Spinal Cord Trauma

Epidemiology

The annual incidence of SCI worldwide is between 11.5 and 57.8 cases per million persons ( ). In the United States, the annual incidence is approximately 40 cases per million, with approximately 12,000 new cases diagnosed a year. There is a bimodal age distribution, with the highest frequency occurring between 15 and 29 years of age and the second occurring at 65 years of age and older ( ). The leading cause of death in patients with SCI relates to respiratory complications ( ). In North American trauma centers, approximately 1 in 40 patients admitted suffers from an acute SCI ( ). The present estimation of SCI victims is reported to be 259,000 ( ). The two most common causes of SCIs are motor vehicle collisions and falls ( ). Other causes of SCI include work-related injuries, sports and recreational injuries, and violence. Typically, SCIs occur more commonly in males than females by a factor of 3 or 4 ( ). The cost associated with care of SCI patients can range from $1.25 to $25 million, but lifetime direct and indirect costs average $1.6 million for paraplegia and $3 million for tetraplegia per individual ( ).

Pathophysiology

When the spinal cord suffers trauma, the initial insult causes immediate damage, but, over time, an acute inflammatory process coupled with astrogliosis contributes to secondary insults to the spinal cord while serving some neuroprotective and neurorestorative functions. Thus SCI is a biphasic process, and understanding the mechanisms of this process is essential for developing effective therapeutic treatment options for SCIs.

Primary injury mechanisms include shearing, laceration, acute stretching, and sudden acceleration-deceleration events that lead to disruption of axons, blood vessels, or cell membranes. There are few instances where the spinal cord is transected completely. Most injuries often leave a “subpial rim” of demyelinated or dysmyelinated axons that act as a substrate for which regeneration can potentially occur. There can also be acute swelling of the cord contributing to cord ischemia. However, at times there may be no visible injuries seen either radiographically or histopathologically. Elevated levels of cytokines, including tumor necrosis factor alpha (TNF-α) and interleukin 1-beta (IL-1β), appear within minutes of the injury. Furthermore, cytotoxic levels of glutamate can be present, owing to dumping of glutamate stores and dysfunction of astrocyte glutamate transporters. This immediate phase of injury can last up to 2 hours after the insult.

Secondary injuries are divided into acute, intermediate, and chronic stages. The acute phase is divided into an early acute phase and a subacute phase. The biochemical processes occurring in the early acute phase of injury are targeted for neuroprotective therapies. Ionic homeostasis is desynchronized during this period and contributes to apoptosis and necrotic cell death. In particular, Ca ²⁺ deregulation leads to a variety of damaging processes such as mitochondrial dysfunction. This in turn leads to low adenosine triphosphate (ATP) levels. Without enough ATP to sustain energy-dependent transporters such as the Na ⁺ /K ⁺ -ATPase membrane transporter, ionic homeostasis is further disrupted. This disruption of ionic homeostasis leads to failure of the Na ⁺ /K ⁺ /glutamate pump, which conceivably leads to elevated levels of glutamate. Glutamate in turn acts on a variety of glutamate receptors such as N -methyl- d -aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainite receptors, leading to an influx of Na ⁺ and Ca ²⁺ . Free radical reactions create membrane damage via lipid peroxidation, further promoting cell lysis, dysfunction of organelles, and calcium deregulation. Free radical production peaks at 12 hours post injury and continues to have an active presence for another week before returning to preinjury levels at 4–5 weeks. The primary mediator of free radical injury is the peroxynitrite radical ( ). In rats the peroxynitrite radical has been shown to cause apoptosis ( ). Antioxidants and inhibitors of peroxynitrite radicals have shown promise as neuroprotective elements. One such compound, methylprednisolone (MPSS), had been previously used because of its suspected role in the inhibition of lipid peroxidation; however, its routine use is currently no longer recommended ( ). Following injury to the spinal cord, the blood–brain barrier has a higher permeability due to injured endothelial cells and astrocytic processes and inflammatory mediators that increase vascular permeability. Animal studies show the peak vascular permeability occurring at 24 hours and tapering off over a 2-week period ( ). In humans, the time course is suspected to be the same. Two mediators upregulated to increase vascular permeability are TNF-α and IL-1β. Other compounds found to have negative effects on the permeability of the blood–brain barrier include reactive oxygen species (ROS; e.g., nitric oxide), histamine, matrix metalloproteinases, and elastase.

