1. 11
An Allergist/Immunologist’sAn Allergist/Immunologist’s
perspective on theperspective on the
behavioral andbehavioral and
developmental disorders indevelopmental disorders in
PediatricsPediatrics
John A. Moissidis, MDJohn A. Moissidis, MD
ALLERGY/IMMUNOLOGY for CHILDREN &ALLERGY/IMMUNOLOGY for CHILDREN &
ADULTSADULTS
DiplomateDiplomate ,, American Board of Pediatrics &American Board of Pediatrics &
American Board of Allergy/ImmunologyAmerican Board of Allergy/Immunology
Affiliated with HYGEIA-MITERA hospitals andAffiliated with HYGEIA-MITERA hospitals and
EUROCLINICEUROCLINIC

2. 2
Non IgE mechanisms may play a role in Allergy as well

3. 3
Allergens and allergic diseasesAllergens and allergic diseases

4. 4
Food sensitivity inFood sensitivity in
Central Nervous System disordersCentral Nervous System disorders
• CASE 1CASE 1
• 10 years old male with ADHD (erratic hyperactivity, sleeplessness,10 years old male with ADHD (erratic hyperactivity, sleeplessness,
dyslexia, reduced attention & concentration, belligerence); Ritalin nodyslexia, reduced attention & concentration, belligerence); Ritalin no
help.help.
• Episodic sweats, edema, painful erythema of the face and ears,Episodic sweats, edema, painful erythema of the face and ears,
injected eyes, throat clogging.injected eyes, throat clogging.
• Work up: CMA in infancy, now AR, BA, eczema. Food allergy inWork up: CMA in infancy, now AR, BA, eczema. Food allergy in
family, skin tests to aeroallergens and food allergens causedfamily, skin tests to aeroallergens and food allergens caused
generalized symptoms.generalized symptoms.
• He craved sugar so much that he scooped up and ate handfuls fromHe craved sugar so much that he scooped up and ate handfuls from
bowls-he did the same with potato chips.bowls-he did the same with potato chips.
• Diet elimination and challenge:Diet elimination and challenge:
• Sugar: facial, ocular, ear inflammation, Wheat: hyperactivity, tomato:Sugar: facial, ocular, ear inflammation, Wheat: hyperactivity, tomato:
belligerent behavior, milk: throat clogging, red food dye: asthma.belligerent behavior, milk: throat clogging, red food dye: asthma.
• Management:Management: Totally asymptomatic on diet rotating safeTotally asymptomatic on diet rotating safe
food, symptoms return on dietary indiscretionfood, symptoms return on dietary indiscretion

5. 5
Food sensitivity inFood sensitivity in
Central Nervous System disordersCentral Nervous System disorders
• CASE 2CASE 2
• 6 years old male with bizarre CNS dysfunction (hyperactivity and6 years old male with bizarre CNS dysfunction (hyperactivity and
autistic features) since 9 mo, daily excruciating headaches.autistic features) since 9 mo, daily excruciating headaches.
• Chronic rhinitis and recurrent otitis media from 2 mo; some foodsChronic rhinitis and recurrent otitis media from 2 mo; some foods
with dyes (Fruit loops, Kool Aid, Skittles) dramatically worsenwith dyes (Fruit loops, Kool Aid, Skittles) dramatically worsen
behavior for several hours; little help from dexedrine and Prozacbehavior for several hours; little help from dexedrine and Prozac
• RAST results (-) for 11 common food allergensRAST results (-) for 11 common food allergens;; eliminationelimination ofof
additives and common foodsadditives and common foods led to 3 days of sleepled to 3 days of sleep
“drunken” behavior followed by unusually persisting calm“drunken” behavior followed by unusually persisting calm
behavior & absence of H/As; Rhinitis improved;behavior & absence of H/As; Rhinitis improved;
• Daily reintroduction of several test foods led to recognition ofDaily reintroduction of several test foods led to recognition of
multiple offendersmultiple offenders
• Course:Course: On long term elimination diet: CNS virtuallyOn long term elimination diet: CNS virtually
NORMAL,NORMAL, except for delayed development and some autisticexcept for delayed development and some autistic
features; no H/A, no need for psychotropic drugs, no evidence offeatures; no H/A, no need for psychotropic drugs, no evidence of
rhinitis or otitisrhinitis or otitis

6. 6
Conclusions- Food and the CNSConclusions- Food and the CNS
• The subject has a variety of associated “allergic” symptoms orThe subject has a variety of associated “allergic” symptoms or
conditions e.g. rhinitis and eczema.conditions e.g. rhinitis and eczema.
• The CNS dysfunction is erratic on a day-to-day basis (one day aThe CNS dysfunction is erratic on a day-to-day basis (one day a
saint, another day monster).saint, another day monster).
• Certain foods and additives have been observed toCertain foods and additives have been observed to
provoke marked CNS dysfunction (e.g. hyperactivity) forprovoke marked CNS dysfunction (e.g. hyperactivity) for
periods lasting several hours after ingestion.periods lasting several hours after ingestion.

7. 7
Effects of Food Allergy on the CentralEffects of Food Allergy on the Central
Nervous SystemNervous System
• Foods, food additives and contaminants canFoods, food additives and contaminants can
affect the CNS in several different ways:affect the CNS in several different ways:
• Pharmacological/toxicologicalPharmacological/toxicological effects e.g. exorphins, xanthines,effects e.g. exorphins, xanthines,
tyramine or histamine,tyramine or histamine,
• ImmunologicalImmunological processes e.g. immune complexesprocesses e.g. immune complexes
• Endogenous mediatorsEndogenous mediators e.g. peptides, cytokines, prostaglandinse.g. peptides, cytokines, prostaglandins
• Metabolic changesMetabolic changes e.g. neurotransmitter precursors, enzymee.g. neurotransmitter precursors, enzyme
defectsdefects
• Neurophysiologic effectsNeurophysiologic effects e.g. limbic and mesolimbic pathwaye.g. limbic and mesolimbic pathway
sensitizationsensitization
None of the previous possible mechanisms derives directly from an IgE-None of the previous possible mechanisms derives directly from an IgE-
mediated process.mediated process.
May be better termed as food sensitivities or food intoleranceMay be better termed as food sensitivities or food intolerance

