Neuroanatomy L4: Acquired spinal cord injury Flashcards
What are 3 conditions that affect spinal cord function?
- Neurotrauma
- Spinal tumours/abscesses
- Diseases
What is neurotrauma?
spinal cord / cauda equina (Traumatic spinal cord injury.
What are spinal tumours? What is the effect of a spinal tumour on the spinal cord?
A tumor inside or next to the spinal cord will narrow or compromise the space of the vertebral canal and begin to exert compression on the spinal cord.`
What is spinal abscess?
on outside of spinal cord
What can spinal tumours and abscesses cause?
Sensory and motor deficits
What is this? What will it cause?
Interspinal tumor - will affect local cells and descending/ascending pathways.
What are 4 diseases that affect spinal cord function?
- Poliomyelitis
- Syphilis
- Amyotrophic lateral sclerosis (ALS)
- Multiple sclerosis
What is poliomyelitis?
Viral infection (rare in the developed world due to vaccination) - infects and kills motor neurons, causing flaccid paralysis - not always uniform or symmetrical - generally unilateral.
How does poliomyelitis affect the spinal cord?
motor neuron loss In anterior horn => flaccid paralysis
What is syphilis?
Sexually trasnmitted disease - treatable and preventable -
How does syphilis affect the spinal cord?
- affects the sensory neurons of the dorsal root ganglia, and the sensory neurons in the dorsal columns degenerate (thus lose sensory input)
- can spread to the brain and cause insanity.
- no dorsal column- what do we use it for then? = sensory input (proprioception, fine discriminative touch (since this no longer there = use visual)
What is the cause of Amyotrophic lateral sclerosis (ALS)?
no known cause
How does Amyotrophic lateral sclerosis (ALS) affect the spinal cord?
lower motor neurons degenerated lower (spinal cord and peripheral nerves) and upper motor neurons (brain)
What is multiple sclerosis?
Autoimmune system becomes activated to proteins in the spinal cord, particularly those associated with myelin around axons - in the image the dark staining is myelin, and there are large areas where the myelin has been removed. If the nerves even survive the inflammation, removing the myelin causes major functional deficits.
How does multiple sclerosis affect the spinal cord? Be specific with which motor neurons are affected.
Autoimmune demyelinating disorder components of white matter (gets attacked) white matter is used for conduction Degeneration of upper (corticospinal) and lower (spinal) motor neurons => paralysis and muscle atrophy
Is ALS very debilitating?
Generally these people die within years of being diagnosed - due to breathing difficulties.
What is a traumatic spinal injury (tSCI)?
starts off with a mechanical force (eg. break back) –> reposition vertebrae –> compromised vertebral canal space
What are 5 examples of trauma that can cause spinal cord injuries?
- Work site/place injuries
- Driving into shallow water
- Sporting injuries
- Motor bike accidents
- Waves –> dumped on sand
Estimated 339,000 Australians living with acquired brain injury. and estimated 10,000 Australians living with spinal cord injury (SCI). This is estimated to cost Australia _______ dollars each year?
10 billion
Spinal cord injuries most affect ____ (males/female) in their _____ to _____ years.
Mostly affects males - the bracket of injury is late teens to 30/40 years.
What are 2 important things that can ensure people with spinal cord injuries can still have normal life expectancy although they are paralysed?
Medical care for early management and rehabilitation
Which horn does sensory information flow in?
Dorsal side
What does the grey matter (inside) consist of?
contains cell bodies of nerve cells that reside in spinal cord
What does the white matter (outside) consist of?
contains nerve fibres (pathways) running to and from the brain
What happens in the white matter?
Sensory feedback up to the brain via the dorsal columns or anterolateral system (pain).
Which matter (grey or white) will be affected first with impact?
White matter (as it on the outside)
Which horn does the motor command go out?
Ventral
What is the ventral horn important for?
Important for limb movement at the cervical and lumbar levels.
How is the spinal cord split up in terms of motor, sensory and intermediate grey?
The pathways located towards the mid-line innervates _____ muscles, and the lateral pathways innervate the _____ muscles.
axial; extremities/peripheral
What is the process from stimulus sensor to effector output happen?
