Practice parameter: screening and diagnosis of autism; EP Magazine will be exploring the causes, effects and treatment of autism through 2003. As a basis for planning these articles, and to invite comment and contributions, we are publishing the "Practice parameter: Screening and diagnosis of autism" from the report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. (EP On Autism).
What are the appropriate developmental screening questionnaires that provide sensitive and specific information? Developmental screening tools have been formulated based on screening of large populations of children with standardized test items. Sensitive and specific developmental screening instruments include: the Ages and Stages Questionnaire, the BRIGANCE Screens, the Child Development Inventories and the Parents' Evaluations of Developmental Status.
The Denver-II (DDST-II, formerly the Denver Developmental Screening Test-Revised) has been the traditional tool used for developmental screening, but research has found that it is insensitive and lacks specificity. The Revised Denver Pre-Screening Developmental Questionnaire (R-DPDQ) was designed to identify a subset of children who needed further screening. However, studies have shown that it detected only 30% of children with language impairments and 50% of children with mental retardation.
How are conventional developmental milestones defined? Conventional developmental language milestones are based on normative data from numerous standardized language instruments for infants. Lack of acquisition of the following milestones within known accepted and established ranges is considered abnormal: no babbling by 12 months, no gesturing (e.g., pointing, waving bye-bye) by 12 months; no single words by 16 months; no 2-word spontaneous (not just echolalic) phrases by 24 months; and any loss of language or social skills at any age. Failure to meet these milestones is associated with a high probability of a developmental disability.
Do parents provide reliable information regarding their child's development? Several studies encompassing 737 children showed that parental concerns about speech and language development, behavior, or other developmental issues were highly sensitive (i.e., 75% to 83%) and specific (79% to 81%) in detecting global development deficits. However, the absence of such concerns had modest specificity in detecting normal development (47%). An additional study that combined parental concern with a standardized parental report found this to be effective for early behavioral and developmental screening in the primary care setting.
Can autism be reliably diagnosed before 36 months of age? Because there are no biological markers for autism, screening must focus on behavior. Recent studies comparing 109 autistic and 33 typically developing children demonstrated that problems with eye contact, orienting to. one's name, joint attention, pretend play, imitation, nonverbal communication, and language development are measurable by 18 months of age. These symptoms are stable in children from toddler age through preschool age. Retrospective analysis of home videotapes has also identified behaviors that distinguish infants with autism from other developmental disabilities as early as 8 months of age.
Current screening methods may not identify children with milder variants of autism, those without mental retardation or language delay, such as verbal individuals with high-functioning autism and Asperger's disorder, or older children, adolescents, and young adults.
Is there an increased risk of having another child with autism (recurrence)? The incidence of autism in the general population is 0.2%, but the risk of having a second (or additional) autistic child increases almost 50-fold to approximately 10 to 20%.
What tools are available with appropriate psychometric properties to specifically screen for autism? Appropriately sensitive and specific autism screening tools for infants and toddlers have only recently been developed, and this continues to be the current focus of many research centers. The Checklist for Autism in Toddlers (CHAT) for 18-month-old infants, and the Autism Screening Questionnaire for children 4 years of age and older, have been validated on large populations of children. However, it should be noted that the CHAT is less sensitive to milder symptoms of autism, as children later diagnosed with PDD-NOS, Asperger's, or atypical autism did not routinely fail the CHAT at 18 months.
The Pervasive Developmental Disorders Screening Test-II (PDDST-II) for infants from birth to 3 years of age, the Modified Checklist for Autism in Toddlers (M-CHAT) for infants at 2 years of age, and the Australian Scale for Asperger's syndrome for older verbal children, are currently under development or validation phases.
What screening laboratory investigations are available for developmental delay, with or without suspicion of autism? Formal audiologic evaluation. The Committee on Infant Hearing of the American Speech-Language-Hearing Association developed guidelines for the audiologic assessment of children from birth through 36 months of age. They recommended that all children with developmental delays, particularly those with delays in social and language development, have a formal audiologic hearing evaluation. Three studies have documented that conductive, sensorineural, or mixed hearing loss can co-occur with autism, and that some children with autism may be incorrectly thought to have peripheral hearing loss. In addition, transient conductive hearing loss associated with otitis media with effusion can also occur in children with autism.
