Autism Spectrum Disorder

Overview

Definition

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a varying range of impairments in communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence, restricted interest, and repetitive behaviors.

Epidemiology

• Recently, worldwide incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency and prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency have rapidly increased:
  • Better qualification and classification of diagnostic criteria
  • Increased awareness of symptoms
  • Increased screening Screening Preoperative Care by primary care providers
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency at 8 years old in the United States:
  • Overall: 1 in 54 
  • Boys: 1 in 34 
  • Girls: 1 in 145 
• By 2 years of age, most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship show behavioral and social signs affecting home and school life.
• Girls are more likely to exhibit intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment than boys.
• Risk factors:
  • Male gender Gender Gender Dysphoria
  • Family history Family History Adult Health Maintenance (particularly siblings)
  • Chromosomal abnormalities
  • Advanced paternal and maternal age 
  • Exposure during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:
    • Toxins
    • Perinatal hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage
    • Prenatal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
• Associated conditions: 
  • Neurodevelopmental disorders:
    • Intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment
    • Language disorders
    • ADHD ADHD Attention deficit hyperactivity disorder is a neurodevelopmental disorder characterized by a pattern of inattention and/or hyperactivity-impulsivity that occurs in at least 2 different settings for more than 6 months. Although the patient has normal intelligence, the disease causes functional decline. Attention Deficit Hyperactivity Disorder
  • Mood disorders:
    • Major depressive disorder Major depressive disorder Major depressive disorder (MDD), commonly called depression, is a unipolar mood disorder characterized by persistent low mood and loss of interest in association with somatic symptoms for a duration of ≥ 2 weeks. Major depressive disorder has the highest lifetime prevalence among all psychiatric disorders. Major Depressive Disorder 
    • Self-injurious behavior
    • Aggressive behavior
    • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep difficulties 
  • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder disorders:
    • Generalized anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder disorder 
    • Obsessive-compulsive disorder Obsessive-compulsive disorder Obsessive-compulsive disorder (OCD) is a condition characterized by obsessions (recurring and intrusive thoughts, urges, or images) and/or compulsions (repetitive actions the person is compelled to perform) that are time-consuming and associated with functional impairment. Obsessive-compulsive Disorder (OCD) 
  • Epilepsy Epilepsy Epilepsy is a chronic brain disorder marked by recurrent and unprovoked seizures. These seizures can be classified as focal or generalized and idiopathic or secondary to another condition. Clinical presentation correlates to the classification of the epileptic disorder. Epilepsy 
  • Genetic disorders:
    • Tuberous sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor
    • Fragile X syndrome Fragile X syndrome Fragile X syndrome (FXS), also known as Martin-Bell syndrome, is a genetic condition with X-linked inheritance. Both boys and girls may be affected, but the severity is much worse in boys. Characteristic features include a long face, prominent forehead and chin, large ears, flat feet, and large testes post-puberty for boys. Fragile X Syndrome
    • Angelman syndrome Angelman syndrome Angelman syndrome (AS) is a rare autosomal neurodevelopmental genetic disorders mapped to a specific region of chromosome 15 attributed to genomic imprinting. A maternally derived chromosome 15 with this deletion results in 15q11-13 maternal deletion syndrome, or AS. Prader-Willi Syndrome and Angelman Syndrome
    • Rett syndrome Rett syndrome Rett syndrome is a rare genetic neurological and developmental disorder that affects the development of the brain. There are various stages of Rett syndrome characterized by different symptoms and clinical signs, including increasing problems with the use of muscles that control movement, coordination, and communication. Rett Syndrome
    • CHARGE syndrome CHARGE Syndrome CHARGE syndrome is a rare genetic condition with autosomal dominant inheritance in which almost all body systems are affected. The acronym CHARGE stands for the constellation of clinical features seen with this condition: Coloboma, Heart defects, Atresia choanae, Growth retardation, Genetic Abnormalities, and Ear abnormalities. CHARGE Syndrome

Pathophysiology

• Pathogenesis is not completely understood: 
  • No evidence to support an association between immunizations and ASD
  • No evidence to support an association between parenting and ASD
• Genetic factor:
  • Estimated median heritability: 81%
  • May be the result of interactions between multiple genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure, which leads to variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables expression
• Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abnormalities: 
  • An overall increase in brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification size 
  • Functional MRI reveals abnormalities in brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification regions associated with socialization (e.g., medial prefrontal cortex, amygdala Amygdala Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the temporal lobe. The amygdala is part of the limbic system. Limbic System: Anatomy).
  • Different gray- and white-matter volumes, brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification chemical concentrations, and neural networks
• Immunological factors: case reports of maternal antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions damaging embryonic neural tissue

Clinical Presentation

Presentation of ASD varies based on the age of presentation.

