WRNMMC Uses New, Brain-Controlled Prosthetic Arm

By Sarah Fortney, Walter Reed National Military Medical Center Public Affairs

Bethesda, Md. (NNS) -- A new prosthetic arm - operated by an individual's thoughts - was used by wounded warriors at the Walter Reed National Military Medical Center (WRNMMC) for the first time Jan. 24.

With nearly as much dexterity as a natural limb, 22 degrees of motion, and independent movement of fingers, the Modular Prosthetic Limb (MPL) was developed as part of a four-year program by the Johns Hopkins University Applied Physics Laboratory (APL), along with WRNMMC and the Uniformed Services University of the Health Sciences (USU). On Jan. 24, a wounded warrior began using the nine-pound device, maneuvering its metallic fingers and wrist.

"We've been working with [the APL] since the start of this project and we're very excited about the opportunity [to have] our first individual using this hand," said Col. (Dr.) Paul Pasquina, chief of Orthopaedics and Prosthetics at WRNMMC and director for the Center of Rehabilitation Sciences at USU. "We believe very strongly that those who are willing to put their lives in harm's way deserve the very best. Through this revolutionizing project, we've worked with the greatest manufacturers across the globe to come up with modern solutions to loss of an upper limb."

Pasquina explained the limb is controlled by surface electrodes, which pick up electric signals generated by the muscles underneath the skin, then convert those patterns in electrical signals into a robotic function.

"We wanted to make [the MPL] as intuitive as possible. Normally, when you move your hand, you think about moving your hand, and a signal comes down from your brain, goes down through your spinal cord, out through your limb and activates muscles in your hand to open or close [the hand]," Pasquina said.

With an amputee, the nerves traveling down the spinal cord are still intact, and they're still connected to some of the muscles in the arm, Pasquina said. "What we try to do is pick up the electrical signals of the muscles that still exist in the arm and interpret those, convert them to a computer signal to then drive a robotic limb," he said. "When an individual is thinking about closing their hand, muscles will activate and the prosthetic limb will respond accordingly."

Pasquina noted the potential future of this limb. Engineers seek to use electrodes underneath the skin for an electrical signal with much higher fidelity. Researchers also look to explore other mechanisms to rewire nerves.

"There are folks working very hard on electrical sensors that can go directly on nerves, and electrical sensors that can be embedded in the brain," he said. "It's very exciting to see that research and we've been privileged to partner with a lot of folks working on that. I think there's still a lot to be learned on how the human body can integrate with computers and computer interface, and I think the sky's the limit in terms of what we will do over the next five to ten years."

The next logical phase in the MPL's development is to incorporate sense of touch, and apply this technology to prosthetic legs in the future, said Cmdr. Jack Tsao, director of the Traumatic Brain Injury Programs for Navy Medicine's Bureau of Medicine and Surgery. A neurologist who also assisted in the project, Tsao said fortunately many amputees have expressed interest and seem willing to participate and help advance this research.

"What I think is fantastic is that we actually, because of this study, now have another option to treat amputees," said Tsao.

Before being fitted to use the device, Tsao explained amputees must first go through "training," using the Virtual Integrated Environment (VIE), which records an individual's muscle movements. By collecting their muscle data, the MPL is then suited for the individual. This gives the amputee time to learn how to use the device, fit them for it, then see how they work with it, he said.

Air Force Tech Sgt. Joe Delauriers, the first patient at WRNMMC to begin using the MPL, described the device as "pretty comfortable," and said he is grateful for the opportunity to be involved with the project.

"It's really fun working with the hand and [exciting] to see what's going to be coming in the future," said Delauriers. "Any input I can put into the program, to help them out, and future amputees, it's an honor for me. It's very rewarding."

Four months ago, Delauriers was injured by an IED blast in Afghanistan, which caused him to lose both his legs and part of his left arm. He said it's an indescribable feeling to be where he is today, thanks to advancements in care.

"I'm living off base, I'm driving, [and] I'm living with my [infant] son. I'm able to hold him without any open wounds, infections," he said. "They do such a great job here, with therapy. It's just amazing." The Airman said he can only imagine what these advancements will lead to in another decade.

"The technology is only going to keep getting better," said Tsao. "If guys like Joe can regain function, this would be revolutionizing to their lives, especially in the multiple limb amputees. Any degree of function and independence you can give back to someone is the most important thing." Pasquina also expressed his enthusiasm for this development, stating that he can recall when the device was merely a sketch on paper.

"It's something I still find amazing," Pasquina said. He is also amazed by the stories of the wounded warriors making such strides in their recovery.

