INTRODUCTION

Multiple sclerosis is a demyelinating disease that has a profound impact on the quality of life of patients. The induced handicap varies from one patient to another, and depends on the location of the demyelinating lesions.¹  Sensory-motor disorders and genito-sphincter dysfunctions are some of the more disabling. Thus, up to 70% of MS  patients suffer from urinary troubles, and half of them have difficulties concerning ambulation after 15 years from the onset of the illness.¹  With MS, damage to the spinal cord and brain interrupts signal transmissions that result in storage problems, emptying (voiding) problems or a combination of both.² Storage dysfunction manifests its symptoms in several ways like urinary frequency, urgency, nocturia, and incontinence.² Voiding dysfunction is common in patients with MS, and few studies have examined the changes in urodynamic patterns in these patients over time.³ It was found that the reported incidence of voiding dysfunction in multiple sclerosis ranges from 33% to 52% in patients.^4,5 Voiding symptoms  include urinary hesitancy, sensation of incomplete emptying, weak urinary streams, and urine retention. The cause of storage & voiding dysfunction could be an overactive or weak detrusor muscle, an overactive or weak urinary sphincter muscle, or combinations.²

It was found that a significant proportion of patients with MS will develop changes in their  urodynamic patterns and detrusor compliance. Therefore, urodynamic evaluations should be done and repeated at regular intervals in symptomatic patients for better management and to reduce complications.³ The purpose of this study is to examine the  nature of the urinary problems and urodynamic  changes in MS  patients with  bladder dysfunctions and to correlate these changes with the clinical parameters of MS as well as with the imaging and neurophysiologic changes.

SUBJECTS AND METHODS

Subjects:

This is a cross sectional study conducted on 34 subjects. Nineteen patients with MS presenting with urinary problems were included in this study. MS was diagnosed according to McDonald criteria⁶ and its revision⁷ and all MS types were included. The patients group included 10 females (52.6%) and 9 males (47.4%). Their age ranged from 13 to 50 years with a mean of 30.58±9.167 years. Fifteen normal controls were included in this study, 8(53.3%) males and 7(46.7%) females. Their age ranged from 20 to 40 with a mean of 30±8.175 years. They were matched in age and sex to patients group.

Exclusion criteria:

Age below 10 or above 50 years. Patients with diabetes mellitus, renal impairment, neurological (other than MS) or connective tissue disorders. Patients with known genitor-urinary diseases e.g.: urinary tract infections, prostatic enlargement, stones, neoplasm or congenital malformation.

Methods:

All subjects were submitted to:

-        History taking and complete medical, neurological and urological examination including Expanded Disability Status Scale (EDSS)⁸, digital rectal examination and pelvic ultrasound.

-        Routine laboratory tests especially blood glucose, CBC, ESR, urine analysis & renal functions.

-        Visual evoked potential (VEP), brain-stem evoked potential (BSEP) and somato-sensory evoked potential (SSEP).

-        MRI brain and cervico-dorsal spine: T1,T2, Proton density weighted images and FLAIR .

-        Urodynamic studies: Urodynamic testing consisted of uroflowmetry, cystometry, pressure flow study performed with the patient in the sitting position. Uroflowmetry was done at the beginning. The voided volume, maximal flow rate, and the flow pattern were recorded. A 6Fr double lumen catheter was inserted trans-urethrally into the bladder. Post-void residual urine volume was measured. The bladder was filled at room temperature with isotonic saline at a maximum filling rate of 50 ml. per minute. Abdominal pressure was measured by a rectal balloon catheter. Detrusor pressure was determined by subtracting abdominal pressure from intravesical pressure. Bladder compliance defined as the relation between changes in volume to change in pressure was calculated from the start till the end of infusion. Electromyography was recorded with surface electrodes placed perineally. Volume at first desire to void, maximum cystometric capacity and maximum detrusor pressure during the voiding phase were recorded. Uninhibited detrusor contraction, urinary incontinence, and detrusor-sphincter dyssynergia were noted.

Statistical Methods:

Computer software package SPSS 15.0 was used. For quantitative variables, median, minimum, maximum were presented. Mean and SD also was used. Frequency and percentages were presented for qualitative variables. Pearson correlation was used to estimate relations between quantitative variables. Mann-Whitney test was used to estimate differences in quantitative variables. Chi-square / Fisher's exact tests were used to estimate differences in qualitative variables.

