malformation and developmental diseases

Question 1

Pathogenic mechanisms

Answer 1

Malformation- intrinsic abnormality
Deformation- extrinsic force
Disruption- destructive force

Question 2

Deformation sequence

Answer 2

Renal ageneisis–> lack of urine into amniotic cavity, death from respiratory insufficiency, fetal compression, altered facies, abnormal positioning of hands and feet, breech presentation

Question 3

amniotic band disruction

Answer 3

wrap around organs and stuff

Question 4

normal development of the CNS

Answer 4

induction, neural tube formation, regionalization and specification, proliferation and migration, connection and selection

Very early in development (3-4 weeks) 3-4 months most of neurons in cerebral hemispheres0 6 latered cortex in 6 mothns

Myelination towards the end

Question 5

Development of the neural tube

Answer 5

tub closure early in gestation, closure occus first in thoracic, then head than face then cab of head and finally the cuadal end

failure of clousure–> ancephaly, spinabfida

Question 6

Oattern of cerebral myelination

Answer 6

posterior fronal lobes, than bottom (from top to bottom

Question 7

cytoarchitecture of cerebral cortex

Answer 7

the bottom layers are most susceptible to wwiered mixed architecture, if its messed up the person is susceptible to seizures, (the higher the malforamtion)

Question 8

Nueral tube defects

Answer 8

Most common category of CNS malformation, disturbance of formation of neuroectodermal and or overlying mesodermal strucutes

Trisomy 13, 18

Environment during pregnancy- folate deficiecny, maternal diabetes, hyperthermia, alcohol, valproic acid

Pathogenesis- failure of closure of neural tube- primary failure of neuroectoderm or mesoder, or reopening or secondary rupture of closed tube

Main categories (spina bfida, anencephaly, encephalocele

Question 9

Detection and prevention of Neural tube defects

Answer 9

failure of closure of the neural tube allows excretion of fetal substances (AFP, acetylcholinesterase) into the amniotic fluid

Diagnosable by ultrasound and/or prenatal screenin of maternal serum for AFP at 16-18 week

Maternal periconceptional use of folate reduces risk by 50%

Question 10

spina bifida

Answer 10

combined malformation of vertebral column and spinal cord, spina bifida occulta least severe

Spina bifida cystica (meningocele, myelomeningocele more common)
x ray, l5 s1

Question 11

Myelomeningocele

Answer 11

can herniate out of the bdy

treatment- prenatally through screening to gaurd the neural tissue

Question 12

Myelomeningo cele

Answer 12

drugs, folate (trimetho prm lead

extent and degree of symptoms depend on the location, flacid paralysis, absent deep tendon reflexes,

Chiari - type 2 herniation, chiari crisis when the brain gets pushed down

Question 13

myelomeningocoele treatment

Answer 13

requires a multidisciplinary approach surgeon, therapist, pediatrician surgery GUt caths to

Intelectual delays, death bfore 4 common

Question 14

Anencephaly

Answer 14

large defect of the calcarium, meninges and scalp not compatable with life, AFP in

cerebral and cere bellar hemispheres are absent, dies in a few days

look kinda like frogs

spina cord with a nub

Question 15

Encephalocele

Answer 15

broad based pedunculated masses of cerebral tissue and dura protruding thru cranial defect covered by skin

Occipital region is commpn

nsal sinus

diagnosis 0 AFP and ultrasound

Meckel gruber- AR, occipital cleft lip , many organs are issues

Question 16

disorders of migration and sulcation

Answer 16

Polymicrogyria, agyria (lissencephaly) and pachygyria

Distrubance of process of neuronal migration from germinal matrix to cortex, sulcation is induced by presence of normally migrated neuronal populatio

Question 17

poly microgyria

Answer 17

too many irregular small fused gyri,results from disordered organization of the neuron in thcortex ate the time of migration, neurite extension, synaptogenesis, and maturation,

Etiology- intrauterine ischemia, poly microglia is associated with in utero ifarcts, twinning, intrauterine CMV toxox zoster syphilis, genetic syndrome, may be focal or diffuse

Question 18

Agyria lissencephaly and pachgyria

Answer 18

agyria is an absence of gyri
Pachygryria- decreased numbers of broad coarse gyrin
brain is small, neurons only migrate partially in the 4th month

chr17 (miller dieker syndrom seizures, mental retardation)

failure to thrive, microcephaly- microophthal

females with DCX mitation

Question 19

schizencephalu

Answer 19

unilateral or bilateral focal lesion in cerebral hemispheres due to an abnormality of morphogeneiss, cleft may be fused

Question 20

disorders of cleavage of forebrain

Answer 20

arrhinecephaly- term applied to this categorty of malformation (absences of olfactory tract/bulbs), but usually much more missing than the olfactory brain, severity of craniofacial defect mirrors severity of underlying brain abnormality (the face predicts the brain cyclopia, hypotelorism)

Question 21

defects in forebrain cleavage pathogenesis

Answer 21

absent cleavage of forebrain during 4th and 6th week of gestation, usually sporadic, SHH 7q26 with trisomies, ethanol accutane

Question 22

holoprosencephaly

Answer 22

incomplete separation of hemispheres, alobar- small brain only one brain with no interhemispheric fissure

Semilobar- partial formation of fissur

Lobar- midline continuity at fronal pole

Question 23

holoprosencephaly symptoms and diagnosis

Answer 23

Clinically present with profound cognitive impairment, seizures, rigidity apnea and temperature imbalance, hydrocphalus can develop with aqueductal obstruction endocrine disorders can present with hypothalami or pituitary malformations
Facial abnormalities- cyclopia, cebacephaly, premaxillary agenesis

Question 24

agenesis of corpus callosum

Answer 24

doesnt do much, associateed with migration defects,

no cingulate gyrus

Question 25

type 1 chiari

Answer 25

chronic tonsilar herniation, associated with hydrocephalus, sdden death, neuro CN palsies, ataxia, long tract signs, can be asymtpomatic

90% have syringomyelia (cysts in sp cd)

Question 26

type 2 chiari

Answer 26

herniated cerebellar tissue with displacement of dorsal medulla causing a hump on spcd

lumbar myelomeningoceles

lower CN defects, arm weakness, spactisity, hydrocephalaus

Vit A def, too large of a cerebellum

Question 27

dandy walker malformation

Answer 27

agenesis of vermis (dilation of 4th ventricle, posterior fossa is large)

Question 28

syringomyelia

Answer 28

syrinx, cysts in sp cd, loss of pain and Temp

chiari 1

Question 29

perinatal hypoxia

Answer 29

cerebral palsy, non progressive neurology, strok in the development

stroke and paralysis
multi stroke spongey brain
gray matter

Question 30

white matter necrosis (leukomalacia

Answer 30

less severe than cp, plaques in wm, common in premies with ischemia and hypoxia, CV or pulmonary disease

watershed, vulnerable is the oligodenderocytes

multicystic encephalopathy of strokes

Question 31

subependymal germinal matrix hemorrhages

Answer 31

premies, imature neurons in the ventricles, big blood supply, bp burst

grade 4 - goes into surface and into the parengchyma