Doctors Restore Some Hand Function to Quadriplegic Patient

Location of spinal cord damage allowed surgeons to bypass damaged nerve in arm

For the first time, surgeons have restored partial mobility to the hand of a quadriplegic patient.

The patient had suffered an injury to the lowest bone in his neck, and it was the specific location of the injury that allowed surgeons to avoid operating on the spine itself.

Instead, the team focused on the patient's still healthy upper arm nerves. Bypassing the hand's original (and now damaged) connection to the injured spine, the team effectively used the upper arm nerves to rewire a fresh connection to the intact motor control region of his brain.

A year of rigorous physical therapy later, the team of surgeons at Washington University School of Medicine in St. Louis reaped their reward: the restoration of the patient's ability to flex his thumb and index finger.

"This procedure is unusual for treating quadriplegia because we do not attempt to go back into the spinal cord where the injury is," surgeon Dr. Ida K. Fox, an assistant professor of plastic and reconstructive surgery, said in a news release from the university. "Instead, we go out to where we know things work -- in this case the elbow -- so that we can borrow nerves there and reroute them to give hand function."

Fox and her colleagues discuss the case in the May 15 online issue of the Journal of Neurosurgery.

The authors pointed out that their surgical approach would only be viable for patients like theirs: namely, those who sustain injury to the C7 (or C6) vertebra, located in the lower region of the neck. While such patients lose hand function, they retain function in their shoulder, elbow and wrist because the spinal region above the injury remains free of damage.

Those who suffer an injury to the C1 through C5 vertebra experience total arm function loss, and would not be eligible for this type of nerve bypass surgery, developed and performed by study senior author Dr. Susan E. Mackinnon, chief of the university's division of plastic and reconstructive surgery.

Mackinnon's initial goal had been more targeted: to restore thumb and index finger function to patients suffering from localized nerve damage. This is the first instance in which the approach was harnessed to overcome damage stemming from spinal cord injury.

The breakthrough, however, relies heavily on arduous post-surgical physical therapy, during which the patient's brain must be taught to recognize that the rewired nerves control the fingers rather than the elbow.

The good news: Any similarly injured patient with intact upper arm nerves would be eligible for this procedure, regardless of how much time has elapsed since the initial spinal cord damage. The current patient was operated on two years after his accident.

One expert explained why such surgery might work so long after a spinal cord injury.

"What this case demonstrated, and what is different from peripheral nerve-injured patients who undergo nerve grafts and nerve transfers, is that the motor neuron pool is intact and the muscle is preserved for a longer time than in peripheral nerve injury," said Dr. Lewis Lane, chief of hand surgery at North Shore University Hospital in Manhasset, N.Y. "If a peripheral nerve is cut, the lower motor neuron cell connection to the muscle is disrupted. However, in spinal cord injury the injury is, by definition, in the spinal cord, so the connection ... is not disrupted because peripheral nerves are intact.

"This connection is important for muscle preservation," Lane added, "and is the subtle but important distinction that allowed the procedure done on the patient in this case report to succeed more than 22 months after the injury."

The Washington University surgeons also noted that the procedure stood a good chance of success because of its simplicity.

"This is not a particularly expensive or overly complex surgery," Mackinnon said in the news release. "It's not a hand or a face transplant, for example. It's something we would like other surgeons around the country to do."

Dr. J. Marc Simard, a professor of neurosurgery, pathology and physiology at the University of Maryland School of Medicine in Baltimore, was excited about the success of the procedure.

"It's very important to caution that this applies only to those with spinal injuries far enough down on the spine that there are remnants of nerves that are still functional above the injury that can be tapped into," he noted.

"But, for these types of patients, this sounds perfectly reasonable and rational," Simard added, "based on the basic science work that's been going on for the last 25 years. And [it's] really a major step in the rehabilitation world."

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Bone Marrow May Hold Key to Stem Cell Breakthrough

PATIENTS suffering from spinal cord injury may soon find help in the form of stem cells drawn from their own bone marrow, thanks to a research project from the University of Western Australia.

UWA Associate Professor Stuart Hodgetts and PhD student Sarah Lovett are using human bone marrow stem cells (BMSCs) to promote an endogenous host response after spinal cord injury (SCI), by isolating stromal cells found in a patient’s own bone marrow and transplanting them back into the injury site in animal models.

A/Prof Hodgetts says the objective is to transplant these multipotent stromal stem cells into the spinal cord to promote the survival of existing neurons and improve repair at the injury site.

