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The mechanisms of muscle spasticity after spinal cord injury are not well understood. Recent
studies indicate that the loss of particular descending axonal pathways most likely results in the
decreased activity of inhibitory interneurons, which causes the overreaction of motor neurons to
excitatory stimuli

Unlike treatments for post-injury pain, medical and surgical treatments for spasticity are
established and highly successful. These include oral medications that act within the central
nervous system (baclofen and diazepam) and one that acts directly on skeletal muscle
(dantrolene). For spasticity that is resistant to drug interventions, surgical rhizotomy or myelotomy
is sometimes performed to sever reflex pathways.

Investigators are currently exploring neuromodulation procedures based on preliminary results
showing that electrical spinal cord stimulation below the injury can modulate spasms. Other
techniques used clinically and experimentally involve implanting pump systems that continuously
supply antispasmodic drugs such as baclofen.

Improving bladder control

A promising area of research on treatments for bladder dysfunction involves using electrical
stimulation and neuromodulation to achieve bladder control. The current treatment for reflex
incontinence includes a surgical procedure that cuts the sacral sensory nerve roots from S2 to S4.
With the hope that a cure for spinal cord injury could be imminent, and the reluctance among men
to lose any of their already compromised sexual function, few patients are willing to have these
nerves cut.

Development of a sacral posterior and anterior root stimulator implant is being explored to better
coordinate bladder and sphincter contractions. In preliminary studies people were able to achieve
suppression of reflex incontinence and clinically useful increases in bladder volume with the use of
the implanted stimulator.

Researchers hope that by combining neuromodulation for reflex incontinence with neurostimulation
for bladder emptying, the bladder could be completely controlled without having to cut any sacral
sensory nerves.

+ Understanding changes in sexual and reproductive function

Sperm count in men may or may not change due to spinal cord injury, but sperm motility often
does. Researchers are investigating whether or not spinal cord injury causes changes in the
chemical composition of semen that make it hostile to sperm viability. Preliminary studies show
that the semen of men with spinal cord injury contains abnormally high levels of immunologically
active leukocytes, which appear to have a negative impact on sperm motility.

Recent animal studies have revealed what appears to be a neural circuit within the spinal cord that
is critical for triggering ejaculation in animal models and may play the same role in humans.
Triggering ejaculation by stimulating these cells might be a better option than some of the current,
more invasive methods, such as electroejaculation.

Top

The Future of Spinal Cord Research

Fueled by significant federal and private funding, the past decade of spinal cord injury research has
produced a wealth of discoveries that are making the repair of injured spinal cords a reachable goal. This
is good news for the 10,000 to 12,000 Americans every year who sustain these traumatic injuries

Because spinal cord injuries happen predominantly to people under the age of 30, the human cost is high.
Major improvements in emergency and acute care have improved survival rates but have also increased
the numbers of individuals who have to cope with severe disabilities for the rest of their lives. The cost to
society, in terms of health care costs, disability payments, and lost income, is disproportionately high
compared to other medical conditions.

Considering the biological complexity of spinal cord injury, discovering successful ways to repair injuries
and create rehabilitative strategies that significantly reduce disabilities is not an easy task. Researchers,
many of them supported by the NINDS, are actively developing innovative research strategies aimed at
making the kinds of exciting new discoveries that will translate into better clinical care and better lives for
all

Top

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After the injury, an excessive release of neurotransmitters (chemicals that allow neurons to signal
each other) can cause additional damage by overexciting nerve cells

Glutamate is an excitatory neurotransmitter, commonly used by nerve cells in the spinal cord to
stimulate activity in neurons. But when spinal cells are injured, neurons flood the area with
glutamate for reasons that are not yet well understood. Excessive glutamate triggers a destructive
process called excitotoxicity, which disrupts normal processes and kills neurons and other cells
called oligodendrocytes that surround and protect axons.

+ An invasion of immune system cells creates inflammation
Under normal conditions, the blood-brain barrier (which tightly controls the passage of cells and
large molecules between the circulatory and central nervous systems) keeps immune system cells
from entering the brain or spinal cord. But when the blood-brain barrier is broken by blood vessels
bursting and leaking into spinal cord tissue, immune system cells that normally circulate in the
blood - primarily white blood cells - can invade the surrounding tissue and trigger an inflammatory
response. This inflammation is characterized by fluid accumulation and the influx of immune cells -
neutrophils, T-cells, macrophages, and monocytes.

Neutrophils are the first to enter, within about 12 hours of injury, and they remain for about a day.
Three days after the injury, T-cells arrive. Their function in the injured spinal cord is not clearly
understood, but in the healthy spinal cord they kill infected cells and regulate the immune
response. Macrophages and monocytes enter after the T-cells and scavenge cellular debris.

The up side of this immune system response is that it helps fight infection and cleans up debris.
But the down side is that it sets off the release of cytokines - a group of immune system
messenger molecules that exert a malign influence on the activities of nerve cells.

For example, microglial cells, which normally function as a kind of on-site immune cell in the spinal
cord, begin to respond to signals from these cytokines. They transform into macrophage-like cells,
engulf cell debris, and start to produce their own pro-inflammatory cytokines, which then stimulate

and recruit other microglia to respond.

Injury also stimulates resting astrocytes to express cytokines. These "reactive" astrocytes may
ultimately participate in the formation of scar tissue within the spinal cord.

Whether or not the immune response is protective or destructive is controversial among
researchers. Some speculate that certain types of injury might evoke a protective immune
response that actually reduces the loss of neurons.

+ Free radicals attack nerve cells
Another consequence of the immune system's entry into the CNS is that inflammation accelerates
the production of highly reactive forms of oxygen molecules called free radicals.

Free radicals are produced as a by-product of normal cell metabolism. In the healthy spinal cord
their numbers are small enough that they cause no harm. But injury to the spinal cord, and the
subsequent wave of inflammation that sweeps through spinal cord tissue, signals particular cells to
overproduce free radicals

Free radicals then attack and disable molecules that are crucial for cell function - for example,
those found in cell membranes - by modifying their chemical structure. Free radicals can also
change how cells respond to natural growth and survival factors, and turn these protective factors
into agents of destruction.

+ Nerve cells self-destruct
Researchers used to think that the only way in which cells died during spinal cord injury was as a
direct result of trauma. But recent findings have revealed that cells in the injured spinal cord also
die from a kind of programmed cell death called apoptosis, often described as cellular suicide, that
happens days or weeks after the injury

Apoptosis is a normal cellular event that occurs in a variety of tissues and cellular systems. It
helps the body get rid of old and unhealthy cells by causing them to shrink and implode. Nearby
scavenger cells then gobble up the debris. Apoptosis seems to be regulated by specific molecules
that have the ability to either start or stop the process.

For reasons that are still unclear, spinal cord injury sets off apoptosis, which kills oligodendrocytes
in damaged areas of the spinal cord days to weeks after the injury. The death of oligodendrocytes
is another blow to the damaged spinal cord, since these are the cells that form the myelin that
wraps around axons and speeds the conduction of nerve impulses. Apoptosis strips myelin from
intact axons in adjacent ascending and descending pathways, which further impairs the spinal
cord's ability to communicate with the brain.

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rhizotomy - an operation to disconnect specific nerve roots in order to stop severe spasticity.

sacral - refers to the part of the spine in the hip area
Schwann cell - the cell of the peripheral nervous system that forms the myelin sheath.
spasticity - increased tone in muscles of the arms and legs (due to lesions of the upper motor neurons).

spinal shock - a temporary physiological state that can occur after a spinal cord injury in which all
sensory, motor, and sympathetic functions of the nervous system are lost below the level of injury. Spinal
shock can lower blood pressure to dangerous levels and cause temporary paralysis.

stem cell - special cells that have the ability to grow into any one of the body's more than 200 cell types.
Unlike mature cells, which are permanently committed to their fate, stem cells can both renew
themselves and create cells of other tissues.

synapse - a specialized junction between two nerve cells. At the synapse, a neuron releases
neurotransmitters that diffuse across the gap and activate receptors situated on the target cell.

