Nelson is the reference of choice for all those who decide to specialize or sub-specialize in pediatrics. While the field of general pediatrics moves relatively slowly, the sub-specialty areas – most of which have a great impact on the practice of general pediatrics – tend to move more quickly. Nelson offers thorough coverage of the entire specialty Check out a sample of Chapter 30 in the latest 19th edition. For purchase, please visit www.asia.elsevierhealth.com

1. 108 ■ Part IV Learning Disorders
PART IV Learning Disorders
in cytokine regulation, a sodium-hydrogen exchange gene, and
Chapter 29 DRD5, SLC6A3, DBH, SNAP25, SLC6A4, and HTR1B.
Neurodevelopmental Function and Abnormal brain structures are linked to an increased risk of
ADHD; 20% of children with severe traumatic brain injury are
Dysfunction in the School-Aged Child reported to have subsequent onset of substantial symptoms of
Desmond P. Kelly and Mindo J. Natale impulsivity and inattention. Children with head or other injury
and in whom ADHD is later diagnosed might have impaired
balance or impulsive behavior as part of the ADHD, thus predis-
A neurodevelopmental function is a basic brain process needed posing them to injury. Structural (functional) abnormalities have
for learning and productivity. Neurodevelopmental variation been identified in children with ADHD without pre-existing iden-
refers to differences in neurodevelopmental functioning. Wide tifiable brain injury. These include dysregulation of the frontal
variations in these functions exist within and between individu- subcortical circuits, small cortical volumes in this region, wide-
als. These differences can change over time and need not repre- spread small-volume reduction throughout the brain, and abnor-
sent pathology or abnormality. Neurodevelopmental dysfunctions malities of the cerebellum.
reflect disruptions of neuroanatomic structure or psychophysio- Psychosocial family stressors can also contribute to or exac-
logic function that may be associated with problems related to erbate the symptoms of ADHD.
cognition, academics, and/or behavioral, emotional, social, and
adaptive functioning.
For the full continuation of this chapter, please visit the Nelson
EPIDEMIOLOGY
Textbook of Pediatrics website at www.expertconsult.com. Studies of the prevalence of ADHD across the globe have gener-
ally reported that 5-10% of school-aged children are affected,
although rates vary considerably by country, perhaps in part due
to differing sampling and testing techniques. Rates may be higher
Chapter 30 if symptoms (inattention, impulsivity, hyperactivity) are consid-
ered in the absence of functional impairment. The prevalence rate
Attention-Deficit/Hyperactivity Disorder in adolescent samples is 2-6%. Approximately 2% of adults have
Natoshia Raishevich Cunningham and Peter Jensen ADHD. ADHD is often underdiagnosed in children and adoles-
cents. Youth with ADHD are often undertreated with respect to
what is known about the needed and appropriate doses of medi-
Attention-deficit/hyperactivity disorder (ADHD) is the most cations. Many children with ADHD also present with comorbid
common neurobehavioral disorder of childhood, among the most psychiatric diagnoses, including opposition defiant disorder,
prevalent chronic health conditions affecting school-aged chil- conduct disorder, learning disabilities, and anxiety disorders (see
dren, and the most extensively studied mental disorder of child- Table 30-3).
hood. ADHD is characterized by inattention, including increased
distractibility and difficulty sustaining attention; poor impulse
control and decreased self-inhibitory capacity; and motor over-
PATHOGENESIS
activity and motor restlessness (Table 30-1). Definitions vary in For the full continuation of this topic, please visit the Nelson
different countries (Table 30-2). Affected children commonly Textbook of Pediatrics website at www.expertconsult.com.
