DYSFUNCTION DUE TO MULTIPLE SCLEROSIS: A LARGE SCALE RETROSPECTIVE
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AKSEL SIVA, IBRAHIM BULDU, OKTAY DEMIRKESEN, BULENT CETINEL
of Urology (BO, IB, OD, BC) and Neurology (AS), Cerrahpasa School of
Medicine, University of Istanbul, Istanbul, Turkey
To assess the outcome of urologic evaluation in patients with voiding
dysfunction due to multiple sclerosis (MS) and to determine the relationship
between urological and neurological parameters of these patients.
Materials and Methods: We retrospectively reviewed the medical records of 249
consecutive patients (162 female and 87 male) with MS who were referred to our
clinic between 1991 and 2006, with a median time of 4 years (range 3 months to
26 years) of MS onset. Data was analyzed with respect to patient demographics
and findings of initial evaluation. Lower urinary tract symptoms were evaluated
by Boyarsky symptom index.
Results: All patients except 13 had lower urinary tract symptoms and 70% manifested
mixed symptoms. Total, storage and voiding symptom scores correlated with expanded
disability status scale scores (p < 0.05). Twelve patients (5%) had abnormal
upper urinary tract. Ultrasound findings of lower urinary tract were abnormal
in 12 patients (5%). No demographic parameters were associated with abnormal
findings of upper urinary tract on univariate analysis. Urodynamic evaluation
of 75 patients (30.1%) revealed detrusor overactivity with or without detrusor-sphincter
dyssynergia in 56 (75%). No correlation was found between urodynamic diagnosis
and upper tract deterioration and urinary symptom scores (p > 0.05).
Conclusions: The prevalence of mixed symptoms in patients with MS is higher than
storage or voiding symptoms alone. Although detrusor overactivity and detrusor-sphincter
dyssynergia were the most common urodynamic diagnoses, upper urinary tract deterioration
was rare in our series.
words: multiple sclerosis; urodynamics; urination disorders; ultrasound
Int Braz J Urol. 2009; 35: 326-33
sclerosis (MS) is a common neurological disease affecting mostly young
adults with a prevalence of 50 to 100/100,000 individuals (1). Regionally,
the median estimated prevalence of MS is the highest in Europe (80 per
100 000), followed by the Eastern Mediterranean (14.9), the Americas
(8.3), the Western Pacific (5), South-East Asia (2.8) and Africa (0.3)
(2). Lower urinary tract symptoms (LUTS) are common and severely disturb
patient quality of life (3). The reported incidence of voiding dysfunction
is found in 33-52% of MS patients sampled consecutively regardless of
urinary symptoms and its incidence is related to disability status (3-5).
Several investigators have emphasized that the urodynamic assessment
is essential for treating voiding dysfunction due to MS (6-9). Moreover,
some authors have underlined that urodynamic evaluation should be repeated
at regular intervals since the pattern of neurologic pathology and voiding
dysfunction could change with time in MS patients. However, other authors
have suggested that a simple algorithm was sufficient for the initial
management of the voiding dysfunction in MS, since upper tract deterioration
was rare (10-12).
The available data indicate that the high proportion of the detrusor overactivity
with detrusor-sphincter dyssynergia (DSD) is not associated with an increased
risk for severe upper urinary tract deterioration (5,13-15). Hence, the evaluation
and follow-up strategy in MS regarding the voiding dysfunction is still controversial.
Furthermore, it was our clinical impression that complex urological investigations
and follow-up strategy increased the management cost and had the side effect
of increasing patient anxiety.
The aim of this study was to determine the outcome of urological evaluation in
patients with voiding dysfunction due to MS referred to our urodynamic unit,
and to assess the relationship between urological and disease related parameters
including the disease activity, its duration, and expanded disability status
scale in these patients.
MATERIALS AND METHODS
We retrospectively reviewed the medical records of 249 consecutive
patients (162 female and 87 male) with MS who had been referred to our
urodynamic unit between 1991 and 2006, with a median time of 4 years
(range 3 months to 26 years) of MS onset. The interval from the age at
diagnosis of MS until the age at last neurourological evaluation was
accepted as the disease duration. The clinical and demographic information
about the neurological diagnosis, including the MS pattern (primary progressive,
relapsing-remitting, or secondary progressive), the date of diagnosis,
and score of expanded disability status scale (EDSS) was obtained from
the patient records of Neurology Department. On the expanded disability
status scale disease severity is scored from 0 to 10 at 0.5 point intervals
The history, physical examination findings, the results of serum creatinine
level, urinalysis (urine culture when necessary), urodynamic investigation
(cystometry-EMG, uroflowmetry, and post-void residual urine volume determination)
and urinary tract ultrasonography findings were recorded from the patient files
of the urodynamic unit.
