Spinal cord injury

The effects of injury depend on the level along the spinal column (left). A dermatome is an area of the skin that sends sensory messages to a specific spinal nerve (right).
Spinal nerves exit the spinal cord between each pair of vertebrae.

Spinal cord injury can be traumatic or nontraumatic,[4] and can be classified into three types based on cause: mechanical forces, toxic, and ischemic (from lack of blood flow).[5] The damage can also be divided into primary and secondary injury: the cell death that occurs immediately in the original injury, and biochemical cascades that are initiated by the original insult and cause further tissue damage.[6] These secondary injury pathways include the ischemic cascade, inflammation, swelling, cell suicide, and neurotransmitter imbalances.[6] They can take place for minutes or weeks following the injury.[7]

At each level of the spinal column, spinal nerves branch off from either side of the spinal cord and exit between a pair of vertebrae, to innervate a specific part of the body. The area of skin innervated by a specific spinal nerve is called a dermatome, and the group of muscles innervated by a single spinal nerve is called a myotome. The part of the spinal cord that was damaged corresponds to the spinal nerves at that level and below. Injuries can be cervical 1–8 (C1–C8), thoracic 1–12 (T1–T12), lumbar 1–5 (L1–L5),[8] or sacral (S1–S5).[9] A person's level of injury is defined as the lowest level of full sensation and function.[10] Paraplegia occurs when the legs are affected by the spinal cord damage (in thoracic, lumbar, or sacral injuries), and tetraplegia occurs when all four limbs are affected (cervical damage).[11]

SCI is also classified by the degree of impairment. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), published by the American Spinal Injury Association (ASIA), is widely used to document sensory and motor impairments following SCI.[12] It is based on neurological responses, touch and pinprick sensations tested in each dermatome, and strength of the muscles that control key motions on both sides of the body.[13] Muscle strength is scored on a scale of 0–5 according to the table on the right, and sensation is graded on a scale of 0–2: 0 is no sensation, 1 is altered or decreased sensation, and 2 is full sensation.[14] Each side of the body is graded independently.[14]

Central cord syndrome

Incomplete lesions of the spinal cord: Central cord syndrome (top), Anterior cord syndrome (middle), and Brown-Séquard syndrome (bottom).

Central cord syndrome, almost always resulting from damage to the cervical spinal cord, is characterized by weakness in the arms with relative sparing of the legs, and spared sensation in regions served by the sacral segments.[24] There is loss of sensation of pain, temperature, light touch, and pressure below the level of injury.[25] The spinal tracts that serve the arms are more affected due to their central location in the spinal cord, while the corticospinal fibers destined for the legs are spared due to their more external location.[25] The most common of the incomplete SCI syndromes, central cord syndrome usually results from neck hyperextension in older people with spinal stenosis. In younger people, it most commonly results from neck flexion.[26] The most common causes are falls and vehicle accidents; however other possible causes include spinal stenosis and impingement on the spinal cord by a tumor or vertebral disk.[27]

Signs (observed by a clinician) and symptoms (experienced by a patient) vary depending on where the spine is injured and the extent of the injury. A section of skin innervated through a specific part of the spine is called a dermatome, and injury to that part of the spine can cause pain, numbness, or a loss of sensation in the related areas. Paraesthesia, a tingling or burning sensation in affected areas of the skin, is another symptom.[37] A person with a lowered level of consciousness may show a response to a painful stimulus above a certain point but not below it.[38] A group of muscles innervated through a specific part of the spine is called a myotome, and injury to that part of the spinal cord can cause problems with movements that involve those muscles. The muscles may contract uncontrollably (spasticity), become weak, or be completely paralysed. Spinal shock, loss of neural activity including reflexes below the level of injury, occurs shortly after the injury and usually goes away within a day.[39] Priapism, an erection of the penis may be a sign of acute spinal cord injury.[40]

The specific parts of the body affected by loss of function are determined by the level of injury. Some signs, such as bowel and bladder dysfunction can occur at any level. Neurogenic bladder involves a compromised ability to empty the bladder and is a common symptom of spinal cord injury. This can lead to high pressures in the bladder that can damage the kidneys.[41]

Complications

Complications of spinal cord injuries include pulmonary edema, respiratory failure, neurogenic shock, and paralysis below the injury site.

