Aktuelle Neurologie 2011; 38(07): 332-338
DOI: 10.1055/s-0031-1287850
Aktuelles Thema
© Georg Thieme Verlag KG Stuttgart · New York

Chronisch venöse Insuffizienz als Ursache der Multiplen Sklerose?

Is Chronic Cerebrospinal Venous Insufficiency a Cause of Multiple Sclerosis?
F. Doepp
3   Abteilung für Neurologie, Segeberger Kliniken, Bad Segeberg
,
F. Paul
1   Abteilung für Neurologie, Universitätsklinikum Charité, Humboldt Universität, Berlin
2   NeuroCure Clinical Research Centre, Universitätsklinikum Charité, Humboldt Universität, Berlin
,
J. M. Valdueza
3   Abteilung für Neurologie, Segeberger Kliniken, Bad Segeberg
,
S. J. Schreiber
1   Abteilung für Neurologie, Universitätsklinikum Charité, Humboldt Universität, Berlin
› Author Affiliations
Further Information

Publication History

Publication Date:
24 October 2011 (online)

Zusammenfassung

Kürzlich wurde die sog. chronische zerebrospinale venöse Insuffizienz („CCSVI“) als neue Hypothese zur Pathogenese der Multiplen Sklerose (MS) von Zamboni et al. postuliert: Hiernach führt eine Behinderung des zerebrozervikalen venösen Abstroms zu einer Stase in zerebralen Venen und zu einer transendothelialen Extravasation von Erythrozyten mit nachfolgender Entzündungsreaktion im Gewebe. Basierend auf dieser Hypothese und eigenen sonografischen sowie angiografischen Daten wurden therapeutische Interventionen mittels Angioplastie zur Behandlung der MS von Zamboni et al. propagiert. Die „CCSVI“-Hypothese, von ihren Erfindern als „die große Idee“ bezeichnet, hat beträchtliches Interesse nicht nur unter Wissenschaftlern und Ärzten, aber auch bei Patienten, Angehörigen und in den Massenmedien erzeugt. Bislang fehlt jedoch eine Reproduktion der Ergebnisse durch unabhängige Arbeitsgruppen, und die Zahl der negativen Publikationen, die mit verschiedenen Verfahren die „CCSVI“-Hypothese in Frage stellen, steigt kontinuierlich. Diese Übersichtsarbeit fasst die „CCSVI“-Theorie und die Zamboni-Daten zusammen und stellt diesen die neueren, überwiegend kritischen Arbeiten gegenüber. Nach dem gegenwärtigen Stand des Wissens gibt es keine wissenschaftliche Plausibilität für die „CCSVI“-Hypothese und keine weiteren Daten, die diese stützen würden. Daher gibt es keine Indikation und Rechtfertigung für angioplastische Interventionen bei Patienten mit MS.

Abstract

Recently, chronic cerebrospinal venous insufficiency („CCSVI“) was suggested as a new pathogenetic hypothesis in multiple sclerosis (MS) by Zamboni and colleagues: impairment of the cerebrocervical venous outflow by venous stenoses or other vessel obstructions should lead to stasis in cerebral veins with transendothelial extravasation of erythrocytes and subsequent inflammatory reactions in brain tissue. Based on this hypothesis and their own sonographic and angiographic data, therapeutic interventions by means of angioplasty were proposed as treatment for MS by Zamboni et al.. The “CCSVI” hypothesis, termed “the big idea” by Zamboni and colleagues, has caused substantial interest in the scientific community as well as amongst patients, caregivers, and the mass media. However, an independent confirmation of the data published by Zamboni et al. is lacking, while the number of negative studies with various techniques that question the „CCSVI“ hypothesis is steadily increasing. The aim of this review is to delineate the „CCSVI“ hypothesis and to summarise the data published by Zamboni et al. and subsequent investigators which mostly refute this hypothesis. According to the current evidence, there is no scientific plausibility of the “CCSVI” hypothesis and no further data that support this pathogenetic concept. Thus, there is no justification for any angioplastic therapies in MS patients.

