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Approach to Treatment

Approach to Treatment. Dr. Chitra Bhakta. Diet. Children should be slowly weaned off gluten products such as wheat, barley, oats, and rye. They should also be slowly weaned off soy, corn, and dairy (from cow’s milk).

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Approach to Treatment

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  1. Approach to Treatment Dr. ChitraBhakta

  2. Diet • Children should be slowly weaned off gluten products such as wheat, barley, oats, and rye. They should also be slowly weaned off soy, corn, and dairy (from cow’s milk). • Gluten-free diets should be the first goal in children with PANS and other autoimmune disorders. • Gluten increases the glycemic index, which in turn increases risk for glycation of proteins. • The glycemic index measures what the blood sugar is between 90 and 120 minutes after consuming a particular food. • Glycation increases inflammation and the production of free radicals and oxidative stress which are related to risk of damage to both the brain and the immune system.

  3. Diet • For example, whole-wheat bread has a glycemic index that is higher than that of white bread and much higher than that of many candy bars. • A study published in neurology in 2005 showed a powerful correlation between glycated hemoglobin (HbA1C) and cognitive decline. • Even serum blood glucose levels of 105 and 110 mg/dL (which most doctors would be satisfied with, actually have a profound effect on the brain and the immune system).

  4. Diet (Gluten) • Gluten containing foods stimulate inflammation in the gut leading to increased bowel permeability and increased blood/brain barrier permeability. • This mechanism deals with the expression of the protein Zonulin brought about by gluten exposure and this reaction to gluten occurs in all humans. • Children should be placed on a low carb, high fat, and high protein diet. • Even gluten free breads, crackers, and pastas are still sources of carbohydrates, as are fruits. Use them in moderation. • It is recommended that we keep the total carbohydrates per day, in children who are active, at around 150 to 200 grams and less in children who are sedentary.

  5. Diet (Fats and Carbs) • The good fats that are recommended are oils such as extra virgin olive oil, coconut oil, avocado oil, walnut oil, and avoidance of modified fats, trans fats, and high hydrogenated modified fats. Coconut oil has MCT which are beneficial. The five major oils to avoid are canola, safflower, soy, vegetable, and corn oils, which contain very high levels of Omega-6 fatty acids, which are pro-inflammatory. • The nuts that are recommended are raw, organic, almonds, and walnuts. They should be soaked overnight in water to remove phytic acids, which block the absorption of minerals from the gut and also have large amounts of enzyme inhibitors which make them hard to digest. Soaking neutralizes these enzymes. Soak lentils and beans prior to cooking as well. • Avoid peanuts (legume) along with cashew nuts. Both are high in aflatoxins.

  6. Diet (Proteins) • For proteins, we recommend wild caught salmon, free range chicken and eggs, and grass-fed beef. • Avoid using high heat during cooking or barbequing meats or vegetables. High heat oxidizes oils and destroys many phytonutrients in vegetables. Cooking meat at high temperature causes chemicals called HCA’s (heterocyclic amines) and PAH’s (polycyclic aromatic hydrocarbons) to form. These carcinogens can cause changes in the DNA that could lead to cancer. • If grilling, try choosing leaner meats and trimming the fat well, because when fat juices drip from the meat, flames flare up and create more smoke, which leads to carcinogen formation. Also, flip frequently to reduce HCA’s by 75-95%. • If you do char meat, trim it away before eating.

  7. Diet (Miscellaneous) • Avoid high starchy vegetables such as potatoes or sweet root vegetables like beets. • Incorporate garlic, ginger and onions in food. • Diet: Gluten free, Casein free, soy free and corn free. • No fruit juices. Avoid High Fructose Corn Syrup, Agave, Maple Syrup, Maltodextrin, sucrose, dextrose etc. Instead use Stevia or Xylitol. • Avoid table salt- it is a processed and bleached product. Instead use Organic sea salt or Himalayan pink salt. They contain important minerals. • Avoid Teflon coated pans- instead use ceramic or stainless steels ones. • Store food in glass containers. Throw away plastic ware. ( Prefer that food cooked be eaten on the day of preparation. Food looses most of its nutritive value on the following day.)

