Impact of Depression, Fatigue, and Pain on Quality of Life in Slovak Multiple Sclerosis Patients.

Introduction

Multiple sclerosis (MS) is a chronic, immune-mediated inflammatory disease of the central nervous system that causes demyelination of the nerve fibers and their direct loss [ 1 ]. According to the latest data, multiple sclerosis affects approximately 2.8 million people worldwide [ 2 ]. It commonly presents in young adults and is more prevalent in females. MS is characterized by a diverse clinical symptomatology and varying degrees of functional disability. The symptoms of the disease encompass a wide spectrum of neurological disorders, resulting from the nature of the lesions, which can be located in various regions of the central nervous system. However, the most common among these include visual disturbances, pyramidal, cerebellar, and vestibular disorders, cognitive impairment, fatigue, and sexual and urinary dysfunction [ 1 ]. MS is diagnosed based on medical history, clinical examination, laboratory tests, and supporting evidence from ancillary tests such as MRI, in accordance with the revised McDonald criteria from 2017 [ 3 ].

The management of MS is multidisciplinary and encompasses several therapeutic approaches aimed at disease modification, relapse treatment, symptomatic therapy, rehabilitation, and psychosocial support. Disease-modifying therapies (DMTs) include immunomodulatory and immunosuppressive agents. The goal of this therapy is to reduce relapse frequency, slow disease progression, and minimize neurodegenerative damage. Comprehensive care for MS patients requires an interdisciplinary approach involving neurologists, rehabilitation specialists, psychologists, and other healthcare professionals to optimize long-term treatment outcomes [ 1 , 3 ].

The course of the disease is characterized by a progressive increase in functional incapacity, leading to physical and mental disability that begins during working age [ 4 ]. The severity of symptoms is reflected in the loss of independence and in restricting participation in social activities, which has a negative impact on all aspects of life [ 5 , 6 ].

Quality of life in MS is a multidimensional concept encompassing physical functioning, the ability to perform daily activities, a subjective sense of well-being, overall life satisfaction, perception of psychological state, and social functioning [ 5 , 7 – 9 ]. The study by Fernández-Jiménez et al [ 10 ] of SM patients in Spain and the USA confirmed that SM negatively affects their quality of life. The study demonstrated that the quality of life in MS patients is significantly lower compared to the general population. Similar findings were reported by Faraclas et al [ 11 ], who, when comparing the quality of life of MS patients and the healthy population, found that MS patients had a lower quality of life across all domains measured by the SF-36 questionnaire. Papuć and Stelmasiak [ 12 ] found that MS patients had a significantly worse global quality of life, as well as lower quality of life in the physical and psychological health domains, a lower level of independence, poorer social relations, and were less satisfied with their surrounding environment compared to healthy controls (p<0.05).

Several studies have cited functional disability as a main cause of reduced quality of life for MS patients [ 13 – 15 ]. Generally, other risk factors negatively affecting quality of life include duration of the disease [ 15 – 17 ], number of relapses in the last 3 months [ 18 ], number of symptoms of the disease [ 19 , 20 ] and the rapidly progressive form of the disease [ 21 , 22 ].

In particular, neurological symptoms are typical for multiple sclerosis, but overlapping psychological symptoms are equally bothersome. According to several authors, the increased prevalence fatigue in patients with MS is associated with a reduced quality of life [ 23 – 25 ]. Other symptoms negatively affecting quality of life include depression [ 7 , 9 , 25 , 26 ], sleep disorders [ 27 ], emotional disorders [ 27 , 28 ], anxiety, and memory disorders [ 29 ].

Over time, the deteriorating functional status of patients with MS and the associated extensive limitations in everyday life require increased care and support from caregivers, who are usually family members [ 30 , 31 ]. Most patients need significant help with personal, home, and leisure activities [ 32 – 34 ]. Social support for caregivers can be a protective factor for a higher level of quality of life for patients [ 35 ]. Each symptom belonging to the entire MS spectrum of symptoms can affect the patient’s self-assessment of their own life situation in terms of personal, social, cultural, or spiritual life [ 36 – 38 ].

Because it is such a serious problem, it is necessary to perform further studies to determine the impact of various factors on quality of life of people with MS. Identifying risk factors related to impaired quality of life can contribute to the effective management of patient care. Therefore, we decided to conduct a study to determine the level of quality of life in relation to individual potential factors that may negatively affect it. This study aimed to evaluate factors associated with quality of life, including disability status, pain, fatigue, and depression, in 176 MS patients in Slovakia.

Material and Methods

The research was carried out in cooperation with the Slovak Multiple Sclerosis Association and the Centre for the Treatment and Diagnosis of Multiple Sclerosis of the J.A. Reiman Faculty Hospital in Prešov. The study was approved by the Ethics Committee of the Faculty of Health Care at the University of Prešov in Prešov on 6 November 2020. The study was performed in accordance with the Declaration of Helsinki. Patients who agreed to participate in the study signed a letter of informed consent. Participation in this study was voluntary and did not involve payment.

We included 204 patients with definitive MS diagnosed in Slovakia by neurologists in specialized MS centers, based on anamnesis, clinical examination, determination of the EDSS (Expanded Disability Status Scale), laboratory tests, and findings from magnetic resonance imaging (MRI), in accordance with McDonald’s criteria (2001, 2005, 2010, 2017) [ 39 – 41 ]. In elderly patients, the diagnosis was confirmed after Poser’s criteria were met [ 42 ]. All patients were diagnosed according to the criteria valid at the time of onset of their disease.

