Fatigue Syndrome in Multiple Sclerosis

Background: symptoms (p value<0.001), and visual symptoms (p value=0.017) was statistically significant. Conclusion: Fatigue is a common compliant in multiple sclerosis. Although, fatigue is a heterogeneous syndrome with various causes, the possibility of its prediction is high in ms patients through clinical evaluation.


INTRODUCTION
Multiple sclerosis is a chronic and often debilitating disease. In MS, the immune system attacks the myelin sheath of neurons in the central nervous system [1,2]. Moreover, myelin in form of small or large and single plates or multiple one is inflamed and destroyed. Depending on the location of the plaques in the central nervous system, the disease symptoms and signs will be different [3]. The most frequent age groups afflicted with MS ranged from 20 to 40 years old. The cause of MS remains unknown, but several factors including environmental factors, genetic background, and family background are considered as important in its occurrence [4,5]. Three major psychiatric symptoms are seen in MS patients include fatigue, psychiatric symptoms and cognitive deficits [6]. More than 80% patients complain about excessive fatigue, which leads to disability and quality life reduction. Both physical and mental fatigues interfere with daily activities such as work [7]. Little information about the mechanisms and pathophysiology of fatigue is available and researchers are attempting to discover its cause [8][9][10]. Fatigue in MS patients intensifies in the afternoon. Fatigue is also one of MS symptoms, but this, as symptoms of depression, is usually in the morning [6]. Depression is also one of the most common complications in MS patients. The rate of depression in patients with MS is about 20-50% in the course of their disease and the point prevalence rate is usually about 10-20% [11,12].
This study attempted to investigate the prevalence of fatigue syndrome in patients with MS and the relationship between frequency of Fatigue and Depression in MS patients referred to MS Society of Yazd province of Iran because of high prevalence of fatigue syndrome in young patients suffered from MS.

MATERIALS AND METHODS
This was a descriptive study. The study population consisted of patients with multiple sclerosis registered in MS society of Yazd province of Iran. 97 patients were enrolled the study which were selected randomly. A questionnaire including age, sex, marital status, duration of MS, the disease symptoms and signs were used.
To evaluate the different degree of fatigue, IOWA Fatigue Scale (IFS) was used and to assess the rate of depression, Beck Depression Inventory (BID) was applied. It is noteworthy that patients had enough mental ability to fill out the questionnaire. IFS include 11 questions and each question has 1 to 5 points that represents the mildest to the most severe degrees of fatigue. For scoring, the scores of questions 2, 4, 7, 10, and 11 were subtracted from the score of question 6; and the obtained score was summed with scores of other questions. Scores rated between11-29 reflects lack of fatigue, 30-39 represents moderate fatigue, and score 40 or more indicates severe fatigue.

Statistical Analysis
The data were analyzed by SPSS software (version 17) through tests of chi square, ANOVA, and fisher exact tests.
The data were analysed by SPSS software (version 17) through of Chi-Square and Fisher Exact Test to evaluate the relationship between fatigue and age, gender, marital status, depression, pyramidal signs, cerebellar signs, sensory, disease duration, and visual symptoms. To compare mean of fatigue with other variable were used the ANOVA test.

