SPINAL CORD INJURY

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OUTLINE

Spinal Cord Anatomy and Structural Changes with SCI

SCI events and natural recovery
Clinical Assessment of SCI
SCI Therapy

SPINAL CORD STRUCTURE &

FUNCTION

SPINAL CORD
WHAT:
Forms part of CNS
Elongated cylinder of nervous tissue and support cells
45cm long and varying width (2 enlargements)
LOCATION:
Extends from the medulla oblongata of the brain
Down the vertebral canal (surrounded/protected by vertebrae)
Ends at 1 st lumbar vertebrae (2/3 of canal)
FUNCTION:
Transmits sensory input from body to the brain
Conducts motor impulses from brain to muscles and organs
Reflex center
Intercepts sensory signals and initiates a reflex signal

GROSS
ANATOMY

31 Segments:
gives rise to 31 pairs
of spinal nerves
4 Regions:
cervical, thoracic,
lumbar, and sacral
2 Enlargements:
cervical, and lumbar
(tapers to conus
medullaris, then
cauda equina)
3 meninges
(fibrous CT): pia,
arachnoid, dura
mater

Grey Matter

White Matter

Neurons: cell bodies, dendrites, proximal axons

Dorsal Horn: sensory neurons
Interneurons: forms reflex arc
Lateral Horn (T2-L1): sympathetic nervous system
Ventral Horn: somatic motor neurons
Central canal: ependymal cells CSF

Tracts: bundles of myelinated axons

Bundles 3 pairs = columns/funiculi:
dorsal, lateral, ventral each have
subdivisions = tracts/fasciculi

CROSS-SECTION

Ascending Tracts
Carry sensory information from the
body, upwards to the brain
Touch
Skin temperature
Pain
Joint position

Descending Tracts
Carry information from the brain
downwards:
Initiate movement
Control body functions.

VASCULATURE
Arteries

Veins

Single anterior spinal a.

Paired posterior spinal a.
Arterial vasocorona (anastomoses)
Segmental/radicular a.

Anterior & posterior spinal veins

Anterior & posterior radicular veins

SCI: LATE CHANGES IN STRUCTURE

Macroscopic Changes

Microscopic Changes

Lesion
Reduction in spinal cord
diameter (spinal atrophy,
neurodegeneration)
Formation of cysts
Formation of syrinx

Loss of white matter integrity:

o Wallerian degeneration: axonal degeneration, tract
demyelination
o Astroglial scar
o Schwannosis
o Mesenchymal scar (esp. after laceration)

SCI EVENTS & HEALING

LETS DEFINE SPINAL CORD INJURY!

Definition: Damage to the vertebrae, ligaments or disks of the
spinal column or to the spinal cord itself.
Results nerve fibres transection and damage to surrounding
tissues via secondary injury
Secondary injury responsible for continued cell death in
intact tissue surrounding the site of injury
Cascade of events
A. Increased activation of neuronal glutamate receptors
B. Increase in calcium influx, protease activity
C. Loss of mitochondrial function
D. Increased free radical oxidative stress with ischaemia
and haemorrhage

SPINAL CORD INJURY

Extensive loss of oligodendrocytes (following days & weeks)
Via necrosis, apoptosis, and autophagy
Oligodendrocyte loss and demyelination => loss of function
+ impacts functional recovery
Typical of traumatic CNS lesion: Exacerbation of primary lesion

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SCI EVENTS AFFECTING HEALING

Damage to blood vessels -> Microhemorrhage in the central
gray matter
Hypoxia and ischaema -> Deprive grey and white matter of
oxygen and nutrients necessary for neural cell survival and
function.
Swelling rapidly occurs at the injury level, and because the
bony spinal canal has a fixed diameter, pressure on the cord
climbs higher than venous blood pressure.
Immediate effect = spinal shock
Continued and selective cell death and demyelination in
previously intact tissue adjacent to the injury epicentre (Silver
& Miller, 2004; Donnelly & Popovich, 2008)