"Time after time, you see people not only recover, but thrive after severe injuries, and they're inspirational to all of us, to us as medical staff who have the honor of taking care of them. It's humbling to be a part of that," he said.

Pasquina added that he'll continue his efforts to make this technology available to all service members and the population at large.

"The hand in itself is so important in terms of one's independence. Your ability to dress yourself, feed yourself, do self-grooming and hygiene is extremely important," said Pasquina. "Many of our injured service members were highly functioning, highly independent, had a great amount of responsibility. To now find themselves in a situation where they have an impairment or disability, that makes them less independent is something that not only affects them physically, but affects them emotionally. Anything we can do to [help] them be more independent and to regain that sense of self is something we're fully committed to doing and very excited about the opportunities that this presents."

USU, NIH study maps hotspots of genetic rearrangement

Findings in mice could aid in understanding how mammals genetically adapt

Researchers at the Uniformed Services University of Health Sciences (USU) and the National Institutes of Health (NIH) are concentrating focus on mouse chromosomes to map hotspots of genetic recombination – sites where DNA breaks and reforms to shuffle genes. Their findings have the potential to improve the detection of genes linked to disease and to help understand the root causes of genetic abnormalities. The research, published online April 3 in Nature, moves scientists one step closer to understanding how mammals evolve and respond to their environments.

Genetic recombination occurs at hotspots in cells that form sperm and eggs. At these sites, rearrangements ensure that the combination of genes passed on to every sperm and egg cell is unique. By studying precursors of mouse sperm cells during the early stages of genetic recombination, the scientists have created a precise, first-of-its-kind map of recombination hotspots in a multi-celled organism.

With this map, researchers also hope to pinpoint where, how and why abnormalities in the number of chromosomes can occur. Such abnormalities – for instance, the extra copy of chromosome 21 that gives rise to Down syndrome – are the leading known cause of miscarriages, congenital birth defects, and mental retardation in the United States.

“We wanted to figure out how recombination varied across the genome,” said R. Daniel Camerini-Otero, M.D., Ph.D., one of the senior authors on the paper and a researcher at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “Hotspots are the starting point for the process that ensures that every person is unique. These hotspots facilitate the adaptation of populations to environmental influences through evolution. Our findings will allow us to explore things like how environment and genetic background affect the recombination landscape.”

“Now that we have mapped recombination hotspots genome-wide, we can actually carry out studies on the whole mouse genome,” said Galina Petukhova, Ph.D., assistant professor in the USU Department of Biology and one of the paper’s senior authors. “This will be very beneficial in extending our knowledge to organisms as complex as humans, as faulty recombination can lead to infertility or birth defects. We continue to move closer to our ultimate goal of helping to prevent these health issues.” "This work is a powerful illustration of the utility of model organisms in the quest to understand fundamental biological processes and their role in human health," said George Santangelo, Ph.D., who oversees Dr. Petukhova's and other genetic recombination grants at the NIH’s National Institute of General Medical Sciences, which helped fund this research.

Camerini-Otero compared the map’s new level of precision to the difference between being able to zoom in to see a city block – all that was available until now – to being able to zoom in to see each and every building on that block. “What we were looking for was resolution that was much higher than ever seen before,” said Camerini-Otero. “Now that we can actually see these individual events, we can begin to understand their molecular structure.”

The researchers – including lead authors Fatima Smagulova, Ph.D., of USU, and Ivan V. Gregoretti, Ph.D., of NIDDK– used cutting-edge DNA sequencing technology and lots of computational power to take a snapshot of all the individual pieces of DNA that were taking part in recombination at a given moment in living cells. They then used this snapshot of short DNA pieces to draw a map of where chromosomes have an increased potential to be broken and to come back together in new ways.

Mice were used as subjects for this study because the researchers needed a population that could be created with a specific and identical genetic background. With this initial study a success, they hope to apply the same techniques to study recombination in people in the near future.

The end result is a catalog of about 10,000 hotspots and resembles a detailed map of where diversity can arise in the genome and of sites where such processes may go awry. The researchers next plan to apply what they’ve seen and learned with this new map to further understand chromosomal abnormalities, genetic recombination, genome stability and evolution.  The study is available at http://www.nature.com/nature/journal/vaop/ncurrent/full/nature09869.html.

The Uniformed Services University of the Health Sciences, or USU, is the nation’s federal health sciences university. USU students are primarily active-duty uniformed officers in the Army, Navy, Air Force and Public Health Service who are being educated to deal with wartime casualties, emerging infectious diseases and other public health emergencies. Of the university’s more than 4,500 physician alumni, the vast majority are supporting operations in Iraq, Afghanistan and elsewhere, offering their leadership and expertise. For more information, visit www.usuhs.mil.

