Neurologic disorders in children are encountered commonly by pediatricians and general physicians. Many neurologic diseases that affect infants and children also affect adults, such as infection, epilepsy, inflammatory and demyelinating diseases, peripheral neuropathies, and myopathies; but some are characteristic of early ages, including develop- mental disorders, malformations, and genetically de- termined conditions. Seizures are among the most common neurologic problems in childhood (see Chapter 15).
The history is the most important component of the evaluation of a child with a neurologic problem. It shares the same principles as described for the adult history but also requires a complete review of the pregnancy, labor, and delivery, especially if a perinatal injury or congenital infection is suspected.
DEVELOPMENT AND MATURATION DEVELOPMENT AND MATURATION
One of the most important elements of the neuro- logic history is a developmental assessment of the child. The Denver Developmental Screening Test is an efficient and reliable method to assess achieve- ment of developmental milestones. It evaluates four components of development: gross motor skills, fine motor adaptive skills, language, and personal-social interaction. Table 25-1 summarizes developmental milestones by age. This is based on averages and therefore can be used only with an understanding of the variability among children. Table 25-2 gives a brief description of primitive reflexes and their significance.
CEREBRAL PALSY CEREBRAL PALSY
Cerebral palsy (CP) is a static disorder due to pre- or perinatal damage to cerebromotor pathways. It can be acquired or genetic. CP occurs in about 2.7 per 1,000 births. Risk factors for CP include hypoxic- ischemic insult to the brain in the perinatal period, prematurity, low birth weight, chorioamnionitis, pre- natal viral infections, and prenatal strokes.
CLASSIFICATION CLASSIFICATION
The most commonly used classification of CP is based on the distribution of the affected limbs: • Hemiparetic: Weakness and spasticity are seen on
one side of the body. Signs include fisting on the affected side, early hand preference, and increased reflexes with upgoing toes on the affected side. • Diparetic:There is spasticity of all four limbs, af-
fecting the legs more than the arms. The children are usually of normal intelligence and are less likely to have seizures than children with other forms of CP.
• Spastic quadriplegic:All four limbs are affected. Seizures usually occur within the first 48 hours of life. The infant may show signs of cerebral hypo- tonia (see later discussion).
CLINICAL
CLINICAL MANIFESTATIONMANIFESTATIONSS
CP may be diagnosed as early as the first week of life: infants may have flaccid weakness, asymmetric limb
Chapter 25 / Pediatric Neurology • 179
Age
Age Adaptive/Fine Motor SkillsAdaptive/Fine Motor Skills Gross Motor SkillsGross Motor Skills LanguageLanguage Personal/SocialPersonal/Social
1 month Grasp reflex; hand fisted Raises head slightly Facial response Stares at face when prone to sounds
2 months Follows objects with eyes Lifts head from prone Coos Smiles in response past midline to 45 degrees to others
4 months Hands open; brings objects Sits, head steady; Laughs and squeals; Smiles to mouth rolls to supine toward voice spontaneously 6 months Palmar grasp of objects; Sits independently; Babbles (consonant Reaches for toys;
starts transfer of objects stands with hands sounds); mimics recognizes strangers held sounds
9 months Pincer grasp; claps hands Pulls to stand Says “mama,” “dada,” Finger-feeds self; nonspecifically; waves bye-bye comprehends “no”;
associates word and action (“bye-bye,” “no,” etc.)
1 year Helps to turn pages of book; Stands independently; 2 to 4 words; Points to indicate tower of two blocks walks with one hand follows command wants
held with gesture
18 months Turns pages of book; imitates Walks up steps 10 to 20 words; Feeds self with vertical lines points to four body spoon; uses cup
parts; obeys simple commands
2 years Solves single-piece puzzles Jumps; kicks ball Combines 2 to 3 Removes coat; words; uses “I” and verbalizes wants “you”; 50 to 300
words
3 years Copies circle; draws person Throws ball overhand; Gives full name, Toilet trained; puts with three body parts; imitates walks up stairs, age, and sex; names on shirt and knows horizontal lines; towers of alternating feet two colors front from back six cubes; draws circles
4 years Counts four objects; identifies Hops on one foot Understands prepo- Dresses with little some numbers and letters; sitions (under, on, assistance; shoes on uses scissors behind, in front of); correct feet
asks “how” and “why”
5 years Prints first name; counts Skips, alternating feet Asks meaning of Ties shoes 10 objects; draws triangle; words; understands
draws person with several parts conjunctions and past tenses; knows colors
TABLE 25-1TABLE 25-1 Developmental Milestones
movements, or seizures. In older children, spasticity, dystonia, developmental delay, and drooling are com- mon presentations.
