Übersicht und Analyse internationaler Fall-Kontroll-Studien zu „Chronischen zerebrospinalen venösen Insuffizienz“ (CCSVI) und Multipler Sklerose

C. Krogias; G. Tsivgoulis; M. Grond; H. P. Hartung; B. Hemmer; W. Oertel; H. Wiendl; R. Gold

doi:10.1055/s-0033-1351271

Aktuelle Neurologie, Table of Contents

Aktuelle Neurologie 2013; 40(08): 445-451
DOI: 10.1055/s-0033-1351271

Übersicht

Übersicht und Analyse internationaler Fall-Kontroll-Studien zu „Chronischen zerebrospinalen venösen Insuffizienz“ (CCSVI) und Multipler Sklerose

Review and Analysis of International Case-Control Studies on CCSVI and Multiple Sclerosis

C. Krogias

¹Neurologische Klinik, St. Josef-Hospital Bochum, Ruhr-Universität Bochum

,

G. Tsivgoulis

²Klinik für Neurologie, „Attikon“ Hospital, Universität Athen, Griechenland

,

M. Grond

³Klinik für Neurologie, Kreisklinikum Siegen

,

H. P. Hartung

⁴Neurologische Klinik, Heinrich-Heine Universität Düsseldorf

,

B. Hemmer

⁵Neurologische Klinik, Klinikum rechts der Isar, Technische Universität München

,

W. Oertel

⁶Klinik für Neurologie, Philipps-Universität Marburg

,

H. Wiendl

⁷Klinik für Neurologie, Universitätsklinikum Münster

,

R. Gold

¹Neurologische Klinik, St. Josef-Hospital Bochum, Ruhr-Universität Bochum

› Author Affiliations

Abstract

Zusammenfassung

Hintergrund:

Die neurosonologische Befundkonstellation „Chronischen zerebrospinalen venösen Insuffizienz“ (CCSVI) wurde initial als hochspezifischer und hochsensitiver Befund bei Patienten mit Multipler Sklerose (MS) beschrieben. Es wurde postuliert, dass ein Rückstau in zerebralen Venen ursächlich für die pathophysiologischen Prozesse bei der MS sei. Inzwischen sind mehrere Fall-Kontroll-Studien zur Prävalenz einer CCSVI bei MS-Patienten mit sehr widersprüchlichen Ergebnissen publiziert worden.

Methoden:

Neben einer Übersicht über die Datenlage zur „venösen Hypothese“ erfolgt eine Meta-Analyse der Ergebnisse aus den bisher publizierten internationalen Fall-Kontroll-Studien.

Ergebnisse:

In 25 Studien wurden 2 012 MS-Patienten und 1 425 gesunde Kontrollen untersucht. Die Konstellation einer „CCSVI“ nach neurosonologischen Kriterien wurde bei 876 (41,7%) der Patienten und 147 (10,3%) der Gesunden beschrieben (OR=3,2; 95% CI=2,5–4,0). Bei der Bewertung dieser Meta-Analyse ist jedoch die hohe Heterogenität (I²=82%) zu berücksichtigen. Die Analyse dreier deutscher Studien ergab eine sehr geringe CCSVI-Prävalenz von ca. 2% in beiden Gruppen (OR=0,5; 95% CI=0,1–3,1) und ist durch keinerlei Heterogenität (I²=0%) in Ihrer Aussage eingeschränkt.

Schlussfolgerungen:

Im Vergleich zur Erstbeschreibung konnte keine der folgenden internationalen Fall-Kontrollstudien die hohe Spezifität bzw. Sensitivität einer CCSVI bei MS reproduzieren. Bei einer allgemeinen Meta-Analyse der teils widersprüchlichen Daten ist die hohe Heterogenität zu berücksichtigen, sodass genauere Meta-Analysen mit erweiterten Sensitivitätsanalysen notwendig sind. Die in Deutschland durchgeführten Studien haben keine Hinweise für eine „venöse Genese“ der MS ergeben. Die Ergebnisse unterstützen nachhaltig die Empfehlung, dass interventionelle Verfahren zur Erweiterung der venösen Halsgefäße nicht mehr außerhalb von klinischen Studien durchgeführt werden sollten.

Abstract

Background:

A constellation of neurosonological findings called “chronic cerebrospinal venous insufficiency” (CCSVI) was introduced as a highly specific and highly sensitive finding in multiple sclerosis (MS) patients. It was postulated that impaired venous cerebral drainage initiates the pathological processes of MS. Several published case-control of studies evaluating the association of CCSVI with MS report inconsistent findings.

Methods:

Besides an overview of the postulated concept of “venous hypothesis”, we performed a meta-analysis of the results from published case-control studies evaluating the association of CCSVI with MS using ultrasound criteria.

Results:

In 25 eligible studies, 2 012 MS patients and 1 425 healthy controls were investigated. The constellation of CCSVI was described in 876 (41.7%) of the patients and in 147 (10.3%) of the controls (OR=3.2; 95% CI=2.5–4.0). However, considerable heterogeneity (I²=82%) across these studies was documented. The analysis of the 3 German studies revealed a very low prevalence of CCSVI of only about 2% in both groups (OR=0.5; 95% CI=0.1–3.1) without heterogeneity (I²=0%).

Conclusions:

Compared to the first description, no subsequent international case-control study could reproduce the high specificity and sensitivity of CCSVI in MS. There is high heterogeneity across the different studies, so that further comprehensive meta-analyses with additional sensitivity analyses are required. The studies conducted in Germany have clearly and consistently shown no evidence for the “venous multiple sclerosis hypothesis”. Interventional procedures should therefore not be performed outside the setting of randomised clinical trials.

Schlüsselwörter

Venen - Ultraschall - Multiple Sklerose

Keywords

veins - ultrasound - multiple sclerosis

Full Text

References

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