At an American university, patients with incomplete spinal cord injuries are treated with targeted doses of reduced oxygen. This simple – yet effective – treatment allows them to increase their mobility.
David Danda slowly enters the room on crutches. The windowless space at the Rehabilitation Centre of Emory University in Atlanta is full of computers and medical equipment, and the typical hospital smell lingers in the air.
Jason Galius enters shortly after. He has no walking aid, even though he is visibly struggling to keep his balance. The two men take a seat to gather strength. They face a long day full of clinical examinations and therapeutic exercises.
Galius, who turned 37 today, was the victim of a violent crime. At the age of 16, the American of Filipino extraction was inadvertently caught up in a shoot-out near Los Angeles. Galius was hit by five bullets. One of them entered his back and exited through his neck. It injured his spinal cord at the level of the seventh cervical vertebra. The diagnosis: incomplete spinal cord injury.
In this context, the term incomplete means that the affected person is not completely paralysed, but retains some residual motor skills and sensitivity.
Galius, for instance, feels nothing at all below the injury site. His bladder control is severely limited. Furthermore, he lacks all sense of the positioning and posture of his own body. “I can walk, but I don’t know how and where to,” he explains.
Just like Galius, Danda has been suffering from severe neurological deficits for several years. The reason is a degenerative spinal disorder. Even a succession of surgical procedures couldn’t help the 68-year-old lawyer. He also has incomplete paralysis. Both men’s greatest wish is to have a body that functions normally. “Probably the biggest thing is to maybe someday be back to normal,” says Danda. This is the reason they are here. The two men are taking part in a clinical trial being conducted by Dr Randy Trumbower, in the hope that it will improve their situation.
Altitude training as therapy
Danda, who is first in line today, is given an oxygen mask that supplies him with varying levels. He breathes normal room air, containing 21 per cent oxygen, for one minute. Then the mask switches to nine per cent for 90 seconds. This low level of oxygen is similar to what one would breathe, for instance, at the summit of Mount Denali (6,190m above sea level), the highest mountain in North America. Danda repeats this breathing cycle 15 times. In order to avoid any health risks, his heart rate, blood pressure and blood oxygen levels are monitored constantly. In technical terms, this form of treatment is called mild intermittent hypoxia.
Professional athletes utilise targeted hypoxia to improve their performance levels and recovery process. The swift change from low oxygen to normal room air also shows positive effects on spinal cord injury patients. “The premise behind our work has been driven by basic research showing that brief intermittent bouts of hypoxia can induce spinal plasticity, and that this plasticity is very beneficial in terms of enhancing motor output,” Dr Trumbower explains.
Dr Trumbower has been working at Emory University since 2009. Now an assistant professor in Physical Therapy and Biomedical Engineering and also the Director of Research for the institution’s Department of Rehabilitation Medicine, he began his career as a physical therapist. At the time, he found himself frustrated by the limited treatment options available for the restoration of bodily functions after a spinal cord injury. As a consequence, he graduated in biomedical engineering and began looking for promising solutions. It was a tragic event in his private life that proved the ultimate motivator to find a cure: Dr Trumbower’s own father suffered a spinal cord injury.
The idea of utilising intermittent hypoxia as a potential therapy for spinal cord injuries was developed during his time as a postdoctoral fellow at the Rehabilitation Institute of Chicago. Dr Trumbower was inspired by the work of research colleagues investigating the effects of hypoxia in their laboratory, and encouraged to explore its possibilities. In 2007, he ran the first series of tests on a patient, and he spent the subsequent years developing this method of treatment. His efforts proved successful: the participants of a recent pilot study – all patients with a chronic incomplete spinal cord injury – were able to walk better, further and faster after the oxygen therapy.
New nerve connections
How is it possible that a treatment that involves breathing air with lower oxygen levels can improve mobility? “The treatment supports the spinal cord in the formation of new nerve connections,” Dr Trumbower explains to Danda and Galius. “This is accomplished in three different stages. The first is the episodic release of serotonin, which then triggers a cascade of cellular changes within the spinal cord that, in turn, leads to the production of a key protein known as BDNF (Brain Derived Neurotrophic Factor). It is this protein that enhances communication across the injury site, thus leading to a greater output from the spinal cord to the muscles.” Dr Trumbower believes that the effect of the treatment is enhanced by combining it with classic rehabilitation.
Gait analysis as performance review
The current study is aimed at finding solutions to unanswered questions, such as: which dose in which frequency has the greatest effect while still remaining safe for the patient? Why exactly can those receiving the treatment walk faster and further? Do they have more power in general and are thus compensating, or has their co-ordination improved? In order to find answers to these questions, Dr Trumbower’s team subjects Danda, Galius and other participants to a comprehensive gait analysis after the oxygen treatment.
Before the two men are asked to walk up and down a predefined route, an assortment of electrodes are attached to their legs. These measure whether and – more importantly – when each muscle is active.
This allows the researchers to draw conclusions in terms of co-ordination. In addition to this, highperformance cameras precisely record the motion of the hip, the knee and the ankle joints. A plate in the floor measures whether Danda and Galius apply their full body weight or rely in part on their walking aids. Finally, the two men are subjected to a reflex test in order to ascertain whether their spasticity has changed.
The data generated from these tests then needs to be analysed. Have Danda and Galius made progress due to the oxygen treatment?
Dr Trumbower and his team will know more in one or two years, which is how long the study still has to run. They are hopeful that the treatment will be applied in clinical practice in the future – not “only” for incomplete spinal cord injury patients, but also for those who have to live with complete paralysis.
However, for Danda and Galius, participation in the study has already paid off. “Since I started here, I feel like my walking has improved. I can take slightly longer steps and it’s made my spasms go down a bit,” says an exhausted but happy Galius after his therapy session.
Danda agrees: “The first time I was in the programme, I walked about 50m in six minutes. Now I walk about 500m in the same time.” Today, he very rarely needs his wheelchair. He is also convinced that he will be able to cast aside his crutches soon.
The participants breathe air of varying oxygen content (intervention group) or normal room air (control group). Gait analysis is conducted after the oxygen treatment. This procedure is repeated for 10 days, followed by various assessments plus a break of at least a month. Then the test subjects switch groups (crossover principle) and the aforementioned treatment starts anew. Which patient is assigned to which group is determined at random (randomised). The patient, the study director and the analysis researchers don’t know which patient is in which group until the end of the study; only the personnel conducting the actual study have this information (double-blind study). For further information: www.inspirlab.com
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