Spinal cord injury: Wikis

  

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Spinal cord injuries
Classification and external resources
ICD-10 G95.9, T09.3
DiseasesDB 12327 29466
eMedicine emerg/553 neuro/711 pmr/182 pmr/183 orthoped/425
MeSH D013119

Spinal cord injuries cause myelopathy or damage to nerve roots or myelinated fiber tracts that carry signals to and from the brain. [1][2] Depending on its classification and severity, this type of traumatic injury could also damage the gray matter in the central part of the cord, causing segmental losses of interneurons and motorneurons. Spinal cord injury can occur from many causes, including:

Contents

Classification

The American Spinal Injury Association (ASIA) defined an international classification based on neurological responses, touch and pinprick sensations tested in each dermatome, and strength of ten key muscles on each side of the body, i.e. shoulder shrug (C4), elbow flexion (C5), wrist extension (C6), elbow extension (C7), hip flexion (L2). Traumatic spinal cord injury is classified into five categories by the American Spinal Injury Association and the International Spinal Cord Injury Classification System:

  • A indicates a "complete" spinal cord injury where no motor or sensory function is preserved in the sacral segments S4-S5.
  • B indicates an "incomplete" spinal cord injury where sensory but not motor function is preserved below the neurological level and includes the sacral segments S4-S5. This is typically a transient phase and if the person recovers any motor function below the neurological level, that person essentially becomes a motor incomplete, i.e. ASIA C or D.
  • C indicates an "incomplete" spinal cord injury where motor function is preserved below the neurological level and more than half of key muscles below the neurological level have a muscle grade of less than 3, which indicates active movement with full range of motion against gravity.
  • D indicates an "incomplete" spinal cord injury where motor function is preserved below the neurological level and at least half of the key muscles below the neurological level have a muscle grade of 3 or more.
  • E indicates "normal" where motor and sensory scores are normal. Note that it is possible to have spinal cord injury and neurological deficits with completely normal motor and sensory scores.

In addition, there are several clinical syndromes associated with incomplete spinal cord injuries.

  • The Central cord syndrome is associated with greater loss of upper limb function compared to lower limbs.
  • The Brown-Séquard syndrome results from injury to one side with the spinal cord, causing weakness and loss of proprioception on the side of the injury and loss of pain and thermal sensation of the other side.
  • The Anterior cord syndrome results from injury to the anterior part of the spinal cord, causing weakness and loss of pain and thermal sensations below the injury site but preservation of proprioception that is usually carried in the posterior part of the spinal cord.
  • Tabes Dorsalis results from injury to the posterior part of the spinal cord, usually from infection diseases such as syphilis, causing loss of touch and proprioceptive sensation.
  • Conus medullaris syndrome results from injury to the tip of the spinal cord, located at L1 vertebra.
  • Cauda equina syndrome is, strictly speaking, not really spinal cord injury but injury to the spinal roots below the L1 vertebra.

Facts and Figures

One can have spine injury without spinal cord injury. Many people suffer transient loss of function ("stingers") in sports accidents or pain in "whiplash" of the neck without neurological loss and relatively few of these suffer spinal cord injury sufficient to warrant hospitalization. In the United States, the incidence of spinal cord injury has been estimated to be about 35 cases per million per year, or approximately 10,500 per year (35 * 300). In China, the incidence of spinal cord injury was recently estimated to be as high as 65 cases per million per year in urban areas. If so, assuming a population of 1.3 billion, this would suggest an incidence of 84,500 per year (65 * 1300).

The prevalence of spinal cord injury is not well known in many large countries. In some countries, such as Sweden and Iceland, registries are available. According to new data collected by the Christopher and Dana Reeve Foundation, in the US, there are currently 1.3 million individuals living with spinal cord injuries- a number five times that previously estimated in 2007. 61% of spinal cord injuries occur in males, and 39% in females. The average age for spinal cord injuries is 48 years old. There are many causes leading to spinal cord injuries. These include motor vehicle accidents (24%), work-related accidents (28%), sporting/recreation accidents (16%), and falls (9%).