T-cell - an immune system cell that produces substances called cytokines, which stimulate the immune
response. thoracic - the part of the spine at the upper-back to mid-back level.

vertebrae - the 33 hollow bones that make up the spine.

Prepared by:

Office of Communications and Public Liaison

National Institute of Neurological Disorders and Stroke
National Institutes of Health

Bethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily
represent endorsement by or an official position of the National Institute of Neurological Disorders and
Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be
obtained through consultation with a physician who has examined that patient or is familiar with that
patient's medical history

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or
the NIH is appreciated.

Reviewed August 21, 2003

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even more effective.

Preliminary clinical trials of another compound, GM-1 ganglioside, indicate that it could be useful in
preventing secondary damage in acute spinal cord injury. A large, randomized clinical trial suggested that
it might also improve neurological recovery from spinal cord injury during rehabilitation.

These observations and others have led to optimism that recovery can be improved by altering cellular
responses immediately after injury. Using what they know about the mechanisms that cause secondary
damage - excitotoxicity, inflammation, and cell suicide (apoptosis) - researchers are creating and testing
additional neuroprotective therapies to prevent the spread of post-injury damage and preserve surrounding
tissue.

Some of the findings in these three different areas follow:
* Stopping excitotoxicity

When nerve cells die, they release excessive amounts of a neurotransmitter called glutamate.
Since surviving nerve cells also release glutamate as part of their normal communication process,
excess glutamate floods the cellular environment, which pushes cells into overdrive and self-
destruction. Researchers are investigating compounds that could keep nerve cells from responding
to glutamate, potentially minimizing the extent of secondary damage.

Recently, investigators tested agents called receptor antagonists that selectively block a specific
type of glutamate receptor that is abundant on oligodendrocytes and neurons. These agents
appear to be effective at limiting damage. Some of these receptor antagonists have already been
tested in human trials as a therapy for stroke. Similar agents could enter clinical trials within
several years for patients with spinal cord injury.

Controlling inflammation

Some time within the first 12 hours after injury, the first wave of immune cells enters the damaged
spinal cord to protect it from infection and clean up dead nerve cells. Other types of immune cells
enter afterwards. The actions of these immune cells and the messenger molecules they release,
called cytokines, are the hallmarks of inflammation in the spinal cord.

Researchers have discovered that these inflammatory processes aren't entirely bad for the injured
spinal cord. Although cytokines can be toxic to nerve cells because they stimulate the production
of free radicals, nitric oxide, and other inflammatory substances that cause cell death, they also
stimulate the production of neurotrophic factors, which are beneficial to cell repair.

Currently researchers are looking for ways to control these immune system cells and the
molecules they produce by encouraging their potential for neuroprotection and reining in their
neurotoxic effects. One approach being tested clinically is to exploit the ability of the PNS to
mount a healing response in macrophages by injecting macrophages already stimulated by injured
peripheral nerves into injured spinal cords. Recent experiments have indicated that selectively
boosting the T-cell response to spinal cord injury could reduce secondary damage. Because of the
possibility that these cells can also damage tissue, they must be very carefully controlled if they
are to be used therapeutically.

Clinical investigators are also looking at how cooling the body protects surviving spinal cord tissue
and nerve cells. Experiments have shown that cooling the body to a state of mild hypothermia
(about 92° F) for several hours immediately following the injury limits damage and promotes
functional recovery. Researchers aren't yet sure why mild hypothermia is neuroprotective, but the
ability of body temperature to affect many different kinds of physiological mechanisms may be one
of the reasons.

* Preventing apoptosis

Days to weeks after the initial injury, apoptosis sweeps through oligodendrocytes in damaged and
nearby tissue, causing the cells to self-destruct. Although genes have been identified that appear
to regulate apoptosis, researchers still don't know enough to be able to specify the exact
biochemical events that cause a cell to switch it on - or turn it off. Further studies are aimed at
understanding these cellular mechanisms more fully. These studies will provide an opportunity to
develop neural protective strategies to combat apoptotic cell death.

By understanding the process of apoptosis, researchers have been able to develop and test
apoptosis-inhibiting drugs. In rodent models, animals given a drug that blocks a known apoptotic
mechanism retained more ambulatory ability after traumatic spinal cord injury than did untreated
animals.

Once the secondary wave of damage ends, the spinal cord is left with areas of scar tissue and
fluid-filled gaps, or cysts, that axons can't penetrate or bridge. Unless these areas are reconnected

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A complete injury is indicated by a total lack of sensory and motor function below the level of injury.

Top

How Does a Spinal Cord Injury Affect the Rest of the Body?

People who survive a spinal cord injury will most likely have medical complications such as chronic pain
and bladder and bowel dysfunction, along with an increased susceptibility to respiratory and heart
problems. Successful recovery depends upon how well these chronic conditions are handled day to day.

Breathing

Any injury to the spinal cord at or above the C3, C4, and C5 segments, which supply the phrenic
nerves leading to the diaphragm, can stop breathing. People with these injuries need immediate
ventilatory support. When injuries are at the C5 level and below, diaphragm function is preserved,
but breathing tends to be rapid and shallow and people have trouble coughing and clearing
secretions from their lungs because of weak thoracic muscles. Once pulmonary function improves,
a large percentage of those with C4 injuries can be weaned from mechanical ventilation in the
weeks following the injury.

Pneumonia

Respiratory complications, primarily as a result of pneumonia, are a leading cause of death in
people with spinal cord injury. In fact, intubation increases the risk of developing ventilator-
associated pneumonia (VAP) by 1 to 3 percent per day of intubation. More than a quarter of the
deaths caused by spinal cord injury are the result of VAP. Spinal cord injury patients who are
intubated have to be carefully monitored for VAP and treated with antibiotics if symptoms appear.

Irregular heart beat and low blood pressure

Spinal cord injuries in the cervical region are often accompanied by blood pressure instability and
heart arrhythmias. Because of interruptions to the cardiac accelerator nerves, the heart can beat at
a dangerously slow pace, or it can pound rapidly and irregularly. Arrhythmias usually appear in the
first 2 weeks after injury and are more common and severe in the most serious injuries.

Low blood pressure also often occurs due to loss of tone in blood vessels, which widen and cause
blood to pool in the small arteries far away from the heart. This is usually treated with an
intravenous infusion to build up blood volume.

Blood clots

People with spinal cord injuries are at triple the usual risk for blood clots. The risk for clots is low in
the first 72 hours, but afterwards anticoagulation drug therapy can be used as a preventive
measure.

Spasm

Many of our reflex movements are controlled by the spinal cord but regulated by the brain. When
the spinal cord is damaged, information from the brain can no longer regulate reflex activity.
Reflexes may become exaggerated over time, causing spasticity. If spasms become severe
enough, they may require medical treatment. For some, spasms can be as much of a help as they
are a hindrance, since spasms can tone muscles that would otherwise waste away. Some people
can even learn to use the increased tone in their legs to help them turn over in bed, propel them
into and out of a wheelchair, or stand.

Autonomic dysreflexia

Autonomic dysreflexia is a life-threatening reflex action that primarily affects those with injuries to
the neck or upper back. It happens when there is an irritation, pain, or stimulus to the nervous
system below the level of injury. The irritated area tries to send a signal to the brain, but since the
signal isn't able to get through, a reflex action occurs without the brain's regulation. Unlike spasms
that affect muscles, autonomic dysreflexia affects vascular and organ systems controlled by the
sympathetic nervous system.