13

SCI EVENTS AFFECTING HEALING

Post SCI - Inflammatory environment
Causes destruction of tissue surrounding the injury
Some have neuro-protective effects
Microglia and macrophages can produce protective growth factors
and cytokines
Limits oligodendrocyte toxicity
CNS macrophages -> axon growth and regeneration.
Chronic phase of injury - loss of central grey matter in surrounding
segments
Fluid-filled cyst with cerebrospinal fluid -> cavitation and cord collapse
Rim of white matter surrounding injury epicentre - Accounts for
functional recovery
Extent of white matter rim
Remaining axonal connections (Tang et. al., 2003; Silver and Miller,
2004)

SCI EVENTS AFFECTING HEALING

Dural scarring - Microinjury and impaired
functional recovery
Highly inflammatory environment - Glial
scar formation
Majority of astrocytes hypertrophy to
bolster surrounding intact neural circuits
from worsening damage
Astrocytic or glial scar - limits growth of
regenerating axons and can persist for
extended periods depending on injury
severity (Tang et. al., 2003)
Within region of forming scar tissue,
axons unable to continue extending swell
and distort into growth cones that can
exist for years within axon tracts
Axonal connections cannot be as
effectively reformed (Silver and Miller,
2004; Kwon et. al., 2002)

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FACTORS AFFECTING PROGNOSIS

Determined following clinical examination according to the

International Standards for Neurological Classification of SCI
General prognostic indicators: Extent of injury, age and the
amount of preserved spinal cord function
Greater functional preservation => Better prognosis for
recovery

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FACTORS AFFECTING PROGNOSIS

Of patients who present in

the first 72 hours
> 80% with distal
movement
> 70% with no motor
strength but sensory ability
(B) were able to recover to
walk again (Masri, 2010)

Patients with A (Complete

injury) but with pin prick
sensation in a partial
preservation zone recover
some functional myotomes
(Consortium for Spinal Cord
Medication, 1999)

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CLINICAL ASSESSMENT
OF SCI

CLINICAL ASSESSMENT OF SCI

Prognoses based on neurological exam done by clinician
2 types of SCI
Complete no motor and sensory function in sacral segments S4-5
Incomplete partial preservation of sensory and/or motor function at
S4-5

Assessment important for determining long-term prognosis

CLINICAL ASSESSMENT OF SCI

(Burns et al, 2011)

CLINICAL ASSESSMENT OF SCI

Light touch and pinprick assessed bilaterally at 28 dermatomes
0-3

Motor function assessed by bringing patients through 5 key

muscle actions
0-5

CLINICAL ASSESSMENT OF SCI

Grade Definition
A
B
C

Complete. No sensory or motor function is preserved in the sacral

segments S4-5
Incomplete. Sensory but not motor function is preserved below the
neurological level and includes the sacral segments S4-5
Incomplete. Motor function is preserved below the neurological level,
and less than half of key muscles below the neurological level have a
muscle grade greater than or equal to 3
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
Normal. Sensory and motor functions are normal.
(Burns et al, 2011)

RELATIONSHIP BETWEEN TIMING OF

ASSESSMENT AND PROGNOSIS

(Goodwin-Wilson, Watkins, Gardner-Elahi, 2010)

RELATIONSHIP BETWEEN TIMING OF

ASSESSMENT AND PROGNOSIS
Evidence-based process maps for SCI rehabilitation
Patient activity matched with ASIA impairment scale
Shown to provide better insight to patient rehabilitation process
(Goodwin-Wilson, Watkins, Gardner-Elahi, 2010)

THERAPY FOR SPINAL

CORD INJURY

T
S

BONE MARROW-DERIVED MESENCHYME STEM

CELLS

BONE MARROW-DERIVED MESENCHYME STEM

CELLS
Capable of directly differentiating into neurons
Able to migrate to areas of injury and inflammation
A study of 20 SCI patients who were administrated
BMMSC showed improvement in motor and sensory
function in 5 out of 7 patients with acute SCI and 1 out
of 13 chronic SCI patients
Not as effective in chronic spinal cord injuries and is
associated with chondroitin sulfate proteoglycans

