Julie A. Griffith, M.D., M.S., C.M.T.Julie A. Griffith, M.D., M.S., C.M.T.Pediatric and Adult Neurologist/Behavioral Pediatric and Adult Neurologist/Behavioral

NeurologistNeurologist1099 D. St., Suite 2081099 D. St., Suite 208San Rafael, CA 94901 San Rafael, CA 94901

415 925-1616415 925-1616www.mybrainhealth.orgwww.mybrainhealth.org, ,

mybrainhealth@comcast.netmybrainhealth@comcast.net

Star AcademySeptember 17th,

2010

Impact of Nutrition, Impact of Nutrition, Infection and Infection and

Environmental Toxins on Environmental Toxins on Learning Disabilities: Learning Disabilities:

Evaluation and Evaluation and Treatment.Treatment.

OutlineOutline

• 1. Learning disorders, define1. Learning disorders, define• 2. Learning disorders, list2. Learning disorders, list• 3. Learning disorders, underlying 3. Learning disorders, underlying

medical causesmedical causes• 4. Treatable underlying medical 4. Treatable underlying medical

problemsproblems

a. testinga. testing

b. treatmentb. treatment• 5. Resources5. Resources

Learning disabilitiesLearning disabilities• According to the regulations for Public Law (P.L.) 101-476 which is entitled According to the regulations for Public Law (P.L.) 101-476 which is entitled The Individuals with Disabilities Education The Individuals with Disabilities Education

ActAct ((IDEAIDEA),), the definition of the definition of Learning Learning DisabilityDisability is “a disorder in one or is “a disorder in one or more of the basic psychological more of the basic psychological processes involved in understanding processes involved in understanding or in using spoken or written or in using spoken or written language, which may manifest itself language, which may manifest itself in an imperfect ability to listen, in an imperfect ability to listen, think, speak, read, write, spell or to think, speak, read, write, spell or to do mathematical calculations.”   do mathematical calculations.”  

Learning disabilitiesLearning disabilities

• AlexiaAlexia• Attention Deficit Disorder (ADD)Attention Deficit Disorder (ADD)• Attention Deficit Hyperactivity Deficit Attention Deficit Hyperactivity Deficit

(ADHD)(ADHD)• Dyslexia Dyslexia • Math disorderMath disorder• Memory difficultiesMemory difficulties• Nonverbal learning disorderNonverbal learning disorder• Reading Comprehension Disorder Reading Comprehension Disorder • Sensory Processing DisordersSensory Processing Disorders

Learning difficulties can be Learning difficulties can be secondary to any of the secondary to any of the

following:following:• InattentionInattention• Low Energy levelLow Energy level• Psychological stressorsPsychological stressors• Seizures (coordination difficulties, Seizures (coordination difficulties,

inattention, memoryinattention, memory difficulties, weakness)difficulties, weakness)

• Sleep disorder (inattention, fatigue)Sleep disorder (inattention, fatigue)Sleep. 2010 Mar 1;33(3):319-25.Sleep. 2010 Mar 1;33(3):319-25.

• GozalGozal D D, , SerperoSerpero LD LD, , Kheirandish-GozalKheirandish-Gozal L L, , CapdevilaCapdevila OS OS, , KhalyfaKhalyfa A A, , TaumanTauman R R., ., Pritzker School of Medicine, University of Chicago Pritzker School of Medicine, University of Chicago

• TNF-alpha levels are increased in pediatric obstructive sleep TNF-alpha levels are increased in pediatric obstructive sleep apneaapnea, and the , and the TNF-alpha levels are primarily driven by sleep TNF-alpha levels are primarily driven by sleep fragmentation and increased body mass indexfragmentation and increased body mass index , and are closely , and are closely associated with the degree of sleepiness, as measured by Multiple Sleep Latency Test. associated with the degree of sleepiness, as measured by Multiple Sleep Latency Test.

Learning disabilities, some Learning disabilities, some common underlying common underlying medical problems medical problems

PediatricsPediatrics. 2009 Aug;124(2):837-44. . 2009 Aug;124(2):837-44.

• ADD/ADHD ADD/ADHD • Autism spectrum disordersAutism spectrum disorders• Dyslexia Dyslexia • Math disorderMath disorder• Nonverbal learning disorder Nonverbal learning disorder • Sensory processing disorders Sensory processing disorders • Speech and language disorders Speech and language disorders • Writing disordersWriting disorders

--

ADD/ADHDADD/ADHD• AllergiesAllergies• hearing loss hearing loss • heavy metal poisoning (Sci Total Environ. 2010 Sep 6 ), heavy metal poisoning (Sci Total Environ. 2010 Sep 6 ),

lead (level 5 caused ADHD and cognitive deficits in lead (level 5 caused ADHD and cognitive deficits in Korean children)Korean children)

• hormonal deficiencies (hypocholesterolemia, hormonal deficiencies (hypocholesterolemia, hypothyroidism)hypothyroidism)

• nutrititional deficiencies (aa, B vitamins, lithium, omega nutrititional deficiencies (aa, B vitamins, lithium, omega 3)3)

• infectionsinfections• painpain• seizures J Learn Disabil. 2008 May-Jun;41(3):195-207seizures J Learn Disabil. 2008 May-Jun;41(3):195-207• sleep disorders (obstructive; seizures, fungal infx, tick sleep disorders (obstructive; seizures, fungal infx, tick

born d)born d)

Snoring-induced ADHDSnoring-induced ADHD

Snoring childrenSnoring children

• 70 children 2-18 yrs of age70 children 2-18 yrs of age

snoring occurred in 33% kids with snoring occurred in 33% kids with ADHD compared to 10% of normal ADHD compared to 10% of normal kidskids

• 81% children with snoring and ADHD 81% children with snoring and ADHD could have their ADHD eliminated if could have their ADHD eliminated if cause of snoring is addressed, this cause of snoring is addressed, this would resolve 25% kids with ADHDwould resolve 25% kids with ADHD

Autisms Autisms Term coined by Dr. Martha Term coined by Dr. Martha

Herbert, MGHHerbert, MGH• Genetic and Environmental Factors• Genetic weakness in the detoxification system, the immune system,

or both

5% genetic/metabolic syndrome, such as a mitochondrial disorder, or neurocutaneous disorders (Neurofibromatosis, Tuberous sclerosis) , Acta Neurobiol Exp 2010, 70: 141–146, The review of most frequently occurring medical disorders

• related to aetiology of autism and the methods of treatment• Magdalena Cubała-Kucharska1,2,3

• Environmental Factors_ Allergies

_ Chronic infection, often polyinfected _ EMF stress (electromagnetic field stress) _ Nutritional deficiencies _Toxins

•

Autisms, environmental Autisms, environmental factorsfactors• Environmental Factors

_ allergies--food and environmental (mold, dust, cat and dog dander, plants) _ Chronic infection

bacterialclostridiaStreptoccalTick born disease ( Bartonella, Borrelia, Erlichia)

fungal infections (Candida, Rhodotorula, others)parasitic infections (Babesia of tick born disease, blastocystis hominis, other)viral infections (HHV6, EBV, HSV Types 1 and 2 and others)

– Toxins • Heavy metal poisoning, most common toxin, most recognized (80%

children improve with removal of heavy metals, if elevated (i.e.Aluminum, Arsenic, cadmium, lead, mercury)

Dis Model Mech. 2010 May-Jun;3(5-6):366-76. Dis Model Mech. 2010 May-Jun;3(5-6):366-76. Neuroligin-deficient mutants of C. Neuroligin-deficient mutants of C. elegans (nematode) have sensory processing deficits and are hypersensitive to elegans (nematode) have sensory processing deficits and are hypersensitive to oxidative stress and mercury toxicity., oxidative stress and mercury toxicity., Our results suggest a possible link between Our results suggest a possible link between genetic defects in synapse formation or function, and sensitivity to environmental factors genetic defects in synapse formation or function, and sensitivity to environmental factors in the development of autism spectrum disorders) in the development of autism spectrum disorders)

Journal of Pediatric Health Care (20)5: P. 350-352, 2006. J.C. Dale.Chlorine (stillbirth, congenital cardiac defects, neural tube defects)

• PCB (polychlorinated biphenyl hydrocarbons) gas stations, landfill

DyslexiaDyslexia– Genetic Genetic – Chromosome 6 (early gray hair, autoimmune, Chromosome 6 (early gray hair, autoimmune,

L-handed) L-handed) – FOXP2 truncation as a novel cause of developmental speech and FOXP2 truncation as a novel cause of developmental speech and language deficits, language deficits, Am J Am J

Hum Genet. 2005 Jun;76(6):1074-80.Hum Genet. 2005 Jun;76(6):1074-80. MacDermot KD, Bonora E, Sykes N, Coupe AM, Lai CS, Vernes SC, Vargha-Khadem F, McKenzie F, Smith RL, Monaco AP, MacDermot KD, Bonora E, Sykes N, Coupe AM, Lai CS, Vernes SC, Vargha-Khadem F, McKenzie F, Smith RL, Monaco AP, Fisher SE.Fisher SE.

