Nervous System Embryology and Congential Malformations Flashcards
What embryological structure does the nervous system develop from?
The Embryonic Ectoderm
When does the CNS begin to develop?
Beginning of the 3rd week
How does the CNS develop?
Thickening of ectoderm anterior to the primitive node = neural plate
Edges thicken and move upwards to form the neural folds
Neural tube folds migrate towards each other and fuse at the midline forming the NEURAL TUBE
Neural tube intitally open at anterior and posterior ends
Anterior (cranial/rostral) neuropore closes 18-20 somatie stage (approx. 25 days)
Posterior (caudal) neuropore closes approx. day 27
How do brain vesicles develop?
Begins with closure of anterior neuropore (approx. day 25, 18-20 somite stage )
What happens in the neural development in the 5th week?
Prosencephalon splits into - telencephalon - diencephalon Mesencephalon stays the same Rhombencephalon splits into - metencephalon - myelencephalon
Flexures of the nervous system development
Cephalic flexure - end of 3rd week - between midbrain and hindbrain Cervical flexure - end of 4th week - between hindbrain and spinal cord Pontine flexure - 5th week - in hindbrain
Parts of the neural tube
Telencephalon Diencephalon Mesencephalon (Midbrain) Rhombecephalon (hindbrain) - Metencephalon - myelencephalon
What does the telencephalon form into?
Cerebral hemispheres
Hippocampus
Basal ganglia
What does he diencephalon form into?
Thalamus
Hypothalamus
Pituitary gland
Pineal
What does the mesencephalon form?
Superior and inferior colliculi
What does the metencephlon form?
Cerebellum
Pons
What does the myelencephalon form?
Medulla
What does the lumen of the neural tube form?
Ventricular system
What week does CSF begin to form?
During the 5th week
What is CSF produced predominately by?
Choroid plexus
- in 3rd and 4th and lateral ventricles
Where does CSF drain into?
Subarachnoid space via openings in roof of the 4th ventricle
Where is CSF absorbed into?
Venous system
Definition of hydrocephalus
Accumulation of CSF leading to enlarged brain and cranium
What is hydrocephalus frequently due to?
Blocked aqueduct
Pathology of hydrocephalus
CSF is prevented from lateral and 3rd ventricles passing into the 4th ventricle so cant drain properly
Causes of hydrocephalus
Genetic
Prenatal viral infection
Intraventricular haemorrhage
Spinal bifida cystica
What cellular differentiation needs to be done in the neural tube?
Neuronal cells need to be made (neurones and glia)
Connect cells together
What produces most of the cells of the CNS?
Neuroepitheliun
In what month does the entire length of the vertebral column extends?
3rd,month
What does the spinal nerves become elongated to form?
The cauda equina
What does the pia mater form?
Terminal filum (long fibrous thread)
What are sympathetic and parasympathetic ganglia formed by?
Neural crest cells
Where are parasympathetic ganglion found?
Near or within the organs they innervate
Where are sympathetic ganglia found?
Chains along side of spinal cord
Preaortic ganglia
Sympathetic organ plexuses (in e.g. heart, lungs, GI tract)
What are the surface or cerebral hemispheres initially like?
Smooth
What is a sulcus?
Groove
What is a gyri?
Elevation
What is lissencephaly?
Smooth brain
Pathology of lissencephaly
Defective neuronal migration
Gyri and sulci fail to develop
Results of lissencephaly
Severe mental impairment Failure to thrive Seizures Abnormal muscles tone Affected children die before 10
What is polymyalgia?
Excessive number of small gyri
Results of polymyalgia
Variable degree of neurological problems
- mental retardation
- seizures
- motor deficits
Causes of microcephaly
Genetic
Drugs
Infection (e.g. zika)
Results of microcepahly
Intellectual impairment Delayed motor functions/speech Hyperactivity Seizures Balance / co cordination problems
Causes of porencephaly
Postnatal stroke
Infection
What is porencephaly?
CSF filled cysts or cavities
What is schizencephaly?
