General Child Neurology
Perinatal hypoxic-ischemic encephalopathy
May. 30, 2022
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Autism spectrum disorder is a neurodevelopmental condition characterized by impairment in social communication, repetitive behaviors, restricted interests, and hyper- or hyposensitivity to sensory stimuli. In this article, the author describes the clinical features of autism spectrum disorder and summarizes recent research regarding etiology, pathogenesis, genetics, diagnosis, and management.
• Autism spectrum disorder is a neurodevelopmental condition characterized by social communication impairment, restricted interests, and repetitive behaviors.
• It is estimated that 1 in 54 children have autism spectrum disorder. Autism spectrum disorder is more than 4 times as common in males as it is in females.
• Autism spectrum disorder is complex with no single or precise etiology.
• Early identification and behavioral treatment lead to better outcomes.
• Pharmacological treatment targets problem behaviors such as hyperactivity, impulsivity, aggression, and perseverative or anxious behaviors.
In 1908, psychiatrist Eugen Bleuler used the term “autistic” to describe a form of schizophrenia. The word has the Greek roots “autos,” meaning self. In 1943, Leo Kanner described “extreme autistic aloneness,” “inability to relate,” “communication difficulties,” and “desire for the maintenance of sameness” in children (21). In 1944, Hans Asperger described 4 children who had difficulty with social interaction. Table 1 shows the changes to the Diagnostic and Statistical Manual of Mental Disorders classification of autism or pervasive developmental disorders over time.
DSM-I (1952) and DSM-II (1968)
No term for autism or pervasive developmental disorder
Pervasive developmental disorders: infantile autism, childhood onset pervasive developmental disorder, atypical autism
Pervasive developmental disorders: autistic disorder, pervasive developmental disorder not otherwise specified
DSM-IV (1994) and DSM-IV-TR (2000)
Pervasive developmental disorders: autistic disorder, Asperger disorder, pervasive developmental disorder not otherwise specified, childhood disintegrative disorder, Rett syndrome
Autism spectrum disorder
Autism spectrum disorder is a neurodevelopment disorder characterized by social communication impairment, restricted interests, repetitive behaviors, and hyper- or hyporeactivity to sensory input.
Parents of children with autism spectrum disorder (ASD) report initial concerns about their child’s development before 18 to 24 months. There is significant heterogeneity in the clinical presentation of autism spectrum disorder. Some children show differences in social interaction in the early months of life, whereas other children may become withdrawn and have language regression in the second year of life. Common early signs of autism are decreased social attention and communication as well as increased repetitive behavior with objects between 12 and 24 months of age. Abnormal body movements and emotional dysregulation are also seen (45).
Commonly observed clinical features are:
• Lack of eye contact and/or facial expressions
• Lack of interest in other children, prefers to play alone
• Failure to form close relationships with peers
• Lack of sharing enjoyment or achievements with other people
• Unaware of others’ feelings or distress
• Difficulty seeing others’ point of view
• Treating others as objects or tools (eg, using mother’s hand to turn the door handle)
• Lining up toy or focused with only 1 part of a toy (eg, spinning wheels)
• Limited or lack of pretend play
• Decreased interest in social games such as peekaboo
• Hand flapping, rocking, or spinning
• Intense interests in certain topics (eg, bridges, trains)
• Distress with small changes to the routine
• Hypo- or hypersensitivity to sensory stimuli (eg, distress with loud noises)
Individuals with autism spectrum disorder may be affectionate and desire social attention, but may lack the skills needed to effectively interact with others. Children may have typical language development or significant impairments in expressive and receptive language. Persons with autism spectrum disorder may not engage in meaningful pragmatic communication and may lack reciprocity, resulting in an impaired ability to sustain conversation. Spoken language may be stereotyped in form and marked by immediate and delayed echolalia, pronominal reversal, and idiosyncratic word usage.
Associated features. Features associated with autism spectrum disorder are as follows:
Intellectual impairment. Prevalence data published by the CDC in 2016 identified that 33% of children with autism were classified in the range of intellectual disability (IQ ≤ 70). Cognitive skills in individuals with autism spectrum disorder may show uneven development.