FOXP2, the first gene to have been FOXP2, the first gene to have been implicated in a developmental communication implicated in a developmental communication disorder, disorder, offers a unique entry point into neuromolecular mechanisms influencing human speech and offers a unique entry point into neuromolecular mechanisms influencing human speech and

language acquisition. Inlanguage acquisition. In multiple members of the well-studied family, a heterozygous missensemultiple members of the well-studied family, a heterozygous missense mutation mutation in FOXP2 causes problems in sequencing in FOXP2 causes problems in sequencing muscle movements required for articulating muscle movements required for articulating speech (developmental verbal dyspraxia), speech (developmental verbal dyspraxia), accompanied by wider deficits in linguistic and accompanied by wider deficits in linguistic and grammatical processing. grammatical processing.

Alexia (cannot read)-Alexia (cannot read)-acquired dyslexiaacquired dyslexia

– stroke stroke (Neurorehabil Neural (Neurorehabil Neural

Repair. 2010 Sep 9)Repair. 2010 Sep 9)

-Tick born disease -Tick born disease http://www.townsendletter.com/July201http://www.townsendletter.com/July2010/savechildren0710.html0/savechildren0710.html

Math disorderMath disorder

• GeneticGenetic

Neurofibromatosis 1- Neurofibromatosis 1- Dev Disabil Dev Disabil Res Rev. 2009;15(1):45-51.Res Rev. 2009;15(1):45-51.Potential influences on mathematical Potential influences on mathematical difficulties in children and adolescents with difficulties in children and adolescents with neurofibromatosis, type 1., neurofibromatosis, type 1., Moore BD.Moore BD.

-polygenetic and polyenvironmental-polygenetic and polyenvironmental -seizures -seizures ( J Learn Disabil. 2008 May-Jun;41(3):195-207.)( J Learn Disabil. 2008 May-Jun;41(3):195-207.)

Memory difficultiesMemory difficulties

• HydrocephalusHydrocephalus• SeizuresSeizures• Sleep disorderSleep disorder• Tick born DiseaseTick born Disease• Viral infection (Herpes simplex Viral infection (Herpes simplex

virus)virus)

Hydrocephalus and Hydrocephalus and learning disabiliiteslearning disabiliites

• Neuropsychology. 1998 Oct;12(4):578-89.Neuropsychology. 1998 Oct;12(4):578-89.• Memory functions in children with early hydrocephalus.Memory functions in children with early hydrocephalus.• Scott MAScott MA, , Fletcher JMFletcher JM, , Brookshire BLBrookshire BL, , Davidson KCDavidson KC, , Landry SHLandry SH, , BohanBohan TC TC, ,

Kramer LAKramer LA, , Brandt MEBrandt ME, , Francis DJFrancis DJ..• Department of Pediatrics, University of Arkansas for Medical Sciences, Department of Pediatrics, University of Arkansas for Medical Sciences,

Springdale 72765-0768, USA. mscott3@aol.comSpringdale 72765-0768, USA. mscott3@aol.com• AbstractAbstract• Children with arrested, shunted, and no hydrocephalus were compared on Children with arrested, shunted, and no hydrocephalus were compared on

verbal and nonverbal memory tasks assessing multiple components of memory. verbal and nonverbal memory tasks assessing multiple components of memory. A gradient of severity was hypothesized, with the shunted hydrocephalus group A gradient of severity was hypothesized, with the shunted hydrocephalus group expected to exhibit the most significant memory impairments and the arrested expected to exhibit the most significant memory impairments and the arrested group expected to perform more poorly than children with no hydrocephalus. group expected to perform more poorly than children with no hydrocephalus. Etiologies of prematurity, spina bifida, and aqueductal stenosis were Etiologies of prematurity, spina bifida, and aqueductal stenosis were represented by represented by 157 157 participants. Results supported the hypothesis; the participants. Results supported the hypothesis; the shunted hydrocephalus group performed poorer on all memory shunted hydrocephalus group performed poorer on all memory measuresmeasures. Differences for the arrested group were less frequently . Differences for the arrested group were less frequently statistically significant relative to children with no hydrocephalus. Irrespective statistically significant relative to children with no hydrocephalus. Irrespective of etiology, the shunted hydrocephalus group exhibited a pattern of of etiology, the shunted hydrocephalus group exhibited a pattern of performance suggestive of performance suggestive of encoding and retrieval deficits on encoding and retrieval deficits on both verbal and nonverbal tasks, showing a both verbal and nonverbal tasks, showing a pervasive disturbance of memory processes.pervasive disturbance of memory processes.

Nonverbal learning Nonverbal learning disorderdisorder

needs head MRI and EEGneeds head MRI and EEG

• Heavy metal poisoning Heavy metal poisoning • HydrocephalusHydrocephalus• Neurofibromatosis Neurofibromatosis Curr Neurol Neurosci Rep. 2003 Mar;3(2):129-36. Review.Curr Neurol Neurosci Rep. 2003 Mar;3(2):129-36. Review. • Seizures in 15%Seizures in 15%• Tick born diseaseTick born disease

Sensory processing Sensory processing disordersdisorders

• Heavy metal poisoning (i.e. mercury)Heavy metal poisoning (i.e. mercury)• Skin-brain condition-neurocutaneous Skin-brain condition-neurocutaneous

disorder, café au lait spots, large head disorder, café au lait spots, large head circumference, Lisch nodules of eyes, circumference, Lisch nodules of eyes, math difficulties, visual spatial difficulties math difficulties, visual spatial difficulties ADHDADHDDev Disabil Res Rev. 2009;15(1):45-51.Dev Disabil Res Rev. 2009;15(1):45-51.Potential influences on mathematical Potential influences on mathematical difficulties in children and adolescents difficulties in children and adolescents with neurofibromatosis, type 1.with neurofibromatosis, type 1.

• Tick born disease (sensory hyperarousal, Tick born disease (sensory hyperarousal, Columbia website; Dr. Leventhal and O’Shea’s Columbia website; Dr. Leventhal and O’Shea’s neuropsych lecture, LIA 2009)neuropsych lecture, LIA 2009)

Speech and language Speech and language disordersdisorders

• Hearing lossHearing loss• Heavy metal poisoningHeavy metal poisoning• HypothyroidismHypothyroidism• Stroke-perinatal injury (dysphagia) Stroke-perinatal injury (dysphagia)

Clin Pediatr (Phila). 2009 Apr;48(3):247-51Clin Pediatr (Phila). 2009 Apr;48(3):247-51

• Tick born diseaseTick born disease• Traumatic brain injuryTraumatic brain injury

Writing disordersWriting disorders

• heavy metals poisoning, heavy metals poisoning,

-seizures J Learn Disabil. 2008 May--seizures J Learn Disabil. 2008 May-Jun;41(3):195-207Jun;41(3):195-207

• tick born diseasetick born disease

GeneticsGenetics

• More difficult to change. Can do More difficult to change. Can do gene therapy, but this is for a gene therapy, but this is for a handful of disorders. For most handful of disorders. For most disorders, there are clinical trials, disorders, there are clinical trials, but not definitive proven benefitsbut not definitive proven benefits

EpigeneticsEpigenetics

• Up to 30,000 different factors which Up to 30,000 different factors which may influence a gene (i.e. nutrition, may influence a gene (i.e. nutrition, radiation, toxins, herbs, medications, radiation, toxins, herbs, medications, exercise, electromagnetic forces, exercise, electromagnetic forces, etc) etc) Dr. Bruce Lipton, previously from Dr. Bruce Lipton, previously from StanfordStanford

3 common learning disabilities 3 common learning disabilities are multifactorial—are multifactorial—

polygenetic and polyenvironmentalpolygenetic and polyenvironmentalJ Dev Behav Pediatr. 2010 Sep;31(7):533-44J Dev Behav Pediatr. 2010 Sep;31(7):533-44

• ADD/ADHDADD/ADHD• Math disorderMath disorder• Reading disorder Reading disorder

Treatable common Treatable common underlying medical underlying medical

problems (epigenetic problems (epigenetic factors):factors):

AllergensAllergensInfectionsInfections

Nutritional deficienciesNutritional deficienciesToxinsToxins

AllergiesAllergies

Clearing allergiesClearing allergies

• Improves attentionImproves attention• Lessens cognitive fog (per my Lessens cognitive fog (per my

practice, not in the literature)practice, not in the literature)• Lessens fatigueLessens fatigue• Lessens snoring/hypoxemia at nightLessens snoring/hypoxemia at night• Improves memory during the day (if Improves memory during the day (if

snoring)snoring)• Lessens anxiety/panic disorder Lessens anxiety/panic disorder • Lessens conductive hearing lossLessens conductive hearing loss

Allergies can cause Allergies can cause anxietyanxiety

• Australian and New Zealand Journal of PsychiatryAustralian and New Zealand Journal of Psychiatry• • Association between allergy and anxiety disorders in youthAssociation between allergy and anxiety disorders in youth• 2001, Vol. 35, No. 6 , Pages 815-821 2001, Vol. 35, No. 6 , Pages 815-821 • • PavelPavel A Kovalenko1, A Kovalenko1, Christina W Hoven2, Christina W Hoven2, Ping Wu2, Ping Wu2, Judith Wicks2, Judith Wicks2,

Donald J Mandell2 and Donald J Mandell2 and QuyenQuyen Tiet2 Tiet2 • 1Virginia Institute for Psychiatric and Behavioural Genetics, Virginia 1Virginia Institute for Psychiatric and Behavioural Genetics, Virginia

Commonwealth University, 800 East Leigh Street, PO Box 980126, Commonwealth University, 800 East Leigh Street, PO Box 980126, Richmond, VA, 23298–0126, USA Richmond, VA, 23298–0126, USA kovalenp@yahoo.comkovalenp@yahoo.com

• 2Department of Child Psychiatry, Columbia University and New York 2Department of Child Psychiatry, Columbia University and New York State Psychiatric Institute, New YorkUSAState Psychiatric Institute, New YorkUSA

•Conclusions:Conclusions: Findings suggest that in some patients Findings suggest that in some patients panic panic disorderdisorder may be associated with may be associated with hypersensitivity of hypersensitivity of immune systemimmune system. Panic disorder should be considered in anxious . Panic disorder should be considered in anxious children reporting allergy when no organic cause of allergy is found, children reporting allergy when no organic cause of allergy is found, and likewise allergy should be considered in children with panic and likewise allergy should be considered in children with panic disorder.disorder.

