Download Autism – A Primary-Care Biomedical Perspective

Autism – A Primary-Care
Biomedical Perspective
03/20/03
John L. Kucera, MD
Autism – A Primary-Care
Biomedical Perspective
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Family Medicine Practice
Preventive / Nutritional Medicine Focus
Toxic Metals Issue–Lead in Paints, Gasoline,
bullets, pottery, waterpipes, batteries
Focus on Lead poisoning by physicians,
especially pediatricians
Lead—possible cause of autism
(Cohen. American Journal of Diseases of Children,
1976)
03/20/03
John L. Kucera, MD
Autism – A Primary-Care
Biomedical Perspective
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Toxicity of Mercury in Some Adults
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Amalgam fillings—mercury, tin, etc.
Fish—pregnancy
Largely ignored by physicians, dentists and
public health officials
Potential Mercury Toxicity of Some Vaccines
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03/20/03
Thimerosal
Aluminum, formaldehyde – Synergistic Toxicity?
John L. Kucera, MD
Toxicity of Mercury
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“Methyl Mercury exposure is a widespread
and persistent problem in the environment
and may cause neurological problems in
60,000 children born in the U.S. each year.”
--National Academy of Science (USA,
7/2000)
03/20/03
John L. Kucera, MD
“Autism Spectrum Disorder”
Not one disorder, but a group of disorders
• Vary widely in presentation; similarities exist
• Many known distinct genetic defects
• Similar effects on neurons of particular areas
of brain
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03/20/03
Purkinje neurons in cerebellum often affected
Amygdala damage in Fragile X Syndrome and in
other autistic individuals and in mercury toxicity
John L. Kucera, MD
“Autism Spectrum Disorder”
Many known genetic disorders, but very rare
• Cannot account for dramatic increase in ASD
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03/20/03
John L. Kucera, MD
Autism: A Unique Type of
Mercury Poisoning
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Bernard, Enayati, Binstock, Roger, Redwood, McGinnis
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Medical Hypothesis, 2001
available on Autism Research Institute Website:
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www.autism.com/ari
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And on Defeat Autism Now Website:
03/20/03
John L. Kucera, MD
Autism & Mercury Poisoning
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Psychiatric Traits
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03/20/03
(Bernard, et. al.)
Social withdrawal, shyness
Anxiety, obsessive/compulsive traits
Depression
Irritability, aggression – severe temper tantrums
Impaired face recognition
Paranoid/psychotic thoughts and behavior
John L. Kucera, MD
Autism & Mercury Poisoning
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Speech/Language/Hearing Deficits
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03/20/03
(Bernard, et. al.)
Speech loss, delay or failure to develop
Dysarthria, slurred or intelligible speech
Echolalia, voice differentiation with other sounds
Sound sensitivity
Hearing loss
Poor performance on language tests
John L. Kucera, MD
Autism & Mercury Poisoning
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Sensory Abnormalities
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(Bernard, et. al.)
Paresthesias in and around mouth & extremities
Abnormal sensitivity to pain
Touch aversion
Proprioceptive (position sense) difficulty
John L. Kucera, MD
Autism & Mercury Poisoning
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Motor Disorder Behaviors
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(Bernard, et. al.)
Flapping, jumping, spinning, jerking
Poor eye-hand coordination, handwriting
Abnormal gait, posture / clumsy / toe walking
Chewing/swallowing problems
Unusual postures
Increase in cerebral palsy; hyper- or hypotonia
Incontinence / toilet training difficulties
Autonomic disturbances: excessive sweating,
poor circulation, elevated heart rate
John L. Kucera, MD
Autism & Mercury Poisoning
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Mental Impairments
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03/20/03
(Bernard, et. al.)
Borderline or retarded intelligence on previously
normal appearing persons
“Reversible” mental retardation in some cases
Poor concentration / short attention span
Difficulty with multiple/complex commands
Deficits with abstract/conceptual thinking
John L. Kucera, MD
Autism & Mercury Poisoning
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Other Unusual Behaviors
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(Bernard, et. al.)
Stereotyped sniffing
Hyperactivity
Insomnia: sleep disturbances
Eating/feeding disorders: food aversion / narrow
food preferences
Unprovoked / prolonged crying
Self-injurious behavior
Masturbatory tendencies
Grimacing / staring spells
John L. Kucera, MD
Autism & Mercury Poisoning
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Visual Impairments
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(Bernard, et. al.)
