Catheter venography for the assessment of internal jugular veins and azygous vein: Position statement by expert panel of the International Society for Neurovascular Disease

Simka M 1,2, Hubbard D 3,4, Siddiqui AH 5, Dake MD 6, Sclafani SJA 7,8, Al-Omari M 9, Eisele CG 10,11, Haskal ZJ 12, Ludyga T 1, Miloševič ZV 13, Sievert H 14,15, Stehling MK 16,17, Zapf S 18, Zorc M 19,20

1

- Euromedic Medical Center, Department of Vascular Surgery, Katowice, Poland - Private Healthcare Institution SANA, Department of Angiology, Pszczyna, Poland 3 - Applied fMRI Institute, San Diego, CA, USA 4 - Alliant International University, San Diego, CA, USA 5 - Departments of Neurosurgery and Radiology, University at Buffalo, State University of New York, Buffalo, NY, USA 6 - Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA 7 - State University of New York, Downstate Medical School, New York City, NY, USA 8 - Fresenius Vascular Care Brooklyn, New York City, NY, USA 9 - Jordan University of Science and Technology, Irbid, Jordan 10 - El Hospital de Niños Ricardo Gutierrez, Buenos Aires, Argentina 11 - Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina 12 - Division of Interventional Radiology, University of Maryland, Baltimore, MD, USA 13 - Clinical Radiology Institute, University Medical Centre, Ljubljana, Slovenia 14 - CardioVasculäre Centrum Frankfurt, Frankfurt, Germany 15 - Johann Wolfgang Goethe University, Frankfurt, Germany 16 – Boston University School of Medicine, Boston, MA, USA 17 - Ludwig-Maximilians-Universität München, Munich, Germany 18 - Institut für Bildgebende Diagnostik, Offenbach am Main, Germany 19 - International Center for Cardiovascular Diseases, Izola, Slovenia 20 - Institute of Histology and Embryology, University of Ljubljana, Ljubljana, Slovenia 2

Corresponding author: Marian Simka postal address: ul. Jednosci 20, 43-245 Studzionka, Poland e-mail: [email protected] phone & fax: +48-327814651 Potential conflicts of interest and financial disclosures: M.S. – travel expenses, consulting fees: Servier International, BIBA Medical, American Access Care, Esaote International; 1

D.H. – no conflict of interest declared; AH.S. – no conflict of interest declared; MD.D. – no conflict of interest declared; SJA.S. – consulting fees: Fresenius Vascular Access Centers; M. A-O. – no conflict of interest declared; CG.E. – no conflict of interest declared; ZJ.H. – no conflict of interest declared; T.L. – co-owner of Euromedic Medical Center; ZV.M. – no conflict of interest declared; H.S. – study honoraries, travel expenses, consulting fees: Abbott, Access Closure, AGA, Angiomed, Arstasis, Atritech, Atrium, Avinger, Bard, Boston Scientific, Bridgepoint, Cardiac Dimensions, CardioKinetix, CardioMEMS, Coherex, Contego, CSI, EndoCross, EndoTex, Epitek, Evalve, ev3, FlowCardia, Gore, Guidant, Guided Delivery Systems, Inc., InSeal Medical, Lumen Biomedical, HL T, Kensey Nash, Kyoto Medical, Lifetech, Lutonix, Medinol, Medtronic, NDC, NMT, OAS, Occlutech, Osprey, Ovalis, Pathway, PendraCare, Percardia, pfm Medical, Rox Medical, Sadra, Sorin, Spectranetics, SquareOne, Trireme, Trivascular, Velocimed, Veryan; MK.S. – no conflict of interest declared; S.Z. – no conflict of interest declared; M.Z. – no conflict of interest declared.

This paper it the position statement of the International Society for Neurovascular Disease and has been drafted at 2nd Annual Meeting of the ISNVD in Orlando, Florida, USA, 18-22 February 2012.