Allergies can cause brain Allergies can cause brain fogfog

• Cerebral hypoperfusion can cause Cerebral hypoperfusion can cause cognitive difficulties: brain fog cognitive difficulties: brain fog (histamine release causes low blood (histamine release causes low blood pressure/leaky vessels, theoretically pressure/leaky vessels, theoretically causing lack of brain causing lack of brain perfusion/leading to suboptimal perfusion/leading to suboptimal brain functioning) brain functioning)

Allergies, congestion, Allergies, congestion, and sleep and sleep

• Curr Allergy Asthma Rep. 2010 Mar;10(2):113-21.Curr Allergy Asthma Rep. 2010 Mar;10(2):113-21.• Congestion and sleep impairment in allergic rhinitis.Congestion and sleep impairment in allergic rhinitis.• Craig TJCraig TJ, , SherkatSherkat A A, , SafaeeSafaee S S..• Hershey Medical Center, Penn State University, 500 University Drive, Hershey, Hershey Medical Center, Penn State University, 500 University Drive, Hershey,

PA, 17033-0850, USA. tcraig@psu.eduPA, 17033-0850, USA. tcraig@psu.edu• AbstractAbstract• Allergic rhinitis is a prevalent disease in developed nations, and its prevalence Allergic rhinitis is a prevalent disease in developed nations, and its prevalence

has been increasing throughout the world. Nasal congestion is the most common has been increasing throughout the world. Nasal congestion is the most common and bothersome symptoms of rhinitis. and bothersome symptoms of rhinitis. Congestion is associated Congestion is associated with sleep-disordered breathing and is thought to be a with sleep-disordered breathing and is thought to be a key cause of sleep impairment in individuals with key cause of sleep impairment in individuals with rhinitisrhinitis. The end result is a . The end result is a decrease in quality of life and decrease in quality of life and productivity and an increase in daytime sleepinessproductivity and an increase in daytime sleepiness. . Treatment with intranasal corticosteroids has been shown to reduce nasal Treatment with intranasal corticosteroids has been shown to reduce nasal congestion. Data on sleep-related end points from clinical trials of intranasal congestion. Data on sleep-related end points from clinical trials of intranasal corticosteroids indicate that this reduction is associated with improved sleep, corticosteroids indicate that this reduction is associated with improved sleep, reduced daytime fatigue, and improved quality of life. Other therapies, such as reduced daytime fatigue, and improved quality of life. Other therapies, such as montelukast, also have a positive influence on congestion and sleep. This review montelukast, also have a positive influence on congestion and sleep. This review examines nasal congestion and the associated sleep impairment of allergic examines nasal congestion and the associated sleep impairment of allergic rhinitis patients. It explores the adverse effects of disturbed sleep on quality of rhinitis patients. It explores the adverse effects of disturbed sleep on quality of life and how these conditions can be reduced by therapies that decrease life and how these conditions can be reduced by therapies that decrease congestion.congestion.

Bacteria and viruses in gut Bacteria and viruses in gut may contribute to may contribute to

development of allergiesdevelopment of allergies• Adv Drug Deliv Rev. 2004 Apr 19;56(6):795-807.Adv Drug Deliv Rev. 2004 Apr 19;56(6):795-807.• Intestinal epithelial tight junctions as targets for enteric bacteria-derived toxins.Intestinal epithelial tight junctions as targets for enteric bacteria-derived toxins.• FasanoFasano A A, , NataroNataro JP JP., Division of Pediatric Gastroenterology and Nutrition, School of Medicine, University of Maryland, ., Division of Pediatric Gastroenterology and Nutrition, School of Medicine, University of Maryland,

Baltimore 21201, USA. afasano@umaryland.eduBaltimore 21201, USA. afasano@umaryland.edu• Ann N Y Acad Sci. 2000;915:214-22.Ann N Y Acad Sci. 2000;915:214-22.• Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin.Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin.• FasanoFasano A A..• Division of Pediatric Gastroenterology and Nutrition, Gastrointestinal Pathophysiology Section, Center for Vaccine Division of Pediatric Gastroenterology and Nutrition, Gastrointestinal Pathophysiology Section, Center for Vaccine

Development, Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Development, Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. afasano@umaryland.eduafasano@umaryland.edu

• AbstractAbstract

• Alteration of epithelial tj is a recently described property for infectious agents. Alteration of epithelial tj is a recently described property for infectious agents. Clostridium difficile Clostridium difficile toxin A and B and influenza and vesicular stomatitis viruses toxin A and B and influenza and vesicular stomatitis viruses have been shown to loosen tight junctionshave been shown to loosen tight junctions in tissue culture in tissue culture monolayersmonolayers. These changes appear to be irreversible and are associated with destruction of the tj complex. We were . These changes appear to be irreversible and are associated with destruction of the tj complex. We were

able to identify an intestinal Zot analogue, which we named zonulin. It is conceivable that the able to identify an intestinal Zot analogue, which we named zonulin. It is conceivable that the zonulins zonulins participate in the physiological regulation of intercellular tj not participate in the physiological regulation of intercellular tj not only in the small intestine, but alsoonly in the small intestine, but also throughout a wide range of extraintestinal epithelia as throughout a wide range of extraintestinal epithelia as

well as the ubiquitous vascular endothelium, including the well as the ubiquitous vascular endothelium, including the blood-brain barrierblood-brain barrier. Dysregulation …may contribute . Dysregulation …may contribute to disease states that involve … developmental and intestinal disorders, and tissue inflammation…to disease states that involve … developmental and intestinal disorders, and tissue inflammation…

• Comment:: when you affect the blood brain barrier, Comment:: when you affect the blood brain barrier, you increase the risk of neuroimmune disease and you increase the risk of neuroimmune disease and also increase the risk to chemical sensitivity.also increase the risk to chemical sensitivity.

Mold severely exacerbates Mold severely exacerbates allergiesallergies

• Allergy. 2003 Apr; 58(4):363-5.Allergy. 2003 Apr; 58(4):363-5.• Does systemic exposure to Does systemic exposure to

aflatoxin B(1) cause allergic aflatoxin B(1) cause allergic sensitization?sensitization?

• KocabaşKocabaş CN CN, , SekerelSekerel BE BE..• Department of Pediatric Allergy and Department of Pediatric Allergy and

Astma, Faculty of Medicine, Astma, Faculty of Medicine, Hacettepe University, Sihhiye, Hacettepe University, Sihhiye, Ankara, Turkey.Ankara, Turkey.

Allergy testingAllergy testing• At least 2 immune reactionsAt least 2 immune reactions1)1) IgE mediated (immediate hypersensitivity)IgE mediated (immediate hypersensitivity)2)2) IgG Type 4 (delayed hypersensitivity) IgG Type 4 (delayed hypersensitivity) 3) Sources3) Sources

a) Environmental (cat, dog, dust, mold, a) Environmental (cat, dog, dust, mold, plant)plant)b) Foodb) Food

4) Testing: Blood, consider Meridian Valley 4) Testing: Blood, consider Meridian Valley serum measures IgG(Type 4) and IgE serum measures IgG(Type 4) and IgE through ELISA. through ELISA. Also, other labs include Alcat or IBT (both Also, other labs include Alcat or IBT (both can meas individual antibody reactions.)can meas individual antibody reactions.)