Despite the inflammatory response exerting deleterious effects, it is crucial in maintaining an environment for regenerative growth and removing cellular debris. Spinal cords taken from autopsy specimens of patients suffering from SCIs were used to study the changes occurring at the cellular level by . This study showed the presence of neutrophils at the injured sites within 4 hours post injury. After peaking between 1 and 3 days post injury, they remained present for as long as 10 days. Microglial cells were also shown to be an important component of the early inflammatory process. They became activated and increased in number during the first 3 days post injury. Like the neutrophils, their presence correlated with areas of increased tissue damage. During the following 5- to 10-day period post injury, the predominant cell population transitioned to the activated microglia and macrophages. It is believed that the secretion of oxidative and proteolytic enzymes by neutrophils, activated microglia, and macrophages during the first 3 days post injury imparts a high degree of secondary injury to the spinal cord ( ). Noncellular mediators that contribute to this process include TNF-α, interferons, and interleukins, as discussed. Inhibition of TNF-α has been found to promote recovery following SCI ( ). However, TNF-α has been found to be neuroprotective in vitro ( ) and in studies with TNF-α–deficient mice ( ). Thus the exact role of TNF-α in SCI must be better defined before future therapeutic modalities can capitalize on the manipulation of this mediator.

Cell death following SCI occurs by one of two mechanisms: apoptosis or necrosis. Potentially, a newly discovered mechanism of cell death known as necroptosis can cause a programmed necrotic event to occur ( ). Numerous studies investigating the therapeutic effect of inhibiting the initiation of apoptotic mechanisms, such as initiation of the caspase cascade, have shown promise in animal models.

The subacute period lasts from 2 days to 2 weeks. It is during this time that the phagocytic response is responsible for removing cellular debris. The removal of growth-inhibiting compounds found in myelin debris can potentially have some beneficial effects on the efforts of axonal recovery ( ). Astrocytes also reach peak numbers in the subacute period. They form a scar that prevents axonal regeneration in rodent studies. The presence of the astroglial scar is less obvious in humans ( ). Despite suspected negative effects on healing, they have important roles in ionic homeostasis and reestablishing the blood–brain barrier, thus limiting the immigration of immune cells and edema.

The intermediate phase is observed between 2 weeks and 6 months post injury and is characterized by maturation of the astrocytic scar and continual axonal regeneration. Following this period, SCIs enter a chronic phase. During the chronic phase, there is maturation and stabilization of the astrocytic scar, formation of syrinx and cavities, and wallerian degeneration. This is the period where most therapies target remyelination and the plasticity of the nervous system.

Clinical Presentation

The majority of SCIs occur in the cervical spine (55%; ). Other injuries are evenly divided among the thoracic, thoracolumbar, and lumbar regions. The most frequent injuries suffered are incomplete tetraplegia followed by complete paraplegia, complete tetraplegia, and incomplete paraplegia.

In general, SCIs can be categorized into complete injuries and incomplete injuries. In complete injuries, there is an absence of motor, sensory, and bowel and bladder function below the level of injury. There is some preservation of neurological function with incomplete injuries. At present, SCIs are graded using the American Spinal Injury Association/International Medical Society of Paraplegia (ASIA/IMSOP) Impairment Scale ( Box 63.1 ) in conjunction with motor grading provided by the Medical Research Council Muscle Grading System ( Table 63.1 ). This grading system provides a standard method by which clinicians and researchers can classify SCIs. In defining the level of the injury, the most caudal segment at which there is normal motor and sensory function is taken into account. This may differ from the level in the vertebral column where the injury occurred. A recent update to this scale in 2019 allows for notation of a deficit likely due to a preexisting neurological deficit with a “∗” and allows for notation of a zone of partial preservation (ZPP) for injuries that lack either voluntary anal contraction or deep anal pressure sensation.