Limited or lack of eye contact
Gaze abnormalities
“Visual impairments”
Light sensitivity
Blurred vision
Constricted visual fields
John L. Kucera, MD
Autism & Mercury Poisoning
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Gastrointestinal Problems
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(Bernard, et. al.)
Diarrhea and/or constipation
Abdominal discomfort
Anorexia, poor appetite
Lesions of ileum & colon
Increased intestinal permeability (“leaky gut”)
Inhibition of endopeptidase enzymes (especially
dipeptidyl peptidase IV) needed for breakdown
of casein and gluten
John L. Kucera, MD
Autism & Mercury Poisoning
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Biochemical Abnormalities
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(Bernard, et. al.)
Sulfate deficiency
Purine / pyrimidine metabolic errors
Tyrosine depletion
Glutathione deficiency, necessary for liver
detoxification of heavy metals
Mitochondrial dysfunction, especially in brain
John L. Kucera, MD
Autism & Mercury Poisoning
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Immune System Abnormalities
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(Bernard, et. al.)
Increased incidence of allergies & asthma
Autoantibodies to myelin basic protein
Increased Th2 subset of lymphocytes
Reduced Natural Killer T-Cell function
John L. Kucera, MD
Autism & Mercury Poisoning
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Central Nervous System Lesions
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Selective damage
Purkinje and granular cells
Pathology in amygdala and hippocampus
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(Bernard, et. al.)
Unable to synthesize glutathione
Social avoidance, lack of facial expression, lack of eye
contact, motor stereotypic behaviors
Neuronal disorganization
Demyelination
Brain stem damage – peripheral polyneuropathy
Seizures, subtle seizure activities, abnormal EEG
John L. Kucera, MD
Autism: A Unique Type of
Mercury Poisoning
Bernard, Enayati, Binstock, Roger, Redwood, McGinnis
Medical Hypothesis, 2001
available on Autism Research Institute Website:
www.autism.com/ari
And on Defeat Autism Now Website:
03/20/03
John L. Kucera, MD
Autism, Mercury and Vaccines
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Thimerosal—until 2001, in many vaccines
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03/20/03
Antibacterial, antifungal
Used as a “preservative”
Removed from animal vaccines years ago
Banned from most over-the-counter products in
1998, but left in vaccines
Vaccine requirements for children birth to age 2
increased from 8 in 1980 to 22 in 2001
Children could have received >100x EPA safe
daily dose in vaccines given one day
John L. Kucera, MD
Autism, Mercury and Vaccines
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Mercury binds to sulfhydryl groups on protein
Can be structural proteins or enzymes
Loss of structural integrity or enzyme function
Thimerosal destroys tubulin & actin in neurons
Thimerosal is potent inhibitor of many critical
enzymes involved in cellular metabolism
Synergistic effect with aluminum and other
chemicals in vaccine mixture
Boyd Haley, Ph.D., 7/01
03/20/03
John L. Kucera, MD
Autism, Mercury and Vaccines
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Complicating Factors
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Infant's hepatic detoxification function not fully
developed
Multiple toxic mechanisms of mercury, including
to immune system, may contribute to
vulnerability to other substances, including
vaccines without thimerosal (MMR)
John L. Kucera, MD
Autism, Mercury and Vaccines
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Thimerosal Study – Centers for Disease
Control
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Screened 110,000 patients for Speech delay,
Neurodevelopmental Disorders, ADD
Official Conclusion: No link to Autism
Primary Investigator says opposite:
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03/20/03
“This screening suggests a possible association between
certain neurological disorders and exposure to mercury
from thimerosal-containing vaccines before the age of six
months.”
