Attention-deficit/hyperactivity disorder (ADHD) is usually diagnosed in elementary school age children. The incidence is estimated at 10% with boys being affected twice as often as girls. The pathophysiology is thought to be secondary to decreased concentrations of dopamine in the striatum. The presenting complaints are hyperactivity, impulsivity, distractibility, inattentiveness, and poor concentration. Typically, the school will express concerns to the parents and suggest pediatric, psychiatric, or neurologic consultation. The parent may initially be in a state of denial or resistance to the diagnosis. There are three recognized ADHD subtypes:

Although boys usually present with hyperactive-impulsive or combined type ADHD, it is common for girls to present with the inattentive type. Inattentiveness can be manifested by prolonged staring spells because of daydreaming, which may be confused with absence epilepsy by the naïve observer. Hyperactivity and impulsivity are characterized by excessive motoric behavior, fidgeting, and inability to stay seated. The child refuses to take turns, blurts out answers, and interrupts or disrupts the classroom. Organizational skills are particularly lacking and the child often fails to turn in homework assignments. ADHD may also be accompanied by comorbid conditions such as anxiety, depression, oppositional defiant disorder, obsessive compulsive disorder, learning disabilities, tics, and Tourette’s syndrome. Some of these disorders are discussed further in Chapter 28.

The history should focus on the child’s development and behavioral patterns. Family history of ADHD symptoms in a parent or sibling is very common. Developmental delays in speech and language should raise concern about autism pervasive developmental disorder (PDD), or mental retardation. Inquiries should be particularly directed to structural heart problems or arrhythmias, which may be a contraindication to pharmacologic management.

Most children with ADHD have normal neurologic examinations. Some may have neurologic soft signs such as mirror movements. However, the child with ADHD hyperactive-impulsive type is easily diagnosed by direct observation of excessive motoric and impulsive behavior in the office. The parent may be embarrassed or oblivious to the situation and unable to control the child. On the other hand, the child with ADHD inattentive type may be perfectly behaved and asymptomatic in the office setting.

It is imperative to auscultate the heart and check resting pulse and blood pressure. If a heart murmur or arrhythmia is detected, consideration should be given to obtaining an EKG and cardiology consultation prior to initiating medications. A history of tics or observation of tics on examination suggests a transient tic disorder or Tourette’s syndrome. Imaging studies are not routinely indicated despite some reports of abnormalities on positron emission tomography scans. EEG is also not routinely required but may be necessary to differentiate inattentive staring from absence seizures. Children with dysmorphic features may warrant chromosome analysis. Screening for thyroid diseases, anemia, or lead toxicity may be indicated in selected cases. Diagnosis is enhanced by psychological testing including standardized behavioral questionnaires and continuous performance testing by computer.

Although once thought to be exclusive to childhood, ADHD is now recognized as an entity in adolescents and adults. The diagnosis is not “outgrown,” although the more visible features of hyperactivity and impulsivity may be less obvious after puberty. It is not uncommon for parents of children diagnosed with ADHD to recognize similar symptoms in themselves and to seek out medical advice.

Children with ADHD should be managed with the so-called multimodal treatment including an individual education plan or 504 plan provided by the local school district. In addition, parent training in behavioral management and counseling for the child and family may be beneficial. Stimulant medications are also an essential component for successful management of ADHD and have been shown to improve long-term outcomes. These are primarily methylphenidate and amphetamine salt combinations. Both are available in extended release formulations that reduce the need for medication administration in school. Nonstimulant medications including atomoxetine, clonidine, and guanfacine are other options.

Infants and toddlers with static encephalopathy fail to achieve motor and/or speech and language milestones on time. The milestone may subsequently be attained, but at a later than expected time or with abnormalities. Once the milestone is achieved, it is generally not lost.

Static encephalopathies can be caused by numerous conditions. These include chromosomal and genetic disorders, cerebral malformations, intrauterine infections, meningitis, encephalitis, trauma, intraventricular hemorrhage, and hypoxic-ischemic encephalopathy. Nevertheless, a substantial percentage of static encephalopathies are idiopathic with regard to etiology. Although most cases of static encephalopathy will result in GDD, milder or more localized cases may result in distinct neurologic or
developmental disorders. Examples include cerebral palsy (CP) and autistic spectrum disorders (ASDs).

Static encephalopathies that primarily affect motor control areas of the brain are described by the term cp. CP occurs with a prevalence of 2.5 per 1,000 live births. A higher prevalence may be seen in premature and low-birth weight infants. It is further classified based on severity and distribution of spasticity. The most severe variant, spastic quadriplegia, results in spasticity in all four extremities. There is marked delay in motor milestones, accompanied by increased tone, brisk deep tendon reflexes (DTRs), and positive Babinski signs. Seizures, microcephaly, feeding difficulties, and psychomo tor retardation are common features. Milder variants of CP such as spastic diplegia are common in premature infants following intraventricular hemorrhage and periventricular leukomalacia. Infants with spastic diplegia show spasticity and weakness primarily in the lower extremities with relative sparing of the arms. Infants with hemiplegic CP present with unilateral weakness and spasticity. Intrauterine arterial infarctions, periventricular hemorrhages, and cerebral malformations are the most common etiologies.

Autism and developmental language disorders may be considered as static encephalopathies that primarily affect speech and language development. Autism is sometimes grouped under the broader heading of PDD. Asperger’s syndrome is considered to be a form of high functioning autism. Children with autism demonstrate a wide range of deficits in socialization and language. Hence, the term ASD is now used to describe these children.