2

Abstract This document by expert panel of International Society for Neurovascular Disease is aimed at presenting current technique and interpretation of catheter venography of the internal jugular veins, azygous vein and other veins draining the central nervous system. Although interventionalists agree on general rules, significant differences exist in terms of details of venographic technique and interpretations of angiographic pictures. It is also suggested that debatable findings should be investigated using multimodal diagnostics. Finally, the authors recommend that any publication on chronic cerebrospinal venous insufficiency should include detailed description of venographic technique used, to facilitate a comparison of published results in this area.

Ziel dieser Veröffentlichung eines Expertenpanels der International

Society for

Neurovascular Disease ist es, die derzeitigen Techniken und Interpretationsmöglichkeiten der Kathetervenographie der Vena jugularis interna, der Vena azygos und anderer Venen, die

das

Zentralnervensystem

drainieren,

zu

präsentieren.

Trotz

prinzipieller

Übereinstimmung in der allgemeinen Vorgehensweise bestehen deutliche Unterschiede in der venographischen Technik und Bildinterpretation. Es wird daher vorgeschlagen, unklare Befunde einer multimodalen Diagnostik zuzuführen. Ebenso sollte jede Publikation zum Thema Chronisch Venöse Cerebro-Spinale Insuffizienz die angewendete venographische Technik

detailliert

auflisten,

um

so

eine

Vergleichbarkeit

verschiedener

Studien zu gewährleisten. Keywords: endovascular therapy; neurovascular interventions; multiple sclerosis; phlebography; vascular malformations. Running head: Catheter venography and CCSVI

3

Introduction The main goal of this document, written by the expert panel under the auspices of the International Society for Neurovascular Disease, is to present “white paper” that describes how catheter venography of the internal jugular veins, the azygous vein and other veins that may be involved in neurological pathology is currently performed and interpreted. It should be emphasized that this document is not aimed at giving recommendation: how to perform catheter venography of these veins and to interpret images. Although interventionalists agree on general venographic rules, big differences exist between the centers in terms of details. Therefore, doctors should be familiar with techniques and interpretations of venographic pictures of these veins. They should also know how these different venographic techniques and interpretations of the images can influence final assessment, safety of endovascular procedure and clinical outcomes. Catheter venography of the veins draining the central nervous system Although catheter venography is widely accepted as “golden standard” for the assessment of venous pathologies, as far as the veins draining the central nervous system are concerned it is actually a “tarnished” standard. Contrary to some well-recognized venous territories, relatively little is known about anatomy, physiological flow and hemodynamics of the internal jugular veins. Even less is known about the azygous vein [1,2,3]. Consequently, catheter angiography and its interpretation are currently performed according to the rules governing examination of the other veins. Still, differences exist between the technique and interpretation amongst centers [4,5,6,7,8,9,10,11,12,16,17,19] Since our knowledge about anatomy and physiology of the veins that may be involved in pathophysiology of neurological disorders (especially: multiple sclerosis) in the setting of the so-called chronic cerebrospinal venous insufficiency (CCSVI) is at its infancy, there are many problems that should be 4

addressed. For the time being, it seems that a widely accepted venographic protocol cannot be created, because scientific evidence supporting a particular technique or interpretation of the images is not yet available. It is know that venography can produce a number of confusing images. In general, authors of this document agree that debatable venographic findings should be thoroughly investigated by means of multimodal approach, integrating classic catheter angiography with intravascular ultrasound (IVUS) and perhaps also other novel intravascular imaging modalities. Still, diagnostic value of such a multimodal approach should also be validated by well-designed studies. The authors agree that venographically-defined abnormalities, which can be relevant for physiological venous outflow from the brain and spinal cord seem to exhibit different clinical meaning. Consequently, they can be categorized into four main groups: 1. Obvious venographic abnormalities of the internal jugular veins and/or azygous vein; most of the interventionalists agree that such venographic pictures reflect a pathology. 2. Debatable venographic abnormalities of the internal jugular veins and/or vertebral veins, and/or azygous vein; at the moment only some centers interpret these findings as abnormal. 3. Angiographic signs of impaired venous outflow in non-cerebrospinal territories, which can be of importance for the proper venous drainage of the central nervous system, e.g. ascending lumbar, left iliac and left renal vein; the meaning of these abnormalities in terms of neurological pathophysiology remains uncertain. 4. Angiographically-defined abnormalities of intracranial veins and sinuses; these lesions seem to be pathological, but safety of diagnostic and therapeutic procedures in this territory is not determined (probably they are less safe if compared with extracranial veins).