The inclusion criteria were: (1) confirmed diagnosis of MS based on medical records, (2) stable MS disease without any episodes of relapse for 3 months before the study, (3) age over 18 years, (4) assessed Mini-Mental State Examination score of 23 and more, and (5) written informed consent to participate in the study. The exclusion criteria were: (1) participants without a confirmed diagnosis of MS, (2) patients with other neurological disorders, (3) patients with insufficient cognitive function, (4) acute attacks of the disease 3 months before the evaluation, (5) people undergoing depression treatment, (6) patients with other psychiatric disorders, (7) age less than 18 years, and (8) unwillingness to cooperate. Of the 204 interviewed patients, 176 patients met the criteria.

We used the following formula to calculate the minimum sample size in a multiple regression model: n=20+5k, where k=number of predictors, recommended by Khaims and Kepler [ 43 ]. With 12 monitored potential prognostic factors in our study, the minimum sample size was estimated to be 80. The total number of respondents was 176 patients.

Measurements

For the purposes of the study, a cross-sectional questionnaire survey was carried out among patients with MS living in Slovakia. The research was based on a subjective assessment of the monitored parameters by the patients themselves. Subjective feelings were expressed by the respondents using standardized questionnaires. We collected information in the form of a personal meeting of the experimenter with patients.

We used a questionnaire obtain socio-demographic and clinical data. The covariance variables of the respondents were evaluated based on the patients’ responses. We collected data on gender, education, working capacity, duration of the disease, course of the disease, and immunomodulatory treatment and duration of its use. In Slovakia, immunomodulating treatment is provided in specialized MS centers. All types of commercially available disease-modifying drugs (DMDs) – beta interferons, glatiramer acetate, monoclonal antibodies (natalizumab, ocrelizumab, alemtuzumab, ofatumumab), dimethyl fumarate, teriflunomide, cladribine, and modulators of 1 S1P receptor – are available to patients. In the questionnaire, the respondents only answered the question of whether they use any of the drugs of this type, without further specifying them.

The study used standardized evaluation questionnaires that meet the criteria for reliability and validity as tools that can be used in clinical practice. We chose the generalized SF-36 (Short Form 36 Health Survey Questionnaire) to evaluate the quality of life. We evaluated fatigue using the Modified Fatigue Impact Scale (MFIS). We rated the intensity of pain according to the Pain Effect Scale. We used Zung’s Self-Rating Depression Scale to assess the level of depression.

Expanded Disability Status Scale (EDSS)

To determine level of disability of patients with MS, we used a 20-degree evaluation system developed by Dr. John Kurtzke, the Expanded Disability Status Scale (EDSS). The neurologist first evaluates the level of disability of the patient in the 8 functional systems (FS) of the CNS and the score achieved in each FS is compared with the standards for patient mobility (eg, the ability to walk a certain distance). The combination of findings in the FS and the ability to walk determine the overall EDSS score, indicating the degree of functional incapacity and disability [ 44 ].

Short Form 36 Health Subject Questionnaire (SF-36)

Evaluation of quality of life of patients with MS was assessed by the Short Form 36 Health Subject Questionnaire (SF-36). This is a standard questionnaire that, due to its good informative value, is often used as a tool for assessing quality of life associated with health-subjective determinants of health. The SF-36 is a questionnaire with 36 items aimed at evaluating 2 dimensions of quality of life: physical (physical component summary [PCS]) and mental (mental component summary [MCS]). The PCS consists of 4 domains: physical functioning, role limitations due to physical problems, bodily pain, and perception of general health. Social functioning, role limitations due to emotional problems, mental health, and vitality are summarized in the MCS. Responses to each question are coded, summed, and converted into a total score for each domain according to a predefined scoring system. Scores in each domain range from 0 (the worst health status measured by the questionnaire) to 100 (the best possible health status). The total score scale (perceived health status [PHS]) was created by averaging the scores of the individual domains, with higher scores indicating better quality of life [ 45 ].

Modified Fatigue Impact Scale (MFIS)

The Modified Fatigue Impact Scale (MFIS) was used for assessing fatigue. In 1998, a shortened 21-point version of the FIS – the Modified Fatigue Impact Scale (MFIS) – was recommended for the evaluation of the severity of fatigue. MFIS is a component of the “MS Quality of Life Inventory” scale. The MFIS evaluates the effect of fatigue on the physical, mental, and psychosocial life of patients. Respondents evaluate individual items from 0 points (no problem) to 4 points (extreme problem). The patient’s task is to evaluate their feelings during the last month. The subscale evaluating physical condition includes 8 items and is scored from 0 (minimum fatigue) to 36 (maximum fatigue). The cognitive subscale includes 10 items and is scored from 0 to 40 points, while the psychosocial subscale includes 2 items and is scored from 0 to 8 points. Higher scores indicate a greater impact of fatigue on physical, cognitive, and psychosocial domains. The total score ranges from 0 to 84 points [ 46 ]. Based on MFIS scores, patients were divided in 2 groups: fatigue with MFIS score of 39.0 or more, and non-fatigue with MFIS of 38.0 or less. Some studies use a total score of 38 as a cutoff to discriminate fatigued from non-fatigued individuals [ 46 , 47 ].