8. 8
Potential relationship between adversePotential relationship between adverse
reactions to foods & behavioral changesreactions to foods & behavioral changes
• TheThe discomfort of symptomsdiscomfort of symptoms associated with food allergies orassociated with food allergies or
intolerance causesintolerance causes secondary emotional reactions.secondary emotional reactions.
• Psychological problems may either directly cause orPsychological problems may either directly cause or
exacerbate allergic symptoms.exacerbate allergic symptoms. TheThe onsetonset ofof
symptoms following exposure to a food allergen leads tosymptoms following exposure to a food allergen leads to intenseintense
anxietyanxiety and significant worsening of the symptoms.and significant worsening of the symptoms.
• There could be also aThere could be also a common causal mechanism-common causal mechanism-
genetic, neuroendocrine, immunologic, or environmental- behindgenetic, neuroendocrine, immunologic, or environmental- behind
both psychological problems and allergic diseaseboth psychological problems and allergic disease

9. 9
Different studies- evidence of a link-Different studies- evidence of a link-
between psychological factors and allergybetween psychological factors and allergy
• Asthmatic patientsAsthmatic patients have been suggested tohave been suggested to be less dominant,be less dominant,
more anxious, and more depressedmore anxious, and more depressed than equivalent controls.than equivalent controls.
• AmongAmong collegecollege students,students, depressiondepression has ahas a higherhigher prevalenceprevalence
amongamong asthmatics.asthmatics.
• ShynessShyness was reported more frequently inwas reported more frequently in hay fever sufferers.hay fever sufferers.
• AtopicAtopic dermatitisdermatitis patients often reportpatients often report sleepingsleeping problems due toproblems due to
itchiness.itchiness.
• Anxiety and depression during stressful periodsAnxiety and depression during stressful periods directlydirectly
enhanceenhance eosinophilic inflammation in response to allergen.eosinophilic inflammation in response to allergen.

10. 10
Study-Asthma and depression / anxietyStudy-Asthma and depression / anxiety
disorders among young personsdisorders among young persons
• Background:Background: AsthmaAsthma andand depression/anxietydepression/anxiety were studied in awere studied in a
cohort of over 1000 young persons over a 21-years period.cohort of over 1000 young persons over a 21-years period.
• Results: Asthma in adolescent and young adulthood was associatedResults: Asthma in adolescent and young adulthood was associated
withwith increased likehood of major depression, panic attacks andincreased likehood of major depression, panic attacks and
anxiety disorders.anxiety disorders.
• The weight of evidence of this study suggests that theseThe weight of evidence of this study suggests that these
associations may reflectassociations may reflect effects of common factorseffects of common factors ratherrather
than direct causal link.than direct causal link.

11. 11
Study-Relation between behavior andStudy-Relation between behavior and
asthma in children with atopic dermatitisasthma in children with atopic dermatitis
• Behavioral problems mayBehavioral problems may precedeprecede asthma onset in young atopicasthma onset in young atopic
children.children.
• In this age group, behavioral problems areIn this age group, behavioral problems are notnot secondarysecondary
psychological reactions to asthma onset.psychological reactions to asthma onset.
• They may act as a marker for stress in the child’s life.They may act as a marker for stress in the child’s life.
• The presence of behavioral problems should alert physicians thatThe presence of behavioral problems should alert physicians that
the child may be at increased risk for transition from Atopicthe child may be at increased risk for transition from Atopic
Dermatitis to Asthma.Dermatitis to Asthma.
Behavior as a precursor of asthma onset

12. 12
Genetic FactorsGenetic Factors
• Both psychological diseases and allergy have a genetic basis.Both psychological diseases and allergy have a genetic basis.
• One studyOne study has investigatedhas investigated allergy in first and second-allergy in first and second-
degree relatives of young children withdegree relatives of young children with inhibited (shy)inhibited (shy)
behaviorbehavior.. There was aThere was a greater prevalence of hay fevergreater prevalence of hay fever
and eczema in the relatives.and eczema in the relatives.
• Conclusion:Conclusion: complex genetic factorscomplex genetic factors -mediating extreme-mediating extreme
degrees of shyness-degrees of shyness- may be responsible for influencingmay be responsible for influencing
immunological vulnerability to eczema and hay fever.immunological vulnerability to eczema and hay fever.

13. 13
Pharmacological effects of FoodPharmacological effects of Food
• Caffeine.Caffeine. In the coffee exhibits potent pharmacological properties byIn the coffee exhibits potent pharmacological properties by
directly activating the cerebral cortex.directly activating the cerebral cortex.
• ChocolateChocolate containscontains vasoactive aminesvasoactive amines —histamine, tryptophan-—histamine, tryptophan-
serotonine, methylxanthine & theobromine.serotonine, methylxanthine & theobromine.
• TyramineTyramine in cheesein cheese andand histaminehistamine in fermented foods andin fermented foods and
poorly stored scomboid fishpoorly stored scomboid fish affects behavior.affects behavior.
• Peptides inPeptides in milkmilk andand wheatwheat containcontain exorthine-like activityexorthine-like activity thatthat
might be predicted to affect behavior.might be predicted to affect behavior.
• Amino acids likeAmino acids like tryptophantryptophan, a precursor of serotonin, may also be, a precursor of serotonin, may also be
predicted topredicted to affect behavior, mood and appetite in highaffect behavior, mood and appetite in high
concentrationsconcentrations
• SerotonineSerotonine influences the degree of hunger for carbohydratesinfluences the degree of hunger for carbohydrates
• Some foods have been hypothesized to induceSome foods have been hypothesized to induce changes in brainchanges in brain
blood perfusionblood perfusion that can mimic the abnormalities found inthat can mimic the abnormalities found in
patients with developmental learning difficultiespatients with developmental learning difficulties
• Food coloring agentFood coloring agent tartrazinetartrazine cancan affectaffect histaminehistamine releaserelease byby
accentuating hyperactive behavioraccentuating hyperactive behavior .. Similar effects may occurSimilar effects may occur
with strawberries, tomatoes, pineapple and alcohol.with strawberries, tomatoes, pineapple and alcohol.

