Lectures 11, 12: CNS Development Flashcards
The nervous system develops from this germ layer, except for these two exceptions…
Ectoderm; microglia and dura mater = mesoderm
Describe gastrulation
Portion of the ectodermal germ layer becomes destined to form the nervous system, forming the neural plate
Describe neurulation
Rapid cell proliferation of the neural plate –> neural groove between neural folds –> neural tube, which separates from the surface ectoderm
Cells lining the neural groove give rise to cells of the ____
CNS
How does the PNS arise?
Cells from the margins of the neural tube detach from the neural folds to form clusters of neural crest cells
What days do the neural tube, anterior and posterior neural pore close?
22, 24, 26
Describe histogenesis
Neural precursor cells (eventually neuro/glioblasts) proliferate and migrate from the neural tube, forming 1) Germinal zone; an internal ependymal layer that will become the ependymal lining of the ventricular system and the epithelium of the telechoroidia and choroid plexus, 2) Mantle zone; a middle layer of cells that will become the gray matter of the CNS, and 3) Marginal zone; an external layer composed of cell processes; this will become the white matter of the CNS
Sulcus limitans
Divides the alar (dorsal) and basal (ventral) half of the neural tube
What happens to the rostral neural tube?
Vesicle formation! Prosencephalon, mesencephalon, rhombencephalon
By the end of the __th week, we have a 5-vesicle brain. What are these and where did they come from?
Pros –> telencephalon, diencephalon; mes –> mesencephalon; rhomb –> metencephalon, myelencephalon
What flexure divides met from myelencephalon? This region also forms the…
Pontine flexure; cerebellum
Describe the flexures
- Mesencephalic flexure (3rd week); 2. Cervical flexure (divides hindbrain/spinal cord); 3. Pontine flexure (near cerebellar region)
Describe the relevance of alar/basal plates for the spinal cord
Alar –> sensory nuclei; Basal –> motor nuclei
Discuss the 3 ways in which brainstem cell column development is different from the spinal cord
(1) In the medulla and pons, the alar plate lies lateral (not dorsal) to the basal plate (2) there are migrations of neuroblasts of both plates from the ventricular floor to other locations, and (3) “special” sensory and motor structures of the head require new/different cell groups for innervation
All cranial nerves except these two are recognizable by which week?
I, II; 5-6 weeks
The rhombic lip is derived from this structure and will become this structure
Tela choroidea; Cerebellum
When is the cerebellum first apparent? Describe development.
5-6 weeks; Up and outward cell proliferation causes the 2 rhombic lips to fuse in the midline to form the cerebellar plate, which covers the IVth ventricle. The fused lips become dumbell-like, forming the vermis and the two hemispheres
At the level of the diencephalon, the sulcus limitans is called what?
Hypothalamic sulcus
Describe telencephalon development
Rapid growth of the telencephalon results in the formation of two (bilateral) expansions, and in rearward growth of the two growing telencephalic hemispheres over the diencephalon
What is the name of the structure separating telencephalon from diencephalon?
Transverse cerebral fissure
What is the most rostral structure of the early telecephalon? What is it’s significance?
Lamina terminalis; only location where nerves can interconnect the two cerebral hemispheres: contains the rudiments of the corpus callosum, anterior commissure and optic chiasm
In what order do the cerebral lobes develop?
Parietal, frontal, occipital, temporal
Describe the “C”-shaped growth
Because the growth of the telencephalon is caudalward, it begins to arch over the tela choridea of the diencephalon, forming the C-shaped underlying structures (lateral ventricles, caudate, fornix)
What accomplishes the secondary fusion of the telecephalon and diencephalon?
Internal capsule
When does neuronal proliferation occur? What about neuronal migration?
2-4 months; 4-9 months
When does myelination begin? When is it most active?
2nd trimester; first 2 years of life
Describe the ordering of myelination
Early for motor-sensory roots, special senses and the brainstem (structures necessary for reflexive behaviors and survival). The corticospinal tract starts to myelinate at 36 weeks gestation and myelination is completed by the end of the 2nd year of life. Myelination begins at the proximal end of the axon (short axons myelinate first).
What are the 4 key postnatal developments?
- Myelination; 2. Postnatal neurogenesis (learning, memory, mood regulation); 3. Critical periods; 4. Synapse formation, stabilization, pruning, plasticity
What are the three stages of CNS development that can be disrupted?
- Neurulation (3-4 weeks gestation); 2. Prosencephalic (5-6 weeks); Cortical formation (8-24 weeks)
Neural tube defects are a disorder of…
Neurulation
Restricted failure of anterior neural tube can result in…(2)
Anencephaly or encephalocele
Anencephaly almost always leads to
Spontaneous abortions
Describe encephalocele
Failure of the anterior neural tube closure leading to meningial +/- cortical tissue extending through a bony defect in the skull
Three types of encephalocele and their characteristics
Sincipital (normal intelligence/surgical treatment), basal (facial abnormalities, require immediate surgery due to CSF leak), occipital (severe; abnormal mental/physical development; requires immediate surgery and may be associated with hydrocephalus)
Restricted failure of posterior neural tube can result in…(definition)
Myelomeningocele, failure of fusion of vertebrae through which a sac bulges containing malformed spinal cord
What are some risk factors for spina bifida?
Medical exposure, folate deficiency, diabetes
Two ways to diagnose neural tube defects
Elevated alpha-fetoprotein and ultrasound findings
What is a Chiari 2 malformation? What can it lead to? (2)
Cerebellum doesn’t fit into the posterior fossa (which requires closed CSF space to develop) so its gets pulled down into the spinal cord; hydrocephalus and brainstem problems (cyanotic spells)
What are the spinal effects of myelomeningocele? What are some other effects? (3)
Affected individuals have loss of motor control and sensory input from the level of the spinal lesion; above L2 = cannot walk, below S2 = can walk; incontinence, sexual dysfunction, spinal cord tethering
What is the treatment for myelomeningocole?
