Trisomy 21 (Down syndrome) – Rudolph 21Down syndrome is caused by trisomy 21 and is the most common autosomal chromosome abnormality in humans. The condition occurs in about 1 in 800 infants and is the most common multiple congenital anomaly/mental retardation syndrome. The use of the term mongolism is no longer appropriate, because this designation is considered pejorative and stigmatizing. The etiology of Down syndrome is related to trisomy of the distal part of the long arm of chromosome 21. Over 90% of individuals with Down syndrome will have three copies of the entire chromosome 21, while less than 10% will have trisomy of only part of the long arm of chromosome 21. The latter is usually caused by unbalanced robertsonian translocation (see Sec. 10.1.3).The phenotypic pattern of Down syndrome is characteristic and consistent enough to permit recognition of an affected neonate. Most of the facial and limb features of individuals with Down syndrome are not morphologically abnormal, but the specific constellation of manifestations is distinctive. The well-known list of phenotypic variations and minor anomalies is described in many sources and will not be summarized here. The brachycephaly, small ears (less than 3.2 cm in longest length in the newborn), upslanted palpebral fissures, flat midface, full cheeks, and distinctive shape of the mouth when crying are very consistent and together evoke a distinctive gestalt in a child of virtually any age. Small ears and hypotonia are observed in over 90% of newborns with Down syndrome. Although epicanthal folds and a single transverse crease (the so-called simian line) are commonly sought when considering the syndrome, these features are not only nonspecific but also occur in only about 50% of persons with Down syndrome. Short, broad fingers (brachydactyly), absent to very small nipple buds, and a central placement of the posterior hair whorl are more specific to Down syndrome than many other well-known findings. Systems for scoring the clinical findings of children in whom the diagnosis of Down syndrome is being entertained have been developed but are rarely needed because of the ease of recognizing most infants with the syndrome.Congenital heart malformations occur in about 40% of children with Down syndrome. About one-third of these malformations fall within the spectrum of an atrioventricular (AV) canal defect and about one-third are ventricular septal defects. Atrial septal defects of the secundum type and tetralogy of Fallot also occur, although they are less frequent. Since a heart murmur is frequently not present in a child with an AV canal defect, clinical examination alone is not enough to exclude the presence of a heart malformation in children with Down syndrome. Referral for an echocardiogram is now considered part of routine health supervision of infants with Down syndrome. If the diagnosis of a shunt lesion is missed in infancy, the early development of pulmonary hypertension characteristically seen in infants with Down syndrome could preclude some surgical options.Obstructive gastrointestinal lesions including duodenal atresia and Hirschsprung disease occur in about 5% of infants with Down syndrome. However, no investigative studies are recommended unless an infant is symptomatic. Congenital cataracts occur in only about 5% of newborns as well, but other ocular problems (eg, strabismus, refractive errors) are common, warranting careful eye examinations in infancy. Other congenital malformations are uncommon in Down syndrome.Individuals with Down syndrome, whether or not a heart defect is present, have an increased mortality rate compared to other children. The higher childhood mortality may, in part, be caused by an increased occurrence of infections, especially pneumonia. Abnormalities that affect the respiratory system, including gastroesophageal reflux, primary pulmonary hypertension, and obstructive sleep apnea, are often the basis for symptoms that occur in infancy including cyanosis, respiratory distress, apnea, and growth deficiency. Although a detailed evaluation of an infant with Down syndrome who has these symptoms is appropriate,

a perspective on increased mortality needs to be communicated to families during the newborn period. For example, about 90% of children without heart defects will live into adolescence and early adulthood.The degree of developmental disability in children with Down syndrome is quite variable, but children learn to walk and develop communication skills. The development of most children progresses steadily, albeit at a slower pace than usual. There is no evidence that function regresses during childhood or adolescence. Early intervention accelerates attainment of development skills in the preschool years, but the long-term effect of these programs on ultimate intellectual functioning is unknown. Nevertheless, referral to early intervention programs is recommended, because these programs help the family in areas other than acquisition of developmental skills by providing emotional support, information regarding the educational system, and feedback regarding a child's individual developmental strengths and weaknesses.Older persons with Down syndrome have an increased risk for a variety of medical problems including atlantoaxial subluxation, cataracts, diabetes mellitus, hypo- and hyperthyroidism, leukemia, and seizures. Most of these problems occur infrequently, but the pediatrician should maintain a high level of suspicion. In the fourth decade of life, some adults with Down syndrome develop increasing cognitive dysfunction including a memory disorder. For this reason, baseline psychometric testing in the twenties is indicated in all young adults with Down syndrome.Guidelines for health supervision and anticipatory guidance in infants, children, and adolescents with Down syndrome are available. The American Academy of Pediatrics (AAP) has published guidelines that are used commonly, and specific recommendations include cardiac evaluation with echocardiogram before 6 months of age; audiologic evaluation including tympanogram by 6 months of age; newborn screening for hypothyroidism and periodic T4 and TSH throughout childhood and into adulthood; ophthalmologic evaluation at 4 years of age; and routine immunizations.Various alternative therapies have been proposed in the treatment and management of infants and children with Down syndrome and information on risks and benefits of these therapies should be discussed with parents.Genetic Basis of Trisomy 21Cytogenetic studies are recommended for all infants who have a clinical phenotype consistent with Down syndrome to rule out the few chromosome syndromes that could mimic Down syndrome (XXXY, partial 10q trisomy), especially in infancy, and to determine if the infant has three complete copies of chromosome 21 or a translocation involving chromosome 21. This latter finding is important because the recurrence risk for parents varies dependent on the type of chromosome abnormality found in the affected child.If a child with trisomy 21 is found to have three complete copies of chromosome 21, the risk that a mother under the age of 35 will have a second affected child with trisomy 21 is about 1 to 2%. Compared to the background risk of having a child with trisomy 21 (1/800 or 0.125%), this is an 8- to 16-fold increase for women who have had one child with trisomy 21. If a woman is over the age of 35, the recurrence risk is thought to be similar to the age-specific risk. Further cytogenetic testing of the parents is not indicated.If a child with trisomy 21 is found to have an unbalanced translocation resulting in partial trisomy 21, cytogenetic analysis should be performed on the parents. If one of the parents carries a balanced translocation involving chromosome 21, the risk of recurrence will depend on the type of translocation and which parent is the carrier. Fathers carrying a balanced robertsonian translocation have a 1 to 2% recurrence risk, whereas mothers who carry it have a 10 to 15% recurrence risk. Families of children with Down syndrome caused by a

