1       Chronic Cerebrospinal VenousInsufficiency (CCSVI) for Multiple Sclerosis  TCT: Plenary Session IX. Endovascular Ho...
Michael Dake, MD             Within the past 12 months, the presenter or   their spouse/partner have had a financial inter...
CCSVI Presentation Outline•   History of multiple sclerosis•   Venocentric lesions•   Blood-brain barrier considerations• ...
Georg Eduard von Rindfleisch (1836-1908)                Department of Cardiothoracic Surgery, Stanford University School o...
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Hand-rendered Depictions of MS Plaques      in Illuminated Brain Sections               Department of Cardiothoracic Surge...
Chronic MS; large periventricular demyelinated                                            MS;plaque with perivenous extens...
Congested Vessels Surrounded by DemyleinationAnn New York Acad Sci 1954 58:582-594   Department of Cardiothoracic Surgery,...
Putnam proposes that the basicetiology of MS is venous obstruction                    Tracey Putnam, Boston City Hospital,...
Chronic cerebrospinal venous  insufficiency and multiple sclerosis         What do we know about Multiple Sclerosis?• Clin...
Degeneration Versus Autoimmunity      In Multiple Sclerosis The most widely accepted hypothesis for the  cause of MS is th...
Department of Cardiothoracic Surgery, Stanford University School of Medicine
AnnNeurology 2009; 66:739-753   Department of Cardiothoracic Surgery, Stanford University School of Medicine
Henderson APD. AnnCardiothoracic Surgery, Stanford University School of Medicine        Department of Neurol 2009;66:2739-...
These obsevations raise questions aboutthe long-held premise that MS is primarily         an auto-immune diseaseTheir find...
To Begin – What Is CCSVI? Chronic Cerebrospinal Venous Insufficiency (CCSVI) has   been hypothesized by Paolo Zamboni and ...
The Association of Chronic Cerebro-Spinal Venous        Insufficiency (CCSVI) and Multiple Sclerosis                Backgr...
7-Tesla MRI Images of Patient with MS         Inflammation surrounding vessels (yellow) in very early lesionsNYU Physician...
Detection of Small Parenchymal Veins within    MS Lesions Using T2-weighted 3T and 7T Imaging               7T Scan       ...
The conceptual framework• The vessel wall responds dynamically to  changes in flow and pressure (pulsatile  shear stress a...
Laminar Flow Promotes Factors that Reduce Inflammation    Disturbed or Reversed Flow Promotes Inflammatory and            ...
Adhesion molecule (VCAM-                                  1) and cytokine expression                                    Ox...
Active Lesions of Multiple Sclerosis                                     Small lymphocyte                                 ...
How Is CCSVI Diagnosed?• Doppler ultrasound• MR venography (CT venography)• Conventional catheter venography              ...
What is the imaging data fromultrasound, venography and MR  in support of the association  between venous obstruction     ...
How Is CCSVI Diagnosed?• Doppler ultrasound• MR venography (CT venography)• Conventional catheter venography              ...
Venous Obstruction (CCSVI) and MS• Abnormalities noted in MS and CCSVI by Duplex Ultrasound   – Reflux/reversal of flow in...
Color doppler reveals abnormal venous    outflow in majority of MS patientsZamboni et al, JNNP 2009                       ...
Detection of CCSVI by color          doppler Normal RIJ                           Stenotic LIJ, with flow                 ...
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Department of Cardiothoracic Surgery, Stanford University School of Medicine
How Is CCSVI Diagnosed?• Doppler ultrasound• MR venography (CT venography)• Conventional catheter venography              ...
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Prominent valve cusps (R>L)           Department of Cardiothoracic Surgery, Stanford University School of Medicine
Narrowed valve orificeMS           Department of Cardiothoracic Surgery, Stanford University School of Medicine
Candy wrapper twisted appearance  of azygous with collateral flowDM            Department of Cardiothoracic Surgery, Stanf...
Where does the extra-cranial  venous obstruction occur andwhat causes the flow disturbance?              Department of Car...
The Association of Chronic Cerebro-Spinal Venous      Insufficiency (CCSVI) and Multiple Sclerosis                   Summa...
