Spinal cord trauma: pathophysiology, classification of spinal cord injury syndromes, treatment principles and controversies

Spinal cord trauma: pathophysiology, classification of spinal cord injury syndromes, treatment principles and controversies

SPINAL INJURIES Spinal cord trauma: pathophysiology, classification of spinal cord injury syndromes, treatment principles and controversies Neurons a...

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SPINAL INJURIES

Spinal cord trauma: pathophysiology, classification of spinal cord injury syndromes, treatment principles and controversies

Neurons are especially vulnerable to injury because of the length, complexity and specificity of their connection. In addition, the receptor and membrane specializations that enable chemical and electrical neuronal transmission cause a high capacity for and vulnerability to major ionic shifts. The spinal cord components are rarely exposed to inflammatory cells and there is a specialized barrier between endothelial cells supported by astroglia that restricts movement of proteins and other molecules.1 Spinal cord salvage and repair are two primary goals of therapy.2 Traditionally, the role of the Spinal Surgeon is in posttraumatic spinal cord salvage focussing on acute care, surgical decompression, vertebral stabilization and management of chronic complications, such as syringomyelia, tethering and deformity.2,4 Neuro-protective and repair strategies are based on understanding of the temporal evolution of injury mechanisms. Spinal teams with surgical and scientific expertise will translate new advances from experimental studies into clinical studies aiming to design and apply new treatments.1e3

George I Mataliotakis Athanasios I Tsirikos

Abstract Acute spinal cord trauma is a devastating injury which often leads to severe disability. The tissue response following the initial insult extends the cord damage, while there is limited repair potential with regards to axon regeneration resulting in permanent neurological deficits. Management of acute cord injury is an area of active research in order to stabilize the spine in a timely manner, minimize the secondary insult and promote regeneration. Methyl-prednisolone administration for limitation of the secondary injury phase and acute versus late operative treatment are areas of current debate among several authors. This article is an overview of all aspects of early and long term spinal cord injury management. It focuses on the patho-physiological mechanisms of the acute injury phase and the different clinical types of cord injury syndromes. The treatment principles are described along with an updated view on the controversial issues.

Epidemiology The estimated annual incidence of acute SCI in the United States among those who survive a traumatic event is 40 per million population or approx. 12 500 per year.1,5 The distribution of age at injury is bimodal; the first peak (approximately 50% new injuries) involves young adults and the second peak involves adults older than 60 years.5,6 The average age of young adults has increased from 28.7 to 42 years.5 Adults older than 60 are vulnerable to SCI due to age related bony changes, such as cervical spondylosis and stenosis, the effects of medication and sensory loss.5 The clinical outcome in patients >60 years is considerably worse than that in younger patients. Approximately 50% of patients have cervical, 35% thoracic or thoracolumbar and 11% lumbar injury; the location of the remaining 4% is unknown or unreported. The single most commonly affected level is C5. The most frequently reported post-SCI neurologic category is incomplete tetraplegia (39.5%); complete paraplegia accounts for 22.1%, complete tetraplegia for 21.7% and incomplete paraplegia for 16.3%.5 At least 20% of patients with SCI have other major injuries such as cerebral contusions or flail chest.5

Keywords cord syndromes; methyl-prednisolone; neuro-plasticity; neuro-protection; spinal cord trauma

Introduction The neural tissues forming the spinal cord are highly susceptible to injury and have little capacity for self-repair. Reversal of spinal cord injury continues to be one of the greatest challenges in medicine. Knowledge of patho-biology is rapidly evolving and components once thought to be detrimental such as glial scarring and inflammation are now believed to have beneficial effects.1,2 Traumatic spinal cord injury (SCI) is typically caused by a contusive force to the spinal cord leading to activation of numerous mechanisms that both extend and limit the injury.3

Mechanisms of cord injury The spinal cord may be injured by compression, contusion, laceration or vascular insult.3 The impact of injury depends on the magnitude of initial insult and the underlying condition of the spinal cord. The difference between compression and contusion is in the rate of deformation.1 In cord contusion, the compressive force exceeds the tissue components tolerance leading to disruption of axons and damage of neuron cell bodies, myelinating cells and vascular endothelium. Mechanical failure of the osseo-ligamentous spinal column structure may lead to SCI by abrupt physical deformation of the cord substance (contusion) and/or by direct laceration/ compression by bone fragments.6 Gunshot injuries may cause direct laceration of the cord by the projectile or indirect injury by the bone/disc fragments.6e8 Abrupt distortion and shearing by the blast cavitation of the projectiles’ kinetic energy may also

George I Mataliotakis MD Fellow in Spinal Deformity Surgery, Scottish National Spine Deformity Centre, Royal Hospital for Sick Children, Edinburgh, UK. Conflicts of interest: none declared. Athanasios I Tsirikos MD FRCS PhD Consultant Orthopaedic and Spine Surgeon, Honorary Clinical Senior Lecturer, University of Edinburgh; Clinical Lead, Scottish National Spine Deformity Centre, Royal Hospital for Sick Children, Edinburgh, UK. Conflicts of interest: none declared.