Treatment of allergiesTreatment of allergies

• For significant antibody response, For significant antibody response, remove foods for 4 monthsremove foods for 4 months

• For moderate antibody response, For moderate antibody response, rotate foods (once every 4 days)rotate foods (once every 4 days)

• Caveat: casein and gluten sensitivity Caveat: casein and gluten sensitivity may need to go on to further testing may need to go on to further testing for difficulties in digestion, if no for difficulties in digestion, if no immune reaction (urine peptide immune reaction (urine peptide testing)testing)

• Antiinflammatory dietAntiinflammatory diet

Allergies-inhalantAllergies-inhalant

• Blood IgE and IgG Type 4Blood IgE and IgG Type 4

Cat, dog, dust, mold, weeds, trees and Cat, dog, dust, mold, weeds, trees and grassesgrasses

Antiinflammatory dietAntiinflammatory diet

• Increase PGE3: Good foods: omega 3 (fish Increase PGE3: Good foods: omega 3 (fish oils, seaweed), 6 (nuts, avocado), 9 oils, seaweed), 6 (nuts, avocado), 9 (cooking with olive oil)(cooking with olive oil)

fish oils: 80 mg/kg (mercury and PCB free), fish oils: 80 mg/kg (mercury and PCB free), frigfrig

Nordic naturals, Carlson possibilities of Nordic naturals, Carlson possibilities of brandsbrands

Wild fish, free range meat and poultry Wild fish, free range meat and poultry • Avoid (decrease PGE2): dairy, grain Avoid (decrease PGE2): dairy, grain

fed/corn fed meats and poultryfed/corn fed meats and poultry

InfectionsInfections

Infections-chronic and/or Infections-chronic and/or recurrentrecurrent

– BacterialBacterial• Lyme disease (Borrelia related complex, BRC, Lyme disease (Borrelia related complex, BRC,

Helicobacter pylori)Helicobacter pylori)

clostridiaclostridia• PANDAS (Strep) -Intermittent flares of anxiety and/or PANDAS (Strep) -Intermittent flares of anxiety and/or

ticstics

– Fungal (Candida, Rhodotorula, Aspergillus)Fungal (Candida, Rhodotorula, Aspergillus)– Parasitic (blastocystis hominis, Giardia, others) Parasitic (blastocystis hominis, Giardia, others) – Viral- EBV, HHV6, HSV, measles, RubellaViral- EBV, HHV6, HSV, measles, Rubella

Less likely, but possible: CMV, human gamma Less likely, but possible: CMV, human gamma retrovirus (co-infection of Tick born disease)retrovirus (co-infection of Tick born disease)

Infections, testingInfections, testing• Blood Blood

_IgE and IgG can assist identifying mold _IgE and IgG can assist identifying mold pathogenspathogens

– Tick born disease – may begin to use CD57, but T Tick born disease – may begin to use CD57, but T cells may not fully mature until 18 yrscells may not fully mature until 18 yrs

Igenex western blot for Borrelia, titers Igenex western blot for Borrelia, titers for Babesia, for Babesia, Bartonella, and ErlichiaBartonella, and Erlichia

Neuroscience testing interleukins, may Neuroscience testing interleukins, may be pd for by be pd for by insuranceinsurance-Viral titers - HHV6, EBV full panel, HSV -Viral titers - HHV6, EBV full panel, HSV Type 1, Type 1,

urine neopterin (screen for virus, and identifies urine neopterin (screen for virus, and identifies inflammation)inflammation)

Stool testingStool testing(possible labs Genova, Great Plains, Doctor’s Data, (possible labs Genova, Great Plains, Doctor’s Data,

DiagnosTechs)DiagnosTechs)

• CulturesCulturesBacteria - Level of healthy bacteria lactobacillus acidophilus Bacteria - Level of healthy bacteria lactobacillus acidophilus and bifidobacter and bifidobacter -pathogenic bacteria-pathogenic bacteria

• fungifungi

Big advantage: better able to identify and grow fungi than Big advantage: better able to identify and grow fungi than other local hospital labs or local national labs, cultures other local hospital labs or local national labs, cultures specific organism (if bacteria or fungus), identifies which specific organism (if bacteria or fungus), identifies which medications or herbs actually effective in clearing organismmedications or herbs actually effective in clearing organism

• parasites parasites • Inflammation (calprotectin)Inflammation (calprotectin)• Insufficient digestion (pancreatic elastase 1)Insufficient digestion (pancreatic elastase 1)• Bile acidsBile acids• pHpH

Lyme-induced autismLyme-induced autism• Med Hypotheses. 2008;70(5):967-74. Epub 2007 Nov 5.Med Hypotheses. 2008;70(5):967-74. Epub 2007 Nov 5.• The association between tick-borne infections, Lyme borreliosis and autism spectrum disorders.The association between tick-borne infections, Lyme borreliosis and autism spectrum disorders.

• BransfieldBransfield RC RC,, WulfmanWulfman JS JS, , Harvey WTHarvey WT, , UsmanUsman AI AI..• Department of Psychiatry, Riverview Medical Center, 225 State Route 35, Red Bank, NJ, United States. bransfield@comcast.netDepartment of Psychiatry, Riverview Medical Center, 225 State Route 35, Red Bank, NJ, United States. bransfield@comcast.net• AbstractAbstract• Chronic infectious diseases, including tick-borne infections such as Borrelia burgdorferi may have direct effects, promote other Chronic infectious diseases, including tick-borne infections such as Borrelia burgdorferi may have direct effects, promote other

infections and create a weakened, sensitized and immunologically vulnerable state during fetal development and infancy leading infections and create a weakened, sensitized and immunologically vulnerable state during fetal development and infancy leading to increased vulnerability for developing autism spectrum disorders. A dysfunctional synergism with other predisposing and to increased vulnerability for developing autism spectrum disorders. A dysfunctional synergism with other predisposing and contributing factors may contribute to autism spectrum disorders by provoking innate and adaptive immune reactions to cause contributing factors may contribute to autism spectrum disorders by provoking innate and adaptive immune reactions to cause and perpetuate effects in susceptible individuals that result in and perpetuate effects in susceptible individuals that result in inflammation,inflammation, molecular mimicry, kynurenine pathway molecular mimicry, kynurenine pathway

changes, increased quinolinic acid and decreased serotonin, changes, increased quinolinic acid and decreased serotonin, oxidative stress, mitochondrial dysfunction oxidative stress, mitochondrial dysfunction and excitotoxicity that impair the development of the amygdala and other neural and excitotoxicity that impair the development of the amygdala and other neural structures and neural networksstructures and neural networks resulting in a partial Klüver-Bucy Syndrome and other deficits resulting in resulting in a partial Klüver-Bucy Syndrome and other deficits resulting in autism spectrum disorders and/or exacerbating autism spectrum disorders from other causes throughout life. Support for this autism spectrum disorders and/or exacerbating autism spectrum disorders from other causes throughout life. Support for this

hypothesis includes hypothesis includes multiple cases of mothers with Lyme disease and multiple cases of mothers with Lyme disease and children with autism spectrum disorders; children with autism spectrum disorders; fetal neurological abnormalities fetal neurological abnormalities

associated with tick-borne diseasesassociated with tick-borne diseases; similarities between tick-borne diseases ; similarities between tick-borne diseases and autism spectrum disorder regarding symptoms, and autism spectrum disorder regarding symptoms, pathophysiology, pathophysiology,

immune reactivityimmune reactivity, temporal lobe pathology, and brain imaging data; , temporal lobe pathology, and brain imaging data; positive reactivity in several studies with autistic spectrum positive reactivity in several studies with autistic spectrum disorder patients for Borrelia burgdorferi (22%, 26% and 20-disorder patients for Borrelia burgdorferi (22%, 26% and 20-30%) and 58% for mycoplasma30%) and 58% for mycoplasma; similar geographic distribution and improvement in autistic ; similar geographic distribution and improvement in autistic symptoms from antibiotic treatment. It is imperative to research these and all possible causes of autism spectrum disorders in symptoms from antibiotic treatment. It is imperative to research these and all possible causes of autism spectrum disorders in order to prevent every preventable case and treat every treatable case until this disease has been eliminated from humanity.order to prevent every preventable case and treat every treatable case until this disease has been eliminated from humanity.

Bacteria endotoxin Bacteria endotoxin association with autismassociation with autism

• Neurosci Lett. 2010 Mar 8;471(3):162-5. Epub 2010 Jan 25.Neurosci Lett. 2010 Mar 8;471(3):162-5. Epub 2010 Jan 25.• Low-grade endotoxemia in patients with severe autism.Low-grade endotoxemia in patients with severe autism.• EmanueleEmanuele E E, , OrsiOrsi P P, , BosoBoso M M, , BrogliaBroglia D D, , BrondinoBrondino N N, , BaraleBarale F F, , didi NemiNemi

SU SU, , PolitiPoliti P P..• Department of Health Sciences, Section of Psychiatry, University of Department of Health Sciences, Section of Psychiatry, University of

Pavia, Via Bassi, 21, I-27100, Pavia, Italy. enzo.em@libero.it Pavia, Via Bassi, 21, I-27100, Pavia, Italy. enzo.em@libero.it <enzo.em@libero.it><enzo.em@libero.it>

• AbstractAbstract• The objective of this study was to examine whether levels of endotoxin The objective of this study was to examine whether levels of endotoxin

and other markers of immuno-inflammatory activation are altered in and other markers of immuno-inflammatory activation are altered in adult patients with severe autism. We determined circulating serum adult patients with severe autism. We determined circulating serum endotoxin levels, its soluble receptor (sCD14), and markers of immuno-endotoxin levels, its soluble receptor (sCD14), and markers of immuno-inflammatory activation (IL-1beta, IL-6, and IL-10) in 22 adult patients inflammatory activation (IL-1beta, IL-6, and IL-10) in 22 adult patients with severe autism and 28 age- and gender-matched healthy controls. with severe autism and 28 age- and gender-matched healthy controls. Compared with healthy subjects, serum levels of endotoxin were Compared with healthy subjects, serum levels of endotoxin were significantly higher in autistic patients and inversely and independently significantly higher in autistic patients and inversely and independently correlated with Socialization scores on the Vineland Adaptive Behavior correlated with Socialization scores on the Vineland Adaptive Behavior Scales (VABS) and ADI-R Domain A score (social). Whether increased Scales (VABS) and ADI-R Domain A score (social). Whether increased endotoxin may contribute to the pathophysiology of inflammation and endotoxin may contribute to the pathophysiology of inflammation and impaired reciprocal social interaction in autism should be further impaired reciprocal social interaction in autism should be further explored in future studies.explored in future studies.

