BIOMEDICAL TREATMENT OF THE YOUNG ADULT WITH AUTISM SPECTRUM DISCORDER

1. BIOMEDICAL TREATMENT OF THE YOUNG ADULT WITH AUTISM SPECTRUM DISCORDER Presented by Michael W. Elice, M.D. and Barbara Fischkin AutismOne, May 2009, Chicago, IL

2. What is ASD? Asperger’s Pervasive Developmental Delay Autism Attention Deficit Disorders

3. DSM IV Diagnostic Criteriafor Autistic Disorder • Impairment in Social Interaction -Impairment in the use of nonverbal behavior -Lack of spontaneous sharing -Lack of social/emotional reciprocity -Failure to develop peer relationships • Impairment in Communication -Delay in or lack of development of spoken language & gestures -Impairment in the ability to initiate or maintain conversation -Repetitive and idiosyncratic use of language -Lack of pretend play • Restricted Repertoire of Activity and Interests -Preoccupation with restricted patterns of interest -Inflexible adherence to routines -Repetitive movements -Preoccupation with parts of objects

4. Increasein Autism Incidence

5. Autism ---- rising incidence • 1/2000 prior to 1970 • 1/500 1996 • 1/166 2005 • 1/150 2007 • And increasing…………….now thought to be 1/80 – 1/100 children!!

6. What is Autism? • A complex array of gene-environment interactions • This demands a rigorous evaluation to search for the unique disease markers that help us understand each child’s individual needs • There is NO usual autism treatment • Only one FDA approved intervention for the agitative, aggressive affects of autism – Risperadone • Beyond this, NOTHING ELSE! • Resources of mainstream medicine are oriented to behavioral therapy, NOT BIOMEDICAL

7. Disorders Associated with ASD • Obsessive Compulsive Disorder • Oppositional Defiant Disorder • Tourette’s Syndrome – Tic Disorder • PANDAS • Bi-Polar Disorder • Metabolic Disorders • Mitochondrial Disorders

8. Find the Source Assess the Underlying Causes • Maldigestion/Malabsorption • Dysbiosis • Infection • Inflammation • Intestinal Permeability (leaky gut) • Immune dysfunction • Food Intolerance/ Allergies • Toxicity

9. Albert Einstein: “If we knew what we were doing, it wouldn’t be called research.”

10. BIOMEDICAL THERAPIES • ELIMINATION DIET • 2. ALLERGY TESTING • 3. ESSENTIAL FATTY ACID/COD LIVER OIL • 4. VITAMINS/MINERALS • 5. DIGESTIVE ENZYMES • 6. METHYL COBALAMIN, FOLINIC ACID, TMG, NAC • 7. AUTOIMMUNE THERAPY • 8. CHELATION • 9. ANTIFUNGALS AND ANTIANEROBICS • 10. INTRAVENOUS GAMMA GLOBULIN • 11. HYPERBARIC OXYGEN

11. Daniel Mulvaney, age 21 years Lived in Mexico City and Hong Kong with parents, Barbara and Jim, journalists • Age 3 years – febrile illness with temp of 106 degrees, otitis media. Hospitalized for dehydration

12. Symptoms: • Loss of interest in other children • Chewing on clothes • Shredding • Loss of expressive language • Loss of interest in toys • Loss of toileting skills • Increase in temper tantrums

13. More Symptoms and Interventions: • PICA – ate glass in playground • Hearing test – positive • Starts BOCES early childhood with ABA, vitamin therapy • Luvox, Risperdal to control ‘violent behavior’ • 2005 – 2 grand mal seizures, EEG inconclusive, MRI - normal

14. Dan meets Dr. Elice, November, 2007Age 20 years • Mouthing – pica, biting • Head pain requiring head compression • Hands move up and down, flapping • Ear flapping • Enjoys being upside down • Prefers to lie down to compress abdomen • Affectionate • Transitions well • Gets very close to people • Clomps feet • Lateral gaze • Occasional crooked smile • Obsesses on rope – uses as a lariat

15. Dan’s Medical History • Product of Barbara’s first pregnancy • Pitocin induced labor – failure to progress • Born in Mexico City • Developmental milestones all on target • Fully immunized without reactions

16. Dan’s Medical History • Diet – craved vegetables, lettuce, sushi and fish • BM’s – loose, frequent, foul smelling, greenish/brown color, 4-5 times/day • Respiratory: frequent coughing • Skin – “chicken skin” red faced • Sleep – terrible!

