Managing Patients with Neurogenic Detrusor Overactivity A Global Approach

european urology supplements 5 (2006) 691 695 available at www.sciencedirect.com journal homepage: www.europeanurology.com Managing Patients with Neurogenic Detrusor Overactivity A Global Approach Pierre Denys *, Alexis Schnitzler, Nicholas Roche Department of Physical Medicine and Rehabilitation, Neuro-Urology Unit, Hôpital Raymond Poincaré, Garches, France Article info Keywords: Global patient management Multidisciplinary Neurogenic overactive bladder Urinary incontinence Abstract Patients with neurogenic detrusor overactivity (NDO) usually have other disorders or disabilities, in addition to bladder dysfunction, that require treatment. A number of different medical specialists are, therefore, involved in the management of an individual patient and may well be working towards different treatment goals. This, together with the possible impact on NDO of treatments for other disabilities and vice versa, means that a global approach to management of a given patient is needed to ensure that patients receive the best possible treatment for all their conditions. This is particularly true for treatments that are used for multiple indications in the same patient, such as botulinum toxin, which has been used for many years as an effective treatment for dystonia and spasticity, and has more recently shown promise in the treatment of NDO and idiopathic detrusor overactivity. The appropriate choice of total dose and staging of dosing is required to maximise safety and efficacy in both indications. Development of multidisciplinary treatment algorithms for the various types of NDO patients could help to promote a global approach to the management of these individuals and to optimise their care. # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Hôpital Raymond Poincaré, Netter Building, 104 Boulevard Raymond Poincaré, F-92380 Garches, France. Tel. +33 1 47 10 70 72; Fax: +33 1 47 10 76 15. E-mail address: pierre.denys@rpc.ap-hop-paris.fr (P. Denys). 1. Introduction Individuals with neurogenic detrusor overactivity (NDO) are some of the most challenging patients to manage [1]. Not only does their bladder dysfunction arise in conjunction with a range of underlying conditions (e.g., spinal cord injury [SCI], multiple sclerosis [MS], diabetes, stroke, and Parkinson disease), but within each condition the severity of NDO can vary widely. This means that the clinical characteristics of patients with NDO vary greatly. Thus, management largely needs to be considered on an individual basis. The situation is further complicated by the fact that there is little correlation between the signs and severity of symptoms of urinary incontinence (UI), so that both need to be considered to gain a clear picture of bladder dysfunction and its impact on the patient [2]. The frequency of other secondary conditions or disorders, such as cognitive impairment, upper limb dysfunction, sexual dysfunction, bowel dysfunction, and neurogenic pain, adds a further level of complexity to the management of many patients. These are in addition to the normal range of 1569-9056/$ see front matter # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eursup.2006.05.005

692 european urology supplements 5 (2006) 691 695 diseases, such as hypertension, infections, and allergy, that are experienced by the nonneurogenic bladder population; these diseases need to be considered when managing these patients. The situation is made even more challenging by the involvement of many different medical specialties in the management of such patients; for example, neurology, physical medicine and rehabilitation, pain management, urology, and gynaecology, each of which has its own specific primary goal of treatment. The choice of specialist to whom patients are initially referred depends on their primary disorder. The primary specialist may then refer patients to other specialists for the management of specific secondary disorders, such as UI, or may initiate treatment themselves and only refer patients in cases of treatment failure or when more specialised treatment is required. This has important implications for the management of UI in neurogenic patients. First, various different specialists are involved in the management of UI. For example, patients with SCI are generally referred to rehabilitation specialists who often initiate treatments for UI, whereas patients with MS are referred to neurologists who then refer their patients to a urologist when they deem treatment for UI to be appropriate. Whereas a urologist will clearly be aware of the most appropriate and effective treatments for UI, other specialists may be less aware of the available options as their focus is on other aspects of the patient s condition. The aim of treatment, as well as the specific therapy chosen, is likely to reflect who treats the patient, as well as the clinical characteristics of their UI. For example, the initial goal of the neurologist in the management of an MS patient who has recently received steroids for an acute exacerbation of the primary disease is to control urinary tract infection. This is as a result of the risk of severe infection associated with this therapy. Second, patients may well be receiving treatments from a number of different specialists and the different treatments may have an impact on other disorders [3 8]. Third, with the involvement of multiple specialists, responsibility for patient follow-up can become unclear and may lead to suboptimal treatment in the long term. Despite these multiple challenges, achieving the optimal management of UI symptoms is clearly very important for neurogenic patients. For patients with SCI or spina bifida, management of NDO is important for the minimisation of risk of damage to the upper urinary tract and renal failure. However, for all neurogenic patients, control of UI symptoms is essential to minimise the impact of UI on their quality of life (QOL) and general well-being [9 11]. Symptoms of UI can profoundly affect self-confidence and self-esteem, as well as limit willingness or ability to lead a normal life. Indeed, for some patients, symptoms of UI may be more distressing and inconvenient than those of the primary condition. For patients with a degree of disability, inadequately managed symptoms can also increase dependence on caregivers, which can have a further negative impact on self-esteem and QOL. Therefore, management of UI is an important part of the care of all neurogenic patients with bladder dysfunction. 2. Treatment considerations There are a number of options for the management of NDO. Pharmacotherapy with anticholinergic therapies, together with intermittent self-catheterisation, is the first-line treatment of choice for most patients. However, responses to anticholinergic therapies are variable and many patients discontinue therapy due to unacceptable side-effects, a particular problem at the higher doses that are required by many neurogenic patients or the inconvenience of daily therapy. Transdermal patches have been developed as an alternative delivery format and have been better tolerated than oral administration [12], whereas intravesical administration of anticholinergics has been used, particularly in children and adolescents, but is yet to be approved [13,14]. However, both alternatives require frequent dosing and intravesical formulations cannot easily be self-administered, increasing the complexity and cost of treatment. Other options include a-blockers, neuromodulation, and surgery (bladder augmentation), as well as treatments that are currently not approved for use in the bladder, such as botulinum toxin. Although data from clinical trials give an indication of the efficacy and safety profile for the available options, the choice of the most appropriate therapy for the individual patient is more complex and should consider various patient-specific factors. For example, whether there are likely to be interactions between the proposed NDO treatment and any other treatments that the patient is receiving must be considered. This is of particular importance when considering the use of botulinum toxin type A (BoNTA). BoNTA has been used in the treatment of dystonia and spasticity for many years and is highly effective for reducing the disabilities that are associated with

