The clinical history and physical examination are the basis of clinical practice and considered as the starting point for the assessment process. The urinary tract should be evaluated in detail. Reported storage symptoms (urgency, frequency, nocturia, incontinence) should be carefully documented. The ICS defined increased daytime frequency as the complaint by the patient of urinating too often during the day [1]. Note that frequency of time voids in the healthy population usually ranges between four and seven per day [24, 25]. The symptom of urgency as defined by the ICS is the complaint of sudden compelling desire to pass urine that is difficult to defer. However, described feelings are highly subjective and difficult to quantitate. Urgency urinary incontinence has been described as a complaint of involuntary leakage of urine either concurrently with, or immediately after, a sense of urgency. Nocturia was set as the number of voids recorded during a night’s sleep with each void preceded and followed by sleep. Patients should also be asked about other urological complaints, for instance, voiding problems (hesitancy, straining, poor and intermittent flow); post-micturition symptoms (sensation of incomplete emptying, post-micturition dribble); and other complaints. Bladder sensation and onset of urological history should also be queried. Careful assessment of symptoms indicating possible complications (hematuria, dysuria, fever) should be conducted to rule out comorbid pathology such as malignancy, urolithiasis, or urinary tract infection. Neurological symptoms related to underlying neurological pathology should also be documented with onset, evolution, and any treatment.

The clinician should assess the severity of bladder symptoms and their influence on the patient’s quality of life and daily activities. Severity can be assessed by asking about pad usage, including pad weight, size, number of pads used, and number of urinary incontinence episodes per day.

The bladder function can be affected by inadequate fluid intake. Storage symptoms may be exacerbated by excessive drinking. Thus, fluid intake habits should be investigated and patients should be asked how much fluid they drink each day, what type of fluids they prefer (with a special consideration for caffeine intake as an exacerbating factor for urgency and frequency), and how many times they void over a 24 h period. Assessment of other potential bladder irritants (alcohol, carbonated drinks) is also important and provides an opportunity to educate patients about modifiable habits [26–29].

As patients with neurourological symptoms may also suffer from neurogenic bowel and sexual dysfunction, bowel and sexual histories are important [30, 31]. Bowel history should elicit information regarding pattern and frequency of defecation, rectal sensation, desire to defecate, and possible episodes of fecal incontinence, constipation, or defecation initiation (digitation, suppository use) [32]. Sexual history should investigate symptoms of genital or sexual dysfunction, presence of sensation in genital area, lack of desire (loss of libido), difficulty in achieving orgasm, possible dyspareunia in the female or erectile dysfunction or ejaculation problems (premature, delayed, retrograde, anejaculation) in the male.

Incontinence and other storage symptoms may be aggravated by different comorbidities. These include endocrine disorders (i.e., complicated and uncontrolled diabetes, diabetes insipidus), urological conditions (i.e., recurrent urinary tract infections, urolithiasis, bladder/prostate cancer), respiratory dysfunctions with chronic cough (i.e., chronic obstructive pulmonary disease ), fecal motility disorders (constipation or fecal incontinence), chronic pelvic pain, mobility deficits, prior pelvic surgeries, pelvic cancers, and pelvic radiation. Incontinent patients should be evaluated for stress urinary incontinence , described as the complaint of involuntary leakage on effort or exertion, or on sneezing or coughing [1]. Therefore, in women, a thorough obstetric and gynecological history should be conducted. Pelvic organ prolapse or previous pelvic surgery for both prolapse and incontinence may influence the success of future treatment [33]. A general obstetric history with labor duration, mode of delivery, birth weights of children, year of delivery, intra-partum complications (e.g., obstetric anal sphincter injury, peri-urethral lacerations, wound breakdown), as well as de novo post-partum urinary symptoms (e.g., urinary retention requiring prolonged catheterization or stress urinary incontinence ), which may be precipitated by cesarean section, epidural block, or prolonged labor, may be necessary for evaluation [34–37]. Continuous incontinence may also be caused by ureteral ectopy, fistula formation, bladder neck erosion (from long-term catheter use), or a scarred, fixed urethra from multiple previous procedures [38]. Those patients will report constant urinary drainage (either at night while supine) and infrequent voids due to the lack of urine storage in the bladder. Psychiatric disorders such as depression, dementia, and anxiety should also be considered, as they may influence voiding patterns [39]. Accidents and operations, particularly those involving central or peripheral nervous system, should be elicited.