Spinal Cord Injury Syndromes

Central Cord Syndrome

Central cord syndrome is present in 9% of all traumatic cord injuries and is the most common of the spinal cord syndromes. This is a condition first reported by Thornburn in 1887 and then popularized by . Hyperextension in the cervical spine, with some preexisting cervical spondylosis, is usually responsible for this type of injury. Imaging the cervical spine in patients with central cord syndrome will reveal stenosis from spondylosis, fracture subluxation, or sequestered disk, with no spinal stenosis. Schneider proposed that these injuries resulted from acute compression from preexisting bone spurs anteriorly and hypertrophied ligamentum flavum posteriorly and contributed to hematomyelia and central cord necrosis ( Fig. 63.1 ). Schneider witnessed weakness in the upper extremities greater than the lower extremities, as well as a variable degree of sensory disturbances and loss of bladder control. It was proposed that involvement of the anterior horn cells led to weakness in the arms greater than the legs, secondary to the topography of the corticospinal tracts. Because of their good recovery, Schneider was in favor of taking a more conservative approach toward treating these patients. Correlations of magnetic resonance imaging (MRI; ) and histopathology ( ) fail to suggest hematomyelia from Schneider’s hypothesis. There is in fact minimal disruption of the central gray matter. Axonal disruption and swelling are more widespread in the white matter.

Anterior Cord Syndrome

Anterior cord syndrome occurs with injuries to the ventral two-thirds of the cord, while sparing the posterior column ( Fig. 63.2 ). It is present in 2.7% of all traumatic SCIs ( ). Motor function is lost distal to the site of the injury. Spinothalamic function may be disrupted, leading to loss of pain and temperature sensation in certain areas. Because the posterior columns remain intact, the sensations of vibration, position, and crude touch will not be affected. Occasionally patients feel hyperesthesia and hypoalgesia below the level of the lesion. Although this syndrome is classically described for anterior spinal artery compromise, in the setting of trauma it is due to flexion injuries or retropulsed disk or bone. Anterior cord syndrome carries a worse prognosis than other cord syndromes.

Posterior Column Syndrome

Posterior column syndrome is a rare condition with an incidence of less than 1%. This syndrome has been linked to neck hyperextension injuries. Injuries occur to the posterior aspect of the cord ( Fig. 63.3 ). Because the posterior columns are injured, there is usually a loss of vibration and position sense, with retained spinothalamic function of pain and temperature sensation. Occasionally, motor function can be affected as well. Although this syndrome has been previously mentioned in the literature, it was omitted from the International Standards for Neurological and Functional Classification of SCI and is not currently recognized as a separate syndrome. This syndrome can also be seen in the context of pernicious anemia.

Brown-Séquard Syndrome

Brown-Séquard syndrome accounts for 1%–4% of all traumatic SCIs. Injuries affect the lateral half of the cord ( Fig. 63.4 ). It occurs most frequently in the cervical spine and is usually due to penetrating injuries and (less commonly) blunt trauma including disk herniations. In cases of blunt trauma, Brown-Séquard syndrome usually occurs in the context of hyperextension injuries, although it has been observed in flexion injuries, locked facets, and compression-related injuries. Below the level of the lesion, it classically manifests with ipsilateral pyramidal deficit, loss of ipsilateral tactile discrimination, position sense, and vibratory sensation, and loss of pain and temperature sensation on the contralateral aspect of the body one to two dermatomes below the level of the injury.

However, this classic presentation of Brown-Séquard syndrome rarely occurs. More frequently, patients presenting with Brown-Séquard syndrome present with a variation of the classic syndrome, termed Brown-Séquard plus ( ). With Brown-Séquard plus, there is asymmetrical hemiplegia as well as hypoalgesia more prominent on the less paretic side. Patients presenting with a clinical picture consistent with a classic Brown-Séquard syndrome injury have a worse prognosis than patients presenting with a variation of the syndrome, but the overall prognosis is good. Brown-Séquard has the best functional motor recovery when compared with other clinical spinal cord syndromes. Most subjects obtain bowel and bladder continence. Patients having predominantly more weakness in the upper extremities compared with the lower extremities have a favorable outcome in regard to ambulating. The symptoms of Brown-Séquard syndrome may appear instantaneously or in a delayed fashion. Furthermore, they may occur in conjunction with other spinal cord syndromes.

Conus Medullaris Syndrome

There is high probability that injuries to the thoracolumbar region can involve the conus medullaris. The conus medullaris represents the transition of the spinal cord from the central nervous system to the peripheral nervous system. The location of this region is highly variable—between the T12 and L1 disk space to the middle third of L2 in the majority of the population ( Fig. 63.5 ).