Audiologic assessment of such children requires modifications of traditional test techniques and environments (e.g., operant test procedures). Electrophysiologic procedures are useful for estimating hearing sensitivity and for examining middle ear, cochlear, and VIIIth nerve or auditory brainstem pathway integrity. Evoked otoacoustic emissions are useful for examining cochlear (sensory) function, and is a frequency-specific, as well as a time-and cost-efficient procedure. Frequency-specific auditory brainstem response (ABR) is the single most useful electrophysiologic procedure for use in estimating hearing thresholds, and has been demonstrated to be highly correlated with behavioral hearing thresholds in children who hear normally and in children who have sensorineural hearing loss. Lead screening. Children with developmental delays who spend an extended period in the oral-motor stage of play (where everything "goes into their mouths") are at increased risk for lead toxicity, especially in certain environments. The prevalence of pica in this group can result in high rates of substantial or recurrent exposure to lead. The National Center for Environmental Health of the Centers for Disease Control and Prevention recommends that children with developmental delays, even without frank pica, should be screened for lead poisoning. Blood levels in children with autism are elevated. In one study, the mean blood lead level in 18 autistic children was higher than in 16 nonautistic "psychotic" children or in 10 normal siblings; 44% of the autistic and psychotic children had lead levels significantly above the mean compared with control subjects. In a more recent study, 17 autistic children treated for lead poisoning were compared with 30 children without autism. The autistic children were older at diagnosis, had higher lead levels, and most were reexposed despite close monitoring of their environment.
Level two: diagnosis and evaluation of autism. Analysis of the evidence. Who should diagnose autism? Although educators, parents, and other health care professionals identify signs and symptoms characteristic of autism, a clinician experienced in the diagnosis and treatment of autism is usually necessary for accurate and appropriate diagnosis. Clinicians must rely on their clinical judgment, aided by guides to diagnosis, such as DSM-IV and the Tenth Edition of the International Classification of Diseases (ICD-10), as well as by the results of various assessment instruments, rating scales, and checklists. These instruments and criteria should be used by practitioners not as experienced in the diagnosis of autism.
What are the medical and neurologic concerns in evaluating children with autism? Family prevalence. Family studies have shown that there is a 50-fold to 100-fold increase in the rate of autism in first-degree relatives of autistic children. Within these families, there are also elevated rates of social difficulties; higher incidences of cognitive, communication, learning and executive function deficits; increased stereotyped behaviors; and anxiety, affective, language, and pragmatic disorders. Monozygotic twin pair studies have also shown a high concordance rate (60%) for DSM-IV Autistic Disorder, 71% for the broader autistic spectrum phenotype, and 92% for an even broader phenotype of social and communication deficits with stereotyped behaviors that nonetheless were clearly differentiated from normal. In contrast, no concordance for autism was noted in dizygotic twin pairs and only 10% were concordant for some form of cognitive, social, or language deficit.
Large head circumference without frank neuropathology. Children with autism have a larger head circumference; only a small proportion have frank macrocephaly. Large head size may not necessarily be present at birth, but may appear in early to mid-childhood, perhaps indicating an increased rate of brain growth. Neuroimaging studies in autism also found larger brain volumes without associated neuropathology.
Association with tuberous sclerosis complex (TSC) and less often with Fragile X (FraX) syndrome. Seventeen to over 60% of mentally retarded individuals with TSC are also autistic, and these patients commonly have epilepsy. In contrast, the number of autistic individuals with TSC has been estimated to be between 0.4% and 3%. This rate increases to 8% to 14% if epilepsy is also present.
Clinical studies report that 3% to 25% of patients with FraX have autism. However, no evidence of FraX in autistic individuals was found using cytogenetic (not DNA analysis) techniques; with molecular genetic analyses, only a few autistic individuals were shown to have FraX.
What are the specific deficits of the autistic child's developmental profile? Speech, language, and verbal and nonverbal communication. Verbal and nonverbal communication deficits seen in autism are far more complex than simple speech delay, but overlap with developmental language disorders or specific language impairments. Expressive language function ranges from complete mutism (as often seen in children 2 to 3 years of age) to verbal fluency, though verbal abilities are often accompanied by many errors in word meaning (semantics) or language and communicative deficits in social contexts (social-pragmatics).
Cognitive deficits. Many autistic individuals demonstrate a particular pattern on intellectual tests that is characteristic of autism, i.e., performance IQ (PIQ) higher than verbal IQ (VIQ), and specific intersubtest scatter, with Block Design typically the highest subtest and Comprehension usually the lowest. However, the PIQ-VIQ split is severity dependent. When Full Scale IQ (FSIQ) and VIQ are both above 70, 80% of autistic individuals will have no significant VIQ-PIQ disparity, and the remainder are evenly divided between those with PIQ > VIQ and those with PIQ < VIQ.
The DSM-IV defines the diagnosis of mental retardation as the combination of subaverage intellectual functioning (IQ> 70) and concurrent deficits in adaptive functioning. Autistic individuals have poorer adaptive function than would be predicted by IQ alone.
Sensorimotor deficits. Impairments of gross and fine motor function are reported as being common in autistic individuals, and are recognized as hypotonia, limb apraxia, or motor stereotypies. Motor deficits are more severe in individuals with lower IQ scores. Hand or finger mannerisms, body rocking, or unusual posturing are reported in 37% to 95% of individuals, and often manifest during the preschool years. Sensory processing abilities are aberrant in 42% to 88% of autistic individuals and include preoccupation with sensory features of objects, over- or under-responsiveness to environmental stimuli, or paradoxical responses to sensory stimuli.
