Outcomes worse for patients who develop pressure sores after acute spinal cord injury

New research provides first evidence that hospital-acquired pressure ulcers are a potent risk factor for poor neurological recovery among patients with acute spinal cord injury (SCI).

This study included 1,282 individuals with spinal cord injury, of which 594 (45.7 per cent) developed pressure ulcers during initial hospitalisation at 20 locations across the country.

“It’s old surgical wisdom that patients who have infections will often develop wound healing problems after surgery. While typical infections in spinal cord injury patients evolve in the lung or the bladder, the skin also can be affected,” said Jan M. Schwab, MD, PhD, co-corresponding author of the study.

“Pressure ulcers often develop in patients with spinal cord injury starting during the early hospitalisation, affecting roughly half of the patients. While under recognised as immunologically active infection site, these wounds also contain bacteria that can spread through the body via the blood stream.”

Schwab is a neurologist and professor of neurology at Ohio State who specialises in the treating individuals with spinal cord injury and researching immune malfunctions interfering with neurological recovery.

“Our study found that patients with pressure ulcers regained significantly less motor function through one year after injury,” said Schwab, who is one of the leaders of Ohio State’s Belford Center for Spinal Cord Injury.

“In addition, their recovery of ‘independence in activities of daily living’ was significantly restricted compared to other patients.”

Pressure ulcers send inflammatory signals throughout the body which may also interfere with healing processes directly at the spinal cord injury site, thereby blocking neurological recovery, said Schwab.

“Our results point to the need to refer acute SCI patients to neurological rehabilitation centres such as Ohio State Dodd Rehabilitation Hospital, with specialised protocols and standards to effectively prevent pressure ulcers,” Schwab said.

During this multi-center study, patients were enrolled from 1996 to 2006 and followed-up until 2016. Patients came from the 20 centers of the prospective SCI Model Systems Database in Birmingham, Alabama.

Key inclusion criteria were acute traumatic cervical SCI with relevant motor impairment as measured by American Spinal Injury Association (ASIA) impairment scale.

Earlier studies by Schwab’s team have shown that SCI patients are immune compromised. As a result, they are more likely to develop infections, such as pneumonia, which delays and blunts their neurological recovery as well.

“We wondered whether just the presence of another inflammatory lesion in the body such as a pressure ulcer – in addition to the spinal cord injury lesion itself – is already sufficient to distract wound healing,” said Schwab, who holds the William E. Hunt, MD & Charlotte M. Curtis Chair in Neuroscience at Ohio State.

The study focused on pressure ulcers that were acquired during the early care phase after SCI spanning surgical or first rehabilitative SCI care.

The primary endpoint for the study focused on the change in the American Spinal Injury Association (ASIA) (motor score at one year after SCI. Secondary endpoints included the recovery of Functional Independence Measure (FIM) motor items at one year after SCI and mortality up to 10 years.

“Patients who develop pressure ulcers face worse long-term disability and increased risk of death,” said co-corresponding author Marcel Kopp, a clinical scientist with Department of Experimental Neurology at Charité in Berlin.

“We believe that preventing pressure ulcers from developing can help protect these patients and lead to improved medical care.”

Brain scan predicts effectiveness of spinal cord surgery

A 10-minute brain scan can predict the effectiveness of a risky spinal surgery to alleviate intractable pain. The result gives doctors a much-needed biomarker to discuss with patients considering spinal cord stimulation.

For patients with chronic pain that cannot be cured in any other way, a surgical procedure called “spinal cord stimulation” is seen as a method of last resort.

The treatment works by implanting leads into the spine of patients and electrically stimulating the spinal cord. Because the spinal cord transmits sensations to the brain from all over the body, the position of the leads is adjusted so that the patients feel the stimulation at the site of the pain.

Kobe University anaesthesiologist UENO Kyohei said: “A big issue is that the procedure is effective for some but not for other patients, and which is the case is usually evaluated in a short trial of a few days to two weeks prior to permanent implantation.

“Although this trial is short, it is still an invasive and risky procedure. Therefore, clinicians have long been interested in the possibility of predicting a patient’s responsiveness to the procedure through non-invasive means.”

Functional magnetic resonance imaging, or fMRI, has become a standard tool to visualise how the brain processes information.

More precisely, it can show which parts of the brain are active in response to a stimulus, and which regions are thus functionally connected with each other.

“In an earlier study, we reported that for the analgesic ketamine, pain relief correlates negatively with how strongly connected two regions of the default mode network are before the drug’s administration,” explained Ueno.

The default mode network, which plays an important role in self-related thought, has previously been implicated in chronic pain. Another relevant factor is how the default mode network connects with the salience network, which is involved in regulating attention and the response to stimuli.

Ueno said: “Therefore, we wanted to examine whether the correlation of the activities within and between these networks could be used to predict responsiveness to spinal cordstimulation.”

The team found that the better patients responded to spinal cord stimulation therapy, the weaker a specific region of the default mode network was connected to one in the salience network.

Ueno commented: “Not only does this offer an attractive biomarker for a prognosis for treatment effectiveness, it also strengthens the idea that an aberrant connection between these networks is responsible for the development of intractable chronic pain in the first place.”

Undergoing an fMRI scan is not the only option. Combining pain questionnaires with various clinical indices has been reported as another similarly reliable predictor for a patient’s responsiveness to spinal cord stimulation.