14. 14
Reactive HypoglycemiaReactive Hypoglycemia
• It has been suggested that individuals withIt has been suggested that individuals with high sugar intakehigh sugar intake
developdevelop reactivereactive hypoglycemiahypoglycemia which produces anwhich produces an aberrationaberration inin
behavior and cognitive function and performancebehavior and cognitive function and performance

15. 15
Squash Drinking SyndromeSquash Drinking Syndrome
• A surveyA survey of the drinking habits of 2-7 years oldof the drinking habits of 2-7 years old
children found thatchildren found that very fewvery few now drink water.now drink water.
• Squash,Squash, a soft drink, was by far the most frequentlya soft drink, was by far the most frequently
consumed drink and in some preschool kids constitutedconsumed drink and in some preschool kids constituted
as much as 50% of recommended daily energy intake.as much as 50% of recommended daily energy intake.
• A group of kidsA group of kids were described who were referred with awere described who were referred with a
range of problems includedrange of problems included poor appetite,poor appetite,
behavioral problems, poor weight gain andbehavioral problems, poor weight gain and
loose stools.loose stools.
• The children received a high percentage of theirThe children received a high percentage of their
daily energy requirements in the form of high-daily energy requirements in the form of high-
energy drinks.energy drinks.
• Their appetite had been poor during meals as aTheir appetite had been poor during meals as a
consequence of the high-energy drinks theyconsequence of the high-energy drinks they
consumed during the day.consumed during the day.

16. 16
Celiac Disease and Psychiatric DisordersCeliac Disease and Psychiatric Disorders
• CD orCD or gluten sensitive-enteropathygluten sensitive-enteropathy is a chronic disease of theis a chronic disease of the
small intestinal mucosa associated with intermittent diarrhea,small intestinal mucosa associated with intermittent diarrhea,
abdominal pain, distention & irritability induced by gliadin, theabdominal pain, distention & irritability induced by gliadin, the
prolamin protein of wheat.prolamin protein of wheat.
• High prevalence of anxiety and depression in CD has beenHigh prevalence of anxiety and depression in CD has been
attributed to the reduction of theattributed to the reduction of the Quality of LifeQuality of Life due to chronicdue to chronic
disease &disease & secondary to reduction of brain monoaminesecondary to reduction of brain monoamine
metabolism due to either malabsortion or impairedmetabolism due to either malabsortion or impaired
transport.transport.
• Significant decrease in anxiety on gluten-free dietSignificant decrease in anxiety on gluten-free diet (reactive(reactive
anxiety)anxiety) and depressionand depression after 6 months on oral pyridoxineafter 6 months on oral pyridoxine
(vitamin B6) diet—suggestive of the metabolic effects of(vitamin B6) diet—suggestive of the metabolic effects of pyridoxinepyridoxine
deficiency on the CNS mechanisms regulating mood in CD.deficiency on the CNS mechanisms regulating mood in CD.

17. 17
Narcolepsy and Food intolerance/addictionNarcolepsy and Food intolerance/addiction
• Narcolepsy is a neurological disorder of REM sleep, characterizedNarcolepsy is a neurological disorder of REM sleep, characterized
byby excessive daytime sleepinessexcessive daytime sleepiness with overpowering sleepwith overpowering sleep
attacks, disrupted nocturnal sleep, cataplexy & hypnagogicattacks, disrupted nocturnal sleep, cataplexy & hypnagogic
hallucinations.hallucinations.
• NarcolepticsNarcoleptics endorse significantly more food cravings,endorse significantly more food cravings,
especially for milk and sweets and more food-induced GIespecially for milk and sweets and more food-induced GI
upsets (from alcohol, Mexican food, candy, onion, pork,upsets (from alcohol, Mexican food, candy, onion, pork,
sausage, popcorn, soda and chocolate) than normalsausage, popcorn, soda and chocolate) than normal
controls.controls.
• It is due to dysfunction ofIt is due to dysfunction of receptors and/or neurochemicalreceptors and/or neurochemical
imbalancesimbalances affecting specificaffecting specific dopaminergicdopaminergic neurons in the limbicneurons in the limbic
system.system.

18. 18
Migraine in ChildhoodMigraine in Childhood
• Recurrent headaches with symptoms freeRecurrent headaches with symptoms free
intervalsintervals plusplus
• Three of the following: abdominal pain or nausea or vomiting,Three of the following: abdominal pain or nausea or vomiting,
unilateral throbbing, relief after sleep, aura (visual, sensory, motor)unilateral throbbing, relief after sleep, aura (visual, sensory, motor)
and family history.and family history.
• PrecipitatingPrecipitating factors; Emotional stress, food, trauma, exertion, URI,factors; Emotional stress, food, trauma, exertion, URI,
hypoglycemia, lactose intolerance, irregular sleep, travel, brighthypoglycemia, lactose intolerance, irregular sleep, travel, bright
light, hormonal.light, hormonal.
• Humoral factors suspected to be involved in the pathogenesisHumoral factors suspected to be involved in the pathogenesis
includeinclude serotonin, histamine, PGL, LTR, Sub P, catecholamines,serotonin, histamine, PGL, LTR, Sub P, catecholamines,
tyramine and phenylethamine.tyramine and phenylethamine.
• TreatmentTreatment: reassurance, pharmacotherapy & behavioral treatment.: reassurance, pharmacotherapy & behavioral treatment.

19. 19
Diet and migraineDiet and migraine
• Tyramine hypothesis:Tyramine hypothesis: It might precipitate H/A’s- it is rich inIt might precipitate H/A’s- it is rich in
pickled herring, chicken livers, canned figs, bananas, pineapple &pickled herring, chicken livers, canned figs, bananas, pineapple &
tomatoes,tomatoes, fishfish,, chocolatechocolate,, alcoholic beveragesalcoholic beverages, and fermented foods, and fermented foods
such assuch as cheesecheese,, soy saucesoy sauce and soy bean,and soy bean, processed meatprocessed meat, and, and
red winered wine..
• Food allergy hypothesis:Food allergy hypothesis: Oligoantigenic diet (elimination andOligoantigenic diet (elimination and
reintroduction).reintroduction).
• Oligoantigenic diets are very demanding and potentially dangerousOligoantigenic diets are very demanding and potentially dangerous
(malnutrition). Should be recommended only for patients with severe(malnutrition). Should be recommended only for patients with severe
and frequent attacks of migraine.and frequent attacks of migraine.
• Rotating diets (diets in whichRotating diets (diets in which majormajor items are eliminateditems are eliminated oneone oror twotwo
at a time) are sometimes used in patients with fewer attacks.at a time) are sometimes used in patients with fewer attacks.
• On diet,On diet, cigarette smoking, pollens, perfumes and other inhalantscigarette smoking, pollens, perfumes and other inhalants
continue to trigger attacks of migraine- role of inhaled antigens ascontinue to trigger attacks of migraine- role of inhaled antigens as
well.well.