Pain Effect Scale (PES)

The Pain Effect Scale (PES) was used to evaluate the level of pain, a method of measuring the impact of pain. The PES is an adapted version of the pain scale from the Medical Outcomes Study Functioning and Well-Being Profile. It assesses the impact of pain and discomfort on various aspects of daily life, including mood, mobility, sleep, work, recreation, and overall life satisfaction. The scale evaluates how unpleasant sensitive sensations (eg, pain, tingling, prickling, burning) affected the patient during the last 4 weeks. The intensity of pain is rated on a scale of 1 to 5: 1=not at all, 2=a little, 3=moderate, 4=strongly, 5=extreme. The scale includes 6 questions, and the total score includes the sum of points earned for all answers. The total score ranges from 6 to 30 points. Based on PES scores, patients were divided into 3 groups: mild pain (6–14), moderate pain (15–22), and severe pain (23–30) [ 48 ].

Zung’s Self-Rating Depression Scale (SDS)

The standardized SDS-Zung’s Self-Rating Depression Scale was used to assess the degree of depression. The Zung Self-Rating Depression Scale is a widely used and reliable questionnaire for assessing depressive symptoms across diverse populations. It consists of 20 items, each rated on a scale from 1 (none or some of the time) to 4 (most or all of the time). The gross score from 20 to 80 is obtained by summing the values of the marked answers. It is then converted to a 100-point scale, the SDS index (total score times 1.25). The results (SDS index score) are interpreted as: less than 50 indicates normal with no signs of depression, 50–59 indicates signs of minimal or mild depression, 60–69 indicates moderate to quite clearly expressed depression, and 70 and higher indicates severe to extremely severe depression [ 49 ].

Modified Social Support Survey (MSSS)

The Modified Social Support Survey (MSSS) was developed as part of medical studies to assess perceived social support. The MSSS is one of the components of the MS Quality of Life Inventory and was modified slightly for use with MS patients following field-testing and psychometric analysis. This tool provides an assessment of several social support areas, including material support, emotional support, positive social interaction, and affection. The MSSS consists of 18 items. Items are scored on a 5-point Likert scale ranging from 1 (never) to 5 (always). The scoring system for the MSSS is relatively complex and generates a total score as well as subscale scores. The scale scores can be transformed to a 0–100 scale using the rewritten formula [ 50 ]. The total scores of social support are 18–35, 36–67, and 68–100, for low social support, moderate social support, and high social support, respectively [ 51 ].

Mini-Mental State Examination (MMSE)

Cognitive function was assessed using the Mini-Mental State Examination (MMSE), also known as the Folstein test, which is one of the most widely used screening tools. The MMSE consists of 30 items across 6 cognitive domains [ 52 ].

Statistical Analysis

All calculations were performed using MedCalc ® Statistical Software version 20. The normality of the distribution of the variables was verified by the Shapiro-Wilk test. Most of the parameters did not show a normal distribution. The correlations between the evaluated observed factors were analyzed using Spearman’s correlation coefficient. The significance of the interaction between several predictors of quality of life (age, sex, education, the working ability of respondents, treatment modality, clinical form of illness, duration of illness, level of functional disability, level of fatigue severity, level of pain, level of depression, social support used) was assessed in multiple regression model analysis performed by applying sigma restriction parametrization for the domains of physical component summary, mental component summary, and for the perceived health scores SF-36. We included in the model items showing a significant association between predictors and response at P <0.05 on multiple analysis.

Results

Patients’ Characteristics

The study included 176 patients with definitive MS, with a mean age of 47.19 years (SD±11.37 min. 21, max. 72), of which there are 25 men (14.2%) and 151 women (85.8%). Most respondents had completed secondary education (71.6%), 3.4% of respondents had a primary education, and 25.0% had higher education. Most (129, 81.5%) respondents were on a disability pension, 36 (20.5%) were working full-time, and 11 (6.3%) were working part-time. There were 121 respondents diagnosed with MS for more than 9 years, 133 (75.6%) from the whole group had a relapsing-remitting form of the disease, 14 (7.9%) had a progressive course of the disease, and 29 (16.5%) had secondary progressive disease. The average EDSS value in the study group was 4.63±1.81 (min.–max: 1–8). There were 65 patients with no or low degree of disability (EDSS 1–3.5), 79 had a moderate degree of disability (EDSS 4–6), and 32 had severe disability (EDSS 6.5–8). Immunomodulatory treatment had been received by 72 (40.9%) respondents. In the questionnaire, the respondents only answered the question of whether they use any of the drugs of this type, without further specifying them. The socio-demographic and clinical data of the respondents are presented in Table 1 .

Table 1 Patient socio-demographic and clinical data. Parameter N %
Number of patients (n)
176 100

Age (years±SD)
47.19±11.37 Min. 21, Max. 72

Gender
Men 25 14.2 Women 151 85.8

Education
Elementary 6 3.4 High school 126 71.6 Higher education 44 25.0

Work capacity
Without restrictions 36 20.5 With restrictions 11 6.3 Disability pension 129 81.5

Disease duration
0–4 years 36 20.5 5–8 years 19 10.8 9 years and more 121 68.8

Course of the disease
Relapsing-remitting 133 75.6 Primarily progressive 14 7.9 Secondary progressive 29 16.5

EDSS (n±SD)
4.63±1.81 Min.1.0, Max. 8.0 EDSS 1–3.5 65 36.9 EDSS 4–6 79 44.9 EDSS 6.5–8 32 18.2

Immunomodulatory therapy
Yes 72 40.9 No 104 59.1 EDSS – Expanded Disability Status Scale (0: minimal disability, 10: death due to MS); Disability level (EDSS): EDSS 1–3.5 – no or low degree of disability; EDSS 4–6 – moderate degree of disability; EDSS 6.5–8 – severe degree of disability; n – number of patients; SD – standard deviation; Min. – minimum values; Max. – maximum values.