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Right side s/p mastoidectomy and neck dissection   In 38% of the 36 specimens examined, the transverse process indents the...
But, the overwhelming majority are     Low Jugular Lesions               Department of Cardiothoracic Surgery, Stanford Un...
INVERTED OR MALFORMED JUGULAR       VALVE MECHANISM BRAIN    BRAIN                              BRAIN                     ...
Department of Cardiothoracic Surgery, Stanford University School of Medicine
ECTRIMS2011– Histological Analysis of VenousStructures in MS Patients and Non-MS Subjects                    Department of...
What about endovasculartreatment of patients with CCSVI?              Department of Cardiothoracic Surgery, Stanford Unive...
Low Jugular Lesions       Department of Cardiothoracic Surgery, Stanford University School of Medicine
LIJ valve with restricted openingSSMSM                Department of Cardiothoracic Surgery, Stanford University School of ...
LIJ post PTA of valveSM          Department of Cardiothoracic Surgery, Stanford University School of Medicine
Internal jugular vein stenosis and reflux                 Department of Cardiothoracic Surgery, Stanford University School...
Internal jugular vein stenosis and reflux                 Department of Cardiothoracic Surgery, Stanford University School...
Right internal jugular vein post PTA               Department of Cardiothoracic Surgery, Stanford University School of Med...
Azygous Department of Cardiothoracic Surgery, Stanford University School of Medicine
Pre/Post stenting of twisted     descending azygous vein JJE              Department of Cardiothoracic Surgery, Stanford U...
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Department of Cardiothoracic Surgery, Stanford University School of Medicine
What are the anticipated short and  long-term clinical outcomes of  endovascular management ofextra-cranial venous insuffi...
Venous Obstruction (CCSVI) and MS• Initial Observations Recorded after Endovascular Treatment of  Venous Stenotic Lesions ...
Liberation Study• Longitudinal Arm (100 patient)• 62% Female, 38% Male• Mean age: 47 years• Multiple Sclerosis Type   • Re...
Liberation Study• Longitudinal Arm (100 patient)• Total # lesions: 174• Location of lesion   • Right IJV: 41%   • Left IJV...
Liberation Study• Longitudinal Arm (100 patient)• Total # lesions: 174• Location of lesion   • Right IJV: 41%   • Left IJV...
Liberation Study• Longitudinal Arm (100 patient)• Mean stenosis: 78% (range 50-100%)• Number of lesions/ patient:       • ...
Liberation Study• Longitudinal Arm (100 patient)• Anticoagulation during procedure• Antiplatelet post-procedure• Immediate...
Liberation Study•   Longitudinal Arm (100 patient)•   Anticoagulation during procedure•   Antiplatelet post-procedure•   I...
Liberation Study: timed 25-Foot walk                         Follow-up 4.5 months                                     Pre ...
Liberation Study: timed 25-Foot walk                     Follow-up 4.5 months                                      Pre-   ...
Liberation Study: timed 25-Foot walk                         Follow-up 4.5 months                                      Pre...
Liberation Study: timed 25-Foot walk                    Follow-up 4.5 months                                     Pre-     ...
Liberation Study                     mean follow-up 4.5 months                                    Pre-      Post-     P-  ...
Liberation Study                     mean follow-up 4.5 months                                    Pre-      Post-     P-  ...
Liberation Study                     mean follow-up 4.5 months                                    Pre-      Post-     P-  ...
Liberation Study                     mean follow-up 4.5 months                                  Patients Reporting Improve...
Liberation Study                     mean follow-up 4.5 months                               Pre  MS Symptoms             ...
Liberation Study                     mean follow-up 4.5 months                               Pre               No         ...
Liberation Study                     mean follow-up 4.5 months                              Pre MS Symptoms               ...
Liberation Study                     mean follow-up 4.5 months                              Pre                           ...
Currently, many unknowns and lots of uncertainty• CCSVI Diagnosis   – Is CCSVI something we are born with, acquire, or bot...
-                                        ChaosAgreement             Zone Of Complexity      +            Control          ...
Department of Cardiothoracic Surgery, Stanford University School of Medicine
What is the evidence for CCSVI ?           2009–2011: 53 reports on CCSVI                   Confusion & Controversy !• < 2...