5

Basing on the already published research, obvious venographic abnormalities of the internal jugular veins and/or azygous vein include the lesions that present with all of the below-presented criteria:  lesion detected in any part of internal jugular vein, uni- or bilaterally (it comprises also lesions of the brachiocephalic veins) (Fig. 1) or lesion of the arch of the azygous vein and/or ascending azygous vein or lesion of the hemiazygous or accessory hemiazygous vein, if these veins constitute primary outflow route from the spinal cord;  at least 50% stenosis of the vein, if compared with the diameter of adjacent segment of the vein; it also comprises: severe hypoplasia (Fig. 2), complete agenesia and secondary occlusion of the vein (for example, thrombotic) or intraluminal structures, such as: webs, septa, membranes, etc., which are associated with at least one additional sign of impaired outflow: o no outflow of contrast from the vein, o outflow of contrast slowed down, i.e. its retention in the examined vein longer that one cardiac cycle, o backward flow of injected contrast (using low-pressure and low-volume injection), o outflow of injected contrast through collaterals, instead of the main vein.  abnormality should be demonstrated using hand injection of the contrast or lowpressure automatic injector. 6

Debatable venographic abnormalities include any of the below-presented findings, which seem to be a reflection of pathological blood outflow from the central nervous system, but do not meet the criteria of an obvious pathology:  lesions of the arch of the azygous vein or ascending azygous vein in the patients with dominant hemiazygous outflow route;  lesions of the distal part of the azygous vein, hemiazygous vein, or their tributaries;  lesions of the hemiazygous or accessory hemiazygous vein, if these veins are not dominant;  abnormalities of the vertebral veins;  lesions revealed using high-pressure injector;  stenosis less than 50%, with no other sign of compromised outflow;  intraluminal structures not associated with the signs of compromised outflow;  stenosis or intraluminal structures associated with prestenotic dilation of the vein, but no other signs of compromised outflow;  phasic stenosis, i.e. a narrowing, which is not visible permanently, but only during a fraction of the cardiac or respiratory cycle;  stenosis, which is visible only using inflation of compliant angioplastic balloon or using IVUS, with no additional venographic signs of compromised outflow. The authors agree that more research is needed (primarily, using multimodal approach) to evaluate diagnostic accuracy of these parameters and criteria. Especially, threshold of 50% degree stenosis, which is actually an extrapolation from arterial pathology, seems debatable. Perhaps, in a case of venous outflow abnormality even a lower degree stenosis is of clinical importance. This—however—needs further exploration.

7

Consequently, the authors of this position document strongly suggest that any publication on CCSVI issues should include detailed description of venographic technique used and detailed definition of pathological result of such a venography. This will enable a comparison of future publications in this field. Unfortunately, already published research often lacks such a detailed description, making analysis of presented data very difficult. Safety and ethical issues Endovascular procedures for CCSVI become an emerging area of interventional radiological practice and at the moment a number of prospective randomized, as well as openlabel clinical studies are underway. International Society for Neurovascular Disease strongly emphasizes the importance of good clinical practice in such trials. The research on this controversial topic should be well designed to avoid unnecessary harm for the patients. In addition to the legal and ethical issues related to endovascular diagnostic and therapeutic procedures in the settings of CCSVI, several technical barriers must also be solved before such procedures become a standard. This include: the technique of invasive and non-invasive diagnostics, interpretation of the findings and qualification of the patients for endovascular interventions. For the purpose of this discussion we will assume that only severe stenoses, associated with significant and apparent flow abnormalities (as noted above, such as: reversal of the flow, collaterals, etc.) should be treated. Of course, such procedures should be performed exclusively within clinical trials, until results of such trials will clearly demonstrate the safety and clinical benefits of the treatment. However, how should we manage not-obviously stenosed jugular valves, narrowings of the azygous vein and internal jugular veins that are not accompanied by significant hemodynamic disturbances, or hemodynamically significant lesions in the veins, which are not clearly involved in neurological pathology (iliac, renal, 8

