You are on page 1of 15

Multiple Sclerosis

http://msj.sagepub.com The neurogenic bladder in multiple sclerosis: review of the literature and proposal of management guidelines
Marianne de Sze, Alain Ruffion, Pierre Denys, Pierre-Alain Joseph, Brigitte Perrouin-Verbe and International Francophone Neuro-Urological expert study group (GENULF) Mult Scler 2007; 13; 915 originally published online Mar 15, 2007; DOI: 10.1177/1352458506075651 The online version of this article can be found at: http://msj.sagepub.com/cgi/content/abstract/13/7/915

Published by:
http://www.sagepublications.com

Additional services and information for Multiple Sclerosis can be found at: Email Alerts: http://msj.sagepub.com/cgi/alerts Subscriptions: http://msj.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav Citations (this article cites 59 articles hosted on the SAGE Journals Online and HighWire Press platforms): http://msj.sagepub.com/cgi/content/refs/13/7/915

Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

ARTICLE

Multiple Sclerosis 2007; 13: 915 928

The neurogenic bladder in multiple sclerosis: review of the literature and proposal of management guidelines
`ze*1, Alain Ruffion2, Pierre Denys3, Pierre-Alain Joseph1 and Brigitte Marianne de Se 4 Perrouin-Verbe and the International Francophone Neuro-Urological expert study group (GENULF)
Vesicourethral dysfunction is very frequent in multiple sclerosis (MS) and has functional consequences for patients quality of life and also an organic impact following complications of the neurogenic bladder on the upper urinary tract. While the functional impact and its management are well documented in the literature, the organic impact remains underestimated and there are no consensual practical guidelines for the screening and prevention of MS neurogenic bladder complications. The aim of this review of the literature, focused on identifying the risk factors of urinary tract complications in MS, is to put forward well informed considerations to help in the definition of practical guidelines for the follow-up of the neurogenic bladder in MS in order to improve its prevention and patient management. Four main risk factors have been identified for upper urinary tract damage: the duration of MS, the presence of an indwelling catheter, highamplitude neurogenic detrusor contractions and permanent high detrusor pressure. Detrusorsphincter dyssynergia, age over 50 and male sex may form three additional risk factors. Recommendations for long-term urological follow-up, taking into account these specific risks are constructed according to the procedures recommended by the French Health Authorities. Multiple Sclerosis 2007; 13: 915 928. http://msj.sagepub.com Key words: multiple sclerosis; neurogenic bladder; overactive bladder; upper urinary tract abnormalities; ureterohydronephrosis; urinary tract infection

Introduction
Urinary tract dysfunction is quite common during the course of multiple sclerosis (MS), not only representing a considerable psychosocial burden, but also often requiring care, hospitalization and posing a great challenge for the treatment team. While the frequency of micturitional disorders in MS is widely recognized, urinary tract morbidity is traditionally considered to be scarce and functional consequences are considered to outweigh organic

impact. However, several studies suggest that upper urinary tract involvement and kidney disease are not exceptional in patients with MS, leading researchers to consider the need for improving their prevention and management. The aim of the first part of this work was to identify, through an exhaustive analysis of the literature, the factors that influence the prognosis of upper urinary tract complications in MS. The second part, prepared jointly with the International Francophone Neuro-Urological expert study group (GENULF) aimed at putting forward well informed

1 dEvaluation et de Traitement du handicap Urinaire, Service de Me decine Physique et de re adaptation, CHU Unite `me nerveux, Universite Victor Segalen Bordeaux 2, 33076 Bordeaux Pellegrin, Equipe de recherche Handicap et Syste Cedex, France 2 pital Henry Gabrielle, CHU Lyon, 69565 Saint Genis Laval Cedex, France Service dUrologie, Ho 3 pital Raymond Poincare e ducation neurologique, Ho , APHP, 92380 Garches Cedex, France Service de Re 4 pital Saint Jacques, CHU de Nantes, 44093 Nantes Cedex, decine Physique et de Re adaptation, Ho Service de Me France `ze, Unite dEvaluation et de Traitement du Handicap Urinaire, Service de Author for correspondence: Marianne de Se decine Physique et de Re adaptation, CHU Pellegrin, 33076 Bordeaux Cedex, France Me E-mail: marianne.de-seze@chu-bordeaux.fr Received 19 July 2006; accepted 4 December 2006

2007 SAGE Publications

10.1177/1352458506075651
Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

916

`ze et al. M de Se

specific recommendations for the medium- and long-term supervision of MS neurogenic bladders according to the methodology recommended by the French Health Autorities [1] (HAS).

Detrusor and sphincter disorders in multiple sclerosis


Epidemiology Detrusor and sphincter disorders are all but inevitable in the evolution of MS. The fluctuations in their prevalence (reports range from 32% to 96.8%) reflect difference in time of examination from onset of MS and diagnosis (namely including urodynamics or not) rather than a real heterogeneity of incidence [2 20] (Table 1). Appearing on average 6 years after the onset of the disease (ranges from 5 to 9.5 years) [2,9,13,14,16,21,23], detrusor and sphincter disorders may affect one patient out of 10 at the time of initial clinical manifestation of MS [24 28]. This inaugural character has been correlated with the severity of the further vesicourethral clinical and urodynamic status and may increase urinary morbidity [29] (LSP1). Clinical presentation and influencing factors (Table 1) The predominance of overactive bladder syndrome [30], characterized by urgency, urinary frequency and/or urge incontinence (irritative symptoms), is constantly reported with a prevalence of 37 99% of patients [2 22]. Obstructive symptoms [30] are also frequently reported, affecting between 34% and 79% of patients and in 25% of cases resulting in chronic urinary retention [2 22]. Irritative and obstructive symptoms often coexist, and may jointly affect up to 59% of men and 51% of women [15]. The clinical presentation of vesicourethral dysfunction (VUD) is variable over time [30]. The appearance of new symptoms, mainly of the irritative type, may affect up to one third of patients over a period of 42 months [31]. Overall, the clinical presentation of VUD offers little information on the type and severity of the detrusor-sphincter disorders [2,9,20]. There is little correlation between the clinical and urodynamic symptomatology and while a combination of irritative symptoms and detrusor overactivity is sometimes reported [8,9], the majority of studies offering a satisfactory methodology do not objectively confirm this systematic coexistence [2,13,21,25,31,32]. Two factors likely to influence the clinical presentation of VUD in MS have an established LSP: the MS duration and the severity of the neurological deficiencies and disabilities. Their independence has not been asserted. There appears to be a significant correlation between the MS duration and the presence and the severity of clinical VUD