Proinflammation in Proinflammation in autismautism

• Brain Behav Immun. 2010 Jan;24(1):64-71. Epub 2009 Aug 8.Brain Behav Immun. 2010 Jan;24(1):64-71. Epub 2009 Aug 8.• Differential monocyte responses to TLR ligands in children with autism spectrum disorders.Differential monocyte responses to TLR ligands in children with autism spectrum disorders.• EnstromEnstrom AM AM, , OnoreOnore CE CE, , Van de Water JAVan de Water JA, , AshwoodAshwood P P..• Departments of Medical Microbiology and Immunology, University of California at Davis, CA 95817, Departments of Medical Microbiology and Immunology, University of California at Davis, CA 95817,

USA.USA.• AbstractAbstract• Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication

deficits, and restricted repetitive interests and behaviors. Recent evidence has suggested that deficits, and restricted repetitive interests and behaviors. Recent evidence has suggested that impairments of innate immunity may play an important role in ASD. To test this hypothesis, we isolated impairments of innate immunity may play an important role in ASD. To test this hypothesis, we isolated peripheral blood monocytes from 17 children with ASDperipheral blood monocytes from 17 children with ASD and 16 age-matched and 16 age-matched typically developing (TD) controls and stimulated these cell cultures in vitro with distinct toll-like typically developing (TD) controls and stimulated these cell cultures in vitro with distinct toll-like receptors (TLR) ligands: TLR 2 (lipoteichoic acid; LTA), TLR 3 (poly I:C), TLR 4 (lipopolysaccharide; receptors (TLR) ligands: TLR 2 (lipoteichoic acid; LTA), TLR 3 (poly I:C), TLR 4 (lipopolysaccharide; LPS), TLR 5 (flagellin), and TLR 9 (CpG-B). Supernatants were harvested from the cell cultures and pro-LPS), TLR 5 (flagellin), and TLR 9 (CpG-B). Supernatants were harvested from the cell cultures and pro-inflammatory cytokine responses for IL-1beta, IL-6, IL-8, TNFalpha, MCP-1, and GM-CSF were inflammatory cytokine responses for IL-1beta, IL-6, IL-8, TNFalpha, MCP-1, and GM-CSF were determined by multiplex Luminex analysis. After in vitro challenge with TLR ligands, differential determined by multiplex Luminex analysis. After in vitro challenge with TLR ligands, differential cytokine responses were observed in monocyte cultures from children with ASD compared with TD cytokine responses were observed in monocyte cultures from children with ASD compared with TD control children. In particular, there was a control children. In particular, there was a marked increase in pro-inflammatory IL-marked increase in pro-inflammatory IL-1beta, IL-6, and TNFalpha responses1beta, IL-6, and TNFalpha responses following TLR 2, and IL-1beta response following TLR 2, and IL-1beta response following following TLR 4 TLR 4 stimulation in monocyte cultures from children stimulation in monocyte cultures from children with ASD (p<0.04with ASD (p<0.04). Conversely, following TLR 9 stimulation there was a decrease in IL-). Conversely, following TLR 9 stimulation there was a decrease in IL-1beta, IL-6, GM-CSF, and TNFalpha responses in monocyte cell cultures from children with ASD 1beta, IL-6, GM-CSF, and TNFalpha responses in monocyte cell cultures from children with ASD

compared with controls (p<0.05). These data indicate that, compared with controls (p<0.05). These data indicate that, monocyte cultures from monocyte cultures from children with ASD are more responsive to signalingchildren with ASD are more responsive to signaling via select TLRs. via select TLRs. As monocytes are key regulators of the immune response, dysfunction in the response of these cells As monocytes are key regulators of the immune response, dysfunction in the response of these cells could result in long-term immune alterations in children with ASD that may lead to the development of could result in long-term immune alterations in children with ASD that may lead to the development of adverse neuroimmune interactions and could play a role in the pathophysiology observed in ASDadverse neuroimmune interactions and could play a role in the pathophysiology observed in ASD

Fungal infection- treatment Fungal infection- treatment improves:improves:

• Attention• diarrhea or constipation• lessens urinary and stool

incontinence• clears cognition• lessens night time sweating and

insomnia

Fungal infectionsFungal infections

• Autism-antifungals is proposed to relieve both gastrointestinal symptoms and helps cognitive functions as well (Sandler et al.,2000

Fungal infection-Fungal infection-examination and testingexamination and testing

• ThrushThrush• RingwormRingworm• Athlete’s foot, nail infection, groin Athlete’s foot, nail infection, groin

infectioninfection• Stool culture and antifungal Stool culture and antifungal

sensitivities (both to medications and sensitivities (both to medications and herbs)herbs)

• Blood IgE and IgG screening against Blood IgE and IgG screening against mold antigens mold antigens

Dust mite endotoxins cause Dust mite endotoxins cause inflammationinflammation

• Int Arch Allergy Immunol. 2010;152(3):279-87. Epub 2010 Feb 12.Int Arch Allergy Immunol. 2010;152(3):279-87. Epub 2010 Feb 12.• Indoor determinants of endotoxin and dust mite exposures in Hong Kong homes with Indoor determinants of endotoxin and dust mite exposures in Hong Kong homes with

asthmatic children.asthmatic children.• Leung TFLeung TF, , Wong YSWong YS, , Chan IHChan IH, , Yung EYung E, , Wong CKWong CK, , Lam CWLam CW, , Wong GWWong GW..• Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin,

Hong Kong, SAR, China.Hong Kong, SAR, China.• AbstractAbstract• BACKGROUND: BACKGROUND: Domestic endotoxin enhances airway inflammation and increases asthma Domestic endotoxin enhances airway inflammation and increases asthma

severity in Caucasian children, but little data are published on indoor endotoxin exposure in Asian severity in Caucasian children, but little data are published on indoor endotoxin exposure in Asian countries. This study investigated house dust endotoxin and Der p 1 levels in Hong Kong families countries. This study investigated house dust endotoxin and Der p 1 levels in Hong Kong families with asthmatic children, and their effects on asthma severity.with asthmatic children, and their effects on asthma severity.

• METHODS: METHODS: 115 asthmatics from a pediatric clinic underwent fractional exhaled nitric oxide 115 asthmatics from a pediatric clinic underwent fractional exhaled nitric oxide (FeNO) and spirometric measurements. Home visits were then made within 2 weeks, during which (FeNO) and spirometric measurements. Home visits were then made within 2 weeks, during which parents completed the International Study of Asthma and Allergies in Childhood questionnaire. parents completed the International Study of Asthma and Allergies in Childhood questionnaire. Settled dust was collected from patients' mattresses, bedroom floors and living room floors. Settled dust was collected from patients' mattresses, bedroom floors and living room floors. Endotoxin and Der p 1 were measured by limulus amebocyte lysate and immunoassay, Endotoxin and Der p 1 were measured by limulus amebocyte lysate and immunoassay, respectively.respectively.

• RESULTS: RESULTS: Endotoxin was detectable in all locations from all families, whereas Der p 1 was Endotoxin was detectable in all locations from all families, whereas Der p 1 was detectable in 58-70% of indoor sites. Floors of both bedroom and living rooms had higher detectable in 58-70% of indoor sites. Floors of both bedroom and living rooms had higher endotoxin but lower Der p 1 levels than mattresses (p < 0.001 for both). Mattress endotoxin level endotoxin but lower Der p 1 levels than mattresses (p < 0.001 for both). Mattress endotoxin level correlated inversely with Der p 1 level (r = -0.308, p = 0.001). Household smoker, feather bedding correlated inversely with Der p 1 level (r = -0.308, p = 0.001). Household smoker, feather bedding and vacuum cleaning were independent determinants of indoor endotoxin. Timing of last bedding and vacuum cleaning were independent determinants of indoor endotoxin. Timing of last bedding change was associated with Der p 1 levels at all sites. Mattress endotoxin level was associated change was associated with Der p 1 levels at all sites. Mattress endotoxin level was associated with frequency of wheezing episodes (p = 0.044), but neither endotoxin nor Der p 1 was associated with frequency of wheezing episodes (p = 0.044), but neither endotoxin nor Der p 1 was associated with FeNO and spirometric parameters.with FeNO and spirometric parameters.

• CONCLUSIONS: CONCLUSIONS: Domestic endotoxin levels are associated with frequency of wheezing episodes Domestic endotoxin levels are associated with frequency of wheezing episodes in asthmatic children but not their FeNO or spirometric measurements.in asthmatic children but not their FeNO or spirometric measurements.

