Commercial trucks waited in a line at the Washington State Patrol truck scales just north of the Oregon border to go through a standard weight and height check.

But every few trucks that rolled by Monday were flagged over for a comprehensive safety inspection as part of a statewide safety emphasis.

Brake checks were the key focus for commercial vehicle officers because this week is Brake Safety Week, said David W. Coppinger, a WSP commercial vehicle officer.

“The goal is to reduce collisions from defective brakes,” he said.

A 2006 U.S. Department of Transportation crash study found defective brakes were a factor in 29.4 percent of all crashes investigated.

Of the more than 1.5 million brakes inspected, 17 percent of vehicles were found to have defective brakes and were forced to stop driving.

“Sometimes the defect is obvious. Sometimes it’s not,” Coppinger said.

By early afternoon Monday, three inspected trucks had brake defects serious enough that the trucks couldn’t be safely driven on the highway.

A fourth truck was parked because the Oregon farmer was more than 150 miles from his farm and didn’t have the required commercial driver’s license.

Inspectors also found a few trucks and drivers with less serious violations for hauling hazardous materials, defective lights and problems with required medical cards. But those weren’t serious enough to stop the trucks, Coppinger said.

All truck scales around the state were open Monday for the special safety emphasis, including on Highway 395 at Pasco, Highway 12 at Wallula and Highway 14 at Plymouth.

It takes about 30 minutes to conduct a comprehensive inspection of a truck and the driver’s information.

The inspections should be consistent from state to state based on the federal inspection program, Coppinger said.

About 1,000 to 1,500 trucks roll through the Port of Entry scale near the southern edge of Benton County. On a typical day, 30 to 50 trucks are inspected.

Not all the inspections, however, are comprehensive checks. Other inspections include basic checks on the drivers or a walk-around look at the truck.

Any driver smelling of alcohol is automatically stopped from driving for 24 hours and anyone with a blood alcohol level of 0.04 percent — half the limit for driving a car — is arrested, Coppinger said.

The WSP also had its Targeting Aggressive Cars around Trucks (TACT) vehicles on the roads Monday to watch for cars following too close, speeding or changing lanes too close to commercial vehicles.

“Trucks are big, they’re heavy and they’re pretty obvious out there,” Coppinger said. “But people need to remember to leave adequate room (around a truck) and never pass on the right.”

What is complex regional pain syndrome?

Complex regional pain syndrome (CRPS) is a chronic pain condition that is believed to be the result of dysfunction in the central or peripheral nervous systems. Typical features include dramatic changes in the color and temperature of the skin over the affected limb or body part, accompanied by intense burning pain, skin sensitivity, sweating, and swelling. CRPS I is frequently triggered by tissue injury; the term describes all patients with the above symptoms but with no underlying nerve injury. Patients with CRPS II experience the same symptoms but their cases are clearly associated with a nerve injury.

Older terms used to describe CRPS are “reflex sympathetic dystrophy syndrome” and “causalgia,” a term first used during the Civil War to describe the intense, hot pain felt by some veterans long after their wounds had healed.

CRPS can strike at any age and affects both men and women, although most experts agree that it is more common in young women.

What are the symptoms of CRPS?

The key symptom of CRPS is continuous, intense pain out of proportion to the severity of the injury (if an injury has occurred), which gets worse rather than better over time. CRPS most often affects one of the extremities (arms, legs, hands, or feet) and is also often accompanied by:

• “burning” pain
• increased skin sensitivity
• changes in skin temperature: warmer or cooler compared to the opposite extremity
• changes in skin color: often blotchy, purple, pale, or red
• changes in skin texture: shiny and thin, and sometimes excessively sweaty
• changes in nail and hair growth patterns
• swelling and stiffness in affected joints
• motor disability, with decreased ability to move the affected body part

Often the pain spreads to include the entire arm or leg, even though the initiating injury might have been only to a finger or toe. Pain can sometimes even travel to the opposite extremity. It may be heightened by emotional stress.

The symptoms of CRPS vary in severity and length. Some experts believe there are three stages associated with CRPS, marked by progressive changes in the skin, muscles, joints, ligaments, and bones of the affected area, although this progression has not yet been validated by clinical research studies.

Stage one is thought to last from 1 to 3 months and is characterized by severe, burning pain, along with muscle spasm, joint stiffness, rapid hair growth, and alterations in the blood vessels that cause the skin to change color and temperature.

Stage two lasts from 3 to 6 months and is characterized by intensifying pain, swelling, decreased hair growth, cracked, brittle, grooved, or spotty nails, softened bones, stiff joints, and weak muscle tone.

In stage three the syndrome progresses to the point where changes in the skin and bone are no longer reversible. Pain becomes unyielding and may involve the entire limb or affected area. There may be marked muscle loss (atrophy), severely limited mobility, and involuntary contractions of the muscles and tendons that flex the joints. Limbs may become contorted.

What causes CRPS?

Doctors aren’t sure what causes CRPS. In some cases the sympathetic nervous system plays an important role in sustaining the pain. The most recent theories suggest that pain receptors in the affected part of the body become responsive to a family of nervous system messengers known as catecholamines. Animal studies indicate that norepinephrine, a catecholamine released from sympathetic nerves, acquires the capacity to activate pain pathways after tissue or nerve injury. The incidence of sympathetically maintained pain in CRPS is not known. Some experts believe that the importance of the sympathetic nervous system depends on the stage of the disease.

Another theory is that post-injury CRPS (CRPS II) is caused by a triggering of the immune response, which leads to the characteristic inflammatory symptoms of redness, warmth, and swelling in the affected area. CRPS may therefore represent a disruption of the healing process. In all likelihood, CRPS does not have a single cause, but is rather the result of multiple causes that produce similar symptoms.

How is CRPS diagnosed?

CRPS is diagnosed primarily through observation of the signs and symptoms. But because many other conditions have similar symptoms, it can be difficult for doctors to make a firm diagnosis of CRPS early in the course of the disorder when symptoms are few or mild. Or, for example, a simple nerve entrapment can sometimes cause pain severe enough to resemble CRPS. Diagnosis is further complicated by the fact that some people will improve gradually over time without treatment.

Since there is no specific diagnostic test for CRPS, the most important role for testing is to help rule out other conditions. Some clinicians apply a stimulus (such as touch, pinprick, heat, or cold) to the area to see if it causes pain. Doctors may also use triple-phase bone scans to identify changes in the bone and in blood circulation.

What is the prognosis?

The prognosis for CRPS varies from person to person. Spontaneous remission from symptoms occurs in certain people. Others can have unremitting pain and crippling, irreversible changes in spite of treatment. Some doctors believe that early treatment is helpful in limiting the disorder, but this belief has not yet been supported by evidence from clinical studies. More research is needed to understand the causes of CRPS, how it progresses, and the role of early treatment.

How is CRPS treated?

Because there is no cure for CRPS, treatment is aimed at relieving painful symptoms so that people can resume their normal lives. The following therapies are often used:

• Physical therapy: A gradually increasing exercise program to keep the painful limb or body part moving may help restore some range of motion and function.
• Psychotherapy: CRPS often has profound psychological effects on people and their families. Those with CRPS may suffer from depression, anxiety, or post-traumatic stress disorder, all of which heighten the perception of pain and make rehabilitation efforts more difficult.
• Sympathetic nerve block: Some patients will get significant pain relief from sympathetic nerve blocks. Sympathetic blocks can be done in a variety of ways. One technique involves intravenous administration of phentolamine, a drug that blocks sympathetic receptors. Another technique involves placement of an anesthetic next to the spine to directly block the sympathetic nerves.
• Medications: Many different classes of medication are used to treat CRPS, including topical analgesic drugs that act locally on painful nerves, skin, and muscles; antiseizure drugs; antidepressants, corticosteroids, and opioids. However, no single drug or combination of drugs has produced consistent long-lasting improvement in symptoms.
• Surgical sympathectomy: The use of surgical sympathectomy, a technique that destroys the nerves involved in CRPS, is controversial. Some experts think it is unwarranted and makes CRPS worse; others report a favorable outcome. Sympathectomy should be used only in patients whose pain is dramatically relieved (although temporarily) by selective sympathetic blocks.
• Spinal cord stimulation: The placement of stimulating electrodes next to the spinal cord provides a pleasant tingling sensation in the painful area. This technique appears to help many patients with their pain.
• Intrathecal drug pumps: These devices administer drugs directly to the spinal fluid, so that opioids and local anesthetic agents can be delivered to pain-signaling targets in the spinal cord at doses far lower than those required for oral administration. This technique decreases side effects and increases drug effectiveness.

Is research currently being done on CRPS?

The National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH), supports and conducts research on the brain and central nervous system. Some studies are conducted at the Institute’s laboratories and clinics on the NIH campus in Bethesda, Maryland. Others are funded through grants to major medical institutions across the country. NINDS-supported scientists are studying new approaches to treat CRPS and intervene more aggressively after traumatic injury to lower the chances of developing the disorder. Other studies to overcome chronic pain syndromes are discussed in the NINDS pamphlet, “Pain: Hope Through Research.”

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 or the Law Firm of Attorney Vaughn Wamsley. 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.

