notes from Bologna and ISNVD from Arlene---


ISNVD Meeting in Bologna 3/14/11-3/15/11
Attending the ISNVD conference was a life changing experience for me. I sat among the best and brightest minds in a variety of fields...from medicine to engineering.  Every attendee shared the same goal...to take the present understanding of CCSVI in MS and fill in the missing pieces. This was the ground floor of creating a new area of science.  I felt like I was joining our American forefathers in drafting the Declaration of Independence. That's how emotionally overwhelming this was. I sat through each and every lecture taking copious notes, understanding much and realizing a lot was above my head.  Fortunately, David and I would debreif daily and we would have fabulous interactions with all the top docs during our down time(which was essentially during dinner).  David and I have made new contacts and friends and will be engaging with them in the future to make sure what we do helps to push the cause in a productive direction. It is with great gratitude that I give you a short synopsis  my observations of the conference.   Sunday March 13...Ultrasound screening for CCSVI, Recommendations for a protocol Erica Menegatti and Karen Marr deliniated a comprehensive doppler protocol for CCSVI testing.  Apparently doppler technicians in the U. S. are not trained in this method.  It takes over an hour,requires special training, and focuses on anatomy especially valve abnormalities.    Monday March 14...Ultrasounds:data review- S. Bastianello Dr Bastianello reviewed doppler protocols for varicose veins in the legs.                                 Ultrasonographic transit time- M. Mancini "Transit Time" is abnormal in MS                                 Intravascular Ultrasounds- S. Sclafani During catheter venography it is possible to visualize the inside of the vein using a special catheter ultrasound probe.                                   CT angiographyV. Iaccarino CT rarely used but can visualize the azygos which Doppler cannot.                                 Fusion imaging technology-P. Zamboni Dr Zamboni hopes that all testing modalities will in the future be able to be combined(fusion) to yield composite information.                                 Catheter Venography-R. Galeotti Dr Galeotti ( the varicose vein specialist) reviewed standard catheter method. Galeotti stated that the doppler protocol must require1. postural,2. dynamic,3.  respiratory sequences. He noted false positives with inexact positioning .   He questioned the accuracy of valve  abnormality detection but many of the doppler specialists at the meeting disagreed .                                   The limits of MRV -R. Zivadinov .Doppler is better than MRV at visualizing the valves but it takes a long time to do and requires a lot of experience and training.                                    Neurovascular Mechanisms in Neurodegenerative Diseases-B Zlokovic  Dr Zlokovic was the keynote speaker and is a world renowned scientist and (opera singer!).He described  the  triad of .: Neuro,inflammatory, and vascular...the perfect storm.  He suggested that new pharmaceuticals would address the vascular component.  He reviewed the literature showing abnormal perfusion, damaged endothelium including micro hemorrhage, periocyte loss in humans and animals.  He is studying novel pharmaceuticals that will target inflammation and endothelial pathology.                                   Iron and oxidative stress in Alzheimers Disease-C. Iadecola Dr Iadecola reviewed the consequences of brain damage when iron breaks through CNS endothelium.He  proposed that iron chelating agents such at tumeric may be therapeutic .                                Iron and veins in MS-R. Zivadinov Dr Zivadinov used an MRI technique developed by Haacke called SWI which measure both Iron accumulation and also small vein anatomy. He showed loss of small cerebral veins in MS  and abnormalities in iron accumulation in MS.  Perivenous inflammation may be key.                                  Mitochondria dysfunction and differentiation of oligodendrocytes.- Bonara Reviewed the biochemistry of iron free radicals on tumor necrotic factor(TNF) and brain cell damage.                                  Iron traffic genetic variants in MS-D Gemmati Reviewed the genetics of iron traffic susceptibilities                                  Update on on Carotid surgery and stroke World experts on arterial disease  and stroke provided updates.                                 Here is a list of the presentations:                                  Carotid plaque echolucency and risk of stroke in carotid stenting                                Serological and morphological markers of vulnerable carotid plaque                                Open carotid surgery in emergency                                Carotid artery angioplasty and stenting following the CREST trial                                  BOLD fMRI responses during cognitive tasks in MS and effects of venoplasty D Hubbard  fMRI was used to compare normals to MS patients pre and post venoplasty.  The BOLD hemodynamic response showed a significantly greater venous undershoot which normalized after venoplasty.                                   A prospective analysis of endovascular treatments of CCSVI in MS-M. Mehta Dr Mehta described treatment of 150 patients and found dramatic improvement in fatigue but no stastistical difference in EDSS scores.                                  Three lectures comparing doppler to CT and MRI- N. liasis, K. Agarwal, and M. Al-Omari Doppler is better at showing valves and other internal jugular vein abnormalities but not as good at measuring flow.                                