Biomedical Individuality and Effective Treatment Strategies ...


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Biomedical Individuality and Effective Treatment Strategies ...

  1. 1. <ul><li>ASI Conference – Oct 2008 </li></ul><ul><li>Aurora, Illinois </li></ul><ul><li>Anju I. Usman, M.D. </li></ul><ul><li>True Health Medical Center </li></ul><ul><li>Naperville, Illinois </li></ul>
  2. 3. Environmental Toxicity And Heavy Metal Burden Genetics Biologic and Immunological Triggers Autism Timing Biomedical Causation Theories and the Web of Interactions Heavy Metal Overload Oxidative Stress Gut Dysfunction Immune Dysregulation Inflammation
  3. 4. <ul><li>Genetic predisposition </li></ul><ul><li>Mother’s Burden </li></ul><ul><li>Toxic Metals </li></ul><ul><li>Environmental Pollutants </li></ul><ul><li>Electromagnetic Fields </li></ul><ul><li>Sensory Input </li></ul><ul><li>Stress/Internal Conflicts </li></ul><ul><li>Dietary and Nutritional Factors </li></ul><ul><li>Microbial/Biofilm </li></ul><ul><li>Immune/Inflammatory Burden </li></ul>
  4. 5. <ul><li>Heavy Metal Overload </li></ul><ul><li>Oxidative Stress </li></ul><ul><li>Impaired Methylation </li></ul><ul><li>Depletion of reduced Glutathione </li></ul><ul><li>Mitochondrial Dysfunction </li></ul><ul><li>Gastrointestinal Dysfunction </li></ul><ul><li>Immune System Dysregulation </li></ul><ul><li>Microglial Activation </li></ul>The above lead to chronic smoldering inflammation in the body and brain
  5. 6. <ul><li>Heavy Metal Overload </li></ul><ul><ul><ul><li>Elevated levels of Mercury, Lead, Aluminum… </li></ul></ul></ul><ul><ul><ul><li>Mineral Deficiencies (Walsh, Adams) </li></ul></ul></ul><ul><ul><ul><li>Abnormal Porphyrins ( Nataf, Geiers) </li></ul></ul></ul><ul><li>Oxidative Stress (James,Salomon,Yorbik,Chauhan,Fuchs,Wagner,Pratico ) </li></ul><ul><ul><ul><li>Impaired Methylation (James, Deth) </li></ul></ul></ul><ul><ul><ul><li>Sulfation Abnormalities (Waring) </li></ul></ul></ul><ul><ul><ul><li>Impaired Detoxification </li></ul></ul></ul><ul><ul><ul><li>Depletion of antioxidants, vitamin cofactors </li></ul></ul></ul><ul><ul><ul><li>Depletion of reduced Glutathione (James) </li></ul></ul></ul><ul><ul><ul><li>Mitochondrial Insufficiency ( Rossignol, Polling, …) </li></ul></ul></ul><ul><li>Gastrointestinal Dysfunction </li></ul><ul><li>Immune System Dysregulation </li></ul>
  6. 7. Oxidative Stress Antioxidant Defense Superoxide Dismutase GSH Peroxidase GSH Reductase Vitamin E Vitamin C Lipoic Acid GSTs GSH Hydroxyl Radical Hydrogen Peroxide Superoxide ONOO- GSSG 4HNE LOO- Cell Death Damage Inflammation
  7. 8. <ul><li>Maldigestion </li></ul><ul><ul><li>Decreased activity of digestive enzymes (Horvath,1999. Buie, 2004) </li></ul></ul><ul><ul><li>High levels of opioid peptides found in urine of autistics. (Reichelt, 1997) </li></ul></ul><ul><ul><li>IgG Food Sensitivities </li></ul></ul><ul><li>Malabsorption </li></ul><ul><ul><li>Fat Soluble Vitamin Deficiencies </li></ul></ul><ul><ul><li>Essential Fatty Acid Deficiencies </li></ul></ul><ul><ul><li>Essential Amino Acid Deficiencies </li></ul></ul><ul><li>Dysbiosis </li></ul><ul><ul><li>Dysbiosis or altered bowel flora (Rossenau, 2004) </li></ul></ul><ul><ul><li>Clostridial overgrowth (Sandler, 2002, MacFabe 2007) </li></ul></ul><ul><ul><li>Persistent measles virus (Wakefield, Krigsman) </li></ul></ul><ul><li>Inflammation/Immune </li></ul><ul><ul><li>Autistic Enterocolitis, Lymphoid Hyperplasia (Wakefield, Krigsman, Balzola ) </li></ul></ul><ul><ul><li>Increased intestinal permeability leading to food sensitivities and autoimmunity (Vodjani, 2002) </li></ul></ul><ul><ul><li>Increased pro-inflammatory cytokines – LP, TNF alpha, IFN gamma </li></ul></ul><ul><ul><li>(Ashwood, 2004) </li></ul></ul><ul><ul><li>Proinflammatory response to dietary proteins (Jyonuchi, 2004) </li></ul></ul>
  8. 9. <ul><li>Th1 and Th2 skewing </li></ul><ul><ul><li>Abnormal cell-mediated immunity </li></ul></ul><ul><ul><li>Abnormal T-cell subsets, decreased NK cells, abnormal cytokines, Th2 skewing (Zimmerman, 1998/Vodjani, 2008) </li></ul></ul><ul><ul><li>Decreased secretory IgA </li></ul></ul><ul><ul><li>Pro-inflammatory Factors in the Gut (Ashwood, Jyonuchi) </li></ul></ul><ul><li>Pro-inflammatory Cytokines in the Brain </li></ul><ul><ul><li>MCP-1, TGF beta-1 (Vargas,Pardo, 2005) </li></ul></ul><ul><ul><li>Abnormal EEG, Seizure activity </li></ul></ul><ul><ul><li>Microglial Activation and perivascular inflammation </li></ul></ul><ul><li>Increased Autoimmunity </li></ul><ul><ul><li>Autoantibodies to neural antigens (Connolly, 1999) </li></ul></ul><ul><ul><li>Myelin basic protein and Neuronal Axonal Filament Protein Antibodies (Gupta, 1996 /Singh, 1997) </li></ul></ul>
