Assessment of the Impact of Lower Urinary Tract Dysfunction on Quality of Life in Multiple Sclerosis Patients in Saudi Arabia—A Cross-Sectional Study

Background: Lower urinary tract dysfunction (LUTD) is caused by neurogenic factors that could lead to permanent injury in affected patients, and therefore result in substantial annual healthcare expenses. LUTD is very prevalent in multiple sclerosis (MS) patients and has a drastic impact on their quality of life (QOL). This study aimed to assess the effect of LUTD on the QOL of Saudi MS patients. Methods: A cross-sectional study was carried out in Saudi Arabia using a self-administered questionnaire that included the World Health Organization Quality of Life (WHOQOL-BREF) and LURN Symptom Index (LURN SI-29). Data were analyzed and presented as frequencies and percentages. Results: There were 428 patients who participated in this study; 270 were females and 158 were males. Most of the patients received a low score in all sections of the LURN part of the questionnaire. The highest scores (urgent need to urinate and excessive urination at night) were recorded in the urgency domain (47.20 ± 36.88) rather than the nocturia domain (44.74 ± 32.91). Meanwhile, the lowest score (complete control of bladder) was recorded in the incontinence domain (22.80 ± 26.80). For the WHOQOL-BREF score, the highest score (more social stability) was in the social domain (65.07 ± 21.16 for females, 60.41 ± 21.54 for males), and the lowest score (less psychological stability) was in the psychological domain (46.36 ± 9.84 for females, 46.20 ± 10.03 for males). However, there was no significant association between the four domains of the WHOQOL-BREF and the gender of the MS patients. Conclusions: LUTD is significantly associated with a lowered quality of life. Therefore, patients are recommended to consult with and be evaluated by appropriately experienced healthcare providers and clinicians. This ensures that the patients receive the best advice, accurate and effective treatment, and long-term analysis that can lead to an improvement in their quality of life.


Introduction
Multiple sclerosis (MS) is a frequent central nervous system (CNS) illness that often appears in early adulthood and varies depending on the origin of inflammation [1][2][3][4].MS is divided into three categories: The most frequent subtype of MS is relapsing-remitting MS, accounting for roughly 85% of patients, and is distinguished by acute neurological symptoms with intervals of recovery [5,6].The primary progressive form (present in 15% of patients) is characterized by gradual and progressive neurological symptoms with few flares [5].The most prevalent autonomic disruption in persons with MS is neurogenic lower urinary tract dysfunction (LUTD), which continues to be a clinical challenge to treat, resulting in significant yearly healthcare expenses and causing significant handicaps in afflicted persons that affect many elements of daily living [2,[7][8][9].
Urinary difficulties are present in 35% of individuals with multiple sclerosis (MS) at the time of diagnosis, and more than 75% have urinary issues at some point during the disease, developing voiding dysfunction and LUTD [1,9,10].However, LUTD symptoms may be recorded in one out of every ten MS patients at the time of the initial MS presentation, while the incidence of LUTD symptoms and dysfunction grows over time, approaching 100% in 10 years because of the progressive nature of MS [9].Urinary abnormalities can also be the first manifestation of the illness, as is seen in 2-10% of patients [11].LUTD is best divided into three categories: urine storage (commonly known as "irritative"), voiding (sometimes known as "obstructive"), and post-micturition symptoms [12,13].Urine storage and voiding are two distinct but linked phases of LUTD [12].The muscle and connective tissue in the bladder and urethra develop an intrinsic tone [12].At rest, the urethral tone maintains wall apposition and aids in incontinence [14].The bladder walls relax and become sensitive during filling (the vesical lumen increases without causing an increase in intravesical pressure) [12].When a specific level of fullness is achieved (which varies depending on circumstances and individuals), the growing afferent activity begins to intrude on consciousness, resulting in awareness that the bladder is filling up [12].Other symptoms include increased daytime and nighttime (nocturia) urination frequency, urinary urgency, and incontinence, whereas voiding symptoms include an interrupted and weak stream, urinary hesitancy, straining to urinate, and the sensation of incomplete bladder emptying after voiding [6,8,13].Even though urine incontinence has a significant impact on patients' lives, the ailment is frequently underreported [8].This is mainly because many patients avoid seeking medical attention since they feel ashamed and shy to share their concerns with healthcare professionals [8].Likewise, healthcare practitioners regularly neglect to mention urine symptoms, and patients risk facing multiple difficulties (like skin infections, urinary tract infections, falls, and fractures) [8].
LUTD is often related to poor-quality sleep, low energy, poor emotional health, and a lower overall quality of life; however, it has also been associated with having a negative influence on an individual's social, occupational, psychological, and sexual life [8,11,[13][14][15][16][17].Because all aspects of life may change and vary, a conceptual model based on the biomedical and social sciences paradigm is required to represent this variegated experience.This model should encompass the psychological, biological, and social dimensions of health and life quality [1,15,18].Studies have shown that UTIs and community-acquired UTIs are related to a lower quality of life (QOL) and health-related QOL [19][20][21].A study on Saudi women with community-acquired UTIs showed that different aspects of their life were impacted due to their infections, and therefore lowered their health-related QOL [21].The study showed that UTIs negatively affected their bed rest, work and schooling, and mobility, and increased their pain [21].Collectively, this leads to a lowered QOL [21].Thus, this study aimed to assess the impacts of LUTD on QOL in MS patients in the Saudi Arabian population.This should provide a basis for further studies to assess the quality of healthcare institutions and medical consultations available to patients in Saudi Arabia, thus aiding in the development of the healthcare system in Saudi Arabia.