Consequences

Divisions of Spinal Segments
Gray 111 - Vertebral column-coloured.png
Segmental Spinal Cord Level and Function
Level Function
Cl-C6 Neck flexors
Cl-Tl Neck extensors
C3, C4, C5 Supply diaphragm (mostly C4)
C5, C6 Shoulder movement, raise arm (deltoid); flexion of elbow (biceps); C6 externally rotates the arm (supinates)
C6, C7 Extends elbow and wrist (triceps and wrist extensors); pronates wrist
C7, T1 Flexes wrist
C7, T1 Supply small muscles of the hand
T1 -T6 Intercostals and trunk above the waist
T7-L1 Abdominal muscles
L1, L2, L3, L4 Thigh flexion
L2, L3, L4 Thigh adduction
L4, L5, S1 Thigh abduction
L5, S1, S2 Extension of leg at the hip (gluteus maximus)
L2, L3, L4 Extension of leg at the knee (quadriceps femoris)
L4, L5, S1, S2 Flexion of leg at the knee (hamstrings)
L4, L5, S1 Dorsiflexion of foot (tibialis anterior)
L4, L5, S1 Extension of toes
L5, S1, S2 Plantar flexion of foot
L5, S1, S2 Flexion of toes

The consequences of a spinal cord injury may vary depending on the type, level, and severity of injury, but can be classified into two general categories:

  • In a complete injury, function below the "neurological" level is lost. Absence of motor and sensory function below a specific spinal level is considered a "complete injury". Recent evidence suggests that less than 5% of people with "complete" spinal cord injuries recover locomotion.
  • In an incomplete injury, some sensation and/or movement below the level of the injury is retained. The lowest spinal segment in humans is located at vertebral levels S4-5, corresponding to the anal sphincter and peri-anal sensation. The ability to contract the anal sphincter voluntarily or to feel peri-anal pinprick or touch, the injury is considered to be "incomplete". Recent evidence suggests that over 95% of people with "incomplete" spinal cord injuries recover some locomotor function.

In addition to loss of sensation and motor function below the level of injury, individuals with spinal cord injuries will also often experience other complications:

  • Bowel and bladder function is regulated by the sacral region of the spine. In that regard, it is very common to experience dysfunction of the bowel and bladder, including infections of the bladder and anal incontinence, after traumatic injury.
  • Sexual function is also associated with the sacral spinal segments, and is often affected after injury. During a psychogenic sexual experience, signals from the brain are sent to spinal levels T10-L2 and in case of men, are then relayed to the penis where they trigger an erection. A reflex erection, on the other hand, occurs as a result of direct physical contact to the penis or other erotic areas such as the ears, nipples or neck. A reflex erection is involuntary and can occur without sexually stimulating thoughts. The nerves that control a man’s ability to have a reflex erection are located in the sacral nerves (S2-S4) of the spinal cord and could be affected after a spinal cord injury. [3]
  • Injuries at the C-1/C-2 levels will often result in loss of breathing, necessitating mechanical ventilators or phrenic nerve pacing.
  • Inability or reduced ability to regulate heart rate, blood pressure, sweating and hence body temperature.
  • Spasticity (increased reflexes and stiffness of the limbs).
  • Neuropathic pain.
  • Autonomic dysreflexia or abnormal increases in blood pressure, sweating, and other autonomic responses to pain or sensory disturbances.
  • Atrophy of muscle.
  • Superior Mesenteric Artery Syndrome.
  • Osteoporosis (loss of calcium) and bone degeneration.
  • Gallbladder and renal stones.

The Location of the Injury

Determining the exact level of injury is critical in making accurate predictions about the specific parts of the body that may be affected by paralysis and loss of function.