ORTHOPAEDICS AND TRAUMA --:-

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Please cite this article in press as: Mataliotakis GI, Tsirikos AI, Spinal cord trauma: pathophysiology, classification of spinal cord injury syndromes, treatment principles and controversies, Orthopaedics and Trauma (2016), http://dx.doi.org/10.1016/j.mporth.2016.07.006

SPINAL INJURIES

cause injury to the cord.7 Knife injuries may cause direct complete or partial laceration of the cord.9 Based on the macroscopic findings, SCI can be classified into four groups: (a) solid cord injury, the least common type, is associated with normal appearance of the cord after injury; (b) contusion, the most common type, is associated with areas of haemorrhage and expanding necrosis/cavitation but with no disruption of the surface of the cord; (c) laceration, where is a clear-cut disruption of the surface anatomy; and (d) massive compression, where the cord is macerated to varying degrees.10 In most instances, the anatomic degree of spinal cord damage does not correlate with the degree of functional loss.

Key-stages of the spinal cord response to closed trauma1,6,11e16 Acute phase (up to 72 hours)

C C C C

C

C

Pathophysiology-neurological insult

C

Intermediate phase (days to weeks)

The predominantly lipid structure of the spinal cord partially accounts for its vulnerability to injury. Aside from the pia matter there is very little connective tissue in the spinal cord in comparison with the peripheral nerves, which are much more resilient.

C

C C C

C

Primary injury

C

After the SCI the spinal cord is contused, may be partially lacerated but is rarely transected. The maximal neurologic deficit is observed immediately after a SCI because axonal transmission is disrupted or blocked by abrupt neuronal cellular damage, endothelial and blood vessel damage, haemorrhage and massive shifts in membrane potential and ionic concentrations.1 This is mostly irreversible.6

C

Chronic phase (months to years)

C C C C C C C

Secondary injury

C

The secondary injury phase begins immediately and may extend for several days. The tissue damage continues during that phase substantially extending the size of the injury. Oedema and haemorrhage within the cord may spread from the primary site of impact over several rostral and caudal levels. Haemorrhage is more evident in the gray matter because of its rich vascularity. Endothelial damage leading to increased permeability and intracellular oedema, is a key factor in the recruitment of inflammatory cells.6 The secondary injury response can be divided into acute, intermediate and chronic phases. The intermediate phase starts a few days after injury and lasts for several weeks. The events of each phase are summarized in Table 1; however there is close interrelation among all phases without distinct borders between them.

Table 1

Endothelial damage is the primary event that initiates the cascade of SCI inflammation. Mechanical gaps between endothelial cells develop within 1.5 minutes of injury leading to damage of perivascular basement membrane, red blood cell extravasation, platelet aggregation and fibrin deposition. Platelet aggregates occlude vessels leading to ischaemia. Endothelial gaps promote influx of fluid and proteins thus producing oedema. Subsequent events promote microglial activation and leucocyte infiltration. The basal laminae are further degraded due to increased endothelial expression of vascular cell adhesion molecule. These events further exacerbate the loss of endothelial integrity, increasing vascular permeability and leucocyte influx. The prominent cytokines present at SCI include IL-1, IL6, TNF-a, and TGF-1. Early expression of TNFa and IL1 by microglia enhances the recruitment of inflammatory cells to the injury site. IL1b is upregulated within one hour of injury, peaks at eight hours after injury and persists at least seven days.1,11,17 The four general classes of inflammatory cells that respond to SCI are microglia, neutrophils, macrophages and lymphocytes. Microglia, neutrophils, macrophages offer innate immunity and lymphocytes offer adaptive immunity.6 Neutrophils enter the damaged spinal cord immediately after injury and reach peak

Vascular injury/inflammatory response The spinal cord is not exposed to inflammation like tissues as skin, bone, lungs, which frequently undergo healing process. Endothelial cells normally form a barrier that excludes the active blood components from the Central Nervous system (CNS).1,17 This blood-CNS barrier is characterized by tight junctions between endothelial cells and strong interactions between the surrounding astrocyte foot processes and basal lamina.1,17 Thus macrophages, lymphocytes and poly-morpho-nuclears are seldom observed in the normal spinal cord and the intrinsic microglia is quiescent. Also, CNS cells are rarely exposed to inflammatory cytokines (Table 2).