Study Population and Ethics Statement
A cross-sectional study was conducted using a validated self-administered questionnaire consisting of demographic and clinical characteristics, the World Health Organization Quality of Life scale (WHOQOL-BREF), and the LURN Symptom Index (LURN SI-29).In total, 428 patients of both genders in Saudi Arabia who were diagnosed with MS and older than 18 years were invited to participate in the study.Data were collected from a survey that was disseminated through social media in collaboration with MS societies from June 2021 to January 2022.Ethical approval was obtained from the local IRB committee before data collection.The purpose and methodology of the study were explained clearly to the participants before they enrolled and provided informed consent.Provisions for protecting privacy were relevant at all stages of the research, including in subject identification, recruitment, participation, and analysis.
Sampling and less-than-true responses may be potential sources of prejudice.To reduce sampling biases, the questionnaires were distributed through MS social media accounts and MS associations to improve visibility and attract more respondents.To address the problem of bias in the responses, we created an anonymous self-administration questionnaire and avoided leading questions and answers.

Measurement Scale WHOQOL-BREF and LURN Scale
The WHOQOL-BREF is a 26-item scale that was created in eighteen countries to be applied as a general assessment of QOL [22].It is a viable tool to assess QOL across cultures and illnesses [22].It is grouped into four domains: physical health, psychological health, social ties, and environmental health [22].Therefore, the questions (Q) in this study were divided as follows: physical/physiological health (9 questions), psychological health (6 questions), social ties (3 questions), and environmental health (8 questions) [22].
To maintain the effectiveness and efficiency of the questionnaire and verify its psychometric validity, the questionnaire document was translated into Arabic by a certified independent translator, who conducted forward and backward translations.In addition, the validity and reliability of the translated questionnaire were examined by a medical sociology professor using face validity.Before the distribution of the questionnaire, pilot testing was conducted to evaluate its reliability and validity.