Material and methods


Our literature review was based on an exhaustive search of the Medline, Embase and Pascal data bases with one or several of the keywords neurogenic bladder , multiple sclerosis , upper urinary tract abnormalities and bladder dysfunction. An analysis of the grey literature, ie, proceedings from conferences or symposia, specifically dedicated to the neurogenic bladder, MS and the consensus conferences of the HAS on MS and nosocomial urinary infections was added to the database search results. In accordance with the HAS guide to literature analysis and scoring of recommendations [1], the publications were classified according to their level of scientific proof (LSP): Level 1, called established scientific proof (LSP1), included high-powered randomized comparative trials, meta-analyses and decision analyses based on properly performed studies. This enabled the presentation of Grade A recommendations. Level 2, called scientific assumption (LSP2), grouped low-powered randomized comparative trials, properly performed non-randomized comparative studies and cohort studies. This enabled the presentation of Grade B recommendations. Levels 3 and 4, called low-level scientific proof, included, respectively, control case studies (LSP3) and comparative studies with substantial levels of bias, retrospective studies, series of cases and descriptive epidemiological studies (LSP4). They enabled the presentation of Grade C recommendations [1].

Literature analysis
Out of the 202 references indexed over the last 30 years in the data bases and in the grey literature addressing the MS neurogenic bladder, 52 gave descriptive or analytical information that was useable for the drafting of this document. Twentytwo of these references were at the HAS Level 1 of scientific proof and 15 at Level 2 [1] (see Tables 1 3).

Multiple Sclerosis 2007; 13: 915 928


Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

http://msj.sagepub.com

Neurogenic bladder in multiple sclerosis

917

VUD, vesicourethral disorder; LSP, ANAES level of scientific proof [1]; U, Unknown; DSD, detrusor and sphincter disorders; VD, voiding dysfunction.

Prevalence of pollakiuria (%)

but not with their clinical presentation [5,6, 20,22,29,33]. The prevalence of clinical VUD appears to be correlated with the severity of the overall deficiencies (EDSS score, Kurtzke scale) [5,6,9,20,33,34]. The prevalence of irritative symptoms is also correlated with the severity of pyramidal damage (Babinskis sign, EDSS pyramidal score) [5,9,20]. The correlation between urinary retention and neurological status is still controversial [35,36]. There is no scientific proof of the influence of the progressive form of MS on the VUD clinical presentation, except for an assumption of proof between the attack of MS and the obstructive syndrome [20]. To date, a link between MRI data and clinical symptoms of VUD has not been established [25,37,38]. Demographically, age has no direct influence. However, as observed in the general population, women may be predisposed to urinary incontinence and to the irritative symptoms and men to the obstructive symptoms [3,6,10,15,20,23, 27,28].

Prevalence of urinary retention (%)

24 32.7

8.3

73.8

34 20

52

Prevalence of dysuria (%)

46 12 36 17.5 49 28

79.5

25

27 47

Prevalence of incontinence/ urgency (%)

80 41.6 69.1

63 50 72

63

42 38.5 65 25 82 60 36.6

67.7 99 32 48 76 66 38 59 36

49 56 19 66

30 48 6 26

49

49

Urodynamic presentation and influencing factors [2,3,5,8 17,19 21,23,27,31 34,39 45] The poor specificity of the clinical symptoms in MS VUD and the identification of specific cystometric risk factors for uronephrologic prognosis argues for the use of urodynamic explorations. This would allow a precise evaluation of functional physiopathology of VUD and of risk factors for urinary tract damage in MS patients, thus helping to plan their optimal management [4,26,33]. The most frequent cystomanometric picture is detrusor overactivity (mean occurrence of 65%, ranges from 34% to 99%) followed by detrusor underactivity (mean occurrence of 25%, ranges from 0% to 40%) and poor bladder compliance (2 10%) (Table 2). Detrusor-sphincter dyssynergia (DSD) is irregularly and diversely estimated with a prevalence of 5 83% and a mean of 35%, but diagnosis criteria vary between studies. Cystometrogram can be considered normal in 1 34% of symptomatic patients [25,26]. The combination of the urodynamic patterns is frequent and detrusor overactivity can be combined with DSD in 43 80% of patients [2,25,45,46] and with detrusor acontractility in 5 9% [29,31]. Cystometrogram may change over time independently of any micturitional and neurological clinical stability [16,31,47]. In Ciancos series, 55% of 22 patients assessed by repeated cystomanometric tests presented changes in their bladder capacity, contractility, pressure or detrusor compliance over 42 months [31]. Only the DSD appeared stable over time, staying present in 60% of the patients [16,31,47]. There is not sufficient argument to claim any direct influence of age on Multiple Sclerosis 2007; 13: 915 928

Prevalence of urgency (%)

72 71 85

85 86 36.6 41.6 69.1

32 70 71 44

Time since onset of VD (years)

Mean duration of MS (years)

Table 1 Clinical presentation of VUD in MS

Number of patients

http://msj.sagepub.com

Amarenco, 1995, LSP1 Andersen, 1976, LSP2 Awad, 1984, LSP2 Bemelmans, 1991, LSP2 Betts, 1993, LSP1 Bradley, 1978, LSP4 de Ridder, 1998, LSP2 Eardley, 1991, LSP2 Gallien, 1998, LSP1 Giannantoni, 1998, LSP1 Goldstein, 1983, LSP4 Gonor, 1985, LSP2 Hennessey, 1999, LSP1 Kasabian, 1995, LSP2 Koldewijn, 1995, LSP1 Philp, 1981, LSP2 Porru, 1997, LSP1

Author, level of proof (LP)