  9. 10. <ul><li>History and Physical Examination </li></ul><ul><li>Laboratory Testing </li></ul><ul><li>Clean Up </li></ul><ul><ul><li>Environmental Controls </li></ul></ul><ul><ul><li>Dietary Interventions </li></ul></ul><ul><ul><li>Address Gastrointestinal Health </li></ul></ul><ul><li>Foundational Nutrients </li></ul><ul><li>Treat underlying Immune Issues and Inflammation </li></ul><ul><li>Support Detoxification/Mitochondrial Pathways </li></ul><ul><li>Heavy Metal/Chemical Detoxification </li></ul>
  10. 11. Intensity of Symptoms = Intensity of Treatment Educational and Behavioral Therapies Environmental Controls Dietary Interventions Nutrient Therapies Gastrointestinal Health Immune Issues and Inflammation Promotion of Natural Detox and Mitochondria Pharmaceutical Detox and other Drug therapy Hyperbaric Oxygen Therapy
  11. 12. <ul><li></li></ul>
  12. 13. <ul><li>Casein/gluten peptides are broken down by DPPIV. This enzyme can be disabled by toxic metals and yeast. </li></ul><ul><li>High levels of opioid peptides (gliadorphin and caseomorphine) found in urine of autistics. (Reichelt, 1997) </li></ul><ul><li>Casein-free, Gluten-free diet may be an effective intervention (Whiteley,1999) </li></ul><ul><li>Presently NIH study underway </li></ul>
  13. 14. <ul><li>Casein – protein from all dairy products </li></ul><ul><ul><li>Caseomorphine= undigested casein peptide, has an opiate effect on the brain </li></ul></ul><ul><li>Gluten – protein found in wheat, rye, oat, barley, malt, spelt </li></ul><ul><ul><li>Gliadorphin= partially digested gluten peptide, has an opiate effect on the brain </li></ul></ul><ul><li>Urinary Peptides can be measured </li></ul>
  14. 15. <ul><li>Jyonouchi H et al (2002) Neuropsychobiology 46 qq </li></ul><ul><li>Croonenberghs J et al (2002) Neuropsychobiology 45 </li></ul><ul><li>Ashwood P et al (2004) J Clin Immuno 24: 664-673 </li></ul><ul><li>Jyonouchi H et al (2005) Neuropsychobiology 51: 77-85 </li></ul>
  15. 16. <ul><li>It remains unclear how and when microglia and astroglia become activated in the brains of patients with autism. Glial responses in autism may be part of intrinsic, or primary, reactions that result from disturbances in glial function or neuronal-glial interactions during brain development. They may also be secondary, resulting from unknown disturbances (such as infections or toxins) in prenatal or postnatal CNS development. Nevertheless, the findings of this study highlight the existence of neuroimmunological processes in autism and provide a setting for new research approaches to the diagnosis and treatment of this debilitating neurological disorder. </li></ul><ul><li>Slides A and C, from patients with autism, show an increase in neuron-supporting cells called glia. This increase is likely a sign of a neuroimmunological response to the disorder. © 2005 Pardo, Vargas et al. </li></ul>
  16. 17. <ul><li>The Neuroscientist, Volume 11, Number 5, 2005. Martha Herbert, MD, PhD , </li></ul><ul><li>&quot;neuroinflammation appears to be present in autistic brain tissue from childhood through adulthood.&quot; Dr. Herbert suggests that chronic disease or an external environmental source (like heavy metals) may be causing the inflammation. Excerpt: &quot; Oxidative stress, brain inflammation, and microgliosis have been much documented in association with toxic exposures including various heavy metals.. .the awareness that the brain as well as medical conditions of children with autism may be conditioned by chronic biomedical abnormalities such as inflammation opens the possibility that meaningful biomedical interventions may be possible well past the window of maximal neuroplasticity in early childhood because the basis for assuming that all deficits can be attributed to fixed early developmental alterations in neural architecture has now been undermined. </li></ul>“ The brains of children with neurological disorders are experiencing severe oxidative stress and inflammation, suggesting an environmental cause.
  17. 18. <ul><li>Glutamates </li></ul><ul><ul><li>Monosodium Glutamate (MSG) </li></ul></ul><ul><ul><li>Hydrolyzed Protein </li></ul></ul><ul><ul><li>Modified Food Starch </li></ul></ul><ul><ul><li>Natural Flavors </li></ul></ul><ul><ul><li>Peas, Mushrooms, Tomatoes </li></ul></ul><ul><ul><li>Parmesan Cheese </li></ul></ul><ul><ul><li>Protein </li></ul></ul><ul><li>Anti- Glutamates </li></ul><ul><ul><li>Pycnogenol </li></ul></ul><ul><ul><li>Rosemary, Lemon Balm </li></ul></ul><ul><ul><li>Skull Cap, Chamomile </li></ul></ul><ul><ul><li>Taurine </li></ul></ul><ul><ul><li>GABA </li></ul></ul><ul><ul><li>L- Theanine </li></ul></ul><ul><ul><li>Vitamin K </li></ul></ul><ul><ul><li>Namenda (drug) </li></ul></ul><ul><ul><li>Minocycline (antibiotic) </li></ul></ul>Excitotoxins = Substances that cause an excess of excitatory neurotransmission in the brain. If inhibitory neurotransmission is lacking, chronic inflammation in the brain may result.
