A) Epidemiology
In the UK in 2000, the general population numbered almost 59 million. In one year, 666 new cases were admitted to a spinal injury centre as a result of a traumatic injury. This doesn't include those purely treated at general district hospitals but one would estimate this number to be very low as almost all patients who sustain a cord injury even if they have a stabilisation procedure performed locally will eventually referred for rehabilitation.
If you look at the breakdown of the causes of traumatic cord injury then about 41% were as a result of various falls, 37% of injuries were from road traffic accidents and about 11% were sports related injuries. Other causes included lifting or collision injuries and assault with sharp trauma. Falling from a height and falling downstairs were the commonest type of fall injury. Road traffic accidents mostly involved motorbikes and four wheeled vehicles. Sports injury breakdown showed diving to be the predominant mechanism followed by rugby and horse riding.
More recent statistics from a single spinal injury centre (Duke of Cornwall, Salisbury) confirmed the frequency of the various causes of traumatic injury. In addition, their statistics showed two to three people a day become paralysed from cord injury, 80% of injured patients are male, and that currently 40,000 people are living with paralysis secondary to cord injury. In terms of the types of cord injuries sustained about 45% were incomplete and so 55% were complete. About 50% of all spinal cord injuries result in quadriplegia, although interestingly 92% cord injuries from sports injury also result in quadriplegia.
Comparing all these statistics with those from the United States show the figures to be generally similar.
B) Pathophysiology
There are three phases of spinal cord injury response that occur after injury: the acute, secondary, and chronic injury processes.
1) Acute phase
This encompasses the moment of injury and extends for the first few days; a variety of processes begin. Upon initial injury, there is immediate mechanical damage to neural and other soft tissue, including endothelial cells of the blood vessels in the vicinity. Cell death, results from these mechanical and ischaemic insults is instantaneous. Then the injured nerve cells respond with an injury-induced barrage of nerve action potentials and concurrent electrolytic shifts, principally involving Na+, K+ and Ca2+ which cause failure in normal neural function and spinal shock, which lasts for about 24-48 hours. Haemorrhage, localised oedema, thrombosis, vasospasm, mechanical damage (both from direct trauma and vertebral or disc displacement), and loss of vasculature autoregulation are the major processes in this phase which compound the cord injury.
2) Secondary phase
Extracellular concentrations of glutamate and other excitatory amino acids reach toxic concentrations as a result of cell lysis from mechanical injury. In addition, lipid peroxidation and free-radical production also occur as a result of glutamate receptor-activated mediated pathways. Apoptosis, programmable cell death, occurs. There is increased expression of glial fibrillary acidic protein (GFAP) and astrocytic proliferation.
As part of an inflammatory response to inflammation, neutrophils and lymphocytes invade the spinal tissue from the circulation reaching peak numbers within 48 hours. These invading inflammatory cells increase the local concentrations of cytokines and chemokines and inhibitory factors and barriers to regeneration are expressed around the injured location. The injury therefore grows in size from the initial core of cell death with cells at risk of dying in the immediate region, to a larger area of cell death.
3) Chronic phase
Over a time course of days to years, apoptosis continues proximally and distally. Scarring and tethering of the cord occurs in the penetrating injuries. Demyelination results in conduction deficit. A cyst can form within the cord and can enlarge (syrinx). Lacerated axons exhibit regenerative and sprouting responses but go no farther than 1mm. Neural circuits are altered due to changes in inhibitory and excitatory input and permanent hyperexcitability develops, which results in chronic pain syndromes in a majority of cord injured patients.
C) Clinical Examination and Investigation
There are three aspects to the initial examination and investigation.
1) ATLS with spine protection
As mentioned earlier, roads traffic accidents and falls are common causes of traumatic cord injury so these patients may also have other life threatening injuries. These other injuries must be sought out and treated before treatment of the cord injury can be considered. These patients when they arrive in hospital should be subjected to ATLS guidelines. In line immobilisation and protection of the spine should be maintained during the entire resuscitation process. The entire spine should be immobilised on a long board with padding and a semi rigid collar should be applied to the neck. At this stage protection is primary and detection is secondary.
2) Suspect Injury
The mechanism of action is key to suspecting an injury. All the common mechanism have been mentioned earlier with RTA's and falls being the commonest but don't forget the sport injuries. Other clinical pointers are the unconscious patient and patients who present with spine pain or tenderness and those who have a neurological deficit.
