Exploring the Biomedical Issues of Autism

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Exploring the Biomedical Issues of Autism

• National Autism Association conference
• Myrtle Beach, Nov 2005
• Bryan Jepson MD
• Thoughtful House Center for Children

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Bio

• Graduated from University of Utah medical school
  in 1995
• Completed residency in emergency medicine in
  Michigan in 1998
• Began career as ER physician in Colorado Springs
  in 1998
• Board certified in emergency medicine 1999

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Why I became involved

• I was told my son would be institutionalized
• There seemed to be a lack of knowledge about
  autism among the general medical community
• What I was reading and seeing was
  disproving/contradicting historical view of
  autism

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The History of Autism
                          
                          
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What is autism?

• All my life, I have been working with children
  whose lives were destroyed because their mothers
  hated them. Bruno Battleheim 1981

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What is autism?

• A developmental disorder with impairments in
  language and social interaction and associated
  with repetitive, stereotyped behaviors.

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What is autism?

• Autism is a genetic illness
• The events leading to the disease happen very
  early in fetal development

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But what about.?
?

• Why is the incidence increasing?
• Why do this kids have chronic bowel problems?
• Why do they have problems with ear infections,
  frequent viral infections and eczema?
• Why do they have nutritional deficiencies?
• Why do most autistic kids develop normally and
  then regress or plateau?

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Where is the research?

• Autism was first described in the early 1940s.
  It was unheard of and unreported before then.
• Until recently it was considered a rare disease.
• The government has spent relatively very little
  money on researching its cause or treatment.
• Even now, the research money is still very small
  compared to less common disorders.
• Most of the research money goes to genetics.

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Research dollars per patient
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Where is the research?

• Only recently has the medical community started
  paying attention to autism.
• It is still too little and too late.

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YOU CAN MAKE A DIFFERENCE!!!!

• Every significant advance that has
• happened for autism is the result of the
• efforts of parents.

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What is autism?
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What are the questions?What we knowWhat we think
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Is autism an epidemic?
?
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California statisticsfrom the department of
developmental services report to the legislature,
2002
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California Statistics-recent
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US statistics
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Is autism an epidemic?

• Broader diagnostic criteria?
• Previous disease misclassification?
• Improved awareness/likelihood of diagnosis by
  physicians and parents?
• More parents seeking services?

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Has the diagnostic criteria changed?

• DSM3 vs DSM4
• They have included several diseases in the
  autistic spectrum including Aspergers, Retts,
  CDD, PDD-NOS
• What would the graph look like if this were the
  reason?

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Younger age group
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MIND Institute study

• Study aim number one
• To investigate whether changes over time in the
  criteria used to diagnose CDER status 1 autism
  account for a significant proportion of the
  increased number of cases in autism
• Conclusion
• The observed increase in autism cannot be
  explained by a loosening in the criteria to make
  the diagnosis.
• Reference 1

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MIND Institute study

• Study Aim 2
• To investigate whether the misclassification of
  some cases of autism as mental retardation in the
  past has contributed to an apparent increase in
  the number of children with autism
• Conclusion
• Some children reported by the Regional Centers
  with mental retardation and not autism did meet
  criteria for autism, but this misclassification
  does not appear to have changed over time.

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Have patients been misclassified (diagnostic
substitution)?

• Croehn suggests that the numbers of autism have
  increased in California at the same rate as a
  decrease in mental retardation thereby explaining
  the epidemic.
• Blaxill et all showed that the data was
  incorrectly interpreted and that in fact there is
  no evidence of diagnostic substitution
• References 2, 3

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Are physicians better at diagnosing autism?

• Diagnosis is based off of behavioral
  characteristics
• Can be made with a history and physical exam
• Does not require improved technology
• There are no diagnostic lab tests or CT scan
  findings
• Most cases still being referred through the
  education system rather than by physicians
• Most physicians still inadequately educated about
  autism, although awareness is improving.
• Age of diagnosis may change through improved
  awareness but not the number of cases per birth
  year.

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Have we been missing cases?

• If incidence has not increased, then rate of
  adults with full-blown autism is 1 in 250 or
  higher.
• At todays rates, there would be over 850,000
  adults (over age of 20) with full-blown autism
  currently living and 1.28 million on autism
  spectrum.
• Where are all of these autistic adults?
• Studies of this issue have failed to find a
  hidden horde of misdiagnosed autistic adults.

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More parents seeking services?

• Autism represents a significant financial and
  emotional drain on all of those involved.
• There is no reason to expect that parents were
  less likely to look for help 10 years ago than
  today
• Unlikely to assume that more than 3000 children a
  year in California alone did not seek any
  services for level one autism in previous years

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What we know

• Autism is an epidemic!!!
• Why does it matter?
• THERE IS NO SUCH THING AS A GENETIC EPIDEMIC.
  AUTISM MUST HAVE AN ENVIRONMENTAL COMPONENT!!!!
• This should guide research
• Gives hope for prevention, treatment and cure!