Statistical Analysis
The information gathered was processed and provided in the form of frequencies and percentages.The chi-squared test, Pearson's correlation, and Fisher's exact test were used to test the quantitative data, and the differences between means were determined using IBM SPSS Statistics software for Windows, version 26.0 (IBM Corp., Armonk, NY, USA).In all analyses, two-sided p-values less than 0.05 were judged statistically significant.The data were reviewed for missing data and outliers before analysis.Means and standard deviations are used to represent continuous variables.Outliers were calculated using the interquartile range (IQR) method.In brief, the data were sorted from low to high, and then the first quartile (Q1), median, and third quartile (Q3) were identified.This was followed by calculating the IQR (Q3 − Q1), and then calculating the upper fence (Q3 + (1.5 × IQR) and lower fence (Q1 − (1.5 × IQR)).Finally, any values that fell outside the fences were considered outliers.

Results
The study questionnaire was completed by 428 people who were asked to participate regardless of the occurrence of LUTD between June 2021 and January 2022, and their answers were assessed using the WHOQOL-BREF and LURN SI-29 scales.There were 270 females (63.10 percent) and 158 men (36.90 percent) who participated.Patients were classified into five age groups based on their age; 72.4 percent of the patients were between the ages of 20 and 40.There were three illiterate participants, and therefore they were unable to fill out their questionnaires by themselves.Thus, the questionnaire was read to them out loud by the data collection contributor, and they were asked to answer by choosing one of the answers verbally.Other participant demographic variables and scale scores are presented in Table 1.As shown in Tables 2 and S1, the majority of the patients mostly had a low score in all sections of the LURN portion of the questionnaire; i.e., the symptoms of LUTD have little or few effects on the MS patients.They are able to completely control their bladder during their different life activities (incontinence part); have either no or little pain, or are comfortable during the urination process (bladder pain); never or a few times have difficulties during urination (voiding difficulties part); never or a few times have an urgent need to urinate; and never or a few times have post-micturition symptoms.Furthermore, the total score of the LURN sections was significantly associated with gender (p-value < 0.05), whereas sections A and E were exceptions.
Regarding the bladder pain section, Q.9 and Q.10 had a p-value of 0.000326 and 0.033, respectively, which indicates that the severity degree of the pain is increased in men.For the voiding difficulty section, 49.3% of females compared to 26.6% of males in the past 7 days never had a delay before they started to urinate and 3.7% of females and 8.2% of males had a delay every time before starting to urinate (Q.12).Once urinating starts, the frequency that the urine flow stops and starts again (Q.13), having a urine flow that is slow or weak (Q.14), and having a dribble or trickle at the end of the urine flow (Q.15) is increased in men compared to women.Nearly 60% of males compared to 40% of females feel a sudden need to urinate about half of the time, most of the time, and every time (Q.16).Female patients more frequently experience post-micturition problems compared to males (Q. 25 and 26).The highest score was obtained for section D (urgency domain) (47.20 ± 36.88) rather than section E (nocturia domain) (44.74 ± 32.91), which was the same for both genders, and the lowest score was for section A (incontinence domain) (22.80 ± 26.80), which was also the same for both genders, as shown in Table 3. Male patients reported high scores (p-value < 0.05) in the bladder pain, voiding difficulty, urgency, and post-micturition domains compared with female patients.Boxplots of the subscale scores and the total scores of the LURN SI-29 of both sexes are shown in Figure 1, indicating that women reported lower scores for all domains, and men reported the highest scores for urgency and nocturia compared to women.Overall, it appears that the average total LUTS and the variability of scores indicate that the burden is higher for men compared to women (LURN SI-29 total median score = 25.29 for women, 30.91 for men, variance 316.97 vs. 241.6,p < 0.001).For the WHOQOL-BREF scores, as are presented in Tables 4 and S2, and Figure 2, the highest score was in the social domain for both genders (65.07 ± 21.16 for females, 60.41 ± 21.54 for males), and the lowest score was in the psychological domain (46.36 ± 9.84 for females, 46.20 ± 10.03 for males).Although there was no significant association between the four domains of the WHOQOL-BREF part of the questionnaire and the gender of the Saudi Arabian MS patients (p-value > 0.05), there were six questions out of the twenty six For the WHOQOL-BREF scores, as are presented in Tables 4 and S2, and Figure 2, the highest score was in the social domain for both genders (65.07 ± 21.16 for females, 60.41 ± 21.54 for males), and the lowest score was in the psychological domain (46.36 ± 9.84 for females, 46.20 ± 10.03 for males).Although there was no significant association between the four domains of the WHOQOL-BREF part of the questionnaire and the gender of the Saudi Arabian MS patients (p-value > 0.05), there were six questions out of the twenty six displaying significant differences between both genders, as demonstrated in Table 4:  The median scores of the WHOQOL-BREF were generally the same for both genders for the subscales and the total scores, and no significant difference was observed between male and female scores (Figure 2); i.e., the quality of life of UTI MS patients was not affected by gender, and so they had the same scores on this questionnaire.displaying significant differences between both genders, as demonstrated in Table 4: Q1 (p-value = 0.043), Q4 (p-value = 0.007), Q13 (p-value = 0.038), Q15 (p-value = 0.008), Q21 (pvalue = 0.002), and Q22 (p-value = 0.011).
The median scores of the WHOQOL-BREF were generally the same for both genders for the subscales and the total scores, and no significant difference was observed between male and female scores (Figure 2); i.e., the quality of life of UTI MS patients was not affected by gender, and so they had the same scores on this questionnaire.