225 62 47 40 170 90 30 24 149 116 86 64 221 32 211 52 120

13.3 12.2 16 5.4 12 U U 11 13 14.5 U 13 U 18 6.5 10 0.1 9

7.8 4.9 U U 6 U U U 6 7.1 U 4.6 U U U 5 U

Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

61

Multiple Sclerosis 2007; 13: 915 928 http://msj.sagepub.com

918 `ze et al. M de Se

Table 2

Urodynamic presentation of VUD in MS Number of patients 225 52 32 57 90 40 170 41 302 22 30 24 149 116 86 64 70 32 212 89 88 52 31 39 113 50 Mean duration of MS (and VD) in years 13.3 (7.8) 12.2 (4.9) 11.8 (U) 16 (U) 5 (U) 5.4 years (U) 12 (6) 12 (7) U U (U) U (U) 11 (U) 13 (6) 14.5 (7.1) U 13 (4.6) U (U) 18 (U) 6.5 (U) 12 (4) 15 (U) 10 (5) U (U) U (U) 9.9 (U) 1 6 (U) Detrusor overactivity (%) 70 63.5 43.7 66 57.7 22.5 91 56 62 68 43 63 41 81 76 78 63 56 34 78 83 99 74 69 70 52 Detrusor hypoactivity (%) 9 32.7 37.5 21 16.6 12.5 0 40 34 14 13 25 24.1 19 20 28 31 8 6 16 0 6 5 15 12 Normal vesical activity (%) 21 3.8 3.1 12 U 32 9 4 24 14 25 34 10.3 6 2 9 13 34 12 1 1 9 15 6 18 Absence of compliance (%) 2 U 3.1 U 5.5 U U U U U U U U 10.3 U U U U U U U U U U U U Detrusor-sphincter dyssynergia (%) 82 30.8 40.6 52 30 U U 30 U 23 36.6 27 59.7 42.2 66 12 21 5 13 6 41 37 47 50 28 12

Author, level of proof (LSP) Amarenco, 1995 96, LSP1 Anderson, 1976, LSP2 Araki, 2003, LSP2 Awad, 1984, LSP2 Barbalias, 1998, LSP2 Bemelmans, 1991, LSP2 Betts, 1993, LSP1 Blaivas, 1979, LSP2 Bradley, 1978, LSP4 Cianco, 2001, LSP2 de Ridder, 1998, LSP2 Eardley, 1991, LSP2 Gallien, 1998, LSP1 Giannantoni, 1998, LSP1 Goldstein, 1982, LSP4 Gonor, 1985, LSP2 Hinson, 1993, LSP2 Kasabian, 1995, LSP2 Koldewijn, 1995, LSP1 Mayo, 1992, LSP2 Petersen, 1984, LSP2 Philp, 1981, LSP2 Piazza, 1979, LSP4 Schoenberg, 1979, LSP2 Sirls, 1994, LSP4 Summers, 1978, LSP4

Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

http://msj.sagepub.com
Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

Table 3

Urinary tract complications in MS Duration of MS (years) median (range) Overall Duration of prevalence VD (years) (%) 7.8 4.9 U U 6 7 6 7.1 4.6 U U U 4 U U U U U 3.3 4 21 20 3.8 0 U 15 U U 56 0 Lower urinary tract infections (%) 36.6 17.3 13.3 0 U U 32.8 U 74 30 U 11.8 19 27 U 21 54 Damage to lower urinary tract (%) 49.4 U 16.6 U U U U 30.1 75 4 U U 12 U U U 29 Dilatation of Vesicoureteral upper tract reflux (%) (%) 3.3 0 6.6 0 0 15 U 5.2 5 U 0 3 3.4 14 U 1.9 4.2 3.8 0 15.5 0 3.6 0 U 6 2.8 11 3.8 0.9 2.2 U 3.3 6.6 1.8

Author (level of proof LSP) Amarenco, 1995 96 (LSP1) Andersen, 1976 (LSP2) Barbalias, 1999 (LSP2) Bemelmans, 1991 (LSP2) Betts, 1992 (LSP1) Blaivas, 1979 (LSP2) Gallien, 1994 1998 (LSP1) Giannantoni, 1998 (LSP1) Gonor, 1885 (LSP2) Henessey 1998 (LSP1) Kasabian, 1995 (LSP2) Koldewijn, 1995 (LSP1) Mayo, 1992 (LSP2) Petersen, 1984 (LSP) Porru, 1997 (LSP1) Sirls, 1994 (LSP4) Sliwa, 1996 (LSP1)

Upper urinary infections (%) 15.5 0 2.2 0 U 0 22.8 U 3 U U 11 U 9 U U U

Renal failure (%) 0 0 U 0 0 U 2 0 0 (n 0/64) 3 U U U U U 0 0

Urinary lithiasis (%) 3.8 U 10 0

225 13.4 52 12.2 90 5 40 4.6 170 12 (0.5 48) 41 12 (2 39) 149 13 116 14.5 64 13 (0.5 40) 221 U 32 18 212 6.5 89 12 88 15 120 0.1 9 113 9.9 48 13.4

U 2 6 U

Neurogenic bladder in multiple sclerosis

3 0 U 2.2 U U 4.7 10.8

Multiple Sclerosis 2007; 13: 915 928

919

920

`ze et al. M de Se
[3,8,9,13,17,18,27,32,33,44,45]. However, the definition of urinary tract infection (diagnostic criteria, diagnostic threshold, symptomatic character or not) is neither consensual nor systematically stated, limiting the true analysis of its prevalence rate. Only one clinical study devoted to the lower urinary infection risk factor in MS was found. It stresses the deleterious influence of the post-void residual volume (180 mL compared to 119 mL on average in patients with or without urinary infections respectively) and of the female gender (42% of urinary infection in women compared to 17% in men) [14]. No study addressing the specific potential risk factors of the MS population, such as exposure to immunosuppressants or cystonephrotoxic treatments, was found. By analogy with other neurogenic populations, and particularly traumatic spinal cord injured patients, an indwelling catheter, high bladder pressures and the existence of a postvoid residual volume of more than 300 mL can be considered to favour the occurrence of lower urinary tract infections [48 51].

the urodynamic presentation of VUD in MS. On the other hand, gender may be an independent factor of influence, with a significant increase in the maximum amplitude of the uninhibited detrusor contractions, of the detrusor leak point pressure (lowest detrusor pressure at which urine leakage occurs in the absence of either a detrusor contraction or increased abdominal pressure) and of the maximum detrusor pressure in men as compared to women [15] (LSP1). Duration of the MS evolution influences the urodynamic presentation of VUD only for DSD, the prevalence of which increases with time, probably due to its low regression rate after its appearance [16,23,31,47] and to its increasing incidence over time [22]. Thus, DSD is present in 13% of patients after 48 months of MS development, in 15% between 48 and 109 months and in 48% after 109 months of MS duration [22]. There is no specific urodynamic presentation linked to progression form, remittent or progressive, although a link has been reported between the MS activity (estimated by the basic protein level in the CSF) and the presence of DSD and/or of detrusor overactivity [20]. Correlations between the neurological and cystomanometric states have been reported. The correlation between detrusor overactivity and the severity of sensory-motor deficiencies (EDSS) or of pyramidal damage appears probable [9,15,29]. A correlation between DSD and pyramidal damage or the degree of disability has been suggested [11,15,29]. No correlation between detrusor undercontractility and neurological status has been found [20]. Finally, the existence of a correlation between certain lesional sites and the cystomanometric data remains controversial [34,37,38], but the presence of encephalic or suprasacral lesions and lesions on the brain stem may be a predisposing factor for DSD and detrusor undercontractility respectively [34,42,46].