In the long term, the loss of muscle function can have additional effects from disuse, including atrophy of the muscle. Immobility can lead to pressure sores, particularly in bony areas, requiring precautions such as extra cushioning and turning in bed every two hours (in the acute setting) to relieve pressure.[49] In the long term, people in wheelchairs must shift periodically to relieve pressure.[50] Another complication is pain, including nociceptive pain (indication of potential or actual tissue damage) and neuropathic pain, when nerves affected by damage convey erroneous pain signals in the absence of noxious stimuli.[51] Spasticity, the uncontrollable tensing of muscles below the level of injury, occurs in 65–78% of chronic SCI.[52] It results from lack of input from the brain that quells muscle responses to stretch reflexes.[53] It can be treated with drugs and physical therapy.[53] Spasticity increases the risk of contractures (shortening of muscles, tendons, or ligaments that result from lack of use of a limb); this problem can be prevented by moving the limb through its full range of motion multiple times a day.[54] Another problem lack of mobility can cause is loss of bone density and changes in bone structure.[55][56] Loss of bone density (bone demineralization), thought to be due to lack of input from weakened or paralysed muscles, can increase the risk of fractures.[57] Conversely, a poorly understood phenomenon is the overgrowth of bone tissue in soft tissue areas, called heterotopic ossification.[58] It occurs below the level of injury, possibly as a result of inflammation, and happens to a clinically significant extent in 27% of people.[58]

Muscle mass is reduced as muscles atrophy with disuse.

People with SCI are at especially high risk for respiratory and cardiovascular problems, so hospital staff must be watchful to avoid them.[59] Respiratory problems (especially pneumonia) are the leading cause of death in people with SCI, followed by infections, usually of pressure sores, urinary tract infections and respiratory infections.[60] Pneumonia can be accompanied by shortness of breath, fever, and anxiety.[24]

Another potentially deadly threat to respiration is deep venous thrombosis (DVT), in which blood forms a clot in immobile limbs; the clot can break off and form a pulmonary embolism, lodging in the lung and cutting off blood supply to it.[61] DVT is an especially high risk in SCI, particularly within 10 days of injury, occurring in over 13% in the acute care setting.[62] Preventative measures include anticoagulants, pressure hose, and moving the patient's limbs.[62] The usual signs and symptoms of DVT and pulmonary embolism may be masked in SCI cases due to effects such as alterations in pain perception and nervous system functioning.[62]

Urinary tract infection (UTI) is another risk that may not display the usual symptoms (pain, urgency, and frequency); it may instead be associated with worsened spasticity.[24] The risk of UTI, likely the most common complication in the long term, is heightened by use of indwelling urinary catheters.[49] Catheterization may be necessary because SCI interferes with the bladder's ability to empty when it gets too full, which could trigger autonomic dysreflexia or damage the bladder permanently.[49] The use of intermittent catheterization to empty the bladder at regular intervals throughout the day has decreased the mortality due to kidney failure from UTI in the first world, but it is still a serious problem in developing countries.[57]

An estimated 24–45% of people with SCI suffer disorders of depression, and the suicide rate is as much as six times that of the rest of the population.[63] The risk of suicide is worst in the first five years after injury.[64] In young people with SCI, suicide is the leading cause of death.[65] Depression is associated with an increased risk of other complications such as UTI and pressure ulcers that occur more when self-care is neglected.[65]

Falling as a part of recreational activities can cause spinal cord injuries.

