Brain development & childhood disorders Flashcards
Fetal alcohol syndrome diagnosis requires abnormalities in what 3 domains?
Growth deficiency, specific pattern of facial anomalies, evidence of CNS dysfx
Klinefelter syndrome
Extra X chromosome XXY VIQ
Neimann-Pick disease Type C
Seizures, gradual onset of dementia, motor abnormalities, mortality by age 40; includes diffuse atrophy with NFTs throughout cerebral cortex & cerebellum
From what germ cell layer do the meninges arise?
Mesoderm
Neuropsychological outcomes of spina bifida
Motor speech deficits, lower than expected overall cognitive ability, nonverbal < verbal, deficits in reading & listening comprehension likely due to difficulties in making inferences, explicit memory deficits, difficulty w/ attentional control, higher rate of behavioral problems, problems with self-esteem, & adaptive bx
If perinatal stroke is large, how does the brain compensate?
Rely on small portion of corticospinal tract that does not cross (uninjured hemisphere to paretic limb)
Periventricular leukomalacia
Injury in the periventricular white matter; can affect migration of fibers to the cortex
If perinatal stroke is small, how does the brain compensate?
Show intact crossing of corticospinal connections from injured hemisphere to paretic limb
Primary processes responsible for brain damage in VLBW/VPTB
hypoxic ischemia w/ associated deprivation of oxygen & glucose, exposure to fetal & maternal infection
Full-term perinatal stroke is most commonly seen in the distribution of what artery? Pre-term perinatal stroke is more often associated with?
MCA; periventricular hemorrhagic infarctions
Migration
Neuroblasts move to permanent location via radial glia; problems can lead to neurons in the wrong layer of the brain, abnormal connections
Ataxia-telangiectasia
Abnormality on chromosome 11 that interferes with DNA repair Progressive ataxic gait due to degeneration of cerebellar vermis; develop telangiectasis of the conjunctiva , chronic sinus & respiratory infections
Patau syndrome
Trisomy 13; Microcephaly & sloping head, lowest ears, cleft lip & palate, impaired hearing, severe MR, death in early childhood
Neurobehavioral outcome in patients with VLBW/VPTB
Deficits in motor/perceptual motor, exec dysfx, problems in math & sometimes reading, attention, memory
Effects of lead poisoning in children (blood lead concentrations exceeding 60-80 pg/dL)
Early symptoms - abdominal pain & arthralgia Progressive encephalopathy characterized by lethargy, anorexia, irritability, ataxia, loss of mental developmental milestones Doss-related declines in IQ, particular effects on attention/exec fx & visuospatial skills
Effects of prenatal maternal stress on cognition & behavior
LBW, hyperactive, irritable, irregular feeding, sleeping, bowel movements, crying
Angelman syndrome
Due to deletion on chromosome 15 inherited from mother Stereotyped involuntary & jerky-ataxic voluntary movements, smiling face, paroxysms of unprovoked laughter Assoc. w/ motor & severe MR, microcephaly, epilepsy
Pruning
Elimination of neuronal overproduction
Megalencephaly
Large head circumference (>2 SDs above the mean); involves increased #s of neurons & glial Typically MR, but may be mild
Common brain abnormalities associated with VLBW/VPTB
hemorrhagic infarctions associated with germinal matrix IVH, ventriculomegaly, periventricular leukomalacia
3 stages of Piaget’s constructivism
1) Sensorimotor (0-2): object permanence, causality, symbolic/representational thought 2) Preoperational (2-7): limited by magical thinking, animism, egocentrism, lack of conservation 3) Concrete Operational (7-11): learn conservation, reflective self 4) Formal Operational (11+): abstraction, relativism, hypothetical-deductive reasoning
Polymicrogyria
Development of many small gyri; associated with LD, severe MR, epilepsy
XYY syndrome
Tendency toward higher activity levels, more negative mood, temper tantrums Delayed speech acquisition & other neurodevelopmental milestones, psych difficulties, avg-below normal IQ
Describe the pattern of CNS development (i.e., direction)
Head -> tail (cephalic -> caudal); near -> far (proximal -> distal), inferior -> dorsal (subcortical -> cortical)
Agenesis of the corpus callosum is associated with an increased incidence of what psychopathology?