Morphological damage to lower urinary tract Morphological damage to the lower urinary tract is reported in an average of 30% of patients (ranges from 4% to 49%), including bladder diverticula, trabeculae and parietal thickening, whose relative extent is not specified [3,8,9,13 15,17 20,22,23,27 29,32,33,44,45].

Bladder cancer Three publications, including one retrospective LSP1 study, suggest that the risk of bladder cancer is greater in MS than in the general population, especially in patients under chronic catheterization (indwelling catheter or suprapubic catheter) and having been treated with immunosuppressants [52 54]. In addition to two control cases of condylomas in two MS patients treated with immunosuppressants for 13 years [53,54], de Ridder et al. report the occurrence of seven vesical cancers, six transitional cell carcinomas and one epidermoid carcinoma in a population of 2351 patients assessed over a period of 31 years [52]. In that series, the 1271 patients with an indwelling or suprapubic catheter benefited from an annual cystoscopic check with a biopsy by forceps in the event of any suspect macroscopic aspect. Six of the seven bladder cancers occurred in patients with an indwelling or suprapubic catheter for 3.3 years and the last in a patient having been under intermittent self-catheterization (ISC) for 4 years. The first alarm signal was haematuria. All seven patients had previously http://msj.sagepub.com

Urinary tract complications from neurogenic bladder in MS


The literature review indicates that the overall prevalence of urinary tract complications in MS is between 0% and 40% in series including patients until 18 years of MS follow-up [3,8,9,13 15,17 20,22,23,27 29,32,33,44,45]. Complications of lower urinary tract Lower urinary tract infections Lower urinary tract infections are reported in 30% of patients on average (ranges from 13% to 80%) Multiple Sclerosis 2007; 13: 915 928

Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

Neurogenic bladder in multiple sclerosis


been treated with cyclophosphamide (mean aggregate dose of 60.8 g), which had been halted on average 5.8 years previously [52]. The overall incidence of bladder cancers in that MS population was 0.29% higher than in the general population (0.018 in men, 0.004 in women)[55] and close to that of the traumatic medullary population (from 0.27 to 9.6%) [56]. The risk of bladder cancers appeared higher in patients with indwelling or suprapubic catheters (an incidence of 0.7%) and in the ISC patients (an incidence of 0.23%), with a maximum risk in the subpopulation of patients under chronic catheterization having been treated with immunosuppressants (incidence of 5.7%) [52].

921

long duration of VUD in MS may have a negative impact on MS mortality but the independence of this factor has not been asserted and the influence of its management has not been documented. Unlike renal failure, a neglected aspect is the infectious mortality from the urinary system, as it has been shown to be high in traumatic spinal cord injury [50,60]. Further studies of this specific aspect are needed.

Risk factors of upper urinary tract complications in MS


MS duration

Other complications Complications of the upper urinary tract are reported in 12% of patients on average (ranges from 0% to 25%) [3,8,9,13 15,17 20,22,23,27 29,32,33,44,45,51]. These include, in order of frequency, upper urinary tract infections, with a median incidence of 8% (ranges from 0% to 23%), dilatations of the upper urinary tract, observed in 8% of patients (0 25%) and vesicoureteral reflux, found in 5% of patients (ranges from 0 to 15%) [3,8,9,13 15,17 20,22,23,27 29,32,33,44,45,51]. Estimates of the prevalence of urinary lithiasis vary from 2% to 11% and its localization on the urinary tree is rarely specified [3,8,9,13 15,17 20,22,23,27 29,32,33,44,45,51]. Finally, the majority of studies report the exceptional character of renal failure in MS [3,8,9,13 15,17 20,22,23,27 29,32,33,44,45,51]. No increased risk of renal failure in the MS population as compared to the general English population has been proven [57]. On the other hand, populations of patients with a traumatic or malformative spinal cord lesion present an increased risk of development of severe renal failure by a factor of 5 and 8 respectively [57].

Seventeen clinical studies provide useable data on the prevalence of upper urinary tract complications in MS [3,8,9,13 15,17 20,22,23,27 29,32,33,44, 45,57]. The majority are retrospective studies, indicating the mean duration of MS and of patient follow-up. Calculation of the cumulative incidences of morbid events which occurred over time in these studies, as shown in Figures 1 4, illustrates an increasing prevalence of complications with passing years. As these studies do not specify the time between the onset of the disease and the appearance of upper urinary tract events, it is difficult to precisely identify the periods with higher risk of complications in the lower and upper urinary tracts of VUD in MS. The slope of the cumulative

Mortality due to urinary tract disorders Mortality due to urinary tract disorders remains underestimated in MS. Two studies mention the rate of death related to a urological cause, one giving 55% of 20 deaths and the other 5% of 75 deaths [58,59]. A Dutch epidemiological study assessing the factors influencing the life expectancy of 216 MS patients fails to prove any death from a urological cause but reports a survival rate after 40 years of MS progression [57]. This rate is significantly lower in those patients with an onset of VUD during the first 10 years of MS progression (6.4% survivors) compared to those patients where VUD occurred after 10 years (29.2% survivors) [57]. The http://msj.sagepub.com

Figure 1 Cumulative incidence of vesicoureteral reux depending on the MS duration (data from 1348 patients in 14 studies 60 cases of reux identied).

Multiple Sclerosis 2007; 13: 915 928


Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

922

`ze et al. M de Se

Figure 2 Annual cumulative incidence of vesicoureteral reux depending on the MS duration (linear hypothesis) (1348 patients, 14 studies, 60 cases).

