neurobiology of disease discussion

Spinal Cord Injury (SCI)

Dr. Katie Dabrowski, PT, DPT

Let’s review some anatomy first

Spinal Cord Structure

• The SC extends to the level of L1/L2 vertebrae • There are 31 pairs of spinal

nerves • 8 cervical nerves (C1-C8) • 12 thoracic nerves (T1-T12) • 5 lumbar nerves (L1-L5) • 5 sacral nerves (S1-S5) • 1 coccygeal nerve

Spinal Cord Structure • The first 7 cervical nerves (C1-C7)

exit above their respective vertebra • C8 exits between C7 and T1

vertebrae • All other spinal nerves exit below

their respective vertebra

Spinal Cord Structure • Conus medullaris = the tapered

lower end of the spinal cord at L1/L2 • Cauda equina = the remaining

spinal nerves that are not considered the spinal cord (remember, the spinal cord formally ends at L1/L2)

Conus medullaris

Cauda equina (Latin for “horse’s tail)

Spinal cord and its relation to the spinal column

Spinal Cord Structure

*Has meninges continuous with the brain

Dura Mater

Arachnoid Mater

Pia Mater

Internal Configuration

Internal configuration

• Each level of the spinal cord has a slightly different configuration • But the organization is the

same: • The grey matter is organized

internally, as the “butterfly” pattern

• White matter is in the surrounding areas

Spinal Cord Cross Section

I. Grey Matter

a. Anterior (ventral) horn

-Motor innervation to skeletal muscle -Specific motor distribution in the anterior horn (proximal muscles represented medially; distal muscles represented more laterally)

*This example is in the lumbar region *This exists similarly in the cervical region, but of course, muscles for the upper extremity

Spinal Cord Cross Section

II. White Matter Ascending and descending tracts

-Ascending tracts are sensory tracts carrying information from the outside world into the spinal cord and into the brain

-Descending tracts are motor tracts carrying information from the brain, to the spinal cord, and to the muscles of the body for motor function

Now we can learn more about SCI

Spinal Cord Injuries

Traumatic:

• Motor vehicle/motorcycle collisions (39.2%)

• Falls (28.3%) • Violence/GSW (14.6%) • Sports (8.2%) • Diving into shallow water (9.7%)

Non-traumatic:

• Cancer • Multiple sclerosis • Inflammation of spinal cord • Arthritis

Complete vs. Incomplete Injuries

• A complete spinal cord injury causes permanent damage to the area of the spinal cord that is damage, and the areas below it • Paraplegia or quadriplegia are results of complete spinal cord injuries • Essentially there is no ability for the brain to send signals to the area below

the site of the injury, therefore no motor or sensory function

• An incomplete spinal cord injury refers to partial damage to the spinal cord - a person will retain some feeling and/or motor function below the injury site

American Spinal Injury Association

(ASIA) Scoring System

How SCIs are scored – we won’t get in- depth on this, but feel free to ask questions if you have any.

Types of Incomplete SCIs: A few examples Central Cord Syndrome:

-Affects center of the spinal cord

-Results mostly in loss of sensation and motor movement in the arms

-Legs are usually less affected Anterior Cord Syndrome:

-Affects the anterior portion of the spinal cord

-Interferes with motor and sensory pathways of touch, pain, and temperature

Brown-Sequard Syndrome: -Rare, but is a lesion of one half of the spinal cord that results in loss of motor and sensory functions below the injury site

Cervical Spinal Cord Injuries

• Cervical portion of the spine = 7 cervical vertebrae (C1-C7) and nerves C1-C8

• Because the cervical spine is the closest to the brain and affects the largest portion of the body, cervical spinal cord injuries are the most severe.

• An injury in the cervical region results in quadriplegia, meaning there is limited or absent feeling or movement below the shoulders/neck.

Cervical Spinal Cord Injuries:

C1-C4

• Most severe spinal cord injury • Paralysis in arms, hands, trunk, and legs • Potential inability to breathe independently, cough, or

control bowel/bladder

• Impaired/reduced ability to speak • Quadriplegia (all 4 limbs affected) • Potential need for complete assistance with activities of

daily living (eating, dressing, bathing, getting in/out of bed) • May be able to use a power chair with special controls • Likely needs 24-hour care • Watch this video here on a C3 level of injury

Cervical Spinal Cord Injuries:

C5

• Can raise arms and bend elbows • Likelihood of some or total paralysis of wrists, hands, trunk,

and legs • Can speak and use diaphragm, but beathing is weakened • Little or no voluntary control of bowel or bladder • Can use power wheelchair to be independent • An example of a C5 injury

