Lec 12 CNS Malformations Flashcards
What is the most common type of malformation of the nervous system?
- neural tube defect
What happens in neural tube defects [NTDs]?
- failure of fusion of neural tube by 28th day [4th wk] post conception
When do disordered of neural tube defects occur?
3-4 wks gestation
What are the 2 most common neural tube defects [NTDs]?
- anencephaly
- myelomeningocele
What are the two categories of NTDs [neural tube defects]?
- failure of anterior [rostral] closure –> anencephaly/ encephalocele
- failure of posterior [caudal] closure –> myelomeningocele
What preventable treatment is associated with NTDs?
- low folic acid intake before conception and during pregnancy associated with neural tube defects
What is anencephaly?
- complete failure of anterior neural tube closure in first 24 days
- absence of forebrain
- open calvarium “frog-like appearance”
- almost always get spontaneous abortion or can be born with brainstem [suck/gag/breath] function and die within days
What confirmatory tests can you do to test for neural tube defects?
- high alpha-fetoprotein [AFP] in amniotic fluid and maternal serum
- high AChE [acetylcholinesterase] in amniotic fluid (b/c fetal AChE in CSF transudates across defect into amniotic fluid)
What are clinical findings in anencephaly?
- high AFP [alpha fetoprotein] in amniotic fluid and maternal serum
- polyhydramnios [no swallowing center in brain]
What is associated with increased risk of anencephaly?
- maternal diabetes type I
- low maternal folate
What happens in encephalocele?
- restricted failure of anterior neural tube closure [around day 26]
- mengingeal +/- cortical tissue extending through a bony defect
- protruding tissue may be normal brain or gliotic tissue with little/no function
- 30% mortality
- diagnosed prenatally by ultrasound in 80% of cases
How do you treat encephalocele?
- usually surgically repaired unless massive, then you have severe microcephaly or other lethal anomally
What are the 3 types of encephalocele?
- sincipital: outcome normal or near normal intelligence without major complications
- basal: requires prompt surgery, risk of meningitis + CSF leak
- occipital: most severe, may get hydrocephalus, 17% have normal mental and physical development, requires immediate surgery
What is a myelomeningocele [meningomyelocele, spina bifida aperta] ?
- restricted failure of posterior neural tube closure
- have absence of overlying skin, menginges
- malformed spinal cord
- impariment in spinal cord + brain, loss of motor control and sensory input from level of spinal lesion
- compatible with life
- more common in females
What are risk factors for meningomyeloceles?
- more common in females
- risk factors: alcohol, medical exposure, folate deficiency, diabetes
How do yo you diagnose meningomyelocele?
- elevated alpha-fetoprotein [AFP] between 15-20 wks
- ultrasound wk 12 –> irregularity of spine/ bulging back, lemon sign, banana sign
What What is chiari 2 malformation?
- significant herniation of cerebellar tonsils through foramen magnum
- elongation/thinning of upper medulla/pons
- hydrocephalus [due to obstruction from chiari]
- aqueductal stenosis
- brainstem dysfunction –> apnea, dysphagia, cyanotic spells
often present with lumbosacral myelomeningocele and paralysis below defect
- lesion above L2 cannot walk, lesions below S1 can walk
How ambulatory is pt with mengingomyelocele above L2? at L3-5? below S1?
above L2: minimal to no walking
L3-L5: walk with assistive devices
S1 and below: normal ambulation or with minor weakness
What happens with bowel and bladder in meningomyelocele?
- higher risk of UTI
- can have urinary reflux, hydronephrosis, renal failure
treat: use catheter, timed toileting and dight high in fiber
What is a meningocele? can you detect with AFP?
menginges [but not spinal cord] herniate through spinal canal defect
normal AFP so can’t use AFP to test
What happens in spina bifida occulta?
- failure of bony spinal canal to close but no structural herniation
- usually seen at lower vertebral levels
- dura is intact
- associated with tuft of hair or skin dimple at level of bony defect
What is syringomyelia?