Anything that causes pain or irritation can set off autonomic dysreflexia: the urge to urinate or
defecate, pressure sores, cuts, burns, bruises, sunburn, pressure of any kind on the body, ingrown
toenails, or tight clothing. For example, the impulse to urinate can set off high blood pressure or
rapid heart beat that, if uncontrolled, can cause stroke, seizures, or death. Symptoms such as
flushing or sweating, a pounding headache, anxiety, sudden high blood pressure, vision changes,
or goosebumps on the arms and legs can signal the onset of autonomic dysreflexia. Treatment
should be swift. Changing position, emptying the bladder or bowels, and removing or loosening

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* Secondary damage takes a cumulative toll
All of these mechanisms of secondary damage - restricted blood flow, excitotoxicity, inflammation,
free radical release, and apoptosis - increase the area of damage in the injured spinal cord.
Damaged axons become dysfunctional, either because they are stripped of their myelin or because
they are disconnected from the brain. Glial cells cluster to form a scar, which creates a barrier to
any axons that could potentially regenerate and reconnect. A few whole axons may remain, but not
enough to convey any meaningful information to the brain.

Researchers are especially interested in studying the mechanisms of this wave of secondary
damage because finding ways to stop it could save axons and reduce disabilities. This could make
a big difference in the potential for recovery.

Top

What Are the Immediate Treatments for Spinal Cord Injury?

The outcome of any injury to the spinal cord depends upon the number of axons that survive: the higher
the number of normally functioning axons, the less the amount of disability. Consequently, the most
important consideration when moving people to a hospital or trauma center is preventing further injury to
the spine and spinal cord.

Spinal cord injury isn't always obvious. Any injury that involves the head (especially with trauma to the
front of the face), pelvic fractures, penetrating injuries in the area of the spine, or injuries that result from
falling from heights should be suspect for spinal cord damage.

Until imaging of the spine is done at an emergency or trauma center, people who might have spinal cord
injury should be cared for as if any significant movement of the spine could cause further damage. They
are usually transported in a recumbent (lying down) position, with a rigid collar and backboard
immobilizing the spine.

Respiratory complications are often an indication of the severity of spinal cord injury. About one third of
those with injury to the neck area will need help with breathing and require respiratory support via
intubation, which involves inserting a tube connected to an oxygen tank through the nose or throat and
into the airway.

Methylprednisolone, a steroid drug, became standard treatment for acute spinal cord injury in 1990 when
a large-scale clinical trial supported by the National Institute of Neurological Disorders and Stroke showed
significantly better recovery in patients who were given the drug within the first 8 hours after their injury.
Methylprednisolone appears to reduce the damage to nerve cells and decreases inflammation near the
injury site by suppressing activities of immune cells

Realignment of the spine using a rigid brace or axial traction is usually done as soon as possible to
stabilize the spine and prevent additional damage.

On about the third day after the injury, doctors give patients a complete neurological examination to
diagnose the severity of the injury and predict the likely extent of recovery. The ASIA Impairment Scale
is the standard diagnostic tool used by doctors. X-rays, MRIs, or more advanced imaging techniques are
also used to visualize the entire length of the spine.

ASIA (American Spinal Injury Association) Impairment Scale*

Classification Description

A Complete: no motor or sensory function is preserved below the level of injury, including
the sacral segments S4-S5
B Incomplete: sensory, but not motor, function is preserved below the neurologic level and

some sensation in the sacral segments S4-S5

Incomplete: motor function is preserved below the neurologic level, however, more than
c half of key muscles below the neurologic level have a muscle grade less than 3 (i.e., not
strong enough to move against gravity)

Incomplete: motor function is preserved below the neurologic level, and at least half of

D key muscles below the neurologic level have a muscle grade of 3 or more (i.e., joints
can be moved against gravity)
E Normal: motor and sensory functions are normal

* Used with permission of the American Spinal Injury Association.

Spinal cord injuries are classified as either complete or incomplete, depending on how much cord width is
injured. An incomplete injury means that the ability of the spinal cord to convey messages to or from the
brain is not completely lost. People with incomplete injuries retain some motor or sensory function below
the injury.

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Rehabilitation programs combine physical therapies with skill-building activities and counseling to provide
social and emotional support. The education and active involvement of the newly injured person and his
or her family and friends is crucial.

A rehabilitation team is usually led by a doctor specializing in physical medicine and rehabilitation (called
a physiatrist), and often includes social workers, physical and occupational therapists, recreational
therapists, rehabilitation nurses, rehabilitation psychologists, vocational counselors, nutritionists, and
other specialists. A case-worker or program manager coordinates care.

In the initial phase of rehabilitation, therapists emphasize regaining leg and arm strength since mobility
and communication are the two most important areas of function. For some, mobility will only be possible
with the assistance of devices such as a walker, leg braces, or a wheelchair. Communication skills, such
as writing, typing, and using the telephone, may also require adaptive devices.

Physical therapy includes exercise programs geared toward muscle strengthening. Occupational therapy
helps redevelop fine motor skills. Bladder and bowel management programs teach basic toileting routines,
and patients also learn techniques for self-grooming. People acquire coping strategies for recurring
episodes of spasticity, autonomic dysreflexia, and neurogenic pain.

Vocational rehabilitation begins with an assessment of basic work skills, current dexterity, and physical
and cognitive capabilities to determine the likelihood for employment. A vocational rehabilitation specialist
then identifies potential work places, determines the type of assistive equipment that will be needed, and
helps arrange for a user-friendly workplace. For those whose disabilities prevent them from returning to
the workplace, therapists focus on encouraging productivity through participation in activities that provide
a sense of satisfaction and self-esteem. This could include educational classes, hobbies, memberships
in special interest groups, and participation in family and community events.

Recreation therapy encourages patients to build on their abilities so that they can participate in
recreational or athletic activities at their level of mobility. Engaging in recreational outlets and athletics
helps those with spinal cord injuries achieve a more balanced and normal lifestyle and also provides
opportunities for socialization and self-expression.

Top
How Is Research Helping Spinal Cord Injury Patients?

Can an injured spinal cord be rebuilt? This is the question that drives basic research in the field of spinal
cord injury. As investigators try to understand the underlying biological mechanisms that either inhibit or
promote new growth in the spinal cord, they are making surprising discoveries, not just about how
neurons and their axons grow in the CNS, but also about why they fail to regenerate after injury in the
adult CNS. Understanding the cellular and molecular mechanisms involved in both the working and the
damaged spinal cord could point the way to therapies that might prevent secondary damage, encourage
axons to grow past injured areas, and reconnect vital neural circuits within the spinal cord and CNS.

There has been successful research in a number of fields that may someday help people with spinal cord
injuries. Genetic studies have revealed a number of molecules that encourage axon growth in the
developing CNS but prevent it in the adult. Research into embryonic and adult stem cell biology has
furthered knowledge about how cells communicate with each other.

Basic research has helped describe the mechanisms involved in the mysterious process of apoptosis, in
which large groups of seemingly healthy cells self-destruct. New rehabilitation therapies that retrain neural
circuits through forced motion and electrical stimulation of muscle groups are helping injured patients
regain lost function.

Researchers, many of whom are supported by the National Institute of Neurological Disorders and Stroke
(NINDS), are focused on advancing our understanding of the four key principles of spinal cord repair:

* Protecting surviving nerve cells from further damage

+ Replacing damaged nerve cells

* Stimulating the regrowth of axons and targeting their connections appropriately
* Retraining neural circuits to restore body functions

A spinal cord injury is complex. Repairing it has to take into account all of the different kinds of damage
that occur during and after the injury. Because the molecular and cellular environment of the spinal cord is
constantly changing from the moment of injury until several weeks or even months later, combination
therapies will have to be designed to address specific types of damage at different points in time.

