Childhood Disorders

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CHILDHOOD DISORDERS

CEREBRAL PALSY

  • Nonscientific term describing permanent, nonprogressive neurologic motor system impairment resulting from CNS injuries of the immature brain (occur pre- or peri-natally, infancy, or early childhood); .2% incidence
    • Can be associated with prematurity (especially as smaller premature infants continue to survive) and low birth weight; however, specific causes have not yet been identified
    • Less than 15% result from a preventable obstetric injury
    • CP is not a single entity and the etiology of its various presentations is not the same
    • It is a general term which doesn’t tell the severity/nature of the disorder (same as “learning disability”)
  • Nonprogressive but not unchanging disorder of movement and posture; changes occur as the nervous system matures (e.g., a baby may be hypotonic but later b/c spastic or rigid; all CP has an early hypotonic phase) – in some instances there is a gradual improvement, but others reach a plateau; many require bracing and surgery
  • Two most common varieties:
    • Spastic paresis (70%)
      • Combination of spasticity (causes slow clumsy movements; usually accompanied by hyperactive deep tendon reflexes, clonus, and Babinski signs) and paresis
      • Affected limbs have growth arrest
      • Results from necrotic areas in the white matter around the ventricles (periventricular leukomalacia) – most closely related to prematurity
    • Extrapyramidal (“dyskinetic”) CP (choreoathetosis) (15%)
      • Characterized by choreoathetosis (involuntary writhing of face, tongue, hands, and feet sometimes overridden by jerking movements of trunk, arms, and legs)
      • Involvement of larynx, pharynx, and diaphragm may lead to severe dysarthria
      • Usually produced by combo of low birth weight, anoxia, and kernicterus that damages basal ganglia and auditory pathways
      • Lowest incidence of epilepsy and MR
  • 15% of the cases are “mixed”
  • Associated complications/disabilities:
    • MR; cognitive dysfxn
    • Epilepsy (generally associated with more global impairment)
    • Vision/hearing impairments
    • LD
    • Language disorders
    • Psychological problems
    • Pseudobulbar palsy
    • Hyperactivity
  • Sometimes the child’s most disabling problems are associated cognitive difficulties (though 50% have normal intelligence); visual-perceptual problems, speech and hearing impairments may influence learning

ABNORMALITIES OF THE NEURAL TUBE AND FUSION DEFECTS

Result from defective embryologic development of CNS during 3rd and 4th weeks gestation

UPPER NEURAL TUBE CLOSURE DEFECTS

ANENCEPHALY

  • Vault of skull absent; brain usually represented by a vascular mass; face grossly abnormal
  • May be due to severe trauma, radiation, infection; abnormal embryonic development between day 18 and week 4 gestation
  • Incompatible with life (die within minutes/hours of birth); interestingly, organs are ideal for transplants

CRANIUM BIFIDUM and ENCEPHALOCELE

  • Skin-covered brain, meninges, or CSF protrudes through skull defect
  • Results from incomplete closure of mesodermal layers over the upper neural tube
  • Cranium bifida = fusion defects of the skull
  • Encephalocele = myelomeningoceles or meningoceles that occur on the skull
  • Many possible behavioral complications arising from associated hydrocephalus – e.g., MR, ataxia, CP, and epilepsy

DANDY-WALKER MALFORMATION

  • Posterior portion of upper neural tube fails to develop; born with rudimentary posterior brain structures
  • Cerebellum/medulla fail to develop past early embryonic stage; fourth ventricle grows into a large cyst
  • Associated with hydrocephalus, agenesis of CC, craniofacial deformities, Klippel-Feil syndrome, DeLange syndrome, macrocephaly, MR
  • Frequent severe psychomotor retardation

ARNOLD-CHIARI MALFORMATION

  • Congenital deformation of the brain stem and cerebellum
  • Some combination of medulla and cerebellum are displaced downward through foramen magnum; aqueductal stenosis; overlying skull and cervical spine defects
  • May be due to traction caused by myelomeningocele or hydrocephalus; may be a dysgenesis of the brainstem
  • Associated with congenital hydrocephalus, spina bifida, myelomeningocele, severe psychomotor retardation; in “asymptomatic” cases, adults may present with headache, bulbar palsy, and neck pain