A carefully conducted patient history is important to ensure that there are no risk factors for potential complications or contraindications for the introduction of pharmacotherapy (anticholinergics ). Conditions to consider include cardiac history, in particular a prolonged QT interval; uncontrolled hypertension; functional gastrointestinal pathology; myasthenia gravis; uncontrolled narrow angle glaucoma; and renal or liver impairment.

The patient’s current medication should also be evaluated. Both prescribed and over-the-counter drugs may worsen incontinence and other storage symptoms. Diuretics and sympathomimetics can induce storage symtpoms including urgency, frequency, and urgency incontinence [40]. Antipsychotics, antidepressants, antihistamines, and anticholinergic respiratory agents may have anticholinergic properties and contribute to voiding problems (see Chap. 8, “Retention”). There is evidence that cumulative use of agents with anticholinergic properties is associated with increased risk of cognitive impairment [41].

A well-conducted medical history should be completed with assessment of the patient’s social situation. Accessibility to care, toileting, and supplies may be limited by financial constraints or other social factors. Family or caregiver support should be ascertained and the patient’s independence should be evaluated.

A proper history should not only aim to diagnose the cause and nature of bladder dysfunction but also to identify associated complications (see Chaps. 10–15).

Clinical examination ought to be a part of the assessment of incontinent patients suspected of NDO. It should begin with a general evaluation of mental status, cognitive impairment, obesity, physical dexterity, mobility, balance, and coordination. Special attention should be paid to mobility. Patients with impaired mobility may not have enough time to reach the toilet before incontinence occurs. Abdominal examination needs to be routinely performed. Pelvic and genital examination should assess tissue quality and sensation (see Chap. 4, “Medical History and Physical Examination,” Fig. 4.​1), urethra, pelvic floor supports/pelvic organ prolapse, and stress incontinence (spontaneous or induced by Valsalva or cough). In incontinent patients, skin quality should be assessed with special attention because chemical irritation from urinary or fecal incontinence as well as impaired sensation may substantially contribute to skin damage. Digital examination of the rectum with assessment of anal sphincter tone and voluntary contraction should be performed [33, 42–44]. Fecal loading of the large intestine and rectum should be described. Evaluation of spinal cord-mediated reflexes (bulbocavernosal, anal, ankle, plantar, patellar, cremasteric) is also important (see Chap. 4, Table 4.​4). In patients with chronic indwelling catheters any abnormalities should be documented. These include traumatic hypospadias in men and bladder neck erosion in women.

The bladder diary is useful because it provides a real-time, semi-objective, patient-reported measure of micturition frequency, fluid intake habits, and bothersome symptoms (see section “Voiding Diary” in Chap. 5, “Testing”). Accurate record of a voiding diary can allow for estimation of functional bladder capacity, calculation of 24-h/nocturnal total urine volume, as well as help in patient counselling and treatment monitoring [45]. Bladder diaries are especially useful in behavioral therapies and bladder training programs. In voiding diaries, NDO patients are usually characterized by small and frequent voids with possible incidents of urinary incontinence preceded by urgency. Physicians should motivate their patients to complete such a diary accurately during 3–7 consecutive days.

Currently there is a wide variety of patient-completed and physicians-administered questionnaires that can be used in the assessment of patients with neurogenic bladder . A number of them have been designed with a special consideration for neurologically impaired individuals. Whereas special questionnaires for SCI patients are presented in Chap. 4, individuals with multiple sclerosis can be examined with other specific questionnaires [32, 46]:

Among them, HAQUAMS, MSISQ-15/MSISQ-19, MSQLI, and MSQoL-54 are the three-condition-specific (bladder, bowel, sexual function) questionnaires. Patients can also be evaluated by generic questionnaires, such as King’s Health Questionnaire (KHQ) or the Short Form 36-item and 12-item Health Survey Questionnaires (SF-36, SF-12). However, such forms may be less sensitive to detect symptom change than more specific questionnaires detailed above [38]. Urge incontinence related to NDO may also be assessed by questionnaires designed for idiopathic overactive bladder (OAB). The International Consultation on Incontinence has developed specific criteria for questionnaires currently in use and has designed a recommendation grading system [47]. Questionnaires with a Grade A recommendation (highly recommended) include:

The questionnaire selected should have been validated in the language that it is going to be used. Of note, each questionnaire can be used alone or in combination with others in order to improve assessment or monitoring of treatment outcomes [48]. Currently available data are insufficient to answer the question of whether or not the use of these questionnaires has an impact on treatment outcomes.

