Spinal Cord Compression

Causes of Spinal Cord Compression

Diseases can affect the spinal cord by parenchymal disruption (intramedullary disease) or by compression of the tissue. Collectively, diseases that cause compression are probably the most common causes of spinal cord dysfunction. Compression can occur from pathology outside the dura (extradural compression) or within the dura (intradural-extramedullary compression). The mechanism of injury, rate of onset, force and kinetic energy of an injury, and the duration of compression all play a role in the severity and progression of clinical signs [1-3]. For example, an acute severe spinal cord compression is more likely to cause acute paraplegia in comparison with a spinal meningioma, which grows slowly and allows functional compensation to occur. However, once the limit of compensation is reached, deterioration of neurologic function can occur rapidly [4]. Clinical signs associated with spinal cord compression depend on the location of the lesion. Clinical signs of spinal cord dysfunction can be found in Chapter 46: Intervertebral Disk Disease. A list of the most common diseases that cause spinal cord compression can be found in Table 42-1. Images of various disease processes that cause spinal cord compression are shown in Fig. 42-1, Fig. 42-2, Fig. 42-3, Fig. 42-4, Fig. 42-5, Fig. 42-6 and Fig. 42-7.

Figure 42.1. Extradural compression: T9 chondrosarcoma in an 11-year-old MC bloodhound with acute deterioration of chronic paraparesis. The tumor was removed and the dog’s neurologic function improved daily. A. T2-weighted, sagittal MRI. The tumor has severely and completely compressed the spinal cord. (arrow) B. T2-weighted, transverse MRI. The compressed spinal cord is indicated by the arrow. C. The tumor has been removed en bloc (ventral view of the dorsal lamina) and is surrounded by tumor capsule and normal muscle tissue. The dorsal lamina has been replaced by chrondrosarcoma (black arrow). The tumor margin has been outlined with paint (white arrow).

Figure 42.2. Extradural compression: Low-grade osteosarcoma of the lamina and pedicles of C6 in a 6-year-old, FS Yorkshire terrier. The tumor was removed en bloc and there was no recurrence until the animal was lost to follow-up 2 years later. A. Lateral image of a myelogram. Note the significant dorsal compression of the spinal cord (arrow). B. Computed tomographic scan following myelogram. The tumor has extended into the pedicle on one side (arrow). C. The tumor has been removed en bloc. D. A radiograph taken 1 year postoperatively.

Figure 42.3. Extradural compression: Cartilaginous exostosis of the C4 caudal articular process in an 11-month-old, MC Airedale terrier mix with a 6-month history of progressive tetraparesis. A. Postmyelogram transverse computed tomographic scan. The spinal cord (large arrow) has been compressed to about 25% of its normal diameter by the mass (small arrow). B. The benign tumor was removed, the dog recovered to normal neurologic status and was still normal at 5 years postoperative.

Figure 42.4. Extradural compression: severe stenosis at the level of the C4-5 facet joint in a 7-year-old, FS Basenji with unremitting cervical pain and mild neurologic dysfunction. A computed tomographic scan of the C4-5 spinal level. The spinal cord is triangular-shaped from the compression. A hyperplastic facet joint is indicated by the arrow. This dog had similar stenoses at 3 other levels in her cervical spine (C3-4, C5-6, and C6-7). She had modified medial facetectomies at all levels and recovered to normal function and her pain resolved. To view click on figure

Figure 42.5. Extradural compression: L1-2, type II intervertebral disk extrusion in a 4-year-old, MC German shepherd dog that displayed mild paraparesis and significant thoracolumbar pain. A. T2-weighted, sagittal MRI. The spinal cord is severely compressed by the disk extrusion (arrow). B. T2-weighted, transverse MRI. The spinal cord is compressed to the right and dorsally (black arrow) by the protruding intervertebral disk (white arrow). (IVD = intervertebral disk)

Figure 42.6. Intradural, extramedullary compression: Multiple arachnoid cysts in a 7-year-old, Springer spaniel that had a history of cervical pain and mild tetraparesis after being hit by a car 2 years earlier. At the time of the MRI the dog was poorly ambulatory. The arachnoid cysts were believed to have formed secondary to arachnoiditis from hemorrhage and inflammation. The arachnoid cysts were addressed surgically and she recovered to ambulatory tetraparesis but began to slowly deteriorate over time. Repeat MRI revealed that the cysts were resolved, but that there were progressive parenchymal changes in the spinal cord. A. Preoperative T2-weighted, sagittal MRI. The arrow indicates one arachnoid cyst. Signal hyperintensity within the parenchyma is seen within the circle. This was likely an area of malacia, edema, or early syrinx formation. B. T2-weighted, transverse MRI. The cysts are indicated by the arrows. The spinal cord has taken on an "apple-core" shape due to the intradural compression.