  8. Diet Alternative Grains: Quinoa, Teff, Brown rice, Amaranth, buckwheat etc. Alternative milks: Almond, coconut Use only dark, bitter unsweetened chocolate with over 75% cocoa. (high in anti-oxidant ) Alternative ice-creams: Coconut milk ice cream ( Rotate foods to prevent food sensitivities)

  9. Probiotics • Probiotics are beneficial bacteria and yeast that are important for gut health. • “We are more bacteria than human” – while it is estimated we have 10 trillion cells in our body, we carry over 100 trillion bacteria on the skin and in our gut. • This community of microorganisms (probiotics) is called the microbiota. • The two most important groups of probiotics are lactobacillus and bifidobacterium. • Each of each these groups of bacteria has different species and each species has different strains.

  10. What do probiotics do? • They boost your immune system by enhancing production of antibodies to certain vaccines. • Produce substances that prevent infection. • Prevent harmful bacteria from attaching to the gut lining and growing there. • Sends signals to the cells of the gut to strengthen mucus production so that it can act as a barrier against infection. • Inhibit or destroy toxins released by disease-causing bacteria.

  11. What do probiotics do? • Produce B-vitamins that are necessary for metabolizing the food, warding off anemia caused by deficiencies in B6 and B12, and maintaining a healthy skin and nervous system. • They also prevent and treat certain skin conditions like eczema and acne. • Promote health in the urinary tract. • Prevent allergies (especially in children).

  12. Probiotics • Different probiotics regulate different systems in the gut. • Lactobacillus caseiShirota has been shown to support the immune system and help move food through the gut. • In children with irritable bowel syndrome (IBS) who may have diarrhea, constipation, or alternating bouts of both, a combination of Bifidobacteriuminfantis, Sacchromycesboulardii, and Lactobacillus plantarum have been shown to regulate the bowel movements and help relieve bloating from gas. • There is evidence that Lactobacillus rhamnosus, Lactobacillus casei along with Sacchromyesboulardii has helped shorten the course of infectious diarrhea caused by bacteria, viruses, or parasites. • Diarrhea caused by Clostridium difficile, especially in children on long-term oral antibiotics, can be prevented by taking probiotics containing Sacchromycesboulardii.

  13. Vitamin B12 (Benefits) • It is vital for the formation of red blood cells. • For the proper functioning of brain and nerve tissue and is important for myelin formation, which acts as an insulation for nerve endings. • Helps our bodies absorb Folic acid, which facilitates the release of energy. • DNA synthesis. • For adrenal hormone production, healthy immune system function, mental clarity, concentration, memory function, proper digestion, food absorption, Iron use, and carbohydrate and fat metabolism. • It is the largest Vitamin in the body and extremely important for Methylation.

  14. Vitamin B12 • B12 has to be obtained from food sources and is present in the natural form only in animal sources of food, such as grass-fed beef, lamb, salmon, and free-range chicken and eggs. • It is a water-soluble vitamin and is stored in your liver, kidneys, and other tissues. • Medications that decrease B12: • Antibiotics. • Anticonvulsants. • Antipsycotics.

  15. Vitamin B12 Deficiency • B12 deficiency can cause: • Neuropathy – numbness and tingling in hands, legs, or feet. • Difficuty walking. • Anemia. • Weakness. • Fatigue. • Cognitive difficulties or memory loss. • Paranoia and hallucinations. • Sleep disturbance. • Hyperactivity

  16. Vitamin B12 • Bacterial infections that decrease B12: • Helicobacter Pylori damages cells of the stomach, which produce intrinsic factor. This is important for the absorption of B12. • Testing for B12 deficiency: • If serum B12 concentration is less than 150 pmol/L, you are considered B12 deficient. • If your B12 concentration is between 150-200 pmol/L, then you should check urinary MMA (methylmalonic acid). • Elevated levels of MMA are an indicator for vitamin B12 deficiency. • Check Homocysteine levels. • Check Serum Phosphorus level.( Also check it if calcium levels are abnl. and if someone is Hypothyroid )

  17. Treatment of B12 Deficiency • Use Methylcobolamin and not Cyanocobolamin. • SQ Methyl B12 is the best way, since it bypasses the gut. Otherwise SL or via nasal spray. • Even if B12 levels are 450pg/ml, but patient is symptomatic, TREAT. • If B12 is nl, but MMA and Homocysteine are high – TREAT.

  18. Glutathione • Is the master antioxidant. • The majority of glutathione in our body is created within our cells. • Glutathione is made by combing 3 amino acids (glutamic acid, cysteine, and glycine). • Glutathione levels are highest for approximately 6 hours after a meal. • Lowest levels of glutathione is in the morning before breakfast. • The secret of its power is the sulfur chemical groups it contains. • Normally, glutathione is recycled in the body – except when the toxic load becomes too great.