  18. 19. <ul><li>2007 study in The Lancet examined the effect of artificial coloring and preservatives on hyperactive behavior in children. After consuming an additive-free diet for six weeks, the children were given either a placebo beverage or one containing a mix of additives in two-week intervals. In the additive group, hyperactive behaviors increased. </li></ul><ul><li>The study caused many pediatricians to rethink their skepticism about a link between diet and A.D.H.D. “The overall findings of the study are clear and require that even we skeptics, who have long doubted parental claims of the effects of various foods on the behavior of their children, admit we might have been wrong,” reported a February issue of AAP Grand Rounds, a publication of the American Academy of Pediatrics. </li></ul>
  19. 20. <ul><li>Inadequate antioxidant status is a major pathway for inflammation.  </li></ul><ul><li>Various free rdicals (ROS), including superoxide, peroxide, hydroxyl and peroxynitrite, are generated through the inflammatory prostaglandin/leukotriene pathways. </li></ul><ul><li>These free radicals can damage or destroy virtually every cellular biomolecule: proteins, fatty acids, phospholipids, glycoproteins, even DNA, leading to cell injury or death.  </li></ul><ul><li>vitamins C and E are the two most important nutritional antioxidants. </li></ul><ul><li>Vitamin C, E, alpha-lipoic acid, Co Q10 and NADH act as a team. </li></ul><ul><li>One of the many ways excitotoxins damage neurons </li></ul><ul><li>is to prevent the intracellular formation of glutathione. </li></ul><ul><li>  </li></ul>
  20. 22. <ul><li>Rosemary Waring found low Sulfate levels in ASD. Low Sulfation leads to poor detoxification of Phenols. </li></ul><ul><li>PST Enzyme helps to detox Phenolic Substances from the body </li></ul><ul><li>Common Phenolic Substances </li></ul><ul><ul><li>Hormones </li></ul></ul><ul><ul><li>Salicylates (grapes, apples, strawberries) </li></ul></ul><ul><ul><li>Neurotransmitters </li></ul></ul><ul><ul><li>Biologic Agents (yeast) </li></ul></ul><ul><ul><li>Pesticides, Herbicides, Perfumes </li></ul></ul><ul><li>Lack of sulfation may manifest as hyperactivity, stimming, lax ligaments, red cheeks and red ears. </li></ul><ul><li>Pyridoxal 5-Phosphate is a co-factor </li></ul><ul><li>Epsom Salts/Magnesium Sulfate Baths may help </li></ul>
  21. 23. <ul><li>Casein-free/Gluten-free /Diet Trial for 3-6 months. </li></ul><ul><li>Avoid sugar and refined starch, replace with whole grains </li></ul><ul><li>Maximize antioxidants and phytonutrients. </li></ul><ul><li>Limit processed and preserved foods; organic is best. </li></ul><ul><li>Avoid excitotoxins (ex. Caffeine, MSG, NutraSweet, red/yellow food dyes, nitrites, sulfites, glutamates, propionates, benzoates). </li></ul><ul><li>Limit intake of phenolics (apples, grapes, strawberries…). </li></ul><ul><li>Drink plenty of filtered water. </li></ul><ul><li>Never microwave in plastics or Styrofoam, do not store food in plastic or foil, or cook on Teflon coated pans. </li></ul><ul><li>Eliminate seafood. </li></ul><ul><li>Add good fats (olive, coconut, flax). Avoid hydrogenated and trans fats and esterified fats. </li></ul><ul><li>Buy hormone-free, antibiotic-free, organic meat and eggs. </li></ul><ul><li>Add fermented foods (coconut kefir, kombucha,…). </li></ul>
  22. 24. Dietary Detours CF/GF Diet Persistent Gut Issues Hyperactivity/Stimming Specific Carbohydrate Diet Body Ecology Diet Low Oxalate Diet Avoid Excitotoxins Low Phenolic/Feingold Diet Low Copper Diet Elimination/Rotation Diet Elimination/Rotation Diet
  23. 25. <ul><li>Ames BN (2002) High dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased Km) : relevance to genetic disease and polymorphisms. Am J Clin Nutr 75: 616-658 </li></ul><ul><li>Vieth R (2001) Vitamin D nutrition and its potential health benefits for bone, cancer and other conditions. J Nutr & environmental med 11: 275-291. </li></ul><ul><li>Fernstom JD ( 2000) Can Nutritional Supplements modify brain function? Am J Clin nutr 71: 1669S-1673S. </li></ul><ul><li>Ames BN (2004) A role for supplements in optimizing health : the metabolic tune-up. Arch Biochem Biophys 421: 227-234 </li></ul>
  24. 26. <ul><li></li></ul>
  25. 27. Dr. Bernie Rimland – Autism Research Institute Studies of High Dosage Vitamin B6 (and often with Magnesium) in Autistic Children and Adults, 1965 - 2005 Twenty-one of twenty-two studies yielded positive results, including 13 double-blind placebo-controlled trials; even minor adverse effects rarely were seen. Compilation of Studies Supporting the Biomedical Approach Scientific Foundations of a Biomedical Approach to ASD