Figure 42.7. Intradural-extramedullary compression: C3 nerve root tumor in a 7-year-old, FS Doberman pinscher that presented with ataxia and cervical pain. Post-myelogram computed tomographic scan with the precontrast image on the left and the postcontrast image on the right. The tumor has caused pressure necrosis of the pedicle and the foramen is widened. (Note the presence of pedicle bone on the left side.) The tumor did not contrast-enhance with the exception of a small blush at the periphery (arrow).

Pathophysiology of Spinal Cord Compression

Morphologic and Histologic Changes

Spinal cord compression can occur relatively slowly over the course of time, with such disorders as developing neoplastic disease, arachnoid cyst, synovial cyst, or soft tissue hypertrophy/hyperplasia associated with caudal cervical vertebral malformation/malarticulation. In a chronic progressive process, the spinal cord tissue compensates for some period of time before clinical signs become evident [5-7]. Typically, this results in a large volume of pathology and severe compression prior to clinical dysfunction and diagnosis.

Acute spinal cord injuries occur as a result of rapid spinal cord compression, such as that seen with acute intervertebral disk extrusion and fracture/luxation. Acute spinal cord injuries involve both primary and secondary pathologic processes [2,8-21]. The primary injury is the inciting mechanical event itself, which then induces a complex series of vascular, biochemical, and cellular events that result in progressive secondary injury to the spinal cord parenchyma. Vascular events include ischemia, hemorrhage, impaired autoregulation of blood flow, microcirculatory disruption, vasospasm and thrombosis [11,13,17,22,23]. Secondary biochemical events ultimately result in edema, lipid peroxidation, and cytotoxic injury [22-27]. These include cellular ion derangement (increased intracellular sodium and calcium and extracellular potassium) [8-10,13]. Extracellular release and accumulation of neurotransmitters (serotonin, catecholamines, and glutamate) occur and are injurious to the spinal cord cells in large quantities [9,13,28]. Induction of the arachidonic acid cascade, production of eicosanoids, and generation of free radicals result in progression of inflammation via cytokines and lipid peroxidation of cellular membranes of all spinal cord elements (endothelium, myelin, neurons, and glial cells) [15,29-32]. Cellular energy failure via loss of adenosine-triphosphate pathways and cellular apoptosis also occurs [13,30].

Most of what is known about the pathophysiology of spinal cord compression comes from acute spinal cord injury, cervical myelopathy, or animal models of spinal cord compression. In a clinical setting, histologic findings of spinal cord compression have been best described in human patients with cervical spondylitic myelopathy, which is a synonymous disease with canine caudal cervical vertebral malformation/malarticulation ("Wobbler's disease") [14,33-35]. When the spinal cord is compressed, the central grey matter and medial portions of the white matter are usually the most severely affected with cystic cavitation (syrinx), gliosis, edema, and demyelination [3,33,36-42]. Wallerian degeneration is observed cranial to the compression site in the posterior and posteriolateral columns [3,,43]. Lower motor neuron dropout occurs at the site of compression, and demyelination and axonal degeneration occur in the corticospinal tracts caudal to the compression site [14,33,39,44]. Studies have shown that clinical signs typically appear after the spinal cord has been compressed by 30%. [8,33,45,46]. In addition, because of the relative tolerance of the cervical spinal cord to encroachment, the development of clinical myelopathy was found to be highly correlated to pre-existing congenitally narrow spinal canal [33,47].

Ogino et al., [48] followed nine patients with cervical myelopathy throughout their clinical course and postmortem. He found that the severity of compression was correlative to the pathologic changes. Minor compression was most associated with degeneration of the posteriolateral white matter (including the corticospinal tracts). Advancing severity of compression resulted in infarction and loss the α-motor neurons in the anterior horn grey matter. As compression became more severe, extensive grey matter infarction ensued. The dorsal horn columns and lateral white matter tracts were also affected only in cases of severe compression. However, anterior white matter appeared remarkably resistant to degeneration, a finding supported by other studies [49]. The severity of histologic findings correlated well to the clinical neurologic findings in all patients.

