Restricted interests and activities are demonstrated in people with autism by play that lacks creativity and imagination. Instead of building with blocks, children with autism may compulsively line them up in rows, or they may become persistently occupied by the sensory features of objects such as buttons on an electrical appliance, buttons on clothing or parts of the body. As they get older, there may be an intense and narrowly focused (obsessional) interest in systems that operate according to immutable rules, such as train timetables, numbers and letters, movements of the planets, escalators and elevators. Repetitive behaviors also may be present, including opening and closing doors and flipping light switches. Motor stereotypes often referred to as "self-stimulatory" behaviors include finger flicking, hand flapping, body rocking, self spinning and running in circles. Stress, excitement or certain stimuli (such as noise) may trigger these repetitive actions. Most often, these children also demand rigid routines. Changes in their environment, their daily schedule or other routines often elicit behavioral resistance and tantrums. They also show extreme reactions to invasion of personal space and extreme resistance to being "hurried."

Cognitive impairment is evident in approximately 70 percent of people with autism and is severe in 40 percent.⁷ Tasks requiring reasoning, interpretation, integration or abstraction are difficult for people with autism to complete.⁸

The majority of people with autism function in the "moderate" range of mental retardation (MR). The severity of MR is defined by a combination of the intensity of support needed for the person to cope with common life demands, how well they meet the standards of personal independence expected of them by age (level of adaptive functioning) and the results of intelligence quotient (IQ) tests (Table 1).

Various nonspecific neurological symptoms or signs may be noted (for example, motor incoordination, delayed development of hand dominance). Seizures (often grand mal) also are common, with more than 30 percent of adolescents having had two or more epileptic seizures.

The diagnosis of autism is based on the patient’s developmental and medical history and on the identification of the aforementioned deficits. To assist the clinician, several instruments (for example, the Modified Checklist for Autism in Toddlers and the Pervasive Developmental Disorder Screening Test) have been developed for taking the patient’s medical history and for recording the observations of the child at play.^10,11 There are no specific genetic, medical or laboratory tests available to confirm the diagnosis, nor are there any prenatal screening tests available to assist prospective parents.

In recent years, it has become apparent that variations in behavioral patterns and severity of illness exist among people with autism. This recognition has led to the development of a number of classification systems, some of which have overlapping diagnostic labels. Pervasive developmental disorder (PDD), sometimes referred to as "autistic spectrum disorder," is an umbrella term used to describe this group of illnesses. Classic autism is the most severe of the three most common PDDs. Children with more social activity, higher empathy and greater interaction are given a diagnosis of "pervasive developmental disorder, not otherwise specified." Children who possess relatively normal language skills and intelligence but who display poor social skills and decreased ability to show empathy, and who often have unusual interests that are pursued with great intensity (for example, may try to read everything they can about dinosaurs), are given a diagnosis of Asperger’s syndrome.¹² A deficit noted in many children with Asperger’s syndrome is their difficulty with pragmatic language skills. For example, they may not understand an expression such as, "It is raining cats and dogs." Speech is taken literally, and they often do not understand sarcasm and have problems understanding the body language and facial expressions of others.

Epidemiology. Epidemiologic studies of autism report a prevalence of 10 to 20 cases of classic autism per 10,000 births and 30 to 50 per 10,000 if the entire spectrum of autism is included.¹³ The male:female ratio is 3:1; however, when the disorder appears in a female, it often is associated with a more severe degree of MR.^14–17 The monozygotic (identical) twin of an person with autism who has virtually 100 percent genetic commonality has an approximately 60 percent chance of having autism and a chance in excess of 90 percent if related PDDs are included. Dizygotic (fraternal) twins and siblings share 50 percent of their genes and have a risk of experiencing autism that is between 3 and 5 percent.¹⁸

Prevalence appears to be unrelated to race, socioeconomic status or level of parental education.¹⁹ Prevalence rates are significantly higher today than in the past. The reason for this is controversial. Many feel that the increase likely is due to increased parental concern, modifications in diagnostic criteria, improved recognition of the disorder by health professionals or overdiagnosis. While there has been controversy about the theory that environmental toxins, vaccines or other exogenous factors contribute to autism, recent studies do not confirm this.^20–22

The cause of autism is not known, though evidence from family and twin studies suggests that it is an inherited disorder involving up to 20 interacting genes.

