Spinal Cord Flashcards
Function of spinal cord
co-ordinates movement and sensation
Where is the spinal cord found?
inside the vertebral column
What does the spinal cord arise from?
specialised dorsal ectoderm
Neural tube closure
occurs at multiple sites from anterior to posterior neuropore in multiple stages
genes for neural tube closure
82 in humans - MTHFR involved in folate metabolism
Primary neurulation
day 22-26
neural ectoderm fold and fuse to form neural tube
secondary neurulation
tail bid cells condense and form secondary neural tube caudally - coccyx and cauda equina
DRG formation
neural folds fuse to form brain and spinal cord
after fusion neural crest cells migrate peripherally to form sensory neurons of DRG
3 layers of the neural tube
ventricular - undifferentiated, lining of central canal
mantle - differentiating neurons form grey matter
marginal - nerve fibres - white matter
alar and basal plate
alar plate - dorsal - sensory
basal - ventral - motor
where do cells in DRG extend sensory fibres?
peripherally and centrally
5 main layers of spinal cord periphery
dura mater - tough, fibrous outer layer
epidural space - between dura and vertebra - loose connective tissue
arachnoid mater
subarachnoid space - CSF
pia mater - vascularised, attached to brain and spinal cord
How does the spinal cord transmit information?
ascending and descending white matter tracts
How does the spinal cord involve reflex integration?
grey matter - spinal reflexes eg knee jerk not initiated voluntarily by the brain
where does human spinal cord end?
L1
2 spinal cord enlargements
cervical C3-T1
lumbar T11-L2
control of limbs
What is the name for the nerve roots which radiate from L1 to coccyx?
cauda equina
How many spinal nerves and what do they contain?
31 pairs - sensory and motor
where are sensory nerve bodies located?
DRG
cervical plexus
C1-5 = neck, head and shoulders
brachial plexus
C5-T1 - shoulder and upper limb
lumbar plexus
T12-L4 - lower abdomen and lower limb
sacral plexus
L4-S4 - legs and feet
central pattern generator
produce rhythmic patterns eg walking
fictive motor patterns - motor output in paralysed/isolated spinal cord
alternate muscle extension and flexion
what are CPGs co-ordinated by?
propriospinal neuron path
cervical and lumbar enlargements
what is cpg refined by?
supraspinal signals - motor cortex
sensory feedback to spinal cord
main problems with NTD
neural tissue exposed to amniotic fluid liable to damage and progressive degeneration over time before birth
examples of neural tube defects
anencephaly, encephalocele, spina bifida
types of spina bifida
occulta, myelomeningocele, meningocele
spina bifida stats
0.5-2/1000
regional variation
95% no FH
What medications can predispose to spina bifida?
antidepressants and anticonvulsants
surgery for spina bifida
in utero or after birth (within 48 hours)
what is often (90%) concomitant with spina bifida?
hydrocephalus - requirement for a shunt
Preventing spina bifida
supplement diet with 400mcg folate
fortified foodstuff
inositol (Vit B8)
spina bifida and shh
shh is responsible for d/v patterning of spinal cord and s present in cilium. Disruptions of signalling can lead to NTD
stats for SCI
2.5M globally, 50 000 UK age 16-30, males
causes for SCI
road accidents, sports, violence, alcohol
complete SCI
45% - total loss of sensation and function below injury level
incomplete SCI
partial loss of sensation and function below injury level - 55%
SCI above C3
usually results in death - diaphragm, phrenic nerve
4 causes of traumatic primary injury
hyperflexion
hyperextension
rotation
vertical/axial compression
2 causes of non-traumatic primary injury
cord compression eg tumour, reduced blood flow
developmental
hyperflexion axial compression
eg fall on buttocks - vertebrae forced together and ligaments stretched
what is the primary injury?
vertebral disc rupture
disc material invades centre of spinal canal and compress cord
what can surgery do for primary injury?
relieve pressure, restore shape of cord but damage persists
where is greatest damage of primary injury?
centre - haemorrhage - grey matter more vascular so vulnerable
what is the secondary injury?
cell death in grey matter
wallerian degeneration in white matter - influx of calcium
tracts lost secondary injury
ascending above lesion and descending below lesion
fibroglial scar components
collagen - produce fibroblasts
astrocytes - activated microglia
macrophages
microlesion
minimally disrupt BBB, axons cannot regenerate
contusive lesion
meninges intact, astrocytes produce CSPGs, macrophages
How are SCI assessed?
ASIA scale
A-E
A is complete, always bladder and bower problems
Treatment of SCI
immobilise C-spine CT/MRI/X-ray within 48-72 hours test sensory and motor function drugs to reduce swelling, maintain bp surgery - remove bone fragments, clots, disc material
What is E on ASIA scale?
motor and sensory normal
ASIA scale and description
A - complete, no sensory or motor below injury through S4-5
B - incomplete. sensory but no motor
C - incomplete - motor below injury and more than half key muscles grade<3
D - same as C but >3
E - normal
what ASIA grade are all complete SCI?
A
What % complete SCI recover significantly?
0.9%
Complications of SCI
pressure sores, infection, DVT, spasticity, autonomic dysreflexia
autonomic dysreflexia
life threatening increase in bp
injury T5 or higher
irritating stimulus below level of SCI eg full bladder
4 main barriers to recovery
cell loss
scar is non-permissive for regeneration (fibroblasts, sema 3-A deflect growth, astrocyte CSPG and tenascin)
spared cells in white matter demyelinated
degrading myelin - Nogo-A, MAG
6 key things for successful repair
damaged nerves must survive or be replaced - prevent secondary injury
surviving neurons must regrow axons despite scar and inhibitory molecules
axons must migrate towards appropriate targets
effective synapses
respond to NT
branching to replace circuitry
Different treatments for complete vs incomplete
incomplete = stimulate reorganisation of spared circuitry complete = neuron grafts, stimulate regrowth
PNS graft
permissive PNS environment encouraged CNS axon regrowth
Forms of axon growth after SCI
new synapse growth and remodelling of new axons
branching and sprouting proximal and distal to lesion
growth through spared tissue
pass through scar
Some things that have been used for acute injuries
PNS grafts - no evidence of functional recovery
cool injury site
methylprednisolone - stopped in 2013
foetal spinal cord transplants - alone or with molecules inhibit mag/nogo-A, grwoth factors
polymer scaffold seeded with stem cells
3 new ways emerging for SCI
modulate cAMP levels - overcome MAG inhibition
stem cells
electric fields
what direction do axons grow in EF?
cathode
EF with cathode distal or proximal to lesion
distal - prevent die back
proximal - enhance die back
acute injury
soon after primary injury
starting treatment timing
acute phase or wait?
acute - hostile, might be better to wait 2 weeks for inflammation and macrophage to stabilise
chronic injury treatment
Christopher Reeve’s
exercise therapy - repattern cpgs?