Nutritional deficienciesNutritional deficiencies

Nutrients-purposesNutrients-purposes

• Antiinflammatory to brainAntiinflammatory to brain• AttentionAttention• EnergyEnergy• Infection, prevent and resolveInfection, prevent and resolve• Neurotransmitter productionNeurotransmitter production• Prevent depression/mood instabilityPrevent depression/mood instability• Prevent seizuresPrevent seizures

Nutritional deficienciesNutritional deficiencies

• Amino acids (neurot, enzym, thyroid h, proteins, Amino acids (neurot, enzym, thyroid h, proteins, mus)mus)

• Essential fatty acids (omega 3, dha)- attn, moodEssential fatty acids (omega 3, dha)- attn, mood• Vitamin A (vision, stop infections, stop acne)Vitamin A (vision, stop infections, stop acne)• Vitamin B1 (stop nervous breakdown)Vitamin B1 (stop nervous breakdown)• Vitamins B2,3,5Vitamins B2,3,5• Vitamin B6 ( prot, neurotrans, energy, sleep, Vitamin B6 ( prot, neurotrans, energy, sleep,

dreams)dreams)• Vitamin B12 (methyl dopamine, anemia, detox, Vitamin B12 (methyl dopamine, anemia, detox,

lowering homocysteine)lowering homocysteine)• Folate-fully methylated form, helps to detoxify, Folate-fully methylated form, helps to detoxify,

attnattn

Nutritional deficiencies-Nutritional deficiencies-testingtesting

• Fasting blood and urineFasting blood and urine

Either local lab, or specialized lab (i.e. Either local lab, or specialized lab (i.e. Metametrix, Genova, others) for Metametrix, Genova, others) for functional needsfunctional needs

Generates amino acid and mvi/mmi Generates amino acid and mvi/mmi recipesrecipes

• Hair-lithium deficiencyHair-lithium deficiency

Nutritional deficiencies-Nutritional deficiencies-treatmenttreatment

• Best, excellent diet, but not enough, JAMA Best, excellent diet, but not enough, JAMA 1999 article, need to supplement with 1999 article, need to supplement with mvi/mmi, likely fish oils.mvi/mmi, likely fish oils.

• Options, try not to include sugar in productsOptions, try not to include sugar in products

amino acid powder amino acid powder

mvi/mmi powdermvi/mmi powder

specific supplements, mvi/mmispecific supplements, mvi/mmi

Fish oils (liquid, chewable capsules, Fish oils (liquid, chewable capsules, capsules)capsules)

lithium orotate pillslithium orotate pills

Nutritional deficiencies Nutritional deficiencies cont’dcont’d

• Methylcobolamine (+/- folinic acid, Methylcobolamine (+/- folinic acid, +/- n-acetylcysteine) subcutaneous +/- n-acetylcysteine) subcutaneous shotsshots

• IV glutathione, vitamin C, IV glutathione, vitamin C, PhospholipidPhospholipid

• Rarely, IV nutrition for severe Tick Rarely, IV nutrition for severe Tick born disease, may also give IV born disease, may also give IV antibiotics antibiotics

Nutritional deficiencies-Nutritional deficiencies-retestretest

• Retest blood (and possibly, urine, Retest blood (and possibly, urine, hair as needed) in approx 1-3 hair as needed) in approx 1-3 months to ensure nutrient levels are months to ensure nutrient levels are improving.improving.

ToxinsToxins

ToxinsToxins• Neurotox Res. 2007 Apr;11(3-4):203-18.Neurotox Res. 2007 Apr;11(3-4):203-18.• Glutamate antagonists are neurotoxins for the developing brain.Glutamate antagonists are neurotoxins for the developing brain.• KaindlKaindl AM AM, , IkonomidouIkonomidou C C..• Department of Pediatric Neurology, Charité, University Medical School, Campus Virchow-Department of Pediatric Neurology, Charité, University Medical School, Campus Virchow-

Klinikum, Augustenburger Platz 1,13353 Berlin, Germany. angela.kaindl@charite.deKlinikum, Augustenburger Platz 1,13353 Berlin, Germany. angela.kaindl@charite.de• AbstractAbstract• Neurotransmitters and neuromodulators are essential for normal nervous system Neurotransmitters and neuromodulators are essential for normal nervous system

development. Disturbances in the expression timetable or intensity of neurotransmitter development. Disturbances in the expression timetable or intensity of neurotransmitter signalling during critical periods of brain development can lead to permanent damage. signalling during critical periods of brain development can lead to permanent damage.

Neuroactive drugs and Neuroactive drugs and environmental toxins interfere environmental toxins interfere with neurotransmitter signalling and may with neurotransmitter signalling and may thereby provide one mechanism underlying thereby provide one mechanism underlying neurological abnormalities. Glutamate is the neurological abnormalities. Glutamate is the main excitatory neurotransmitter in the main excitatory neurotransmitter in the mammalian central nervous system and mammalian central nervous system and mediates neurotransmission across most mediates neurotransmission across most excitatory synapsesexcitatory synapses. In this article we review the timely expression of the . In this article we review the timely expression of the excitatory neurotransmitter glutamate and its receptors during brain development, briefly excitatory neurotransmitter glutamate and its receptors during brain development, briefly review glutamate receptor antagonists and present clinical and experimental evidence review glutamate receptor antagonists and present clinical and experimental evidence describing their adverse effects in the developing brain.describing their adverse effects in the developing brain.

ToxinsToxins

• Biotoxins (bacteria, fungi) (common)Biotoxins (bacteria, fungi) (common)• EMF stress (common)EMF stress (common)• Heavy metal poisoning (very common, Heavy metal poisoning (very common,

most heavily studied and documented)most heavily studied and documented)• PCB (polychlorinated biphenyl HC’s) PCB (polychlorinated biphenyl HC’s)

poisoningpoisoning• Screening from history of exposure, Screening from history of exposure,

pesticides are common consider pesticides are common consider Metametrix, US Biotek Metametrix, US Biotek

Heavy metal poisoningHeavy metal poisoning

• AluminumAluminum• ArsenicArsenic• CadmiumCadmium• LeadLead• MercuryMercury• ThalliumThallium• tintin

Heavy metal poisoningHeavy metal poisoning

• Lead-greatest toxicant in hx of Lead-greatest toxicant in hx of worldworld

• mercury-signif for children, mercury-signif for children, vaccines, dental amalgams, fish, vaccines, dental amalgams, fish, water (Marin mercury is 3-4 parts per water (Marin mercury is 3-4 parts per trillion, too high per Dr. William Rea, trillion, too high per Dr. William Rea, Ctr for Env Health, Dallas, Tx)Ctr for Env Health, Dallas, Tx)

• Bay area hot spot on the mercury Bay area hot spot on the mercury map of US- San Jose mercury map of US- San Jose mercury mine,gold mining in Sierras, power mine,gold mining in Sierras, power plants, oil refiningplants, oil refining

Mercury map of USMercury map of UShttp://water.epa.gov/type/watersheds/datait/maps/posterhttp://water.epa.gov/type/watersheds/datait/maps/poster

.cfm.cfm

Heavy metal testingHeavy metal testing

• Urine fractionated porphyrins bestUrine fractionated porphyrins best• Old std: rbc or 24 hour urineOld std: rbc or 24 hour urine• Hair, may be helpful if elevated vs artifact, also Hair, may be helpful if elevated vs artifact, also

some children fail to excrete, therefore test some children fail to excrete, therefore test may be false positivemay be false positive

• Other physicians: chelation flush of heavy Other physicians: chelation flush of heavy metals, problematic if not have nutrients and if metals, problematic if not have nutrients and if not stoolingnot stooling

• High MCV on blood cell count, defic zinc, High MCV on blood cell count, defic zinc, magnesium, manganese, selenium and magnesium, manganese, selenium and molybdenummolybdenum

Heavy metal Heavy metal detoxificationdetoxification

• Stop exposure Stop exposure • Not eat mercury containing fish, not eat out of Not eat mercury containing fish, not eat out of

aluminum cans, carpet free of cadmium, no thimerosol aluminum cans, carpet free of cadmium, no thimerosol in vaccinesin vaccines

• Stooling 2-3x.dayStooling 2-3x.day• Epsom salt baths, 1 cup bath 20 minute soakEpsom salt baths, 1 cup bath 20 minute soak• Zinc, magnesium, manganese, molybdenum, seleniumZinc, magnesium, manganese, molybdenum, selenium• Amino acidsAmino acids• Antioxidants (vitamins C, E, glutathione and after body Antioxidants (vitamins C, E, glutathione and after body

cleared of heavy metal then alpha lipoic acid)cleared of heavy metal then alpha lipoic acid)• Methylation (methylb12, 5tetramethylhydrofolate)Methylation (methylb12, 5tetramethylhydrofolate)• Water filtration (distilled or reverse osmosis)Water filtration (distilled or reverse osmosis)• Chelation may be needed if genetics of detoxification Chelation may be needed if genetics of detoxification

very weak or if degree of heavy metal poisoning is very weak or if degree of heavy metal poisoning is severesevere

BiotoxinsBiotoxins

• BacteriaBacteria--Clostridium difficile (antibiotic-induced bacterial overgrowth Clostridium difficile (antibiotic-induced bacterial overgrowth

gut)gut)– PLoS One. 2010 Jun 11;5(6):e11071.PLoS One. 2010 Jun 11;5(6):e11071.

