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Alsulihem et al. Neuroimmunol Neuroinflammation 2019;6:13 I http://dx.doi.org/10.20517/2347-8659.2019.007 Page 7 of 13

Table 3. Limitations of CISC [18,19]
Limitations of CISC Examples
Limited upper extremity motor function Quadriplegia
Anatomic limitation Inability to reach urethra due to obesity or in female patients
Limited functional bladder capacity (below 300 mL) Poor bladder compliance or untreated NDO
Obstructed urethra Severe urethral damage, urethral stricture, non-relaxing sphincter

CISC: continuous intermittent self-catheterization; NDO: neurogenic detrusor overactivity

[22]
suprapubic) should be changed every 4-6 weeks, and the use of silicon catheters is recommended . It
should be kept in mind that indwelling catheters (urethral and suprapubic) associated with increased risk
of bladder cancer (up to 10%) in the long term [27,28] , therefore, screening cystoscopy has been recommended
to start 10 years after indwelling catheter insertion. In cases of increased urethral leakage, recurrent urinary
tract infection, or increased sediments and frequent catheter blockages, cystoscopy is also recommended to
rule out the presence of bladder stones [22,28] .

Therefore, we discourage the utilization of indwelling urethral catheterization and prefer the use of
suprapubic catheters as a second-line option if clean IC (first line option) is not a feasible option for SCI
patient.

Systemic medications to treat neurogenic detrusor over-activity
Systemic medications have been used to reduce detrusor storage pressure, increase bladder capacity,
and improve urinary incontinence [8,12,13,22] . The most commonly used medications are anticholinergics
(antimuscarinics), and beta-3 agonists. Systemic medications, along with CISC, constitute the first-line
management of NDO in SCI patients [13,29] . Follow up after starting the systemic medication is warranted,
[12]
which includes follow-up of symptoms improvement and urodynamic study in 3 months .
Antimuscarinics (anticholinergics), antimuscarinic receptor antagonists are the most commonly used
medications in the treatment of NDO [8,12] . Several medications in this class are available and in multiple
forms [Table 4]. It is expected to decrease the maximum detrusor pressure by 30%-40%, and to increase the
[30]
bladder capacity by 30%-40% . It increases the maximum cystometric capacity by 49.79 mL and lowers
[31]
detrusor pressure at the strongest contraction by 38.3 cm/H O . The possible adverse reactions should be
2
monitored, along with improvement in symptoms and urodynamic parameters. Common adverse reactions
include dry mouth, dry eyes, constipation, blurred vision, cognitive impairment (confusion), prolonged
[29]
Q-T interval, and headache . Anticholinergics should be avoided in patients with glaucoma, myasthenia
gravis, gastrointestinal obstruction, and severe ulcerative colitis . Another form of anticholinergics
[32]
administration includes intravesical administration of 10 mL of 0.1% of oxybutynin three times daily,
[33]
which shown to be equally effective to oral oxybutynin and with fewer systemic side effects . The choice
of specific anticholinergic medication is based on availability, tolerability, and side effect profile [Table 4].

Beta-3 agonists, mirabegron, the commercially available beta-3 agonist to treat detrusor overactivity, has
been introduced recently. It acts on beta-3 receptors on the detrusor muscle to induce relaxation of the
[29]
detrusor muscle . Its use in NDO has been shown to increase the volume at the first detrusor contraction
and to improve bladder compliance, with a non-significant increase in bladder capacity when compared
[33]
[34]
to placebo . The usual dose of Mirabegron is 25-50 mg/day, which can be increased to 100 mg/day .
[29]
The possible adverse reactions include hypertension, urinary tract infection, and headache . The use of
mirabegron is currently limited in neurogenic bladder patients, as limited evidence exists to support its use
in this population [8,31] . It might be considered as an alternative in patients with contraindication to using
anticholinergics, or as an add-on treatment to anticholinergics [35,36] .