Discoveries in Basic Research

A decade ago, researchers demonstrated a small but significant neuroprotective and anti-inflammatory
effect from an adrenal corticosteroid drug called methylprednisolone if it was given within 8 hours of

injury. It is the only treatment currently available to limit the extent of spinal cord injury and its risks are
relatively low. Researchers continue to search for additional anti-inflammatory treatments that might prove

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Table of Contents

* A Short History of the Treatment of Spinal Cord Injury

How Does the Spinal Cord Work?

What Happens When the Spinal Cord Is Injured?

What Are the Immediate Treatments for Spinal Cord Injury?

How Does a Spinal Cord Injury Affect the Rest of the Body?

How Does Rehabilitation Help People Recover From Spinal Cord Injuries?
How Is Research Helping Spinal Cord Injury Patients?

The Future of Spinal Cord Research

Information Resources

Glossary

A Short History of the Treatment of Spinal Cord Injury

Accounts of spinal cord injuries and their treatment date back to ancient times, even though there was
little chance of recovery from such a devastating injury. The earliest is found in an Egyptian papyrus roll
manuscript written in approximately 1700 B.C. that describes two spinal cord injuries involving fracture or
dislocation of the neck vertebrae accompanied by paralysis.* The description of each was “an ailment not
to be treated."

Centuries later in Greece, treatment for spinal cord injuries had changed little. According to the Greek
physician Hippocrates (460-377 B.C.) there were no treatment options for spinal cord injuries that resulted
in paralysis; unfortunately, those patients were destined to die. But Hippocrates did use rudimentary
forms of traction to treat spinal fractures without paralysis. The Hippocratic Ladder was a device that
required the patient to be bound, tied to the rungs upside-down, and shaken vigorously to reduce spinal
curvature. Another invention, the Hippocratic Board, allowed the doctor to apply traction to the
immobilized patient's back using either his hands and feet or a wheel and axle arrangement.

Hindu, Arab, and Chinese physicians also developed basic forms of traction to correct spinal deformities
These same principles of traction are still applied today.

In about 200 A.D., the Roman physician Galen introduced the concept of the central nervous system
when he proposed that the spinal cord was an extension of the brain that carried sensation to the limbs
and back. By the seventh century A.D., Paulus of Aegina was recommending surgery for spinal column
fracture to remove the bone fragments that he was convinced caused paralysis.

In his influential anatomy textbook published in 1543, the Renaissance physician and teacher Vesalius
described and illustrated the spinal cord in all its parts. The illustrations in his books, based on direct
observation and dissection of the spine, gave physicians a way to understand the basic structure of the
spine and spinal cord and what could happen when it was injured. The words we use today to identify
segments of the spine - cervical, thoracic, lumbar, sacral, and coccygeal - come directly from Vesalius.

With the widespread use of antiseptics and sterilization in surgical procedures in the late nineteenth
century, spinal surgery could finally be done with a much lower risk of infection. The use of X-rays,
beginning in the 1920s, gave surgeons a way to precisely locate the injury and also made diagnosis and
prediction of outcome more accurate. By the middle of the twentieth century, a standard method of
treating spinal cord injuries was established - reposition the spine, fix it in place, and rehabilitate
disabilities with exercise. In the 1990s, the discovery that the steroid drug methylprednisolone could
reduce damage to nerve cells if given early enough after injury gave doctors an additional treatment
option.

Top
What Is a Spinal Cord Injury?

Although the hard bones of the spinal column protect the soft tissues of the spinal cord, vertebrae can
still be broken or dislocated in a variety of ways and cause traumatic injury to the spinal cord. Injuries can
occur at any level of the spinal cord. The segment of the cord that is injured, and the severity of the
injury, will determine which body functions are compromised or lost. Because the spinal cord acts as the
main information pathway between the brain and the rest of the body, a spinal cord injury can have

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advance between the tangles of long, branching molecules that form the extracellular matrix. A
recent experiment successfully used a bacterial enzyme to clear away this underbrush so that
axons could grow.

A treatment that combines both these approaches - turning off growth-inhibiting proteins and using
enzymes to clear the way - could create an encouraging environment for axon regeneration. But
before trials of such a treatment can be attempted in patients, researchers must be sure that it
could be controlled well enough to prevent dangerous miswiring of regenerating axons.

Neurotrophic factors (or neurotrophins) are key nervous system regulatory proteins that prime cells
to produce the molecular machinery necessary for growth. Some prevent oligodendrocyte death,
others promote axon regrowth and survival, and still others serve multiple functions. Unfortunately,
the natural production of neurotrophins in the spinal cord falls instead of rises during the weeks
after injury. Researchers have tested whether artificially raising the levels post-injury can enhance
regeneration. Some of these investigations have been successful. Infusion pumps and gene
therapy techniques have been used to deliver growth factors to injured neurons, but they appear to
encourage sprouting more than they stimulate regeneration for long distances.

Axonal growth isn't enough for functional recovery. Axons have to make the proper connections
and re-establish functioning synapses. Guidance molecules, proteins that rest on or are released
from the surfaces of neurons or glia, act as chemical road signs, beckoning axons to grow in some
directions and repelling growth in others.

Supplying a particular combination of guidance molecules or administering compounds that induce
surviving cells to produce or use guidance molecules might encourage regeneration. But at the
moment, researchers don't understand enough about guidance molecules to know which to supply
and when.

Researchers hope that combining these strategies to encourage growth, clear away debris, and
target axon connections could reconnect the spinal cord. Of course, all these therapies would have
to be provided in the right amounts, in the right places, and at the right times. As researchers learn
more and understand more about the intricacies of axon growth and regeneration, combining
therapies could become a powerful treatment for spinal cord injury.

Discoveries in Clinical Research

Advances in basic research are also being matched by progress in clinical research, especially in
understanding the kinds of physical rehabilitation that work best to restore function. Some of the more
promising rehabilitation techniques are helping spinal cord injury patients become more mobile.

+ Restoring function through neural prostheses and computer interfaces

While basic scientists strive to develop strategies to restore neurological connections between the
brain and body of spinal cord injured persons, bioengineers are working to restore functional
connections via advanced computer modeling systems and neural prostheses. Discovering ways
to integrate devices that could mobilize paralyzed limbs requires a unique interface between
electronics technology and neurobiology. A functional electrical stimulation (FES) system is one
example of this kind of innovative research.

FES systems use electrical stimulators to control muscles of the legs and arms to encourage
functional walking and to stimulate reaching and gripping. Electrodes are taped to the skin over
nerves or surgically implanted and then controlled by a computer system under the command of
the user. For example, to assist reaching, electrodes can be placed in the shoulder and upper arm
and controlled by movements of the opposite shoulder. Through a computer interface, the spinal
cord injured person can then trigger hand and arm movements in one arm by shrugging the
opposite shoulder.

These systems are useful not just for restoring functional movements. They also help people
exercise paralyzed muscle systems, which can provide significant cardiovascular benefits. So far,
relatively few people utilize them because the movements are so robotic, they require extensive
surgery and electrode placement, and the computer interface systems are still limited.
Bioengineers are working to develop more natural interfaces.

Because the brain plans voluntary movements several seconds before the command is sent out to
the muscles, people whose spinal cords no longer carry signals to their limbs might still be able to
complete the planning phase in their brains but use a robotic device to carry out the command. A
recent experiment used microwires implanted in the motor cortex area of the brain (in this case a
monkey's brain) to record brain-wave activity, which was then relayed to a computer that analyzed
the data, predicted the movement, and sent the command to a robotic arm. A device such as this
could be used to control a wheelchair, a prosthetic limb, or even a patient's own arms and legs.