• -Staph aureus Regulation of hemolysin expression -Staph aureus Regulation of hemolysin expression and virulence of Staphylococcus aureus by a and virulence of Staphylococcus aureus by a serine/threonine kinase and phosphatase.serine/threonine kinase and phosphatase.

• Burnside KBurnside K, , LemboLembo A A, , de Los Reyes Mde Los Reyes M, , IliukIliuk A A, , BinhtranBinhtran NT NT, , Connelly JEConnelly JE, , Lin WJLin WJ, , Schmidt BZSchmidt BZ, , Richardson ARRichardson AR, , Fang FCFang FC, , Tao WATao WA, , RajagopalRajagopal L L..

• Department of Pediatric Infectious Diseases, University of Department of Pediatric Infectious Diseases, University of Washington and Seattle Children's Hospital Research Washington and Seattle Children's Hospital Research Institute, Seattle, Washington, USA.Institute, Seattle, Washington, USA.

• AbstractAbstract• Exotoxins, including the hemolysins known as the alpha Exotoxins, including the hemolysins known as the alpha

(alpha) and beta (beta) toxins, play an important role in the (alpha) and beta (beta) toxins, play an important role in the pathogenesis of Staphylococcus aureus infectionspathogenesis of Staphylococcus aureus infections

BiotoxinsBiotoxins•

– MoldMoldestrogenic mycotoxin estrogenic mycotoxin produced by severalproduced by several

fungi of Fusarium genera, a mold which fungi of Fusarium genera, a mold which can contaminate food can contaminate food Toxicon. 2010 Toxicon. 2010

Nov;56(6):956-63. Epub 2010 Jul 6.Nov;56(6):956-63. Epub 2010 Jul 6. Int J Food Microbiol. 2010 May 15;139(3):210-3. Epub 2010 Feb 13.Int J Food Microbiol. 2010 May 15;139(3):210-3. Epub 2010 Feb 13.

– Ochratoxin A production by Ochratoxin A production by Aspergillus Aspergillus isolated from isolated from cereals and cereals and derived products, dried fruits, cacao, derived products, dried fruits, cacao, grape juice grape juice Food Chem Toxicol. 2009 Food Chem Toxicol. 2009 Nov;47(11):2847-52. Epub 2009 Sep 9 and Nov;47(11):2847-52. Epub 2009 Sep 9 and grapes grapes Int J Int J Food MicrobiolFood Microbiol. 2010 May 15;139(3):210-3. Epub . 2010 May 15;139(3):210-3. Epub 2010 Feb 13.2010 Feb 13. , ,

Biotoxins, mold, cont’dBiotoxins, mold, cont’d– pistacio nuts pistacio nuts Food Microbiol. 2008 Aug;25(5):683-9. Epub 2008 Food Microbiol. 2008 Aug;25(5):683-9. Epub 2008

Mar 26. ,Mar 26. , corn, cornflakes corn, cornflakes Int J Food Microbiol. 2008 Mar Int J Food Microbiol. 2008 Mar 31;123(1-2):81-7. Epub 2007 Dec 23.31;123(1-2):81-7. Epub 2007 Dec 23.

–Distribution ofDistribution of fumonisins and aflatoxins in corn fumonisins and aflatoxins in corn fractions fractions during industrialduring industrial cornflake cornflake processing.processing.

– pine nuts pine nuts Lett Appl Microbiol. 2007 Jan;44(1):68-72.,Lett Appl Microbiol. 2007 Jan;44(1):68-72.,Contamination of pine nuts byContamination of pine nuts by fumonisin fumonisin (mycotoxin) (mycotoxin) produced by strainsproduced by strains of Fusarium of Fusarium proliferatum proliferatum isolated from Pinus pinea.isolated from Pinus pinea.

– rice rice Distribution of totalDistribution of total aflatoxins aflatoxins in milled fractions of hulled rice., Castells M, Ramos AJ, Sanchis V, Marín in milled fractions of hulled rice., Castells M, Ramos AJ, Sanchis V, Marín S.S.

– J Agric Food Chem. 2007 Apr 4;55(7):2760-4. Epub 2007 Mar 10.J Agric Food Chem. 2007 Apr 4;55(7):2760-4. Epub 2007 Mar 10.

– Colors of molds help to identify -golden Colors of molds help to identify -golden staphyloxanthin of Staphylococcus aureus staphyloxanthin of Staphylococcus aureus (bacteria), the blue-green pyocyanin of (bacteria), the blue-green pyocyanin of Pseudomonas spp., and the dark brown or black Pseudomonas spp., and the dark brown or black melanin pigments of Cryptococcus neoformans and melanin pigments of Cryptococcus neoformans and Aspergillus Aspergillus spp. Trends Microbiol. 2009 Sep;17(9):406-13. Epub spp. Trends Microbiol. 2009 Sep;17(9):406-13. Epub 2009 Aug 31. 2009 Aug 31.

Molds induce food allergies Molds induce food allergies via mycotoxinsvia mycotoxins

• Toxicol Appl Pharmacol. 2009 May 15;237(1):41-8. Toxicol Appl Pharmacol. 2009 May 15;237(1):41-8. • The The food contaminant deoxynivalenol, decreases food contaminant deoxynivalenol, decreases

intestinal barrier permeabilityintestinal barrier permeability and reduces claudin and reduces claudin expression.expression.

• PintonPinton P P, , NougayrèdeNougayrède JP JP, , Del Rio JCDel Rio JC, , Moreno CMoreno C, , Marin DEMarin DE, , Ferrier LFerrier L, , BracarenseBracarense AP AP, , Kolf-ClauwKolf-Clauw M M, , Oswald IPOswald IP, Toulouse, France., Toulouse, France.

• • Deoxynivalenol (DON) is a mycotoxin that commonly contaminates Deoxynivalenol (DON) is a mycotoxin that commonly contaminates

cereals and causes various toxicological effects. We demonstrated that, cereals and causes various toxicological effects. We demonstrated that, in intestinal epithelial cell lines from human (Caco-2) origin, DON in intestinal epithelial cell lines from human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. These alterations of barrier function were associated monolayers. These alterations of barrier function were associated with a specific reduction in the expression of claudins. In conclusion, with a specific reduction in the expression of claudins. In conclusion, DON alters claudin expression and decreases the barrier function of DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and may induce intestinal damage and has consequences for human and animal health. (JG: food allergies)animal health. (JG: food allergies)

Toxins cause oxidative Toxins cause oxidative stress, autonomic disease, stress, autonomic disease,

and proinflammationand proinflammation• Curr Opin Pediatr. 2009 Apr;21(2):222-9.Curr Opin Pediatr. 2009 Apr;21(2):222-9.• Moving towards making social toxins mainstream in children's environmental health.Moving towards making social toxins mainstream in children's environmental health.• Wright RJWright RJ..• The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical

School, 181 Longwood Avenue, Boston, MA 02067, USA. rerjw@channing.harvard.eduSchool, 181 Longwood Avenue, Boston, MA 02067, USA. rerjw@channing.harvard.edu• AbstractAbstract• PURPOSE OF REVIEW: PURPOSE OF REVIEW: Although traditional disciplinary research theory and methods have focused Although traditional disciplinary research theory and methods have focused

separately on how social and physical environmental factors affect children's health, evolving research separately on how social and physical environmental factors affect children's health, evolving research underscores important integrated effects.underscores important integrated effects.

• RECENT FINDINGS: RECENT FINDINGS: This review outlines the specific reasons why social determinants should be This review outlines the specific reasons why social determinants should be considered mainstream in children's environmental health research with particular focus on interactive considered mainstream in children's environmental health research with particular focus on interactive effects between social and physical hazards. These include sensitivity of overlapping physiological effects between social and physical hazards. These include sensitivity of overlapping physiological systems, via epigenesis, programming, and plasticity to social and physical environmental moderation systems, via epigenesis, programming, and plasticity to social and physical environmental moderation that may impact health across the life span; ways in which social environmental vulnerabilities moderate that may impact health across the life span; ways in which social environmental vulnerabilities moderate the effects of physical environmental factors, providing specific examples related to respiratory health the effects of physical environmental factors, providing specific examples related to respiratory health and neurodevelopment; overlapping exposure distribution profiles; and relevance to pediatric health and neurodevelopment; overlapping exposure distribution profiles; and relevance to pediatric health disparities.disparities.