In a study by Yamaura et al., [35] twy/twy mice, which spontaneously develop dorsolateral calcified deposits at C1 and C2 vertebrae by four months of age, were used to study chronic spinal cord compression. At six months of age, the spinal cords in these mice were already significantly compressed. Grey matter degeneration was observed as small, flattened neurons that were decreased in number, especially in the dorsal horns where the compression was most significant. Loss of axonal and glial elements and myelin destruction were observed in the white matter at the site of the compression as well as in descending tracts caudally and ascending tracts cranially.

Cellular Apoptosis in Spinal Cord Compression

Apoptosis, or programmed cell death, is a natural process of self-destruction in certain cells that are genetically programmed to have a limited life span or are damaged. Apoptosis plays an important role in development and homeostasis by controlling cellular density and deletion of abnormal cells [33,50]. Apoptosis is differentiated from necrosis by the lack of inflammation, karyorhhexis, and karyolysis. In apoptosis, the cells disintegrate into membrane-bound particles that are then eliminated by phagocytosis [23,33,51,52]. Apoptosis can be induced either by a stimulus, such as trauma, compression, irradiation, or toxic drugs or by the removal of a repressor agent. Necrosis can be induced by similar injuries to the spinal cord, and which cellular pathway is taken may depend on the severity of cellular damage [23].

Apoptosis in the central nervous system has been shown to be controlled by several promoting and blocking genes [33,53-55]. Apoptosis of neuronal and glial cells has been reported with pathologic processes in the spinal cord, including injury, ischemia, and neurodegenerative conditions such as amyotrophic lateral sclerosis and spinal muscular atrophy [33,40,56-66]. Apoptosis in acute spinal injury has been proposed as a mechanism of degeneration of neuronal elements at the site of the injury and as a cause of chronic demyelination some distance away from the injury [40,56,59-61,66]. In the previously mentioned twy/twy mouse chronic compression model,35 apoptosis was identified in both the white and grey matter at the most severely compressed location. Oligodendrocytes displayed markers of apoptosis, suggesting that programmed loss of these cells may be a cause of demyelination and of poorly myelinated cells some distance from the lesion.

Derangements in Neuronal Conduction

Alterations in myelin (demyelination and remyelination) and axonal integrity and caliber occur soon after spinal cord injury and impact the conduction capabilities of axons at both the site of injury and for some distance from the site of injury [3,67-71]. Changes in axonal conduction and spinal cord morphology following spinal cord injury have been studied in several different animal models [69,71-84] and in postmortem evaluation of human patients [85,86]. Morphologically, significant reduction in axonal numbers, axonal degeneration, and reactive astrocytosis has been reported. In addition, myelin sheaths are thinner, and remyelination of axons by invading Schwann cells (peripheral nervous system myelinating cells) as well as by oligodendrocytes (central nervous system myelinating cell) has been observed [71,74,75,77-80,87-89]. In a study by Wrathall et al., [90] mRNA levels of important myelin structural proteins (myelin basic protein and proteolipid protein) were decreased in the chronically injured spinal cord of rats, suggesting either aberrant metabolism of or a decrease in the number of functional oligodendrocytes. Changes in axonal diameter, observed as either reduced median diameter in a spinal tract or enlarged axonal swellings, are dependent on the white matter tract evaluated and possibly the species as well. [3,71,72,74,75,77-80,87,91-94]. Swollen axons are likely terminal bulbs, which are the accumulation of organelles that occurs when axonal transport is disrupted [71,85].

Electrophysiologic testing has revealed that the injured spinal cord axons display decreased compound action potential (CAP) amplitude, reduced conduction velocity, prolonged refractory periods, and inability to respond to high-frequency stimulation. These axons were considerably less excitable and required a much higher stimulus intensity to elicit even half the maximal response of that seen in the spinal cords of the non-injured control group [71,76]. Reduction in the amplitude of the CAP is a function of many factors including axonal density, axonal diameter, and axonal input resistance and channel activation [71]. Reduction in the CAP in spinal cord injury can be explained by the altered spinal cord morphology (reduced axonal numbers, reduced axonal diameter) as well as by the changes in conduction (increased stimulus intensity required to cause an action potential and prolonged refractory period) that would result in lower than normal number of axons conducting during testing [71]. Conduction velocity depends on the fastest conducting fibers, thus the large caliber, heavily myelinated fibers. Alterations in the axonal size, myelin loss, reduced myelin thickness, and disrupted axonal integrity observed in these studies would all result in reduced conduction velocity [71]. Myelin reduces capacitance and limits the exchange of ions to the nodes of Ranvier and, allows more rapid repolarization of the axonal membrane. The faster membrane repolarization occurs, the faster action potentials can be propagated. Therefore, the alterations of myelin in injured spinal cord axons previously described would also explain the prolongation of the refractory period and inability to respond to high frequency stimulation [71].