Figure 4 Aggregate annual incidence of upper tract dilatations depending on the MS duration (linear hypothesis) (1200 patients, 11 studies, 52 cases).

incidences (Figures 1 4) nonetheless suggests that the risk of occurrence of an upper urinary tract complication increases as of a period between the sixth and eighth year of survival. Two studies take into account the overall prevalence of upper

urinary tract complications according to the duration of the disease [15,44]. These indicate that this is greater within the subpopulations of patients presenting complications of the upper urinary tract than among patients without any complications, with respective values of 15.2 years as against 11 years [44] and 17.8 years as against 13.4 years [15]. A correlation between the duration of MS and the risk of pyelonephritis [13,14] or damage to the lower urinary tract [15] has also been reported.

Gender No direct correlation between gender and upper urinary tract complications has been found [15,44]. However, in men the greater frequency of urodynamic criteria predisposing towards damage to the upper urinary tract (high detrusor pressure and frequent uninhibited contractions of the detrusor) may constitute an additional risk factor [15] (LSP1). A greater risk of pyelonephritis has also been reported in men suffering from low urinary infections [13,14].

Age Two LSP1 studies find that the average age is higher in the population of patients with upper complications compared to the population without complications (50.6 as against 46 years [2] and 53.1 as against 45.5 years, respectively) [15]. The http://msj.sagepub.com

Figure 3 Cumulative annual incidence of infections of the upper tract depending on the MS duration (linear hypothesis) (961 patients, 9 studies, 95 cases).

Multiple Sclerosis 2007; 13: 915 928


Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

Neurogenic bladder in multiple sclerosis


deleterious influence of age may, however, reflect that of a prolonged duration and severity of MS. Progression of MS No influence of the type of progression of MS, remittent or progressive, on the urinary tract prognosis has been proven [9,15]. Pyramidal symptoms A correlation between the severity of pyramidal symptoms and the prevalence of complications of the upper urinary tract has been reported [14,15,46], with mean EDSS pyramidal scores of 4.1 and 3.1 respectively in patients with and without damage to the upper urinary tract [15]. However, this finding is not reported systematically and may reflect a risk inherent to the prolonged duration of the disease, as is the case with age. Urologic clinical symptom Other risk factors The influence of the urologic clinical symptom on the urinary tract prognosis is modest [15,44]. In patients presenting a postmicturitional residue /30% of the vesical capacity, only an increased frequency of pyelonephritis has been reported [14]. Urodynamically, correlations have been reported between the prevalence of complications of the upper urinary tract and the high amplitude of uninhibited contractions of the detrusor [4,15]. Similarly, morphological damage to the lower urinary tract is positively correlated with high maximum detrusor pressures and negatively correlated with detrusor hypocontractility [15]. DSD The influence of DSD on the urinary tract prognosis in MS is controversial. Several LSP1 publications fail to prove any correlation between the prevalence of DSD and urinary complications [2,15,29,44], but one meta-analysis reports that 7 out of 2076 patients with an upper tract complication presented a DSD [20] and a correlation between the presence of a DSD and the incidence of pyelonephritis has been stressed [46]. There are also arguments in support of an indirect influence of DSD on upper urinary tract complications, insofar as the presence of a DSD has been correlated with the severity of the neurological status, which itself impacts on the urinary tract prognosis [11,16,20]. http://msj.sagepub.com

923

The respective dangerousness of the various types of DSD remains unknown [7].

Mode of urinary drainage An indwelling catheter is a recognized risk factor for deterioration of the upper urinary tract, for upper and lower urinary infection [10,13,15,25,42, 46,48,49], and for increasing the risk of the occurrence of bladder cancer in MS patients under immunosuppressants [52]. No specific study devoted to the influence of the other voiding modes on the urinary tract prognosis in MS was found. By analogy with other neurological pathologies, and in particular traumatic and congenital impairments of the spinal cord, it is considered that the presence of upper urinary tract complications decreases successively depending on whether the voiding mode is based on an indwelling catheter, intermittent catheterization, suprapubic catheter, intermittent self-catheterization or voluntary voiding [48 50].

Finally, there is no documentation on the influence of the type of therapeutic management (pharmacological, functional or surgical), of the interest of an early management or of exposure to urotoxic treatments on the urinary tract prognosis in MS. Thus, four main risk factors for the deterioration of the upper and lower urinary tracts have an established level of proof (LSP1), resulting from studies of good metrological quality and/or that are recognized by the majority of authors: the duration of MS, especially after the 15th year of duration, the presence of an indwelling catheter, the high maximum amplitude of the uninhibited contractions of the detrusor and the permanent high detrusor pressures during filling (threshold /40 cm H2O in ref. [4], LSP1). Three other factors benefit from an assumption of proof (LSP2). They are all recognized by at least one study of good metrological quality, but remain controversial in the literature: the DSD, age over 50 years (for which independence with respect to the duration of the disease has not been established) and male sex through the presence of negative urodynamic factors. It thus appears possible to consider the existence of two types of urinary tract situations in MS patients: risk-free patients not presenting any of the LSP1 risk factors and no more than one LSP2 factor, and patients at risk with at least one LSP1 risk factor or more than two LSP2 factors (Table 4). Multiple Sclerosis 2007; 13: 915 928

Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

924
Table 4

`ze et al. M de Se
Risk factors of upper urinary tract complications in MS Definite risk factors Probable risk factors 2. Assumption of proof Detrusor-sphincter dyssynergia Age over 50 years Male sex Risk group Risk patient: at least one definite risk factor or more than two probable risk factors Risk-free patient: No definite risk factor and no more than two probable risk factors

Level of scientific proof Nature of risk factor

1. Established level of proof - MS duration beyond 15 years - Indwelling urinary catheter - Ample uninhibited contractions of the detrusor - High detrusor pressure

Practical guide to diagnosis and follow-up of neurogenic bladder in MS (Figure 5)


Recommendations for medium- and long-term neurourological monitoring, constructed according to the procedures recommended by the health authorities [1,61], and taking into account the specific risks of these two populations, risk-free patients and risk patients, have been developed by the International Francophone Neuro-Urological Study Group (GENULF), which involves urologists, neurologists and physical medicine and rehabilitation practicians.

recommended to perform the evaluation at distance from the relapse. If micturitional disorders are discovered, it is recommended to address the patient to a practician experienced in neurourology.

