1

Integrative Family Medicine Leigh Ann Chapman ND

2013 AUTISM UPDATE NEW DIAGNOSTICS CURRENT RESEARCH

AND EMERGING TREATMENTS

Leigh Ann Chapman ND

1567 SE Tacoma Street Portland OR 97202

ph 5032338113

wwwSellwoodFamilyMedicinecom

ABSTRACT

The CDC has announced that autism is the fastest growing developmental disability in the United States

With this staggering increase in diagnoses all primary care providers must be poised to evaluate and treat children and

adults with autism spectrum disorders This presentation will review the most up to date diagnostic criteria research and

treatments for patients with autism spectrum disorders

CDC reports autism is 1 in 88

bull 1 in 88 translates to 1 in 54 boys and 1 in 252 girls

bull 23 increase compared to 2006 (1 in 110)

bull 78 increase compared to 2002 (1 in 150)

bull 2008 surveillance year covered a total population of 337093 children aged 8 years

bull What about state by state statistics

bull MMWR Surveill Summ 2012 Mar 3061(3)1-19

South Korea- 1 in 38

bull Prevalence of autism spectrum disorders in a total population sample Kim YS Leventhal BL Koh

YJ Fombonne E Laska E Lim EC Cheon KA Kim SJ Kim YK Lee H Song

DH Grinker RR Am J Psychiatry 2011 Sep168(9)904-12

bull Population screening and direct assessment

bull 264 of children in a South Korean community in 2006 have and ASD

bull What does this mean

Risk Factors and Characteristics- endorsed by the CDC

bull Identical twins if one child has an ASD then the other will be affected about 36-95 of the time

bull Parents who have a child with an ASD have a 2ndash18 chance of having a second child who is also affected

bull ASDs tend to occur more often in people who have certain genetic or chromosomal conditions About 10 of children with autism are also identified as having Down syndrome fragile X syndrome tuberous sclerosis and other genetic and chromosomal disorders

bull The majority (62) of children with ASDs did not have intellectual disability

bull Children born to older parents are at a higher risk for ASDs bull A small percentage of children who are born prematurely or with

low birth weight are at greater risk for having ASDs bull ASD commonly co-occurs with other developmental psychiatric

neurologic chromosomal and genetic diagnoses

Autism Diagnostic criteria

bull New and improved as of May 2013

bull The DSM-5 manual is the only location for diagnostic criteria for Autism

bull This is a psychiatric manual and does not account for the evolution of biological whole systems medicine

2

DSM 5 - Change 1

bull Elimination of subcategories of

ndash Asperger syndrome

ndash PDD-NOS

ndash childhood disintegrative disorder

ndash autistic disorder

All of these subcategories are folded into the broad term autism spectrum disorder (ASD)

DSM-5 change 2

DSM-4- three domains of impairment social impairment

languagecommunication impairment

repetitiverestricted behaviors

DSM-5- Two categories social communication impairment

restricted interestsrepetitive behaviors

New symptom will be included hyper- or hypo-reactivity to sensory input or unusual

interests in sensory aspects of the environment

Sensory Processing

ldquoIt is obvioushellipthat sensory processing abnormalities in ASD are distributed rather than localized sensory abnormalities in ASD obviously span multiple dimensions of latency adaptation magnitude and behavior abnormalities with both enhanced and impaired behavior associated with aberrant cortical responses Given this diversity in findings the heterogeneity of ASD and broad variability seen over and over again in the ASD groups almost irrespective of the study it is hard to imagine that one single theory could account for all of these observationshellip It is therefore probable that several mechanisms and neuronal abnormalities most likely at multiple levels (from single neurons through to inter-area connections) all contribute to varying degrees to the abnormal sensory processing observed in ASD It is also likely that no single mechanism is unique to one sensory modality which is why we see such a widely distributed range of abnormalities across modalitiesrdquo Kenet T 2011 Sensory functions in ASD In The Neuropsychology of Autism edited by D Fein New York Oxford University Press

DSM 5 change 3

bull Each person evaluated will also be described in terms of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems

Currently or by history must meet criteria A B C and D

A Persistent deficits in social communication and social interaction

across contexts not accounted for by general developmental delays and

manifest by all 3 of the following

1 Deficits in social-emotional reciprocity

2 Deficits in nonverbal communicative behaviors used for social

interaction

3 Deficits in developing and maintaining relationships

B Restricted repetitive patterns of behavior interests or activities as

manifested by at least two of the following

1 Stereotyped or repetitive speech motor movements or use of objects

2 Excessive adherence to routines ritualized patterns of verbal or

nonverbal behavior or excessive resistance to change

3 Highly restricted fixated interests that are abnormal in intensity or

focus

4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory

aspects of environment

CSymptoms must be present in early childhood (but may not become

fully manifest until social demands exceed limited capacities)

DSymptoms together limit and impair everyday functioning

DSM-5 Change 4

bull Fourth the work group added a new category called Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior

3

Naturopathic medicine and the autism community

bull Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders

bull Be mindful of person centered language

ndash Advocate and support vs defeat and recover

Does this child have a problem

Tools to identify a struggle need for a referral

Parent Reported- Ages and Stages Questionaire

ndash ASQ- wwwasqoregoncom

ndash Developmental Milestones checklist (Bright Futures)

Practitioner delivered assessment

ndash MCHAT- Modified checklist for autism in toddlers

ndash 18 and 24 months wwwM-chatorg

MCHAT wwwM-CHATorg

bull 2 Does your child take an interest in other children Yes No

bull 5 Does your child ever pretend for example to talk on the phone or take

bull care of dolls or pretend other things Y N

bull 7 Does your child ever use hisher index finger to point to indicate interest in something Yes No

bull 9 Does your child ever bring objects over to you (parent) to show you

bull something Yes No

bull 14 Does your child respond to hisher name when you call Yes No

bull 15 If you point at a toy across the room does your child look at it Yes No

bull 20 Have you ever wondered if your child is deaf Yes No

RITVO (RAADS-R)- Scale for adults

bull Diagnostic scale for adults

bull 64 or less indicates that it is highly unlikely that a patient has autism

bull A score of 77 or higher indicates a high probablility of ASD

bull Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089

This patient needs a referral

bull Who should you refer to bull Psychologist bull Educational Assessment Early Intervention bull Behavioral Pediatrician bull Neurologist- if you suspect seizure activity order

a sleep deprived EEG and refer

3

Naturopathic medicine and the autism community

bull Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders

bull Be mindful of person centered language

ndash Advocate and support vs defeat and recover

Does this child have a problem

Tools to identify a struggle need for a referral

Parent Reported- Ages and Stages Questionaire

ndash ASQ- wwwasqoregoncom

ndash Developmental Milestones checklist (Bright Futures)

Practitioner delivered assessment

ndash MCHAT- Modified checklist for autism in toddlers

ndash 18 and 24 months wwwM-chatorg

MCHAT wwwM-CHATorg

bull 2 Does your child take an interest in other children Yes No

bull 5 Does your child ever pretend for example to talk on the phone or take

bull care of dolls or pretend other things Y N

bull 7 Does your child ever use hisher index finger to point to indicate interest in something Yes No

bull 9 Does your child ever bring objects over to you (parent) to show you

bull something Yes No

bull 14 Does your child respond to hisher name when you call Yes No

bull 15 If you point at a toy across the room does your child look at it Yes No

bull 20 Have you ever wondered if your child is deaf Yes No

RITVO (RAADS-R)- Scale for adults

bull Diagnostic scale for adults

bull 64 or less indicates that it is highly unlikely that a patient has autism

bull A score of 77 or higher indicates a high probablility of ASD

bull Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089

This patient needs a referral

bull Who should you refer to bull Psychologist bull Educational Assessment Early Intervention bull Behavioral Pediatrician bull Neurologist- if you suspect seizure activity order

a sleep deprived EEG and refer

4

The Culture of Autism

bull With the rising population of ASDs- it is critical that we begin ndash Supporting listening and advocating

ndash Including individuals with ASD into our society

ndash Accepting differences

ndash Moving beyond the imposition of our cultural norms onto the culture of autism

ndash Karlarsquos ASD Blog on Facebook

ndash ASAN- httpautisticadvocacyorg

Rethinking Autism

Brain-based or Systemic

Correlation does not imply mechanism- how but not why

bull wwwautismwhyandhoworg

bull Genes ndash Inherited and acquired mutations ndash Gene expression

bull Environment ndash Too much bad not enough good ndash Different levels of environment Physical biological social emotional

