Prof. Joesoef Simbolon, SpKJ (K)

Characterized by severe and pervasive impairment in several areas of development:Reciprocal social interaction skillsCommunication skillsPresence of stereotyped behavior, interests and activities Qualitative impairments are distinctly deviant relative to developmental level or mental age.Usually evident in the first years of lifeOften associated with some degree of mental retardationSometimes observed with a diverse group of other general medical conditions

* Pragmatic and/or social language may be impaired

Characteristics of DSM-IV subtypes of PDDCharacteristicAutistic DisorderAspergers DisorderPDD not otherwise specifiedRetts DisorderChildhood Disintegrative Disorder (CDD)Age at onset< 3 yrsVariableVariable5-30 mos2-10 yrsPresence of regressionMild; in minorityNoNoYesYesGenderM/F ratio 4:1M>FM>FF primarilyM>FMental retardationPresent in majorityAbsent in majorityVariableOften severeOften severeSocial impairmentYesYesYesYesYesCommunication impairmentYesNo*VariableYesYesRestricted interests/ repetitive behaviorYesYesVariableYesYes

Can be a lack of interest in social interaction or a lack of skills to facilitate interactionManifested as:Marked impairment in non-verbal gesturesFailure to develop appropriate peer relationshipsLack of seeking to share enjoymentLack of social/emotional reciprocityEven among high-functioning individuals, social interactions remain impaired into adulthood

Closely connected with social interaction Delay in, or lack of, spoken language or a non-spoken proxyStructural or pragmatic language can be affectedStereotyped or unusual use of language (echolalia, pronoun reversal, neologisms)Comprehension can also be affected, especially around non-literal language

Inflexible adherence to non-functional routinesStereotyped and repetitive motor mannerismsPersistent preoccupation with parts of objectsEncompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal in:IntensityFocus

Irritability/tantrumsHyperactivitySelf-injurious behaviorOdd responses to sensory stimuliLack of fear or excessive fearfulness

Cognitive impairment (~70%)Seizures (~30%)Macrocephaly (~30%)MicrocephalyMental retardationGI and sleep disturbancesPsychiatric comorbiditiesAny = ~70%, two or more = ~40%ADHD = ~30%Anxiety, phobia, OCD = ~44%Depressive disorder ~1%

Known causes include: Chromosomal abnormalities Herpes Simplex Virus (HSV) Malaria Congenital causes

Laboratory findings:When Autistic Disorder is associated with a general medical condition, laboratory findings are consistent with that general medical conditionGroup differences in some measures of serotonergic activity not diagnostic for Autistic DisorderImaging studies may be abnormal no specific pattern clearly identifiedEEG abnormalities are common even in the absence of seizure disordersPhysical examination findings and general medical conditions:Various nonspecific neurological symptoms, e.g.:Primitive reflexes, Delayed development of hand dominanceSometimes observed in association with a neurological or other general medical conditionFragile X syndromeSeizures may develop in as many as 25% of cases (mostly in adolescence)Microcephaly and Macrocephaly

Multidisciplinary Evaluation Team for a Comprehensive Diagnostic EvaluationPsychologist, preferably a specialist in child development to administer tests such as the ADOS, ADINeurologist to assess seizures, assess need for imaging, check for other possible etiologiesPsychiatrist to evaluate for related illnesses such as ADHD, anxiety, and OCDSpeech-Language Pathologist or Therapist to evaluate language capabilities and initiate a treatment planSocial worker and/or special education teacher to assess caregiver needs and facilitate entry into appropriate support and education services

Appropriate types of assessments, not all may be performedBasic neurological assessment Genetic check for Fragile X Syndrome or other genetic disorders, especially if dysmorphism or family history is presentIn-depth cognitive testing, usually by a psychiatrist or neuropsychologistFormal hearing test by the PCP, a speech/language pathologist, or hearing specialistLead screening (heavy metal) test, especially if pica is apparent

DSM-IV-TR Diagnostic Criteria for Autistic DisorderThe person fulfills a total of at least 6 criteria from the following:Impaired social interaction (at least 2):Markedly deficient regulation of social interaction by using multiple non-verbal behaviors such as eye contact, facial expression, body posture and gestures.Lack of peer relationships that are appropriate to the developmental level.Doesn't seek to share achievements, interests or pleasure with others.Lacks social or emotional reciprocity.Impaired communication (at least 1):Delayed or absent development of spoken language for which the patient doesn't try to compensate with gestures.In person's who can speak, inadequate attempts to begin or sustain a conversation.Language that is repetitive, stereotyped or idiosyncratic.Appropriate to developmental stage, absence of social imitative play or spontaneous, make-believe play.Activities, behavior and interests that are repetitive, restricted and stereotyped (at least 1):Preoccupation with abnormal (in focus or intensity) interests that are restricted and stereotyped (such as spinning things).Rigidly sticks to routines or rituals that don't appear to have a function.Has stereotyped, repetitive motor mannerisms, such as hand flapping.Persistently preoccupied with parts of objects.

Additionally:Before age three, the person shows delays or abnormal functioning in at least one of the following:Social interaction Language used in social communication Imaginative or symbolic play

These symptoms exhibited by the patient are not better explained by a diagnosis of Childhood Disintegrative Disorder or Rett's Disorder.

BehavioralApplied behavior analysisAdaptive skillsIntegrationNon-verbal communication methods (picture exchange, eye-contact coaching)EducationalSpecialized classes, low student: teacher ratios, early intervention

SSRIs: OCD-like behaviors, aggression, anxietyStimulants: ADHD-like behaviorsMood-stabilizers: impulsivity, mood labilityAntipsychoticsRisperidoneAripiprazoleSmall, mostly open-label trials with the others

Treatment PharmacologicMedications are frequently used to address behaviors or symptoms of autism.