translocation should be referred for genetic counseling. Prenatal testing of future pregnancies can be offered to the families of any child with trisomy 21.The etiology and pathogenesis of trisomy 21 are unknown. The extra copy of chromosome 21 is thought to result from altered segregation of the chromosomes during meiosis, a phenomenon called nondisjunction, which may explain why the only factor that is consistent throughout all studies is that the prevalence of Down syndrome increases with advancing maternal age. No environmental factors have been implicated as causes for trisomy 21.Counseling the Family of a Newborn with Down SyndromeThe pediatric practitioner often has the responsibility of informing the parents that their newborn baby has Down syndrome. The approach to this situation is complex because every family differs in their expectations and preconceived notions about developmental disability and about the meaning of children within their family. The principles around these informing sessions and guidelines for effective and empathetic communications are outlined in Table 10-7.Several retrospective studies on parents' reactions to the birth of a child with Down syndrome indicate that families prefer to know the diagnosis as soon as possible. If the diagnosis is not in question and the infant does not have an associated life-threatening malformation, suggestions for planned counseling include the following: Arrange a private meeting with both parents together; avoid initiating the discussion while on an open postpartum ward or with other parents in the room; sit down with the family as opposed to standing; refer to the infant by first name if known; plan to meet the parents daily for the first few days of the infant's life and set up a structure for these interviews; use the initial interview to present the diagnosis and the concept of a syndrome; be realistic but hopeful about the information; mention that all children with trisomy 21 have developmental disability but that it varies in degree; have current and accurate information on natural history, the developmental disability, and health supervision available; and avoid presenting details about the genetic basis of trisomy 21 at the initial interview. Information on issues such as the recurrence risk and feasibility of prenatal diagnosis is usually not appropriate to present at the first meeting unless parents specifically ask for it. This additional information can be presented at follow-up visits.Let the second interview attempt to assess the parents' feelings and their state of mind. Create an opportunity to discuss their various reactions, listen to their personal concerns, and recognize individual feelings of each parent. When the results of the chromosome analysis are available, discuss any further implications and confirmation of the diagnosis. When the infant is being discharged, use the physical exam to emphasize the many normal aspects of the child as well as manifestations of the syndrome.During the first few days after the diagnosis has been made, recall that parents are not only grieving the loss of an expected normal child but also going through the natural process of bonding to a newborn baby. After the first few interviews, the parents should be acquainted with community resources and can be referred to the appropriate agency or infant programs that deal with children with developmental difficulties. Many parents express particular interest during this time in meeting other parents who have a child with Down syndrome and to have accurate and current reading material. The internet offers hundreds of contact points regarding Down syndrome. The web pages for two of the large support groups, Down Syndrome Congress and Down Syndrome Society, are excellent resources. Referral to a local support group or parent-to-parent contact is always appropriate in these situations and has become a component of routine care.Each family will proceed through this adjustment process at a different rate. Feelings of denial, anger, guilt, and sadness mixed with natural tendencies to bond to their newborn baby will affect the family's understanding and perhaps even the reception of technical

information. Over the last two decades, a clear trend toward presenting information in a hopeful and optimistic manner has been the approach rather than overemphasizing disabilities and problems. Eliminating the inappropriate and misleading stigma that has surrounded the diagnosis of Down syndrome for decades goes a long way toward improving parental adjustment in this setting.

Physical Examination

Meticulous physical examination is crucial for accurate diagnosis in dysmorphic infants and children. In addition to the routine procedures described in Chapter 1, special attention should be paid to the neonate's physical measurements (Figure 33–11). Photographs are helpful and should include a ruler for reference.

Down Syndrome - Nelson essentialsDown syndrome is the most common of all the abnormalities of chromosomal number. Occurring in 1 of every 800 births, most cases (92.5%) of Down syndrome are due to nondisjunction; in 80%, the nondisjunctional event occurs in maternal meiosis phase I. As a result of nondisjunction, there are three copies of chromosome 21 (trisomy 21); using standard cytogenetic nomenclature, trisomy 21 is designated 47,XX,+21 or 47,XY,+21. In 4.5% of cases, the extra chromosome 21 is part of a robertsonian translocation, which occurs when the long arms (q) of two acrocentric chromosomes (chromosomes 13, 14, 15, 21, or 22) fuse at the centromeres, and the short arms (p), containing copies of ribosomal RNA, are lost. The most common robert-sonian translocation leading to Down syndrome is between chromosomes 14 and 21; standard nomenclature is 46,XX,t (14q21q) or 46,XY,t (14q21q). In approximately 3% of cases of Down syndrome, mosaicism occurs. In these individuals, there are two populations of cells: one with trisomy 21 and one with a normal complement of chromosomes. This mosaicism occurs because of a nondisjunction event that occurs after fertilization and after a few cell divisions or from what is referred to as trisomic rescue. The loss of this aneuploidy returns the cell to 46,XX or 46,XY, and "rescues" this cell. This is a rescue not of the entire organism, but of some of the cell lines. The person is referred to as a mosaic for these two populations of cells and according to standard nomenclature is designated 47,XX,+21/46XX or 47,XY,+21/46,XY. Although it is widely believed that these individuals are more mildly affected, there are wide variations in the clinical findings of these individuals. Children with Down syndrome are most likely to be diagnosed in the newborn period. Although these infants have normal birth weight and length, they have hypotonia. The characteristic facial appearance, with brachycephaly, flattened occiput, hypoplastic midface, flattened nasal bridge, upward slanting palpebral fissures, epicanthal folds, and large protruding tongue, is apparent at birth. Infants also have short broad hands often with a transverse palmar crease and a wide gap between the first and second toes. The severe hypotonia may cause feeding problems and decreased activity (Table 49-1). Approximately 40% have congenital heart disease. Mostly caused by endocardial cushion defects, these anomalies include atrioventricular canal, ventriculoseptal or atrioseptal defects, and valvular disease. Approximately 10% of newborns with Down syndrome have gastrointestinal tract anomalies. The three most common defects are duodenal atresia, annular pancreas, and imperforate anus.

One percent of infants with Down syndrome are found to have congenital hypothyroidism, which is identified as part of the newborn screening program. Acquired hypothyroidism is a more common problem. Thyroid function testing must be monitored periodically during the child's life.

Table 49-1. Clinical Findings That May Be Present with Trisomy 21*Stature smaller than peer age groupDevelopmental delaysCongenital heart disease (e.g., endocardial cushion defect and ventricular septal defect)Structural abnormalities of the bowel (e.g., tracheoesophageal fistula, duodenal atresia, annular pancreas, duodenal web, and Hirschsprung disease)Central hypotoniaBrachycephalyDelayed closure of fontanelsSmall midface, hypoplastic frontal sinuses, myopia, and small (short) ears

Lax joints, including laxity of the atlantoaxial articulation (the latter predisposing the patient to C1-2 dislocation)Short, broad hands, feet, and digits; single palmar crease, clinodactylyExaggerated space between first and second toeVelvety, loosely adhering mottled skin (cutis marmorata) in infancy; coarse, dry skin in adolescenceStatistically increased risk for leukemia, Alzheimer disease, hypothyroidism

*An individual may exhibit any combination of these findings. There is no correlation between the number of physical findings and eventual level of mental performance. The increased risk for leukemia is significant, but probably no greater than 1% for any individual. Alzheimer disease is relatively common in persons with trisomy 21 who die in middle adult life, but the frequency in all adults with Down syndrome is not known.