17. Rosacea Urticaria Gout ADD Arthritis Alcoholism Cardiovascular disease ADM MS Alzheimers Disease Asperger’s Syndrome ADD Thyroiditis Colitis, ulcers Seasonal allergies Colon cancer Breast cancer Family History

18. Lab Investigation

19. Complete Blood Count w/ differential and platelet count, ESR Serum Metabolic Assay (Complete) Thyroid Profile (T3, T4 and TSH), AutoAntibodies Amino Acid Profile, Plasma Methylenetetrahydrofolate Reductase (MTHFR) Organic Acid Profile, Urine Ammonia Level Lactic Acid Level (Lactate) Pyruvic Acid Level (Pyruvate) Folic Acid, Homocysteine, Vit B1, B6, B12, D3 levels Heavy Metal Profile (Lead, Mercury, Arsenic and Cadmium), Blood Antigliadin Antibodies and Transglutaminase (Celiac Panel) Measles, Mumps and Rubella, all vaccine antibody titers Chromosome Analysis (include Fragile X), genomic array analysis IgG, IgA, IgM, IgE levels IGG Subclasses B and T cell function tests Myelin basic protein and neural axon filament antibodies ASLO and Anti Dnase Antibodies

20. NEGATIVE RESULTS Folic acid: elevated MTHFR: + mutation, A and C sites Ammonia: elevated Herpes Simplex I: + antibodies Strep B: + antibodies; ASO and antiDNAse B Serologic immunity to mumps and rubella BUT NOT measles Epstein Barr Virus: + antibodies POSITIVE RESULTS LFT’s: within normal limits B12, B6, B1: within normal limits Amino acids: within normal limits Plasma catecholamines: normal Pyruvate, lactate, insulin, homocysteine: normal Antigliadin Antibodies: negative Dan’s Lab Results

21. Laboratory InvestigationHair analysis for metals 8 years old Elevated: - aluminum - cadmium - lead - mercury - silver - uranium - titanium

22. “Association of MTHFR Gene Variants with Autism” Marvin Boris, M.D., Allan Goldblatt, P.A., Joseph Galanko, PhD., S. Jill James, PhD. J. Of Physicians and Surgeons. 9:4. Winter Edition, 2004

23. MTHFR

24. Methyl Cobalamin (B12) • Alterations in this pathway can induce chronic metabolic imbalances. Data indicates that these alterations occur frequently in ASD children. • Vitamin B12 is an essential cofactor for this pathway. B12 deficiency is well known to have neuropsychiatric consequences in adults and adversely affect neurodevelopment during infancy. Therefore, the abnormal metabolic profile observed in a significant proportion of autistic children suggests the possibility that the behavioral features characteristic of these children could be a manifestation of a genetically based systemic metabolic derangement. • Methyl cobalamin inhibits the toxic effect of mercury on the development of nerve fibers and glial cells. This explains why the administration of injectible methyl cobalamin has resulted in many of these children becoming more aware of the environment, starting to speak and acting like other children

25. MTHFR ASSOCIATED DISEASES • NEURAL TUBE DEFECTS • CARDIOVASCULAR • CEREBRAL VASCULAR • INFLAMMATORY BOWEL DISEASE • CANCER- COLORECTAL, GI • LEUKEMIA • MULTIPLE PSYCHIATRIC DISORDERS

