malformation and developmental diseases Flashcards
Pathogenic mechanisms
Malformation- intrinsic abnormality
Deformation- extrinsic force
Disruption- destructive force
Deformation sequence
Renal ageneisis–> lack of urine into amniotic cavity, death from respiratory insufficiency, fetal compression, altered facies, abnormal positioning of hands and feet, breech presentation
amniotic band disruction
wrap around organs and stuff
normal development of the CNS
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
Development of the neural tube
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
Oattern of cerebral myelination
posterior fronal lobes, than bottom (from top to bottom
cytoarchitecture of cerebral cortex
the bottom layers are most susceptible to wwiered mixed architecture, if its messed up the person is susceptible to seizures, (the higher the malforamtion)
Nueral tube defects
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
Detection and prevention of Neural tube defects
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%
spina bifida
combined malformation of vertebral column and spinal cord, spina bifida occulta least severe
Spina bifida cystica (meningocele, myelomeningocele more common)
x ray, l5 s1
Myelomeningocele
can herniate out of the bdy
treatment- prenatally through screening to gaurd the neural tissue
Myelomeningo cele
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
myelomeningocoele treatment
requires a multidisciplinary approach surgeon, therapist, pediatrician surgery GUt caths to
Intelectual delays, death bfore 4 common
Anencephaly
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
Encephalocele
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
disorders of migration and sulcation
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
poly microgyria
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
Agyria lissencephaly and pachgyria
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
schizencephalu
unilateral or bilateral focal lesion in cerebral hemispheres due to an abnormality of morphogeneiss, cleft may be fused
disorders of cleavage of forebrain
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)
defects in forebrain cleavage pathogenesis
absent cleavage of forebrain during 4th and 6th week of gestation, usually sporadic, SHH 7q26 with trisomies, ethanol accutane
holoprosencephaly
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
holoprosencephaly symptoms and diagnosis
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
agenesis of corpus callosum
doesnt do much, associateed with migration defects,
no cingulate gyrus
type 1 chiari
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)
type 2 chiari
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
dandy walker malformation
agenesis of vermis (dilation of 4th ventricle, posterior fossa is large)
syringomyelia
syrinx, cysts in sp cd, loss of pain and Temp
chiari 1
perinatal hypoxia
cerebral palsy, non progressive neurology, strok in the development
stroke and paralysis
multi stroke spongey brain
gray matter
white matter necrosis (leukomalacia
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
subependymal germinal matrix hemorrhages
premies, imature neurons in the ventricles, big blood supply, bp burst
grade 4 - goes into surface and into the parengchyma