bull Physiology ndash Molecules ndash different molecules different molecular interactions ndash Biochemistry and metabolism ndash some pathways working harder other pathways stuck ndash Organ systems ndash gastrointestinal immune endocrinehormone

bull Brain ndash Brain modules under- or over-active ndash Brain networks and connections differently mapped or differently active ndash Brain cells and tissue affected by physiological problems like inflammation and oxidative stress ndash Too much or not enough of brain chemicals like neurotransmitters or neuropeptides ndash Electrophysiology

bull Total load allostatic load cumulative stress ndash Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental supports

all shift the functioning of the system

bull Global crisis

Research Advances in 2013

bull Deeper Understanding of Link between Chemical Pollutants and Autism

bull Hundreds of Tiny Mutations Linked to Autism

bull Insights into Immune Changes amp Autism

Autism and our planet

Autism may be a development reflecting environmental change

bull Environmental pollutants continue to be implicated neurodevelopmental issues

bull Beyond physical toxicants- EMF

bull Disconnect from Nature and GAIA

EPA Builds List of Potentially Dangerous Chemicals

bull As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders

bull httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf

5

List of Implicated Toxicants bull 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in cosmetics bull Acibenzolar-S methyl -- a fungicide bull Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is also

manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke

bull Aldicarb ndash a pesticide bull Allethrin ndash a pesticide bull Aluminum (lactate) -- used in lotions to treat very dry skin bull Aminopterin ndash chemical originally developed for use in cancer treatment bull Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from agricultural

and industrial practices bull Aspartame ndash an artificial sweetener bull Benomyl ndash a fungicide bull Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also formed

from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke

bull Bioallethrin (s-bioallethrin) ndash a pesticide bull Bis(tri-n-butyltin)oxide ndash a biocide bull Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles and

food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans bull Butylated Hydroxy Anisole ndash a food additive better known as BHA

bull Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products

bull Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air

bull Carbaryl -- insecticide

bull Carbon monoxide -- an odorless and colorless toxic gas

bull Chlordecone ndash an insecticide

bull Chlorine dioxide ndash a chemical mostly used to disinfect water

bull Chlorpyrifos -- insecticide

bull Cypermethrin --insecticide

bull DEET ndash a common ingredient in insect repellents

bull Deltamethrin -- insecticide

bull Diazinon ndash a pesticide

bull Dieldrin ndash an insecticide no longer produced in the US but still found in the environment

bull Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes

bull Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides

bull Fluazinam ndash a fungicide

bull Heptachlor ndash a non-agricultural insecticide whose use is now very limited

bull Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States

bull Hexachlorophene ndash a disinfectant

bull Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air

bull Lindane ndash a chemical used to treat scabies and lice bull Maneb ndash a fungicide bull Methanol ndash also known as wood alcohol an alternative fuel and other uses bull Methylparathion ndash a pesticide bull Monosodium Glutamate ndash a flavor enhancer used as a food additive bull Nicotine ndash the addictive drug in tobacco bull Methoxyethanol 2 ndash an organic compound used mainly as a solvent bull Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air

when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated bull Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level bull Paraquat ndash an herbicide bull Parathion (ethyl) ndash an insecticide bull PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes

Some types of PBDEs have been banned or phased out but industry has developed others to replace them bull PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in

electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment

bull Permethrin ndash an insecticide bull Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic products bull Tebuconazole ndash a fungicide bull Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream

lubricating oils paint thinners bull Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and

biocides in marine antifouling paints and in wood preservatives bull Trichlorfon ndash an insecticide bull Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a

water contaminant

In Utero Exposures and Autism

bull The only in prenatal exposure well documented in autism is Valproic acid ndash Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to

antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4

bull All contaminants are not equal

ndash Organohalogens higher in mom than baby ndash PCBs higher in baby than mom ndash Mercury is high uniform in all matrices

bull Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger

Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010

bull National Childrenrsquos Study wwwnationalchildrensstudygov

PDBEs Halt Flames and Neurodevelopment

Cord Blood PDBE levels have neurodevelopmental consequences

bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack

Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719

Indoor environment counts

bull Increased risk of developing an ASD if living in a house with PVC flooring ndash Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations

between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31

bull Increased risk of ASD if living near a freeway ndash Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal exposure

to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41

ndash Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17

6

Autism and Heavy Metals

Children with ASD have high amounts metals bull Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia

S Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640

bull Children with ASD have Normal amounts of metals

bull Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31

Why heavy metals in Autism

Direct Exposure- lead mercury aluminum or

arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead

to sluggish biotransforamationdetoxification and metabolic storage

ndash Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large

Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001

ndash Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94

The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm bull CDC 2001 Except for influenza thimerosal is removed from or

reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market

bull Main Preservative 2-phenoxyethanol bull Aluminum used as an adjuvant

bull Bishop N J Morley R Day J P Lucas A (1997) Aluminum

neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61

bull Aluminum exposure in the first six months of life bull 4mg from vaccines bull 10mg from breast milk bull 40mg from dairy infant formula bull 125 mg from soy based infant formula bull wwwvaccinechopedu

Too much too soon

bull Destefano F Price CS Weintraub ES Increasing Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29

bull 256 ASD and 752 controls bull summation analysis of the content of Antibody-Stimulating

Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received

bull Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD

Disconnect From Gaia

Environment and Genetics

Environmental toxicants interfere with faulty epigenetics and the end result is oxidative stress

and neuroinflammation

bull Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10

bull Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How

environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201

bull Herbert MR Russo JP Yang S et al Autism and environmental genomics

Neurotoxicology 2006 27(5)671-84

7

Genetics and ASD

Age of father will contribute to the frequency of de novo genetic mutations

bull Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5

bull Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41

bull So what mutations are we looking at

Enzyme SNPrsquos Studied In Autism

bull MTHFR - Methylenetetrahydrofolate reductase ndash Defective folate metabolism

ndash Elevated homocysteine levels

ndash Defective ability to methylate DNA

ndash Global loss of methyl groups ndash James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal

Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008

bull COMT-Catechol-O-methyltransferase ndash Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association

of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD

and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash

1551

ndash OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-

methyltransferase activity in erythrocytes of children with autism Clinical and

Experimental Pharmacology and Physiology 3 9ndash14

Enzyme SNPrsquos Studied In Autism

bull CBS - Cystathionine Beta- Synthase ndash Joins the methyl and sulfur pathways

ndash This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione

ndash No research ndash only presumptive at this point

bull Glutathione-S-transferase ndash Conjugate glutathione with toxins for Phase 2

biotransformation and elimination bull Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert

GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr

What should we do about it

bull Education and Awareness

bull Limit Exposure

bull Everyday detox

ndash Dietary intervention

ndash Methylation support GSH

bull Investigate toxic levels more thoroughly

bull Treat more aggressively when toxicants are suspected and confirmed

Autism ldquoPhenomerdquo Project

bull Medical evaluations An initial exam is conducted by a pediatrician with expertise in developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits

bull Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins

bull Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules

bull Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder

bull Brain structure MRI EEG data

bull Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses

bull UC Davis MIND Institute- 1800 kids- WOW

8

wwwBioInitiativeorg

Findings in Autism (ASD) Consistent with Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)

Martha Herbert MD PhD

Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital

Harvard Medical School Cindy Sage MA

For the BioInitiatve Working Group December 2012

EMF and RFR in Autism

Electromagnetic Frequency and Radio Frequency Radiation

Exposures have outpaced precautions

ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo

- Sage C and D O Carpenter 2009 Public health implications of wireless technologies

Pathophysiology 16 (2-3)233-46

EMF and RFR in Autism

Neuropathology of ASD demonstrates striking parallels in the physiological impacts of

electromagnetic frequency and radiofrequency exposures (EMFRFR)

bull molecular cellular and tissue damage

bull cellular stress (oxidative stress the heat shock response and protein misfolding)

bull injury of membranes

bull aberrant calcium signaling

bull compromise of junctions and barriers

What to do about it

bull Children with existing neurological problems that include cognitive learning

attention memory or behavioral problems should as much as possible be

provided with wired (not wireless) learning living and sleeping environments

bull Special education classrooms should aim for no wireless conditions to reduce

avoidable stressors that may impede social academic and behavioral progress

bull All children should reasonably be protected from the physiological stressor of

significantly elevated EMFRFR (wireless in classrooms or home environments)

bull School districts that are now considering all-wireless learning environments