Polycythemia at birth (hematocrit levels >70%) is common and may require treatment. Some infants with Down syndrome show a leukemoid reaction, with white blood cell counts of 100,000/mm3. Although this reaction resembles congenital leukemia, it usually is a self-limited condition, resolving on its own over the first month of life. Nonetheless, there is an increased risk for leukemia for children with Down syndrome. This increased risk is estimated to be 10 to 18 times the risk of individuals without Down syndrome. In children with Down syndrome younger than 1 year of age, congenital and infantile leukemia is generally acute nonlymphoblastic leukemia. In individuals with trisomy 21 older than 3 years, the types of leukemia are similar to children without Down syndrome, with the predominant type being acute lymphoblastic leukemia. Down syndrome patients also are more susceptible to infection. They are more likely to develop cataracts. Also, approximately 10% have atlantoaxial instability, an increased distance between the first and second cervical vertebrae, which may predispose to spinal cord injury. Most individuals older than 35 years of age develop Alzheimer-like features. Seventy-five percent of affected infants are born to women younger than 35 years old. Because only 5% of all infants are born to women older than 35, but 25% of Down syndrome infants are born to women older than 35, the risk for a child with Down syndrome increases strikingly with increasing maternal age. Four pregnancy-related markers (maternal serum AFP, uE3, inhibin A, and HCG) are studied to develop a risk profile for a woman's chance for having an infant with Down syndrome. This is a screening test; it is able only to identify women who are at increased risk for having an infant with Down syndrome and other

trisomies, essentially indicating which women should be referred for more definitive testing. Amniocentesis should be offered to women who are identified by the screening test to be at increased risk. The recurrence risk for parents who have had a child with Down syndrome depends on the child's cytogenetic findings. If the finding was 47,XX,+21 or 47,XY,+21 (i.e., trisomy 21), the recurrence risk based on empirical observation is approximately 1% (added to the age-specific risk for women <35 years old; use just the age-specific risk for women >35 years old) for subsequent pregnancies. If a translocation occurred to cause Down syndrome, chromosomal analysis of both parents must be performed. In approximately 65% of cases, the translocation is found to have arisen de novo (i.e., spontaneously, with both parents having normal karyotypes), but in 35% of cases, one of the parents has a balanced translocation. The recurrence risk depends on which parent is the carrier: if the mother is the carrier, the risk of recurrence is 10% to 15%; if the father is the carrier, the recurrence risk is 2% to 5%.

Currents Pediatric 18

Pneumonia

Pneumonia is an inflammation of the parenchyma of the lungs. Although most cases of pneumonia are caused by microorganisms, noninfectious causes include aspiration of food or gastric acid, foreign bodies, hydrocarbons, and lipoid substances, hypersensitivity reactions, and drug- or radiation-induced pneumonitis. The causes of lung infection in neonates (see Chapter 109 ) and immunocompromised hosts (see Chapter 177 ) are distinct from those affecting otherwise normal infants and children.

EPIDEMIOLOGY.

Pneumonia is a substantial cause of morbidity and mortality in childhood (particularly among children <5 yr of age) throughout the world, rivaling diarrhea as a cause of death in developing countries. With an estimated 146–159 million new episodes per yr in developing countries, pneumonia is estimated to cause approximately 4 million deaths among children worldwide. Currently, the incidence of community-acquired pneumonia in developed countries is estimated to be 0.026 episodes per child-year compared to 0.280 episodes per child-year in developing countries.

In the United States from 1939–1996, mortality caused by pneumonia in children declined by 97%. It is hypothesized that this decline is attributable to the introduction of antibiotics, vaccines, and the expansion of medical insurance coverage for children. Haemophilus influenzae type b (see Chapter 192 ) was an important cause of bacterial pneumonia in young children but has become uncommon with the routine use of effective vaccines. The introduction of heptavalent pneumococcal conjugate vaccine and its impact on pneumococcal disease (see Chapter 181 ) has reduced the overall incidence of pneumonia in infants and children in the United States by ≈30% in the 1st yr of life, ≈20% in the 2nd yr of life, and ≈10% in children >2 yr of age.

ETIOLOGY.

The cause of pneumonia in an individual patient is often difficult to determine because direct culture of lung tissue is invasive and rarely performed. Cultures performed on specimens obtained from the upper respiratory tract or “sputum” generally do not accurately reflect the cause of lower respiratory tract infection. Using “state-of-the-art” diagnostic testing, a bacterial or viral cause of pneumonia can be identified in 40–80% of children with community-acquired pneumonia. Streptococcus pneumoniae (pneumococcus) is the most common bacterial pathogen, followed by Chlamydia pneumoniae and Mycoplasma pneumoniae. In addition to pneumococcus, other bacterial causes of pneumonia in previously healthy children in the United States include group A streptococcus (Streptococcus pyogenes; see Chapter 182 ) and Staphylococcus aureus (see Chapter 180.1 ) [ Table 397-1 ].

TABLE 397-1 -- Causes of Infectious Pneumonia

Bacterial

Common

Streptococcus pneumoniae

Group B streptococci Neonates

Group A streptococci

Mycoplasma pneumoniae[*] Adolescents;summer-fall epidemics

Chlamydia pneumoniae[*] Adolescents

Chlamydia trachomatis Infants

Mixed anaerobes Aspiration pneumonia

Gram-negative enteric Nosocomial pneumonia

Uncommon

Haemophilus influenzae type B Unimmunized

Staphylococcus aureus Pneumatoceles;infants

Moraxella catarrhalis

Neisseria meningitides

Francisella tularensis Animal, tick, fly contact

Nocardia species Immunosuppressed persons

Chlamydia psittaci[*] Bird contact

Yersinia pestis Plague

Legionella species[*] Exposure to contaminated water; nosocomial

Viral

Common

Respiratory synctial virus Bronchiolitis

Parainfluenza types 1–3 Croup

Influenza A, B High fever; winter months

Adenovirus Can be severe; often occurs between January and April

Metapneumovirus Similar to RSV

Uncommon

Rhinovirus Rhinorrhea

Enterovirus Neonates

Herpes simplex Neonates

Cytomegalovirus Infants, immunosuppressed persons

Measles Rash, coryza, conjunctivitis

Varicella Adolescents

Hantavirus Southwestern United States, rodents

SARS agent Asia

Fungal

Histoplasma capsulatum Geographic region; bird, bat contact

Cryptococcus neoformans Bird contact

Aspergillus species Immunosuppressed

Mucormycosis Immunosuppressed

Coccidioides immitis Geographic region

Blastomyces dermatitides Geographic region

Rickettsial

Coxiella burnetii[*] Q fever, animal (goat, sheep, cattle) exposure

Rickettsia rickettsiae Tick bite

Mycobacterial

Mycobacterium tuberculosis Developing countries

Mycobacterium avium-intracellulare Immunosuppressed persons

Parasitic

Pneumocystis carinii Immunosuppressed, steroids

Eosinophilic Various parasites (e.g., Ascaris Strongyloides species)

