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Autism, Autism Spectrum Disorders, Pervasive Developmental Delay, PDD, Asperger Disorder, Asperger Syndrome, Disintegrative Disorder, Childhood Disintegrative Disorder

  • History
  1. First described in 1943 by psychiatrist Leo Kanner
  • Epidemiology
  1. Gender predominance: Males by 2 to 4:5 ratio
  2. Prevalence
    1. Pervasive Developmental Disorder: 63 per 10,000
    2. Autism Prevalence if sibling has Autism: 3-7%
    3. Autism Spectrum Disorders diagnoses have increased in U.S. markedly over time
      1. Prevalence 1996: One in 294 (3.4 per 1000)
      2. Prevalence 2002: One in 151 (6.6 per 1000)
      3. Prevalence 2006: One in 111 (9 per 1000)
      4. Prevalence 2008: One in 88 (11.3 per 1000)
      5. Prevalence 2012: One in 68 (14.6 per 1000)
      6. Christensen (2016) MMWR Surveill Summ 65(3): 1-23 [PubMed]
        1. https://www.cdc.gov/mmwr/volumes/65/ss/ss6503a1.htm
    4. Autism increased Prevalence causes
      1. Increased diagnosis (DSM 5 criteria, well child screening, social awareness, school screening)
  • Pathophysiology
  1. Information processing is disordered
  2. Weak central coherence
    1. Only details seen (not greater picture)
  • Risk Factors
  1. Advanced maternal age and paternal age
  2. Maternal conditions
    1. Gestational Diabetes Mellitus
    2. Maternal Hypertension
    3. Maternal Obesity
  3. Maternal infections
    1. Rubella infection
    2. Cytomegalovirus infection
    3. Herpes Simplex Virus Infection
  4. In Utero exposures
    1. Thalidomide
    2. Pesticides
    3. Traffic-related Air Pollution
    4. Valproate
      1. Hernández-Díaz (2024) N Engl J Med 390(12):1069-79 +PMID: 38507750 [PubMed]
  5. Syndromes
    1. Tuberous sclerosis
    2. Untreated Phenylketonuria
    3. Fragile X Syndrome
    4. Down Syndrome
    5. Fetal Alcohol Syndrome
  6. Other associated factors
    1. Anoxic brain injury
    2. Low birth weight
    3. Preterm delivery
    4. Cerebral Folate Deficiency
      1. Associated with Folate Receptor Alpha Autoantibodies in some cases
      2. May respond to Leucovorin (Folinic Acid)
      3. Rossignol (2021) J Pers Med 11(11):1141 +PMID: 34834493 [PubMed]
  7. Disproved factors (not associated with Autism)
    1. Mercury preserved Vaccines
    2. Yeast infection
    3. Celiac Sprue
    4. Casein allergy
    5. Measles Mumps Rubella Vaccine (MMR)
      1. Taylor (1999) Lancet 353:2026-9 [PubMed]
      2. DeStafano (2000) J Pediatr 136:125-6 [PubMed]
  • Causes
  1. Idiopathic (80% of cases)
  2. Genetic predisposition contributes to 50% of patients
  3. Multifactorial (numerous mutations)
  • Types
  • Autism Spectrum Disorders
  1. Background
    1. Autism Spectrum Disorders encompasses 4 previously separate diagnoses
  2. Autistic disorder (classic childhood Autism)
    1. Unlikely to function independently as adults
  3. Asperger Disorder
    1. Social deficits, narrow interests and clumsiness
    2. IQ exceeds 70
  4. Disintegrative Disorder
    1. Normal development until age 2 to 10 years
    2. Sudden and dramatic regression
      1. Affects social, verbal and cognitive skills
      2. Permanent deficits
  5. Pervasive Developmental Delay (PDD), not otherwise specified
    1. Autism not consistent with other subtypes
  • Associated Conditions
  1. Intellectual Disability (20-50% Prevalence)
  2. Maladaptive Behaviors
    1. Self-Injury Behavior
    2. Aggressive Behavior
  3. Seizure Disorder (11-26% Prevalence)
    1. Screening with EEG is not recommended unless signs, symptoms suggest this
    2. Have a high index of suspicion for Epilepsy in autistic patients
    3. Risk increases with girls and if comorbid Intellectual Disability
  4. Gastrointestinal disorders