What are 5 SCI management & repair strategies require?
- Preservation of neural tissue (at and around site of impact)
- Preservation of white matter (ascending and descending pathways)
- Replacement of lost cells (incl. grey matter at site of impact)
- Regrow damaged pathways
- Appropriately rewire circuitry
With spinal injuries, the primary injury is the mechanical injury due to the trauma. The only thing we can possibly do for this is stem cells to ____ pathways, and then link these up with the cortical mapping. This is probably far off into the future.
regrow
After a traumatic spinal injury, the first step after injury in the hospital is to relieve _______on the tissue, and to ______the spine as quickly as possible.
compression; realign
The only part of an axon that can survive a lesion is the part connected to the ________.Thus there is a loss of the _____ axons up to the brain above the lesion, and loss of _____ axons after the lesion peripherally in the spinal cord.
cell body (Wallerian degeneration); sensory; motor
Degeneration of the grey matter at the site of the injury due to the lesion - the immediate consequence is loss of ___ output and ___ input. Thus at the level of the lesion there will be ____ paralysis, and loss of _____ from that level. Symptoms indicate the number of segments affected.
motor; motor; flaccid; sensation
What are the 2 types of spinal cord injuries?
- Primary
- Secondary
What is classified as a primary SCI? What is it caused by?
Immediate cell death and neural circuit interruption compression and displacement of spinal cord
What are symptoms of a primary SCI?
There is immediate paralysis or loss of function due to the mechanical injury. There is an enormously heterogeneous population - due to different mechanisms and severity of injury. The primary lesion is almost always anatomically incomplete. To determine the extent of function loss, you test sensory discrimination in dermatomes, and motor deficits in myotomes.
What causes a secondary SCI caused by?
If the compression is maintained on the tissue, then progression of damage occurs. There are many factors that contribute to progression of damage beyond the area that was initially damaged. These are amenable to intervention to slow/limit progression.
What are 4 drivers of secondary SCI?
- Excitotoxicity
- Oedema & Ischaemia
- Oxidative stress
- Post-traumatic inflammation
What is excitotoxocity in regards to a secondary SCI?
Ion balances are disturbed with the lesion, and nerves release neurotransmitter as a result of the primary injury.
An excess of neurotransmitter overwhelms unaffected neurons (causing too much calcium in the cell) and death occurs. too much excitation= cell death
What is oedema & ischaemia in regards to a secondary SCI?
O:tissue swelling
I: if you starve the tissue of nutrients and oxygen, this contributes to loss of tissue.
What is post traumatic inflammation?
In CNS injuries the inflammatory response is deregulated and overactive/over-exaggerated, and release of inflammatory chemicals may cause further damage that spreads beyond this primary injury area.
What are the 2 types of post traumatic inflammation?
- Cell-mediated
- Granulocytes, monocytes, macrophages, microglia !
- Humoral immunity
- complement, antibodies, cytokines, chemokines
What does a secondary SCI cause? Why is it a problem?
Lesion expanding upward or downward can be a concern in the cervical spinal cord - ie. phrenic nerve - one level can be the difference between breathing independently and breathing on a ventilator.
What does a spinal cord look like shortly after contusion injury?
profound bleeding most vascularised- grey matter
What does a spinal cord look like 2 years after a contusion injury?
‘Final appearance’ of the lesion site is the ‘________’ of both primary and secondary injury
end product
Primary injury caused by _____ impact. This is _____ (reversible/irreversible) - Secondary injury is driven by ______ processes => This processes is ______ (amendable/not amendable) to intervention.
mechanical; irreversible; biological; amendableWhat
What does the vivo imaging reveal in spinal cord atrophy from the acute to chronic period?
What does IVIG stand for?
intravenous immunoglobulin (IVIG) therapy
What is the purpose for IVIG?
Targeting post-traumatic inflammation in SCI
What is IVIG?
Liquid formulation containing purified immunoglobulin isolated from pooled blood plasma of >1,000 healthy donors
What does IVIG contain?