However, the researchers write that: “Although the cost of an MRI scan is controversial, the burden on both patients and providers will be reduced if the responsiveness to spinal cord stimulation can be predicted by one 10-minute resting state fMRI scan.”

In total, 29 patients with diverse forms of intractable chronic pain participated in this Kobe University study. On the one hand, this diversity is likely the reason why the overall responsiveness to the treatment was lower compared to similar studies in the past and also made it more difficult to accurately assess the relationship between brain function and the responsiveness.

On the other hand, the researchers also say that: “From a clinical perspective, the ability to predict outcomes for patients with various conditions may provide significant utility.”

Ueno added: “We believe that more accurate evaluation will become possible with more cases and more research in the future. We are also currently conducting research on which brain regions are strongly affected by various patterns of spinal cord stimulation.

“At this point, we are just at the beginning of this research, but our main goal is to use functional brain imaging as a biomarker for spinal cord stimulation therapy to identify the optimal treatment for each patient in the future.”

Tools developed to examine neighbourhood economic effects on spinal cord injury outcomes

Researchers have developed robust measures of neighbourhood economic factors to study how social determinants influence health outcomes after spinal cord injury (SCI). The study reveals that individuals in disadvantaged neighbourhoods face higher risks of poor health, emphasising the need for public policy to address environmental inequities.

Research scientists developed and validated two composite measures – neighbourhood socioeconomic status and socioeconomic disadvantage – using data from the U.S. Census Bureau’s American Community Survey and the national Spinal Cord Injury Model Systems database, respectively.

“These measures are an advancement for studying social determinants of health in SCI research. They provide critical tools that other researchers can use so that including indicators of neighbourhood environmental factors can become standard in future rehabilitation outcomes studies,” said lead author and principal investigator Dr. Amanda Botticello.

“Our findings highlight the importance of understanding how the environment influences health, community integration, and the development of disparities in these outcomes over time. This research can guide targeted interventions to improve quality of life for those living with SCI.”

The authors write: “…exposure to adverse conditions such as poverty and unemployment that limit access to broader resources to promote health may negatively affect all residents of an area irrespective of personal income, education, and employment status.

“These results are consistent with the sizable literature on the negative effects of neighbourhood disadvantage on health in the general population and add to the call to improve the conditions of highly disadvantaged areas to address broader inequalities in health and wellbeing.”

Then go on to say: “The results of our validity analysis suggest that the neighbourhood SES measure may be a useful proxy for personal SES characteristics such as income, which are often difficult to obtain from survey respondents and may be complex to measure for people with disabilities, who may receive assistance from government programs and other resources to supplement living expenses.

“Our neighbourhood disadvantage measure may be used in future SCIMS research to identify health inequalities and inform where community-based interventions and policies can be directed to improve the environmental factors that are critical to shaping the opportunities for people with SCI.”

Overcoming muscle spasms to help paraplegics walk again

Electrical stimulation of the spinal cord is a promising strategy for re-establishing walking after spinal cord injury. However, for patients suffering from muscle spasms, the stimulation protocols have a limited effect due to the unpredictable behaviour of involuntary muscle stiffness related to spasticity.

Scientists have now found a promising way to address and reduce muscle spasticity in patients with incomplete spinal cord injury.

It involves zapping the spinal cord with high-frequency electrical stimulation that blocks the abnormal muscular contractions. This high-frequency treatment gives patients suffering from spasticity access to rehabilitation protocols that were previously inaccessible to them with a very good clinical outcome.

“We’ve found that high frequency electrical stimulation of the spinal cord, coupled with the usual continuous, low-frequency spinal stimulation, is effective during rehabilitation after spinal cord injury, overcoming muscular stiffness and spasms in paralysed patients and effectively assisting the patients during locomotion,” said Silvestro Micera, professor at EPFL’s Neuro X Institute and Scuola Sant’Anna.

“This is a safe and effective surgical procedure that offers a new perspective in the treatment of patients with severe damage to the spinal cord. We are planning to extend the indications to different clinical conditions we will define in the next month. We are deeply grateful to the patients who trusted us,” said Pietro Mortini, professor of neurosurgery at the University Vita-Salute San Raffaele.

Electrical stimulation of the spinal cord is an indirect way to reach the motor neurons that make muscles move because the backside of the spinal cord contains sensory neurons which in turn communicate with the motor neurons.

In muscle spasticity, it is known that the spinal sensory-motor circuits are overreactive. In fact, the spinal cord is naturally overreactive to stimuli, which is good since it leads to fast reflexes.

Normally, that over-reactivity is balanced out by the brain that inhibits the motor circuits. In spinal cord injury, the patient loses messaging from the brain and these inhibitory mechanisms. By indirectly stimulating the motor circuits, the research team has found that high-frequency stimulation of the spinal cord is an artificial and safe way to inhibit that over-reactivity without producing discomfort in patients.

During the clinical trial at San Raffaele Hospital, coordinated by Mortini and Micera, Simone Romeni, first author of the study and researcher at EPFL and Università San Raffaele, proposed to implement high-frequency stimulation taking inspiration from previous work on high-frequency kilohertz blocks of motor circuits by stimulating peripheral nerves.

“At this stage, we can only speculate that high-frequency stimulation acts as a kilohertz block that prevents muscle spasticity,” said Micera.

“The clinical data with the two patients point to the benefits of implementing high-frequency stimulation for reducing muscle stiffness and spasms in paralysis. More experiments will be necessary to confirm the potentials of this approach,” said Mortini.