The symptoms observed after a spinal cord injury differ by location (refer to the spinal cord map on the right to determine location). Notably, while the prognosis of complete injuries are generally predictable, the symptoms of incomplete injuries span a variable range. Accordingly, it is difficult to make an accurate prognosis for these types of injuries.

Cervical injuries

Cervical (neck) injuries usually result in full or partial tetraplegia (Quadriplegia). However, depending on the specific location and severity of trauma, limited function may be retained.

  • C3 vertebrae and above : Typically results in loss of diaphragm function, necessitating the use of a ventilator for breathing.
  • C4 : Results in significant loss of function at the biceps and shoulders.
  • C5 : Results in potential loss of function at the shoulders and biceps, and complete loss of function at the wrists and hands.
  • C6 : Results in limited wrist control, and complete loss of hand function.
  • C7 and T1 : Results in lack of dexterity in the hands and fingers, but allows for limited use of arms. C7 is generally the threshold level for retaining functional independence.

Thoracic injuries

Injuries at or below the thoracic spinal levels result in paraplegia. Function of the hands, arms, neck, and breathing is usually not affected.

  • T1 to T8 : Results in the inability to control the abdominal muscles. Accordingly, trunk stability is affected. The lower the level of injury, the less severe the effects.
  • T9 to T12 : Results in partial loss of trunk and abdominal muscle control.

Lumbar and Sacral injuries

The effects of injuries to the lumbar or sacral regions of the spinal cord are decreased control of the legs and hips, urinary system, and anus.

Central Cord and Other Syndromes

uncomplete cord syndromes

Central cord syndrome (picture 1) is a form of incomplete spinal cord injury characterized by impairment in the arms and hands and, to a lesser extent, in the legs. This is also referred to as inverse paraplegia, because the hands and arms are paralyzed while the legs and lower extremities work correctly.

Most often the damage is to the cervical or upper thoracic regions of the spinal cord, and characterized by weakness in the arms with relative sparing of the legs with variable sensory loss.

This condition is associated with ischemia, hemorrhage, or necrosis involving the central portions of the spinal cord (the large nerve fibers that carry information directly from the cerebral cortex). Corticospinal fibers destined for the legs are spared due to their more external location in the spinal cord.

This clinical pattern may emerge during recovery from spinal shock due to prolonged swelling around or near the vertebrae, causing pressures on the cord. The symptoms may be transient or permanent.

Anterior cord syndrome (picture 2) is also an incomplete spinal cord injury. Below the injury, motor function, pain sensation, and temperature sensation is lost; touch, proprioception (sense of position in space), and vibration sense remain intact. Posterior cord syndrome (not pictured) can also occur, but is very rare.

Brown-Séquard syndrome (picture 3) usually occurs when the spinal cord is hemisectioned or injured on the lateral side. On the ipsilateral side of the injury (same side), there is a loss of motor function, proprioception, vibration, and light touch. Contralaterally (opposite side of injury), there is a loss of pain, temperature, and deep touch sensations

Potential Treatments

Treatment options for acute, traumatic non-penetrating spinal cord injuries include the administration of a high dose of an anti-inflammatory agent, methylprednisolone, within 8 hours of injury. This recommendation is primarily based on the National Acute Spinal Cord Injury Studies (NASCIS) I and II. However, in a third study, methylprednisolone failed to demonstrate an effect in comparison to placebo. Additionally, due to increased risk of infections, the use of this anti-inflammatory drug after spinal cord injuries is no longer recommended [4][5]. Presently, administration of cold saline acutely after injury is gaining popularity, but there is a paucity of empirical evidence for the beneficial effects of therapeutic hypothermia.

