Contracture: understanding mechanisms and testing treatments

As part of a new National Health and Medical Research Council Program Grant on motor impairment, Prof Rob Herbert aims to advance the transfer of new understanding of physiology and pathophysiology in motor impairment toward the clinical outcome of improved motor function.

Prof Rob Herbert

Prof Rob Herbert

Motor impairment is a common consequence of a number of illnesses and injuries. One type of motor impairment that is an important cause of physical disability is muscle contracture. A contracture is a stiffening of the muscles that limits normal joint movement, and severe contractures cause deformities that are the most visible manifestation of brain damage. Contractures arise when brain lesions, including those that arise from stroke or traumatic brain injury, cause paralysis or spasticity. Paralysis and spasticity change the mechanical environment of muscles – that is, they cause muscles to experience different patterns of activity, different changes in length and different forces than would normally be experienced. The muscles adapt in response to their altered mechanical environment by becoming stiffer, causing joints to become less mobile.

Contracture is a common problem. In a recent study, my colleagues and I monitored 200 consecutive people admitted to a Sydney hospital with the diagnosis of stroke. Six months after admission, half of all those people had developed at least one contracture. Contractures are also common in people with many other sorts of brain lesions. For example, contractures are prevalent in people who have had a traumatic brain injury, or who have multiple sclerosis or cerebral palsy.

Contractures prevent joint movement, so they cause physical disability. For example, many people who have had a stroke or traumatic brain injury develop contractures of the calf muscles. Calf muscle contractures impede ankle motion, making it difficult to stand up from a chair or walk normally. In the same way, contractures of shoulder muscles can impair the ability to reach and contractures of wrist and finger muscles can impair grasp. Severe muscle contractures can cause the limb to adopt a fixed position. For many people, contractures become a much greater impediment to normal movement than the paralysis or spasticity that initially caused the contracture to develop.

There has been surprisingly little research into the mechanisms of contracture. As a result, the mechanisms are poorly understood. Studies on animals have shown that it is possible to make muscles become short or stiff with a number of experimental procedures. For example, leg muscles can be made short by immobilising the leg in a plaster cast, and diaphragm muscles can be made short by inducing emphysema (a lung disease). These studies show that the stiffening of muscles can occur either because of changes in the muscle tissue (the muscle “fibres” or “fascicles”), or because of changes in the tendons that join muscle fascicles to bones. But studies on animal muscles can’t tell us about the mechanisms of contractures seen in human populations. Surprisingly, it is still not clear whether contractures in people who have had a stroke or traumatic brain injury are due to changes in the muscle fascicles or tendons.

There is just as much uncertainty about how to prevent and treat contracture. For the last half-century, physiotherapists and nurses have applied stretches to muscles, or passively moved limbs, or applied splints or casts to stretch the limb, with the aim of preventing or treating contractures. But recent research suggests these interventions have little effect. For example, in one study, 63 volunteers who had experienced a stroke were randomly allocated to receive either a wrist splint or no splint. Two months later there was no discernable difference in the stiffness of the wrist of people who had or had not been splinted. There have now been over 35 studies like these, and they quite consistently show little or no effect of stretch or movement-based interventions. For now at least, there are no treatments that have been clearly shown to prevent or reverse contracture.

Eventually, scientific research will provide answers, both about the mechanisms of contracture, and about how to prevent and treat contracture. The first steps have been made in identifying the abnormalities of gene expression that are ultimately expressed as contracture. New ideas for treatments are being generated by basic research, for subsequent testing in clinical trials. Our motor impairment program will study human volunteers and patients to learn more about normal motor function and the mechanisms of motor impairment, and to test the clinical efficacy and mechanisms of novel treatment interventions. The development of new techniques for imaging and measuring the internal architecture of muscles using MRI provides one promising advance. One study will look at how muscle tendons and fascicles are recruited during movement, which will inform subsequent clinical studies in people in whom contracture is common, such as people with stroke, spinal cord injury and multiple sclerosis.

Hopefully, the next decade will see major advances in both our understanding of the mechanisms of contracture and how to treat them.

An example of one of the unique muscle images generated by Prof Herbert's team. In the centre is a human leg muscle. The blue lines show the course of muscle cells in six locations in the muscle. The insets provide information about how the cells terminate on the tendinous sheets that cover the upper and lower surfaces of the muscle.

An example of one of the unique muscle images generated by Prof Herbert’s team. In the centre is a human leg muscle. The blue lines show the course of muscle cells in six locations in the muscle. The insets provide information about how the cells terminate on the tendinous sheets that cover the upper and lower surfaces of the muscle.

Plasticity in the spinal cord

Siobhan Fitzpatrick’s PhD work aims to give back movement.

Conditions that decrease a person’s ability to control their muscles, such as spinal cord injury and stroke, have devastating and debilitating consequences for individuals and their loved ones.

Siobhan_6030_lrImagine not being able to pick up your mug of coffee, or do up the button on your coat. Small daily tasks, that many take for granted, can prove impossible for those with damage to the neural pathways responsible for muscle control.

My PhD, being conducted within the Taylor Group here at NeuRA, is focused on the use of a variety of brain, spinal cord and nerve stimulation techniques to induce changes (plasticity) at the connections (synapses) between nerve cells in the spinal cord, with the ultimate goal of enhancing the control of muscles.

How to stimulate movement 

Two techniques our group uses are known as transcranial magnetic stimulation (TMS), and electrical peripheral nerve stimulation (PNS); both are non-invasive methods that can be used to stimulate parts of the nervous system.

We can use TMS to stimulate parts of the brain that control specific muscles of the arm, and PNS to excite peripheral nerves that supply the arm. Repetitive pairing of these two stimuli at specific timing intervals can induce synaptic plasticity in the spinal cord in pathways that control voluntary muscle activity.

This technique can enhance muscle activity of the biceps in able-bodied participants  and can improve manual dexterity of the hand in participants with incomplete spinal cord injury.

The technique has the potential for enhancing activity at any remaining synapses in the spinal cord that can transmit commands from the brain to the muscles; therefore this protocol would be more relevant for those with incomplete spinal cord injuries, when some spinal nerve fibers are preserved. However, even with clinically diagnosed complete injuries where there is an absence of all sensory and muscle activity below the site of injury, there could be some nerve cells within the spinal cord that have the potential to respond to the technique.

Although there are a large number of studies that investigate plasticity in the brain, there is limited knowledge of the effects of magnetic and electrical stimulation on plasticity of spinal cord pathways. I am interested in optimising the methods we use. For example, I am asking, is more necessarily better? Indeed, in the most recent study for my PhD, we found that by doubling the number of stimulus pairs we could induce more reliable, longer lasting spinal cord plasticity.

What could this mean in the future? 

What we are aiming for with these methods is small, but functionally relevant improvements in muscle control which, as an example, could be the difference between being able to pick up a cup or not.

Work in this area is still in its early days; however my vision for the future is that an optimised technique could be used clinically in conjunction with other forms of rehabilitation, such as physiotherapy, to improve motor control in those with conditions such as incomplete spinal cord injury and stroke.

Busy bee visits NeuRA

Australia’s brainiest teen shows off her trophy

NeuRA was lucky enough to host one of Australia’s brainiest teenagers, Uma Jha, when she visited last week for a work experience placement.

At just 14, the Perth native beat 3000 hopefuls to become the champion of the 2009 Australian ‘Brain Bee’; a neuroscience competition. As the sole representative of Australia, Uma continued to the international Brain Bee championships in San Diego and came head-to-head with students and high-school graduates as old as 18 from seven different countries.

“It was pretty incredible to be representing Australia. It was just good to be there,” she says. Continue reading