Patient socio-demographic and clinical data.

EDSS – Expanded Disability Status Scale (0: minimal disability, 10: death due to MS); Disability level (EDSS): EDSS 1–3.5 – no or low degree of disability; EDSS 4–6 – moderate degree of disability; EDSS 6.5–8 – severe degree of disability; n – number of patients; SD – standard deviation; Min. – minimum values; Max. – maximum values.

Descriptive Characteristics Study Variables

The average values of the monitored parameters, median, range, and minimum and maximum values are presented in Table 2 . The total average score for perceived health status of the SF-36 questionnaire was 42.64 (SD±17.90), the average score for the physical component summary domain was 39.88 (SD±21.78), and the average score for the mental component summary domain was 45.41 (SD±18.80). The average total MFIS score was 45.98 (SD±15.66). The average MFIS score for the non-fatigued group was 27.47 (SD±9.58), while the average MFIS score for the fatigued group was 54.39 (SD±9.38). The average PES score was 17.03 (SD±15.66) in the monitored group. The highest number of patients (n=92) reported pain at the PES 15–22 level, the highest impact of pain (PES 23–30) was reported by 30 patients, and the lowest impact (PES 6–14) was reported by 54 patients. The average MSSS score was 64.08 (SD±24.40). Depressive symptoms were present in 48% of patients with MS, with signs of minimal or mild depression in 33%, and moderate to quite clearly expressed depression in 15% of patients.

Table 2 Descriptive characteristics of study variables. Parameters n % Mean±SD Me Range Min.–Max. SF-36 PCS 176 100 39.88±21.78 38.75 93.75 5.00–98.75 SF-36 MCS 176 100 45.41±18.80 39.72 88.50 2.25–90.75 SF-36 Perceived health status 176 100 42.64±17.90 40.56 84.06 3.63–87.69 MFIS – 0–38 55 31 27.47±9.58 30.00 33.00 5.00–38.00 MFIS – 39–84 121 69 54.39±9.38 54.00 42.00 39.00–81.00 MFIS – total score 176 100 45.98±15.66 47.50 76.00 5.00–81.00 SDS – 25–49 91 52 41.24±6.71 44.00 24.00 25.00–49.00 SDS – 50–59 58 33 55.24±2.87 56.00 9.00 50.00–59.00 SDS – 60–70 27 15 62.37±1.64 62.00 8.00 60.00–68.00 SDS – total score 176 100 49.09±9.90 49.00 43.00 25.00–68.00 PES – 6–14 54 31 9.88±2.89 11.00 8.00 6.00–14.00 PES – 15–22 92 52 17.26±2.22 18.00 7.00 15.00–22.00 PES – 23–30 30 17 24.73±1.84 24.00 7.00 23.00–30.00 PES – total score 176 100 17.03±15.66 18.00 24.00 6.00–30.00 MSSS – 18–35 18 10 14.06±11.24 14.57 33.33 0.00–33.33 MSSS – 36–67 73 41 53.16±9.15 54.16 30.55 36.11–66.66 MSSS – 68–100 85 48 84.06±9.97 84.72 30.56 69.44–100.00 MSSS – total score 176 100 64.08±24.40 65.96 100.00 0.00–100.00 SF-36 – Short Form 36 Health Subject Questionnaire (0: min. quality of life, 100: max. quality of life); PCS – physical component summary; MCS – mental component summary; MFIS – Modified Fatigue Impact Scale (0: min. fatigue, 84: max. fatigue); SDS – Zung’s Self-Rating Depression Scale (less than 50: no depression, more than 70 severe depression); PES – Pain Effect Scale (6: min. pain, 30: max. pain); MSSS – Modified Social Support Survey (0: min. support, 100: max. support); n – number of patients; SD – standard deviation; Me – Median, Min. – minimum values; Max. – maximum values.

Descriptive characteristics of study variables.

SF-36 – Short Form 36 Health Subject Questionnaire (0: min. quality of life, 100: max. quality of life); PCS – physical component summary; MCS – mental component summary; MFIS – Modified Fatigue Impact Scale (0: min. fatigue, 84: max. fatigue); SDS – Zung’s Self-Rating Depression Scale (less than 50: no depression, more than 70 severe depression); PES – Pain Effect Scale (6: min. pain, 30: max. pain); MSSS – Modified Social Support Survey (0: min. support, 100: max. support); n – number of patients; SD – standard deviation; Me – Median, Min. – minimum values; Max. – maximum values.

Correlations of Monitored Predictors with PCS, MCS, and PHS Among Multiple Sclerosis Patients

Table 3 shows the relationships between the physical component summary and mental component summary of quality of life, overall perceived health status, and monitored variables. Stronger correlations between the level of overall perceived health and the education of respondents were observed (r=0.284, P <0.0001), with patients with higher education showing higher scores. The respondents’ working ability positively affects the overall quality of their lives (r=−0.384, P <0.0001). Employed patients had higher scores than patients on partial and total disability pension. Clinical factors negatively affecting the overall perception of health by patients include the duration of the disease (r=−0.217, P <0.0001), primary and secondary progressive form of the disease (r=−0.278, P <0.0001), higher disability scores (r=−0.476, P <0.0001), lack of immunomodulation therapy (r=0.388, P <0.0001), higher degree of fatigue (r=−0.678, P<0.0001), higher degree of depression (r=−0.662, P <0.0001) and higher degree of pain (r=−0.580, P <0.0001). Patients with more social support had a higher quality of life (r=0.433, P <0.0001).