  26. 28. <ul><li>Pyridoxal 5-phosphate (P5P) active form of vitamin B6 </li></ul><ul><li>Conversion of B6 to P5P requires: ATP, Mg, Zn, Vit B2 </li></ul><ul><li>Used by 112 enzymes </li></ul><ul><li>Transamination reactions </li></ul><ul><li>Decarboxylation ( L-Dopa to Dopamine, 5HTP to Serotonin, Glutamic Acid to GABA) </li></ul><ul><li>Tryptophan metabolism </li></ul><ul><ul><li>breakdown of hydroxykynurenin </li></ul></ul><ul><ul><li>niacin production </li></ul></ul><ul><li>Glycogenolysis </li></ul><ul><li>(breakdown of glycogen) </li></ul><ul><li></li></ul>
  27. 29. <ul><li>Symptoms </li></ul><ul><ul><li>Morning nausea </li></ul></ul><ul><ul><li>Frequent mood swings </li></ul></ul><ul><ul><li>Difficult handling transitions </li></ul></ul><ul><ul><li>Poor short term memory </li></ul></ul><ul><ul><li>Poor stress handling </li></ul></ul><ul><ul><ul><li>Avoidance </li></ul></ul></ul><ul><ul><ul><li>Seclusion </li></ul></ul></ul><ul><ul><ul><li>Over reaction, meltdowns </li></ul></ul></ul><ul><ul><ul><li>Overly dramatic </li></ul></ul></ul><ul><ul><li>Sensory issues (light, sound, touch, taste, smell) </li></ul></ul><ul><ul><li>Burn easy in sun, do not tan </li></ul></ul><ul><ul><li>Poor dream recall </li></ul></ul><ul><ul><li>Vivid dreams, nightmares </li></ul></ul><ul><ul><li>Nervousness, Panic, Anxiety </li></ul></ul><ul><ul><li>Irish ancestry </li></ul></ul><ul><ul><li>Seizure disorder </li></ul></ul><ul><li>Physical Exam </li></ul><ul><ul><li>Glossitis, mouth ulcers </li></ul></ul><ul><ul><li>Dry skin, cracked lips and nails </li></ul></ul><ul><ul><li>Spleen tenderness </li></ul></ul><ul><ul><li>China doll skin </li></ul></ul><ul><ul><li>Spider veins </li></ul></ul><ul><ul><li>Sweet breath </li></ul></ul><ul><ul><li>Crowded upper front teeth </li></ul></ul><ul><ul><li>Red hair, blue eyes </li></ul></ul><ul><ul><li>Peripheral neuropathy </li></ul></ul><ul><li>Laboratory Findings </li></ul><ul><ul><li>Urinary Kryptopyrrole Level Above 10 mcg/dl </li></ul></ul>
  28. 30. <ul><li>.5 </li></ul><ul><li>1.0 </li></ul><ul><li>1.5 </li></ul><ul><li>2.0 </li></ul><ul><li>10 </li></ul><ul><li>25 </li></ul><ul><li>50 </li></ul><ul><li>75 </li></ul><ul><li>90 </li></ul><ul><li>Percentile </li></ul><ul><li>Cu/Zn Ratio </li></ul><ul><li>Autistics </li></ul><ul><li>Controls </li></ul><ul><li>503 Patients with ASD </li></ul><ul><li>Mean Cu/Zn ratio 1.63 in ASD </li></ul><ul><li>Mean Cu/Zn ratio 1.15 in Controls </li></ul>Pfeiffer Treatment Center Data 2001
  29. 31. <ul><li>Neurotransmitter imbalances (high platelet serotonin, low dopamine, high norepinephrine) </li></ul><ul><li>Abnormal EEG and seizure activity </li></ul><ul><li>Hyperactivity </li></ul><ul><li>Poor attention span </li></ul><ul><li>Explosive Temper </li></ul><ul><li>Poor Short Term Memory </li></ul><ul><li>Speech Delay </li></ul><ul><li>Yeast Overgrowth </li></ul>
  30. 32. <ul><li>Treat Zinc deficiency until Zinc level optimized (100mcg/dl) </li></ul><ul><li>Induce Metallothionein (MT) production using Selenium and Glutathione </li></ul><ul><li>Add Manganese and Molybdenum in small doses </li></ul><ul><li>Provide adequate amounts of vitamin B6/Magnesium </li></ul><ul><li>Optimize Vitamin C dose </li></ul><ul><li>Avoid Sources of Copper </li></ul><ul><ul><li>Tap water (Cu pipes) </li></ul></ul><ul><ul><li>Swimming pools and hot tubs (Cu algaecide) </li></ul></ul><ul><ul><li>Chocolate, Carob, Soy, Shellfish, Liver </li></ul></ul><ul><li>Avoid Red/ Yellow dyes and MSG (deplete Zn) </li></ul><ul><li>Consider Carnosine supplementation </li></ul>
  31. 33. <ul><ul><li>Improves methylation, glutathione, oxidative stress. </li></ul></ul><ul><ul><li>Jill James Study. </li></ul></ul><ul><ul><li>Methylation also helps with the production and metabolism of Dopamine, Serotonin, Norepinephrine and Epinephrine. </li></ul></ul><ul><ul><li>Shown to help cognitive ability, abstract thinking, attention, focus, awareness, language, behavior, OCD, anxiety, ….(Neubrander, 2004). </li></ul></ul><ul><ul><li>No test for methylB12 deficiency. </li></ul></ul><ul><ul><li>Consider 3 month trial. </li></ul></ul><ul><ul><li>Side effects – increased energy, hyperactivity, agitation, stimming. </li></ul></ul><ul><ul><li>Protocol 75 mcg/kg subcutaneous injection </li></ul></ul><ul><ul><li>every 3 rd day </li></ul></ul><ul><ul><li>Parents give the preservative-free, </li></ul></ul><ul><ul><li>methyl B12 injections themselves. </li></ul></ul>
