An X-Ray Vision

Spinal injury can devastate a life. But new research by St George’s neurosurgeon Marios Papadopoulos and his colleagues could one day bring hope to patients facing a bleak future

LIKE so many victims, he was a young man. The lesion was high up in the spinal cord at the level of the fifth and sixth vertebrae.

He was near death when he came in, but they saved him: his mind intact, his body paralysed from the neck down.

It was years ago, yet even now the patient’s words to the medical team still haunt Marios Papadopoulos: ‘I hate you all. You resuscitated me — and I can’t even kill myself.’

Back then Marios was a second-year registrar at the old Atkinson Morley Hospital, now part of St George’s. Today, as consultant neurosurgeon and senior lecturer, he continues to see the devastating effects of neurological injury.

‘Spinal cord injury is bad because it happens to young people. Any way you look at it, the outcome is pretty devastating,’ says Marios, 41.

‘You are looking at someone who is going to have near-normal life expectancy, but is going to be disabled for the rest of their life. There is no treatment to improve outcome.

‘These people are so desperate. If you are paralysed from the neck down, what is there to do?’

New research by Marios and colleagues, to be published in the journal Brain, may go some way towards answering that question. It follows several years of work on aquaporins — water-channel proteins — in the central nervous system.

In the brain, AQP4 (aquaporin-4) is important in water balance and in scar formation in the glial cells that support neurones. Both are major factors that affect the outcome of an injury.

The team’s new work focuses on the way in which AQP4 allows excess water to enter damaged spinal cord, leading to swelling and pressure — and, often, loss of function. Studies show that inhibiting AQP4 may protect the spinal cord and prevent what can otherwise be catastrophic injury.

For a patient with a spinal lesion, even limited damage prevention could make a significant difference, says Marios: ‘Unlike in the brain, in the spinal cord any neurones you save are useful. For example, it could be enough for you to stand and walk.’

Even if a patient were confined to a wheelchair, they could still retain, say, bowel and bladder function. Patients like the American actor Christopher Reeve, who was dependent on a ventilator for most of his life after spinal injury, might retain the ability to breathe unaided.

As yet no method of downregulating AQP4 has been identified. This is the next task for Marios and his colleagues. One possibility is siRNA (small inhibitory RNA) technology, which involves using short molecular fragments to ‘switch off’ genes. Widely used in the lab, the process of using it on patients is more challenging.

Inevitably, such research is expensive. Funding so far has come from the Neurosciences Research Foundation, and the team is seeking grants to take their work further.

Marios and his St George’s colleagues, including Wellcome Trust Fellow Samira Saadoun, work not only in Tooting but also at the ‘fantastic’ facilities of the University of California, where collaborator Alan Verkman is based.

It’s a long-term partnership that demonstrates the high international profile of St George’s work in neuroscience. The hospital’s neuroscience centre, based in Atkinson Morley Wing, has an international reputation spanning 50 years.

It was at the Atkinson Morley Hospital in 1971 that the first CT brain scan was carried out. Today, American universities send their trainee neurosurgeons to hone their craft at St George’s, where seven consultants serve a population of around three million across south-west London.

The unit is one of the busiest in the country — and, apart from the National Hospital for Neurology and Neurosurgery at Queen Square, the only one to combine clinical practice and academic medicine.

Marios divides his time between patients and research. He believes surgical training pays dividends in academic terms. ‘In surgery, when you’re there at 3am and things are going wrong, you become good at seeing a shorter way from point A to point B.’

He thrives on the inherent uncertainty of neurosurgery: ‘It’s like a fighter pilot. They send you to achieve a mission, but there are so many unknowns in the way.

‘You can only find out by doing it. You can’t learn as a junior doctor on the wards. You have to be there, holding the knife.

‘But there’s confidence, and there’s arrogance. Anything can go wrong at any time. Humility is the best quality you can have, because at the end of the day in neurosurgery you are operating on an organ that you can’t even begin to understand.’

To make a donation to Neurofund, the fundraising arm of the Neurosciences Research Foundation, contact neurosurgery@sgul.ac.uk or write to St George’s, University of London Academic Neurosurgery Unit, Cranmer Terrace, London SW17 0RE