Download Evaluation of the Child with a Suspected Autism Spectrum Disorder

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]