etc.)? Although both venography and balloon angioplasty are safe, they are not risk-free. Thus, venography should not be performed in every assessable vein, but only in the veins that are likely to be both affected and manageable. The more extensive the examination is, the higher are: the contrast load, nephrotoxicity risk, vascular iatrogenic complications and cumulative radiation dose. Similarly, angioplasty should be performed only to address the lesions, which have been implicated as causal for neurological pathology. Which of the above-mention measures should be applied, remains an open question. This dilemma is likely to be solved only by well-designed prospective studies, but some preliminary conclusions can potentially be drawn from currently available literature. It should be assumed that a vein responsible for neurological pathology is draining the part of the central nervous system containing anatomical structures that are responsible for this neurological deficit. For example: ataxia is usually caused by cerebellar plaques. Then, the symptom is more likely to be caused by abnormal outflow from the jugular veins, which drain the cerebellum than by abnormal azygous outflow. On the contrary: plaques in the thoracic segment of the spinal cord are more likely to be linked to pathological azygous outflow. Technical dilemma associated with catheter venography Uncertainties related to the technique and interpretation of catheter venography in CCSVI patients can be grouped into several domains: 1. Vascular access. Most venographies are currently performed through femoral access. Access through an upper extremity vein is a theoretical option in the case of agenesis of inferior vena cava. A direct puncture of the internal jugular vein can also be used, but can be technically challenging if such a vein is hypoplastic or collapsed. Alternatively, an access through great saphenous vein 9

under sonographic control can be used. Still, femoral access is the preferred route. However, there are some issues, which need to be considered when using femoral access. Firstly, if venography is accompanied by pressure gradient measurements, the pressure measurement in the internal jugular vein may not be reliable (jugular valve is potentially kept open by the diagnostic catheter – possibly reducing or eliminating any cross-valve pressure differential). Options may include using a smaller caliber device such as a pressure-sensing wire, which is less disruptive to the valves. Alternatively for accurate pressure measurement a direct jugular access may be considered. Secondly, there is a discussion about which femoral vein (right or left), should be punctured. Insertion of the catheter through the left femoral vein allows a much easier assessment of the left iliac vein (May-Thurner syndrome), the ascending lumbar veins and the left renal vein (nutcracker syndrome). On the other hand, an access through the right femoral vein makes the angiography and angioplasty of the left internal jugular and azygous veins much easier, particularly in a case of tortuous iliac and left brachiocephalic veins. In addition, there is currently no evidence to support angioplasty of asymptomatic stenosis of the left iliac or left renal vein, thus a potential benefit from left femoral access is not clear. We therefore recommend the right femoral (or saphenous) vein access for routine assessment and possible consideration of an angioplasty of the internal jugular and azygous veins. Left femoral vein access may be an option if the screening of additional veins, such as left iliac vein is planned. 2. Angiographic contrast. Angiographic contrast may be used diluted (1:1) or non-diluted. Diluted contrast allows a better visualization of endoluminal structures (valve leaflets, webs, etc.). However, nondiluted contrast allows a better opacification of epidural and other collaterals, as well as a better estimation of overall features of the veins. 10