Attention, mood, and behavioral disorders. Individuals with autism spectrum disorder may show hyperactivity, impulsivity, and short attention span. There may be abnormalities of mood or affect. Anxiety can be prominently manifested by excessive fears, transition-related stress, excessive startle, or obsessions and compulsions. They may demonstrate inappropriate (excessive or lack of) reaction to perceived dangers. Some parents have reported that their child does not appear to react to pain or seems to be oversensitive to sound or touch. They may show increased temper tantrums, aggressiveness, and a variety of self-injurious behaviors including head banging and self-biting. Studies show conditions such as attention deficit hyperactivity disorder, anxiety, obsessive compulsive disorder, mood disorders, and conduct disorders are identified in 70% to 90% of children and youth with autism spectrum disorder (20).
Seizures. The prevalence of epilepsy is higher in children with autism spectrum disorder than in the general population. A systematic review of the literature showed that 12% of people with autism spectrum disorder also had epilepsy (24). Routine EEG is not recommended for all individuals with autism spectrum disorder but should be considered if there is atypical regression, seizures, or other neurologic symptoms that would warrant an EEG (20).
Gastrointestinal problems. Children with autism spectrum disorder have a higher incidence of constipation and food selectivity/feeding issues. In a sample of 2973 children with autism spectrum disorder enrolled in the autism treatment, 24% had at least one type of chronic gastrointestinal problem (constipation, abdominal pain, bloating, diarrhea, or nausea lasting 3 or more months). Sensory over-responsivity and anxiety were highly associated, and the results indicate that anxiety, sensory over-responsivity, and gastrointestinal problems are possibly interrelated phenomenon for children with autism spectrum disorder (26).
Sleep problems. Disturbed sleep is commonly seen in children with autism spectrum disorder and can affect behavior and performance during the day. A study of 335 children with autism or pervasive developmental disorder not otherwise specified were evaluated using Behavioral Evaluation of Disorders of Sleep (BEDS) scores to measures of intelligence and adaptive behavior. Children who slept fewer hours per night had lower overall intelligence, verbal skills, overall adaptive functioning, daily living skills, socialization skills, and motor development (39).
Autism spectrum disorder is typically considered a disorder of childhood; however, most persons have significant functional impairment throughout life. A broad range of syndrome expression is seen in autism spectrum disorder. About 9% of people diagnosed with autism spectrum disorder as a young child no longer met criteria as an adult. Intelligence and language ability in childhood can help predict outcome in adulthood. Quality of life in adults with high functioning autism spectrum disorder was associated with family and community support (20).
Increased awareness has aided in the early identification of autism spectrum disorder so more children are now benefiting from early intervention.
A 2-year-old male was referred for delay in language development. He had no functional communication, but was able to repeat words and phrases. His favorite thing to do was to watch YouTube videos in different languages. He did not play with toys in the typical manner, but would instead lie on the ground so that he could “sight” horizontal lines on toys such as cars. He was very affectionate toward his parents and frequently attempted to sit in their laps to cuddle. However, he showed no interest in the activities of other children his age. He displayed few problem behaviors at home, but became very agitated in novel situations (such as a visit to the doctor’s office), and at these times, he was inconsolable and cried continuously until taken home. He did not have any dysmorphic features and genetic testing did not reveal an etiology for his symptoms. The child was unable to participate in any direct testing of IQ or language skills due to difficulty staying seated and lack of a pointing response.
It is generally accepted that autism spectrum disorder is a complex neurodevelopmental disorder with no single etiology. A genetics evaluation of persons with autism spectrum disorder is estimated to result in an identified etiology in 30% to 40% of individuals (34). There are hundreds of susceptibility genes and possibly environmental and epigenetic factors (45). Advanced maternal and paternal age, prematurity, and other neonatal complications have also been reported as risk factors for the development of autism. The Center for Disease Control and Prevention (CDC), along with many other investigators, continue to research risk factors and causes for autism. Vaccinations have not been associated with the development of autism spectrum disorder. Additionally, the components of the vaccines (thimerosal or mercury) or multiple vaccines (MMR) are not associated with the development of autism spectrum disorder (38).