Serotonin re-uptake inhibitors:Effective in treating depression, obsessive-compulsive behaviors and anxietyCould reverse some of the symptoms of serotonin dysregulation found in 1/3 of individuals with autismStudied: fluvoxamine (Luvox), fluoxetine (Prozac).May reduce frequency/intensity of repetitive behaviors, may decrease irritability, tantrums, agressive behaviors. Sometimes shows improvement in eye contact and responsiveness.

Source: Autism Society of America

Treatment PharmacologicAntipsychotic medications:Most widely studied of psychopharmacologic agents in autismDeveloped for treating schizophrenia and found to decrease hyperactivity, stereotypical behaviors, withdrawal and agression in individuals with autismExamples: clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify)Studied in adults with autism and FDA approved: risperidone (Risperdal)Need careful monitoring due to side effects, including sedationSource: Autism Society of America

Treatment PharmacologicStimulants:Ritalin, Adderall and DexedrineUsed to treat hyperactivity in children with ADHDFew studies but anecdotal evidenceMay increase focus and decrease impulsivity and hyperactivity in autism, particularly in children who are not as severely affectedNeed careful monitoring of dosages due to behavioral side effectsSource: Autism Society of America

Excessively active at home, school, work or elsewhereInjures self on purposeListless, sluggish, inactiveAggressive to other children or adults (verbally or phisically)Seeks isolations from othersMeaningless, recurring body movementsBoisterous (inappropriately noisy & rough)Screams inappropriatelyTalks excessivelyTemper tantrum/outburstsStereotyped behavior,abnormal,repetitive movementsPreoccupied, stares into spaceImpulsive (acts without thinking)Irritable and whinyRestless, unable to sit stillWithdrawn; prefers solitary activitiesOdd, bizzare in behaviorDisobedient, difficult to controlYells at inappropriate timeFixed facial expression; lacks emotional responsiveness

Disturbs othersRepetitive speechDoes nothing but sit and watch othersUncooperativeDepressed moodResists any form of phisical contactsMoves or rolls head back and forth repetitivelyDoes not pay attention to instructionDemands must be met immediatelyIsolates himself/herself from other children or adultsDisrupts group activitiesSits or stands in one position for a long time Talks to self loudlyCries over minor annoyances and hurtsRepetitive hand,body, or head movementsMood changes quicklyUnresponsive to structured activities (does not react)Does not stay in seat (e.g during lesson or training periods, meals, ect)Will not sit still for any length of timeIs difficult to reach, contact or get through toCries and scream appropriatelyPrefers to be aloneDoes not try to communicate by word or gesturesEasily distractableWaves or shakes the extremities repeatedlyRepeats a word of phrase over and overStamps feet or bangs objects or slams doors

Constantly runs and jumps around the roomRocks body back and forth repeatedlyDeliberately hurts himself/herselfPays no attention when spoken toDoes physical violence to selfInactive, never moves spontaneuslyTends to be excessively activeResponds negatively to affectionDeliberately ignores directionsHas temper outburts or tantrums when he/she does not get own wayShows few social reactions to other

Mean Change in the Aberrant Behavior Checklist - Irritability Subscale by Week (LOCF)Mean baseline scores (SE): Pbo = 30.8 (1.0); Ari = 29.6 (1.0)****************** p < 0.05, ** p < 0.005, *** p < 0.001 vs. placeboMean Change in ABC-IWeek

Mean Change from Baseline in the Aberrant Behavior Checklist - Irritability Subscale by Week (LOCF)* p < 0.05, 15 mg arm only, ** p < 0.05 all arms, *** p < 0.01 all arms vs. placeboMean Change in ABC-I****************Mean baseline scores (SE): Pbo = 26.9 (1.0); Ari 5 mg = 28.3 (1.0), 10 mg = 27.6 (0.9), 15 mg = 28.3 (1.0)

Mean Change from Baseline in the Aberrant Behavior Checklist - Irritability Subscale by Week (LOCF)* p < 0.05, 15 mg arm only, ** p < 0.05 all arms, *** p < 0.01 all arms vs. placeboMean Change in ABC-I****************Mean baseline scores (SE): Pbo = 26.9 (1.0); Ari 5 mg = 28.3 (1.0), 10 mg = 27.6 (0.9), 15 mg = 28.3 (1.0)

Mean Change from Baseline in Aberrant Behavior Checklist Subscales at Endpoint (LOCF)Placebo Aripiprazole 5 mg Aripiprazole 10 mg Aripiprazole 15 mg***p0.05; **p0.01; ***p

Mean Change from Baseline in Aberrant Behavior Checklist Subscales at Endpoint (LOCF)Placebo Aripiprazole 5 mg Aripiprazole 10 mg Aripiprazole 15 mg***p0.05; **p0.01; ***p

8-week Autistic-StudyEfficacy in Autistic Pediatric PatientMean Change in Aberrant Behavior Checklist(6 17 years old)IRRITABILITIYMean Change inChildren Yale-Brown Obsessive Compulsive Scale(Week-8)COMPULSIONAbilify

Most children diagnosed with autism (average age 5 years) retain that diagnosis at 9 yearsOutcomes are better for PDD-NOSEarly and intensive intervention is keyLong-term prognosis is poorMost autistic individuals as adults are highly dependent on caregiversEven those who are able to work and function independently have difficulties with interpersonal relationshipsIQ tends to remain stable, and outcomes are generally better with individuals with a high IQ

MEDAN, 10 MARET 2011