“We believe the donor BMSCs are responsible for producing an endogenous repair mechanism, essentially providing factors to help the host system repair itself. Our animal models have shown BMSCs promote good functional improvement beyond many other cell types used over the last 5–10 years,” he says.

Ms Lovett says the research does not specifically aim to differentiate BMSCs into neurons or supportive glial cells, but instead reduce the amount of secondary damage that occurs after the initial injury.

“We found BMSCs reduce inflammation in the injury site as well as reduce secondary damage. Also, while extracting cells from bone marrow might be regarded as an invasive procedure, it’s actually quite routine,” she says.

“If you can take bone marrow from an injured patient, after about 3 weeks’ culture you would have enough cells to transplant back into that person.”

Ms Lovett uses a contusion model in rats that best replicates the most common SCI in humans.

“The animals show good functional recovery if BMSCs are transplanted into the cord a week after injury. However, BMSCs are soon destroyed by the animal’s immune response against them,” she says.

Prof Hodgetts says part of the research is to modulate the immune response by inhibiting “TNF-alpha” molecules and “natural killer”, immune cells that may target the transplanted cells.

“Interestingly, within that window of four weeks, BMSCs are able to induce a response that markedly improves the locomotory ability of these animals.”

“If we can improve BMSC survival, we may be able to get them to further improve functional recovery for longer,” he says.

Prof Hodgetts’ Fellowship and this SCI research project is funded by the Neurotrauma Research Program of Western Australia.

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New Technique May Help Severely Damaged Nerves Regrow and Restore Function

Engineers at the University of Sheffield have developed a method of assisting nerves damaged by traumatic accidents to repair naturally, which could improve the chances of restoring sensation and movement in injured limbs.

In a collaborative study with Laser Zentrum Hannover (Germany) published April 23, 2012 in the journal Biofabrication, the team describes a new method for making medical devices called nerve guidance conduits or NGCs.

The method is based on laser direct writing, which enables the fabrication of complex structures from computer files via the use of CAD/CAM (computer aided design/manufacturing), and has allowed the research team to manufacture NGCs with designs that are far more advanced than previously possible.

Currently patients with severe traumatic nerve damage suffer a devastating loss of sensation and/or movement in the affected limb. The traditional course of action, where possible, is to surgically suture or graft the nerve endings together. However, reconstructive surgery often does not result in complete recovery.

"When nerves in the arms or legs are injured they have the ability to re-grow, unlike in the spinal cord; however, they need assistance to do this," said University of Sheffield Professor of Bioengineering, John Haycock. "We are designing scaffold implants that can bridge an injury site and provide a range of physical and chemical cues for stimulating this regrowth."

The new conduit is made from a biodegradable synthetic polymer material based on polylactic acid and has been designed to guide damaged nerves to re-grow through a number of small channels.

"Nerves aren't just like one long cable, they're made up of lots of small cables, similar to how an electrical wire is constructed," said lead author Dr Frederik Claeyssens, of the University's Department of Materials Science and Engineering. "Using our new technique we can make a conduit with individual strands so the nerve fibres can form a similar structure to an undamaged nerve."

Once the nerve is fully regrown, the conduit biodegrades naturally. The team hopes that this approach will significantly increase recovery for a wide range of peripheral nerve injuries.

In laboratory experiments, nerve cells added to the polymer conduit grew naturally within its channelled structure and the research team is now working towards clinical trials.

"If successful we anticipate these scaffolds will not just be applicable to peripheral nerve injury, but could also be developed for other types of nerve damage too. The technique of laser direct writing may ultimately allow production of scaffolds that could help in the treatment of spinal cord injury" said Dr Claeyssens.

"What's exciting about this work is that not only have we designed a new method for making nerve guide scaffolds which support nerve growth, we´ve also developed a method of easily reproducing them through micromolding.

"This technology could make a huge difference to patients suffering severe nerve damage," he added. This research was funded by the Engineering and Physical Sciences Research Council.

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MS Drug the Next Treatment for Spinal Cord Injuries?

A drug found to slow some of the physical problems and reduce the number of flareups of multiple sclerosis (MS) could also show promise for treating spinal cord injuries, according to a new Japanese study.

Researchers from the Jichi Medical University School of Medicine and the Universisty of Tokyo's Graduate School of Medicine found that FTY720, also known as Gilenya, helped mice with spinal cord injuries (SCIs) recover some motor function when they were given the drug immediately after the injuries.