LOWER NEURAL TUBE CLOSURE DEFECTS

SPINA BIFIDA OCCULTA

  • Asymptomatic spinal lesion discovered incidentally; possibly 20% of population
  • Abnormal fusion of spinal lumbar vertebra
  • Often asymptomatic; may be associated with lipoma, congenital dermal sinuses, dimples
  • No documented cognitive deficits

SPINA BIFIDA CYSTICA

  • Spinal defect that includes a cystic-like sac (meningomyelocele), which may or may not contain the spinal cord; 1-2: 1,000 live birth incidence
  • Meningocele – meninges & skin protrude through lumbosacral spine defect to form CSF-filled bulge (no spinal cord) = good prognosis, though may cause gait impairment, kidney and bladder problems, loss of tissue barriers that protect CNS
  • Myelomeningocele or meningomyelocele (much more common) – tangle of rudimentary spinal cord, lumbar and sacral nerve roots, meninges protruding into sac = 80-90% chance of developing hydrocephalus and have many other problems (incl. meningitis, Arnold-Chiari)
    • Clinical deficits worsen during childhood and during growth spurts despite early surgical intervention
    • Most all are MR and paraplegic
    • May be due to autosomal recessive genetic abnormality; radiation, folic acid deficiency, toxins, and AEDs also implicated

OTHER DEFECTS

HYDRANENCEPHALY

  • Cerebral hemispheres replaced by cystic sacs containing CSF
  • May be due to vascular occlusion causing necrosis
  • May initially look like hydrocephalus; eye movement disturbances, feeding problems, hyponatremia
  • Incompatible with life

PORENCEPHALY

  • Large cystic lesion develops, usually bilateral
  • Disturbed cortical development between month 5-7 gestation; may be due to severe trauma, vascular occlusion, infection
  • May be asymptomatic; often associated with MR, epilepsy, other malformations (e.g., polymicrogyria)
  • Gyri often form radial patterns around cyst

STENOSIS OF THE AQUEDUCT OF SYLVIUS

  • Obstruction of the aqueduct and CSF circulation
  • Evidence for familial transmission
  • Often insidious onset of symptoms associated with hydrocephalus
  • Shunted children may have learning/behavioral problems; nonverbal IQ worse than VIQ

NEUROMIGRATIONAL DISORDERS (NMD’S) (malformations of the cerebral cortex et al.)

Disorders due to errors in the development of the brain (cells migrating incorrectly)

LISSENCEPHALY (AGYRIA – absent gyri, smooth cortical surface/PACHYGYRIA – few, course gyri)

  • Disorders of cell migration; arrest of migration of neuroblasts from periventricular matrix to cortex
  • Characteristic facial appearance: prominent forehead, short nose, protuberant upper lip, and small jaw
  • Associated with agenesis of CC, micrencephaly, epilepsy, severe growth and developmental retardation, decreased spontaneous activity; early death due to intercurrent disease common
  • May have difficulty swallowing or eating; may respond minimally to visual or auditory stimuli
  • Seizures

POLYMICROGYRIA

  • Development of many small gyri
  • Possibly due to focal necrosis during neuroblast migration between 5-6 months gestation
  • Associated with LD (dyslexia), severe MR, epilepsy; may be asymptomatic

FOCAL DYSPLASIA (heterotopias)

  • Focal abnormalities of the cortical cytoarchitecture; areas of disordered layering and displaced cells
  • Disruption of neuroblast migration
  • Reported in pts with epilepsy and LD

MEGALENCEPHALY

  • Refers to a large head (circumference > 2 SD’s above the mean)
  • Involves increased numbers of neurons and glia.
  • Typically mentally retarded, but may be mild

SCHIZENCEPHALY

  • Characterized by clefts in parasylvian region and in precentral/postcentral gyri of one or both hemispheres
  • Often accompanied by hydrocephalus, mental retardation and significant motor handicap