RESULTS

1.            Clinical results:

The duration of illness in patients group ranged from 1 to 14 years with a mean of 5.79±4.131. As regard the clinical type of MS, 12(63.2%) patients were presenting with relapsing remitting (RR) type, 7(36.8%) patients with progressive form (primary progressive was found in one patient of them). The number of relapse in patient with RR type ranged from 1 to 15with a mean of 4.58±4.141.The EDSS ranged from 1 to 7 with a mean of 3.21±1.66. Fifteen patients (78.9%) were presenting by pyramidal manifestations, 9 patients (47.4%) with cerebellar dysfunction. Brainstem manifestations were found in 7 patients (36.8%). Visual manifestations were found in 3 patients (15.8%) and sensory affection also in 3 patients (15.8%). Mental affection was found in one patients (5.3%).The bladder dysfunctions were in the form of storage, voiding dysfunction, Storage problems appeared as precipitancy in 14(73.7%) patients and incontinence in 4(21.1%) patients. Voiding problems were in the form of hesitancy in 5(36.3%) patients and retention in one (5.3%) patient.

2.            Imaging study:

Abnormal MRI was found in15 (84%) patients. Three patients (15.8%) had demyelinating plaques in dorsal and cervical spine and 3 patients (15.8%) in brain stem (pons and medulla) and cerebellum. The other patients had plaques in the periventricular white matter.

3.            Evoked potentials:

Abnormal VEP was found in 10(56%) patients. Abnormal SSEP was found in 2(14.3%) and abnormal BSEP in one (7.7%) patient.

4.            Urodynamic studies:

Urodynamic studies were done for both patients and controls. Hyper reflexive bladder was found in 5(38.5%) patients. Detrusor sphincter dyssynergia was found in one patient (5.3%). Statistically significant difference was found between patients and controls as regards the mean of  detrusor  pressure at voiding phase and Q max (maximum flow rate) being less in patients (P=0.049 and 0.00) respectively. Significant decrease in detrusor pressure at voiding phase in patients is denoting hypocompliance, reduced capacity or exaggerated sensation of the bladder (Table 1).

-        Association of types of urinary problems with the clinical data: Statistically significant association was found between types of MS and hesitancy being significantly encountered in progressive MS (57.1% in progressive type compared to 8.3% in RR type and P value was 0.038) (Table 2). No statistically significant correlation was found between the other clinical data and the types of urinary problems (P˃0.05).

-        Association of urodynamic changes with the clinical data: Statistically significant association was found between sex and compliance of the bladder being significantly more compliant (less pressure in relation to volume) in females compared to males (p=0.034) (Table 3). Compliance was significantly increased in patients presenting with hesitancy (p=0.03) (Table 3). No statistically significant correlation was found between the other clinical data and other urodynamic parameters (p˃0.05). Although compliance was increased in progressive form of MS compared to RR type, yet p-value was not significant, only was approaching the significant value (P=0.07).Increased compliance above its limit denotes some degree of detrusor underactivity.

-        Correlation of urodynamic changes to MRI and evoked potentials findings: Statistically significant association was found between SSEP and Qmax and between detrusor pressure and VEP. The two parameters of urodynamic studies were significantly increased in patients with abnormal SSEP and VEP (p=0.046 and 0.044 respectivley) respectively. Statistically significant association was found between abnormal VEP and increased volume at first desire in males patients only (p=0.046). Out of the 5 patients with hyperreflexive bladder, 3(60%) had plaques in the periventricular white matter. Moreover, the only patient with detrusor sphincter dyssynergia had also plaques in the periventricular area. However, no significant relation was found between lesions sites in MRI and urodynamic parameters or urinary troubles.

Table 1. The urodynamic studies in patients with MS and controls.

*Significant at p<0.05 **Significant at p<0.01

Table  2. Relation of types of urinary problems with types of MS.

*Significant at p<0.05

Table 3. Relation of urodynamic changes to some clinical data.