    1. Feeding difficulties (up to 75% of cases)
    2. Chronic or recurrent Abdominal Pain
    3. Diarrhea
    4. Constipation
    5. May provoke daytime behavior problems (see maladaptive behaviors above)
  5. Insomnia and other Sleep Disorders (50-80% of cases)
    1. Circadian rhythm disturbance
    2. Periodic Limb Movements of sleep
  6. Psychiatric conditions including Mood Disorders (63-96%)
    1. Major Depression
    2. Anxiety Disorder
    3. Bipolar Disorder
    4. Obsessive-Compulsive Disorder
    5. Attention Deficit Hyperactivity Disorder
  7. Motor disorders (51% at diagnosis, decreases to 38% of patients over time)
    1. Hypotonia
    2. Apraxia (poor motor planning)
    3. Clumsiness
    4. Toe Walking
    5. Gross motor deficits
    6. Clumsiness
  1. Language deficits or regression (see below)
  2. Social skills impaired
    1. Social orienting absent (by age 9-12 months)
      1. Does not turn and make eye contact on Hearing his or her name called
    2. Joint attention absent (by age 12-15 months)
      1. Not able to coordinate own attention between another person and a distant object (shared attention)
      2. Does not turn and look at an object across room as directed by medical provider or Caregiver
    3. Imperative pointing absent (by age 12-15 months)
      1. Does not point to request an object
    4. Declarative pointing absent (by age 18-24 months)
      1. Does not point for experience sharing
    5. Pretend play absent (by age 24 months)
  3. Inflexible
    1. Temper tantrums for changed routine
    2. Unimaginative monotonous play
    3. Intolerant of change in routine
  4. Sensory deficit
    1. Sound intolerance
    2. Gaze aversion
    3. Child stares at shadows
  5. Restricted interest
    1. Unusual play (may focus on only a small part of a toy)
    2. Carries unusual comfort item (e.g. stick or rock)
  6. Repetitive purposeless movements
    1. Provocative: Stress
    2. Palliative: Decreases as children grow older
    3. Examples of stereotypical movements
      1. Repeatedly lines up objects in a row
      2. Hand flapping
      3. Toe Walking
      4. Finger flicking near their eyes
      5. Rocking
      6. Pacing
  • Symptoms
  • Language deficits suggesting Autism
  1. All ages
    1. Language regression (ominous sign)
    2. Child will not turn to name
    3. Difficulties with language comprehension
    4. Mutism with rare spontaneous clear speech
  2. Infants (9 months)
    1. No babbling
    2. Does not take turns vocalizing back and forth
    3. Lacks variation in vocalizing
    4. Fails to wave bye bye
    5. Does not raise arms overhead to be lifted
    6. Fails to respond to Caregiver's voice or environmental sounds
    7. Makes unusual or high pitched sounds
  3. Toddlers
    1. Child does not point by one year
    2. Child does not speak words by 14 months
    3. Vocabulary includes less than 12 words by 18 months
    4. No two word sentences by 24 months
    5. No sentences by 36 months
    6. Delayed shake or nod to signify yes or no answers
  4. Preschool and older children
    1. Child does not answer questions
    2. Child "talks to talk," but does not communicate
    3. Echolalia (esp. if only form of language at 24 months of age)
    4. Confuses pronouns (e.g. You and Me)
    5. Refers to self by name
    6. Child repeats overlearned expressions verbatim
    7. Child perseverates on a single favorite topic
    8. Unable to tell a story coherently
    9. Robotic, monotonous speech
      1. High-pitched
      2. Sing-song
      3. Lack of inflection
  • Symptoms
  • Teens and Adults (late presentations)
  1. Social Interactions
    1. Atypical or decreased eye contact
    2. Awkward initiation of social interactions
    3. Absence of personal space awareness
    4. Overly literal