AGENESIS OF THE CORPUS CALLOSUM

  • Failure (complete or partial) of CC to develop; <.7% incidence
  • Evidence for familial transmission
  • Interruption of normal embryogenesis at 12-22 weeks gestation
  • Increased incidence in schizophrenics; and is seen in association with spina bifida, facial and ocular deformities, micrencephaly, megalencephaly, hydrocephalus, Dandy-walker Syndrome and Leigh’s syndrome; epilepsy and MR may occur; may see EEG abnormalities
  • Can follow intrauterine exposure to toxins (e.g., FAS)
  • Associated with specific, but different patterns of neuropsychological deficits including:
    • Visual spatial deficits
    • Impaired syntactic ability (comprehending, producing or repeating complex sentences)

NEUROCUTANEOUS DISORDERS

  • Embryologic defects in the ectoderm
  • Often include abnormalities of other ectoderm and nonectoderm organs
  • Most are inherited in an autosomal dominant pattern
  • Usually stable through adulthood, though cerebral lesions may undergo malignant transformation

TUBEROUS SCLEROSIS

  • Smooth and firm nodules on malar surface of face (adenoma sebaceum or facial angiofibromas) don’t appear until adolescence
  • Infancy and childhood – subtle hypopigmented areas on skin, scaly lesions on trunk (shagreen patches), and periungual fibromas of the fingers
  • Classic Triad (occurs in minority): epilepsy (usually intractable), MR, hypopigmented areas or adenoma sebaceum; includes speech and language delays
  • Some eventually decline to the point of dementia; some have autistic features – overall, highly variable (partly attributable to location of abnormal gene – chromosome 9 or 16)
  • CNS correlate of skin lesions are cerebral tubers (“potato-like brain nodules”) – cause epilepsy and cognitive impairment; may become malignant; may develop retinal, renal, cardiac tumors

NEUROFIBROMATOSIS

  • NF Type I (aka von Recklinghausen’s disease, or “peripheral type” NF)
    • Inherited on chromosome 17 in autosomal dominant pattern; though often (upto 50%) arises spontaneously
    • Classic Triad: café au lait spots, neurofibromas (emerge along peripheral nerves; may reach grotesque proportions), Lisch nodules (multiple, asymptomatic, macroscopic, melanocytic hamartomas on the iris – pathognomonic) (brain hamaratomas often observed on imaging)
    • Also involves intracerebral tumors (e.g., astrocytomas, optic nerve gliomas)
    • High association with ADHD and LD (1/3-2/3 of affected children); lower IQ
  • NF Type II (aka familial acoustic neuroma, or “central type” NF)
    • Bilateral acoustic neuromas (hallmark) that impair hearing until deaf
    • Inherited on chromosome 22 in autosomal dominant pattern
    • May manifest meningiomas; mental impairment only if they compress critical brain region

STURGE-WEBER SYNDROME (aka encephalo-trigeminal angiomatosis)

  • Facial (port wine stain in region of trigeminal nerve) and cerebrovascular malformations
  • NO known genetic basis
  • Cerebral component – calcified vascular region accompanied by atrophy in one hemisphere
  • Tend to have MR, LD, behavioral disturbances, refractory epilepsy; may also have focal physical deficits depending on site of lesion
  • Presence of seizures associated with much poorer prognosis

ATAXIA-TELANGIECTASIA

  • Inherited in a recessive pattern; abnormality on chromosome 11 – interferes with DNA repair
  • Consistently associated with immunodeficiency (little or no IgA or IgE)
  • First manifestations – chronic sinus and respiratory tract infections; later, lymphomas and neoplasms
  • Neurologic manifestations at age 3-5: progressive ataxic gait (due to degeneration of cerebellar vermis)
  • Develop cognitive impairments
  • Cutaneous component – small dilated vessels (telangiectasia) on conjunctiva, nose bridge, and cheeks

