Good afternoon. It's my pleasure to introduce our next speaker. Dr. Allison Vested is a hematological pathologist. She graduated with her medical degree from McMaster University in Hamilton, Ontario, Canada, and her fellowship from the University of Toronto, Ontario, Canada. Her fellowship training included clinical and laboratory hematology, anatomic pathology, genetics, immunohematology, internal medicine, and oncology. She received her American Diplomate Integrative Medicine in 2017. For the past 30 years, Dr. Vested has been devoted to treating patients with complex chronic medical conditions, including myalgic encephalomyelitis, or chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities. Dr. Vested co-authored two books, Hope and Help for Chronic Fatigue Syndrome and Fibromyalgia, and the Complete Fibromyalgia Health Diet Guide and Cookbook. Dr. Vested is an associate professor and the chair of integrative medicine in the Dr. Kiran C. Patel College of Osteopathic Medicine at Nova Southeastern University. Her current research interest is in exploring the treatment of hyperbaric oxygen therapy for veterans with mild traumatic brain injury or post-concussion syndrome. Dr. Vested will discuss an off-label drug indication, low-dose naltrexone. She has no other disclosures. So without further ado, Dr. Vested. Hello, I'm Dr. Allison Vested. I work at Nova Southeastern University and I'm the chair of integrative medicine. It's my pleasure to give you my chat today about chronic fatigue syndrome or myalgic encephalomyelitis, currently going into long COVID. I'm going to be covering the path of physiology, diagnosis and management strategies to treat chronic fatigue syndrome and myalgic encephalomyelitis. I have no disclosures. I will be discussing slightly low-dose naltrexone. I'd like to acknowledge the following people who have been so helpful in helping me understand this complex area of medicine, including Drs. Marshall, Ray, Kerr, Mallott, Stein, Logan, McRindle and Margaret Parler. I'd also like to thank the Dean of the KP Comm. School of Osteopathic Medicine here at NSU for developing the integrative medicine program. And I'd also like to thank my fellow workers in the Institute for Neuromedicine, Drs. Nancy Klimas and our clinicians, Dr. Ray and Annette Fornos, our nurse practitioners who have their diplomat in nursing practice, Violetta Roneska, Irina Rosenfeld and Denise Krasinski. And I'd also like to thank my patients who teach me so much and are my inspiration. Today's goals are to identify the clinical criteria needed to diagnose ME-CFS, to understand the pathophysiology of ME-CFS, to understand the prevalence of ME-CFS and chronic fatigue syndrome in the United States, and to identify the best treatment modalities for patients with ME-CFS with examples of a case. So what is the nomenclature for ME-CFS? What's in the name? This is not a new illness. This goes back, you can find it in the 1400 BC, the Ebers papyrus, and it was described there as chronic fatigue post-infectious illness after either a viral parasitic or bacterial infection. In the 1800s, it was described as neurasthenia. In 1956, the World Health Organization described it after an outbreak as myalgic encephalomyelitis. We commonly call it ME now. And in 1988, there was an outbreak in Incline Village in Nevada, USA, and it was renamed chronic fatigue syndrome. In 2003, there was a Canadian consensus criteria written by Carothers and others in Canada. And in 2015, it was recalled, named SEAD from the Institute of Medicine in a review. It is currently listed in the ICD-10 coding book as myalgic encephalomyelitis, and there is a neurology. It's underlisted under neurology, and the code is G93.3. So what is the prevalence of ME? We know that it ranges between 0.4 to 2.5% of the adult population in the United States. And the reason for this wide variation is because there are currently 21 different definitions listed around the world. So today, I will try to simplify this for you. And ME can occur either after sporadically, the odd person gets it here and there, or there can be cluster outbreaks as there have been in the past. There's a peak incidence of being present at age 33. Children as young as three have been described as having it. It occurs in all racial and ethnic groups, and it is twice as common in women as in men. And I would refer you to the work by Jason below if you're interested in the actual prevalence. So what exactly is ME-CFS? It's a chronic, complex, multi-system physical disease, and it involves all these different systems listed below. The most important one is on the bottom right. It has severe post-exertional fatigue and malaise with an abnormal metabolism. There is immune dysfunction with decreased natural killer cell activity and an innate immune dysfunction. The brain is affected with cognitive problems, dysfunction, sleep problems, anxiety, and often HBA axis dysregulation. There is pain present, often that's new. It may be headaches. It may be migratory in the muscles and joints. And there is autonomic dysfunction present, often with orthostatic intolerance as seen in research studies with low blood volume and low blood mass present. So the most important thing that you can do for your patient is to make the diagnosis. This is the key. ME-CFS is a physical disease and it needs to be treated as such. And as mentioned previously, the ICD-10 code under the World Health Organization lists it as myalgic encephalomyelitis under neurology with the ICD-10 code G93.3. So please use this in your diagnosis so that it can be tracked as to actually find out the prevalence of ME in the United States. So what is a patient's experience? They often, story goes, there were 20 of us at the Christmas party. We all got sick. 19 out of 20 people got better. What happened to me? I never recovered after this flu-like illness. So there's a failure to recover from a prior infection and abnormal unrefreshed sleep. 25% of the patients are bed or housebound at some point in their illness as a result. The symptoms persist for years and most patients never regain their pre-illness level of health or functioning. The ME-CFS patients experience a loss of productivity and high medical costs that can contribute to a total economic burden of between 17 to $24 billion annually. And it has been found that 25% of the patients are either unemployed or receiving disability insurance. So 25% of all patients list fatigue as the reason for their visit to their family doctors or their primary care visits office. So what are the barriers to patients getting the diagnosis made? The first thing is number one, physicians have not been taught how to diagnose ME in medical or graduate school. So I'm fortunate to be able to teach this here to you today so that you can understand how to recognize ME-CFS in your patient population. As of 2019, I was basically taught teaching ME-CFS, one of the first medical schools to do this. And the second reason that there's a problem with ME-CFS in understanding the pathophysiology and moving things along is because the research has been very poorly funded. As a result, 85 to 90% of ME adult patients are not funded, are not diagnosed rather. In terms of the research, now there is post-COVID funding. So we're hoping that this will impact on the ME-CFS population as well because post-COVID is the latest virus resulting in ME-CFS. How do you diagnose ME-CFS? You take a comprehensive history, you do a thorough physical examination, you order laboratory tests to exclude other fatiguing illnesses because there is no specific diagnostic blood tests or any other. So I'm going to walk you through the Canadian Clinical Working Case Definition criteria today to help you diagnose your patients. This is the most straightforward criteria, in my opinion, having been doing this for 30 years, and I think you'll find it very helpful. So these are the criteria that patients with ME have, and they have to have in order to meet the criteria. The first is fatigue. The fatigue is new, it's onset, it's basically profound, it's pathological, and it involves both the mental and physical activities, and it reduces or impairs the person's ability to do normal daily activities. So this is a severe fatigue. This is not something, oh, I'll get a cup of coffee and feel better later. The person has difficulty getting up to have a cup of coffee, and afterwards they may have to rest for half an hour. There's number two is post-exertional fatigue or malaise. As a result of doing an activity, the person may push themselves beyond their available energy, and they may have symptoms of a severe relapse of their symptoms, which includes all of the symptoms we're listing below. And this may involve physically, cognitively, and after an emotional effort. There's a very slow recovery. It takes at least 24 hours, and sometimes it may take days to weeks. The sleep is unrefreshing. Patients go to bed exhausted and wake up exhausted. They have new pain. It may be muscle pain, it might be joint pain, there might be new headaches. There is no redness, and there is no swelling. And this pain seems to migrate throughout the different body parts. There's cognitive dysfunction, often patients describe as brain fog. They have poor concentration, poor word retrieval, difficulty with short-term memory, slow processing, and the inability to multitask. When they have this cognitive dysfunction that may be associated with crashing, and there may also be anxiety present with this brain fog. The other symptoms include one symptom from one of the following three categories, and the three categories are the autonomic nervous system, the neuroendocrine system, and the immune system. So you have to have one symptom from three categories. The first is the autonomic nervous system. There's orthostatic intolerance, which basically when you stand a person up, their blood pressure drops. They may have POTS, which is another form of that, which is postural orthostatic tachycardia syndrome. You stand the person up, they basically have a drop in blood pressure, and their heart rate may go up. The associated symptoms they may have with the orthostatic intolerance include vertigo, nausea, feeling lightheaded. They also might have, as part of the autonomic nervous system symptoms, irritable bowel syndrome, urinary bladder dysfunction, cardiac arrhythmia, and palpitations. The neuroendocrine symptoms include an abnormal appetite. The