should be strongly cautioned that wired environments are likely to provide better

learning and teaching environments and prevent possible adverse health

consequences for both students and faculty in the long-term

bull Monitoring of the impacts of wireless technology in learning and care

environments should be performed with sophisticated measurement and data

analysis techniques that are cognizant of the non-linear impacts of EMFRFR and

of data techniques most appropriate for discerning these impacts

Immune Abnormalities

bull Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)

bull Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 ndash little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy

were associated with ASDinfantile autism

ndash maternal influenza infection was associated with a twofold increased risk of infantile autism

ndash prolonged episodes of fever caused a threefold increased risk of infantile autism

ndash and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism

bull ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo ndash Moises Velasquez-Manoff

Emerging treatments for ASD

bull Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what

bull Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine

9

Folate Autoantibodies in ASD

bull Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol

Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi

101038mp2011175 Epub 2012 Jan 10

bull Testing contact Department of Biochemistry BSB 7-15

bull SUNY Downstate Med Center

bull 450 Clarkson Avenue

bull Brooklyn NY 11203 USA

bull Ph 718 270-4203

bull Fax 718 270-3316

bull E Mail Edwardquadrosdownstateedu

When to suspect CFD

bull Low-functioning autism bull Mitochondrial disease or dysfunction bull Rett syndrome bull Epilepsy or seizures bull Abnormal electroencephalogram subclinical bull electrical discharges or slowing bull Ataxia bull Microcephaly bull Dyskinesia choreoathetosis ballismus bull Irritability bull Insomnia bull Frontotemporal atrophy

Folate Supplementation

bull Start folinic acid at dose of 05 mgkgday in two divided doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses

bull Discontinue drugs that can interfere with folate metabolism

bull Consider cobalamin supplementation (vitamin B12)

bull Stop folic acid supplementation bull Start a cowrsquos milk-free diet bull Monitor for changes in cognition and behavior bull Monitor adverse effects

Arbaclofen

bull Seasides drug STX209 or arbaclofen works to control an overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain

ndash First studied with Fragile X

bull Arbaclofen = GABA agonist

bull GABA 250-3000 mg day

Oxytocin bull Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of the

oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783

bull Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16

ndash Found differences after six weeks of treatment- quality of life and social cognition

bull Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618

Oxytocin

bull Available as a daily nasal spray or sublingual drop

bull No taste no smell no burn

bull Dose is 10 to 40 units per day

bull Compounded

bull No documented or observed negative side effects

10

Decreased Tryptophan metabolism

bull Boccuto L Chen CF Pittman AR Skinner CD McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16

bull Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function

bull Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs

Melatonin

bull Malow B Adkins KW McGrew SG et al Melatonin for sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37

bull Dose of 1-3 mg qhs significantly improved sleep in children with ASDs

bull No negative side effects were observed

NAC- now in phase 2 trial

bull Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61

bull N-Acetyl Cysteine

bull Improvements in irritability hyperactivity and stereotypy

bull Dose 900 mg TID

Qi Gong Massage

bull Qigong Sensory Training (QST)

bull wwwqstiorg

bull Parent delivered

bull May see improvements in sensory symptoms sleep and bowels

Remember the foundation

bull Clean up the diet and ADD Nutrition

bull Heal the gut mind the brain ensure sleep

bull Address allergies immune issues and sensitivities

bull Methyl B12 injections q 3d (or other methylation support)

bull Get outside Commune with animals and nature

11

QUESTIONS Mind in the Eyes Test

bull httpwwwquestionwritertrackercomquiz61Z4MK3TKBhtml

bull It is not as easy as you think Do you think this is an accurate reflection of social competancy

8

wwwBioInitiativeorg

Findings in Autism (ASD) Consistent with Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)

Martha Herbert MD PhD

Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital

Harvard Medical School Cindy Sage MA

For the BioInitiatve Working Group December 2012

EMF and RFR in Autism

Electromagnetic Frequency and Radio Frequency Radiation

Exposures have outpaced precautions

ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo

- Sage C and D O Carpenter 2009 Public health implications of wireless technologies