  32. 34. <ul><li>Essential fatty acids, DHA and human brain development Indian J.Pediatr Mar 2005 </li></ul><ul><ul><li>Infants of mothers supplemented with EFAs and DHA had higher mental processing, psychomotor scores, and eye-hand coordination. EFAs may prevent ADHD in preschoolers. </li></ul></ul><ul><li>Long chain polyunsaturated fatty acids in childhood developmental and psychiatric disorders Lipids Dec 2004 </li></ul><ul><ul><li>LC-PUFA help with childhood behavior and learning difficulties. </li></ul></ul><ul><li>Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study </li></ul><ul><ul><li>EFA helped with hyperactivity and sterotypy in ASD children. </li></ul></ul>
  33. 35. <ul><li>Essential Fats are fats that your body can not manufacture. They need to be consumed. </li></ul><ul><li>These fats are essential for neuronal transmission, cell to cell communication, normalizing excitation, maintaining skin, hair, joint structure, and minimizing inflammation. </li></ul><ul><li>Omega 3 </li></ul><ul><ul><li>Fish, Flax, Seaweed </li></ul></ul><ul><li>Omega 6 </li></ul><ul><ul><li>Safflower, Sunflower, Corn, </li></ul></ul><ul><ul><li>Borage, Evening Primrose </li></ul></ul><ul><li>Omega 9 </li></ul><ul><ul><li>Olive, Avocado, Coconut </li></ul></ul>
  34. 36. <ul><li>Minerals </li></ul><ul><ul><li>Zinc 2-3mg/kg </li></ul></ul><ul><ul><li>Magnesium 10-30mg/kg </li></ul></ul><ul><ul><li>Selenium 100-200mcg </li></ul></ul><ul><ul><li>Molybdenum 100-250mcg </li></ul></ul><ul><ul><li>Calcium 200-1000mg per day </li></ul></ul><ul><li>Vitamins </li></ul><ul><ul><li>B6 100-500mg/day </li></ul></ul><ul><ul><li>Methyl B12 injections </li></ul></ul><ul><li>Antioxidants </li></ul><ul><ul><li>Vitamin C 500-1500mg/day </li></ul></ul><ul><ul><li>Vitamin E 200-800 IU/day </li></ul></ul><ul><ul><li>Vitamin A 2500-15,000iu/day </li></ul></ul><ul><ul><li>Vitamin D 2000 IU/day </li></ul></ul><ul><ul><li>Glutathione 200mg per day </li></ul></ul><ul><ul><li>Melatonin 1-3 mg/day </li></ul></ul><ul><li>EFA </li></ul><ul><ul><li>Omega 3 EFA 1000mg </li></ul></ul>
  35. 37. <ul><li>Daily bowel movements are a goal. </li></ul><ul><li>Add digestive enzymes with meals. </li></ul><ul><li>Start high potency probiotics (acidophilus and bifidus) or probiotic containing foods. </li></ul><ul><li>Start treatment for dysbiosis depending on symptoms and labs. </li></ul><ul><li>Check for high ammonia , treat accordingly. </li></ul><ul><li>If persistent symptoms: </li></ul><ul><ul><li>Eliminate disaccharides from diet for 3-6 months </li></ul></ul><ul><ul><ul><li>Specific Carbohydrate Diet (SCD) </li></ul></ul></ul><ul><ul><li>Consider referral to knowledgeable GI specialist </li></ul></ul><ul><ul><li>Consider trial of IV or nasal Secretin. </li></ul></ul><ul><ul><li>Treat with natural anti-inflammatories. </li></ul></ul>
  36. 38. <ul><li>CBC </li></ul><ul><li>Comprehensive Metabolic Panel </li></ul><ul><li>Serum Copper </li></ul><ul><li>Plasma Zinc </li></ul><ul><li>Ceruloplasmin </li></ul><ul><li>Hair Analysis </li></ul><ul><li>Thyroid profile </li></ul><ul><li>Blood Lead </li></ul><ul><li>Ammonia </li></ul><ul><li>Intracellular Minerals and Metals </li></ul><ul><li>Urine Essential Minerals </li></ul><ul><li>Essential Fatty Acids </li></ul><ul><li>Amino Acids </li></ul><ul><li>Plasma cysteine, sulfate, rGSH </li></ul><ul><li>Urine Organic Acids Test (OATS) </li></ul><ul><li>Stool Microbiology </li></ul><ul><li>Stool Mycology </li></ul><ul><li>Stool Parasitology </li></ul><ul><li>Immune Markers </li></ul><ul><ul><li>Immunoglobulin Levels </li></ul></ul><ul><ul><li>T lymphocyte Panel </li></ul></ul><ul><ul><li>Natural Killer Cell Activity </li></ul></ul><ul><ul><li>PANDA’s Profile </li></ul></ul><ul><ul><li>Anti MBP Ab </li></ul></ul><ul><ul><li>Anti NAFP Ab </li></ul></ul><ul><ul><li>IgG Food Ab Panel </li></ul></ul><ul><ul><li>Vaccine Titers </li></ul></ul><ul><ul><li>Viral Titers </li></ul></ul><ul><li>Urinary Peptides </li></ul><ul><li>Hormone Studies </li></ul><ul><li>Neurotransmitter Levels </li></ul><ul><li>Genomics – SNPs </li></ul><ul><li>Urine/ Fecal Toxic Metals </li></ul><ul><li>Urinary Porphryins </li></ul><ul><li>Urinary Neopterin </li></ul><ul><li>Urinary 8-OH Guanosine </li></ul><ul><li>Organophosphate Levels </li></ul>
  37. 39. <ul><li>These agents create inflammation, free radicals and oxidative stress. </li></ul><ul><li>Some of these biologic agents produce neurotoxins and excitotoxins and other toxic by-products. </li></ul><ul><li>Some agents increase cell membrane permeability. </li></ul><ul><li>Our body may produce antibodies to these agents. These antibodies may cross react with our own tissue creating an autoimmune reaction. This is called molecular mimicry. </li></ul>
  38. 40. Clostridia produce toxins (propionic acid) and enzymes that create severe gut inflammation, produce watery diarrhea, and can cause behavior changes.