Existing storage symptoms, including incontinence caused by neurogenic bladder , may worsen during urinary tract infection. Moreover, presented symptoms may not reflect the presence of infection within the urinary tract [49]. Therefore, a dipstick urinalysis can be used to screen patients but it should be noted that individuals with neurogenic bladder may be colonized by strains of resistant bacteria, thus a dipstick test may be more useful to exclude than to prove urinary tract infection [50]. If any evidence of infection is detected, urine culture with antibiotic sensitivity is required [51, 52]. Note that asymptomatic bacteriuria (>10⁵ CFU/mL), highly prevalent in individuals suffering from neurogenic lower urinary tract dysfunction, older persons, diabetic, and catheterized patients, should not be routinely treated except in pregnant women and before urological procedures within the urinary tract [53–55]. Patients should be counselled in terms of proper urine collection. Appropriate urine samples include clean-catch midstream samples, samples taken from a freshly inserted intermittent sterile catheter, and samples taken from a catheter port [56]. Samples from leg bags should not be analyzed.

The pad test is a non-invasive, inexpensive tool in the diagnosis of incontinence and assessment of its severity. It has been defined by the International Consultation on Incontinence (ICI) as a diagnostic method to detect and quantify urine loss based on weight gain of absorbent pads during a test period under standardized conditions [57]. The Committee stressed that the pad test is not diagnostic for the cause of the incontinence. Furthermore, there are few data on its utility in neurologically impaired patients [58]. Several different standards have been developed, and tests can be divided into four groups, according to test length: <1, 1, 24, and 48 h. Despite the test duration, pad weighting tests can also be divided into two groups: quantitative and qualitative. The quantitative variant is used to determine the presence of urinary incontinence if the diagnosis is not clear or requires objective confirmation. This method may be improved with a colored dye, administered orally, parentally, or directly into bladder. The quantitative variant is used to measure the amount of urine leakage after executing a standardized set of activities or a normal daily routine. The amount of leakage is calculated from the formula:

Because defining continence is difficult and not universally well-understood among patients, the ICI Committee defined the result of the test to be positive when pad weight gains >1.3 g during 24 h or >1 g during 1 h [57]. The ICI investigation concluded that a 24 h test correlates well with symptoms of incontinence and is characterized by good reproducibility. A test lasting longer than 24 h has been proved to have little advantage with poorer compliance and a test lasting shorter than 24 h may lack the ability to quantify the amount or volume of incontinence. Thus, the 24 h pad test is recommended. The ICI Committee qualified the pad test as an optional investigative tool in routine evaluation of urinary incontinence . The major limitations include the fact that the pad test cannot distinguish between urodynamic stress incontinence and detrusor overactivity. Moreover, false positives can be caused by excessive vaginal secretions or menstrual flow, particularly in younger women.

Renal evaluation considers both function and structure. Measuring serum creatinine, blood urea nitrogen, and electrolytes levels, as well as calculating the glomerular filtration rate, helps to assess renal function. Creatinine clearance provides more precise data but requires a 24 h urine collection to assess creatinine excretion. Incomplete collection can result in underestimation of renal function. Renal scintigraphy with assessment of glomerular filtration rate is recommended when renal function is poor, muscle mass reduced, if function for each kidney has to be assessed separately, and in high-risk patients [2]. A renal ultrasound is commonly used for general assessment of kidney structure and may reveal hydronephrosis, abnormal masses, scarring, stones, and other structural changes affecting the parenchyma (see Chap. 5, Figs. 5.​2, 5.​3, and 5.​4). Functional and structural renal evaluation should be considered especially in patients who are at risk of upper urinary tract deterioration and incorporated into baseline assessment and routine follow-up plan with proper regularity .

