Asperger Syndrome

Article Author:
Seyed Alireza Hosseini
Article Editor:
Mohammed Molla
Updated:
6/22/2020 6:05:20 PM
PubMed Link:
Asperger Syndrome

Introduction

Asperger syndrome (AS) was first described by Hans Asperger in 1944, as the behavioral characterization of individuals who have difficulties in communication and social interaction.[1] Since then, AS has always been a topic of significant interest and debate. Although AS was introduced as a discrete diagnostic category in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-4, 1994), almost 20 years later, its diagnostic label was removed in the Diagnostic and Statistical Manual of Mental Disorders (DSM–5), and it was encompassed in a more general category of autism spectrum disorders (ASD).[2] According to the DSM-5, there are varying degrees of ASD that are categorized based on the severity of symptoms and the required levels of support, and what was formerly called Asperger syndrome shall now be regarded as ASD.[3] Autism spectrum disorders (ASD) include a group of neurodevelopmental abnormalities with broadly varying degrees and manifestations, usually begin in early childhood, and characterized by problems in social communication and interaction, along with behavioral problems such as restricted interests and repetitive behaviors.[4][5] DSM-5 changes on ASD classification led to some controversy about the loss of the unique Asperger identity,[6] and literature continue to debate about AS and its formulation within ASD.[7] Due to Asperger syndrome's extensive history, rich semiology, and relatively characteristic clinical presentations, specialists continue to use this diagnosis as a subtype of ASD with no language delay and a normal or superior IQ.[6]

In this topic review, we will describe the essential aspects of autism spectrum disorder and Asperger syndrome. For greater transparency, we refer to (1) Asperger syndrome (AS) as a subpopulation of pervasive developmental disorders (PDD) according to DSM-IV-TR, (2) ASD according to DSM-5, and (3) Autism spectrum disorder of an Asperger syndrome type (ASD-AS) as a subpopulation that is included in the DSM-5 as ASD of level 1 severity without intellectual impairment.

Historical Perspective

In 1944, and about a year after Leo Kanner described infantile autism, Hans Asperger introduced autistic psychopathy in the form of a case report. In 1980, the American Psychiatric Association (APA) recognized autism as a distinct category in the DSM-3 and introduced it as infantile autism. In 1981, Wing L. restarted Asperger researches and renamed autistic psychopathy as Asperger syndrome. A few years later and in 1989, the first diagnostic criteria for AS was proposed,[7] and the 10th Revision of the International Classification of Diseases (ICD-10) was the first major classification system that recognized AS (1993). Finally, in 1994, AS was introduced in DSM-4 as a specific entity along with autistic disorder, within pervasive developmental disorders (PDD). While during this period, researches were focused on the development of measures with the ability to diagnose AS and differentiate it from high functioning autism (HFA), the DSM-5 removed the diagnostic category of AS in 2013.[5] The World Health Organization (WHO) also followed a similar approach in ICD-11, which will come into effect in 2022.[2]

DSM Classification

The systematic description of psychiatric disorders is quite complicated, particularly in child and adolescent psychiatry. Asperger syndrome was included in the DSM-IV-TR in the large family of pervasive developmental disorders (PDD). PDD had five subtypes:

  • Autistic disorder
  • Asperger syndrome
  • Childhood disintegrative disorder
  • Pervasive developmental disorder-not otherwise specified (PDD-NOS)
  • Rett syndrome

Symptoms and clinical specifiers for autistic disorder of PDD were described to fall into three broad categories in DSM IV-TR: (1) social interaction, (2) communication, and (3) restricted, repetitive behavior.[8] The diagnosis of AS required:[7]

  • At least two symptoms of social interaction impairment and at least one each from symptoms of communication and restricted, repetitive behavior (RRB)
  • Delays or abnormal functioning in at least one of the areas of (1) social interaction, (2) language as used in social communication, or (2) symbolic or imaginative play with onset prior to age 3 years.
  • Diagnostic criteria for autistic disorder (or another specific PDD) should not be met (otherwise, the AS diagnosis is excluded, and autistic disorder diagnosis should have precedence).