experience academic underachievement, problems with interper-
sonal relationships with family members and peers, and low
self-esteem. ADHD often co-occurs with other emotional, behav-
CLINICAL MANIFESTATIONS
ioral, language, and learning disorders (Table 30-3). Development of the Diagnostic and Statistical Manual of Mental
Disorders, 4th edition (DSM-IV) criteria leading to the diagnosis
of ADHD has occurred mainly in field trials with children 5-12 yr
ETIOLOGY of age (see Table 30-1). The current DSM-IV criteria state that
No single factor determines the expression of ADHD; ADHD the behavior must be developmentally inappropriate (substan-
may be a final common pathway for a variety of complex brain tially different from that of other children of the same age and
developmental processes. Mothers of children with ADHD are developmental level), must begin before age 7 yr, must be present
more likely to experience birth complications, such as toxemia, for at least 6 mo, must be present in 2 or more settings, and must
lengthy labor, and complicated delivery. Maternal drug use has not be secondary to another disorder. DSM-IV identifies 3 sub-
also been identified as a risk factor in the development of ADHD. types of ADHD. The 1st subtype, attention-deficit/hyperactivity
Maternal smoking and alcohol use during pregnancy and prena- disorder, predominantly inattentive type, often includes cogni-
tal or postnatal exposure to lead are commonly linked to atten- tive impairment and is more common in females. The other 2
tional difficulties associated with the development of ADHD. subtypes, attention-deficit/hyperactivity disorder, predominantly
Food colorings and preservatives have inconsistently been associ- hyperactive-impulsive type, and attention deficit/hyperactivity
ated with hyperactivity in previously hyperactive children. disorder, combined type, are more commonly diagnosed in males.
There is a strong genetic component to ADHD. Genetic studies Clinical manifestations of ADHD may change with age. The
have primarily implicated 2 candidate genes, the dopamine trans- symptoms may vary from motor restlessness and aggressive and
porter gene (DAT1) and a particular form of the dopamine 4 disruptive behavior, which are common in preschool children, to
receptor gene (DRD4), in the development of ADHD. Additional disorganized, distractible, and inattentive symptoms, which are
genes that might contribute to ADHD include DOCK2 associ- more typical in older adolescents and adults. ADHD is often
ated with a pericentric inversion 46N inv(3)(p14:q21) involved difficult to diagnose in preschoolers because distractibility and
108

2. Chapter 30 Attention-Deficit/Hyperactivity Disorder ■ 109
Table 30-1 DSM-IV DIAGNOSTIC CRITERIA FOR ATTENTION-DEFICIT/ Table 30-2 DIFFERENCES BETWEEN U.S. AND EUROPEAN CRITERIA
HYPERACTIVITY DISORDER FOR ADHD OR HKD
A. Either 1 or 2 DSM-IV ADHD ICD-10 HKD
1. Six (or more) of the following symptoms of inattention have persisted for
SYMPTOMS
≥6 mo to a degree that is maladaptive and inconsistent with development
level: Either or both of following: All of following:
Inattention At least 6 of 9 inattentive symptoms At least 6 of 8 inattentive symptoms
a. Often fails to give close attention to details or makes careless At least 6 of 9 hyperactive or At least 3 of 5 hyperactive symptoms
mistakes in schoolwork, work, or other activities impulsive symptoms At least 1 of 4 impulsive symptoms
b. Often has difficulty sustaining attention in tasks or play activities PERVASIVENESS
c. Often does not seem to listen when spoken to directly Some impairment from symptoms is Criteria are met for >1 setting
d. Often does not follow through on instructions and fails to finish present in >1 setting
schoolwork, chores, or duties in the workplace (not due to oppositional
behavior or failure to understand instructions) ADHD, attention-deficit/hyperactivity disorder; DSM-IV, Diagnostic and Statistical Manual of
e. Often has difficulty organizing tasks and activities Mental Disorders, 4th edition; HKD, hyperkinetic disorder; ICD-10, International Classification of
Diseases, 10th edition.
f. Often avoids, dislikes, or is reluctant to engage in tasks that require From Biederman J, Faraone S: Attention-deficit hyperactivity disorder, Lancet 366:237–248,
sustained mental effort (such as schoolwork or homework) 2005.