Post-voiding residual (PVR) volume, free flowmetry, bladder ultrasound, cystoscopy, computed tomography, and magnetic resonance imaging (MRI) should be performed when clinically indicated, based on patient history as well as relevant symptoms and signs. Uninhibited detrusor contractions in NDO patients provoke incontinence and lead to small PVR. PVR should be evaluated in patients with obstructive symptoms, as NDO may coexist with detrusor-sphincter dyssynergia. PVR measurement can also be considered in patients with history of either prostatic or incontinence surgery. Ultrasound measurement of PVR is preferable to catheterization, and portable scanners can be easily used in daily clinical practice [59–63]. Elevated PVR should raise attention regarding the existence of other possible pathologies. When PVR measurement is indicated, it should be supported with free flowmetry. Bladder ultrasound and cystoscopy may be considered to exclude other causes for storage symptoms (bladder tumor, carcinoma in-situ, ulcers, bladder stones, foreign bodies, cystitis) and should be conducted in patients with recurrent urinary tract infection, persistent pyuria, hematuria, bladder pain, history of stress incontinence or pelvic surgery; and those with suspected fistula, urethral diverticulum, or urinary tract malformation. Cystoscopy should also be considered in patients with possible obstructive pathology. Ultrasound measurement of detrusor/bladder wall thickness is not currently recommended (see section “Urinary Tract Ultrasound” in Chap. 5). Advanced imaging techniques (computed tomography and MRI) should be performed when clinically indicated.

As detrusor overactivity has been defined as involuntary detrusor contractions during the filling phase that may be spontaneous or provoked, urodynamic investigation is the cornerstone in the diagnosis and management of patients suffering from incontinence due to NDO [1]. The urodynamic components of NDO are isolated to the filling phase, and special attention should be paid to this portion of the test (Fig. 7.1) [64]. Investigated abnormalities may include involuntary detrusor contractions, decreased compliance, increased bladder sensation , and decreased cystometric capacity .

The ICS described certain patterns of detrusor overactivity [1]:

Analyzing filling phase of urodynamics , clinicians may encounter two measurable leak point pressures named the detrusor leak point pressure (DLPP) and abdominal leak point pressure (ALPP) . Nonetheless, the recently updated consensus document of the ICS entitled “Good Urodynamic Practices and Terms ” introduced only one term—leak point pressure (LPP) [69]. It has been defined as the pressure (spontaneous or provoked) that has caused fluid to be expelled from the bladder at the moment that it is visible outside the urethra (may also be used for extra-urethral urine loss or stoma). This may refer to abdominal, cough, or Valsalva LPP or detrusor LPP . Provocation and pressure recording site (“type of LPP”) should be reported. This newly introduced term is concurrent with current recommendations that DLPP should be interpreted with caution in neurogenic patients due to low sensitivity in estimating the risk to the upper urinary tract or for secondary bladder damage [32].

Some studies suggest that NDO can be distinguished from idiopathic detrusor overactivity based on findings from a filling phase of urodynamics [69, 70]. Lemack et al. reported that patients with NDO may have a greater amplitude of the first overactive contraction and maximum detrusor contraction. Using a cut-off value of 30 cm H₂O for amplitude of the first overactive contraction, the authors achieved a positive predictive value of 88% for identification of underlying neurological disease. However, it is important to note that NDO and idiopathic detrusor overactivity may also look identical on urodynamics [71]. This emphasizes that NDO is a clinical diagnosis of urodynamically confirmed detrusor overactivity in patients with underlying neurological pathology. NDO is strictly defined by the patient’s neurologic status and not by the presence of involuntary detrusor contractions on the urodynamics tracings [64].

In neurological patients, detrusor overactivity may often coexist with detrusor-sphincter dyssynergia further described in Chap. 8. Nevertheless, clinicians should keep in mind that NDO is a diagnosis derived from the filling phase of urodynamics (storage), whereas detrusor-sphincter dyssynergia occurs during the pressure-flow study (voiding) [64].

The current recommendation is to measure compliance between the start of bladder filling and the attainment of cystometric capacity (or immediately before the start of any detrusor contraction that causes significant leakage). Both points are measured excluding any detrusor contraction. Compliance is considered to be one of the most reproducible and reliable urodynamic measurements [72].