There is no clear consensus on whether the contrast should be hand- or pressure-injected. Hand injections are performed using smaller volumes of contrast under lower pressure. Pressure injectors are higher volume and higher pressure. There are proponents for both approaches. While hand injection mimics physiological venous flow, pressure injectors are more accurate, reproducible and make some flow-related analyses quantifiable. Either or both approaches may be utilized, depending on the objectives desired. There are some modern injectors that allow a low-pressure administration of the contrast and perhaps such equipment should be preferentially used. 3. Interpretation of venographic pictures. Left versus right jugular vein It may seem obvious that venography of both internal jugular veins should be interpreted in the same way. But there are some arguments favoring a different approach to the right vs. left (or: dominant vs. non-dominant) jugular vein. Right internal jugular vein is usually bigger, its valve has longer leaflets; left internal jugular vein is smaller and has more transversally oriented valve leaflets. Perhaps these parameters should be taken into account while deciding if the vein assessed should be interpreted as normal (Fig. 3) or pathological [4]. These dilemmas will be of special importance if the definition of pathology is based on quantitative assessment of the flow, which in most normal individuals is asymmetric. It should also be emphasized that asymmetry between the jugular veins is not pathological. However, other attributes, such as stenoses, need to be considered in the context of each individual jugular vein. In terms of what should be regarded as a stenosis, little consensus has been reached. The authors of already published research have utilized an arbitrary definition of 50% luminal restriction when compared to nominal diameter of the proximal vein. However, the jugular vein stenosis is more difficult to evaluate because it usually dilates cranially to the valve (Fig.

11

4). Therefore, perhaps a nominal diameter of the vein proximal to the bulb, or most dilated part of the distal jugular vein should be utilized. Besides, unless the diagnostic catheter is placed at the level of the skull base, it is likely to miss a number of anatomical and flow related anomalies in the upper jugular vein (Fig. 5). Also, if an angled catheter is used and is positioned medially, the injected contrast preferentially opacifies the vertebral and cervical epidural plexuses through the mastoid and condylar emissary veins, suggesting an underlying hemodynamic anomaly, when none actually exists. Therefore, it is important that an angled catheter is directed laterally at the level of the jugular foramen. Frequently the transverse process of the C1 vertebra visibly indents the jugular vein (since the vein lies on this bony structure). However, in such a case a compliant balloon inflated under low pressure and Valsalva maneuver usually confirm that no pathology actually exists. Venography with neck rotation to the opposite direction can reveal if such a compression is transient (position-dependent) or a fixed one. It is also known that aberrant neck muscles, especially omohyoid muscle, can significantly squeeze IJV and that such a compression may be poorly visible on standard venography [18]. 4. Interpretation of venographic pictures. Jugular valve. What should be regarded as a pathologic valve? Currently there are two ways of thinking. Firstly, some authors interpret jugular valve as abnormal if a narrowing at its level is detected: using venography, through inflating a compliant angioplastic balloon, or through intravascular ultrasound (IVUS). Secondly, some suggest that the valve should be interpreted as abnormal if flow disturbances are found (no outflow through the vein, venous outflow slowed down, reversed flow direction, outflow through collaterals, etc.) in addition to anatomical stricture. Probably more research in healthy individuals is needed to solve this problem [13,14,15] Such

12

a research—however—will not be easy to perform taking into account an invasive nature of venography. 5. Interpretation of venographic pictures. Azygous vein There is a huge discordance between performance and interpretation of azygous venograms. Firstly, there are no standards as to where exactly along the course of the azygous vein should a contrast injection be made. Any injection made in the arch is likely to miss pathology in more distal portions of the vein, while abdominal injections in a much smaller caliber vessel may artificially induce reverse flow and evidence of collaterals, including epidural venous channels. A standard position of diagnostic catheter may be at the level of the diaphragm (T12), since this allows estimation of essentially the entire spinal cord venous outflow, since the spinal cord conus (terminal segment of the spinal cord) is typically located at L1. Secondly, interpretation of venography varies as well, with some authors suggesting that any narrowing more than 50% is pathological, while others interpret a narrowing as pathological only if it is accompanied by reversed flow or outflow through collateral network (Fig. 6). Consequently, azygous vein pathology in multiple sclerosis patients is diagnosed in some centers in 80-90% of the cases [7,12], while others find pathology less frequently [16,21] or only in 5-10% [4,5,9]. The valve of the azygous vein is typically seen at its junction with the superior vena cava. Sometimes it is very difficult to negotiate with diagnostic wires and catheters across this valve. For the time being it remains unclear if such a difficult passing through represents a pathology, or is the sign of a perfectly competent valve. It should also be remembered that the azygous vein is typically narrowed where it is arching over the right main bronchus and a “stenosis” in this area is not necessarily pathological. In addition, some azygous lesions are simply reflective of intra-thoracic pressures. Therefore they are likely to be a product of 13