Symptomatic patient (Figure 5) When micturitional symptoms are discovered or spontaneously reported during the minimal evaluation, the patient should be referred to an experienced neurourology practician, who will conduct a baseline evaluation based on six mean parameters: 1) 2) 3) 4) 5) 6) a three-day voiding chart, an ultrasound scan of the urinary tract, a urine bacteriology, a urodynamic study, a urinary creatinine clearance an evaluation of the impact of urinary symptoms on a quality-of-life scale (which may be based on the specific and validated Qualiveen Questionnaire [62].

Urinary asymptomatic patient (a patient who does not spontaneously report any urinary disorders) [Figure 5] In the absence of urinary symptoms, the MS followup is usually performed by a neurologist and a treating physician; patients are not referred to a neurourologic unit. In these patients, a minimal evaluation is advocated, on the initiative of the neurologist, the rehabilitation doctor or the general physician (GP). This evaluation is based on two simple parameters: 1) A specific questionnaire about voiding (frequency, number and easiness of voiding, appraising voiding volume, sensation of complete emptying or not), continence (number and appraising volume of leakage, use of pads), symptoms of urinary tract infection and anorectal symptoms. A measure of postvoid residual urine by suprapubic ultrasonography.

2)

If this minimal evaluation does not reveal urinary disorders, a simple survey based on the above minimal evaluation is recommended at each visit for MS follow-up. In relapsing form, it is Multiple Sclerosis 2007; 13: 915 928

The necessity to perform a complete urodynamic study in all symptomatic MS patients is not fully established in the literature. In MS patients suffering from overactive bladder symptoms, some authors have recommended to restrict the initial evaluation to the association of uroflowmetry and a postvoid residual measure, claiming that these exams are sufficient to start the initial treatment [63]. For the management of non-neurologic patients presenting overactive bladder symptoms, the first step is to determine whether there is an incomplete voiding (and urinary tract infection), and if not, to introduce anticholinergic drugs, reserving the full urodynamic evaluation to nonresponder patients [64]. This view is not yet consensual regarding MS patients, for whom detrusor impairment and/or uronephrologic risk factors relating to high detrusor pressure may be underestimated due to a limited evaluation excluding cystometry. A randomized trial would be required http://msj.sagepub.com

Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

Neurogenic bladder in multiple sclerosis


ASYMPTOMATIC PATIENT Minimal evaluation Specific questionnaire of VUD Post void residual
Micturitional symptoms ?

925

SYMPTOMATIC PATIENT Neuro-Urologic physician

Baseline evaluation 3-days voiding chart

Urinary Echography

No

Yes

Urine bacteriology Urodynamic study


Urinary creatinin clearance Quality of Life related to VUD

Analysis of risk factors

Minimal evaluation at each MS follow-up visit Specific questionnaire of VUD


Post void residual

Risk-free patient Annual evaluation 3-days voiding chart Uroflowmetry Post void residual

Risk patient Annual evaluation 3-days voiding chart Post void residual Urinary echography Urinary creatinin clearance Quality of Life VUD Urodynamics(1 to 3 year)

Change in risk factors No Yes

Urodynamics every 3 years

Urodynamics

Upper Urinary tract deterioration Multidisciplinary consideration Complementary exam

Risk of bladder cancer

Annual cystoscopy Annual cytolopy

Figure 5 Recommendations for diagnosis and follow-up of neurogenic bladder in MS.

to address whether these two different first-line evaluations have any influence on management and prognosis of vesicourethral dysfunction in MS patients. In the absence of such a study, most authors agree with the view that a thorough urodynamic evaluation is mandatory for effectively diagnosing urinary tract dysfunction, detecting the risk factors for upper urinary tract and planning urinary tract management in MS patients, although this view is challenged by other authors [4,26,33,64,65]. The rhythm and modality of subsequent evaluations are then determined according to the nature and number of urinary tract morbidity risk factors identified at the above initial evaluation (Table 4,

Figure 5). Two risk situations can be distinguished: a risk-free situation, in patients who do not present any of the LSP1 risk factors and no more than one LSP2 factor, and a risky situation in patients who presented at least one LSP1 risk factor or more than two LSP2 factors. Risk-free patients For risk-free patients, a systematic annual evaluation is advocated, including a three-day voiding chart, uroflowmetry (measurement of urinary flow rate) and a postvoid residual measure. If symptoms and risk factors remain stable, a three-year urodynamic exam is recommended. If symptoms and/or

http://msj.sagepub.com

Multiple Sclerosis 2007; 13: 915 928


Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

926

`ze et al. M de Se
urinary tract complication during the first 18 years of disease duration. Better knowledge of the risk factors for neurogenic bladder in MS with a urinary tract impact, and of their progressive profile, should lead to a controlled and consensual use of monitoring examinations. This could further the adoption of preventive and curative therapeutic measures aimed at improving the quality of care and life of MS patients with a positive individual and economic impact on public health as a result.

risk factors have changed, a new evaluation of the urodynamic status is then required. Risk patients For risk patients, the annual evaluation should be more complete, based on five systematic parameters: 1) 2) 3) 4) 5) a three-day voiding chart, a postvoid residual measure, an ultrasound scanning of the urinary tract, a urinary creatinine clearance, an evaluation of quality of life relative to VUD.

