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Autism 2007 Moissidis

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  • <number>
    Revised definitions and nomenclature have been proposed by the European Academy of Allergy and Clinical Immunology.
    Allergy is a hypersensitivity reaction initiated by immunological mechanisms, either defined or strongly suspected.
    Allergy can be antibody or cell mediated. In most patients, the antibody typically responsible for allergic reaction is of the IgE type and patients are said to have IgE-mediated allergy. Inhalation of antigens (allergens) stimulate the immune system to produce antibodies.
    Reference
    Johansson SG, Hourihane JO, Bousquet J, et al. EAACI (the European Academy of Allergology and Clinical Immunology) nomenclature task force. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy. 2001;56:813-824.
  • <number>
  • Transcript

    • 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!

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