Overview
Spinal cord injury (SCI) is a serious injury to the central nervous system and a serious threat to human life and health. Most of them are caused by traffic injuries, fall injuries, violence or sports, etc. There is a high incidence and disability rate in modern society. Early and comprehensive medical intervention and rehabilitation have an extremely important impact on reducing the degree of spinal cord injury and improving the quality of life of SCI patients in the future.
[Pathogenesis].
Studies have shown that there are two mechanisms of injury involved in SCI, namely primary injury (including mechanical damage, hemorrhage, etc.) and secondary injury. Primary injury occurs passively within a short time after injury (generally considered within 4 h) and is irreversible. In contrast, secondary spinal cord injury develops gradually within minutes to days after the primary injury and is accompanied by a series of intracellular metabolic and genetic changes, sometimes producing more tissue destruction than the primary injury.
Due to the intervenable nature of secondary injury, it can be prevented and mitigated by early, aggressive, and correct medical intervention. Therefore, how to study the mechanism of its occurrence and give effective treatment strategies has become a hot topic of attention in recent years. There are many mechanisms of secondary injury, including vascular mechanism, free radical damage mechanism, excitatory amino acid toxicity, apoptosis, calcium-mediated mechanism, nitric oxide mechanism, etc.
1.Vascular mechanism
The vascular changes after SCI are immediate and delayed local effects and systemic effects. Local effects include progressive decrease of microcirculation, disturbance of spinal blood flow autoregulation and decrease of spinal cord blood flow (SCBF). Systemic effects include systemic hypotension, neurogenic shock, decreased peripheral resistance, and decreased cardiac output.
The specific mechanisms are as follows
(i) After severe SCI, sympathetic tone decreases, cardiac output decreases, blood pressure drops, and the spinal cord loses its ability to automatically regulate blood flow, making the local blood supply to spinal cord tissues inadequate.
②Microvascular spasm, vascular endothelial cell injury or edema.
③Vasoactive amines (catecholamines) and some biochemical factors such as oxygen free radicals, nitric oxide, platelet activating factor, peptides, arachidonic acid metabolites, endothelin, thromboxane A2, etc. produced after injury can affect microvessels, causing increased vascular permeability, platelet aggregation and vascular embolism.
④ The presence of early and extensive small hematomas in the spinal cord after trauma, especially the intra-gray matter hematoma can lead to ischemia in the white matter surrounding the gray matter, because the blood supply to the white matter in the inner half of the spinal cord comes from the branches of the sulcus arteriosus through the gray matter. These vascular changes lead to spinal cord ischemia in the injury area and, if severe ischemia is prolonged, can cause post-injury spinal cord infarction. The degree of spinal cord ischemia has a linear dose-response relationship with the degree of injury and dysfunction, and is progressively worse in the first few hours after injury and lasts for at least 24h.
2. Mechanism of free radical (FR) injury
The spinal cord tissue is rich in lipids and is extremely sensitive to lipid peroxidation. Under physiological conditions, the body produces certain free radicals (FR) to maintain the integrity of various cellular and subcellular structures, but endogenous oxidation systems such as superoxide dismutase (SOD) and catalase (CAT) can effectively eliminate FR. After SCI, FR can be increased through various links:
(1) Mitochondrial dysfunction due to ischemia, hypoxia and hemorrhage in spinal cord tissue, ATP degradation, incomplete oxygen reduction and oxygen radical generation;
(2) Hypoxic metabolism of vascular endothelial cells and neuronal cells generates large amounts of FR through the xanthine-xanthine oxidase system;
(3) polymorphonuclear leukocytes produce large amounts of O2-, OH・ and H2O2 during phagocytosis; (4) the activity of antioxidant substances such as SOD and CAT decreases significantly.
On the other hand, free radicals can inhibit prostaglandins, making prostaglandin synthesis inhibition unable to counteract the vasoconstrictive effect of endothelin, leading to vasospasm and occlusion.
3, Excitatory amino acids (EAA) mechanism of action
Excitatory amino acids (EAA) include glutamic acid (Glu) and aspartic acid (Asp). They exert neurotransmitter effects under physiological conditions; however, they have neurotoxic effects under pathological conditions. Currently, many studies have suggested that EAA and its receptors play an important role in triggering secondary pathophysiological responses after SCI.The mechanism of EAA involvement in secondary SCI injury is twofold: on the one hand, the massive release of EAA after SCI leads to altered permeability of nerve cells and cytotoxic edema caused by Na+ and H2 O inward flow; on the other hand, the massive release of EAA after injury over-activates NMDA receptors, making the receptor-dependent Ca2 On the other hand, the massive release of EAA after injury over-activates NMDA receptors, causing a large number of receptor-dependent Ca2+ channels to open, leading to Ca2+ inward flow and causing delayed neuronal injury.
