Sleep disorders in patients with multiple sclerosis

Abstract

Background

Multiple sclerosis (MS), affected about 2.8 million people worldwide in 2020, is often associated with sleep disorders. These disturbances may arise from the disease itself—such as pain—or as side effects of symptomatic and immunological treatments.

Methods

The present study is cross-sectional- analytic study. The population studied consists of MS patients living in Kashan city. The sample size under investigation is comprised of 174 patients diagnosed with MS. The information was gathered through demographic information questionnaires, the hospital anxiety and depression scale(HADS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and Multiple Sclerosis Impact Scale (MSIS). The data were analyzed through Chi-square tests and logistic regression using Stata version 14 software.

Results

: Of 174 MS patients (81.76% female, mean age 34.16 ± 7.62), Mild insomnia affected 17.05%, and 68.18% experienced frequent night awakenings. Significant predictors of sleepiness included education level (OR: 18.20; p = 0.03), insomnia severity (OR: 5.24; p = 0.04), and morning dysfunction (OR: 6.49; p = 0.04), as well as MS medication. Most patients were not taking sleep medication (86.05%). Mild anxiety and baseline depressive symptoms were prevalent (69.32% and 80.68%, respectively), and 80.11% reported low quality of life.

Conclusions

The final model demonstrated an effective relationship between the Sleepiness and variables of education level, drugs used in MS, Insomnia Severity, and morning dysfunction in the presence of other variables.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12883-025-04247-9.

Introduction

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system. This disease significantly impacts both the mental and physical functioning of individuals [1]. According to the Atlas of MS (2020), approximately 2.8 million people are affected by this disease [2]. It can occur at any age, although it is more prevalent among young individuals and women. The global incidence rate is 33 cases per 100,000 individuals, with significant variations across different geographic areas; the highest prevalence is reported in Europe and North America [3, 4]. In Iran, the prevalence of MS is estimated to be 29.3 per 100,000 individuals(2019) [5] also the age-adjusted mean annual incidence of MS is 6.7 per 100,000 individuals, which is higher in females (10.5) compared to males (3.0) [6].

The primary causes of this disease are not yet fully understood, but genetics is recognized as a significant risk factor. Several environmental factors, such as vitamin D deficiency, Epstein-Barr virus infection, smoking, increasing body mass during adolescence, stress, and certain bacterial infections, have also been proposed as risk factors [7]. In this disease, the myelin of the brain and spinal cord becomes damaged, disrupting the electrical impulses transmitted through the nerves to various parts of the body [8].

Symptoms of the disease include fatigue, imbalance, pain and spasms, cognitive impairment and depression, vision problems, tingling and numbness in the limbs, bladder issues, and sexual dysfunction [9]. About half of MS patients report experiencing sleep disorders [10, 11].These disorders may be associated with depression, anxiety, and mental health issues resulting from MS. The most common sleep problems among MS patients include insomnia, sleep apnea, restless legs syndrome, narcolepsy, and Rapid Eye Movement )REM( sleep behavior disorder [12].

Sleep disorders in MS patients can have multiple causes, potentially initiated by symptomatic and immunological treatments as well as factors related to MS itself, such as pain [13]. Shengli Ma, the prevalence of insomnia among MS patients was 64.9%, with a significant correlation found between sleep disorders and variables such as gender, antidepressant use, pain, and fatigue [13]. Another study conducted in Kermanshah(Iran) indicated that over 87% of surveyed individuals experienced sleep problems in some form, with the highest frequency associated with anxiety, sleep onset disorder (insomnia), and difficulty maintaining sleep continuity [14].

