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Autism Spectrum Disorders PowerPoint Presentation

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Description : Check out this medical PowerPoint presentation titled "Autism Spectrum Disorders" by Isabelle Rapin.
This medical PowerPoint presentation talks about Autism Spectrum Disorders (ASD), a group of neurodevelopmental disorders that affect communication, social interaction, and behavior.
ASD is a spectrum disorder, meaning that it affects people in different ways and to different degrees. Some people with ASD may have significant challenges with communication and social interactions, while others may have only mild difficulties.
ASD is typically diagnosed in early childhood, although some people may not receive a diagnosis until later in life. The exact cause of ASD is not known, but it is believed to involve a combination of genetic and environmental factors.

Tags : Autism Spectrum Disorders, ASD, neurodevelopmental disorders, Child Neurology PowerPoint presentation, Neurology PowerPoint presentation

Published on : Mar 21, 2023 | Views : 730 | Downloads : 3

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Slide 1-

Autism Spectrum Disorders Isabelle Rapin Seminar on developmental disorders Child neurology No conflict of interest
Slide 2-

Goldman et al. 2009
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What is autism? (2013) A developmental behaviorally-defined syndrome/phenotype Impacts social skills & communication Associated with narrow, rigid, repetitive behaviors NOT A “DISEASE” ! Affects the immature, developing brain
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Causes of autism Many genetic influences in most cases multiple most with small effects on brain development Interacting environmental (epigenetic) influences via their pathophysiologic effects on molecular networks cellular networks brain circuitry
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Hierarchies: genes to behavior Classification - BEHAVIORAL – MAINLY DESCRIPTIVE (dimensional) Living, behaving whole person – many behaviors Mechanisms – BIOLOGIC PATHOPHYSIOLOGY Brain – molecules, cells, networks Cells – molecules, networks Molecules - networks Classification - ETIOLOGY, BIOLOGIC CAUSES – MAINLY CATEGORICAL (discrete, yes/no) Genetics Environment Both (incl. epigenetics)
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Severity: Bell - shaped at the behavioral levelBehavioral diagnoses = arbitrary cuts in a continuum  NOT DICHOTOMOUS
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Behavioral classification Arbitrary cuts in a continuum  entities with fuzzy margins entities not either/or (i.e., not discrete, dichotomous) overlap with “normality” overlaps with one or more other entities (“co-morbidities”)
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Overlapping syndromes – One brain ! Autism OCD MR Learning disability, language disorder, dyslexia, etc. Tourette ADHD Etc.
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Biologic classification For the most part yes/no (dichotomous) But: often many different mutations in a given gene  different phenotypes, severity, penetrance each gene affects complex molecular/cellular networks a given network is vulnerable to many different gene mutations gene expression modified by genetic background epigenetic (environmental) influences
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Early Genetic Evidence Was 4/10,000 for autistic disorder Now 1/88 ASD Recurrence risk: < 10%, thus single mendelian genes rare  mostly multigenic Multiplex families in Utah (Ritvo 1985-90s) Male dominance, yet male/male transmission  not often x-linked Stoppage rule
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Current Genetic Views Now known etiologies no longer rejected Association with known mono-genetic disorders PKU Tuberous sclerosis Fragile-X Angelman, Cornelia de Lange, etc., etc. Candidate gene studies Multiplex families Linkage studies (cytogenetics, CNVs [microdeletions, duplications, translocations], loci, genes) Whole genome searches – gwas (genome-wide association studies, microarrays) mono- vs. heteroallelic expression multiple genes with small effects vs. single genes with stronger effects
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Genes that influence Type 1A diabetes New Engl J Med April 16, 2009 One disease –type 1A diabetes: many genes, only one for insulin !
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Some of the direct and indirect targets of networks of differentially methylated and expressed genes Courtesy Dr. V.W.Hu et al
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Genes Brain Behaviors Genes do not program behaviors ! Brain networks program behaviors Cellular metabolic microcircuitry Anatomo-physiologic networks CAVEAT !
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Differentiate levels of investigation! AUTISM SPECTRUM -/- THE AUTISMS behavioral biologic severity etiologies dimensional enumerative
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DSM-5 (2013):Autism Spectrum Disorder (ASD) Deficient social communication and interaction (all 3) Marked deficit in nonverbal and verbal social communication Lack of social reciprocity Poor development and maintenance of peer relationships Restricted repetitive patterns of behavior, interests and activities (at least 2) Stereotyped motor or verbal behaviors or unusual sensory behaviors Excessive routines & ritualized patterns of behavior Restricted, fixated interests Clinically significant, persistent, present since early childhood
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DSM - 5 Diagnosis: based entirely on behavioral criteria Encompasses the entire range of severity Associated symptoms reflect biologic etiologies irrelevant to a behavioral diagnosis ! critical to unraveling pathophysiologies (i.e., what other brain/somatic networks are also affected) critical to optimal management