Derangements in Spinal Cord Blood Flow and Cerebrospinal Fluid Flow

Considerable evidence exists that interruption to the vascular supply of the spinal cord plays a role in the pathophysiology of spinal cord compression [33,34,36,37,39,48,95-103]. The spinal cord is relatively protected from circulatory insufficiency owing to segmental blood flow and a rich vascular plexus. The arterial supply to the spinal cord arises from the usually paired segmental spinal arteries adjacent to the spinal nerve roots within the intervertebral foramen [104]. These arteries bifurcate into ventral and dorsal radicular arteries that supply rich anastamotic networks on the ventral and dorsal pial surfaces of the spinal cord [104]. The dorsal spinal arteries are paired and tortuous on the dorsal pial surface, whereas the ventral spinal artery is a distinct single artery located in the ventral spinal fissure [104]. These arteries are connected by several anastomotic connections. The ventral spinal artery gives rise to the vertical arteries, which penetrate the ventral fissure of the spinal cord and supply most of the grey matter and some white matter of the spinal cord [104]. Radial arteries arise from the superficial surface arteries to supply much of the white matter and some peripheral grey matter (Fig. 42-8) [104-111]. The capillary network within the spinal cord and nerve roots are continuous and lined with vascular endothelial cells bound by tight cellular junctions that form the blood-spinal cord or blood-nerve barrier [112]. In one study, an intravenous injection of a protein tracer did not leak through the blood-nerve barrier; but when it was injected into the cerebrospinal fluid, it was taken up by capillary pinocytotic vesicles and excreted in to the veins, suggesting that there is no blood/spinal fluid barrier [113].

Figure 42.8. Schematic of the lumbar spinal cord blood flow. Spinal arteries (a) traverse the intervertebral foramen with the spinal nerves. In most cases these arteries are bilateral and present at every level. The spinal artery branches into the dorsal radicular artery (b) and the ventral radicular artery (c). The dorsal spinal arteries (d) that arise from the dorsal radicular arteries are paired and take a more tortuous course than depicted in the drawing. The unpaired ventral spinal artery (e) arises from branches of the ventral radicular arteries and perforates the ventral fissure of the spinal cord, giving rise to the vertical arteries (f) that supply much of the spinal cord grey matter and ventral white matter. (g) Radial arteries arise from the superficial surface arteries to supply much of the white matter and some peripheral grey matter. Venous blood from the capillaries goes to the surface veins (h) that drain into the venous sinuses (i) that are found on the floor of the spinal canal. (With permission from Wheeler SJ, Sharp NJH. Functional anatomy. In Small Animal Spinal Disorders: Diagnosis and Surgery. Wheeler SJ, Sharp NJH (eds). London: Mosby-Wolfe, 1994. Illustration by Joseph E. Trumpey, North Carolina State University).

The venous drainage occurs via radial veins that drain into a network of surface veins that ultimately drain into the vertebral venous plexus located on the floor of the vertebral canal. The venous plexus also receives venous drainage from the vertebral bodies. The venous plexus drains via the intervertebral veins that are also associated with the spinal nerve root at the intervertebral foramen (Fig. 42-8) [104,109-111].

In cervical spondylotic myelopathy in people, the relative sparing of the anterior columns and subpial posterior columns is believed to be related to the architecture of the blood supply [33,97]. For example, the dorsal spinal arteries are paired and tortuous and are, thereby, resistant to tension when the cord elongates in flexion [33,97]. The anterior spinal artery travels in a longitudinal direction, and forces that compress the spinal cord tend not to disrupt the flow. In contrast, the transversely oriented perforating vessels that arise from the vertical artery in the ventral sulcus supply and the grey and medial white matter may be more susceptible to compression [33,97].

Ligation of a single radicular artery in animal models was not shown to induce spinal cord dysfunction [112,114-116]. In one study in dogs, ligation of five pairs of thoracic spinal nerve roots and associated radicular arteries and veins resulted in only a 20% to 30% reduction in blood flow and oxygen tension and did not result in clinical loss of neurologic function [112]. The findings of this study suggest that collateral circulation from the pial vascular plexus and intact segmental arteries were adequate to maintain spinal cord metabolism. It was also hypothesized that the cerebrospinal fluid flow system plays a supplementary role in supplying nutrients to the spinal cord [117].