Genetics. Autism spectrum disorder is heritable with a high rate of concordance in monozygotic twins and increased rates among siblings. Certain genetic syndromes have an increased rate co-occuring with autism spectrum disorder, including fragile X, tuberous sclerosis, and Rett syndrome. Genetic testing is recommended for all patients with autism spectrum disorder (19).
Neuroanatomical abnormalities. A multicenter MRI study was conducted in men with autism spectrum disorder. They found that individuals with autism spectrum disorder had significantly increased gray matter volume in the anterior temporal and dorsolateral prefrontal regions and significant reductions in the occipital and medial parietal regions compared with controls. These regional differences were significantly correlated with the severity of specific autistic symptoms (14). Another study revealed larger brain volume in the frontal lobes, whereas the occipital lobes are smaller in size in individuals with autism (29). Autopsied brain samples from patients with autism spectrum disorder have revealed a loss of Purkinje cells in the hippocampus, amygdala, and cerebellum.
Approximately 30% of persons with autism spectrum disorder have increased head size and brain volume. The largest study evaluating age-related changes in brain size in subjects from 12 months to 50 years of age showed early brain overgrowth during infancy and the toddler years in children with autism spectrum disorder, followed by an accelerated rate of decline in size and perhaps degeneration with age (09). A study evaluated infants using brain magnetic resonance imaging and found that those who later developed autism spectrum disorder (n=10) had significantly greater extraaxial fluid at 6 to 9 months, which remained elevated at 18 to 24 months. The amount of extraaxial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. These infants also had significantly larger total cerebral volumes. This study raises the potential for magnetic resonance imaging to help with early detection in individuals at higher risk for autism spectrum disorder (36). There is a lower prevalence of definite pathology on brain MRI in children with autism spectrum disorder without abnormal neurologic exam, headaches, or seizures (6.5% in children with only autism spectrum disorder compared to around 25% in those with autism spectrum disorder and other neurologic symptoms) (08).
Neurotransmitters. Many neurochemical pathways are likely involved in autism spectrum disorder. Serotonin and dopamine appear to play a role in the pathophysiology of autism spectrum disorder. Oxytocin and vasopressin are pituitary neuropeptides that have been shown to play a role in social behavior. Single nucleotide polymorphisms (SNPs) in oxytocin and arginine-vasopressin receptors have been associated with autism spectrum disorder. More research is needed to determine the mechanism of how these receptor polymorphisms contribute to autism spectrum disorder (06). GABA modulators (eg, arbaclofen) have been studied in open label trials, but additional studies are needed before they could be considered in the treatment of core symptoms of autism spectrum disorder. Glutamate is an excitatory neurotransmitter, and 2 of its receptors have been implicated in autism spectrum disorder (25).
Hormones. High fetal testosterone levels have been associated with traits of autism spectrum disorder in toddlers and older children. This supports the extreme male brain theory of autism advanced by Baron-Cohen (03). Hypothalamic pituitary adrenal dysregulation in persons with autism spectrum disorder have been explored and identified through cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone measurements. The 11 human studies that measured cortisol found few differences in subjects and controls, but a larger study (N= 48) found higher cortisol levels in subjects with severe autistic spectrum disorder indicating a mechanism of possible neurotoxic effect of cortisol (22).
Immunology. Significant increases in plasma levels of a number of cytokines, including IL-1beta, IL-6, IL-8, and IL-12p40, have been found in an autism spectrum disorder group compared with typically developing controls. It was noted that the increased cytokine levels were predominantly in children who had a regressive form of autism spectrum disorder, and increasing cytokine levels were associated with more impaired communication and aberrant behaviors (02). A study of dynamic adaptive cellular immune function conducted with 66 children with autism spectrum disorder and 73 control subjects showed altered T-cell function in the autism spectrum disorder group.
