Management of neurogenic lower urinary tract dysfunction due to spinal cord injury

Abbreviations

AC

augmentation cystoplasty

autonomic dysreflexia

AUS

artificial urinary sphincter

BNR

bladder neck reconstruction

BNS

bladder neck sling

BOO

bladder outlet obstruction

BoNT-A

type A botulinum toxin

CIC

clean intermittent catheterization

DO

detrusor overactivity

DSD

detrusor sphincter dyssynergia

DU

detrusor underactivity

FVC

frequency volume chart

HCC

hydrophilic-coated catheter

LUT

lower urinary tract

NLUTD

neurogenic lower urinary tract dysfunction

PAG

periaqueductal gray

PMC

pontine micturition center

PVR

postvoid residual

QOL

quality of life

PVC

polyvinyl catheter

SARS

sacral anterior root stimulation

SCI

spinal cord injury

SNM

sacral neuromodulation

UI

urinary incontinence

UTI

urinary tract infection

UUT

upper urinary tract

VUDS

video-urodynamic study

Introduction

Since Sir Ludwig Guttmann introduced sterile intermittent catheterization in the 1940s at Stoke Mandeville Hospital ( ), management of lower urinary tract (LUT) dysfunction has been an important part of the clinical practice of patients with spinal cord injury (SCI). This chapter begins with a brief overview of normal LUT function and pathophysiological aspects of neurogenic LUT dysfunction (NLUTD) due to SCI. Then, it outlines the key points of assessment as well as treatment of LUT dysfunction according to the pathway of management of patients with NLUTD due to SCI, as shown in Fig. 1 .

Fig. 1, Clinical pathway of management of patients with neurogenic lower urinary tract dysfunction due to spinal cord injury. Please see “ Pathway of NLUTD management ” section for details. To achieve the prevention of renal impairment and symptomatic UTI, proper urinary management and pharmacological treatment are determined, based on the basic and optional assessment. Then, further treatment will be considered if these outcomes are not achieved, or obtaining social urinary continence is warranted. CIC , clean intermittent catheterization; PVR , postvoid residual; QOL , quality of life; UTI , urinary tract infection; VUDS , video-urodynamic study.

Physiology of storage and emptying

The urinary tract consists of the upper urinary tract (UUT) and LUT. While UUT includes the kidneys and ureters, LUT includes the urinary bladder and urethra with the external urethral sphincter. During the storage phase, the bladder gradually distends, which activates myelinated A-delta afferent fibers mainly entering S2 to S4 ( ). Then, information about bladder filling ascends the spinal cord and stimulate sympathetic nerves innervating the LUT as well as the pudendal nerve innervating the external urethral sphincter, while eventually reaching the periaqueductal gray (PAG), from which the information is relayed to the relevant areas of the brain ( ). Ultimately, the medial prefrontal cortex probably determines urine storage or bladder emptying (Griffiths). Once a decision is made to empty the bladder, the medial prefrontal cortex activates the pontine micturition center (PMC) via PAG (Griffiths).

In terms of the peripheral nervous system during the storage phase, the sympathetic nerves from T10 to L1 relax the detrusor via β3-adrenoceptors and contract smooth muscle from bladder neck to proximal urethra via α1-adrenoceptors ( ). In addition, the pudendal nerve from S2 to S4 (Onuf’s nucleus) controls external urethral sphincter activity ( ). These nerve activities result in urine storage at low pressure and of sufficient volume without urinary incontinence (UI). During the emptying phase, once PMC is activated, the parasympathetic nerves from S2 to S4 contract the detrusor via muscarinic receptors (M3 receptors), while sympathetic and pudendal nerves are inhibited, resulting in residual-free voiding with good urinary flow without high pressure ( ). The coordination between the detrusor and external urethral sphincter during the emptying phase requires intact neural pathways between PMC and the sacral cord.

Pathophysiology of NLUTD due to SCI

Classification of NLUTD due to SCI

NLUTD due to SCI is divided into two types: supra-sacral NLUTD due to damage above the sacral cord, and sacral NLUTD due to damage to the sacral cord ( ). During the acute phase of SCI (spinal shock phase), LUT in the supra-sacral NLUTD reveals an acontractile detrusor with a closed bladder outlet, which lasts about for a few weeks to 3 months. However, a recent report warned that unfavorable urodynamic findings leading to high intravesical pressure were found in two-thirds of patients even during the spinal shock phase ( ). In the chronic phase, the supra-sacral NLUTD is characterized by detrusor overactivity (DO) with a discordant external urethral sphincter (detrusor sphincter dyssynergia, DSD), resulting in high-pressure storage as well as emptying. DO can causes reflex UI. In addition, besides DSD during the emptying phase, detrusor underactivity (DU) due to disruption of signal transmission from supra-spinal centers to the sacral cord may contribute to emptying dysfunction ( ). The sacral NLUTD is characterized by impaired detrusor contractility (DU or acontractile detrusor) with an incompetent urethral closure mechanism (intrinsic sphincter deficiency, ISD) during storage and inadequate urethral relaxation (nonrelaxing sphincter) during emptying, resulting in refractory stress UI as well as incomplete bladder emptying. The bladder sensation is reduced or absent regardless of the level of injury.

