Under pressure 

Doctors in the intensive care unit (ICU) stabilise patients with spinal cord injury when they arrive. To date, it has not been possible to monitor the damaging reactions within the spinal cord itself. Now, two researchers from London are striving to change this in order to save the patients’ important body functions. Their special field of expertise: the pressure within the injured spinal cord.

Immediately after injuring his spinal cord, Peter was still able to speak, move his arms, and call for help. However, his condition had deteriorated dramatically after just a few days. When he awoke from artificial deep sleep, a tube was protruding from his throat. Peter needed artificial respiration; he was neither able to communicate with his voice nor his arms. It was a nightmare within a nightmare. Many victims of spinal cord injuries share Peter’s fate. Spinal cord injury worsens after the accident and patients lose control of further bodily function in a process called secondary injury, which can be even more serious than the initial injury.

Following the initial trauma, cell death automatically releases substances that trigger inflammatory reactions in the tissue, which, in turn, leads to swelling. This results in further tissue damage and worsens the extent of the injury.

It is the hunt for ways to limit secondary injury and to prevent intact nerves from dying on which Professor Marios Papadopoulos and Doctor Samira Saadoun from St George’s University Hospital in London have focused their research. The two have been a team for the past 15 years: he is a doctor, she, a researcher. Together they form the perfect symbiosis for pursuing a science project that is destined to work its way from their laboratory and into clinics. “Our goal is to improve the early care of patients with spinal cord injuries,” says Papadopoulos, who completed his studies at the elite universities of Cambridge and Oxford.

To this end, he and his scientific colleague, Saadoun, focus primarily on the pressure in the injured spinal cord. The injury leads to inflammation and swelling, which increases the pressure in the spinal cord, which, in turn, is bad for nerve cells. “The higher the intraspinal pressure, the more nerve cells are destroyed,” explains Saadoun, a neuroscientist born in Morocco. The problem is that the exact pressure in an injured spinal cord has never been determined before. It is also impossible to determine the optimal pressure conditions to protect the spinal cord from further damage. Currently, there is no clinical monitoring of the reactions within the spinal cord. Until now, early treatment focuses primarily on stabilising the patients’ general vital functions and – if necessary – on repairing the bone fracture. In the case of patients with severe brain injuries, medical management is different: in addition to life-sustaining measures, their brain pressure is monitored and adjusted in the ICU to reduce brain damage risk.

In their clinical study, Papadopoulos and Saadoun use a similar technique. After stabilising the spine of a trial participant, Papadopoulos places a probe on the surface of the injured spinal cord.

This can be done without additional surgery. The probe measures the spinal pressure at the site of injury. Data is transmitted from the probe within the body to computer via a thin nylon cable.

Subsequently, the neurosurgeon attaches a second probe to the tissue. This second probe provides information about the metabolic condition in the spinal cord.

“The micro-dialysis probe allows us to determine the metabolism of the injured cells. Are the cells still alive? Are they getting enough oxygen? Are they getting enough food? Are toxic substances building up inside the tissue?” explains Saadoun, who had the idea for this project back in 2008.

The probes remain in the patient’s body for one week, during which time, the gathered data is constantly investigated. An increase in pressure, in combination with a worsening of tissue metabolism, presents a warning sign for the physicians. “In such cases, we need to urgently relieve the high pressure,” says Papadopoulos. One possible way to achieve this is decompression, which means that parts of the vertebrae are surgically removed to give the swelling more room. Papadopoulos and Saadoun argue that the dura mater, a thick membrane surrounding the spinal cord, should also be cut open to relieve the spinal cord pressure. “In addition”, says Saadoun, “we have found that lying the patients on their side, rather than on their back, can further reduce the pressure.” Another means of regulation is the perfusion pressure or blood flow. Among other things, the high tissue pressure compresses the blood vessels. As a consequence, the blood flow is impaired. The tissue does, however, need an optimal blood and nutrient supply in order to survive. Papadopoulos and Saadoun achieve this by adjusting the blood pressure where possible.

Papadopoulos and Saadoun have already monitored 42 patients at St George’s in this manner. Thirty more will follow. As is common in all clinical studies, all participating patients have to meet the study’s strict criteria and give their informed consent. In line with current care standards, many patients only undergo surgery one to two days after the accident, which means there is sufficient time to inform them about the study and how to participate. While the timing makes implementing the study easier, Saadoun believes it is, however, not ideal for the patients: “In our experience, one should not wait for the surgery. The spinal cord needs to be monitored straight away.”

So far, Papadopoulos and Saadoun have not identified any major side effects. “Initially, we were worried that infections could occur or that the probes would cause further spinal cord damage. These worries have not been confirmed,” says Papadopoulos. This makes the positive results of the study all the more impressive. As soon as Papadopoulos and Saadoun optimise the spinal cord perfusion pressure, patients often find their ability to feel below the injury site has improved, so the level of paralysis has decreased. Therefore, Papadopoulos dares to be optimistic for a time when their technique becomes more widespread. “Some patients who would normally be completely paralysed will be able to leave the hospital with partial paralysis. In other cases, we will be able to decrease the level of paralysis by one or more segments. It does make a huge difference, after all, if you can move your fingers or not.”

The study will continue for at least another three years, and the researchers hope to gain further insights during this time, to determine the optimal pressure conditions in real time for example. In addition, both researchers are pondering whether the optimal perfusion pressure range changes during the course of the healing process. They also want to know whether a change of pressure causes abnormal electrical activity in the injured spinal cord tissue. In order to find answers to all these questions, the project has decided to add an engineer to its ranks to push ahead with programming special software to handle the complex computing tasks.

Papadopoulos and Saadoun have started to travel to conferences to present their findings. “We hope that doctors at other ICUs try our technique, too,” says Saadoun. “Then we can get together and compare our results.” The hope is that their method will set a new care benchmark in five years’ time. That is the dream of these scientists, who are devoting their lives to treating patients with spinal cord injuries.