Provided by

National Institute of Neurological Disorders and Stroke

“Complex Regional Pain Syndrome Fact Sheet,” NINDS. Publication date November 2003.
NIH Publication No. 04-4173

http://www.ninds.nih.gov/disorders/reflex_sympathetic_dystrophy/detail_reflex_sympathetic_dystrophy.htm

January 18-19, 2001
Pooks Hill Marriott, Bethesda, MD

Introduction
Injury to the spinal cord initiates a complex series of events that has devastating consequences such as partial or complete paralysis, muscle atrophy, compromised ability to breathe, lack of bladder and bowel control, sexual dysfunction and chronic pain. The quarter of a million patients with spinal cord injury (SCI) in the United States require specialized care to deal with these problems every day for the rest of their lives. A major cause of dysfunction arises from damage to nerve fibers passing through the injury site or lesion. We are dependent on long fibers that traverse the length of the cord to coordinate messages between the brain and other parts of the body. Interruption of these fibers can disrupt the voluntary control of movement and the experience of sensation. In developing treatments for SCI, a central question is how to restore connectivity by promoting the regeneration of axons in the environment of the damaged nervous system and the establishment of new and appropriate synaptic contacts within the spinal cord.

To address this question, this workshop focused on “bridging” damaged tissue, encouraging re-growth of axons across the lesion, and facilitating reconnection to synaptic targets beyond the site of injury. However, it was recognized that complementary efforts to limit cell death, reduce inflammation-related damage, optimize the function of surviving neurons, and train intact local circuits would all contribute to functional recovery from SCI.

Presentations and discussions revolved around the following topics:

1. Spurring adult neurons to grow axons again
2. Changing the environment encountered by regenerating axons
3. Altering the response of neurons to a non-permissive environment
4. Reforming connections - interactions between neurons and their targets
5. Making the most of what remains after injury

Finally, a number of recommendations arose from the discussion that could move the field of SCI research forward.

Inducing adult neurons to grow axons again
Damaged neurons in the adult mammalian central nervous system (CNS) typically do not regenerate axons in vivo. In experimental situations, it has been observed that injuring a nerve more than once leads to more robust regeneration after the second injury. However impractical it may be in a clinical setting, the phenomenon of a pre-injury, termed a “conditioning lesion”, seems to prime the nervous system, and suggests that intracellular conditions can be changed so that neurons are more in a growth state. Several growth-associated molecules are “switched on” following a conditioning lesion. GAP43 and CAP23 are growth cone membrane proteins that are up-regulated by peripheral nerve injury and whose expression is correlated with regenerative potential. Although over-expression of either protein alone does not result in axonal regeneration, both proteins together in transgenic mice mimic the effects of a conditioning lesion and lead to higher numbers of regenerating axons in the spinal cord. DNA microarrays have also been used to identify several thousand genes that are regulated in response to injury. The challenge now is to elucidate the function of these genes, and to identify the ones that are crucial for spinal cord repair.

Changing the environment around regenerating axons
Getting axons to grow across the cavity or “cyst” that often develops at the site of injury is a major challenge in SCI, and many strategies have been proposed to bridge this gap. Cells and substances that have been tested as bridge material include Schwann cells, olfactory ensheathing glia, peripheral nerve segments, collagen embedded with neurotrophic or growth factors, and a variety of stem/progenitor cells. Although many of these bridges and scaffolds have supported axon growth, the axons tended to stay within the bridge and do not extend beyond it to innervate targets on the other side of the lesion. To entice axons out of the bridge, it may be possible to introduce or genetically engineer in factors such as neurotrophins into the distal side of the host cord to lead axons onward.

Scar tissue surrounding the injury site is well known to inhibit axonal growth. Some of this activity is caused by accumulations of extracellular matrix such as chondroitin sulfate proteoglycans. When growth cones contact this inhibitory barrier, they remain motile and can persist for months, but make no further progress along the cord. However, the long-term persistence of these dystrophic endings raises the possibility that axons might resume growing should conditions around them improve and become more permissive, even at times long after the initial injury.

One direct approach to optimize the environment was to replace the injured tissue with transplants of fetal rat spinal cord. When these were grafted into newborn rats, axons regenerated through the transplant and into the host cord. When similar studies were conducted in older rats, axon regeneration through the transplant diminished, even though the same transplant material (fetal cord) was used, suggesting that the age of the host was responsible for the difference in regeneration. The numbers of axons growing into the transplant increased however, if exogenous neurotrophic factors such as BDNF, CNTF, NT-3, NT-4 were supplied to the older rats. Interestingly, if transplantation was delayed for 2 weeks after the initial injury to the cord, descending axons now were able to traverse completely through the graft and into the host cord at the caudal end. The effects of the delayed transplantation may have mimicked that of a conditioning lesion. In addition, the developing glial scar may have been removed during the surgery to insert the graft. The best behavioral recovery was seen when transplantation of fetal cord was delayed for 2 weeks, and with exogenous neurotrophins. Under this regimen, animals had near normal weight support and stepping behavior, although coordinated quadrupedal movement was not sustained.

Change response of neurons to non-permissive environment
Understanding the neuronal response to inhibitory molecules may provide hints on how to manipulate the intracellular signals and pathways that regulate this response. We may then develop strategies and design molecules to override the “no-growth” signals. Over the last decade, numerous molecules have been shown to have inhibitory, or growth-stopping effects on neuronal growth cones. Some are molecules that are present during development where they act to facilitate correct guidance when pathways are first laid down. Others appear to be components of myelin and prominent in white matter tracts in the adult nervous system

The semaphorins are a family of proteins, some of which are secreted and others membrane bound. They interact with a receptor complex made up of neuropilins and plexins. Because family members can act as antagonists by competing for binding to the same receptor, the activity of semaphorins can be modulated from inhibitory for growth to positive for outgrowth. Intracellular signaling pathways activated by semaphorins involve rac-1 and rho, small GTPases that control actin polymerization in the cytoskeleton.

The ephrins, a second family of proteins with inhibitory activity, play an important role in organizing the retinotopic projection to the tectum. Ephrin receptors are tyrosine kinases and activate downstream signaling cascades that are also linked to rac and rho pathways. Reverse signaling has been documented for ephrins where the ligand-bearing cell responds as well as the receptor-bearing cell.

The netrins and slits are two other classes of guidance molecules. In the developing spinal cord, netrin acts as an attractant cue guiding commissural axons to the floor plate. However, netrin activity can be modulated from being an attractant to being a repellent. In nematodes, netrin functions as a repellent when associated with another protein such as UNC5. Like netrin, Slit is found at the midline where it acts to keep axons that have crossed over from returning. Its receptor, Robo, is present on axons.

While these molecules play importance guidance roles in the developing nervous system, they may have a deleterious function during regeneration. The expression of molecules such as semaphorins, ephrins, netrins, and slits after SCI needs to be explored, as well as the expression of their respective receptors. If any are expressed after injury, their actions could be inactivated by selective use of antagonists and thus allow regeneration of certain axonal tracts or pathways in the cord.

One consequence of trauma is the disruption of oligodendrocytes with the concomitant release of myelin proteins. Many of these proteins exert a highly inhibitory effect on axonal growth. Some of myelin’s inhibitory activity may reside in a recently identified protein, NOGO that is expressed only by mature oligodendrocytes. Different fragments of NOGO cause growth cone collapse in a classic in vitro test of motility inhibiting effects. MAG is a second inhibitory molecule present in myelin. The response of neurons to MAG is modulated by a cAMP dependent pathway. If cAMP levels are raised, protein kinase A is activated and inhibition by MAG is blocked. Intracellular levels of cAMP can be increased by exposure to neurotrophins. Other agents include the nonhydrolyzable cAMP analog dibutyrl-cAMP, and rollipram, an inhibitor of the phosphodiesterase that inactivates cAMP; all overcome inhibition by MAG and myelin.

How does elevated cAMP promote neurite outgrowth even when the extracellular environment is hostile to growth? One enzyme activated by cAMP is arginase-1, which converts arginine to ornithine which in turn is converted by ornithine decarboxylase to putrescine. Treating neurons with putrescine alone overcame inhibition by MAG.

Rho, another downstream target of the cAMP signaling cascade, is a GTPase that regulates actin polymerization. Neurite outgrowth is reduced when Rho is activated. Rho activity can be blocked by C3, a bacterial toxin from clostridium botulinum. Treatment of neurons in tissue culture with C3 blocks inhibition by MAG. The application of C3 to the site of a dorsal hemisection in adult mice resulted in good regeneration and behavioral recovery. Although these results seem encouraging, it was puzzling that recovery seemed too rapid (measurable after 24 hours) to be due to regeneration.

In summary, manipulating different stages of the cAMP pathway appears effective in overcoming the inhibitory actions of myelin components and may provide an entrée into intracellular mechanisms to change the response of the neuron.