Association between neurological level of SCI and NLUTD

The neurological level of SCI is represented by the lowest segment of the cord with residual function, which corresponds to the upper limit of the extent of SCI. On the other hand, as described above, NLUTD is classified according to whether the lower limit of SCI involves the sacral cord. Therefore, it is difficult to accurately predict the NLUTD condition based on the neurological level of SCI regardless of its completeness of SCI, and a video-urodynamic study (VUDS) is required for the assessment of the status of NLUTD after the end of the spinal shock phase (see “Basic and Optional assessments ” section).

Elderly SCI

Elderly SCI is characterized by incomplete cervical SCI without bone injury, and central cord syndrome ( ). Central cervical SCI damages the function of the upper extremities much more than the lower extremities, and the patients often recover well except for impaired hand dexterity. Theresultant impairment in hand dexterity poses serious problems for implementing clean intermittent self-catheterization. While the incidence of LUT dysfunction was reported to be low ( ), unfavorable urodynamic findings such as DSD were higher than previously reported, and some patients manifested urinary tract complications ( ). Therefore, in patients with NLUTD due to central cord injury, VUDS should be performed to assess NLUTD, and regular urological surveillance is mandatory. Moreover, it should be noted that aging in SCI patients worsens their daily life activities, and eventually converts clean intermittent self-catheterization to indwelling catheterization ( ). Besides this, renal impairment due to NLUTD or diseases other than NLUTD, urolithiasis, and cognitive impairment due to an excessive anti-cholinergic load should be carefully monitored in these patients ( ; ).

Overview of management of patients with NLUTD due to SCI

Clinical outcomes of management of NLUTD

The critical clinical outcomes or goals of the clinical practice in NLUTD due to SCI are prevention of urinary tract complications [e.g., renal impairment (renal dysfunction/UUT deterioration), symptomatic urinary tract infection (UTI), urolithiasis, gross hematuria, urethral stricture, urethrocutaneous fistula, bladder cancer, and catheter obstruction], attainment of social urinary continence, and improvement of quality of life (QOL) ( ).

Pathway of NLUTD management

Recently, patient-reported outcomes have become more important in the field of NLUTD than before, and QOL has been increasingly included in clinical outcomes of treatment for NLUTD ( ). Even though improvement of QOL is crucial, prevention of urinary tract complications, some of which are closely related to the patient’s survival, remains the most important clinical outcome to be achieved in patients with NLUTD due to SCI. Therefore, as shown in Fig. 1 , in order to prevent urinary tract complications, the first step is to determine the appropriate urinary management and pharmacological treatment aimed at preventing urinary tract complications, especially renal impairment and symptomatic UTI. Once the appropriate urinary management and pharmacological treatment has been determined, periodic follow-up assesses whether this outcome has been achieved. If the clinical outcomes of prevention of renal impairment and symptomatic UTI are not achieved, correcting urinary management as well as revisiting pharmacological treatment should be considered. If these outcomes are achieved, obtaining social urinary continence and enhancing QOL are the subsequent important clinical outcomes. To this end, urinary management and pharmacological treatment should be optimized without compromising the outcomes of prevention of renal impairment and symptomatic UTI. Because UI is associated with poor QOL, strategies to attain social continence should be actively addressed with careful consideration of the individual patient’s preference, characteristics, and social environment. When maximum conservative treatment fails to achieve the above outcomes, surgical intervention becomes an option in carefully selected patients.

Basic and optional assessments

All the patients with NLUTD due to SCI should be assessed by basic assessment ( Table 1 ) ( ). The basic assessment includes a history taking ( ), assessment of QOL ( ; ; ), focused physical and neurological findings ( ), a frequency volume chart (FVC) or a bladder diary, urinalysis, blood tests to screen for renal dysfunction ( ), a morphological evaluation of the urinary tract usually assessed by abdominal ultrasound, measurement of postvoid residual (PVR) and uroflow in patients with voiding ( ), and VUDS ( ; ). In addition to the basic assessment, optional assessment may be performed, which includes static and/or dynamic renal scintigrams in cases of renal dysfunction or vesico-ureteral reflux, and cystourethroscopy in cases of suspicious of urethral pathology, anatomical bladder outlet obstruction (BOO), bladder stones, or bladder cancer ( ). VUDS and cystourethroscopy should be performed with caution against developing autonomic dysreflexia (AD) during examinations ( ). Performing the basic as well as optional assessment identifies the presence or absence of risk factors for renal impairment, symptomatic UTI, UI, and QOL ( Table 2 ) ( ). In addition, the presence or absence of high-pressure voiding due to functional BOO, significant PVR (> 100 mL) due to BOO or DU/acontractile detrusor, and marked bladder deformity defined as grade 2 (bladder having mild pseudodiverticula) or higher by Ogawa’s classification should be noted ( ).