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Autism A new paradigm
bullet
gun
damage
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Autism A new paradigm
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What we know

• Autistic children are predisposed to
  environmental toxicity because of underlying
  metabolic abnormalities

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The methylation cycle

• Children with autism have blocks in their
  methylation cycle resulting in low glutathione
  levels
• The blocks can be reversed with TMG, folinic acid
  and methyl B12 supplementation
• Reference 4

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Can low glutathione create problems with
environmental toxicity?
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The importance of Glutathione

• The major intracellular antioxidant
• Prevents oxidation of cysteine residues in
  protein
• Maintains mitochondrial integrity and ATP
  production
• Maintains integrity of gut epithelium
• Maintains normal T cell subsets and immune
  function
• Stimulates SAM synthesis
• Detoxifies heavy metals and other chemicals
• Maintains Vit C and Vit E in active form

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What we think

• Many of the symptoms of autism may be related to
  problems caused by environmental toxins.
• Trying to correct the underlying metabolic
  abnormalities and using methods to remove
  environmental toxins can help autistic children
  get better.

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• What are the environmental toxins that are
  implicated in autism?
• Is autism caused by a single environmental insult
  or an accumulation of multiple insults?

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The case against mercury
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What we know about mercury

• Highly neurotoxic
• Dangerous to developing brains
• Impacts on cognitive thinking, memory, attention,
  language, and fine motor and visual spatial
  skills
• Concentrations are rising in environment
• Sources
• Coal burning power plants
• Fish consumption
• Dental amalgams
• Medical products

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Mercury cycle
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EPA concerns (cont)

• the developing nervous system of the fetus may
  be more vulnerable to methylmercury than is the
  adult nervous system. The mothers may be
  asymptomatic.
• 630,000 of the roughly 4 million babies born
  annually in the United States twice as many as
  previously thought may be exposed to dangerous
  levels of mercury in the womb
• Given the new finding that umbilical cord blood
  has higher concentrations of mercury, the EPA
  believes that the safe level for mercury in
  mothers' blood is 3.5 parts per billion. About
  15 of women of childbearing age had blood levels
  that high, according to the CDC study.

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Autism and mercury

• Symptoms of mercury poisoning mimic those of
  autism
• Reference 5

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What are other sources of mercury exposure?

• 1998 FDA thimerosal discovery
• Children receiving potentially toxic doses of
  mercury through vaccines containing thimerosal.
• On a single day, children could receive over 100
  times safe standard of organic mercury based off
  of oral ingestion guidelines.

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Removing thimerosal

• FDA recommended a phase-out
• No recall was done
• Still thimerosal on shelves with expirations in
  2002
• Still contained in certain vaccinesRhogam,
  influenza
• Still being shipped to developing countries

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What is thimerosal?

• 50 ethyl mercury
• Used as a preservative
• Known to be toxic by manufacturers in the 30s.
  Vaccine makers aware of rising levels in the
  80s.
• Removed from animal vaccines in early 1990s.

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Thimerosal research--questions

• Is thimerosal dangerous?
• Ethyl vs methyl mercury
• What are the toxic dose guidelines?
• What is the half-life?

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Epidemiological studies--Con

• There is no evidence linking thimerosal with
  autism
• References 7, 8, 9

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Safeminds Rebuttals

• Each of the studies that defend thimerosal have
  significant design flaws and inherent biases that
  invalidate results
• References 9, 10, 11

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Epidemiology studies--Pro

• Thimerosal in vaccines is related to the rise in
  autism
• References 12, 13, 14

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Evidence of Harm

• www.evidenceofharm.com.
• Also look at www.nomercury.org,
  www.safeminds.org, www.nationalautismassociation.o
  rg.

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Epidemiology is unlikely to answer the question.

• Lies, damn lies and statistics

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Is there biological plausibility?

• Is thimerosal neurotoxic?