Current Thoughts and Ruminations           Regarding CCSVI and MS• Exploring leads to the pathogenesis of MS   – It is lik...
Department of Cardiothoracic Surgery, Stanford University School of Medicine
Conclusions• There has been a growing understanding of  CCSVI in MS as studies are performed all  over the world.• It is h...
Department of Cardiothoracic Surgery, Stanford University School of Medicine
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Dr Dake presentation ICCCV nov 2011

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Présentation du Dr Dake lors du plus grand congrès de cardiologie interventionnelle.
Présentation faite en salle plénière devant plus de 800 personnes.

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Dr Dake presentation ICCCV nov 2011

  1. 1. 1 Chronic Cerebrospinal VenousInsufficiency (CCSVI) for Multiple Sclerosis TCT: Plenary Session IX. Endovascular Horizons Interventional Hot Topics II Wednesday, November 9, 2011 Michael D. Dake, M.D. Thelma and Henry Doelger Professor Department of Cardiothoracic Surgery Stanford University School of Medicine Falk Cardiovascular Research Center
  2. 2. Michael Dake, MD Within the past 12 months, the presenter or their spouse/partner have had a financial interest/arrangement or affiliation with the organization listed below. • Research/Research Grants, • Officer, Director, Board Member or Clinical Trial Support other Fiduciary Role – W. L. Gore – VIVA Physicians Group – Cook Medical • Speaker’s Bureau • Consulting Fees/Honoraria – None – W. L. Gore – Abbott Vascular• Equity Interests/Stock Options – NovoStent – Vatrix – Amaranth – CVRx – Endoluminl Sciences – REVA Medical – TriVascular – Cytograft Tissue Engineering Department of Cardiothoracic Surgery, Stanford University School of Medicine
  3. 3. CCSVI Presentation Outline• History of multiple sclerosis• Venocentric lesions• Blood-brain barrier considerations• CCSVI hypothesis• Extracranial venous lesions• Diagnosis of CCSVI• Treatment of CCSVI• The Future Department of Cardiothoracic Surgery, Stanford University School of Medicine
  4. 4. Georg Eduard von Rindfleisch (1836-1908) Department of Cardiothoracic Surgery, Stanford University School of Medicine
  5. 5. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  6. 6. Hand-rendered Depictions of MS Plaques in Illuminated Brain Sections Department of Cardiothoracic Surgery, Stanford University School of Medicine
  7. 7. Chronic MS; large periventricular demyelinated MS;plaque with perivenous extension into adjacent WM ChronicLassmann H. Phil Trans R Soc Lond 1990;354:1635. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  8. 8. Congested Vessels Surrounded by DemyleinationAnn New York Acad Sci 1954 58:582-594 Department of Cardiothoracic Surgery, Stanford University School of Medicine
  9. 9. Putnam proposes that the basicetiology of MS is venous obstruction Tracey Putnam, Boston City Hospital, developed an experimental dog model of venous obstruction to study MS. At the end of his paper, he stated: “The similarity between such lesions and many of those seen in cases of multiple sclerosis in man is so striking that the conclusion appears almost inevitable that venular obstruction is the essential immediate antecedent to the formation of typical sclerotic plaques.” Putnam (1935). Studies in multiple sclerosis: encephalitis and sclerotic plaques produced by venular obstruction. Arch. of Neurol. and Psychiatry. 33: 929-940. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  10. 10. Chronic cerebrospinal venous insufficiency and multiple sclerosis What do we know about Multiple Sclerosis?• Clinical manifestations: Motor, Somatosensory, Cognitive• Differential diagnosis: Inflammatory, Infectious, Metabolic, Neoplastic• No cure• Treatments: Immunosuppression Department of Cardiothoracic Surgery, Stanford University School of Medicine
  11. 11. Degeneration Versus Autoimmunity In Multiple Sclerosis The most widely accepted hypothesis for the cause of MS is that a CD4 T-cell-mediated autoimmune reaction is directed against myelin-related proteins; in addition myelin-specific T- and B-cell responses are memorized as a permanent adaptive immunity, perpetuating the disease. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  12. 12. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  13. 13. AnnNeurology 2009; 66:739-753 Department of Cardiothoracic Surgery, Stanford University School of Medicine
  14. 14. Henderson APD. AnnCardiothoracic Surgery, Stanford University School of Medicine Department of Neurol 2009;66:2739-753.