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Cord oedema, intracellular swelling Haemorrhage Regional cord perfusion shifts Inflammatory response: free radical production, lipid peroxidation and cytokine release Membrane instability: shifts in electrolytes and accumulation of neurotransmitters Demyelination Cell necrosis and apoptosis Proximal and distal extension of oedema, necrosis and apoptosis Continued inflammatory response Vascular angiopathy Peak levels of astrocyte and macrophage activity Initial scar formation Neuroplasticity Spasticity Formation of fluid e filled cavity Wallerian degeneration Glial scar formation Demyelination Schwann cell proliferation Syringomyelia Tethered cord Neurite sprouting, altered neurocircuits and chronic pain syndromes

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Please cite this article in press as: Mataliotakis GI, Tsirikos AI, Spinal cord trauma: pathophysiology, classification of spinal cord injury syndromes, treatment principles and controversies, Orthopaedics and Trauma (2016), http://dx.doi.org/10.1016/j.mporth.2016.07.006

SPINAL INJURIES

production phase (glial cell line derived neutrophilic factor). Blockade of metabotropic glutamate receptor subunit 5 on microglia is associated with reduced microglial activation and improvement in tissue and functional outcome after SCI. Macrophages and microglia are removing the growth inhibitory components of myelin debris promoting regeneration.12 However, macrophages are associated with chondroitin sulphate proteoglycan deposition, which may inhibit axon growth. Experimental studies showed that reduced T lymphocyte response resulted into less extensive tissue loss and decrease in secondary SCI.12,13

Patient function recovery according to spinal cord injury level Level

Patient function

C1eC3

C C C

C3eC4

C

C

C5

C C C

C

C6

C C

C

C7

C C

C8-T1

C C C

T2eT6

C C C

T7eT12

C C

L1eL5

C C C

S1eS5

C C C

Ventilator dependent Limited talking Electric wheelchair with head control Initially ventilator dependent; may become independent Electric wheelchair with head control Ventilator independent Present biceps, deltoid, and elbow flexion No wrist extension and supination (cannot feed him/her self ) Electric wheelchair with hand control, minimal manual wheelchair function (independent ADL’s) Better function than C5 Wrist extension and supination intact (can feed him/herself ) Manual wheelchair, transfers with sliding boards, drive car with manual controls (independent) Triceps strength present Manual wheelchair and independent transfers Hand and finger strength present Manual dexterity Fully independent transfers Normal upper limbs function Improved trunk control Wheelchair Abdominal muscle control Seated activities unsupported Variable lower limb function Variable bowel and bladder function Variable requirement of assisting devices and bracing Variable bowel and bladder function Variable sexual function Walking with minimal or no assistance

Ionic dysregulation Ionic homoeostasis is lost immediately after SCI. Failure of the cell membrane and the transmembrane adenosine pumps causes loss of regulation of extracellular concentrations of sodium, glutamate and other molecules.14 Subsequently, the mitochondrial membrane breaks down and various receptors become activated, leading to numerous changes in gene regulation and production of free radicals. Glutamate excitotoxicity damages the oligodendrocytes (myelinating cells of the CNS) and axons.11,17 Free e radical mediated damage Oxidative damage may continue as long as five days. Molecular oxygen causes damage to membranes, proteins and nucleic acids by lipid peroxidation, protein nitration and activation of redox esensitive signalling cascades.1,6 Lipid peroxidation coincides with the initial influx of neutrophils, macrophage and microglia activation. Neutrophils and activated microglia are the major source of nicotinamide adenine dinucleotide sulphate oxidasederived reactive oxygen in the injured cord.17 Oxidation of membrane lipids increases permeability to ions and causes failure of the transmembrane adenosine triphosphate-driven pump function. The glial scar Proliferation of astrocytes to the SCI site leads to the development of glial scar. The reactive astrocytes secrete chondroitinsulphate proteoglycans which is the main glial scar component.18 Its formation is regulated by the TGFb and acts as a physical barrier to regenerating axons.11,16 Chronic changes Local disruption of CNS connections after SCI is followed by trans- and retro-grade neuronal degeneration, segmental sprouting of axons, plasticity and alterations in neuronal excitability. The clinical manifestations include spasticity, autonomic dysreflexia and neuropathic pain.6 A syrinx secondary to SCI can cause delayed neurologic dysfunction such as ascending paralysis, brainstem symptoms and pain. Myelomalacia and spinal cord tethering may also complicate the chronic lesion.

Table 2

numbers within six hours. Macrophages follow and peak within two to seven days persisting as long as 2 weeks after injury.11,17 Lymphocytes entry is delayed and protracted; the cells are detectable several months after injury. The acute inflammatory response lasts approximately 10 days. Inflammatory cell counts are generally not elevated in CSF later than three weeks after injury. Neutrophil depletion reduces histologic recovery from injury. The activation of microglia (intrinsic inflammatory cells of the cord) begins almost immediately after injury and is correlated with increase in tissue damage.12 Upregulation of TNFa, IL1b and IL6 is detectable within minutes of injury and increases during the first four days after injury.12 Microglia gets activated during the early acute inflammation phase and during the neurotrophin

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Endogenous reparative process Animal studies showed that new stem cells are formed around the ependyma, which actively replace some depleted cells, especially oligodendroglia.18 In-migration of Schwann cells may also lead to functional myelin repair of CNS axons. Administration of sonic hedgehog protein or transduced transcription factors may further increase new cell formation.