Discussion
Urinary abnormalities are an initial indicator of LUTD in 2% to 10% of MS patients, and they are present from the start of the disease [10].A recent study in the United States showed that uncomplicated UTIs (the most common UTIs) severely cause mobility impairments [24].Consequently, UTIs affect the health-related QOL and productivity of female patients [24].LUTD is found quite frequently in MS patients (75%) and it is sometimes cited as the disease's worst symptom [25], as it includes voiding and urine retention symptoms (25%), storage symptoms (50%), and/or a combination of symptoms (25%) [25].Failure to empty the bladder is caused by detrusor-distal sphincter dyssynergia or areflexia.Furthermore, urgent incontinence is common for both sexes and is associated with voiding trouble and having decreased sensation [1].These symptoms not only create a major psychosocial burden, but also necessitate medical intervention and hospitalization, and present a significant obstacle for the care team [1,10,25]; in addition, they have a considerable detrimental influence on MS patients' quality of life [9,11,13,25,26].
This study aimed to measure the effect of LUTD on the QOL of Saudi MS patients.Several studies have been conducted to investigate the negative impact of LUTD on daily living activities and health-related QOL in people with MS [6].Urine symptoms in MS have a detrimental influence on QOL as they restrict involvement in daily activities, negatively influence emotional status, social roles, and employment, and can lead to an increased risk of falls in older MS patients [7].The QOL of MS is influenced not only by urinary symptoms and other health-related complications, but other factors such as social life, physical activity, and environment can play a critical role.Therefore, measuring the effect of LUTD on the QOL of MS patients in the context of different populations and cultures can give different insights into the issue.The results of our study confirmed that improving these factors can help to improve the QOL of MS patients.
Patients should inquire about the following symptoms with the clinician: frequency, urgency, urge or stress incontinence, bladder discomfort, hematuria, dysuria, or retention [23].The duration, intensity, and level of annoyance should all be established.A review of the patient's surgical and medical history may identify disease processes that are directly connected to their concerns [27].Accurate drug determination is particularly critical because many medicines might have a direct influence on lower urinary tract function [22,23].A comprehensive obstetric and menstrual history should be collected for female patients.Standardized validated surveys are great instruments for identifying symptoms, their level of bother, and their influence on QOL.More than 30 questionnaires in English have been made available to assess neurogenic bladder symptoms and their influence on a patient's QOL [28].
This study revealed, through asking incontinence-related questions, that a significant number of both male and female patients mostly have control over their bladder during different life activities (Tables 2 and S1).When patients where asked about bladder pain or discomfort and voiding difficulty, a majority of them had no or only a few instances of pain/discomfort and voiding difficulty during the urination process (Tables 2 and S1).From the urgency section (Q16-Q18), it was found that about 33.30% to 39.60% of both male and female patients never felt a sudden need to urinate or difficulty in waiting more than a few minutes, whereas 32.90% (Q16) and 34.80% (Q18) of male patients felt a sudden need to urinate about half of the time and found it somewhat difficult to wait more than a few minutes before urinating (Tables 2 and S1).According to the nocturia section, about 31.50% and 32.90% of female and male patients, respectively, wake up one time and urinate during a typical night.Moreover, 35.90% of female patients wake up at least once a few nights in a week and 31% of male patients wake up at least once about half of the nights in a week to urinate.About 40% of female and 50% of male patients urinate 4-7 times in a typical day during waking hours.Moreover, 58% of female and 57% of male patients need 3-4 h between urination.Additionally, about 43% and 42% of female and male patients, respectively, felt a few times that their bladder was not completely empty after urination.Also, a majority of patients never dribble urine after zipping their pants or pulling up their underwear.About 48% of female patients and 44% of male patients never experienced spraying or splitting of the urine stream.When patients were asked about urinary symptoms bothering them, about 39% of females and 49% of males said they were somewhat bothered.