Patients with sleep disorders are at an increased risk for other health issues, such as heart disease, obesity, and diabetes, which can further threaten their long-term health [15]. Treating sleep disorders in individuals with MS is crucial due to the severity of both physical and mental health challenges these patients face [15]. Additionally, it has been shown that sleep disorders can serve as indicators of the quality of life for affected individuals. Therefore, to enhance sleep quality and mitigate potential associated problems in MS patients, it is essential to understand risk factors of sleep disorders. If sleep disorders are not treated in MS patients, they could have serious consequences. To prevent this issue, it is necessary to study this issue in different regions. In the present study, the objective was to investigate sleep disorders in patients with (MS) residing in Kashan, Iran. Given the high prevalence of MS in Iran and the limited research on sleep disorders in MS patients within this region, this study aims to provide new insights into the relationship between MS and sleep quality. While previous studies have explored the prevalence of sleep disturbances in MS patients globally, most of these studies have been conducted in Western populations, where healthcare, socio-cultural factors, and disease management may differ significantly from those in Iran. By investigating these factors, this study will contribute to a more comprehensive understanding of how sleep disorders affect the quality of life of MS patients. Additionally, it will provide valuable data that can be used to inform regional -specific healthcare strategies and interventions aimed at improving the management of sleep disturbances in MS patients.

Methods

The present study is a cross-sectional analytic. Data were collected from March 5, 2020, to March 5, 2023. Initially, after obtaining authorization from the esteemed Research Vice-Chancellor of Kashan University of Medical Sciences and the ethics committee, the necessary introductions for the hospital and clinic were secured. This study was approved by the Ethics Committee of Kashan University of Medical Sciences(IR.KAUMS.MEDNT.REC.1397.058). The study population consists of (MS) patients residing in Kashan, who were selected based on availability and entered the study following diagnosis and interviews conducted by a neurologist.

Informed consent was obtained from all participants regarding the research conditions and their involvement in the study. All questionnaires were anonymous and it was stated that all information would remain confidential. The neurologist conducted interviews with the patients, explaining the purpose of the research and ensuring the confidentiality of their information. Participants were informed about the demographic information required, and the neurologist collected specific clinical data, including the Expanded Disability Status Scale (EDSS), type of MS, disease duration, hospitalization frequency, and the use of psychiatric medication(supplementary file). All study participants gave a written informed consent. The study was approved by the Ethical Committee of our Institution and was conducted according to the Declaration of Helsinki. All patients underwent clinical and neurophysiological examination.

Inclusion criteria

The inclusion criteria for this study encompassed all MS patients who have: at least basic literacy skills to complete the questionnaire, been diagnosed by a neurologist, provided informed consent to participate, a history of MS for more than six months, passed at least three months since their last attack and do not have physical disabilities that would prevent them from completing the questionnaire.

In the present study, the diagnosis of patients was based on the McDonald criteria2017 [16], these criteria facilitate early and accurate diagnosis of MS, enabling timely therapeutic intervention.

Exclusion criteria

Exclusion criteria included the presence of any acute illness requiring hospitalization and any reluctance to continue participating in the study. Thyroid disorders, smoking, and the use of psychoactive substances were considered exclusion criteria.

Initially, patients completed a demographic characteristics questionnaire. Under the supervision of a neurologist, they then filled out several standardized assessments, including the (HADS), (PSQI), (ESS), (ISI), (MSIS), which assesses the quality of life of MS patients. The neurologist addressed any ambiguities that arose during the completion of these questionnaires. Biases, such as information bias and interviewer bias, were anticipated. To mitigate these risks, training was provided to the data collectors before data collection commenced.

Tools used in the research

Hospital Anxiety and Depression Scale (HADS) [17].

The HADS is a self-report scale with 14 items designed to assess the presence and severity of depression and anxiety symptoms in patients aged 16 and older. It consists of two subscales: one for depression and one for anxiety, each containing seven items that exclude physical symptoms to minimize false positives. The depression subscale focuses on the absence of happiness. Scores range from 0 to 21 for both subscales, with interpretations as follows: 0–7 (normal), 8–10 (mild), 11–14 (moderate), and 15–21 (severe) [18, 19]. In a study conducted in Iran, the Cronbach’s alpha for the anxiety and depression subscales was 0.78 and 0.86, respectively [17].

Pittsburgh Sleep Quality Index (PSQI) [20].

The PSQI assesses sleep quality, with scores ranging from 0 to 39; higher scores indicate poorer sleep quality. A score of 39 reflects the lowest sleep quality, while 0 is the best. In Iran, the Cronbach’s alpha for the PSQI was 0.77, with subscale correlations ranging from 0.3 to 0.75 [20].

Epworth Sleepiness Scale (ESS) [21].