Surgery and shunt placement
T/F: There is no increased risk of a NTD if a sibling has had one
False, 50x risk of general population, supplement w/ 4 mg folic acid
What is an example of a disorder of prosencephalic development?
Holoprosencephaly
What are the three types of holoprosencephaly?
Lobar (distinct hemispheres), semilobar (some posterior separation, mostly fused), alobar (failure of hemispheric division)
What can individuals affected by holoprosencephaly have?
Midline facial defects (cyclopia, cleft lip/palate), hypothalamic/pituitary dysfunction, epilepsy, and cognitive impairment
Is holoprosencephaly common? Most common environmental etiology.
No! Rare. Diabetes.
What is another disorder of midline development? Associated symptoms.
Agenesis of corpus callosum; seizures/mental retardation (but can be totally silent)
What are the three stages of cortical formation?
Cell proliferation, neuronal migration, cortical organization
What is a disorder of differentiation/maturation?
Focal cortical dysplasia: cortex contains large dysplastic neurons that are not organized into typical layers and underlying white matter is hypomyelinated; often leads to epilepsy
Two disorders of migration and description
Heterotopias (neurons outside cortex, may be assymptomatic) and lissencephaly (decreased gyri/sulci = smooth brain)
Type I lissencephaly
Results from arrest of neuronal migration, areas of agyria and areas of pachygyria in which there are abnormally broad and flat gyri; epilepsy and developmental delays
Type II lissencephaly
Results from overmigration beyond the pia into the subarachnoid space, areas of polymicrogyria in which there are an excessive number of abnormally shallow gyri; developmental delays, epilepsy and several congenital muscular dystrophies
Cerebellar agenesis/hypoplasia presents as…
Cerebellar ataxia
Dandy Walker malformation
Hypoplasia of vermis, 4th ventricle becomes large cyst
Types of Chiari malformations
Chiari 1: downward herniation of cerebellar tonsils through the foramen magnum; symptoms: occipital/cough related headache, syringomyelia or lower cranial neuropathies; treatment: with suboccipital decompression; Chiari Type 2 (Arnold-Chiari malformation) downward displacement/herniation of vermis, 4th ventricle, brainstem and tonsils through the foramen magnum, likely hydrocephalus; most have myelomeningocele
Syringomyelia
Fluid filled cavity within the spinal cord typically associated with Chiari 1 malformations; assymptomatic or slow clinical presentations
Tethered spinal cord
Spinal cord is fixed to a lower immobile structure; progressive motor and sensory dysfunction with abnormal gait and bladder incontinence
Describe differences b/t cleft lip +/- cleft palate and cleft palate alone
Lip + palate: 2/3 nonsyndromic, ethnic variance (highest in Asians), more common in males; Palate alone: 1/2 are nonsyndromic, no ethnic variance, more common in females
Which is more common, cleft lip, palate, or both?
Trick question! All three are equally divided
Cleft lip/palate etiology
Genetic, teratogenic exposure (drugs, smoking, alcohol), or environmental (obesity, folate deficiency)
Define cerebral palsy
Permanent disorder of movement and posture related to a nonprogressive prenatal or perinatal event
List three prenatal and three perinatal cerebral palsy causes/risk factors. How frequently are the causes of CP not identified?
Prenatal: intrauterine stroke, CNS malformations, periventricular leukomalacia; Perinatal: prematurity, low birth weight, and asphyxia; 30% of the time
What is periventricular leukomalacia
Periventricular white matter focal necrosis and cyst formation
Three classifications of CP
- Spastic; 2. Dyskinetic; 3. Ataxic
Describe spastic syndromes. What are the three manifestations?
Upper motor neuron; spasticity, weakness, increased reflexes, extensor plantar reflexes, clonus (repetitive contractions). The plegias (hemi, quadri, di)
Hemiplegia. Common etiology?
Most common form of CP, full term/normal birth weight, usually vascular etiology, intelligence often normal, often not noticed until later manifestations
Quadriplegia
Low birth weight/intrauterine disease/cerebral malformation/asphyxia, seizures early and late, mental retardation
Diplegia
All 4 limbs, but legs > arms, asphyxia/premature, normal intelligence
Describe dyskinesia
Presents with early hypotonia and abnormal movements around age 2-3; typically occurs in term infants with acute asphyxia; basal ganglia and thalamus are affected
Choreoathetoid
Athetosis: slow, smooth writhing movements of distant muscles; Chorea: rapid, irregular, unpredictable contraction of individual muscles
Dystonia
Repetitive patterned twisting and sustained movements of the trunk or limbs
Describe ataxia
Results from prenatal injury to the cerebellum; early, affected individuals are hypotonic and then develop ataxic movements and speech
How is CP diagnosed?
History, exam, and imaging are important to making the diagnosis over 2 visits; history will reveal delayed motor milestones and early handedness; exam may show upper motor neuron signs or hypotonia, persisting primitive reflexes and delayed protective reflexes; imaging (MRI) to look for etiology; 85% of MRIs are abnormal and in ¼, there may be a treatable cause
Associated health problems of CP
Impaired cognition (in 50%), epilepsy, scoliosis, bowel and bladder dysfunction, pain, and oromotor/visual dysfunction
What are 3 goals of care for toddlers with CP? Describe treatment.
Goal is to optimize motor development, maintain range of motion and prevent contractures; PT, medications (benzos, Botox, baclofen), dorsal rhizotom
