Deconstructing Reconstruction

Early intervention replaces 'wait and see' for brachial plexus injuries

Drawing a picture, throwing a ball or swinging from the bars of a jungle gym seem like simple activities for most kids. But the inner workings of nerves and muscles that make those movements possible are anything but.

And when an injury to the brachial plexus makes it impossible for a child to use her arm for even basic activities, restoring those inner workings is a task that has challenged doctors for decades.

Traditionally, doctors have delayed treating brachial plexus injuries, thinking that they often heal on their own. The Brachial Plexus Center at Cincinnati Children’s, where as many as 1,000 children might be seen in one year, takes a different approach.

“In the old days, parents might be told, ‘We’re going to do nothing for a year, then start to decide,’ ” says Charles Mehlman, DO, MPH, a pediatric orthopaedic surgeon and co-director of the Brachial Plexus Center. “Now we see these children when they’re just a couple days old.”

This approach, explains Mehlman, is based on extensive, well-documented outcome studies showing that children fare much better with close monitoring and when no improvement is seen, quick action.

Infants can be treated

“We see children at a week, a month, 2 months old,” Mehlman says. “If we’re not seeing significant recovery in kids with bad injuries, they may get reconstructive nerve surgery by 3 months. That is current state-of-the-art care.”

Even if children are not completely “fixed,” he says, “They’re going to have a chance to recover to a much better level than they would under the old protocol. If they don’t have as complete a recovery as we might hope, there’s additional reconstructive surgery we can do at 2 or 3 years of age that can help them work on moving their muscles.”

A better surgery

Improving the timing and technique of that additional reconstructive surgery has been the focus of the work of Roger Cornwall, MD. Cornwall is a colleague of Mehlman’s and another of the orthopaedic surgeons at Cincinnati Children’s who treat brachial plexus injuries.

A few years ago, Cornwall developed a modification to the traditional surgery used to repair stiffness in kids’ shoulder muscles. The modification eliminated a major complication of the surgery and worked just as well. He presented his success with the technique at an international conference. But he was not satisfied.

“I thought, ‘This is a great thing,’ ” he recalls, “except that it made absolutely no sense why it worked.”

With brachial plexus injuries, he explains, one muscle in the shoulder gets very tight; most surgeons believed this was due to the unopposed activity of that muscle. So they cut most, if not all, of the muscle, causing loss of its function. Cornwall’s modification was to cut only part of it.

“But I was correcting the part of the muscle that was paralyzed, not the part that was working. It made no sense,” he says. “There had to be something we didn’t understand about why these contractures occur, why these joints get tight. We needed a better understanding of the physiology of the process.”

The role of nerves in muscle growth

So Cornwall developed a mouse model of the injury. Since arriving at Cincinnati Children’s two years ago, he worked with scientists in our Division of Developmental Biology to set up a lab. They set out to answer a question: does the lack of nerve input at birth or shortly thereafter from injury to the brachial plexus prevent the muscles from growing?

Their research has shown that it does.

“We’ve been able to show in a mouse model that muscle growth impairment causes the contractures in the upper limb,” Cornwall says. “We’re beginning to investigate the molecular and electrical means by which the nerves and the muscles communicate so that we can replace the missing signals while we’re waiting for the nerves to recover.”

This would allow the muscles to keep growing as if they had nerve input until doctors could surgically repair the nerves or until the nerves recovered fully on their own.

Previously, scientists had studied how nerve input affects muscle strength, Cornwall says, but no one had looked at their effect on growth in length. His team’s findings were published March 2011 in the Journal of Bone and Joint Surgery. They also have presented their findings at national and international meetings and have won a New Investigator Recognition Award for their work.

More new findings

Cornwall’s lab is also looking at ways to replace the missing molecular signals. They have been able to culture stem cells from the muscles, even from those that are not growing. In a Petri dish, those stem cells make muscle.

Why doesn’t that happen in the body?

“Something is actively telling them to not make muscle,”

Cornwall says. “It may be that they’re busy making other things, like fat or scar tissue, which also develop in these muscles in the absence of nerve input.”

A new mouse model will allow Cornwall’s lab to study what happens to these muscle stem cells after nerve injury – and if they’re turning into other types of tissue. “If we can understand that this is happening, it simply becomes a matter of telling the stem cells what they should make,” he says.

The researchers have submitted a grant to the Pediatric Orthopedic Society of North America to study three compounds that decrease muscle wasting after nerve injury in adults. They hope to see if the compounds also play a role in muscle growth – or its impairment – after nerve injury at birth. They hope their findings could lead to medical treatments to prevent muscle contractures altogether.

Although the treatment that will revolutionize brachial plexus care is not at hand just yet, research is bringing doctors closer than ever.

“We still operate under certain assumptions because we don’t have new answers, which is why we started this research,” says Cornwall. “It’s far from translating into a different clinical treatment. But our hope is that it will prevent wasted time on treatments based on incorrect assumptions.”