  19. Glutathione • You can test genes involved in glutathione metabolism – GSTM1, GSTP1, etc. • Nearly all very sick patients are missing this function (GSTM1). This gene is important in the process of creating and recycling glutathione in the body. • It is critical for recycling antioxidants. • When our bodies are overwhelmed with exposure to too many toxins, both within and without as well as an increase in oxidative stress, then glutathione becomes depleted and we can no longer protect ourselves against free radicals and infections and we are unable to get rid of toxins. • The liver uses Glutathione for De-toxification.

  20. Glutathione • Glutathione works by: • Boosting our immune system. • Helping in detoxification. • Helps in the repair of cell membranes. • Helps in neutralizing free radicals and decreasing oxidative stress. • A powerful anti-inflammatory. • Important for the proper functioning of vitamin C, vitamin E, and alpha lipoic acid.( All anti-oxidants)

  21. Glutathione • Ways to increase glutathione: • Sulfur rich foods such as garlic, onions, and the cruciferous vegetables (broccoli, kale, collards, cabbage, cauliflower, watercress). • Bioactive whey protein, which is a great source of cysteine and the amino acid building block for glutathione synthesis. Bioactive means you should choose non-pasteurized and non-industrially produced milk that contains no pesticides, hormones, or antibiotics (IMMUNOCAL is a prescription bioactive non-denatured protein that is listed in the physician’s desk reference). • Exercise boosts glutathione levels, such as walking or jogging or sports and including strength training for 20 minutes three times a week.

  22. Glutathione • Glutathione supporting supplements • NAC (N-acetyl-cysteine – 400-500 mg). • Alpha lipoic acid (800-1000 mg), which is a close second to glutathione in importance in our cells and is involved in energy production, blood sugar control, brain health, and detoxification. The body usually makes it but it becomes depleted during stressors such as infection, toxin exposure, etc. • Methylation nutrients (folate and vitamins B6 and B12). These are perhaps the most critical to keep cell production of glutathione. Folate should be taken as folinic acid (800 mcg/day), B6 (in the active form of P5P – 25 mcg/day), and B12 (in the active form of methylcobalamin – 1000 mcg/day).

  23. Glutathione • Glutathione supporting supplements (continued): • Selenium (25 mcg). This mineral helps the body recycle and produce more glutathione. • A family of antioxidants including vitamin C (1000 mg) & E (in the form of mixed tocopherols). • Milk thistle (silymarin) has been used in liver disease and helps boost glutathione levels. • I recommend the oral glutathione Trifortify (Researched Nutritionals), which is a liposomal-based glutathione at a dose of one teaspoon daily.(Orange flavor) • In very sick patients , It should be also given Intravenously. (600mg in 50cc of Normal Saline) once a week along with daily oral dose.

  24. Other Supplements • Digestive enzymes are important in children with inflammation to help promote digestion and absorption of foods. Taken with food 3xdaily. • Also recommended are good Omega-3 with a higher DHA versus EPA ratio, such as Carlsons at a dose of 1000 mg two times daily. • A complete multivitamin, multi mineral, and antioxidant supplement to be taken on a daily basis. (eg. Klaire Labs – Vitaspectrum powder or capsules) • All children on antibiotics must take Probiotics 3x daily. • Methylcobolamine SQ injection (best method) or SL 1000mcg 3-5xweekly. • CoQ 10 100mg daily. • Trifortify (Glutathione) 1 tsp. daily.

  25. Methylation Cycle. • This cycle not only methylates but also trans-sulfurates, to form Glutathione. • What helps to create Methyl Groups? • HCL- Hydrochloric Acid or stomach acid. • Methyl Gps.(CH3) are vital for normal cell function at the level of DNA. They literally turn genes “on” or “off”.

  26. Methylation • When Methyl Gps. are depleted (esp. with poor diet, toxins, other stressors), then bad genes are turned on and good genes are turned off, leading to neurodegenerative disorders, autoimmune conditions, birth defects, depression, cognitive decline, diseases, cancers, and probably autism.

  27. Methylation • Methyl groups are also vital for Phase II liver • Detox, protein methylation, homocysteine metabolism( increase in methyl gps. results in decreased inflammation), neurotransmitter synthesis, nucleic acid synthesis. Test for HCL: Total protein, serum globulin, BUN,Phosphorus. ( If some or all are abnormal, then most likely HCL is low).