Table 3 Correlations of monitored predictors with PCS, MCS, and PHS SF-36 among multiple sclerosis patients. Parameters Physical component summary Mental component summary Perceived health status
Mean±SD or r Me or P Mean±SD or r Me or P Mean±SD or r Me or P

Age
−0.191 0.010 −0.036 0.748 −0.124 0.136

Gender
0.023 0.203 0.117 0.101 0.053 0.118
Men 37.38±24.05 33.75 39.42±14.83 35.62 38.40±17.82 34.12 Women 40.29±20.25 38.75 46.40±19.24 42.32 43.35±17.87 42.68

Education
0.338
0.0001
0.117 0.052 0.284
0.0001

Elementary 20.43±10.62 20.62 34.45±10.20 35.50 27.44±10.40 20.06 High school 37.80±21.05 21.05 44.54±18.92 39.81 41.17±18.33 38.53 Higher education 48.48±17.77 43.43 49.40±18.72 49.97 48.94±15.36 48.60

Work capacity
0.491
0.0001
−0.200
0.0001
−0.384
0.0001

Without restrictions 60.03±22.92 58.43 54.88±17.00 57.12 57.46±18.47 57.08 With restrictions 50.79±19.17 45.62 50.30±19.73 52.75 50.55±17.93 45.75 Disability pension 33.32±15.82 33.75 42.35±18.36 38.00 37.84±15.14 35.50

Disease duration
−0.327
0.0001
−0.153 0.043 −0.217
0.0001

0–4 years 55.41±27.16 47.50 51.36±19.66 50.55 53.38±22.47 48.05 5–8 years 47.34±15.63 50.62 45.23±13.51 42.32 46.28±12.08 45.87 9 years and more 34.08±16.26 33.75 43.67±19.02 39.25 38.88±15.72 35.50

Course of disease
−0.384
0.0001
−0.097 0.052 −0.278
0.0001

RR MS 44.68±19.46 42.50 45.58±18.67 40.25 45.13±17.66 42.43 PR MS 34.73±14.59 31.43 43.01±18.00 37.78 38.87±13.11 37.61 SR MS 25.90±14.33 24.50 41.16±20.31 33.25 33.53±15.54 32.18

EDSS
−0.604
0.0001
−0.238
0.0001
−0.476
0.0001

EDSS 1–3.5 52.63±22.53 48.12 49.07±18.24 49.75 50.85±18.90 46.93 EDSS 4–6 37.16±14.13 35.62 46.56±17.90 41.25 41.86±21.50 39.68 EDSS 6.5–8 20.67±12.17 17.81 35.14±19.03 29.25 27.91±13.48 23.96

Immunomodulatory therapy
−0.439
0.0001
0.239
0.0001
0.388
0.0001

No 30.60±13.46 30.31 40.43±17.44 35.75 35.51±13.51 34.12 Yes 50.04±22.63 46.25 50.86±18.82 50.90 50.45±18.90 49.09

MFIS
−0.610
0.0001
−0.606
0.0001
−0.678
0.0001

MFIS 0–38 57.10±21.19 50.62 61.28±15.69 65.87 59.19±15.86 59.62 MFIS 39–84 32.05±15.17 31.87 38.20±15.39 35.00 35.12±13.10 33.25

SDS
−0.594
0.0001
−0.605
0.0001
−0.662
0.0001

SDS 25–49 49.60±21.44 45.62 54.31±17.58 56.75 51.96±17.58 49.75 SDS 50–59 31.88±14.58 32.81 39.28±13.25 37.87 35.58±11.94 34.56 SDS 60–70 24.27±11.08 24.37 27.33±8.36 28.75 26.44±9.28 28.06

PES
−0.519
0.0001
−0.507
0.0001
−0.580
0.0001

PES 6–14 53.42±24.54 48.12 56.39±18.72 62.18 54.91±18.69 54.06 PES 15–22 35.63±15.92 35.93 42.58±16.14 38.53 39.12±14.22 39.15 PES 23–30 28.30±14.95 27.18 34.23±15.89 31.75 31.38±12.50 31.40

MSSS
0.369
0.0001
0.403
0.0001
0.433
0.0001

MSSS 68–100 48.49±22.67 45.00 68.95±13.42 72.00 50.96±18.74 49.37 MSSS 36–67 33.47±14.87 33.75 45.57±15.81 41.37 36.47±12.62 34.12 MSSS 18–35 25.15±13.91 21.25 33.80±15.45 29.43 28.41±12.82 27.59 SF-36 – Short Form 36 Health Subject Questionnaire; PHS – perceived health status; PCS – physical component summary; MCS – mental component summary; MFIS – Modified Fatigue Impact Scale (0: min. fatigue, 84: max. fatigue); SDS – Zung’s Self-Rating Depression Scale (less than 50: no depression, more than 70 severe depression); PES – Pain Effect Scale (6: min. pain, 30: max. pain); MSSS – Modified Social Support Survey (0: min. support, 100: max. support); RR MS – relapsing-remitting MS; PR MS – primary progressive MS; SR MS – secondary progressive MS; SD – standard deviation; Me – median; Min. – minimum values; Max. – maximum values; r – Spearman correlation coefficients; P – level of significance.