References
1. ANAES. Guide to literature analysis and scoring of recommendations. ANAES, January 2000. Retrieved from: http//www.anaes.fr 2. Amarenco G, Kerdraon J. Bladder and sphincter dysfunction in multiple sclerosis. Clinical, urodynamical and neurophysiologic study of 225 cases. Rev Neurol 1995; 151: 722 30. 3. Andersen JT, Bradley WE. Abnormalities of detrusor and sphincter function in multiple sclerosis. Br J Urol 1976; 48: 193 98. 4. Andrews KL, Husmann DA. Bladder dysfunction and management in multiple sclerosis. Mayo Clin Proc 1997; 72: 1176 83. 5. Awad S, Gajewski J, Sogbein S, Murray TJ, Field CA. Relationship between neurological and urological status in patients with multiple sclerosis. J Urol 1984; 132: 499 502. 6. Bakke A, Myhr KM, Gronning M, Nyland H. Bladder, bowel and sexual dysfunction in patients with multiple sclerosis a cohort study. Br J Urol 1996; 179: 61. 7. Blaivas JG, Bhimani G, Labib KL. Vesicourethral dysfunction in multiple sclerosis. J Urol 1979; 122: 342 47. 8. Bemelmans B, Hommes O, Van Kerrebroek P, Doesburg WH, Debruyne FM. Evidence for early tract dysfunction in clinically silent multiple sclerosis. J Urol 1991; 145: 1219 24. 9. Betts C, DMellow M, Fowler C. Urinary symptoms and the neurological features of bladder dysfunction in multiple sclerosis. J Neurol Neurosurg Psychiatry 1993; 56: 245 50. 10. Bradley WE. Urinary bladder dysfunction in multiple sclerosis. Neurology 1978; 28: 52 58. 11. de Ridder D, Vermeulen C, de Smet E, Van Poppel H, Ketelaer P, Baert L. Clinical assessment of pelvic oor dysfunction in multiple sclerosis: urodynamic and neurological correlates. Neurourol Urodyn 1998; 17: 537 42. 12. Eardley I, Nagendran K, Lecky B, Chapple CR, Kirby RS, Fowler CJ. Neurophysiology of the striated urethral sphincter in multiple sclerosis. Br J Urol 1991; 68: 81 88. 13. Gallien P, Robineau S, Nicolas B, Le Bot MP, Brissot R, Verin M. Vesicourethral dysfunction and urodynamic ndings in multiple sclerosis: a study of 149 cases. Arch Phys Med Rehabil 1998; 79: 255 57. 14. Gallien P, Nicolas B, Robineau S, Le Bot MP, de Crouy AC, Durue A et al . Urological complications in multiple sclerosis: study of risk factors. Ann Re adaptation Me d Phys 1998; 41: 155 58.

The urodynamic follow-up should be systematic, with a timing adapted to the severity of the risk factors, including a cystometry every one to three years. A morphologic study should be mandated to explore and follow an upper urinary tract deterioration. Patients with upper urinary tract deterioration In patients presenting upper urinary tract deterioration or severe risk factors, especially permanent high detrusor pressure, the management should be conducted with multidisciplinary consideration, taking into account the advice of a neurourologist expert, a neurologist, a physical rehabilitation practician, the treating physician and the patient, in order to define the best therapeutic option, adapted to the urinary tract function as well as the general deficiency and the patients environment. The nature and rhythm of complementary exams should be decided by this multidisciplinary staff and could include imaging techniques (cystourethrography, scans, cystoscopy . . .), and functional exams (renal scintigraphy . . .). Patients with risk of bladder cancer Lastly, in patients presenting specific risk of bladder cancer, in particular those with chronic permanent catheterization, annual cytology and annual cystoscopy are recommended.

Conclusion
This literature review suggests that the urinary tract prognosis, commonly reputed to be satisfactory in MS, needs to be reconsidered. More than one patient out of ten is likely to develop an upper

Multiple Sclerosis 2007; 13: 915 928


Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

http://msj.sagepub.com

Neurogenic bladder in multiple sclerosis


15. Giannantoni A, Sciviletto G, Di Stasi SM, Grasso MG, Vespasiani G, Castellano V. Urological dysfunctions and upper urinary tract involvement in multiple sclerosis patients. Neurourol Urodyn 1998; 17: 89 98. 16. Goldstein I, Siroky M, Sax S, Krane RJ. Neurourologic abnormalities in multiple sclerosis. J Urol 1982; 128: 541 45. 17. Gonor S, Caroll D, Metcalfe J. Vesical dysfunction in multiple sclerosis. Urology 1985; 25: 429 31. 18. Henessey A, Robertson NP, Swingler R, Compston DA. Urinary, faecal and sexual dysfunction in patients with multiple sclerosis. J Neurol 1999; 246: 1027 32. 19. Kasabian NG, Krause I, Brown WE, Khan Z, Nagler HM. Fate of upper urinary tract in multiple sclerosis. Neurourol Urodyn 1995; 14: 81 85. 20. Koldewijn EL, Hommes OR, Lemmens WA, Debruyne FM, Van Kerrebroeck PE. Relationship between lower urinary tract abnormalities and diseaserelated parameters in multiple sclerosis. J Urol 1995; 154: 169 73. 21. Philp T, Read J, Higson R. The urodynamic characteristics of multiple sclerosis. Br J Urol 1981; 53: 672 75. 22. Porru D, Campus G, Garau A, Sorgia M, Pau AC, Spinici G. Urinary tract dysfunction in multiple sclerosis: is there a relation with disease-related parameters? Spinal Cord 1997; 35: 33 36. 23. Blaivas J, Bhimani G, Labib K. Vesico-urethral dysfunction in multiple sclerosis. J Urol 1979; 122: 342 47. 24. Phadke JG. Survival pattern and cause of death in patients with multiple sclerosis: results from an epidemiological survey in north-east Scotland. J Neurol Neurosurg Psychiatry 1987; 50: 523 31. 25. Litwiller SE, Frohman M, Zimmern PE. Multiple sclerosis and the urologist. J Urol 1999; 161: 743 57. 26. Leboeuf L, Gousse AE. Multiple sclerosis. In Corcos J, Schick E eds. Textbook of neurogenic bladder. Adults and children . Martin Dunitz, 2004: 275 92. 27. Mayo M, Chetner M. Lower urinary tract dysfunction in multiple sclerosis. Urology 1992; 39: 67 70. 28. Sliwa JA, Bell HK, Mason KD, Richard MG, Nanninga J, Cohen B. Upper urinary tract abnormalities in multiple sclerosis patients with urinary symptoms. Arch Phys Med Rehabil 1996; 77: 247 51. 29. Giannantoni A, Sciviletto G, Di Stasi SM, Grasso MG, Finazzi Agro E, Collura G et al . Lower urinary tract dysfunction and disability status in patients with multiple sclerosis. Arch Phys Med Rehabil 1999; 80: 437 41. 30. Abrams P, Cardozo L, Fall M, Grifths D, Rosier P, Ulmsten U. The standardisation of terminology of lower urinary tract function: report for the standardisation subcommittee of the International Continence Society. Neurourol Urodyn 2002; 21: 167 78. 31. Cianco S, Mutchnik S, Rivera V, Boone TB. Urodynamic pattern changes in multiple sclerosis. Urology 2001; 57: 239 45. 32. Petersen T, Petersen E. Neuro-urodynamic evaluation of voiding dysfunction in multiple sclerosis. Acta Neurol Scand 1984; 69: 402 11. 33. Sirls L, Zimmern P, Leach G. Role of limited evaluation and aggressive medical management in multiple sclerosis: a review of 113 patients. J Urol 1994; 151: 946 50. 34. Araki I, Matsui M, Ozawa K, Takeda M, Kuno S. Relationship of bladder dysfunction to lesion site in multiple sclerosis. J Urol 2003; 169: 1384 87.

