39 Spinal Cord Injury
Ashraf N. El Naga, Joseph R. Mendelis, Anthony M. DiGiorgio, Sigurd H. Berven
SUMMARY OF KEY POINTS
• Spinal cord injury results from both the primary injury
and a subsequent secondary injury cascade.
• Understanding the secondary cascade of spinal
cord injury has identified potentially modifiable
components, and may translate to future treatment
strategies in patients with acute spinal cord injury.
• Prognosis following spinal cord injury largely depends
on the initial neurological deficits.
• Clinical manifestations of incomplete cord injuries are
reflective of spinal cord functional anatomy.
• An understanding of incomplete cord injuries can
guide patient prognosis and expected functional
needs.
Spinal cord injuries (SCIs) encompass a diverse spectrum of
injury mechanisms and severity. SCIs can be devastating inju-
ries with significant morbidity that have detrimental effects
on patients’ quality of life, functional status, employment,
and independence. Patients with significant neural functional
loss often require extensive treatment and rehabilitation. The
impact of SCI is important and significant, with measurable
personal, economic, and societal costs.1 The purpose of this
chapter is to review the epidemiology, mechanisms, patho-
physiology, and classification of SCI.
EPIDEMIOLOGY OF SPINAL CORD INJURY
The global incidence of SCI has been estimated at between 10
and 83 cases per million people per year.1-3 Estimates of global
prevalence are limited by regional differences in the collection
and reporting of new and existing cases, particularly in devel-
oping countries.1 In the United States, incidence per year has
been estimated to be 40 cases per million people, with approx-
imately 11,000 new cases each year.4 The incidence of high
cervical injury in the United States has been steadily increasing
over the past few decades, which is attributed to an increase in
geriatric spine trauma, as well as advances in prehospital resus-
citation and care.5,6 Men sustain these injuries more frequently
than women, at a ratio of 4:1.5 With regards to age, similar to
most trauma, there is a bimodal distribution, with a large peak
between the ages of 15 and 29 years and a second peak at ages
greater than 65 years.7  and subacute phases (∼2 days to 2 weeks),6 resulting in further
MECHANISMS OF SPINAL CORD INJURY
The mechanism of acute SCI varies widely. Blunt trauma
remains the most common mechanism of injury, including
motor vehicle and auto–pedestrian collisions, as well as falls.
Falls appear to be accounting for the increase in SCIs amongst
older patients.2,5,8 Crush and penetrating injuries account
for substantially fewer injuries, but carry specific consider-
ations regarding their treatment (Fig. 39.1). The proportion of
traumatic SCI caused by motor vehicle collisions is decreasing
in developed countries but increasing in developing countries.2
In the elderly, low-energy falls account for a greater proportion
of traumatic SCI in developed countries.2 The mechanism and
energy of an injury are important determinants of the injury’s
impact on spinal cord function. 
PATHOPHYSIOLOGY
The past few decades have brought a better understanding
of the underlying pathophysiology of acute SCIs. Knowledge
of the early cellular injury and inflammatory processes that
accompany SCI may translate to improved treatment modali-
ties for patients. These advances have changed our understand-
ing regarding the initial medical and critical care management
of SCI patients, the timing of surgery, and the potential of
neuroprotective and neuroregenerative strategies. The current
framework for understanding SCIs involves both a primary
injury and a secondary cascade (Fig. 39.2).
Primary Injury
The primary injury is the direct result of the inciting traumatic
event—this leads to failure of the mechanical stability of the
spine (e.g., fracture or dislocation) such that it no longer can
perform its function of protecting the neural elements. This
results in a combination of direct impact and dissipation of
force and energy, causing injury to axons, cell membranes, and
the microvasculature responsible for local perfusion.9 At the
site of injury, disruption of sympathetic output at the interme-
diolateral column can lead to hypotension and bradycardia
(neurogenic shock), with further hypoperfusion resulting in
worsening of spinal cord ischemia.10,11 This initial insult can
also lead to death and disruption of local cells, and to local
cytokine and glutamate release. The primary injury then trig-
gers a secondary cascade responsible for ongoing ischemia,
cell and tissue injury, and expansion of the zone of injury. 
Secondary Cascade
After the initial traumatic insult, there is a secondary cascade
that leads to further injury. This is characterized by spinal cord
ischemia and vascular disruption, cellular ischemia, excitotox-
icity, free radical production, delayed apoptotic cell death, and
eventual local tissue remodeling.9 The secondary cascade con-
sists of immediate (∼0–2 hours), acute (∼2 hours to 2 days),
local tissue destruction and expansion of the zone of injury,
whereas the primary injury cascade immediately follows the
inciting trauma and is characterized by microvascular injury
and local cell death. During the initial injury period, local
hemorrhage, thrombosis, and edema result in subsequent dis-
turbances to local tissue perfusion and ischemia. Direct injury
from the inciting event also damages the blood–spinal cord
barrier, permitting inflammatory mediators to enter the zone
of injury,12 which in turn leads to the release of proinflam-
matory substances, cytotoxic chemicals, and ions, including
371
372 PART 2  Pathophysiology of Spinal Disorders
Fig. 39.1. Axial computed tomography scan of a gunshot wound to
the cervical spine, demonstrating multiple fragments and a resultant
