What are the common symptoms and treatment options for a pediatric patient with Autism Spectrum Disorder (ASD)?

Autism Spectrum Disorder: Core Symptoms and Treatment

Core Diagnostic Features

ASD is defined by two core symptom domains: persistent deficits in social communication and interaction across multiple contexts, and restricted, repetitive patterns of behaviors, interests, or activities. 1, 2

Social Communication Deficits

The social communication impairments manifest as:

• No response to name when called, particularly in the first 2 years of life 2
• Lack of or limited use of gestures in communication 2
• Avoidance of eye contact and difficulty with reciprocal social interaction 3
• Idiosyncratic, one-sided conversational style, often focused on circumscribed interests 1
• Absence of imaginative or pretend play 2, 3

Restricted and Repetitive Behaviors

The behavioral domain includes:

• Stereotyped movements and repetitive motor mannerisms 1
• Restricted interests that are abnormal in intensity or focus 1
• Insistence on sameness and inflexible adherence to routines 1
• Sensory abnormalities (hyper- or hypo-reactivity to sensory input) 1

Common Comorbidities

Approximately 75% of individuals with ASD have comorbid psychiatric conditions that significantly impact morbidity and quality of life. 4

The most prevalent comorbidities include:

• Depression occurs in 20% of individuals with ASD versus 7% in the general population 2
• Anxiety affects 11% versus 5% in the general population 2
• ADHD symptoms are highly prevalent and often require specific treatment 4
• Sleep difficulties affect 13% versus 5% in the general population, with insomnia prevalence ranging from 53-78% in children with ASD 1, 2
• Epilepsy occurs in 21% of individuals with co-occurring intellectual disability versus 0.8% in the general population 2
• EEG abnormalities and seizure disorders are observed in 20-25% of individuals with ASD 1

Treatment Approach

First-Line: Intensive Behavioral Interventions

Intensive behavioral interventions are the primary treatment for core ASD symptoms and should be initiated as early as possible, ideally in children 5 years or younger. 2

• Early Start Denver Model and similar intensive behavioral programs demonstrate small to medium effect sizes for improving language, play, and social communication 2
• Behavioral interventions targeting social skills show promise in improving social interaction and verbal communication 4
• For insomnia, parent education in behavioral approaches should be the first-line intervention 1

Pharmacological Treatment for Target Symptoms

Medications are indicated for co-occurring psychiatric conditions and specific behavioral symptoms, not for core social communication deficits. 2

For Irritability and Aggression

Risperidone and aripiprazole are FDA-approved for treating irritability associated with autistic disorder in children and adolescents aged 5-17 years. 5

• These agents demonstrate large effect sizes (standardized mean difference of 1.1) for reducing irritability and aggression compared to placebo 2
• Risperidone dosing is weight-based: 1.25 mg/day for patients 20 to <45 kg, and 1.75 mg/day for patients ≥45 kg 5
• Common adverse effects include weight gain (mean 2 kg in short-term trials), somnolence, and hyperprolactinemia (49% of pediatric patients develop elevated prolactin) 5
• Approximately 33% of risperidone-treated patients experience >7% weight gain versus 7% in placebo groups 5

For ADHD Symptoms

Psychostimulants are effective for comorbid ADHD in ASD with moderate effect sizes (standardized mean difference of 0.6). 2

• Alpha-2 adrenergic agonists like guanfacine provide an alternative for ADHD symptom management 4
• Monitor for adverse effects including changes in appetite, weight, and sleep 2

For Sleep Disturbances

Melatonin trials show promise for treating insomnia in children with ASD, though evidence remains limited. 1

• All children with ASD should be screened for insomnia given the 53-78% prevalence 1
• Screen for contributing medical factors before initiating pharmacotherapy 1
• Behavioral interventions should precede medication trials 1

Critical Assessment Components

Diagnosis requires a comprehensive multidisciplinary evaluation including standardized direct observation and caregiver interview. 1, 2

Mandatory Evaluations

• Physical examination including Wood's lamp examination for tuberous sclerosis 1
• Hearing screen to rule out auditory deficits 1
• Genetic testing: chromosomal microarray is the standard of care with 24% diagnostic yield 1
• Fragile X testing (0.57% yield) and G-banded karyotype (2.5% yield) 1
• Psychological assessment measuring cognitive ability and adaptive skills 1

Standardized Diagnostic Measures

• Autism Diagnostic Observation Schedule-Second Edition has 91% sensitivity and 76% specificity 2
• Autism Diagnostic Interview has 80% sensitivity and 72% specificity 2
• Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) for screening 3

Additional Testing When Indicated

Obtain EEG, neuroimaging, or specialized genetic testing when history suggests regression, dysmorphology, staring spells, or family history of specific conditions. 1

• Rule out Landau-Kleffner syndrome if marked aphasia develops with distinctive EEG abnormalities 1
• Test for MeCP2 gene in cases suggestive of Rett's disorder 1

Important Clinical Pitfalls

Avoid diagnostic overshadowing—the tendency to miss other conditions when ASD is present. 6

• Systematically evaluate for comorbid conditions rather than attributing all symptoms to ASD 1
• Distinguish between ASD-specific restricted interests and true delusions or obsessive-compulsive symptoms 7
• Recognize that behavioral issues like aggression or inattention may be secondary to untreated sleep disorders 1
• Cultural, ethnic, and socioeconomic factors may affect assessment and lead to underdiagnosis in disadvantaged populations 1

Monitoring and Follow-Up

Long-term monitoring is essential given the chronic nature of ASD and potential medication adverse effects. 5

• Track weight gain systematically during risperidone or aripiprazole treatment 5
• Monitor prolactin levels, particularly in children and adolescents, as 82-87% develop elevated levels 5
• Assess for tardive dyskinesia, though incidence is low (0.1% in pediatric trials) 5
• Evaluate treatment effectiveness and tolerance after any intervention 1
• The long-term effects on growth and sexual maturation have not been fully evaluated in children 5