  15. 15. These obsevations raise questions aboutthe long-held premise that MS is primarily an auto-immune diseaseTheir findings strongly suggest that the early loss of oligodendrocytes/demyelination is not by adaptive immune attack; taken together, their results areconsistent with autoimmunity/inflammation being a secondary reaction to some unidentified process triggering death of oligodendrocytes and degeneration of myelin that is independent of a primary cell-mediated or humorally-mediated immune reaction. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  16. 16. To Begin – What Is CCSVI? Chronic Cerebrospinal Venous Insufficiency (CCSVI) has been hypothesized by Paolo Zamboni and others to explain the pathogenesis of Multiple Sclerosis (MS) and/or many of its associated symptoms. CCSVI has itsbasis in the observed relationship between the cerebral veins and lesions of MS. It proposes that extracranialvenous obstruction interferes with the venous drainagefrom the CNS, leads to changes in the normal intra- and extracranial hemodynamics, and contributes to the development and progression of MS. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  17. 17. The Association of Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and Multiple Sclerosis Background and Hypothesis• MS plaques venocentric – Lesions extend counter-current to normal venous flow direction – Distribution of lesions often peri-ventricular where higher vein density – Peri-venous cuffs similar to appearance noted in chronic venous disease• BBB breakdown – Vessel wall breakdown which leads to micro-bleeds – Iron acts as an inflammatory agent (histo and MR SWI show increased iron content in plaques developing in pattern identical to venous counter-current – Ischemic areas associated with shunting of blood volume and vessel atrophy• Extracranial venous obstruction – Lesion site is non-specific (dural sinus, jugular, brachiocephalic, azygous veins alone or in combination) – Lesion etiology is non-specific (congenital/hereditary, osseous impingement, arterial compression, post-inflammatory, arachnoid granulation, etc., alone or in combination) Department of Cardiothoracic Surgery, Stanford University School of Medicine
  18. 18. 7-Tesla MRI Images of Patient with MS Inflammation surrounding vessels (yellow) in very early lesionsNYU Physician 2008 60:16-17 Department of Cardiothoracic Surgery, Stanford University School of Medicine
  19. 19. Detection of Small Parenchymal Veins within MS Lesions Using T2-weighted 3T and 7T Imaging 7T Scan 3T Scan 7T Scan 3T ScanInvestigative Radiology 2009 44:491-494 Department of Cardiothoracic Surgery, Stanford University School of Medicine
  20. 20. The conceptual framework• The vessel wall responds dynamically to changes in flow and pressure (pulsatile shear stress and cyclic strain)• Alterations in venous flow and pressure may elicit inflammation, thrombosis and tissue injury Department of Cardiothoracic Surgery, Stanford University School of Medicine
  21. 21. Laminar Flow Promotes Factors that Reduce Inflammation Disturbed or Reversed Flow Promotes Inflammatory and Thrombotic PhenotypeBergan J. New England Jour Med 2006 355;488-498. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  22. 22. Adhesion molecule (VCAM- 1) and cytokine expression Oxidative stress, nFKB activation, reduced NOS activity Leukocyte rolling and adhesion Immune cell infiltration of vein wall VSMC hyperplasia Microhemmorhage and parenchymal cell death From studies of vein pathology after experimental AV fistula, venous occlusion, or vein grafts Traub and Berk, ATVBDepartment of Cardiothoracic Surgery, Stanford University School of Medicine
  23. 23. Active Lesions of Multiple Sclerosis Small lymphocyte adherent to vascular Blood vessel with RBCs endothelium, and another in the lumen is ringed by has almost traversed into small lymphocytes the peri-vascular space through a gap (arrow) Human Tissue Mouse Spinal CordNew England Jour of Med 2006 354:942-955 Department of Cardiothoracic Surgery, Stanford University School of Medicine
  24. 24. How Is CCSVI Diagnosed?• Doppler ultrasound• MR venography (CT venography)• Conventional catheter venography Department of Cardiothoracic Surgery, Stanford University School of Medicine
  25. 25. What is the imaging data fromultrasound, venography and MR in support of the association between venous obstruction and multiple sclerosis? Department of Cardiothoracic Surgery, Stanford University School of Medicine