  39. 41. <ul><li>American Journal of Biochemistry and Biotechnology 4 (2): 146-166, 2008 </li></ul><ul><li>Derrick F. MacFabe </li></ul><ul><li>Innate neuroinflammatory changes, increased oxidative stress and disorders of glutathione metabolism may be involved in the pathophysiology of autism spectrum disorders (ASD). Propionic acid (PPA) is a dietary and gut bacterial short chain fatty acid which can produce brain and behavioral changes reminiscent of ASD following intraventricular infusion in rats treatment day, specific brain regions were assessed for neuroinflammatory or oxidative stress markers. .. </li></ul><ul><li>Immunohistochemical analyses revealed reactive astrogliosis (GFAP), activated microglia (CD68,Iba1) without apoptotic cell loss (Caspase 3’ and NeuN) in hippocampus and white matter (external capsule) of PPA treated rats. Biomarkers of protein and lipid peroxidation, total glutathione (GSH) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) were examined in brain homogenates. Some brain regions of PPA treated animals (neocortex, hippocampus, thalamus, striatum) showed increased lipid and protein oxidation accompanied by decreased total GSH in neocortex. Catalase activity was decreased in most brain regions of PPA treated animals suggestive of reduced antioxidant enzymatic activity. GPx and GR activity was relatively unaffected by PPA treatment while GST was increased, perhaps indicating involvement of GSH in the removal of PPA or related catabolites. Impairments in GSH and catalase levels may render CNS cells more susceptible to oxidative stress from a variety of toxic insults. Overall, these findings are consistent with those found in ASD patients and further support intraventricular PPA administration as an animal model of ASD. </li></ul>
  40. 42. <ul><li>Symptoms </li></ul><ul><ul><li>Aggressive </li></ul></ul><ul><ul><li>Temper </li></ul></ul><ul><ul><li>Agitation </li></ul></ul><ul><ul><li>Irritable </li></ul></ul><ul><ul><li>Very foul stools </li></ul></ul><ul><ul><li>Mucus in stools </li></ul></ul><ul><ul><li>Severe diarrhea following antibiotic use </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Probiotics, High Potency single strain </li></ul></ul><ul><ul><li>Sacchyromyces Boulardii </li></ul></ul><ul><ul><li>Antibiotics </li></ul></ul><ul><ul><ul><li>Vancomycin </li></ul></ul></ul><ul><ul><ul><li>Metronidazole (Flagyl) </li></ul></ul></ul><ul><ul><li>Immune modulators </li></ul></ul><ul><ul><li>Homeopathics </li></ul></ul><ul><ul><li>HBOT </li></ul></ul>
  41. 43. <ul><li>Symptoms </li></ul><ul><ul><li>Spacey </li></ul></ul><ul><ul><li>Foggy thinking </li></ul></ul><ul><ul><li>Inappropriate laughter </li></ul></ul><ul><ul><li>Sugar cravings </li></ul></ul><ul><ul><li>Poor sleep </li></ul></ul><ul><ul><li>Frequent diaper rash </li></ul></ul><ul><ul><li>Frequent urination </li></ul></ul><ul><ul><li>History of frequent antibiotics </li></ul></ul><ul><ul><li>Treatment Options </li></ul></ul><ul><ul><li>Limit carbs, sugar, yeast </li></ul></ul><ul><ul><li>Probiotics </li></ul></ul><ul><ul><li>Sacchromyces Boulardii </li></ul></ul><ul><ul><li>Zinc, Molybdenum </li></ul></ul><ul><ul><li>Antifungals </li></ul></ul><ul><ul><ul><li>Drugs </li></ul></ul></ul><ul><ul><ul><ul><li>Nystatin, Amphotericin B </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Fluconazole </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Itraconazole </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Ketoconazole </li></ul></ul></ul></ul><ul><ul><ul><li>Herbals </li></ul></ul></ul><ul><ul><ul><ul><li>Berberine </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Grapefruit Seed Extract </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Oil of Oregano, Pau d’Arco </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Garlic, Samento, … </li></ul></ul></ul></ul><ul><ul><li>Enzymes </li></ul></ul><ul><ul><li>Homeopathics </li></ul></ul>
  42. 44. <ul><li>Symptoms </li></ul><ul><ul><li>Bizarre Behavior </li></ul></ul><ul><ul><li>Insatiable Appetite </li></ul></ul><ul><ul><li>Aggressive </li></ul></ul><ul><ul><li>Worse at full moon </li></ul></ul><ul><ul><li>Picking, biting, licking, itching, grinding </li></ul></ul><ul><ul><li>Fecal smearing </li></ul></ul><ul><ul><li>Restlessness </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Probiotics </li></ul></ul><ul><ul><li>Antiparasitic Drugs </li></ul></ul><ul><ul><ul><li>Flagyl </li></ul></ul></ul><ul><ul><ul><li>Paromomycin </li></ul></ul></ul><ul><ul><ul><li>Mebendazole </li></ul></ul></ul><ul><ul><li>Natural Remedies </li></ul></ul><ul><ul><ul><li>Wormwood(artemesia) </li></ul></ul></ul><ul><ul><ul><li>Black Walnut </li></ul></ul></ul><ul><ul><ul><li>Pumpkin Seeds </li></ul></ul></ul><ul><ul><ul><li>Clove </li></ul></ul></ul><ul><ul><ul><li>Coconut Oil </li></ul></ul></ul><ul><ul><li>Homeopathics </li></ul></ul><ul><ul><ul><li>Combo remedies </li></ul></ul></ul><ul><ul><ul><li>Cina </li></ul></ul></ul>