appetite may be increased or decreased, a marked weight change, their stress intolerance, and either heat or cold intolerance. And these stay consistent in the person. So if a person has cold intolerance, they always have cold intolerance. These do not switch back and forth. The immune system symptoms include recurrent sore throats, tender lymph nodes, often cervical, axillary, groin. There might be flu-like symptoms, symptoms of general malaise, allergies, new sensitivities to foods, medications, and plus or minus synthetic chemicals, such as cleaning fluids. And the length of time that has to be present in order to make the diagnosis is in adults, it's greater than six months, and it's children, it's greater than three months. So in order to diagnose ME-CFS, the treatable illnesses that have similar symptoms must be ruled out first. And because appropriate treatment of other conditions may resolve the patient's symptoms totally. So this involves ruling out any other symptoms from the endocrine system, including primary adrenal insufficiencies, diabetes, any other infectious diseases that might be present, such as HIV, tick-borne illnesses, hepatitis, gastrointestinal disorder, such as celiac disease, inflammatory bowel disease, small intestinal bacterial overgrowth, or SIBO, environmentally-related environmental exposures, such as heavy metal toxins, mold, or mycotoxin exposures, any rheumatological disorders, such as systemic lupus or rheumatoid arthritis, any treatable sleep disorders, such as sleep apnea, narcolepsy, et cetera, any cardiovascular disorders, including cardiomyopathy, coronary artery disease, any untreated oncology disorders, such as primary or secondary cancers, any untreated undiagnosed neurological disorders, such as MS, Parkinson's, Chiari malformation, traumatic brain injury, spinal stenosis, and cranial cervical instability or seizures, any primary psychiatric disorders have not been treated, such as severe anxiety, depression, bipolar, any hematological disorders, such as hematology, anemia, iron deficiency, other treatables, iron overload, other chronic leukemias, et cetera, and miscellaneous things, such as obesity, overwork syndrome, overtraining asthma, and obstructive pulmonary disease. So all these things must be ruled out and treated before the diagnosis of ME-CFS is made. So how do you rule out these basic illnesses? This is where the laboratory is very helpful. So you order, these are the basics that you would order. So you would order a CBC with a differential to rule out your iron anemias, iron deficiency anemias, sedimentation rate to a C-reactive protein to rule out disorders of inflammation, such as rheumatological disorders, your electrolytes, calcium phosphorus, fasting glucose in order to rule out your diabetic problems, liver function tests, such as alkaline phosphatase, bilirubin, AST, ALT, GGT to rule out liver problems, including your protein albumin and globulin ratios. You do kidney function to rule out kidney problems. You'd look at your thyroid functions, TSH, free T4, possibly free T3 to rule out treatable thyroid problems. Your ANA would be part of your screening for rheumatological disorders. You'd look at your iron studies. You'd look at your B12 and folate to make sure you don't have an absorption problem, small intestinal, possibly, problem. You'd order a vitamin D3-25 hydroxyl in order to rule out vitamin D deficiency. We're finding that more than half of our patients have vitamin D deficiency or depletion. And then if you're suspected of irritable bowel symptoms, you'd look at the celiac screening for gluten, including your transglutaminase, IgA and IgG, and your urinalysis to make sure that you don't have any ongoing chronic infections or other kidney problems that you're not aware of. So these are additional tests that can be done, which are indicated from the specific person's symptoms. So one size does not fit all with these people. You need to have a very complete history to make sure that you're looking at the entire spectrum of illnesses to rule them out. So you might want to do allergic skin testing or elimination, re-ingestion challenges. If you think that there are food problems and food sensitivities, you might order an EKG or cart echo or possibly a tilt table test, if you have an experienced center, to rule out POTS, the postural orthostatic tachycardia syndrome. You might want to order an endocrine four-part salivary cortisol levels to see just how depleted the adrenals glands are and all the other glands as well. You could order the endocrine function and testosterone as well. I usually recommend an overnight sleep study just to be sure you're not dealing with sleep apnea in order to rule this out, because even thin patients may have sleep apnea. And this also documents the difficulty with the sleep the patient is having. So this is one more validation that there is a problem with the ongoing sleep in these patients with ME. A cytokine panel is helpful if you can do it to show that there is increased inflammation possibly present depending on the phase of the illness. A gastrointestinal stool analysis may be helpful if there is problems with irritable bowel symptoms that you're suspecting. Also, you might look at the ultrasound of the gallbladder if you're having symptoms there. Again, gynecological and ultrasound if it's warranted. Immunologically, you might want to look at double-stranded DNA, looking at autoimmune functions, and looking at responses to pneumococcal vaccinations if you think the person has a problem there. In infectious diseases, you want to test for possible other problems of exposure, especially those people who are exposed to tick bites and other tick-borne illnesses. An Epstein-Barr virus is commonly found in reactivation, so I find it often helpful in all my patients to order an Epstein-Barr virus with the early antigen, the nuclear antigen, and the viral capsid antigen. And that way, if you find an elevation in all three of the antibodies, that's the IgG antibodies, you know there's reactivation of the Epstein-Barr virus. Neurologically, you want to basically rule out any GRE malformations or cervical stenosis if you suspect that. And if there's a pulmonary problem, of course, you'd need to do pulmonary function tests. And if there are chronic symptoms of urology, symptoms such as chronic infections or chronic difficulty with urination, you might want to refer to a urologist for a cystoscopy. So what are the physical symptoms of ME-CFS? The patients are often either one extreme or the other. They're either underweight or overweight, and there's about 50-50 of each. We see often patients who are severely underweight, but there are also patients who are overweight depending on how long they've been ill and if they use food as a way to comfort themselves during their illness. If you shine an indirect light into the patient's eyes and you basically look at the pupils, you will probably see pupillary oscillation. So you'll see the pupils contract and dilate, and that goes along with their pulse rate. And this is an indication of the severity of the fatigue and the fact that the pupillary, the iris muscles basically do not have the strength to stay contracted as the light is being shined indirectly into them. I find it's a very helpful physical finding. If you look at the back of the throat, you'll see this is the uvula here, and this is both sides of the soft palate, and you'll see what's called red crescents. They're non-exudative and described as either red crescents or non-exudative pharyngitis. This is a common finding you'll find with ME. Sometimes it extends right down to the uvula, and when patients are feeling better, it may get lighter in color, it may get faded, and as they get sicker, have a reactivation of the virus, you'll see that it becomes more prominent. Associated with this, this is the symptom they get is a sore throat, and they may have tender cervical lymph nodes or left supraclavicular or axillary lymph nodes or groin lymph nodes as well, and these nodes are often mobile, shoddy, and tender when they're in a relapse. They may have postural hypotension. When the person is standing up, they basically have a drop in their pressure, and there is a test called the lean test where the patient leans their shoulders against a wall and you take their blood pressure every 10 minutes, and you can actually document the drop in their pressure over time. Sometimes you get an increase in their pulse as well. That's called a lean test, L-E-A-N. They often have cold hands and feet, and their nail beds may be slightly pale, sometimes blue, indicating they also may have Raynaud's. So this is an example of a patient that I saw. This was Dorothy at age 55. She was a full-time manager at a store, and she also volunteered at a symphony. She had lots of energy until she developed a flu-like illness three years before I saw her. When I saw her, she was sleeping almost all the day in bed. She went to this Christmas party where everybody got sick. They recovered, but six months later, she still had these symptoms. She had severe fatigue. Her energy was 3 out of 10. Normal is 9 to 10 on the functional capacity scale, which I will review in a minute. This was new to her. It was profound, pathological, and as a result, she could not work. She had post-exertional fatigue. She had relapse of her symptoms, and she crashed for more than 24 hours if she basically walked more than five minutes. Her sleep was unrefreshed, and she slept most of the day and most of the night. She had muscle pain over her body, and she was worse when she was sitting up. She had cognitive difficulties with poor concentration, focus, and understanding information. She had difficulty reading. She had autonomic nervous system problems. She felt dizzy when she stood up. She felt like she was going to faint. She had orthostatic intolerance and irritable bowel syndrome. She had alternating diarrhea and constipation. Her neuroendocrine symptoms include cold intolerance. She had stress intolerance and a reduced appetite. She had nausea, vomiting, and vomiting. She had a low appetite. She had hypersensitivity to light, noise, odors, and medications. As you saw initially on her picture, she was so underweight, I was concerned that she had a primary cancer. I kept looking for about a year afterwards to see if I could uncover one, and fortunately, it was never found. She had classic ME. This