Prenatal and perinatal factors. A linked database cohort study of infants born between 1990 and 2002 was performed in Canada (11). They found that mothers with prepregnancy weight of 90 kg or more and an 18 kg weight gain during pregnancy were independent risk factors for autism. The authors proposed that leptin levels during pregnancy may be involved. In addition, women who delivered less than 18 months after a previous delivery and women with no previous deliveries were at increased risk to have a child with autism. Prenatal exposure to valproic acid, ethanol, thalidomide, and misoprostol has been shown to be associated with an increased incidence of autism spectrum disorder (12). Prenatal cytomegalovirus infection has been associated with autism spectrum disorder (15).
A metaanalysis of 40 studies evaluating perinatal and neonatal risk factors for autism was conducted. Factors associated with autism risk in the meta-analysis were abnormal presentation, umbilical-cord complications, fetal distress, birth injury or trauma, multiple birth, maternal hemorrhage, summer birth, low birth weight, small for gestational age, congenital malformation, low 5-minute Apgar score, feeding difficulties, meconium aspiration, neonatal anemia, ABO or Rh incompatibility, and hyperbilirubinemia. Factors not associated with autism risk included anesthesia, assisted vaginal delivery, postterm birth, high birth weight, and head circumference (16).
Autism spectrum disorder is one of the most common neurodevelopmental diseases in children. Surveillance data revealed that the estimated prevalence in the United States is 1 in 54 children. This is significantly higher than in previous surveillance estimates. Autism spectrum disorder is more than 4 times more common in males as it is in females. Autism spectrum disorder is reported to occur in all racial, ethnic, and socioeconomic groups. Autism spectrum disorder tends to occur more often in people who have certain genetic or chromosomal conditions. Children born to older parents are at a higher risk for having autism spectrum disorder (10). For autism of unknown cause, it is estimated that the recurrence risk is 10%. For families with 2 or more affected children, the recurrence risk approaches 35%. Male siblings have a higher risk of having autism than female siblings (27).
Possible reasons for the steady rise in prevalence include increased awareness, increased services, and changes to the diagnostic criteria. However, the possibility of a true increase in incidence has not been conclusively ruled out.
• Avoidance of known teratogens that can increase the risk of autism spectrum disorder such as ethanol, thalidomide, valproic acid, and misoprostol.
• Genetic counseling for families with 1 or more affected children.
The differential diagnosis for autism spectrum disorder includes:
• Hearing impairment
• Developmental language disorder
• Rett syndrome
• Selective mutism
• Intellectual disability
• Stereotypic movement disorder
• Complex motor tics
• Obsessive-compulsive disorder
• Reactive attachment disorder
• Christianson syndrome
It may be difficult to determine if the additional diagnosis of autism spectrum disorder is warranted in severe or profound intellectual disability. If there are qualitative deficits in social and communication skills for level of cognitive functioning, and the specific behavioral characteristics of autism spectrum disorder are present, an additional diagnosis of autism spectrum disorder can be considered. The compulsive, perseverative, or self-stimulatory behavior of a person with intellectual disability can look like autism spectrum disorder, yet the other typical impairments are absent. The ritualistic behavior of a person with intellectual disability with obsessive-compulsive disorder may be confused with the repetitive and stereotypic pattern of behavior of a person with autism spectrum disorder.
Screening. The American Academy of Pediatrics recommends that an autism-specific standardized screen be administered at the 18- and 24-month health maintenance visits. Developmental surveillance at all visits is recommended (20). The Modified Checklist for Autism in Toddlers Revised with Follow-Up (M-CHAT-R/F) is a short parent checklist valid for use between 16 and 30 months of age (30). For children over the age of 4 years, The Social Communication Questionnaire has been found to be an effective screening instrument (13). The Communication and Symbolic Behavior Scales Developmental Profile (CSBS:DP) is not autism-specific, but it is a useful parent-completed screening tool to evaluate eye gaze, gestures, sounds, words, understanding, and play in children 6 to 24 months of age (42).
The Screening Tool for Autism in Two-Year-Olds (STAT) is an interactive screening measure for autism that assesses play, communication, and imitation skills. It correlates well with the Autism Diagnostic Observation Schedule (ADOS) (37).