Reforming connections - Interactions between the neuron and the target
Re-establishing connections with the appropriate targets is the next critical hurdle to functional recovery. Unfortunately, the rules governing synapse formation are not well understood, and those for synapse re-formation after injury are even less clear. What is clear is that a great deal of communication occurs between potential pre- and post-synaptic partners when synapses first form during development. Some studies suggest that the initial contact may come from the postsynaptic cell. When Mauthner neurons extend the first axons down the zebrafish spinal cord, they grow past their target motor neurons in each segment without a pause or change in their rate of extension. Target motor neurons, however, actively explore the environment with their dendritic protrusions. Dendrites contacting a Mauthner axon becomes stabilized, and synaptic specializations can form within 30 minutes of the initial contact. Complex interactions between the presynaptic and postsynaptic cells have also been observed in Drosophila development.

Making the most of what remains after injury
While the focus of the workshop was on regeneration of axons and reformation of synapses, awareness of the need to make the most of remaining neurons and circuits after injury was high. One approach is to identify ways to facilitate endogenous mechanisms for recovery.

Unlike central nerves, peripheral nerves face fewer barriers, and because they do regenerate in the adult nervous system, investigators have turned to this model system to explore ways that encourage appropriate regrowth following injury. Brief electrical stimulation of the cut femoral nerve greatly enhanced the speed of axonal regeneration. With electrical stimulation, all motor neurons regenerated axons after 3 weeks, rather than requiring 10 weeks.

In the nervous system, how well a circuit functions depends on the levels of synaptic communication between the contiguous neurons making up the circuit. Synaptic function can be enhanced by regulating the presence of neurotransmitter receptors as well as their function. For example, AMPA receptors mediate excitatory synaptic transmission in the spinal cord, and recent studies find that phosphorylation potentiates their activity by increasing open channel probability. Receptor function can also be regulated by mobilization and insertion of receptors into active zones. As the intracellular pathways involved in receptor trafficking start to be understood, it may be possible to change and optimize synaptic function. For example, reduction of these receptors after injury may prevent excitotoxicity. Conversely their upregulation may enhance residual synaptic function.

Recommendations from the participants

1. Collaborations between groups and investigators
   Research in SCI now requires laboratory methods that range from molecular genetics to animal behavior - essentially the entire range of modern biomedical research techniques. Workshop participants discussed the daunting task faced by individual investigators in acquiring the expertise in their own laboratories to conduct molecular biological, cell biological, and animal behavioral studies. Ways to share expertise, and ways for investigators with one specialty to learn new techniques were frequently discussed and generally felt to be crucial for the field to move forward. The specific recommendations were:
   1. Resurrect linked RO1’s, so that investigators at different institutions can collaborate on a formal basis. This would help small laboratories with limited resources to broaden their research goals. Since these are like PPGs without walls, they should be reviewed by a review panel that routinely reviews PPGs rather than having the individual proposals go to different study sections, as they do in the current review mechanism. Encourage or popularize the R21 mechanism and bioengineering research grants. These types of mechanisms can be vehicles to fund “descriptive” research, exploratory science that may generate important reagents or models but may not be highly hypothesis-driven and therefore are doomed in regular study sections.
   2. Provide supplemental funding to reimburse shipping costs, as well as the costs of producing extra animals. Animals that were generated or produced through NIH funding should be required to be generally available. However, this entails extra costs. Laboratories that are willing to share resources are often hindered from doing so for purely financial reasons. Shipping of special animals (rare and precious transgenics, experimentally injured animal models such as cats etc.) and international shipping are is an additional problems and courier services such as those used by NASA are very expensive.
   3. Support a public repository for animals or reagents and spinal cord tissue. Animals that were engineered with NIH funding could be deposited at such a facility that would handle breeding, shipping, reagent production, and quality control. A tissue bank that stores spinal cord tissue with different types of injury could be a resource for future testing of genes and proteins.
   4. Establish a central core or a national laboratory to facilitate SCI research. Participants were interested in a central site where new techniques could be learned, new models/molecules/genes could be tested, old and new injury models could be standardized, and experimental results compared. The exact format/organization was not defined but examples such as the Woods Hole Marine Laboratories and the Brookhaven National Laboratory were brought us.
2. Development of needed research tools for the community. These include:
   1. bridges/polymers
   2. GFP mice with specific tracts labeled
   3. high through-put screens
   4. exogenous delivery systems
   5. source(s) of growth factors and recombinant proteins
3. Imaging
   The discussion on imaging combined aspects of both of the items above. New techniques needed to be developed, and new facilities needed to be available to make imaging studies available and useful for SCI research. These include:
   1. Developing microPET, fMRI and optical imaging for viewing different aspects of the spinal cord
   2. Developing 2-photon microscopy for viewing and re-constructing damaged spinal cord
   3. Developing new, noninvasive methods to look deep into an intact animal
   4. Increase funding to buy and operate equipment. Currently, the ceiling for shared instrumentation grants is low ($450,000), and do not cover operating costs and support personnel. NCI currently funds mall animal imaging centers.
   5. Establish a National Laboratory (such as Brookhaven) to image recovery from spinal cord damage.
4. Injury models and outcome measures The participants agreed that new animal models and functional outcome measures (for example for pain) needed to be developed and standardized. A manual for SCI that “catalogues” the pros and cons of each injury model would be useful for the field and for new researchers.
5. Partnerships with private organizations and foundations NINDS can “flag” promising but unfounded SCI grants for consideration by private organizations. The participants also encouraged the use of administrative supplements to enable NINDS grantees who are not currently working in SCI to expand their funded project into the SCI field.

Provided by

National Institute of Neurological Disorders and Stroke

http://www.ninds.nih.gov/news_and_events/proceedings/damaged_spinal_cord2001.htm

I. Introduction

A wealth of new tools is paving the way for the development of more effective rehabilitation practices and neural prostheses for the treatment of spinal cord injury (SCI). The development of microelectrode arrays capable of selectively stimulating small functional sets of cells, for example, provides hope that we may, in the future, be able to replace the activity lost with damage to neurons. On the other hand, the use of rehabilitative protocols that provide weight-loading and sensory feedback highlight the spinal cord’s adaptability and its capacity for re-training. Both avenues could lead to restoration of functional capabilities, such as locomotion and bladder control, while minimizing invasive surgery and risk.

Much remains to be done however, before the full potential of these and other advances are translated into patient benefits. Gaps in our knowledge regarding the function of healthy spinal circuitry prevent us from optimizing strategies for harnessing natural mechanisms of plasticity and repair. In addition, a scarcity of objective and quantitative outcome measurements in both animal models and patient trials have hindered careful assessment of candidate therapies and comparisons between studies. Finally, critical information, such as the priorities of patients and the relative tractability of their symptoms, has been overlooked at times, due to a lack of communication between patients, clinicians, and basic scientists.

In the second workshop in the series “New Strategies in Spinal Cord Injury,” held in Los Angeles, CA in June 2000, the National Institute of Neurological Disorders and Stroke (NINDS) took a first step towards addressing these issues. Workshop participants discussed and assessed strategies to replace the function of damaged neurons, facilitate their regeneration, and retrain the injured spinal cord. They also discussed opportunities for cross-fertilization between the study of SCI and space physiology. The National Aeronautics and Space Administration (NASA) co-sponsored the workshop, recognizing that astronauts exposed to microgravity experience some of the same physiological alterations that affect SCI patients.

II. Background

Understanding the spinal cord’s structure and function lies at the heart of developing technologies that aim to replace, and/or retrain neural function following SCI. As the mediator of communications between the body and the brain, the spinal cord shuttles sensory information from neurons distributed throughout the body to the brain, and motor instructions from the brain to the limbs and organs. Far from being a mere conduit of information, however, the endogenous circuitry within the spinal cord plays crucial roles in coordinating complex behaviors. For example, the spinal cord harbors a central pattern generator (CPG) -a group of neurons that generates oscillatory patterns of activity and coordinates movements required for locomotion. The CPG is not simply a hard-wired clock or pacemaker that sets a fixed pace for locomotion; it is modulated by sensory feedback which plays a key role in triggering successive movements. In addition, the spinal cord appears to contain collections or modules of neurons that activate specific groups of muscles, and allow the CPG, as well as supraspinal and reflex pathways, to translate their signals into actions. In amphibians and some mammals, different combinations of these modules, also known as “primitives”, appear to be capable of generating a large range of complex movements.

One of the most exciting attributes of the spinal cord is its ability to adapt to change, and, when appropriately harnessed, it has the potential to overcome functional disruptions caused by SCI. Even when completely disconnected from the brain, the spinal cord is capable of learning and storing memories. Although the cellular and biochemical mechanisms underlying this “plasticity” or ability to change are not well understood, recent studies have shown that spinal cord neurons can undergo long-term potentiation, and long-term depression, two mechanisms believed to underlie memory and learning in the brain. Growth factors are some of the cues that may mediate adaptive changes in the spinal cord. Several growth factors, including Brain Derived Growth factor (BDNF), Neurotrophin-3 (NT-3) and Neurotrophin-4/5 (NT-4/5) are synthesized by neurons in the adult spinal cord. When stimulated by the glutamate agonist, kainic acid, subsets of these neurons show specific increases in their expression of BDNF and NT-4/5, suggesting that signaling between neurons controls the availability of these factors, that, in turn influence the properties of local circuits within the cord.