• 0–2 years:
  • A deficit or delay in social skills:
    • No social smile
    • No stranger or separation anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
    • Lack of pretend or symbolic play by 18 months of age
  • A deficit or delay in language:
    • No babbling by 9 months
    • No pointing or gestures
    • Lack of orientation Orientation Awareness of oneself in relation to time, place and person. Psychiatric Assessment to name by 12 months of age
    • No single words by 16 months of age 
    • Loss of language skills
• Preschool age:
  • A deficit in social communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence and interaction:
    • Lack of normal language development 
    • Slow or no response to name
    • Prefers to play alone (may be aggressive toward other children)
    • Lack of nonverbal communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence 
    • Unable to sustain social interactions or share emotions/interests
    • No reaction to normal stimuli (noise, texture Texture Dermatologic Examination, smells)
  • A pattern of restricted, repetitive, and limited behaviors:
    • Repetitive motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology movements (running in circles, shaking the head)
    • Resistant to changes in routine (reacts with crying/ aggression Aggression Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism. Oppositional Defiant Disorder)
    • Atypical play (lines up objects, opens/closes doors repeatedly, turns lights on/off repeatedly)
    • Overly attentive to parts of toys (e.g., stares at spinning wheel)
• School-age and older:
  • A deficit in social communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence and interaction:
    • Lack of normal language development
    • Lack of nonverbal communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence (no eye-to-eye contact)
    • Prefers to be alone (lacks friends, does not attend social gatherings)
    • Does not understand norms of social communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence
    • Anger toward the invasion of personal space
    • Unable to sustain social interactions or share emotions/interests
  • A pattern of restricted, repetitive, and limited behaviors (resists any changes in routine):
    • Atypical play (not cooperative or imaginative)
    • Abnormal response to sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology stimuli: hyper- or hyporeactivity (excessively touching other people/objects, unusually smelling other objects)

Diagnosis

Pediatricians should systematically screen children of appropriate age for ASD at well-child visits. 

• History and physical exam, including thorough mental-status examination, are the key to diagnosis.
• Standardized questionnaires are often utilized at 16–30 months of age:
  • Modified checklist for autism in toddlers (MCHAT)
  • Autism mental status exam (AMSE)
• Initial assessment may also include laboratory screenings:
  • Genetic 
  • Complete metabolic panel 
  • Endocrine 
  • Infectious 
  • Toxic
• EEG EEG Seizures may be recommended.

Management and Prognosis

Management

• No cure is available; rather, manage with individualized, multimodal, interdisciplinary plans.
• Improve the core features of the disorder and target any comorbid behavioral or medical conditions. 
• Behavioral therapy:
  • To improve social communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence and help achieve independence
  • Combination of behavioral and educational modalities (e.g., family therapy Family therapy A form of group psychotherapy. It involves treatment of more than one member of the family simultaneously in the same session. Psychotherapy)
• Pharmacotherapy:
  • Medications to treat comorbid conditions
  • Irritability and aggression Aggression Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism. Oppositional Defiant Disorder may be treated by 2nd-generation antipsychotics (e.g., risperidone Risperidone A selective blocker of dopamine D2 receptors and serotonin 5-HT2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. Second-Generation Antipsychotics).
  • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder and depressive mood symptoms may be treated with selective serotonin reuptake inhibitors Selective Serotonin Reuptake Inhibitors Serotonin Reuptake Inhibitors and Similar Antidepressants (e.g., fluoxetine Fluoxetine The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. Serotonin Reuptake Inhibitors and Similar Antidepressants).
  • Symptoms of hyperactivity Hyperactivity Attention Deficit Hyperactivity Disorder, inattention Inattention Attention Deficit Hyperactivity Disorder, and impulsivity Impulsivity Attention Deficit Hyperactivity Disorder may be treated with psychostimulants (e.g., methylphenidate Methylphenidate A central nervous system stimulant used most commonly in the treatment of attention deficit disorder in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. Stimulants).

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• Early diagnosis and intervention improve outcomes.
• The most prognostic factors for independent living: cognitive and verbal capacity before 6 years of age.
• Approximately 15% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship live independently.
• 10%–15% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship need community living support.

Differential Diagnosis