3) Diagnose Injury
A full neurological examination should be carried out and documented. This should also be repeated to detect any improvement or deterioration subsequently. The ASIA (American Spinal Injury Association) chart is now the standard form on which all neurological examination should be recorded. This removes the ambiguity at some levels regarding the precise innervations of muscles and boundaries of sensory regions.
Imaging should include plain radiographs, CT and MRI scanning to assess an injury. There are clear guidelines issued by BOAST (British Orthopaedic Association for Standards in Trauma) on the type and extent of imaging required to clear a patient of spinal injury. The salient points from the guidelines are:
i) If it is anticipated a patient will remain unconscious, unassessable or unreliable for clinical examination for more than 48 hours, radiological spinal clearance imaging should be undertaken.
ii) For the cervical spine, the appropriate standard is a thin slice (2-3mm) helical CT scan from the base of the skull to at least T1 with both sagittal and coronal reconstructions; extending that scan to T4/5 overcomes the difficulties of imaging the upper thoracic spine.
iii) The remaining thoracic and lumbar spine may be adequately imaged either by AP and lateral plain radiographs or by sagittal and coronal reformatting of helical CT scans of the chest, abdomen and pelvis undertaken as part of a modern CT trauma series (<5mm slices).
iv) MRI is the urgent investigation of choice for spinal cord injury.
D) Treatment
There are three treatment arms to the management of cord injury.
i) Treat associated injuries and reduce complications of cord injury
The important principles are to reverse hypoxia and reverse hypotension. Intubation of the patient may be required to provide supplemental oxygen. Maintaining cord perfusion is extremely important to minimise any further ischaemia to the spinal cord.
Reducing immediate complications of cord injury includes several aspects. Pressure sores can develop very rapidly, are painful and can be difficult to treat. As they are generally preventable care should be taken to ensure that spinal boards are well padded and that the board should be removed as soon as is possible and safe to do so. Urinary function is often lost in cord injury and so catheterisation should be performed if not contraindicated by injury and this protects the bladder from overdistension. The patient if they require surgery may well be nil by mouth and the enteric nervous system may be affected with subsequent gut disturbance. Intravenous ranitidine should be administered for gut mucosa protection and a nasogastric tube should also be inserted as paralytic ileus can be a feature of cord injury. Remember to keep the patient warm as they may develop hypothermia from shock.
Ventilatory compromise in cord injury may be significant. For lesions above C6 there may be inspiratory and expiratory muscle paralysis. There is often an accompanying loss of effective cough with atelectasis. Fatigue of respiratory muscles also plays a part. Other problems include pulmonary oedema and pulmonary embolism. The higher the level of injury, the worse the ventilatory compromise. Cardiac compromise includes various aspects including autonomic dysreflexia, abnormal blood pressure, heart rate variability, arrhythmias and a blunted cardiovascular response to exercise. Thromboembolic disease is also more common with cord injury. Mechanical treatment should be employed and chemical prophylaxis is controversial but should be considered.
This aspect of treatment requires skilled physicians with experience in the management of spinal cord injury.
Some definitions which are often confusing in this area are that of spinal and neurogenic shock.
Spinal shock follows severe injury to the spinal cord, the portion of the cord distal to the level of the injury shuts down and no activity (inc reflexes) occurs. There is a flaccid paralysis with no sensation. The final prognosis and whether the injury is complete or not can only be determined after shock has passed which is heralded by the return of bulbocavernosus reflex.
Neurogenic shock refers to loss of autonomic activity following cord injury. Sympathetic outflow is interrupted resulting in bradycardia with low blood pressure. There is loss of vasomotor tone resulting in peripheral vasodilatation. This may require treatment with beta agonist drugs to maintain perfusion.
ii) Prevent further neurological deficit and improve neurological function
From the three phases of response to cord injury one can see that there is very limited ability to affect the acute stage. Most patients will not have reached hospital by the time this stage has occurred so unless something is produced which can be delivered by paramedics at the location of the accident one must concentrate on strategies to affect the secondary and chronic phases. Several processes can be targeted.
1) Reduction of oedema and free radical production
Steroids have been trialled extensively for this and in most units in the UK steroids are not routinely given. The North American Spinal Cord Injury studies (NASCIS) have had three studies which showed a small benefit but the study design had several deficiencies which diminished its recommendations.
2) Reduction of damage by abnormally high extracellular glutamate concentrations
Several drugs eg dizocilipine have shown some promise in animal studies but human trials have not completed to date.