4. Apoptosis mechanism
Apoptosis is the active programmed cell death under certain conditions. Numerous studies have confirmed that a large number of neurons and glial cells apoptosis occurs 4-24 h after SCI, in which the expression of pro-apoptotic factors such as Bax and caspase-3 increases, while the expression of inhibitory factors such as Bcl-2 and c-kit decreases. Activated glial cells protect spinal cord tissue during the first few weeks after injury and participate in the recovery of spinal cord function in the immediate post-injury period. They do this by migrating to the injury site, densifying the injury site, and preventing the entry of neutrophils. Glial cells also produce neurotrophic factors, scavenge oxygen free radicals, and support neuronal survival.
It has been shown that the cytokine TNF-α plays an important role in the apoptosis of glial cells, and the downregulation of TNFR1 receptor after injury can reduce the apoptotic effect of TNF-α on glial cells. Apoptotic glial cells do not express specific acidic glial proteins (astrocyte-specific proteins, CRAF), and morphologically appear as oligodendrocytes. Oligodendrocytes are distributed in the gray and white matter of the spinal cord and are arranged in rows between the fibers of the white matter, which wrap around the axons and form myelin sheaths; apoptosis of oligodendrocytes causes demyelination of myelinated nerve fibers, axonal degeneration, and subsequent glial scarring.
5, nitric oxide (NO) mechanism of action
NO is an important messenger molecule, which has the functions of relaxing blood vessels, inhibiting platelet aggregation, increasing blood flow, protecting cells and promoting regeneration, so moderate amount of NO can protect nerve cells and promote nerve regeneration. However, excessive NO can mediate severe neurotoxicity and cytotoxicity and cause further tissue damage. Studies have shown that excessive NO production after SCI can aggravate secondary spinal cord injury:
(i) mediating the neurotoxicity of excitatory amino acids.
(ii) Reacting with superoxide anion to form highly toxic peroxynitrite anions and hydroxyl radicals, causing extensive lipid peroxidation and protein tyrosine nitration.
(3) Binding to the iron-sulfur center of many enzymes in the cell, interfering with the DNA duplex and affecting its transcription and translation.
6.Other
The mechanisms of secondary injury include intracellular Ca2+ overload, neuropeptide mechanism, endothelin action mechanism, prostaglandin action mechanism, etc. These mechanisms are intertwined and cascaded in the spinal cord secondary injury, and play an important role together.
Classification and grading
A. Etiological classification and diagnosis
1, traumatic spinal cord injury
2, non-traumatic spinal cord injury
Second, according to the severity of the injury can be divided into four levels.
1, spinal cord anatomical transection, this type is seen in severe spinal fracture dislocation, spinal canal penetration injury, etc., fracture fragments invade the spinal canal injury spinal cord; 6h central gray matter liquefaction necrosis. 6w after the injury, the spinal cord is replaced by glial and fibroblastic cells and scarring within 1-50px of the severed end.
2, complete spinal cord injury, this kind of injury is more common, the trauma itself determines the severity of spinal cord injury, the spinal cord anatomically continuous, but the conduction function is completely lost, the clinical manifestations of the spinal cord injury below the plane of sensory, motor, sphincter function is completely lost. At 15min-3h after injury, the central canal is hemorrhagic, the gray matter is multifocal, and the nerve cells in the hemorrhagic area are partially degenerated; at 6h, the hemorrhage is all over the gray matter; at 24-48h, the nerve cells are barely visible in the gray matter, and the axons in the white matter are degenerated, and in some places, necrosis begins. Most of the spinal cord was necrotic at 1-2 w after injury. 6 w later, the neural tissue of the spinal cord was completely lost and replaced by glial tissue.
The secondary injuries such as edema, hemorrhage, microcirculatory disorders, and oxygen radical release are more severe and progressive, and without intervention eventually often lead to spinal cord necrosis. However, within 6-8 hours after spinal cord injury, although there is hemorrhage and edema in the center, it is not yet necrotic and the surrounding white matter is intact, which is the best time for treatment. Subsequent secondary injuries such as edema, hemorrhage, microcirculatory disorders, and oxygen radical release are more severe and progressive, and often lead to spinal cord necrosis if no intervention is made.