european urology supplements 5 (2006) 691 695 693 Table 1 Treatments commonly used in neurologic patients that could affect bladder function Treatment Indication Consequence/consideration Treatment having a positive effect on bladder function/symptoms Anticholinergics Parkinson disease Constipating side-effects should be Depression (tricyclic antidepressants) Allergy (antihistamines) considered in patients with bowel dysfunction Baclofen Spasticity Modulates detrusor contraction strength MS and micturition characteristics Apomorphine/L-dopa Parkinson disease May alleviate voiding difficulty but has been shown to aggravate urgency and urge incontinence Treatment having a potentially negative effect Corticosteroids Acute MS relapse Increased susceptibility to infection (especially UTI) Deep brain stimulation Parkinson disease Change bladder storage characteristics Antibiotics (aminoglycosides) UTIs Potential nephrotoxicity Acetylcholinesterase inhibitors Alzheimer disease Prolong effects of acetylcholine (counteracts effects of anticholinergics) MS = multiple sclerosis; UTI = urinary tract infection. these conditions. More recently, BoNTA has been showntobeeffectiveinreducingthesymptomsof UI that are associated with NDO [15 18]. Therefore, to ensure that the patient gains maximum benefit from BoNTA in the treatment of both conditions, appropriate choice of the total dose and staging of dosing is required. Possible interactions between treatments for bladder dysfunction and the primary disorder also need to be considered when different therapies are proposed for the management of the different disorders (Table 1). Some treatments for NDO can help decrease spasticity and permit sexual function, thus making them particularly appropriate for patients with these conditions. Similarly, baclofen, which is used to relieve spasticity and apomorphine, or L-dopa, which is used in the treatment of Parkinson disease, can both improve bladder function [3 5]. However, some treatments for primary conditions can adversely affect bladder function, for example, deep brain stimulation treatment for Parkinson disease [7,8]. The overall medication and side-effect burden that patients may experience as a result of all the treatments they are receiving also needs to be considered, especially because this is likely to affect patient satisfaction and long-term compliance with treatment. In this respect, one-off procedures such as surgery offer some benefits because compliance is not an issue. However, many patients may be unwilling to undergo an irreversible treatment, particularly if it is likely to limit their treatment options in the future. In addition, the risk of complications and patient fitness to undergo surgical procedures need to be considered. 3. A global approach to management The current International Continence Society Guidelines [19,20] contain a comprehensive section on the evaluation and management of neurologic UI as well as a review of the data generated to date with pharmacologic therapies thought to be of value in managing UI, regardless of its cause. The specificity of the recommendations for each subpopulation of neurogenic bladder is enhanced by the splitting of patients and stages of therapy by site of lesion and certain patient specifics, such as cooperative or uncooperative and with or without detrusor sphincter dyssynergia. Although undoubtedly a valuable reference source, the documents are largeandcanbeexpensivetoobtain,whichmay limit their use [21]. Furthermore, nonurologic specialists may be unaware of such guidelines or not have the time to keep abreast of latest developments in the diversity of other associated conditions in addition to those focussing on their own speciality. This clearly has implications in terms of adherence to best practice guidelines and awareness of alternative approaches to UI management. To take into account the possible interactions between the different treatments patients with NDO are likely to require and their overall impact on the patient, a multidisciplinary approach is clearly required. This would allow the total treatment needs for the individual patient to be considered so that maximum improvement is gained across the range of symptoms and disabilities, with minimal tolerability or compliance issues.