fracture of the vertebral body.
glutamate, calcium, and sodium. Along with other potential
mediators, neurochemical toxicity of inflammatory mediators
leads to local excitotoxicity to cells, ionic dysregulation, and
free radical production, all of which contribute to further tis-
sue injury in the secondary cascade. Disruption of local per-
fusion, either by ongoing neural and vascular compression
or local microvascular injury, leads to further vasospasm and
vasoconstriction that can progress over the first 24 hours after
initial injury.
The early hypoperfusion, proinflammatory disturbances,
ionic dysregulation, and local excitotoxicity lead to further
vasogenic and cytotoxic edema and cellular injury.9 Cellular
necrosis and disruption of cell membranes leads to the release
of inflammatory mediators and to further local cell death, and
the inflammatory milieu leads to further acute local ischemia.
The local excitotoxicity, such as that mediated by glutamate
and the increase in local calcium concentration, leads to local
apoptosis in cells, including local oligodendrocytes, which
can affect the myelinated pathways that were not initially
injured during the primary cascade. Inflammatory cytokines
also mediate local neutrophil infiltration—the release of
cytokines results in the eventual macrophage infiltration,
reactive astrocytosis, fibrotic and glial scar formation, and
the resolution of edema that characterizes the subacute phase
of cord injury. This reactive astrogliosis that typically occurs
around the zone of injury is associated with deposition of
chondroitin sulfate proteoglycans and cells expressing neural/
glial antigen 2—impediments to axonal regeneration.13 This
is a complex process regulated by several mediators, including
bone morphogenetic proteins, matrix metalloproteinases,
and growth factors, which may provide targets for future
therapeutic intervention.
The events of the primary injury cascade occur early in
the injury process and have little potential for significant
modification. However, identification of potentially modifiable
components within this secondary cascade may guide effective
treatment strategies in patients with acute SCI. A better
understanding of the effects of local tissue hypoperfusion have
led to advocacy for earlier decompression and spinal cord
reperfusion strategies, including initial resuscitative efforts
October 06, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.
and early blood pressure and spinal cord perfusion support.
Several strategies for neural protection are currently under
investigation to disrupt and halt portions of the secondary
cascade, including interventions to limit excitotoxicity and to
moderate the inflammatory cascade that results in late tissue
injury. 
CLINICAL MANIFESTATIONS OF SPINAL CORD
INJURY
Patients with SCIs present with a wide spectrum of deficits.
Early identification of neural injury is paramount to guiding
early treatment of patients with SCI. The presence of any
motor or sensory deficit in the spine trauma patient warrants
an evaluation for SCI with advanced imaging of the neural
axis. In an awake, responsive, and examinable patient, neu-
ral injury can be identified early through thorough physical
examination. However, in the patient who is unresponsive
or otherwise unable to participate in examination, recog-
nition of other signs of SCI is important for an early diag-
nosis. Early signs of SCI include hemodynamic instability,
characterized by bradycardia indicating neurogenic shock,
flaccid paralysis, priapism, the absence of response to pain-
ful stimuli in the extremities, and paradoxical or unequal
chest wall movement.14 Spinal shock, or the transient loss of
reflex, motor, and sensory function below a level of injury,
may have a variable duration but usually resolves within
24 hours. The primary survey, resuscitation, operative, and
medical treatments of patients with acute SCIs are discussed
in subsequent chapters in this textbook. Once the presence
of an SCI or neural deficit is identified, the extent of the
injury must be better characterized to guide prognosis and
further care.
American Spinal Injury Association Classification
Identification and classification of the neural status of injured
patients is paramount to the effective short- and long-treat-
ment, prognosis, and care planning for SCIs. A common clas-
sification system allows for accurate communication between
providers and researchers working with SCI patients.15 In
conjunction with the International Spinal Cord Society,
the American Spinal Injury Association (ASIA) published
the most recent edition of the International Standards for
Neurological Classification of Spinal Cord Injury (ISNCSCI) in
2019.16 This scoring system is currently recommended for use
by all physicians treating SCI patients, and consists of three
components: light touch and pinprick in each dermatome,
manual strength examination in ten specific muscle groups
on the right and left side, and an anorectal examination. The
distinction between complete and incomplete cord injuries is
based on the presence of sensation at S4‒S5 and is made after
resolution of spinal shock and return of the bulbocavernosus
reflex. 
PATTERNS OF INCOMPLETE SPINAL CORD INJURY
There is a wide spectrum of SCI patterns. At the most severe
end of the spectrum are complete cord injuries, described as
ASIA impairment scale (AIS) A in the ISNCSCI scoring sys-
tem (Box 39.1). Complete SCIs account for approximately
half of all SCI patients.1 Although some studies indicate that
only 10% to 15% of patients with a complete lesion on ini-
tial evaluation will convert to an incomplete cord injury,6 in
one series Catapano et al. showed that 33% of patients who
present after SCI as AIS A and 76% of patients who present as
AIS B/C may improve by one grade or more before hospital
discharge.17
 Spinal Cord Injury 373