Symptoms of autism usually begin in the second year of life. Parents often report that early motor milestones developed normally. However, there is marked delay in the acquisition of speech and language. Echolalia is frequently present with the child simply repeating or parroting phrases. It is typical for the child not to respond to his or her name and to appear socially withdrawn or aloof. Stereotypic behaviors, such as spinning, rocking, or hand flapping, are commonly observed. Children and adults with Asperger’s syndrome may have normal speech and cognition but lack age appropriate understanding of language nuances and socialization skills. They tend to be loners with a narrow range of interests, mechanical speech patterns, and stereotypic behaviors. The incidence of ASD appears to be rising and is currently estimated at 1 in 110 live births. However, it is speculated that this increased incidence may in part be because of enhanced public awareness and inclusion of children with Asperger’s syndrome.

The etiology of autism is unknown but appears to be multifactorial. In the past two decades, several alternative hypotheses including measles immunization, thiomersal toxicity, and gluten-casein sensitivity have been promulgated and subsequently refuted. Genetic predisposition clearly plays an important role as indicated by concordance in twins and siblings. Autism has been linked to tuberous sclerosis, fragile X syndrome, Rett’s syndrome, and Angelman’s syndrome. In addition, numerous suspicious genetic duplications and deletions as well as copy-number variations are being identified by chromosome microarray analysis.

In progressive cognitive impairment, acquisition of milestones initially decelerates. Subsequently, there is a loss of previously achieved skills. There may be a combined loss of motor, coordination, and sensory and cognitive functions. Alternatively, loss of skills and functions in one area may precede losses in other areas. The pattern and sequence of regression may yield clues to the diagnosis.

initially present with loss of motor milestones and increasing spasticity. There may also be a loss of vision. MRI scans demonstrate white matter demyelination. Peripheral neuropathy is often a characteristic feature as well. This can be demonstrated by slowing of peripheral nerve conduction velocities. Visual and auditory evoked response studies may also demonstrate slowing. Some examples of leukodystrophies include globoid cell leukodystrophy, metachro matic leukodystrophy, Alexander’s disease, Canavan’s disease, Pelizaeus-Merzbacher’s disease, and adrenoleukodystrophy. Age of onset, patterns of loss of function, genetic testing, and MRI findings can help to distinguish the various leukodystrophies.

often present with seizures and loss of cognitive skills. These include amino and organic acidurias, Tay-Sachs’ disease, ceroid lipofuscinosis, Rett’s syndrome, and AIDS encephalopathy.

include Wilson’s disease (hepatolenticular degeneration), pantothenate kinase associated neurodegeneration, and Niemann-Pick’s disease. These may present with dysarthria, dysphagia, dystonia, chorea, and spasticity. Juvenile Huntington’s disease and Parkinson’s disease may present with chorea, rigidity, and tremor. Ataxia is a prominent feature of ataxia telangiectasia, Refsum’s disease, abetalipoproteinemia, and Friedreich’s ataxia.

These genetic conditions are characterized by skin lesions and CNS findings. Developmental delays are observed as well. Neurofibromatosis type 1 (Von Recklinghausen’s disease) has an autosomal dominant pattern of transmission and has been localized to chromosome 17. Spontaneous mutations are also common. The condition is characterized by multiple café au lait spots, often with axillary freckling and neurofibromas on the skin. Increased head circumference is associated as are Lisch nodules in the iris, scoliosis, pseudoarthosis, and hypertension. There is a higher incidence of optic gliomas and other CNS tumors, so that periodic neuroimaging of the brain and orbits is recommended. Neurofibromatosis type 2 is less common and is characterized by café au lait spots and vestibular schwannomas. Tuberous sclerosis complex has several characteristic skin lesions including scattered hypopigmented macules, shagreen patches, adenoma sebaceum, and subungual fibromas. Subependymal nodules and giant cell astrocytomas are seen in the brain. Cardiac rhabdomyomas and renal angiomyolipomas also occur. Affected children are at risk for infantile spasms, partial seizures, ASDs, and GDDs.

Sturge-Weber syndrome presents with port wine birthmarks in the trigeminal nerve distribution and ipsilateral brain hemangiomas. Affected children also have contralateral focal motor seizures and hemiparesis. Other rare neurocutaneous syndromes associated with developmental delays and epilepsy are incontinentia pigmenti and hypomelanosis of Ito.

Children referred for specialty evaluation of developmental delay should have already been screened by their pediatricians. The American Academy of Pediatrics recommends such screening utilizing a standardized test at the 9 month, 18 month, and 24 or 30 month well-child care visits. In the absence of such screening, the neurologist should consider administering a standardized general developmental screening test as a preliminary assessment. Examples of validated developmental screening tests include the Ages and Stages Questionnaires, Child Development Inventory, and the Bayley Infant Neurodevelopmental Screen. When screening for autism or Asperger’s syndrome, more specific inventories such as the Childhood Autism Rating Scale, Modified Checklist for Autism in Toddlers, and the Asperger Syndrome Diagnostic Scale should be utilized.

A thorough history should be obtained with particular attention to gestational age, pregnancy, labor, and delivery. Hospitalizations in the NICU at birth should be reviewed for high-risk neurologic problems including neonatal seizures, intraventricular hemorrhages, meningitis, and hydrocephalus. Family history should be reviewed for close relatives with similar delays or diagnosed causes of developmental delay. Developmental milestones should be tabulated to assess for patterns of static or progressive encephalopathies.