DIAGNOSTIC EVALUATION DIAGNOSTIC EVALUATION
The diagnosis of CP is based on the clinical symp- toms and signs. The cause may not be determined,
but the presence of a static (not worsening) disorder is suggestive. One must rule out other entities that may present with dystonia, ataxia, or spasticity but which progress with time (e.g., metabolic disorders, metachromatic leukodystrophy, and movement dis- orders such as levodopa-responsive dystonia). MRI is indicated only to exclude other structural causes such as tumor, stroke, or AVMs.
• Severe: 25 to 40 • Profound: less than 25
There are many causes of mental retardation. Among them are prenatal and postnatal trauma (e.g., intracerebral hemorrhage and hypoxic-anoxic en- cephalopathy); congenital and postnatal infection (e.g., congenital rubella, syphilis, cytomegalovirus, toxoplasmosis, and HIV infection); chromosomal abnormalities (e.g., Down syndrome, fragile X syn- drome, Angelman syndrome, Prader-Willi syn- drome); chromosomal translocations (e.g., cri du chat syndrome); inherited metabolic disorders (e.g., hy- pothyroidism, galactosemia, Tay-Sachs disease); and toxic, nutritional, and environmental causes. Table 25-3 summarizes some chromosomal abnormalities associated with mental retardation.
Developmental delayis the failure to acquire age- appropriate cognitive, language, fine or gross motor skills, or social skills. The Denver Developmental Assessment is a standard test that can help establish the diagnosis. Many of the etiologies of developmen- tal delay are similar to those responsible for mental retardation and include intrauterine toxins and infec- tions, genetic abnormalities, migrational disorders, hypoxic-ischemic encephalopathy, and inborn errors of metabolism. Most often, though, no cause for de- velopmental delay is found, in which case it is labeled idiopathic.
TREATMENT TREATMENT
In general, a multidisciplinary approach is necessary, with early infant stimulation, physical and occupa- tional therapy, orthopedic and psychological evalua- tion, and speech therapy.
MENTAL RETARDATION AND MENTAL RETARDATION AND DEVELOPMENTAL DELAY DEVELOPMENTAL DELAY
Mental retardationis the failure to develop normal mental capacities. It can be classified by the results of standard intelligence tests such as the Stanford-Binet IQ and the Wechsler Preschool and Primary Scale of Intelligence–Revised. Normal IQ is 100 with a stan- dard deviation of 15. Mental retardation is classified as follows:
• Mild: IQ between 55 and 70 • Moderate: IQ between 40 and 55
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Reefflleexx SSiiggnniiffiiccaannccee ApApppeeaarrss DDiissaappppeeaarrss
Moro Elicited by head extension. Two phases: extension Term newborns 3 months and abduction of arms and leg extension, followed
by slower abductions of arms.
Asymmetry indicates central nervous system disease such as hemiparesis, spinal cord lesion or brachial plexus injury.
Tonic neck Turning head: arm and leg extended on the side 1 month 5 months of the turn, with flexion on the other side (fencing
posture). If infant is unable to move out of posture, implies possible brain pathology.
Traction response Lift baby by traction in both hands. Head lag after Birth 6 months 6 months is pathologic and indicates hypotonia.
Parachute Elicited by plunging suspended infant downward. 6 months Persists Arms should thrust forward symmetrically as if throughout life breaking the fall. Also elicited with baby in sitting
position and pushed forward. Arms should try to break the fall. Asymmetry suggests hemiparesis, spinal cord lesion, or brachial plexus pathology.
TABLE 25-2TABLE 25-2 Primitive Reflexes
• Cerebral palsy (CP) is a static disease; if the disease is progressing, it is not CP.