Neuroprotective agents
Mechanisms Timeline Methylprednisolone 39
Naloxone
Primary injury: Injury Nimodipine
• Compression event Tirilizad
• Laceration Minocycline
• Distraction Riluzole
• Shearing Basic fibroblast growth factor
Magnesium-polyethylene glycol
Seconds
Intact myelinated
axon

Immediate:
• Hemorrhage
• Decreased ATP
• Increased lactate
concentration (acidosis)

Minutes

Epicenter
Early acute: of injury
• Vasogenic edema
• Microvessel vasospasm
• Thrombosis
• Ion balance
• Loss of sodium gradient
• Release of neurotoxic opioids Hours
• Inflammation
• Lipid peroxidation
• Glutamatergic excitoxicity Demyelinated Severed
• Cytotoxic edema axon axon
• Formation of free radicals

Neuroregenerative agents
GM-1 (Sygen)
Subacute: Cethrin
• Microglial stimulation Anti-Nogo
• Macrophage activation Days/ Chondroitinase ABC
• Apoptosis weeks Neural stem cells

A B
Fig. 39.2. Mechanisms of spinal cord injury related to trauma. A, Primary and secondary mechanisms of injury determining the final extent of
spinal cord damage. The primary injury event starts a pathobiological cascade of secondary injury mechanisms that unfold in different phases
within seconds of the primary trauma and continue for several weeks thereafter. B, Longitudinal section of the spinal cord after injury. The
epicenter of the injury progressively expands after the primary trauma as a consequence of secondary injury events. This expansion causes
an increased region of tissue cavitation and, ultimately, worsened long-term outcomes. Within and adjacent to the injury epicenter are severed
and demyelinated axons. The neuroprotective agents listed act to subvert specific secondary injuries and prevent neural damage, whereas the
neuroregenerative agents act to promote axonal regrowth once damage has occurred. ATP, Adenosine triphosphate. (From Wilson JR, Forgione
N, Fehlings MG. Emerging therapies for acute traumatic spinal cord injury. CMAJ. 2012;185(6):485-492.)