Contains mostly polyclonal Immunoglobulin G (IgG; >98%), in monomeric form, with the remainder being IgA and IgM
Has IVIG therapy been used in clinical treatment of SCI?
• Already used clinically for an=body replacement therapy, and as an immunomodulatory agent in autoimmune disorders, including a number of neurological conditions.
What effect does acute administration of IVIg (1 hr post-injury) have on SCI?
Improves the outcome from SCI in a dose-dependent manner
What effect does acute administration of IVIg (1 hr post-injury) have on functional outcome of SCI?
The treatment resulted in increased ability to walk along the beam without the lower end of the body falling off the beam.
The treatment is anti-inflammatory and stops the secondary injury, thus reducing the overall damage from the lesion.
What effect does acute administration of IVIg (1 hr post-injury) have on myeline content of SCI?
Increased preservation of white matter.
What effect does acute administration of IVIg (1 hr post-injury) have on lesion volume/length of SCI?
Lesion length and volume is reduced.
What effect does acute administration of IVIg (1 hr post-injury) have on astrogliosis of SCI?
Scarring is reduced.
*scarring is due to astrophytes
IVIg therapy at a dose of 0.5 g/kg or above improves _____ from SCI
recovery
IVIg therapy in the effective dose range (0.5-2 g/kg) also ____ (increases/decreases) myelin content, ________(increases/decreases) lesion size and ________(increases/decreases) extent of astrogliosis
increases; decreases; decreases
IVIg therapy at a dose of 0.1 g/kg or below was ____ (effective/ineffective) in improving the functional outcome from SCI
ineffective
What are the outcome measures in animal models VS human SCI? ADDDDD
IVIg therapy also leads to improved ______ & increased presence of NF200+ axonal profiles
tractography
What is the Inclusion criteria for the Open-label Phase I Clinical Trial in the INFUSE (Intravenous Immunoglobulin for Acute Spinal Injuries)?
NOT IMPORTANT
- Aged 16+ and able to provide informed consent
- Acute, non-penetra=ng cervical or thoracic SCI (down to T9); AIS grade A, B or C on admission
- Able to initiate IVIg treatment within 12 hours of SCI
- Spine surgery / decompression within 24 hours post-SCI
What is the outcome measure for the Open-label Phase I Clinical Trial in the INFUSE (Intravenous Immunoglobulin for Acute Spinal Injuries)? NOT IMPORTANT
- Safety &Feasibility
- Pharmacokinetics
- Recovery & Adverse Event Incidence
Immediately after injury, the spinal cord usually goes through a phase of ‘_____’. What does this mean? What is the proper name for this?
depression
All functions below the level of the injury site are (transiently) lost
What is spinal shock?
Transient loss of all neurological function at and below the level of the lesion site (including spinal reflexes)
Spinal shock originates from a loss of _________ and disruption of the _________.
descending information / input; blood brain barrier
A moderate injury with transient loss of function is _____ (more/less )likely to regain function, but we don’t have a great ability to assess the severity of the injury.
more
In spinal shock, what are 3 reflexes that can be lost?
- Somatic reflexes (stretch, withdrawal, crossed extension reflex)
- Autonomic reflexes
- Autonomic regulation of blood pressure (hypotension)
When do the reflexes return? What is a complication
within several weeks; hyper-reflexia can develop
What is hyper-reflexia?
Due to lack of descending inhibition, as well as local plasticity of neurons in the spinal cord itself. This hyper-reflexia can be due to a sensory stimulus - ie. somatic reflexes, or it can be an autonomic reflex - ie. when transferred from lying to sitting there is an enormous spike in blood pressure due to hyper-reflexive autonomic reflexes.
What happens in the sub-acute and/pr chronic stage of a spinal cord injury?
spinal shock has resolved • neurological deficit becomes ‘stable’
When diagnosing & predicting recovery in SCI (heterogeneity vs. homogeneity), what are we able to know?
the moderate injury animal regains a great deal of function, and the severe injury isn’t recovering very much function at all.
What is hypotonia?
Flacidity
What are 3 causes of hypotonia?