3, incomplete spinal cord injury, this kind of injury is similar to the changes of complete injury, but the injury itself is relatively light, the spinal cord anatomical continuity is intact, partial loss of conduction function, clinical manifestations of the spinal cord injury below the plane of sensory, motor, sphincter function exists in varying degrees. Depending on the site of injury, there are five syndromes: anterior spinal cord injury, posterior spinal cord injury, central spinal cord injury, semi-transverse spinal cord injury, cone and cauda equina injury.
At 1-3 h after injury, there is exudation and hemorrhage in the central canal and several punctate or focal hemorrhages in the gray matter: at 6 h, some nerve cells in the gray matter hemorrhage area begin to degenerate. at 24 h, a few white matter degenerates. at 6 w, there is no hemorrhage in the spinal cord. The nerve cells are present and a few are still degenerating. The secondary injury is relatively mild and non-progressive, with partial recovery of function, but foci of softening necrosis may remain in the gray and white matter.
(1) Anterior/posterior cord syndrome: Anterior cord syndrome: Injury to the anterior part of the spinal cord, which is characterized by loss of motor and nociceptive sensation below the level of injury. The posterior spinal column is not damaged, but proprioception is present. Posterior cord syndrome: Injury to the posterior portion of the spinal cord, which is characterized by loss of proprioception below the level of injury and the presence of motor and pain-temperature sensation. Most often seen in patients with vertebral plate fractures.
(2) hemisection syndrome (Brown-Sequard’s Symdrome): hemisection of the spinal cord, showing loss of contralateral pain and temperature below the plane of injury, and loss of ipsilateral proprioception and motor sensation.
(3) Central cord syndrome (central cord syndrome): It is common in cervical cord injury. The loss of upper limb movement, but the lower limb motor function exists or the loss of upper limb motor function
Significantly more severe than the lower extremity. The tendon reflexes in the plane of injury are absent, but the tendon reflexes below the plane of injury are hyperactive.
(4) Cone injury syndrome: damage to the spinal cone and the lumbar spinal nerve in the spinal canal, no obvious motor deficits in the two lower extremities, saddle-like sensory deficits in the anus and perineum, sexual dysfunction (impotence or inability to ejaculate); urinary and fecal incontinence or retention, and loss of anal reflexes. Occasionally, the bulb-anal reflex and the voiding reflex can be preserved.
The superior conus syndrome (L4-S2) is relatively uncommon. In contrast to conus syndrome, in this syndrome, the height of the lesion can determine whether it produces bradykinesia or chronokinesia. External rotation and dorsiflexion of the hip (straight leg raise), possible flexion of the knee (L4, S2), and flexion and extension of the ankle and toe joints (L4, S2) may be diminished or lost. The Achilles reflex is absent, but the knee reflex is preserved. The bladder and rectum can be emptied only by reflex. Despite loss of sexual ability, penile erection may occasionally be present. Occasionally, the sacral reflex is preserved. Cone syndrome (S3-C) is also rare, with injury to the thoracolumbar segment, and L1 violent fractures can cause cone injury, as well as injury to the spinal cord and nerve roots.
(5) cauda equina syndrome (Injury of cauda equina syndrome): damage to the lumbosacral nerve in the spinal canal, characterized by significant asymmetric damage to the lower extremities, clinical manifestations in addition to the corresponding motor or sensory deficits, no reflex bladder and bowel movement disorders, and loss of lower extremity function including reflex activity. The nature of the cauda equina is actually a peripheral nerve, and the prognosis is better. If the cauda equina nerve is damaged for various reasons, the clinical symptoms of sensory, sphincter function and sexual dysfunction in the saddle area are called cauda equina syndrome.
4, spinal cord oscillation, is the most mild spinal cord injury, the clinical manifestation is incomplete paraplegia. Histologically, there may be small focal hemorrhages and degeneration of neural tissue in the gray matter, but no foci of necrosis are formed, and the symptoms and signs generally disappear within 24-48h after the injury. Most of them do not leave neurological sequelae.
Three, paraplegia index
The degree of loss of various functions after spinal cord injury can be expressed by the paraplegia index: “0” represents completely normal or nearly normal function. “1” represents partial loss of function. A “2” represents a complete or near complete loss of function. Generally, the function of voluntary movement, sensation and bowel movement are recorded. The index can reflect the degree of spinal cord injury and its development, which is easy to record and also comparable to the treatment effect.