Divija Autism spectrum Disorder PPT.pptx

Autism spectrum Disorder

1. Autism spectrum disorders Moderator: Dr. Sireesha madam Presenter: Dr. Divija

2. Plan of presentation History Epidemiology Etiology Clinical features Differential diagnosis Comorbidities Assessment tools Diagnosis Course and prognosis Management

3. Epidemiology 1 in 68 children M:F- 2:1(community sample) and up to 4+:1(clinical sample) Familial patterns are well established 19% chance of having autism if one sibling has ASD. Twin studies show 60 –85% concordance for identical twins vs. 10% for fraternal twins

4. Etiology Multifactorial Genetic causes- most significant cause for ASD. Numerous possible genes and chromosomal regions have been identified- FMR1 (20 – 60% of affected kids are autistic) 15q11-13 (PWS & Angelman) 17q11-21 SHANK3 (chromosome 22) Copy Number Variations (CNVs)

5. Medical and Environmental factors- Prenatal, antenatal, postnatal factors- advanced age in either parent, DM, Thyroid problems in mother, bleeding, and use of drugs like sodium valproate, thalidomide. Immunological -Prenatal exposure to Rubella or CMV Neuroanatomical and neurochemical factors- increase in size of amygdala and elevated serotonin levels in platelets Epigenetics - DNA methylation and histone modification. Psychosocial - parenteral emotional factors

6. Cognitive and emotional process Theory of mind (fMRI studies demonstrated decreased activity in mirror neurons in the inferior frontal gyrus) Executive dysfunction Weak central coherence Enhanced perceptual functioning

7. DSM 5 Deficient social communication and interaction ( all 3 ) Marked deficit in nonverbal and verbal social communication Lack of social reciprocation 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 Inflexible adherence to routines & ritualized patterns of behavior Highly restricted, fixated interests Clinically significant, persistent since early developmental period. Symptoms limit and impair everyday functioning Disturbances are not explained by intellectual disability

8. ICD 10

9. When does autism appear? Two patterns are observed. 1. Symptoms present in the first year of life. (children will fail to initiate baby games peek-a-boo, giggling interactions with parents at 4-6 months) and not able to communicate common emotions pain, hunger well. 2. Apparent normal development for the first 12 – 24 months of life prior to the onset of symptoms/ Regression. Can be seen as early as 9 months. More evident by 18 months.

10. Social and emotional reciprocity Social interaction is rarely initiated spontaneously Complete lack of attachment to parents Excessive familiarity with strangers due to the absence of social inhibitions and stranger anxiety. Prefers to play alone (Aloof in crowd) Lacks pretend or imaginative play

11. Communication Improper use of language Receptive Language Lacks communicative intent of others Expressive language Semantics absent Lacks use of language/ gestures to communicate Poor eye contact Echolalia

12. Stereotypies Motor Rocking. Jumping and spinning Hand flapping. Toe Walking Vocal Echolalia Repeating same words/ non-specific sounds

13. Fixed interests Pre-occupied with unusual objects/ parts of objects Threads Beads Pencils Spinning objects Rituals Lining up objects

14. Sensory issues Child may show - Indifference or excessive reaction to pain Abnormal interest in feeling the textures Abnormal reaction to sounds by covering their ears Have excessive smelling or touching of object in unusual manner May have fascination with lights or moving objects

15. Savant syndrome / Splinter skills / savant skills/ precocious skills Skills at which they excel are usually found in one or more of 5 major areas: art, memory, arithmetic, musical abilities, and spatial skills (by rote memory). The most common are calendrical savants/human calendars. Hyperlexia- remarkable ability to read but with poor comprehension

16. Asperger ’ s Disorder Age-7.2years, Boys: girls- 8:1 It is characterized by severe, sustained, clinically significant impairment of social interaction, and RRB’s. Clinically- no delay in language or cognitive development. Obsessive interest in a single subject is a major symptom. Their expertise, high level of vocabulary and formal speech patterns make them seem like little professors. They have trouble reading social cues and recognizing other people's feelings. Problems with motor skills (late learning to ride a bike) Treatment focuses on the three main symptoms: poor communication skills, obsessive or repetitive routines, and physical clumsiness.