Changes or plasticity within the spinal cord does not always result in improved function. Working with larval lampreys, Avis Cohen identified dysfunctional changes that can result from SCI. These animals demonstrated functional recovery when allowed to recuperate at room temperature from experimentally-induced crushing of their spinal cords,. Yet when recovery took place at 40C - which is closer to the ambient temperature at which lampreys live in the wild - Cohen discovered that the coupling of oscillatory activities between segments of the cord was disrupted. These studies show that altered coupling during recovery can wreak havoc in a simple system such as lamprey swimming. The fact that a relatively minor difference in recovery conditions had such a dramatic effect on the outcome underscores the difficulty in predicting the response to injury in higher vertebrates with more complex networks of coupled oscillators.

There are a multitude of injury-induced changes that have consequences upstream and downstream of the spinal cord. Imaging studies of the brain, for example, reveal changes in the cortical maps of patients with SCI indicating a functional reorganization of their primary sensorimotor cortices. In addition, as muscles become deprived of their normal synaptic inputs and weight-bearing activity, they begin to atrophy and undergo changes in the complement and levels of many muscle-specific proteins, altering their functional properties. These alterations, in turn, have retrograde effects on the metabolic state and health of the motor neuron innervating the muscles. The lack of weight-bearing activity also affects bones, causing them to de-mineralize. In summary, SCI affects normal physiology well beyond the central nervous system.

III. Workshop Discussion

IIIA. TOOLS FOR EXTENDING BASIC UNDERSTANDING

Animal models

Although rats, cats, and lampreys provide powerful models for examining particular aspects of SCI, additional animal models are needed. Studies in larger animals, such as primates, are needed to mimic the human disorder more closely. Also, some researchers are turning to mouse models to take advantage of the recent revolution in genetics and the availability of mutant animals. The need for developing chronic models of injury was also stressed. The majority of current studies focus on acute SCI which do not reflect the status of the tens of thousands of patients who have lived with SCI for years.

Spinal cord circuitry

Circuitry maps describing functional connectivity within the normal spinal cord are greatly needed if we are to understand how the spinal cord is altered by injury. To address this need, one approach is the use of neurotropic viruses, such as the pseudorabies and herpes simplex viruses, which invade permissive cells, replicate, and move to infect other neurons tran-synaptically, that is, from one neuron to the next connected by active synapses. The viruses act as self-amplifying tracers that light up specific pathways or circuits. Viral strains vary in their direction of motion - retrograde or anterograde - and in their ability to infect different classes of neurons. By choosing the appropriate viral strains, it is possible to map a wide variety of neuronal circuits.

Reginald Edgerton applied this technique to compare the connections of soleus motor neurons between healthy controls and injured animals. By back-label motor neurons from identified muscles, he found that the virus spread to more neurons in injured animals than in healthy controls. The increased distribution may be due to the establishment of new synapses through sprouting as a result of the injury, or to the appearance of gap junctions between motor neurons. Other groups have observed the formation of gap junctions between lumbar spinal motor neurons in the adult cat following injury to the peripheral nerve. This electrical coupling may be a compensatory or protective mechanism that helps keep motor neurons alive until they reestablish synaptic connections.

Lea Ziskind-Conhaim is employing a different method - optical imaging - to examine spinal cord circuitry. To understand how the CPG is set up during development, she uses voltage-sensitive dyes and large arrays of photo detectors to monitor the simultaneous activities of large groups of neurons in real-time. Both sides of the cord fire in synchrony early in development, but begins to fire in alternating bursts at the time when descending fibers arrive from the brain and when afferent, sensory inputs arrive from the periphery. This correlation suggests that these inputs, from the brain and/or from the periphery, influence the endogenous pacemaker circuits in the cord. She plans to use semi-intact preparations, including the brainstem, spinal cord, and hindlimbs, to dissect the system’s functional modules in a systematic fashion, and identify the regions of the spinal cord where oscillations originate. Finally, she will extend her imaging findings with electrical recordings to pinpoint the individual neurons involved in the process.

IIIB. THERAPEUTIC STRATEGIES

a. Replacing cell activity

Cell transplantation is one of the strategies that could help replace lost function in SCI. Animal studies have shown that multipotent neural progenitors and stem cells can integrate into the central nervous system and restore function. For example, stem cells have been used to replace damaged cerebellar Purkinje neurons in mice. Ongoing research suggests that multipotent cells can also be used to replace genes and provide neuroprotective molecules, such as growth factors. Using genetic engineering, it is possible to create stem cells that package and produce vectors carrying specific genes, or create cells that synthesize and secrete the products of inserted genes.

Although less versatile, electrodes offer a potentially safer alternative for restoring lost function because they can be controlled more easily. The time, place, magnitude, and polarity of stimulating currents can be regulated with great precision. Recording electrodes can also be used as sensors to provide feedback for modulating the activities of stimulating electrodes. If spinal cord primitives are identified in humans, a few strategically positioned electrodes could, in principle, control and produce a variety of complex motions, including those involved in locomotion.

Graham Creasey explained that electrical prostheses to directly stimulate bladder and sphincter muscles, or their motor neurons, already provide some control for micturition. Although the prostheses can’t coordinate the timing of contractions as precisely as uninjured circuits, they can generate out-of-phase contractions that allow voiding or emptying of the bladder. Because the muscle wall of the bladder contracts at a slower but more sustained rate than the sphincter that prevents release, a somatic nerve reflex can be used to achieve voluntary control of voiding. The somatic efferent is surgically connected to the bladder to trigger micturition by a voluntary act, such as scratching a limb. Identification of a primitive that drives micturition allow the design of potentially even better solutions. William Agnew showed that micturition can be induced with a single, unilateral electrode implanted near the central canal in sacral levels of the cord in normal, anesthetized cats.

Despite these promising results, electrodes have drawbacks. One challenge is to keep them anchored for extended periods of time. In addition, the cables that connect the electrodes to the stimulating and recording devices are cumbersome. Finally, the process of inserting electrodes causes tissue damage and the connective tissue that ultimately encapsulates them can block their function.

Many of these problems have been reduced and new advantages have been gained by the development of microelectrode arrays. Using photo-lithographic technologies adopted from the semiconductor industry, McCreery and others are creating microelectrodes with stimulation radii as small as ten microns that are capable of stimulating single neurons. Since each probe can hold multiple electrodes, a single array can stimulate several sites simultaneously, and the number of wires can be drastically reduced. Because of their increased stability, the arrays are also better than conventional electrodes for long-term applications. Once an array has been designed and optimized, its mass production is easy and cheap. McCreery is now trying to improve the arrays using new materials to make electrodes that are stiffer, longer and more slender; these properties should increase stability and reduce the trauma induced by penetration.

b. Regeneration

Growth factors can be powerful tools for repairing the nervous system because they protect neurons against death and induce them to sprout or regenerate. By administering NT-3, Mark Tuszynski obtained partial recovery of function after a selective lesion of the corticospinal tract. To avoid inducing sprouting in unaffected areas and provide some guidance in regeneration, this approach could be combined with genetic engineering to control local expression of growth factors, or conversely, to down-regulate growth factor receptors in non-target areas. The development of increasingly small, hollow microelectrodes for the targeted delivery of minute volumes may also help localize the effects of specific growth factors. Pico- and nano-liter pumps, with no moving parts, could allow further control by providing both localized and time-regulated delivery.

Protecting neurons and encouraging them to sprout are not the only challenges in promoting regeneration. Cut nerve fibers in the central nervous system often sprout spontaneously, but fail to elongate along their original pathways. Inhibitory factors on the surface of glial cells and in the extracellular matrix contribute to an environment that is inhospitable for regeneration. In contrast, neurons in the peripheral nervous system are capable of retracing their paths and restoring proper connections. Several researchers are attempting to repair injured spinal cords by transplanting segments of peripheral nerve or Schwann cells cultured from peripheral nerves as scaffolding or paths for axons to use. Although these efforts have allowed cut nerve fibers from the spinal cord to regenerate into the transplants, the fibers fail to leave the transplants and re-enter the host nervous system.

An alternate approach was described by Almudena Ramon-Cueto. Noting that neurons in the mammalian olfactory bulb are able to elongate and connect with their targets in adulthood, she transplanted olfactory ensheathing glial cells to promote regeneration in the cord. In contrast to peripheral grafts, the olfactory glia allowed axons of injured central neurons in rats to elongate for long distances well into the segments of the cord caudal to the lesion, accompanied by a striking recovery of function. Paraplegic rats regained locomotor and sensimotor reflexes and were able to move their hindlimbs voluntarily, and respond to touch and propioceptive stimuli applied to their hindlimbs.

c. Retraining

For the past 25 years, rehabilitation practices have focused on compensation rather than recovery. Assistive devices have been used to supplement visible functions - mostly intact voluntary movements - but little effort has been directed at understanding and exploiting the nervous system’s capacity for retraining. Recent work has greatly enhanced rehabilitation strategies by demonstrating how weight-loading and propioceptive feedback can lead to recovery of locomotor function.

