In addition to those noted in the previous sections, there are a variety of other approaches that have been investigated to address the consequences of neurogenic bladder associated with SCI. These include the use of desmopressin acetate (DDAVP) as an adjuvant therapy to manage the effects of an overactive bladder otherwise refractory to conventional treatment such as nocturnal enuresis (i.e., night-time emission of urine) or the requirement for too frequent catheterizations. It is important to note that overactive bladder may be caused by other urologic abnormalities (e.g., benign prostatic hyperplasia, or UTI that can coexist with other consequences of neurogenic bladder secondary to SCI. Therefore, urodynamic evaluation is critical to assessing overactive bladder before adjuvant therapy is administered. If needed, DDAVP is a synthetic analogue of antidiuretic hormone most commonly administered by intravenous infusion for treatment of bleeding disorders. It can also be taken in the form of a pill or intranasal spray for reducing urine production as in the present application (Chancellor et al. 1994; Zahariou et al. 2007). DDAVP is thought to bind to V2 receptors in renal collecting ducts to increase water reabsorption.
Others have employed alternative approaches such as electroacupuncture (Cheng et al. 1998) or nerve crossover surgery / spinal root anastomoses (Livshits et al. 2004; Lin et al. 2008; Lin et al. 2009) to enhance recovery of bladder function. The utility of spinal root anastomosis in SCI came from groups rediverting the ipsilaterial C7 root to repair brachial plexus injuries with significant long-term effects of motor and sensory function of the upper extremities as a result of compensatory action of the other nerve roots (Gu et al. 2005). Since the brachial and sacral plexuses are organized similarily, the rediversion of local lower extremity nerve roots has been considered a possible, albeit highly invasive, treatment option.
Zahariou et al. (2007) and Chancellor et al. (1994) conducted a pre-post (n=11) and a case series (n=7) investigation, respectively, to investigate the use of intranasal DDAVP as an alternative therapy to reduce urine production in the hopes of reducing nocturnal emissions or reducing the need for overly frequent catheterization during the day. In each case, DDAVP was employed as an adjuvant therapy in addition to standard therapies of anticholinergics and intermittent catheterization which had resulted in less than satisfactory results. With use of DDAVP just before bedtime, Zahariou et al. (2007) reported a statistically significant increase in urine production rate during the day (p<0.001) and a decrease in nocturnal urine production (p<0.001). After DDAVP treatment, participants had reduced or complete elimination of nocturnal enuresis (Chancellor et al. 1994; Zahariou et al. 2007). In addition, the proportion of persons requiring clean IC in the night while still maintaining continence was greatly reduced (Zahariou et al. 2007) and three individuals used DDAVP during the day at work and were able to achieve an additional 3.5 hours between catheterizations (Chancellor et al. 1994). These improvements persisted for a mean of 12 months. These small scale studies provides only preliminary evidence and encourages further study, although DDAVP is in fairly widespread use for SCI-related neurogenic bladder.
Another adjunctive therapy that has been investigated is the use of electroacupuncture. For example, Cheng et al. (1998) conducted a RCT (n=60) investigating the effectiveness of electroacupuncture administered in combination with conventional bladder management method (i.e., intermittent catheterization, tapping and trigger point stimulation) as compared to those not receiving electroacupuncture. Their primary outcome measure was the time to achieve bladder balancing which was defined as the time when 1) the patient could easily pass adequate urine at low pressure, 2) residual urine of approximately 100 ml or less and 3) absent UTIs. Although employing a randomized, controlled design, some limitations (i.e., lack of blinding, concealed allocation or intent to treat) constrained the level of evidence assigned to this trial (i.e., Level 2). Regardless, those receiving electroacupuncture had a reduced time to achieve bladder balancing for both those with upper motor lesions (p<0.005) and lower motor neuron lesions (p<0.01). In addition, if electroacupuncture was started within three weeks of SCI, bladder balancing was achieved sooner than those which started after three weeks (p<0.005).
Reports regarding microanastamosis to reinnervate the paralyzed bladder reveal recovery of neurogenic bladder dysfunction. These include surgical anastomosis of the intercostal nerve (Livshits et al. 2004; n=11), T11 nerve root (Lin et al. 2008, n=10), L5 nerve root (Xiao et al. 2003, n=15) or the S1 nerve root (Lin et al. 2009, n=12; Lin & Hou 2013, n=9) to the S2 or S3 spinal nerve roots. Mean follow-up of patients was between 2 to 3 years and restitution of bladder function was observed in the majority of patients. Significant results were reported for pre and post-surgical findings including reduced bladder capacity with increased urine volume under increased force of detrusor contractions and increased voiding pressure. There was also reduced residual urine volume and both detrusor tone and sphincter resistance were increased. Results from individual subjects in Livshits et al. (2004) were presented for each of these showing consistency across these measures although statistical analysis techniques were inappropriate consisting of individual Wilcoxon signed rank tests for each variable. Patient self-report measures showed increases within a few months following surgery. Similar findings were evident in 100%, 67%, 71%, and 78% of patients undergoing T11, L5, and S1 microanastamosis, respectively (Lin et al. 2009, Xiao et al. 2003, Lin et al. 2008 and Lin & Hou 2013). Full recovery of renal function and an absence of UTI was observed at follow-up (i.e., 6-18 months). Of the 7 of 9 patients in the Lin and Hou (2013) study that recovered full bladder storage and voiding function, the return of bladder sensation (able to sense full bladder and desire to void) also accompanied the lack of nocturnal urinary incontinence by 8-12 months postoperatively. Important considerations of this surgical approach are that it is far more invasive than other approaches (i.e., indwelling catherization); and some patients do not show any improvement postoperatively. In particular, accidental voiding may be triggered by unintentional dermatomal stimulation or Achilles tendon stretch. Furthermore, considering the potential for up to 30% failure rates and serious side effects (i.e. neuromas) this invasive procedure must be weighed cautiously against other approaches to treatment of bladder dysfunction.
There is level 2 evidence (from one RCT; Cheng et al. 1998) that early treatment with electroacupuncture may shorten the time that it takes to develop low pressure voiding/emptying with minimal residual volume, when combined with conventional methods of bladder management.
There is level 4 evidence (from one pre-post study and one case series study; Zahariou et al. 2007; Chancellor et al. 1994) that intranasal DDVAP may reduce nocturnal urine production with fewer night-time emissions and also may reduce the need for more frequent catheterizations in persons with SCI with neurogenic bladder that is otherwise unresponsive to conventional therapy.
There is level 4 evidence (from four pre-post studies; Lin et al. 2009; Xiao et al. 2003; Lin et al. 2008; Lin & Hou 2013) that nerve crossover surgery (anastomosis of more rostral ventral nerve roots to S2-S3 spinal nerve roots) may result in improved bladder function in chronic SCI.
Early electroacupuncture therapy as adjunctive therapy may result in decreased time to achieve desired outcomes.
Intranasal DDVAP may reduce nocturnal urine emissions and decrease the frequency of voids (or catheterizations).
Anastomosis of the T11, L5 or S1 to the S2-S3 spinal nerve roots may result in improved bladder function in chronic SCI.