g. Often loses things necessary for tasks or activities (e.g., toys, school
assignments, pencils, books, tools)
h. Is often easily distracted by extraneous stimuli
Table 30-3 DIFFERENTIAL DIAGNOSIS OF ATTENTION-DEFICIT/
i. Is often forgetful in daily activities
2. Six (or more) of the following symptoms of hyperactivity-impulsivity have HYPERACTIVITY DISORDER
persisted for ≥6 mo to a degree that is maladaptive and inconsistent with PSYCHOSOCIAL FACTORS
developmental level: Response to physical or sexual abuse
Hyperactivity Response to inappropriate parenting practices
a. Often fidgets with hands or feet or squirms in seat Response to parental psychopathology
b. Often leaves seat in classroom or in other situations in which Response to acculturation
remaining seated is expected Response to inappropriate classroom setting
c. Often runs about or climbs excessively in situations in which it is
inappropriate (in adolescents or adults, may be limited to subjective DIAGNOSES ASSOCIATED WITH ADHD BEHAVIORS
feelings of restlessness) Fragile X syndrome
d. Often has difficulty playing or engaging in leisure activities quietly Fetal alcohol syndrome
e. Is often “on the go” or often acts as if “driven by a motor” Pervasive developmental disorders
f. Often talks excessively Obsessive-compulsive disorder
Impulsivity Tourette’s syndrome
g. Often blurts out answers before questions have been completed Attachment disorder with mixed emotions and conduct
h. Often has difficulty awaiting turn MEDICAL AND NEUROLOGIC CONDITIONS
i. Often interrupts or intrudes on others (e.g., butts into conversations or Thyroid disorders (including general resistance to thyroid hormone)
games) Heavy metal poisoning (including lead)
B. Some hyperactive-impulsive or inattentive symptoms that caused impairment Adverse effects of medications
were present before 7 yr of age Effects of abused substances
C. Some impairment from the symptoms is present in 2 or more settings Sensory deficits (hearing and vision)
(e.g., at school [or work] or at home) Auditory and visual processing disorders
D. There must be clear evidence of clinically significant impairment in social, Neurodegenerative disorder
academic, or occupational functioning Post-traumatic head injury
E. Symptoms do not occur exclusively during the course of a pervasive Post-encephalitic disorder
developmental disorder, schizophrenia, or other psychotic disorder, and are
not better accounted for by another mental disorder (e.g., mood disorder, Note: Coexisting conditions with possible ADHD presentation include oppositional defiant
anxiety disorder, dissociative disorder, personality disorder) disorder, anxiety disorders, conduct disorder, depressive disorders, learning disorders, and
language disorders. Presence of one or more of the symptoms of these disorders can fall within
CODE BASED ON TYPE the spectrum of normal behavior, whereas a range of these symptoms may be problematic but
314.01 Attention-deficit/hyperactivity disorder, combined type: if both criteria A1 fall short of meeting the full criteria for the disorder.
and A2 are met for the past 6 mo From Reiff MI, Stein MT: Attention-deficit/hyperactivity disorder evaluation and diagnosis: a
314.00 Attention-deficit/hyperactivity disorder, predominantly inattentive type: if practical approach in office practice, Pediatr Clin North Am 50:1019–1048, 2003. Adapted from
criterion A1 is met but criterion A2 is not met for the past 6 mo Reiff MI: Attention-deficit/hyperactivity disorders. In Bergman AB, editor: 20 Common problems
in pediatrics, New York, 2001, McGraw-Hill, p 273.
314.01 Attention-deficit/hyperactivity disorder, predominantly hyperactive-
impulsive type: if criterion A2 is met but criterion A1 is not met for the past
6 mo
Reprinted with permission from American Psychiatric Association: Diagnostic and statistical variety of sources, including the child, parents, teachers, physi-
manual of mental disorders, fourth edition, text revision, Washington, DC, 2000, American cians, and, when appropriate, other caretakers.
Psychiatric Association. Copyright 2000 American Psychiatric Association.
Clinical Interview and History
The clinical interview allows a comprehensive understanding of
inattention are often considered developmental norms during this whether the symptoms meet the diagnostic criteria for ADHD.
period. During the interview, the clinician should gather information
pertaining to the history of the presenting problems, the child’s
overall health and development, and the social and family history.
DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS The interview should emphasize factors that might affect the
A diagnosis of ADHD is made primarily in clinical settings after development or integrity of the central nervous system or reveal
a thorough evaluation, including a careful history and clinical chronic illness, sensory impairments, or medication use that
interview to rule in or to identify other causes or contributing might affect the child’s functioning. Disruptive social factors,
factors; completion of behavior rating scales; a physical examina- such as family discord, situational stress, and abuse or neglect,
tion; and any necessary or indicated laboratory tests. It is impor- can result in hyperactive or anxious behaviors. A family history
tant to systematically gather and evaluate information from a of 1st-degree relatives with ADHD, mood or anxiety disorders,

3. 110 ■ Part IV Learning Disorders
learning disability, antisocial disorder, or alcohol or substance Although ADHD is believed to result from primary impair-
abuse might indicate an increased risk of ADHD and/or comor- ment of attention, impulse control, and motor activity, there is a
bid conditions. high prevalence of comorbidity with other psychiatric disorders
(see Table 30-3). Of children with ADHD, 15-25% have learning
Behavior Rating Scales disabilities, 30-35% have language disorders, 15-20% have diag-
Behavior rating scales are useful in establishing the magnitude nosed mood disorders, and 20-25% have coexisting anxiety
and pervasiveness of the symptoms, but are not sufficient alone disorders. Children with ADHD can also have co-occurring diag-
to make a diagnosis of ADHD. There are a variety of well- noses of sleep disorders, memory impairment, and decreased
established behavior rating scales that have obtained good results motor skills.
in discriminating between children with ADHD and control sub-
jects. These measures include, but are not limited to, the Vander-
bilt ADHD Diagnostic Rating Scale, the Conner Rating Scales
TREATMENT
(parent and teacher); the ADHD Index; the Swanson, Nolan, and Psychosocial Treatments
Pelham Checklist (SNAP); and the ADD-H: Comprehensive Once the diagnosis of ADHD has been established, the parents
Teacher Rating Scale (ACTeRS). Other broadband checklists, and child should be educated with regard to the ways ADHD can
such as the Achenbach Child Behavior Checklist (CBCL), are affect learning, behavior, self-esteem, social skills, and family
useful, particularly in instances where the child may be experienc- function. The clinician should set goals for the family to improve
ing co-occurring problems in other areas (anxiety, depression, the child’s interpersonal relationships, develop study skills, and
conduct problems). decrease disruptive behaviors.
Physical Examination and Laboratory Findings Behaviorally Oriented Treatments
There are no laboratory tests available to identify ADHD in Treatments geared toward behavioral management often occur
children. The presence of hypertension, ataxia, or a thyroid dis- in the time frame of 8-12 sessions. The goal of such treatment is
order should prompt further diagnostic evaluation. Impaired fine for the clinician to identify targeted behaviors that cause impair-
motor movement and poor coordination and other soft signs ment in the child’s life (disruptive behavior, difficulty in complet-
(finger tapping, alternating movements, finger-to-nose, skipping, ing homework, failure to obey home or school rules) and for the
tracing a maze, cutting paper) are common, but they are not suf- child to work on progressively improving his or her skill in these
ficiently specific to contribute to a diagnosis of ADHD. The clini- areas. The clinician should guide the parents and teachers in
cian should also identify any possible vision or hearing problems. implementing rules, consequences, and rewards to encourage
The clinician should consider testing for elevated lead levels in desired behaviors. In short-term comparison trials, stimulants
children who present with some or all of the diagnostic criteria, have been more effective than behavioral treatments used alone;
if these children are exposed to environmental factors that might behavioral interventions are only modestly successful at improv-
put them at risk (substandard housing, old paint). Behavior in ing behavior, but they may be particularly useful for children with
the structured laboratory setting might not reflect the child’s complex comorbidities and family stressors, when combined with
typical behavior in the home or school environment. Therefore, medication.
