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Autism Workup

  • Author: James Robert Brasic, MD, MPH; Chief Editor: Caroly Pataki, MD  more...
 
Updated: Dec 01, 2015
 

Approach Considerations

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

Currently, children who display some features of autism are broadly categorized in the class of autism spectrum disorders. Experienced clinicians are able to identify particular deficits in children with autism spectrum disorder and institute effective treatments. Identification of the key dimensions characteristic of autism spectrum disorders may be a more accurate means of distinguishing subtypes of these conditions.[105]

The utilization of broader criteria for autism spectrum disorders will likely result in innovations in the identification of affected children. There will also likely be further developments in the institution of interventions for these conditions.[25]

Metabolic studies

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

Neuroimaging

There is currently no clinical evidence to support the role of routine clinical neuroimaging in the diagnostic evaluation of autism, even in the presence of megalencephaly.[1] 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 seizure disorder (present in a third of children with autism), acquired aphasia with convulsive disorder (Landau-Kleffner syndrome), biotin-responsive infantile encephalopathy, and related conditions.

Psychophysiologic assessment

Psychophysiologic assessment is indicated in children with autism. Children 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 autism may also demonstrate auditory overselectivity.

Polysomnography

Polysomnography may facilitate the diagnosis of treatable comorbid disorders. Most children with autism have sleep disturbances, including early morning awakening, frequent arousals, and fragmented sleep.[106] Additionally, children with autism 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 autistic children who meet any of the following criteria[1] :

  • The child has mental retardation
  • Mental retardation cannot be excluded
  • There is a family history of fragile X or undiagnosed mental retardation
  • Dysmorphic features are present
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Neuroimaging

MRI

Magnetic resonance imaging (MRI) studies in patients with autism 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.[107, 108] Although vermal hypoplasia is found in some individuals with autism, vermal hyperplasia is identified in others.[109]

The volume of the gray matter is bilaterally decreased in the amygdala, the precuneus, and the hippocampus of people with autism spectrum disorder. Adolescents with autism spectrum disorder have shown greater decreases in the volume of the gray matter of the right precuneus than have adults. The volume of the gray matter in the middle-inferior frontal gyrus has been found to be slightly increased in people with autism spectrum disorder.[110]

Imaging studies in patients with autistic disorder 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 autism.[111] Study subjects who developed autism 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 autism spectrum disorder 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.[112]

Children with autism and their healthy siblings demonstrate significant reductions in fractional anisotropy (FA) in association, commissural, and project tracts, in contrast to control groups.[113, 114] Alterations in FA in the white matter of the frontal, parietal, and temporal lobes suggest an inherited trait characteristic of a vulnerability to develop autism.

CT scanning

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

PET scanning

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

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.[115]

See PET Scanning in Autism Spectrum Disorders for further information, including the PET scan of a boy with autism in the video files posted throughout the article.

SPECT (single-photon emission CT) scanning

Chiron et al 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 autism. 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.[116]

Regional cerebral blood flow assessed with technetium-99m (99m Tc) labeled to hexamethylpropyleneamine oxide (HMPAO), a lipophilic substance, in children with autistic disorder 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 autistic disorder. Biologic classes may have specific types of regional cerebral blood flow dysfunction.

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Electroencephalography

As stated earlier, electroencephalography is useful for ruling out seizure disorder (present in a third of children with autism), 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 autism.[1]

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 autism are clinical seizures (or suspicion of subclinical seizures) and clinically significant loss of social and communicative function, especially in toddlers and preschoolers.[1]

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, including the EEG of a boy with autism seen in the video files posted within this article.[117]

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Contributor Information and Disclosures
Author

James Robert Brasic, MD, MPH Assistant Professor, Russell H Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine, Johns Hopkins University School of Medicine; Active Staff, Department of Radiology and Radiological Science, Division of Nuclear Medicine, Johns Hopkins Hospital; Courtesy Staff, Department of Radiology, Johns Hopkins Bayview Medical Center

James Robert Brasic, MD, MPH is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Academy of Neurology, International Parkinson and Movement Disorder Society

Disclosure: Received royalty from Medscape for other; Received royalty from Neuroscience-Net, LLC for other; Received grant/research funds from National Institutes of Health for other.

Chief Editor

Caroly Pataki, MD Health Sciences Clinical Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, David Geffen School of Medicine

Caroly Pataki, MD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, New York Academy of Sciences, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Acknowledgements

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Acknowledgments

This research is supported by the Essel Foundation, the Brain and Behavior Research Foundation (NARSAD), the Tourette Syndrome Association Inc, the National Institutes of Health, the Department of Psychiatry of Bellevue Hospital Center, and the New York University School of Medicine. The cooperation of the Health and Hospitals Corporation of the City of New York is gratefully acknowledged.

The author also gratefully acknowledges the technical assistance in the preparation of the video portions of this article of the Digital Media Center at the Skirball Institute of Biomolecular Medicine at the New York University Medical Center.