A team led by Edgerton discovered that mammals with thoracic transections of the spinal cord could relearn to step on a treadmill when they experienced the sensory input normally associated with stepping. They then extended these studies to humans and examined the role of sensory information in modifying the motor patterns of patients suffering from SCI. Using various levels of “loading”, they analyzed the movements and electrical activities of the patients’ leg muscles during assisted-stepping on a treadmill with body weight support. As suggested by the animal studies, they concluded that weight-loading provides cues that enable the human spinal cord to correct its output in a way that helps stepping.

The results also indicated that traditional rehabilitation practices could be optimized. When a patient is asked to move a joint voluntarily and produces a very low electromyographic response, physicians typically assume that the function is lost, and try to compensate for it with assistive devices. Yet the treadmill studies show that several of these patients can generate robust electromyographic responses when they receive appropriate sensory feedback. Susan Harkema, Bruce Dobkin, Edgerton, and others have applied these findings to retrain the spinal cords of SCI patients, and have, in many cases, succeeded in improving their locomotion.

Edgerton is now exploring the use of robotic training devices to make training more consistent, and to tailor the procedure to the evolving conditions of individual patients. Robotic devices could allow physicians to control critical parameters, such as weight-loading and stepping-speed, accurately and reproducibly. In addition, these devices could help to track patients’ progress quantitatively. Paritcipants also noted the possibility of using microelectrode arrays to directly retrain neural circuits.

d. Combination therapies

Most participants predicted that the path to successful treatments would involve a combination of approaches, as illustrated by the work of Hugues Barbeau. He trained spinalized cats on a treadmill after injecting them with the noradrenergic alpha-2 agonist, clonidine. Although clonidine enhances locomotion for only 4-6 hours after administration, it creates a permissive state during which training is much more effective. Consequently, they were able to reduce the three week process of teaching spinalized cats to walk to approximately six days.

Beyond creating permissive states, a combinatorial approach can bolster specificity. Combining electrical stimulation with growth factors, for example, could allow selective modulation of targeted cell populations. Combining cell transplantation with growth factors or anti-myelin antibodies could enhance local regeneration.

IV. Workshop Conclusions and Recommendations

Participants discussed how to strike a balance between accelerated paths that could lead to therapy and careful, robust pre-clinical research, and proposed the following recommendations for advancing SCI research:

IVA. THERAPEUTIC PRIORITIES

a. Promote therapies in advanced stages of development

Findings on weight-bearing training and proprioceptive feedback should be incorporated into rehabilitation regimens and practices. An intermediary phase in clinical trials in which the effects of new candidate therapies are tested in combination with more established approaches, such as retraining rehabilitation should be encouraged.

b. Increase focus on the more tractable problems of SCI

Most SCI research has focused on locomotion -one of the most complex functions affected by SCI. Re-directing some efforts towards more tractable problems, such as micturition and blood pressure control, could yield quicker and more tangible results.

c. Increase focus on patient priorities

Most research efforts have focused on locomotion as an outcome, even though patients often rank sexual dysfunction, bladder control and bowel control as their most immediate and pressing problems. To improve communication, patients could be invited on grant-awarding advisory boards. Setting up websites to foster discussions is another possibility. In addition, private foundations could conduct surveys of the patient population to help establish patient priorities, which could then help governmental funding agencies set priorities.

d. Test candidate therapies for dysfunctional side-effects

Participants criticized some ongoing efforts that apply experimental findings to humans before they have been tested thoroughly in animals. Given the unpredictability of the spinal cord’s responses to injury and the potential for eliciting dysfunctional changes, it is crucial to require comprehensive pre-clinical studies before conducting clinical trials. It will also be important to determine the critical time periods for each candidate therapy.

e. Develop objective and quantitative outcome measurements.

Creating adequate outcome measurements for humans was considered a top priority. Three basic approaches were identified as potential candidates: 1) the use of imaging technologies - including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET)– to track changes in the activity of the brain and spinal cord, 2) electrophysiological monitoring, including the use of electromyograms and microelectrode arrays, and 3) the use of robotic devices to measure movement trajectories, speed of movements, and degree of weight bearing.

IVB. BASIC SCIENCE PRIORITIES

a. Elucidate key components of spinal cord circuitry

The development of neural prostheses and rehabilitation regimens will require a better understanding of the normal circuitry of the spinal cord. For example, understanding how the CPG is linked to cortical and sensory inputs should help guide the development of prostheses with feedback systems, and help optimize the sensory stimuli used for rehabilitation. In addition, identifying movement primitives in human and non-human primates could aid the development of prostheses that trigger complex behaviors, such as locomotion. If the primitives exist, determining how they are regulated by sensory and supraspinal inputs will also be necessary to develop appropriate feedback devices.

A relatively new area of research is to understand the contribution of trophic- and activity-dependent influences between neurons within a circuit, and how these factors establish, maintain and modulate function. There has been few studies investigating structural re-modeling in the spinal cord; this is an important mechanism of plasticity in other areas of the nervous system, such as the hippocampus. Finally, understanding the development of spinal cord circuitry, including the establishment of the CPG, during embryogenesis and neonatal life should help reveal the developing cord’s capacity for change, and how this becomes limited in adulthood.

b. Identify areas of cross-fertilization between SCI and space physiology

Astronauts exposed to microgravity suffer from physiological alterations that resemble those experienced by patients with SCI, including muscle atrophy, bone loss, disruption of locomotion and coordination, and impairment of functions regulated by the autonomic system. Although astronauts suffer from a mostly reversible and milder degree of the symptoms, the similarities are significant enough to suggest that both areas of research could benefit from each other’s findings and therapeutic developments.

For example, one of Edgerton’s recent space flight studies suggests that alterations that occur during spaceflight may also occur in SCI. He found that the control of motor pools changes in response to changes in weight-bearing activity. After exposure to microgravity for 14 days, rhesus monkeys showed adaptations in the tendon force and electromyographic amplitude ratios of different muscles, indicating that their patterns of muscle recruitment were reorganizing. Since SCI also involves changes in weight-bearing activity, it is possible that motor output in SCI is affected by similar reorganizations of muscle recruitment.

c. Support projects that avoid conflicts over intellectual property rights

Collaborations can fall apart when researchers perceive a risk of losing their intellectual rights to a new discovery or invention. Although it is impossible to predict the exact evolution of a project, the probability of establishing successful collaborations could be increased by setting up projects where the roles of each team were clearly defined from the outset, and competitive overlap was minimized.

Provided by

National Institute of Neurological Disorders and Stroke

http://www.ninds.nih.gov/news_and_events/proceedings/spinalcircuitrywkshp.htm

You’re working at your desk, trying to ignore the tingling or numbness you’ve had for months in your hand and wrist. Suddenly, a sharp, piercing pain shoots through the wrist and up your arm. Just a passing cramp? More likely you have carpal tunnel syndrome, a painful progressive condition caused by compression of a key nerve in the wrist.

What is carpal tunnel syndrome?

Carpal tunnel syndrome occurs when the median nerve, which runs from the forearm into the hand, becomes pressed or squeezed at the wrist. The median nerve controls sensations to the palm side of the thumb and fingers (although not the little finger), as well as impulses to some small muscles in the hand that allow the fingers and thumb to move. The carpal tunnel - a narrow, rigid passageway of ligament and bones at the base of the hand - houses the median nerve and tendons. Sometimes, thickening from irritated tendons or other swelling narrows the tunnel and causes the median nerve to be compressed. The result may be pain, weakness, or numbness in the hand and wrist, radiating up the arm. Although painful sensations may indicate other conditions, carpal tunnel syndrome is the most common and widely known of the entrapment neuropathies in which the body’s peripheral nerves are compressed or traumatized.

What are the symptoms of carpal tunnel syndrome?

Symptoms usually start gradually, with frequent burning, tingling, or itching numbness in the palm of the hand and the fingers, especially the thumb and the index and middle fingers. Some carpal tunnel sufferers say their fingers feel useless and swollen, even though little or no swelling is apparent. The symptoms often first appear in one or both hands during the night, since many people sleep with flexed wrists. A person with carpal tunnel syndrome may wake up feeling the need to “shake out” the hand or wrist. As symptoms worsen, people might feel tingling during the day. Decreased grip strength may make it difficult to form a fist, grasp small objects, or perform other manual tasks. In chronic and/or untreated cases, the muscles at the base of the thumb may waste away. Some people are unable to tell between hot and cold by touch.

What are the causes of carpal tunnel syndrome?

Carpal tunnel syndrome is often the result of a combination of factors that increase pressure on the median nerve and tendons in the carpal tunnel, rather than a problem with the nerve itself. Most likely the disorder is due to a congenital predisposition - the carpal tunnel is simply smaller in some people than in others. Other contributing factors include trauma or injury to the wrist that cause swelling, such as sprain or fracture; overactivity of the pituitary gland; hypothyroidism; rheumatoid arthritis; mechanical problems in the wrist joint; work stress; repeated use of vibrating hand tools; fluid retention during pregnancy or menopause; or the development of a cyst or tumor in the canal. In some cases no cause can be identified.