AS contrasted from autistic disorder in:[9]

  • Absence of diagnostic criteria in the communication domain
  • Absence of a requirement for onset before age 3
  • Addition of criteria specifying the absence of a language delay
  • Addition of criteria specifying the absence of a deficit in cognitive development

This classification suggested a differential diagnosis between AS and the type of Autistic disorder associated with normal cognitive functioning, also known as high functioning autism (HFA). As a result, it sparked substantial debate over uncertainty in defining AS criteria and the clinical overlap between AS and HFA, which has appeared in literature with contradictory results. Although there has been a considerable number of researches showing some fine differences between the two disorders, most studies have emphasized the meaningful similarities between AS and HFA. 

Ultimately, the DSM-5 removed PDD and its categorization and merged four of its subtypes into one unifying category with the concept of a continuum named autistic spectrum disorders (ASD). This major alteration was mostly due to the assumption that PDD subgroups cannot be differentiated from one another certainly and reliably.[7] These changes include the following:[2][8] Another major alteration was the inclusion of social communication and social interaction related deficits in one criterion and exclusion of deficit specifically related to spoken language.

  • Elimination of PDD and its subtypes
  • Creation of a new diagnostic category called autistic spectrum disorders (ASD), encompassing autistic disorder, Asperger syndrome, childhood disintegrative disorder, and PDD-NOS.
  • Addition of three levels of severity, and clinical specifiers about the presence of cognitive and language impairment, to better characterize the diagnosis
  • Changing from previous PDD 3-domain criteria to ASD 2-domain criteria, composed of impaired social communication/interaction and restricted, repetitive behavior, interest, and activities (merging domains of social interaction and communication)
  • Addition of sensory symptoms in the RRB component of diagnostic criteria
  • Changing the specification of the age of onset from age 3 to "early childhood."
  • Creation of a new diagnostic category called "social communication disorder" (SCD) to include individuals who have difficulties in social communication/interaction but do not meet RRB criteria found in ASD
  • Removal of Rett syndrome from the classification, on the basis of recent genetic data

Controversy over the New Classification of ASD

The new classification of ASDs has been criticized in the literature in different ways. Some authors have suggested that the new classification will narrow the criteria for ASD; thus, some patients may no longer meet the criteria for ASD, in particular, cognitively able individuals and individuals diagnosed with AS and PDD-NOS. In short, the argument is although this reduced sensitivity is associated with higher specificity, it has the potential to exert negative effects on the service eligibility, as well as the ability of researchers to integrate information and data from researches conducted under these criteria.[9][6] Other authors claim that the elimination of the specific diagnostic category for Asperger syndrome will increase stigma towards individuals previously diagnosed with AS, based on the assumption that autism-phobic societies perceive autism as a significant disability, whereas AS is associated with the more positive stereotypes.[10][2]

In addition, previous research has demonstrated the association of autism with disability and dysfunction, and the association of AS with positive features. Thus, the new inclusion of AS in the category of ASD may have a negative effect on the identity of the individuals who have adopted this label as an identity. However, the literature on the potential impact of the DSM-5 changes on individuals previously diagnosed with AS is limited, and the results can be categorized into those who are supportive, those who are opposed, and those who express mixed feelings concerning the changes.[2]

Etiology

Theories about autism etiology have evolved. The initial concept of “refrigerator mothers,” a theory attributing ASD to cold and unemotional mothers, is now considered obsolete. Also, factors such as family lifestyle and income and educational level are no longer considered risk factors in ASD onset.[11] ASDs are significantly heterogeneous in their etiology. Although many genetic, neurobiological, and environmental factors have been recognized to contribute to ASD etiology, the exact underlying mechanisms are not entirely understood.[12]