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SPINAL INJURIES

SCI associated conditions

The nine elements of inflammatory response

1. Neurogenic shock is the acute complication following SCI leading to disruption of autonomic pathway. There is temporary loss of sympathetic tone while the parasympathetic tone is maintained. The neurogenic shock may last for one to three weeks and manifest over hours to days, due to the secondary injury.6 This condition manifests with hypotension, bradycardia and circulatory collapse due to decreased systemic vascular resistance.4,6,19 It can be treated with: a) fluid resuscitation until the dilated intravascular volume is filled to the normal central venous pressure and b) use of vasopressors with both a and b adrenergic actions to counter the loss of sympathetic tone and provide inotropic/chronotropic support. Swan-Ganz catheter is recommended to monitor the central venous pressure (CVP) and prevent overload.4,6,19 Apart from sinus bradycardia, orthostatic hypotension may also be due to loss of sympathetic tone in the acute phase. 2. Spinal shock is an acute post-injury neurophysiologic condition affecting the cord, caused by hyperpolarization of the neurons rendering them unresponsive to brain stimuli.20,21 It is manifested as temporary loss of cord function and reflex activity below the injury level. It is characterized by flaccid areflexic paralysis, loss of sympathetic tone causing bradycardia, hypotension and absence of the bulbocavernosus reflex.20,21 The extent of neurologic deficit cannot be fully evaluated in the presence of the spinal shock. The initial clinical picture usually resolves within 48 hours and is signified by the return of the bulbocavernosus reflex.21 Conus or cauda equina injuries may lead to permanent loss of the bulbocavernous reflex. The spinal shock can be divided into four phases: (a) areflexia/hyporeflexia; (b) initial reflex return; (c) early hyper-reflexia; (d) late hyperreflexia, which is due to the underlying neuroplasticity after SCI. Over subsequent weeks and months after the return of reflexes, reflex axons grow new synapses to mediate hyperreflexia. The synapse growth appears to be axon-length, activity-dependent and competitive.20 Both neurogenic and spinal shock need to be differentiated in the acute setting from hypovolemic shock which is caused by decreased cardiac preload due to blood loss and results in hypotension associated with tachycardia. 3. Other injuries manifesting with altered neurology and interfering with the examination are: a) closed head injuries; b) other non-contiguous or unstable spinal fractures; c) vertebral artery injuries. Vertebral artery injuries may be caused by cervical spinal fractures/dislocations, can be diagnosed with Magnetic Resonance (MR) Angiography, and can produce basilar artery insufficiency which is an indication for stenting.

1 2 3 4 5 6 7 8 9

Table 3

Council Grade, MRC Grade) distal motor and 0/2 distal sensory scores (absent perianal sensation). In an incomplete SCI there is some preserved motor or sensory function below the injury level and it is classified as ASIA B, C or D (Table 3). This includes voluntary anal contraction (sacral sparing), palpable or visible muscle contraction below injury level or present perianal sensation. The level of neurologic injury is the lowest segment with intact sensation and antigravity muscle strength (3/5 grade MRC or more). In regions where no myotomal testing exists, the motor level is presumed to be the same as the sensory level. Injury to the cervical spinal cord may lead to tetraplegia causing impaired function in the upper limbs, trunk, lower limbs, bowel and bladder. Upper cervical spinal injuries may lead to diaphragm paralysis and respiratory compromise. Injury to the thoracic cord, conus or cauda equina may lead to paraplegia. In paraplegia, there is sparing of the upper limbs and impaired function in the trunk, lower limbs, bowel and bladder depending on the level of injury. Depending on the cord involvement following injury, the patient can develop different types of cord syndromes: A. Central cord syndrome is the most common SCI. It usually happens in older individuals sustaining hyperextension injuries to the cervical spine.22,23 It occurs from an abrupt contusion of the cord with a pincer type mechanism between the hypertrophied ligamentum flavum posteriorly and the osteophytes anteriorly.23 It involves the grey matter and central portion of the cord more than the peripheral.22 Because of the anatomical arrangement of the motor tracts to the upper limbs being more medial followed by thoracic, lumbar and sacral components this syndrome manifests with greater weakness of the upper than the lower limbs.22,23 The majority of patients will have bowel and bladder control. The prognosis is good with 75% recovery; although spasticity may remain, almost all young and 50% of elderly patients will regain ambulatory function. Most of the patients will not recover fine motor use of the hands.24 B. Anterior cord syndrome is the second most common SCI syndrome and involves the anterior two thirds of the spinal cord. It is either of vascular origin or due to a retro-pulsed fracture fragment onto the cord.6,8,24 It manifests as complete motor and sensory loss below the level of the injury.