  28. Methylation • How to increase HCL in Children? • Use Himalayan Pink Salt. • Low HCL : usually wake up at night. • Imp. Vitamins and Minerals: Folate as Folinic Acid ( this bypasses the MTHFR defects), B-Complex esp. Methyl B12, B6 as P5P, Vit.D3, vit.K, SAMe, Zn, Mg, Selenium , Mn etc.

  29. Overmethylation • Suspect it in individuals with food and chemical sensitivities, Adrenal issues, depression, underachievers, worsening of depression with SSRI’s (eg. Prozac, Celexa etc.) • Lab test: serotonin levels, STAT ammonia levels • Avoid: SAMe, inositol, Copper, Methionine, TMG and DMG • Use: B3,B6,B12, Vit.C & E, Zn, Mn, Omega 3.

  30. Mitchondrial Function • Increased Lactate and Pyruvate levels indicate defects in the ETC. Abnl ratios of the 2 may help identify the part of the chain that is blocked. • Serum CreatinineKinase: slightly increased in Mito.Dz. but usually only increased in cases of mitochondrial DNA depletion. • CoQ10 and Free and Total Carnitine.

  31. Mitochondria • Family History is Important. • Deafness, short stature, migraine HA’s, Seizures, Ataxia, muscle weakness, learning disabilities, heart defects, DM2, cataracts etc. • 3 or more of the above symptoms strongly suggest Mitochondrial disease. • Muscle Biopsy • Blood enzyme tests • Genetic Tests- Known mutation and unknown mutations.

  32. Tests • CBC with Differential. • CMP • Serum Ferritin • Serum Copper • Ceruloplasmin • RBC Zinc • RBC Magnesium • Phosphorous • Thyroid Function Tests: TSH, Free T3, Free T4, TPO Ab. (Hashimoto’s Thyroiditis), ThyroglobulinAb

  33. Tests • ANA with Reflex. • Sex Hormone Panel: DHEA, androstenedione, Free and Total Testosterone. • Anti-streptolysin O titer • DNAse B • Streptozyme screen with reflex to titer • Cunningham Panel • Vit.D3 • Serum Vit.B12 • Urine MMA ( Methymalonic Acid)

  34. Tests • Homocysteine • cs- CRP ( Cardiac Specific) • Lipid Profile • HbA1c • Carnitine (Free and Total) • CoQ10 • Serum CreatinineKinase • Serum Lactate and Pyruvate

  35. Tests • STAT Ammonia levels (only done if severe,sudden bloating and sudden change in behavior) • GSTM1 ( to check for Glutathione deficiency) • Candida: IgM, IgG, IgA • H.Pylori • Mold Allergy Panel • UA • VEGF ( Vascular Endothelial Growth Factor) • C4a ( If high, reveals poor perfusion) • Serum Leptin and MSH • Arginine Vasopressin (ADH)

  36. Tests • MTHFR • Urine heavy metal test (Doctors Data) • Organic Acid Test (OAT)/ Great Plains Lab • Methylation Test/ Amy Yasgo • Courtagen- whole Mitochondrial Genome Analysis (OPTIONAL) • EEG • EKG • CT sinuses, head

  37. Tests • MRI- Brain. • Food sensitivity test • Allergy Testing • EBV, HHV-6, CMV, West Nile virus, Parvovirus B19, Coxsackie A and B (1-6) titers, HSV-1 • Mycoplasma (IgM,IgG) • Lyme- Elisa, WB, Lyme culture test( Advanced Lab)

  38. Tests • Babesia (FISH test)/IgM,IgG • Bartonella (IgM, IgG)/PCR • Anaplasma (IgM, IgG)/PCR • (All of the viral, bacterial, spirochaetal, yeast tests can be ordered from MDL labs. No matter how many tests you order, they charge a flat rate of $225.00) • Immunology tests will be discussed under IVIG.

  39. Miscellaneous • ERMI (Environmental Residual Mold Index). Order online from Mycometrix.com( It gives instructions on how to test for mold in your home) Costs approx. $300/- • Use HEPA filter in the bedroom • If child tolerates, recommend Oxygen @2L/min. via nasal cannula or face mask at bedtime.

  40. Miscellaneous • Change mattresses if > 8-10 years old (use hypoallergenic sheets ,pillows, pillowcases.) • Use only Fluoride free toothpastes, Sulfite free shampoos and hypoallergenic soaps and lotions. • Install a REVERSE OSMOSIS filtration system in your home to remove all fluoride from your water supply for both drinking and bathing. Fluoride is also absorbed via skin. • Add minerals to the drinking water after removal of Fluoride.( Fluoride actively competes with Calcium and affects teeth, bone and nutritional health in Children and Adults.) Calcium is also important for absorption of Vit.B12 etc.

