It's not what you do, it's how hard you do it

The poster session today was dominated by all things motor. A paper that caught my eye was presented by K Leech [presentation #74.05]. We accept that rehabilitation has an important part to play in recovery from SCI but how much is optimal and for how long should it be given?

Animal studies have shown that high intensity rehab increases the amount of a neurotrophic factor called brain derived neurotrophic factor, or BDNF, which is associated with improved recovery of stepping. BDNF is a potent promoter of neurite growth, has neuroprotective activity, can enhance plasticity and even give rise to re-myelination (see Weishaupt et al, Exp Neurol, 2012). It is actively being researched as a possible candidate treatment for SCI. Exercise is known to cause changes in BDNF levels in the periphery and in the central nervous system.

Leech’s findings are important because they shed a little light on the possible mechanisms by which BDNF might be beneficially modulated in patients with SCI. Leech and colleagues monitored the level of BDNF in the blood and compared levels after various regimes of rehabilitation exercise. They found that only high-intensity exercise elevated BDNF levels whilst low to moderate levels had no effect. Increasing the duration of moderate exercise didn’t change matters either suggesting that a threshold of intensity is needed for that all important hit of the neurotrophin.

Future studies will look at whether the increase in BDNF is related positively to better outcomes in patients. Interestingly, some patients studied had a common genetic variation which means for them it is harder to achieve elevated BDNF levels and their BDNF response to high-intensity exercise was “blunted”. Such understanding might lead to better rehab regimes tailored to the individual for optimal neurological effect.

Much to be learned from rehab

A number of interventions are now in early clinical trial and more are being proposed, yet there is a growing concern that existing measures to test efficacy may be inadequate, particularly if we accept that initial improvements may be poor (though still promising). Development of objective neurophysiological as well as functional measures has become an increasingly active area of research. Spinal Research recognised this some years ago and established its “Clinical Initiative” to address this need.

As part of this initiative, research funded by us at the Scottish Centre for Innovation in Spinal Cord Injury (SCISCI) in Glasgow has been specifically focused on developing outcome measures, the aim being to objectively study recovery following SCI whether it be due to natural recovery (i.e. spontaneous) and through any proposed intervention. Assessing neurophysiology – such as being able to measure changes in nerve conduction properties – may seem a tad esoteric to those only interested in practical and functional changes that represent improvements in quality of life, but if we understand more about how the two are related we will surely be better placed to discover the mechanisms of repair and importantly how to improve or optimise future treatments. We don’t want to throw the baby out with the bathwater.

The group from SCISCI presented two posters (SfN2009 Programme #542.7 & #741.9) at the recent Society for Neuroscience meeting in Chicago. They used Lokomat-driven Body Weight Supported Treadmill Training (BWSTT) as their test “intervention” and although primarily focused on developing outcome measures, one of the interesting findings of the study was that in acute patients (less than 6 months following injury) with incomplete SCI, the functional improvements seen with Lokomat were only significant during the first 3 weeks training, not beyond that. This has huge implications clinically as most research to date on BWSTT has adopted 8+ week rehab programmes and clinically there remains controversy over the optimum timing of initiation of rehab treatment. They suggest BWSTT performed for shorter periods such as 3 weeks and given early may benefit patients with incomplete SCI. Two other posters at the Society for Neuroscience (SfN2009 Programme #176.13 & #542.24) would seem to support this. In both, the beneficial effects of exercise in animals were observed within 3-4 weeks post injury. The animal studies and the clinical study at Glasgow, suggest BWSTT or exercises during the acute phase of SCI may facilitate recovery during a relatively short 3-4 weeks. Is there an optimal recovery window for interventions in the spinal cord injury common to both animals and humans and if so, what are the implications when planning future interventions in acute incomplete SCI subjects?

[My thanks to Dr Sujay Galen from the Scottish Centre for Innovation in Spinal Cord Injury who supplied the original report on which this post is based.]