Decreased (poor, low) bladder compliance signifies an abnormal increase in detrusor pressure between measurement points. There is no agreement on absolute value for bladder compliance. Studies suggest that compliance values below 10–15 mL/cm H₂O should be considered as abnormal [73, 74]. Decreased compliance leads to high bladder pressures that can throw the upper urinary tract into jeopardy. This may present as upper tract deterioration, vesicoureteral reflux, and pyelonephritis [73]. It is agreed that a sustained bladder pressure of greater than 40 cm H₂O can cause significant risk to the upper tracts. Poor bladder compliance can be observed in multiple neurological disorders, including stroke , spinal cord injury, multiple sclerosis , multiple system atrophy, spina bifida, transverse myelitis, or iatrogenic nerve damage from pelvic surgery. Non-neurological entities may also result in low bladder compliance, for instance bladder outflow obstruction, chronic cystitis, chronic urinary tract infection, or even chronic catheterization as a consequence of connective tissue scarring of the bladder wall [75]. Decreased compliance substantially contributes to storage symptoms, including urgency, frequency, and incontinence.

Measurement of bladder compliance can be altered by anatomic variations (e.g., bladder diverticula) or intrinsic sphincter deficiency as consequences of additional urine capacity or urine leakage, respectively [72]. Low bladder compliance can be exaggerated by high filling rate. Moreover, phasic detrusor overactivity can sometimes be misleading and confused for abnormal compliance, particularly when it is prolonged and of low amplitude. Stopping of fluid infusion may help in proper diagnosis. If detrusor pressure returns to baseline, then the rise in detrusor pressure is caused by an involuntary detrusor contraction; if the detrusor pressure remains elevated, then the rise in detrusor pressure is caused by abnormal compliance [72].

It has been proposed that the first sensation of filling in healthy individuals should appear at mean bladder volume 222.5 ± 151 mL in men and 175.5 ± 95.5 mL in women. The first desire to void should be reported at 325 ± 140.5 mL (male) and 272 ± 106 mL (female) of mean volume of the bladder. Strong desire to void can be expected at 453 ± 93.5 mL (male) and 429 ± 153 mL (female) of mean bladder volume [76]. Another proposal emphasized that the first sensation of bladder filling occurs at an average of 40% of maximal cystometric capacity, while strong desire to void occurs at an average 70% of maximal cystometric capacity [77]. In neurologically impaired patients, increased bladder sensation results from involuntary detrusor contractions and impaired compliance [78].

Maximum cystometric capacity is the volume at which the patient feels he/she can no longer delay micturition. At maximum cystometric capacity, patients have a strong desire to void, and they report that they cannot hold any more in their bladder. Note that according to terminology introduced by the ICS, maximum cystometric capacity should be defined only for patients with normal bladder sensation [1]. As individuals with neurogenic bladder dysfunction often have impaired bladder sensation, this parameter should not be reported in this specific group of patients.

Conservative treatment is cheap, widely available, and rarely complicated. It includes behavioral techniques, lifestyle changes, and management of other medical conditions. Although there is a paucity of well-conducted studies in neurologically impaired patients, conservative treatment should be employed. This usually requires support from caregivers and health-care professionals to be successful. It is beneficial to introduce conservative treatment in conjunction with education about lower urinary tract function for the patient and/or their family members and carers [56]. Some aspects of presented techniques are described in Chap. 17, “Patient Education.”

Behavioral techniques include two main treatment options: bladder training (BT) and pelvic floor muscle therapy (PFMT) . BT includes the use of bladder diaries, bladder control strategies, timed voiding, prompted or scheduled voiding, or delayed voiding. These are all used to alter patient voiding patterns. PFMT has been shown to improve urinary frequency, number of daily incontinence episodes, and mean cystometric capacity in patients with multiple sclerosis [83]. A recently published study on patients with NDO after spinal cord injury provided evidence that a 6-week program of PFMT may have a beneficial effect on promoting voluntary control of NDO and can reduce incontinence in selected cases with a motor incomplete spinal cord lesion [84]. PFMT may also include urgency suppression, control strategies, and biofeedback. Combined treatment of PFMT , biofeedback, and neuromuscular electrical stimulation has been found to be safe and effective in women with multiple sclerosis [85].

