AUTISM

Autism is a neurodevelopmental disorder characterized by a behavioural phenotype that includes qualitative impairment in the areas of language development or communication skills, social interactions and reciprocity, and imagination and play. It is a type of pervasive development disorder of which the rest are: a) Asperger disorder- similar but language skills intact b) Rett syndrome- affects girls; regression in skills between 6-18 mo. of age. c) Childhood disintegrative disorder- clinically significant regression in skills before 10yrs of age. It develops and is typically diagnosed before 36mo. of age.

Epidemiology
Prevalence of all pervasive developmental disorders is 58.7/10,000 children. Autism- 22/10,000 Asperger syndrome- 11/10,000 Childhood disintegrative disorder- 0.9/10,000 Pervasive developmental disorders- 24.8/10,000

Aetiology
Unknown but thought to be multifactorial with a strong genetic influence. Genetic component believed to be attributed to 100 genes, and genetic abnormalities have been identified in mitochondrial genes and all chromosomes except chromosome 14 & 20. Certain chromosomes have been implicated more than others i.e. chromosomes 7q, 2q & 15q11-13. Thought that multiple genes interact with varied environmental causes to produce the disorder. Autism and Asperger syndrome are 4 and 8 more times prevalent in males respectively, suggesting a strong X-linked component.

It also linked with other neurodevelopmental disorders e.g. seizure disorder, fragile X syndrome and tuberous sclerosis.

However autism is not associated with certain emotionally distant parenting styles refrigerator mothers or the MMR (measles-mumps-rubella) vaccine as previously thought.

Clinical features
Presentation varies with severity of impairment. Most children have some impairment in joint attention or pretend play. Joint attention is the ability to use eye contact and pointing for the purposes of sharing experiences with others. It develops by 18 mos. Precursor skills to joint attention that are also absent include protoimperative pointing (use of pointing to obtain an object of desire) and protodeclarative pointing (use of pointing to an object of interest simply to have another share in the interest with him/her). Symptoms vary from some making no eye contact and seeming totally aloof to showing intermittent engagement with the environment and may make inconsistent eye contact, smile and hug.

Varying verbal abilities range from nonverbal to advanced speech capable of imitating songs, rhymes or TV commercials. Speech has an odd prosody/intonation and may be characterized by echolalia, pronoun reversal, nonsense rhyming and other idiosyncratic language forms. Intellect also varies from mental retardation to superior intellectual functioning in select areas e.g. puzzles, music and art. Play skills are aberrant with little symbolic play, ritualistic rigidity and preoccupation with parts of objects. Stereotypical body movements, marked need for sameness and narrow range of interests are common. They are often withdrawn and spend hours in solitary play. Ritualistic play/behavior prevails showing need for a consistent, predictable environment. Tantrum-like rages may accompany disruptions of routine.

Neuroanatomical findings
The head circumference is normal or slightly smaller at birth till 2mo. of age. Theres then a rapid increase in head circumference from 6-14mo. of age till 2yrs of age. There is increased brain volume characterized by increased volume of the cerebellum, cerebrum and amygdala. Abnormal growth in the first 2yrs is most

marked in the frontal, temporal, cerebellar and limbic regions in the brain. These are the regions responsible for higher-order cognitive, language, emotional and social functions. There are anatomic changes in the anterior cingulate gyrus which is responsible for decision making and ascription of feelings and thoughts. Deficits in the reticular activating system, structural cerebellar changes, forebrain hippocampal lesions and radiologic abnormalities in the prefrontal and temporal lobes may be present. Early abnormal growth processes in the brain in the first 2yrs underlie the emergence of preclinical behavioural abnormalities. This period of early, accelerated brain growth appears to stop early in childhood and is followed by abnormally slow or arrested growth resulting in areas of underdeveloped and abnormally circuitry in the brain.

Diagnosis
Red flags that should prompt an immediate evaluation include early social skill deficits e.g. abnormal eye contact, failure to orient to name, failure to use gestures to point or show, a lack of interactive play, failure to smile, lack of sharing and lack of interest in other children. These precede the emergence of odd or stereotypical behaviours or unusual language usage seen in autism in later years.