respiratory cycles (phasic stenosis) and not true anatomical lesions. Thus, if a lesion is identified, it should be investigated during an inspiratory arrest to induce maximal thoracic venous return. Also, IVUS that will show variations in luminal dimensions during the various respiratory phases can be applied. 6. Classification of outflow abnormalities. According to the published classification [4], abnormal venographic flow patterns can be categorized into four grades:  grade 1: venous outflow slowed down, no reflux detected;  grade 2: venous outflow slowed down, mild reflux and/or pre-stenotic dilation of the vein;  grade 3: venous outflow slowed down, with reflux and outflow through collaterals;  grade 4: no outflow through the vein, huge outflow through collaterals. Of as yet, an alternative classification has not been suggested (which does not mean that the above-presented scale is perfect). 7. The role of IVUS in the assessment of CCSVI. Should IVUS be an integral part of the venography? What are advantages and disadvantages of such an approach? Doctors who are using IVUS routinely have found this diagnostic tool to be incredibly helpful as an adjunctive to catheter venography [5, 22,23]. It is well known that venography is less sensitive than IVUS in detecting endoluminal anomalies (septae, chronic organized/recanalized thrombi, valve leaflet anomalies, phasic variability, etc.). IVUS can be performed safely, with minimal change in guidewires and catheters utilized, fluoroscopy time and contrast volume. While many multiple sclerosis patients demonstrate venographic 14

anomalies, IVUS reveals even more lesions, since CCSVI appears to be principally an endoluminal disease (Fig. 7). Thus, a combination of venography and IVUS provides a comprehensive assessment of venous anatomy, endoluminal structures and the flow. Although at the moment the use of IVUS could be recommended for the diagnosing CCSVI, an actual value of this test should be evaluated by future research. Of special importance will be the problem: whether the treatment of lesions that can be detected by IVUS only, and not with catheter venography alone, will give an additional clinical benefit to the patients.

How to evaluate and to manage stenoses in the upper part of the internal jugular vein, especially at the level of jugular foramen? In some patients the upper (cranially to the facial vein) internal jugular vein is narrowed, hypoplastic, sometimes with associated outflow impairment. The questions regarding this particular problem are:  should we interpret such a vein as pathological according to the diameter measurements (if yes, which cutoff should be applied);  alternatively, should we rather look at flow disturbances, especially at backflow of the injected contrast;  what is the best mode of the management of such stenosed venous segment: standard balloon angioplasty (pro – a relatively safe procedure; contra – high rate of restenosis), stenting (pro – more efficient than PTA; contra – risk of migration, risk of thrombosis or occlusion due to intimal hyperplasia), cutting balloon (pro − more efficient than PTA, more safe than stenting; contra – thrombotic or bleeding complications possible).

15

Should we assess stenoses of intracranial sinuses? Catheterization, mechanical and chemical thrombolysis, angioplasty and stenting of intracranial venous sinuses are performed by neurointerventionalists for venous thrombosis, pseudotumor cerebri associated with venous stenosis and a few other uncommon disorders. However, the magnitude of possible complications is significantly higher than in a case of similar interventions in the extracranial veins. The most dramatic potential complication is a perforation of the jugular bulb or sinus, or perforation with a wire of cortical or cerebellar vein, with devastating and usually fatal intracerebral hemorrhage. In addition, intracranial veins are not very plastic and compliant, since these venous channels are encased partly in bone and partly in rigid leafs of the dura permeated by delicate and rather “unpredictable” draining veins. The questions regarding the management of intracranial sinuses are:  should we perform venography of these veins routinely, or only in very selected cases, since most of the doctors will not manage a lesion in this location even if detected, while the risk of diagnostic venography in this particular area cannot be neglected;  should we perform therapeutic procedures in this territory, or rather should we wait until an evidence of clinical benefit from the treatments performed in other venous territories (like the internal jugular veins) will be more obvious;  pre-procedural evaluation of intracranial vein routinely consists of MR venography; it is well-known that there is a lot of artifacts associated with this imaging test, for example very often the left transverse sinus does not show at MRV, while actually it is perfectly patent;  what is the best way to evaluate intracranial sinuses before and after endovascular treatment?