* Atypical pneumonia syndrome; atypical in terms of extrapulmonary manifestations, low-grade fever, patchy diffuse infiltrates, poor response to penicillin-type antibiotics, and negative sputum Gram stain. SARS, severe acute respiratory syndrome.

Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus are the major causes of hospitalization and death from pneumonia among children in developing countries, although in children with HIV infection, Mycobacterium tuberculosis (see Chapter 212 ), atypical mycobacterium, Salmonella (see Chapter 195 ), Escherichia coli (see Chapter 197 ), and Pneumocystis jirovecii Viral pathogens are a prominent cause of lower respiratory tract infections in infants and children <5 yr of age. Viruses are responsible for 45% of the episodes of pneumonia identified in hospitalized children in Dallas. Unlike bronchiolitis, for which the peak incidence is in the 1st yr of life, the highest frequency of viral pneumonia occurs between the ages of 2 and 3 yr, decreasing slowly thereafter. Of the respiratory viruses, influenza virus ( Chapter 255 ) and respiratory syncytial virus (RSV) ( Chapter 257 ) are the major pathogens, especially in children <3 yr of age. Other common viruses causing pneumonia include parainfluenza viruses, adenoviruses, rhinoviruses, and metapneumovirus. The age of the patient may help identify possible pathogens ( Table 397-2 ).

TABLE 397-2 -- Etiologic Agents Grouped by Age of the Patient

AGE GROUP FREQUENT PATHOGENS (IN ORDER OF FREQUENCY)

Neonates (<1 mo)

Group B streptococcus, Escherichia coli, other gram-negative bacilli, Streptococcus pneumoniae, Haemophilus influenzae (type b,[*] nontypable)

1–3 mo

Febrile pneumonia

Respiratory syncytial virus, other respiratory viruses (parainfluenza viruses, influenza viruses, adenoviruses), S. pneumoniae, H. influenzae (type b,[*] nontypable)

Afebrile pneumonia

Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, cytomegalovirus

3–12 mo Respiratory syncytial virus, other respiratory viruses (parainfluenza viruses, influenza viruses, adenoviruses), S. pneumoniae, H. influenzae (type b,[*] nontypable), C. trachomatis, Mycoplasma pneumoniae, group A streptococcus

2–5 yr Respiratory viruses (parainfluenza viruses, influenza viruses, adenoviruses), S. pneumoniae, H. influenzae (type b,[*] nontypable), M. pneumoniae, Chlamydophila pneumoniae, S. aureus, group A streptococcus

5–18 yr M. pneumoniae, S. pneumoniae, C. pneumoniae, H. influenzae (type b,[*] nontypable), influenza viruses, adenoviruses, other respiratory viruses

≥18 yr M. pneumoniae, S. pneumoniae, C. pneumoniae, H. influenzae (type b,[*] nontypable), influenza viruses, adenoviruses, Legionella pneumophila

From Kliegman RM, Marcdante KJ, Jenson HJ, Behrman RE: Nelson Essentials of Pediatrics, 5th ed Philadelphia, Elsevier, 2006, p. 504.

* H. influenzae type b is uncommon with universal H. influenza type b immunization.

Lower respiratory tract viral infections in the United States are much more common in the fall and winter, related to the seasonal epidemics of respiratory viral infection that occur each yr. The typical pattern of these epidemics usually begins in the fall when parainfluenza infections appear and most often manifest as croup. Later in winter, RSV, metapneumovirus, and influenza viruses cause widespread infection, including upper respiratory tract infections, bronchiolitis, and pneumonia. RSV attacks infants and young children, whereas influenza virus causes disease and excess hospitalization for acute respiratory illness in all age groups. The knowledge of the prevailing viral epidemic may lead to a presumptive initial diagnosis.

Immunization status is relevant because children fully immunized against H. influenzae type b and S. pneumoniae are less likely to be infected with these pathogens. Children who are immunosuppressed or who have an underlying illness may be at risk for specific pathogens, such as Pseudomonas spp. in patients with cystic fibrosis.

PATHOGENESIS.

The lower respiratory tract is normally kept sterile by physiologic defense mechanisms, including the mucocil iary clearance, the properties of normal secretions such as secretory immunoglobulin A (IgA), and clearing of the airway by coughing. Immunologic defense mechanisms of the lung that limit invasion by pathogenic organisms include macrophages that are present in alveoli and bronchioles, secretory IgA, and other immunoglobulins.

Viral pneumonia usually results from spread of infection along the airways, accompanied by direct injury of the respiratory epithelium, resulting in airway obstruction from swelling, abnormal secretions, and cellular debris. The small caliber of airways in young infants makes them particularly susceptible to severe infection. Atelectasis, interstitial edema, and ventilation-perfusion mismatch causing significant hypoxemia often accompany airway obstruction. Viral infection of the respiratory tract can also predispose to secondary bacterial infection by disturbing normal host defense mechanisms, altering secretions, and modifying the bacterial flora.

When bacterial infection is established in the lung parenchyma, the pathologic process varies according to the invading organism. M. pneumoniae attaches to the respiratory epithelium, inhibits ciliary action, and leads to cellular destruction and an inflammatory response in the submucosa. As the infection progresses, sloughed cellular debris, inflammatory cells, and mucus cause airway obstruction, with spread of infection occurring along the bronchial tree, as it does in viral pneumonia.

S. pneumoniae produces local edema that aids in the proliferation of organisms and their spread into adjacent portions of lung, often resulting in the characteristic focal lobar involvement.

Group A streptococcus infection of the lower respiratory tract results in more diffuse infection with interstitial pneumonia. The pathology includes necrosis of tracheobronchial mucosa; formation of

large amounts of exudate, edema, and local hemorrhage, with extension into the interalveolar septa; and involvement of lymphatic vessels and the increased likelihood of pleural involvement.