We found that MS male patients reported higher scores in all domains in the LURN SI-29 (Table 3), indicating that they were more affected by LUTD compared to females (mean total scores: 25.29 and 30.91 for females and males, respectively) with a p-value < 0.05.Males reported higher bladder pain, voiding difficulty, urgency, and post micturition compared to females (p-value < 0.05).A recent study has shown that bladder management improved the QOL of MS female patients with UTIs [29].This was determined through consultations that involved bladder training programs and Kegel exercises over a 3-month period [29].
In this study, the highest score was in the social domain for both genders (65.07 ± 21.16 for females, 60.41 ± 21.54 for males) (Figure 2), and the lowest score was in the psychological domain (46.36 ± 9.84 for females, 46.20 ± 10.03 for males).Although there was no significant association between the four domains of the WHOQOL-BREF and the gender of the Saudi Arabian MS patients (p-value > 0.05), six questions showed significant differences between both genders including QOL rate (Q1), medical treatment needed to function in their daily life (Q4), the availability of information that they need in day-to-day life (Q13), the ability to get around (Q15), sex life satisfaction (Q21), and the support they get from friends (Q22).In the physical/physiological domain, when patients were asked about their sleep satisfaction, ability to perform daily living activities, and capacity for work, their responses ranged from neither satisfied nor dissatisfied to satisfied.About 46% (female) and 44% (male) of patients reported that physical pain can moderately prevent them from doing what they need to do.Moreover, 38% (female) and 32% (male) of patients reported moderate energy for everyday life.In the psychological domain, 42% (female) and 42% (male) of patients enjoy life to a moderate amount.Interestingly, about 35% to 39% of patients felt that their life is meaningful to an extreme amount.Moreover, about half of the patients were able to moderately concentrate.The highest percentage of both female and male patients' reported responses that ranged from neither satisfied/dissatisfied to satisfied occurred when they were asked questions about their social life (such as personal relationship, sex life, and friends' support).In the environmental domain, our results showed that about 31% of patients feel safe in their daily life to a moderate amount, and 37% claimed that their physical environment is moderately healthy.Additionally, the highest percentage of patients were satisfied with the conditions of their living place, as well as with their access to health services and transportation.
Urinary difficulties in MS patients vary due to the multifocal pattern of MS lesions and the disease's history of numerous exacerbations [10,30].Using urodynamic tests to identify the kind of bladder-sphincter dysfunction is crucial for guiding therapy selection and avoiding upper urinary tract abnormalities [10,30].One essential objective of treating urinary troubles in MS patients is to reduce complications and improve their health-related QOL (HRQOL) [10].
Self-report bias and participants' capacity to adequately record their sickness condition, drugs, symptoms, and therapy are potential study limitations that come with this survey technique.Another constraint is selection bias.This convenience sample consisted of patients who self-selected to join in this study and who were required to have an Internet connection; therefore, they may have had characteristics that are not shared by the overall MS population.Patients in the later stages of the disease, for example, may have been less interested in completing a questionnaire due to weariness, mobility issues, or the ability to concentrate on a computer screen for long periods.In addition, there is poor communication among healthcare professionals and fewer referrals of people with MS to specialist services due to a lack of understanding of these specialized services.Another further limitation is that the results of the current study do not provide generalized results regarding MS patients worldwide.However, it is a step in the right direction for further understanding the state and quality of life of MS patients.This could eventually help in providing sustainable solutions for MS patients to increase their quality of life and improve their physiological, psychological, and social well-being.A longitudinal study to further assess the QOL of Saudi MS patients with LUTD is suggested.This could further justify and clarify the impact of these diseases on the QOL of Saudi patients and provide a basis for a comparison of the development of healthcare systems and social acceptance between Saudi Arabia and other countries.