• It occurs in almost 3 per 1,000 births. • The most common abnormality is spasticity.
CLINICAL MANIFESTATIONS CLINICAL MANIFESTATIONS
Autism is characterized by a combination of social, behavioral, and language abnormalities with onset be- fore age 3. Marked deficiencies in social and commu- nication skills manifest as a lack of attachment to other members of the family and poor social interactions. A restricted range of behaviors, interests, and activities is demonstrated and may include repetitive and stereo- typed behaviors such as toe walking, rocking, flapping, banging, and licking. Abnormal language features in- clude echolalia and stereotyped speech.
DIAGNOSTIC EVALUATION DIAGNOSTIC EVALUATION
The diagnosis is clinical. Differential diagnosis in- cludes other causes of speech and language prob- lems, such as deafness, mental retardation, and seizures (Landau-Kleffner syndrome). Asperge r syndrome can be considered a variant of autism
AUTISTIC SPECTRUM DISORDERS AUTISTIC SPECTRUM DISORDERS
Autism is a developmental disorder of brain function. Usually, the etiology is unknown. Autism is the most common of the disorders that fall under the banner ofpervasive developmental disorder.
Chapter 25 / Pediatric Neurology • 181
Treatment for both mental retardation and devel- opmental delay includes referral to early intervention programs for special education and training.
C
Coonnddiittiioonn EEppiiddeemmiioollooggyy GeGenneettiic c DDeeffeecctt ClliinC niiccaal l CChhaarraacctteerriissttiiccss
Down’s syndrome Most common inherited Trisomy 21 MR; upslanting palpebral fissures; MR protuding tongue; simian crease;
Brishfield spots
Fragile X syndrome Relatively common Defect in the X 20% males are normal; 30% of males form of MR; chromosome; mutation carrier females are mildly affected; affects males more in the 5end of the gene moderate mental retardation; than females with amplification of a behavioral problems; somatic
CGG repeat (200 or abnormalities: long face, enlarged more copies) ears, and macro-orchidism Prader-Willi Uncommon inherited Absence of segment 11 Mental retardation; decreased syndrome disorder to 13 on the long arm muscle tone; short stature;
of the paternally derived emotional lability and insatiable chromosome 15 appetite (obesity)
Angelman’s Uncommon neurogenetic Deletion of segment 11 Mental retardation; abnormal gait; syndrome disorder to 13 on the maternally speech impairment; seizures;
derived chromosome 15 inappropriate happy behavior that includes laughing, smiling, and excitability (“happy puppet” syndrome)
Rett’s syndrome Progressive neuro- Causal gene is MeCP2, Normal development until 6 to 18 developmental disorder; found on the long arm of months; a first sign is hypotonia; generally affects only chromosome X (X 28). autistic-like behavior; stereotyped females; incidence of hand movements (wringing and 1 in 10,000 births waving); lag in brain and head
growth; gait abnormalities; seizures
MR, mental retardation.
TABLE 25-3 Mental Retardation Syndromes Associated with Chromosomal AbnormalitiesTABLE 25-3
• Mental retardation implies a substantially below- average cognitive ability and adaptive behavior. • Developmental delay implies inability to achieve
developmental milestones at the usual age. It is not synonymous with mental retardation.
characterized by social isolation and eccentric behavior with normal intelligence and language development.
