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Evaluation of the Child with a Suspected Autism Spectrum Disorder Prachi Shah, MD Associate Professor, Pediatrics Division of Developmental and Behavioral Pediatrics Center for Human Growth and Development [email protected] Objectives 1. To present the DSM-V diagnostic criteria of ASD 2. Highlight the neurobiological origins, and neuroanatomical findings of autism 3. Review the clinical symptoms of autism. 4. Discuss the Physician’s role in the diagnosis of children with suspected ASD 1. Diagnostic Criteria of ASD Autistic Spectrum Disorders (ASD) Overview • Neurodevelopmental disorder of unknown etiology • Strong genetic basis • Behaviors present by 36 months of age • Behavioral phenotype characterized by persistent deficits as follows: 1. Persistent social communication and social interaction AND 2. Restricted and repetitive patterns of behavior (DSM-5, 2013) (Diccico-Bloom, Lord, et al, 2006) DSM-V Diagnostic Criteria for Autism Spectrum Disorder ≥3 Persistent deficits in social communication and social interaction in multiple contexts: 1. Deficits in social-emotional reciprocity 2. Deficits in nonverbal communicative behaviors used for social interaction 3. Deficits in developing, maintaining, and understanding relationships • Difficulties adjusting behavior to suit various social contexts • Difficulties in sharing imaginative play or in making friends; to absence of interest in peers. DSM-V Diagnostic Criteria for Autism Spectrum Disorder ≥ 2 Restricted, repetitive patterns of behavior, interests, or activities: 1. Stereotyped or repetitive motor movements, use of objects, or speech 2. Insistence on sameness, inflexible adherence to routines, or ritualized patterns or verbal nonverbal 3. Highly restricted, fixated interests that are abnormal in intensity or focus 4. Hyper- or hyporeactivity to sensory input or unusual interest in sensory symptoms. DSM-5 : Severity of Symptoms Severity Level for ASD • Level 1: Requiring Support • • Level 2: Requiring Substantial Support Level 3: Requiring Very Substantial Support Restricted Interests & Repetitive Behaviors Social Communication • • Difficulty initiating social interactions, and clear examples of atypical or unsuccessful response to social overtures of others. May appear to have decreased interest in social interactions Marked deficits in verbal and nonverbal social communication skills; Social impairments apparent even with supports in place Limited initiation of social interactions; and reduced or abnormal responses to social overtures from others • Severe deficits in verbal and nonverbal social communication skills causing severe impairments in functioning • Very limited initiation of social interactions, and minimal response to social overtures from others. • • • • • • • • • Inflexibility of behavior causes significant interference with functioning in one or more contexts. Difficulty switching between activities. Problems of organization and planning hamper independence. Inflexibility of behavior, difficulty coping with change, or other restricted/repetitive behaviors Behaviors are obvious to the observer and interfere with functioning in a variety of contexts. Distress and/or difficulty changing focus or action. Inflexibility of behavior, extreme difficulty coping with change, or other restricted/repetitive behaviors Behaviors markedly interfere with functioning in all spheres. Great distress/difficulty changing focus or action. 2. Neurobiological Origins of Autism Epidemiology • Prevalence of all Autistic Spectrum Disorders is ~ 1/68 • Increase in the number of children diagnosed likely reflects changes in the diagnostic criteria of autism to include autism spectrum d/o • Increased prevalence of ASD in males vs. females – 2:1 to 6.5: 1 (Fombonne, 2003; MMWR, 2007 ) – 15: 1 in high functioning autism (Volkmar, 2005) MMWR Surveillance Summer 2007; 56(1) : 1-44 Etiology • Exact cause unknown, but cause is felt to be multifactorial with a strong genetic etiology • Environmental risks modulate the phenotypic expression of the disorder – Advanced Paternal age (Paternal age > 40yo) (Reichenberg, 2006; Croen, 2007) Parental Age and Risk for ASD • Increased paternal age associated with increased de novo mutations (DNM) (p= 0.0045) – Rate of DNM : 1.5 / year for every increased year of father’s age • NO association with increased maternal age (p= 0.37) Candidate Genes in Autism • Over 100 genes implicated, on most chromosomes with the strongest implications as follows: • Chr 2 : 2q32.2 • Chr 3: 3q26.32 • Chr 7 : 7q32( UBE2H -seen in specific language impairment) • Chr 15: 15q 11-13 (UBE3A: Ubiquitin protein ligase E3A) • Chr 17: 17q11 : 5HTT transporter gene and promoter regions • Chr 22: Del 22q13 (SHANK3: synaptic adaptor protein) • X