694 european urology supplements 5 (2006) 691 695 Such an approach necessitates interactions among all the specialties that are involved in the management of these patients. Whereas the value of such an approach can be readily accepted, achieving this in practice is much more difficult. Ideally, this would be achieved by face-to-face discussions among the specialists who are involved in the management of a given patient, but this is clearly impractical as well as time-consuming. An alternative approach would be to involve such specialists in the development of treatment algorithms for the main types of patient. The algorithms would include details of the possible approaches for different types of patient, appropriate points for referral, and recommendations for who should follow up the patient and in what time frame. Ideally, such algorithms would be produced on a local basis to ensure their applicability to each centre. In addition, local involvement should help encourage widespread awareness of the availability of guidelines and adherence to the recommendations, potentially overcoming some of the barriers to uptake seen with the internationally produced guidelines, highlighted above. Production of such algorithms should not only help patients to receive the treatment they deserve, but would also help promote a greater understanding of UI and its effect on QOL and daily functioning among all specialists who are involved in managing neurogenic patients. In addition, sharing of expertise across disciplines should help to ensure that all specialties are aware of current developments in the management of UI so that patients can have access to the most effective treatments that are currently available. 4. Conclusions Managing the symptoms of UI is an important part of the treatment of neurogenic patients, given the impact of symptoms on the patient s well-being and the risk of further damage for some patients if NDO is not treated appropriately. However, most patients with NDO have other disorders and disabilities that require medical treatment and often take priority over the management of NDO. Treatment of NDO therefore needs to be considered within the context of the patient s other medical conditions. This is particularly important given that treatments for the other medical conditions may have an impact on NDO and vice versa. A global approach to the management of patients with NDO should allow treatments for the different disorders to be coordinated. Ideally, this would be achieved by discussions among the specialists who are involved in the management of a given patient. However, given the impracticality of such an approach, the local, multidisciplinary development of treatment guidelines could be used to promote a global approach to the management of individual patients. This would allow patients to gain the maximum benefit from therapy and improvement in their QOL. Conflict of interest Professor Denys has been an investigator and consultant for Allergan, and an investigator for Medtronic. Acknowledgements This article forms part of a supplement based on an International Continence Society workshop Botulinum Toxin in the Overactive Bladder held in Montreal, August 2005, and supported by an unrestricted educational grant from Allergan. References [1] Denys P, Corcos J, Everaert K, et al. Improving the global management of the neurogenic bladder patient: part I. The complexity of patients. Curr Med Res Opin 2006; 22:359 65. [2] Litwiller SE, Frohman EM, Zimmern PE. Multiple sclerosis and the urologist. J Urol 1999;161:743 57. [3] Andersson KE, Pehrson R. CNS involvement in overactive bladder: pathophysiology and opportunities for pharmacological intervention. Drugs 2003;63:2595 611. [4] Watanabe T, Perkash I, Constantinou CE. Modulation of detrusor contraction strength and micturition characteristics by intrathecal baclofen in anesthetized rats. J Urol 1997;157:2361 5. [5] Aranda B, Cramer P. Effects of apomorphine and L-dopa on the parkinsonian bladder. Neurourol Urodyn 1993; 12:203 9. [6] Uchiyama T, Sakakibara R, Hattori T, Yamanishi T. Shortterm effect of a single levodopa dose on micturition disturbance in Parkinson s disease patients with the wearing-off phenomenon. Mov Disord 2003;18:573 8. [7] Seif C, Herzog J, van der Horst C, et al. Effect of subthalamic deep brain stimulation on the function of the urinary bladder. Ann Neurol 2004;55:118 20. [8] Dalmose AL, Bjarkam CR, Sorensen JC, Djurhuus JC, Jorgensen TM. Effects of high frequency deep brain stimulation on urine storage and voiding function in conscious minipigs. Neurourol Urodyn 2004;23:265 72. [9] Clanet MG, Brassat D. The management of multiple sclerosis patients. Curr Opin Neurol 2000;13:263 70. [10] Westgren N, Levi R. Quality of life and traumatic spinal cord injury. Arch Phys Med Rehabil 1998;79:1433 9.

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