Ann Neurol 2011;69:90-9
15. 15. Sundsrom P, Wahlin A, Ambarki K, et al. Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control study. Ann Neurol 2010; 68: 255–9.
16. 16. Zaniewski M, Kostecki J, Kuczmik W, et al. Neck duplex Doppler ultrasound evaluation for assessing chronic cerebrospinal venous insufficiency in multiple sclerosis patients. Phlebology 2012;22.
17. 17. Georgios Tsivgoulis et all. Chronic cerebrospinal venous insufficiency and multiple sclerosis: a comprehensive meta-analysis of case–control studies. Ther Adv Neurol Disord. 2014 Mar; 7(2): 114–136.
18. 18. Bastianello S, Romani A, Viselner G, et al. Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicenter study. BMC Neurol 2011;11:132.
19. 19. Nicolaides AN, Morovic S, Menegatti E, Viselner G, Zamboni P. Screening for chronic cerebrospinal venous insufficiency (CCSVI) using ultrasound: recommendations for a protocol. Funct Neurol. 2011;26:229-48.
20. 20. Doepp F, Paul F, Valdueza JM, et al. No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 2010;68: 173–83
21. 21. Neglen P, Darcey R, Olivier J, Raju S. Bilateral stenting at the iliocaval confluence. J Vasc Surg. 2010;51:1457–66
22. 22. Zamboni P, Galeotti R, Menegatti E, et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg 2009;50:1348–58.
23. 23. Simka M, Kostecki J, Zaniewski M et al. Extracranial Doppler sonographic criteria of chronic cerebrospinal venous insufficiency in the patients with multiple sclerosis. Int Angiol 2010 29:109-14.
24. 24. Zivadinov R, Marr K, Cutter G, et al. Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology 2011;77:138-44