Genetic Factors

Among factors associated with ASD pathogenesis, the genetic contribution is widely accepted.[4][13][11] Genome sequencing data implies that there are hundreds of genes linked with ASD, although no specific mutation has been recognized that is unique to ASD.[14] It is estimated that 400 to 1000 genes are likely to lead to a predisposition to autism.[15] Genes contributing to ASD are involved in a variety of biological functions related to brain development and function.[14][4] For instance, individuals with AS and multiple other endophenotypes relevant to autism are more likely to carry specific variations in a gene (GABRB3) that has been previously implicated in individual differences in empathy.[16] Copy number variants (CNVs), which are DNA deletions or duplications that alter the function of genes, have been found in approximately 9% of individuals with ASD in clinical samples.[14] There is a significant genetic overlap between ASD and other neurological, psychiatric, and neurodevelopmental conditions such as epilepsy, intellectual disability, and schizophrenia.[14][4] It is our understanding that these genetic factors disrupt brain development through the disruption of important biological pathways, which will lead to disease development.[17] Neuroimaging studies have shown abnormalities in different brain regions such as the frontal cortex, hippocampus, cerebellum, and the amygdaloid nucleus.[4] Also, brain overgrowth and accelerated head growth during infancy have been found in children with ASD.[18] Higher incidence of autism in siblings compare with the general population;[19] the strong role of inheritance in twins with 98% concordance in monozygotic and 53% to 67% concordance in dizygotic twins, and heritability estimates range from 64% to 91%; [14] and unequal sex distribution (male predominance), are some of the supports for the substantial genetic contribution to the development of ASD.[20]

Environmental Factors

The role of many potential environmental factors related to ASD etiology is an area of active ongoing researches. Identification of modifiable risk factors associated with ASD is essential, particularly for reducing exposure of children and pregnant women to known neurotoxicants. Environmental factors may act as an independent risk factor or may affect existing genetic factors in individuals with a genetic predisposition, and include parental age, perinatal and obstetric events, maternal factors, fetal environment, and exposure with toxins and teratogens.[14] There is strong evidence that shows that advanced paternal and maternal age is associated with an increased risk of having a child with ASD.[12] Perinatal factors such as preterm birth, low birth weight, intrapartum hypoxia, intrauterine exposure to valproic acid and thalidomide, and neonatal encephalopathy are also associated with increased risk for ASD. Other prenatal conditions that may be associated with increased ASD risk include short interpregnancy interval, multiple gestations, maternal obesity, gestational diabetes, and prenatal infections such as rubella and cytomegalovirus.[14][12]

It is important to note that, based on the systematic reviews of multiple large epidemiologic studies, there is no evidence to support an association between ASD and immunization as an environmental risk factor; thus, children with ASD should be vaccinated according to the routine recommended schedule.[14]

Epidemiology

The new classification of ASD in the DSM-5 presents challenges and limitations for monitoring ASD prevalence over time.[21] Different studies have shown a trend of increasing prevalence rate, which has been mostly attributed to factors such as changes in case definition, enhanced and more widespread screening, and increased awareness; however, an actual increase in the prevalence of ASD is also possible. Different estimates of ASD prevalence have been reported depending on the study population and methodology, ranging from 0.7 in 10,000 to 72.6 in 10,000. Centers for Disease Control and Prevention estimated ASD prevalence in the United States as 11.3 in 1,000.[22] Worldwide, one person out of 132 (7.6 in 1000) is affected by ASD.[23] The overall prevalence of AS is not completely clear, and it has been estimated at 2–7 in 1000.[1] In general, ASD occurs more frequently in males than females, and the male-to-female ratio is approximately 4:1. However, a 2017 systematic review and meta-analysis recommended that the actual male-to-female ratio is closer to 3:1, meaning that girls with ASD are at higher risk of not receiving a clinical diagnosis.[20] Females with autism also tend to have a more severe intellectual disability.[22]

Co-existence with other psychiatric and physical disorders is a common phenomenon in ASD (>70%), particularly in young children. This may have great effects on the patient and family functioning as well as clinical management. Intellectual disability, attention deficit hyperactivity disorder (ADHD), tic disorders, anxiety, depression, and epilepsy are common co-occurring conditions associated with ASD, while ADHD, depression, bipolar disorders, anxiety and tic disorders, are common co-occurring conditions associated with AS and HFA subpopulation of ASD.[21][24]

History and Physical

Here we present a review of the core features and various clinical presentations in ASD, with a particular focus on individuals with autism spectrum disorder of an Asperger syndrome type (ASD-AS). 