 
  • Literatur

  • 1 Zamboni P. The big idea: iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis. J R Soc Med 2006; 99: 589-593
  • 2 Zamboni P, Menegatti E, Bartolomei I et al. Intracranial venous hemodynamics in multiple sclerosis. Curr Neurovasc Res 2007; 4: 252-258
  • 3 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: 21-27
  • 4 Zamboni P, Galeotti R, Menegatti E et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009; 80: 392-399
  • 5 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: 1348-1358
  • 6 Khan O, Filippi M, Freedman MS et al. Chronic cerebrospinal venous insufficiency and multiple sclerosis. Ann Neurol 2010; 67: 286-290
  • 7 Wattjes M, Doepp F Bendszus et al. „Chronic cerebrospinal venous insufficiency“ in multiple sclerosis – is multiple sclerosis a disease of the cerebrospinal outflow system?. RoFo 2011; 183: 523-530
  • 8 Stolz E, Kaps M, Kern A et al. Transcranial color-coded duplex sonography of intracranial veins and sinuses in adults. Reference data from 130 volunteers. Stroke 1999; 30: 1070-1075
  • 9 Nicolaides AN. The international consensus group. “The investigation of chronic venous insufficiency. A consensus statement”. Circulation 2000; 102: 126-163
  • 10 Nedelmann M, Eicke BM, Dieterich M. Functional and morphological criteria of internal jugular valve insufficiency as assessed by ultrasound. J Neuroimaging 2005; 15: 70-75
  • 11 Walter C. Duplexsonografischer Befund einer retrograden Strömung in der linken V. jugularis interna durch atem- und lageabhängige Kompression der V. brachiocephalica sinistra: Fallbericht und Lteraturübersicht. Ultraschall in Med 2002; 23: 260-263
  • 12 Lichtenstein D, Saifi R, Augarde R et al. The internal jugular veins are asymmetric. Usefulness of ultrasound before catheterization. Intensive care Med 2001; 27: 301-305
  • 13 Hoffmann O, Weih M, von Münster T et al. Blood flow velocities in the vertebral veins of healthy subjects: A duplex sonography study. J Neuroimaging 1999; 9: 198-200
  • 14 Doepp F, Schreiber SJ, von Münster T et al. How does the blood leave the brain? A systematic ultrasound analysis of cerebral venous drainage patterns. Neuroradiology 2004; 46: 565-570
  • 15 Valdueza JM, von Münster T, Hoffmann O et al. Postural dependency of the cerebral venous outflow. Lancet 2000; 355: 200-201
  • 16 Krogias C, Schröder A, Wiendl H et al. „Chronische cerebrospinale venöse Insuffizienz“ und Multiple Sclerose. Kritische Analyse und erste Untersuchungen an einem unselektierten MS-Kollektiv. Nervenarzt 2010; 81: 740-746
  • 17 Doepp F, Paul F, Valdueza JM et al. No cerebro-cervical venous congestion in patients with multiple sclerosis. Ann Neurol 2010; 68: 173-183
  • 18 Mayer CA, Pfeilschifter W, Lorenz MW et al. The perfect crime? CCSVI not leaving a trace in MS. J Neurol Neurosurg Psychiatry 2011; 82: 436-440
  • 19 Baracchini C, Perini P, Calabrese M et al. No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset. Ann Neurol 2011; 69: 90-99
  • 20 Zivadinov R, Marr K, Cutter G et al. Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology 2011; 77: 138-144
  • 21 Tanaka M, Uchizumi H, Tanaka K. Evaluation of blood flow and the cross-sectional area of internal jugular vein in Japanese multiple sclerosis and neuromyelitis optica patients. Rinsho Shinkeigaku 2011; 51: 430-432
  • 22 Centonze D, Floris R, Stefanini M et al. Proposed chronic cerebrospinal venous insufficiency criteria do not predict multiple sclerosis risk or severity. Ann Neurol 2011; Jul 70: 52-59