S. aureus pneumonia manifests in confluent bronchopneumonia, which is often unilateral and characterized by the presence of extensive areas of hemorrhagic necrosis and irregular areas of cavitation of the lung parenchyma, resulting in pneumatoceles, empyema, or, at times, bronchopulmonary fistulas.

Recurrent pneumonia is defined as 2 or more episodes in a single yr or 3 or more episodes ever, with radiographic clearing between occurrences. An underlying disorder should be considered if a child experiences recurrent bacterial pneumonia ( Table 397-3 ). Additional factors that promote pulmonary infection include trauma, anesthesia, and aspiration.

TABLE 397-3 -- Differential Diagnosis of Recurrent Pneumonia

Hereditary Disorders

Cystic fibrosis

Sickle cell disease

Disorders of Immunity

AIDS

Bruton agammaglobulinemia

Selective IgG subclass deficiencies

Common variable immunodeficiency syndrome

Severe combined immunodeficiency syndrome

Disorders of Leukocytes

Chronic granulomatous disease

Hyperimmunoglobulin E syndrome (Job syndrome)

Leukocyte adhesion defect

Disorders of Cilia

Immotile cilia syndrome

Kartagener syndrome

Anatomic Disorders

Sequestration

Lobar emphysema

Esophageal reflux

Foreign body

Tracheoesophageal fistula (H type)

Gastroesophageal reflux

Bronchietasis

Aspiration (oropharyngeal incoordination)

From Kliegman RM, Marcdante KJ, Jenson HJ, Behrman RE: Nelson Essentials of Pediatrics, 5th ed, Philadelphia, Elsevier, 2006, p. 507.

Slowly resolving pneumonia refers to the persistence of symptoms or radiographic abnormalities beyond the expected time course. The time course varies, depending on the organism involved, the extent of disease, and the presence of associated complicating conditions.

CLINICAL MANIFESTATIONS.

Viral and bacterial pneumonias are often preceded by several days of symptoms of an upper respiratory tract infection, typically rhinitis and cough. In viral pneu monia, fever is usually present; temperatures are generally lower than in bacterial pneumonia. Tachypnea is the most consistent clinical manifestation of pneumonia. Increased work of breathing accompanied by intercostal, subcostal, and suprasternal retractions, nasal flaring, and use of accessory muscles is common. Severe infection may be accompanied by cyanosis and respiratory fatigue, especially in infants. Auscultation of the chest may reveal crackles and wheezing, but it is often difficult to localize the source of these adventitious sounds in very young children with hyperresonant chests. It is often not possible to distinguish viral pneumonia clinically from disease caused by Mycoplasma and other bacterial pathogens.

Bacterial pneumonia in adults and older children typically begins suddenly with a shaking chill followed by a high fever, cough, and chest pain. In older children and adolescents, a brief upper respiratory tract illness is followed by the abrupt onset of shaking chills and high fever accompanied by drowsiness with intermittent periods of restlessness; rapid respirations; a dry, hacking, unproductive cough; anxiety; and, occasionally, delirium. Circumoral cyanosis may be observed. Many children are noted to be splinting on the affected side to minimize pleuritic pain and improve ventilation; they may lie on their side with their knees drawn up to their chest.

Physical findings depend on the stage of pneumonia. Early in the course of illness, diminished breath sounds, scattered crackles, and rhonchi are commonly heard over the affected lung field. With the development of increasing consolidation or complications of pneumonia such as effusion, empyema, or pyopneumothorax, dullness on percussion is noted and breath sounds may be diminished. A lag in respiratory excursion often occurs on the affected side. Abdominal distention may be prominent because of gastric dilation from swallowed air or ileus. Abdominal pain is common in lower lobe pneumonia. The liver may seem enlarged because of downward displacement of the diaphragm secondary to hyperinflation of the lungs or superimposed congestive heart failure. Nuchal rigidity, in the absence of meningitis, may also be prominent, especially with involvement of the right upper lobe.

Symptoms described in adults with pneumococcal pneumonia may be noted in older children but are rarely observed in infants and young children, in whom the clinical pattern is considerably more variable. In infants, there may be a prodrome of upper respiratory tract infection and diminished appetite, leading to the abrupt onset of fever, restlessness, apprehension, and respiratory distress. These infants appear ill with respiratory distress manifested by grunting; nasal flaring; retractions of the supraclavicular, intercostal, and subcostal areas; tachypnea; tachycardia; air hunger; and often cyanosis. Results of physical examination may be misleading, particularly in young infants, with meager findings disproportionate to the degree of tachypnea. Some infants with bacterial pneumonia may have associated gastrointestinal disturbances characterized by vomiting, anorexia, diarrhea, and abdominal distention secondary to a paralytic ileus. Rapid progression of symptoms is characteristic in the most severe cases of bacterial pneumonia.

DIAGNOSIS.

The chest radiograph confirms the diagnosis of pneumonia and may indicate a complication such as a pleural effusion or empyema. Viral pneumonia is usually characterized by hyperinflation with bilateral interstitial infiltrates and peribronchial cuffing ( Fig. 397-1 ). Confluent lobar consolidation is typically seen with pneumococcal pneumonia ( Fig. 397-2 ). The radiographic appearance alone is not diagnostic and other clinical features must be considered. Repeat chest x-rays are not required for proof of cure for patients with uncomplicated pneumonia.

The peripheral white blood cell (WBC) count can be useful in differentiating viral from bacterial pneumonia. In viral pneumonia, the WBC count can be normal or elevated but is usually not higher than 20,000/mm3, with a lymphocyte predominance. Bacterial pneumonia (occasionally, adenovirus pneumonia) is often associated with an elevated WBC count in the range of 15,000-40,000/mm3 and a predominance of granulocytes. A large pleural effusion, lobar consolidation, and a high fever at the onset of the illness are also suggestive of a bacterial etiology. Atypical pneumonia due to C. pneumoniae or M. pneumoniae is difficult to distinguish from pneumococcal pneumonia by x-ray and other labs, and although pneumococcal pneumonia is associated with a higher WBC count, erythrocyte sedimentation rate (ESR), and C–reactive protein (CRP), there is considerable overlap.

The definitive diagnosis of a viral infection rests on the isolation of a virus or detection of the viral genome or antigen in respiratory tract secretions. Growth of respiratory viruses in tissue culture usually requires 5–10 days. Reliable DNA or RNA tests for the rapid detection of RSV, parainfluenza, influenza, and adenoviruses are available and accurate. Serologic techniques can also be used to diagnose a recent respiratory viral infection but generally require testing of acute and convalescent serum samples for a rise in antibodies to a specific viral agent. This diagnostic technique is laborious, slow, and not generally clinically useful because the infection usually resolves by the time it is confirmed serologically. Serologic testing may be valuable as an epidemiologic tool to define the incidence and prevalence of the various respiratory viral pathogens.