Incomplete SCI patterns are important to identify, and carry
a better prognosis for partial or complete recovery of neural
function when compared with complete SCI. Incomplete
SCI patterns include central cord syndrome, anterior cord
syndrome, posterior cord syndrome, Brown–Séquard
syndrome, and conus medullaris syndrome. Incomplete cord
syndromes account for between 21% and 33% of all patients
with cord injuries.18,19 Identification of such patterns can
guide patient prognosis and planning for future care.19 The
clinical manifestations and symptoms reflect the portions of
the cord that are injured (Fig. 39.3). An understanding of the
anatomy of the spinal cord is important to understand the
clinical manifestation of SCI patterns.
Central Cord Syndrome
Central cord syndrome is characterized by weakness in the
arms, particularly the hands, that is more pronounced than
leg weakness. Sensory deficits are variable but often mir-
ror the motor findings. The most common presentation for
this incomplete cord syndrome is an older patient sustaining
a hyperextension injury in the setting of preexisting cervi-
cal stenosis (Fig. 39.4). With hyperextension, cord compres-
sion occurs between the anterior osteophytes and posterior
infolding of the ligamentum flavum. Central cord syndrome
accounts for the greatest proportion of all traumatic incom-
plete SCIs, representing 44% of incomplete SCI syndromes and