Cervical Spinal Cord Injuries:

C6

• Can raise arms and bend elbows and move wrists • Likelihood of some or total paralysis of hands, trunk, and

legs • Can speak and use diaphragm, but beathing is weakened • Little or no voluntary control of bowel or bladder, but may

be able to manage independently with catheters due to hand function

• Can move in and out of wheelchair and bed with assistive equipment

• Watch a person with a C6 injury transfer from bed to wheelchair

Cervical Spinal Cord Injuries:

C6, C7, C8

C6: • Can raise arms and bend elbows and move wrists • Likelihood of some or total paralysis of hands, trunk, and legs • Can speak and use diaphragm, but beathing is weakened • Little or no voluntary control of bowel or bladder, but may be able to

manage independently with catheters due to some hand function • Can move in and out of wheelchair and bed with assistive equipment • Watch a person with a C6 injury transfer from bed to wheelchair

C7: • Can straighten arm and have normal movement of shoulders • More independent • Can drive an adaptive vehicle • Little or no voluntary control of bowel or bladder, but may be able to

manage independently with catheters due to some more hand function

C8: • Can grasp and release objects with hand • Same as above, otherwise

Thoracic Spinal Cord Injuries

• Thoracic portion of the spine = 12 thoracic vertebrae (T1-T12) and nerves T1-C12

• Nerves T1-T5 affect muscles of upper chest, mid back, and abdominals; these nerves also help control the rib cage, lungs, and diaphragm for breathing function

• Nerves T6-T12 affect muscles of abdominals and back. These nerves are important for balance and posture, as well as coughing.

Thoracic Spinal Cord

Injuries

T1-T5: • Typically affect abdominal and lower back muscles, as well

as the legs, and result in paraplegia • Arm and hand function is usually normal

T6-T12: • Paraplegia • Little or no voluntary control of bowel/bladder, but can

manage on their own with special equipment

In general: • Have normal arm, hand, and upper-body movement • Use a manual wheelchair • Learn to drive a modified car • Stand in standing frame or walk with braces

Lumbar Spinal Cord Injuries

• Lumbar portion of the spine = 5 lumbar vertebrae (L1-L5) and nerves L1-L5

• In general, loss of function in hips and legs but upper extremities and trunk are fine

• Little or no voluntary control of bowel/bladder, but can manage on heir own with special equipment

• Depending on leg strength, may require wheelchair or walking with braces

Sacral Spinal Cord Injuries • Sacral portion of the spine = sacrum = 5 bones

fused together. • S1 nerves affect hips and groin • S2 nerves affect backs of thighs • S3 nerves affect buttocks • S4 nerves affect perineal area

• Some loss of function hips and legs • Little or no voluntary control of bladder/bowel

but can manage with special equipment • Affects sex organs • Usually can walk

Pathophysiology of SCI

Pathophysiology of SCI

Primary injury to the spinal cord typically occurs via one of these mechanisms – and can be traumatic (gun shot wound, fall, knife) or atraumatic (medical condition, inflammation, cancer): • Transection • Contusion • Compression

But what really causes lasting damage are the secondary injuries of spinal cord injury.

Secondary Injury of SCI • Secondary injury begins

within minutes following the initial primary injury

• It continues for weeks or months, causing progressive damage of spina cord tissue surrounding the legion site

• It is suggested that these biochemical processes are more damaging to the spinal cord than the primary injury itself

Secondary Injury of SCI: Acute Phase

• Begins immediately following SCI • Includes: • Vascular damage • Ionic imbalance • Neurotransmitter accumulation (excitotoxicity) • Free radical formation • Calcium influx • Lipid peroxidation • Inflammation • Edema • Necrotic cell death

Secondary Injury of SCI: Sub-Acute Phase

• Includes: • Apoptosis • Demyelination of surviving axons • Wallerian degeneration • Axonal dieback/retraction • Matrix remodeling • Formation of a glial scar around the injury site

Secondary Injury of SCI: Chronic Phase

• Includes: • Formation of a cystic cavity • Progressive axonal dieback/retraction • Maturation of the glial scar

Let’s dive deeper into pathophysiology of SCI secondary injury

I. Vascular injury, ischemia, and hypoxia

• Disruption of SC vascular supply and decreased perfusion of blood to the area is one of the earliest consequences of injury

• Shock in SCI patients due to excessive bleeding and neurogenic shock results in even less SC perfusion, and therefore ischemia