is the ME-CFS Clinical Diagnostic Criteria Worksheet, which comes from the Canadian Consensus Criteria. This is a helpful worksheet for you to use in your office so that you can describe all the symptoms in one spot. It's also helpful when you're dealing with insurance disability and in required forms. This is a very helpful way to organize your symptoms. It just goes through exactly what we did a second ago. You just check off the boxes, and so she would have all these checked off. Fatigue, post-exertional malaise, sleep, pain, neurological problems, autonomic, neuroendocrine, and immune manifestations. Her illness persisted for at least six months. This is called the ME-CFS Clinical Diagnostic Criteria Worksheet. This is the second page of this worksheet. It lists all of the exclusions that you have done in order to basically make sure that there's nothing else that's treatable. There's a handout for this. Just to point out that ME can be present with other illnesses and other diagnoses might be present, such as fibromyalgia is quite common, TMJ, temporal and mandibular joint syndrome, irritable bowel syndrome, etc. You can have more than one diagnosis, and it's seen as a comorbid entity. Then if you think the person meets the criteria, you would check that the patient meets the criteria for ME-CFS. You would sign it, date it, and put your physician's stamp here. I think it's a very helpful tool that has been very helpful for educating the patients and the insurance companies about ME-CFS. Now I'm going to go through the pathophysiology of ME-CFS as we know it now. We're hoping that this will improve as time goes on and we'll have a better understanding. However, we have a lot of information that shows that this is a physical illness and it impacts the patients severely. The pathophysiological evidence includes genetics, the endocrine system, the autonomic function system, the cardiac system, muscle metabolism. It looks at the infectious etiology, immunology, homeostatic hypothesis, and the hypometabolic state. We know that we're all born with genetic susceptibilities and we know that we have genetics. Basically, this is called as genetic loads the gun, but our environment pulls the trigger. The environment can be anything from our infectious triggers. It might be environmental things and it might be our food. Anything in the environment may possibly trigger this. We know with ME-CFS that the trigger is a post-infectious trigger. There were genetic profiles done in ME. In Spanish research, they looked at 1500 patients with ME-FM and they genetically analyzed them using the SNP, the single nuclear polymorphic technology. They found that ME and FM can be genetically distinguished from normal. They looked at 620 patients with ME-CFS and three generations of data that was collected in Salt Lake City, Utah. This was the first population base that was ever computer accessed. They found that there was a significant number of first and second degree relatives in patients with ME. There are also twin studies done. It showed a much higher possibility of getting ME in twins who are monozygous, identical twins compared to dizygotic twins. This was seen in the genomic studies in twin research of human genetics. There's ample evidence that there is a genetic susceptibility in patients with ME. Then there was a study done by Jonathan Kerr. He looked at the SNP technology and he basically found genetic correlation between how severe the patients were and their SNP technology. The kind of patients that I'm normally seeing are number seven. These are the most complex chronic patients. They have pain that's usually a post-infectious etiology suspected. They have musculoskeletal problems, sleep, neurological, gastrointestinal, neurocognitive, and anxiety and depression. This just shows this is the more severe of the phenotypes, but you can also get milder phenotypes as well. We know that there is central nervous system dysfunction. This can be shown on neurocognitive testing that is done by psychologists. It can show the difficulty with poor concentration, slow processing, difficulty with word retrieval, and multitasking. A good neuropsychologist can show this cognitive dysfunction that is present in ME patients. The physical findings, you can find poor balance and poor integration of ability to multitask. This is found if you do the tests for the Rhomberg tests and the tandem tests, which are often positive. The overnight sleep studies are often positive. In fact, in all my patients I've never seen that it has not been positive. It shows there's a decrease in stage four sleep. Stage four sleep is the stage of sleep where the brain restores it and heals itself. If you do not get this sleep, the body often does not heal. This would account for the patients going to bed exhausted and waking up exhausted. They often have multiple alpha wave intrusions, which shows that the brain has a constant awakening throughout the night. This is why the patients have difficulty getting to sleep and staying asleep. The endocrine dysfunction is shown in the measures of the cortisol levels. If you do a first morning cortisol level or a four-part cortisol level, you will see most of the time a decreased level of cortisol level. It shows that the adrenals are not fully functioning. We don't know whether it's because of adrenal depletion or there is reduced functioning of the HPA axis that affects the function of the adrenal glands. We do know that the adrenal glands do look reduced compared to normal. This is the opposite of what's present in a major depression and anxiety and post-traumatic stress disorder, where often the cortisol levels are elevated. We know that there is autonomic and cardiac dysfunction as shown by the postural orthostatic intolerance. You can see this with the tilt table tests. When you stand people up, their blood pressure drops and often their heart rate goes up. There's also a decreased heart rate variability, which shows that these patients are not physically managing very well. There is a decreased cardiac output and reduced blood volume. That blood volume is reduced as a result of reduced red cell mass, as well as reduced plasma volume. The 24-hour Holter EKGs are often abnormal with flattening of their T waves or inversions in tachycardia. You have to ask for this information in order to get it on the Holter monitor. As mentioned previously, the autonomic nervous system and cardiac dysfunction together are affected because of the reduced red cell mass and plasma volume presence. As a result of the reduced cardiac volume, there's higher levels of brain natriuretic peptide and there's often reduced aldosterone present by the zona glomerulosa of the adrenal cortex, which causes less sodium to be reabsorbed in the kidney nephrons. It has a post-infectious etiology. There was a study done in Australia that tracked all these different viruses and looked at how people were down the lane. They found that the people who were most severely affected, which was 10% of these people who had these viruses, who had a higher incidence of developing ME-CFS. These viruses they tracked in Australia was the enterovirus, Parvo-B19, Astine-Barr virus, Ross-River virus, Coxiella, CMV, HHV-V6, enterovirus, and also now Giardia has been tracked as well after an outbreak. It's post-infectious, not necessarily virus, but it can be parasitic also. We know that there is an immune dysfunction in ME-CFS. There's natural killer cell function abnormalities. The functionality is decreased for the natural killer cells. We know that there is a Th2 shifted immunity where people tend to be developing more allergic responses or autoimmune responses. There's decreased T suppressor lymphocyte subsets, CD838 and CD811B. There also may be elevated cytokines depending on how long the person has been ill. Initially, these cytokines may be elevated, these pro-inflammatory cytokines. As time goes on, though, this may change, but they are always distinctly different from normal cytokine patterns. This is what's being shown here, the altered homeostasis in the person who is normal versus the person who has ME-CFS. These are all the different cytokines listed here, IL-17, IL-5, IL-1. This is the normal person and how the cytokines interact with each other on the left-hand side. On the right-hand side is a person who has ME-CFS. You can see that there's much more interaction of certain cytokines, the inflammatory cytokines, TNF-alpha, IL-4. These are much more active in this particular patient. You can see the actual levels of cytokines may not be distinctly different, but the interactions with each other, the homeostasis, is distinctly different. Also, looking at the genetics, there are microRNAs expressed in ME after modified stress challenges. There were 11 circulating microRNAs that were found in ME compared to healthy controls. The presence of these related to the severity of their symptoms after a post-exertional stress challenge test. What a challenge test is, you ask the person to go on the bicycle, stay on the bicycle as long as they can, and push themselves to their physical limits. This is what happens as a result. All of these microRNAs started circulating. This was also related to the immune response. It just shows there was a post-exertional reaction that's happening in the body as a result of a physical stress in a challenge test. There's evidence of neuroinflammation in ME in PET and neuroquant studies. There are increased ligand or proteins expressed by activated astrocytes. This is demonstrating widespread brain inflammation. There's also increased interferon gamma. This is released by lymphocytes in response to viral or intracellular bacterial infections. The severity of this related to the severity of the patient's cognitive symptoms. Also, there is elevated inflammatory and anti-inflammatory cytokines in the serum and cerebral spinal fluids. There's also the presence of autoantibodies in a subgroup of patients with ME CFS. There was a study done and looking at the use of rituximab to treat these patients. They found it was very successful. However, the second time around, it was not as successful because what they discovered was that in the second group, there were not as many people who had the antibodies. I think what we're looking at is subgrouping ME CFS and trying to target the subgroups that we can discover. We know that there is mitochondrial dysfunction in ME. On the