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374 PART 2  Pathophysiology of Spinal Disorders
BOX 39.1  American Spinal Injury Association
Impairment Scale
A = Complete. No sensory or motor function is preserved in the
sacral segments S4–S5.
B = Sensory Incomplete. Sensory but not motor function is
preserved below the neurological level and includes the sacral
segments S4–S5 (light touch or pin prick at S4–S5 or deep
anal pressure) and no motor function is preserved more than
three levels below the motor level on either side of the body.
C = Motor Incomplete. Motor function is preserved at the
most caudal sacral segments for voluntary anal contraction
or the patient meets the criteria for sensory incomplete
status (sensory function preserved at the most caudal sacral
segments S4–S5 by light touch, pin prick or deep anal
pressure), and has some sparing of motor function more than
three levels below the ipsilateral motor level on either side of
the body.
(This includes key or nonkey muscle functions to determine
motor incomplete status.) For American Spinal Association
(ASIA) impairment scale (AIS) C—less than half of key muscle
functions below the single neurological level of injury (NLI) have
a muscle grade ≥3.
D = Motor Incomplete. Motor incomplete status as defined
above, with at least half (half or more) of key muscle functions
below the single NLI having a muscle grade ≥3.
E = Normal. If sensation and motor function as tested with the
International Standards for Neurological Classification of Spinal
Cord Injury are graded as normal in all segments, and the
patient had prior deficits, then the AIS grade is E. Someone
without an initial spinal cord injury does not receive an AIS
grade.
ND = Not Defined. To document the sensory, motor and NLI
levels, the AIS grade, and/or the zone of partial preservation
when they are unable to be determined based on the
examination results.
From American Spinal Injury Association (ASIA). International Standards for
Neurological Classification of Spinal Cord Injury (ISNCSCI) worksheet.
Richmond: ASIA; 2019.
9% of SCIs overall.18,19 Prognosis for improvement is favor-
able with central cord syndrome. Thompson et al. reviewed
patients with central cord syndrome and demonstrated that
80% of patients with an ASIA motor score greater than 60 on
admission were able to ambulate independently at hospital
discharge, whereas 80% of patients with an ASIA motor score
less than 50 could not ambulate independently at hospital
discharge.20 Older patients (age >50 years) have a worse prog-
nosis for independent ambulation, independence in self-care,
and bowel and bladder function, as compared with younger
patients.21 Central cord syndrome must be differentiated from
an incomplete cervical cord injury in which the lower extremi-
ties are affected more than the upper extremities, which has a
significantly worse prognosis for complete recovery.  conus medullaris may lead to a variable degree of bowel and
Anterior Cord Syndrome
Anterior cord syndrome was first described as a lesion affecting
the anterior two-thirds of the spinal cord, with preservation
of the posterior columns. The injury pattern is defined by the
perfusion of the spinal cord by the anterior and posterior spi-
nal arteries. The characteristic clinical presentation is complete
paralysis below the level of the lesion but with preservation
of proprioception, vibratory sense, two-point discrimination,
and light touch. This constellation of symptoms is present
in approximately less than 1% to 3% of all incomplete SCI
October 06, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.
syndrome patients.18,19 Anterior cord syndrome is commonly
associated with vascular insufficiency seen with disruption
of the anterior spinal artery, such as with ischemia or aortic
surgery, although pathology that results in an anterior canal
compression, such as with a cord level disc herniation, dis-
placed bony fragment, or hematoma, have been described.22
Prognosis for improvement is poor with anterior cord syn-
drome, as these patients demonstrate the greatest rehab length
of stays as compared with other incomplete cord syndromes.19 
Posterior Cord Syndrome
The least frequent of the incomplete cord injuries is posterior
cord syndrome, accounting for less than 1% of incomplete cord
injury patients.18 Posterior cord syndrome is characterized by
loss of proprioception and light touch, with preservation of
pain and temperature sensation. Motor deficits can arise with
injury to the lateral corticospinal tracts. Associated pathologies
include hyperextension-type injuries, posterior spinal artery
occlusion, and compression secondary to malignancy. 
Brown–Séquard Syndrome
Brown–Séquard syndrome was first described in patients with
hemitransection of the spinal cord. It is characterized by a cord
lesion that results in ipsilateral proprioceptive and motor loss
and contralateral loss to pain and temperature sensation below
the level of the lesion. Brown–Séquard syndrome accounts for
1% to 4% of all traumatic SCIs.18,19 Although Brown–Séquard
syndrome is classically described in patients with penetrat-
ing stab injuries, “Brown–Séquard-plus syndrome” has been
used to describe the scenario of relative ipsilateral hemiplegia
and relative contralateral hemianalgesia. The injury pattern is
owing to the pattern of decussation of motor and sensory tracts
within the spinal column, with motor tract decussation occur-
ring cephalad, in the medulla oblongata, and decussation of
the afferent sensory tracts occurring distally, shortly after entry
into the spinal cord. In addition to hemitransection of the
spinal cord, Brown–Séquard syndrome is more commonly
observed in other pathologies as well, including blunt trauma,
diving injuries, and acute disc herniations.23-25 Brown–Séquard
syndrome resulting from blunt trauma carries the best progno-
sis of the incomplete SCI syndromes, with over 75% of patients
being able to ambulate independently at the time of discharge,
and higher rates of recovery amongst patients sustaining blunt
trauma as compared with penetrating trauma.18,19,23,26 
Conus Medullaris Injury
The caudal end of the spinal cord is the conus medullaris and
is typically found at the L1 level, although it can be seen as
high as T11 and as low as L3. It is continuous with the epi-
conus (L4-S1 nerve roots) and also includes the S2‒S5 nerve
roots. The lumbosacral nerve roots continue inferiorly to the
conus as the cauda equina.27 Compression at the level of the
bladder dysfunction, as well as lower extremity motor deficits,
sensory deficits, and severe allodynia (Fig. 39.5). Injuries at the
level of the conus lead to combined upper and lower motor
neuron signs. When associated with thoracolumbar trauma,
approximately one-half of patients will have persistent bowel,
bladder, or sexual dysfunction at final follow-up.28,29 
Cauda Equina Syndrome
Injuries distal to the level of the conus medullaris can accom-
pany spine trauma. However, the pathophysiology and prog-
nosis following such injuries are reflective of peripheral nerve
 Spinal Cord Injury 375

Efferent tracts Afferent tracts

(descending, motor) (ascending, sensory) 39
Dorsal column
medial lemniscus
Gracile Cuneate
fasciculus fasciculus
Anterior corticospinal tract