Classification of SCI SCI is divided into complete and incomplete. Complete is a SCI when there is no spared motor or sensory function below the affected level. A SCI can only be characterized as complete after resolution of the spinal shock and is further classified as American Spinal Injury Association (ASIA) grade A (Table 3). This includes no voluntary anal contraction, 0/5 (Medial Research

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Endothelial damage and activation Activation of resident microglia In migration of polymorphonuclear leukocytes In-migration of macrophages Dysregulated oxidative metabolism and release of free radicals Free radical mediated damage of membranes, proteins and nucleic acids Propagation of excitotoxicity, toxic calcium and sodium concentrations Necrotic and apoptotic cell death Local and systemic activation and recruitment of anti CNS antigen reactive T and B cells

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SPINAL INJURIES

initial assessment, acute treatment, definitive treatment (including non-operative and surgical) and rehabilitation. Despite the ongoing advances in trauma prevention with the use of helmets, protective garments, airbags etc 50% of SCIs are still due to Road Traffic Accidents (RTA). The treatment starts at the site of injury and attention should be drawn towards proper immobilization of the patient with rigid collars, standard log roll techniques and transportation on a firm spinal board. Upon reaching the Trauma Centre, the primary and secondary surveys are based on Advanced Trauma Life Support (ATLS) protocol.2,6 Absence of posterior midline tenderness in the awake, alert patient predicts low probability of significant cervical injury. Emphasis should be given to SCIs proximal to C5, which may require intubation.6 Abdominal bruising following a high energy injury should raise suspicion of flexion-distraction injuries of the thoracolumbar spine. Rotational deformity may indicate a unilateral facet dislocation.

Only the dorsal columns are spared which provide deep touch, proprioception and vibration sensation. The motor loss is greater in the lower than the upper limbs.8 The prognosis is poor with only 10% neurological recovery.6,24 C. Brown-Sequard syndrome occurs with damage of the lateral half of the cord (hemisection).6,25,26 It is manifested as ipsilateral motor, position and proprioception loss and contralateral loss of pain and temperature, which affects two levels below the injury.6,25 It is usually the result of a penetrating injury. The prognosis is very good with almost 90% recovery of bowel/bladder function and ambulation.26 D. Posterior cord syndrome is rare and involves loss of posterior column function, which provides deep touch, proprioception and vibration sensation.6,24 These patients maintain the ability to ambulate but they rely on visual input for spatial orientation.6,24

Persistent spinal cord compression Neuroprotective drugs

Continued compression of the injured spinal cord by disc, bone or blood clot in the epidural space may exacerbate the magnitude of the ischaemic and secondary injury cascades.6,23 Persistent compression is common after SCI and may be caused by a ruptured disc, bony fragmentation or dislocation. Ischaemia is the presumptive mechanism of persistent compression.1 Persistent compression after contusive SCI causes potentially reversible additional injury in animal studies and decompression improved the outcome in mild and moderate but not in severe SCI.1,6 Neurological recovery was inversely related to the duration of compression.23

The American National Acute Spinal Cord Injury Study (NASCIS) phases IeIII studied the use of methylprednisolone sodium succinate (MPSS) in various protocols regarding dose and timing of administration following an acute SCI. Post-hoc analysis of the NASCIS II data revealed that those patients receiving MPSS within eight hours of injury had significant improvement in sensory and motor function after one year.2,28,29 Post-hoc analysis of the NASCIS III data demonstrated that if the treatment starts within three hours from injury there is no need to extend treatment beyond 24 hours, whereas if it starts after three hours the motor recovery is better if the treatment extends to 48 hours.30 The MPSS administration protocol requires a loading dose of 30 mg/kg over the first hour and an infusion of 5.4 mg/kg/hour for 23 hours if started in less than three hours post-injury or for 47 hours if started three to eight hours post-injury. Indication for MPSS administration is non-penetrating SCIs within eight hours of injury and contraindications include: a) pregnancy; b) age under 13 years; c) brachial plexus injuries; d) more than eight hours after injury. However, patients treated with MPSS have increased incidence of wound infections pneumonia, sepsis and death from respiratory complications.28,30 Partly for this reason in 2013 the AANS/CNS Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injury released a level one recommendation that the administration of MPSS for the treatment of acute SCI was not recommended.2 The controversy still exists as recent evidence suggests that surgery within 24 hours of injury in conjunction with 24 hours of MPSS may improve neurological recovery and reduce adverse events.31,32 The National Institute of Clinical Excellence (NICE) guidelines do not recommend the standard use of methylprednisolone following the acute stage after traumatic SCIs.33 Encouraging results have been found with Riluzole, a drug for patients with Amyotrophic Lateral Sclerosis, which was shown to reduce motor neuron degeneration and prolong survival. The phase I study showed significant improvements in recovery of motor function and a multicentre clinical trial has commenced.2 Also minocycline, a chemical derivative of tetracycline has been shown to reduce apoptosis and increase neuroprotective effects in animal SCI models but is not ready for clinical use.2 Similarly