LUTS were evaluated by Boyarsky symptom index. The symptom index score comprises
storage (0-10) and voiding symptom index scores (0-12). Total symptom index
score was calculated by adding the storage and voiding symptom index scores.
The severity of LUTS was further stratified according to the total symptom
index score on the questionnaire: mild- score lower than 7; moderate- score
8-14; severe- score 15-22. A nurse from the urodynamic unit helped the patients
to fill out the symptom score evaluation form.
Upper urinary tract status was analyzed with respect to patient characteristics
including age, gender, disease duration, MS pattern, EDSS score of MS, serum
creatinine levels, urodynamic findings, symptom index scores, and post-void
Chi-square, Fisher’s exact test, Mann-Whitney U, analysis of variance
(ANOVA), and Pearson Correlation tests were performed for statistical analysis.
The Chi-square test was used except in cases where the expected number of patients
in any unit (or category) was less than 5, in which case the Fisher’s
exact test was used. We used the value of p < 0.05 as the level of statistical
The median age of patients during the initial urological evaluation
was 38 years (range 8 to 68 years). Patient characteristics are outlined
in Table-1. Of the 249 patients, 230 (92.3%) underwent urinary tract
ultrasonography, 198 (79.5%) completed the Boyarsky symptom index and
75 (30.1%) were evaluated by urodynamic testing.
Median total, storage and voiding symptom scores in 198 evaluated by
Boyarsky symptom score of 249 patients were 5, 3 and 1, respectively.
All except 13
patients had LUTS, while 129, 47, and 9 of 185 symptomatic patients manifested
mixed, storage, and voiding symptoms, respectively. Total, storage and voiding
symptom scores weakly correlated with EDSS scores (p < 0.05) (Table-2).
Twelve patients (5%) had abnormal upper urinary tract, which were unilateral
or bilateral hydronephrosis. Ultrasound findings of lower urinary tract were
abnormal in 12 patients (5%), with thick bladder wall as the most common finding
(Table-3). No demographic parameter (age, gender, disease duration, MS pattern,
or expanded disability MS status score) was associated with upper urinary tract
abnormality on univariate analysis (Table-4). All patients who had unilateral
or bilateral hydronephrosis remained stable with conservative management during
Urodynamic study performance rate gradually decreased from 100% to 13% during
the period studied (Figure-1). Urodynamic evaluation of 75 patients revealed
detrusor overactivity in 26 (35%), detrusor overactivity with detrusor-sphincter
dyssynergia in 30 (40%), detrusor overactivity with impaired contractility
in 1 (1%), a poor compliance bladder in 7 (9%) and normal findings in 11 (15%).
No correlation was found between urodynamic diagnosis and upper urinary tract
deterioration (p > 0.05) (Table-4).
In this series 70% of MS patients had mixed LUTS and symptom scores
were correlated with EDSS score. The rate of upper urinary tract deterioration
was low (5%), and all patients were stable with conservative management.
Although urodynamic studies most often revealed LUTS (85%), no correlation
was found between upper tract deterioration and urodynamic abnormality.
Since our study was retrospective, it may have limited implications.
However, this study at least gives a clear message that prospective randomized
studies are strongly needed in order to clarify the initial urologic
evaluation, since there is no established protocol for this subject in
the guidelines. This might lead to a decrease in management cost and
Our series is fairly typical of those previously reported, with a majority
of women, as usually found in MS (3,5,7,17,18). In our series 65% women and
42% of patients had a relapsing-remitting pattern of MS. This is quite comparable
with the patients reported by Ciancio (68% women and 41% relapsing-remitting
pattern) (6). This suggests that our findings are typical and likely to be
comparable to other authors.