left-hand side, this is a mitochondria, which is a small organelle that produces ATP and is the energy production of our body. You can see the normal outline of the envelope, and then you can see these little striations, which are cristae. This is where the energy is being produced on the lipids of the mitochondria. And you can see typical ME patient is bloated, it's abnormal, and you can see the lack of internal structure. So obviously this mitochondria would not function as well, and there'll be reduced energy production. So in terms of muscle metabolism, we know that the patients with ME, their skeletal muscles do not use glucose as well as healthy controls. We know that they have reduced production of ATP. We think that this is a result of mitochondrial dysfunction, and we know that they have post-exertional fatigue if the person is stressed. And so this is looking at the aerobic metabolism. So if you push a person to go beyond their abilities and you max them out, they're actually at the maximum of their aerobic metabolism. This is where athletes who are in the gifted athlete area, this is where they try to push themselves. If we push our patients to function at this high level, they cannot do it. They do not have adequate aerobic metabolism. So this was demonstrated in a study by Davenport when they looked at couch potatoes, which are on day one. They're the white curve here. They push them to their aerobic capacity, and then they basically leveled off. They also looked at the ME patients. They pushed them to their aerobic capacity and they leveled off. So the couch potato and the ME patients on day one were exactly the same, but on day two, this is where the difference showed up. On day two, the couch potato had recovered so they could do this again. However, the metabolism of the ME patient had not recovered and this is where they could not muster the same amount of energy, and they basically showed the severe change in their metabolism. So aerobically, they just could not produce. This is another way of looking at ME as looking at the metabolomic study. So they looked at ME as a defense mechanism of the body to be in a reduced state in order to be in a survival state. So this is called basically a hibernation state or a dour state. And the other word for it is the integrated stress response. So what happens in rats is they identify this hypothalamic nucleus where basically when the rat was in severe stress, all non-essential energy processes all non-essential energy processes were turned down. And this is one theory that they're thinking may happen with ME patients when they push themselves and they go beyond their physical limits that their body may go into this integrated stress response where they are forced to rest. And they did find an ME CFS chemical signature in the researchers who did this work. So this is another evidence that this is a physical response. So I think the most important thing I can ask you to do is to make the diagnosis because it has the most significant impact if you validate your patient and the earlier you make the diagnosis, the better the outcome will be for your patient. So as an integrated medicine clinician, I use an integrated medicine approach but I think this is just good medicine. This is mind, body, spirit and emotions approach to our patients, which we all do. So just to show you what are the principles of integrated medicine if you're not aware of this is these are the principles here. The first is the patient and the practitioner are partners in the healing process. All factors that influence health, wellness and disease are taken into consideration including mind, body, community, as well as the body. We use appropriate use of both conventional and alternative methods to help the body heal itself. As a hematologist, I use all of my skills there and the new things that I have learned. I use effective interventions that are natural and less invasive if possible. I do not reject conventional medicine. I use it ongoing and I basically do not accept alternative therapies uncritically. These have to have past muster and they must have levels of evidence before they are used. Good medicine is based on good science and it's inquiry driven and open to new paradigms. So these are the new paradigms, a few of which I will introduce you to here. There are broader concepts of health promotion and prevention of illness are paramount along with treatment. And the last thing is I think essential for us is practitioners of integrative medicine should exemplify its principles and commit themselves to self-assessment and self-development. And I bring this up in particular because the burnout rate of clinicians is roughly 50%. And this is something that we have to be very careful of and guard ourselves so that we do not burn out as we try to practice medicine today. So looking at an integrative medicine approach, this is allopathic medicine, as we've all been taught. And we also introduce an integrative medicine, other modalities, we emphasize osteopathic medicine or manipulative kind of medicine to help the body realign. We also may be using herbal medicine. We look at the person's spirituality and how to help the person to deal with a chronic illness. We look at functional medicine, which is looking at personalized medicine and trying to understand the specific ongoing causes of the problem. We of course use nutrition and possibly Chinese medicine. And this is just a brief overview of possible modalities that might be helping patients in general. And these are something you're familiar with. These are the multiple determinants of health. And these reflect also the holistic principles. And these are from the World Health Organization, which are very similar to what we've just seen. And so we look at the patient from, can they work or not? What are their genetics? What are their coping skills? What kind of health access do they have and their income and social support to help them deal with their chronic illness? So the treatment overview to helping patients with MME are giving them supportive symptomatic care. There is not one specific treatment and not one size fits all. So you need to look at the individual in front of you, but there are general principles that I will review with you here. So the management strategies include improving symptoms, the functionality and the quality of life of the patient, symptoms, the functionality and the quality of life of the patient who has chronic illness, the secondary prevention of worsening of their symptoms and helping the patient to have support and also to support the family or support network of the patient. So the treatment of MME is based on the pathophysiology. We know that there is impaired function or fatigue or post-exertional fatigue or malaise with the patient with MME. And then one of the best things you can do to help your patients is to teach them how to pace. Pacing is by using activity logs or a Fitbit and the steps they're taking per day, you help them to look at what their activity levels are and how to intersperse activities with rest periods. So you're teaching them how to stop pushing and crashing and how to honor their body's limits and expand their activity levels slowly by keeping their heart rate low, because we remember they have an abnormal metabolism and we want them to avoid high aerobic exercise. And we know that there is impaired aerobic metabolism as seen on the two-day bicycle ergometry testing. And this is the reason that graded exercise therapy, which is pushing a patient every single day to do more, regardless of the person's energy that's available in the moment, has found to be harmful to the patients. So I'm all in favor of having the patients to walk as they can, but it's determined by the ability of the body's available energy on that day, which changes every day. So you can't push a person to walk five minutes one day, 10 minutes next day, 15 minutes the next day, 20 minutes the next day, because every day is variable and they have good days and bad days. So you have to gear their exercise according to the available energy the person has on that particular date and time. So what you want to look at is avoiding pushing themselves and crashing. So this is the crashing pattern on the top. And the person, this line on top is this squiggly line. It shows good days and bad days. And what happens is the person on the good day, they keep pushing, pushing, pushing themselves, and they end up having bad days. So by doing the pushing and crashing overall, the pattern of energy availability gets worse and worse over time. And this is what we see patients come in. They describe themselves initially as having energy levels of six to seven out of 10. By the time you see them two, three years later, their energy levels are down to three to four out of 10. So what you try to teach the person has how to pace themselves. And overall, they still have bad days and good days. This is the bad day at the bottom, the good day at the top. But overall, they stay within the energy envelope that they have, and slowly over time, they begin to recover and their energy levels begin to improve. So now I think it's helpful if we take a break at this point in time, if people need to get up and stretch. Welcome back after the break. And as you recall, we left off at patients either pushing themselves and crashing or pacing themselves and starting to recover. So in more depth, we'll be looking at the severity of these patients so you have an idea of how severely disabled they may be. So I'm gonna review with you the Short Form 36, and it has different functional capacity domains. And today I will be looking at the RLP, which is Role Limitations, Physical Health Problems, and the EF, which is the Energy and Fatigue, because I want to show you, this is a well-recognized report form that's been well used in patients of many different fatiguing illnesses to show you where these patients fit in terms of their energy and their available ability to do things. So on the Y-axis, we have the different role domains, and on the Y-axis, we have degrees of functionality. And this was a study that was done on people that we were seeing at the Environmental Health Clinic in Toronto, Ontario. And you can see across the top, the blue represents the normal person. And as you can see, the blue is very high and it's mostly between 70s and 90s. The patients with chronic fatigue