B7.047 Neurodevelopmental Disorders

Question 1

classes of neurodevelopmental disorders

Answer 1

1. affecting cognition
   - intellectual disability (mental retardation)
   - autism (socialization disability)
2. affecting motor function
   - cerebral palsy
3. disease acquired in childhood

Question 2

characterize encephalopathies acquired during childhood

Answer 2

lesion: brain
manifestations: vary
etiologies: anything that can damage the brain during childhood

Question 3

definition of intellectual disability

Answer 3

intelligence substantially below average
important limitations in adaptive function
-difficulty coping with life demands
onset before age 18
IQ < 70 (2.5% of population)

Question 4

description of IQ

Answer 4

average = 100
standard deviation = 15
< 70 is 2 SDs below normal

Question 5

severity of intellectual disability

Answer 5

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

Question 6

cause of intellectual disability

Answer 6

unknown in 33%
common causes:
genetic
-downs (trisomy 21)
-fragile x (boys > girls)
-rett syndrome (girls)
malnutrition
toxin exposure: lead
neonatal injury

Question 7

definition of autism

Answer 7

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

Question 8

autism spectrum disorder

Answer 8

included people with more mild forms that may have been detected after age 3

Question 9

lifelong nature of autism

Answer 9

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

Question 10

epidemiology of autism

Answer 10

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

Question 11

theory of mind

Answer 11

humans understand mental state of others

explain and predict behaviors of others

Question 12

lack of mutual attention

Answer 12

faces preferred over objects

abnormal gaze in social situations (don’t focus on eyes like people without autism)

Question 13

presentation of autism

Answer 13

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

Question 14

where is the pathology in autism

Answer 14

no specific pathological change
functional imaging defects:
-orbitofrontal cortex
-anterior cingulate cortex
-amygdala

Question 15

cause of autism

Answer 15

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

Question 16

characterize cerebral palsy

Answer 16

encephalopathy (brain lesion)
acquired early (before age 3)
manifested by disorder of movement or posture

Question 17

static nature of CP

Answer 17

brain lesion does not progress

clinical manifestations can progress as child and nervous system mature

Question 18

prevalence of CP

Answer 18

2-2.5 per 1000 birth worldwide

10,000 babies born in US per year

Question 19

classification of CP

Answer 19

based on motor manifestations
spastic (UMN)
ataxic (cerebellar)
dyskinetic (basal ganglia)
hypotonic

Question 20

symptoms of spastic CP

Answer 20

most common
spasticity
hyperreflexia
upgoing toes

Question 21

symptoms of dyskinetic CP

Answer 21

rigidity
abnormal involuntary movements: choreoathetosis
difficulty with voluntary motor control

Question 22

patterns of spastic CP

Answer 22

spastic diplegia (legs only, most common)
spastic hemiplegia
spastic quadriplegia

Question 23

symptoms of ataxic CP

Answer 23

least common
severe appendicular and gait ataxia
vermian system defect

Question 24

signs of CP in general

Answer 24

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

Question 25

findings associated with CP

Answer 25

30-50% have intellectual disability communication may be impaired expression of intellectual capacity may be difficult 15-60% have epilepsy

Question 26

etiology of CP

Answer 26

``` any prenatal, perinatal, or postnatal event affecting the brain multiple risk factors: -preterm birth -multiple gestation -male sex -low apgar -intrauterine infection -birth asphyxia ```

Question 27

clinical manifestations of early brain injury (non genetic)

Answer 27

because brain is not fully functional at time of insult, the sequelae become obvious only with time hypotonia (floppy baby)

Question 28

major events in brain development

Answer 28

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

Question 29

what is the germinal matrix

Answer 29

area of developing brain located in the subependyma of the ventricular walls

Question 30

function of germinal matrix

Answer 30

at 8-28 weeks gestation, the matrix produces neurons and glial cells, which migrate to populate the cerebral cortex -neurons earlier, glial cells later

Question 31

involution of germinal matrix

Answer 31

begins late in second trimester | nearly complete by 32 weeks gestation

Question 32

structure of germinal matrix

Answer 32

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

Question 33

pathogenesis of germinal matrix hemorrhage

Answer 33

- poor autoregulation of blood flow and blood pressure - thin microvasculature is susceptible to rupture - fluctuations in blood pressure injure vessels leading to hemorrhage

Question 34

result of germinal matrix hemorrhage

Answer 34

hypo-perfusion and hypoxia can lead to infarction | hemorrhage can occur in infarcted regions after reperfusion as well

Question 35

discuss the vulnerability of premature infants to germinal matrix hemorrhage

Answer 35

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)

Question 36

selective vulnerability of brain to hypoxia

Answer 36

brain is most oxygen dependent organ | within minutes of oxygen deprivation, permanent damage results

Question 37

mechanisms of ischemic injury of brain

Answer 37

pure hypoxia pure hypo-perfusion mixed

Question 38

what is a watershed zone

Answer 38

last area where blood perfuses | if a circulation problem occurs, these zones don't get enough oxygen and typically suffer first

Question 39

watershed zones of the brain preterm

Answer 39

periventricular region | -watershed between penetrating arterial vessels from the cortex and vessels arising from deep ventricular margins

Question 40

watershed zones of the brain after term

Answer 40

area between ACA and MCA | area between PCA and MCA

Question 41

periventricular leukomalacia (PVL)

Answer 41

second most common CNS complication in preterm infants | caused by ischemia in the preterm watershed territory

Question 42

regions most commonly affected in perinatal vascular insult

Answer 42

optic radiations trigone of corpus callosum frontal periventricular region

Question 43

regions affected by PVL

Answer 43

corticospinal tract sensory association fibers visual tract auditory tract

Question 44

effects of ischemia on oligodendroglia

Answer 44

myelination is impaired

Question 45

selective vulnerability of fibers to the leg to periventricular pathology

Answer 45

leg portion of the cortices (based on homunculus) is closest to the periventricular region, thus most susceptible to issues there

Question 46

spastic diplegia in premature infants

Answer 46

may result from parenchymal-intraventricular hemorrhage or periventricular leukomalacia no risk factors identified in term infants

Question 47

vascular injuries after term

Answer 47

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

Question 48

pure hypoxia vulnerability of brain

Answer 48

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

Question 49

kernicterus

Answer 49

bilirubin induced neuro dysfunction primarily premature infants with very high bilirubin uncommon can lead to dyskinetic CP