Chromosome: NLGN-3, NLGN-4X: cell adhesion molecules involved in synaptic function – Fragile X: most common cause of MR and AD (Jamain, 2003: Dykens, 2004; Wassink, 2004; Vorstman, 2006 Abrahams, 2008) Candidate Genes in Autism • Over 100 genes implicated, on most chromosomes with the strongest implications as follows: • Chr 2 : 2q32.2 • Chr 3: 3q26.32 • Chr 7 : 7q32( UBE2H -seen in specific language impairment) • Chr 15: 15q 11-13 (UBE3A: Ubiquitin protein ligase E3A) • Chr 17: 17q11 : 5HTT transporter gene and promoter regions • Chr 22: Del 22q13 (SHANK3: synaptic adaptor protein) • X Chromosome: NLGN-3, NLGN-4X: cell adhesion molecules involved in synaptic function – Fragile X: most common cause of MR and AD (Jamain, 2003: Dykens, 2004; Wassink, 2004; Vorstman, 2006 Abrahams, 2008) Environmental Risk Factors • Prenatal: exposure to thalidomide and valproic acid (Arndt, 2005) • Perinatal : history of newborn encephalopathy (Badawi, 2006; Koloevzon, 2007) • Postnatal – MMR : no evidence to support an association between MMR vaccine and autism (DeStephano, 2004; Richler, 2006) – Mercury : no evidence to support an association between increased mercury concentration and autism (Stehr-Green, 2003; Nelson, 2003; IOM, 2004) Neuroanatomic Findings • Macrocephaly – Normal/ decreased head circ. between 0-6mo – Rapidly increasing head circumference between 614 months of age (Pelfrey, 2004; McCaffery, 2005) • BDNF (Brain Derived Neurotrophic Factor) implicated: – Regulates neuronal survival, synaptogenesis and neuronal differentiation (Tsai, 2005) – ↑[BDNF] in autistic patients (Mizayaki, 2004) – Hypothesized that ↑[BDNF] increases synaptogenesis and interferes with normal apoptotic mechanisms • MRI studies suggest brain volume of children with autism in the frontal, cerebellar and limbic regions of the brain (Courchesne, 2001, Parks, 2002; Courchesne, 2004) Brain Structures affected in Autism Anterior Cingulate Gyrus: -Decision making -Ascription of feelings and thoughts FRONTAL Cortex : -Cognition -Language Functioning Cerebellum Amygdala : -Emotional processing Pelfrey, 2004; Sigman, 2004 Functional Neuroanatomy and Autism: fMRI and Face Perception • Persons with ASD have deficits in face perception R L (Derulle,2004; Klin, 1999) • The Fusiform Face Area (FFA) is strongly activated during face perception (Haxby, 1994; Kanwisher, 1997; Schultz, 2005) • fMRI studies of facial perception demonstrate > activation of the R FFA FFA Schultz, RT Intl J. Dev Neuroscience 23 (2005) 125-141 Functional Neuroanatomy and Autism: fMRI and Face Perception R • Autistic patients demonstrate differences on fMRI during face discrimination tasks compared with non-autistic controls: A.. – hypoactivation of the R FFA (Schultz, Normal Control 2000; Aylward, 2004; Curby, 2003; Davidson, 2004) perception of facial identity L B. – hypoactivation of the amygdala (Baron-Cohen, 1999; Critchley, 2000; Pierce, 2001) perception of emotion perception Autistic Patient Eye Tracking in Autism • Klin et al. explored visual scanning patterns in patients with autism, and matched controls • 15 males with autism/15 matched controls • Watched short video clips of “Who’s Afraid of Virginia Wolf?” • Infrared eye tracking technology measured visual scanning paths • Viewers with autism focused more on the mouth than the eyes Eye Tracking in Autism Viewer with Autism Normal Comparison (Klin, 2002) Eye Tracking in Autism Viewer with Autism Normal Comparison Klin, 2002 Eye tracking in Autism Viewer with Autism Normal Comparison Klin, 2002 Eye tracking and Infant ASD Diagnosis • 110 infants enrolled in a prospective eye tracking study – 59 high risk infants (ASD sibling) – 51 low risk infants • Infants viewed naturalistic interactions, and eye tracking was assessed at 2,3,4,5,6,9,12,15 & 24 months • Autism diagnosis confirmed at 36 Jones & Klin, Nature (2013) months with the ADOS Eye tracking and Infant ASD • Percentage of time in visual fixation to eyes assessed Autism Typically Developing Eye tracking and Infant ASD • ASD infants: decreased fixation on eyes from 2-6 months • Decline in eye fixation from 2-6 months predicts later socialaffective disability Autism Typically Developing 3. The Clinical Picture of Autism Clinical Symptoms of Autism DSM-V • Deficits in Social Communication – Deficits in social reciprocity • Limited eye contact • Impairment in joint attention Social – Impaired nonverbal communication • Restricted, Repetitive Patterns of Behavior – – – Repetitive motor movements Inflexible adherence to routines Highly restricted, fixated interests • Atypical Sensory Profile Play/ Behavior Baron-Cohen, 2004 Clinical Symptoms of Autism • Deficits in Social Communication – Deficits in social reciprocity • Limited eye contact • Impairment in joint attention Social – Impaired