17. Retts syndrome It occurs almost exclusively in females, very rarely in males. Typically normal development until between 7 and 18 months of age, then developmental regression in verbal communication. Slowing of head growth (acquired microcephaly),development of distinctive, repetitive hand movements such as hand clapping, rubbing, or “wringing”; and loss of control of voluntary movements required for coordination of walking (gait apraxia). Breathing irregularities, feeding and swallowing difficulties, growth retardation, and seizures(75%). Mutation in the  mecp2  gene on the X chromosome. Rx – symptomatic, physiotherapy, AED’s, BT.

18. Comorbidities Intellectual disability Epilepsy Hyperactivity/ Inattention Anxiety and depressive disorders Obsessive/ compulsive symptoms Sleep Disorders SLD Gastrointestinal symptoms

19. Differential diagnosis Retts syndrome, Aspergers disorder Childhood disintegrative disorder/ Hellers syndrome Selective mutism Language disorders and Social (pragmatic) communication disorder. Intellectual disability with behavioural problems Landau Kleffner syndrome(acquired aphasia with convulsive disorder) Undiagnosed / congenital hearing impairment Schizophrenia

20. Red Flags”/Early suspicion Delayed speech and communication skills (No 2-word spontaneous (not echolalic ) phrases by 24 months). Regression of attained speech and communication skills. Repetitive mannerisms Not consistently responding to name Lack of persistence in social interaction Echolalia Self injurious behaviour Significant disturbances in sleep and feeding habits(pica).

21. Why is Early Dx Important? Intervention provided before age 3 has a much greater impact than intervention provided after age 5. May help speed the child’s overall language development Improvement in IQ scores Gains in initiation of spontaneous communication Lead to better long-term functional outcomes

22. Three generation family history Autism/ ASD Language delay Intellectual disability Fragile X syndrome, Retts, Angelman syndrome, Prader -Willi syndrome, Tuberous sclerosis. Learning disorders/ Obsessive-compulsive disorders Extreme shyness, social phobia, or mutism Seizures Psychosocial History for family support

23. History and Examination Medical history of child and family Physical examination Tuberous sclerosis- Hypopigmented macules/ Adenoma sebaceum / shagreen patch Fragile X syndrome- Long Face/ large ears/ large testes ( postpubertal ) Examine for tone(mild hypotonia +)/ reflexes. Focal neurologic findings, such as asymmetry in tone or reflexes, require further neurologic evaluation and possible neuroimaging

24. Investigations Hearing assessment EEG/Genetic testing/ Neuroimaging Cytogenetic/Molecular Screening may include: Fragile X DNA Probe DNA for MECP2 for Rett Syndrome Chromosome/karyotype analysis DiGeorge /VCF Syndrome (22q11) Prader -Willi Syndrome, Angelman Syndrome (15q11q13)

25. Comprehensive evaluation Objectives: Definitive diagnosis of ASD Identification of co morbid conditions that have implications for treatment or genetic counselling. Determination of the child's level of functioning and profile of strengths and weaknesses.

26. Diagnosis Screening MCHAT - Toddlers (16-36 months,5-10 min to administer) (Robin et al., 1999) Adolescent AQ - 12- 15yrs ; Adult AQ - >16yrs Diagnosis by DSM 5, ICD 10 criteria Generic- Autism Diagnostic Observation Schedule( G-ADOS) (Lord et al., 1989) CARS questionnaire- Most widely used dx instrument,24 months - childhood ages, Parent/caregiver questionnaire(( Schopler et al., 1980) ISAA by NIMH

27. Scoring algorithm No = 1 point (except questions 2, 5, 12 where yes =1 point) Low risk : score 0-2 (If child is less than 24 months, screen again after second birthday) Medium risk : score 3 – 7 ( Administer M-CHAT Follow up) Follow up score : 2 or higher, refer for diagnostic evaluation Follow up score : 0-1 , rescreen at future visits High Risk : score 8-20 ( immediate diagnostic evaluation)

28. Course and Prognosis Prognosis is highly dependent upon the level of functioning Association with ID/language impairment/epilepsy By school age, autistic children can be divided into 3 groups: Low Functioning- Verbal and non-verbal IQ < 70 Mid-Functioning- Non-verbal IQ > 70,verbal IQ < 70 High Functioning- IQ > 70,average adaptive skills, communicative language by 5-7 years.