syndrome, they are in the red, and I'm going to particularly draw your attention to the physical functioning role. They are down to 10%, and the energy availability is down to 20%. So they're extremely fatigued and they have great difficulty doing activities of daily living. And just while we're in the ballpark, I'll also point out the fibromyalgia patients, which are in green, and they often had even reduced energy, and they were more severe than the patients with ME. So what I like to teach my patients is how to basically think of their energy differently. So I ask them to think about spending their available energy in terms of money. So where does their energy go? It goes physically when they take a walk, mentally when they pay a bill or on their computer, or emotionally when they fight with either their mother or their spouse or their children. And because their energy levels are so low, once they've used their energy, that's it for the day. They don't have it to do anything else. So how do you get people to be more aware of their energy and how they're spending it? What I ask them is to basically be aware to find the questions, basically to record their activities daily and their energy levels without judgment for a week, and I'll show you a plan in a second. I ask them to find their best time of day to listen to their body, stop before they crash, and I also ask them to plan for health. So these are the questions that I basically ask them, and I call this the best-hits pacing method. And basically the first question is number one, body in this moment, what do I need? And I would sit there with them, and I'd say that physically close your eyes and ask yourself body in this moment, what do I need? And you can do this when you're at the conference. And often the answer is rest. So then the person would say, close their eyes again and say, body in this moment, how many minutes of rest do I need? Then I would ask them to keep their eyes shut and ask them to scroll through the 10 times table, 10, 20, 30, often an hour would come up. And if they were at home, I would ask them to lie down, close their eyes and either meditate or try to sleep. And before they did that, I would ask them to set their alarm. So it would notify them when the resting time was over. They would do this the same if they were doing an activity. So their body said, I'd like to go for a walk. And they could say, I can walk for 10 minutes. They would set their alarm. Often their phone is very helpful and very convenient, put it for 10 minutes. But if you're going for a walk, it means walking away from where you are for five minutes and back for five minutes. So you might want to ask them to actually set their alarm for five minutes. And then they would come back for five minutes. And then the next thing they would say, body, in this moment, what do I need? So basically throughout the day, you would be asking your body to take control of what your body can physically do. And this helps them to expand their energy levels, do more and heal. So what I'm asking for people to do is to make a paradigm shift. On the left-hand side, you see the pilot at this airplane. And this represents the brain. So, and then on the right-hand side, you see the co-pilot, which, and this represents the body. So normal people, the brain has all the ideas and the co-pilot, the body just goes ahead and does it because there's no more available energy present. So for example, the brain might say, I'd like to go shopping at the mall today. And the body would say, okay, let me grab my wallet and go to the bathroom. And away you go. And that's how normal people function because they have a lot of available energy. They have resilience and they have reserve. So what I'm asking patients to do is to change seats. I'm asking the body to become in the pilot seat. In other words, to have the final say and the brain to sit in the co-pilot seat. So the brain still has the ideas. The brain says, let's go shopping at the mall today. But in a patient with ME, they might say, well, we've already been to the doctor. The body would say, I'm not so sure we have the energy. Let's do it tomorrow. Let's plan for it tomorrow. And the brain says, okay. So this is changing the way the body functions and the way your available energy can be taken into account to put the body in charge of the activities of daily living. So this is an example of an activity log that one of my patients did for me. And as you can see, it's just a daily diary. It has days of the week at the top and along the left-hand side, it has hours of the day. He was up at slightly different times, so he changed them. So what I ask my patients to do is to use these questions, body in this moment, what do I need in order to determine what they need to do in that time? So he filled out on Monday, he was awake at 11. He had breakfast, his energy level was four. He had a rest and his energy level was five. Then he went for a shower and he had another little rest, just five. So you can see he had alternating rest periods, which are marked with the blue color with the white activities where he actually did the activities. And he wrote this down in real time. So as you can see, Monday looked the same, alternating activities and rests. Tuesday looked the same. But Wednesday, you can see there's no rests in the Wednesday afternoon period. And he went out for dinner and a movie with his friends. And at the end of it, he put down too much. And the next day he went back to his resting in blue and activities in white. And his energy levels were slightly better, six. But then the next day he said, I don't remember what I did on the Friday. And I said, I know what you did. I said, you crashed your bed all day long. And he says, you're right, I did. So I marked that in on blue. And then on the Friday, on the Saturday and Sunday, he went back to his normal resting and activities in between. And as you can see, his energy levels went up slightly to six most of the time. So I demonstrate this as showing how patients can crash either the day after they've done too much, or sometimes they don't remember what they've done. So by writing down their activities and rest periods, you can see exactly what your patients are doing. And they can learn from this too. They can learn what is working for them and what is not working for them. And rest for this purpose means lying down, eyes shut, either meditating or sleeping. So it doesn't mean watching TV or being on the phone or doing the computer work. It means giving your brain a break. And this is a functional capacity scale that I created with Dr. Marshall. And we basically created this because we found that we had really no good conceptual idea of what fatigue meant to these particular patients and this patient population. So we created it as a 10 as a supernormal. Apparently, this is like Alexander the Great. He could go drink all night and get up and party all night long and can get up at five o'clock the next morning and go to war. A lot of CEOs of corporations apparently are 10, most of us are nine. We have full days of work and social life, we can exercise whenever we want, we can pull the odd all-nighter and we're fine. And the energy level goes down slowly over time. So this fellow, he was the number five most of the time, he had mild symptoms at rest with fairly good concentration for short periods of time, only 15 minutes, but he needed to rest in the morning and the afternoon. He could do independent self-care, which is either taking a shower or taking a wash at the sink. And he could do moderate activities of daily living, like making lunch or making food. And he did have slight post-exertional fatigue if you overdid it, but he could walk 10 to 20 minutes most of the day. So when I saw this fellow, initially his activity levels were about a three. And by doing this ongoing resting, alternating with activities, he was able to go from a three up to an eight, and he was able to go back to work after a period of time. So it just shows that when you stay within the available energy, the body does heal itself. And this is an example of just what a normal activity level looks like. This person has very good sleep. Sleep quality is measured at the top from one to five. So this person slept every night very well. The yellow represents normal energy. There was energy available all the time the person was up, and the energy level was nine to 10 out of 10. Person had a good night's sleep, and it could exercise whenever they wanted to. This is just a classic example of a person who's crashing. So their energy level, their normal energy was four to five, which is designated as yellow. So they needed rest periods in between. This particular day, they did not rest once, twice, three times, and they did four times. So they had four extra hours of energy that they used that they did not have. So they crashed for three days in a row. So their energy went down to a three, which is designated in orange, and they had multiple rest periods throughout the day in order for them to recover after three days, and their energy level went up to four. So a person, their energy level changes over time. So this person's energy, normal energy level for them was a four to five. So you can see the difference in resting and pacing themselves versus pushing themselves on one day and crashing for three days afterwards. And this is an example of a person in a recovery pattern. So their normal energy level was a six out of 10, and they had to maintain the activities and rest throughout the day, which meant that they had better energy level in the morning because it was a yellow, and they had reduced energy level in the afternoon, which for them might've been a four or five, but they still needed to rest throughout the day. But by doing this, they could plan activities in the morning, and they could actually go for walks 20 minutes on a daily basis in order to improve their metabolism, because all new muscles that are formed have normal muscle and have better energy and ATP production available. So how else can you help your patient? Nutrition is the key. If the person is not eating nutritionally, this is the time that they need to change their diet, and they need to eat clean or use the term, the anti-inflammatory diet. The problem with some of the patients who are severely disabled and who do not have disability insurance premiums coming in is they have food