The NIDDK conducts and supports research in diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic, and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe, and disabling conditions affecting Americans. For more information about NIDDK and its programs, see www.niddk.nih.gov.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

This research also was funded in-part by the National March of Dimes Foundation.

Navy Doctor’s Work in ‘Mirror Therapy’ Benefits Military Amputees

In the last five years, through my academic affiliation appointment at the Uniformed Services University, I’ve had the opportunity to work with some amazing people at Walter Reed Army Medical Center including COL Paul Pasquina (head of Orthopaedics and Rehabilitation) and COL (ret.) Charles Scoville to examine why Mirror Therapy seems to be an effective treatment in what is a common phenomenon in Wounded Warriors with amputation: Phantom Limb Pain (PLP).

Phantom Limb Pain is the sensation that a limb is still present and experiencing pain following amputation and occurs in 90 percent of amputees. Often an amputee begins to experience this phenomenon immediately after surgery; this is typically followed by a gradual fading of the limb from memory. Patients frequently report that this phantom limb is stuck in an uncomfortable position or has the sensation of pain, electric shocks, or itching. There are an infinite variety of sensations associated with PLP, from merely uncomfortable to debilitating, but they have one thing in common: pharmacologic therapies are generally ineffectual.

Besides trauma, PLP can and often does accompany an amputation of an arm or leg due to cancer, diabetes or other causes. One can also have, for example, phantom breast pain after a mastectomy. Research explains why this is a neurologic phenomenon not “psychiatric.” There are three main theories for why PLP happens. Phantom pain may be due to mismatched signaling in the neurons responsible for vision and proprioception, or the sense a limb’s position in 3-dimensional space. The neurons controlling the limb, which are still intact after amputation, do not match up to visual signals that tell the brain the limb is no longer there. The brain then interprets the conflicting signals as the phantom limb is still present and experiencing pain.

The second theory is that phantom pain may be due to aberrant new brain neuronal connections. It’s not clear how these new connections would mediate pain, but studies have shown that the more extensive the new connections are the more severe the pain is.

Finally, phantom pain may be due to a phenomenon termed “proprioceptive memory.” We think there may be stored memories of various limb positions and when the phantom is experienced the brain draws on the memories of the limb’s position. I think that all of these theories are valid to varying degrees. It may be that some combination of these theories explains PLP, but the origins are still not fully elucidated.

Let’s say a patient complains that “my phantom hand [or foot] is often stuck in a painful uncomfortable position,” or maybe “the fingernails of my phantom hand are digging into my phantom palm.” Mirror therapy has proven to be an effective and simple treatment for many such cases.

Mirror therapy first came to my attention when I saw a 1995 study by V.S. Ramachandran and colleagues at the University of California, San Diego that stated 60% (9 out of 15) of their patients in a small case series showed improvement in PLP symptoms after mirror therapy. His study group consisted a small series of upper-extremity amputees who were years to decades post-amputation. Mirror therapy uses a flat mirror placed parasagittally along the patient’s body so that when the patient moves the intact limb, the mirror provides the optical illusion that the phantom limb is moving at the same time.

There were, however, no controlled trials of mirror therapy for phantom limb pain after the 1995 study, until my colleagues and I conducted one, funded by the Military Amputee Research Program.

In our clinical trial, we designed a randomized, sham-controlled trial of mirror therapy and mental visualization therapy for lower extremity amputees with PLP. Volunteer subjects were randomized into three groups, each using a different therapy: mirror, covered mirror and mental visualization. Mirror therapy subjects moved their phantom leg/foot while observing a reflection of the intact leg/foot moving in a mirror, covered mirror subjects moved their phantom leg/foot while moving their intact leg/foot (but the mirror was covered by a white bed sheet, and mental visualization subjects were asked to close their eyes and move their phantom leg/foot. The treatment went on for 15 minutes a day, five days a week over a period of four weeks. Covered mirror and mental visualization subjects were then offered the opportunity to switch over to mirror therapy for another four weeks. Some of our conclusions after our initial trial were:

■Mirror therapy is more effective than covered mirror or mental visualization therapies

■6 of 6 mirror and 8 of 9 cross-over subjects improved on mirror therapy – total 14 of 15 (93%) subjects improved

■The first noticeable change was a decrease in the intensity of the pain, followed by a decrease in the length of each episode and then the number of daily episodes.