The ESS is an eight-question tool that measures daytime sleepiness, scoring each question from 0 to 3. Total scores are categorized as follows: 0–5 (sufficient sleep), 6–10 (mild sleepiness), 11–15 (moderate sleepiness), and 16–24 (severe sleepiness) [21]. A study reported a reliability coefficient of 0.73 for this questionnaire.

Insomnia Severity Index (ISI) [22, 23].

The ISI assesses insomnia severity over the past two weeks with five questions, scoring from 0 to 28. Higher scores indicate greater severity and a need for clinical support [22, 23]. In Iran, the Cronbach’s alpha for this index was estimated to be 0.82 [24].

Multiple Sclerosis Impact Scale (MSIS) [25].

The MSIS evaluates the quality of life for MS patients. It includes 29 questions—20 assessing physical effects and 9 assessing psychological effects—with responses scored from 1 to 5. Total scores are converted to a scale from 0 to 100, where higher scores indicate lower quality of life. The Cronbach’s alpha in a study conducted in Iran was greater than 0.7 [25].

Data analysis

After data collection and refinement, the Kolmogorov–Smirnov test was employed to assess the normality of continuous variables, and the assumption of normality was satisfied.descriptive analysis was performed using STATA(ver14) software, including central tendency and dispersion indices for quantitative variables and frequency distributions for qualitative variables. Chi-square tests were used for comparisons when statistical assumptions were Met. Logistic regression analysis was employed to predict variables affecting sleepiness, first examining the model as a single variable and then incorporating statistically significant and clinically important variables into a final multivariate model using the forward method.

Participants were categorized into two groups based on their disability level. According to the neurologist’s opinion, a cutoff score of 4.5 on the EDSS was used.

All analyses were conducted with a significance level of less than 0.05 and a 95% confidence interval.

Results

The study consisted of a total of 172 participants. The mean age was 34.16 years (± 7.62), with a maximum age of 52 years and a minimum of 18 years. Among the participants, 81.76% (139) were female and 18.24% (31) were male. While 70.93% (122) individuals were married, 29.07% (50) individuals were single The educational levels were as follows: 55.23% (95) had a diploma, 34.30% (59) held a bachelor’s degree, 7.56% (13) had a master’s degree, and 2.91% (5) possessed a doctorate.

Notably, 97.08% (166) of participants worked non-shift jobs. Additionally, 96.51% (166) did not smoke; 98.85% did not use psychotropic drugs (Table 1).

Table 1.

Table of demographic characteristics of patients with MS

Gender	Frequency	Percentage
Male	31	18.24
Female	139	81.76
Education
Diploma	95	55.23
Bachelor’s degree	59	34.30
Master’s degree	13	7.56
Doctoral degree	5	2.91
Marital status
Single	50	29.07
Married	122	70.93
Shift (job)
Yes	5	2.96
No	166	97.08
EDSS disability assessment
Score < 4.5	169	98.26
Score > 4.5	3	1.74

In terms of medication, 58.83% (103) of patients were receiving injectable drugs (such as Beta interferon 1a, glatiramer acetate); 25.21% (50) were on oral medications (including fingolimod, dimethylfumarate, triflunomide); 15.97% (19) received infusion treatments (such as Rituximab, Tysabri, ocrelizumab). Among the participants, 98.83% (169) had relapsing-remitting multiple sclerosis (RRMS); 1.17% (2) were classified as having secondary progressive multiple sclerosis (SPMS). In terms of disability level, 98.26% (169) of participants had an EDSS score of less than 4.5 (Table 1).

Regarding insomnia, 76.70% (133) of participants reported normal sleep conditions; 15.34% (27) experienced mild anxiety. Additionally, 1.70% (3) were identified as suffering from severe depression; 80.11% (142) indicated a low quality of life (Table 2).

Table 2.