Correlations of monitored predictors with PCS, MCS, and PHS SF-36 among multiple sclerosis patients.

SF-36 – Short Form 36 Health Subject Questionnaire; PHS – perceived health status; PCS – physical component summary; MCS – mental component summary; MFIS – Modified Fatigue Impact Scale (0: min. fatigue, 84: max. fatigue); SDS – Zung’s Self-Rating Depression Scale (less than 50: no depression, more than 70 severe depression); PES – Pain Effect Scale (6: min. pain, 30: max. pain); MSSS – Modified Social Support Survey (0: min. support, 100: max. support); RR MS – relapsing-remitting MS; PR MS – primary progressive MS; SR MS – secondary progressive MS; SD – standard deviation; Me – median; Min. – minimum values; Max. – maximum values; r – Spearman correlation coefficients; P – level of significance.

Multiple Regression Model

A multiple regression model was conducted to examine the variables associated with the physical component summary SF-36, the mental component summary SF-36 and the perceived health status SF-36. Among the assessed independent variables, we selected age, gender, education, working capacity, treatment method, clinical form of the disease, duration of the disease, level of functional disability, severity of fatigue, level of pain, level of depression, and social support.

Multiple Regression Model for Physical Component Summary SF-36

The clinical form of the disease, the degree of severity of fatigue, the level of pain, and level of depression were among the predictors affecting the impact of the disease on the assessment of the level of physical health. Patients with SP MS in the form of the disease received a lower score in the physical dimension of quality of life than those with RR MS. A higher degree of fatigue, pain, and depression predicted a lower quality of life in the physical area. In the monitored model, MFIS (β=−0.246, P =0.002), PES (β=−0.619, P =0.003), SDS (β=−0.423, P =0.001) negatively correlates with the physical dimension score. This model explained 68% of the total variance of the total score of the physical component SF-36 (R 2 =0.68, ΔR 2= 0.65, F=22.01, P <0.0001) ( Table 4 ).

Table 4 Multiple regression model for PCS, MCS, and PHS SF-36 among multiple sclerosis patients. Variables Physical component summary Mental component summary Perceived health status β (SE) t
P
β (SE) t
P
β (SE) t
P
Constant 90.718 66.567 76.876 Age 0.113 (0.108) 1.047 0.297 0.767 (0.120) 0.637 0.525 0.107 (0.091) 1.178 0.241 Gender −2.172 (3.033) −0.716 0.475 7.214 (3.377) 2.136
0.034
2.730 (2.565) 1.064 0.289 Education 2.755 (2.217) 1.243 0.216 0.765 (2.469) 0.310 0.757 1.664 (1.875) 0.888 0.376 Work capacity −3.545 (1.837) −1.929 0.056 −1.967 (2.045) −0.962 0.338 −2.667 (1.554) −1.717 0.088 Immuno-modulatory therapy 4.401 (2.474) 1.779 0.077 2.905 (2.754) 1.055 0.293 3.939 (2.092) 1.883 0.062 Disease duration −2.799 (1.411) −1.982
0.049
0.978 (1.571) 0.622 0.535 −1.014 (1.194) −0.849 0.397 Course of disease −2.434 (1.490) −1.634 0.104 1.208 (1.659) 0.729 0.467 −0.524 (1.260) −0.416 0.678 EDSS −1.654 (0.944) −1.725 0.082 1.588 (1.051) 1.511 0.133 −0.059 (0.798) −0.074 0.940 MFIS −0.246 (0.077) −3.162
0.002
−0.361 (0.086) −4.178
0.000
−0.303 (0.065) −4.620
0.000
PES −0.619 (0.203) −2.989
0.003
−0.663 (0.230) −2.875
0.004
−0.673 (0.175) −3.842
0.000
SDS −0.423 (0.132) −3.202
0.001
−0.548 (0.147) −3.722
0.000
−0.464 (0.111) −4.150
0.000
MSSS 0.068 (0.044) 1.530 0.128 0.151 (0.049) 3.055
0.002
0.112 (0.037) 2.990
0.003
Model characteristic R 2 =0.68, ΔR 2 =0.65, F=22.01, P <0.0001 R 2 =0.57, ΔR 2 =0.53, F=13.49, P <0.0001 R 2 =0.70, ΔR 2 =0.67, F=24.42, P <0.0001 SF-36 – Short Form 36 Health Subject Questionnaire; PHS – perceived health status; PCS – physical component summary; MCS – mental component summary; EDSS – Expanded Disability Status Scale; MFIS – Modified Fatigue Impact Scale; PES – Pain Effect Scale; SDS – Zung’s Self – Rating Depression Scale; MSSS – Modified Social Support Survey; Me – median, Min. – minimum values; Max. – maximum values; β – Beta – coefficients; SE – standard error; R 2 - coefficient of determination; ΔR 2 – squared coefficient of determination; F – test statistic of F test; t – test statistics; P – level of significance.

Multiple regression model for PCS, MCS, and PHS SF-36 among multiple sclerosis patients.

SF-36 – Short Form 36 Health Subject Questionnaire; PHS – perceived health status; PCS – physical component summary; MCS – mental component summary; EDSS – Expanded Disability Status Scale; MFIS – Modified Fatigue Impact Scale; PES – Pain Effect Scale; SDS – Zung’s Self – Rating Depression Scale; MSSS – Modified Social Support Survey; Me – median, Min. – minimum values; Max. – maximum values; β – Beta – coefficients; SE – standard error; R 2 - coefficient of determination; ΔR 2 – squared coefficient of determination; F – test statistic of F test; t – test statistics; P – level of significance.