Approximately 15 percent of people with autism can achieve reasonable self-sufficiency (that is, attain a high school education or above, are continually employed, have own apartment) as adults, and another 15 to 20 percent are able to function moderately well with periodic family or governmental support. These two groups consist mainly of people with IQ scores in the below-normal range (70–90). The remaining people almost always are profoundly dependent on others throughout their lives. One follow-up study of autistic children at age 20 found that 30 percent were living with their families and the rest were in group homes or institutions.²³ People with autism can have a normal life span, with the estimated costs to society of approximately $4 million (using 1998 U.S. dollars) per person.^24–26

Etiology. The cause of autism is not known, though evidence from family and twin studies suggests that it is an inherited disorder involving up to 20 interacting genes. Genes located on chromosomes 2, 7, 15, 16 and 19 have been suggested. The preponderance of males with the disorder suggests an X-linked disorder, and recent genome-wide screenings by two separate groups have found evidence of linkage to the female chromosome.^27–29 A recent study, however, has noted that the father’s age at the time of an offspring’s birth influences the child’s risk of developing autism.³⁰ Children whose fathers were 40 years or older at the time of their births are 5.75 times more likely to have autism than are children whose fathers were younger than 30 years at the time of their births. The cause or causes for this finding remain unclear, though it has been suggested that it may arise from age-related alterations in the father’s sperm-producing cells. Research findings also indicate that mild forms of autismlike symptomology may occur in one or both parents and siblings of people with autism.³¹ These family members have an increased rate of communicative, social and behavioral abnormalities (that is, social reticence, impulsiveness, irritability, teenage-onset anorexia nervosa and an increased incidence of mood and anxiety disorders, including obsessive-compulsive disorder), a preference for and difficulty with change in daily routines and language-related cognitive difficulties.^32–42 The clustering of these conditions in families with autistic people suggests the expression of an underlying predisposition to autism.⁴³

Structural neuroimaging studies suggest that during the first two years of life, and even possibly during the prenatal period, there is an abnormal overgrowth of the brain (or possibly a lessening of programmed cell death [apoptosis] and selective elimination [pruning] of synapses and axonal processes) in the neural systems known to be impaired in autism.⁴⁴ Magnetic resonance imaging (MRI) and positron emission tomography have shown that some people with autism have abnormal structure, function or both of the limbic system (that is, the amygdala, cingulate gyrus and hippocampus).⁴⁵ The limbic system is responsible for emotional and social behaviors, including deciphering the facial expressions of other people as to their thoughts, feelings and intentions. For example, when adults who do not have autism are asked to judge the expression of a human face, their amygdalas are activated, whereas people with autism do not exhibit such activation.⁴⁶ These results are consistent with the frequent observation that people with autism have difficulty understanding someone else’s emotions and that they treat other human beings as inanimate objects.⁴⁷ Functional MRIs show that many of people with autism also lack the ability to activate areas in the cerebellum traditionally thought to be associated with motor integration. These deficits may contribute to certain diagnostic features of the disorder, such as the development of stereotyped behaviors and impaired attention, perception, communication, social interactions and novelty exploration.^48,49 These findings are consistent with postmortem studies of people with autism that show increased cell-packing density and smaller neuronal size in areas of the limbic system (including the amygdala and hippocampus) and a deceased number of Purkinje cells in the cerebellum.^50,51

Medical treatment. Comprehensive management of patients with autism includes parental counseling, special education (often with emphasis on behavioral interventions [modification]) in a highly structured environment, speech therapy and social skills training, with the ultimate goal of achieving independence in activities of daily living and self-care. Intensive behavioral intervention before age 2 years initially involves identifying the social and communication skills that the child lacks. These skills then are broken down into simpler actions, taught separately and, once mastered, integrated and sequenced in a process formally known as "applied behavior analysis," initially developed by O. Ivar Lovaas at the University of California in the early 1980s.

Medication often is used to treat specific behaviors that interfere with educational interventions for or that could lead to residential placement of a person with autism.

Early diagnosis followed by aggressive, appropriately targeted intervention before age 2 years significantly improves a child’s long-term outcome, especially in behavior, communication and social skills.⁵² Some children learn to feed and dress themselves and to conduct themselves in a socially acceptable fashion. Preliminary findings from ongoing studies also show positive outcomes in terms of IQ gains and reductions in severity of symptomatic rituals and self-destructive actions.⁵³

Medication often is used to treat specific behaviors that interfere with educational interventions for or that could lead to residential placement of a person with autism. These drugs have no effect on the person’s ability to socialize or communicate but are effective in controlling some of the associated symptoms of the disorder: hyperactivity (for example, methylphenidate), repetitive behaviors (for example, fluoxetine and sertraline) and aggressive behaviors (for example, carbamazepine, valproate, risperidone and olanzapine).^54–59

Desperate parents sometimes turn to untested and often expensive treatments that later prove to be ineffective. In addition to the standard therapies, the patient’s family may choose these therapies. Treatment with vitamins A, C and B₆, as well as magnesium salts, special diets (for example, no gluten or casein), steroids, antibiotics, antifungal agents, intravenous immunoglobulins, electroconvulsive therapy and the pancreatic enzyme secretin have not proved effective in controlled trials.^60–62