In the future, researchers expect that these kinds of brain-machine interfaces could be planted

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by functioning nerve cells, the spinal cord remains disabled. Discovering how to bridge the gap
between functioning axons and figuring out how to encourage axons to grow and make new
connections could be the key to spinal cord repair.

Promoting regeneration

Researchers are experimenting with cell grafts transplanted into the injured spinal cord that act as
bridges across injured areas to reconnect cut axons, or that supply nerve cells to act as relays.
Several types of cells have been studied for their potential to promote regeneration and repair,
including Schwann cells, olfactory ensheathing glia, fetal spinal cord cells, and embryonic stem
cells. In one group of experiments, investigators have implanted tubes packed with Schwann cells
into the damaged spinal cords of rodents and observed axons growing into the tubes.

One of the limitations of cell transplants, however, is that the growth environment within the
transplant is so favorable that most axons don't leave and extend into the spinal cord. By using
olfactory ensheathing glia cells, which are natural migrators in the PNS, researchers have gotten
axons to extend out of the initial transplant region and into the spinal cord. But it remains to be
seen whether or not regenerated axons are fully functional.

Fetal spinal cord tissue implants have also yielded success in animal trials, giving rise to new
neurons, which, when stimulated by growth-promoting factors (neurotrophins), extend axons that
stretch up and down several segments in the spinal cord. Animals treated in these trials have
regained some function in their limbs. Some patients with long-term spinal cord injuries have
received fetal tissue transplants but the results have been inconclusive. In animal models, these
transplants appear to be more effective in the immature spinal cord than in the adult spinal cord.

Stem cells are capable of dividing and yielding almost all the cell types of the body, including
those of the spinal cord. Their potential to treat spinal cord injury is being investigated eagerly, but
there are many things about stem cells that researchers still need to understand. For example,
researchers know there are many different kinds of chemical signals that tell a stem cell what to
do. Some of these are internal to the stem cell, but many others are external - within the cellular
environment - and will have to be recreated in the transplant region to encourage proper growth and
differentiation. Because of the complexities involved in stem cell treatment, researchers expect
these kinds of therapies to be possible only after much more research is done.

Researchers are also looking at ways to compensate for axons that, having lost their myelin
sheaths, have a decreased ability to conduct the electrical impulses essential for axonal
communication. Preliminary studies with compounds known as potassium channel blockers, which
block the flow of ions through the demyelinated membrane and increase the potential for
messages to get through, have shown some success, but mostly in terms of reducing spasticity in
muscles. Further studies might show how remyelinating axons could also improve function.

Stimulating regrowth of axons

Stimulating the regeneration of axons is a key component of spinal cord repair because every axon
in the injured spinal cord that can be reconnected increases the chances for recovery of function.

Research on many fronts reveals that getting axons to grow after injury is a complicated task.
CNS neurons have the capacity to regenerate, but the environment in the adult spinal cord does
not encourage growth. Not only does it lack the growth-promoting molecules that are present in the
developing CNS, it also contains substances that actively inhibit axon extension. For axon
regeneration to be successful, the environment has to be changed to tum off the inhibitors and tum
on the promoters.

Investigators are looking for ways to take advantage of the chemicals that drive or halt axon
growth: growth-promoting and growth-inhibiting substances, neurotrophic factors, and guidance
molecules.

In the developing CNS, thread-like axons grow and lengthen behind the axonal growth cone, an
active tip only a few thousandths of a millimeter in diameter, which interacts with chemical signals
that encourage growth and direct movement. But the environment of the adult CNS is hostile to
axon growth, primarily because growth-inhibiting proteins are embedded in myelin, the insulating
material around axons. These proteins appear to preserve neural circuits in the healthy spinal cord
and keep intact axons from growing inappropriately. But when the spinal cord is injured, these
proteins prevent regeneration.

At least three growth-inhibitory proteins operating within the axonal tract have been identified. The
task of researchers is to understand how these inhibitory proteins do their job, and then discover
ways to remove or block them, or change how the growth cone responds to them.

Growth-inhibiting proteins also block the glial scar near the injury site. To get past, an axon has to

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tight clothing are just a few of the possibilities that should be tried to relieve whatever is causing
the irritation.

* Pressure sores (or pressure ulcers)

Pressure sores are areas of skin tissue that have broken down because of continuous pressure on
the skin. People with paraplegia and quadriplegia are susceptible to pressure sores because they
can't move easily on their own.

Places that support weight when someone is seated or recumbent are vulnerable areas. When
these areas press against a surface for a long period of time, the skin compresses and reduces
the flow of blood to the area. When the blood supply is blocked for too long, the skin will begin to
break down.

Since spinal cord injury reduces or eliminates sensation below the level of injury, people may not
be aware of the normal signals to change position, and must be shifted periodically by a caregiver.
Good nutrition and hygiene can also help prevent pressure sores by encouraging healthy skin.

« Pain

People who are paralyzed often have what is called neurogenic pain resulting from damage to
nerves in the spinal cord. For some survivors of spinal cord injury, pain or an intense burning or
stinging sensation is unremitting due to hypersensitivity in some parts of the body. Others are
prone to normal musculoskeletal pain as well, such as shoulder pain due to overuse of the
shoulder joint from pushing a wheelchair and using the arms for transfers. Treatments for chronic
pain include medications, acupuncture, spinal or brain electrical stimulation, and surgery.

+ Bladder and bowel problems

Most spinal cord injuries affect bladder and bowel functions because the nerves that control the
involved organs originate in the segments near the lower termination of the spinal cord and are cut
off from brain input. Without coordination from the brain, the muscles of the bladder and urethra
can't work together effectively, and urination becomes abnormal. The bladder can empty suddenly
without warning, or become over-full without releasing. In some cases the bladder releases, but
urine backs up into the kidneys because it isn't able to get past the urethral sphincter. Most people
with spinal cord injuries use either intermittent catheterization or an indwelling catheter to empty
their bladders.

Bowel function is similarly affected. The anal sphincter muscle can remain tight, so that bowel
movements happen on a reflex basis whenever the bowel is full. Or the muscle can be
permanently relaxed, which is called a "flaccid bowel," and result in an inability to have a bowel
movement. This requires more frequent attempts to empty the bowel and manual removal of stool
to prevent fecal impaction. People with spinal cord injuries are usually put on a regularly scheduled
bowel program to prevent accidents.

+ Reproductive and sexual function

Spinal cord injury has a greater impact on sexual and reproductive function in men than it does in
women. Most spinal cord injured women remain fertile and can conceive and bear children. Even
those with severe injury may well retain orgasmic function, although many lose some if not all of
their ability to reach satisfaction.

Depending on the level of injury, men may have problems with erections and ejaculation, and most
will have compromised fertility due to decreased motility of their sperm. Treatments for men
include vibratory or electrical stimulation and drugs such as sildenafil (Viagra). Many couples may
also need assisted fertility treatments to allow a spinal cord injured man to father children.

Once someone has survived the injury and begun to psychologically and emotionally cope with the
nature of his or her situation, the next concern will be how to live with disabilities. Doctors are now
able to predict with reasonable accuracy the likely long-term outcome of spinal cord injuries. This
helps patients set achievable goals for themselves, and gives families and loved ones a realistic
set of expectations for the future.

Top
How Does Rehabilitation Help People Recover From Spinal Cord Injuries?
No two people will experience the same emotions after surviving a spinal cord injury, but almost everyone

will feel frightened, anxious, or confused about what has happened. It's common for people to have very
mixed feelings: relief that they are still alive, but disbelief at the nature of their disabilities.

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skills, as well as sensations in the arms and legs.

The Nervous Systems
Together, the spinal cord and the brain make up the central nervous system (CNS).