Neuroprotection The primary injury usually does not transect the spinal cord; post-mortem studies of acutely injured spinal cords found that a sub-pial rim of spared but damaged long tract axons frequently spans the lesion. It is found in animal studies that significant neurological function can be maintained if only 1.4e12% of the total number of axons is spared across the injury.3 Neuroprotection aims to reduce the secondary injury and limit the injury to the level of damage initially done by the trauma. Diverse compounds ranging from hormonal receptor agents such as tamoxifen and oestrogen to polyethylene glycol have neuroprotective effects on numerous mechanistic pathways.3,27 Repair of inadequately myelinated residual axons is an important target of therapy aimed at improving conduction of spared axons. The inflammatory response has also a major role in the expansion and resolution of SCI and is a key target for neuroprotection. Spinal cord inflammation is a topic of current active research. Experimental studies showed that chondroitinase enzyme degraded the glial scar leading to partial restoration of sensory function.16

Treatment The goals of management of an acute SCI are to prevent further injury, maintain blood flow, relieve neural compression and provide vertebral stabilization in order to allow early rehabilitation, whereas attention to systemic physiology influences the final outcome. The treatment can be subdivided into prevention,

ORTHOPAEDICS AND TRAUMA --:-

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any point the patient develops neurology, the radiographs show over-distraction or there is failure of reduction the process should be discontinued.

other agents, such as tirilazad mesylate, gangliosides and glutamate antagonists have been investigated for the treatment of acute SCI, which require further trials before introduction to clinical practice.

Operative treatment-clinical evidence on the timing for decompression Most incomplete SCIs have an indication for decompression in order to preserve as much as possible of the spared function. The aim is to relieve the spinal cord from continuous pressure and micro-trauma caused by the fracture or disc fragment, and realign/stabilize the injured area providing a stable environment, therefore limiting the effect of the secondary injury to the cord.1 The goals of surgery are to remove the compressive forces on the spinal cord, restore anatomical alignment and re-establish spinal stability.1 Decompression should take place if the patient is deteriorating neurologically or if there is a foreign body retained into the spinal canal (i.e. gunshot wounds). Controversy exists regarding the timing of surgical intervention in non-deteriorating patients, as initial prospective studies demonstrated no benefit from decompression within 72 hours post-injury.1 The Spine Study Trauma Group recommended that patients with acute SCIs but no other life threatening injuries should receive decompression within 24 hours of injury.38 Preliminary results indicated that 24% of patients who received decompressive surgery within 24 hours had an improvement of at least two grades of the ASIA scale compared to 4% in those who had later surgery. Also, the overall rate of complications among those who received early decompression was 20% lower than that of patients who received treatment later. The Surgical Timing in Acute Spinal Cord Injury Study (STASCIS), a multicenter, international, prospective cohort study showed that at six month follow-up a 2-grade ASIA improvement was 2.8 times higher among those who had surgical intervention within 24 hours postinjury.31 A prospective study by Wilson et al.39 showed superior motor neurological outcomes at six months in patients who had decompressive surgery within 24 hours after SCI. There is insufficient evidence (level III) regarding timing of treatment of traumatic central cord syndrome. This entity presents no spinal instability and shows spontaneous clinical improvement with good prognosis despite myelomalacic cord changes being present.2,22 Similarly, there is no substantive evidence for decompression in the thoracic cord. In complete SCIs, surgical treatment should take place to stabilize the spine and facilitate early rehabilitation with as less external devices as possible. In the long term and following the final neurological status of the patient, appropriate tendon transfers should be considered in order to maximize function.

Support of spinal cord perfusion The autoregulation is altered after SCI so that the cord is increasingly vulnerable to systemic hypotension.1 The mean spinal cord perfusion pressure is equivalent to the mean arterial (MAP) minus Cerebro-Spinal Fluid (CSF) pressure.1 Appropriate fluid resuscitation and use of vasopressors to keep the MAP above 90 mmHg is mandatory in order to maintain tissue perfusion.34 Intensive Care Unit (ICU) level of care for cardiopulmonary management is most appropriate in the acute phase to facilitate careful haemodynamic monitoring and implement pulmonary protocols.1 Additionally, fever or hyperthermia are harmful for cord tissue preservation.

Treatment of spinal injury Injuries to the spine tend to occur at areas of maximal mobility and are closely related to the spinal cord trauma.6 Injuries occur when significant forces to the spinal column cause fractures, ligamentous disruption or combined injuries that result in direct compression and injury to the spinal cord. Injuries to the vertebral column are commonly classified by location (craniocervical, subaxial cervical or thoracolumbar) and mechanism of injury (flexion, extension or axial load). White and Punjabi defined spinal stability as “the loss of the ability of the spine under physiological loads to maintain relationships between vertebrae in such a way that there is neither damage nor subsequent irritation to the spinal cord or nerve roots, in addition, there is no development of incapacitating deformity or pain due to structural changes”.35 The ‘‘three column’’ concept of thoracolumbar spine injuries was described by Denis in 1984 and dictates that at least 2e3 spinal columns need to be disrupted to be considered unstable and subject the spinal cord to risk of damage.36 More recently, the Thoraco-Lumbar Injury Classification score (TLICS) included the neurological post-injury function in a classification system for spinal injuries to assist on defining indications for surgical treatment of a thoracolumbar spinal injury (Table 4).37 Acute-non operative treatment of SCI In case of a fracture or dislocation with spinal cord injury in an alert oriented patient it would be indicated to apply axial traction for closed reduction and cord decompression. The technique involves application of GardnereWells tongs and/or a Halo ring. 4.54 Kg traction weight is applied and then weight is added in 2.27 Kg increments with serial lateral radiographs until the cervical spine is aligned. The general guideline is 4.54 Kg for the head and 2.27 Kg for each level until the level of injury. There must be about 15e20 minutes between each increment in order to allow for the ligaments to relax, the patient to be examined for any change in neurology and an X-ray to take place. Small doses of diazepam may contribute to muscle relaxation, whilst keeping the patient alert. Even though recent reports mention that even 63.5 Kg of weight can be tolerated, most surgeons would not exceed 22.68e31.75 Kg of maximum traction. Once the facet gets disimpacted the manoeuvres for reduction can be applied. If at