16

Phasic stenosis Should a narrowing of the vein, which is not visible permanently, but only during a fraction of the cardiac or respiratory cycle, be regarded as a pathology? And does such a lesion require the treatment? Balloon angioplasty is not likely to be successful in such a case. Stenting of the “phasic” stenosis may be associated with a high risk of stent migration. Moreover, intimal hyperplasia inside the stent in these cases seems to be a big problem. Perhaps such lesions should be left untouched, until other therapeutic strategies are developed.

17

References: 1. Al-Omari MH, Al-Bashir A. Internal jugular vein valve morphology in the patients with chronic cerebrospinal venous insufficiency (CCSVI); angiographic findings and schematic demonstrations. Rev Recent Clin Trials 2012; 7: 83-7. 2. Beelen R, Maene L, Castenmiller P, Decoene V, Degrieck I. Evolution in quality of life and epidemiological impact after endovascular treatment of chronic cerebro-spinal venous insufficiency in patients with multiple sclerosis. Phlebology 2012;27 Suppl 1:187-9. 3. Eisele G, Schulte C, Cannellotto M, Savino A, Simonelli D, Spirito G. Experiencia inicial en el tratamiento de la insufficientia venosa cerebro espinal crónica: resultados preliminares en 15 pacientes. Flebologia y Linfologia Lecturas Vasculares 2012; 7: 1124-7. 4. Ludyga T, Kazibudzki M, Simka M, Hartel M, Swierad M, Piegza J, Latacz P, Sedlak L, Tochowicz M. Endovascular treatment for chronic cerebrospinal venous insufficiency: is the procedure safe? Phlebology 2010; 25: 286-95. 5. Lugli M, Morelli M, Guerzoni S, Maleti O. The hypothesis of patho-physiological correlation between chronic cerebrospinal venous insufficiency and multiple sclerosis: rationale of treatment. Phlebology 2012; 27 Suppl 1:178-86. 6. Mandato KD, Hegener PF, Siskin GP, Haskal ZJ, Englander MJ, Garla S, Mitchell N, Reutzel L, Doti C. Safety of endovascular treatment of chronic cerebrospinal venous insufficiency: a report of 240 patients with multiple sclerosis. J Vasc Intervent Radiol 2012; 23: 55-9. 7. Petrov I, Grozdinski L, Kaninski G, Iliev N, Iloska M, Radev A. Safety profile of endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Endovasc Ther 2011; 18: 314-23. 8. Sclafani S. Chronic cerebrospinal venous insufficiency: a new paradigm and therapy for multiple sclerosis. Endovascular Today 2010; July:41-6. 9. Sclafani SJ. Intravascular ultrasound in the diagnosis and treatment of chronic cerebrospinal venous insufficiency. Tech Vasc Interv Radiol 2012; 15: 131-43. 10. Simka M, Janas P, Ludyga T, Latacz P, Kazibudzki M. Endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. Vasc Dis Manag 2012; 9: E149-54. 18

