Research Summary
Research topic: Investigating how brachial plexus birth palsy changes the structure and functionality of upper extremity muscle and bone
Research results: An understanding of the mechanism that causes shoulder deformity after brachial plexus birth palsy
Patient care application of results: Treatments that prevent or reduce shoulder deformities in brachial plexus birth palsy patients, helping them to live fully active and healthy lives
Simplified patient care application: Treatments that help brachial plexus birth palsy patients live fully active and healthy lives
Getting to the Why of Birth Palsy Shoulder Deformity
Researchers make gains with the help of OREF, POSNA
Sharon Johnson
Obstetric monitoring and delivery techniques are better than ever in the industrialized world. Still, the incidence of brachial plexus birth palsy (BPBP) is going up.
BPBP is a traumatic neuromuscular injury affecting peripheral nerves. It occurs in as many as 4.6 of every 1,000 live births each year, and up to one-third of children affected sustain permanent osseous shoulder deformity and contracture leading to lifelong functional impairment.1
Katherine R. Saul, PhD, associate professor in the Department of Mechanical and Aerospace Engineering at North Carolina State University, Raleigh, N.C., is leading a team of colleagues looking for a better prognosis for children with BPBP.
With support from a 2013 Pediatric Orthopaedic Surgeons of North America (POSNA)/Orthopaedic Research and Education Foundation (OREF) Research Grant in Pediatric Orthopaedics, the team is investigating how BPBP changes the structure and functionality of upper extremity muscle and bone. The study is a step toward finding targeted treatments that will prevent or reduce these shoulder deformities and help more children live fully active and healthy lives.
Aftermath of BPBP
When a baby sustains BPBP, Dr. Saul explained, there is frequently weakness in the upper limb, limited range of motion, and abnormal bone growth. The postural and bony deformities have been attributed to some muscles being paralyzed and therefore unable to offer any opposition to unaffected muscles. This creates an imbalance in how muscles act on the bones. Bones normally grow in response to the forces upon them. When those forces are imbalanced, bones develop abnormally.
More recent research posits that nerve damage caused by BPBP prevents muscles from growing properly so that they become stunted, too short to function properly.
Dr. Saul explained, “The bone tries to keep growing but the muscle would essentially become like a stretched out rubber band. Abnormal, high force on a bone from a muscle that is too short and being stretched too far could cause deformity and restrict motion.”
Learning which of these two effects of BPBP is responsible for bone deformity and restricted motion will help orthopaedic surgeons to better treat patients.
Multiple disciplines, dual methodology
A collaborative effort from its inception, the design for Dr. Saul’s study draws on the team's expertise in basic research, mechanical engineering, neuromuscular biomechanics, computational modeling and clinical-surgical orthopaedic care. Dr. Saul’s study hypothesizes that the primary contributor to shoulder deformity after BPBP is strength imbalance due to paralysis of external rotator muscles. To test this hypothesis, Dr. Saul and her research team are combining two models, both developed by team members: a novel animal model and a computational model intended to translate animal findings into the human context.
To learn whether one of the effects of BPBP is more responsible for bone deformation and inhibited motion than the other, Dr. Saul and her research team are looking at an in-vivo model developed by co-principal investigator L. Andrew Koman, MD, professor and chair of the Department of Orthopaedic Surgery at Wake Forest, and Zhongyu Li, MD, PhD, associate professor in the Department of Orthopaedic Surgery. The team will compare the biomechanics of both scenarios by placing five-day-old rats into four groups:
• strength imbalance group: primary external rotators injected with
botulinum neurotoxin A to inactivate them but leave the nerves intact.
• impaired growth group: C5 and C6 nerve roots excised, and primary internal rotators injected with botulinum neurotoxin A to balance internal and external rotation strength
• strength imbalance and impaired growth group: excision of the C5 and C6 nerve roots (most representative of the clinical scenario)
• control group: uninjured and intact contralateral limbs from other groups
Micro-CT imaging will quantify bone deformity. The team will also assess range of motion, muscle structure, and histological composition.
The computational model replicates the musculoskeletal biomechanics of the human shoulder. Using it, the team will evaluate the sensitivity of human shoulder posture and bone and joint loading to the neuromuscular changes associated with BPBP. The computational model was validated in previous studies of C5-C6 brachial plexus injuries, the same nerve roots most commonly affected by BPBP.
Potential to have a lifetime impact
“We want to elucidate what's causing limits on function, or causing progression to deformity from a biomechanical standpoint and give that information to clinicians so they can make better treatment choices for these children,” Dr. Saul said. “We have an opportunity make a really big impact on these families' lives.”
For Dr. Saul, that opportunity comes with a responsibility for valid conclusions. "We need to be rigorous and very clear about where our conclusions are strong and where there are limitations so that we only improve patient care. Our work is not just hypothetical. Our findings can really affect people, so we want to make sure we're right."
Collaboration key today, tomorrow
Asked how important the POSNA/OREF grant is to conducting the research, Dr. Saul said the funding is “critical” for the current study. Further, she said, such research grants represent a commitment to “improving research and a knowledge base for orthopaedics, which is important to do in conjunction with training the people who are going to be implementing this work in the clinic. That interaction makes both the training and the research stronger. We’ve trained students and residents with this project, giving them new skills. For example, my graduate student who began the project with training in computational studies is now also trained in animal work and will take that forward.”
Dr. Saul also pointed to OREF’s peer review process as an important learning component for experienced researchers on the team. “OREF provides excellent, very specific feedback that improves the science,” she said. “I'm very appreciative of the process and the time that the reviewers spend because their guidance is really valuable.”
1Pearl, M.L., Shoulder Problems in Children with Brachial Plexus Birth Palsy: Evaluation and Management. Journal of the American Academy of Orthopaedic Surgeons, 2009. 17(4): p. 242-254.