Retrospective, non-interventional case-control study, the patients were asked about their first lower-urinary tract symptoms and the date of their onset, using a structured interview. The information was matched with the medical records.

This retrospective non-interventional case-control study will be conducted at a single tertiary referral Multidisciplinary Centre for Diagnostics and Treatment of MS at the University Hospital, Ostrava, Czech Republic. The study will be performed per the Declaration of Helsinki, World Health Organization. The study protocol has been approved by the Ethics Committee of University Hospital Ostrava, Nr.289/19.

The database of the Center includes medical records of all consecutive patients, who have visited the center at least once, starting from 1996 until the present day. Based on the inclusion criteria of proven multiple sclerosis (MS) diagnosis and the current age over 18 years, the initial database search identified eligible 2348 individuals. During the routine follow-up visit of the patients at the Center, a structured in-person interview led by a physician will be performed.

The data from this interview will be cross-checked with the medical records. In addition to standard demographic variables, the following data will be obtained:

Age 1 - Age at the onset of the first symptoms of MS Age 2 - Age at the time of diagnosis of MS Age 3 - Age at the time of data collection MS course - patients with a primary progressive, secondary progressive, or progressive relapsing disease at the time of data collection will be included in the group "Progressive MS course". The "Relapsing-remitting MS course" group will include patients who had a relapsing-remitting disease and those with isolated clinical symptoms at the time of data collection.

CPS - The "CPS yes" group will include patients who experienced cerebellar and/or pyramidal symptoms (CPS) as the first manifestation of MS. Patients with other first manifestations, such as optic neuritis, sensory disturbances, etc., will be included in the "CPS no" group.

OCB - The "OCB yes" group will include patients with oligoclonal bands (OCB) in the cerebrospinal fluid at the time of diagnosis of MS. Patients in whom OCB in the cerebrospinal fluid at the time of diagnosis of MS will not be identified, will be assigned to the "OCB no" group.

LUTS - The "LUTS yes" group will include patients with the presence of at least one LUTS at the time of the structured interview. In this group, a complete list of LUTS with layman descriptions will be given to each patient. The patients will be asked to indicate, which of the lower urinary tract symptoms (LUTS) occurred as the very first one. The "LUTS no" group will include patients without LUTS.

EDSS 1 - The Expanded Disability Status Scale (EDSS) total score will be collected after stabilization following the first MS relapse before the disease-specific treatment will be initiated, and will be defined as the baseline EDSS at the time of MS diagnosis.

EDSS 2 - EDSS at the time of first onset of LUTS. D1- duration of MS symptoms, i.e. time elapsed since the onset of first symptoms attributable to MS.

D2 - MS disease duration, i.e. the time elapsed since the diagnosis of MS will be determined.

D3 - duration of LUTS, i.e. the time elapsed since the first LUTS appeared.

Based on the above-mentioned data, collected during the interview, the researchers will calculate the following variables:

T1 - Time between the presentation of first symptoms attributable to MS and the onset of first LUTS (T1= D1-D3) T2 -Time between the diagnosis of MS and the onset of first LUTS (T2= D2-D3)

Based on LUTS presence and its relationship to the time of diagnosis of MS, the patients will be divided into 3 groups:

Group A - Patients in whom LUTS appeared after the first neurological symptom which could be attributed to the MS has developed and diagnosis of MS was established; Group B - Patients who have not developed LUTS yet; Group C - Patients in whom LUTS appeared before the diagnosis of MS was established.

STATISTICAL ANALYSIS Numerical variables will be expressed as the median and the interquartile range. Categorical variables will be presented as the absolute frequencies and relative frequencies in percentages. Defined groups will be compared using the Mann-Whitney test, the Kruskal-Wallis test, or the Chi-square test of independence for contingency tables. The first two mentioned tests will be also used to test the difference between other subgroups of interest. The statistical dependence of two numerical variables will be tested and evaluated using Spearman's rank correlation coefficient and its test of significance. The univariate logistic regression will be used to assess the significance of selected factors in relation to the development of LUTS. The results will be presented with the odds ratios and corresponding confidence intervals and will be visualized using the forest plot. Finally, the methods of survival analysis - the Kaplan-Meier curve and the Cox proportional-hazards model, will be used for the analysis of survival without LUTS. All statistical analyses will be performed using R software (version 4.0.2, www.r-project.org) and the significance level will be set to 0.05.

Inclusion Criteria:

• diagnosis of multiple sclerosis
• adult patients
• signed informed consent

Exclusion Criteria:

- none

Patients with the diagnosis of MS, with or without LUTS.

There is no plan to make the individual participant data available to other researchers. The data may be provided upon request.