There is little clinical data to prove whether repetitive and forceful movements of the hand and wrist during work or leisure activities can cause carpal tunnel syndrome. Repeated motions performed in the course of normal work or other daily activities can result in repetitive motion disorders such as bursitis and tendonitis. Writer’s cramp - a condition in which a lack of fine motor skill coordination and ache and pressure in the fingers, wrist, or forearm is brought on by repetitive activity - is not a symptom of carpal tunnel syndrome.

Who is at risk of developing carpal tunnel syndrome?

Women are three times more likely than men to develop carpal tunnel syndrome, perhaps because the carpal tunnel itself may be smaller in women than in men. The dominant hand is usually affected first and produces the most severe pain. Persons with diabetes or other metabolic disorders that directly affect the body’s nerves and make them more susceptible to compression are also at high risk. Carpal tunnel syndrome usually occurs only in adults.

The risk of developing carpal tunnel syndrome is not confined to people in a single industry or job, but is especially common in those performing assembly line work - manufacturing, sewing, finishing, cleaning, and meat, poultry, or fish packing. In fact, carpal tunnel syndrome is three times more common among assemblers than among data-entry personnel. A 2001 study by the Mayo Clinic found heavy computer use (up to 7 hours a day) did not increase a person’s risk of developing carpal tunnel syndrome.

During 1998, an estimated three of every 10,000 workers lost time from work because of carpal tunnel syndrome. Half of these workers missed more than 10 days of work. The average lifetime cost of carpal tunnel syndrome, including medical bills and lost time from work, is estimated to be about $30,000 for each injured worker.

How is carpal tunnel syndrome diagnosed?

Early diagnosis and treatment are important to avoid permanent damage to the median nerve. A physical examination of the hands, arms, shoulders, and neck can help determine if the patient’s complaints are related to daily activities or to an underlying disorder, and can rule out other painful conditions that mimic carpal tunnel syndrome. The wrist is examined for tenderness, swelling, warmth, and discoloration. Each finger should be tested for sensation, and the muscles at the base of the hand should be examined for strength and signs of atrophy. Routine laboratory tests and X-rays can reveal diabetes, arthritis, and fractures.

Physicians can use specific tests to try to produce the symptoms of carpal tunnel syndrome. In the Tinel test, the doctor taps on or presses on the median nerve in the patient’s wrist. The test is positive when tingling in the fingers or a resultant shock-like sensation occurs. The Phalen, or wrist-flexion, test involves having the patient hold his or her forearms upright by pointing the fingers down and pressing the backs of the hands together. The presence of carpal tunnel syndrome is suggested if one or more symptoms, such as tingling or increasing numbness, is felt in the fingers within 1 minute. Doctors may also ask patients to try to make a movement that brings on symptoms.

Often it is necessary to confirm the diagnosis by use of electrodiagnostic tests. In a nerve conduction study, electrodes are placed on the hand and wrist. Small electric shocks are applied and the speed with which nerves transmit impulses is measured. In electromyography, a fine needle is inserted into a muscle; electrical activity viewed on a screen can determine the severity of damage to the median nerve. Ultrasound imaging can show impaired movement of the median nerve. Magnetic resonance imaging (MRI) can show the anatomy of the wrist but to date has not been especially useful in diagnosing carpal tunnel syndrome.

How is carpal tunnel syndrome treated?

Treatments for carpal tunnel syndrome should begin as early as possible, under a doctor’s direction. Underlying causes such as diabetes or arthritis should be treated first. Initial treatment generally involves resting the affected hand and wrist for at least 2 weeks, avoiding activities that may worsen symptoms, and immobilizing the wrist in a splint to avoid further damage from twisting or bending. If there is inflammation, applying cool packs can help reduce swelling.

Non-surgical treatments

Drugs - In special circumstances, various drugs can ease the pain and swelling associated with carpal tunnel syndrome. Nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen, and other nonprescription pain relievers, may ease symptoms that have been present for a short time or have been caused by strenuous activity. Orally administered diuretics (”water pills”) can decrease swelling. Corticosteroids (such as prednisone) or the drug lidocaine can be injected directly into the wrist or taken by mouth (in the case of prednisone) to relieve pressure on the median nerve and provide immediate, temporary relief to persons with mild or intermittent symptoms. (Caution: persons with diabetes and those who may be predisposed to diabetes should note that prolonged use of corticosteroids can make it difficult to regulate insulin levels. Corticosterioids should not be taken without a doctor’s prescription.) Additionally, some studies show that vitamin B⁶ (pyridoxine) supplements may ease the symptoms of carpal tunnel syndrome.

Exercise - Stretching and strengthening exercises can be helpful in people whose symptoms have abated. These exercises may be supervised by a physical therapist, who is trained to use exercises to treat physical impairments, or an occupational therapist, who is trained in evaluating people with physical impairments and helping them build skills to improve their health and well-being.

Alternative therapies - Acupuncture and chiropractic care have benefited some patients but their effectiveness remains unproved. An exception is yoga, which has been shown to reduce pain and improve grip strength among patients with carpal tunnel syndrome.

Surgery

Carpal tunnel release is one of the most common surgical procedures in the United States. Generally recommended if symptoms last for 6 months, surgery involves severing the band of tissue around the wrist to reduce pressure on the median nerve. Surgery is done under local anesthesia and does not require an overnight hospital stay. Many patients require surgery on both hands. The following are types of carpal tunnel release surgery:

Open release surgery, the traditional procedure used to correct carpal tunnel syndrome, consists of making an incision up to 2 inches in the wrist and then cutting the carpal ligament to enlarge the carpal tunnel. The procedure is generally done under local anesthesia on an outpatient basis, unless there are unusual medical considerations.

Endoscopic surgery may allow faster functional recovery and less postoperative discomfort than traditional open release surgery. The surgeon makes two incisions (about ½” each) in the wrist and palm, inserts a camera attached to a tube, observes the tissue on a screen, and cuts the carpal ligament (the tissue that holds joints together). This two-portal endoscopic surgery, generally performed under local anesthesia, is effective and minimizes scarring and scar tenderness, if any. One-portal endoscopic surgery for carpal tunnel syndrome is also available.

Although symptoms may be relieved immediately after surgery, full recovery from carpal tunnel surgery can take months. Some patients may have infection, nerve damage, stiffness, and pain at the scar. Occasionally the wrist loses strength because the carpal ligament is cut. Patients should undergo physical therapy after surgery to restore wrist strength. Some patients may need to adjust job duties or even change jobs after recovery from surgery.

Recurrence of carpal tunnel syndrome following treatment is rare. The majority of patients recover completely.

How can carpal tunnel syndrome be prevented?

At the workplace, workers can do on-the-job conditioning, perform stretching exercises, take frequent rest breaks, wear splints to keep wrists straight, and use correct posture and wrist position. Wearing fingerless gloves can help keep hands warm and flexible. Workstations, tools and tool handles, and tasks can be redesigned to enable the worker’s wrist to maintain a natural position during work. Jobs can be rotated among workers. Employers can develop programs in ergonomics, the process of adapting workplace conditions and job demands to the capabilities of workers. However, research has not conclusively shown that these workplace changes prevent the occurrence of carpal tunnel syndrome.

What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health, is the federal government’s leading supporter of biomedical research on neuropathy, including carpal tunnel syndrome. Scientists are studying the chronology of events that occur with carpal tunnel syndrome in order to better understand, treat, and prevent this ailment. By determining distinct biomechanical factors related to pain, such as specific joint angles, motions, force, and progression over time, researchers are finding new ways to limit or prevent carpal tunnel syndrome in the workplace and decrease other costly and disabling occupational illnesses.

Randomized clinical trials are being designed to evaluate the effectiveness of educational interventions in reducing the incidence of carpal tunnel syndrome and upper extremity cumulative trauma disorders. Data to be collected from a National Institute for Occupational Safety and Health-sponsored study of carpal tunnel syndrome among construction workers will provide a better understanding of the specific work factors associated with the disorder, furnish pilot data for planning future projects to study its natural history, and assist in developing strategies to prevent its occurrence among construction and other workers. Other research will discern differences between the relatively new carpal compression test (in which the examiner applies moderate pressure with both thumbs directly on the carpal tunnel and underlying median nerve, at the transverse carpal ligament) and the pressure provocative test (in which a cuff placed at the anterior of the carpal tunnel is inflated, followed by direct pressure on the median nerve) in predicting carpal tunnel syndrome. Scientists are also investigating the use of alternative therapies, such as acupuncture, to prevent and treat this disorder.

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 or the Law Firm of Attorney Vaughn Wamnsley. 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.

Provided By

National Institute of Neurological Disorders and Stroke

http://www.ninds.nih.gov/disorders/carpal_tunnel/detail_carpal_tunnel.htm

“Carpal Tunnel Syndrome Fact Sheet,” NINDS. Publication date November 2002.
NIH Publication No. 03-4898

The paperwork arrives on my desk, containing pertinent information about my clients scheduled for the day’s evaluations. In the packet are the intake forms, name, address, and phone number, referring physician, dates of intake interview, the interviewer’s notes, and important medical record history. The routine is familiar and one that I engage in with ease. I open the chart for review and begin preparing for my portion of the interview and professional assessment.