  26. 26. How Is CCSVI Diagnosed?• Doppler ultrasound• MR venography (CT venography)• Conventional catheter venography Department of Cardiothoracic Surgery, Stanford University School of Medicine
  27. 27. Venous Obstruction (CCSVI) and MS• Abnormalities noted in MS and CCSVI by Duplex Ultrasound – Reflux/reversal of flow in IJV irrespective of body position – Retrograde flow in deep cerebral veins by TCD – Direct detection of stenotic IJV lesion – Absent flow in jugular - even with increase in negative thoracic pressure – Loss of normal postural drainage pattern between IJV and vertebral veins – 2 OR MORE DUPLEX PARAMETERS IN 100% OF MS PATIENTS – MEAN # OF ABNORMAL PARAMETERS IN MS: 3.8 (normals: 0.12) Department of Cardiothoracic Surgery, Stanford University School of Medicine
  28. 28. Color doppler reveals abnormal venous outflow in majority of MS patientsZamboni et al, JNNP 2009 Department of Cardiothoracic Surgery, Stanford University School of Medicine
  29. 29. Detection of CCSVI by color doppler Normal RIJ Stenotic LIJ, with flow reversal Zamboni et al, JNNP 2009 Department of Cardiothoracic Surgery, Stanford University School of Medicine
  30. 30. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  31. 31. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  32. 32. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  33. 33. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  34. 34. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  35. 35. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  36. 36. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  37. 37. How Is CCSVI Diagnosed?• Doppler ultrasound• MR venography (CT venography)• Conventional catheter venography Department of Cardiothoracic Surgery, Stanford University School of Medicine
  38. 38. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  39. 39. Prominent valve cusps (R>L) Department of Cardiothoracic Surgery, Stanford University School of Medicine
  40. 40. Narrowed valve orificeMS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  41. 41. Candy wrapper twisted appearance of azygous with collateral flowDM Department of Cardiothoracic Surgery, Stanford University School of Medicine
  42. 42. Where does the extra-cranial venous obstruction occur andwhat causes the flow disturbance? Department of Cardiothoracic Surgery, Stanford University School of Medicine
  43. 43. The Association of Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and Multiple Sclerosis Summary Analysis• Extracranial venous obstruction – Lesion site is non-specific (dural sinus, jugular, brachiocephalic, azygous veins alone or in combination) – Lesion etiology is non-specific (congenital/hereditary, osseous impingement, arterial compression, post-inflammatory, arachnoid granulation, etc., alone or in combination) Department of Cardiothoracic Surgery, Stanford University School of Medicine
  44. 44. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  45. 45. Right side s/p mastoidectomy and neck dissection In 38% of the 36 specimens examined, the transverse process indents the posterior wall of the vein; in 8% a more severe kink is notedSurgical Neurology 1999; 51:500-505 Department of Cardiothoracic Surgery, Stanford University School of Medicine
  46. 46. But, the overwhelming majority are Low Jugular Lesions Department of Cardiothoracic Surgery, Stanford University School of Medicine
  47. 47. INVERTED OR MALFORMED JUGULAR VALVE MECHANISM BRAIN BRAIN BRAIN BRAIN R B E L F O C L No K U reflux X CHEST CHESTHEALTHY CONTROL CCSVI-MS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  48. 48. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  49. 49. ECTRIMS2011– Histological Analysis of VenousStructures in MS Patients and Non-MS Subjects Department of Cardiothoracic Surgery, Stanford University School of Medicine
  50. 50. What about endovasculartreatment of patients with CCSVI? Department of Cardiothoracic Surgery, Stanford University School of Medicine
  51. 51. Low Jugular Lesions Department of Cardiothoracic Surgery, Stanford University School of Medicine
  52. 52. LIJ valve with restricted openingSSMSM Department of Cardiothoracic Surgery, Stanford University School of Medicine
  53. 53. LIJ post PTA of valveSM Department of Cardiothoracic Surgery, Stanford University School of Medicine
