Spinal cord injury can result in partial or total paralysis of the limbs. Research has led to treatment advances in the last 25 years. These advances are set to continue, with promising avenues of research being explored.
A spinal cord injury (SCI) is defined as damage or trauma to the spinal cord that in turn leads to a loss of or impaired function resulting in reduced mobility or feeling. The nerves which carry signals back and forth from the brain along the spinal tract are called upper motor neurons. The spinal nerves that branch out to the body are the so-called lower motor neurons. These spinal nerves exit and enter at each vertebral level. The sensory portions within the ascending tracts carry sensation from the skin such as pain, temperature, touch and joint position to the brain. The motor portions within the descending tracts send signals from the brain to initiate actions such as muscle movement.
The clinical picture of a SCI depends on the neurological level and the extent of lesion. The spinal cord is divided into 31 segments, each with a pair of anterior (motor) and dorsal (sensory) spinal nerve roots. People with tetraplegia (paralysis of all four limbs – from the Greek “tetra“ for “four“ and “plegia“ for “paralysis“) have sustained injuries to one of the seven neck or cervical segments of the spinal cord; cases with paraplegia (paralysis of the lower extremities – in Greek: “para“ means “two“) are affected with a lesion in one of the regions of the twelve thoracic, five lumbar, or the five sacral vertebrae.
There are two types of lesions associated with a SCI, also known as complete and incomplete injuries. In case of a complete injury, the individual is completely paralysed below their lesion; whereas an incomplete injury means only part of the spinal cord is damaged. A person with an incomplete injury may still have sensation below their lesion but no movement, or vice versa.
Life expectancy, i.e. the average remaining years of life for persons with SCI, continues to increase, but is still somewhat below life expectancy for individuals without SCI. Mortality rates are significantly higher during the first year after injury, particularly for severely injured people. In years past, the leading cause of death was renal failure. Since then, significant advances in urologic management have changed the mortality rates of SCI. Today, the causes of death with great impact on life expectancy are pneumonia, pulmonary embolism and septicaemia.
Motor vehicle crashes account for 50 per cent of SCI cases. The next most common cause of SCI is falls, followed by recreational sporting activities and acts of violence. SCI primarily affects young adults between the ages of 16 and 30 years. However, as the median age of the general population has increased, the average age at injury is also increasing. Moreover, the percentage of people older than 60 years of age at injury is growing. One possible reason for the observed trend might be higher survival rates of older people at the scene of the accident. About 80 per cent of SCIs occur among males.
Based on conservative average annual incidence of 22 people per million population in the western world, it is estimated that over 130,000 people each year survive a traumatic SCI. The annual incidence, not including those who die at the scene of the accident, is approximately 19 cases per million population in Germany, 27 per million in the Netherlands, 13 per million in France, 12 per million in the UK and in Italy, which corresponds to some 9,000 new cases annually in Europe. Altogether, 200,000 individuals with SCI are estimated to live in the EU.
In the USA, the incidence is 40 cases per million population or approximately 11,000 new cases each year. In 2005, the number of people with SCI in the USA has been estimated to be approximately 250,000 people. Worldwide, about two million people are living with SCI.
Treatment of SCI has changed dramatically during the past 25 years. Major advances have been achieved to diagnose the damage to the spinal cord and vertebrae, including the development of the first effective therapy with a corticosteroid compound for use in the first eight hours just after injury. The molecule reduces the damage to cellular membranes, inhibits inflammation near the injury and suppresses immune cells that contribute to neuronal damage.
Current management of acute SCI involves diagnosing and relieving gross misalignments and other structural problems of the spine, minimising cellular-level damage, and stabilising the vertebrae to prevent further injury. Once a patient is stabilised, supportive care and rehabilitation strategies promote long-term recovery.
As SCI results in significant loss of muscle mass, investigators are studying the effect of an anabolic steroid which has been shown to promote gain in body weight and muscle mass after trauma or severe illness. To date there are no studies that have evaluated this effect in people with chronic SCI. Endpoints of the study are effects on strength, lean body mass, pulmonary function, and ability to walk.
A number of medications have been used to treat SCI pain, but, so far, no compound has been consistently helpful, and some patients continue to suffer from severe chronic pain. There are several clinical studies underway to evaluate the pain-relieving effects of antidepressants, anti-inflammatory substances, and anti-convulsant medicines in chronic neuropathic pain after SCI.
An investigational oral, sustained-release formulation of a compound which inhibits specialised potassium channels on nerves (axons) is in phase 3 clinical studies. When, after injury, an axon loses its insulating layer, called myelin, large numbers of these potassium channels leak potassium ions, causing the nerve to “short circuit“. In laboratory studies, the molecule has improved impulse conduction in nerve fibres in which the myelin has been damaged.
The majority of patients who sustain SCIs do not suffer a complete transsection of their spinal cords, even when there is complete paralysis. Rather, while the initial impact interrupts neurons at the site of injury and disrupts the structure of the skeleton, a proportion of the spinal cord can escape intact. This spared tissue is subject to a number of processes that cause further damage.
Following SCI, highly reactive chemicals called “free radicals“ are released. These compounds attack critical cell structures. Trauma also causes release of excess neurotransmitters, leading to secondary damage from overexcited nerve cells. Abnormalities also include disturbance of electrolytic equilibrium, low level of oxygen, and inflammation. Preclinical studies have demonstrated that neurological function can be mediated by small amounts of spared cord tissue, and in this regard, small neuroprotective effects might reap functional benefits to individuals.
Animal studies point to several avenues for developing new therapies for SCI, including medicines that promote regeneration and transplantation strategies. Neuroprotective medicines may present interesting opportunities for therapeutic intervention. These include antioxidants, calcium channel blockers, and molecules that control the action of neurotransmitters.
Preliminary clinical trials of GM-1 ganglioside have shown that the agent may be useful in preventing secondary damage in acute SCI, and other studies suggest that it may also improve neurological recovery during rehabilitation. Compounds that enhance nerve signalling form another category of potential therapies.
New insights about how cells die will affect research and development in SCI. Until recently, most cell death in SCI was attributed to necrosis, in which cells swell and break open. Scientists have shown that some cells die as a result of apoptosis, a form of controlled death in which damaged cells die with less harm to their surrounding area. Blocking apoptosis may be another avenue to improve recovery after SCI.
Medicines designed to promote regeneration, factors governing the supply of nutrients to the nerve cells, and growth-inhibiting substances make up another class. Other interventions, such as transplantation and peripheral nerve grafts, may also show promise in regrowing spinal cord tracts and promoting recovery of function.