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Parras and Baskin studies

• Thimerosal is toxic to brain cells
• References 15, 16, 17

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Hornig study

• Thimerosal causes damage to brain cells in
  individuals predisposed to autoimmune reactions
  and results in autistic-like behaviors.
• Reference 18

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Burbacher study

• Compared to methylmercury, ethylmercury cross
  blood-brain barrier more readily and is more
  rapidly converted to inorganic mercury which is
  much more difficult to excrete.
• Reference 19

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Havarinasab study

• Mercury compounds, particularly inorganic
  mercury, can induce autoimmune reactions
• Reference 20

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Are children with autism predisposed to problems
with mercury?
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James study

• Autistic children have impaired methylation and
  glutathione depletion
• Thimerosal depletes glutathione in brain cells
  making them prone to damage.
• Reference 21

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Waly study

• Thimerosal can interrupt methylation by
  interfering with methionine synthase.
• Reference 22

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Holmes study

• Children with autism have significantly less
  mercury output in their hair suggesting an
  impaired excretion capacity
• Reference 23

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Bradstreet study

• On single-dose chelation challenge, autistic
  children have significantly higher levels of
  mercury output than do neurotypical children.
• Neurotypical children do not seem to retain
  mercury from vaccination exposure (better
  excretors.)
• Reference 24

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Do autistic children improve with mercury removal
treatment?
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What we think

• Open Trial of Chelation with DMSA and Lipoic Acid
  in Children with Autism Drs. Jane El-Dahr, Amy
  Holmes and Stephanie CaveAbstract presented at
  IMFAR 11/10/01 San Diego.

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Chelation results

• Improvements in 152 patients with DSMIV Autism
  after at least 4 months of LA/DMSA after DMSA

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Chelation results-percentages
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ARI questionnaire

• Over 23,000 parents questioned about effective
  treatments
• With chelation 73 reported that their children
  improved, 25 reported no change, 2 reported
  worsening.
• Compare to ritalin 29 report improvement, 26
  report no change, 44 worse.
• http//www.autismwebsite.com/ari/treatment/form34q
  .htm

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Adams chelation study

• A double-blind, placebo-controlled study of
  chelation affects on autistic children using
  DMSAin process

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Do children with autism have gastrointestinal
problems?
Gastrointestinal
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What we know

• Many autistic children have severe constipation
• Many autistic children have evidence of abnormal
  intestinal permeability
• Many autistic children have inflammation that can
  exist anywhere in the GI tract
• References 25, 26, 27

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Autistic enterocolitis

• Autistic children with GI symptoms have a bowel
  disease distinct from other chronic inflammatory
  bowel disorders
• References 28-35

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What we think

• Undiagnosed abdominal issues are the cause of
  many of the behavior symptoms of autism
• The inflammatory process in the bowel may result
  in secondary inflammation in the brain
• Addressing GI issues decreases autistic symptoms
• Reference 36

Neuro
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Do autistic children have immune problems?
Immunological
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What we know

• Autistic children have abnormal immune systems
  including low natural killer cell function,
  chronic inflammation and autoimmune reactions
• Reference 37, 38

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How does the immune system and the gut interact?
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Food issues

• Children with autism react against many common
  foods
• References 39-43

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Dietary Interventions

• Many autistic children respond to exclusionary
  diets
• Reference 44-48

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Nutritional Intervention

• Many autistic children respond to
  multivitamin/multimineral therapy
• Reference 49

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How does the immune system and the neurological
interact?
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Vargas study

• Autistic children have excess levels of
  inflammation in their brains
• The inflammation pattern is not consistent with
  the brain as the primary source.
• Reference 50

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Viral issues

• Does measles virus play a role?

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What we know

• The immune cell patterns in children with autism
  are consistent with a viral mechanism
• Vaccine strain measles virus has been found in
  the enlarged lymph nodes in the bowels of
  autistic children
• MMR antibodies are associated with anti-brain
  autoimmune antibodies in autistic children
• Measles virus has been recovered from the
  cerebrospinal fluid in autistic children
• References 51-58

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What we think

• Identifying and addressing causes of immune
  reactions improve autistic symptoms
• Breaking the inflammation cycle is important.

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Biological impairments in autism

• Chronic diarrhea/constipation
• Yeast/bacterial overgrowth of bowels
• Inability to clear heavy metals
• Impaired sulfation
• Leaky gut syndrome
• Imbalance immune system
• Mineral deficiencies-zinc, magnesium, selenium
• Malabsorption/malnutrition
• Impaired neuronal development
• Disrupted hippocampus/amygdala
• Gluten/casein sensitivity
• Impaired secretin signaling

• Impaired detoxification
• Impaired antioxidation
• Omega-3 fatty acid deficiency
• Significant food allergies
• Impaired pancreatic function
• Frequent viral and bacterial infections
• Vitamin deficiencies
• Autoimmunity
• Neurotransmitter imbalance/dysfunction
• Sensitivity to vaccinations
• seizures

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A new paradigm in autism

• Autism is an environmental illness with a genetic
  component.
• It is a complex metabolic disease, not just a
  developmental disability.
• Autism is treatable!
• A cure is possible!

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Contact Information

• Thoughtful House Center for Children3001 Bee
  Caves RoadAustin, TX 78746Telephone
  512-732-8400Fax [phone]Email
  info_at_thoughtfulhouse.org