ORTHOPAEDICS AND TRAUMA --:-

Stem cells-future operative treatments More than half of the astrocytes in the glial scar are generated by ependymal cells, the neural stem cells in the cord.18 Also, multipotent endogenous progenitor cells exist in the sub-ventricular zone throughout the neuraxis and can be harvested during neurosurgical procedures. The neural stem cell-derived scar component has several beneficial functions, including restricting tissue damage and neural loss after SCI.18 Following differentiation guidance to the oligodendrocyte lineage in experimental SCI models, it was found that they can re-myelinate the cord. However, ineffective tissues and cells connectivity in the cord

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mechanical and pharmacological prophylaxis. The first consists of anti-embolism stockings, foot impulse or intermittent pneumatic compression devices. The second is based on administration of low molecular weight (LMWH) or un-fractioned heparin (UFH) for patients with severe renal impairment. The VTE prophylaxis continues until the patient resumes mobility.42

The American Spinal Injury Association (ASIA) impairment scale classifies the extent of spinal cord injury in five categories ASIA impairment scale A

Complete

B

Incomplete

C

Incomplete

D

Incomplete

E

Normal

No motor or sensory function is preserved in the sacral segments S4eS5 Sensory function preserved but not motor function is preserved below the neurological level and includes the sacral segments S4eS5 Motor function is preserved below the neurological level, and more than half of key muscles below the neurological level have a muscle grade less than 3 Motor function is preserved below the neurological level, and at least half of key muscles below the neurological level have a muscle grade of 3 or more Motor and sensory function is normal

Skin problems Pressure sores are a common cause of deep infection and sepsis.43 The patient must be removed from the immobilization board as soon as possible. Regular log rolling and use of pressure redistributing air mattresses have reduced skin complications.43 Autonomic dysreflexia (AD) AD is a potentially fatal clinical syndrome which develops in patients with SCI and presents with uncontrolled hypetension.44 It is caused by injuries proximal to T6 level most likely due to imbalanced sympathetic discharge. Lesions below T6 allow enough descending parasympathetic control to modulate splachnic tone and prevent hypertension. Apart from the unopposed autonomic equilibrium, the increased responsiveness of the peripheral blood vessel alpha-adrenergic receptors may also explain the development of hypertension. These receptors decrease their threshold secondary to low resting catecholamine following a SCI.44 Another possible mechanism includes loss of supraspinal inhibitory control of the medulla-oblongata bulbospinal pathways over serotonin in the inter-medio-lateral nucleus of the spinal cord. The unabated serotonin causes strong vasoconstriction. This syndrome is considered medical emergency and if left untreated may cause seizures, retinal haemorrhage, pulmonary oedema, renal insufficiency, myocardial infarction, cerebral haemorrhage and death. Ageing decreases the AD symptoms and the magnitude of diastolic blood pressure elevation possibly due to decreased baroreceptor sensitivity.44 The treatment of AD should be etiologic and symptomatic. Continuous blood pressure monitoring is required. The patient should be sat more upright in bed if possible. The patient should be catheterized and checked that any indwelling urinary catheter is working properly. The patient should also be checked for faecal impaction and manual evacuation is recommended. In all these steps the blood pressure should be assessed. Short acting anti-hypertensives, such as nifedipine or nitrates are recommended if the systolic blood pressure is above 150 mmHg. Recurrence should be anticipated if the causative factor is not identified. In inability to control the symptoms intensive care treatment is advised.19,44

Table 4

injury environment is still a major hindrance for application of stem cells in clinical practice.

Neurological and functional recovery following SCI The more severe the SCI the less the anticipated neurological recovery. Similarly, less severe initial ASIA grade and score >50 predicted better functional status; whereas worse functional outcome was predicted in older patients and in the presence of oedema or haemorrhage on MRI.40 Apart from the severity of neurological injury and patient age other predictors of long-term functional outcome include the injury level and reflex pattern.41 Only 10e15% of complete lesions will develop sensation and/or motor function distal to the level of injury.2 Regarding incomplete injuries, 30% of ASIA B patients will end up to ASIA C and another 30% to ASIA D; whereas 70% of ASIA C will improve to ASIA D. Very few patients though will reach ASIA E level. Complete injuries in the cervical spine seem to have better neurological recovery than those in the thoracic level; similar recovery rates are expected in incomplete injuries.40,41 After the initial therapeutic window for neuroprotection, repair strategies have been used for treating severe SCIs with the aim of restoring CNS communication above and below the injury. These strategies focus on the residual autonomous function of the spinal cord, rehabilitation and prevention of long-term complications.