--Dr. Thomas Verstraeten
John L. Kucera, MD
Autism—Testing
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Basic Biochemical testing
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Establish baseline before interventions
Liver/renal function – treatments can affect
Complete blood chemistry
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03/20/03
CLUES: low bicarbonate (CO2): acidic stress
Low protein: inadequate intake or absorption
High protein: enzyme deficiencies
Low normal AST/ALT: Zinc deficiency
John L. Kucera, MD
Autism—Testing
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Other labs
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CBC
Thyroid function
Ammonia level
ANA
Immunoglobin Levels (IgG, A, M, E)
Myelin Basic Protein
Serum Copper, Plasma Zinc for Copper/Zinc ratio
John L. Kucera, MD
Autism—Testing
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Organic acids—urine
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Metabolic waste (like analysis of engine exhaust)
Metabolites of carbohydrates, proteins and fats
Waste products of yeast, bacteria
Kreb's Cycle Intermediates
John L. Kucera, MD
Autism—Testing
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Organic acids—urine
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Indicators of Mitochondrial Dysfunction
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Partial blocks in Kreb's Cycle—increase intermediates
Uncoupling of oxidative phosphorylation for energy
– Elevated fatty acid metabolites
– Elevated lactate
– Elevated hydroxymethylglutarate
03/20/03
John L. Kucera, MD
Autism—Testing
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Comprehensive Stool Analysis—Importante
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Identifies beneficial bacteria, potential pathogens
Identifies yeast and parasites
Measures digestive and absorptive function of gut
Measures indicators of inflammation and immune
function
Measures markers of Intestinal health
03/20/03
John L. Kucera, MD
Autism—Testing
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Comprehensive Food Allergy Panel
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Uncovers unknown food sensitivities
IgE and IgG
Better to wait until initial treatment completed
John L. Kucera, MD
Autism--Testing
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Toxic and Essential Mineral Screening
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Serum—useful only for very recent high exposure
RBC—good only for exposure in prior 3-4 months
Hair metals–reliable only if ability to detoxify intact,
but unreliable for infants and children with immature
or impaired detoxification
Fecal—more useful if recent exposure/ingestion or
after beginning chelation
03/20/03
John L. Kucera, MD
Autism--Testing
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Toxic and Essential Mineral Screening
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Urine Challenge—controversial; best available tool
for assessing body burden
Unchallenge urine--unreliable as indicator of
mercury exposure (Arch Environ Health 6:480-3, 1963
Pre-challenge urine baseline unnecessary
Challenge (provocative) agents vary in affinities for
each toxic metal and nutrient mineral
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03/20/03
DMSA (meso-2, 3-dimercaptosuccinic acid)
DMPS (sodium 2,3 dimercaptopropane-1-sulfonate)
John L. Kucera, MD
Autism--Testing
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DMSA—Rx Chemet (Sanofi
Pharmaceuticals), Succimer (Thorne),
DiSulfhydryl (Kirkman)
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Sulfur-thiol, forms stable complex with metals
FDA approved
Long-term experience in US with pediatric lead
toxicity (Safety and efficacy of DMSA in children with elevated blood
lead concentrations. J Toxicol Clin Toxicol 2000; 38(4):365-75)
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Majority (40-60%) remains in intestine (little or
no chelation of toxic metals); excreted in feces
Three-day dosing before urine collection
John L. Kucera, MD
Autism--Testing
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DMPS--Dimaval (Heyl); generic available via
compounding pharmacies
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Rapidly absorbed orally, peaking in 4 hours
Majority (45-60%) excreted in urine; rest in feces
Appears to have greater affinity for lead and
mercury than arsenic and cadmium
Extensively researched in Europe for safety and
efficacy
Challenge test is one-time oral dose (50-250 mg)
followed by 6-hr collection (one-time collection OK)
03/20/03
John L. Kucera, MD
Autism Treatment
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“The pathetic fact is that the standard of
care in America for a child with 'autism' is
no care at all – other than a diagnosis by a
psychiatrist after behavioral observations,
and a prescription for psychotropic
medications.”
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--from Don't GIVE UP – Matthew's Story
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by Liz Birt and Maurice Lopez
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Mothering, May-June, 2000
03/20/03
John L. Kucera, MD
Autism Treatment – Diet
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Casein-free, Gluten-free Diets
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Decrease opioid-peptides into circulation
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Improves cognitive / behavioral function
Improves gut motility
Decrease allergic reactions
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John L. Kucera, MD
Diet
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Casein Restriction
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All dairy products
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Cow's milk, goat's milk, buttermilk
Yogurt
Butter
Cheese
Whey
Caseinates
All foods with dairy products, casein
Reading labels necessary but not always accurate
John L. Kucera, MD
Diet
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Casein Restriction
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Milk/casein-free substitutes
– Rice, potato, soy
– Dairy-free cheeses, yogurts, margarines
– Comprehensive IgG food allergy testing very helpful
 Uncovers unknown food allergies (e.g., eggs)
 Reveals many foods to which child is NOT allergic
 Helps in expanding food options safely
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John L. Kucera, MD
Diet
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Gluten (or gliadin) Restriction—more difficult
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Wheat and most grains:
Barley, Kamut, Oats, Rye, Seminola, Spelt, Triticale
Most bakery, cereals and prepared foods
Often “hidden” in dressings, flavorings, spices, etc.
Reading labels necessary but not always accurate
Not always noted on list of ingredients
Contamination in manufacturing or packaging
equipment/materials
Contamination at home—kitchen utensils, etc.