History and examination. A detailed developmental and behavioral history should be taken. Information should also be obtained regarding history of maternal infections during pregnancy, perinatal or postnatal insult to the patient's brain, meningitis, encephalitis, or seizures. An inquiry should be made into family history of autism and other genetic disorders, related developmental disorders, or psychiatric disorders.
Physical examination should include assessment of any dysmorphic features or neurologic deficits. Mental status examination should attempt to assess: (1) the child's relatedness to and interest in the professionals, caregivers, siblings, peers, and other people in the child's environment; (2) the quality of reciprocal social exchange in verbal and nonverbal communication (eye contact, gestures, facial expression, stereotyped speech, echolalia, pronominal reversal); (3) the child's ability to engage in reciprocal imaginative play with representational toys; (4) the presence of perseverative, stereotypic, and ritualistic behavior; and (5) the presence of problematic behaviors, such as attentional difficulties, high activity level, aggression, and self-injurious behavior. Any child presenting with self-injurious head banging should be evaluated for the presence of a medical cause for this behavior (eg, otitis media, sinus infection).
Autism-specific assessment instruments. A comprehensive assessment should include both parent interview and child observation. Parent report instruments include checklists and parent interviews such as The Autism Diagnostic Interview-Revised (31). Standardized child observation instruments include The Childhood Autism Rating Scale, 2nd edition and the Autism Diagnostic Observation Schedule, 2nd edition (23; 35). Training is required to ensure reliability on these instruments.
Cognitive assessment. Assessment of the child's current level of cognitive functioning, adaptive and maladaptive behaviors, language skills, and educational strengths and weaknesses is crucial in treatment planning.
A formal educational assessment should be obtained in the school-aged child. This assessment will be helpful in planning an individualized educational program for the child and in providing specific guidelines for intervention to the classroom teacher. A formal behavioral assessment and consultation by a behavioral specialist may be needed to recommend specific interventions and strategies if the child presents with behavioral problems that interfere with learning or adaptation to the classroom or if the child presents a potentially dangerous situation for the child or others.
Medical investigation. Hearing should be tested, especially if there is speech delay. If the child is unable or unwilling to cooperate with audiometry, or the initial test is suboptimal or equivocal, hearing should be tested with brainstem auditory evoked response.
Genetic testing is recommended for children diagnosed with autism spectrum disorder. Microarray analysis and testing for fragile X syndrome is usually first line testing. A referral to a genetic specialist should be considered. Whole exome sequencing is being performed in some children whose microarray and fragile X testing did not reveal an etiology.
An EEG should be obtained if the history is suggestive of seizures, behavioral regression, or loss of language. Metabolic screening, amino acid chromatography, serological tests for evidence of intrauterine infections, and tests for phenylketonuria, serum copper, and ceruloplasmin are indicated if symptoms of autism appeared after 3 years of age or are progressive.
Other consultations (eg, neurology, genetics, endocrinology, developmental pediatrics, psychology, psychiatry, speech therapy, occupational therapy, and physical therapy) may be indicated based on a particular patient's symptomatology.
Early intervention is extremely important and children with autism spectrum disorder (or suspected autism spectrum disorder) should be referred to early intervention programs as soon as possible. The National Standards Project classified treatments for autism into the following categories based on scientific evidence: established, emerging, unestablished, and ineffective/harmful (28). Examples of established treatments include comprehensive behavioral treatment for young children, schedules, and story-based intervention packages. Emerging treatments include picture exchange communication system, language therapy, music therapy, and social skills training. Unestablished treatments include auditory integration training and the gluten-free casein-free diet. Often well-controlled studies have not been conducted, so a treatment continues to be viewed as “experimental” due to lack of investigation. Healthcare professionals must communicate objective findings to parents so they can make the most informed decisions and avoid potentially costly and unproven treatment. The quest for a “cure” can deplete a family’s resources, both emotionally and financially.