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The significance of answers to individual Autism Screening Checklist items is as follows: Item 1- A "yes" occurs in healthy children and children with some pervasive developmental disorders; a "no" occurs in children with autism, Rett syndrome, and other developmental disorders. Item 2 - A "yes" occurs in healthy children, not children with autism. Item 3 - A "yes" occurs in healthy children and children with Asperger syndrome (ie, high-functioning autism); a "no" occurs in children with Rett syndrome; children with autism may elicit a "yes" or a "no"; some children with autism never speak; some children with autism may develop speech normally and then experience a regression with the loss of speech. Item 4 - A "yes" occurs in healthy children and children with Asperger syndrome and some other pervasive developmental disorders; a "no" occurs in children with developmental disorders; children with autism may elicit a "yes" or a "no." Items 5-10 - Scores of "yes" occur in some children with autism and in children with other disorders. Item 11 – A "yes" occurs in healthy children; a "no" occurs in some children with autism and in children with other disorders. Items 12, 13 - Scores of "yes" occur in some children with autism and in children with other disorders. Items 14-19 - Scores of "yes" occur in children with schizophrenia and other disorders, not in children with autism, Asperger syndrome, or other autism spectrum disorders. The higher the total score for items 5-10, 12, and 13 on the Autism Screening Checklist, the more likely the presence of an autism spectrum disorder.
Serotonin syndrome checklist.
Clinicians are advised to videotape the process of verbally explaining the protocol and answering questions. Permission must be explicitly given to perform the procedure and cannot continue until the parents agree. Parents are asked to give permission to complete this protocol. The entire process is videotaped. In this segment, the mother of a healthy, normal control child gives informed consent to participate as a volunteer in a research study of autism. Occasionally, parents decline to give consent, and the procedure must cease. An earlier version of this videotape is in the New York University Medical Library, New York, New York.
A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner repeated movements of the telephone receiver and tapping on the telephone receiver initially exhibited by the subject. The examiner repeated the subject's actions several times in an attempt to elicit repetition of the movement by the subject. Instead, the subject does not acknowledge the presence of the examiner. He looks away from the examiner. He turns his back to the examiner. The subject spins by rotating on a central vertical axis in his body. He exhibits nonfunctional play with the telephone. He displays frequent finger wiggling and the other hand stereotypies. He frequently vocalizes indecipherable sounds and briefly rocks. He tilts his head and looks out of the corner of his eye for a few seconds. Please note that media file represents a diagnostic assessment of a child. The child is allowed to exhibit the abnormal behaviors to demonstrate those items on a video for confirmation by blind raters. If the child exhibited behaviors danger to himself, such as self-injurious behaviors, or dangerous to other, such as attacking others, then the examiner would intervene to prevent injury to the child and others. The media files does not in any way represent treatment for the disorder.
The examiner may attempt to establish a sequence of taking turns hitting a plate with a block. The examiner says, "My turn," and then taps the plate. The examiner gives the block to the subject and says, "Your turn." The subject may be physically assisted in the activity if the desired response does not occur. The following is a clinical example: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner attempted to elicit turn-taking by hitting the plate with a block. The child repeatedly jumps and rotates. He exhibits nonfunctional play with the telephone. He tilts his head and peers out of the corner of his eye. He is interested in the feel of the stick. He exhibits quick hand movements with small toys. When his father and his brother leave the room, the child does not acknowledge their departure. When his father returns to the room, he does not run to greet him. He appears indifferent to the departure and the return of his father. He repeatedly touches the surface of the wooden block. He touches the surface of a furlike cloth. He also places this cloth to his mouth to feel the texture on his lips. He is also fascinated with a string of yarn. He moves the string of yarn up and down and back and forth. This is nonfunctional play with ordinary items. Please note that media file represents a diagnostic assessment of a child. The child is allowed to exhibit the abnormal behaviors to demonstrate those items on a video for confirmation by blind raters. If the child exhibited behaviors danger to himself, such as self-injurious behaviors, or dangerous to other, such as attacking others, then the examiner would intervene to prevent injury to the child and others. The media files does not in any way represent treatment for the disorder.
The following is a clinical example that continues the segment of prior video: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. He appears indifferent to the departure of his brother from the room. He also does not respond with a greeting when his brother returns. He appears interested in his nonfunctional play. He displays minimal acknowledgment of the departure and return of his brother. In particular, he does not respond to his brother's touching him on the shoulder to greet him. Instead, he demonstrates inappropriate friendliness with the psychologist who is evaluating the procedures. Although he never saw her before this assessment, he suddenly goes to her to kiss her. Please note that media file represents a diagnostic assessment of a child. The child is allowed to exhibit the abnormal behaviors to demonstrate those items on a video for confirmation by blind raters. If the child exhibited behaviors danger to himself, such as self-injurious behaviors, or dangerous to other, such as attacking others, then the examiner would intervene to prevent injury to the child and others. The media files does not in any way represent treatment for the disorder.
 
 
 
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