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John L. Kucera, MD
Diet
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Gluten/grain alternatives:
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Corn—may have allergen (corn 'gluten')
Soy—may have allergen or sensitivity
Lentils
Potato
Rice
Legumes (bean flours, e.g., garbanzo)
Comprehensive IgG food allergy testing helpful
(necessario)
John L. Kucera, MD
Diet
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Guidelines for dietary, nutritional intervention
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Be willing to experiment
Observe closely for positive or negative reactions
A “negative” reaction is not always bad—may be
sign of new or recovered brain function, “sensory
overload” or “withdrawal”
If no obvious improvement after reasonable trial,
be willing to stop the treatment—again observe!
Consider retrials later
Record responses /dates of trials (muy importante)
03/20/03
John L. Kucera, MD
Diet
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Resources
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“Special Diets for Special Kids”--Lisa Lewis, Ph.D
“Unraveling the Mystery of Autism and Pervasive
Developmental Disorder”--Karyn Seroussi
Website: www.gfcfdiet.com
Autism Network for Dietary Intervention
newsletter, The ANDI News, POBox 77111,
Rochester, New York USA 14617-0711. E-mail:
[email protected]
03/20/03
John L. Kucera, MD
Mercury/Heavy Metal
Detoxification
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Throughout treatment
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Appropriate nutritional support
Appropriate monitoring tests
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See DAN! Consensus Paper
Monitor for side effects and benefits
John L. Kucera, MD
Mercury/Heavy Metal Detoxification
Defeat Autism Now! (DAN!)
Mercury Detoxification Consensus Group
Position Paper
Available online: dan.com; autism.com/ari
03/20/03
John L. Kucera, MD
Mercury/Heavy Metal Detoxification
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Pre-treatment testing
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Locate toxic metal sources and stop exposure
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see DAN! Consensus paper
Food, drinks, toys, clothing/bedding (antimony),
wooden playground equipment (arsenic)
Correct as much as possible:
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Intestinal dysbiosis
Intestinal permeability (leaky gut)
Nutritional derangements
03/20/03
John L. Kucera, MD
Intestinal Dysbiosis
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Dietary Treatment
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Sugar restriction
No milk and dairy—lactose promotes Candida
Avoid mold and yeast-containing foods (cheeses,
dried fruits, peanuts, alcoholic drinks, juices,
some B-vitamins
Address food allergies
Pancreatic enzymes (proteases)
John L. Kucera, MD
Intestinal Dysbiosis
Attempt to eradicate potential pathogens seen
on Stool Analysis and/or Organic Acid Testing
• Yeast
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Nystatin—safe; start low dose to prevent (“die-off”)
Probiotics—1-10 billion L. acidophilus, B. bifidum/d.
Saccharomyces boulardii
Natural agents against Candida
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Caprylic Acid (enteric-coated, time-release)
Oregano Oil (100x more potent than caprylic acid)
Berberine (goldenseal)--broad-spectrum activity against
fungi including C. albicans, pathogenic bacteria, protozoa
Garlic
John L. Kucera, MD
Intestinal Dysbiosis
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Treat parasites and pathogenic bacteria
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Try natural options first
Sulfamethoxazole/trimethoprim
Metronidazole (antifungal and antiparisitic)
Yodoxin (antifungal and antiparisitic)
John L. Kucera, MD
Mercury/Heavy Metal Detoxification
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DMSA–most commonly used
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Usually oral dosing; can be rectal
About every 8 hours; do not interrupt sleep
Usually given for 3 days, then eleven days off
Re-check CBC, biochemical profile and urine
metal challenge after two or three cycles
Not effective for aluminum chelation
John L. Kucera, MD
Mercury/Heavy Metal Detoxification
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DMPS—usually reserved for persistently
elevated mercury or other metals
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More rapid chelator
More effective chelator of mercury
Can be used for challenge test after DMSA
treatment
John L. Kucera, MD
Mercury/Heavy Metal
Detoxification
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Precautions
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Supplement trace minerals
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Make sure bowels moving
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Some metals cleared through gut
Increase fiber—e.g., psyllium at bedtime
Laxatives, if necessary—try Cascara sagrada or senna
Support, protect liver—major detoxifying organ
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Chelators bind with nutritional minerals, too
Glutathione
Extra Vitamin C and E
Milk thistle (Silybum marianum), silymarin flavonoids-50-250mg up to three times daily
John L. Kucera, MD
Case Studies
03/20/03
John L. Kucera, MD
03/20/03
John L. Kucera, MD