DISORDERS DUE TO GENETIC AND CHROMOSOMAL ANOMALIES

Remain stable post-puberty; do not cause signs of white matter disease (leukodystrophies), do not cause metabolic storage disease

Genetic imprinting – when the same autosomal dominant abnormality produces different syndromes depending on whether it is transmitted from mom or dad (as in Prader-Willi and Angelman syndromes)

AUTOSOMAL CHROMOSOMAL DISORDERS

DOWNS SYNDROME

  • 1:600 births
  • Trisomy 21 (3 chromosomes or parts of chromosomes instead of two – the entire chromosome 21 is not required; it is possible that the variation in the amount of chromosome is related to the variability of the cognitive deficits)
  • Risk increases with maternal age
  • Affects organ systems (e.g., may have increased risk for congenital heart defect); alters antibody rxn to vaccine; increased risk for otitis media; increased risk of leukemia and seizures
  • Alzheimer’s is invariably found over the age of 40 (increased risk from age 10 on! 15% of those from 10 – 20; 36% in those 21 – 30 yrs; 100% if over 30)
  • Mean IQ is approximately 44.3; range from mild to moderate MR
  • Visuospatial abilities are generally preserved and language is impaired; motor delays; intact social skills
  • Difficulty processing sequential information

PRADER-WILLI SYNDROME (chromosome 15 – get this disorder if passed from father “Prader-Willi is passed in a paternal pattern”) ~ although some cases are sporadic

  • Due to a deletion in a chromosome
  • Obese, voracious appetites (hyperphagia); poorly controlled food-seeking behavior (will steal food from classmates, rummage through garbage, etc.) and they gain wait at an accelerated rate (doesn’t appear until the preschool years; prior to this they are pleasant and not obese); short stature, hypogonadism
  • Outbursts of aggressive, angry behaviors; some repetitive, compulsive skin picking
  • Mental retardation, obsessive-compulsive personality, decreased sensitivity to pain
  • Major language production deficits (affect articulation)

ANGELMAN SYNDROME (“Happy Puppet”) (chromosome 15 – get this disorder if passed from mother)

  • Rare (also due to a deletion in chromosome)
  • Associated with motor and severe mental retardation, microcephaly, epilepsy
  • Stereotyped involuntary and jerky-ataxic voluntary movements, smiling face, paroxysms of unprovoked laughter
  • Appear to be normal at birth but rapidly drift off developmental course
  • Speech is limited to a few words at best but can communicate with gesture
  • Hyperactive
  • Girls are sometimes misdiagnosed as Rett’s syndrome (MR, microcephaly, involuntary movements); others may be diagnosed as autistic

WILLIAMS SYNDROME (chromosome 7)

  • Minute deletion on 7 which disrupts elastic properties of arteries, root of aorta, skin, and other organs
  • Characteristic elfin face; facial features become more prominent with age
  • No gross neurological abnormalities, though motor delays and fine and gross motor clumsiness
  • Mild to moderate MR; impaired reading and writing; visuospatial deficits; difficulty w/nonverbal tasks
  • Inexplicably, extraordinary talents in music (gifted) and verbal fluency (though devoid of substance)

PKU (chromosome 12)

  • Amino acid metabolism disorder; autosomal recessive
  • Aminoacidurias (another aminoacidurias is maple syrup urine disorder which can also be treated with diet)
  • Prevents normal metabolism of phenylalanine to tyrosine; prevents normal synthesis of dopamine, subsequent neurotransmitters, and melanin; phenylketones are excreted in urine
  • Untreated leads to severe MR, decreased attention, lack of responsiveness to environmental stimuli, seizures, spasticity, hyperactive reflexes, tremors, “psychiatric illness”
  • Treatment diet (no phenylalanine) leads to short stature and weight, anemia, and hypoglycemia
  • Even when treated, tend to show executive deficits, ADHD symptoms and below average IQ

SEX-LINKED CHROMOSOMAL DISORDERS

x-linked disorders – may be rare in females if it is a recessive trait unless there is a mutation in the other X (or if they both contain the disorder); if it is dominant it will be expressed in both genders