927

35. Kirchlof K, Fowler CJ. The value of Kurtzke Functional Systems scales in predicting incontinence bladder emptying. Spinal Cord 2000; 38: 409 13. 36. Kragt JJ, Hoogevorst EL, Uitdehaag BM, Polman CH. Relation between objective and subjective measures of bladder dysfunction in multiple sclerosis. Neurology 2004; 63: 1716 18. 37. Kim YH, Goodman C, Omessi E, Rivera V, Kattan MW, Boone TB. The correlation of urodynamic ndings with cranial magnetic resonance imaging ndings in multiple sclerosis. J Urol 1998; 159: 972 76. 38. Pozzilli C, Grasso M, Bastianello S, Anzini A, Salvetti M, Bozzao L et al . Structural brain correlates of neurological abnormalities in multiple sclerosis. Eur Neurol 1992; 32: 228 30.36. 39. Summers JL. Neurogenic bladder in the woman with multiple sclerosis. J Urol 1978; 120: 555 56. 40. Schoenberg HW, Gutrich J, Banno J. Urodynamic pattern in multiple sclerosis. J Urol 1979; 122: 648 50. 41. Piazza D, Diokno A. Review of neurogenic bladder in multiple sclerosis. Urology 1979; 14: 33 35. 42. Mac Guire E, Sanastano J. Urodynamic ndings and long term outcome management of patients with multiple sclerosis induced lower urinary tract dysfunction. J Urol 1984; 132: 713 15. 43. Hinson JL, Boone TB. Urodynamics and multiple sclerosis. Urol Clin N Am 1996; 23: 475 81. 44. Amarenco G, Bosc S, Boiteau F. Urological complications of multiple sclerosis. 180 cases. Presse Me d 1996; 25: 1007 10. 45. Barbalias GA, Nikiforidis G, Liatsikos EN. Vesicourethral dysfunction associated with multiple sclerosis: clinical and urodynamic perspectives. J Urol 1998; 160: 106 11. 46. Blaivas J, Barbalias G. Detrusor external sphincter dyssynergia in men with multiple sclerosis: an ominous urologic condition. J Urol 1984; 131: 91 94. 47. Wheeler JS, Siroky MB, Pavlakis AJ, Goldstein I, Krane RJ. The changing neurological pattern of multiple sclerosis. J Urol 1983; 130: 1123 26. ` ze M, Shao E, Joseph PA. Nosocomial urinary 48. de Se infection and patients with a neurogenic bladder in rehabilitation. Me d Mal Inf 2003; 33: 298s 310s. 49. Botto H. Nosocomial urinary infection: consensus report 2002. Med Mal Inf 2003; 33: 370 75. 50. National Institute on Disability and Rehabilitation Research Consensus Statement (NIDRR). The prevention and management of urinary tract infections among people with spinal cord injuries. J Am Paraplegia Soc 1992; 15: 194 204. ` ze M. Sphincter and bladder dysfunction 51. Joseph P, de Se in multiple sclerosis. Rev Neurol 2001; 8 9: 1051 59. 52. de Ridder D, Van Poppel H, Demonty L, DHooghe B, Gonsette R, Carton H et al . Bladder cancer in patients with multiple sclerosis treated with cyclophosphamide. J Urol 1998; 159: 1881 84. 53. Van Poppel H, Stessens R, de Vos R, van Damme B. Isolated condyloma acuminatum of the bladder in a patient with multiple sclerosis: etiological and pathological considerations. J Urol 1986; 136: 1071 73. 54. Wiedemann A, Diekmann WP, Holtmann G, Kracht H. Report of a case with giant condyloma (Buschke-Lowenstein tumor) localized in the bladder. J Urol 1995; 154: 1222 24. 55. Esteve J, Kricker A, Ferlay J, Parkin DM. Facts and gures of cancer in the European Community. International Agency for Research on Cancer, 1993. 56. Panneck J. Transitional cell carcinoma in patients with spinal cord injury. Spinal Cord 2000; 38: 661 68.

http://msj.sagepub.com

Multiple Sclerosis 2007; 13: 915 928


Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

928

`ze et al. M de Se
Working Group. IX. A method for grading health care recommendations. JAMA 1995; 22: 1800 804. Bonniaud V, Jackowski D, Parratte B, Paulseth R, Grad S, Margetts P. Quality of life in multiple sclerosis patients with urinary disorders: discriminative validation of the English version of Qualiveen. Qual Life Res 2005; 14: 425 31. Fowler CJ. Investigation of the neurogenic bladder. J Neurol Neurosurg Psychiatry 1996; 60: 6 13. Anderson KE, Appell R, Cardozo L, Chapple C, Drutz H, Fourcroy J et al . Pharmacological treatment of urinary incontinence. In Abrams P, Cardozo L, Khoury S, Wein A eds. Incontinence, vol 2. Management. Health Publication, 2005: 808 54. Chancellor MB, Blaivas JG. Multiple sclerosis. In Problems in urology , Volume 7, no. 1. JB Lippincott Company, 1993: 15 33.

57. Lawrenson R, Wyndaele JJ, Vlachonikolis I, Farmer C, Glickman S. Renal failure in patients with neurogenic lower urinary tract dysfunction. Neuroepidemiology 2001; 187: 138 43. 58. Samellas X, Rubin B. Management of upper urinary tract complications in multiple sclerosis by means of urinary diversion to ileal conduit. J Urol 1965; 95; 548. 59. Leibowitz U, Kahana E, Jackson SG, Alter M. The cause of death in multiple sclerosis. In Leibowitz U ed. Progress in multiple sclerosis: research and treatment . Academic Press, 1972: 196 209. 60. Soden RJ, Walsh J, Middleton JW, Craven ML, Rutkowski SB, Yeo JD. Causes of death after spinal cord injury: a fty year investigation. Spinal Cord 1998; 36: 266 74. 61. Guyatt GH, Sacket DL, Sinclair JC, Hayward R, Cook DJ, Cook RJ. for the Evidence-Based Medicine

62.

63. 64.

65.

Multiple Sclerosis 2007; 13: 915 928


Downloaded from http://msj.sagepub.com by Marianne de Sze on September 24, 2007 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.

http://msj.sagepub.com

You might also like