20. 20
The Food Allergy HypothesisThe Food Allergy Hypothesis
• IdealIdeal oligoantigenicoligoantigenic dietdiet (turkey, cabbage, sprouts, cauliflower,(turkey, cabbage, sprouts, cauliflower,
broccoli, potato, banana, soya oil, water, salt, calcium and vitamins)broccoli, potato, banana, soya oil, water, salt, calcium and vitamins)
• AlternativeAlternative oligoantigenicoligoantigenic diet –diet – (lamb, carrots, parsnips, rice,(lamb, carrots, parsnips, rice,
pears, sunflower oil, water, salt, calcium and vitamins).pears, sunflower oil, water, salt, calcium and vitamins).
• ModifiedModified oligoantigenicoligoantigenic dietdiet (greater variety of foods which(greater variety of foods which
seldom provoked symptoms in the early patients).seldom provoked symptoms in the early patients).
• Free of colors medicines were also given.Free of colors medicines were also given.

21. 21
The hyperkinetic syndromeThe hyperkinetic syndrome
• HyperactivityHyperactivity: short attention span, impulsive behavior &: short attention span, impulsive behavior &
overactivity associated with aggressiveness,overactivity associated with aggressiveness,
distractibility, excitability, disinhibition and sudden mooddistractibility, excitability, disinhibition and sudden mood
changes.changes.
• Aggressive and antisocial behavior, specific learningAggressive and antisocial behavior, specific learning
problems and emotional lability are part of the syndrome.problems and emotional lability are part of the syndrome.
• 1.2% to 20% of all school kids.1.2% to 20% of all school kids.
• Male to female 4:1 to 6:1Male to female 4:1 to 6:1
• Overactivity per se diminishes with ageOveractivity per se diminishes with age,, but psychoticbut psychotic
and criminal behavior often become majorand criminal behavior often become major
issues.issues.

22. 22
The hyperkinetic syndromeThe hyperkinetic syndrome
• Suspected causes:Suspected causes: Inherited hyperkinetic syndrome,Inherited hyperkinetic syndrome,
adverse psychological situations, brain damage andadverse psychological situations, brain damage and
dysfunction, epilepsy, anticonvulsants, lead poisoning,dysfunction, epilepsy, anticonvulsants, lead poisoning,
maternal smoking and alcohol intake during pregnancy,maternal smoking and alcohol intake during pregnancy,
atopy,atopy, sensitivity to ASA and synthetic foodsensitivity to ASA and synthetic food
additives and food allergy.additives and food allergy.
• Genetic predisposition.Genetic predisposition.
• Effect of diet:Effect of diet: FeingoldFeingold reported thatreported that 70% of70% of
overactive children responded to a diet avoidingoveractive children responded to a diet avoiding
coloring, preservatives and ASAcoloring, preservatives and ASA ,, but controlledbut controlled
studies did not show such an effect.studies did not show such an effect.
• Randolph proposed thatRandolph proposed that any food could cause itany food could cause it &&
this hypothesis was supported by a big DBPC crossoverthis hypothesis was supported by a big DBPC crossover
trial.trial.

23. 23
The hyperkinetic syndrome-The hyperkinetic syndrome-
TherapyTherapy
• Psychostimulants-Psychostimulants- amphetamines, dexamphetamines andamphetamines, dexamphetamines and
methylphenidate (Ritalin).methylphenidate (Ritalin).
– They increase the alertness and control of theThey increase the alertness and control of the
attention process and decrease socially inappropriateattention process and decrease socially inappropriate
behavior.behavior.
– Side effects are insomnia, appetite suppression,Side effects are insomnia, appetite suppression,
tachycardia abdominal pain, weight loss, growthtachycardia abdominal pain, weight loss, growth
suppression.suppression.
• Behavioral therapy.Behavioral therapy.
• Diet.Diet.

24. 24
Study-Effects of Diets High in Sucrose orStudy-Effects of Diets High in Sucrose or
Aspartame on the Behavior and CognitiveAspartame on the Behavior and Cognitive
Performance of ChildrenPerformance of Children (NEJM)(NEJM)
• Background:Background: Both dietary sucrose and the sweetenerBoth dietary sucrose and the sweetener
aspartameaspartame have been reported tohave been reported to produce hyperactivity andproduce hyperactivity and
behavioral problems in childrenbehavioral problems in children
• Methods: DB two groups-Methods: DB two groups- 25 normal preschool and 23 school25 normal preschool and 23 school
children described as sensitive to sugar.children described as sensitive to sugar.
– One dietOne diet highhigh in sugar,in sugar, nono aspartame,aspartame,
– Second diet wasSecond diet was lowlow in sugar &in sugar & containedcontained aspartame,aspartame,
– ThirdThird lowlow in sugar andin sugar and saccharinsaccharin (placebo) as a sweetener.(placebo) as a sweetener.
• Conclusions:Conclusions: Even when intake exceeds typical dietary levels,Even when intake exceeds typical dietary levels,
neither dietary sucrose, nor aspartame affectsneither dietary sucrose, nor aspartame affects
children's behavior or cognitive function.children's behavior or cognitive function.

25. 25
Study-Dietary characteristicsStudy-Dietary characteristics
of hyperactive & control boysof hyperactive & control boys
• The mothersThe mothers of 32 hyperactive boys 7-12 years old and 26of 32 hyperactive boys 7-12 years old and 26
matched controls completed amatched controls completed a 3-day diet records and food3-day diet records and food
frequency interviews.frequency interviews.
• TheThe hyperactive boyshyperactive boys were also evaluated for impulsivity,were also evaluated for impulsivity,
compliance, attention, motor activity, memory and learning.compliance, attention, motor activity, memory and learning.
• No differences were found in any of the measures ofNo differences were found in any of the measures of
dietary content between the hyperactive and the controldietary content between the hyperactive and the control
groups.groups.
• Conclusion:Conclusion: The diets of a group of hyperactiveThe diets of a group of hyperactive boys wereboys were similarsimilar
to those of ato those of a controlcontrol group.group.

