Eur Radiol (2012) 22:970–979 DOI 10.1007/s00330-011-2338-5
HEAD AND NECK
Chronic cerebrospinal venous insufficiency: does ultrasound really distinguish multiple sclerosis subjects from healthy controls? Fatih Kantarci & Sait Albayram & Nuri Onat Demirci & Asim Esenkaya & Derya Uluduz & Omer Uysal & Sabahattin Saip & Aksel Siva
Received: 17 August 2011 / Revised: 19 September 2011 / Accepted: 27 September 2011 / Published online: 29 November 2011 # European Society of Radiology 2011
Abstract Objectives To investigate the differences between multiple sclerosis (MS) and control subjects by using extracranial venous grey-scale, colour and spectral Doppler ultrasound. Methods The study included 62 subjects with a definitive diagnosis of MS and 54 control subjects. The cross sectional area (CSA), reflux during Valsalva manoeuvre, presence or absence of flow in the internal jugular vein (IJV) were assessed in upright and supine positions. The IJVand vertebral vein (VV) flow volumes (BFV) were also studied. Results Reflux in the IJV, an upright CSA greater than a supine CSA, and the presence or absence of flow in the IJV were not different between MS and control subjects. A CSA ≤ 0.3 cm2 was observed to be significantly higher in MS subjects. The IJV BFV was not significantly different between the groups; however, the VV BFV was significantly higher on the right side and lower on the left side in MS subjects. Conclusions Our use of ultrasound criteria reported in the literature for MS reveals differences between healthy controls and MS subjects that also overlap. Our experience suggests F. Kantarci (*) : S. Albayram : A. Esenkaya Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300 Kocamustafapasa, Istanbul, Turkey e-mail:
[email protected] N. O. Demirci : D. Uluduz : S. Saip : A. Siva Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey O. Uysal Department of Biostatistics, Medical Faculty, Bezmi Alem Vakıf University, Istanbul, Turkey
that Doppler ultrasound may not be clinically reliable and more studies are needed to clarify its role, if any. Key Points • Chronic cerebrospinal venous insufficiency is a controversial topic in multiple sclerosis. • Ultrasound assessment of extracranial veins has yielded different results in the literature. • These differences may be due to dependence on Doppler and selection bias. • We found variations in vertebral vein flow in patients with multiple sclerosis. Keywords Multiple sclerosis . Jugular veins . Venous insufficiency . Ultrasonography . Ultrasonography . Doppler
Introduction Multiple sclerosis (MS) is regarded as an immune-mediated disease of the central nervous system (CNS), characterised by inflammation and demyelination [1, 2]. Clinically and radiologically, MS is characterised and defined by symptoms and signs that reflect lesion dissemination in space and time in the CNS [3, 4]. Chronic cerebrospinal venous insufficiency (CCSVI) was recently suggested to be a causative factor of MS [5]. However, this concept is controversial [6] because venous drainage from the CNS is frequently impaired in MS patients, but not in healthy control subjects [5]. Chronic venous reflux and hypertension have been proposed to possibly lead to increased iron deposition in the brain, resulting in subsequent MS symptoms, including inflammation and neurodegeneration [7]. The concept of CCSVI was first defined by Zamboni et al. and was based primarily on Doppler ultrasound and
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In total, 62 MS and 54 control healthy subjects were enrolled in the study. The MS subjects were grouped according to the clinical course, as described by Lublin and Reingold [15]. Of the 62 subjects, 17 had primary progressive MS (PPMS), 32 had relapsing remitting MS (RRMS), and 13 had secondary progressive MS (SPMS). Subjects who had a relapse within the previous 30 days, a history of cerebral venous thrombosis, transient global amnesia, thrombosis of the jugular vein(s), a central venous catheter in the IJV, head and neck surgery, or heart or lung disease were ineligible for this study. The degree of disability was assessed using the expanded disability status score scale (EDSS) [16] before the ultrasound studies. The local ethics committee of the study hospital approved the study proposal. Written informed consent was obtained from all participants.
venography findings [5, 8]. The authors focused particularly on five anomalous parameters of cerebral venous drainage on Doppler ultrasound: (1) reflux in the internal jugular vein (IJV) and vertebral veins (VV), (2) reflux in the deep cerebral veins, (3) high-resolution B-mode evidence of IJV stenosis, (4) flow not detectable by Doppler ultrasound in the IJV and/or the VV, and (5) reverted postural control of the main cerebral venous outflow pathways. Controversial results exist in the literature regarding extracranial Doppler ultrasound findings of the IJV and VV in subjects with MS (Table 1) [5, 8–14]. A major point of criticism is that ultrasound studies are strongly operator-dependent, and that intracranial venous blood flow is difficult to measure [6, 9]. Because this issue will have an effect on MS pathogenesis and treatment concepts, independent research is needed to confirm or refute the original findings. The aim of this study was to examine MS and healthy control (HC) subjects using extracranial venous grey-scale, colour and spectral Doppler ultrasound and to present our results. We studied the same extracranial ultrasound parameters that were studied by Zamboni et al. [5, 8]. Additionally the blood flow volumes of the IJVs and VVs were studied.
Ultrasound technique A 5.0- to 12.0-MHz linear array transducer (Logic 9, GE) was used for the Doppler ultrasound examinations. The subjects were examined between 10 a.m. and 12 noon in a quiet, temperature-controlled room. Examinations were performed in the upright and supine positions. The upright examination was performed first, after 30 min of standing or sitting depending on the subjects’ physical condition. Examination in the supine position was performed after 10 min of rest on the examination table. Examinations were performed with the heads of subjects slightly extended in both positions. The physician, who performed the ultra-
Materials and methods Subjects and clinical assessments The study was performed between March 2010 and January 2011 in subjects with a definitive clinical diagnosis of MS.
Table 1 Literature summary of Doppler ultrasound findings described by Zamboni et al. [5, 8]
Zamboni et al. [5] Zamboni et al. [8] Doepp et al. [13] Mayer et al. [9] Simka et al. [10] Al-Omari and Rousan [11] Zivadinov et al. [12] Marder et al. [14] Current study
HC (n=235)
IJV stenosis
IJV ΔCSA
1 (