Pathophysiology 16 (2-3)233-46

EMF and RFR in Autism

Neuropathology of ASD demonstrates striking parallels in the physiological impacts of

electromagnetic frequency and radiofrequency exposures (EMFRFR)

bull molecular cellular and tissue damage

bull cellular stress (oxidative stress the heat shock response and protein misfolding)

bull injury of membranes

bull aberrant calcium signaling

bull compromise of junctions and barriers

What to do about it

bull Children with existing neurological problems that include cognitive learning

attention memory or behavioral problems should as much as possible be

provided with wired (not wireless) learning living and sleeping environments

bull Special education classrooms should aim for no wireless conditions to reduce

avoidable stressors that may impede social academic and behavioral progress

bull All children should reasonably be protected from the physiological stressor of

significantly elevated EMFRFR (wireless in classrooms or home environments)

bull School districts that are now considering all-wireless learning environments

should be strongly cautioned that wired environments are likely to provide better

learning and teaching environments and prevent possible adverse health

consequences for both students and faculty in the long-term

bull Monitoring of the impacts of wireless technology in learning and care

environments should be performed with sophisticated measurement and data

analysis techniques that are cognizant of the non-linear impacts of EMFRFR and

of data techniques most appropriate for discerning these impacts

Immune Abnormalities

bull Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)

bull Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 ndash little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy

were associated with ASDinfantile autism

ndash maternal influenza infection was associated with a twofold increased risk of infantile autism

ndash prolonged episodes of fever caused a threefold increased risk of infantile autism

ndash and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism

bull ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo ndash Moises Velasquez-Manoff

Emerging treatments for ASD

bull Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what

bull Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine

9

Folate Autoantibodies in ASD

bull Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol

Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi

101038mp2011175 Epub 2012 Jan 10

bull Testing contact Department of Biochemistry BSB 7-15

bull SUNY Downstate Med Center

bull 450 Clarkson Avenue

bull Brooklyn NY 11203 USA

bull Ph 718 270-4203

bull Fax 718 270-3316

bull E Mail Edwardquadrosdownstateedu

When to suspect CFD

bull Low-functioning autism bull Mitochondrial disease or dysfunction bull Rett syndrome bull Epilepsy or seizures bull Abnormal electroencephalogram subclinical bull electrical discharges or slowing bull Ataxia bull Microcephaly bull Dyskinesia choreoathetosis ballismus bull Irritability bull Insomnia bull Frontotemporal atrophy

Folate Supplementation

bull Start folinic acid at dose of 05 mgkgday in two divided doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses

bull Discontinue drugs that can interfere with folate metabolism

bull Consider cobalamin supplementation (vitamin B12)

bull Stop folic acid supplementation bull Start a cowrsquos milk-free diet bull Monitor for changes in cognition and behavior bull Monitor adverse effects

Arbaclofen

bull Seasides drug STX209 or arbaclofen works to control an overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain

ndash First studied with Fragile X

bull Arbaclofen = GABA agonist

bull GABA 250-3000 mg day

Oxytocin bull Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of the

oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783

bull Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16

ndash Found differences after six weeks of treatment- quality of life and social cognition

bull Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618

Oxytocin

bull Available as a daily nasal spray or sublingual drop

bull No taste no smell no burn

bull Dose is 10 to 40 units per day

bull Compounded

bull No documented or observed negative side effects

10

Decreased Tryptophan metabolism

bull Boccuto L Chen CF Pittman AR Skinner CD McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16

bull Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function

bull Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs

Melatonin

bull Malow B Adkins KW McGrew SG et al Melatonin for sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37

bull Dose of 1-3 mg qhs significantly improved sleep in children with ASDs

bull No negative side effects were observed

NAC- now in phase 2 trial

bull Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61

bull N-Acetyl Cysteine

bull Improvements in irritability hyperactivity and stereotypy

bull Dose 900 mg TID

Qi Gong Massage

bull Qigong Sensory Training (QST)

bull wwwqstiorg

bull Parent delivered

bull May see improvements in sensory symptoms sleep and bowels

Remember the foundation

bull Clean up the diet and ADD Nutrition

bull Heal the gut mind the brain ensure sleep

bull Address allergies immune issues and sensitivities

bull Methyl B12 injections q 3d (or other methylation support)

bull Get outside Commune with animals and nature

11

QUESTIONS Mind in the Eyes Test

bull httpwwwquestionwritertrackercomquiz61Z4MK3TKBhtml

bull It is not as easy as you think Do you think this is an accurate reflection of social competancy