DEVELOPMENTAL DEVELOPMENTAL
REGRESSION AND INHERITED REGRESSION AND INHERITED NEURODEGENERATIVE DISORDERS NEURODEGENERATIVE DISORDERS
Developmental regression is defined as a loss of previ- ously attained developmental milestones. It is often related to an inherited neurodegenerative disorder. It is one of the most distressing complaints confronted by pediatricians and neurologists. An extensive bat- tery of diagnostic tests is the wrong approach. A com- plete history, physical and neurologic examination, and additional tests based on those findings are fun- damental in reaching an accurate diagnosis. Always differentiate regression from developmental delay (see previous). Table 25-4 shows common causes of
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Onnsseet t bbeeffoorre e AAgge e 22 OOnnsseet t aafftteer r AAgge e 22
Mitochondrial disorders AIDS
Hypothyroidism Congenital syphilis
Neurocutaneous syndromes Subacute sclerosing panencephalitis Tuberous sclerosis complex Enzymatic lysosomal disorders Neurofibromatosis Gaucher disease Gray matter disorders Gangliosidosis
Infantile ceroid lipofuscinosis Late-onset Krabbe disease Rett syndrome Metachromatic leukodystrophy White matter disorders Other gray matter disorders
Alexander disease Ceroid lipofuscinosis Canavan disease Huntington disease
Neonatal adrenoleukodystrophy Mitochondrial disorders (MERRF) Pelizaeus-Merzbacher disease (peroxisomal disorders) Other white matter disorders Disorders of amino acid metabolism Adrenoleukodystrophy
Homocystinuria Alexander disease Maple syrup urine disease
Phenylketonuria Enzymatic disorders Gangliosidosis Gaucher disease Krabbe disease Mucopolysaccharidoses Metachromatic leukodystrophy
AIDS, acquired immunodeficiency syndrome; MERRF, myoclonic epilepsy with ragged red fibers.
TABLE 25-4TABLE 25-4 Causes of Progressive Encephalopathy
• Autism is characterized by a combination of social, behavioral, and language abnormalities.
KEY POINTS
TREATMENT TREATMENT
The treatment of autism includes support and behav- ior modification. No cures are available at present.
Chapter 25 / Pediatric Neurology • 183
progressive encephalopathy at different ages that can produce developmental delay or regression.
The inherited neurodegenerative diseases are classified according to the involved cellular ele- ment: the lysosome, peroxisome, mitochondria, Golgi apparatus, and cell membrane. Whatever the cellular and molecular mechanism responsible, it is possible to recognize common patterns of disease expression according to the age of onset, symp- toms, and systems involved. The most common clinical features of neurometabolic diseases pre- senting in infancy and childhood are developmental delay or regression.
Lysosomal disorders are caused by genetic de- fects of lysosomal enzymes and cofactors that result in the accumulation of undegraded substrates in lysosomes. They are classified according to the ac- cumulated material: sphingolipidoses, mucopolysac- charidoses, mucolipidoses, glycogen storage disease type II, sialidoses, and neuronal ceroid lipofusci- nosis. Some of the most important characteristics of these clinical entities are reviewed in Table 25-5.
Peroxisomal disordersare a heterogeneous group of syndromes characterized by abnormalities in lipid metabolism. Multiple enzyme deficiencies have been characterized. They are rare. The most important are X-linked adrenoleukodystrophy and Zellweger syn- drome (see Table 25-5). Most of the degenerative diseases of infancy and childhood are not treatable. However, attempts to reach a final diagnosis are important in order to provide parents with genetic counseling, prognosis, and further management advice.
NEUROCUTANEOUS DISORDERS NEUROCUTANEOUS DISORDERS
Neurocutaneous disorders (phakomatoses) are char- acterized by lesions in the CNS and PNS, skin, eyes, and other organs. A summary of neurocutaneous disorders and their clinical features is given in Table 25-6.
THE HYPOTONIC INFANT THE HYPOTONIC INFANT
Hypotonia is a reduction in postural tone. It may be the manifestation of a CNS or PNS disorder or of both.
The most common cause of hypotonia iscerebral hypotonia, a static encephalopathy from pre- or peri- natal brain injury. The most useful diagnostic finding in this group of disorders is not the hypotonia but the other signs of CNS dysfunction. Seizures, micro- cephaly, dysmorphic facies, and mental retardation point to the brain as the source of hypotonia. Usually, DTRs are increased and plantar reflexes are extensor.
Other causes of hypotonia include spinal cord dis- ease (e.g., transection during breech presentation), anterior horn cell lesions (spinal muscular atrophy), neuromuscular junction abnormalities, and my- opathies (congenital, metabolic, etc.). The physical exam and presence or absence of “central” signs may help to localize the site of disease.
KEY POINTS
• Hypotonia can be central, peripheral, or both. • Cerebral hypotonia is usually associated with other
signs of CNS dysfunction (seizures, developmental delay, etc.).
• Infants with severe hypotonia but only marginal weakness usually do not have a disorder of the lower motor unit.