The CNS controls most functions of the body, but it is not the only nervous system in the body. The
peripheral nervous system (PNS) includes the nerves that project to the limbs, heart, skin, and other
organs outside the brain. The PNS controls the somatic nervous system, which regulates muscle
movements and the response to sensations of touch and pain, and the autonomic nervous system, which
provides nerve input to the internal organs and generates automatic reflex responses. The autonomic
nervous system is divided into the sympathetic nervous system, which mobilizes organs and their
functions during times of stress and arousal, and the parasympathetic nervous system, which conserves
energy and resources during times of rest and relaxation.

The spinal cord acts as the primary information pathway between the brain and all the other nervous
systems of the body. It receives sensory information from the skin, joints, and muscles of the trunk,
arms, and legs, which it then relays upward to the brain. It carries messages downward from the brain to
the PNS, and contains motor neurons, which direct voluntary movements and adjust reflex movements.
Because of the central role it plays in coordinating muscle movements and interpreting sensory input, any
kind of injury to the spinal cord can cause significant problems throughout the body.

Top
What Happens When the Spinal Cord Is Injured?

A spinal cord injury usually begins with a sudden, traumatic blow to the spine that fractures or dislocates
vertebrae. The damage begins at the moment of injury when displaced bone fragments, disc material, or
ligaments bruise or tear into spinal cord tissue. Axons are cut off or damaged beyond repair, and neural
cell membranes are broken. Blood vessels may rupture and cause heavy bleeding in the central grey
matter, which can spread to other areas of the spinal cord over the next few hours.

Within minutes, the spinal cord swells to fill the entire cavity of the spinal canal at the injury level. This
swelling cuts off blood flow, which also cuts off oxygen to spinal cord tissue. Blood pressure drops,
sometimes dramatically, as the body loses its ability to self-regulate. As blood pressure lowers even
further, it interferes with the electrical activity of neurons and axons. All these changes can cause a
condition known as spinal shock that can last from several hours to several days.

Although there is some controversy among neurologists about the extent and impact of spinal shock, and
even its definition in terms of physiological characteristics, it appears to occur in approximately half the
cases of spinal cord injury, and it is usually directly related to the size and severity of the injury. During
spinal shock, even undamaged portions of the spinal cord become temporarily disabled and can't
communicate normally with the brain. Complete paralysis may develop, with loss of reflexes and
sensation in the limbs.

The crushing and tearing of axons is just the beginning of the devastation that occurs in the injured spinal
cord and continues for days. The initial physical trauma sets off a cascade of biochemical and cellular
events that kills neurons, strips axons of their myelin insulation, and triggers an inflammatory immune
system response. Days or sometimes even weeks later, after this second wave of damage has passed,
the area of destruction has increased - sometimes to several segments above and below the original
injury - and so has the extent of disability.

* Changes in blood flow cause ongoing damage
Changes in blood flow in and around the spinal cord begin at the injured area, spread out to
adjacent, uninjured areas, and then set off problems throughout the body.

Immediately after the injury, there is a major reduction in blood flow to the site, which can last for
as long as 24 hours and becomes progressively worse if untreated. Because of differences in
tissue composition, the impact is greater on the interior grey matter of the spinal cord than on the
outlying white matter.

Blood vessels in the grey matter also begin to leak, sometimes as early as 5 minutes after injury.
Cells that line the still-intact blood vessels in the spinal cord begin to swell, for reasons that aren't
yet clearly understood, and this continues to reduce blood flow to the injured area. The
combination of leaking, swelling, and sluggish blood flow prevents the normal delivery of oxygen
and nutrients to neurons, causing many of them to die.

The body continues to regulate blood pressure and heart rate during the first hour to hour-and-a-half
after the injury, but as the reduction in the rate of blood flow becomes more widespread, self-
regulation begins to turn off. Blood pressure and heart rate drop.

+ Excessive release of neurotransmitters kills nerve cells

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Information Resources

For information on other neurological disorders or research programs funded by the National Institute of
Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network
(BRAIN) at:

BRAIN

P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
www.ninds .nih.gov

A number of private organizations offer services and information for those with spinal cord injury and their
families, including:

Christopher Reeve Paralysis Foundation/ Paralysis Resource Center
500 Morris Avenue

Springfield, NJ 07081

info@crpf.org; research@crpf.org

http://www. christopherreeve.org
Tel: 973-379-2690 800-225-0292

Fax: 973-912-9433

Daniel Heumann Fund for Spinal Cord Research
6516 Truman Lane

#100

Falls Church, VA 22043-1821

dannycuse@aol.com

http://www. heumannfund.org
Tel: 703-442-8797

Fax: 703-448-6914

Geoffrey Lance Foundation for SCI Research and Support
132 S. 10th Street, #375 Main

c/o Regional SCI Center of Delaware Valley

Philadelphia, PA 19107

info@geofflance.com

http://www. geofflance.com

Tel: 877-GLANCE1 (452-6231)

Fax: 215-955-5152

Miami Project to Cure Paralysis/ Buoniconti Fund
P.O. Box 016960

R48

Miami, FL 33101-6960
mpinfo@miamiproject.med.miami.edu

http://www. themiamiproject.org

Tel: 305-243-6001 800-STANDUP (782-6387)

Fax: 305-243-6017

National Spinal Cord Injury Association
6701 Democracy Blvd.

#300-9

Bethesda, MD 20817

info@spinalcord.org

http://www. spinalcord.org

Tel: 301-214-4006 800-962-9629

Fax: 301-881-9817

Paralyzed Veterans of America (PVA)

801 18th Street, NW

Washington, DC 20006-3517

info@pva.org

http://www.pva.org

Tel: 202-USA-1300 (872-1300) 800-424-8200
Fax: 202-785-4452

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an excitatory neurotransmitter.

growth-i

iting proteins: protein molecules that inhibit axon regeneration.

guidance molecules - molecules that guide axons to their target. Some guidance molecules attract
certain axons while repelling others.

hypothermia - abnormally low body temperature.

interneurons - neurons with axons that remain within the spinal cord.

intubation - the process of putting a tube into a hollow organ or passageway, often into the airway.
ligament - a tough band of connective tissue that connects various structures such as two bones.

lumbar - the part of the spine in the middle back, below the thoracic vertebrae and above the sacral
vertebrae.

macrophage - a type of white blood cell that engulfs foreign material. Macrophages are key players in the
immune response to foreign invaders such as infectious microorganisms Macrophages also release
substances that stimulate other cells of the immune system.

methylprednisolone - a steroid drug used to improve recovery from spinal cord injury.

microglia - glial cells that function as part of the immune system in the brain and spinal cord.

monocyte - a white blood cell that has a single nucleus and can engulf foreign material. Monocytes
emigrate from blood into the tissues of the body and evolve into macrophages

myelin - a structure of cell membranes that forms a sheath around axons, insulating them and speeding
conduction of nerve impulses.

myelotomy - a surgical procedure that cuts into the spinal cord.

neural prostheses - prosthetic devices that can respond to signals from the brain.

neurogenic pain - generalized pain that results from nervous system malfunction.

neuromodulation - a series of techniques employing electrical stimulation or the administration of
medication by means of devices implanted in the body. These techniques allow the treatment of a range

of disorders including certain forms of pain, spasticity, tremor, and urinary problems.

neuron - also known as a nerve cell; the structural and functional unit of the nervous system. A neuron
consists of a cell body and its processes: an axon and one or more dendrites.

neurostimulation - the act of stimulating neurons with electrical impulses delivered via electrodes
attached to the brain

neurotransmitter - a chemical released from neurons that transmits an impulse to another neuron,
muscle, organ, or other tissue.

neurotrophic factors - proteins responsible for the growth and survival of neurons.

neutrophil - a type of white blood cell that engulfs, kills, and digests microorganisms
oligodendrocyte - a type of nerve cell in the brain and spinal cord that surrounds and insulates axons.
olfactory ensheathing glia - non-myelinating glial cells that ensheath olfactory axons within both the
PNS and CNS portions of the primary olfactory pathway. They are being used in experiments to build
bridges between damaged areas of the spinal cord.

paralysis - the inability to control movement of a part of the body.

paraplegia - a condition involving complete paralysis of the legs.

pressure sore (also known as a pressure ulcer or bed sore) - a reddened area or open sore caused by
unrelieved pressure on the skin over bony areas such as the hip-bone or tailbone.

quadriplegia - a condition involving complete paralysis of the legs and partial or complete paralysis of
the arms.

receptor - a structure on the surface or interior of a cell that selectively receives and binds to a specific
substance.

regeneration - repair, regrowth, or restoration of tissues; opposite of degeneration.

