Keywords:
Fibromyalgia - Quality of Life - Activities of Daily Living - Fatigue
Palabras clave:
Fibromialgia - Calidad de Vida - Actividades Cotidianas - Fatiga
INTRODUCTION
Multiple sclerosis (MS) is an autoimmune, inflammatory, demyelinating, and neurodegenerative
disorder that has been more commonly seen in women, which is characterized by relapsing
neurological dysfunction. In developed countries, MS is the most common cause for
neurological disability in younger adults. Relapsing remitting MS (RRMS) has been
more commonly seen in younger age groups and has had a course characterized by attacks[1],[2],[3].
In addition to organic disorders, many physical and psychiatric comorbidities may
develop during the disease course in MS patients. It has been reported that physical
disorders, such as fibromyalgia syndrome (FMS), and psychiatric disorders, such as
depression and anxiety disorders, euphoria, fatigue, sleep disorder, bipolar disorder
and schizophrenia are frequently seen in MS patients who have been exposed to severe
physical and psychosocial stressors. In previous studies, physical and psychiatric
disorders were seen in approximately two-thirds of MS patients, even though treatment
has not been indicated in all cases[4],[5].
FMS is a clinical condition that presents many symptoms, such as chronic, widespread
pain and fatigue, sleep disorder, cognitive dysfunction, and depressive episodes[6]. It generally affects women aged 30-50. In previous studies, the prevalence of FMS
was found as 1 to 4% in general population, while it varied between 0 and 4% among
men and 2.5 to 10.5% among women. Quality of life is impaired due to physical and
psychological disorders caused by FMS, which is associated with widespread pain (hyperalgesia
and/or allodynia), tenderness in certain anatomic regions (tender points), chronic
fatigue, sleep disorder, rigidity, and subjective swelling. Some literature studies
suggest that comorbid FMS frequency is increased in MS patients, causing delayed diagnosis,
disability progression, quality of life worsening, and hospitalization rate increase[7].
This study aimed to investigate the frequency and effects of FMS on activities of
daily living (ADL) without known psychiatric problem or severe disability in patients
with MS, which is known to be a chronic disease in young adults.
MATERIALS AND METHODS
This study prospectively included patients with definitive MS diagnosis, based on
McDonald criteria (2010), who were at the RR form interictal period and were followed
up in 2017 and March, 2018[8]. In all patients, diagnosis, identification of clinical form and follow-up were
performed at the MS Outpatient Clinic of Kayseri Training and Research Hospital. The
study was approved by the Local Ethics Committee and conducted following the Helsinki
Declaration. All participants provided a written informed consent.
We recorded the age, gender, disease duration, medications, education level, occupation
and neurological systems involved during disease course, findings of neurological
examination, duration of follow-up, and overall number of attacks in all the patients.
The Expanded Disability Status Scale (EDSS) was applied to assess functionality in
MS patients[9]. Patients with EDSS score>4.5, younger than 18 or older than 50, with known FMS,
menopausal women and that used neuropsychiatric agents six months before were excluded.
Diagnosis for FMS according to the American College of Rheumatology (ACR) 2016 revision
should fulfil: generalized pain (at least four of five regions); persistent symptoms
for at least three months; widespread pain index (WPI)≥7, and Symptom Severity Scale
(SSS) score≥5 or WPI 4-6 and SSS score≥9; and a diagnosis of FMS is valid irrespective
of other diagnoses, and a diagnosis of FMS does not exclude the presence of other
clinically important illnesses[10]. The severity of FMS was assessed using the Fibromyalgia Impact Questionnaire (FIQ)
with ten categories. Its score ranges from 0 to 80 points (maximum impact)[11].
Quality of life was assessed by means of the MS Quality of Life Instrument (MSQOL-54),
which analyzes and measures physical and mental health-related quality of life status
(PHS and MHS, respectively). The item scores range from 0 (poor health) to 100 (optimal
health). In addition, the multiple item scales of each of these scores can be analyzed
individually to understand more clearly the changes on the composite scores. The physical
health composite score is computed from the individual scores of the following scales:
physical function, health perceptions, energy and fatigue, role limitations - physical,
pain, sexual function, social function, and health distress. The mental health composite
score is computed based on the individual scores of the following scales: health distress,
overall quality of life, emotional well-being, role limitations - emotional, and cognitive
function[12],[13].