26. Biomedical Interventions • Dan starts on vitamin, mineral, antioxidants, probiotics and essential fatty acids • Methyl cobalamin (B12) injections • Dan is allowed gluten, casein • Dan is told to avoid corn syrup, preservatives, dyes and fast food, where ingredients/preparation is unknown • Prescription medications: • Haldol • Luvox • Tenex • Zonisamide

27. Clinical Observations • Enuresis – decreases • Bowel movements decrease in frequency from 8 to 2 per day • Attention – increases – Dan goes to the movies and sits for 1 hour 45 minutes • Dan plays ice hockey with increased concentration

28. Next: more biomedical • Addition of folinic acid and N-acetyl cysteine to methyl cobalamin injections • PANDAS protocol, per NIMH studies – induction with 5 days of prednisone followed by penicillin, 1 gram daily • Actos (PPAR gamma agonist) • Celebrex (COX-2 enzyme inhibitor) • Diamox (carbonic anhydrase inhibitor)

29. Clinical Observations • Increased concentration • Prompted use of words, says “Hi” without prompt • GI – now 1-2 bowel movements/day, formed and normal appearance • Increased interaction with other adults • Sleep is uninterrupted by urination; he is dry at night • No longer appearing to have headaches • Summer camp – Dan gets “raves” – staff cannot believe how his behavior has changed

30. Who is Dan? After 6 months of biomedical intervention, his primary care pediatrician says “he looks like a different person!”

31. One year later……… • Increased concentration, now on Face Book communicating with 130 “friends” • Health is excellent • GI and GU all functioning normally • Haldol is discontinued without psychotic behavior or sleep disruption • Nemenda (glutamate receptor antagonist) is added due to increase in bizarre motor behavior, e.g. hands in mouth, walking with a list to one side, strange finger movements and inability to perform tasks previously mastered

32. Plan for Dan • Continue the immune support • Heavy metal detoxification (chelation) • Hyperbaric Oxygen Therapy • Intravenous Gamma Globulin (IVIG)

33. WHY CHELATE?

34. Mercury • Epidemic trends in ASD in the 1990’s • Thimerosal – an ethylmercury compound added to vaccines • Increase in the number of vaccines given to infants and toddlers • All these vaccines add up to as much as 200 micrograms in the first 6 months! • In 1999 AAP requires thimerosal to be removed from all pediatric vaccines ASAP • Remaining thimerosal containing vaccines expired by 2003 • Thimerosal still present, in very small amount in DT, Tetanus Toxoid, Menomune and certain Flu vaccines

35. Mercury: What can it do? • Increases oxidative stress • Decreases glutathione production • Increases inflammatory cytokines • Causes cell death • Accumulates in brain, liver, and other organs

36. What about Lead? • Lead is ubiquitous in our environment – 4-5 million tons have been deposited in the environment from car exhaust alone • It can be found in the water, air, soil and dust • Ingestion occurs by hand to mouth transmission • 80% of lead poisoned children can be asymptomatic • Lead has a half life in the body of 20 years! • Lead exposure can result in neurological damage, learning and behavioral problems and lowered intelligence • Fetal exposure to lead affects neurodevelopment

37. Symptoms of Metal Poisoning • Emotional lability, irritability, behavioral changes • Poor focus and attention • Hyperactivity • Loss of developmental milestones, language delay • Learning delays • Criminal, delinquent behavior • Abdominal pain, loss of appetite, vomiting, constipation • Headache, ataxia, • Lethargy, somnolence, seizures, stupor, coma • Muscle weakness • Impaired fine motor coordination • Visual-spatial impairment • Hearing defects, auditory processing problems • Delayed growth

38. Other Toxins: Aluminum - no physiologic need - ability to cross blood brain barrier enhanced by fluoride - found in vaccines - inhibitor of Magnesium, calcium and iron - increases oxidative stress - decreased glutathione - increases lipid peroxidation - synergistic with mercury to increase toxicity exponentially - deposited in brain, bone, muscle, kidney and liver