NEUROTROPHIN-3

NEUROTROPHIN-3
Useful in modulating neuronal survival, axonal
growth and synaptic plasticity
It works through interaction with trk receptors
Enhancing the regeneration of damaged tissue
and is used combination with stem cell
transplantation

EXTRACELLULAR MATRIX MODIFICATION

Another possible avenue of treatment of spinal cord injury (SCI)
involves the modification of extracellular matrix
ECM creates an environment less than optimal during SCI through
the restriction of plasticity and regeneration
Chondroitin sulphate proteoglycans (CSPGs) are a component of
the ECM which are detrimental to the repair of the CNS
Administration of chondroitinase ABC (ChABC), an enzyme which
inhibits CSPGs has clinical potential
Genetic evidence of this was in a study involving ChABC
transgenic mice with dorsal root injuries who exhibited improved
function through repair of nociceptive axons

LIMITATIONS
Stem Cell:
Also In a systematic review of in-vivo models only 19 out of 162
studies involved human cells, with the majority utilizing rat
models (Tetzlaff et al., 2011)
NGF:
No single experimental treatment can tackle all of these factors
limiting ability to augment axonal regeneration
Modification of ECM:
The delivery of ChABC to the CNS still has issues in its safety,
biodistribution, and thermal stability
Another pitfall is the lack of larger mammals as test subjects with
the majority being rodent models.

TEAMWORK

BELBIN MODEL
First and second years
We did Belbin for personal assessment to understand the roles we
play in our group and discover any aspects we could improve.
Member

Before

After

Team Worker, Completer Finisher

Coordinator, Completer Finisher

Monitor Evaluator, Team Worker,

Shaper

Implementer, Resource Investigator,

Monitor Evaluator, Team Worker

Implementer, Team Worker, Completer Implementer, Team Worker

Finisher

Implementer, Team Worker, Shaper,

Resource Investigator

Implementer, Completer Finisher, Plant

Plant, Team Worker, Coordinator

Plant, Team Worker, Implementer,

Shaper

BELBIN MODEL ANALYSIS

Strong Team Workers and
Implementers
Versatile, efficient in carrying
out practical plans

Implementer
80
70
Completer Finisher

60

Coordinator

50
40

Consistency; the team having

a variety of roles to balance
each others weaknesses Team Worker

30
20
10
Shaper

Monitor Evaulator

Plant

Resource Investigator
Before
After

CHALLENGES AND STRENGTHS

Challenges: Getting organised, deadlines
Positive: Good teamwork dynamics, efficient meetings, effective task
distribution and feedback, helping each other with understanding
difficult tasks

REFERENCES
Dasari, V. R., Veeravalli, K. K., & Dinh, D. H. (2014). Mesenchymal stem cells
in the treatment of spinal cord injuries: A review. World journal of stem
cells,6(2), 120.
Jones, L. L., Oudega, M., Bunge, M. B., & Tuszynski, M. H. (2001).
Neurotrophic factors, cellular bridges and gene therapy for spinal cord
injury.The Journal of physiology, 533(1), 83-89.
Satake, K., Lou, J., & Lenke, L. G. (2004). Migration of mesenchymal stem
cells through cerebrospinal fluid into injured spinal cord
tissue. spine, 29(18), 1971-1979.
Skaper, S. D. (2012). The neurotrophin family of neurotrophic factors: an
overview. In Neurotrophic Factors (pp. 1-12). Humana Press.
Ichim, T. E., Solano, F., Lara, F., Paris, E., Ugalde, F., Rodriguez, J. P., ... &
Riordan, N. H. (2010). Feasibility of combination allogeneic stem cell
therapy for spinal cord injury: a case report. Int Arch Med, 3, 30.
Burns, A. S., Marino, R. J., Flanders, A. E., & Flett, H. (2012). Clinical
diagnosis and prognosis following spinal cord injury. Verhaagen, J. and
mcdonald, J. W. III.(eds) handbook of clinical neurology (pp. Chapter 3)
Elsevier BV
Goodwin-Wilson, C., Watkins, M., & Gardner-Elahi, C. (2009). Developing
evidence-based process maps for spinal cord injury
rehabilitation. Epub, 48(2), 122-127.

Dont be spineless

Q&A