The lumbar parasympathetic fibers, sacral sympathetic fibers, and sacral somatic nerves originate in the conus medullaris. The classic presentation entails lower-extremity weakness, absent lower-limb reflexes, and saddle anesthesia. There is usually mixed upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Loss of the bulbocavernosus and anal reflexes is permanent, differentiating conus medullaris syndrome from SCIs that have a return of these reflexes within 48 hours of the injury. Patients typically have an areflexic bowel and bladder (low-pressure, high-capacity bladder). The most common injuries to the vertebral column resulting in this condition are burst fractures or fracture-dislocation. There is no strong clinical evidence favoring surgical intervention over nonsurgical intervention for conus medullaris injuries. Furthermore, if surgical intervention is performed, there is no compelling evidence to suggest that earlier decompression affects functional outcome.

Cauda Equina Syndrome

The cauda equina is defined as the region of the neuroaxis occupied by the filum terminale. The only neurological structures in this region include the lumbar and sacral roots. Injuries in this location are typically a pure LMN injury ( Fig. 63.6 ). Findings often include absent bulbocavernosus reflex, absent deep tendon reflexes, flaccid urinary bladder, and reduced lower-extremity muscle tone. It is differentiated from conus medullaris syndrome by the presence of asymmetrical weakness and the absence of UMN involvement ( Table 63.2 ). Like conus medullaris syndrome, burst fracture and fracture-dislocation are the most common vertebral column injuries associated with this condition. Cauda equina injuries have better recoveries owing to the resiliency of the roots to injuries and the greater regeneration capacity of the roots compared with the spinal cord. However, the sacral roots are very delicate, and injuries to them may be permanent. In general, cauda equina syndrome in the setting of herniated disk pathology is treated early (within 24 hours) if possible, to prevent residual symptoms ( ). However, functional outcome in a traumatic setting is similar to conus medullaris syndrome. There is no strong evidence correlating functional outcome to surgical decompression, nor is there any evidence that suggests cauda equina injuries fare better with early versus late decompression.

TABLE 63.2

Similarities and Differences Between Conus Medullaris Syndrome and Cauda Equina Syndrome

Conus Medullaris Syndrome	Cauda Equina Syndrome
Upper and lower motor neuron involvement	Lower motor neuron involvement
Symmetrical motor impairment	Asymmetrical motor impairment
Vertebral column injuries between T12 and L2	Vertebral column injuries distal to L2
Absent deep tendon reflexes	Absent deep tendon reflexes
Permanent areflexic bladder	Permanent areflexic bladder
Absent bulbocavernosus reflex	Absent bulbocavernosus reflex

Transient Spinal Cord Syndromes

Transient spinal cord syndromes have been documented in the literature, with multiple reported incidents occurring in contact sports. The term “burning hand syndrome” was initially coined to describe a severe burning sensation in the upper extremities occurring in athletes who suffer injuries in contact sports. It is likely related to lesions of the spinothalamic tract in central cord injuries. Because the most medial fibers of the spinothalamic tract provide pain and temperature sensation to the hands and fingers, injuries to these fibers would explain the dysesthesias of the hand, so this syndrome is most suggestive of a mild central cord syndrome. Although it has been noted to occur with central cord syndrome, it can occur in isolation. Unilateral burning pain down the arm to the hand can signify root injury and has been termed a “burner” or “stinger”; they typically last seconds to hours but rarely longer than 24 hours. Stingers occur more frequently with baseline cervical stenosis, which leads to a narrow intervertebral foramen. Traction or direct trauma to the brachial plexus can mimic cervical root injury. A positive Spurling test can suggest compression of the nerve root as the cause of symptoms.

An estimated 7.3 out of 10,000 football participants suffer a cervical cord neuropraxia ( ). Cervical cord neuropraxia is typically described as any motor or sensory complaints in any extremity lasting 15–30 minutes, but some cases can last up to 24–48 hours ( ). This injury is typically due to hyperextension, hyperflexion, or axial loading of the cervical spine. Cervical cord neuropraxia has been attributed to local anoxia and elevation of intracellular calcium ( ). Bailes described “pathophysiologically similar to cerebral contusions, spinal cord concussion has become accepted to define those instances in which sufficient forces result in temporary inhibition of spinal cord impulse transmission without causing structural damage to the vertebral column or spinal cord, and is known to occur in athletes.” Bailes also concluded that “a single episode of temporary spinal cord dysfunction in an athlete with spinal stenosis will substantially increase the risk of future catastrophic SCI.” In his series, patients who returned to contact sport activities with no effacement of cerebrospinal fluid (CSF) around the cord or any radiographic abnormalities suggestive of cord damage encountered no further episodes of recurrent transient SCI with a mean follow-up period of 40 months.