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places where the spinal cord is vulnerable to direct injury.

The spinal cord is also organized into segments and named and numbered from top to bottom. Each
segment marks where spinal nerves emerge from the cord to connect to specific regions of the body.
Locations of spinal cord segments do not correspond exactly to vertebral locations, but they are roughly
equivalent.

* Cervical spinal nerves (C1 to C8) control signals to the back of the head, the neck and shoulders,
the arms and hands, and the diaphragm.

* Thoracic spinal nerves (T1 to T12) control signals to the chest muscles, some muscles of the
back, and parts of the abdomen.

+ Lumbar spinal nerves (L1 to L5) control signals to the lower parts of the abdomen and the back,
the buttocks, some parts of the external genital organs, and parts of the leg.

* Sacral spinal nerves (S1 to S5) control signals to the thighs and lower parts of the legs, the feet,
most of the external genital organs, and the area around the anus.

The single coccygeal nerve carries sensory information from the skin of the lower back.
Spinal Cord Anatomy

The spinal cord has a core of tissue containing nerve cells, surrounded by long tracts of nerve fibers
consisting of axons. The tracts extend up and down the spinal cord, carrying signals to and from the
brain. The average size of the spinal cord varies in circumference along its length from the width of a
thumb to the width of one of the smaller fingers. The spinal cord extends down through the upper two
thirds of the vertebral canal, from the base of the brain to the lower back, and is generally 15 to 17 inches
long depending on an individual's height

The interior of the spinal cord is made up of neurons, their support cells called glia, and blood vessels.
The neurons and their dendrites (branching projections that help neurons communicate with each other)
reside in an H-shaped region called "grey matter."

The H-shaped grey matter of the spinal cord contains motor neurons that control movement, smaller
interneurons that handle communication within and between the segments of the spinal cord, and cells
that receive sensory signals and then send information up to centers in the brain.

Surrounding the grey matter of neurons is white matter. Most axons are covered with an insulating
substance called myelin, which allows electrical signals to flow freely and quickly. Myelin has a whitish
appearance, which is why this outer section of the spinal cord is called "white matter."

Axons carry signals downward from the brain (along descending pathways) and upward toward the brain
(along ascending pathways) within specific tracts. Axons branch at their ends and can make connections
with many other nerve cells simultaneously. Some axons extend along the entire length of the spinal
cord.

The descending motor tracts control the smooth muscles of internal organs and the striated (capable of
voluntary contractions) muscles of the arms and legs. They also help adjust the autonomic nervous
system's regulation of blood pressure, body temperature, and the response to stress. These pathways
begin with neurons in the brain that send electrical signals downward to specific levels of the spinal cord.
Neurons in these segments then send the impulses out to the rest of the body or coordinate neural
activity within the cord itself.

The ascending sensory tracts transmit sensory signals from the skin, extremities, and internal organs
that enter at specific segments of the spinal cord. Most of these signals are then relayed to the brain. The
spinal cord also contains neuronal circuits that control reflexes and repetitive movements, such as
walking, which can be activated by incoming sensory signals without input from the brain.

The circumference of the spinal cord varies depending on its location. It is larger in the cervical and
lumbar areas because these areas supply the nerves to the arms and upper body and the legs and lower
body, which require the most intense muscular control and receive the most sensory signals.

The ratio of white matter to grey matter also varies at each level of the spinal cord. In the cervical
segment, which is located in the neck, there is a large amount of white matter because at this level there
are many axons going to and from the brain and the rest of the spinal cord below. In lower segments,
such as the sacral, there is less white matter because most ascending axons have not yet entered the
cord, and most descending axons have contacted their targets along the way.

To pass between the vertebrae, the axons that link the spinal cord to the muscles and the rest of the
body are bundled into 31 pairs of spinal nerves, each pair with a sensory root and a motor root that make
connections within the grey matter. Two pairs of nerves - a sensory and motor pair on either side of the
cord - emerge from each segment of the spinal cord.

The functions of these nerves are determined by their location in the spinal cord. They control everything
from body functions such as breathing, sweating, digestion, and elimination, to gross and fine motor

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significant physiological consequences.

Catastrophic falls, being thrown from a horse or through a windshield, or any kind of physical trauma that
crushes and compresses the vertebrae in the neck can cause irreversible damage at the cervical level of
the spinal cord and below. Paralysis of most of the body including the arms and legs, called quadriplegia,
is the likely result. Automobile accidents are often responsible for spinal cord damage in the middle back
(the thoracic or lumbar area), which can cause paralysis of the lower trunk and lower extremities, called
paraplegia.

Other kinds of injuries that directly penetrate the spinal cord, such as gunshot or knife wounds, can either
completely or partially sever the spinal cord and create life-long disabilities.

Most injuries to the spinal cord don't completely sever it. Instead, an injury is more likely to cause
fractures and compression of the vertebrae, which then crush and destroy the axons, extensions of nerve
cells that carry signals up and down the spinal cord between the brain and the rest of the body. An injury
to the spinal cord can damage a few, many, or almost all of these axons. Some injuries will allow almost
complete recovery. Others will result in complete paralysis.

Until World War II, a serious spinal cord injury usually meant certain death, or at best a lifetime confined
to a wheelchair and an ongoing struggle to survive secondary complications such as breathing problems
or blood clots. But today, improved emergency care for people with spinal cord injuries and aggressive
treatment and rehabilitation can minimize damage to the nervous system and even restore limited
abilities.

Advances in research are giving doctors and patients hope that all spinal cord injuries will eventually be
repairable. With new surgical techniques and exciting developments in spinal nerve regeneration, the
future for spinal cord injury survivors looks brighter every day.

This brochure has been written to explain what happens to the spinal cord when it is injured, the current
treatments for spinal cord injury patients, and the most promising avenues of research currently under
investigation.

Facts and Figures About Spinal Cord Injury

* There are an estimated 10,000 to 12,000 spinal cord injuries every year in the United States

* A quarter of a million Americans are currently living with spinal cord injuries

* The cost of managing the care of spinal cord injury patients approaches $4 billion each year.

* 38.5 percent of all spinal cord injuries happen during car accidents. Almost a quarter, 24.5 percent,
are the result of injuries relating to violent encounters, often involving guns and knifes. The rest are
due to sporting accidents, falls, and work-related accidents.

+ 55 percent of spinal cord injury victims are between 16 and 30 years old.

* More than 80 percent of spinal cord injury patients are men
Source: Facts and Figures at a Glance, May 2001. National Spinal Cord Injury Statistical Center.

Top

How Does the Spinal Cord Work?

To understand what can happen as the result of a spinal cord injury, it helps to know the anatomy of the
spinal cord and its normal functions.