Conclusions
LUTD is characterized by several medical symptoms, including storage, voiding, and post-micturition phases.LUTD is also associated with considerable morbidity in persons with MS, leading to mobility limitations and a worse health-related QOL.In this study, two scales were included in the questionnaire, which were used to measure QOL in MS patients with LUTD.In both, LUTD is substantially associated with a low quality of life.As a result, patients should be assessed and treated by appropriately competent healthcare consultants who can choose one of the numerous successful treatment choices available, and therefore enhance their patients' QOL.Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.

Figure 1 .
Figure 1.LURN SI-29 scale and subscale total scores by sex.(The line in the box and the lower and upper edges of the box indicate the median and the 25th (Q1) and 75th (Q3) percentiles, respectively.The whiskers represent the minimum (extends to Q1 − 1.5 * interquartile range) and maximum (extends to Q3 + 1.5 * interquartile range).Circles indicate outliers.)LURN SI-29, Lower Urinary Tract Dysfunction Research Network Symptom Index-29.

Figure 1 .
Figure 1.LURN SI-29 scale and subscale total scores by sex.(The line in the box and the lower and upper edges of the box indicate the median and the 25th (Q1) and 75th (Q3) percentiles, respectively.The whiskers represent the minimum (extends to Q1 − 1.5 * interquartile range) and maximum (extends to Q3 + 1.5 * interquartile range).Circles indicate outliers.)LURN SI-29, Lower Urinary Tract Dysfunction Research Network Symptom Index-29.

Figure 2 .
Figure 2. The WHOQOL-BREF scale and subscale total scores by sex (270 females and 158 males).(The line in the box and the lower and upper edges of the box indicate the median and the 25th (Q1) and 75th (Q3) percentiles, respectively.The whiskers represent the minimum (extends to Q1 − 1.5 * interquartile range) and maximum (extends to Q3 + 1.5 * interquartile range).Circles indicate outliers.).

Figure 2 .
Figure 2. The WHOQOL-BREF scale and subscale total scores by sex (270 females and 158 males).(The line in the box and the lower and upper edges of the box indicate the median and the 25th (Q1) and 75th (Q3) percentiles, respectively.The whiskers represent the minimum (extends to Q1 − 1.5 * interquartile range) and maximum (extends to Q3 + 1.5 * interquartile range).Circles indicate outliers.).

Table 1 .
Sociodemographic characteristics of MS patients who responded to the WHOQOL-BREF and LURN scale questionnaire.

Table 2 .
The significant LURN questionnaire scores of the participants.

Table 3 .
The total section scores of the LURN SI-29.

Table 3 .
The total section scores of the LURN SI-29.

Table 4 .
The significant WHOQOL-BREF questionnaire scores of the participants.

Table 4 .
The significant WHOQOL-BREF questionnaire scores of the participants.