Spinal cord injuries are most often caused by physical trauma.[21] Forces involved can be hyperflexion (forward movement of the head); hyperextension (backward movement); lateral stress (sideways movement); rotation (twisting of the head); compression (force along the axis of the spine downward from the head or upward from the pelvis); or distraction (pulling apart of the vertebrae).[66] Traumatic SCI can result in contusion, compression, or stretch injury.[4] It is a major risk of many types of vertebral fracture.[67] Pre-existing asymptomatic congenital anomalies can cause major neurological deficits, such as hemiparesis, to result from otherwise minor trauma.[68]

In the US, Motor vehicle accidents are the most common cause of SCIs; second are falls, then violence such as gunshot wounds, then sports injuries.[69] In some countries falls are more common, even surpassing vehicle crashes as the leading cause of SCI.[70] The rates of violence-related SCI depend heavily on place and time.[70] Of all sports-related SCIs, shallow water dives are the most common cause; winter sports and water sports have been increasing as causes while association football and trampoline injuries have been declining.[71] Hanging can cause injury to the cervical spine, as may occur in attempted suicide.[72] Military conflicts are another cause, and when they occur they are associated with increased rates of SCI.[73] Another potential cause of SCI is iatrogenic injury, caused by an improperly done medical procedure such as an injection into the spinal column.[74]

SCI can also be of a nontraumatic origin. Nontraumatic lesions cause anywhere from 30 to 80% of all SCI;[75] the percentage varies by locale, influenced by efforts to prevent trauma.[76] Developed countries have higher percentages of SCI due to degenerative conditions and tumors than developing countries.[77] In developed countries, the most common cause of nontraumatic SCI is degenerative diseases, followed by tumors; in many developing countries the leading cause is infection such as HIV and tuberculosis.[78] SCI may occur in intervertebral disc disease, and spinal cord vascular disease.[79] Spontaneous bleeding can occur within or outside of the protective membranes that line the cord, and intervertebral disks can herniate.[11] Damage can result from dysfunction of the blood vessels, as in arteriovenous malformation, or when a blood clot becomes lodged in a blood vessel and cuts off blood supply to the cord.[80] When systemic blood pressure drops, blood flow to the spinal cord may be reduced, potentially causing a loss of sensation and voluntary movement in the areas supplied by the affected level of the spinal cord.[81] Congenital conditions and tumors that compress the cord can also cause SCI, as can vertebral spondylosis and ischemia.[4] Multiple sclerosis is a disease that can damage the spinal cord, as can infectious or inflammatory conditions such as tuberculosis, herpes zoster or herpes simplex, meningitis, myelitis, and syphilis.[11]

Vehicle-related SCI is prevented with measures including societal and individual efforts to reduce driving under the influence of drugs or alcohol, distracted driving, and drowsy driving.[82] Other efforts include increasing road safety (such as marking hazards and adding lighting) and vehicle safety, both to prevent accidents (such as routine maintenance and antilock brakes) and to mitigate the damage of crashes (such as head restraints, air bags, seat belts, and child safety seats).[82] Falls can be prevented by making changes to the environment, such as nonslip materials and grab bars in bathtubs and showers, railings for stairs, child and safety gates for windows.[83] Gun-related injuries can be prevented with conflict resolution training, gun safety education campaigns, and changes to the technology of guns (such as trigger locks) to improve their safety.[83] Sports injuries can be prevented with changes to sports rules and equipment to increase safety, and education campaigns to reduce risky practices such as diving into water of unknown depth or head-first tackling in association football.[84]

X-rays (left) are more available, but can miss details like herniated disks that MRIs can show (right).[85]

A person's presentation in context of trauma or non-traumatic background determines suspicion for a spinal cord injury. The features are namely paralysis, sensory loss, or both at any level. Other symptoms may include incontinence.[86]