Pyramidal tracts
Lateral

Lumbar
corticospinal tract

l
vica
cic
Sacral

Thora

Cer
mb l
cra
Posterior

ora ar
Sa

cic
spinocerebellar tract

l
Lu

a
vic
Th

er
Spinocerebellar

C
Ce tracts
rvic

Sacral
Lumbar
Thora
a
Rubrospinal tract Anterior
spinocerebellar tract

cic
Lateral spinothalamic tract
Anterolateral
Extrapyramidal system
Reticulospinal tract Anterior spinothalamic tract
tracts

Spinoolivary fibers
Olivospinal tract

Vestibulospinal tract

Fig. 39.3. Spinal cord afferent and efferent pathways. (From Jörg Mair, Munich, Germany. In: Hombach-Klonisch S, Klonish T, Peeler J. Sobotta
Clinical Atlas of Human Anatomy. Munich: Elsevier GmbH, Urban & Fischer; 2019.)

injuries rather than frank SCIs. They are more fully described
in Chapter 38.  injuries, and those patients were younger and more likely to
SPECIAL CONSIDERATIONS
Cervicomedullary Injury
SCIs between the midbrain and C4 present specific problems.
In patients with injury to the upper cervical spine, particu-
larly patients with complete injuries, respiratory function may
be compromised. Chest expansion is dependent on the dia-
phragm and the intercostal muscles. Diaphragm function is
solely dependent on innervation via the phrenic nerve (C3‒
C5). Intercostal muscles are innervated by the thoracic nerves,
and may be compromised in cervical spine injuries because
the thoracic nerves are below the level of injury. Patients with
injury to the cervicomedullary region of the spinal cord present
with respiratory compromise, and may have prolonged ventila-
tor dependence even if breathing unassisted on initial presen-
tation. Patients with high cervical injuries may have unusual
patterns of sensory and motor deficits, as the decussation of
descending motor nerve tracts occurs the level of the midbrain.
Furthermore, patients may have cranial nerve involvement,
such as facial sensory loss or abducens nerve palsy, believed to
be the result of traction at the time of injury with displacement
of the brainstem in relation to its native position. Amongst all
SCI patients, patients with high cervical SCI have the highest
mortality rate because of numerous factors including cardio-
vascular dysfunction and respiratory failure.  without fracture, and penetrating injuries. The primary injury
Penetrating Cord Injuries
Gunshot injuries are amongst the leading causes of penetrat-
ing SCIs in the United States, with penetrating stab wounds
occurring less frequently. In one series evaluating penetrating
spinal trauma, Morrow et al. reported that 13.5% of spinal
fractures from 2012 to 2018 were secondary to penetrating
be male.30 Additionally, 92.2% of penetrating injuries in that
series were because of firearms, and 40.9% had a concomi-
tant spinal cord or cauda equina injury. Whereas stab incisions
may lead to direct injury such as a dural tear or partial ver-
sus complete cord transection, blast injuries such as gunshot
wounds cause significant damage from the direct path, as well
as local heat and energy dissipation, and cord injury from frac-
ture fragments. In both gunshot and stab penetrating injuries,
damage to adjacent structures such as the great vessels or the
lungs must be suspected and treated. Antibiotics are admin-
istered in accordance with open fracture protocols. Surgery is
generally indicated for (1) cord compression with an incom-
plete injury, (2) a discrepancy between the clinical examina-
tion and the missile trajectory with a complete myelopathy,
(3) a migratory missile fragment, (4) spinal instability, (5)
associated infection, and (6) persistent cerebrospinal fluid
leak.31-33 Overall, 60% of patients with stab wounds are able
to ambulate at 1-year follow-up, compared with 24% of those
with SCI because of gunshot wounds.34 
CONCLUSION
SCI has an important and significant impact on the health of
affected patients, and on healthcare economies in the United
States and internationally. Mechanisms of SCI include frac-
tures and dislocations of the spine, spinal cord contusion
cascade involves direct cell trauma and cell injury because
of ischemia. The secondary injury cascade is important, and
involves mechanisms that may be modifiable, including spi-
nal cord perfusion, inflammatory cytokines, cell wall injury,
and ionic dysregulation. Understanding the molecular and
cellular biology of the secondary cascade is important for the
development of therapeutic interventions.

October 06, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.