■Side effects – 2 subjects in the mirror group had brief grief reactions, none in covered mirror or mental visualization groups had grief reactions, even after crossing over to using mirror

Mirror Therapy is now used at all three of our military amputee centers: Walter Reed Army Medical Center in Washington, DC, Brooke Army Medical Center in San Antonio, TX, and the Naval Medical Center San Diego, San Diego, CA. I’m extremely gratified for the support of the rehabilitation staff at Walter Reed Army Medical Center and especially our brave wounded warriors who volunteered for a clinical trial not knowing if the treatment they were being randomized to would help treat their pain.

Although mirror therapy has helped many patients (both military and civilian), it doesn’t help everyone. To better understand what is happening to the brain when mirror therapy is used, we have now started functional magnetic resonance imaging to map out brain activation patterns in patients treated with mirror therapy. We hope to have preliminary results soon. Also since there appears to be a small percentage of amputees who never develop PLP, we are investigating whether there might be a genetic component mediating the development of PLP.

Uptick in Hospital-based C difficile Infections in Children Raising Concerns

Clostridium difficile is a bacterium commonly found in the intestinal tract. (Image: CDC)

This blog post was shared by The Uniformed Services University of the Health Sciences is the nation’s federal health sciences university.

Hospitalized children in the United States are becoming infected with the bacteria Clostridium difficile more frequently and children who acquire the infection are more likely to die or require surgery, according to researchers from the Uniformed Services University of the Health Sciences (USU) and Cincinnati Children’s Hospital Medical Center. The findings, which will appear in the May print issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals, are available online.

C difficile, which can colonize the gastrointestinal tract and lead to infection, may show no symptoms in infected patients, while others develop diarrhea, toxic megacolon (extreme inflammation and distention of the large intestine), perforated bowels or other potentially fatal complications. “In recent years, the incidence of C difficile infection, number of hospitalizations, associated deaths and severity in adults have been increasing,” the authors write.

According to study lead author Air Force Major (Dr.) Cade Nylund, an assistant professor of Pediatrics at the USU and pediatric gastroenterologist at the National Capital Consortium pediatric gastroenterology fellowship at Walter Reed Army and National Navy Medical Centers, “When pediatric patients are finally hospitalized they tend to be more complex and more susceptible to infections like C difficile. At the same time, the patients, especially hospitalized children, are less able to fend off the serious effects of these infections, making them more likely to die.”

Dr. Nylund performed this research during his fellowship in pediatric gastroenterology at Cincinnati Children’s in collaboration with Drs. Anthony Goudie, Jose Garza, Gerry Fairbrother, and Mitchell Cohen. Nylund adds that a strain of C difficile found in hospitals, known as the North American Pulse Field type 1 (NAP1), may be a partially to blame for the increasing trend of C difficile infections in children. “There may also be increasing awareness among health care providers, leading to increased testing in symptomatic patients,” said Nylund.

Based on national hospital discharge data from 1997, 2000, 2003 and 2006 collected by the Agency for Healthcare Research and Quality, the researchers reviewed records representative of more than 10.5 million patients, of whom 21,274 (0.2 percent) had C difficile. They found the number of cases increased by 15 percent each year, from 3,565 in 1997 to 7,779 in 2006. Additionally, children with C difficile infection had an increased risk of death or colectomy (surgery to remove all of part of the colon), longer hospital stays and higher hospitalization charges.

Some children appeared more likely to become infected, including those who had other co-occurring diseases, such as inflammatory bowel disease, organ transplant, or cancer. The risk of infection was also higher among those who were white, lived in the West or in urban areas, or had private insurance. “We don’t know exactly why we see these populations have an increased risk.

However, it likely has much to do with antibiotic exposure, which is a major risk factor for development of C difficile,” Nylund said. “The population-based data in our study provide additional evidence that C difficile infection cases have a significant effect on the pediatric population. Our study supports previous reports that C difficile infection is increasing among hospitalized children and provides a background for understanding changing trends and risk factors of C difficile infection in children. Increasing awareness of these risk factors and of an upward trend in hospitalized children with C difficile infection is the first step in controlling this infection.”

USU is the nation’s federal health sciences university. USU students are primarily active-duty uniformed officers in the Army, Navy, Air Force and Public Health Service who are being educated to deal with wartime casualties, emerging infectious diseases and other public health emergencies. Of the university’s more than 4,500 physician alumni, the vast majority are supporting operations in Iraq, Afghanistan and elsewhere, offering their leadership and expertise. For more

information, visit http://www.usuhs.mil/.