26. 26
The Food Allergy HypothesisThe Food Allergy Hypothesis
• Double-blind trial. Seventy-six childrenDouble-blind trial. Seventy-six children socially handicapped bysocially handicapped by
behavior and hyperactivity.behavior and hyperactivity.
• 82% responded to an oligoantigenic diet.82% responded to an oligoantigenic diet. OnlyOnly
27% recovered completely.27% recovered completely. Most of the associated symptomsMost of the associated symptoms
also improved with diet.also improved with diet.
• During the reintroduction, the commonest foods thatDuring the reintroduction, the commonest foods that
caused the problem werecaused the problem were tartrazine and benzoictartrazine and benzoic
acid.acid. The interval between the provoking food andThe interval between the provoking food and
reaction varied from a few minutes to more than 7 daysreaction varied from a few minutes to more than 7 days
but usually 2-3 days. There was NO difference betweenbut usually 2-3 days. There was NO difference between
synthetic additives and foods.synthetic additives and foods.
• The oligoantigenic diet: one meat, one carbohydrateThe oligoantigenic diet: one meat, one carbohydrate
source a few vegetables (brassicas) and one fruit.source a few vegetables (brassicas) and one fruit.

27. 27
The Food Allergy HypothesisThe Food Allergy Hypothesis
• IdealIdeal oligoantigenicoligoantigenic dietdiet (turkey, cabbage, sprouts, cauliflower,(turkey, cabbage, sprouts, cauliflower,
broccoli, potato, banana, soya oil, water, salt, calcium and vitamins)broccoli, potato, banana, soya oil, water, salt, calcium and vitamins)
• AlternativeAlternative oligoantigenicoligoantigenic diet –diet – (lamb, carrots, parsnips, rice,(lamb, carrots, parsnips, rice,
pears, sunflower oil, water, salt, calcium and vitamins).pears, sunflower oil, water, salt, calcium and vitamins).
• ModifiedModified oligoantigenicoligoantigenic dietdiet (greater variety of foods which(greater variety of foods which
seldom provoked symptoms in the early patients).seldom provoked symptoms in the early patients).
• Free of colors medicines were also given.Free of colors medicines were also given.

28. 28
Vitamins and minerals whichVitamins and minerals which will bewill be
affected by restricted dietaffected by restricted diet
AllergeAllerge
nn
Vitamin and MineralsVitamin and Minerals
MilkMilk Vitamin A, vitamin D, riboflavin,Vitamin A, vitamin D, riboflavin,
pantothenic acid, vitamin Bpantothenic acid, vitamin B1212 , calcium, &, calcium, &
phosphorusphosphorus
EggEgg Vitamin B12, riboflavin, pantothenic acid,Vitamin B12, riboflavin, pantothenic acid,
biotin, & selenium.biotin, & selenium.
SoySoy Thiamin, riboflavin, pyridoxine, folate,Thiamin, riboflavin, pyridoxine, folate,
calcium, phosphorus, magnesium, iron, &calcium, phosphorus, magnesium, iron, &
zinczinc
WheatWheat Thiamin, riboflavin, niacin, iron, & folate ifThiamin, riboflavin, niacin, iron, & folate if
fortifiedfortified
PeanutPeanut Vitamin E, niacin, magnesium, manganese,Vitamin E, niacin, magnesium, manganese,
& chromium& chromium

29. 29
Who should be treated by diet?Who should be treated by diet?
• Diets are socially disruptive, expensive and dangerous if notDiets are socially disruptive, expensive and dangerous if not
properly supervised and areproperly supervised and are justified only in patients withjustified only in patients with
severe disease.severe disease.
• MostMost of the hyrerkinetic associated symptoms ofof the hyrerkinetic associated symptoms of
recurrent abdominal pains and H/A’s as well as achingrecurrent abdominal pains and H/A’s as well as aching
limbs, excessive thirst, enuresus and feverlimbs, excessive thirst, enuresus and fever are relievedare relieved
on oligoantigenic diets.on oligoantigenic diets.
• The combination of symptoms often suggest anThe combination of symptoms often suggest an underlyingunderlying
psychosomatic illness.psychosomatic illness.
• These symptoms are caused byThese symptoms are caused by FOOD ALLERGYFOOD ALLERGY andand
polysymptomatic patients often respond to diet as well as those withpolysymptomatic patients often respond to diet as well as those with
single symptoms.single symptoms.
• Family pressures. Children in aFamily pressures. Children in a negative parent-childnegative parent-child
environment are not suitable for dietary therapyenvironment are not suitable for dietary therapy asas
adverse psychosocial situationsadverse psychosocial situations affect a dietary response.affect a dietary response.

30. 30
Trace elements in child hyperkineticTrace elements in child hyperkinetic
disordersdisorders
ESSENTIALS TRACE ELEMENTS
• Zinc:Zinc: thethe most important essential trace element in human behaviormost important essential trace element in human behavior
Reduced melatonin and serotonin associated with ZINC deficiency,Reduced melatonin and serotonin associated with ZINC deficiency,
which is found in high prevalencewhich is found in high prevalence in conduct disorders andin conduct disorders and
ADHDADHD
• Iron deficiencyIron deficiency is associated with impaired learned motoris associated with impaired learned motor
behavior and cognitive functionbehavior and cognitive function
• Magnesium deficiencyMagnesium deficiency causes sweating, apathy, depression,causes sweating, apathy, depression,
poor memory, mild to moderate delirium, convulsions, muscularpoor memory, mild to moderate delirium, convulsions, muscular
twitching and tremors.twitching and tremors.
• Chromium and seleniumChromium and selenium have been implicated, but furtherhave been implicated, but further
studies need to be done.studies need to be done.