Schizophrenia
What are some influences on prenatal brain development?
Physiology of egg & sperm, intrauterine environment, genetic transmission, errors, mutations, mother’s stress hormones & self-care behaviors
Sturge-Weber syndrome
Facial (port wine stain in region of CN V) & cerebrovascular malformations Tend to have MR, LD, behavioral disturbances, refractory epilepsy, may also have focal deficits depending on sit of lesion
Hurler syndrome (MPSI)
Autosomal recessive disease with genetic abnormality on chromosome 4, results in glycosaminoglycans (GAGs) not being degraded properly by lysosomes
Neurobehavioral consequences of prenatal exposure to rubella
Classic triad: heart disease, vision problems, hearing loss
Cranium bifidum & encephalocele
Skin-covered brain, meninges, or CSF protrudes through the skull defect
Spina bifida affects the development of the brain in what 2 major ways?
1) failure of neuroembryogenesis results in anomalies in the regional development of the brain 2) children w/ myeloceningocele experience additional injury to the brain b/c of hydrocephalus & its treatment
How is language development affected by perinatal stroke?
Order of emergence of skills remains the same but demonstrate delays at each new level of linguistic challenge regardless of which hemisphere is involved In RH stroke, LH remains dominant; B representations emerge in LH stroke
Prader Willi syndrome
Deletion on chromosome 15 inherited from father Obese, hyperphagia, poorly controlled food-seeking behavior, MR, OC personality, major language production deficits, hypogonadism, outbursts of aggressive behavior
2 types of periventricular leukomalacia
Cystic (lesions around ventricles), noncystic (WM injury)
What portion of children with myelomeningocele are missing one or more parts of the corpus callosum?
about 1/2
Untreated PKU leads to
Severe MR, decreased attention, lack of responsiveness to environmental stimuli, seizures, spasticity, hyperactive reflexes, tremors, psych illness
What are the 4 major concurrent aspects of cytodifferentiation?
1) Development of cell body 2) Selective cell death (40-75% of all neurons die during development) 3) Axonal & dendritic development 4) Synaptogenesis
Williams syndrome
Disruption of elastic properties of arteries, root of aorta, skin, & other organs No gross neuro abnormalities but motor delays & fine & gross motor clumsiness; mild-mod MR; imparied reading & writing, visuospatial deficits, difficulty w/ nonverbal tests
Duchenne muscular dystrophy
Absence of dystrophin in muscle; associated with mild MR
White matter abnormalities associated with perinatal stroke
Decreased CC size related to sections that would have connected the affected site to the other hemisphere, decreased white matter volume in uninjured hemisphere
Which part of the brain is last to be myelinated?
Prefrontal areas
Cerebellum development follows a ______ pattern
Outside-in
In what ways can treatment for childhood cancer effect the CNS?
Cortical atrophy, leukoencephalopathy, mineralizing microangiopathy
When do neural tube defects occur?
3-4 weeks gestation
Risk factors for childhood psychopathology
Severe marital discord, low SES, overcrowding, parent criminality, maternal psychopathology, child placed outside the home
Dandy-Walker malformation
Posterior portion of the upper neural tube fails to develop, child is born with rudimentary posterior brain structures; frequent severe mental retardation
What maternal infections have significant effects on prenatal development?