Comprehensive treatment approaches. The treatment with the most research support is applied behavior analysis therapy. Applied behavior analysis therapy involves setting individualized goals for the child and teaching skills by breaking them down into small steps. Teaching techniques are based on scientifically derived principles of behavior. Numerous studies have investigated the use of intensive applied behavior analysis with children with autism. The outcomes of these studies showed that the children receiving applied behavior analysis treatment made significant gains in areas such as cognitive functioning, language, social interaction, and adaptive skill development. A review of the existing research regarding applied behavior analysis concluded that a clear and considerable body of evidence exists to support the use of applied behavior analysis with children with autism (01).
Floor Time is a child-directed therapy where parents typically set aside regularly scheduled short periods of play with their child, with emphasis on promoting purposeful and positive reciprocal social exchange (17). A chart review of 200 children with autism or pervasive developmental disorder has been used as support for the floor time model (18). However, the study lacked experiment control, did not use a validated outcome measure, and was based on the progress evaluation of a single clinician who was not blind to the hypotheses of the review.
The TEACCH (Treatment and Education of Autistic and Related Communication Handicapped Children) Program was developed at the University of North Carolina at Chapel Hill. The program is based on the use of a structured teaching curriculum and extensive environmental modifications and supports. A number of studies have followed young children receiving TEACCH services and have described good outcomes. However, direct treatment outcome studies have not been reported.
Curriculum development. Educational interventions must be individualized based on the child’s unique pattern of strengths and weaknesses. A comprehensive educational plan for a child with autism spectrum disorder should include the following areas: communication, social skills, cognitive skills, sensory and motor development, adaptive behaviors, and problem behaviors.
Alternative modes of communication should be introduced if there is little or no progress in speech. One popular approach to augmentative communication is the Picture Exchange Communication System program (05). The program involves teaching children to exchange pictures in order to fulfill wants and needs (eg, handing an adult a picture of a toilet to indicate the need to use the restroom). Research suggests that the use of augmentative communication do not interfere with the development of spoken language and can promote the use of speech in some children.
Children with autism spectrum disorder typically need direct social skills training to help address social deficits. Intervention approaches include parent training, peer training, modeling, groups, and direct instruction in social skills.
For teenagers and young adults, it is particularly important to provide vocational counseling and training. Higher functioning individuals may be able to hold jobs or attend college. Other individuals may do well in supported employment situations. Physical and occupational therapy can be helpful for motor, self-help, and sensory processing impairments.
Family support. It is important to alleviate family distress by helping the family gain an understanding of their child's behavior. Myths and misplaced guilt regarding the etiology of autism can contribute to marital, individual, and sibling stress. Family members need to be engaged as co-therapists in the child's treatment and fully participate in the child's education, language and socialization development, and behavior management. Families need professional and personal support to help them deal with guilt and frustration, and with slow or seeming lack of progress. They must advocate for their child's educational needs, and for their financial needs for various therapeutic interventions. They need respite care to enable them to attend to other members of the family. There are many self-help and support groups available through the local branches of the Autism Society of America.
Pharmacotherapy. Pharmacological interventions to reduce or eliminate maladaptive and injurious behaviors have an important role in the treatment of autism spectrum disorder. It is imperative that pharmacotherapy be instituted only in conjunction with a comprehensive individualized behavioral and family treatment program and it is suggested that behavioral interventions be implanted prior to the initiation of any psychopharmacologic interventions. It is important to note that medications are not specific to autism spectrum disorder and do not treat core aspects of the disorder.
Neuroleptics. Risperidone and aripiprazole are the only medications approved by the FDA for autism spectrum disorder. They are used to treat irritability associated with autism spectrum disorder (44). Risperidone is a potent dopamine D2 or serotonin (5HT) receptor antagonist with powerful antipsychotic properties. It was approved for individuals 5 to 16 years of age with autism and disruptive behavior (41). Weight gain and sedation are common. Extrapyramidal side effects are rare and generally occur with higher doses. Aripiprazole is an atypical antipsychotic agent with a relatively high affinity for dopamine D2 and D3 receptors and serotonin 5-HT1A and 5-HT2A receptors. It was approved for the treatment of irritability associated with autism spectrum disorder in children ages 6 to 17 years. Aripiprazole has a relatively lower risk for weight gain, but body mass index and metabolic profiles should be monitored with both risperidone and aripiprazole (44).