- associated wtih chiari 1 malformation
- most common at C8-T1
- cystic enlargement of central canal of spinal cord
- crossing fibers of spinothalamic tract are damaged
- get cape-like bilateral loss of pain and temperature sensation i upper extremities
Where is syringomyelia most common?
at C8-T1
What is normal process of prosencephalic development [3 stages]?
- at wks 5-6
- prosencephalon develops into telencephalon and diencephalon through 3 stages –> formation, cleave, midline development
What does the diencephalon normally become?
- thalamus, hypothalamus, subthalamic nuclei
What does the telencephalon normally become?
cerebral hemispheres
What happens inholoprosencephaly? Cause?
- failure of left and right hemispheres to separate
- due to mutations in sonic hedgehog [SHH] signalling pathway
What are 3 types of holoprosencephaly?
- lobar: mid line distinct
- semilobar: separation posteriorly, but frontal and parietal lobes fused
- alobar: complete failure of forebrain to divide
What is correlation between hemispheric separation and neuro disfunction?
- the greater the hemispheric separation, the more mild the neurologic dysfunction
What are symptoms of moderate vs severe holoprosencephaly?
- moderate = cleft lip/palate
- severe = cyclopia
can be pretty normal facial appearance or dramatically altered
What is cause of holoprosencephaly?
- may be related to mutations in sonic hedgehog
- maternal diabetes increases risk
What are the 3 stages of cortical formation?
- cell proliferation: 2-4 mos, neural and glial precursors generated
- neuronal migration: 3-5 mos, neurons move into cortical mantle
- cortical organization: neurons develop into 6 layers
What is focal cortical dysplasia?
- neurons exhibit immature or glial features
- cortex has large dsyplastic neurons that are not orgnaized into typical layers and underlying white matter hypomyelinated
on image:
- wider than normal gyri
- blurred gray/white junction
- often have epilepsy, requiring surgery
occurs 2-4 mos
What are heterotopias?
- disorder of neuron migration
- have collections of neurons outside cortex
- neurons are normal
- cortex overlying heterotopias maybe thing with shallow sulci
What is periventricular heterotopia?
- periventricular nodules of neurons rest beneath otherwise normal cortex
- most patients have normal intelligence
- 1/4 of pts are asymptomatic but may have undiagnosed learning disability
- epilepsy commonly develops in teen age
What is lissencephaly? two types?
- decreased pattern of gyri/sulci, brain appears smooth
type 1 [classical]: arrest of neuronal migration –> fewer number of abnormally broad/flat gyri
type 2[cobblestone]: overmigration beyond pia into subarachnoid space –> excessive number small cortical gyri
What happens in classical lissencephaly?
- brain has agyria and pachygyria
- agyria = diminished white matter, shallow or absent sylvian fissure
- pachygryia = fewer number of abnormally broad and flat gyri
due to disruption of platelet ativating factor which interacts with microtubules
What is etiology of classical lissencephaly?
- genetic = double cortin on X chromosome, males have more severe
What is clinical presentation of classical lissencephaly?
- depends on amount of agyria vs pachygyris [greater gyral simplification = greater impairement]
- epilepsy
- developmental delay
What is etiology of cobblestone lissencephaly?
- associated with several congenital muscular dystrophies
What is dandy-walker? etiology?
- hypoplasia or absence of cerebellar vermis
- 4th ventricle transformed into large cystic cavity [failure of luschka and magendie to open]
- posterior fossa is large and lateral sinuses and torcula are elevated
- associated with hydrocephalus and spina bifida
etiology: sporadic or due to mom taking isoretinoin [accutane] during pregnancy
What are chiari malformations?
- anatomic anomolies of cerebeullum, brainstem, craniocervical junction
- downward displacement of cerebellum with or without lower medulla into spinal cord
What is chiari 1?
abnormally shaped cerebellar tonsils displaced below foramen magnum
- can be isolated radiologic finding
symptoms: occipital/cough related headache, syringomyelia or lower cranial neruopathies
treat: suboccipital decompression
What is chiari 2?