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Some Standardized Behavioral Diagnostic Tests Childhood Autism Rating Scale – CARS (Schopler et al., 1980) Autism Diagnostic Interview – ADI (Lord et al., 1989) Autistic Diagnostic Observation Schedule – ADOS (Lord et al., 1989) Modified Checklist for Autism in Toddlers -- M-CHAT (Robin et al., 1999) Etc.
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Physical/neurologic featuresNone present in all cases or required for diagnosis Abnormal head growth curve Physical abnormalities/symptoms Motor findings Atypical sensory responses Sleep problems Language abnormalities Autistic-language regression Epilepsy
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Trajectory of brain growth in ASD(Courchesne et al, 2007) Selectively affected areas: Frontal lobe Temporal lobe Cerebellum Amygdala
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Neuropathology 1980: 4 cases with severe MR: cerebellar + other brain abnormalities (Williams et al.) 1985-2002: Cerebellum + limbic pathology (Bauman and Kemper) No major brain anomalies/lesions Loss of Purkinje cells in cerebellar cortex, neurons in deep cerebellar nuclei, inferior olive Stunted neurons in diencephalon, amygdala Pathology progressive in adults compared to children? 1996: brainstem malformation in one case (Rodier et al.) HOXA1 gene Thalidomide, valproate toxicity
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22 Autism: Hippocampal Neurons(Bauman & Kemper 1985-1994)
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Cortical minicolumns in cortical area 4 lamina III in autism vs control brain Normal control brain ASD brain Casanova 2006
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Current emphases Dysfunctional networks Cortical neurons (GABA inter-neurons) White matter networks Synapses (H. Zogbi, Science, 2003) Neuro-transmitters/-modulators Serotonin Dopamine Acetylcholine Glutamate Oxytocin/vasopressin Etc.
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Frequently reported somatic abnormalities Minor anomalies, dysmorphic features Many known syndromes/genetic disorders Middle ear infections,URIs GI symptoms Immunologic abnormalities THEY DO NOT INVALIDATE AN ASD DX HAVE TO DO WITH BIOLOGIC CAUSES
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Open questions Are somatic features symptoms of ASD? Is ASD ↑ genetic vulnerability to environmental stresses (physical & emotional) ? (e.g., Herbert, 2012) Optimal physical health is good for all But to what extent does striving for optimal physical & emotional health (holistic medicine) improve ASD symptoms? To what extent are ASD symptoms reversible by optimizing health?
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Frequent motor findings Stereotypies motor, +/- object behavioral Dystonic postures Toe walking Increased joint laxity (hypotonia) Clumsiness Dyspraxia
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Frequent sensory findings:hyper- & hypo-sensitivity Touch Pain, temperature Proprioception Vestibular Audition Vision Taste Smell
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Sleep problems Difficulty falling asleep Difficulty staying asleep Need for less sleep time Need for excessive sleep Inadequate circadian entrainment
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Levels of language coding (1) Phonology – speech sounds - phonetics…...segmental - prosody……..suprasegmental Grammar −sentence structure - syntax………..word order - morphology…word endings, etc.
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Levels of language coding (2) Semantics – meaning of utterance - lexicon…….word dictionary in brain - meaning of connected speech Pragmatics – conversational language - verbal………turn taking, referencing, etc. - nonverbal….facial expression, gestures, body posture, prosody
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Impaired language in autism At preschool Comprehension: ~ always impaired Expression: pragmatics always impaired + (1) no language / language regression: often presenting sign or (2) verbiage, echolalia, impaired conversational use (pragmatics) and prosody At schoolage More than one subtype of language deficit Pragmatics impaired life-long
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Subtypes of dysphasia in ASD Nonverbal/dysfluent ↓ phonology, syntax, semantics & pragmatics impaired (impoverished language) ↓ comprehension, even up to VAA Verbal, mostly fluent (semantic-pragmatic) Phonology, syntax OK Atypical vocabulary; some anomic ↓ comprehension of discourse (questions) - worse than expression Impaired pragmatics, conversation, chatterboxes Atypical prosody, delayed echolalia, perseveration
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(62 ASD school-agers) (M) (-1 sd) (-1 sd) (M)
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Language / Autistic Regression Parents: language/autistic regression in ~ 1/3 of toddlers Mean age 21 months (~12-36 mos.) Triggers? Infectious/immunologic? Psychological stress? Improvement but not full recovery Relation to long-term prognosis ?
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Language regression(N = 177 children) Age < 3 years 91% autistic 14% seizures Age > 3 years 58% autistic 53% seizures Shinnar et al. 2001
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Language RegressionEEG sleep study (N = 177 children) Without seizures 21% EEG abnormal 92% autistic With seizures 78% EEG abnormal 69% autistic (Shinnar et al, 2001)
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Epilepsy in autism Related to the severity, location, type of brain pathology/cognitive level Related to type of language disorder Rare in high functioning children Peaks in early childhood and in adolescence Rarely the cause of autistic regression
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Autistic Regression and Epilepsy Relation to Landau-Kleffner syndrome (language regression with either seizures or a subclinical epileptiform EEG)? Relation to status epilepticus in slow wave sleep (ESES)? Limited value of all-night EEG monitoring TO TREAT OR NOT TO TREAT ???
Slide 40-