Vascular derangements in spinal cord compression may actually be associated with impairment in venous blood flow rather than with impairment in arterial flow [4,112,118-120]. In one dog model, chronic compression as a result of chronic arachnoid scarring was induced by applying a circumferential silicone tube for three months. Histologic evaluation at termination revealed a patent superficial medullary artery, whereas the superficial medullary vein was compressed and thrombosed. In addition to these findings, syrinx formation was identified in the dorsal column [121]. A study using kaolin injection in the subarachnoid space in rabbits resulted in total circumferential occlusion of the arachnoid space in 86% of the animals and partial occlusion in 14%. In the animals in which total occlusion occurred, intramedullary edema secondary to increased vascular permeability was also present. In addition, syringomyelia and/or hydromyelia were found histologically in this group [122]. The findings from both studies suggest that total circumferential ablation of the subarachnoid space results in loss of nutrient supply and lack of removal of cellular waste products via the cerebrospinal fluid as well as disturbing venous blood flow, resulting in spinal cord edema, necrosis, syrinx formation, and neurologic dysfunction [24,26,27,41,121,122]. A comparison of the effects in the spinal cord from arterial obstruction (thoracic aorta) versus venous obstruction (caudal vena cava) was studied in a dog model. The blood-nerve (spinal cord) barrier remained intact when the thoracic aorta was obstructed. However, the blood-spinal cord barrier was disrupted as revealed by leakage of an Evans Blue albumin protein tracer and edema in the parenchyma of the spinal cord and nerve roots [123]. The results of these laboratory models may correlate with the findings of parenchymal edema and formation of syringomyelia and/or hydromyelia seen on T2-weighted magnetic resonance imaging and histologically in chronic myelopathy (Fig. 42-9) [3,24,26,27,41,124,125].

Figure 42.9. Syrinx progression in an 11-year-old, MC Dalmatian that was treated for an extradural compression from a C6-7 intervertebral disk extrusion. He initially presented with mild neurologic deficits and mild spinal discomfort. He recovered well from surgery but at 1 year postoperative, developed progressive tetraparesis and severe, unremitting pain. A. Preoperative T2-weighted, sagittal MRI. The C6-7 intervertebral disk (black arrow) has protruded and is compressing the spinal cord. There is signal hyperintensity in the spinal cord, which may have indicated edema, malacia, or syrinx formation. B. T2-weighted, transverse MRI. Note the signal hyperintensity in the middle of the parenchyma. The disk extrusion is indicated by the arrow. C. T2-weighted, sagittal MRI taken 18 months postoperative. The spinal cord has been decompressed at C6-7 but the signal hyperintensity in the parenchyma has progressed. D. The severity of progression in the parenchyma is best observed on the T2-weighted, transverse MRI. This was believed to be a large syrinx at the time. Because the dog was in a great deal of pain and surgery was unlikely to result in resolution of pain, the dog was euthanized. To view click on figure

Role of Duration of Spinal Cord Compression

Much debate has occurred in human as well as veterinary medicine on the timing of decompression. Compression is considered to play a role in initiation and progression of secondary spinal cord injury [126]. Whereas several studies and clinical experience have shown the importance of decompression in mitigating secondary spinal cord injury, poor consensus exists on the appropriate timing for surgical intervention [126-136]. Several animal studies have been done on the time-dependent pathologic effects of spinal cord compression. Many of these studies have established a relationship between increased duration of compression and neurologic recovery [126].,134-138 In a dog study by Carslon et al., [2] thoracic spinal cord compression was induced by a loading device precalibrated to indent the spinal cord at a constant of 0.17 mm/min and maintained for either 30 or 180 minutes. The loading pressure of the spinal cord was maintained at a constant once the somatosensory evoked potentials were decreased by 50% of baseline values. The peak loading spinal cord interface pressures were highest at the end of dynamic loading and actually decreased by more than 50% once sustained compression was maintained for five minutes. After 30 minutes of sustained pressure, the interface pressures decreased to 25% of the peak pressure. Dogs were allowed to recover and were evaluated for 28 days by parameters that included spinal cord somatosensory evoked potentials (intraoperative and preterminally), functional neurologic assessment, magnetic resonance imaging, and histologic study. Amplitude of somatosensory evoked potentials (SSEP) decreased to about 90% of baseline values at the time of peak loading pressures. SSEP amplitudes improved to 63% of baseline within 90 minutes after decompression in the 30-minute compression model. Recovery of SSEP did not occur in the 180-minute compression model. All dogs in the 30-minute compression model had functional recovery and were walking normally or with mild deficits within 21 days of the surgery. Only 50% of the dogs in the 180-minute compression model developed the ability to bear weight, but none were ever able to walk with, at best, minimal deficit. T2-weighted MRI imaging at 28 days postoperatively revealed increased signal intensity in the central area of the spinal cord; these lesions were significantly larger in volume in the 180-minute compression model. Both groups of dogs developed central cavitation in the spinal cord (syrinx formation), but the 180-minute compression group had significantly larger lesions, correlating to the finding on magnetic resonance imaging. These findings agreed with an earlier model of compression by Delmarter et al., [137] using circumferential ligature and decompression at time zero, 1, 6, and 24 hours, and 6 weeks after compression.