RESULTS
This descriptive study was carried out on 97 patients suffered from MS. These patients were referred to the MS Society of Yazd. The age of the patients ranged from 18-52 years old with mean age of 34.5±8.5. The study population included 15 men (15.5%) and 82 female (84.5%). Patients were divided in two age groups of 18-34{53 patients (54.5%)} and 35-52 years {44 patients (45.5%)}. 21 (22%) were single and 76 (78%) were married. Based on IFS, out of 97 patients, 33 patients (34%) had no fatigue, 40 patients (41%) had moderate fatigue and 24 patients (25%) had severe fatigue. According to Beck questionnaire, the following results were obtained: 30 (31%) with no sign of depression, 25 (25.7%) with mild depression and 22 (22.7%) with moderate depression and 20 (20.6%) with severe depression. The findings of this study showed that a high percentage of these patients (66%) suffered from some degree of fatigue, which was mostly moderate. The relationship between fatigue and other variables, mainly marital status, depression, pyramidal signs, cerebellar signs, sensory and visual symptoms were statistically significant. Table 1 show that 65.9% of patients with MS suffered from some degree of fatigue. There is no statistically significant relationship between age classification and mean of fatigue in patients with multiple sclerosis ( Table 2). The fatigue status in patients with MS in the age groups of 18-34 and 35-52 had no difference (P value=0.386). According to acquired data, state of fatigue in patients with MS had no relation with sex (P value=0.664). Fatigue in the married patients with MS was more than fatigue in single patients (P value=0.008) (Table 3). Fatigue in the married MS patients had no significant relation to the level of education (P value=0.964). The degree of fatigue in patients with MS was unrelated to duration of their disease (P value=0.075). Being fatigue in patients with MS had significant and direct relationship with depression (Table 4). Fatigue had direct relation with pyramidal symptoms (P value= 0.039). Fatigue in the married patients suffered from MS correlated with cerebellar symptoms (P value= 0.039). Fatigue had direct relation with sensory symptom. Fatigue and sphincter symptoms were unrelated (P value=0.548). The relationship between frequency of fatigue and disease duration in MS patients was summarized in Table 5. There is no significant relationship between frequency of Fatigue and Disease duration (P value=0.075). Degree of fatigue in patients with MS intensified due to visual symptom (P value= 0.017).    In control group (n=400), 94 (23.5%) persons had fatigue and 23 (5.75%) had sever fatigue (Total=29.25%). So based on our study, prevalence of fatigue in patient s with MS (66%) is significantly higher than healthy population [14].
According to Beck questionnaire, the following results were obtained: 30 patients (31%) with no depression, 25 patients (25.7%) with mild depression, 22 patients (22.7%) with moderate depression and 20 patients (20.6%) with severe depression. The data showed that 69.9% of patients had sign of depression which was similar to Dehghani et al. [15] study. Dehghani study showed that a high percentage of patients (66%) suffered from some degree of fatigue, which was mostly moderate. The relationship between fatigue and other variables, mainly marital status, depression, pyramidal signs, cerebellar signs, symptoms and visual symptoms was statistically significant. In another study by Mohr et al. [16] in Denmark, the effect of treating depression on fatigue in MS patients was explored and showed that there was a relationship between depression and fatigue. These findings were also consistent with our study. In 2008, Schwarts et al. [17] showed a significant relation between depression and fatigue which is consistent with our study. However in this study, there was significant relationship between fatigue and depression, but 10 patients with fatigue had no rate of depression. This finding supports the hypothesis that fatigue is a separate issue from depression [6]. In a study by Flachenecker et al. [18], the relationship between fatigue in MS patients and clinical parameters was explored. They reported that fatigue had relation with physical disability and depression but had no relation with age, duration of disease which is consistent with the findings of this study. In another study by Iriarte et al. [19], the relation between degree of fatigue in MS patients and clinical and biological factors was investigated. The following results were concluded: the relationship between fatigue and pyramidal symptoms which is consistent with this study. Mills and Yonge in [20] had conducted a study to find out the relationship between fatigue and other MS clinical symptoms. The results showed that the prevalence of fatigue in patients with MS was 60% and fatigue intensified with inability and had relationship with depression and anxiety. Moreover, no association between fatigue and duration of the disease and patient's age was found which is in line with our study. [20]. In a study by Eghbali et al in 1390, the relationship between fatigue in MS and clinical status was explored. They showed that the frequency of fatigue in patients with MS was 65% and in terms of the relationship between fatigue and pyramidal symptoms, cerebellar symptoms, and sensory symptoms associated with fatigue, it was in line with our study. However, regarding to the relation between patient's age and sphincter symptoms; it was in contrast with the current study [13]. Niino et al. in [21] investigate the factors associated with depression apathy and fatigue. They reported that fatigue had no relationship with duration of the disease. These results were in line with this study. The results of this study were consistent with a number of previous studies [22][23][24]. The discrepancy between the results of our study and other research may be due to racial differences, differences in lifestyle and environmental differences and differences in data collection.

CONCLUSION
Our study showed that the frequency of fatigue in MS Society of Yazd province of Iran was as follows: 41% and 25% suffered from moderate and severe fatigue, respectively. The major objective of this study was to investigate the relationship between fatigue and demographic features (age, sex and marital status), symptoms and sign of the disease. The majority of patients had evidence of fatigue and depression. The results showed the high prevalence of fatigue in MS patients. Due to negative impact of fatigue and depression on treatment compliance and quality of life, evaluation of patients for these factors is necessary.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.