Congenital malformations and mental retardation

Question 1

7 landmarks of nervous system development

Answer 1

• Neural tube closure: starts at day 22 and ends around day 28
• Outgrowth of telencephalic vesicles: 5th week
• Proliferation: occurs throughout development but mostly up to the end of the 2nd trimester
• Cell migration: begins 7 weeks and ends by 16 weeks
• Gyration: starts around week 24
• Myelination: begins at week 20
• Synaptic development: occurs throughout life

Question 2

Neural tube closure defects: spina bifida

Answer 2

• 3 types of spinal bifida
• Spina bifida occulta: bony defect in vertebra (usually lumbosacral) that can be silent. Can be associated w/ minor neurological defects and/or lower back pain
• Spina bifida meningocele: meninges herniate through the bony defect (can occur in the brain)
• Spina bifida myelomeningoceles: both meninges and CNS tissue herniate through the bony defect (in brain is called encephaloceles or hydroencephaloceles if it includes ventricle)

Question 3

Anencephaly

Answer 3

• Most severe manifestation of neural tube closure defect
• Due to lack of fusion of anterior neuropore, and thus no development of an overlying skull (leads to mechanical destruction of cerebrum)
• Children may be still born or born alive (if born alive only live a few hours)
• Folic acid deficiency is a known risk factor for neural tube defects
• Incidence: 1 in 5,000

Question 4

Failure of diverticulation of telencephalic vesicles: holoprosencephaly (HPE)

Answer 4

• HPE is a defect in the forebrain and mid face that results in incomplete development and separation of midline structures
• Most severe is alobar HPE (usually incompatible with life): failure of forebrain to divide into left and right hemispheres. Also present w/ clefting of mid face, cyclopia
• Other less severe forms produce microcephaly, hypotelorism (close set eyes), single maxillary central incisor
• Incidence: 1 in 250 in embryogenesis, 1 in 16,000 newborns

Question 5

Hydrocephalus

Answer 5

• Almost all cases due to blockage of CSF flow (obstructive hydrocephalus)
• If obstruction occurs w/in the brain its a non-communicating hydrocephalus
• Most common causes of non-communicating hydrocephalus are: developmental malformation (aqueduct stenosis), inflammation, and neoplasm (ependymoma of 4th ventricle are examples), arnold chiari
• If obstruction occurs in subarachnoid space or arachnoid granulations its a communicating hydrocephalus (also includes CSF-secreting neoplasm: choroid plexus papilloma)
• Causes: subarachnoid hemorrhage, meningitis, and dural sinus thrombosis

Question 6

Arnold-chiari malformation

Answer 6

• Malformation of the posterior fossa structures, causing herniation of cerebellar tissue (vermis) through foramen magnum and often misplaced medulla and 4th ventricle
• Downward displacement of brainstem
• Pts can develop obstructive hydrocephalus in 2 sites: foramen magnum or aqueduct of sylvius
• This is a non-communicating hydrocephalus
• Chiari type I: low lying cerebellar tonsils

Question 7

Mental retardation

Answer 7

• Defined as significantly sub-average intelligence (IQ less than 70) with concurrent deficits in adaptive behavior (communication, social skills, work) and onset during developmental period
• Overal prevalence is 2-3% of population
• Etiology:
• Prenatal factors: chromosome abnormalities, metabolic and nutritional problems, congenital infections, drug exposure
• Perinatal factors: prematurity, small size, bleeding in germinal matrix
• Postnatal factors: severe infections of CNS, lead or mercury poisoning, asphyxia