Here is the list of presentations:                                  The role of three dimensional magnetic resonance venography in confirming of color                                 doppler ultrasound findings                                Evaluating the presence of abnormal venous vasculature in a non-MS population using                                CT angiography                                The CCSVI syndrome;angiographic findings and doppler correlation   Tuesday March 15...Hypoperfusion of brain parenchyma in CCSVI-R. Zivadinov Reviewed evidence that hypoperfusion precedes MS lesions                                  Hypoxia-like aspect of MS- B Trapp Cortical neurons unable to compensate for oxidative needs of demyelinated axons. Dr Trapp calls for objective testing of vascular insufficiency.                                A murine model of CCSVI is associated with mild but significant impairment of gait as                                assessed by neurobehavioral testing- P. Thanaporn Stanford's mouse lab showed mild neurobehavioral effects of bilateral jugular ligation,( not surprising because acute venous obstruction  is compensated for by collaterals).                                  The pathology of the extracranial venous wall in MS- G Gabbiani He showed abnormalities in the vein wall in MS which could not be explained by traditional atherosclerotic disease.                                CCSVI and fluid mechanics: implications in MS-CB Beggs A bioengineer, described how the absence of Starling Receptors in the deep venous CNS drainage system may explain why MS lesions occur in the periventricular white matter.                                  Vascular Mechanisms in Neurological disorders. The ISNVD society embraces the importance of venous disease in all neurological diseases.                                Here is a list of the presentations:                                  Risk factors in vascular dementia-G Zuliani                                Vascular dysregulation in Alzheimers Disease-C Iadecola                                Rare clinical manifestations associated with CCSVI-MS extrapyramidal syndrome and                                normotensive hydrocephalus- F Salvi                                Seasonality in vascular disorders and preliminary data in MS-R Manfredini                                  CCSVI and CSF flow dynamics-S. Gianesini Gianesini  and Shepherd demonstrated that hemodynamics are abnormal in MS                                  Cerebral arterial and venous flow measurements in the neck for patients with MS W Feng Dr Feng's laboratory tabulated flow quantification in MS patients.                                  Cervical plethysmography: is this is the ideal screening tool?-P Zamboni Dr Zamboni described a new way to measure CNS venous drainage using a neck blood pressure cuff.                                  Plethysmography and multiple sclerosis: analysis of novel data-S.J. Shepherd Dr Shepherd, an engineer showed that  neck venous flow could be modeled with simple mathmatical algorithms.                                  B.R.A.V.E. DR.E.A.MS:study design of a multicenter RCT-G. Fillippini Dr Fillippini an MS specialist described her study proposal for sham venoplasty in 650 patients in many Italian clinics.  The experts raised serious questions about the design.                                  Integrating intraoperative diagnostic information:  A. Siddiqui Dr Siddiqui a neurosurgical interventionalist at SUNY Buffalo delineated a comprehensive double blind placebo controlled trial of CNS venoplasty for MS using doppler, MR and neuropsych measures in 20 subjects.  Sham patients will be offered treatment at study completion at no charge.                                  Short term evaluation of venous angioplasty in patients with CCSVI-M Zarebinski A large number of MS patients were compared to non MS patients but the lower jugular could not be evaluated.                                MRI in treatment planning- M Haacke Dr Haacke, the acknowledged expert in MR explained the superiority of MR.  MR is the gold standard for describing MS lesions, it's the only technology that describes iron accumulation,it's the only technology that visualizes small veins, and it's the only technology that describes and objectively quantifies venous flow independent of operator expertise,  which allows objective pre and post treatment comparison.                                  Optical coherence tomography findings in patients with CCSVI-M Simka Reviewed an opthalmic visualization method and its possible application for optic neuritis in MS patients and other diagnoses.                                  Clinical disability and venous vessel pathology in MS-M Denislic Carefully summarized data collection of MS patients with CCSVI                                  Intraluminal and extraluminal extra-cranial structural and functional venous                                abnormalities in MS patients and healthy controls- R Zivadinov He compared doppler and MRV in MS patients and healthy controls and described different patterns                                  Prevalence of internal jugular vein abnormalities on contrast-enhanced 3D T1 GRE MR                                images in patients with MS-A Cieszanowski Used high quality contrast enhanced 3D MR images to compare MS to normal.                                    4D Magnetic Resonance Velocity Measurements in the Internal Jugular veins-CJ Elkins Dr Dake presented for Dr Elkins. Catheter venography is a"tarnished" gold standard. CNS venous flow,not anatomy ,is the key to pathophysiology. New MR venous flow techniques show abnormal flow amplitude and phase in MS patients. New MRV technique provides detailed information on venous flow.