CCSVI Exploring the Relationship: Chronic Cerebrospinal Venous Insufficiency & Multiple Sclerosis James F. McGuckin, M.D. Director, Philadelphia Vascular Institute Founder, Vascular Access Centers www.vascularaccesscenters.com

Introduction: Dr. James McGuckin Double major in Mechanical Engineering and Pre-Medical from the University of Notre Dame in 1983, M.D. from Hahnemann University in 1987, Masters Degree in Bioengineering at the University of Pennsylvania in 1990, Diagnostic Imaging in 1995, and Fellowship in Interventional Radiology at the Hospital of the University of Pennsylvania in 1996. Many invited lectures annually in the USA and Internationally. Founded Philadelphia Vascular Institute, Rex Medical, and Vascular Access Centers (www.vascularaccesscenters.com). I am a full-time practicing Interventional Radiologist and am licensed in over 20 states in the USA. I primarily see Western Canadian citizens in Seattle and Eastern Canadians in Philadelphia and New Jersey. Research interests include: over 150 medical device patents, CCSVI, Cardiovascular Systems, Endoscopy and Endosurgery, Peripheral Arterial Disease, Limb Salvage, Percutaneous Oncologic Therapy, End Stage Renal disease and recanalization of Central Venous Occlusion using RF ablation. I have collaborated with Drs. Lindsay Machan (BC), C.S. HO (Toronto General) and Dr. Sandy McDonald (Ontario) and I fully believe that the Canadian physicians will be up to the clinical challenge of treating the patients with MS from the vascular health perspective.

Autoimmune Theory Commonly held beliefs about MS For more than fifty years, medical doctors and scientists have believed and adhered to the theory that MS is an autoimmune disease. Autoimmune disease occurs when an overactive immune system—the system that naturally protects the human body against disease—mistakenly attacks a healthy part of the body as if it is a dangerous pathogen (like a virus) that must be destroyed. Proponents of the autoimmune theory believe that the disease develops when the immune system mounts an aggressive, misguided attack against the myelin sheath that insulates and protects the nerves of the Central Nervous System (CNS). They have yet to identify exactly why the immune system would initiate the attack. *Medicine changes and evolves- when I was in medical school Peptic Ulcer disease was caused by acid not bacteria, Non-A Non-B Hepatitis became Hepatitis C, Breast Cancer had an incidence of 1:11 later to become 1:7, and CABG (Coronary Artery Bypass) was the mainstay- not the fall back plan if all else fails. This will be review for some, but it does give context for CCSVI.

CCSVI – The Vascular Theory How is the CCSVI theory different? The CCSVI theory as it relates to MS does not contradict the fact that there is autoimmune activity and myelin damage within most MS lesions. It simply helps to explain how and why this activity and damage got its start- and why the MS symptoms follow similar patterns. According to the CCSVI theory, deformities in the veins that drain the CNS disrupt proper outflow of deoxygenated blood from the brain and spinal column- this is why we look for stenoses involving the drainage of the Jugulars, Azygous, Renal, and Pelvis. These deformities include malformed valves, significant narrowing, and membranous tissue or webbing inside the vein. When the blood leaving the brain encounters these deformities, it often refluxes back into the brain or stays too long within the brain because of delayed drainage.

“The Call” and The Hippocratic Oath Can you open the blocked vein in my neck? The first patient- “can you open the blocked vein in my neck?” “I think I can open your blocked vein, but I don’t know what it will do to your MS symptoms.” I was naive. An amazing experience-five wheelchair bound patients getting out of the chair and walking in our office in one week. The artist who could only see a circle on the wall- the circle that became a clock with numbers and minute hash marks between the numbers while still on the procedure table. The doctor speaks and nystagmus ceases. After three years of silence the physician-patient with MS said his three children’s names and sang Happy Birthday to his wife. His 10 years of constantly roving brainstem controlled eye movement stopped post-procedure and his eyes are now steady and controlled. Having a patient discharged from a nursing home and going home again- a joy to any caregiver. A patient on the table saying-“I see colors again.” “The pain in my head is gone.” These treated deformities include malformed valves, significant narrowing, and membranous tissue or webbing inside the vein.

Correlative Vascular Theory in Liver Cirrhosis -Budd-Chiari Disease Vascular outflow obstruction from the liver leads to portal hypertension (localized high venous blood pressure) causing cirrhosis secondary to iron deposition and inflammation. This venous disease (narrowing) is treated by venous angioplasty and stenting if needed. (Remember this picture you will see it again.) This will be review for some, but it does give context for CCSVI.

Prevalence of CCSVI “Many different groups from all over the world clearly showed by the means of gold standard catheter venography that the prevalence of CCSVI in MS [patients] is more than 90% of the cases studied (USA, Greece, Poland, Jordan, etc.)” *International Society for Neurovascular Disease, Bologna 2010

Treating CCSVI What can be done today? The structural problems of CCSVI can be treated effectively through balloon venoplasty—angioplasty of the veins. Ballooning disrupts venous irregularities by increasing the diameter of the vein. Increased diameter leads to improved blood flow, which helps reduce venous insufficiency.

Catheter entry-point Femoral access vein Access the patient easily through the Left Femoral vein with ultrasound guidance.

CCSVI: -Extremely safe -Conscious sedation Rapid Recovery Azygos systems Internal jugular veins Renal Veins Femoral access vein Renal veins Iliac veins CCSVI: -Extremely safe -Conscious sedation Rapid Recovery Check and treat the venous narrowings

The Right Internal Jugular is selected and studied by venogram- the narrowing is treated by veno/balloon angioplasty and the collaterals or side-street vessels go away because the resistance to flow is gone through valve disruption.

Dramatic dilation by balloon angioplasty of the Left Internal Jugular narrowing with resolution of the parallel vessels showing the resistant to flow by the abnormal valve being treated.

The picture on the left is the Left Internal Jugular vein again- the picture on the right is the Budd-Chiari venogram- upside down. Venous narrowing look the same regardless of location.

The Azygous vein behind the heart with dramatic congestion because of an outflow venous narrowing treated successfully with angioplasty

47 yo MSx 17 yrs pre-CCSVI procedure

Secondary Progressive MS pre-CCSVI

24 hours post- procedure

4 days post-procedure

CCSVI – Summary I have personally studied hundreds of patients with MS. They all have had CCSVI. The majority of these patients are citizens of Canada, and most of them are enrolled in the Hubbard Registry. None of these MS patients were normal on venography and all had truncal venous abnormalities. These deformities include malformed valves, significant narrowing, and membranous tissue or webbing inside the vein. Over 80% of patients have had a positive response to the treatment with a reduction in their symptoms. The focus of MS research should include discovering the etiology of MS, improving treatments for MS patients, evaluating the safety and efficacy of treating the vascular abnormalities associated with CCSVI/MS, and developing therapies that augment and preserve the improvements developed through endovascular treatment.