Neuropsychological, behavioral, and academic impairments. Specific neuropsychological impairments can be identified, even in young children with autism, that correlate with the severity of autistic symptoms. Performance on tasks that rely on rote, mechanical, or perceptual processes are typically spared; deficient performance exists on tasks requiring higher-order conceptual processes, reasoning, interpretation, integration, or abstraction. Dissociations between simple and complex processing are reported in the areas of language, memory, executive function, motor function, reading, mathematics, and perspective-taking. There is no reported evidence that confirms or excludes a diagnosis of autism based on these cognitive patterns alone.
When and what laboratory investigations are indicated for the diagnosis of autism? Genetic testing. A chromosomal abnormality reported in possibly more than 1% of autistic individuals involves the proximal long ann of chromosome 15 (15q11-q13), which is a greater frequency than other currently identifiable chromosomal disorders. Those with the 15q abnormalities typically have moderate to profound mental retardation. The duplication is usually maternally inherited, either pseudodicentric 15 (inverted duplication 15) or other atypical marker chromosomes, with one or two extra copies of the area roughly corresponding to the typical Angelman syndrome (AS)/Prader Willi syndrome (PWS) deletion region of approximately four million base pairs. Conversely, AS is usually due to a deletion of maternally inherited 15q11-q13 material and has been found in patients with autism and profound mental retardation.
Metabolic testing. Inborn errors in amino acid, carbohydrate, purine, peptide, and mitochondrial metabolism, as well as toxicologic studies, have been studied, but the percentage of children with autism who have a metabolic disorder is probably less (and some experts agree that it is considerably less) than 5%
Electrophysiologic testing. The prevalence of epilepsy in autistic children has been estimated at 7 to 14%, whereas the cumulative prevalence by adulthood is estimated at 20% to 35%. Seizure onset peaks in early childhood and again in adolescence. Mental retardation, with or without motor abnormalities and family history of epilepsy, was a significant risk factor for the development of seizures in autistic individuals.
It is unclear whether there is a relationship between autism and an early regressive course (before 36 months), childhood disintegrative disorder ([CDD] after 36 months), Landau-Kleffner syndrome, and electrical status epilepticus during slow wave sleep (ESES). Autism with regression and CDD have both been associated with seizures or epileptiform sleep-deprived EEG (with adequate sampling of slow wave sleep). A higher incidence of epileptiform EEG abnormalities in autistic children with a history of regression has been reported when compared to autistic children with clinical epilepsy. Seizures or epileptiform discharges were more prevalent in children with regression who demonstrated cognitive deficits. Regression in cognition and language in adolescence associated with seizure onset has also been observed, but little is known about its cause or prevalence. There may be a causal relationship between a subgroup of children with autistic regression and EEG-defined "benign focal epilepsies." There is insufficient evidence to suggest a role for event-related potentials or magnetoencephalography in the evaluation of autism.
Neuroimaging. CT studies, ordered as standard assessments of children diagnosed with autism during the 1970s and 1980s, reported a wide range of brain imaging abnormalities and suggested that there was an underlying structural disorder in patients with autism. This view changed when Damasio et al. demonstrated that such abnormalities were incidental to coexisting anatomic disorders unrelated to autism. A very low prevalence of focal lesions or other structural abnormalities was found; their inconsistent localization marked them as coincidental. Prevalence of lesions on MRI in children with autism is similar to normal control subjects. CT and MRI studies of autistic subjects screened to exclude those with disorders other than autism confirmed the absence of significant structural brain abnormalities.
Functional imaging modalities such as functional MRI (fMRI), single-photon emission CT (SPECT), or positron-emission tomography (PET) are currently only research tools in the evaluation of autism. There is no evidence to support a role functional neuroimaging studies in the clinical diagnosis of autism at the present time.
Other tests. There is insufficient evidence to support the use of other tests such as hair analysis for trace elements, celiac antibodies, allergy testing (particularly food allergies for gluten, casein, candida, and other molds), immunologic or neurochemical abnormalities, micronutrients such as vitamin levels, intestinal permeability studies, stool analysis, urinary peptides, mitochondrial disorders (including lactate and pyruvate), thyroid function tests, or erythrocyte glutathione peroxidase studies.
P.A. Filipek, MD; P.J. Accardo, MD; S. Ashwal, MD; G.T. Baranek, PhD, OTR/L; E.H. Cook, Jr., MD; G. Dawson, PhD; B. Gordon, MD, PhD; J.S. Gravel, PhD; C.P. Johnson, MEd, MD; R.J. Kallen, MD; S.E. Levy, MD: N.J. Minshew, MD; S.Ozonoff, PhD; B.M. Prizant, PhD, CCC-SLP; I. Rapin, MD; S.J. Rogers, PhD; W.L. Stone, PhD; S.W. Teplin, MD; R.F. Tuchman, MD; and ER. Volkmar, MD
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|Publication:||The Exceptional Parent|
|Date:||Oct 1, 2002|
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