ASD is a heterogeneous disorder with a wide verity of clinical manifestations, ranging from slight to significant impairment, and is characterized by abnormal social communication and social interaction; and restricted and repetitive patterns of behavior. Symptoms present in the early developmental period, although they may not become fully evident until social demands exceed limited capacities. Specifiers include associating intellectual disability, language impairment, medical or genetic condition, catatonia, and other neurodevelopmental, mental, or behavioral disorders. There are three levels of severity for each core symptom domain, which is classified based on the severity of symptoms and the required levels of support to assist with impairments, and separate ratings are required for each domain (table 1).[15] Asperger syndrome is a subpopulation on the autism spectrum, presenting with core symptoms of ASD in the absence of intellectual disability or language delay. The clinical features are very heterogeneous, varying according to age and psychiatric comorbidities.[25] While ASD early symptoms can be identified as early as the age of 1 to 3 years (with the average age of 5 years at the time of diagnosis), AS is commonly associated with delayed clinical diagnosis often until the age of 11 or even later.[26][25]

Illustrative examples of impaired social communication and interaction[15]

1- Deficits in social-emotional reciprocity:

  • Absent or limited interest in social interactions
  • Abnormal social approach
  • Failure of normal back and forth conversation
  • Reduced sharing of interests, emotions, or affects
  • Failure to start or appropriately respond to social interactions

2- Deficits in nonverbal communication behaviors used for social interaction

  • Poorly integrated verbal and nonverbal communication
  • Abnormal eye contact
  • Abnormal body language, facial expressions, and nonverbal communication
  • Abnormalities in understanding and use of gestures

3- Deficits in developing, sustaining, and understanding relationships

  • Failure to adjust behavior to suit different social contexts
  • Absence of interest in peers
  • Difficulties in making friends

Illustrative examples of restricted and repetitive behavior, interests, and activities[15]

1- Stereotyped and repetitive behaviors

  • Patterns of restricted and repetitive motor movements such as hand or finger flapping, toe walking
  • Patterns of restricted and repetitive use of objects
  • Patterns of restricted and repetitive speech

2- Insistence on sameness and inflexible adherence to routines

  • Resistance to change routines such as eating particular foods, repetitive questioning about a particular topic
  • Ritualized patterns of verbal or nonverbal behavior

3- Highly restricted interests that are unusual and abnormal in intensity or focus

4- Atypical sensory behaviors, hyperreactivity or hyporeactivity to sensory input, unusual interest in sensory aspects of the environment

There are specific symptoms that are mainly relevant to specific age groups or certain subpopulation of individuals with ASD. For instance, lack of orientation to name or lack of following a pointing gesture are reliable indicators of autism in toddlers and preschool children but not in older children and adults. Also, not having close friends is not a developmentally appropriate factor for a toddler, and it is a more problematic factor for adults.[27]

Identifying the various clinical situations associated with ASD at different ages of life allows clinicians to provide appropriate screening, referral, diagnosis, and treatment. Here, we discuss several situations at different ages of life in patients with ASD-AS, which are commonly encountered by practitioners in the clinical setting.

Children and Adolescents

Social isolation and bullying at school:

Friendship is an essential social experience for children. It provides them with a context in which they can practice and develop the social skills required for friendship, including good social adaptability, understanding of emotions, empathy, and concern for others. Children with ASD-AS have difficulties with these social skills and therefore struggle to build friendships. However, research has shown that they are interested in having a relationship, ask themselves the reason for their loneliness, and identify the feeling of loneliness at an early stage. Children with ASD-AS have difficulty in interpreting details of nonverbal language, gestures, and facial expressions, do not fully understand humor and metaphors, have limited and sometimes unusual interests, and may speak with an unnatural intonation. All these challenges and the lack of social skills cause them to be at higher risk of interpersonal difficulties and lead them to be a target of mockery by their peers. More than 40% of children with ASD have been victims of bullying and intimidation at school. It is not uncommon to see individuals with AS who dropped out of school due to developing significant anxiety and depressive symptoms as a result of their interpersonal difficulties.

Limited fields of interest, awkwardness, and clumsiness:

Some children with ASD-AS play repetitive and stereotypical games with no creativity. They can play the game of “pretending” for days. They are preoccupied with limited interests that are unusual or abnormal by their intensity or focus. Children with ASD-AS are often interested in certain objects such as technical train data, mechanics, space, history, music, or meteorology, and they are good at memorization. Motor coordination disorders and unusual gait and posture are common; thus, they have little interest in sports, and they experience difficulties when performing activities such as drawing, writing, or fastening shirt buttons.