• Small spinal arteries often rupture

II. Ionic imbalance, excitotoxicity, and oxidative damage

• Within a few minutes after primary SCI, the combination of direct cellular damage and ischemia/hypoxia triggers a significant rise of extracellular glutamate (the main excitatory neurotransmitter in the CNS)

• This results in calcium influx inside of cells, and this calcium overload results in oxidative damage and mitochondrial failure

• Increased calcium also damages white matter, astrocytes, oligodendrocytes, and myeline sheaths

• Within the first few hours after injury, myelin density decreases and calcium- mediated apoptosis occurs

II. Ionic imbalance, excitotoxicity, and oxidative damage

• Mitochondrial calcium overload also results in ATP depletion, therefore disabling the ATP-dependent Na+/K+ pump that is so crucial for maintaining ion balance in neurons

• This causes an increase in intracellular Na+, and also further increases intracellular Ca2+

• The more the cell depolarizes because of the Na+ and Ca2+ infiltration, more Cl- and water enters the cell, causing swelling and edema and furthering the ionic imbalance

• Axons are more susceptible to damage when ionic imbalance is in the picture

II. Ionic imbalance, excitotoxicity, and oxidative damage

• SCI also results in the production of free radicals and nitric oxide (NO)

• This leads to glycolysis failure, ATP depletion, and cell death

• Oxidation of lipids and proteins marks one of the key mechanisms of secondary injury following SCI

III. Cell Death

• Following SCI, neurons and glial cells die via necrosis as a result of the mechanical damage at the time of primary injury

• This continues along through the acute and subacute stages of injury

• Necrosis occurs due to: Toxic blood component accumulation, glutamate excitotoxicity and ionic imbalance, ATP depletion, inflammatory molecule increases, and free radicle formations

• Apoptosis occurs within hours after primary injury – it occurs primarily in the cells that survive the primary injury

IV. Neuroinflammation

• Inflammation can be both beneficial and detrimental for the outcome of SCI

• 0-2 days post injury: Recruitment of microglia, astrocytes, and neutrophils to injury site

• 3 days post injury: Recruitment of macrophages, B- and T-lymphocytes to injury site to produce antibodies • In SCI, the production of antibodies

against injured spinal cord tissue exacerbates neuroinflammation and causes further tissue destruction

• Inflammation is of course present in the beginning stages of injury, but can persist for the remainder of a patient’s life

IV. Neuroinflammation: Astrocytes

• Astrocytes aren’t an immune cell per se, but they play vital roles in the neuroinflammatory process in CNS injury and disease

• In the normal CNS, astrocytes play a major role in maintaining CNS homeostasis via: • Maintaining structure and function of

blood-brain barrier • Provide nutrients and growth factors to

neurons • Remove excess fluids, ions, and

neurotransmitters • Astrocytes react to CNS injury via:

• Increasing cytokine and chemokine production to increase inflammatory molecules

V. Glial Scar • Traumatic SCI triggers the formation of a glial

scar tissue around the injury epicenter

• The glial scar begins to form within the first hours after SCI, and remains chronically in the spinal cord tissue

• It serves as a protected barrier that prevents the spread of infiltrating immune cells into adjacent spinal segments

• Despite this protective role of the glial scar, its evolution and persistence in the subacute and chronic stages of injury is considered an inhibitor for spinal cord repair and regeneration

What do we see

clinically?

What do we see

clinically?

What do we see

clinically?

What do we see

clinically?

A success story! • One of my favorite patients of all times! • He came into the SCI unit with a central cord injury at the C6 level,

meaning his major deficits were in his upper extremities but he also had extreme spasticity and ataxia of his lower extremities, so he could not walk.

• For the majority of our time working together, he was in a power wheelchair and we worked on him learning to move around his bed, sit at the edge of the bed, transfer to/from the bed and wheelchair, and eventually stand with a LOT of support in front of a mirror.

• By the end of our time together, he was able to stand in the parallel bars (again, with a LOT of support)

• On his last day of inpatient rehab with me, he told me his final goal was to stand and hug me.

• A year later, I visited him and his family and was greeted by him walking to open the door of a restaurant, completely unassisted. Yeah, I may have cried a little…

Permission was given for using these photos.

Optional Discussion Board Post: Q&A

• I’ve included an optional discussion board post for any further questions on SCI • I’ve worked extensively in SCI rehab and it is by far one of my favorite

populations to treat – please don’t hesitate if you have any questions at all or curiosities you want to explore!