Spine Anatomy

The soft, jelly-like spinal cord is protected by the spinal column. The spinal column is made up of 33
bones called vertebrae, each with a circular opening similar to the hole in a donut. The bones are stacked
one on top of the other and the spinal cord runs through the hollow channel created by the holes in the
stacked bones.

The vertebrae can be organized into sections, and are named and numbered from top to bottom according
to their location along the backbone:

* Cervical vertebrae (1-7) located in the neck

* Thoracic vertebrae (1-12) in the upper back (attached to the ribcage)
« Lumbar vertebrae (1-5) in the lower back

* Sacral vertebrae (1-5) in the hip area

* Coccygeal vertebrae (1-4 fused) in the tailbone

Although the hard vertebrae protect the soft spinal cord from injury most of the time, the spinal column is
not all hard bone. Between the vertebrae are discs of semi-rigid cartilage, and in the narrow spaces
between them are passages through which the spinal nerves exit to the rest of the body. These are

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directly into the brain using microchips that would do the processing and transmit the results
without wires. Work is already being done with hybrid neural interfaces, implantable electronic
devices with a biological component that encourages cells to integrate into the host nervous
system.

+ Retraining central pattern generators

Scientists have known for years that animals’ spinal cords contain networks of neurons called
central pattern generators (CPG) that produce rhythmic flexing and extension of the muscles used
in walking. They assumed, however, that the bipedal walking of humans was more dependent on
voluntary control than on CPG activation. Therefore, scientists thought that without control from
the brain, movements produced by a spinal CPG weren't likely to be useful in restoring successful
walking without regulation from the brain. Current research is showing, however, that these
networks can be retrained after spinal cord injury to restore limited mobility to the legs.

Using a technique called sensory patterned feedback, researchers are attempting to retrain CPG
networks in spinal cord injured patients with special programs that break down walking movements
into their component patterns and force paralyzed limbs to repeat them over and over again. In one
of these programs, the patient is partially supported by a harness above a moving treadmill while a
therapist moves the patient's legs in a stepping motion. Other researchers are experimenting with
combining body weight support and electrical stimulation with actual walking rather than treadmill
training.

Another technique uses an FES bicycle in which electrodes are attached to hamstrings,
quadriceps, and gluteal muscles to stimulate the pedaling motion. Several studies have shown that
these exercises can improve gait and balance, and increase walking speed. NINDS is currently
funding a clinical trial with paraplegic and quadriplegic subjects to test the benefits of partial
weight-supported walking.

Relieving pressure through surgery

The timing of surgical decompression (alleviating pressure on the spinal cord from fractured or
dislocated vertebrae or disks) is a controversial topic. Animal studies have shown that early
decompression can reduce secondary damage, but similar results haven't been reliably reproduced
in human trials. Other studies have shown neurological improvement without decompression
surgery, which has led some to believe that either avoiding or delaying surgery, and using
pharmacologic interventions instead, is a reasonable (and non-invasive) treatment for spinal cord
injuries. Additional research is needed to determine if early surgical intervention is sufficiently
beneficial to offset the risk of major surgery in acute trauma.

+ Treating pain

Two thirds of people with spinal cord injury report pain and a third of those rate their pain as
severe. Nonetheless, both diagnosis and treatment of post-injury pain still remain a clinical
challenge. There is no universally recognized scheme for classifying pain from spinal cord injury,
nor is there a uniformly successful medical or surgical treatment to prevent or reduce it. The
mainstays of neuropathic pain treatment are antidepressants and anticonvulsants, even though
they are not uniformly effective.

Research suggests that spinal cord pain syndromes stem from the spread of secondary damage to
spinal cord segments above and below the injury site. Pain can be at the level of the injury or
below the level of the injury, even in areas where sensation is limited or absent. Findings indicate
that at-level (junctional) pain probably results from damage to grey and white matter one or more
segments above the injury site, whereas pain below the injury results from the interruption of axon
pathways and the formation of abnormal connections within the spinal cord near the site of injury.

Studies suggest that functional changes in neurons, which make them hyperexcitable, could be a
cause of chronic pain syndromes. Consequently, giving more aggressive treatment for spinal cord
injury in the first few hours after injury could limit secondary damage and prevent or reduce the
development of chronic pain afterwards.

Investigators are currently testing neuroprotective and anti-inflammatory strategies to calm
overexcited neurons. Other studies are also looking at pharmacological options, including sodium
channel blockers (such as lidocaine and mexiletine), opioids (such as alfentanil and ketamine), and
a combination of morphine and clonidine. Drugs that interfere with neurotransmitters involved in
pain syndromes, such as glutamate, are also being investigated. Other researchers are exploring
the use of genetically engineered cells to deliver pain-relieving neurotransmitters. These
treatments appear to alleviate pain in animal models and in preliminary clinical studies with
terminally ill cancer patients.

+ Controlling spa: ity

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12/20/2015

Spinal Cord Injury: Hope Through Research

Spinal Cord Society
19051 County Highway 1
Fergus Falls, MN 56537
NA

http://members.aol.com/scsweb
Tel: 218-739-5252 or 218-739-5261
Fax: 218-739-5262

Top
Glossary

agonist - a drug capable of combining with a receptor and initiating action.

antagonist - a drug that opposes the effects of another by physiological or chemical action or by a
competitive mechanism.

apoptosis - also called programmed cell death. A form of cell death in which a programmed sequence of
events leads to the elimination of old, unnecessary, and unhealthy cells.

arrhythmia - an abnormal heart rhythm. The heartbeats may be too slow, too rapid, too irregular, or too
early.

astrocyte - a type of glial cell responsible for neurotransmission and neuronal metabolism.

autonomic dysreflexia - a potentially dangerous complication of spinal cord injury in which blood
pressure rises to dangerous levels. If not treated, autonomic dysreflexia can lead to stroke and possibly
death.

axial traction - the application of a mechanical force to stretch the spine; used to relieve pressure by
separating vertebral surfaces and stretching soft tissues.

axon - the long, thin extension of a nerve cell that conducts impulses away from the cell body.

axonal growth cone - dynamic structures present at the tip of developing and regenerating axons that
respond to chemical cues for growth and direction.

central pattern generators (CPG) - neural circuits that produce self-sustaining patterns of behavior
independent of their sensory input. Researchers have found evidence of a locomotor CPG in the spinal
cord that synchronizes muscle activity during alternating stepping of the legs and feet.

cervical - the part of the spine in the neck region.
coccygeal - the part of the spine at the bottom of the spinal column, above the buttocks

cytokine - a small protein released by immune cells that has a specific effect on the interactions between
cells, or communications between cells, or on the behavior of cells. dendrite - a short arm-like
protuberance from a neuron. Dendrite is from the Greek for "branched like a tree." disc - shortened
terminology for an intervertebral disc, a disc-shaped piece of specialized tissue that separates the bones
of the spinal column.

electroejaculation - a technique that uses an electric probe to stimulate ejaculation.

embryonic stem cells - undifferentiated cells from the embryo that have the potential to become a
wide variety of specialized cell types.

excitotoxicity - a neurological process that is the result of the release of excessive amounts of the
neurotransmitter glutamate.

extracellular matrix - the material found around cells composed of structural proteins, specialized
proteins, and proteoglycans

fetal spinal cord cells - cells used by scientists to derive undifferentiated embryonic stem cells for
transplant into the damaged spinal cord.

free radicals - highly reactive chemicals that attack molecules and modify their chemical structure.
functional electrical stimulation (FES) - the therapeutic use of low-level electrical current to stimulate
muscle movement and restore useful movements such as standing or stepping; also called functional
neuromuscular stimulation.

glia -supportive cells in the brain and spinal cord. Glial cells are the most abundant cell types in the
central nervous system. There are three types: astrocytes, oligodendrocytes, and microglia. glutamate -

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