ADHD and Autism:

Attention deficit disorder with or without hyperactivity disorder (ADHD) is the most frequent mental disorder in children and adolescents. Studies have shown several symptoms overlap in ADHD and AS; therefore, ASD-AS should be sought when diagnosing ADHD with serious interpersonal difficulties. High distractibility in ADHD and lack of mental flexibility in ASD-AS may present as a decrease in attention level. Besides, both conditions may lead to interpersonal difficulties, and both may show an extraordinary ability to engage their interests profoundly.

Heterogeneous neurocognitive profile:

The neurocognitive profile of children with AS has been very heterogeneous, although the verbal intelligence quotient (IQ) is generally higher than the performance IQ. Despite popular belief, not all patients with Asperger are geniuses, and there is significant inter-individual variability in most cognitive tasks. It appears that ASD-AS subjects have deficits in their executive functions and in tasks that require comprehensive treatment, while their strength is in the areas of fluid intelligence and problem-solving.

Sensory and perceptual characteristics:

More than 90% of autistic subjects experience atypical sensory perceptions that could involve all senses and may lead to serious anxiety. Hypersensitivity is a common observation that may present with food selectivity, or overreaction to a noisy environment, certain types of contacts, or body odor. Hyposensitivity symptoms such as lower pain thresholds, indifference to temperature, or circular movements could also be present.[6]

Adults

Delayed diagnosis:

It is not uncommon for ASD-AS to be diagnosed in adulthood. This delay in diagnosis is more likely due to the fact that this subpopulation of ASD can fairly compensate for their social difficulties. Individuals with ASD-AS have average or superior intelligence, which can lead them to be able to mask their deficits in social interaction and communication skills to a certain extent. However, it is difficult to maintain these compensatory strategies as the social environment becomes increasingly complicated. Also, this mood of function eventually fails due to their inflexibility of behavior and difficulties in coping with changes such as living in a couple or starting a professional activity, causing them to be at risk of anxiety and depression. Warning signs in these individuals lack specificity and are mostly related to social interactions.

Potential for misdiagnosis as schizophrenia:

The accurate distinction between schizophrenia and AS is not always easy. Misdiagnosing Asperger syndrome as schizophrenia may prevent effective therapy and cause serious problems. Impaired social communication and interaction, limited interests, and delusions of persecution apparently are clinical features that can be presented in both conditions. The apparent lack of affect, visual contact, and facial expressiveness in individuals with AS can be mistaken for the discordance of schizophrenia. Also, the alteration of social interactions may be difficult to differentiate with the withdrawal period in schizophrenia subjects. Besides, impaired communication skills in AS may appear similar to the thought disorder, which is a feature of schizophrenia. However, there are clinical features that are more characteristic of AS, such as younger age at onset, repetitive behaviors, impaired pragmatic language, lack of imagination, oddities of intonation, and willingness for a conversation about their favorite subject. It is also important to note that patients with ASD-AS may display transient psychotic episodes, consisting of depersonalization, derealization, and hallucinatory experiences.[6]

Decrease in symptoms into adulthood:

Studies have found that ASD symptoms will decrease into adulthood for most individuals with ASD. This decrease in symptoms tends to be more significant in those with average or superior intelligence, compare with individuals who have ASD and intellectual disability. Social difficulties, perceptual deficits, struggles with nonverbal communication, and in particular, restricted and repetitive behaviors have been reported to be stable over time.[28]

Sexuality:

Regarding sexuality, individuals with ASD-AS do not appear to be significantly different from the general population. Autistic people have sexual and romantic desires, and they pursue romantic relationships. However, they lack the required social skills, and their attitude may be interpreted as being bizarre or disturbing. Failure to understand the appropriateness of behaviors in different social situations may lead to inappropriate public behaviors such as unclothing, masturbating, awkward sexual conversation, or improper attempts at seduction, which can be interpreted as harassment by others. Their repetitive and restricted behaviors, as well as sensory fascinations, may also disturb their sexual development; thereby, they may develop obsessions with sexual references, abnormal sexual fears, or compulsive masturbation with an object in a manner similar to fetishism.