A radiographic evaluation using an X-ray, CT scan, or MRI can determine if there is damage to the spinal column and where it is located.[9] X-rays are commonly available[85] and can detect instability or misalignment of the spinal column, but do not give very detailed images and can miss injuries to the spinal cord or displacement of ligaments or disks that do not have accompanying spinal column damage.[9] Thus when X-ray findings are normal but SCI is still suspected due to pain or SCI symptoms, CT or MRI scans are used.[85] CT gives greater detail than X-rays, but exposes the patient to more radiation,[87] and it still does not give images of the spinal cord or ligaments; MRI shows body structures in the greatest detail.[9] Thus it is the standard for anyone who has neurological deficits found in SCI or is thought to have an unstable spinal column injury.[88]

Neurological evaluations to help determine the degree of impairment are performed initially and repeatedly in the early stages of treatment; this determines the rate of improvement or deterioration and informs treatment and prognosis.[89][90] The ASIA Impairment Scale outlined above is used to determine the level and severity of injury.[9]

Holly Koester incurred a spinal injury as a result of a motor vehicle collision and is now a wheelchair racer.

Spinal cord injuries generally result in at least some incurable impairment even with the best possible treatment. The best predictor of prognosis is the level and completeness of injury, as measured by the ASIA impairment scale.[121] The neurological score at the initial evaluation done 72 hours after injury is the best predictor of how much function will return.[75] Most people with ASIA scores of A (complete injuries) do not have functional motor recovery, but improvement can occur.[121][122] Most patients with incomplete injuries recover at least some function.[122] Chances of recovering the ability to walk improve with each AIS grade found at the initial examination; e.g. an ASIA D score confers a better chance of walking than a score of C.[75] The symptoms of incomplete injuries can vary and it is difficult to make an accurate prediction of the outcome. A person with a mild, incomplete injury at the T5 vertebra will have a much better chance of using his or her legs than a person with a severe, complete injury at exactly the same place. Of the incomplete SCI syndromes, Brown-Séquard and central cord syndromes have the best prognosis for recovery and anterior cord syndrome has the worst.[28]

People with nontraumatic causes of SCI have been found to be less likely to suffer complete injuries and some complications such as pressure sores and deep vein thrombosis, and to have shorter hospital stays.[11] Their scores on functional tests were better than those of people with traumatic SCI upon hospital admission, but when they were tested upon discharge, those with traumatic SCI had improved such that both groups' results were the same.[11] In addition to the completeness and level of the injury, age and concurrent health problems affect the extent to which a person with SCI will be able to live independently and to walk.[8] However, in general people with injuries to L3 or below will likely be able to walk functionally, T10 and below to walk around the house with bracing, and C7 and below to live independently.[8] New therapies are beginning to provide hope for better outcomes in patients with SCI, but most are in the experimental/translational stage.[3]

One important predictor of motor recovery in an area is presence of sensation there, particularly pain perception.[36] Most motor recovery occurs in the first year post-injury, but modest improvements can continue for years; sensory recovery is more limited.[123] Recovery is typically quickest during the first six months.[124] Spinal shock, in which reflexes are suppressed, occurs immediately after the injury and resolves largely within three months but continues resolving gradually for another 15.[125]

Sexual dysfunction after spinal injury is common. Problems that can occur include erectile dysfunction, loss of ability to ejaculate, insufficient lubrication of the vagina, and reduced sensation and impaired ability to orgasm.[52] Despite this, many people learn ways to adapt their sexual practices so they can lead satisfying sex lives.[126]

Although life expectancy has improved with better care options, it is still not as good as the uninjured population. The higher the level of injury, and the more complete the injury, the greater the reduction in life expectancy.[80] Mortality is very elevated within a year of injury.[80]