FTY720 acts in a number of ways, the study authors wrote. The drug, provided by its manufacturer, Novartis, for this study, suppresses the immune system, which reduces inflammation that occurs after injuries. Inflammatory effects, they explained, can worsen the damage done by SCIs. The drug also helped the mice's damaged tissue regenerate, among other effects.

"The main biological activity responsible for these actions is believed to be immunological, but our data suggest that nonimmunological role(s) of FTY720 are also important in the treatment of SCI," they wrote.

The drug still needs to be evaluated in larger animals before determining whether it is effective in treating SCIs, but still has promise, the authors added.

Experts not involved with the study, however, are a bit more skeptical. Many interventions work in mice, so determining the utility of Gilenya for SCIs in humans is a long way off, if it happens at all.

"Another issue is that in this study, the drug was given immediately after the SCI, and rarely do we have the opportunity to give a drug immediately after this type of injury in humans," said W. Dalton Dietrich, professor and scientific director of the Miami Project to Cure Paralysis at the University of Miami's Miller School of Medicine. "One big question is if the drug delivery is delayed, will it work?"

Few Early Treatment Options Available

Studies have found that in some people, the steroid drug methylprednisolone has been effective at restoring a little bit of function if given within eight hours of injury.

But other drugs -- mostly experimental -- that clinicians have tried with post-SCI patients have not been particularly effective.

"Acutely, we really don't have any drugs to try to protect the nervous system," said Dr. Bruce Dobkin, director of the Neurologic Rehabilitation and Research Program at UCLA's Geffen School of Medicine. "The most important thing is rehabilitation."

"Right now, during the time right after an injury, we focus on providing good stabilization of the spinal cord, physiological monitoring and early spinal decompression surgery if it's appropriate," Dietrich said.

Despite more and more research into possible treatments for spinal cord injuries over the past decade or so, Dobkin said formerly promising options have not lived up to their hype.

"All the things we've done to try and improve walking haven't turned out to be that great, like robotics, electrical stimulation and other interventions," he said.

Newer therapies include the use of stem cells to rebuild damaged nerve pathways and the use of cooling shortly after spinal cord injuries.

"In more than 30 patients, we tried mild cooling in the emergency room after patients came in with spinal cord injuries, and in those patients, the therapy seems to be safe and to provide some improvement in function," Dietrich said.

Although few effective therapies are out there right now, experts are optimistic.

"It's hopeful that within five or 10 years, we will have a couple of interventions we can use early that will give people more function," Dobkin said.

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Surgery less than 24 hours after traumatic cervical spinal cord injury leads to improved outcomes

Researchers at the Rothman Institute at Jefferson have shown that patients who receive surgery less than 24 hours after a traumatic cervical spine injury suffer less neural tissue destruction and improved clinical outcomes. The results of their study, the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) are available in PLoS One.

"This practice-changing study is the first to show that the timing of surgery after traumatic spinal cord injury (SCI) matters," says Alexander Vaccaro, MD, PhD, professor of Orthopaedics and Neurosurgery at Jefferson Medical College of Thomas Jefferson University and attending surgeon at Thomas Jefferson University Hospital, the largest spinal cord injury center in the country.

The multicenter study recruited 313 patients; 182 of whom underwent surgery less than 24 hours after traumatic cervical SCI and 131 of whom underwent surgery at or after 24 hours post-SCI.

For both groups, the degree of neurologic improvement was measured by change in American Spinal Injury Association's (ASIA's) ASIA Impairment Scale (AIS). A two-grade improvement in AIS scores post-surgery was associated with improved neurologic outcomes. Baseline neurological assessments were performed within 24 hours of injury on all subjects.

A total of 222 patients were followed to six months post-surgery.

In the early surgery group (surgery performed less than 24 hours post-injury), 42.7 percent showed no improvement, 36.6 percent had a one grade improvement, 16.8 percent had a two-grade improvement and 3.1 percent had a three grade improvement. Comparatively, in the late surgery group (surgery performed at 24 hours or more post-injury), 50 percent showed no improvement, 40.7 percent had a one grade improvement and 8.8 percent had a two grade improvement.

"What this tells us is that the odds of a significant (at least two grade) improvement in neurologic status is 2.8 times higher when surgery is performed within 24 hours post-injury. This can be the difference between walking and not for the rest of one's life," says Vaccaro.

Complications occurred in 24.2 percent of early surgery patients versus 30.5 percent of late surgery patients.

"Previous research has been inconclusive on the issue, with the common thought among most surgeons that you can wait up to five days post-injury and have the same outcomes. We should not practice that way anymore armed with this new information," says Vaccaro.

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