9

Folate Autoantibodies in ASD

bull Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol

Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi

101038mp2011175 Epub 2012 Jan 10

bull Testing contact Department of Biochemistry BSB 7-15

bull SUNY Downstate Med Center

bull 450 Clarkson Avenue

bull Brooklyn NY 11203 USA

bull Ph 718 270-4203

bull Fax 718 270-3316

bull E Mail Edwardquadrosdownstateedu

When to suspect CFD

bull Low-functioning autism bull Mitochondrial disease or dysfunction bull Rett syndrome bull Epilepsy or seizures bull Abnormal electroencephalogram subclinical bull electrical discharges or slowing bull Ataxia bull Microcephaly bull Dyskinesia choreoathetosis ballismus bull Irritability bull Insomnia bull Frontotemporal atrophy

Folate Supplementation

bull Start folinic acid at dose of 05 mgkgday in two divided doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses

bull Discontinue drugs that can interfere with folate metabolism

bull Consider cobalamin supplementation (vitamin B12)

bull Stop folic acid supplementation bull Start a cowrsquos milk-free diet bull Monitor for changes in cognition and behavior bull Monitor adverse effects

Arbaclofen

bull Seasides drug STX209 or arbaclofen works to control an overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain

ndash First studied with Fragile X

bull Arbaclofen = GABA agonist

bull GABA 250-3000 mg day

Oxytocin bull Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of the

oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783

bull Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16

ndash Found differences after six weeks of treatment- quality of life and social cognition

bull Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618

Oxytocin

bull Available as a daily nasal spray or sublingual drop

bull No taste no smell no burn

bull Dose is 10 to 40 units per day

bull Compounded

bull No documented or observed negative side effects

10

Decreased Tryptophan metabolism

bull Boccuto L Chen CF Pittman AR Skinner CD McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16

bull Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function

bull Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs

Melatonin

bull Malow B Adkins KW McGrew SG et al Melatonin for sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37

bull Dose of 1-3 mg qhs significantly improved sleep in children with ASDs

bull No negative side effects were observed

NAC- now in phase 2 trial

bull Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61

bull N-Acetyl Cysteine

bull Improvements in irritability hyperactivity and stereotypy

bull Dose 900 mg TID

Qi Gong Massage

bull Qigong Sensory Training (QST)

bull wwwqstiorg

bull Parent delivered

bull May see improvements in sensory symptoms sleep and bowels

Remember the foundation

bull Clean up the diet and ADD Nutrition

bull Heal the gut mind the brain ensure sleep

bull Address allergies immune issues and sensitivities

bull Methyl B12 injections q 3d (or other methylation support)

bull Get outside Commune with animals and nature

11

QUESTIONS Mind in the Eyes Test

bull httpwwwquestionwritertrackercomquiz61Z4MK3TKBhtml

bull It is not as easy as you think Do you think this is an accurate reflection of social competancy

10

Decreased Tryptophan metabolism

bull Boccuto L Chen CF Pittman AR Skinner CD McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16

bull Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function

bull Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs

Melatonin

bull Malow B Adkins KW McGrew SG et al Melatonin for sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37

bull Dose of 1-3 mg qhs significantly improved sleep in children with ASDs

bull No negative side effects were observed

NAC- now in phase 2 trial

bull Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61

bull N-Acetyl Cysteine

bull Improvements in irritability hyperactivity and stereotypy

bull Dose 900 mg TID

Qi Gong Massage

bull Qigong Sensory Training (QST)

bull wwwqstiorg

bull Parent delivered

bull May see improvements in sensory symptoms sleep and bowels

Remember the foundation

bull Clean up the diet and ADD Nutrition

bull Heal the gut mind the brain ensure sleep

bull Address allergies immune issues and sensitivities

bull Methyl B12 injections q 3d (or other methylation support)

bull Get outside Commune with animals and nature

11

QUESTIONS Mind in the Eyes Test

bull httpwwwquestionwritertrackercomquiz61Z4MK3TKBhtml

bull It is not as easy as you think Do you think this is an accurate reflection of social competancy

11

QUESTIONS Mind in the Eyes Test

bull httpwwwquestionwritertrackercomquiz61Z4MK3TKBhtml

bull It is not as easy as you think Do you think this is an accurate reflection of social competancy