A diagnostic criterion as per DSM-IV-TR 2000 is:

AUTISTIC DISORDER A. A total of 6 (or more) items from (1),(2), and (3), with at least 2 from (1) and 1
each from (2) and (3): 1. Qualitative impairment in social interaction, as manifested by at least 2 of the following:

a. Marked impairment in the use of multiple nonverbal behaviors, such as eye-toeye gaze, facial expression, body postures, and gestures to regulate social interaction b. Failure to develop peer relationships appropriate to developmental level c. Lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest) d. Lack of social or emotional reciprocity 2. Qualitative impairments in communication, as manifested by at least 1 of
the following:

a. Delay in, or total lack of, development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication,

such as gesture or mime) b. In individuals with adequate speech, marked impairment in ability to initiate or sustain a conversation with others c. Stereotyped and repetitive use of language or idiosyncratic language d. Lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level 3. Restricted, repetitive, and stereotyped patterns of behavior, interests, and
activities, as manifested by at least 1 of the following:

a. Encompassing preoccupation with 1 stereotyped and restricted pattern of interest that is abnormal in either intensity or focus b. Apparently inflexible adherence to specific, nonfunctional routines or rituals c. Stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting or complex whole body movements) d. Persistent preoccupation with parts of objects B. Delay or abnormal functioning in at least 1 of the following areas, with onset < age 3 yrs. : (1) social interaction,(2) language as used in social communication, or (3) symbolic or imaginative play C. The disturbance is not better accounted for by Rett disorder or childhood disintegrative disorder

Screening tools include: a) Checklist for Autism in Toddlers (CHAT) - for use with 18mo. old children. It has high positive predictive value but has low sensitivity. b) Modified- CHAT (M-CHAT) - good sensitivity and specificity. c) Pervasive developmental disorder screening test (PDDST) - targets children from birth-3yrs of age. Comprehensive evaluation: a) Through physical exam Head circumference(25% may have macrocephaly which may not be apparent till the 2nd yr. of life) Other physical stigmata e.g. exam of the skin with a Wood lamp to look for hypopigmented lesions(tuberous sclerosis); long face, large ears, large testes(fragile X syndrome); ataxic gait, broad mouth(Angelman syndrome)

b) Audiologic evaluation and a comprehensive speech and language evaluation if language delays present. c) Lead levels if has signs of pica or lives in a high-risk environment d) Chromosomal analysis if there is evidence of mental retardation and dysmorphic features. e) EEG if signs of developmental regression or suspicion of seizures present.

Treatment
a) Intensive behavioural therapy beginning before 3yrs targeted towads speech and language development b) Parent education, training and support c) Older children and adolescents with relativcely higher intelligence but poor social skills and psychiatric symptoms (depression, anxiety, and obsessivecompulsive disorder) may require psychotherapy, behavioural or cognitive behavioural therapy and pharmacotherapy. Behavior modification is a major part of overall treatment. d) Pharmacotherapy is used to ameliorate target behaviours: Atypical neuroleptics e.g. risperidone, olanzapine, improve social relatedness and treats hyperactivity, tantrums, physical aggression, self-injurious behavior, stereotypies and anxiety symptoms(OCD behaviours) Naltrexone, an opoiate antagonist, is used for self-injurious behavior Clomipramine, a TCA, inhibits serotonin uptake thus reduces compulsions and stereotypies. Its adverse effects include lowers seizure threshold, agranulocytosis, cardiotoxicity and behavior toxicity. Others include stimulants, SSRIs (diminishes hyperactive, agitated and obsessive-compulsive behaviours) and clonidine.

Prognosis
Some of those with speech may grow up to live self-sufficient employed though isolated lives in the community. Many however remain dependent on their family for their everyday lives or may need placement in facilities. No increased risk of schizophrenia in adulthood though the cost of late diagnosis is high.

The symptom profile may change as they grow older and seizures or other selfinjurious behavior becomes more common. Delayed diagnosis has a poor prognosis. Favourable prognosis is related to higher intelligence, functional speech and less bizarre symptoms and behavior.