Sleep disorder was assessed by means of Pittsburgh Sleep Quality Index (PSQI), which
provides information about sleep quality and type and severity of sleep disorder in
the prior month. Sleep quality is considered good when PSQI score is lower than five[14]. Anxiety was analyzed by means of Beck Anxiety Inventory (BAI). It provides four
options in 21 symptom categories, and the highest scores indicated more severe anxiety[15]. Fatigue was assessed by means of the Fatigue Severity Scale (FSS), in which a mean
value higher than four was considered an indication of clin ically significant fatigue[16]. Depression was measured by means of the Beck Depression Inventory II (BDI-II).
The cut-off scores used were: 0-13 for mini mal depression; 14-19 for mild depression;
20-28 for moderate de pression; and 29-63 for severe depression[17].
All analyses were performed using the International Business Machines (IBMM) of the
Statistical Package for the Social Sciences (SPSS) for Windows, version 20.0. Numerical
variables are summarized as mean±standard deviation. Qualitative variables are presented
as counting and percentages. For each continuous variable, normality was checked by
the Kolmogorov-Smirnov test. Differences in numerical variables between the groups
were also analyzed with the t-test for independent groups when the parametric test
hypotheses were met, and with Mann-Whitney’s U test, when they were not. Pearson's
correlation coefficient was applied to assess the association between numerical variables.
A p-value lower than 0.05 was statistically significant.
RESULTS
Overall, 103 patients with RRMS were included in the study. Mean age was 35.04±8.72
years (21-48) in the study population. Of the patients, 43 (52.4%) were women, while
49 (47.6%) were men. Mean age was 35.55±6.81 years among women and 35.35±7.60 years
among men. Mean EDSS score was 2.20±0.88 for females, whereas 2.21±0.97 for males.
Mean disease duration was 7.51±4.27 years in the study population.
The FMS was detected in 20 patients (19.4%) including 14 women (70%) and 6 men (30%).
The most common comorbidity was fatigue (66%); followed by depression (54.3%), anxiety
(50.4%) and sleep disorder (48.5%), as seen in [Table 1].
Table 1
Comorbid conditions in multiple sclerosis patients.
|
Comorbid conditions
|
Yes
|
No
|
|
Fibromyalgia
|
20 (19.4%)
|
83 (80.6%)
|
|
Fatigue
|
68 (66%)
|
35 (44.0%)
|
|
Depression
|
56 (54.3%)
|
47 (45.7%)
|
|
Anxiety
|
52 (50.4%)
|
51 (49.6%)
|
|
Sleep disorder
|
50 (48.5%)
|
53 (51.5%)
|
Quality of life was assessed using the MSQOL-54 in MS patients. Mean MSQOL-54 score
was 34.8±9.14 in MS patients with FMS, while 72.67±13.95 in those without FMS, indicating
a significant difference between groups (p<0.001). When other comorbid conditions
were assessed, depression, anxiety, fatigue, and sleep disorder were significantly
more severe in MS patients with FMS (p<0.001). The EDSS score was significantly higher
in MS patients with FMS than in those without it (p<0.05). No significant difference
was detected in disease duration between MS patients with or without FMS (p>0.05),
as in [Table 2].