FRAGILE-X SYNDROME

  • 2nd most common form of mental retardation (second to Down Syndrome); most common inherited form (responsible for as much as 10% of all MR cases)
  • Trinucleotide (CGG) repeat in defective gene; people with >200 repeats are invariably affected; size of repeat increases with successive generations which results in earlier onset (“anticipation”) and more pronounced symptoms
  • Fragile-x males (1:1500) –
    • Head circumference and weight > peers; by adulthood only the head remains large; elongated face; enlarged testicles
    • IQ ranges from normal to profoundly mentally retarded (70% moderate to severe MR; 20% seemingly normal); studies suggest IQ declines b/t childhood and adulthood
    • Tend to plateau with regard to their ability to learn more complex and abstract information, typically during early puberty
    • Dysfluent, apraxic speech, echolalia, palilalia and cluttering are characteristic; receptive language relatively preserved
    • Frequent behavioral abnormalities, including ADHD; also, LD, mood disorder, repetitive purposeless involuntary movements, autism, PDD (15%)
  • Fragile-x females (1:3000) –
    • In contrast to other sex-linked disorders, 1/3 of female carriers express some of its characteristics
    • Often lack dysmorphic features seen in males
    • Specific frontal lobe deficits have been seen
    • No evidence of right hemispheric impairment, dyslexia or short-term verbal memory deficit; but another book states there is!! (e.g., problems with spatial skills and math)
    • Attention deficits, distractibility, shyness, impaired organizational skills and difficulty with transitions
    • IQ – 80’s to 100; often below 85
    • Behavioral abnormalities (see above) less common than in boys

RETT’S SYNDROME

  • Females only; abnormality assumed lethal in males
  • Onset begins after about 6 months of normal development, then regress in all areas of psychomotor development over several years until no language, walking, cognitive capacity, etc.
    • profound MR
  • Two virtually unique physical characteristics: stereotypies (often incessant hand clapping and wringing) and acquired microcephaly (after 6 months of normal growth)
  • 50% have seizures
  • Shares features with autism, but also have progressive loss of motor ability and develop microcephaly
  • Of note: Rett’s, Angelman’s and Fragile X should all be differentials for autism

KLINEFELTER’S SYNDROME (XXY)

  • Seen in males
  • Tall stature, but “eunuchoid” after puberty (often diagnosed after puberty, sometimes in context of fertility workup – sterile, testicular dysgenesis)
  • In general, IQ below average (80-90); 25% have some degree of MR (usually mild)
  • Tend to have dyslexia and LD
  • Some describe as “passive” or with decreased libido

TURNER’S SYNDROME (XO)

  • Seen in females (often associated with miscarriage; only 1% of affected fetuses are born)
  • Due to various genetic defects; missing X chromosome (XO), some are XO/XX mosaics
  • Dysmorphic features – small stature, poorly developed secondary sex characteristics, sexual dysfxn in puberty/adulthood, webbed neck, broad chest, deformed bend in forearm, low set hairlines, low set ears and atypical facies; usually no neurological abnormalities
  • Do not have a consistent npsych profile; considerable heterogeneity in the profile and severity; MR is rare or mild (20% have mild)
  • Verbal strengths contrast with nonverbal; visuospatial deficits are common (PIQ<VIQ is usual; but 10 – 20% show the opposite); typically show a pattern consistent with NVLD
  • Math difficulty is common; social deficits and impaired facial recognition; at risk for NVLD; some say striking deficits in perception of form and space; may see LD and ADD
  • May have anxiety/depression

XYY SYNDROME

  • Extremely tall; severe acne persists beyond adolescence
  • Cerebral development may include migrational abnormalities and maturational delays
  • Tendency toward higher activity levels, more negative mood and temper tantrums have been noted
  • Historically, research on “supermales” conducted in prisons, and indicated deviant, violent, aggressive behavior, but, obviously, ascertainment bias
  • Modern studies: delayed speech acquisition and other neurodevelopmental milestones, characterologic problems, psychiatric difficulties, average to below normal IQ; legal/medical now reject relationship between XYY and violent criminal behavior