nonverbal communication • Restricted, Repetitive Patterns of Behavior – – – Repetitive motor movements Inflexible adherence to routines Highly restricted, fixated interests • Atypical Sensory Profile Play/ Behavior Baron-Cohen, 2004 Early Signs of Social Cognition: Imitation • Related to our ability to socially connect with another – Capacity that is present at birth – Meltzoff, 1977: infants are able to see and imitate the facial expressions of others as early as 42 minutes of age – Impaired in children with autism (Meltzoff, 1977) Social Behaviors Typically Absent in Autism • Joint Attention: Ability to use eye contact and pointing to share experiences with others • Protoimperative pointing: use of pointing to obtain an object of desire (12 months) • Protodeclarative pointing: use of pointing to an object just to have another share interest (18 months) Joint Attention (8 months) Joint Attention, Social Referencing (18 months) Clinical Symptoms of Autism • Deficits in Social Communication – Deficits in social reciprocity Social • Limited eye contact • Impairment in joint attention – Impaired nonverbal communication • Restricted, Repetitive Patterns of Behavior – – – Repetitive motor movements Inflexible adherence to routines Highly restricted, fixated interests • Atypical Sensory Profile Play/ Behavior Baron-Cohen, 2004 Limited Eye contact, No Joint Attention, Impaired Communication Clinical Symptoms of Autism • Deficits in Social Communication – Deficits in social reciprocity • Limited eye contact • Impairment in joint attention Social – Impaired nonverbal communication • Restricted, Repetitive Patterns of Behavior – – – Repetitive motor movements Inflexible adherence to routines Highly restricted, fixated interests • Atypical Sensory Profile Play/ Behavior Baron-Cohen, 2004 Restrictive Repetitive Behaviors Restrictive, Repetitive Behavior Observing Child Behavior : Important Diagnostic Keys Diagnostic “Gestalt” • “Ceiling Fan Question” • Checking your Countertransference 4. The Physician’s Role in the Diagnosis of ASD The Role of the Physician • Screen – Using a validated screening tool • Suspect – Autism if a failed screen • Direct – Patient for a comprehensive ASD evaluation Actively Screen for ASD • American Academy of Pediatrics Guidelines – Screen for ASD at 18 and 24 months • http://www.pediatrics.org/cgi/content/full/peds.20072361v1 • Use a validated screening tool for Autism – Social Communication Questionnaire (SCQ) – Modified Checklist for Autism in Toddlers (MCHAT) Screen: Social Communication Questionnaire (SCQ) • 40-item parent report questionnaire – Administration: 5-10 minutes – Scoring : 30 seconds • Screens for autism-related symptoms – Current form : symptoms in the last 3 months – Lifetime form: symptoms throughout the lifespan • Scores >15 suggestive of ASD SUSPECT http://www.wpspublish.com/store/p/2954/social-communication-questionnaire-scq M-CHAT-R: Modified Checklist Screen: for Autism in Toddlers • Parent Report Checklist – Age : 16-48 months (use at 18-24 mo.) – Sensitivity= 0.85 / Specificity = 0.93 • Scoring: Y/N – Failed items = NO except – # 2,5,12 : Failed item = YES – INTERPRETATION : • 0-2 Low Risk • 3-7 Moderate Risk : followup • 8-20: Refer for ASD Diagnostic Evaluation SUSPECT https://www.m-chat.org/_references/mchatdotorg.pdf Robbins, 2009 Direct: Autism Spectrum Disorder Comprehensive Evaluation • Developmental / behavioral assessment – Confirm presence of ASD using DSM-V criteria – Assess cognitive and adaptive functioning with standardized measures • Genetics Referral – Assess for dysmorphic features – Laboratory assessment : Chromosomal microarray, Fragile X • Consider Speech and OT evaluation • NO need for MRI or EEG PEDIATRICS, Volume 120, Number 5, November 2007 Direct: ASD Comprehensive Evaluation Michigan Requirements • Medical – Medical evaluation to confirm ASD Diagnosis – DBP; Neurologist; Geneticist • Behavioral – Behavioral assessment to confirm ASD diagnosis – Includes ADOS or ADI – Psychologist; Psychiatrist; DBP • Speech – Assess language and social pragmatics Services individualized based on patient’s needs Autism A.L.A.R.M. • A: Autism is prevalent • L: Listen to parents • A: Act early • R: Refer • M: Monitor www.firstsigns.org Resources • American Academy of Pediatrics Is Your One Year Old Communicating With You? Elk Grove Village, IL: American Academy of Pediatrics (2004) • American Academy of Pediatrics Understanding Autism Spectrum Disorders Elk Grove Village, IL: American Academy of Pediatrics (2005) • ASD toolkit from the AAP : www.aap.org – Toolkit was developed to support pediatricians in the identification and ongoing management of children with autism spectrum disorders (ASDs) • http://www.pediatrics.org/cgi/content/full/peds.2007-2361v1 Thank you! [email protected]