I am a physical therapist working with a team of highly skilled professionals. My 20 years of experience helping folks with chronic pain combine with the 12 years of my desk partner, an occupational therapist. Across the hall is the private office of the psychologist on my team, who has more than 25 years in physical restorative rehabilitation and pain management. He even managed another pain clinic earlier in his career. The biofeedback therapist has her office just steps from my desk. The pharmacist, with 15 years in pain control under his belt, is located just down the hall.

All this superior education and expertise would not matter much if it were simply dry and clinical and adding the numbers together. But I have the enormous privilege of standing with my co-workers, learning from them, problem-solving with them, and sometimes engaging in confronting discussions with them. I know them to be incredibly caring, sensitive, hard-working, creative and knowledgeable professionals. Each one is willing to rise to the challenge, to come alongside our clients who are asking for help and relief from the experience of chronic pain. We blend and work together like a well-oiled machine, empowering our clients along the way. Nearly 60 percent of our clients, incidentally, have been diagnosed with fibromyalgia or chronic pain syndrome.

Take a “typical” client, “Gayle.”

Gayle learned about our program from a brochure at her doctor’s office. She had to ask him to write the referral; he wasn’t reluctant, but he hadn’t thought about therapy as an option anymore. After all, Gayle had had physical therapy for many sessions, and all she did was hurt more. But the additional services we offer, like biofeedback, seemed different—and all the therapies would take place in the same general clinic. It seemed like a worthwhile try.

Gayle called us and the receptionist arranged for an interview appointment with the program coordinator—odd, Gayle thought, since no other clinics had “interviewed” her. When she actually met with the Program Coordinator, she was asked to tell her story of developing chronic pain. Then she toured the clinic. She left the meeting after making an appointment with one of the managing physicians of this team of professionals.  She didn’t know whether she was going to receive treatment, but she was willing to go through the process.  What did she have to lose?

When she met the physician, he reviewed her medical records, inquired about various tests she’d already had, performed his own physical examination, and explained the next step: Gayle was to go through a three and one-half hour interview with the rest of the treatment team. That length of evaluation process seemed almost impossible to imagine since she could only stay up three hours at a time. How could she get through it without severe pain increase? She mentioned her limited endurance to the scheduler, and the assessment was arranged to occur over two days instead of one.

So Gayle met each professional individually. To the pharmacist she gave her medication history and a list of her current meds; the psychologist gained her trust as he listened to her feelings and information about relationships; the occupational therapist asked questions about time management and how she arranged her day, and the physical therapist examined her physical function. The whole process culminated in a team meeting, where they planned the next step to help her learn to manage the chronic pain that was controlling her life. There were no guarantees, but she knew by now not to expect any. Gayle was ready to take on the task of learning to make changes. The pain was not going to win!

I would never claim to truly understand what fibromyalgia sufferers must feel or go through, since I have not experienced that kind of invasion in my life, but I can tell you that teaching them pain control skills and nurturing their success is like watching a miracle unfold.  People who have experienced their lives shrinking so small that a trip to the grocery store is a big deal, or an outing to a restaurant with friends is unthinkable—these are my typical clients.

The miracle begins with the person suffering from fibromyalgia daring to dream what life could be like if pain were controlled. The dream takes hold. Then they act on that dream, one small step at a time, with a little support from those who care, education from those who teach, and skills honed by practice.

It is like watching a butterfly emerge from his claustrophobic cocoon. With consistent and focused determination to practice pain control skills, life takes shape and colorful wings begin to unfold. It is an enormous privilege to see this miracle of people “getting their life back”—each person in his own way, according to his own dream.

My colleagues and I are well aware that if you cannot feel, think and taste what life may look like with pain controlled, the battle is so much harder. We work hard at helping you see your own vision, and then support you to take the risk to get there.

Elaine Larson, PT, DPT, works at St Jude Medical Center in Fullerton, California. You can reach her team by calling administrative assistant Shelley Labs at (714) 446-5661.

This article was provided by the National Fibromyalgia Association. For more information, visit www.fmaware.org.

So, you’ve broken a bone. Only those who have experienced a fracture can truly understand how painful and debilitating it can be. Recovering should be your first priority. However, you and your doctor also will want to determine whether this fracture is a symptom of osteoporosis. If you have this underlying disorder, it puts you at greater risk for future fractures. If you are age 50 or older, there is a very good chance your fracture is related to osteoporosis. This fact sheet will help you better understand the relationship between fracture and osteoporosis, so you can take action now to strengthen and protect your bones.

Many people are unaware of the link between a broken bone and osteoporosis. Osteoporosis, or “porous bone,” is a disease characterized by low bone mass. It makes bones fragile and more prone to fractures, especially the bones of the hip, spine, and wrist. Osteoporosis is called a “silent disease” because bone loss occurs without symptoms. People typically do not know that they have osteoporosis until their bones become so weak that a sudden strain, twist, or fall results in a fracture.

Osteoporosis is a major public health threat for an estimated 44 million Americans, 68 percent of whom are women. In the United States today, approximately 10 million people already have the disease and nearly 34 million more are believed to have low bone mass, which leaves them at increased risk for osteoporosis. Of the 10 million Americans estimated to already have osteoporosis, 8 million are women and 2 million are men.

One in two women and one in four men will have an osteoporosis-related fracture in their lifetime. At least 90 percent of all hip and spine fractures among older white women can be attributed to underlying bone fragility. Moreover, women near or past menopause who have sustained a fracture in the past are twice as likely to experience another fracture. Yet, unfortunately, only 5 percent of patients with osteoporotic fractures are referred for an osteoporosis evaluation and medical treatment.

• The Osteoporosis Evaluation
• Strategies to Reduce Your Risk of Fractures
• Where can I go for more information?

The Osteoporosis Evaluation

I’ve already had a fracture. Is it too late to talk to my doctor about osteoporosis?
It is never too late. Ideally, you should talk to your doctor during your recovery about whether you might be a candidate for an osteoporosis evaluation. But even if your fracture has healed, you can be evaluated and begin taking steps to protect your bones now.

What kind of doctor should I see about getting an osteoporosis evaluation?
Many different kinds of doctors can evaluate and treat osteoporosis. Start with your primary care doctor or the doctor treating your fracture. He or she probably can conduct the evaluation and may then refer you to a specialist, such as an endocrinologist or rheumatologist, if you require treatment.

What does an osteoporosis evaluation involve?
One thing your doctor will do is ask about your medical history and lifestyle to determine whether you have risk factors for osteoporosis. Some of the factors that increase the risk of developing osteoporosis include personal or family history of fractures; low levels of the hormone estrogen or testosterone; and the use of certain medications, such as glucocorticoids or anti-seizure medications, that may contribute to bone fragility. Your doctor also may want to test your blood or urine and may suggest that you have a bone mineral density test.

What is a bone mineral density test? Is it painful?
A bone mineral density (BMD) test is the best way to determine your bone health. This test can identify osteoporosis, determine your risk for fractures (broken bones), and measure your response to osteoporosis treatment. The most widely recognized BMD test is called a dual-energy x-ray absorptiometry, or DXA test. The test is safe and painless, a bit like having an x ray, but with much less exposure to radiation. It can measure bone density at your hip and spine and takes only 15 minutes to complete. For a DXA test, you will be asked to lie on a table while a machine above you measures your bone density.

Some private insurance plans will cover BMD tests ordered by your doctor. Medicare also may pay for a BMD test under certain circumstances for women and men age 65 or older. Your doctor and his or her office staff can help you determine if Medicare will cover a BMD test for you.

Strategies to Reduce Your Risk of Fractures

If I am diagnosed with osteoporosis, what should I do next?
You may feel concerned or even frightened after being diagnosed with osteoporosis. However, the good news is that, armed with information and the support of your doctor, you can significantly improve your bone health and reduce your risk of future fractures with a combination of medication, diet, exercise, and lifestyle modifications.

Some of my friends take medication for osteoporosis. Should I consider this?
Yes. Several medications are available to prevent and treat osteoporosis. These products have been proven effective at minimizing additional bone loss and reducing fracture risk. Your doctor can help you understand the benefits and risks of each of the following medications and select one that is right for you:

• bisphosphonate drugs: alendronate (Fosamax),¹ risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast)
• calcitonin (Miacalcin and Fortical)
• raloxifene (Evista), a selective estrogen receptor modulator (SERM)
• teriparatide (Forteo), a form of the parathyroid hormone (PTH), which is secreted by the parathyroid glands
• estrogen therapy (also called hormone therapy when estrogen and another hormone, progestin, are combined).

¹ Brand names included in this publication are provided as examples only, and their inclusion does not mean that these products are endorsed by the National Institutes of Health or any other Government agency. Also, if a particular brand name is not mentioned, this does not mean or imply that the product is unsatisfactory.

In men, reduced levels of testosterone may be linked to the development of osteoporosis. Men with abnormally low levels of testosterone may be prescribed testosterone replacement therapy to help prevent or slow bone loss.

What else can I do to protect my bones?
In addition to taking your medication, some of the most important things you can do are to follow a diet rich in calcium and vitamin D, maintain an adequate daily intake of protein, monitor your sodium intake, and get plenty of exercise.