LESCH-NYHAN SYNDROME

  • X-linked disorder
  • Self-injurous behavior
  • Extrapyramidal involvement
  • Behavioral disturbances
  • Neuropsych presentation is variable

DEGENERATIVE DISORDERS

LEUKODYSTROPHIES (LD)

  • Rare group of genetic disorders which involve the destruction of CNS white mater (may also affect PNS)
  • Like MS, can also cause optic nerve, cerebellum, and spinal cord demyelination
  • Usually manifest as infants, but sometimes not until teens or young adults
  • Unremitting physical and mental deterioration

ADRENAL LEUKODYSTROPHY

  • X-linked, recessive
  • Typically first produces neurologic symptoms and adrenal insufficiency in boys between 5 and 15 years
  • Occasionally develops in men aged 20-30 yrs, then associated by mania, gait impairment, and eventual dementia
  • “Lorenzo’s Oil” – reduces the accumulation of VLCFA’s, but DOES NOT alter the disease course
  • similarly, treatment by adrenal hormone replacement does not arrest the demyelination

DISORDERS DUE TO INFECTION/INTOXICATION

  • Prenatal infections can lead to severe MR, convulsions, micro- or hydrocephalus
  • Maternal infections with psychological consequences: syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes simplex, mumps, hepatitis, chicken pox (“STORCH”)

RUBELLA

  • Low birth weight, meningoencephalitis, psychomotor and MR, cataracts/retinopathy, abnormalities of heart and major blood vessels

CYTOMEGALOVIRUS

  • One of most common intrauterine infections
  • Enlargement of spleen and liver, intrauterine growth retardation, various congenital malformations, damage to visual and auditory systems, microcephaly, MR

INTOXICATION

  • Kernicterus, bilirubinemia (secondary to blood-type incompatibilities between mother and fetus), FAS

NUTRITIONAL DISORDERS

  • Protein-calorie malnutrition is a major problem worldwide
  • Protein/lipid deficiencies are developmental disorders with problems of myelination
  • Following two disorders are commonly combined rather than presenting separately

KWASHIORKOR

  • Protein deficient diet

MARASMUS

  • Calorie deficient diet

ANOXIC EPISODES

  • Period around time of birth is time of greatest risk
  • Premature infant at particularly high risk because it is essentially unprepared for birth
  • May lead to MR, motor deficits, seizures, CP
  • Neurobehavioral sequelae vary depending on type of damage; in some cases, there is no sequelae

BRAIN INJURY AND NEOPLASM

  • Perinatal mechanical damage can lead to intracranial hemorrhage and CNS tissue damage
  • Head injury from falls, MVA, abuse
  • >60% of all childhood cerebral neoplasms and >75% of all intracranial tumors are gliomas (i.e., glial cell tumors – e.g., astrocytoma, medulloblastoma, ependymoma)

CONVULSIVE DISORDERS

NEONATAL SEIZURES

  • First week of life
  • Most frequent neonatal neurological emergency
  • Usually result of serious perinatal conditions (e.g., anoxic episodes, hemorrhage)

INFANTILE SPASMS

  • Peak between 4-6 months
  • Characterized by spasms, severe MR, markedly abnormal EEG
  • Poor prognosis
  • Important to differentiate from reflux (as may look similar at first glance)

FEBRILE SEIZURES

  • Typically occur 6 months-5 years
  • Little lasting effects with single seizure

EPILEPSY

  • Etiology may be trauma plus all pre-, peri-, and post-natal disorders (e.g., metabolic d/o, infection, anoxic episode)

Miscellaneous Info

  • Insulin-Dependent Diabetes – onset < 7years old and chronic course (>5 years) more likely to show reading and memory difficulties and slow response times
  • Brain dysfunction in children is associated with increased risk of psychiatric disorder, and vice versa; specifically, perinatal cerebral injuries constitute at least a weak risk factor for schizophrenia