• SUMMARY: SUMMARY: Because of the covariance across exposures, and evidence that Because of the covariance across exposures, and evidence that social stress and social stress and other environmental toxins (e.g., pollutants, tobacco smoke) other environmental toxins (e.g., pollutants, tobacco smoke) may influence common physiological pathways (e.g., oxidative may influence common physiological pathways (e.g., oxidative stress, proinflammatory immune pathways, autonomic stress, proinflammatory immune pathways, autonomic disruption),disruption), understanding the potential synergistic effects promises to more completely inform understanding the potential synergistic effects promises to more completely inform

children's environmental health risk. Although this discussion focuses around the children's environmental health risk. Although this discussion focuses around the respiratory respiratory and neurological systemsand neurological systems, these concepts extend more broadly to , these concepts extend more broadly to

children's psychological and physical developmentchildren's psychological and physical development

Treatment of toxin Treatment of toxin elevationelevation

• General principles:General principles:Organic, fresh (lessens mold ingestion), whole Organic, fresh (lessens mold ingestion), whole

foods (no preservatives)foods (no preservatives)Water filtration-distilled or reverse osmosisWater filtration-distilled or reverse osmosisDetermine exposure and stop exposureDetermine exposure and stop exposureRetest to ensure recoveringRetest to ensure recoveringBoost detoxification system of body, liverBoost detoxification system of body, liverTest phase 1 and phase 2 detox system (Genova Test phase 1 and phase 2 detox system (Genova

oxid stress)oxid stress)Antioxidants (urine lipid peroxides Genova oxid Antioxidants (urine lipid peroxides Genova oxid

stress or DNA and RNA oxidative stress, stress or DNA and RNA oxidative stress, Laboratoire Phillipe Auguste)Laboratoire Phillipe Auguste)

PCB poisoningPCB poisoning

•Polychlorinated hydrocarbons, Polychlorinated hydrocarbons, exposure from gasoline, before it exposure from gasoline, before it was removed (old filling stations, was removed (old filling stations, soil)soil)

•Test: urine fractionated Test: urine fractionated porphyrinsporphyrins

•Treatment: general detoxification Treatment: general detoxification principles, stop PICA (provide principles, stop PICA (provide minerals, nutrients, etc) minerals, nutrients, etc)

Antiinflammation improves Antiinflammation improves brain health –whether brain health –whether inflammation is from inflammation is from

allergy, infection or toxinallergy, infection or toxin• Brain Res. 2010 Jun 21;1339:60-9. Epub 2010 Apr 24.Brain Res. 2010 Jun 21;1339:60-9. Epub 2010 Apr 24.• Curcumin protects pre-oligodendrocytes from activated microglia in vitro and in vivo.Curcumin protects pre-oligodendrocytes from activated microglia in vitro and in vivo.• He LFHe LF, , Chen HJChen HJ, , QianQian LH LH, , Chen GYChen GY, , BuzbyBuzby JS JS..• Shanghai Institute for Pediatric Research, Xinhua Hospital affiliated to Shanghai Jiao Tong Shanghai Institute for Pediatric Research, Xinhua Hospital affiliated to Shanghai Jiao Tong

University School of Medicine, Shanghai, PR China. waxflying@yahoo.com.cnUniversity School of Medicine, Shanghai, PR China. waxflying@yahoo.com.cn• AbstractAbstract• Infection and inflammation leading to injury or death of pre-oligodendrocytes (preOLs) is one of Infection and inflammation leading to injury or death of pre-oligodendrocytes (preOLs) is one of

the principal initiating mechanisms in the pathogenesis of preterm periventricular leukomalacia the principal initiating mechanisms in the pathogenesis of preterm periventricular leukomalacia (PVL). The present study explores the possible protective effect of curcumin against the toxicity of (PVL). The present study explores the possible protective effect of curcumin against the toxicity of lipopolysaccharide (LPS)-activated microglia on preOLs in vitro and in vivo. In vitro, preOLs in lipopolysaccharide (LPS)-activated microglia on preOLs in vitro and in vivo. In vitro, preOLs in coculture with microglia exhibited increased apoptosis after exposure to LPS. LPS also induced coculture with microglia exhibited increased apoptosis after exposure to LPS. LPS also induced significantly increased expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase significantly increased expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase (NOX) subunits, p67-phox and gp91-phox in microglia. Our results suggest that iNOS and NOX (NOX) subunits, p67-phox and gp91-phox in microglia. Our results suggest that iNOS and NOX contribute to the apoptosis of preOLs by activated microglia. The potential anti-inflammatory contribute to the apoptosis of preOLs by activated microglia. The potential anti-inflammatory effects of curcumin were tested to determine if they could help to minimize microglia-mediated effects of curcumin were tested to determine if they could help to minimize microglia-mediated damage. Curcumin (10 microg/ml) was found to significantly inhibit the apoptosis of preOL and damage. Curcumin (10 microg/ml) was found to significantly inhibit the apoptosis of preOL and expression of either iNOS or NOX in the LPS-activated microglia. In vivo, curcumin was expression of either iNOS or NOX in the LPS-activated microglia. In vivo, curcumin was administered (50 mg/kg/day, i.p.) to two-day-old neonatal Sprague-Dawley rats subjected to administered (50 mg/kg/day, i.p.) to two-day-old neonatal Sprague-Dawley rats subjected to intracerebral injection of LPS. Treatment with curcumin either 1h before or immediately after LPS intracerebral injection of LPS. Treatment with curcumin either 1h before or immediately after LPS injection significantly ameliorated white matter injury and loss of preOLs, decreased activated injection significantly ameliorated white matter injury and loss of preOLs, decreased activated microglia, and inhibited microglial expression of iNOS and translocation of p67phox and gp91phox microglia, and inhibited microglial expression of iNOS and translocation of p67phox and gp91phox to the microglial cell membranes in neonatal rat brains following LPSto the microglial cell membranes in neonatal rat brains following LPS injection. These results suggest injection. These results suggest

that that curcumin has a protective effect on curcumin has a protective effect on infection-driven white matter injuryinfection-driven white matter injury, which is , which is associated with suppression of iNOS and NOX activation. Consequently, curcumin may have potential as a protective associated with suppression of iNOS and NOX activation. Consequently, curcumin may have potential as a protective

agent against immature white matter injuryagent against immature white matter injury..

ResourcesResources

PharmaciesPharmacies

• Compounding pharmaciesCompounding pharmaciesRoss Valley , Greenbrae, Marin County, CA 415 Ross Valley , Greenbrae, Marin County, CA 415 924-2454924-2454

• Nutrient recipe based:Nutrient recipe based:Amino acid recipe powder-HRI pharmacy, Amino acid recipe powder-HRI pharmacy, Warrenville, IL, 630 505-0300Warrenville, IL, 630 505-0300Multivitamin/multimineral powder-HRI pharmacyMultivitamin/multimineral powder-HRI pharmacy

• Sterile injectablesSterile injectablesAbbott’s-Berkeley, California, 510 548-8777Abbott’s-Berkeley, California, 510 548-8777Grandpa’s pharmacy, Placerville, California, 530 Grandpa’s pharmacy, Placerville, California, 530 622-2323622-2323Hopewell, Hopewell, NJ, 800 792 6670Hopewell, Hopewell, NJ, 800 792 6670

LabsLabs

• Labs Labs • Doctor’s Data West Chicago, IL, 800 323-Doctor’s Data West Chicago, IL, 800 323-

27842784, , www.doctorsdata.comwww.doctorsdata.com

• Genova Asheville, NC, 800 522-4762, Genova Asheville, NC, 800 522-4762, www.GDX.netwww.GDX.net

• Great Plains, Lenexa, KS, 913 341-8949, Great Plains, Lenexa, KS, 913 341-8949, www.greatplainslaboratory.comwww.greatplainslaboratory.com

• Igenex, Palo Alto, CA 800 832-3200, Igenex, Palo Alto, CA 800 832-3200, www.igenex.comwww.igenex.com

• Meridian Valley Lab, Renton, WA 425 271-8689 Meridian Valley Lab, Renton, WA 425 271-8689 www.www.meridianvalleymeridianvalleylab.comlab.com

• Metametrix, Duluth, GA, 800 221-4640, Metametrix, Duluth, GA, 800 221-4640, www.metametrix.comwww.metametrix.com

Useful websitesUseful websites• http://www.autism.comhttp://www.autism.com The Autism Research Institute (ARI) is the The Autism Research Institute (ARI) is the

hub of a worldwide network of parents and hub of a worldwide network of parents and professionals concerned with autismprofessionals concerned with autism

• http://www.childneurologysociety.org/http://www.childneurologysociety.org/The Child Neurology Society is the The Child Neurology Society is the preeminent non-profit professional preeminent non-profit professional association of pediatric neurologists in the association of pediatric neurologists in the United States United States

• http://www.ldonline.org/questions/nonverbalhttp://www.ldonline.org/questions/nonverbal Comprehensive site, lots of info, can ask Comprehensive site, lots of info, can ask

questions of experts, glossary, definitions of questions of experts, glossary, definitions of LDLD

More websitesMore websites

• http://www.interdys.org/http://www.interdys.org/ The International Dyslexia Association (IDA) is The International Dyslexia Association (IDA) is

a non-profit organization dedicated to helping a non-profit organization dedicated to helping individuals with dyslexia, their families and the individuals with dyslexia, their families and the communities that support them communities that support them

• http://ilads.org/http://ilads.org/ International Lyme And Associated Diseases International Lyme And Associated Diseases

Society Society ILADS promotes understanding of Lyme and its ILADS promotes understanding of Lyme and its

associated diseases through research and associated diseases through research and education education