• Calcium is needed to maintain healthy, strong bones throughout your life. Unfortunately, most Americans do not get enough calcium from their diets. Dairy products such as milk, cheese, and yogurt are excellent sources of calcium, and some nondairy foods such as broccoli, almonds, and sardines can provide smaller amounts. In addition, many foods that you may already enjoy - juices, breads, and cereals - can now be found fortified with calcium. Calcium supplements can ensure that you get enough calcium each day, especially in people with a proven milk allergy. The Institute of Medicine recommends a daily calcium intake of 1,000 mg (milligrams) for men and women, increasing to 1,200 mg for adults age 50 and older.

  Calcium supplements are available without a prescription in a wide range of preparations and strengths. Many people ask which calcium supplement they should take. The “best” supplement is the one that meets your needs based on tolerance, convenience, cost, and availability. In general, you should choose calcium supplements that are known brand names with proven reliability. Also, you will absorb calcium better if you take it several times a day in smaller amounts of 500 mg or less each time.

• Vitamin D plays a significant role in helping your body absorb calcium. The relationship between calcium and vitamin D is similar to that of a locked door and a key. Vitamin D is the key that unlocks the door, allowing calcium to enter your bloodstream. As we age, our bodies become less able to absorb calcium, which makes getting enough vitamin D even more important. The recommended daily intake for vitamin D is 400 to 600 IU (International Units). Many people get this amount through natural exposure to sunlight, which our bodies use to make vitamin D, and by consuming vitamin D-fortified foods such as milk. In addition, many calcium supplements are fortified with vitamin D.

• Sodium, a main component of table salt, affects our need for calcium by increasing the amount of it we excrete in urine. As a result, people with diets high in sodium, or table salt, appear to need more calcium than people with low-sodium diets to ensure that, on balance, they retain enough calcium for their bones.

• Protein in excess amounts also increases the amount of calcium we excrete in urine, but it provides benefits for bone health as well. For example, protein is needed for fracture healing. In addition, studies have shown that elderly people with a hip fracture who do not have enough protein in their diets are more likely to experience loss of independence, institutionalization, and even death after their fracture. The recommended daily intake for protein is 56 grams for men and 46 grams for women.

I’ve always been active, but I don’t want to risk breaking another bone. Maybe I need to spend more time “on the sidelines” from now on.
It is perfectly understandable that you want to avoid another fracture. No one who has broken a bone wants to revisit that pain and loss of independence. However, living your life “on the sidelines” is not an effective way to protect your bones. Remaining physically active reduces your risk of heart disease, colon cancer, and type 2 diabetes. It may also protect you against prostate and breast cancer, high blood pressure, obesity, and mood disorders such as depression and anxiety. If that isn’t enough to convince you to stay active, consider this: exercise is one of the best ways to preserve your bone density and prevent falls as you age.

What type of exercise is best to reduce my risk of another fracture?
Exercise can reduce your risk of fracturing in two ways – by helping you build and maintain bone density and by enhancing your balance, flexibility, and strength, all of which reduce your chance of falling.

• Building and maintaining bone density: Bone is a living tissue that responds to exercise by becoming stronger. Just as a muscle gets stronger and bigger with use, a bone becomes stronger and denser when it is called upon to bear weight. Two types of exercise are important for building and maintaining bone density: weight-bearing and resistance. Weight-bearing exercises are those in which your bones and muscles work against gravity. Examples include walking, climbing stairs, dancing, and playing tennis. Resistance exercises are those that use muscular strength to improve muscle mass and strengthen bone. The best example of a resistance exercise is weight training, with either free weights or weight machines.
• Reducing the risk of falling: You can significantly reduce your risk of falling by engaging in activities that enhance your balance, flexibility, and strength.
  • Balance is the ability to maintain your body’s stability while moving or standing still. You can improve your balance with activities such as tai chi and yoga.
  • Flexibility refers to the range of motion of a muscle or group of muscles. You can improve your flexibility through tai chi, swimming, yoga, and gentle stretching exercises.
  • Strength refers to your body’s ability to develop and maintain strong muscles. Lifting weights will increase your strength.

Smart Moves

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  • Walking
  • Strength training
  • Dancing
  • Tai chi
  • Stair climbing
  • Hiking
  • Bicycling
  • Swimming
  • Gardening

How can I exercise safely if I have osteoporosis?
If you have osteoporosis, it is important for you to get plenty of exercise. However, you will need to choose your activities carefully. Be sure to avoid activities with a high risk of falling, such as skiing or skating; those that have too much impact, such as jogging and jumping rope; and those that cause you to twist or bend, such as golf.

Unfortunately, some people become so afraid of breaking another bone that they become more sedentary, which leads to further loss of bone and muscle. Rest assured, however, that by practicing proper posture and learning the correct way to move, you can protect your bones while remaining physically active. Every activity can be adapted to meet your age, ability, lifestyle, and strength. Your doctor or a physical therapist can help you design a safe and effective exercise program. In the meantime, here are some general guidelines for safe movement:

Don’t:

• wear shoes with slippery soles
• slouch when standing, walking, or sitting at a desk
• move too quickly
• engage in sports or activities that require twisting the spine or bending forward from the waist, such as conventional sit-ups, toe touches, or swinging a golf club.

Do:

• pay attention to proper posture. This includes lifting your breastbone, keeping your head erect and eyes forward, keeping your shoulders back, lightly “pinching” your shoulder blades, and tightening your abdominal muscles and buttocks.
• make sure to use a handrail when climbing stairs
• bend from the hips and knees and never from the waist, especially when lifting.

Before embarking on any exercise program, be sure to consult your doctor.

My fracture happened after I tripped on a rug in my own home. How can I prevent another fall?
Falls are a major source of fractures. The likelihood that you will fall depends on both personal and environmental factors.

·         Personal factors: A fall may occur because your reflexes have slowed over time, making them less able to react quickly to a sudden shift in body position. Loss of muscle mass may occur as you age, which can diminish your strength. Changes in vision and hearing can also affect your balance, as can the use of alcohol and certain medications. People with chronic illnesses that affect their circulation, sensation, mobility, or mental alertness are more likely to fall. To reduce your risk of falling, keep this personal safety checklist in mind:

Personal safety checklist

•  
  • Stay active to maintain muscle strength, balance, and flexibility.
  • Have your vision and hearing checked regularly and corrected as needed.
  • Discuss your medications with your doctor to see if one of them (or their combination) might lead to falls.

• Environmental factors: At any age, people can make changes in their environment to reduce their risk of falling and breaking a bone. The following safety checklists provide a few tips that should help:

Indoor safety checklist

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  • Use nightlights throughout your home.
  • Keep all rooms free from clutter, especially the floors.
  • Keep floor surfaces smooth but not slippery. When entering rooms, be aware of differences in floor levels and thresholds.
  • Wear supportive, low-heeled shoes even at home. Avoid walking around in socks, stockings, or floppy slippers.
  • Check that all carpets and area rugs have skid-proof backing or are tacked to the floor, including carpeting on stairs.
  • Keep electrical cords and telephone lines out of walkways.
  • Be sure that all stairways are well lit and that stairs have handrails on both sides. Consider placing fluorescent tape on the edges of top and bottom steps.
  • Install grab bars on bathroom walls beside tubs, showers, and toilets. If you are unstable on your feet, consider using a plastic chair with a back and nonskid leg tips in the shower.
  • Use a rubber bathmat in the shower or tub.
  • Keep a flashlight with extra batteries beside your bed.
  • Add ceiling fixtures to rooms lit only by lamps, or install lamps that can be turned on by a switch near the entrance to the room.
  • Use at least 100-watt light bulbs in your home.

Outdoor safety checklist

•  
  • In bad weather, consider using a cane or walker for extra stability.
  • In winter, wear warm boots with rubber soles for added traction.
  • Look carefully at floor surfaces in public buildings. Many floors are made of highly polished marble or tile that can be very slippery. When floors have plastic or carpet runners in place, try to stay on them whenever possible.
  • Use a shoulder bag, fanny pack, or backpack to leave hands free.
  • Stop at curbs to check height before stepping up or down. Be cautious at curbs that have been cut away to allow access for bikes or wheelchairs. The incline may lead to a fall.

What is hip padding? Should I consider it?
Research has shown that hip protectors can decrease the risk of hip fracture among people who are at high risk for falls. Most hip protectors are washable undergarments that fit over the hips. On each side of the garment is a thin layer of lightweight foam plastic. Hip protectors are typically worn by people who have an unstable stride or posture and by people who tend to fall down (with the main impact near the hip) rather than the more typical fall forward (with the main impact on the hands or knees).

However, studies have found that up to one-third of people refused to wear hip protectors or wore them for only limited periods.

Is there anything else I can do?
If you are a smoker, now would be a good time to quit. Tobacco is toxic to your bones, putting you at higher risk for low bone mass and osteoporosis. Excessive alcohol intake also may be damaging to your bones, and people who drink heavily tend to have more bone loss and fractures due to poor nutrition and an increased risk of falling.

Provided By

National Institute of Arthritis and Musculoskeletal and Skin Disease

http://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/Fracture/default.asp