1. Introduction and Overview  Although it has been over 25 years since the CDC investigated an outbreak of this disease in northern Nevada, Chronic fatigue syndrome is still lacking an appropriate name, a concise biological definition and an agreed upon medical category.

2. 1988: How Can Anyone Mistaken this illness for Depression or Fatigue?  Strep throat and non-EBV mono in the same week. She had a fever, lymphadenopathy, severe pain and muscle weakness.  Doesn’t recover but returns to school  First physical diagnosis: Adrenal insufficiency.

3. Our 26 year Long Battle isn’t Over  Number of years to diagnosis: 2  Number of major medical institutions visited: 4  Doctors and specialists consulted over 26 years includes: pediatricians, gastroenterologists,(gastro-paresis) cardiologists,(tachycardia) endocrinologists, psychiatrists, psychologists, internists, infectious disease specialists,(infections) hematologist oncologist,(severe anemia) surgeons,(gall bladder disease) family medicine, complementary

4. This is what patients want; You can them get here! Living healthy, happy and full of energy

5. This is where we are today: people are still asking “What is fatigue?” “Are you sick or tired?” Simple: “Can you exercise the next day?”

6. ME is :  Characterized by: inflammation, abnormal immune function, multiple infections, mitochondrial dysfunction, rapid disability and exercise intolerance  Complex and chronic  Relapsing and remitting and/or progressive

7. ME is not :  Psychological depression  A benign disorder (one which resolves completely with therapy or does not impact lifespan)  A Somatization disorder (one in which there is no physical cause of disease)  A matter of will-power  Caused by too little sleep/tiredness  Caused by working too hard  Caused by childhood abuse

8. Medical Challenges  How does one explain an illness called, Fatigue?  Inappropriate name for one common symptom  Symptomatic Definition/diagnosis of exclusion  Lack of medical knowledge/not adequately explained  Physician shortage/those willing to treat patients  Diagnostics  Treatments/great variation depending upon physician  Lack of coordinated medical care with other medical specialists  Medical subspecialty (disease experts)  Public information is misleading, causing confusion and lack of support of those who are ill

9. A Disease with Many Names or are there Many Diseases?  Myalgic Encephalomyelitis, ME  Post Infectious Fatigue or Chronic Fatigue Syndrome, Fatigue, CFS, CFS/ME  Other similar diseases or subgroups :  Gulf War Illness: Multi-symptom illness resulting in loss of physical and mental stamina  Mycotoxin Illness: Multi-symptom illness due to mitochondrial and immunological damage from mold infections and their mycotoxins along with other pathogens found in water damaged buildings  Chronic /Post-Lyme Disease  Autism

10. The name “Chronic Fatigue Syndrome” has got to go!  Fatigue has been reduced to “tiredness”  Fatigue is only one of many symptoms  Fatigue is not the most severe symptom  Fatigue is difficult to quantify and often confused with depression

11. Before “Chronic Fatigue Syndrome” it was called Myalgic Encephalomyelitis (ME) Dr. Ramsey described ME in 1956 A neurological disease Abnormal immunological response of the patient to the organism. Circulatory disorder Abnormal cerebral activity Any excessive physical or mental stress is likely to precipitate a relapse. Tends to be chronic

12. Compare Symptoms/Not Definitions  ME  Acute onset follows respiratory or gastrointestinal illness/low grade fever  Circulatory abnormalities/cold extremities/ashen pale  Cerebral symptoms/memory, concentration, emotional liability  Abnormal immunological response  Fluctuating symptoms  Chronic  CFS  Follows infectious illness/environmental toxins  Chronic infectious symptoms  Muscle pain/weakness  Neurological symptoms/memory, concentration/ ataxia, seizures,  Dysautonomia  Post exercise malaise  Relapsing/remitting symptoms  Chronic

13. 2011: Myalgic Encephalomyelitis International Consensus Criteria  Myalgic Encephalomyelitis is an acquired neurological disease with complex global dysfunction.  Pathological dysregulation of nervous, immune and endocrine systems with impaired cellular energy metabolism, and ion transport are prominent features.

