L3 - Disorders of Neural Development Flashcards
1. Learn about abnormalities of neural development including neural tube defects and abnormalities of cortical development. 2. Understand cerebral palsy and the neurological effects of birth injury.
What is a focal lesion?
Circumscribed areas of injury to brain tissue following brain injury.
May occur:
- object penetrates skull and directly injures brain.
- vascular damage (closed head injury)
Define: Sporadic
Occurring at irregular intervals or only in a few places.
Define: Monogenetic
Having a single source.
Define: Oligogenetic
Caused by relatively few genes.
Define: Polygenetic
Caused by many different genes, each having only a limited impact on phenotype.
Define: Idiopathic
Relating to any disease which arises spontaneously or for which the cause is unknown.
Define: Epigenetic
- Study of changes in organism
- caused by modification of gene expression
- rather than alteration of the genetic code itself.
Briefly describe neuralation?
- Neuroectodermal cells -(differentiate)-(thicken)- neural plate.
- Neural plate -(dorsally bends)-(ends join)- Neural crest
- Neural tube -(closes)-(disconnects)- from neural crest and will form epidermis
- Notochord-(degenerates)
What will neural crest cells differentiate into?
Cells of peripheral nervous system (neurones and glia)
- sensory ganglia (dorsal root ganglia)
- (symp & parasymp ganglia)
- neural plexuses with specific tissues and organs
Brain vesicles from rostral neural tube will contribute to what structure?
Brain CNS.
- Proencephalon - telencephalon (cerebrum) & diencephalon (hypothalamus and optic vesicles)
- Mesencephalon - midbrain
- Rhombencephalon - metencephalon (pons & cerebellum)
What happens to the neural tube in adulthood?
Outgrown by skeleton - cord ends at L1 vertebra.
Preserved as
- central grey of cord
- periaqueductal grey of midbrain
What is a radial glial cell?
- Where do they arise from?
- Role?
- Arise during expansion of neural tube.
- Bi-polar progenitor cells.
- Responsible for producing all neurones in cerebral cortex.
- Newborn neurones use radial glia as scaffolds
- traveling along radial glial fibers to reach final destination.
How does the neural tube rapidly develop?
Acquires regional distinctions via inductive cues.
- Retinoic acid and sonic hedgehog (notochord) induces transcription factors
- result in generation of motor neurones and oligodenrocytes from VENTRAL neural tube.
- Local signaling by Wnt and BMP in DORSAL regions generates neural crest and sensory neuron precursors.
What is BMP4?
Bone Morphogenetic Protein 4.
- protein coding gene
- part of transforming growth factor-beta family
- found in early embryonic development
- involved in bone and cartilage development.
What is the role of BMP4 in humans embryonic development?
Where is it secreted from?
- Critical signalling molecule required for early differentiation of embryo.
- secreted from dorsal part of notochord.
- acts with sonic hedgehog (ventral part of notochord)
- establishes dorsal and ventral axis
What is chordin?
- Bone morphogenetic protein antagonist
- Dorsalizes developing embryo by binding ventralizing TGF-beta proteins such as BMPs
What is noggin?
Inhibitor of BMPs
Promotes somite patterning in developing embryo.
Released from notochord.
Causes formation of head and other dorsal structures.
Describe pruning?
- Selective degeneration of axons.
- Neurone axons will be pruned via apoptosis.
- Casp6 - mediator of axon degeneration, activated following nerve growth factor (NGF) deprivation.
What is neurofibromastosis type 1?
- Genetic condition causing tumours to grown along nerves.
- Autosomal dominant.
- Caused by mutation in neurofibromin gene as part of the RAS system.
What are some features of neurofibromastosis type 1?
Ectoderm - dermal neurofibromata - Cafe-au-lait spots - Axillary freckling Neural tube effects - glial cell tumour Neural crest effects - schwann cell tumours
What is dermal neurofibromata?
- non cancerous
- tumours growing from small nerves in skin
- appear as small lumps during puberty
Describe disorders related to development, neural tube defects?
- Rostral/ caudal end of neural tube (neural pores) may fail to close.
- May lead to neural tube defects (spinal bifida)
What is anencephaly?
Failure of brain to develop.
Neural tube closed but membrane around it may not have.
Describe the severity of spina bifida occulta?
- mild / commoner form
- discovered on X-rays
- most never become aware they have it
Describe spina bifida cystica? (4)
examples:
- Meningocoele
- Myelocoele
- Encephalocoele
- Encephalomyelocoele
Key role of folic acid?
Co-factor in cell division.
Describe meningocele?
- coverings of spinal cord (meninges) pass back through opening in spine to form a cyst like swelling.
Describe myelomeningocele?
- spinal cord enclosed in cyst.
- most serious type of spina bifida
Define Paraparesis
Partial paralysis of lower limbs.
Define: Paraplegia
Paraplegia - impairment in motor or sensory function of the lower extremities
What are some effects of lost neural function?
- Limb deformity
- Urine infection risk
- Hydrocephalus
- Immobility
- Obstetric complications
What is cortical heterotropia?
Cortical cells (grey matter) are present in inappropriate locations in brain.
- almost always cause epileptic seizures
- may or may not be associated with learning disability
What is microcephaly?
babies with smaller heads.
What is Chiari malformation?
Brain tissue extends into spinal canal.
Relatively mild abnormalities of skull base may cause altered flow of CSF.
What is Syringomyelia?
symptoms?
Generic term, cyst or cavity forms within the spinal cord.
- cyst can expand, elongate over time, destroying the spinal cord.
Symptoms: loss of feeling, paralysis, weakness, stiffness in back, shoulders and extremities
What is infant Hypoxic Ischemic Encephalopathy?
Type of brain damage that occurs when an infant’s brain doesn’t receive enough oxygen and blood.
What is Strabismus?
Condition where patient cannot align both eyes simultaneously under normal conditions.
What is Duane’s syndrome?
- Limitation of horizontal eye movement.
- Caused by weakness in lateral rectus.
- Inability to move eye inward toward the nose (adduction), outward toward ear (abduction) or in both directions
What may occur during adduction in a person with Duane’s syndrome?
Eyeball pulls in and eye opening (palpable fissure) narrows.
Another word for lazy eye…
Amblyopia
- when vision in one eye is reduced as eye and brain are not working together properly.
Give an example of a treatment which may help in a patient with Strabismus?
Occlusion treatment.
- Covering the good eye allows brain to become receptive to connections from weak eye, previously suppressed if any discrepancy of ocular axes.