The definitive diagnosis of a bacterial infection requires isolation of an organism from the blood, pleural fluid, or lung. Culture of sputum is of little value in the diagnosis of pneumonia in young children. Blood cultures are positive in only 10% of children with pneumococcal pneumonia. In M. pneumoniae infections, cold agglutinins at titers >1 : 64 are found in the blood in ≈50% of patients. Cold agglutinins are nonspecific, however, because other pathogens such as influenza viruses may also cause increases. Acute infection caused by M. pneumoniae can be diagnosed on the basis of a positive PCR test or seroconversion in an IgG assay. Serologic evidence such as the anti-streptolysin O (ASO) titer may be useful in the diagnosis of group A streptococcal pneumonia.

TREATMENT.

Treatment of suspected bacterial pneumonia is based on the presumptive cause and the clinical appearance of the child (see Tables 397-1 and 397-2 [1] [2]). For mildly ill children who do not require hospitalization, amoxicillin is recommended. In communities with a high percentage of penicillin-resistant pneumococci, high doses of amoxicillin (80–90 mg/kg/24 hr) should be prescribed. Therapeutic alternatives include cefuroxime axetil or amoxicillin/clavulanate. For school-aged children and in those in whom infection with M. pneumoniae or C. pneumoniae (atypical pneumonias) is suggested, a macrolide antibiotic such as azithromycin is an appropriate choice. In

adolescents, a respiratory fluoroquinolone (levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin) may be considered for atypical pneumonias.

The empirical treatment of suspected bacterial pneumonia in a hospitalized child requires an approach based on the clinical manifestations at the time of presentation. Parenteral cefuroxime (150 mg/kg/24 hr), cefotaxime, or ceftriaxone is the mainstay of therapy when bacterial pneumonia is suggested. If clinical features suggest staphylococcal pneumonia (pneumatoceles, empyema), initial antimicrobial therapy should also include vancomycin or clindamycin.

If viral pneumonia is suspected, it is reasonable to withhold antibiotic therapy, especially for those patients who are mildly ill, have clinical evidence suggesting viral infection, and are in no respiratory distress. Up to 30% of patients with known viral infection may have coexisting bacterial pathogens. Therefore, if the decision is made to withhold antibiotic therapy based on presumptive diagnosis of a viral infection, deterioration in clinical status should signal the possibility of superimposed bacterial infection and antibiotic therapy should be initiated.

Indications for admission to a hospital are noted in Table 397-4 . In developing countries, oral zinc (20 mg/day) helps accelerate recovery from severe pneumonia.

TABLE 397-4 -- Factors Suggesting Need for Hospitalization of Children with Pneumonia

Age <6 mo

Sickle cell anemia with acute chest syndrome

Multiple lobe involvement

Immunocompromised state

Toxic appearance

Severe respiratory distress

Requirement for supplemental oxygen

Dehydration

Vomiting

No response to appropriate oral antibiotic therapy

Noncompliant parents

RESPONSE TO TREATMENT.

Typically, patients with uncomplicated community-acquired bacterial pneumonia respond to therapy with improvement in clinical symptoms (fever, cough, tachypnea, chest pain) within 48–96 hr of initiation of antibiotics. Radiographic evidence of improvement substantially lags behind clinical improvement. A number of factors must be considered when a patient does not improve on

appropriate antibiotic therapy (slowly resolving pneumonia): (1) complications, such as empyema; (2) bacterial resistance; (3) nonbacterial etiologies such as viruses and aspiration of foreign bodies or food; (4) bronchial obstruction from endobronchial lesions, foreign body, or mucous plugs; (5) pre-existing diseases such as immunodeficiencies, ciliary dyskinesia, cystic fibrosis, pulmonary sequestration, or cystic adenomatoid malformation; and (6) other noninfectious causes (including bronchiolitis obliterans, hypersensitivity pneumonitis, eosinophilic pneumonia, aspiration, and Wegener granulomatosis). A repeat chest x-ray is the 1st step in determining the reason for delay in response to treatment.

COMPLICATIONS.

Complications of pneumonia are usually the result of direct spread of bacterial infection within the thoracic cavity (pleural effusion, empyema, pericarditis) or bacteremia and hematologic spread ( Fig. 397-3 ). Meningitis, suppurative arthritis, and osteomyelitis are rare complications of hematologic spread of pneumococcal or H. influenzae type b infection.S. aureus, S. pneumoniae, and S. pyogenes are the most common causes of parapneumonic effusions and of empyema ( Table 397-5 ). The treatment of empyema is based on the stage (exudative, fibrinopurulent, organizing). Imaging studies including ultrasonography and CT are helpful in determining the stage of empyema. The mainstays of therapy include antibiotic therapy and drainage with tube thoracostomy. Additional approaches include the use of fibrinolytic therapy (urokinase, streptokinase, alteplase) and selected video-assisted thoracoscopy (VATS) to debride, lyse adhesions, and drain loculated areas of pus. Early diagnosis and intervention, particularly with VATS, may obviate the need for thoracotomy and open debridement.

TABLE 397-5 -- Differentiation of Pleural Fluid

TRANSUDATE EXUDATE COMPLICATED EMPYEMA

Appearance Clear Cloudy Purulent

Cell count <1000 >1000 >5000

Cell type Lymphocytes, monocytes PMNs PMNs

LDH <200 U/L >200 U/L >1000 U/L

Pleural/serum LDH ration <0.6 >0.6 >0.6

Protein >3 g Unusual Common Common

Pleural/serum protein ratio <0.5 >0.5 >0.5

Glucose[*] Normal Low Very low[*](<40 mg/dL)

pH[*] Normal (7.40–7.60) 7.20–7.40 <7.20, chest tube placement required

Gram stain Negative Usually positive >85% positive unless patient received prior antibiotics

* Low glucose or pH may be seen in malignant effusion, tuberculosis, esophageal rupture, pancreatitis (positive pleural amylase), and rheumatologic diseases (e.g., systemic lupus erythematosus). LDH, lactate dehydrogenase; PMNs, polymorphonuclear neutrophils.

Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Copyright © 2007 Saunders, An Imprint of Elsevier

593.2 Unprovoked Seizures

FIRST SEIZURE.