Autistic Regression vs Disintegrative Disorder Heller (1908 & 1930): behavioral and language regression in preschooler/schoolage children, including ADL Poor prognosis Heterogeneous disorder (a few degenerative diseases, most not) Are late autistic regression and DD on a continuum ???
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ERPs / Imaging ERPs – oddball method: real time measures of sensory processing  data in the msec. domain Parcellated morphometry white matter enlargement in radiate fibers (Herbert) reversed asymmetry of language areas (also in DLD !) fMRI to study sensory processing by altered blood flow in activated regions  networks PET ditto, but also study of metabolism using ligands (e.g., glucose, serotonin, DA, AMPA…) Diffusion tensor imaging to study connectivity
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Goals of Intervention Stop looking for a cure Stop striving for ‘normality’ Think adaptation, i.e., fixing, circumventing Consider the individual’s needs Tolerate socially acceptable differences Welcome the unique contributions of some
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Where to go: biology Elucidate pathophysiology, i.e., what goes on in the brain (neurotransmitters, neuromodulators, epilepsy, etc…) Pathophysiology more likely to lead to new drugs than genetics Elucidate basis of autistic regression Devise a rational treatment for autistic regression
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Where to go: genetics In the clinic: Limited referral based on family history & phenotype Probability of a specific genetic diagnosis low Always discuss recurrence risk ! Lack of prenatal diagnosis unless etiology known For research (paid for by research funds !) Strongly encourage enrollment in a funded comprehensive study, but ~ never results in specific Rx of child
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Where to go: medical interventions Discourage use of medical/dietary treatments that have no reasonable rationale Urgent need to evaluate efficacy of medical and educational interventions in well studied subgroups of individuals