11. Simka M, Latacz P, Ludyga T, Kazibudzki M, Swierad M, Janas P, Piegza J. Prevalence of extracranial venous abnormalities: results from a sample of 586 multiple sclerosis patients. Funct Neurol 2011; 26: 197-203. 12. Simka M, Ludyga T, Latacz P, Kazibudzki M. Diagnostic accuracy of current sonographic criteria for the detection of outflow abnormalities in the internal jugular veins. Phlebology 2012; doi: 10.1258/phleb.2012.011125 13. Simka M, Majewski E, Fortuna M, Zaniewski M. Internal jugular vein entrapment in a multiple sclerosis patient. Case Rep Surg. 2012; 293568. 14. Tsuladze II. The selective phlebography of the large tributaries of the vena cava system in the diagnosis of venous circulatory disorders in the spinal complex. Zh Vopr Neirokhir Im N N Burdenko 1999; 2: 8-13. 15. Valecchi D, Bacci D, Gulisano M, Sgambati E, Sibilio M, Lipomas M, Macchi C. Internal jugular valves: an assessment of prevalence, morphology and competence by color Doppler echography in 240 healthy subjects. Ital J Anat Embryol 2010; 115: 185-9. 16. Weber J. Phlebographie: Bein- Becken- und Abdominalvenen in Anatomie und Funktion. Rabe Verlag, Bonn 2010. 17. Werner JD, Siskin GP, Mandato K, Englander M, Herr A. Review of venous anatomy for venographic interpretation in chronic cerebrospinal venous insufficiency. J Vasc Interv Radiol 2011; 22: 1681-90. 18. Yamout B, Herlopian A, Issa Z, Habib RH, Fawaz A, Salame J, Wadih A, Awdeh H, Muallem N, Raad R, Al-Kutoubi A. Extracranial venous stenosis is an unlikely cause of multiple sclerosis. Mult Scler 2010; 6:1341-8. 19. Zamboni P, Consorti G, Galeotti R, Gianesini S, Menegatti E, Tacconi G, Carinci F. Venous collateral circulation of the extracranial cerebrospinal outflow routes. Curr Neurovasc Res 2009; 6: 204-12. 20. Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Tacconi G, Dall’Ara S, Bartolomei I, Salvi F. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009; 80:392-399. 21. Zamboni P, Galeotti R, Weinstock-Guttman B, Kennedy C, Salvi F, Zivadinov R. Venous angioplasty in patients with multiple sclerosis: results of a pilot study. Eur J Vasc Endovasc Surg 2012; 43: 116-22.

19

22. Zivadinov R, Marr K, Cutter G, Ramanathan M, Benedict RH, Kennedy C, Elfadil M, Yeh AE, Reuther J, Brooks C, Hunt K, Andrews M, Carl E, Dwyer MG, Hojnacki D, Weinstock-Guttman

B.

Prevalence,

sensitivity,

and

specificity

of

chronic

cerebrospinal venous insufficiency in MS. Neurology 2011; 77: 138-44. 23. Scalise F, Farina M, Manfredi M, Auguadro C, Novelli E. Assessment of jugular endovascular malformations in chronic cerebrospinal venous insufficiency: colourDoppler scanning and catheter venography compared with intravascular ultrasound. Phlebology 2012; doi: 10.1258/phleb.2012.012079.

20

Fig.1 – Transverse membrane (arrow) compromising outflow from the left brachiocephalic vein.

21

Fig.2 – Complete occlusion of the left internal jugular vein (arrowhead). Contrast is flowing out through the external jugular vein (arrow).

22

Fig.3 – Normally-appearing left internal jugular vein. Valve leaflets are visible (arrow), but no stenosis is detected and contrast is freely flowing to the brachiocephalic vein.

23

Fig.4 – Typical stenosis of the left internal jugular vein at the level of malformed jugular valve (arrow) with dilatation of middle part of the vein.

24

Fig.5 – Tandem stenosis of the right internal jugular vein: There is a minor stenosis at the level of jugular valve (arrow) and a tight stenosis below the skull (arrowhead).

25

Fig. 6 – Severe stenosis of the azygous vein distally from the arch (arrows) with outflow of injected contrast through collateral network (arrowheads)

26

Fig.7 – Stenosis of the left internal jugular vein at the level of jugular valve. A: venographic picture of malformed valve (arrows); B: IVUS reveals an immobile thickened valve; C: longitudinal IVUS reformation shows an echogenic material (circled areas) illustrating intraluminal nature of the stenosis.

27