  43. 45. <ul><li>J Neurosci Res. 2007 Apr;85(5):1143-8. </li></ul><ul><ul><li>Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and human herpes virus-6 coinfections in the blood of patients with autistic spectrum disorders. </li></ul></ul><ul><ul><li>Nicolson GL , Gan R , Nicolson NL , Haier J . </li></ul></ul><ul><ul><li>We examined the blood of 48 patients from central and southern California diagnosed with autistic spectrum disorders (ASD) by using forensic polymerase chain reaction and found that a large subset (28/48 or 58.3%) of patients showed evidence of Mycoplasma spp. infections compared with two of 45 (4.7%) age-matched control subjects (odds ratio = 13.8, P < 0.001). Because ASD patients have a high prevalence of one or more Mycoplasma spp. and sometimes show evidence of infections with Chlamydia pneumoniae, we examined ASD patients for other infections. Also, the presence of one or more systemic infections may predispose ASD patients to other infections, so we examined the prevalence of C. pneumoniae (4/48 or 8.3% positive, odds ratio = 5.6, P < 0.01) and human herpes virus-6 (HHV-6, 14/48 or 29.2%, odds ratio = 4.5, P < 0.01) coinfections in ASD patients. We found that Mycoplasma-positive and -negative ASD patients had similar percentages of C. pneumoniae and HHV-6 infections, suggesting that such infections occur independently in ASD patients. Control subjects also had low rates of C. pneumoniae (1/48 or 2.1%) and HHV-6 (4/48 or 8.3%) infections, and there were no coinfections in control subjects. The results indicate that a large subset of ASD patients shows evidence of bacterial and/or viral infections (odds ratio = 16.5, P < 0.001). The significance of these infections in ASD is discussed in terms of appropriate treatment. (c) 2007 Wiley-Liss, Inc. PMID: 17265454 [PubMed - indexed for MEDLINE] </li></ul></ul>
  44. 46. <ul><li>Medical Hypothesis </li></ul><ul><li>The Association between Tick-Borne Infections, Lyme Borreliosis and Autism Spectrum Disorders </li></ul><ul><li>Robert C Bransfield, MD </li></ul><ul><li>       A Lyme Induced Autism Foundation conference was held in June 2007 in Irvine, California to explore the association between infectious diseases, tick-borne infections, including Lyme Borreliosis ( Borrelia burgdorferi ) and autism spectrum disorders. There are multiple cases of mothers with Lyme disease and children with autism spectrum disorders; significant fetal neurological abnormalities associated with tick-borne diseases; improvement in autistic symptoms in some autism spectrum disorder patients from antibiotic treatment; similarities between the clinical manifestations of tick-borne diseases and autism spectrum disorder regarding pathophysiology, treatment responses, immune reactivity, temporal lobe pathology, and brain imaging data. </li></ul><ul><li>       Pilot studies of autism spectrum disorder patients demonstrate positive reactivity for Borrelia burgdorferi at 22% (Vojdani) and 26% (Lyme Induced Autism Foundation) and 58% for Mycoplasma ( including M. fermentans and M. pneumoniae ), 8% for Chlamydia pneumoniae and 29% for Human Herpes Virus-6 (Nicolson). In addition, geographical patterns of a greater incidence of autism spectrum disorders approximate regions that are more endemic for tick-borne diseases. </li></ul><ul><li>        It is hypothesized that chronic infectious diseases, including tick-borne infections such as Borrelia burgdorferi may have direct effects, promote other infections and create a weakened, sensitized and immunologically vulnerable state during fetal development and infancy leading to increased vulnerability for developing autism spectrum disorders. </li></ul>
  45. 47. <ul><li>Symptoms </li></ul><ul><ul><li>Ritualistic </li></ul></ul><ul><ul><li>Repetitive </li></ul></ul><ul><ul><li>Verbal tics </li></ul></ul><ul><ul><li>Obsessive </li></ul></ul><ul><ul><li>Compulsive </li></ul></ul><ul><ul><li>Verbal stims </li></ul></ul><ul><ul><li>Frequent strep infections </li></ul></ul><ul><ul><li>Frequent bacterial infections </li></ul></ul><ul><ul><li>Treatment Options </li></ul></ul><ul><ul><li>Probiotics </li></ul></ul><ul><ul><li>Alkalinization </li></ul></ul><ul><ul><li>Xylitol </li></ul></ul><ul><ul><li>Antibacterial Herbs </li></ul></ul><ul><ul><ul><li>Goldenseal, Berberine </li></ul></ul></ul><ul><ul><ul><li>Artemesia </li></ul></ul></ul><ul><ul><ul><li>Neem </li></ul></ul></ul><ul><ul><li>Immune modulators </li></ul></ul><ul><ul><ul><li>Oral Immunoglobulins </li></ul></ul></ul><ul><ul><ul><li>Transfer Factors </li></ul></ul></ul><ul><ul><ul><li>Colostrum </li></ul></ul></ul><ul><ul><ul><li>Mushroom Extracts </li></ul></ul></ul><ul><ul><ul><li>Glycans </li></ul></ul></ul><ul><ul><ul><li>Plant Sterols </li></ul></ul></ul><ul><ul><li>Drugs </li></ul></ul><ul><ul><ul><li>Penicillin </li></ul></ul></ul><ul><ul><ul><li>Zithromax </li></ul></ul></ul>