39. Other Toxins: Organic Pollutants • Phthalates, pesticides, herbicides, PCB’s, Bisphenols • Difficult to detox, stored in fat, cord blood, breast milk • Tiny doses may interfere with hormonal signals that regulate human organs, development and metabolism • NO SAFE LEVELS! • DNA damage • Carcinogenic • Neurotoxic • Damage sperm • Allergies, asthma, diabetes, heart disease, thyroid disease

40. Vicious cycle of toxicity

41. Heavy Metal Detoxification (the politically correct term for Chelation) • Testing for toxic metal exposure • Chelation agents - DMSA - DMPS - EDTA - D-penicillamine • Maintain adequate levels of glutathione • Maintain adequate levels of vitamins and minerals • Continue checking urine for metals until excretion levels are significantly reduced

42. Clinical Response to Chelation of Lead • Improved eye contact • Decreased hyperactivity • Emerging language; words and sentences • Decreased scripted language, echolalia • Improved GI function • Improved skin, hair, nails • Markedly improved learning abilities in school • Increased social skills

43. HYPERBARIC OXYGEN THERAPY

44. Hyperbaric Oxygen Therapy • Dates back to 1662 • Therapeutic uses: - wound healing - GI disease - Infectious diseases - Migraine syndromes - Sleep disorders - Peripheral vascular disease - Stroke - Brain injury - Rheumatoid Arthritis - Chronic fatigue syndrome - Multiple sclerosis - Parkinson’s Disease And……………………………………………………………

45. Hyperbaric Oxygen Therapy • Autism • Autistic Spectrum Disorders

46. Hyperbaric oxygen therapy may improve symptoms in autistic children. Med Hypotheses.  2006; 67(2):216-28 (ISSN: 0306-9877) Rossignol DA; Rossignol LW • neuroinflammation and increased oxidative stress • decreased cerebral perfusion confirmed by SPECT and • PET scans • temporal regions of the brain related to speech, language • and auditory processing • HBOT is successful in known hypoperfusion syndromes • - cerebral palsy • - fetal alcohol syndrome • - closed head injury • - stroke • HBOT can normalize oxygen concentration in ischemic • tissues • HBOT has potent anti-inflammatory effects by reducing • oxidative stress

47. Hyperbaric Oxygen Therapy • Oxygen is our primary source of energy • Oxygen: - promotes immune support - destruction of toxins - promotes new cell growth - displaces harmful free radicals - destroys harmful bacteria, parasites and other microbes - enhances absorption of vitamins, minerals, amino acids, and other nutrients

48. Hyperbaric Oxygen Therapy RESULTS • Statistically significant changes in autistic symptoms, such as: - language - eye contact - interactive play - cognition - improved GI function - improved health and physical behavior

49. Intravenous Gamma Globulin (IVIG) Therapy Improvement in children with autism treated with intravenous gamma globulin Marvin Boris MD;  Allan Goldblatt PA-C; Stephen M. Edelson PhD Journal of Nutritional & Environmental Medicine, Volume 15, Issue 4 December 2005 , pages 169 - 176 Purpose. Immune dysfunction has been associated with children with autism. One study found a beneficial response of intravenous gamma globulin (IVIG) therapy in autistic children. The present study further evaluated the administration of IVIG to these children. Results. The participants' overall aberrant behaviors decreased substantially soon after receiving their first dose of IVIG. Further analysis of the total scores revealed decreases in hyperactivity, inappropriate speech, irritability, lethargy and stereotypy. However, 22 of the 26 children regressed to their pre-IVIG status within 2-4 months of discontinuing the IVIG.

50. IVIG Conclusions. Significant improvement occurred in autistic children receiving monthly IVIG. There is a reasonable rationale considering the risk/reward ratio to utilize IVIG therapy in children with autism. A well-controlled placebo double-blind study would be important to further clarify the use of IVIG in autism and its duration of benefits