RAPID COMMUNICATIONS Venous and Cerebrospinal Fluid Flow in Multiple Sclerosis: A Case-Control Study Peter Sundstro ¨ m, MD, PhD, 1 Anders Wåhlin, MSc, 2 Khalid Ambarki, MSc, PhD, 2 Richard Birgander, MD, PhD, 2 Anders Eklund, MSc, PhD, 2,3,4 and Jan Malm, MD, PhD 1 The prevailing view on multiple sclerosis etiopathogen- esis has been challenged by the suggested new entity chronic cerebrospinal venous insufficiency. To test this hypothesis, we studied 21 relapsing-remitting multiple sclerosis cases and 20 healthy controls with phase- contrast magnetic resonance imaging. In addition, in multiple sclerosis cases we performed contrast- enhanced magnetic resonance angiography. We found no differences regarding internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux. Three of 21 cases had in- ternal jugular vein stenoses. In conclusion, we found no evidence confirming the suggested vascular multiple sclerosis hypothesis. ANN NEUROL 2010;68:255–259 A new hypothesis about the etiopathogenesis in multi- ple sclerosis (MS), chronic cerebrospinal venous insuf- ficiency (CCSVI), has in a short time gained enormous at- tention in the media, among patients as well as in the scientific community. MS-CCSVI suggests that MS may develop secondarily to an impaired venous outflow from the central nervous system (CNS). 1 Stenoses of the internal jugular vein (IJV), possibly treatable by angioplasty or stenting, have been suggested as a cause of this impaired outflow. 2,3 Zamboni et al used ultrasound and transcranial Doppler to show that venous reflux is a common finding in MS, but never seen in controls. 4 The hypothesis is that venous reflux may lead to the accumulation of iron in the CNS, triggering secondary autoimmune events leading to MS. 1 A marked decrease of MS cerebrospinal fluid (CSF) flow through the cerebral aqueduct, correlating with the Doppler sonography pattern, is also described. 5,6 MS-CCSVI and the vascular hypothesis of MS have been questioned. 7 Does imbalance of venous outflow have etiological relevance for MS, or are the findings just a sec- ondary phenomenon compatible with the prevailing view on MS etiopathogenesis? Magnetic resonance imaging with phase contrast (PC-MRI) makes it possible to nonin- vasively and accurately evaluate the flow direction and flow rate of intracranial blood and CSF. 8 –13 Using contrast- enhanced magnetic resonance angiography (CE-MRA), venous anatomy and pathology can be described as well. The present study is a joint project between a hy- drocephalus research group specializing in CSF dynamics and blood flow, and the MS research group at Umeå University. To test the most vital part of the vascular MS hypothesis, that is, the obstructed IJV flow, blood flow of the internal carotid arteries, the vertebral arteries, and the IJVs, as well as the anatomy of the vessels, was assessed in 21 MS patients and 20 healthy controls. Subjects and Methods MS Patients and Controls Twenty-one relapsing-remitting MS (RRMS) patients fulfilling the revised McDonald diagnostic criteria, 14 and in whom a new MRI examination was clinically motivated, were invited during February to April 2010 (Table 1). All patients accepted partici- pation. The MS population at the Department of Neurology, From the 1 Department of Clinical Neuroscience and 2 Department of Radiation Sciences, Umeå University; 3 Department of Biomedical En- gineering and Informatics, Umeå University Hospital; and 4 Center for Biomedical Engineering and Physics, Umeå University, Umeå , Swe- den. Address correspondence to Dr. Sundstro ¨ m, Department of Neurology, Umeå University Hospital, SE- 901 85 Umeå , Sweden. E-mail: peter.sundstrom@neuro.umu.se Received May 2, 2010, and in revised form Jun 4, 2010. Accepted for publication Jun 17, 2010. Published in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ana.22132 TABLE 1: Characteristics of 21 Multiple Sclerosis Cases and 20 Controls Characteristics Cases Controls Demographic Median age (range) 31 (19–56) 31 (24–52) Women:men, No. 13:8 8:12 Clinical Median disease duration, yr (range) 5 (1–25) Median EDSS (range) 2 (0–3.5) Median MSSS (range) 2.0 (0.20–7.5) There was no significant difference for age or sex between cases and controls. Sixteen cases were on disease-modifying treatment: interferon (n=7), natalizumab (n=6), rituximab, alemtuzumab, and mitoxantrone. EDSS = Kurtzke’s Expanded Disability Status Scale (assessed within the past year); MSSS = Multiple Sclerosis Severity Score. Sunderstro ¨ m et al: Venous and CSF Flow in MS August, 2010 255