  41. Thoughts on IVIG • Children with recurrent otitis Media, sinusitis, bronchitis (strep infections), pneumonia, gastrointestinal infections (such as diarrhea), and also autoimmunity should be tested for common variable immunodeficiency (CVID). • Antibody production deficiency is the most common primary immunodeficiency (PI) in the United States. • Those patients with chronic recurrent sinusitis should get a CT scan of the sinus and brain to rule out any occlusions in the sinuses. • If there is any occlusion, those children should be sent to an ENT for probable surgery. • These recurrent infections can be due to poor quantity or quality of antibody (we are looking at immunoglobulin antibodies – IgG). • Antibody abnormalities and poor responses can occur in the setting of normal IgG quantities.

  42. Thoughts on IVIG • Insurance companies require that the provider prove poor functionality of immunoglobulin G prior to getting approval for intravenous immunoglobulin G (IVIG). • Initial workup include CBC with differentials, C3 (complement), C4 (complement), IgM, IgE, IgA (with subclasses 1 and 2), and IgG (with subclasses 1, 2, 3, and 4), Streptococcus pneumoniae titers (23 serotypes), tetanus antitoxoid antibody IgG, and diptheriaantitoxoid antibody IgG. • Once these lab tests are drawn, the patient is given the pneumovac vaccine from Merck in a single dose vial (0.5 mL – thimerosol free). • Another lab requisition is given for Strep pneumoniae titers (23 serotypes) to be drawn 4 weeks from the time of the vaccine injection. • If the immune response is adequate, the post-vaccine titers should increase by 2-fold or 4-fold in the majority of the serotype titers.

  43. Thoughts on IVIG • If this is not seen, then the patient has a poorly functioning immune system and is therefore eligible for receiving IVIG. • In PANS, children should be given high doses of IVIG and generally calculated at 1 gram per kilogram body weight given in two divided doses over two consecutive days. • The half life of IgG is approximately 3 weeks and is not dose dependent. In an ideal scenario, IVIG should be given every 3 weeks. • However, given the nature of insurance company requirements, we usually get IVIG once a month. These children cannot get one or two doses, but should be given a minimum of 1 year with one session every 4 weeks. • At the end of 1 year, they should be re-evaluated.

  44. What does IVIG do? • IVIG is a blood product prepared from the serum of between 1000 - 15000 donors per batch. • It is a choice for patients with antibody deficiencies. • It is used in neurology, immunology, dermatology, rheumatology, and nephrology. • It is used in the treatment of primary antibody deficiency. It is also used in the treatment of neurological disorders as well. • IVIG is used as a “replacement dose” at 200-400 mg per kilogram body weight given every 3 weeks. • In contrast, “high dose” IVIG given at 1-2 grams per kilogram per month, is used as an immunomodulatory agent in an increasing number of immune and inflammatory disorders.

  45. What does IVIG do? • Both antigen dependent and antigen independent responses are inhibited by IVIG in a dose dependent manner. • IVIG may also contain antibodies to important molecules such as tumor necrosis factor (TNF-α), interferon (IFN-γ) and interleukin (IL-1α). This shows it has a strong anti-inflammatory effect. • High dose IVIG inactivates immune complexes, selectively attenuating complement amplification. • IVIG itself may contain molecules including soluble cytokine inhibitors, soluble CD4, and MHC (class II major histocompatibility complex).

  46. Adverse Effects of IVIG • Immediate infusion related (with either low or high dose IVIG): • Mild to moderate reactions: • Headache, backache, muscle pains. • Chills. • Nausea (occurs in approximately 1 percent of infusions and are largely rate related) • Severe reactions: • Anaphylaxis may occur VERY RARELY in IVIG recipients who have high titers of anti-IgG antibodies.

  47. Adverse Effects of IVIG • No Transmission of infective agents since 1994 because of an additional antiviral step introduced by most manufacturers. There have been no Hepatitis C outbreaks since then. • Prions – no documented cases to date. • Consequences of increasing serum IgG (mostly with high dose IVIG) • Renal – reversible renal-impairment (majority of cases). • Hematological – cerebral and coronary thomboses, neutropenia • Neurological – acute aseptic meningitis. • Dematological – eczema, urticaria, erythmamultiformecutaneousvasculitis. • These are extremely rare.

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