Scientists are investigating many promising avenues for treatment of spinal cord injury. Numerous articles in the medical literature describe research, mostly in animal models, aimed at reducing the paralyzing effects of injury and promoting regrowth of functional nerve fibers. Despite the devastating effects of the condition, commercial funding for research investigating a cure after spinal cord injury is limited, partially due to the small size of the population of potential beneficiaries. Despite this limitation, a number of experimental treatments have reached controlled human trials. In addition, therapeutic strategies involving neuronal protection and regeneration are also being investigated in other neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis and Multiple sclerosis. There are many similarities between these conditions of the CNS and spinal cord injuries, thus increasing the potential for discovery of a treatment after spinal cord injuries.

Advances in identification of an effective therapeutic target after spinal cord injury have been newsworthy, and considerable media attention is often drawn towards new developments in this area. However, aside from methylprednisolone, none of these developments have reached even limited use in the clinical care of human spinal cord injury in the U.S.. Around the world, proprietary centers offering stem cell transplants and treatment with neuroregenerative substances are fueled by glowing testimonial reports of neurological improvement. Independent validation of the results of these treatments is lacking.[6] However, in January 2009, the Geron Corporation received FDA clearance to begin human safety testing of its stem cell treatment candidate, GRNOPC1, on newly injured patients with complete thoracic injury.[7] A diverse array of other treatments are being researched, including biomaterial solutions,[8] cell replacement therapies, and electronic stimulative devices.

See also

hESC - Derived Therapies (GRNOPC1)

Geron is planning a Phase I multi-center trial that is designed to assess the safety and tolerability of GRNOPC1 in patients with "complete" American Spinal Injury Association (ASIA) grade A subacute thoracic spinal cord injuries.

Patients who will be eligible for the Phase I trial must have documented evidence of functionally complete spinal cord injury with a neurological level of T3 to T10 spinal segments and agree to have GRNOPC1 injected into the lesion sites between seven and 14 days after injury.

Although the primary endpoint of the trial will be safety, the protocol will include secondary endpoints to assess efficacy, such as improved neuromuscular control or sensation in the trunk or lower extremities. Once safety in this patient population has been established and the FDA reviews clinical data in conjunction with additional data from ongoing animal studies, Geron plans to seek FDA approval to extend the study to increase the dose of GRNOPC1, enroll subjects with complete cervical injuries and expand the trial to include patients with severe incomplete (ASIA grade B or C) injuries to enable access to the therapy for as broad a population of severe spinal cord-injured patients as is medically appropriate.

Currently there are no sites enrolling patients for this study. The Investigational New Drug application (IND) has been placed on clinical hold by the FDA pending the agency's review of new nonclinical animal study data submitted by the company.([1])

External links

References

  1. ^ Spinal Cord Medicine: Principles and Practice (2002) Lin VWH, Cardenas DD, Cutter NC, Frost FS, Hammond MC. Demos Medical Publishing
  2. ^ Spinal Cord Medicine (2001) Kirshblum S, Campagnolo D, Delisa J. Lippincott Williams & Wilkins
  3. ^ Klebin, Phil Sexual Function of Men with Spinal Cord Injury May 2007
  4. ^ "UpToDate Inc.". http://www.uptodate.com/online/content/topic.do?topicKey=medneuro/10703&selectedTitle=3~150&source=search_result.  
  5. ^ "BestBets: Steroids in acute spinal cord injury". http://www.bestbets.org/bets/bet.php?id=105.  
  6. ^ Dobkin, BH.; Curt, A.; Guest, J. “Cellular transplants in China: observational study from the largest human experiment in chronic spinal cord injury.” Neurorehabilitation and Neural Repair, v. 20 issue 1, 2006, p. 5-13.
  7. ^ Geron press release January 23 2009: Geron Receives FDA Clearance to Begin World's First Human Clinical Trial of Embryonic Stem Cell-Based Therapy
  8. ^ See for example Benton Martin, Eric Minner, Sherri Wiseman, Rebecca Klank, Ryan Gilbert, 2008, “Injectable agarose and methylcellulose hydrogel blends for nerve regeneration applications,” Journal of Neural Engineering, Vol. 5, No. 2, pp. 221-231.







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