  • 23 Auriel E, Karni A, Bornstein NM et al. Extra-cranial venous flow in patients with multiple sclerosis. J Neurol Sci 2011; 309: 102-104
  • 24 Tsivgoulis G, Mantatzis M, Bogiatzi C et al. Extracranial venous hemodynamics in multiple sclerosis: A case-control study. Neurology 2011; 77: 1-5
  • 25 Baracchini C, Perini P, Causin F et al. Progressive multiple sclerosis is not associated with chronic cerebrospinal venous insufficiency. Neurology 2011; 30;77: 844-850
  • 26 Sundström P, Wåhlin A, Ambarki K et al. Venous and cerebrospinal fluid flow in multiple sclerosis: a case control study. Ann Neurol 2010; 68: 255-259
  • 27 Wattjes MP, van Oosten BW, de Graaf WL et al. No association of abnormal cranial venous system drainage with multiple sclerosis: A MR venography and flow-quantification study. J Neurol Neurosurg Psychiatry 2010; 82: 429-435
  • 28 Zivadinov R, Lopez-Soriano A, Weinstock-Guttmann B et al. Use of MR venography for characterization of the extracranial venous system in patients with multiple sclerosis and healthy control subjects. Radiology 2011; 258: 262-270
  • 29 Schreiber S, Lürtzing F, Götze R et al. Extrajugular pathways of human cerebral venous blood drainage – assessed by duplex ultrasound. J Appl Physiol 2003; 94: 1802-1805
  • 30 Batson OV. Anatomical problems concerned in the study of cerebral blood flow. Fed Proc 1944; 3: 139-144
  • 31 Eckenhoff JE. The physiologic significance of the vertebral venous plexus. Surg Gynec Obst 1970; 131: 72-78
  • 32 Fitz-Hugh GS, Robins RB, Craddock WD. Increased intracranial pressure complicating unilateral neck dissection. Laryngoscope 1966; 76: 893-906
  • 33 Gius JA, Grier DH. Venous adaptation following bilateral radical neck dissection with excision of the jugular vein. Surgery 1950; 28: 305-321
  • 34 Corgill DA. Complications of neck dissection. In: Conley J. ed. Cancer of the head and neck. London: Butterworth & Co Ltd; 1967: 191-201
  • 35 Royster HP. The relation between internal jugular vein pressure and cerebrospinal fluid pressure in the operation of radical neck dissection. Ann Surg 1953; 137: 826-832
  • 36 Yamout B, Herlopian A, Issa Z et al. Extracranial venous stenosis is an unlikely cause of multiple sclerosis. Mult Scler 2010; 16: 1341-1348
  • 37 Doepp F, Würfel JT, Pfueller CF et al. Neurology 2011; in press
  • 38 Zivadinov R, Galeotti R, Hojnacki D et al. Value of MR Venography for detection of internal jugular vein anomalies in multiple sclerosis: a pilot longitudinal study. AJNR 2011; 32: 938-946
  • 39 Worthington V, Killestein J, Eikelenboom MJ et al. Normal CSF ferritin levels in MS suggest against etiologic role of chronic venous insufficiency. Neurology 2010; 75: 1617-1622
  • 40 Meyer-Schwickerath R, Haug C, Hacker A et al. Intracranial venous pressure is normal in patients with multiple sclerosis. Multiple Sclerosis 2011; 17: 637-638
  • 41 Orton SM, Herrera BM, Yee IM et al. Sex ratio of multiple sclerosis in Canada: A longitudinal study. Lancet Neurol 2006; 5: 932-936
  • 42 Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part I: The role of infection. Ann Neurol 2007; 61: 288-299
  • 43 Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol 2007; 61: 504-513
  • 44 McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 2007; 9: 913-917
  • 45 Koch-Henriksen N. The Danish Multiple Sclerosis Registry: a 50 year follow up. Mult Scler 1999; 5: 293-296