- downwart displacemnt of vermis and tonsils, 4th ventricle, and brainstem through foramen magnum
- 4th ventricle obstructed, hydrocephalus likely
most have spinal [lumbosacral] meningomyelocele
What is tethered spinal cord?
spinal cord fixed to lower immobile structure
- have progressive motor and sensory dysfunction with abnormal gait and bladder incontinence
What is the most common type of craniofacial malformation?
cleft lip/palate
What is distribution cleft lip vs palate vs both?
1/3 combined
1/3 isolated cleft lip
1/3 isolated cleft palate
What happens in pts with cleft lip +/- palate?
- 2/3 are nonsyndromic
Who is most likely to get cleft lip +/- palate?
highest in asians/native americans, lowest in american blacks
more common in males
What happens in pts with cleft lip?
- 1/2 are nonsyndromic
Who is most likely to get cleft palate?
- more common in females
- no variance in ethnicity
What is the etiology of cleft lip/palate?
genetic: complex, up to 20 genes interact
drugs: alcohol, cigarettes, methotrexate
environmental: folate deficiency, maternal obesity
What is the embryology of cleft lip +/- palate?
- failure of fusion of maxillary and medial nasal processes
- can produce unilateral/bilateral or median lip clefting
What is embryology of isolated cleft palate?
- lack of fusion of palatine processes/shelves
What is treatment for cleft lip/palate?
- may have airway issues and feeding problems, use special nipple for babies with cleft lip/palate
- get primary lip repair at 3 mos old, palate repair at 6 mos
- speech therapy
- also may have higher rate ear infections and may have missing/crooked teeth
What is cerebral palsy?
- permanent disorder of movement and posture causes activity limitation
- due to non-progressive disturbance that occured in fetal or infant brain
- often accompanied by: disturbance of sensation/perception/cognition/communition, epilepsy, 2ndary MSK problems
What is cause of cerebral palsy?
- hermorrhagic or ischemic stroke [acquired/hereditary thrombophilia or placental issues
- CNS malformations/infections
- periventricular leukomalacia [white matter focal necrosis + cyst formation]
- asphyxia in perinatal
What are risk factors for cerebral palsy?
- > 2 previous abortions
- maternal menstrual regulation
- bleeding during pregnancy
- preeclampsia
- placental infection
- multiple births
- maternal hypothyroidism
- low birth weight
What are spastic syndrome?
- syndromes in which upper motor neuron signs include spasticity, weakness, increased reflexes
What is hemiplegia?
- weakness on one side of body
- most common form of cerebral palsy usually affecting term infants of normal birth weight
What is most common etiology of inborn hemiplegia? signs?
usually vascular
signs: early – unilateral fisting, early handedness; late – delayed motor milestones, siezures in first 2 years
- intelligence often not affected
What is quadriplegia? etiology?
- all 4 limbs affected, delayed milestones, epilepsy, mental retardation, microcephaly
etiology: low birth weight, intrauterine disease, cerebral malformation, asphyxia in full term infamt
What is diplegia? etiology?
all 4 limbs affected but legs more than arms, can walk independently, normal intelligence
etiology: asphyxia or prematurity
What is dyskinesia? who gets it? symptoms?
- acute perinatal asphyxia affects basal ganglia and thalamus
- usually term infants
symptoms:
- early hypotonia [decreased muscle tone followed by abnormal movement around age 2
What is ataxia? who gets it? symptoms?
- due to prenatal injury to cerebellum
- usually in children born to term
- show hypotonia early on, delayed motor and language development
- speech typically jerky/slow
- ataxia improves with time
What are clues for diagosis of cerebral palsy?
- history of motor delay but without loss of skills
- early handedness
- persisting primitive reflexes
- lack of development protective reflexes
What health problems are associated with cerebral palsy?
- epilepsy in 40%
- scoliosis
- prolonged puberty in nonambulatory girls
- pain in hips
- visual impairment in 1/3
What is treatment for cerebral palsy spasticity and dyskinesias?
- oral medicine
- botox for spasticity/dystonia
- selective dorsal rhizotomy