- cerebellar disorders
- lower motor neuron lesions
- temporarily (acute phase) after upper MN lesion (spinal or cerebral shock)
What is hypertonia?
(strong resistance to passive stretch)
What are 3 causes of hypertonia?
- chronic upper MN lesions
- some basal ganglia disorders
- Due to loss of descending inhibition.
What is the treatment for basal ganglia disorders? How does it work?
Baclofen treatment (GABAB receptor agonist Activates inhibitory interneurons, thus reducing some of the hypertonia.
What is the ASIA impairment scale?
A = Complete
No sensory or motor function is preserved in the sacral segments S4-5. (can still have function in other areas)
B = Sensory
Incomplete Sensory but no motor function is preserved below the neurological level and includes the sacral segments S4-5.
C = Motor Incomplete
Motor function is preserved below the neurological level, and more than half of key muscles below the neurological level have a muscle grade less than 3.
D = Motor Incomplete
Motor function is preserved below the neurological level, and at least half of key muscles below the neurological level have a muscle grade greater than or equal to 3.
E = Normal
Sensory and motor function are normal
What is a AIS A?
A = Complete
No sensory or motor function is preserved in the sacral segments S4-5. (can still have function in other areas)
What is an AIS B?
B = Sensory Incomplete
Sensory but no motor function is preserved below the neurological level and includes the sacral segments S4-5
What is an AIS C?
C = Motor Incomplete
Motor function is preserved below the neurological level, and more than half of key muscles below the neurological level have a muscle grade less than 3.
What is an AIS D?
D = Motor Incomplete
Motor function is preserved below the neurological level, and at least half of key muscles below the neurological level have a muscle grade greater than or equal to 3.
What is an AIS E?
E = Normal
Sensory and motor function are normal
What are the motor and sensory areas in a spinal cord? SUMMARY SLIDES
What is the cause of an anterior cord syndrome?
Interruption of blood supply to the anterior part of the spinal cord
What are the 3 consequences of an anterior cord syndrome?
- Paralysis
- Nociception
- Proprioception
- Loss of lower motor neurons at the level of the affected level - causes flaccid paralysis.
- Below the affected level there would be loss of upper motor neurons descending through the pyramidal pathways - which would cause spastic paralysis / hypertonia.
- Preservation of dorsal column sensory function - ie. proprioception.
What is the cause of a central cord syndrome?
overextension of the spine (more common in elderly people)
What are the 2 consequences of a central cord syndrome?
Bilateral loss of
- pain
- temperature
- The second order neuron in the anterolateral pain pathway is affected (crosses at the anterior commissure).
- As the lesion progresses there will be more symptoms in the dorsal column/medial lemniscus pathway and the descending motor pathways.
How does injury location dictate functional deficits.
POSSIBLE EXAM QUESTION
What are 2 types of quadriplegia? Where is the lesion?
- Impairment of arm, trunk, lower limb and pelvic region
- Lesion C4 - above: cannot breath independently
What happens with a cervical lesion?
Quadriplegia
What happens with a thoracic lesion?
Autonomic function is also lost at the thoracic region - ie. sexual function, bladder and bowel control. There can also be impaired immune function, because of the loss of descending control from the brain that affects the autonomic innervation of the spleen and bone marrow (causes increased susceptibility to infection and decreased wound healing).
What are the 2 paraplegia / paresis?
- Arm function is spared
- Function of trunk, lower limbs and pelvic region depends on level and severity
ADDD
What is framework of locomotor control?
Central pattern generators generate _____ movements that don’t require direct cortical control.
stereotyped
What are conceptual models for functional recovery after spinal cord injury?
If there was no CPG, what would happen?
We would need to regrow every single transected neuron and reconnect them.
If there is a CPG that is still intact, what would happen?
We only need to form a relay or a new connections bypassing the lesion through tissue that was spared to return some level of function.
What causes a Brown Séquard spinal injury?
Hemisection
What are some effects that a Brow Séquard spinal injury has caused?
- Contralateral loss of pain & temperature
- Ipsilateral motor, proprioception & discriminative touch.
- At injury side: Motor & loss of all sensory.