insecurity. They have no money to buy their food. So this is where you, the clinician, is so helpful when you can get their disability forms completed and get insurance for them so they can start to get food into the house. They may need a home nurse assessment to see if they need help with bathing, getting in and out of the bathtub, or if they can get any kind of meals on wheels or any kind of a food being brought into their house. The other thing is that patients often forget to eat. This is why keeping the activity logs is very helpful, because they can see it's time for me to eat. Sometimes they're also too tired to chew, and this is where having some sort of a liquid protein shake is very helpful to at least get the amino acids and the carbohydrates and the fats into them on a regular basis. Usually these patients should be having a nutritious food with no additives and avoiding any foods that they know they're sensitive to. There is a working group that's called the Environmental Working Group for people who are very chemically sensitive. It lists the foods that have organic that you must have if you have severe chemical sensitivities and the foods that are clean. It's called the 15 clean and the 12 ones to avoid that have a lot of pesticides in them. They also need to drink adequate intake of water for their fluids and also electrolytes, because they tend to get dehydrated. They need to be supplemented, particularly I think with a multivitamin, vitamin D, and fish oil, because all of our cells are made out of the bifosyl lipid layers, and we need to supplement the cells in order for them to heal properly. Often patients are low on magnesium, and you can measure red blood cell magnesium, and for the women who are menstruating, they're often low on iron. Ideally you need to assess their nutritional input by looking also at their bowel movements, and if they have arrow bowel syndrome with altering diarrhea and constipation, you may need to treat their dysbiosis. This is an example of a comprehensive stool analysis that has also parasitology in it, and it shows which fibers are being broken down. If not, they may need to be supplemented with a digestive enzyme. It may show exactly how they're absorbing the foods, if they're not absorbing. It may show what kind of bacteria they have, if they have too much of one kind of bacteria that might need to be supplemented with a probiotic, or if there's too much of a mold like candida present, this may be need to address. It also rules out any particular parasites that they may have encountered. We live with our animals, half of our animals get dewormed on a regular basis, so every time your animal gets dewormed, think about your patient, do they need to be dewormed also? It also shows if you have a distinctive problem, this one had Klebsiella, it shows you not only the particular medication that might be helpful, but also shows you some natural agents if you are using herbs as well, it might be helpful for your patient. If you're not familiar with these, I think that this is a good tool for you to get to know and order in your patients, particularly who are having a lot of irritable bowel symptoms, who've been to the gastroenterologist, had a normal colonoscopy, but they're still having ongoing problems. This might be very helpful for you then, and if you don't know how to interpret these, you can make an appointment with the person whose lab you've ordered it from. I bring this up because we were looking at a number of our own stools initially, because we had all these patients who had irritable bowel symptoms, we couldn't figure out why we couldn't get to an answer, and we actually did our own in-house wet preps. We saw all these little round little creatures here, which represented blastocystis hominis, so we actually called head of infectious diseases in the laboratory, the parasitologist, and we asked them to come over and look at our slides if we'd accumulated, and sure enough, we discovered blastocystis hominis present, which was giving our patients a lot of trouble with chronic diarrhea in particular. So after we requested this, we had to request that all non-parasitic infections were reported, and when we requested this, then we had the blastocystis showing up on our reports, and then they were treated appropriately, and they improved quite dramatically. So it's just something to be aware of. So you might want to get to know your local parasitology lab and find out what exactly are they reporting on your reports if you're asking for parasitology. Sleep is key. If you do not sleep, you do not heal. So you need to introduce the concept of sleep hygiene after you've done an overnight sleep study, because you need to show the patient that their sleep is not normal, and they need to take action into how to make it improve. So ideally, the first thing is you need to teach them how to pace their activities, because what happens is that if patients get a second wind, and for example, they're up at 10 o'clock on Sunday, they get a call, and they're talking to their mother for the next hour and a half, they get wired, and they get this little burst of adrenaline. It's called being tired and wired, and when they go to bed, they can't turn their brain off. So ideally, you need to teach them to get to bed at the same time on a regular bedtime rhythm, no exciting TV or news before going to bed, have a dark bedroom, use a relaxation response or meditation while they're trying to go to sleep or if they wake up during the night. And the purpose of the relaxation response, this is by Herbert Benson. He was the initial person who introduced us into meditation. He went and looked at the Tibetan monks, and he discovered that they could lower their heart rate to a point where it looked like they had stopped having a heart rate, and they could either increase or lower their temperature. And by doing this, basically, they would go into this deep meditative, this is the deep four stage of sleep. And by introducing your patients into the meditation, you are helping them to get into this deep stage four sleep where the body and the brain heals. So ideally, when they're resting, either in the daytime or at night when they can't sleep, ask them to meditate because this is the next best thing you can get them into stage four sleep to help their brains to heal. Other things that help are calcium, magnesium, herbal teas, melatonin. And there are a variety of sleep medications that I've tried over the years, and you can see the list is very long. You must have adequate pain control for sleeping. But I find the number one things that help people is the meditation. All these are the medications I've tried at different points throughout time. I find they're helpful if you can have them as a breakthrough when the patient is absolutely exasperated, but I have not found having them on a regular medication at night helps. And after a while, they develop a tolerance to the medication anyway, so it's better off if you use it as an intermittent sort of idea, something like gravel or the occasional zopiclone or the occasional Ambien, but have them really try to meditate their way in and out of their interrupted sleep cycle. And for adequate pain control, again, meditation is very helpful. I used to teach the Kabat-Zinn meditation as a way to help patients to manage their pain. And the other thing, and I found it very helpful, and the other thing I found very helpful is using the low-dose naltrexone in a very small dose to start off with, often using a liquid tincture with 0.1 milligrams until, and you can raise it slowly over time, until the person develops, often the biggest side effect is to develop severe nightmares, so you cut it back to the point where they can tolerate it. And there's lots of literature about this. You can go to whole conferences about low-dose naltrexone, so something I think that's worth reading up about if you haven't done it already, and it helps reduce the brain inflammation as well as it helps basically the body to relax. And these other things are also helpful as well, CBD, acupuncture, homeopathy, osteopathy, massage, restorative yoga, all these things help break the pain cycle. For cognitive problems, excuse me, I find the best thing is if you have a person who's able to work and they have the energy as accommodation, so if they can possibly stay home some of the time where they can put their feet up, if they have orthostatic hypotension or take breaks throughout the day, this is really helpful. They need to pace their activities. Again, they may be better off in the morning than at night, so getting their heavy work duties over in the morning and in the afternoon perhaps, dealing with emails, performing their mental work lying down, like sitting up with their legs up to help treat their orthostatic hypotension, and you're also treating their insomnia, pain, depression, or anxiety, either helping them with cognitive behavioral therapy if you find it helpful, or learning reduction stress techniques, and we talked about the relaxation response by Dr. Herbert Benson. They need frequent snacks and drinks throughout the day, and they need to be reducing the over-stimulation, and this can be done by either homeschooling if they're in school or at work, and reducing the amount of sound and light that they are exposed to, and ideally, cognitively, they're really helped by joining online support groups to prevent isolation. As long as support groups are uplifting and they learn something from them, this shouldn't be a woe is me kind of support group where they walk away feeling more depressed than did before they joined, but there are very healthy support groups online, so I would recommend those as well. In terms of treating the orthostatic intolerance, this is the autonomic nervous system dysfunction, which results from reduced riblet cell mass and reduced plasma volume. They feel worse when they're standing or sitting upright, and better when they're lying down, and again, you can diagnose this by using a lean test, and their pressure drops by 20 millimeters systolically or 10 diastolically, and the treatment for this is increasing their fluids two to three liters a day with salt and salted foods. I often ask people to measure out a teaspoon of salt first thing in the morning and use it up by the end of the day and see if that helps their symptoms of feeling lightheaded when they stand up. They can increase it