    5. Difficulty appreciating more than one perspective
    6. Difficulty anticipating another persons's feelings or thoughts
    7. Difficulty answering open ended questions and frequently tangential
    8. Monologue-like conversation
  2. Repetitive and Restricted Interests
    1. Hoarding items
    2. Ordering items
    3. Inflexible adherence to routine
    4. Memorized dialogues recited
    5. Obsession and atypical preoccupations with facts and details
    6. Dislike of specific sounds, smells and tastes
  • Evaluation
  1. Clinical evaluation
    1. Careful history and physical
    2. Careful Neurologic Exam
    3. Hearing Testing
  2. General Developmental Screening
    1. Parents' Evaluation of Developmental Status (PEDS)
    2. Ages and Stages Questionnaire (ASQ)
    3. Infant Development Inventory (IDI) and Child Development Review (CDR)
  3. Specific Autism Screening
    1. Indications for immediate evaluation
      1. Language or social regression
      2. Age 12 months: No babbling, pointing or gestures
      3. Age 16 months: No single words
      4. Age 24 months: No 2 word spontaneous phrases
    2. Tests
      1. Modified Checklist for Autism in Toddlers (M-CHAT)
        1. High efficacy, public domain survey and most widely used
        2. Poor Positive Predictive Value (and high False Positive Rate) when used alone without other evaluation
      2. Modified Checklist for Autism in Toddlers - Revised with follow-up (M-CHAT-R/F)
        1. Two staged parent reported screening tool
        2. http://mchatscreen.com/wp-content/uploads/2015/09/M-CHAT-R_F.pdf
      3. Pervasive Developmental Disorders Screening (PDDST)
        1. Publisher: Porter Psychiatric Institute
        2. Phone: 415-476-7385
      4. Autism Screening Questionnaire
      5. Australian Scale for Asperger Syndrome
  4. Formal diagnostic testing
    1. Autism Diagnostic Observation Schedule, 2nd ed
    2. DSM V Criteria (see below)
  • Differential Diagnosis
  • Autism
  1. Other Pervasive Developmental Disorder (see above)
  2. Selective Mutism
  3. Stereotypic Movement Disorder
  4. Childhood onset Schizophrenia
  5. Rett Syndrome
  • Labs (if indicated)
  1. Genetic Testing
    1. Chromosomal Microarray Testing is typical in 2023 (may be shifting to full genome sequencing)
    2. Fragile X Testing
      1. Children (esp. boys) with Family History of males with Intellectual Disability
  2. Other testing as indicated
    1. Lead Level
    2. Urine for Phenylketonuria (if not screened as newborn)
    3. Folate Receptor Alpha Autoantibodies (investigational)
      1. Among the causes of Cerebral Folate Deficiency
      2. May respond to Leucovorin (Folinic Acid)
      3. Rossignol (2021) J Pers Med 11(11):1141 +PMID: 34834493 [PubMed]
  • Diagnostics
  1. MRI and EEG are not routinely recommended in isolated Autism spectrum disorder
  • Diagnosis
  • Autism Spectrum Disorder (DSM V)
  1. Persistent deficits in social communication and social interaction across multiple contexts
    1. Social-emotional reciprocity deficits (e.g. failed 2-way conversation, lacks shared interests, emotions, affect)
    2. Nonverbal communication deficits (e.g. abnormal eye contact, body language, gestures, lack of facial expression)
    3. Relationship deficits (e.g. difficulty making friends, sharing imaginative play, lack of interest in peers)
  2. Restricted, repetitive patterns of behavior, interests or activities as manifested by at least 2 of the following
    1. Repetitive movement or speech (e.g. lines up toys, repeatedly flips objects, Echolalia or repeated phrases)
    2. Adheres rigidly to routine, ritualized behavior (e.g. distress with small changes or transitions, rigid thinking, same meals)
    3. Restricted, fixated interests (e.g. attachment to unusual objects, Perseveration about certain interests)