One important difference between this and many other studies evaluating the effects of spinal cord compression was that, in most of the other studies, spinal cord compression was applied with an unremitting interface force utilizing weights, balloon, or dynamic clips in which interface forces did not rapidly decline. It is hypothesized that the clinical causes of spinal cord compression were associated with interface pressures that were greatest at the time of impact with relaxation of interface pressures ensuing. This phenomenon is known as a visoelastic relaxation response to dynamic spinal cord loading [1,139]. There appears to be a range of maximum pressures that occur prior to declines in SSEP amplitudes; pressures above this limit may cause aberrations in regional blood flow [1,140,141]. This was determined in a previous dog study by Carlson et al., [1]. The spinal cord was compressed until SSEP amplitudes were diminished to 50% of baseline. The spinal cord was then either decompressed at 5 minutes or subjected to sustained compression for 3 hours without decompression. Regional spinal cord blood flow was evaluated using a fluorescent microsphere extraction technique. Spinal cord blood flow decreased by about 33% at the time of maximum interface pressures. Within 5 minutes of sustained compression, interface pressure dissipated by 51%; however, the SSEP amplitudes continued to decrease to 16% of baseline values. In the group that underwent decompression, regional blood flow and SSEP amplitudes recovered to baseline within 30 minutes. This initial hyperemic response was followed by a mild decline in regional spinal cord blood flow. In the 3-hour sustained compression group, interface pressures relaxed to 13% of the maximum values within 90 minutes, but there was no recovery of SSEP values. Regional spinal cord blood flow remained significantly lower than baseline values at 30 minutes, but was similar to the decompression group at 180 minutes. Results of both of these studies imply that, in spite of visoelastic relaxation, sustained compression was associated with regional hypoperfusion and ischemia, poorer SSEP recovery, poorer functional outcome, and lesions visible on magnetic resonance imaging and histologic evaluation [1,2].

Dynamic movement of the spine in addition to static spinal cord compression also plays a role in spinal cord injury [142-144]. This phenomenon is most commonly observed in the condition of cervical myelopathy associated with vertebral malformation/malarticulation. In a cat study by Wolfa et al., [144] a C3 corpectomy was performed and the vertebra was replaced with a hinged anterior compression device with and without C3 dorsal laminectomy to evaluate the impact of spinal movement on the pathologic processes of static compression. The results of this study revealed several findings. First, in the cats that did not undergo laminectomy, as the degree of compromise of the spinal canal rose above 20%, the epidural pressure began to rise as well, suggesting that some compensatory mechanism exists in the spinal cord and dura until that point. At spinal canal compromise greater than 20%, the compensatory mechanisms are overwhelmed, and it is at this point that clinical dysfunction and electrophysiologic (somatosensory evoked potential) changes occur [1,144]. Epidural pressures were higher in cervical extension than in a neutral position, whereas pressures were not affected in flexion. This finding supports the hypothesis that the dorsal structures (ligamentum flavum and joint capsule) contribute to compression when the neck is in extension [144]. Another important finding in this study was that the mean epidural pressure was significantly higher during passive neck movement than was the mean pressure in neutral positioning. It appears that during repeated flexion and extension visoelastic relaxation does not have time to occur, resulting in increases of both mean and maximum epidural pressures. In the laminectomized animals with spinal canal compromise of less than 75%, mean epidural pressure was remarkably lower in neutral positioning, in all degrees of spinal compromise associated with flexion and extension, and during spinal neck movement, supporting the benefit of dorsal decompression on mitigating progressive spinal cord injury.

Spasticity and Spinal Cord Compression

Spasticity is an inevitable consequence of chronic spinal cord injury or disease [145,146] and contributes to clinical complications such as limb contractures and decubital ulcers [145,146]. Spasticity is defined as an abnormal increase in tone (hypertonicity), which is observed as a resistance to passive limb movement that is proportional to the velocity of the movement [145,146]. The velocity-dependent stiffness of the affected limbs is associated with increased stretch-evoked reflexes [147-151]. However, decreased compliance of the surrounding soft tissue structures of the limb (muscles, tendons and ligaments) may also contribute to spacticity [152,153].