until they reach the amount where they feel like they're a little bit puffy, then they can back it up, and the other thing I have them use is elevation of their legs all the time and use the compression pantyhose because I find that they need to be at 40 millimeters of pressure in order to maintain the compression on their venous return helps as well. There are some medications that help. These are sometimes worth trying. Everyone's individual. There are volume expanders. The flutocortisone is helpful in some people. The vasoconstrictors, the midrogen, is helpful in some people, and the beta blockers are helpful with the patients who have increased heart rate, so these are some tools that you could try with your individual patients. The pain spiral as we know is severe, and the problem is that if you don't deal with the pain, the person goes from being injured to resting all the time to losing their functionality and ended up basically full-time in bed, and you want to avoid this process, and you need to encourage them to be as active as they can be, so you ideally need to help to treat the pain, and you need to look at the migraine, reducing the tick triggers. Often, if you increase the blood volume by salt loading compression stockings, it often helps the migraines, and plus having them eat regularly is helpful. It helps to reduce their stress as well. Making the diagnosis is really critical for this, and knowing that they have something wrong with them, I think, really helps them to deal with the fact that other people don't believe that they're ill as well, and that's a big problem with these patients. They go often a long time with even their family members not supporting them, so having you getting the family supporting them as well as you supporting them is really helpful to deal with their stress. Sometimes there are preventive medications that you can use for migraines as well as B6, osteopathic treatments, acupuncture, and magnesium often helps. Just to note that about 30% of patients with ME have fibromyalgia as well, and they also might benefit from hot packs, massage, yoga, osteopathy, and aqua therapy as well, and meditation as well often helps patients to deal with their pain. Just a quick note about fibromyalgia because it is such a common overlap. These are the 18 tender points that may be present in these people. They need to have 11 out of 18 positive to be identified as fibromyalgia, and fibromyalgia patients, and these are where the actual tender points are, and you need to press on these points with four kilos of pressure, so if you're pressing on your desk, you press on it until your finger blanches. You don't necessarily have to do all the tender points to that degree. As soon as you start to press, if you get a positive painful result, then it's positive, but for some of the patients, they may need to have the full four kilometers of pressure, and these patients have widespread pain diagnosis. They have 11 out of 18 positive tender points. The symptoms they have are fatigue, sleep dysfunction, neurological manifestations. They call it central nervous system sensitization, and it's also seen abnormal brain mapping. They have autonomic and neuroendocrine manifestations and morning stiffness, so these are the common symptoms. There's a big overlap, as you can see, between ME and fibromyalgia, and for the patients who you suspect have fibromyalgia but have negative tender points, they've also come out with, the ACR came up with a fibromyalgia diagnostic criteria, and they have this widespread pain index and a scoring system, so if you're not sure, and this I often do in the men, because men have much more muscle mass, so I find that I cannot press hard enough to elicit a painful response in the men. And I want to point out this to you, there's been some new literature out talking about fibromyalgia as a post-concussive brain syndrome. And the reason I bring this to your attention is because there may be patients in your practice who've had multiple car accidents, who've had multiple coup, counter coup injuries. If you order a brain spec scan that has a three-dimensional header on it that you can actually measure the blood flow, you may see decreased blood flow into these microscopic areas that have been injured by the post-traumatic brain injured area of the brain. And there was a recent paper that came out, and this is by Shea Afraidy, and he actually measured the brain spec scans before and after they did 40 treatments of hyperbaric oxygen therapy, and their symptoms of pain and ability to function improved quite dramatically. So I think this is an area where we're learning about, but I just bring it to your attention in case this rings a bell with you. And afterwards, he looked at the brain spec scans, and there was increased blood flow to the previously reduced areas of blood flow in the brain. So this might be something that further down in a few years' time, this might be a better treatment for fibromyalgia if there is this history of multiple traumatic brain injuries or post-concussion syndrome. So in terms of the GI, irritable bowel problems with reflux, there may be dysbiosis present. A lot of people have this because of the use of recurrent antibiotics or undiagnosed parasites. There might be food sensitivities that are non-IgG-mediated or IgG-mediated that might have common sensitivities to the things that, these are the most commonly found things, are milk, soy, wheat, and eggs. So one of the things you can do is elimination re-ingestion food challenge. You take, if you suspect all four of these, you take them out of your diet for a week, and then you reintroduce them. You have the person look in the mirror, check to see what color their face is, check their pulse, check their breathing, have them say, for example, it's wheat, you have them have a quarter cup of cream of wheat, eat it, and see if their face changes, if they get redness of their face, if they feel hot, if their pulse goes up, or if their breathing increases. And this is basically an elimination re-ingestion food challenge. And I find it's very helpful for patients not only to find out are they reacting to the food, but what kind of reaction are they having? Can they cope with the food and cope with the food reaction, or is this something they really would want to avoid? And obviously, you don't do this with any foods that are suspected to be anaphylactic. And these are basically overlapping conditions that you may have with ME. Just to point this out to you, I won't spend a lot of time on it, but just to show you that just because you have ME doesn't necessarily mean you don't have other problems with your symptoms. So what I'm looking for for my patients is to look at them from the fact that they're homeostatic imbalanced. So often, they're sedentary, they're deconditioned, they're not getting support they need, they have a diet that's either they're not eating and they're eating a lot of junk food or fast food, they may be having an environment problem. Basically, they might be having ongoing infections that they're not aware of, and they might be having ongoing sleep problems, difficulty problems, difficulty getting to sleep, staying asleep, and actually having circadian rhythm disturbances. So how I help the patients is I have tried to develop a supportive therapeutic relationship with them. I try to educate the patient, the family, do an individualized patient treatment program. I empower the patient to trust their own experiences, particularly learning how to listen to their bodies, and learn how to schedule their days so that they have a more successful day so they stop crashing and start pacing themselves. So I look at this as the weed, seed, and feed approach to health. And I also want to point out that mold exposure may be a problem. So it's an environmental history you need to look at in case a person has been living in a an apartment or a house that's had a roof leak, and they have ongoing exposure to molds or mycotoxins, which also may cause a lot of these symptoms. So what I'm looking to do is to help them balance all these things so that they get into a more homeostatic response, and they adapt to their environment, adapt to their illness, and slowly start to improve. So this was the diagnosis of age of my patient Dorothy at age 55. As you can see, she was pale, cachectic, she lost like 35 pounds, she was sleeping in bed all day long, and she had no life. And this is Dorothy at age 72. Her energy had gone from a 2 to 3 out of 10 to a 6 to 7 out of 10, and she was retired obviously by this time, but she was able to volunteer full time, and she was also able to care as a live-in personal care worker for a person that she had an employment relationship with. So just to show you the difference between the before and the after. And as you can see, she's absolutely glowing. So how do you work with your patients? You basically, in your time with them, it's very short, I know that. At your initial visit, you give them a questionnaire, and you ask them to write down how their illness started, the date it started, and you ask them to complete activity logs as best they can. And you do this before they come to the visit, so you have an idea of what their symptoms are, their frequency or severity, if they stopped working, do they have any help, who's their help, their job description they used to have, and do they have any public or private disability insurance, and the medications they're on. So you need to collect this information before they come in, because if you don't, they do not remember a lot of these things, and the interview will go very poorly if you haven't collected information ahead of time. The follow-up visit, once you've made the diagnosis, you need to have a regular follow-up. For the first patients I see, I usually like to see them once a month, regularly. I like to review the activity logs with them, I need to go over what's working for them, and I often ask them what has improved since the last visit. Why? Because the patient often forgets to tell you. So if you write it down, have them write it down, they'll remember, oh my sleep got a little bit better, oh I'm eating a little bit more frequently, I'm not as lightheaded, and then you ask them to list the top three problems, because they have a whole arm's length worth of problems, and you cannot possibly get to all of them every visit, so you basically prioritize what