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.