31. 31
NON-ESSENTIAL ORNON-ESSENTIAL OR
TOXIC TRACE ELEMENTSTOXIC TRACE ELEMENTS
• Lead-Lead- negative classroom behaviors, juvenile delinquency andnegative classroom behaviors, juvenile delinquency and
violent behaviorviolent behavior
• Cadmium-Cadmium- childhood aggressionchildhood aggression
• Aluminum-Aluminum- antisocial behavior and learning problemsantisocial behavior and learning problems
• Mercury-Mercury-neurotoxinneurotoxin
• Trace elements analysis ofTrace elements analysis of three groups of young offendersthree groups of young offenders ––
28 violent offenders, 15 who had committed armed robbery, and 2528 violent offenders, 15 who had committed armed robbery, and 25
burglary- showedburglary- showed cleared evidence ofcleared evidence of raisedraised lead, aluminum andlead, aluminum and
cadmium, andcadmium, and decreaseddecreased iron, chromium, calcium, selenium andiron, chromium, calcium, selenium and
zinc in blood and washed scalp hair.zinc in blood and washed scalp hair.

32. 32
Azo Dyes on Hyperactive childrenAzo Dyes on Hyperactive children
• A study of 486 hyperactive children showed that more thanA study of 486 hyperactive children showed that more than 60%60%
had a positive behavioral response in consuminghad a positive behavioral response in consuming beveragebeverage
containingcontaining tartrazine, sunset yellow, or amaranth.tartrazine, sunset yellow, or amaranth.
• These patients had significantThese patients had significant reductions in blood serum Zincreductions in blood serum Zinc
and increased urine Zincand increased urine Zinc output following the drinking ofoutput following the drinking of
beverages containing the above chemicals.beverages containing the above chemicals.
• TheThe mode of actionmode of action of these azo dyes and other chemicals thatof these azo dyes and other chemicals that
induce behavioral changes isinduce behavioral changes is not knownnot known..
• AA diet or environment free of these chemicalsdiet or environment free of these chemicals has beenhas been
shown to improve the behavior and well being ofshown to improve the behavior and well being of
hyperkinetic children.hyperkinetic children.

33. 33
Study-The effects of an artificial foodStudy-The effects of an artificial food
colorings and benzoate preservativecolorings and benzoate preservative
challenge on hyperactivity in the generalchallenge on hyperactivity in the general
population sample of preschool childrenpopulation sample of preschool children
• Methods: 1873 children subjected to a dietary challenge with a drinkMethods: 1873 children subjected to a dietary challenge with a drink
containingcontaining artificial colorings and Benzoate preservatives.artificial colorings and Benzoate preservatives.
Behavior was assessed by a tester blind to dietary status and byBehavior was assessed by a tester blind to dietary status and by
parents’ ratings.parents’ ratings.
• Conclusions: There is a general adverse effect of artificial foodConclusions: There is a general adverse effect of artificial food
coloring & benzoate preservatives on the behavior of 3coloring & benzoate preservatives on the behavior of 3
year old children which is detectable by parents, but notyear old children which is detectable by parents, but not
by a simple clinic assessment.by a simple clinic assessment.
• Subgroup areSubgroup are NOT made more vulnerableNOT made more vulnerable to this effect by theirto this effect by their
prior levels of hyperactivity or by atopy.prior levels of hyperactivity or by atopy.

34. 34
Autistic Spectrum DisordersAutistic Spectrum Disorders
(ASD)(ASD)

35. 35
Autistic Spectrum Disorders (ASD)Autistic Spectrum Disorders (ASD)
• Collection of disorders:Collection of disorders: deficits in communication,deficits in communication,
social interaction and behaviorsocial interaction and behavior
• Large genetic component, with unknown etiologyLarge genetic component, with unknown etiology
• Associated medical disorders or symptomsAssociated medical disorders or symptoms ::
seizures, immune system dysregulation, GI symptomsseizures, immune system dysregulation, GI symptoms
(diarrhea, GERD, constipation, abdominal pain and(diarrhea, GERD, constipation, abdominal pain and
others).others).
• TreatmentTreatment isis complexcomplex andand time-intensive.time-intensive.
• First lineFirst line is a comprehensive, intensive program ofis a comprehensive, intensive program of
educational intervention, developmental therapies andeducational intervention, developmental therapies and
behavioral treatment.behavioral treatment.
• Other alternative medical treatmentsOther alternative medical treatments have beenhave been
pursued either as a substitute to or in conjunction withpursued either as a substitute to or in conjunction with
accepted treatments.accepted treatments.

36. 36
Comorbidities are common inComorbidities are common in
Autistic childrenAutistic children
• Children with ASD areChildren with ASD are 23 times23 times more likely to bemore likely to be
diagnosed with a behavioral or conduct disorder,diagnosed with a behavioral or conduct disorder,
• 8 times8 times to have a diagnosis ofto have a diagnosis of ADHDADHD
• 15 times15 times to have a diagnosis ofto have a diagnosis of depressiondepression oror anxietyanxiety
• 4.5 times4.5 times to have ato have a food allergyfood allergy
• 2.4 times2.4 times to suffer fromto suffer from headacheheadache

37. 37
Study-Autism and AllergyStudy-Autism and Allergy
• Immunologic abnormalities, glutenImmunologic abnormalities, gluten
sensitivity and food allergy are common.sensitivity and food allergy are common.
• In a study of 36 autistic children;In a study of 36 autistic children;
• They found that autistic patientsThey found that autistic patients had elevatedhad elevated
IgE,IgE, andand antibodies to casein, alpha-antibodies to casein, alpha-
lactalbumin, beta- lactoglobin andlactalbumin, beta- lactoglobin and
ovalbumin.ovalbumin.
• They placed onThey placed on elimination diets for 8elimination diets for 8
weeksweeks and at the end of the period they wereand at the end of the period they were
evaluated for symptomatic or behavioralevaluated for symptomatic or behavioral
modification using the Behavior Summarizedmodification using the Behavior Summarized
Evaluation (BSE) scale, which was compared toEvaluation (BSE) scale, which was compared to
the BSE at the beginning of the study.the BSE at the beginning of the study.
• Symptoms returnedSymptoms returned after reintroduction of theafter reintroduction of the
suspected foods.suspected foods.