    4. Hyper- or hypo-reactivity sensory response (e.g. indifferent to pain/temp, intolerance to specific sounds/textures)
  3. Symptoms start in early development (but may fully manifest later with increasing social demands)
  4. Symptoms cause Clinically Significant social, occupational or other functional Impairment
  5. Not explained by Intellectual Disability or global Developmental Disorder
  6. Severity
    1. Level 3 (Requires very substantial support)
      1. Social communication deficits: Minimal social interaction, primarily unintelligible speech
      2. Restricted/repetitive behaviors: Inflexible behavior, cannot cope with change, impaired global function
    2. Level 2 (Requires substantial support)
      1. Social communication deficits: Limited communication (e.g. simple sentences), special interests, odd behavior
      2. Restricted/repetitive behaviors: Restricted, repetitive behaviors interfere with function, poorly copes with change
    3. Level 1 (Requires support)
      1. Social communication deficits: Speaks in full sentences and communicates, but 2-way fails, trouble making friends
      2. Restricted/repetitive behaviors: Inflexible behavior, difficulty switching between activities, planning, organization
  7. Additional features
    1. With or without intellectual Impairment
    2. With or without language Impairment
    3. Associated with known medical condition, genetic condition or environmental factor
    4. Associated with another neurodevelopmental, mental or behavioral disorder
    5. With Catatonia
  8. Consider other conditions if Autism Spectrum Disorder criteria not met
    1. Pragmatic or Social Communication Disorder
      1. Severe social communication deficits without meeting ASD criteria
  9. References
    1. (2013) DSM 5, APA, Washington, p. 50-1
  • Evaluation
  • Interaction Pearls (at medical encounters)
  1. Interview parents aside first
    1. Learn about the child's likes and dislikes
    2. Identify where on Autism spectrum child lies
    3. What works and does not work for behavioral coping strategies and medical management
    4. What are the most significant sensory triggers
  2. Allow for a controlled, quiet, calm environment
    1. Minimize distractions and loud noises
    2. Dim lights
    3. Patient may keep their own clothes on instead of a hospital gown
    4. Noise canceling headphones
    5. Deep pressure blankets
    6. Eye masks
    7. Distracting toys
  3. Prepare children and the parents in advance for pending interventions
    1. Prepare the parents first for the overall plan
    2. Talk to the child (even if non-verbal) and let them know exactly what you plan to do
    3. Tell patients the order of tasks and what is the last task you plan to perform
    4. Tell patients how long each task will take
      1. I am going to listen to your lungs for 5 seconds ("You count")
    5. Allows for adequate processing time (delayed in Autism)
  4. Early recognition of acute Agitation
    1. Evaluate for pain causes of Agitation
    2. Avoid excessive talking
    3. Back off and take a break from evaluation
    4. Employ distraction and other deescalation measures
    5. Consider medications for Agitation if other deescalation measures are failing
    6. Avoid Physical Restraints unless other measures are exhausted
  5. References
    1. Claudius in Majoewsky (2012) EM:Rap 13(1): 4
    2. Drapkin and Brickley (2023) Chilcren with Autism in the ED, EM:Rap 23(11)
  • Management
  • Nonpharmacologic
  1. Arrange a multidisciplinary team
    1. Audiologist
    2. Developmental pediatrician or pediatric neurologist
    3. Genetic counselor (evaluate for associated syndromes)
    4. Occupational therapist
    5. Speech pathologist