Worldwide, the number of new cases since 1995 of SCI ranges from 10.4 to 83 people per million per year.[103] This wide range of numbers is probably partly due to differences among regions in whether and how injuries are reported.[103] In North America, about 39 people per every million incur SCI traumatically each year, and in Western Europe, the incidence is 16 per million.[107][128] In the United States, the incidence of spinal cord injury has been estimated to be about 40 cases per 1 million people per year or around 12,000 cases per year.[129] In China, the incidence is approximately 60,000 per year.[130] The estimated number of people living with SCI in the world ranges from 236 to 4187 per million.[103] Estimates vary widely due to differences in how data are collected and what techniques are used to extrapolate the figures.[131] Little information is available from Asia, and even less from Africa and South America.[103] In Western Europe the estimated prevalence is 300 per million people and in North America it is 853 per million.[128] It is estimated at 440 per million in Iran, 526 per million in Iceland, and 681 per million in Australia.[131] In the United States there are between 225,000 and 296,000 individuals living with spinal cord injuries,[132] and different studies have estimated prevalences from 525 to 906 per million.[131]

SCI is present in about 2% of all cases of blunt force trauma.[96] Anyone who has undergone force sufficient to cause a thoracic spinal injury is at high risk for other injuries also.[99] In 44% of SCI cases, other serious injuries are sustained at the same time; 14% of SCI patients also suffer head trauma or facial trauma.[21] Other commonly associated injuries include chest trauma, abdominal trauma, pelvic fractures, and long bone fractures.[90]

Males account for four out of five traumatic spinal cord injuries.[24] Most of these injuries occur in men under 30 years of age.[9] The average age at the time of injury has slowly increased from about 29 years in the 1970s to 41.[24] Rates of injury are at their lowest in children, at their highest in the late teens to early twenties, then get progressively lower in older age groups; however rates may rise in the elderly.[133] In Sweden between 50 and 70% of all cases of SCI occur in people under 30, and 25% occur in those over 50.[70] While SCI rates are highest among people age 15–20,[134] fewer than 3% of SCIs occur in people under 15.[135] Neonatal SCI occurs in one in 60,000 births, e.g. from breech births or injuries by forceps.[136] The difference in rates between the sexes diminishes in injuries at age 3 and younger; the same number of girls are injured as boys, or possibly more.[137] Another cause of pediatric injury is child abuse such as shaken baby syndrome.[136] For children, the most common cause of SCI (56%) is vehicle crashes.[138] High numbers of adolescent injuries are attributable in a large part to traffic accidents and sports injuries.[139] For people over 65, falls are the most common cause of traumatic SCI.[4] The elderly and people with severe arthritis are at high risk for SCI because of defects in the spinal column.[140] In nontraumatic SCI, the gender difference is smaller, the average age of occurrence is greater, and incomplete lesions are more common.[75]

The ancient Egyptian Edwin Smith Papyrus is the earliest known description of SCI.[141]

SCI has been known to be devastating for millennia; the ancient Egyptian Edwin Smith Papyrus from 2500 BC, the first known description of the injury, says it is "not to be treated".[141] Hindu texts dating back to 1800 BC also mention SCI and describe traction techniques to straighten the spine.[141] The Greek physician Hippocrates, born in the fifth century BC, described SCI in his Hippocratic Corpus and invented traction devices to straighten dislocated vertebrae.[142] But it was not until Aulus Cornelius Celsus, born 30 BC, noted that a cervical injury resulted in rapid death that the spinal cord itself was implicated in the condition.[141] In the second century AD the Greek physician Galen experimented on monkeys and reported that a horizontal cut through the spinal cord caused them to lose all sensation and motion below the level of the cut.[143] The seventh-century Greek physician Paul of Aegina described surgical techniques for treatment of broken vertebrae by removing bone fragments, as well as surgery to relieve pressure on the spine.[141] Little medical progress was made during the Middle Ages in Europe; it was not until the Renaissance that the spine and nerves were accurately depicted in human anatomy drawings by Leonardo da Vinci and Andreas Vesalius.[143]