*Significant at p<0.05

DISCUSSION

The purpose of this study is to examine the nature of urinary problems and  urodynamic  changes in MS patients with bladder dysfunctions and to correlate these changes with the clinical parameters of MS as well as with the imaging and neurophysiologic changes. In this study, storage problems appeared as precipitancy in 14(73.7%) patients and incontinence in 4(21.1%) patients. Voiding problems occurred in the form of hesitancy in 5(36.3%) patients, and retention in one (5.3%) patient. In agreement to our study, previous reports from Western countries indicate that storage symptoms are the predominant urinary symptoms in multiple sclerosis.^9,10 Other studies found that the prevalence of voiding symptoms was equal to or higher than that of storage symptoms in patients with multiple sclerosis.^5,11 As regard the neurological manifestations, different studies in multiple sclerosis were characterized by more common involvement of the optic nerve, spinal cord and probably brainstem, and by less common involvement of the cerebellum and cerebrum.^12,13 However in our study, 78.9% were presenting by pyramidal manifestation, 47.4% were presenting by cerebellar dysfunction. Less common, brainstem manifestations ,visual manifestations, sensory affection and mental affection. Hyper reflexive bladder was found in 5(38.5%) patients and detrusor sphincter dyssynergia was found only in one patient (5.3%).  Storage problems were more common than voiding problems. In Japan, the proportions of detrusor hyporeflexia and detrusor sphincter dyssynergia in MS patients were somewhat higher than those reported from Western countries.¹⁴ Detrusor-sphincter dyssynergia and detrusor hyporeflexia disturb urine discharge and cause voiding symptoms.¹⁵ It is a possible reason why the prevalence of voiding symptoms is high in Japanese cases of multiple sclerosis.⁹ Also we can attribute our results to the same reason as detrusor sphincter dyssynergia was found only in one patient so storage problems were more common than voiding symptoms. It was found that in urodynamic evaluation of 75 MS patients,  detrusor overactivity with or without detrusor-sphincter dyssynergia was present in 56 (75%).¹⁶ However, in our study, hyperreflexive bladder (detrusor overactivity) was found only in 5(38.5%) patients. Previous reports indicate that storage symptoms correlated well with expanded disability status scale scores(EDSS) and disease duration but voiding symptoms did not.⁵  Another study found that total, storage and voiding symptom scores correlated with expanded disability status scale scores (p<0.05).¹⁶ However the previous  study was retrospective and may have limited implications.¹⁶ On the other hand, we did not find such relation between urinary symptoms and EDSS or duration which can be attributed to small sized sample. In our study, there was a statistically significant association  between types of MS and hesitancy being significantly encountered in progressive MS (P=0.038). However some studies found that  the risk of voiding symptoms seems to increase during exacerbation.^10,17   

Koldewijn et al. reviewed 14 MS series of 2.076 patients regarding upper urinary tract deterioration and found its incidence to be as low as 0.34%.¹⁰ Meta analysis of 1.882 patients showed that abnormal urodynamic findings in MS patients with LUTS (lower urinary tract symptoms) were common whereas neurogenic detrusor overactivity and detrusor sphincter dyssynergia being the most common.^10,18 This was in agreement in part with our study as we found significant difference  between patients and controls as regards  detrusor  pressure at voiding phase and Q max being less in patients(P=0.049 and 0.00) respectively and we  did not find upper urinary tract deterioration. In contrast to detrusor sphincter dyssynergia (DSD) in spinal cord injury, DSD in MS patients are rarely associated with upper tract deterioration while the reason for this is unclear.^10,18 Moreover, it was found that a significant proportion of patients with MS will develop changes in their urodynamic patterns and detrusor compliance.³ These findings were coinciding with our results as we found  statistically significant association between MS female patients & patients presenting with hesitancy and increased compliance of the bladder (P=0.034, 0.03). It was found that the cerebral cortex, pontine tegmentum and sacral spinal cord are the major central components responsible for voiding.^19,20 Lesions at and between these areas exert different effects on voiding function in a lesion site dependent fashion.¹⁹ For example, a cerebral lesion often induces detrusor hyperreflexia, whereas a pontine or sacral cord lesion causes detrusor hyporeflexia. A suprasacral cord lesion may result detrusor hyperreflexia with detrusor-sphincter dyssynergia.¹⁹  Isao et al. found a significant correlation between pontine lesion in MRI and detrusor hyporeflexia, and for a cervical cord lesion in MRI  and detrusor-sphincter dyssynergia.¹⁴ However, in our study, we did not find such correlation between MRI changes and urodynamic parameters. This may be attributed to small sized sample and racial difference. Moreover, we found statistically significant association between SSEP and Qmax of  the bladder and between detrusor pressure and VEP. The two parameters were significantly increased in patients with abnormal SSEP and VEP  (P=0.046 and 0.044) respectively. Also we found statistically significant association between abnormal VEP and increased volume at first desire in males patients only (p=0.046). However, Sau et al.²¹ found significant abnormalities of the evoked potentials in  MS  patients with urodynamic changes especially pudendal SSEP. They postulated that the use of  pudendal SSEP  may provide information of diagnostic relevance and plays a role in screening patients for urodynamic testing. In conclusion, urodynamic evaluations should be done and repeated at regular intervals in symptomatic MS patients to optimize clinical management, reduce complications, and better enable these patients to manage their neurogenic bladder dysfunctions.

[Disclosure: Authors report no conflicts of interest]

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