Professional scope:

Lack of skills that are required to use language in context successfully (i.e., impaired pragmatic language) may cause ASD-AS subjects to communicate very formalized, direct, and without attempting to avoid offending others. This weakness can cause problems in the workplace, particularly in certain occupations such as work positions that need teamwork. Also, their limited cognitive flexibility may cause them to follow certain rituals in a very strict manner, and any interruption of these rituals may generate anxiety. For instance, they may place their items in a certain place on their desk or chose to start and finish their working day at a precise time. Even with a university degree, it can be difficult to find the first job due to the difficulties that they may experience in job interviews. They may have difficulty in stating their skills and behave in a disconcerting manner. However, they may also have many valuable potentials, such as punctuality, honesty, creativity, and logical reasoning abilities.[6]

Evaluation

There is a general agreement that the key features of AS are similar to other subpopulations under the ASD umbrella. This article reviews the available ASD evaluation methods in two separate sections, screening, and diagnostic assessment.

1. Screening

Screening tests are not used for diagnosis; instead, they help to identify individuals who require further evaluation. General developmental screening for identification of language, cognitive, and motor delays are recommended at 9, 18, and 30 months of age. However, these tests are not sensitive enough to capture differences in social interaction, playing, and repetitive behaviors associated with ASD. Thereby, it has been recommended to screen for ASD through a combination of:

A- Routine developmental surveillance at all visits: Developmental surveillance for ASD includes asking parents or caregivers about their concerns, observing caregiver-child interactions, and monitoring of symptoms in every routine well-child visit.

B- Standardized autism-specific screening tests at 18 and 24 months of age: Screening tools are designed based on the early manifestations of ASD that can be detected by providers or their caregivers. Some of these early indicators are called “red flags,” meaning that they should alert providers to a higher risk for ASD (table 2).[14]

Screening tools commonly used to screen ASD:

  • Quantitative Checklist for Autism in Toddlers (Q-CHAT): one of the oldest methods, and used to detect autism in children younger than age 24 months.[29]
  • Modified Checklist for Autism in Toddlers (M-CHAT): A modified version of Q-CHAT, and the most studied and widely used tool for screening toddlers for ASD. It is useful for children younger than 30 months of age.[14]
  • Modified Checklist for Autism in Toddlers, Revised, with Follow up (M-CHAT-R/F): A two-phase parent screening method that is useful for research, educational and clinical purposes. It is useful for children younger than 30 months of age.
  • Screening Tool for Autism in Toddlers and Young Children (STAT): A tool to screen children aged between 24 and 36 months. The STAT is administered by a trained professional examiner and requires specific training. It can be used to support a preliminary diagnosis of ASD.
  • Autism Screening Instrument for Educational Planning, 3rd Version (ASIEP-3): A tool that is designed to identify children younger than 2 years and 11 months to 13 years, with a high level of autistic behavior. It is the most time-consuming screening tool, taking approximately 90–120 min to complete.
  • Autism Behavior Checklist (ABC): The ABC is a subtest of ASIEP’s third version.
  • Childhood Asperger Syndrome Test (CAST): A tool to screen children aged between 5 and 11 years who are suspected of having AS.[29]
  • Social Communication Questionnaire (SCQ): A tool to screen children older than 30 months of age.[14]
  • Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R): A self-scoring ASD screening tool developed for adults[29]

2. Diagnostic Assessment

Once the screening or developmental surveillance indicates a risk for diagnosis of ASD, a comprehensive diagnostic evaluation is indicated to determine the presence of ASD and the need for early intervention. 

2.1 Standard psychiatric assessment

A standard psychiatric assessment involving a full interview with patients and caregivers is needed to obtain a thorough history including descriptions of behavior during formal testing, reports of behavior in other environments, past and current educational and behavioral interventions, family history, and relevant psychosocial issues. The history and examination should be conducted with careful consideration of diagnostic criteria according to DSM-5.[22][14]

2.2. Assessment Tools

Various tools for the assessment of ASD have been developed. Although none of these questionnaires alone is sufficient for diagnosis, they can provide a structured approach and support a knowledgeable clinician in applying diagnostic criteria of ASD.[14]

  • Autism Diagnostic Interview-Revised (ADI-R)
  • Autism Diagnostic Observation Schedule, Second Edition (ADOS-2)
  • Diagnostic Interview for Social and Communication Disorders (DISCO)[22]
  • The Asperger Syndrome Diagnostic Scale (ASDS)[5]