38. 38
Study-Plasma amino acid profiles inStudy-Plasma amino acid profiles in
children with autism:children with autism:
potential risk of nutritional deficienciespotential risk of nutritional deficiencies
• Methods: TheMethods: The plasma amino acid profilesplasma amino acid profiles of 36 childrenof 36 children
with ASD were reviewed to determine thewith ASD were reviewed to determine the impact of dietimpact of diet
on amino acid patterns.on amino acid patterns.
• Ten of these children were onTen of these children were on gluten and caseingluten and casein
restricted dietsrestricted diets while thewhile the other 26 consumedother 26 consumed
unrestricted diets.unrestricted diets.
• There is a trend for children with ASD who were onThere is a trend for children with ASD who were on
restricted dietsrestricted diets to have anto have an increased prevalenceincreased prevalence
of essential amino acid deficienciesof essential amino acid deficiencies and lowerand lower
plasma level of amino acid including the neurotransmitterplasma level of amino acid including the neurotransmitter
precursors tyrosine and tryptophan, than both controlsprecursors tyrosine and tryptophan, than both controls
and children with autism on unrestricted diets.and children with autism on unrestricted diets.

39. 39
Evidence for General ImmuneEvidence for General Immune
Dysfunction or Autoimmunity in ASDDysfunction or Autoimmunity in ASD
• Primary immune deficienciesPrimary immune deficiencies have been suggested because ofhave been suggested because of
reports of increased frequency of OTITIS MEDIA.reports of increased frequency of OTITIS MEDIA.
• Antibodies to COW MILK protein have been identified in someAntibodies to COW MILK protein have been identified in some
children with ASD. 46% of families had two or more family memberschildren with ASD. 46% of families had two or more family members
with autoimmune disorders.with autoimmune disorders.
• Environmental exposures (VACCINATION) that alter theEnvironmental exposures (VACCINATION) that alter the
immune function (?)immune function (?)
– (1) immune response directed toward a vaccine that(1) immune response directed toward a vaccine that crosscross
reactsreacts with host antigenswith host antigens
– (2) host responses to a vaccine that would result in(2) host responses to a vaccine that would result in production ofproduction of
cytokines and autoimmunitycytokines and autoimmunity
– (3) component of the vaccine(3) component of the vaccine (preservative thimerosal)(preservative thimerosal) thatthat
would bewould be toxic to the immune or nervous systemtoxic to the immune or nervous system

40. 40
MMR vaccination and pervasiveMMR vaccination and pervasive
developmental disorders (twodevelopmental disorders (two
studies)studies)
• There isThere is no associationno association betweenbetween
Measles-Mumps-Rubella and anMeasles-Mumps-Rubella and an
increased risk of pervasive developmentalincreased risk of pervasive developmental
disorder.disorder.

41. 41
Dietary restriction of known allergensDietary restriction of known allergens
in ASDin ASD
• If documented food allergy is present,If documented food allergy is present, symptoms ofsymptoms of
discomfort might be related to behavioraldiscomfort might be related to behavioral
symptoms of irritability, food refusal & sleepsymptoms of irritability, food refusal & sleep
disorder-alldisorder-all of the above may be perceived asof the above may be perceived as
negative behaviors.negative behaviors.
• In one study up to 1/3 of 36 kids with ASD, they wereIn one study up to 1/3 of 36 kids with ASD, they were
found to have food allergies documented with SPT.found to have food allergies documented with SPT.
Elimination & challengeElimination & challenge of these foods after 8 weeksof these foods after 8 weeks
of restriction resulted on behavioral deteriorationof restriction resulted on behavioral deterioration asas
measured on a rating scale.measured on a rating scale.
• Dietary treatment of isDietary treatment of is not typicallynot typically based onbased on
conventional understanding ofconventional understanding of FOOD ALLERGY orFOOD ALLERGY or
intoleranceintolerance but on the hypothesis of alteredbut on the hypothesis of altered
neuropeptide ability in the CNS.neuropeptide ability in the CNS.

42. 42
Novel treatments for ASDNovel treatments for ASD
• Secterin. Horvath [1998] published a report of 3 children receivedSecterin. Horvath [1998] published a report of 3 children received IVIV
secretin infusion with resolution of symptoms.secretin infusion with resolution of symptoms.
• Secretin is a GI hormone member of the family of the brain-gutSecretin is a GI hormone member of the family of the brain-gut
peptides including VIP, glucagon, GHRH, that is located peripherallypeptides including VIP, glucagon, GHRH, that is located peripherally
and centrally.and centrally. It might stimulate the CNSIt might stimulate the CNS and exerts immunoactiveand exerts immunoactive
role at the Purkinje cells, central cerebellar nuclei, hippocampus androle at the Purkinje cells, central cerebellar nuclei, hippocampus and
amugdala.amugdala.
• The identification of secretin and its receptors in the brain may beThe identification of secretin and its receptors in the brain may be
not relevant to the treatment of the autism symptoms, however.not relevant to the treatment of the autism symptoms, however.
• More than 12 studies with > 700 children FAILED to confirmMore than 12 studies with > 700 children FAILED to confirm
therapeutic effecttherapeutic effect..
• A possible beneficial role in some kids appears to be an increase inA possible beneficial role in some kids appears to be an increase in
formed stools.formed stools.
• Conclusion: It is appropriate to continue studying the contribution ofConclusion: It is appropriate to continue studying the contribution of
neuropeptides to the pathophysiology & evolution of the symptomsneuropeptides to the pathophysiology & evolution of the symptoms
of ASD.of ASD.

43. 43
Antiviral agentsAntiviral agents
• Treatment strategies have arisen toTreatment strategies have arisen to target virusestarget viruses that arethat are
suggested causes of ASD, ADHD and other chronic diseases.suggested causes of ASD, ADHD and other chronic diseases.
• No known literatureNo known literature to identify the mechanism or the specificto identify the mechanism or the specific
viruses that might be responsible for the neurological symptoms butviruses that might be responsible for the neurological symptoms but
suggesting that clinical practice supports treatment with antiviralsuggesting that clinical practice supports treatment with antiviral
agents.agents.
• No peer-reviewed publicationsNo peer-reviewed publications address safety or efficacy ofaddress safety or efficacy of
with long term acyclovir-with long term acyclovir- major concern has been expressedmajor concern has been expressed
regarding that chronic administration of acyclovir is boneregarding that chronic administration of acyclovir is bone
marrow suppression.marrow suppression.