Although the occurrence of a seizure in a child without a provocative stimulus such as high fever is often considered a harbinger of a chronic seizure disorder or epilepsy, less than half of these children go on to develop a 2nd seizure. A careful history is warranted to ascertain a potential family history of epilepsy, a prior neurologic disorder, or history of seizure with fever, which may increase the likelihood of recurrence. Laboratory testing of serum electrolytes, toxicology screening, or urine and serum metabolic testing should be chosen based on individual clinical circumstances rather than on a routine basis. Serum glucose should be evaluated with the 1st afebrile seizure. In the child with a 1st nonfebrile seizure, a lumbar puncture is of limited value and should be used primarily when there is concern about possible meningitis, encephalitis, sepsis, subarachnoid hemorrhage, or a demyelinating disorder. An EEG is recommended as part of the neurodiagnostic evaluation of the child with an apparent 1st unprovoked seizure because it is useful for diagnosis of the event, prediction of recurrence risk, and identification of specific focal abnormalities and/or epileptic syndromes. Neuroimaging is generally not recommended after a 1st unprovoked seizure unless there is an indication for it on neurologic examination (focal neurologic deficits). If it is obtained, however, MRI of the brain is recommended over CT scanning. Anticonvulsant medication is generally not recommended after a single seizure. MRI may also be indicated in infants and adolescents with their 1st seizure.

RECURRENT SEIZURES.

Two unprovoked seizures >24 hr apart suggest the presence of an epileptic disorder within the brain that will lead to future recurrences. It is important to perform a careful evaluation to look for the cause of the seizures as well as to assess the need for treatment with antiepileptic drugs and estimate the potential for response to treatment and remission of seizures in the future.

The history can provide important information about the type of seizures. Some parents can precisely act out or recreate a seizure. Children who have a propensity to develop epilepsy may experience the 1st convulsion in association with a viral illness or a low-grade fever. Seizures that occur during the early morning hours or with drowsiness, particularly during the initial phase of sleep, are common in childhood epilepsy. In retrospect, irritability, mood swings, headache, and subtle personality changes may precede a seizure by several days. Some parents can accurately predict the timing of the next seizure on the basis of changes in the child's disposition. The physical portrayal of the convulsion by the parent or caregiver is often surprisingly similar to the actual convulsion and is much more accurate than the verbal description. Aside from the description of the seizure pattern, the frequency, time of day, precipitating factors, and alternation in the type of convulsive disorder are important. Although generalized tonic-clonic seizures are readily

documented, the frequency of absence seizures is often underestimated by parents. A prolonged personality change or intellectual deterioration may suggest a degenerative disease of the CNS, whereas constitutional symptoms, including vomiting and failure to thrive, might indicate a primary metabolic disorder or a structural lesion. It is essential to obtain details of prior anticonvulsant medication and the child's response to the regimen and to determine whether drugs that may potentiate seizures, including chlorpromazine or methylphenidate, were prescribed. The description of the seizure along with the family history can provide clues to the presence of possible genetic epileptic syndromes ( Table 593-1 ). These include autosomal dominant nocturnal frontal lobe epilepsy, familial benign neonatal convulsions, familial benign infantile convulsions, autosomal dominant febrile seizures, partial epilepsy with auditory symptoms, autosomal dominant frontal lobe progressive epilepsy with mental retardation, absence epilepsy, and febrile seizures with later partial complex seizures.

TABLE 593-1 -- Identified Genes for Epilepsy

FUNCTION LOCUS EPILEPSY SYNDROME SEIZURE TYPES

GABRA1 Partial inhibition of GABA-activated currents

5q34 AD JME TCS, mycolonic, absence

GABAA, α1 receptor subunit

GABRG2 Rapid inhibition of GABAergic neurons

5q31 FS, CAE, GEFS+ Febrile, absence, TCS, myoclonic, clonic, partial

GABAA,receptor γ2 subunit

GABRD Decreased GABAA receptor current amplitudes

1p36 GEFS- Febrile and afebrile seizures

GABAA receptor δ2 subunit

SCN2A Fast sodium influx initiation and propagation of action potential

2q24 GEFS- BFNIC Febrile, afebrile generalized tonic and TCS

Sodium channel α2 subunit

SCN1A Somatodendritic sodium influx 2q24 GEFS- SMEI Febrile, absence, myoclonic, TCS, partial

Sodium channel α1 subunit

SCN1B Coadjuvate and modulate α subunit

19q13 GEFS- Febrile, absence, tonic clonic, myoclonic.

Sodium channel β1 subunit

KCNQ2 M current interacts with KCNQ3 20q13 BFNC Neonatal convulsions

Potassium channel

KCNQ3 M current interacts with KCNQ2 8q24 BFNC Neonatal convulsions

Potassium channel

FUNCTION LOCUS EPILEPSY SYNDROME SEIZURE TYPES

ATP1A2 Dysfunction of ion transportation 1q23 BFNIC and familial hemiplegic migraine

Infantile convulsions

Na1, K1-ATPase pump

CHRNA4 Nicotinic current modulation; interacts with β2 subunit

20q13 ADNFLE Sleep-related focal seizures

Acetylcholine receptor α4 subunit

CHRNB2 Nicotinic current modulation; interacts with α4 subunit

1p21 ADNFLE Sleep-related focal seizures

Acetylcholine receptor β2 subunit

LGI1 Disregulates homeostasis, interactions between neurons and glia?

10q24 ADPEAF Partial seizures with auditory or visual hallucinations

Leucine-rich, glioma activated

CLCN2 Neuronal chloride efflux 3q26 IGE TCS, myoclonic, absence

Voltage-gated chloride channel

EFHC1 Reduced mouse hippocampal induced apoptosis

6p12-p11

JME TCS, myoclonic

Protein with an EF-hand motif

BRD2 (RING3) ? 6p21 JME TCS, myoclonic

Nuclear transcriptional regulator

AD, autosomal dominant; ADNFLE, autosomal dominant nocturnal frontal lobe epilepsy; ADPEAF, autosomal dominant partial epilepsy with auditory features; BFNC, benign familial neonatal convulsions; BFNIC, benign familial neonatal-infantile convulsion; GEFS+, generalized epilepsy with febrile seizures plus; JME, juvenile myoclonic epilepsy; MAE, myoclonic astatic epilepsy; SMEI, severe myolconic epilepsy of infancy; TCS, tonic-clonic seizures; XL, X-linked.

The physical, ophthalmologic, and neurologic examination can provide information about the presence of increased intracranial pressure, neurocutaneous syndromes, and structural brain abnormalities including malformations, injuries, infections, or tumors.

The EEG is indicated in all cases of epilepsy and is useful for determining the type of epilepsy and the future prognosis. Measurement of serum electrolytes including calcium and magnesium is not recommended as a routine practice. Metabolic testing, including administration of pyridoxine or pyridoxal phosphate for suspected pyridoxine-responsive seizures, serum lactate and pyruvate, and urine organic acids, is also not recommended routinely but should be dictated by clinical circumstances. Lumbar puncture should be considered for children with repeated seizures and other evidence of neurodevelopmental disability. It may be useful for detecting low CSF glucose in the

glucose transporter disorder; alterations in amino acids, neurotransmitters, or cofactors in metabolic disorders; or evidence of chronic infection. Neuroimaging with MRI is indicated during the evaluation of children with newly diagnosed epilepsy, especially for those with neurologic deficits, partial seizures, or focal EEG abnormalities that are not part of an idiopathic localization-related epilepsy syndrome. In some cases, an electrocardiogram may be warranted to rule out prolonged QT syndrome, which can, though rarely, cause seizures and syncope (see Chapter 594 ).