    6. Social worker
    7. Child psychiatrist
    8. Child psychologist
  2. Early intervention
    1. Early and intensive interventions significantly improve longterm functioning and IQ
      1. Initiate before age 3
      2. Intensive treatment for 25-40 hours per week for at least 1 year
      3. Eldevik (2008) J Clin Child Adolesc Psychol 38(3): 439-50 [PubMed]
      4. Rogers (2008) J Clin Child Adolesc Psychol 37(1): 8-38 [PubMed]
    2. Teach communication and socialization skills
      1. Targeted play
      2. Social skills training (if no intellectual dysfunction)
    3. Augmented communication (e.g. letter board)
    4. Behavioral modification
      1. Structured environment
      2. Respond consistently to behaviors
        1. Reward desired behaviors
        2. Do not reward undesired behavior
        3. Shaping
          1. Reinforce behaviors near desired behavior
          2. Child steps closer and closer to goal
          3. Master simple skills
            1. Systematically build on these to develop more complex skills
      3. Lovaas Program (Discrete Trial Training)
        1. Behavioral techniques
        2. Intensive and expensive program for 2 years or more
        3. Short-term and long-term efficacy is unclear
    5. Developmental intervention
      1. Applies child development theory to Autism
      2. No evidence to support to date
    6. Structured Teaching (TEACCH Autism Program)
      1. Combines both behavioral and developmental methods
      2. Highly organized, structured environments present clear concrete visual information
      3. Evidence suggests significant improvement on motor and non-verbal skills
  3. School Evaluation
    1. Mainstream child in classroom
    2. Plans include Individualized Education Plan (IEP) and 504 Plan
    3. Start IEP Transition plan at age 14 to 16 years
    4. Special education may be extended for those who qualify up to age 22 years
  4. Transition to Adulthood
    1. General
      1. Start the transition preparation in teen years (14 to 16 years old)
      2. Transition discussion should be included in the school Individualized Education Plan (IEP)
    2. Decision Making
      1. Guardianship
        1. Legal approach to revoking a person's rights to make their own independent decisions
        2. Process may take >1 year (start early)
      2. Shared Decision Making
        1. Person chooses the support person that can help with specific decisions
    3. Resources
      1. ARC Guide to Decision Making
        1. https://arcminnesota.org/resource/arc-guide-to-guardianship/
      2. Autism readiness to drive
        1. https://www.research.chop.edu/car-autism-roadmap/driving-and-asd-determining-readiness
      3. Decision to reveal Autism diagnosis to employers
        1. https://www.autismspeaks.org/tool-kit-excerpt/disclose-or-not-disclose
      4. Transitioning to Life After High School (PACER Center)
        1. https://www.pacer.org/students/transition-to-life/
  5. Other measures
    1. Applied Behavioral Analysis (ABA) Therapy
    2. Cognitive Behavioral Therapy (CBT)
      1. Consider Trauma-Focused CBT (e.g. TFCBT) for Children with Trauma History
    3. Music Therapy (making music, recreating songs, improvising, listening to a therapist play music)
      1. Geretsegger (2022) Cochrane Database Syst Rev (5):CD004381 [PubMed]
  6. Treat comorbid conditions
    1. Attention Deficit Disorder
    2. Manic Depression
    3. Anxiety Disorder
  • Management
  • Medications
  1. Precautions
    1. Strongly consider specialty referral when medication therapy is considered
    2. Reserve medications for moderate to severe behaviors
      1. Medication adverse effects are common (especially Atypical Antipsychotics)