Table 2
Scales assessing activities of daily living and other comorbid conditions in multiple
sclerosis patients with or without Comorbid Fibromyalgia Syndrome.
|
Comorbid conditions
|
With Comorbid Fibromyalgia Syndrome (n=20)
|
Without Comorbid Fibromyalgia Syndrome (n=83)
|
p-value
|
|
Activities of daily living
|
34.80±9.14
|
71.67±13.95
|
<0.001
a
|
|
Anxiety
|
29.25±8.05
|
10.19±6.33
|
<0.001
a
|
|
Depression
|
26.95±7.85
|
11.66±6.23
|
<0.001
a
|
|
Sleep disorder
|
10.00±2.15
|
4.69±2.11
|
<0.001
a
|
|
Age
|
37.55±5.34
|
34.95±7.47
|
0.146
|
|
Disease duration/year
|
9.85±3.54
|
6.95±4.25
|
0.006
a
|
|
EDSS
|
3.50*
|
2.00*
|
<0.001
b
|
|
Fatigue
|
6.71*
|
4.24*
|
<0.001
b
|
aindependent Student’s t-test; bMann-Whitney’s U test; significant p-values (p<0.05) are given in italic type; *median
values are given; EDSS: Expanded Disability Status Scale.
There was a significant and negative correlation between FIQ and MSQOL-54 in patients
with FMS (p<0.05), as in [Figure 1]. In addition, there were significant positive correlations between FIQ and BAI or
BDI (p<0.05). However, the positive correlations with PSQI, FSS and EDSS scores did
not reach statistical significance (p>0.05), based on [Table 3].
Figure 1 Correlations between fibromyalgia impact questionnaire and activities of daily living.MSQOL-54:
Multiple Sclerosis Quality of Life Instrument.
Table 3
Correlations between the Fibromyalgia Impact Questionnaire and other comorbid conditions.
|
Fibromyalgia Impact Questionnaire
|
|
r
|
p-value*
|
|
Beck Anxiety
|
0.533
|
0.016
|
|
Beck Depression
|
0.726
|
<0.001
|
|
PSQI
|
0.292
|
0.212
|
|
FSS
|
0.202
|
0.392
|
|
EDSS
|
0.373
|
0.105
|
|
Disease duration/year
|
-0.067
|
0.780
|
*p: Pearson’s correlation coefficient; PSQI: Pittsburgh Sleep Quality Index; FSS:
Fatigue Severity Scale; EDSS: Expanded Disability Status Scale.
In the MSQOL-54 test, mean score of physical health domain was 33.61±10.06 in MS patients
with FMS, whereas 71.60±12.86 in those without it. The mean score of cognitive health
domain was 35.99±9.42 in MS patients with FMS, whereas 71.73±16.00 in those without
it. Differences in both domains were found to be statistically significant (p<0.05).
DISCUSSION
In our study, we investigated the effects of FMS frequency on ADL as well as anxiety,
depression, fatigue, and sleep disorder in MS patients. Our results revealed that
ADL were significantly more impaired in MS patients with FMS that in those without
it. In the subgroup analysis, there was a significant difference in the frequency
of anxiety, depression, fatigue, and sleep disorders between MS patients with or without
FMS.
Although the etiopathogenesis of FMS could not be fully established, hormonal disorders,
dysfunction of nervous system, immune problems, micro-circulation disorders in muscles
and genetic predisposition may be involved in FMS. In some studies, FMS prevalence
was reported to be 2 to 7% in general population with female preponderance[18]. In a study on MS patients and healthy volunteers, Marrie et al. found that FMS
frequency was 3.5 folds higher in MS patients when compared to the general population[19]. However, to the best of our knowledge, there is no study addressing FMS frequency
in the context of ADL and its effects on sleep and chronic fatigue. In our study,
FMS frequency was increased by 3.5 folds in MS patients in agreement with literature.
In addition, this increase was associated with impairment in ADL, sleep disorder,
and chronic fatigue. Our findings show that early diagnosis and timely intervention
to FMS in MS patients will result in improvement in ADL and quality of life. Moreover,
effectiveness and tolerability to primary drugs might be improved with FMS treatment.