Syphilis, toxoplasmosis, rubells, cytomegalovirus, herpes simplex, mumps, hepatitis, chicken pox
Lissencephaly
Agyria or pachygyria caused by arrest of migration of neuroblasts from periventricular matrix to cortex Assoc. w/ severe growth & developmental retardation, decreased spontaneous activity, difficulty swallowing or eating, minimal response to visual or auditory stimuli
Tay Sachs disease
Lysosomal storage disorder Primarily affects Ashkenazi Jews
Neimann-Pick disease Type B
Visceral form, little to no neuro involvement, survival into teens or early adulthood
NP deficits associated with childhood cancer treatment
10 pt drop in IQ; nonverbal < verbal; arithmetic < reading; nonverbal memory < verbal memory, attention problems, difficulty focusing & planning responses, exec deficits, diminished response time & motor speed
Even when treated, patients with PKU may show
Exec fx deficits, ADHD symptoms, < avg IQ
Spina bifida occulta
Occurs when vertebral arches fail to close, resulting in an opening in the spine but no other abnormalities in spinal cord or sac; may be present in at least 5% of the general population
Which subtype of cerebral palsy is most closely related to prematurity?
Spastic paresis
What is the age of peak incidence of acute lymphoblastic leukemia
3-5 years
Neurofibromatosis Type II
B acoustic neuromas that impair hearing until deaf
Bronfenbrenner’s ecological model
Microsystem (family, school) Mesosystem (microsystems interacting) Macrosystem (environment/society) Exosystem (environmental influences on microsystem)
Hallmark feature of fetal alcohol exposure
Attention deficit; also see exec fx deficits throughout lifespan
Porencephaly
Large cystic lesion develops due to disturbed cortical development between months 5-7 gestation
Cognitive profile of Down’s syndrome
Mean IQ ~ 44.3 Visuospatial abilities generally preserved & language impaired, motor delays, intact social skills, poor memory
When to brain divisions occur in the embryo?
5-7 weeks
Acute disseminated encephalomyelitis
Acute demyelinating disease that typically follows infection
Critical periods
A window of opportunity during which skills need to be consolidated so that that particular system can then establish interconnections with other systems
Aggregation
Cellular masses or layers are formed by lamination, w/ neurons adhesing together or aligning with neighbors
Tuberous sclerosis
Sclerotic masses (scarring due to glial overgrowth) form in cerebral cortex, usually resulting in MR & epilepsy; also results in adenoma sebaceum (nodules on face)
Resiliency factors against childhood psychopathology
Reduced stress, easy temperament, stable support
Cerebral hemisphere development follows a ______ pattern
inside-out
What complications/disabilities are associated with cerebral palsy?
MR, cognitive dysfx, epilepsy, vision/hearing impairments, LD, language disorders, psych problems, pseudobulbar palsy, hyperactivity
Lesch-Nyhan disorder
Inborn error of purine meatbolism leading to increased levels of uric acid in blood & urine MR in most, movement disorder including choreoathetosis & spasticity, self mutilation
Stages of prenatal brain development
Proliferation, migration, aggregation, cytodifferentiation, pruning
Cerebral palsy
Permanent, nonprogressive neurologic motor system impairment resulting from CNS injuries of the immature brain
3 main processes for CNS elaboration
Dendritic arborization, myelination, synaptogenesis
Presentation of cri-du-chat syndrome
Abnormal cry like a kitten, severe MR, epicanthal folds, moon face
Which subtype of cerebral palsy is less likely to be associated with epilepsy or MR?
Extrapyramidal
Teratogens
Substances that can cross the placenta and lead to birth defects
Meningocele
Malformation in which the meninges alone herniate through the spinal defect, creating a sac that is filled with cerebral spinal fluid; can affect ambulation, bladder/bowel control
Neurobehavioral consequences of prenatal cocaine exposure
Small for gestational age, seizures, LBW, exaggerated startle, increased tone & motor activity, impaired fine motor coordination, auditory impairments, high-pitched cry, sleep & feeding problems, difficulty to comfort, developmental delays, bx & attentional problems
Acute lymphoblastic leukemia
Cancer of blood-forming cells in bone marrow
Two subtypes of cerebral palsy
Spastic paresis (most common), extrapyramidal
Proliferation
Cell generation by mitosis inside the neural tube; problems can lead to fewer neurons at the beginning of life (e.g, MR)
Global cognitive & academic deficits associated with VLBW/VPTB
Low average range, higher rates of grade retention & sped, internalizing & externalizing behavior, smaller than peers
Neurofibromatosis Type I
Triad of cafe au lait spots, neurofibromas, & Lisch nodules Assoc. w/ LD & ADHD, MR-avg IQ, deficits in language, reading, spelling, exec fx, visuospatial, visuomotor skills
Effects of low-level prenatal lead exposure
Mild growth retardation in utero & mild developmental delay up to ages 1-2, recovery by school age
What are the three main processes for CNS elaboration?