44. 44
Thimerosal and Chelation: DMSA,Thimerosal and Chelation: DMSA,
Clay BathsClay Baths
and Natural Chelating agentsand Natural Chelating agents
• Thimerosal is an ethylmercury derivative to stabilize killed virusThimerosal is an ethylmercury derivative to stabilize killed virus
vaccinations packaged in multidose vials. It may decrease T cellvaccinations packaged in multidose vials. It may decrease T cell
and NK cell activity.and NK cell activity. It is no longer present in childhoodIt is no longer present in childhood
vaccinations.vaccinations.
• In different studies, no consistent association wasIn different studies, no consistent association was
identified nor causality was implied between ASD andidentified nor causality was implied between ASD and
thimerosal. The IOM did not endorse an association ofthimerosal. The IOM did not endorse an association of
thimerosal and ASD based on the data available.thimerosal and ASD based on the data available.
• Dimercaptosuccinic acid (DMSA)Dimercaptosuccinic acid (DMSA) is used in clinical practice foris used in clinical practice for
chelation of lead and other heavy metals. Although effective ofchelation of lead and other heavy metals. Although effective of
removing lead and mercury, follow up studies do not demonstrateremoving lead and mercury, follow up studies do not demonstrate
resolution of neurodevelopmental problems. There areresolution of neurodevelopmental problems. There are NONO
publications showing efficacy of chelation agents for thepublications showing efficacy of chelation agents for the
treatment of ASD.treatment of ASD.
• The same applies to the use ofThe same applies to the use of mud baths or dietary fibersmud baths or dietary fibers

45. 45
Gluten-free/Casein-free dietGluten-free/Casein-free diet
• The gluten-free/casein-free diet isThe gluten-free/casein-free diet is currently one of the mostcurrently one of the most
commonly used noneducationally or developmentallycommonly used noneducationally or developmentally
based treatment for symptoms of autism.based treatment for symptoms of autism.
• It is healthy, noninvasive approach and supposedly has a rapidIt is healthy, noninvasive approach and supposedly has a rapid
response.response.
• Based on the assumption that ASD kids have a “leakyBased on the assumption that ASD kids have a “leaky
gut” with the inability to completely breakdown selectedgut” with the inability to completely breakdown selected
proteins (gluten and casein).proteins (gluten and casein).
• These gliadinomorphins (from barley, rye, oats & wheat) &These gliadinomorphins (from barley, rye, oats & wheat) &
casomorphins (from all dairy products) actcasomorphins (from all dairy products) act centrally ascentrally as
endogenous opioids (which remains speculative as aendogenous opioids (which remains speculative as a
cause of ASD).cause of ASD).
• Attention to theAttention to the nutritional status is important as milknutritional status is important as milk is ais a
significant source of protein, calcium and vitamin D.significant source of protein, calcium and vitamin D.
• In the futureIn the future more data will be availablemore data will be available to allow forto allow for
informed decisions regarding gluten-free/casein-free diet.informed decisions regarding gluten-free/casein-free diet.

46. 46
Specific Carbohydrate dietSpecific Carbohydrate diet
• It includes carbohydrates ofIt includes carbohydrates of smaller molecular weightsmaller molecular weight so theyso they
do not need to be broken down.do not need to be broken down.
• No published studiesNo published studies ..
• Attention to the nutritional sufficiency.Attention to the nutritional sufficiency.
• It placesIt places additional pressure on families to implement theadditional pressure on families to implement the
diet and provides higher expectations and an additionaldiet and provides higher expectations and an additional
source of guiltsource of guilt if changes are not seen.if changes are not seen.

47. 47
Supplements; Modulation of centralSupplements; Modulation of central
neurotransmitters and neuropeptidesneurotransmitters and neuropeptides
• Vitamin C.Vitamin C. It is an antioxidant and a regulator of the immuneIt is an antioxidant and a regulator of the immune
function. It has a limited popularity as a CAM treatment despitefunction. It has a limited popularity as a CAM treatment despite
positive results of a study describing decreasing stereotypedpositive results of a study describing decreasing stereotyped
behavior in 18 children.behavior in 18 children.
• Folic acid.Folic acid. The potential mechanism could be provision of additionalThe potential mechanism could be provision of additional
substrate in catecholamine synthesis. No clinical trials have beensubstrate in catecholamine synthesis. No clinical trials have been
donedone
• B6 and Magnesium.B6 and Magnesium.
• B12.B12.
• DMG (Dimethylglycine).DMG (Dimethylglycine). It is metabolized in the liver to form glycine,It is metabolized in the liver to form glycine,
an excitatory neurotransmitter. It remains a popular intervention,an excitatory neurotransmitter. It remains a popular intervention,
despite of lack of evidence for either safety or efficacy.despite of lack of evidence for either safety or efficacy.
• Tryptophan & Tyrosine supplementation.Tryptophan & Tyrosine supplementation.
• Cyproheptadine.Cyproheptadine.
• D-Cycloserine.D-Cycloserine.
• Carnosine SupplementationCarnosine Supplementation (presumed to act on GABA receptors).(presumed to act on GABA receptors).

48. 48
Last one- Nonbiological interventionsLast one- Nonbiological interventions
• Auditory Integration Training (AIT).Auditory Integration Training (AIT).
– Language disorders in ASD is complicated by difficulties with auditoryLanguage disorders in ASD is complicated by difficulties with auditory
perception (hyperacusis or sound sensitivity) and might cause agitation.perception (hyperacusis or sound sensitivity) and might cause agitation.
AIT usesAIT uses repeated exposure to altered sounds by earphone torepeated exposure to altered sounds by earphone to
“retrain” the ear and central listening mechanism“retrain” the ear and central listening mechanism ..
• Behavioral Optometry.Behavioral Optometry.
– ASD children have stereotyped behaviorsASD children have stereotyped behaviors relative to visual scrutinyrelative to visual scrutiny
or inspection at the periphery of their visual fields.or inspection at the periphery of their visual fields. NotNot
recommended by the AAP.recommended by the AAP.
• Craniosacral manipulation.Craniosacral manipulation.
– Purports to be able toPurports to be able to sense the fluid waves of spinal fluid bysense the fluid waves of spinal fluid by
touch and to be able to manipulate them.touch and to be able to manipulate them.
• Facilitated Communication.Facilitated Communication.
– Refers to a specific intervention where aRefers to a specific intervention where a facilitator physicallyfacilitator physically
guides the hand of a nonverbal person to use aguides the hand of a nonverbal person to use a
computerized or other device to spell.computerized or other device to spell.

49. 49
THE ENDTHE END
THANK YOU!THANK YOU!