Multiple Regression Model for Mental Component Summary SF-36

Male gender, a higher degree of fatigue, pain, and depression predict a lower quality of life in the psychological area. Men had a significantly lower score of the mental health dimension than women (β=7.214, P =0.034). In the monitored model, MFIS (β=−0.361, P <0.0001), PES (β=−0.663, P =0.004), SDS (β=−0.548, P =0.0001) negatively correlates with the psychological dimension score. Social support from the family (MSSS) was significantly positively associated with the assessment of the overall dimension of mental health (β=0.151, P =0.002). This model explained 57% of the total variance of the total score of the psychological component SF-36 (R 2 =0.57, ΔR 2 =0.53, F=13.49, P <0.0001) ( Table 4 ).

Multiple Regression Model for Perceived Health Scores SF-36

The most relevant independent predictive factors of poorer quality of life among patients with MS (perceived health scores SF-36) in our study were depression, fatigue, pain, and lack of social support. In the regression model for the total quality of life score measured by the SF-36 questionnaire, MFIS (β=−0.303, P ≤0.0001), PES (β=−0.673, P ≤0.0001), SDS (β=−0.464, P ≤0.0001), and MSSS (β=0.112, P =0.003) had a significant association with the perceived health status of the respondents. This model explained 70% of the total variance of the total score SF-36 (R 2 =0.70, ΔR 2 =0.67, F=24.42, P <0.0001) ( Table 4 ).

Discussion

In our study, depression, fatigue, and pain were the most significant independent predictors of poorer quality of life in MS patients, as assessed by the SF-36 questionnaire. In recent years, several evaluations have concluded that psychological symptoms have a serious impact on the quality of life, regardless of the physical condition of patients [ 7 , 9 , 23 – 26 ].

Depression and fatigue have been proven as individual factors that significantly deteriorate the quality of life among patients in almost all areas of life [ 13 , 26 ].

In the available literature, the incidence of depression is 25–54% [ 53 , 54 ]. In our study, depressive symptoms were present in 48% of patients, which is consistent with the reported prevalence. Depression was a strong predictor of reduced quality of life, as also confirmed by the results of other studies [ 24 , 29 , 55 – 60 ]. Many authors cite the impact of depression on the reduction of the quality of life among patients with MS, which is not related to the degree of physical disability [ 12 ]. On the contrary, Brola et al [ 61 ] found that in patients with MS, the incidence of depression can reduce the quality of life and found a correlation between the degree of disability (measured by EDSS) and the occurrence of depression. Other research confirms that physical condition is an moderate independent predictor of depression in patients with relapsing-remitting MS [ 62 , 63 ]. Berrigan et al [ 64 ] reported that although the direct impact of physical comorbidities on quality of life was moderate, comorbidities worsen the symptoms of depression, anxiety, and fatigue, which are important determinants of the quality of life of people with MS. Lobentanz et al [ 65 ] found a correlation between the depression, fatigue, sleep disorders, and quality of life. Depressive symptoms were also repeatedly demonstrated to be associated with immunosuppressive treatment [ 66 ]. Depression can worsen the symptoms and course of the disease, associated with negative attitude, increased morbidity and mortality, and lower overall quality of life [ 67 , 68 ].

Fatigue is another important factor affecting quality of life. In our study, the mutual statistical relationship between the degree of fatigue and the level of quality of life was confirmed. Regression analysis confirmed the opinion presented in published studies that fatigue significantly affects the physical, and even more significantly, the mental component of quality of life [ 69 – 74 ]. Studies dividing fatigue into its various cognitive and physical components showed that the relationship between depression and fatigue was more pronounced for cognitive fatigue compared to physical fatigue [ 75 ]. This finding suggests that specific components of fatigue should be considered in the evaluation, as it is a heterogeneous entity with somatic and non-somatic symptoms [ 76 ]. Fernández-Muñoz et al [ 24 ] found an association between fatigue and the mental health dimension of quality of life of MS patients. The connection was explained by the fact that fatigue reduces cognitive functions, which promotes depressive symptoms, followed by increased fatigue, forming a vicious cycle [ 24 , 77 ]. Fatigue in MS patients is not precisely understood and is assumed to be heterogeneous, with various underlying pathophysiological mechanisms leading to the same subsequent symptomatology [ 76 ]. While some authors see fatigue as a direct consequence of the MS disease process itself [ 78 ], others interpret it as a consequence of depression or sleep disorders [ 79 ]. A study directly comparing 4 models predicting fatigue among patients with MS emphasized depression and sleep disorders as strong predictors of fatigue regardless of the severity of the disease [ 80 ]. The disabling nature of non-somatic depressive symptoms can contribute to fatigue in patients with MS, although it is possible that it is mainly limited to the secondary aspect of fatigue [ 81 ].

In our study, a multiple regression model showed that pain is a relevant independent predictor of quality of life in the physical and mental area of life among MS patients. Pain is a common problem among patients with MS and is another important symptom that affects quality of life. It occurs with varying frequency and intensity at the time of performing normal daily activities. Pain and its impact on quality of life has been examined in several studies and confirmed as an important risk factor [ 74 , 82 , 83 ].