Researchers also have shown that the presence of a child with autism in the family produces stresses on parental and family life. Some researchers have found negative outcomes for the siblings of people with autism, including loneliness and embarrassment about their brother’s or sister’s behavior.⁶³ Other familial stressors include loss of employment and income as one or both parents participate in the care of the person with autism, as well as out-of-pocket expenses and lost leisure time. Not surprisingly, these stresses also may affect the marital relationship adversely, causing parental conflict and decreased marital satisfaction.⁶⁴

	ADVERSE EFFECTS OF DRUG THERAPY AND THEIR DENTAL IMPLICATIONS

TOP ABSTRACT AUTISM ADVERSE EFFECTS OF DRUG... DENTAL TREATMENT OF PATIENTS... CONCLUSIONS REFERENCES

 
Many of the drugs used to treat the associated features of autism have systemic side effects (Table 2), orofacial side effects and adverse orofacial interactions with drugs used in dentistry (Table 3, pages 1524 and 1525).^65–71

Fluoxetine and sertraline, which are classified as selective serotonin reuptake inhibitors (SSRIs), are antidepressants that often are prescribed to people with autism to manage their symptoms of fear, anxiety, depression, desire for sameness and repetitive thoughts and behaviors. Side effects include diarrhea, nausea, dizziness, sexual dysfunction and occasionally hepatic injury with alteration in the coagulation profile.^73,74 Fluoxetine and sertraline also have been shown to cause xerostomia in approximately 18 percent of patients, dysgeusia (altered taste sensations), stomatitis and glossitis. The use of fluoxetine also is associated with an increased risk of developing involuntary orofacial movements (dyskinesia). These extrapyramidal side effects may manifest as sucking, smacking and pursing movements with the lips and protrusion of the tongue. The mechanisms through which fluoxetine induces movement disorders is unknown, but they may involve serotonergic influences on striated dopamine or glutamate pathways.^75,76

Patients with autism will exhibit wide variation in their level of understanding and ability to cooperate during dental treatment.

Adverse interactions between SSRIs and some medications used in dentistry may occur because SSRIs inhibit certain metabolic pathways. Specifically, these SSRIs inhibit the cytochrome P450 2D6 isoenzymes needed to metabolize codeine to its active metabolite morphine. The ability of fluoxetine to inhibit cytochrome P450 3A isoenzymes causes it to potentiate the benzodiazepines alprazolam, triazolam and midazolam. Conversely, erythromycin and clarithromycin may inhibit the metabolism of fluoxetine, leading to changes in mood or wakefulness. Therefore, these dental therapeutic agents should be used cautiously and in reduced dosages.⁷⁷

Carbamazepine and valproate—anticonvulsant agents with mood-stabilizing properties—often are prescribed to people with autism to manage aggression, mood fluctuations and seizures. Long-term use of valproate and carbamazepine is associated with approximately 9 percent of patients’ developing leukopenia, 7 percent developing thrombocytopenia and a lesser percentage having a decrease in fibrinogen concentration.^78,79 When either of these medications is combined with aspirin or nonsteroidal anti-inflammatory drugs, excessive bleeding may result if the analgesic agents already have impaired normal hemostatic mechanisms. Erythromycin and clarithromycin may cause carbamazepine toxicity by inhibiting its metabolism in the liver.

Clonidine, a centrally acting antihypertensive agent, is used to control symptoms of inattention, impulsivity, irritability, hyperactivity and oppositional behavior in people with autism. The medication may cause orthostatic hypotension and potentiate the CNS depression of other CNS depressants used in dentistry.

Methylphenidate tends to decrease hyperactivity and impulsivity and improve attention spans in patients with autism. As a CNS stimulant, it may promote anorexia and decreased weight gain in children, as well as insomnia and tachycardia. Long-term use may cause thrombocytopenia, leukopenia and anemia rarely. A hypertensive episode also may occur if local anesthetics with vasoconstrictors are given in excess or by inadvertent intravascular injection.

	DENTAL TREATMENT OF PATIENTS WITH AUTISM

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Patients with autism will exhibit wide variation in their level of understanding and ability to cooperate during dental treatment. A preliminary office visit to assess their capabilities, obtain a medical history and gauge the extent of dental disease should be arranged. It is best to conduct the first two components of this analysis in the dentist’s private office rather than in the operatory, because the dental examination light and the noise of a dental engine (even if in another operatory) may be stressful for people with autism who have visual and auditory hypersensitivity. Children with autism also generally dislike being touched.^80,81

Patients’ medical histories can offer many valuable clues to help successfully manage their dental treatment. People with mild MR and an absence of severe behavioral problems may be able to cooperate during treatment when local anesthesia and, when necessary, nitrous oxide-oxygen sedation are used.⁸² The presence of parents or aides in the operatory is helpful and appears to comfort the patients and augment cooperation. Compliance is further enhanced by use of the tell-show-do technique and by giving short, clear commands and positive and negative verbal reinforcement.^83,84 Use of a dental mouth prop to help patients keep their mouths open is helpful; however, use of "hand over mouth" and restraints such as a "papoose board" is controversial.