The majority of our patients (185 of 198) had LUTS, since the patients developing
urologic complaints during the follow-up in the Neurology Department were referred
to our clinic. In our study, the rates of mixed, storage and voiding symptoms
were found to be 70, 25, and 5%, respectively. Our results are similar to the
reports from Western countries which revealed that storage symptoms such as
urgency, frequency were the predominant urinary symptoms in MS (5,7). Araki
et al. reported that voiding symptoms were equal to or higher than that of
storage symptoms in Japan (19). However, in their study, the proportions of
detrusor hyporeflexia and detrusor sphincter dyssynergia were higher than our
study and those reported from Western countries.
When evaluating the relationship between neurologic and urologic abnormalities,
we found a weak correlation between severity of EDSS and storage, voiding and
total symptom scores. In some studies no correlation was found (20,21), whereas
in others a direct correlation between EDSS score and storage and/or voiding
score was reported (3,8,22). Araki et al. found that storage symptoms correlated
well with expanded disability status scale scores but voiding symptoms did
not. Variability in the correlation probably relates to the clinical course
of MS which is characterized by exacerbations and remissions.
Multiple sclerosis is a disease with frequent presentation of LUTS whereas
upper tract deterioration is rare. Many other studies including ours also showed
that progression to upper tract deterioration in MS was usually the exception
rather than the rule (1,5,12,23). In the current series 5% of the patients
had upper tract deterioration, although mild hydronephrosis was present in
all except one patient. Koldewijn et al. reviewed 14 MS series of 2,076 patients
regarding upper tract deterioration and found its incidence to be as low as
Meta analysis of 1,882 patients showed that abnormal urodynamic findings in
MS patients with LUTS were common whereas neurogenic detrusor overactivity
and detrusor sphincter dyssynergia being the most common (10,23). In contrast
to detrusor sphincter dyssynergia in spinal cord injury, DSD in MS patients
are rarely associated with upper tract deterioration while the reason for this
is unclear (5,23-26). It has been speculated that possibility of poorly sustained
detrusor contractions and less severe degree of DSD in MS could be responsible
for this distinction (23,27). Detrusor overactivity and detrusor sphincter
dyssynergia were the most common urodynamic diagnoses in our study as in the
previous studies, and also no urodynamic finding was determined to be a risk
factor for upper tract deterioration as in the study of Litwiller et al. (23).
Not surprisingly, we found no association between the high proportion of detrusor
overactivity/detrusor-sphincter dyssynergia and incidence of upper urinary
tract abnormalities. Lemack et al. investigated the risk factors for deterioration
of upper tract and showed that no disease related or urodynamic parameters
were predictive of abnormalities on renal ultrasonography. In addition, no
patients in their series had any indication of obstructive uropathy more severe
than mild hydronephrosis (18). Our findings agree with this stance in that
only one of our patients had unilateral non-functional kidney. Moreover, our
ratio of upper tract deterioration was found to be low and comparable to those
in other series, which ranged between 0-25% (5,14,18,23,28). In a recent study
done by Lemack et al. these authors compared the detrusor pressures between
MS patients with and without DSD and observed non-significant elevations in
detrusor pressures in both groups. This finding could explain the relatively
low incidence of upper tract damage in patients with MS (15).
Our urodynamic study performance rate gradually decreased from 100% to 13%
during the study period. Although our data is far from providing strong evidence
for the overuse of urodynamic studies during initial urologic evaluation of
MS patients, on the basis of the literature mentioned above and our increasing
experience with MS patients this suggests that the multichannel urodynamic
studies might be used only in the evaluation of patients with upper tract deterioration
or with conservative treatment failure. We believe that this policy might lead
to a decrease in the management cost and patient anxiety.
A weakness of our study was that our data was collected retrospectively. However,
the literature is fully supportive of our local data. Another potential weakness
of our study is that we were not able to use a unique protocol for initial
urologic evaluation of these patients, since there is no previously established
protocol for this subject in the guidelines. Despite these limitations, we
believe that our results provide a useful insight for clinicians when counseling
patients with MS.
The prevalence of mixed symptoms in patients with MS is higher than
storage or voiding symptoms alone. Although detrusor overactivity and
detrusor-sphincter dyssynergia were the most common urodynamic diagnoses,
upper urinary tract deterioration was rare in this series. Prospective
randomized studies are needed to clarify initial urologic evaluation
for MS patients.
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Accepted after revision:
February 27, 2009
Dr. Bulent Onal
Cerrahpasa School of Medicine
Fatih, Istanbul, 34730, Turkey