Selective serotonin reuptake inhibitors. A Cochrane review of selective serotonin reuptake inhibitors on the symptoms of autism spectrum disorder found “no evidence of effect of selective serotonin reuptake inhibitors in children and emerging evidence of harm, and limited evidence of effectiveness in adults” (43). Nine randomized, controlled trials with a total of 320 participants were included in the review. Fluoxetine, fluvoxamine, fenfluramine, and citalopram were studied. Five studies included only children and 4 studies included only adults. One large, high-quality study in children showed no evidence of positive effect of citalopram (43). Selective serotonin reuptake inhibitors may still be used to treat symptoms of anxiety, depression, and obsessive-compulsive disorder, which can occur in individuals with autism spectrum disorder.
Mood stabilizers. Mood stabilizers (eg, lithium, lamotrigine, valproic acid, carbamazepine, carbamazepine, topiramate, oxcarbazepine, and levetiracetam) are occasionally tried on a case-by-case basis for behavioral symptoms in children with autism spectrum disorder such as aggression and self-injury. Some of these medications are antiepileptic medications, which are used to treat seizures in children with autism spectrum disorder.
Stimulants. Stimulants can be helpful for short attention span, hyperactivity, and impulsivity in some individuals; however, close follow-up is needed as stimulants may potentially worsen the behavior and stereotypies in some individuals with autism. Stimulants can be useful, but less so than in typically developing children, vulnerability to adverse effects is common, and low doses may be most useful (33).
Atomoxetine. An open-label study of 12 children with autistic disorder was conducted (07). The participants received atomoxetine for 10 weeks. There was no change to the hyperactivity subscale of the Aberrant Behavior Checklist compared to baseline. However, a similar small study found a significant reduction of 21% in the hyperactivity subscale of the Aberrant Behavior Checklist (40).
Alpha adrenergic receptor agonists. The hyperarousal behaviors (eg, stereotyped body movements, self-stimulation, hypervigilance, and hyperactivity) evident with many individuals with autism have been successfully treated with clonidine, an alpha2 adrenergic receptor agonist. Sedation and fatigue are common side effects. Tolerance may develop to the sedative but not the therapeutic effects of clonidine. Guanfacine, another alpha2 agonist, has less sedative side effects, and this medication has been studied in this population, with irritability (30%) and sedation (24%) noted (33). Long-acting forms of guanfacine and clonidine have become available, with an indication for attention deficit hyperactivity disorder.
Beta adrenergic blockers. Propranolol can be useful in the management of aggression in developmental disorders, especially with coexisting agitation and anxiety. The half-life of propranolol is short (about 4 hours) and, therefore, frequent administration is necessary. Some positive effects have also been seen in verbal problem solving, social skills, and conversation reciprocity in single dose studies. Side effects include hypotension and bradycardia. It can also cause increased airway resistance; therefore, propranolol is contraindicated in asthmatic patients and is not frequently used (32).
Cannabinoids. There is growing interest in the use of cannabinoids for children with autism spectrum disorder. More clinical trials are needed in this area. A prospective study of 93 patients with autism treated with cannabinoids for 6 months found that 30% of patients were reported to have significant improvement, and 60% were reported to have moderate improvements, in their symptoms (04). The most common side effect was restlessness (6.6%). The treatment in the majority of patients was based on cannabis oil containing 30% cannabidiol and 1.5% delta9-tetrahydrocannabiol.
Outcomes in children diagnosed with autism spectrum disorder are variable. With treatment there may be improvement in social functioning. Patients may develop improved social relatedness and communication, but it may never be of normal quality or quantity.
Caroline DiBattisto MD MSCR
Dr. DiBattisto of Prisma Health-USC Medical Group has no relevant financial relationships to disclose.See Profile
Bernard L Maria MD
Dr. Maria of Thomas Jefferson University has no relevant financial relationships to disclose.See Profile
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