14. Other Biological Disease Definitions  Lupus is a chronic, autoimmune disease that can damage any part of the body (skin, joints, and/or organs inside the body) LFA  Multiple sclerosis (MS) is …. A disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. ( MS society )

15. ICD-10 Chapter VI Diseases of the nervous system (G00-G99)  G93.3  Post viral fatigue syndrome  Benign myalgic encephalomyelitis  They are joined

16. Challenges: Yesterday and Today  Doctors  Patients  Families of those with ME  Researchers

17. Challenges for Physicians  No approved biological diagnostic tests  No FDA approved pharmaceutical treatments  Insurance coverage denied for testing and treatments  Need guidelines for emergency room, anesthesia or surgery

18. Challenges for ME/ CFS Patients  Name of illness trivializes impact and ignores reality of infectious and immunological aspects of disease  Lack of understanding of complexity and severity of disease  Difficulty finding doctors who are knowledgeable about ME  Lack of means to pay for appropriate medical care

19. Challenges for Families  Lack of centralized accurate information  Lack of emotional support for entire family  Lack of medical support  Lack of financial support for medical care  Loss of income and/or functioning family member  Lack of educational support/guidelines

20. Challenges for Researchers  Too little research funding  Research definition lacks specificity  Patients are all grouped together  Groups of patients often dependent upon physician’s practice  No national repository of patient samples  No clinical centers of excellence

21. Obstacles to Progress  Disagreement by most physicians and researchers  Definition: needs to add biological information to be more concise  Most significant underlying feature should be stressed  ME has an ICD10 medical category (neurological) but it is not listed in the NIH research home: NINDS, why not?  For most, CFS is still a diagnosis of exclusion  Most biological research has been ignored in government definition

22. Doctors Who Misunderstand  Internist: “If I don’t know what it (abnormal viral titers) means it can’t be important.”  Neurologist: “I didn’t read her medical reports because the facts might get in the way of my theory.”  Neurologist: “I couldn’t read her MRI: it probably wasn’t important anyway.”  Surgeon: “I won’t do her gallbladder surgery because she has CFS.”  Cardiologist: “I can’t treat her tachycardia because she has CFS.”  ER doctor: “I could give her fluids if she had an immune deficiency.”

23. CDC Definition Lacks Scientific Information for CFS  Chronic fatigue syndrome (CFS ) is a debilitating and complex disorder characterized by intense fatigue that is not improved by bed rest and that may be worsened by physical activity or mental exertion.  Systemic Lupus Erythematosus is an autoimmune disease in which the immune system produces antibodies to cells within the body leading to widespread inflammation and tissue damage.

24. A New Beginning

25. Possible Solutions: A Fresh Start because ME has become CFS  Rename the disease: perhaps after the person who first described ME: Dr. Ramsey ; Ramsey’s  Use the CCC criteria for clinical definition and add a biological one sentence definition.  Seek international input to create suggested diagnostic and treatment protocols based on biological science not on psycho-social theories  Select a medical specialty to focus on this disease: Neurology and/or infectious disease?

26. Why is a Name so Important?  Disease name and definition determines research emphasis and funding  Research identifies biomarkers of disease  Industry develops and sells diagnostic tests  Diagnostic tests lead to pharmaceutical treatments  Mandatory insurance coverage of testing and treatment  Knowledge equals better physician education

27. Keys to Defining Disease  Concise description: one sentence that categorizes the disease: neurological,autoimmune, infectious, toxic, inflammatory, mitochondrial, etc.  Identifies the effect of the disease on various parts of the body  Identifies the risks or complications associated with the disease

28. Biological Abnormalities Associated with ME/CFS  Immunological  low NK cell function and number  Gut pDCs produce HERV proteins (auto antibodies)  Inflammatory cytokines  Neurological  abnormal brain scans  EEG results abnormal  Dysautonomia  Disordered sleep  Seizures  Cardiovascular  Gastrointestinal  Musculoskeletal  Endocrine  Systemic  Infections  low glutathione, low blood volume and abnormal VO2 max.  Energy deficits