29. Management

30. Non pharmacological Psychosocial interventions Family/ caretaker education/ parent training approaches Early Intervention (EIBI)- ESDM, Lovaas based model Applied Behavioral Analysis (ABA) Social skills training Educational interventions Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) Speech Therapy (PECS) Occupational Therapy

31. Applied behavioral analysis (ABA) Based on principles of learning (reinforcement). Encourages positive behavior as well teaching new skills. Focuses on teaching small, measurable units of behavior in a systematic way. Typically a question or command is given, a clue or hint is given as necessary. Correct response earns immediate reward and in case of incorrect responses are ignored and multiple trials are given.

32. Pharmacological Antipsychotics for agitation, RRB’S & stereotypies Treat comorbid Axis I disorders SSRIs for repetitive behaviors, anxiety, depression Stimulants (MP) for ADHD BDZ’s, mirtazapine, Ramelteon , Zolpidem, Zaleplon for sleep. Intranasal Oxytocin spray(trials)

33. Risperidone- 0.5-3.5mg (2006) and Aripiprazole -5-15 mg (2009) FDA-approved for the treatment of behavior-related problems (irritability, repetitive behaviors, aggression, deliberate self-injury, and temper tantrums) in children and adolescents with ASD

34. CAM Biological CFGF diet Detoxification (chelation) Probiotics, antifungals Stem Cell Therapy MVT Essential fatty acids aa’s carnosine and carnitine Secretin Non-biological Sensory, Auditory Integration Therapy Music Therapy Yoga

35. Stem Cell Therapy Based on the unique ability of stem cells to influence metabolism, immune system and restore damaged neuronal connections, improvement of synaptic transmission by development of the new neuron connections. Immunity. Communication ability. Learning capacity Better tolerance of different foods and improved digestion. Less or no fear of loud noises, strangers and bright colors (gradual improvement). Improved self-care skills. Improved attention span and concentration.

36. Diet Some kids with ASD showed symptom improvement when gluten (wheat products) and casein (dairy products) are removed from their diet. The hypothesis states that G and C may be difficult for these kids to digest and that metabolites of this problematic digestion may include opioid like substances. Opioids can be tested for in the urine, and some PDD children with self-injurious behavior have been found to have higher levels of opioids in their urine.

37. Take home message ASD is a complex neurodevelopmental disorder where the exact cause is not known (multifactorial in origin). It includes difficulties in social communication, language development and repetitive behaviors and strict adherence to routine practices. It has varied clinical presentations and of different severities(some may live independently, some may require more support). No cure is available. Medications, behavioral therapies, OT,ST may improve the QOL, and make them function independently. Research is still under progress.

38. References Sadock,b.J., Sadock . V.A.,& Ruiz..P .(2017).Kaplan and Sadock’s comprehensive textbook of psychiatry (tenth edition).Philadelphia. Wolters Kluwer. Sadock,b.J., Sadock.V.A .,& Ruiz..P .(2017).Kaplan Sadock’s synopsis of psychiatry(11 th edition).Philadelphia, Baltimore, Newyork.Wolters Kluwer. Rutter, M. (2008). Rutter's child and adolescent psychiatry. Malden, Mass: Blackwell Pub. Vijay Sagar KJ. Research on autism spectrum disorders in India. AP J Psychol Med 2011;12 (1): 69–72. Management of Children With Autism Spectrum Disorders, Scott M. Myers and Chris Plauche ́ Johnson Pediatrics 2007;120;1162; AAP, DOI: 10.1542/peds.2007-2362 Eshraghi AA, Liu G et al.(2018) Epigenetics and Autism Spectrum Disorder: Is There a Correlation? Front. Cell. Neurosci . 12:78. doi : 10.3389/fncel.2018.00078