Although spasticity has been studied in numerous experimental models, the exact mechanisms that induce spasticity are not completely understood. Spasticity is most often associated with chronic spinal cord disease in which spasticity develops in a time-dependent fashion with lasting neuroanatomic, neurophysiologic, and neuropharmacologic changes in the spinal cord [145,146,154-156]. Once established chronically it is unlikely to improve without pharmacologic and/or surgical intervention [145,146,154-156]. It is proposed that the changes in the spinal cord are related to increased excitability of the monosynaptic reflexes that originate in the muscle-stretch receptor and synapse on the α-motoneuron that directly innervates the same muscle (e.g., the patellar reflex) [145,147,151,157-161]. Studies in cats and rats (as well as observations from clinical cases) have demonstrated increased magnitude of the lumbar monosynaptic reflexes (hyperreflexia) caudal to severe thoracic transverse myelopathy (i.e., hemisection of the spinal cord) [155,156,162-164]. The changes in reflex responses have been shown to be associated with fundamental processes that control reflex excitability, namely reduction in rate modulation of synaptic activity during repetitive stimulation [145,146,156]. In normal rat monosynaptic reflex neurons, the amplitude of recorded CAPs declines as the frequency of afferent stimulation is increased [146]. In animals with midthoracic spinal cord contusion injuries, the influence of rate-depression on the reflex CAP magnitude is attenuated and decreases in a time-dependent manner following injury [146,165-167]. Rate-depression of reflex magnitude is just one of three processes, including facilitation and potentiation, that compete to control the expression of the monosynaptic reflex [146,168-172]. The change in the magnitude of the reflex is not related to decreased action potential or to excitability of the α-motoneuron directly, but rather is associated with long-acting presynaptic inhibition in the spinal cord afferent neurons mediated by γ-aminobutyric acid (GABA) and the GABAB receptor [145,173-177]. GABA is one of the most important inhibitory neurotransmitters in the central nervous system and the GABAB receptor modulates voltage-gated calcium channels [145,173-177]. Calcium entry into the terminal axon is necessary for neurotransmitter release; therefore, activation of voltage-gated calcium channels on the presynaptic afferent neuron in the reflex arc leads to decreased amplitude of the postsynaptic excitatory potentials without altering the conductive properties of the α-motoneuron itself [145,173].

In addition to altered GABAB receptor function, loss of spinal cord interneurons has also been implicated in alterations in rate depression [145]. Loss of interneurons at the site of injury does not explain changes in rate depression in segments caudal to the lesion. It is recognized that the interneurons that mediate presynaptic inhibition are influenced by descending input from other spinal cord regions, the brain stem, and the cerebral cortex [178-186]. It has been postulated that the time-dependent development of spasticity is associated with secondary pathology that occurs in the descending pathways [145,154-156]. One descending pathway believed to be involved in modulation of sensory input and rate depression is the midbrain nucleus locus coeruleus which has been shown to send axons to all levels of the spinal cord [146,187]. Norepinephrine is the primary neurotransmitter in this pathway. The influence of this system on spinal cord spasticity has been studied by using an immunotoxin for dopamine β-hydroxylase, an enzyme in the cellular pathway that produces norepinephrine [156,188-190]. Results of these studies have suggested that loss of input from descending noradrenergic fibers that contribute to GABAB-mediated rate depression in the monosynaptic reflex contributes to the development of spasticity in the chronically injured spinal cord [145,146]. The development of spasticity and altered rate depression serving as an adaptive recovery process rather than a maladaptive process has been proposed an alternative theory [191-194].

Pain and Spinal Cord Compression/Injury

Pain that originates from the spinal cord or nervous tissue (also referred to as central pain syndrome) is reported primarily in human patients following severe spinal cord injury [170,195,196]. Following initial injury, the patient usually manifests acute pain, which is the result of injury to the spinal column and adjacent soft tissue. This nociceptive type of pain is most often described as dull, aching, and movement-related. It tends to resolve well with appropriate treatment such as rest, opioids, and anti-inflammatory medications, as well as time [4]. Pain associated with spinal cord injury tends to occur months to years after the initial injury and is difficult to manage and treat [195-201]. This type of pain should be considered a disease in and of itself, rather than a clinical manifestation of some other problem. The incidence is reported to be between 10% and 90% of all spinal cord injured patients and is often more of a concern to the patient than the residual functional disabilities [202-204]. This is not a commonly recognized phenomenon in veterinary patients that are managed long-term following spinal cord injury, but is reported in rodent models of spinal cord injury [195,200,205-209].