2.3. Evaluation of cooccurring developmental conditions

Attention to other potential comorbid diagnoses is also an essential component of assessment. Cooccurring conditions may impact the symptomology of ASD in different ways and at different ages of life. Therefore, formal assessment of language, cognitive, motor, sensory, and adaptive functions is an important part of the diagnostic process.[22]

2.4. Medical workup

  • Genetic testing: providers should recommend and offer a genetic evaluation to all families as part of the etiologic assessment. Potential benefits of establishing a genetic etiologic diagnosis include improved counseling provided to patient and family, preventing morbidity by treating medical conditions associated with the genotype, refining treatment options, and avoiding additional unnecessary tests.
  • Neuroimaging: MRI is not recommended for routine assessment, although it may be indicated in the presence of certain conditions such as atypical regression, micro- or macrocephaly, seizures, or abnormal neurologic examination.
  • EEG: is not recommended for routine assessment, although it may be indicated in certain cases with seizures, atypical regression, or other neurologic symptoms.[14]

2.5. Physical Examination

A thorough and differential diagnosis directed physical examination is essential to guide appropriate workup. This includes evaluation of growth, organomegaly, dysmorphic features, neurologic abnormalities, and skin manifestations of neurocutaneous disorders.[14]

Treatment / Management

Treatment strategies in individuals with ASD may vary according to patient age, strengths, weaknesses, and needs, as well as modality of delivery and targets of intervention. The goal of treatment includes minimizing core deficits, maximizing functional independence, and decreasing problematic behaviors that may restrict functional skills.[14] While various types of interventions have been shown to be useful for individuals with ASD, many of them do not have a strong evidence base, and none has emerged as superior.[22] The understanding of intervention terminology helps clinicians to appropriately and effectively communicate and advise families on therapy choices.

Behavioral Interventions

Behavioral interventions are started early in life through an intensive delivery format and designed to target the core symptoms of ASD based on the principles of behavior modification and learning theory.[15] The most evidence-based intervention models are based on the principles of Applied Behavioral Analysis (ABA), which is a process of intensive behavioral interventions to improve socially desirable behaviors and decrease undesirable behaviors that may interfere with an individual’s progress. ABA interventions are designed and supervised by behavior analysts and have different approaches based upon goals, age, or the targeted skill.[14] A widely supported ABA program is Early Intensive Behavioral Intervention for young children, which is a highly individualized program that uses different trials to educate developing simple skills and progressing to more complex skills. ABA techniques have been found to be effective as applied to social skills, academic tasks, communication, adaptive living skills, and occupational skills.[22]

Educational Interventions

There is an agreement that children with ASD need a structured educational plan involving strategic, intensive, and individualized interventions.[22] The two most effective classroom-based models include Learning Experiences and Alternative Programs for Preschoolers and their Parents (LEAP) and Treatment and Education of Autism and related Communication handicapped Children program (TEACCH).[14] Although the curricula are various among different programs, the goal is enhancing verbal and nonverbal communication, as well as social, academic, and motor skills.[22] 

Speech and Language Interventions

Communication is an essential focused intervention in ASD management. Speech-language therapy is the most common intervention provided for children with ASD, which includes strategies such as reinforcement of speech sounds, exaggerated imitation, enhancing communicative acts, and imitation of the sounds.  Augmentative and Alternative Communication (AAC) is introduced for children who do not speak spontaneously. AAC modalities include picture exchange communication systems, sign language, speech-generating devices, communication boards, and visual supports. There are also several methods to enhance pragmatic language skills available for individuals with fluent speech but impaired pragmatic language skills.[14][22]

Developmental Interventions

Developmental interventions are designed based on developmental theory. Children learn social interaction, communication, and emotional regulation through interaction with others. Developmental interventions are focused on the relationship between patient and adult (parents or caregivers). These interventions teach adults to increase their level of responsiveness and educate them to engage in nondirective interactive strategies that can help the child to develop social and communication skills in the context of playing activities.[14]

Pharmacologic Interventions

Currently, there is no medication for the core social and communication symptoms of ASD. There are only two medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of symptoms associated with ASD. Risperidone and Aripiprazole can be used for short-term symptomatic treatment of aggression, self-injury, irritability, and tantrums in children and adolescents with ASD.[15]