Psychological disorders Approximately 11% of patients with SCIs suffer from major depressive disorders, which may lead to suicidal ideation in both the acute and chronic phases. A supportive environment providing explanations and reassurance in a familiar atmosphere is important. Interventions, such as pain relief, adequate sleep and pharmacological treatment are indicated to improve patient’s psychological status during rehabilitation.4,41

Complications in patients with SCI Deep venous thrombosis There is anticipation of a prolonged recumbent period in SCI patients. Unless there is coagulopathy or active bleeding, all patients should receive venous thromboembolism (VTE)

ORTHOPAEDICS AND TRAUMA --:-

Rehabilitation Traumatic SCIs may cause long lasting impairment in many organ systems and together with permanent changes in function

7

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SPINAL INJURIES

Three predictors of thoraco-lumbar injury severity score 1

2

3

Morphology (immediate stability)

Integrity of PLC (long-term stability) Neurological status

Compression Burst C Translation/ rotation C Distraction C Intact C Suspected C Injured C Intact C Nerve root C Complete cord C Incomplete cord C Cauda Equina Operative management C C

1 2 3 4 0 2 3 0 2 2

X-rays CT

 MRI

Clinical examination





3 3 0e3 4

C

>4

C

C

Non-surgical Surgeons’ choice Surgical



Table 5

lead to higher morbidity and lower quality of life.4 The goal of rehabilitation is to assess and identify mechanisms for reintegration into community based on functional level and daily needs.45 Milestones in rehabilitation are transferring techniques, self-care, mobilization and hand function (Table 5). In patients with neurological improvement potential, electrical stimulation techniques are utilized to keep the muscles activated until final neurological recovery. Physiotherapy and joint mobility preservation is of utmost importance to keep the limbs functional. Tendon transfers can be used to improve function in affected upper limbs and hands.







Conclusion  Cord contusion is the most common mechanism of injury. Partial laceration may be present but cord transection is rare.  The initial mechanism is causing the primary cord injury resulting in maximal neurological deficit, which is mostly irreversible.  The secondary cord injury starts immediately following injury; it is based on the vascular, inflammatory and cellular cord tissue response and extends the injury zone several proximal and distal levels.  Neurogenic shock is an acute temporary loss of sympathetic tone following SCI, manifesting with hypotension, sinus bradycardia and circulatory collapse due to decreased systemic vascular resistance. It may last for one to three weeks and may manifest over hours to days postinjury due to the secondary injury. Differential diagnosis with hypovolemic shock is needed.  Spinal shock is an acute neurophysiologic condition of the cord caused by unresponsive neurons due to post-injury hyper-polarization. It manifests as temporary loss of spinal cord function and reflex activity below the SCI level

ORTHOPAEDICS AND TRAUMA --:-

with flaccid a-reflexic paralysis and bradycardia due to loss of sympathetic tone. It usually resolves within 48 hours signified by the return of the bulbo-cavernosus reflex; thereafter the extent of the SCI may be assessed. Differential diagnosis with hypovolemic shock is needed. Central cord syndrome is the most common SCI. It is caused by a pincer type cord contusion following hyperextension of the cervical spine. It affects the motor function of the upper more than the lower limbs. It has 50e75% prognosis with regards to return of ambulation; fine hand motor function does not recover in most patients. The goal of treatment is to reduce the insult of the secondary injury mechanisms on the cord, to decompress and stabilize the spine. Spinal autoregulation is altered following SCI rendering the cord vulnerable to systemic hypotension. Tissue perfusion maintenance is mandatory by keeping the MAP above 90 mmHg with the use of appropriate fluid resuscitation and vasopressors. Neuroprotection: Initial studies regarding the use of high dose methylprednisolone within three to eight hours of injury showed significant improvement of sensory and motor function after one year. Subsequent studies showing increased systemic complication rate suggested not regular use of methylprednisolone in SCI patients. Persistent compression is common after SCI due to a ruptured disc, bony fragmentation or dislocation. It may exacerbate the magnitude of ischaemic and secondary injury cascades if left untreated. Recent evidence suggests that patients showed improved motor function at six months follow up if they were surgically decompressed and stabilized within 24 hours from injury. Complications in patients with SCI include: a) deep venous thrombosis; b) pressure sores; c) urinary sepsis; d) autonomic dysreflexia; e) neuropathic pain; f) myelomalacia; g) syrinx; h) psychological disorders. Milestones in rehabilitation are transferring techniques, self-care, mobilization and hand function. A

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