Large clefts or slits
Causes of schizencephaly
Genetic
In utero
Infection
Results of schizencephaly
Paralysis
Seizures
Intellectual impairment
Developmental delay
What is diastematomyelia?
Split cord manifestation where the spinal cord is split longitudinally into 2 parts
Presentation of diastematomyelia
Scoliosis Weakness of lower extremities Hairy patch over lower back Foot deformities Loss of sensation
Causes of intellectual impairment
Genetic (e.g. Downs) Radiation Infectious agents (e.g. rubella, CMV) Birth trauma Post natal insults Maternal alcohol abuse
Examples of post natal insults that would cause intellectual impairment
Head injury
Infections e.g. meningitis
Lead exposure
What is closure of the neural tube essential for?
Normal development and function
When does the neural tube close?
Begins day 18
Completed by end of 4th week (approx. day 27)
What does failure to the neural tube to close result in? Give some examples of these
Neural tube defects
- ancencephaly
- Encephalocele
- Spina bifida
Pathology of ancenecephaly
Failure of anterior neuropore to close
Presentation of ancenecephaly
Skull fails to form
Brain tissue degenerates
Incompatible with life
What is cranioarchischisis?
Failure of neural tube closure along the entire neuroaxis - resulting in degeneration and death
What is encephalocele?
Herniation of cerebral tissue through a defect in the skull
Pathology of encephaloecele
Failure in the closure of rostral neural tube
Types of encephaloecele
Fronto-nasal
Occipital
Most common site for encephalocele
Occipital region
Presentation of encephalocele
Variable degree of neurological deficits
Symptoms depend on location of the brain
Pathology of spina bifida
Defective closure of the causal neural tube
Non fusion of vertebral arches
Affects the tissues overlying the spinal cord
Types of spinda bifida
Spina bidifa occulta
Spina bifida Cystica
What is the most minor form of spina bifida?
Spina bifida occulta
Pathology of spina bifida occulta
Failure of embryonic halves of vertebral arch to grow normally and fuse
Underlying tissue is completely fine
Where does spina bifida occulta occur?
L5 and L6 vertebrae
Presentation of spina bifida occulta
Usually no clinical symptoms
May result in dimple with small turft of hair
Pathology of spina bifida cystica
Protrusion of spinal cord and/or meninges through the defect in the vertebral arches
Pathology of spina bifida with meningocele
Protrusion of meninges and CSF forming a fluid filled sac outside the spine
(Impact minimal as no neural damage)
What is the rarest form of spina bifida?
Spina bifida with menigocele
Pathology of spina bifida with meningomyelocele
Nerve roots and/or spinal cord included in the fluid filled CSF sac
Presentation of spida bifida with meningomyelocele
Neurological deficits
Loss of sensation
Muscle paralysis
Area affected determined by level of lesion
What is spina bifida with meningomyelocele often associated with?
Hydrocephalus
What can be taken to prevent neural tube defects?
Folic acid supplements (400ug / day)
Prenatal diagnosis of neural tube defects is done by….
Maternal blood screening - AFP levels in serum Amniocentesis - AFP in amniotic fluid USS - anecephaly from 12 weeks - spina bifida from 16-20 weeks
Risk factors for neural tube defects
Genetic Nutritional - too little folate - too much vitamin A Environmental - hyperthermia - taking drugs e.g. sodium valproate
What week does the nervous system start to develop?
Week 3
Inheritance of tuberous sclerosis
Autosomal dominant
Presentation of tuberous sclerosis
Cutaneous features
- depigmented “ash leaf” spots which fluorescence under UV light
- roughened patches of skin over lumbar spine (Shagreen patches)
- Adenoma sebaceum (angiofibroma); butterfly distribution over the nose
- fibromata beneath nails (subungual fibroma)
- Café au lait spots may be seen
Neurological features
- developmental delay
- Epilepsy
- intellectual impairment
Retinal haemorrhages
Rhabdomyomas of the heart
Gliomatous changes that occur in brain lesions
Polycystic kidneys, renal angiomyolipomata
lymphangioleiomyomatosis: multiple lung cysts
What are axillary freckles indicative of?
NF type 1