Some of the findings presented in our work can be compared with the results of Solaro et al [ 84 ], who assessed the prevalence of pain in MS. Based on 1672 returned questionnaires, the authors evaluated the incidence of pain among patients with MS. Kalia and O’Connor [ 85 ] found that pain was correlated with the level of quality of life associated with health, especially in mental health dimensions. The level of chronic pain was significantly related to anxiety and depression in a group of women. Svedsen et al [ 86 ] indicated that pain in MS patients negatively affects physical and social functioning.

Gustavsen et al [ 27 ] stated that the invisible symptoms of patients with MS can be very burdensome for the patient, even those with mild disability. Fatigue, pain, and sleep disorders had the strongest associations with the overall quality of life score.

In our study, we found that patients with a higher degree of disability had a lower quality of life rating, especially in regards to physical functioning. The state of the patient’s functional disability is one of the factors negatively affecting the quality of life of patients with MS, as described in the literature [ 6 – 8 , 87 , 88 ]. Other authors state that a higher degree of disability is accompanied by reduced independence and self-care ability. The result is a negative view of quality of life [ 89 , 90 ]. Gupta et al [ 87 ] studied a group of 74 451 people with MS, and found that patients with a higher degree of disability evaluated their health-related quality of life at a lower level, and the reduction in the ability to move independently has the strongest correlation with poor quality of life. Despite the statistical significance, the multivariate analysis indicated that the degree of disability is not the main predictor of the low score of the total domains of the SF-36 questionnaire. Similarly, Yalachkov et al [ 91 ], in the analysis of several predictors, did not find any significant impact of cognitive or motor fatigue on quality of life. They explained these seemingly surprising findings by the mediating effect of mental comorbidity.

The clinical form of the disease is a strong predictor of lower quality of life in the physical domain. PMS patients with progressive forms of the disease had lower scores on perception of quality of life, especially in the physical area. A similar finding was presented by Gross et al [ 22 ], who compared a group of patients with the SP MS form of the disease with those who had the RR MS form. Patients with SP MS regarded their disease as more serious, reported several neurological symptoms more often, and had a higher rate of hospitalization compared to patients with RR MS. Patients with SP MS had more problems getting a job than patients with RR MS, due to greater disability. Patients with SP MS rated the physical dimension of quality of life significantly lower compared to patients with RR MS. Zhang et al [ 21 ] focused on assessing the quality of life level in groups of patients with progressive disease (primarily progressive, relapsing-progressive, and secondary progressive) and non-progressive form (relapsing-remitting, benign form), reporting that people with the progressive versus the non-progressive form of MS have different perceptions of quality of life. The set of symptoms was a general predictor of the quality of life subscales, with the exception of the social functioning of people with progressive MS. The study recommended comprehensive therapy of disease symptoms.

In the multiple regression model, male gender was a strong negative predictor of quality of life in the psychological area of the respondents. However, Lobentanz et al [ 65 ], Miller and Dishon [ 92 ], and Pfaffenberger et al [ 93 ] found that female gender was associated with worse quality of life. Neurological symptoms are typical for multiple sclerosis, but overlapping psychological symptoms are equally bothersome.

Our findings suggest that patients’ quality of life is partly mediated by perceived social support. Social support proved to be a positive predictor of quality of life, especially its psychological dimension. A similar finding was presented by Jaracz et al [ 5 ], who emphasized the positive role of social support and that its protective function may be weakened when interacting with other factors. Several other studies have identified social support as a predictor of perceived health status, both physical and mental, through its role in relieving stress [ 94 – 96 ]. Higher social support not only allows patients to become more independent, but also gives them the opportunity to rely on their loved ones if necessary. This study confirmed that clinical symptoms have a major impact on quality of life, while other studies have emphasized the influence of socioeconomic factors on the quality of life of MS patients [ 17 , 97 ].

Our study shows that identification of risk and protective factors is a key element in the implementation of strategies to improve quality of life among MS patients. Studies aimed at assessing the level of quality of life can indicated society-wide sensitivity and openness to solving the problems of people with disabilities.

Study Limitations

We recognize that this study has limitations. The Short Form 36 (SF-36) questionnaire is widely accepted as the standard for general health measurement [ 98 ]. Although there are other instruments specifically designed to assess quality of life in MS patients, such as the Multiple Sclerosis International Quality of Life and Multiple Sclerosis Quality of Life-54 (MSQOL-54) questionnaires [ 98 ], none of these scales were available in the Slovak language at the time of the study. On the contrary, the SF-36 questionnaire has been translated into Slovak. However, there are studies evaluating its use in clinical trials for multiple sclerosis [ 10 , 11 , 99 ].

The research is influenced by the inconsistency, heterogeneity, and complexity of the disease itself. Another problematic point of the research was the possibility of influencing the monitored parameters based on a subjective assessment in the patient’s current mental state. When analyzing the impact of selected factors on the level of the monitored parameters, there was an uneven division of respondents into groups. Our study, due to its cross-sectional nature, does not allow the monitoring of changes in the quality of life over time.

Conclusions

The present study concludes that the quality of life of MS patients is primarily affected by clinical symptoms of the disease, such as depression, fatigue, and pain. The results encourage conclusions that social support and social interactions are an important aspect in the lives of patients with chronic disease and significantly affect the subjective perception of quality of life by patients. The study points out that the identification of risk and protective factors is a key element in the implementation of strategies to improve the quality of life among MS patients.

Footnotes

Conflict of interest: None declared

Department and Institution Where Work Was Done: The research was performed at the Department of Physiotherapy, Faculty of Health Care, University of Prešov in Prešov, Slovakia.

Financial support: None declared

References