CLASSIFICATION OF SEIZURES.

It is important to classify the type of seizure ( Table 593-2 ). The seizure type may provide a clue to the cause of the seizure disorder. Precise delineation of the seizure may allow a firm basis for making a prognosis and choosing the most appropriate treatment. Anticonvulsants may readily control generalized tonic-clonic epilepsy in a child, but a patient with multiple seizure types or partial seizures may fare less well with the same type of therapy. Infants with benign myoclonic epilepsy have a more favorable outlook than patients with infantile spasms. Similarly, a school-aged child who has benign partial epilepsy with centrotemporal spikes (rolandic epilepsy) has an excellent prognosis and is unlikely to require a prolonged course of anticonvulsants. Clinical classification of seizures may be difficult because the manifestations of different seizure types may be similar. The clinical features of a child with absence seizures may be almost identical to those of another patient with complex partial epilepsy. An EEG is a useful adjunct to the classification of epilepsy because of the variability of seizure expressivity in this age group.

TABLE 593-2 -- International Classification of Epileptic Seizures

PARTIAL SEIZURES

Simple partial (consciousness retained)

Motor

Sensory

Autonomic

Psychic

Complex partial (consciousness impaired)

Simple partial, followed by impaired consciousness

Consciousness impaired at onset

Partial seizures with secondary generalization

GENERALIZED SEIZURES

Absences

Typical

Atypical

Generalized tonic-clonic

Tonic

Clonic

Myoclonic

Atonic

Infantile spasms

UNCLASSIFIED SEIZURES

Epilepsy in children has also been classified by syndrome ( Table 593-3 ). Using the age at onset of seizures, cognitive development and neurologic examination, description of seizure type, and EEG findings, including the background rhythm, it has been possible to classify ≈50% of childhood seizures into specific syndromes. The syndromic classification of seizures provides a distinct advantage over previous classifications by improving management with appropriate anticonvulsant medication, identifying potential candidates for epilepsy surgery, and providing patients and families with a reliable and accurate prognosis. Examples of epilepsy syndromes include infantile spasms (West syndrome), benign myoclonic epilepsy of infancy, the Lennox-Gastaut syndrome, febrile convulsions, Landau-Kleffner syndrome, benign childhood epilepsy with centrotemporal spikes (rolandic epilepsy), Rasmussen encephalitis, juvenile myoclonic epilepsy (Janz syndrome), and Lafora disease (progressive myoclonic epilepsy). Certain syndromes have a more favorable outcome ( Table 593-4 ).

TABLE 593-3 -- Classification of Epilepsies and Epileptic Syndromes

LOCALIZATION-RELATED (FOCAL, PARTIAL) EPILEPSIES

Idiopathic

Benign childhood epilepsy with centrotemporal spikes

Childhood epilepsy with occipital paroxysms

Symptomatic

The subclassification is determined by the anatomic location suggested by the clinical history, predominant seizure type, interictal and ictal EEG, and imaging studies; thus, SPS, CPS, or secondarily generalized seizures arising from frontal lobes, parietal, temporal, occipital, multiple lobes or an unknown focus

Localization related but uncertain symptomatic or idiopathic

GENERALIZED EPILEPSIES

Idiopathic

Benign neonatal familial convulsions

Benign neonatal convulsions

Benign myoclonic epilepsy in infancy

Childhood absence epilepsy (pyknoepilepsy)

Juvenile absence epilepsy

Juvenile myoclonic epilepsy (impulsive petit mal)

Epilepsy with grand mal seizures upon awakening

Other generalized idiopathic epilepsies that do not conform exactly to the syndromes just described

Cryptogenic or symptomatic generalized

West syndrome (infantile spasms)

Lennox-Gastaut syndrome

Epilepsy with myoclonic astatic seizures

Epilepsy with myoclonic absences

Symptomatic

Nonspecific cause

Early myoclonic encephalopathy

Specific disease states manifesting with seizures

EPILEPSIES AND SYNDROMES UNDETERMINED AS FOCAL OR GENERALIZED

With both generalized and focal seizures

Neonatal seizures

Severe myoclonic epilepsy in infancy

Epilepsy with continuous spike-and-wave patterns during slow-wave sleep

Acquired epileptic aphasia (Landau-Kleffner syndrome)

Without unequivocal generalized or focal features

All cases with GTCS in which the EEG findings do not allow classification as definitely generalized or localization-related:e.g., sleep GTCS

SPECIAL SYNDROMES

Situation-related seizures

Febrile convulsions

Isolated seizures or isolated status epilepticus

Acute symptomatic seizures:e.g., alcohol withdrawal seizures, eclampsia, uremia

CPS, complex partial seizures; EEG, electroencephalogram; GTCS, generalized tonic-clonic seizures; SPS, simple partial seizures. From Kliegman RM, Greenbaum LA, Lye PS:Practical Strategies in Pediatric Diagnosis and Therapy, 2nd ed. Philadelphia, Elsevier, 2004, p 680.

TABLE 593-4 -- Childhood Epileptic Syndromes with Generally Good Prognosis

SYNDROME COMMENT

Benign neonatal familial convulsions

Dominant, may be severe and resistant during a few days. Febrile or afebrile seizures (benign) may occur later in a minority

Infantile familial convulsions

Dominant, seizures often in clusters (overlap with benign partial complex epilepsy of infancy)

Febrile convulsions In some families, febrile and afebrile convulsions occur in different members, the so-called GEFS+ (generalized epilepsy with febrile seizures +);the old dichotomy between febrile convulsions or epilepsy does not always hold

Benign myoclonic Often seizures during sleep, one rare variety with reflex myoclonic seizures (touch, noise)

SYNDROME COMMENT

epilepsy of infancy

Partial idiopathic epilepsy with rolandic spikes

Seizures with falling asleep or on awakening;focal sharp waves with centrotemporal location on EEG;genetic

Idiopathic occipital partial epilepsy

Early childhood form with seizures during sleep and ictal vomiting, may present as status epilepticus. Later forms with migrainous symptoms;not always benign

Petit mal absence epilepsy

Cases with absences only, some have generalized seizures.60–80% full remission;in most cases, absences disappear on therapy but there are resistant cases (unpredictable)

Juvenile myoclonic epilepsy

Adolescence onset, with early morning myoclonic seizures and generalized seizures during sleep;often history of absences in childhood