  54. 54. Internal jugular vein stenosis and reflux Department of Cardiothoracic Surgery, Stanford University School of Medicine
  55. 55. Internal jugular vein stenosis and reflux Department of Cardiothoracic Surgery, Stanford University School of Medicine
  56. 56. Right internal jugular vein post PTA Department of Cardiothoracic Surgery, Stanford University School of Medicine
  57. 57. Azygous Department of Cardiothoracic Surgery, Stanford University School of Medicine
  58. 58. Pre/Post stenting of twisted descending azygous vein JJE Department of Cardiothoracic Surgery, Stanford University School of Medicine
  59. 59. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  60. 60. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  61. 61. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  62. 62. What are the anticipated short and long-term clinical outcomes of endovascular management ofextra-cranial venous insufficiency? Department of Cardiothoracic Surgery, Stanford University School of Medicine
  63. 63. Venous Obstruction (CCSVI) and MS• Initial Observations Recorded after Endovascular Treatment of Venous Stenotic Lesions – Global symptoms attributable to MS, but not referrable to a specific neuro-anatomic loci (ie., fatigue, headache, heat sensitivity, “brain fog“, urinary urgency,etc.), show short-term improvement and in some cases (low EDSS) completely resolve. This suggests that these particular “MS“ symptoms may be more accurately categorized as related to venous obstruction. – Early-term follow-up of functional mobility (high EDSS) is not conspicuously changed from pre- procedure. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  64. 64. Liberation Study• Longitudinal Arm (100 patient)• 62% Female, 38% Male• Mean age: 47 years• Multiple Sclerosis Type • Relapsing Remitting: 54% • Secondary Progressive: 34% • Primary Progressive: 12%Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  65. 65. Liberation Study• Longitudinal Arm (100 patient)• Total # lesions: 174• Location of lesion • Right IJV: 41% • Left IJV: 49%Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  66. 66. Liberation Study• Longitudinal Arm (100 patient)• Total # lesions: 174• Location of lesion • Right IJV: 41% • Left IJV: 49% • Azygous Vein: 10%Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  67. 67. Liberation Study• Longitudinal Arm (100 patient)• Mean stenosis: 78% (range 50-100%)• Number of lesions/ patient: • 1: 22% • 2: 52% • 3: 20% 1.7 lesion/ pt. (mean) • 4: 6%Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  68. 68. Liberation Study• Longitudinal Arm (100 patient)• Anticoagulation during procedure• Antiplatelet post-procedure• Immediate success <30% residual stenosis: 82%Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  69. 69. Liberation Study• Longitudinal Arm (100 patient)• Anticoagulation during procedure• Antiplatelet post-procedure• Immediate success <20% residual stenosis: 82%• Mean follow-up 4.5 months (N=79)• Restenosis >50%: 8%• Occlusion: 2%• Other complications: 0.8% (new onset A-fib)• Major complications: 0%• Death: 0%Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  70. 70. Liberation Study: timed 25-Foot walk Follow-up 4.5 months Pre Post- N P-value Procedure Procedure All MS Types 79 11.47 10.42 0.01Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  71. 71. Liberation Study: timed 25-Foot walk Follow-up 4.5 months Pre- Post- N P-value Procedue Procedure All MS Types 79 11.47 10.42 0.01 Relapsing 53 10.67 10.44 0.02 RemittingMehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  72. 72. Liberation Study: timed 25-Foot walk Follow-up 4.5 months Pre- Post- N P-value Procedue Procedure All MS Types 79 11.47 10.42 0.01 Relapsing 53 10.67 10.44 0.02 Remitting Secondary 20 10.75 9.83 0.03 ProgressiveMehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  73. 73. Liberation Study: timed 25-Foot walk Follow-up 4.5 months Pre- Post- N P-value Procedue Procedure All MS Types 79 11.47 10.42 0.01 Relapsing 53 10.67 10.44 0.02 Remitting Secondary 20 10.75 9.83 0.03 Progressive Primary 6 13.00 11.00 0.03 ProgressiveMehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  74. 74. Liberation Study mean follow-up 4.5 months Pre- Post- P- Procedure Procedure Value MS QOL – Physical Health Composite Score 40.2 59.2 0.002 (Mean)Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  75. 