Autism Spectrum Disorder Workup

Updated: Mar 18, 2020
  • Author: James Robert Brasic, MD, MPH; Chief Editor: Caroly Pataki, MD  more...
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Workup

Approach Considerations

Several instruments have been developed to diagnose ASD. Administering these tools in a reliable and valid manner requires extensive training and experience. Therefore, unless they have considerable experience with children with ASD and understand the concepts implicit in the diagnostic criteria and rating scales, pediatricians and other clinicians are advised to refer patients with possible ASD [1] to experienced clinicians for definitive diagnostic evaluations.

Experienced clinicians are able to identify particular deficits in children with ASD and institute effective treatments. Identification of the key dimensions characteristic of ASD may be a more accurate means of distinguishing subtypes of this disorder. [140]

The utilization of broader criteria for ASD will likely result in innovations in the identification of affected children. There will also likely be further developments in the institution of interventions for this disorder. [32]

Metabolic studies

Several metabolic abnormalities have been identified in investigations of people with ASD. However, biologic markers for ASD do not yet exist. No blood studies are recommended for the routine assessment of children with ASD.

Neuroimaging

There is currently no clinical evidence to support the role of routine clinical neuroimaging in the diagnostic evaluation of ASD, even in the presence of megalencephaly. [3] Studies of various imaging techniques have yielded inconsistent results, and although characteristic abnormalities have been identified, no single finding is diagnostic.

Electroencephalography

Electroencephalography is useful for ruling out a seizure disorder (present in a third of children with autism spectrum disorder), acquired aphasia with convulsive disorder (Landau-Kleffner syndrome), biotin-responsive infantile encephalopathy, and related conditions.

Psychophysiologic assessment

Psychophysiologic assessment may be useful to evaluate children with ASD. Children with ASD are not likely to show the response habituation in respiratory period, electrodermal activity, and vasoconstrictive peripheral pulse amplitude response to repeatedly presented stimuli seen in typical children. Children with ASD may also demonstrate auditory overselectivity.

Polysomnography

Polysomnography may facilitate the diagnosis of treatable comorbid disorders. Most children with ASD have sleep disturbances, including early morning awakening, frequent arousals, and fragmented sleep. [141] Additionally, children with ASD often display prolonged sleep onset and abnormal sleep architecture. Polysomnography may be useful not only in identifying sleep disorders, but also in demonstrating seizure discharges.

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Genetic Testing

Practice guidelines from the American Academy of Neurology and the Child Neurology Society recommend genetic testing (eg, with high-resolution chromosome studies and DNA analysis) for fragile X in children with ASD who meet any of the following criteria: [3]

  • The child has an intellectual disability

  • Intellectual disability cannot be excluded

  • There is a family history of fragile X or undiagnosed intellectual disability 

  • Dysmorphic features are present

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Neuroimaging

MRI

Magnetic resonance imaging (MRI) studies in patients with ASD yield inconsistent results. However, typical findings include enlargement of the total brain, the total brain tissue, and the lateral and fourth ventricles, along with reductions in the size of the midbrain, the medulla oblongata, the cerebellar hemispheres, and vermal lobules VI and VII. [142, 143] Although vermal hypoplasia is found in some individuals with ASD, vermal hyperplasia is identified in others. [144]

The volume of the gray matter is bilaterally decreased in the amygdala, the precuneus, and the hippocampus of people with ASD. Adolescents with ASD have shown greater decreases in the volume of the gray matter of the right precuneus than adults. The volume of the gray matter in the middle-inferior frontal gyrus has been found to be slightly increased in people with ASD. [145]

Imaging studies in patients with ASD who exhibit head banging may show enlargement of the diploic space in the parietal and occipital bones, with loss of gray matter adjacent to the bony changes. These findings resemble those of posttraumatic encephalopathy in athletes in contact sports (eg, football, hockey) and professional boxers (dementia pugilistica).

In one study, MRI performed during the presentation of a bedtime story during natural sleep in children aged 12-48 months provided evidence of atypical hemispheric lateralization for language in toddlers who develop ASD. [146] Study subjects who developed ASD failed to exhibit the left hemispheric response to spoken language that is typical of normally developing toddlers and instead demonstrated abnormal right temporal cortical responses.