3) Control of inflammation
Several drugs such as cyclo-oxygenase (COX2) inhibitors have shown success in animal models. Hypothermia has also shown to be of some benefit by locally reducing the number of cytokines but has not gained wide acceptance.
4) Reduce apoptosis
Groups of chemicals called caspases and calpains have shown some effect on apoptosis. A ganglioside called Sygen has shown the best promise in several trials in improving neuroprotection with improved neural function.
5) Repair of demyelination and conduction deficits
Some ion channel blockers particularly potassium channel blockers have lessened the electrolyte shifts and abnormal action potential generation which causes demyelination and conduction deficits. But this has only been shown in animal studies so far.
6) Promotion of nerve growth through improved extracellular environment
Reduction of nerve growth inhibition has been targeted following the discovery of several inhibitory factors eg NoGo and IN1 antibody to it. Growth factors have also been discovered of which GDNF has been the most promising. These are all undergoing trials at the moment.
7) Cell replacement therapies
Hopefully these tissues would provide a regenerative pathway for injured nerves, which would then promote the regeneration of the cord circuits and restore function after injury. Many nerve fibres persist as demyelinated fibres, so transplantation of cells that produce new myelin may restore conduction deficits. Cells that have been tried with some success in animal models include olfactory ensheathing cells, stem cells, oligodendrocytes, and Schwann cells.
8) Efforts to bridge the gap with transplantation approaches
Nerve fibres that do demonstrate regenerative growth or collateral sprouting encounter an inhibitory environment and a physical gap that requires a bridging substance. Bridges such as cells, foetal tissue en bloc, or artificial material have been implanted with some success. To date, promising work has been the use of foetal spinal cord transplants into the adult spinal cord in rats, mice, and primates.
iii) Provide the healing environment for a painless, stable and optimally functioning spine in the long term
Spinal rehabilitation at a specialist centre is the mainstay of this treatment. Specific aspects include aggressive functional physiotherapy. This tries to retrain the brain and reawaken spinal circuits and activate central pattern generators in the spinal cord. This approach can help in retrieval of locomotor function.
There are a variety of functional electrical stimulation (FES) approaches that may prove useful. FES is based on transcutaneous or direct electric stimulation of distal ends of innervating nerves, lower motor neurons and peripheral nerves which are intact. FES for strengthening the lower extremities and for cardiovascular conditioning, which has met with some success in terms of increased muscle mass, improved blood flow, and better bladder and bowel function.
Chronic pain following cord injury is common but poorly understood. Central neuropathic pain has led to the successful utilisation of non opioid analgesics delivered by indwelling pump systems or given orally. Drugs such as baclofen, and the anticonvulsant gabapentin have had some success. The tricyclic antidepressant amitriptyline, shown effective in treatment of dysesthetic pain although its mechanism of action is unclear.
Tendon transfer surgery can also be useful by transferring tendons whose innervations is intact to other areas in the same region which have no functioning tendons eg wrist & elbow transfers can improve a patient's ability to independently feed.
In World War Two, the life expectancy for a cord injured patient was about three months and now it's about 30 years. Spinal cord injury management is a challenging area with much ongoing research which will hopefully continue to improve the outcomes for these unfortunate patients.
References
- Recent Advances in Pathophysiology and Treatment of Spinal Cord Injury Hulsebosch CE – Advan. Physiol. Edu. 26: 238-255, 2002
- Observations on the Pathology of Several Types of Human Spinal Cord Injury, With Emphasis on the Astrocyte Response to Penetrating Injuries Bunge RP, Puckett WR, and Hiester ED – Adv Neurol 72: 305-315, 1997
- Experimental and clinical studies of the pathophysiology and management of acute spinal cord injury Tator CH – J Spinal Cord Med 19: 206-214, 1996
- Biology of neurological recovery and functional restoration after spinal cord injury Tator CH – Neurosurgery 42: 696-708, 1998
- Chronic central pain after spinal cord injury Christensen MD and Hulsebosch C – J Neurotrauma 14: 517-537, 1997
- Nonoperative Management of Acute Spinal Cord Injury Nockels R - Spine 26: 24(S) S31-37, 2001
- Management of Spinal Cord Injury Murthy T – Indian Journal of Neurotrauma 4(1) pp. 15-19, 2007
- Critical Care of Spinal Cord Injury Ball PA – Spine 26:24(S) p S27-S30 2001
