The value of cerebral Doppler venous haemodynamics in the assessment of multiple sclerosis

Iron stores in the white and deep grey matter in course of multiple sclerosis (MS) have never been explained and could be related to abnormalities in venous drainage, but this possibility has never before been investigated. From an initial cohort of 320 subjects, after application of exclusion criteria, we selected 109 patients affected by MS, and 177 controls respectively composed by age- and sex-matched, healthy aged, and patients affected by other neurological diseases. They blindly underwent transcranial and extracranial Color-Doppler sonographic examination (TCCS-ECD), aimed at investigating five parameters related to normal cerebral venous outflow haemodynamics. Overall we analyzed 1430 TCSS-ECD parameters. In controls we found 861 normal parameters of cerebral venous return vs. 24 anomalous, whereas in MS 288 parameters were normal and 257 anomalous, respectively. Consequently, each of the considered Doppler haemodynamic parameters, when compared to revised McDonald criteria as a gold standard of MS diagnosis, showed separately a highly significant sensitivity and a noteworthy specificity. However, the detection >or=2 parameters in the same subject, never observed in controls, perfectly overlapped the diagnosis of MS (value, 95%CI: sensitivity 100%, 97-100; specificity 100%, 98-100; positive predictive value 100%, 97-100, negative predictive value 100%, 98-100; p<0.0001). Moreover, this study demonstrates a significant impairment of cerebral venous drainage in patients affected by MS, a mechanism potentially related to increased iron stores.

[1]  S. Vukusic,et al.  Natural history of multiple sclerosis: a unifying concept. , 2006, Brain : a journal of neurology.

[2]  R. Klingebiel,et al.  Extrajugular pathways of human cerebral venous blood drainage assessed by duplex ultrasound. , 2003, Journal of applied physiology.

[3]  Lublin Fd,et al.  Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. , 1996 .

[4]  M. Kaps,et al.  Transcranial color-coded duplex sonography of intracranial veins and sinuses in adults. Reference data from 130 volunteers. , 1999, Stroke.

[5]  F Barkhof,et al.  MR venography of multiple sclerosis. , 2000, AJNR. American journal of neuroradiology.

[6]  J. Beard,et al.  Iron-deficient mice fail to develop autoimmune encephalomyelitis. , 2003, The Journal of nutrition.

[7]  G. Schmid-Schönbein,et al.  Chronic venous disease. , 2006, Minerva cardioangiologica.

[8]  T. Fog The topography of plaques in multiple sclerosis with special reference to cerebral plaques. , 1965, Acta neurologica Scandinavica. Supplementum.

[9]  C. W. Adams,et al.  Perivascular iron deposition and other vascular damage in multiple sclerosis. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[10]  Edmus Coordinating Natural history of multiple sclerosis: A unifying concept , 2006 .

[11]  J. Karemaker,et al.  Human cerebral venous outflow pathway depends on posture and central venous pressure , 2004, The Journal of physiology.

[12]  A. Hofman,et al.  Mutations in the hemochromatosis gene (HFE), Parkinson's disease and parkinsonism , 2003, Neuroscience Letters.

[13]  R. Weller A Colour Atlas of Multiple Sclerosis and Other Myelin Disorders , 1989 .

[14]  F. Salvi,et al.  Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[15]  Stephan J. Schreiber,et al.  How does the blood leave the brain? A systematic ultrasound analysis of cerebral venous drainage patterns , 2004, Neuroradiology.

[16]  J. Kurtzke Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[17]  P. Zamboni,et al.  Inflammation in venous disease. , 2008, International angiology : a journal of the International Union of Angiology.

[18]  Carlo Ciulla,et al.  Establishing a baseline phase behavior in magnetic resonance imaging to determine normal vs. abnormal iron content in the brain , 2007, Journal of magnetic resonance imaging : JMRI.

[19]  P. Zamboni The Big Idea: Iron-Dependent Inflammation in Venous Disease and Proposed Parallels in Multiple Sclerosis , 2006, Journal of the Royal Society of Medicine.

[20]  S. Schreiber,et al.  Postural dependency of the cerebral venous outflow , 2000, The Lancet.

[21]  F. Schelling Damaging venous reflux into the skull or spine: relevance to multiple sclerosis. , 1986, Medical hypotheses.

[22]  Rohit Bakshi,et al.  Role of MRI in multiple sclerosis II: brain and spinal cord atrophy. , 2004, Frontiers in bioscience : a journal and virtual library.

[23]  P. Zamboni The Big Idea: Iron-Dependent Inflammation in Venous Disease and Proposed Parallels in Multiple Sclerosis , 2006 .

[24]  J. Sullivan Is stored iron safe? , 2004, The Journal of laboratory and clinical medicine.

[25]  A. Nirkko,et al.  Transoccipital power-based color-coded duplex sonography of cerebral sinuses and veins. , 1997, Stroke.

[26]  D. Lichtenstein,et al.  The internal jugular veins are asymmetric. Usefulness of ultrasound before catheterization , 2001, Intensive Care Medicine.

[27]  M. Dieterich,et al.  Functional and Morphological Criteria of Internal Jugular Valve Insufficiency as Assessed by Ultrasound , 2005, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[28]  Paolo Zamboni,et al.  Intracranial venous haemodynamics in multiple sclerosis. , 2007, Current neurovascular research.

[29]  R. Poston,et al.  Pathology, histochemistry and immunocytochemistry of lesions in acute multiple sclerosis , 1989, Journal of the Neurological Sciences.

[30]  M. Barnett,et al.  The pathology of multiple sclerosis: a paradigm shift , 2006, Current opinion in neurology.

[31]  M Worwood,et al.  Iron genes, iron load and risk of Alzheimer’s disease , 2006, Journal of Medical Genetics.

[32]  Dirk Sander,et al.  New insights into transient global amnesia: recent imaging and clinical findings , 2005, The Lancet Neurology.

[33]  Paolo Zamboni,et al.  Doppler haemodynamics of cerebral venous return. , 2008, Current neurovascular research.

[34]  S. Reingold,et al.  Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria” , 2005, Annals of neurology.

[35]  Ernest Beutler,et al.  Brain Iron Metabolism and Neurodegenerative Disorders , 2002, Developmental Neuroscience.