  46. 48. DA
  47. 49. <ul><li>Gillberg IC. </li></ul><ul><li>Autistic syndrome with onset at age 31 years: herpes encephalitis as a possible model for childhood autism. </li></ul><ul><li>Dev Med Child Neurol. 1991 Oct;33(10):920-4. PMID: 1743418 [PubMed - indexed for MEDLINE] </li></ul><ul><li>DeLong GR, Bean SC, Brown FR 3rd . </li></ul><ul><li>Acquired reversible autistic syndrome in acute encephalopathic illness in children. </li></ul><ul><li>Arch Neurol. 1981 Mar;38(3):191-4. PMID: 6162440 [PubMed - indexed for MEDLINE] </li></ul><ul><li>Caruso JM, Tung GA, Gascon GG, Rogg J, Davis L, Brown WD. </li></ul><ul><li>Persistent preceding focal neurologic deficits in children with chronic Epstein-Barr virus encephalitis. </li></ul><ul><li>J Child Neurol. 2000 Dec;15(12):791-6. PMID: 11198493 </li></ul><ul><li>Sweeten TL , Posey DJ , McDougle CJ . </li></ul><ul><li>Brief report: autistic disorder in three children with cytomegalovirus infection. </li></ul><ul><li>J Autism Dev Disord. 2004 Oct;34(5):583-6. PMID: 15628611 </li></ul>
  48. 50. <ul><li>Symptoms </li></ul><ul><ul><li>Easy Fatigue </li></ul></ul><ul><ul><li>Visual Issues </li></ul></ul><ul><ul><ul><li>Squinting </li></ul></ul></ul><ul><ul><ul><li>Divergent Gaze </li></ul></ul></ul><ul><ul><ul><li>Poor Eye Contact </li></ul></ul></ul><ul><ul><li>Cold sores </li></ul></ul><ul><ul><li>Warts </li></ul></ul><ul><ul><li>History of Regression after MMR or other live viruses </li></ul></ul><ul><ul><li>Treatment Options </li></ul></ul><ul><ul><li>Antiviral Agents </li></ul></ul><ul><ul><ul><li>Olive Leaf Extract, Elderberry </li></ul></ul></ul><ul><ul><ul><li>Caprylic Acid </li></ul></ul></ul><ul><ul><ul><li>High Dose Vitamin A </li></ul></ul></ul><ul><ul><li>Antiviral Drugs </li></ul></ul><ul><ul><ul><li>Acyclovir </li></ul></ul></ul><ul><ul><ul><li>Valacyclovir </li></ul></ul></ul><ul><ul><ul><li>Famvir </li></ul></ul></ul><ul><ul><ul><li>Imunovir </li></ul></ul></ul><ul><ul><li>Immune Support </li></ul></ul><ul><ul><ul><li>Low Dose Naltrexone </li></ul></ul></ul><ul><ul><ul><li>Red. Glutathione </li></ul></ul></ul><ul><ul><ul><li>Zinc </li></ul></ul></ul><ul><ul><ul><li>Immune Modulators </li></ul></ul></ul>
  49. 51. <ul><li>Mol Pathol. 2002 Apr;55(2):84-90. </li></ul><ul><ul><li>Potential viral pathogenic mechanism for new variant inflammatory bowel disease. </li></ul></ul><ul><ul><li>Uhlmann V , Martin CM , Sheils O , Pilkington L , Silva I , Killalea A , Murch SB , Walker-Smith J , Thomson M , Wakefield AJ , O'Leary JJ . </li></ul></ul><ul><ul><li>A new form of inflammatory bowel disease (ileocolonic lymphonodular hyperplasia) has been described in a cohort of children with developmental disorder. This study investigates the presence of persistent measles virus in the intestinal tissue of these patients (new variant inflammatory bowel disease) and a series of controls by molecular analysis. METHODS: Formalin fixed, paraffin wax embedded and fresh frozen biopsies from the terminal ileum were examined from affected children and histological normal controls. The measles virus Fusion (F) and Haemagglutinin (H) genes were detected by TaqMan reverse transcription polymerase chain reaction (RT-PCR) and the Nucleocapsid (N) gene by RT in situ PCR. Localisation of the mRNA signal was performed using a specific follicular dendritic cell antibody. RESULTS: Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients. Measles virus was identified within the follicular dendritic cells and some lymphocytes in foci of reactive follicular hyperplasia. The copy number of measles virus ranged from one to 300,00 copies/ng total RNA. CONCLUSIONS: The data confirm an association between the presence of measles virus and gut pathology in children with developmental disorder. </li></ul></ul>
  50. 52. <ul><li>Healing the New Childhood Epidemics (Autism, ADHD, Asthma and Allergies, Ken Bock MD </li></ul><ul><li>Autism: Effective Biomedical Treatments , Pangborn and Baker </li></ul><ul><li>Children with Starving Brains , Jaquelyn McCandless MD </li></ul><ul><li>Special Diets for Special Kids , Lisa Lewis </li></ul><ul><li>Evidence of Harm , David Kirby </li></ul><ul><li>Excitotoxins, the Taste that Kills , Russel Blaylock MD </li></ul><ul><li>Websites </li></ul><ul><ul><ul><li> ( </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul>
  51. 53. PHONE: (630) 995-4242 FAX: (630) 995-4243