Pain associated with spinal cord injury may be spasticity related or may arise from the nervous system or both. The types of pain sensations reported are variable among patients [145,196]. In people, pain of spinal cord injury can be divided into transitional-zone pain and central dysesthesia syndrome. Transitional-zone pain occurs at the level of the spinal cord injury and is often associated with nerve root injury. This type of pain seems to arise most commonly with injuries at the thoracic level. It is often present at a few contiguous spinal segments and is often asymmetrical. Transitional-zone pain often "mimics" pain sensations that have been felt in the past. The pain occurs early as allodynia or hyperalgesia and may improve spontaneously [196]. This type of pain is often addressed early in the course of the disease, therefore decreasing the chances of it's becoming a long-standing illness. Severe, persistent cases are often treated with nerve blocks or dorsal root entry zone (DREZ) procedures [196].

Central dysesthesia syndrome is associated with a "burning" sensation below the level of the spinal cord injury [196]. In contrast to transitional-zone pain, it is often diffuse and symmetrical. The pathophysiology behind this syndrome has been studied but remains somewhat of an enigma. Multiple hypotheses have been generated, but it is not known if the same mechanisms underlie all central pain syndromes, because there appears to be no one lesion type or location that is associated with a higher relative risk. This type of pain has been attributed to abnormal associations of the spinothalamic and dorsal column pathways that transmit pain information [145,210]. The functional spinothalamic tracts, which normally transmit protopathic sensations such as temperature and pain, are severely impaired. The dorsal column pathways, which normally transmit epicritic information about light touch, discrimination of touch, and vibratory sensations, are spared. In central pain, it is believed that the dorsal column pathways begin to transmit pain sensations normally transmitted by the spinothalamic pathways. Patients with central pain often have abnormal pain and temperature sensibilities. Of interest is that lesions within the spinothalamic pathways are not required to induce this phenomenon, but rather tend to influence the character of the abnormal sensations. It appears that the critical disinhibition occurs in the ventroposterior, medial, and intralaminar thalamic nuclei that receive and integrate information from the spinothalamic pathways [211-213]. These thalamic regions in general tend to have an inhibitory influence on pain sensation. Abnormal functioning in this pathway results in abnormally high levels of pain and hypersensitivity. How these cells ultimately become disinhibited after spinal cord injury is not truly known [145,214]; however, on a cellular level excitatory amino acids, glutaminergic N-methyl-D-aspartate (NMDA), and serotonergic receptors have been implicated [17,214-216]. The excitatoxic amino acids may influence cytokine production, breakdown of structural proteins, second messengers, and transcriptional proteins in ways that result in abnormal signaling in the pain processing pathways [145,170,200,217,218]. In experimental models of spinal cord injury, abnormal electrical activity has been identified in segments surrounding the injury site on electrophysiologic testing [206,219,220]. The abnormal activities reported include increased stimulus response, increased spontaneous background activity, and increased after-discharge responses. In a rat spinal cord clip-compression study by Bruce et al., [214] the influence of serotonin in development of central pain of spinal cord injury was investigated. Serotonin immunoreactivity in the dorsal horn was found to be decreased caudal to the thoracic injury site (T9-11) and increased three-fold in regions rostral to it. The decrease caudal to the injury was believed to be consistent with loss of descending serotonergic antinociceptive pathways. The presence of increased serotonin activity in dorsal horns rostral to the injury was an unexpected finding. Because serotonin is also known to possess pronociceptive properties, it was postulated that this observation may be involved in the disruption of inhibition of pain pathways.

Central pain may remain stable, escalate in severity, or decrease over time and it can be very difficult to treat [145,210,221,222]. Autonomic dysnergia, such as distended bladder or constipation, can result in increased pain transmission, raising baseline pain levels in these patients [223].

Another complication of spinal cord injury is the development of syrinx within the parenchyma of the spinal cord (syringomyelia) [196,198]. This injury most commonly occurs years after the injury and is associated with ascension of the sensory and motor level dysfunction owing to the expansion as well as to the development of new pain sensations. Typically, this pain is located in the region of the syrinx but may cause a burning-type pain above the level of the injury or syrinx. The natural course of syringomyelia is continued escalation of the pain that is often not responsive to medications or surgical intervention with syringopleural shunting. Post-injury or post-compression syrinx formation appears to be a more common source of pain in dogs than is the enigmatic central pain syndrome (Fig. 42-9).