Lifestyle changes include fluid, caffeine, diet management, and weight loss. Patients should individually identify bladder irritants. Presented strategy also includes making the toilet more accessible and improving the patient’s mobility. Patients should be informed about incontinence pads and protective products. Male incontinent patients can be candidates for a condom catheter connected to a collection bag. The penile clamp is contraindicated in NDO patients because of the risk of further increase in intravesical pressure [32].

Management/treatment of other medical conditions includes optimization of bladder-related comorbidities, changes in drug intake if these influence diuresis and/or bladder function, as well as treatment of other physical and psychosocial issues such as constipation, depression, or anxiety.

In neurological patients suffering from neurogenic bladder, the recommendation is to use drug treatment in conjunction with conservative modalities [86]. Pharmacological management of neurogenic bladder is primarily aimed at controlling and alleviating bothersome symptoms of urgency, frequency, and urinary incontinence . There is currently no curative pharmacological treatment of this condition. Available literature includes several individual studies and systematic reviews. Drugs can be administered orally, transcutaneously, or intravesically.

Antimuscarinic drugs have been widely used for many years to treat patients with NDO and they are currently recommended as the first-line choice for treatment of NDO [32]. They have an antagonistic action on muscarinic receptors throughout the body, but improve detrusor overactivity symptoms by blocking the M2 and M3 receptors in the bladder, and therefore are thought to reduce storage pressures, prevent involuntary detrusor contractions, improve bladder compliance, increase bladder capacity, and reduce episodes of storage symptoms, including incontinence [87].

A recently published meta-analysis has confirmed that anticholinergic treatment in patients with NDO is associated with better patient-reported cure and improvement of urodynamic parameters when compared with placebo [82]. Researchers have not proved the superiority of one drug over another and suggested that the only difference between drugs is their side-effect profiles. They emphasized that there is still uncertainty about which anticholinergic drugs are most effective and which doses should be chosen. An update of a systematic review of the efficacy, tolerability, and safety of oral antimuscarinics in neurogenic bladder dysfunctions has also failed to answer these questions [88].

The choice of antimuscarinic agent has been analyzed by the Expert Panel of European Association of Urology in their Neurourology Guidelines [32]. The panel reported that oxybutynin, trospium, tolterodine, and propiverine are established, effective, and well-tolerated treatment modalities for NDO, even in long-term use. Similar results have been shown in efficacy of darifenacin and solifenacin evaluated in patients with spinal cord injury and multiple sclerosis . Experts emphasized that there is a paucity of clinical data for the use of fesoterodine in treatment of NDO.

Anticholinergic therapy is frequently prescribed at higher doses than in idiopathic overactive bladder. Studies comparing standard to higher dose of different anticholinergic therapies showed that this attitude may improve outcomes [88–93]. Higher dosages or double anticholinergic therapies were regularly associated with better improvement in patient-reported outcomes and urodynamic parameters. Current data suggest that the appearance of side effects is comparable to that of normal-dosed antimuscarinics [88, 89]. Combined antimuscarinic treatment by using two different antimuscarinics with slightly different receptor profiles might also be a right option for patients affected by neurogenic bladder , particularly in those refractory to previous antimuscarinic monotherapy [94]. Proposed strategies might slow down or delay other more invasive treatments. Of note, clinicians should be aware that such practices are usually outside of the regulatory licenses for the overactive bladder [95].

Antimuscarinics are contraindicated in patients with narrow-angle glaucoma, as their anticholinergic action can induce or precipitate acute angle closure [96]. Antimuscarinic drugs contribute to the overall anticholinergic burden, adding to the polypharmacy of patients with other anticholinergic effects. Anticholinergic burden has been linked to cognitive dysfunction [41], but also with increased mortality and cardiovascular risk [97]. As neurogenic bladder dysfunctions are usually lifelong, these effects should be considered. Potential side effects include dry mouth, constipation, visual disturbance, skin reactions, cognitive impairment, and reduction in bladder emptying. Urinary retention is possible in those who void spontaneously [91, 92, 98]. Thus, the National Institute for Health and Care Excellence Guidelines recommend monitoring residual urine volume in people who are not using intermittent or indwelling catheterization after starting antimuscarinic treatment [56]. Dose titration in those individuals should be done carefully [99]. Available data suggest that oxybutynin may be less well tolerated than other antimuscarinics [95]. Data from studies on idiopathic overactive bladder emphasize that immediate release formulations of antimuscarinics should be avoided if extended-release formulations are available [100]. The longer-acting formulations were found to be more effective and have decreased side effects, but little evidence supports the use of one long-acting agent over another [99].

