B7.047 Neurodevelopmental Disorders Flashcards
classes of neurodevelopmental disorders
- affecting cognition
- intellectual disability (mental retardation)
- autism (socialization disability) - affecting motor function
- cerebral palsy - disease acquired in childhood
characterize encephalopathies acquired during childhood
lesion: brain
manifestations: vary
etiologies: anything that can damage the brain during childhood
definition of intellectual disability
intelligence substantially below average important limitations in adaptive function -difficulty coping with life demands onset before age 18 IQ < 70 (2.5% of population)
description of IQ
average = 100
standard deviation = 15
< 70 is 2 SDs below normal
severity of intellectual disability
borderline: IQ 70 to 84
mild: IQ 50 to 69
- often not noticed until school
- reading and writing typical of a child aged 9-12
- often become independent
moderate: IQ 35 to 49
- delayed speech development
- usually require lifelong partial support
severe: IQ 20 to 34 or profound: IQ <20
- usually require lifelong support
cause of intellectual disability
unknown in 33% common causes: genetic -downs (trisomy 21) -fragile x (boys > girls) -rett syndrome (girls) malnutrition toxin exposure: lead neonatal injury
definition of autism
impaired socialization detected before age 3
-impaired social interaction
-impaired communication (verbal and non verbal)
-restricted interests with stereotyped behaviors
more than half with associated intellectual disability
autism spectrum disorder
included people with more mild forms that may have been detected after age 3
lifelong nature of autism
not progressive
special educational programs can lead to improvements with age
most with life-long difficulty in social situations
preferences for routine and restricted behavior patterns
epidemiology of autism
prevalence: 1%
increasing: may be due to changing definition, improved recognition, or a true epidemic
males > females
-overall 4:1
-within subset without intellectual disability (aspergers) 8:1
theory of mind
humans understand mental state of others
explain and predict behaviors of others
lack of mutual attention
faces preferred over objects
abnormal gaze in social situations (don’t focus on eyes like people without autism)
presentation of autism
parents first to notice by definition, changes before age 3 early socialization normal -gaze to faces -social smile -vocalization to others early manifestations 12-18 months -baby does not turn when called by name -does not attend to person or object of other people's attention more severe = earlier signs aspergers often not diagnosed until school age
where is the pathology in autism
no specific pathological change functional imaging defects: -orbitofrontal cortex -anterior cingulate cortex -amygdala
cause of autism
NOT a simple environmental exposure strong genetic component -10-15% have known genetic disease -monozygotic twins: 60-91% concordance -dizygotic twins: 10-30% concordance -polygenetic inheritance -many likely x-linked
characterize cerebral palsy
encephalopathy (brain lesion)
acquired early (before age 3)
manifested by disorder of movement or posture
static nature of CP
brain lesion does not progress
clinical manifestations can progress as child and nervous system mature
prevalence of CP
2-2.5 per 1000 birth worldwide
10,000 babies born in US per year
classification of CP
based on motor manifestations spastic (UMN) ataxic (cerebellar) dyskinetic (basal ganglia) hypotonic
symptoms of spastic CP
most common
spasticity
hyperreflexia
upgoing toes
symptoms of dyskinetic CP
rigidity
abnormal involuntary movements: choreoathetosis
difficulty with voluntary motor control
patterns of spastic CP
spastic diplegia (legs only, most common)
spastic hemiplegia
spastic quadriplegia
symptoms of ataxic CP
least common
severe appendicular and gait ataxia
vermian system defect
signs of CP in general
symptoms range from mild to severe lack of muscle coordination exaggerated reflexes (spasms) one foot or leg dragging difficulty swallowing, speaking difficulty with precise movements
findings associated with CP
30-50% have intellectual disability
communication may be impaired
expression of intellectual capacity may be difficult
15-60% have epilepsy
etiology of CP
any prenatal, perinatal, or postnatal event affecting the brain multiple risk factors: -preterm birth -multiple gestation -male sex -low apgar -intrauterine infection -birth asphyxia
clinical manifestations of early brain injury (non genetic)
because brain is not fully functional at time of insult, the sequelae become obvious only with time
hypotonia (floppy baby)
major events in brain development
primary neurulation- weeks 3-4 of gestation
prosencephalic development- months 2-3 of gestation
neuronal proliferation- months 3-4 of gestation
neuronal migration- months 3-5 of gestation
organization- month 5 to years postnatal
myelination- birth to years postnatal
what is the germinal matrix
area of developing brain located in the subependyma of the ventricular walls
function of germinal matrix
at 8-28 weeks gestation, the matrix produces neurons and glial cells, which migrate to populate the cerebral cortex
-neurons earlier, glial cells later
involution of germinal matrix
begins late in second trimester
nearly complete by 32 weeks gestation
structure of germinal matrix
metabolically active with a rich supply of blood via a thin, fragile capillary network
premature babies at risk of bleeding since germinal matrix is still present at birth
pathogenesis of germinal matrix hemorrhage
- poor autoregulation of blood flow and blood pressure
- thin microvasculature is susceptible to rupture
- fluctuations in blood pressure injure vessels leading to hemorrhage
result of germinal matrix hemorrhage
hypo-perfusion and hypoxia can lead to infarction
hemorrhage can occur in infarcted regions after reperfusion as well
discuss the vulnerability of premature infants to germinal matrix hemorrhage
most cases occur in first week of life for these infants (65%)
approximately 50% in first day of life
high risk: neonates born at <32 weeks’ gestation and with birth weights less than 1500 g
unusual after 34 weeks gestation (germinal matrix is gone)
selective vulnerability of brain to hypoxia
brain is most oxygen dependent organ
within minutes of oxygen deprivation, permanent damage results
mechanisms of ischemic injury of brain
pure hypoxia
pure hypo-perfusion
mixed
what is a watershed zone
last area where blood perfuses
if a circulation problem occurs, these zones don’t get enough oxygen and typically suffer first
watershed zones of the brain preterm
periventricular region
-watershed between penetrating arterial vessels from the cortex and vessels arising from deep ventricular margins
watershed zones of the brain after term
area between ACA and MCA
area between PCA and MCA
periventricular leukomalacia (PVL)
second most common CNS complication in preterm infants
caused by ischemia in the preterm watershed territory
regions most commonly affected in perinatal vascular insult
optic radiations
trigone of corpus callosum
frontal periventricular region
regions affected by PVL
corticospinal tract
sensory association fibers
visual tract
auditory tract
effects of ischemia on oligodendroglia
myelination is impaired
selective vulnerability of fibers to the leg to periventricular pathology
leg portion of the cortices (based on homunculus) is closest to the periventricular region, thus most susceptible to issues there
spastic diplegia in premature infants
may result from parenchymal-intraventricular hemorrhage or periventricular leukomalacia
no risk factors identified in term infants
vascular injuries after term
most often in the distribution of the middle cerebral artery, resulting in a spastic hemiplegic CP
also susceptible to hypo-perfusion, which targets watershed areas of the cortex resulting in spastic quadriplegic CP
pure hypoxia vulnerability of brain
BP is ok, but lung function not
areas a risk:
1. cerebral cortex: intellectual disability
-layer 3 (laminar necrosis)
-mesial temporal lobe (hippocampus)
2. basal ganglia (globus pallidus): dyskinetic CP
3. purkinje cells of the cerebellum: ataxic CP
kernicterus
bilirubin induced neuro dysfunction
primarily premature infants with very high bilirubin
uncommon
can lead to dyskinetic CP