29. Major Symptoms  Cognitive Impairment  Dysautonomia  Pain; nerves, joints, muscles  Lymphadenopathy, sore throat, severe headaches, low grade fevers  Disordered and unrefreshing sleep  Gastrointestinal distress/gastro paresis/nausea, vomiting, hypoglycemia  Tachycardia, chest pain, dehydration, fainting,  Profound loss of energy: post exercise fatigue

30. How important are mitochondria to those with ME/CFS?  Mitochondrial disease: Symptoms may include loss of motor control, muscle weakness and pain, gastrointestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures, visual or hearing problems, lactic acidosis, developmental delays and susceptibility to infection.  Adult onset is becoming more prevalent

31. #1:Change the Name: Drop Fatigue and ME  Name for first person to describe ME after UK outbreak: Dr. Ramsey  Knowledge of disease changes over time without having to change the name  Subgroups can be identified such as Ramsey 1, Ramsey 2, etc.  New name will end old stigmas and misinformation

32. #2 Improve the Biological Definition  …….. is a complex (neuro-inflammatory) disease. It is triggered by infection and toxic environmental exposures which result in…..  Symptoms include mild cognitive impairment….  This disease may follow a relapsing and remitting course or become progressively worse over time.  It is associated with an abnormal immune response to various pathogens most notably borrelia, herpes viruses, entero-viruses and mycoplasma in addition to fungi and their mycotoxins.  It is chronic and can be severely debilitating

33. #3 Identify a Medical Specialty as Needed  Disease affects the nervous system and is immune and pathogen driven  Disease is debilitating  Disease is difficult to manage because of changing nature and complexity  Evaluation should be comprehensive  Diagnosis and treatment may be complicated  Treatment may require intravenous drugs or drug mixtures/knowledge of long term treatment protocols

34. #4 Educate the Medical Profession and the Public  Information should be kept up to date  Based on biological science  Consistent from one entity to another  Continue to change and add new information as it becomes available  Seek input from physicians, researchers and patients

35. Future Action Items for ME Experts  Create science based medical education text and online seminars  Identify lead NIH research institutes  Improve funding and focus of research  Help to develop medical standards, for emergency room visits, anesthesia and surgery

36. Can We Learn from Responders?  Ampligen  Antivirals  Anti-retrovirals  Immune Support  Anti-fungals  Anti-bacterials Clinical Studies Backed by Research Can Tell Us What we Need to Know!

37. Create a Research Road Map  Innate immunity  Mitochondria  Autoimmunity  Chronic infections  Genetic Susceptibility  Environmental Toxins

38. Create National Research Resources  Patient Registry  Cell lines  Bio bank  Animal model

39. What One Patient Wished the Doctors Knew  I have very bad days when I am too sick to see you  I have many other medical problems that you might be able to treat  My disease has many other symptoms that are much worse than fatigue.  Don’t blame all of my symptoms on my illness: you may miss something important  I try everyday to help myself through diet, limited exercise, supplements and prayer  I want to get well more than anything!

40. Follow progress of other disease groups to improve the lives of those with this disease!  MS:  Lupus:  Cancer:  Mitochondrial disease: Thank you!

41. 1990: Symptoms at age 12  Fever, painful joints and muscles, nerve pain, muscle weakness, severe head ache, sore throat  HHV-1 antibody titers abnormally high  Pale, dark circles under eyes, tender lymph nodes, new allergies  Unable to stand, feeling faint, dizzy, low temperature, low blood pressure  Disordered Sleep  Nausea, vomiting, diarrhea, constipation  Post exercise fatigue/could not play  Trouble with memory and concentration

42. 1990-2000 Illness Worsens  Level 0: Severe symptoms on a continuous basis. Bed ridden constantly, unable to care for herself  Gall bladder and appendix diseased and removed  Tachycardia and gastro-paresis  At 21 years: Doctors suggest two pace makers

43. Complementary Medicine Added  Acupuncture  Chinese herbs for multiple viral pathogens  Homeopathy  Supplements  Protein drinks  Dietary changes to avoid food allergies

44. 2006: A Major Relapse  While in remission of symptoms was given MMR vaccine for college, experienced severe relapse of all symptoms within 5 days.  0-10: Severe symptoms on a continuous basis