Diffusion tensor imaging

On MRI studies, diffusion tensor imaging can provide information about connections among different brain regions. Children with ASD demonstrated higher values for the apparent diffusion coefficient (ADC) in the whole frontal lobe, as well as the long and short association fibers of the frontal lobe. [147]

Children with ASD and their healthy siblings demonstrate significant reductions in fractional anisotropy (FA) in association, commissural, and projection tracts, in contrast to control groups. [148, 149] Alterations in FA in the white matter of the frontal, parietal, and temporal lobes suggest an inherited trait characteristic of a vulnerability to develop ASD.

Computed tomography

Results of computed tomography (CT) studies of the head are inconsistent in patients with ASD. However, they may reveal deficits, including enlargement of the ventricles, hydrocephalus, parenchymal lesions, and reduction in size of the caudate nucleus.

Positron emission tomography scanning

Positron emission tomography (PET) scanning reveals multiple deficits, but no finding characterizes all people with ASD, and the results vary with each individual. [37, 150]

On 18-fluoro-2-deoxyglucose (FDG) PET scans, the anterior rectal gyrus is larger on the left than the right in some patients, a finding opposite to the asymmetry seen in typical individuals. Some individuals also exhibit an increased glucose metabolic rate in the right posterior calcarine cortex and a decreased glucose metabolic rate in the left posterior putamen and the left medial thalamus. [151]

Decreased dopaminergic neurotransmission occurs in the anterior medial prefrontal cortex of children with ASD. [152]  The dopamine transporter has been reported to be increased in the orbital frontal cortex of adults with ASD and decreased in the striatum of children with ASD. [152]

Decreased serotonin receptors were observed in the thalami of people with ASD and in the cortices of the parents of children with ASD. [152]

Increased metabotropic glutamate receptor type 5 (mGluR5) was demonstrated in the postcentral gyrus and the cerebellum of men with ASD in contrast to age- and sex-matched healthy controls without ASD. [153]

See PET Scanning in Autism Spectrum Disorders for further information.

SPECT (single-photon emission CT) scanning

Chiron and colleagues found that the normal asymmetry of regional cerebral blood flow (ie, higher in the left hemisphere in right-handed individuals) was lacking in some people with ASD. Tests of regional cerebral blood flow with xenon-133 (133 Xe) revealed left-hemispheric dysfunction, especially in the cortical areas devoted to language and handedness. [154]

Regional cerebral blood flow assessed with technetium-99m (99m Tc) labeled to hexamethylpropyleneamine oxide (HMPAO), a lipophilic substance, in children with ASD demonstrates variable anomalies, including reductions in the vermis, the cerebellar hemispheres, the thalami, the basal ganglia, and the parietal and temporal lobes. These findings suggest that no single abnormality characterizes all individuals with ASD.

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Electroencephalography

Electroencephalography (EEG) is useful for ruling out seizure disorder (present in a third of children with ASD), acquired aphasia with convulsive disorder (Landau-Kleffner syndrome), biotin-responsive infantile encephalopathy, and related conditions. The American Academy of Neurology and the Child Neurology Society found inadequate evidence to recommend an electroencephalogram (EEG) in all individuals with ASD. [3]

Consultation with an electroencephalographer may help to determine appropriate procedures for individual cases.

A single normal EEG does not rule out a paroxysmal abnormality, such as a seizure disorder. When a routine EEG does not reveal unequivocal evidence of a seizure disorder in a patient who may have one (eg, partial seizures with complex symptomatology), specialized procedures may help to clarify the diagnosis. Measurements of electroencephalographic activity after sleep deprivation and after stimulation with light, noise, and tactile sensations using nasopharyngeal leads, as well as the use of video monitoring simultaneously with electroencephalography, may be helpful in such cases. Neurologic consultation can also be beneficial.

Indications for performing a sleep-deprived EEG with appropriate sampling of slow-wave sleep in patients with ASD are clinical seizures (or suspicion of subclinical seizures) and clinically significant loss of social and communicative function, especially in toddlers and preschoolers. [3]

Admission to a specialized unit for simultaneous 24-hour video monitoring of electroencephalography and movement of the patient for a few days of assessment may facilitate the establishment of or the exclusion of diagnosis of a paroxysmal disorder. See PET Scanning in Autism Spectrum Disorders for further information. [155]

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