reliance on observed behavior in a physician’s office can result in
an incorrect diagnosis. Computerized attentional tasks and elec- Medications
troencephalographic assessments are not needed to make the The most widely used medications for the treatment of ADHD
diagnosis, and compared to the clinical gold standard they are are the psychostimulant medications, including methylphenidate
subject to false-positive and false-negative errors. (Ritalin, Concerta, Metadate, Focalin, Daytrana), amphetamine,
and/or various amphetamine and dextroamphetamine prepara-
Differential Diagnosis tions (Dexedrine, Adderall, Vyvanse) (Table 30-4). Longer-
Chronic illnesses, such as migraine headaches, absence seizures, acting, once-daily forms of each of the major types of stimulant
asthma and allergies, hematologic disorders, diabetes, childhood medications are available and facilitate compliance with treat-
cancer, affect up to 20% of children in the U.S. and can impair ment. The clinician should prescribe a stimulant treatment, either
children’s attention and school performance, either because of the methylphenidate or an amphetamine compound. If a full range
disease itself or because of the medications used to treat or of methylphenidate dosages is used, approximately 25% of
control the underlying illness (medications for asthma, steroids, patients have an optimal response on a low (<20 mg/day),
anticonvulsants, antihistamines) (see Table 30-3). In older chil- medium (20-50 mg/day), or high (>50 mg/day) daily dosage;
dren and adolescents, substance abuse (Chapter 108) can result another 25% will be unresponsive or will have side effects,
in declining school performance and inattentive behavior. making that drug particularly unpalatable for the family.
Sleep disorders, including those secondary to chronic upper Over the first 4 wk, the physician should increase the
airway obstruction from enlarged tonsils and adenoids, often medication dose as tolerated (keeping side effects minimal to
result in behavioral and emotional symptoms, although such absent) to achieve maximum benefit. If this strategy does not
problems are not likely to be principal contributing causes of yield satisfactory results, or if side effects prevent further dose
ADHD (Chapter 17). Behavioral and emotional disorders can adjustment in the presence of persisting symptoms, the clini-
cause disrupted sleep patterns. cian should use an alternative class of stimulants that was
Depression and anxiety disorders (Chapters 23 and 24) can not used previously. If a methylphenidate compound is unsuc-
cause many of the same symptoms as ADHD (inattention, rest- cessful, the clinician should switch to an amphetamine product.
lessness, inability to focus and concentrate on work, poor orga- If satisfactory treatment results are not obtained with the 2nd
nization, forgetfulness), but can also be comorbid conditions. stimulant, clinicians may choose to prescribe atomoxetine, a
Obsessive-compulsive disorder can mimic ADHD, particularly noradrenergic reuptake inhibitor that is superior to placebo
when recurrent and persistent thoughts, impulses, or images are in the treatment of ADHD in children, adolescents, and adults
intrusive and interfere with normal daily activities. Adjustment and that has been approved by the U.S Food and Drug Admin-
disorders secondary to major life stresses (death of a close family istration (FDA) for this indication. Atomoxetine should be
member, parents’ divorce, family violence, parents’ substance initiated at a dose of 0.3 mg/kg/day and titrated over 1-3 wk
abuse, a move) or parent-child relationship disorders involving to a maximum dosage of 1.2-1.8 mg/kg/day. Guanfacine, an
conflicts over discipline, overt child abuse and/or neglect, or antihypertension agent, is also FDA approved for the treatment
overprotection can result in symptoms similar to those of ADHD. of ADHD.

4. Chapter 30 Attention-Deficit/Hyperactivity Disorder ■ 111
Table 30-4 MEDICATIONS USED IN THE TREATMENT OF ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
GENERIC NAME BRAND NAME DURATION DOSAGE RANGE SIDE EFFECTS
METHYLPHENIDATE
Immediate-release Ritalin, Methylin 3-4 hr 5, 10, 20 mg tabs Moderate appetite suppression, mild sleep disturbances, transient
weight loss, irritability, emergence of tics
Extended-release Metadate ER, Methylin ER, 4-6 hr 10, 20 mg extended-release Moderate appetite suppression, mild sleep disturbances, transient
tabs weight loss, irritability, emergence of tics