During the clinical examination, between 20 and 40 percent of toddlers, some children and possibly some adults may be found to have macrocephaly because the circumference of their heads has enlarged to accommodate the excessive growth of their brains.⁸⁵ The presence of bruises and abrasions about the head and face and traumatic ulcerations of the oral cavity also are likely to be noted and should be recorded in the patient’s chart, even though they are most often the result of self-injurious behaviors (face tapping, head banging, picking or poking the mucosa with fingernails) rather than abuse by parents or care-givers.^86,87 The dentition should be evaluated carefully for signs of erosion because some pediatric gastroenterologists have noted that children with autism regurgitate their food and acidic stomach contents (gastroesophageal reflux disease) more than once a week.^88–91 If evidence of dental erosion is present, it should be brought to the attention of the parents and an appropriate medical consultation should be obtained. The dentition also should be evaluated for evidence of bruxism. Parental reports indicate that between 20 and 25 percent of children with autism brux during sleep.^92,93

Determining the presence of dental disease by means other than inspection often is difficult in patients with autism. The patients’ inability to communicate effectively often precludes obtaining an accurate dental history. Complicating the matter are parental reports and medical literature indicating that people with autism have an "increased pain threshold" and that they may endure major pain without complaint.⁹⁴ It is hypothesized that this insensitivity to pain arises from their repetitive stereotypic motor behaviors that cause self-injury, thereby increasing brain opioid activity. However, recent research using sophisticated recordings of the patient’s facial expressions while undergoing a painful venipuncture procedures belies this theory, and most people viewing videotapes of these studies interpret them as indicating acute distress.⁹⁵

Sometimes parents or guardians request treatment for dental disease in a person with autism because the person refuses to eat any foods that are not pureed. Demands for low-textured foods from patients with autism are relatively common and do not necessarily imply dental pathology.⁹⁶ Confirmation of clinical findings by use of dental radiographs often is frustrated by the patient’s inability to cooperate with the radiographic examination.

If surgical procedures are planned, patients taking medications that adversely influence the hematopoietic system (such as carbamazepine, methylphenidate, risperidone, valproate) may need a complete blood count, including platelets. These data often are available from treating psychiatrists because they usually monitor hematopoietic status twice yearly.

Patients with a history of moderate-to-profound MR and behavioral problems severe enough to warrant psychiatric medication usually are unable to cooperate fully with care. The degree of sedation and respiratory depression provided by oral sedative medications is difficult to gauge and control even in patients without autism, and, thus, oral sedative medications are best avoided in this vulnerable population. Administration of intravenous sedative agents in an office setting may be appropriate by an experienced clinician; however, dentists have reported atypical responses and a need to abort some cases.⁹⁷ Long and involved treatment procedures are best performed in a surgical center or hospital setting under general anesthesia.⁹⁸ General anesthesia permits the dentist to perform a comprehensive, unhurried radiographic examination, as well as necessary preventive, restorative and surgical treatments at one appointment.

Long-term care consists of increasing oral hygiene frequency and efficiency with the help of the parents and caregivers, using a topical fluoride gel or rinse daily, limiting cariogenic food and having frequent preventive recall appointments. A key component in this process is the assessment of the patient’s ability to use a toothbrush, because some people with autism have deficits in motor skills.^99–102 Parents or aides able to help those having difficulty brushing provide a meaningful service. Placing pictures in the bathroom that depict an appropriate brushing technique appears to reinforce the learning process and help children with autism who have intact motor skills improve their oral hygiene.¹⁰³

	CONCLUSIONS

TOP ABSTRACT AUTISM ADVERSE EFFECTS OF DRUG... DENTAL TREATMENT OF PATIENTS... CONCLUSIONS REFERENCES

 
With the high prevalence of children with autism, dentists are likely to have one or more children with this disorder in their practice. As dentists, we must exhibit compassion as we provide care to patients with autism, as well as to their family members and caregivers when they request assistance in the preventive aspects of care. Our expectations as dentists, however, must be tempered by the realization that the patient’s preventive dental needs constitute only a small component of their total need. Families of people with autism often are exhausted by the need for constant supervision, feeding, toileting, diapering, bathing and dressing of people with autism and often are unable to comply fully with dental hygiene requests. Lastly, dentists and staff members also must be aware that parents of patients with autism also may have social or behavioral abnormalities or deficits in problem-solving skills that impede the collaborative treatment process.