Differential Diagnosis

  • Intellectual disability
  • Language disorders
  • Sensory impairments (hearing impairment)
  • Reactive attachment disorder
  • Obsessive-compulsive disorder
  • Anxiety disorders including selective mutism
  • Childhood-onset schizophrenia
  • Rett syndrome
  • Social (pragmatic) communication disorder[22]
  • Attachment disorder[30]
  • Tic disorders (stereotypic movement disorder)[31]

Prognosis

In general, the presence of intellectual disability with ASD is associated with the most difficulty developing social competence. Also, ASD with language impairment further increases the risk of social difficulties. In other words, intelligence and language ability in childhood are predictive for outcome in adulthood. Approximately 9% of children with early ASD diagnosis may no longer meet the criteria for ASD in adulthood. Higher cognitive skills and participation in early intervention services are predictive for a better outcome. Individuals who have a more significant increase in tested verbal IQ are more likely to have improved severity scores in adulthood. It is important to note that the presence of family and community supports is a more critical factor than ASD symptoms in reported quality of life of adults with high functioning autism.[14]

The outcome for patients with ASD-AS has shown to be variable in the literature, depending on the study sample size and population, inclusion criteria, case definition, and outcome measures. However, there are several factors that appear to be related to prognosis, including IQ, language skills, and co-occurring psychiatry conditions.[32] A longitudinal study of patients with AS has found that approximately 23 percent of patients had a restricted outcome, 47 percent had a fair outcome, and 27 percent had a good outcome.[33]

Deterrence and Patient Education

Parents and families who have children diagnosed with ASD encounter many challenges, such as frustration, social isolation, relationship conflicts, and financial difficulties. They may experience more stress, and they are more likely to face negative consequences than parents of children with other disabilities.[34] However, parents and family involvement is an essential aspect of ASD management. Some interventions involve trained parents and may be provided in the home. Parent support interventions are knowledge-based training programs that provide indirect benefits to the child by improving parental self-efficacy; and include care coordination and psychoeducation. Parent mediated interventions are technique focused, involve trained parents or other caregivers, and provide direct benefits to the child. Parents or caregiver role is also important in teaching social skills, particularly in young children. The importance of this responsibility needs to be emphasized for families. Moreover, educational interventions through social skill instruction is an important component of management in an individual with ASD.[14]

Enhancing Healthcare Team Outcomes

All patients with autism spectrum disorder should have a thorough medical assessment, including standard psychiatric assessment, physical examination, hearing screening, eye examination for signs of tuberous sclerosis, and genetic testing. Medical geneticists have recommended chromosomal microarray as the standard of care for the initial evaluation of children with ASD or other developmental disabilities.[22][35] [Level 1]

Additional evaluations may be indicated if the child has any unusual features such as significant family history, dysmorphology, or a history of regression. Other potential organic etiologies such as infections, endocrinopathies, metabolic disorders, trauma, or fetal alcohol syndrome should also prompt further evaluation. Landau-Kleffner syndrome, which is a neurodevelopmental disorder associated with highly distinctive EEG abnormalities, should be considered to rule out. Neurologic consultation, neuroimaging, EEG, and additional laboratory tests may be indicated depending on history or physical examination.[22] [Level 1]

For diagnostic evaluation, most patients with ASD need to see specialists such as a psychiatrist, psychologist, developmental-behavioral or neurodevelopmental pediatrician, or neurologist. Earlier clinical diagnosis is essential to facilitate the initiation of services. A detailed history of behavioral symptomology, as well as direct observation of symptoms, is necessary to make a diagnosis since there are no diagnostic laboratory tests available at this time.[14] [Level 1]

Psychological assessment is indicated for treatment planning and helps to determine the areas of strength and weakness. Measurements of cognitive ability and adaptive skills are useful in designing intervention programs. Intelligence tests may show different and significantly scattered results. Unusual forms of abilities or special interests may be present, particularly in higher functioning children. However, the single-minded pursuit of these interests may negatively influence the learning abilities. Receptive and expressive vocabulary, as well as social and pragmatic language, are measured to assess communication. Occupational assessment may be indicated to evaluate sensory and motor deficits. Finally, sleep evaluation is also an important component of assessment. Careful planning with multidisciplinary coordination helps optimize outcomes.[22] [Level 1]


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