Dendritic arborization, myelination, synaptogenesis
Turner’s syndrome
XO; no consistent NP profile, but at risk for NVLD; small stature, poorly developed secondary sex characteristics, sexual dysfx in puberty/adulthood, webbed neck, broad chest
Edwards syndrome
Trisomy 18; slow growth, seizures, severe MR, lowest ears, mottled skin, clenched fist with 3rd finger over index finger, death in early infancy
How is visual pattern processing affected by perinatal stroke?
Do not show progression from piecemeal to global-local integration at 10-12 years old RH stroke = retention of details/local characteristics but no global characteristics; LH stroke = retention of global characteristics w/ paucity of details
CNS abnormalities seen in Turner’s syndrome
Increased ventricular volume, increased CSF, decreased gray matter & white matter in parietal/occipital lobe
Risk factors associated with childhood cancer treatment effects
Age (
Leukodystrophies
Inherited deficiency of a specific enzyme; abnormalities interfere with enzyme or protein synthesis; results in buildup of neurotoxins in the brain
Clinical presentation of acute disseminated encephalomyelitis
Confusion, somnolence, seizures, fever, stiffness of neck, ataxia, myoclonus, choreoathetosis
Heterotopias
Focal abnormalities of cortical cytoarchitecture; areas of disordered layering & displaced cells Reported in patients with epilepsy & LD
Which syndrome is often associated with extraordinary talents in music & verbal fluency?
Williams syndrome
Chiari II malformation
Small cerebellum & brainstem, herniation of cerebellum & portions of medulla & pons through an enlarged foramen magnum
Risk factors for negative outcome in VLBW/VPTB
Lower birthweight, younger gestational age, neonatal neurological complications of IVH & PVL, chronic lung disease, environmental disadvantages
Hydranencephaly
Cerebral hemispheres replaced by cystic sacs containing CSF
Environmental influences on development of spina bifida
Folic acid deficiency, maternal diabetes & obesity, maternal illness & hyperthermia
Neimann-Pick disease
Group of inherited disorders causing disruption in individual’s ability to metabolize cholesterol & other lipids
Rett’s syndrome
After 6 months of normal development, regression in all areas of psychomotor development over several years leading to profound MR, acquired microcephaly Abnormality is assumed lethal in males
What type of glia are involved in migration?
Radial glia & Bergmann glia
Neimann-Pick disease Type A
Severe neurological & physical deficits, death by age 4
Cytodifferentiation
Development of cells into different functions, formation of axonal & dendritic processes
Neurobehavioral consequences of prenatal narcotic exposure
Neonatal abstinence syndrome, LBW, small head, SIDS, childhood academic problems
Females with Fragile X syndrome present with
Relative strengths in verbal & facial recognition, relative weaknesses in visuospatial processing & exec fx
Myelomeningocele
Involves the protrusion of spinal cord along with the meninges through the spinal defect; more likely to be associated with severe brain abnormalities or major neurobehavioral deficits
Neuropsychological deficits associated with acute disseminated encephalomyelitis
Deficits in attention/concentration, memory, language, visuoperception, executive, and/or motor skills Can see global impairment after recovery with severe ADEM, assoc. w/ the extent of underlying neuropathology present
Effects of maternal cytomegalovirus on fetus
Enlargement of spleen & liver, intrauterine growth retardation, various congenital malformations, damage to visual & auditory systems, microcephaly, MR