Table 1

Basic assessment.

Evaluations	Comments
History taking	The level of injury: neurological findings due to SCI are essential in determining urinary management, as residual upper extremity function and the ability to hold a sitting position or open the legs are important factors for clean intermittent self-catheterization. Urinary management during and after the acute phase The presence or absence of symptomatic UTI, urinary incontinence, AD Concomitant medications The status of anorectal and sexual function Current co-morbid diseases Past medical and surgical histories
Assessment of QOL	Qualiveen 30 The Neurogenic Bladder Symptom Score Intermittent Self-Catheterization Questionnaire
Focused physical and neurological examinations of the lumbosacral region	Sensation in the perianal area Ability to voluntarily contract the external anal sphincter The presence or absence of anal reflex (S2–S5) and bulbospongiosus reflex (S2–S4)
Frequency volume chart (or bladder diary)	Useful for Evaluating bladder storage function Detecting nocturnal polyuria Confirming proper frequency/interval of CIC Measuring treatment outcomes
Urinalysis	Also need urine bacteriology in case of suspected symptomatic UTI
Blood chemistry	Serum creatinine or cystatin C For early detection of renal impairment, cystatin C is more useful than serum creatinine Prostate-specific antigen for middle-aged or older male patients, if indicated
Transabdominal ultrasonography	Screening test for upper and lower urinary tract abnormalities, such as Hydroureteronephrosis Bladder wall thickening/trabeculation Urolithiasis Prostatic enlargement
Postvoid residual and uroflowmetry ^a in patients with voiding	Screening test for lower urinary tract dysfunction in patients managed with voiding
Video-urodynamic study	Indispensable functional examination for NLUTD due to SCI, regardless of complete or incomplete injury, because neurological levels of injury do not always predict the nature of NLUTD Identification of risk factors for renal impairment, symptomatic UTI, and UI to provide convincing evidence for urinary management and pharmacological treatment Assessment of AD during the micturition cycle “As low as reasonably achievable (ALARA)” should be kept in mind

The basic assessment provides clues for the optional assessment and evidence for urinary management and pharmacological treatment.

AD , autonomic dysreflexia; CIC , clean intermittent catheterization; NLUTD , neurogenic lower urinary tract dysfunction; QOL , quality of life; SCI , spinal cord injury; UTI , urinary tract infection.

a Only patients enabled to urinate on a uroflowmeter.

Table 2

Risk factors for clinical outcomes.

	Risk factors
Renal impairment (renal dysfunction ^a /upper urinary tract deterioration ^b )	Video-urodynamic findings: decreased maximal bladder capacity, high pressure, and/or sustained detrusor overactivity, detrusor sphincter dyssynergia, decreased bladder compliance, high detrusor leak point pressure Urinary management: indwelling urethral catheterization, bladder reflex triggering Level and severity of the injury: tetraplegia, complete paralysis
Symptomatic urinary tract infection ^c	Video-urodynamic findings: vesico-ureteral reflux secondary to lower urinary tract dysfunction, that is, decreased maximal bladder capacity, detrusor overactivity, detrusor sphincter dyssynergia, decreased bladder compliance, high detrusor leak point pressure Urinary management: indwelling urethral catheterization Level and severity of injury: cervical cord injury, A or B on American Spinal Injury Association impairment scale
Urinary incontinence	Video-urodynamic findings: detrusor overactivity, decreased bladder compliance, intrinsic sphincter deficiency
Quality of life	Negative impact: indwelling catheterization, clean intermittent catheterization by attendants Positive impact: fewer worries about and fewer restrictions arising from urinary incontinence, less concerns about urinary tract infection as well as deterioration of bladder function

The presence or absence of risk factors is relevant to management of lower urinary tract dysfunction.

a Renal dysfunction: increased serum creatinine level, decreased glomerular filtration rate, or renal scarring on renal scintigraphy.

b Upper urinary tract deterioration: hydroureteronephrosis, vesico-ureteral reflux, febrile upper urinary tract infection, or upper urinary tract stones.

c Symptomatic urinary tract infection: significant bacteriuria, pyuria, and symptoms suggestive of urinary tract infection, such as discomfort and/or pain in renal or supra-pubic area in incomplete injury, cloudiness of urine, worsening of urine odor, development or worsening of urinary incontinence or leakage around the catheter, pain on micturition, worsening of spasticity discomfort/lethargy/anorexia, autonomic dysreflexia, and fever or chills, without any obvious causes for those findings and symptoms.

Urinary management ( Table 3 )

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