Metadate-CD 8-10 hr 10, 20, 30 mg extended-
release caps
Ritalin LA 8-10 hr 20, 30, 40 mg caps
Concerta 10-12 hr 18, 27, 36, 54 mg caps Moderate appetite suppression, mild sleep disturbances, transient
weight loss, irritability, emergence of tics
Sustained-release Ritalin SR, Methylphenidate SR 4-6 hr 20 mg sustained release Moderate appetite suppression, mild sleep disturbances, transient
tabs weight loss, irritability, emergence of tics
Transdermal system Daytrana ≥12 hr patch Moderate appetite suppression, mild sleep disturbances, transient
weight loss, irritability, emergence of tics
DEXMETHYLPHENIDATE
Focalin 4-6 hr 2.5, 5, and 10 mg tabs Moderate appetite suppression, mild sleep disturbances, transient
weight loss, irritability, emergence of tics
Extended-release Focalin XR 6-8 hr Moderate appetite suppression, mild sleep disturbances, transient
weight loss, irritability, emergence of tics
DEXTROAMPHETAMINE
Short-acting Dexedrine, DextroStat 4-6 hr 5, 10, and 15 mg tabs Moderate appetite suppression, mild sleep disturbances, transient
weight loss, irritability, emergence of tics
Intermediate-acting Dexedrine Spansule 6-8 hr 5, 10, and 20 mg tabs Moderate appetite suppression, mild sleep disturbances, transient
weight loss, irritability, emergence of tics
Lisdexamfetamine Vyvanse ≤12 hr 30 mg, 50 mg and 70 mg Moderate appetite suppression, mild sleep disturbances, transient
tablets weight loss, irritability, emergence of tics
MIXED AMPHETAMINE SALTS
Intermediate-acting Adderall 4-6 hr 5, 10, 20 mg tabs Moderate appetite suppression, mild sleep disturbances, transient
weight loss, irritability, emergence of tics
Extended-release Adderall XR 8-12 hr 5, 10, 15, 20, 25, 30 mg Moderate appetite suppression, mild sleep disturbances, transient
caps weight loss, irritability, emergence of tics
ATOMOXETINE
Extended-release Strattera 12 hr 10, 18, 25, 40, 60 mg caps Nervousness, sleep problems, fatigue, stomach upset, dizziness,
dry mouth
Can lead in rare cases to severe liver injury or to suicidal ideation
Bupropion Wellbutri 4-5 hr 100 150 mg tabs Difficulty sleeping, headache, seizures
Bupropion Wellbutrin SR, Wellbutrin XL 100, 150, 200 mg tabs
TRICYCLIC ANTIDEPRESSANTS
Imipramine Tofranil Variable See Table 19-4 Nervousness, sleep problems, fatigue, stomach upset, dizziness,
dry mouth, accelerated heart rate
Desipramine* Norpramin
Nortriptyline Aventyl, Pamelor
α-AGONISTS
Clonidine 6-12 hr 3-10 μg/kg/day bid-qid Sedation, depression, dry mouth, rebound hypertension on
discontinuing, confusion
Guanfacine Tenex, Intuniv 6-12 hr 1, 2, 3 mg tabs Hypotension, lightheadedness
*Has been associated with deaths due to cardiac problems. Not recommended for children.
cap, capsule; tab, tablet.
The clinician should consider careful monitoring of medica- psychiatrist or psychologist can also be beneficial to determine
tion a necessary component of treatment in children with ADHD. the next steps for treatment, including adding other components
When physicians prescribe medications for the treatment of and supports to the overall treatment program. Evidence suggests
ADHD, they tend to use lower than optimal doses. Optimal treat- that children who receive careful medication management,
ment usually requires somewhat higher doses than tend to be accompanied by frequent treatment follow-up, all within the
found in routine practice settings. All-day preparations are also context of an educative, supportive relationship with the primary
useful to maximize positive effects and minimize side effects, and care provider, are likely to experience behavioral gains for up to
regular medication follow-up visits should be offered (4 or more 24 mo.
times/yr) vs the twice-yearly medication visits often used in stan- Stimulant drugs used to treat ADHD may be associated with
dard community-care settings. an increased risk of adverse cardiovascular events, including
Medication alone is not always sufficient to treat ADHD in sudden cardiac death, myocardial infarction, and stroke in young
children, particularly in instances where children have multiple adults and rarely in children. In some of the reported cases, the
psychiatric disorders or stressed home environments. When chil- patient had an underlying disorder, such as hypertrophic obstruc-
dren do not respond to medication, it may be appropriate to tive cardiomyopathy, which is made worse by sympathomimetic
refer them to a mental health specialist. Consultation with a child agents. These events are rare, but they nonetheless warrant