Incontinence doesn't kill you.....

…. it just takes away your life".

Is not a bad way to start a talk. It is a quote from a woman who had an overactive bladder. The session was on “Autonomic Nerves as Targets for Precision Bioelectronic Medicines”, the talk [#6.02] was by John Hokanson from Duke University, Durham, NC.

For the purposes of this discussion let's say the lady in question was otherwise healthy but we know the underlying cause was not SCI. Nevertheless, it does resonate with those with SCI as it reflect just one of the many secondary consequences of paralysis. Arguably, incontinence per se might not kill you in the context of SCI, but bladder dysfunction can and does cause serious complications in SCI patients and resolving bladder function consistently rates highly as a major priority for people with SCI.

Treatment for overactive bladder (OAB) is varied and includes physical therapy, drugs and as a third tier, Botox and sacral nerve stimulation (e.g. Medtronic InterStim(R) System). For those that are offered neurostim, approximately 32% are treated successfully, says Hokanson. So that means 68% aren't well treated by neuromodulation.

Hokanson described current work being done to optimise the sacral nerve stimulation parameters. In animals models, he showed that increasing the stimulation frequency (1 Hz to 20 Hz) led to broadly doubling the bladder capacity (how they did this without busting the bladder is another story but involves filling the bladder with a solution containing prostaglandins for those who are interested). Increasing stimulation strength led to further increases in bladder capacity.

The take home here appeared to be that increased stimulation frequencies help sustain bladder filling but stimulation strength ultimately proves the deciding parameter where capacity is concerned.

But for SCI, high bladder pressure causes the real problems as it backs up to the kidneys causing renal damage. Neuromodulation to increase bladder volume might not be a good idea. Whilst Hokanson could increase bladder capacity he also stated this was at the expense of voiding efficiency - the bladder retained too much urine. Not good either. Hokanson demonstrated that a switch in stimulation parameters at time of voiding took good care of that problem. As a final aside, he also showed data to suggest neuromodulation led to (beneficial) plasticity within the system. Little is currently know about the physiology of this and further work was promised.

So, neuromodulation of the bladder may be getting some helpful refinement in the future.

But we could do with more helpful in vivo outcome models of bladder function to help translate the above studies to SCI and speed up assessment of potential therapies. That's why I liked Faiza Qureshi's poster [#59.08]. Qureshi set out to determine whether there was any benefit to be had from treadmill training on recovery of bladder function after SCI. The experiment was simple in concept - test baseline cystometric parameters (bladder volume, thresholds, peak pressures etc.) - perform SCI and record changes in the above parameters in two groups, one receiving treadmill training the other not.

What was particularly nice about the study was the development of an effective method of taking these measurements in individual animal over many time points without using terminal studies or chronically indwelling catheters and electrodes that can result inflammation, infection etc.

 Each time they wanted to take a measurement they simply anaesthetised the animal, placed a catheter into the bladder, placed a recording electrode on the urethral sphincter. They could do this multiple times on each animal throughout the experiment, gathering data. A little more validation is needed but it could lead to an effective method for repeated evaluation of therapeutic interventions for bladder function.

And what of the effect of treadmill training? Well, a full control is needed but treadmill training might result in some benefit a number of key bladder and sphincter measures. But we need that control.

Spinal Research is committed to developing clinical therapies for this unmet medical need by setting up a Special Emphasis Network of researchers and clinical experts. Learn more about our Special Emphasis Networks on our website www.spinal-research.org.