The presence of comorbid FMS in MS patients has been associated with increased disability,
decreased labor force, ADL and quality of life, and social losses. However, the relationship
between FMS and MS has not been fully elucidated[19]. In MS patients, the FMS has been seen upon early phases of disease, and incidence
increases as disability severity becomes higher. However, the varying prevalence rates
for FMS were found in different series. Therefore, the presence of FMS varies according
to age, gender, geographic region, disability status, and comorbid conditions. Clemenzi
et al. found a FMS frequency of 17.3% in MS patients and 3.8% in the general population[20]. In a cohort study by Davis et al., FMS frequency was reported as 14.06% in MS patients[21]. Authors reported that FMS frequency was higher among women and that it was increased
when EDSS scores were higher. In our study, MS patients with EDSS>4.5 were excluded
to standardize our work and to show that it may be FMS in the early phase of the disease.
Furthermore, FMS frequency was 19.4% and FMS could be seen upon the early phases of
MS and it increased by making EDSS score higher, which is in agreement with previous
literature. In addition, FMS presence was independent from age and disease duration,
and marked female preponderance was present.
Besides FMS, the incidence of several physical and psychiatric comorbidities, such
as depression, anxiety, fatigue or sleep disorder, is markedly higher in MS patients,
affecting more than 50% of patients[22]. Depression is the most common psychiatric disorder seen in MS, which is a chronic
disease resulting in disability in young adults. Depression prevalence ranged from
27 to 54% in several series using different, but valid, scales[23],[24]. It is seen three folds higher than other chronic diseases. Lifetime prevalence
of depression is higher than other medical and neurological diseases in MS patients.
It is accepted that depression seen in MS may be due to the combination of organic
and psychological effects of MS. Anxiety is another widely seen psychiatric comorbidity
in MS[25]. In a study by Stenager et al., a significant relationship was reported between
anxiety and physical losses. FMS and depression share similar pathophysiological pathways.
However, the relationship between depression and increase in FMS has not been assessed
in studies on MS patients. In our study, we concluded that the presence of MS is correlated
with FMS development in MS. In subgroup analysis, we found that depression and anxiety
severity was increased in MS patients with FMS.
MS-related fatigue is defined as physical and mental energy deprivation observed by
patient or caregiver. In previous studies, 75 to 87% of MS patients suffered from
fatigue. Of these patients, two-thirds reported it as one of the three worst symptoms
of the disease[25]. In MS, fatigue is more frequent when compared to healthy adults and individuals
with chronic disorders and has more influence on ADL. The fatigue incidence has been
reported as 78 to 94%. However, no specific underlying mechanism has been revealed
for fatigue seen in FMS or MS[26]. In a study on 207 MS patients, Kroencke et al. assessed patients using the FSS
and Self-Rating Depression scales. Authors found that fatigue scores were highly correlated
with depression scores and EDSS[27]. However, the effect of FMS on fatigue has not been evaluated so far. In our study,
we found that fatigue severity was higher in MS patients with FMS.
Sleep disorder is another comorbid condition in MS patients, considering that perceived
stress is higher in MS patients when compared to healthy individuals[28]. In a study on MS patients, Figved et al. investigated neuropsychiatric symptoms
and found that sleep disorder is the second most common comorbidity (48%) following
depression in MS patients[29]. In our study, sleep quality was assessed through the PSQI and impaired sleep quality
was found in MS patients with FMS when compared to those without it.
Although comorbid FMS and psychiatric disorders have been assessed in large series
and population-based studies, their effects on ADL, fatigue and sleep disorder and
their correlation among each other have not been evaluated. Relatively small sample
size and lack of comparison with health controls are limitations of our study. Another
limitation is that the study included only the RRMS. It is known that such comorbidities
are more common, and ADL are more strongly affected in progressive forms of MS. This
may lead to an underestimation of our results.
In conclusion, FMS and accompanying anxiety, depression, fatigue, and sleep disorders
are a commonly seen comorbidity in MS patients. They can be seen in every phase of
MS without the presence of severe disability. Comorbid conditions can be overlooked
since clinicians focus on the treatment of primary disease. These comorbidities lead
to a delay in diagnosis, disability progression, decreased quality of life, and increased
admission rates. To the best of our knowledge, there is no study addressing effects
of FMS on quality of life in MS patients. Our study is the first showing such relationship.
Questioning and appropriately managing FMS in clinical practice are important to improve
quality of life in MS patients.