      2. Adverse effects include Extrapyramidal Side Effects, Tremor, sedation, weight gain
      3. Use the lowest effective dose
    3. Exclude underlying medical causes (e.g. pain) resulting in maladaptive behaviors
      1. Headaches
      2. Sinusitis
      3. Gastrointestinal conditions
    4. Efficacy of medications in Autism may be less effective than when used in patients without Autism
      1. SSRIs may have only modest effect on anxiety and may offer little benefit in repetitive behaviors
      2. Methylphenidate may have only marginal effect on ADHD in Autism
    5. References
      1. (2012) Presc Lett 19(5): 30
  2. Aggressive behaviors (aggression, outbursts, self-injury)
    1. Fluvoxamine (Luvox)
      1. Has been studied in adults with Autism
      2. McDougle (1996) Arch Gen Psychiatry 53(11): 1001-8 [PubMed]
    2. Aripiprazole (Abilify)
      1. Approved for children 6 to 17 years old
      2. Marcus (2009) J Am Acad Child Adolesc Pscyhiatry 48(11): 1110-9 [PubMed]
    3. Risperidone (Risperdal) effective for short-term aggressiveness
      1. Approved for children 5 to 16 years old
      2. McCracken (2002) N Engl J Med 347:314-21 [PubMed]
  3. Anxiety Disorder
    1. Fluoxetine (Prozac)
  4. Obsessive-compulsive symptoms (rigidity, repetition)
    1. Risperidone (Risperdal)
    2. Fluoxetine (Prozac)
    3. Fluvoxamine (Luvox)
  5. Hyperactivity, impulsivity or inattention
    1. Alpha-2 Agonists such as Clonidine (Catapres) or gunafacine
    2. Atomoxetine (Strattera)
    3. Stimulants such as Methylphenidate (Ritalin)
      1. Less effective than in children without ASD
  6. Sleep Disorders
    1. Trazodone
    2. Melatonin
      1. Start 0.5 to 1 mg taken 30-60 minutes before bedtime
      2. Titrate to a maximum dose of 10 mg as needed
  7. Complimentary and Alternative Medicine (CAM)
    1. Melatonin (for Sleep Disorders as above)
    2. Massage therapy (parents may perform)
      1. May improve sleep and language and decrease anxiety, and repetitive behaviors
    3. Other measures are not recommended due to lack of efficacy and risk of toxicity and adverse effects
      1. Vitamin B6 supplementation
      2. Magnesium Supplementation
  • Associated Conditions
  • Common Medical Diagnoses
  1. Restricted Diet Related
    1. Constipation
    2. Vitamin Deficiency (e.g. Vitamin B12 Deficiency)
  2. Dental Infections
  3. Subtle Seizures
  4. High Pain threshold
    1. Occult Fractures with delayed presentation
  • Prognosis
  • Predictors of best outcomes
  1. Lower Autism spectrum disorder severity
  2. IQ >70
  3. Early referral
  4. Intensive intervention
  5. Behavioral modification more than medication therapy
  6. Better person-environment fit
    1. Improved with daytime recreational activities, community inclusion
  • Resources
  1. Autism Society of America
    1. http://www.autism-society.org
    2. Phone: 800-328-8476
  2. Association for Science in Autism Treatment
    1. http://www.asatonline.org
  3. UCLA PEERS (Social skill development in teens)
    1. https://www.semel.ucla.edu/peers
  4. Autism Speaks
    1. http://www.autismspeaks.org
  5. CDC Autism Resources
    1. http://www.cdc.gov/ncbddd/autism
  6. American Academy of Pediatrics Autism Resources
    1. http://www2.aap.org/healthtopics/autism.cfm
  • References
  1. Katusic (2024) Mayo Clinic Pediatric Days, attended lecture 1/14/2024
  2. Leventhal in Tasman (1997) Psychiatry, p. 650-667
  3. Carbone (2010) Am Fam Physician 81(4): 453-61 [PubMed]
  4. Filipek (1999) J Autism Dev Disord 29:439-82 [PubMed]
  5. Myers (2007) Pediatrics 120(5) [PubMed]
  6. Prater (2002) Am Fam Physician 66(9):1667-74 [PubMed]
  7. Rapin (2001) JAMA 285:1749-57 [PubMed]
  8. Robins (2008) Autism 12(5): 537-56 [PubMed]
  9. Sanchack (2016) Am Fam Physician 94(12): 972-79 [PubMed]