75. Liberation Study mean follow-up 4.5 months Pre- Post- P- Procedure Procedure Value MS QOL – Physical Health Composite Score 40.2 59.2 0.002 (Mean) MS QOL – Mental Health Composite Score 52.7 70.5 0.006 (Mean)Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  76. 76. Liberation Study mean follow-up 4.5 months Pre- Post- P- Procedure Procedure Value MS QOL – Physical Health Composite Score 40.2 59.2 0.002 (Mean) MS QOL – Mental Health Composite Score 52.7 70.5 0.006 (Mean) Modified Fatigue Impact 15.8 12.2 0.001 Score (Mean)Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  77. 77. Liberation Study mean follow-up 4.5 months Patients Reporting Improvement MS QOL – Physical Health Composite 84% Score (Mean) MS QOL – Mental Health Composite 92% Score (Mean) Modified Fatigue 82% Impact Score (Mean)Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  78. 78. Liberation Study mean follow-up 4.5 months Pre MS Symptoms Procedue Loss of Balance 89% Lower Extremity 84% Weakness Bladder incontinence 71% Decreased Co- 74% ordination Vertigo 47%Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  79. 79. Liberation Study mean follow-up 4.5 months Pre No P- MS Symptoms Improved Procedue Change value Loss of Balance 89% 65% 35% <0.05 Lower Extremity 84% 79% 21% <0.05 Weakness Bladder incontinence 71% 67% 33% <0.05 Decreased Co- 74% 61% 39% <0.05 ordination Vertigo 47% 71% 29% <0.05Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  80. 80. Liberation Study mean follow-up 4.5 months Pre MS Symptoms Procedue Fatigue 89% Heat Intolerance 68% Memory Loss 57% Depression 45%Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  81. 81. Liberation Study mean follow-up 4.5 months Pre No P- MS Symptoms Improvd Procedue Change value Fatigue 89% 79% 21% <0.05 Heat Intolerance 68% 62% 38% <0.05 Memory Loss 57% 71% 29% <0.05 Depression 45% 74% 26% <0.05Mehta et al. Presented SVS 2011, In press JVS Department of Cardiothoracic Surgery, Stanford University School of Medicine
  82. 82. Currently, many unknowns and lots of uncertainty• CCSVI Diagnosis – Is CCSVI something we are born with, acquire, or both? – What % of MS patients and healthy controls have CCSVI? – Is CCSVI a consequence of MS or part of the disease pathogenesis? – How do we reliably diagnose CCSVI and know if it is physiologically relevant? (Doppler ultrasound, MRV with flow, IVUS, cervical plethysmography, cerebral perfusion, etc.) – How does CCSVI fit into the current immune concept of MS pathogenesis or doesn‘t it? – How can we engage neurologists in meaningful collaboration to study a concept they truly regard as total lunacy? Department of Cardiothoracic Surgery, Stanford University School of Medicine
  83. 83. - ChaosAgreement Zone Of Complexity + Control + Certainty - Department of Cardiothoracic Surgery, Stanford University School of Medicine
  84. 84. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  85. 85. What is the evidence for CCSVI ? 2009–2011: 53 reports on CCSVI Confusion & Controversy !• < 20% of published studies: Evaluate evidence for or against CCSVI• > 80% of published reports: Commentaries, interpretations, opinions, diatribes, rants, HIPA violations Department of Cardiothoracic Surgery, Stanford University School of Medicine
  86. 86. Current Thoughts and Ruminations Regarding CCSVI and MS• Exploring leads to the pathogenesis of MS – It is like a detective story. New evidence surfaces; clues are investigated; research may produce conflicting, supporting and refuting observations that confound, bolster, or dispel prior notions; pieces of the puzzle are ultimately put in place. Each step may only illuminate the next step to take as we progress along a path toward understanding the multi-dimensional interplay that triggers disease. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  87. 87. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  88. 88. Conclusions• There has been a growing understanding of CCSVI in MS as studies are performed all over the world.• It is helpful to understand what we know and we don’t know for obvious reasons: – To help effectively communication with potential patients. – To make sure that discussions with neurology are balanced. – To be certain that research is directed towards answering the unanswered questions. Department of Cardiothoracic Surgery, Stanford University School of Medicine
  89. 89. Department of Cardiothoracic Surgery, Stanford University School of Medicine

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