It is well known that adherence and persistence with anticholinergics is poor in idiopathic overactive bladder, but there is little evidence on this subject in NDO. A retrospective analysis of 26,922 patients with neurogenic bladder revealed that 38% of patients discontinued oral therapy within 1 year [101].

Commonly used antimuscarinic drugs for management of NDO has been recently evaluated by Panicker et al. [2]. A summary of their findings with updates is presented in Table 7.1 [102].

Beta-3-adrenergic receptor agonists have recently been introduced. Mirabegron has been reliably evaluated in idiopathic overactive bladder, proving its efficacy. However, there is a paucity of data for neurological patients. Hypothetical efficacy of mirabegron in patients with spinal cord injury and neurogenic bladder has been described in one retrospective analysis [103] and one animal study with transected rats [104]. Authors of both papers stated that mirabegron therapy could be an effective treatment option, but further research is warranted.

Intravesical drug treatment has also been reported with vanilloids, capsaicin, and resiniferatoxin [112, 113]. However, the European Association of Urology recommended that currently there is no indication for the use of these substances, which are not licensed for intravesical treatment [32]. Corcos and Ginsberg stressed that no protocol has been proposed to control detrusor overactivity with these modalities [114]. Furthermore, studies have shown that botulinum toxin A injections provide superior clinical and urodynamic benefits compared to intravesical resiniferatoxin [115]. Therefore, these substances are not currently used in daily practice .

Not all patients achieve continence or urinary tract safety with antimuscarinics alone. Given the widespread use of botulinum toxin A (BTX-A) injections and its proven clinical efficacy , this treatment is currently considered as a second line therapy and the most effective minimally invasive strategy [32]. BTX-A inhibits acetylcholine exocytosis , an important excitatory neurotransmitter in the bladder that stimulates detrusor contractions via M2 and M3 receptors (see Chap. 2, “Neurogenic Bladder Pathophysiology ”) [116]. Treatment of NDO with BTX-A has been shown to significantly improve urodynamic parameters such as maximal cystometric bladder capacity and detrusor pressures, as well as clinical parameters including urinary incontinence . BTX-A also improves patient’s quality of life and significantly contributes to preservation of renal function [117, 118]. Its clinical efficacy has been extensively proved in recently published meta-analyses of patients with NDO after spinal cord injury and with multiple sclerosis [119, 120]. Some case series have also reported satisfying results for other conditions, such as cerebrovascular accident, Parkinson disease, and multiple system atrophy [121–123].

BTX-A injections are recommended when anticholinergic therapy has shown to be ineffective or poorly tolerated. Patient selection involves preprocedural urodynamic study to diagnose NDO. Those with incontinence related to other causes may not benefit from detrusor BTX-A injections [119]. Currently, three different formulations of BTX-A are commercially available in Europe and the USA: onabotulinumtoxinA (Botox^®, Allergan Inc., Irvine CA, USA), abobotulinumtoxinA (Dysport^®, Ipsen Limited, Paris, France), and incobotulinumtoxinA (Xeomin^®, Merz Pharmaceuticals, Raleigh NC, USA) [124]. However, only onabotulinumtoxinA and abobotulinumtoxinA are supported with reliable and adequate clinical data in the field of urology. Both of them have already been characterized by the level A recommendation for NDO treatment with proved safety and efficacy [124, 125]. Clinicians should also be aware that utilization of both formulations depends on local health care authorities, and in many countries only onabotulinumtoxinA is approved for use in NDO [124]. Moreover, onabotulinumtoxinA is the only formulation approved by the U.S. Food and Drug Administration [2].