are the top one, two, or three problems. And again, you have them list all the medications and supplements and doses they're taking. When patients initially come to me, they come to me with bagfuls of supplements, and you basically want to know exactly what they're putting in their mouth and on their skin. And I also want to just emphasize that, you know, as you see these patients, don't assume that their new symptoms are just more of the same ME. If they develop a new cluster of symptoms, you really need to investigate them, because it might be something else that they're developing. So the prognosis for ME is better the sooner you make the diagnosis. Excuse me, 90% of patients do not fully recover, in my opinion, because they've been diagnosed too late. 10% of the patients stay bedridden at 10%, and you can measure the functionality by using this short form 36-RAND questionnaire that I demonstrated to you earlier. Suicide is six times as common as the normal population, and I think most of that is due to their isolation. So seeing patients on a regular basis really helps with this situation, and I think really helps you to help them. There is an increased risk of autoimmunity or lymphoproliferative disorders, so you have to keep a lookout for that. And adolescents often report better recovery, but I wonder, quite frankly, if they've ever known what normal energy is. So there's a lot of unknowns about the prognosis, but people can improve and they can get a more functional life. That I have seen in the last 30 years. So one of the most important things you can do for patients is filling out their disability insurance forms. And the reason what you need to do is to fill out why this person is unable to work. These are the reasons. Brain function. They have cognitive dysfunction, poor short-term memory, broken for words, concentration problems. And if you're fortunate enough to get a neuropsychological test done, include that, or you can get one from CNS Vital Signs. That's an online service that's very helpful. You need to record their fatigue levels. This is where the activity logs are extremely helpful. Energy, less than 6 out of 10, is inconsistent and not reliable. And in my experience, I have found that these people cannot work consistently. Documenting their sleep studies is helpful to show that their ongoing sleep dysfunction, showing their architecture, this abnormal interrupted sleep patterns and insufficient deep sleep. And then you can add any abnormal laboratory studies you've found, if you found chronic Epstein-Barr activation, or if you're able to do cytokine levels or do any kind of, I put the neuropsychological testing here as well, because I find it's very helpful to document why the person can't work. They can't work because they can't concentrate, they can't focus, and they cannot show up consistently on a daily basis to work full-time. I put this up. This is the epigenetics way to look at pathways. In some of your patients, they may have difficulties with detoxification or difficulty with energy production, and they may bring these in to show you. And some of the patients in particular may have problems with their methylation pathways. This is just to show you what level of testing is available for these metabolic pathways. If you're interested, I would suggest you take courses on how to interpret these. If a patient brings one into you, you can phone up the particular laboratory and get them to walk you through this. Sometimes it's very helpful to document that the patient has a particular gene that's abnormal, and it needs to be supplemented. Like this is the MTHFR gene that's abnormal, and they need to be supplemented with methylated vitamins, folate or B12, in order to help the person's energy production improve. Now we're into the COVID era, and we have patients who have post-COVID syndrome, or they're called long-haulers, which is not a very great name, but I think should be called post-COVID-19 virology problems. And these patients basically are identical to ME. They have ongoing fatigue, body aches, difficulty sleeping, headaches, brain fog. In addition, depending on where the virus went in their body, they may have ongoing shortness of breath associated with lung problems and heart problems as well, and they may have loss of taste and smell. So these patients are the next wave of ME patients that are coming down. There are grants that have been available for NIH and CDC grants. I think this will be very helpful long-term to uncover exactly what the pathophysiology is of these patients, and will help, I think, with future research with ME, because this in from my perspective is just the latest virus where patients will develop these ME symptoms. And we don't know, but depending on the literature, you can see between 10 to 30 patients who have had COVID may develop post-COVID symptoms long-term, or long-haulers. So in review, I hope that I've helped you to diagnose ME-CFS using the clinical diagnostic criteria. I hope that you'll be encouraged to make the diagnosis so that you'll be able to diagnose your patients sooner and have them stay functioning much longer, and hopefully the ability to function improved much quicker. I've hopefully showed you the pathophysiology of ME and the treatment of ME, which is supportive symptomatic treatment. And these are some online resources for you. This is the clinical ME-CFS Clinician Coalition, of which I'm a member. We've put together a bunch of teaching information online. I wrote a review myself. There is the primer that has also another clinician's help for the clinicians who want to read more about ME. There's Institute of Medicine's recent overview of SEAD. And there's the website from the ME-FM Action Network that actually lists the ME Canadian consensus criteria definition, if you want a lot more detail. And this is the primer for the clinicians that was redone in 2014. And then there's the website, which I basically talk about pacing. I did a pacing video. You can get the activity logs and functional capacity scale there. And also, I've written a couple books for you to help your patients. They're written in layman's language to help them as well. So I thank you very much for your time. And I hope if you have any questions, I'll entertain them now. Thank you very much. Well, very good. I'm going to drag this over to the big screen for our customers here in the room. There were a couple of questions in the chat. Some of this crash and fatigue reminds me of being lactic acidotic, perhaps low and high. I'll let you read. Have you considered creatine or D-vivos? Yes. Both of those, I've tried and have the other clinicians as well. They work sporadically, and they don't seem to work consistently. There seems to be sort of a, you get some improvement, and then it stops. So again, if you want to try it, it's fine. But I think that if a person pushes themselves beyond their metabolism, that's when things just don't go forward. And the question was about there are certain occupations. Are there certain occupations or working environments that incur slightly or significant differences in the incident rates of ME? No one has ever done the occupations. That would be a lovely study to do. So that would be a great study that perhaps we could do. So no, it has not been done. My first fibromyalgia, chronic fatigue syndrome, CME, was about 18, 20 years ago. And at that time, they were postulating that it might be certain environmental exposures. So I should know if that was something we were still looking into. Yeah. So I think with the fibromyalgia, the more common element is this history of trauma, which is really interesting, I think. So this history of motor vehicle accidents. So I think that's something that's really worth looking into with that particular study. I was quite amazed by the results. And in my personal clinic, I always take a trauma history because I'm always interested and I've always had, I've always found rather that many of my fibromyalgia patients, I would say the vast majority have had a history of trauma, either motor vehicle accidents or falling off a horse or when they were cheerleading, they got injured, things like that. So I did have a couple patients recently, and I did order some brain spec scans. They were positive and they showed reduced blood flow to the brain. And these patients, they did go for 40 treatments of hyperbaric oxygen therapy at 1.5 atmospheric pressures and their cognitive abilities improved and so did their energy level. So I was really interested in these particular cases. I'd love to do a trial on this myself. Thank you, doctor. I have a question. You mentioned that CFS is partially a diagnosis made by exclusion, and there's quite a few other entities that need to be excluded. I was just wondering if there was a, if you had an estimate of the average or minimal cost of the panels that you do when you're excluding all these conditions to make a diagnosis for CFS, because it seems to be a lot of tests that you'd be doing. That's a good question. No, I do not have an estimate, but what I have found is that by the time the patients come to see me, they have already been to see usually seven to 10 other clinicians, and the diagnosis has not been made. So I think that the cost has already been incurred most of the time, and I usually don't have to order an awful lot more in the ways of testing. That's been my experience. So if you're the primary clinician, I would stick to that first page and look at those particular tests, just to rule out the obvious things, and only go into the other things as they're specifically needed. Any final thoughts or questions for Dr. Veston? Well, I think you're officially off the hook, and we'll yield back the last 30 minutes of our scheduled time. Well, good. Well, thank you very much. It's been a pleasure. If anybody ever wants to contact me, please do. I'd be happy to help you out with this. Absolutely. So thanks, everyone, and we'll see you tomorrow morning for our final three lectures, one of which is a two-hour module on lacerations and injury repair. So appreciate everybody. Y'all have a blessed evening and enjoy your dinner. Great.

chronic fatigue syndrome

myalgic encephalomyelitis

Dr. Allison Vested

early diagnosis

post-COVID conditions

neuroinflammation

immune dysfunction

mitochondrial irregularities

activity pacing

integrative medicine

long COVID

symptom management

patient outcomes