In 1762 a surgeon named Andre Louis removed a bullet from the lumbar spine of a patient, who regained motion in the legs.[143] In 1829 the surgeon Gilpin Smith performed a successful laminectomy that improved the patient's sensation.[144] However, the idea that SCI was untreatable remained predominant until the early 20th century.[145] In 1934, the mortality rate in the first two years after injury was over 80%, mostly due to infections of the urinary tract and pressure sores.[146] It was not until the latter half of the century that breakthroughs in imaging, surgery, medical care, and rehabilitation medicine contributed to a substantial improvement in SCI care.[145] The relative incidence of incomplete compared to complete injuries has improved since the mid-20th century, due mainly to the emphasis on faster and better initial care and stabilization of spinal cord injury patients.[147] The creation of emergency medical services to professionally transport people to the hospital is given partial credit for an improvement in outcomes since the 1970s.[148] Improvements in care have been accompanied by increased life expectancy of people with SCI; survival times have improved by about 2000% since 1940.[149] In 2015/2016 23% of people in nine spinal injury centres in England had their discharge delayed because of disputes about who should pay for the equipment they needed.[150]

Scientists are investigating various avenues for treatment of spinal cord injury. Therapeutic research is focused on two main areas: neuroprotection and neuroregeneration.[73] The former seeks to prevent the harm that occurs from secondary injury in the minutes to weeks following the insult, and the latter aims to reconnect the broken circuits in the spinal cord to allow function to return.[73] Neuroprotective drugs target secondary injury effects including inflammation, damage by free radicals, excitotoxicity (neuronal damage by excessive glutamate signaling), and apoptosis (cell suicide).[73] Several potentially neuroprotective agents that target pathways like these are under investigation in human clinical trials.[73]

Human bone marrow derived mesenchymal stem cells seen under phase contrast microscope (63 x magnification)

Stem cell transplantation is an important avenue for SCI research: the goal is to replace lost spinal cord cells, allow reconnection in broken neural circuits by regrowing axons, and to create an environment in the tissues that is favorable to growth.[73] A key avenue of SCI research is research on stem cells, which can differentiate into other types of cells—including those lost after SCI.[73] Types of cells being researched for use in SCI include embryonic stem cells, neural stem cells, mesenchymal stem cells, olfactory ensheathing cells, Schwann cells, activated macrophages, and induced pluripotent stem cells.[151] Hundreds of stem cell studies have been done in humans, with promising but inconclusive results.[139] An ongoing Phase 2 trial in 2016 presented data[152] showing that after 90 days, 2 out of 4 subjects had already improved two motor levels and had thus already achieved its endpoint of 2/5 patients improving two levels within 6–12 months. Six-month data is expected in January 2017.[153]

Another type of approach is tissue engineering, using biomaterials to help scaffold and rebuild damaged tissues.[73] Biomaterials being investigated include natural substances such as collagen or agarose and synthetic ones like polymers and nitrocellulose.[73] They fall into two categories: hydrogels and nanofibers.[73] These materials can also be used as a vehicle for delivering gene therapy to tissues.[73]

One avenue being explored to allow paralyzed people to walk and to aid in rehabilitation of those with some walking ability is the use of wearable powered robotic exoskeletons.[154] The devices, which have motorized joints, are put on over the legs and supply a source of power to move and walk.[154] Several such devices are already available for sale, but investigation is still underway as to how they can be made more useful.[154]

Preliminary studies of epidural spinal cord stimulators for motor complete injuries have demonstrated some improvement.[155]

In 2014 Darek Fidyka underwent pioneering spinal surgery that used nerve grafts, from his ankle, to 'bridge the gap' in his severed spinal cord and olfactory ensheathing cells (OECs) to stimulate the spinal cord cells. The surgery was performed in Poland in collaboration with Prof. Geoff Raisman, chair of neural regeneration at University College London's Institute of Neurology, and his research team. The OECs were taken from the patient's olfactory bulbs in his brain and then grown in the lab, these cells were then injected above and below the impaired spinal tissue.[156]

• Paralyzed Veterans of America

• Spinal cord injury at Curlie