  • 46 Frischer JM, Bramow S, Dal Bianco A et al. The relationship between inflammation and neurodegeneration in multiple sclerosis brains. Brain 2009; 132: 1175-1189
  • 47 De Jager PL, Jia X, Wang J et al. Meta-analysis of genome scans and replication identify CD6, IRF8, and TNRSF1A as new multiple sclerosis susceptibility loci. Nat Genet 2009; 41: 776-782
  • 48 Clemens HJ. Die Venensysteme der menschlichen Wirbelsäule. Morphologie und funktionelle Bedeutung. Berlin: Walter de Gruyter &Co; 1961
  • 49 Lang J. Klinische Anatomie der Halswirbelsäule. Stuttgart: Thieme; 1991: 104ff
  • 50 Ruiz DSM, Gailloud P, Rüfenacht DA et al. the craniocervical venous system in relation to cerebral venous drainage. Am J Neuroradiol 23: 1500-1508
  • 51 Alemans HJ. Die Venensysteme der menschlichen Wirbelsäule. Morphologie und funktionelle Bedeutung 1961; 19-35
  • 52 Cown TD, Krinsky M, Zarowitz H. Metastatic brain abscess. The role of the vertebral vein circulation. Am Pract Digest Trweat 1950; 1: 792-794
  • 53 Gowin W. die Bedeutung des Wirbelsäulensystems bei der Metastasenbildung. Strahlentherapie 1983; 159: 682-689
  • 54 Sander D, Winbeck K, Etgen T et al. Disturbance of venous flow patterns in patients with tranient global amnesia. Lancet 2000; 356: 1982-1984
  • 55 Akkawi NM, Agosti C, Rozzini L et al. Transient global amnesia and disturbance of venous flow patterns. Lancet 2001; 357: 957
  • 56 Schreiber SJ, Doepp F, Klingebielm MR et al. Internal jugular vein valve incompetence and intracranial venous anatomy in transient global amnesia. J Neurol Neurosurg Psychiatry 2005; 76: 509-513
  • 57 Chung CP, Wang PN, Wu YH et al. More severe white matter changes in the elderly with jugular venous reflux. Ann Neurol 2011; 69: 553-559
  • 58 Ludyga T, Kazibudzki M, Simka M et al. Endovascular treatment for chronic cerebrospinal venous insufficiency: is the procedure safe?. Phlebology 2010; 25: 286-295
  • 59 Petrov I, Grozdinski L, Kaninski G et al. Safety profile of endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Endovasc Ther 2011; 18: 314-323
  • 60 Zamboni P, Galeotti R, Weinstock-Guttman B et al. Venous angioplasty in patients with multiple sclerosis: results of a pilot study. Eur J Vasc Endovasc Surg 2011; in press
  • 61 Kostecki J. An endovascular treatment of Chronic Cerebro-Spinal Venous Insufficiency in Multiple Sclerosis patients – 6 month follow-up results. Neuro Endocrinol Lett 2011; 30: 32
  • 62 Imperial College CCSVI Investigation Group. Thapar A, Lane TR, Pandey V et al. Internal jugular thrombosis post venoplasty for chronic cerebrospinal venous insufficiency. Phlebology 2011; 26: 254-256
  • 63 Burton JM, Alikhani K, Goyal M et al. Complications in MS Patients after CCSVI Procedures Abroad (Calgary, AB). Can J Neurol Sci 2011; 38: 741-746
  • 64 Samson K. Experimental multiple sclerosis vascular shunting procedure halted at Stanford. Ann Neurol 2010; 1: A13-A15
  • 65 Vedantham S, Benenati JF, Kundu S et al. Interventional endovascular management of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a position statement by the society of interventional radiology, endorsed by the canadian interventional radiology association. J Vasc Interv Radiol 2010; 21: 1335-1337
  • 66 Reekers JA, Lee MJ, Belli AM et al. Cardiovascular and interventional radiological society of europe commentary on the treatment of chronic cerebrospinal venous insufficiency. Cardiovasc Intervent Radiol 2011; 34: 1-2