Frequency of measurement of sleepiness, clinical anxiety scale, clinical depression scale, insomnia severity, and the quality of life of MS patients (MISS)

Scale	Description	Frequency	Percentage	(Mean ± SD)
Epworth Sleepiness Scale (ESS)	no clinically significant insomnia	133	76.70	3.47 ± 4.17
	Mild insomnia	30	17.05
	Moderate insomnia	7	3.98
	Severe insomnia	4	2.27
Anxiety Scale (HADS)	Normal range of anxiety	120	69.32	5.54 ± 4.80
	Mild anxiety	27	15.34
	Moderate anxiety	17	9.66
	Severe anxiety	10	5.68
Depression Scale (HADS)	baseline depressive symptoms	140	80.68	4.15 ± 4.04
	Mild depression	20	11.36
	Moderate depression	11	6.25
	Severe depression	3	1.70
Insomnia Severity Index (ISI)	Insomnia is not clinically significant	114	65.91	5.79 ± 5.98
	Insomnia below the clinical threshold	40	22.73
	Moderate clinical insomnia	19	10.80
	Severe clinical insomnia	1	0.57
Measuring the quality of life of MS patients (MISS)	Low quality of life	142	80.11	45.34 ± 18.36
	The average quality of life	26	14.77
	High quality of life	6	3.41

On average, patients took 25.93 min to fall asleep, with a mean effective sleep duration of 6.79 h. Furthermore, 16.48% (28) of individuals did not experience sleep disturbances, such as waking at night, while 6.40% (11) used sleeping medications three or more times per week (Table 3).

Table 3.

Pittsburgh sleep quality index results based on its 7 components (PSQI)

Component	Description	Frequency	Percentage	Mean ± SD
Sleep Quality	Very good	59	65.91	0.85 ± 0.77
	Good	85	22.73
	Bad	20	10.80
	Very bad	10	0.57
Sleep Latency				25.93 ± 27.69 (minutes)
(Actual amount of sleep at night) Duration of useful sleep				6.79 ± 1.59 (in hours)
Sufficient sleep	Above 85%	111	66.47	0.59 ± 0.97
	75 to 84%	27	16.17
	65 to 74%	14	8.38
	Less than 65%	15	8.98
Sleep Disorder (measured by waking up at night)	0	28	16.48	0.98 ± 0.56
	1–9 times	120	68.18
	10–18 times	26	15.34
	19–27 times
Medication Usage (times used medicine to sleep)	Never during the last month	148	86.05	0.13 ± 0.34
	Less than once a week	6	3.49
	Once or twice a week	7	4.07
	Three or more times a week	11	6.40
Morning Performance (problems caused by poor sleep experienced during the day)	0	67	38.07	0.94 ± 0.91
	1 to 2 times	64	36.36
	3 to 4 times	33	18.75

The final model has been adjusted and and consists of the variables of age (p = 0.36)), gender((female to male))(p = 0.48), education level(Master’s to Bachelor’s)(P = 0.03), MS medication, clinical anxiety scale(p = 0.73), clinical depression scale (p = 0.31), severity index of insomnia(people with insomnia disorder to without clinically significant insomnia) (p = 0.04), measuring the quality of life of MS patients(people with medium and high quality of life to people with low quality of life)(p = 0.47), sleep latency (p = 0.33), sleep disorder(people who took medicine in the last week to people who did not take medicine)(p = 0.40), and morning dysfunction(people with insomnia problems to people without problems)(p = 0.04).

The results of the final model indicated that a higher level of education (from a bachelor’s to a master’s degree) significantly correlated with an increase in the Sleepiness. Specifically, the rate of sleepiness among individuals with a master’s degree was 18.20 times greater than that of individuals with a bachelor’s degree. Additionally, when considering other variables, those taking oral medications experienced 12.17 times more sleepiness compared to individuals on other MS treatments (Table 4).

Table 4.

Results of univariate and multivariate odds ratio in Epworth sleepiness Scale(ESS)

Variables	Unadjusted odds ratio	P- value	Adjusted odds ratio	P- value
Age	1.05 (1-1.10)	0.042	1.06 (0.93–1.20)	0.363
Gender (female to male)	0.66 (0.27–1.58)	0.353	0.49 (0.06–3.66)	0.488
Education level (Master’s to Bachelor’s)	3.26 (1–10)	0.050	18.20 (0.90–36)	0.035
Intramuscular injection drugs Beta interferon 1a, Beta interferon 1b, glatiramer acetate,	1.7 (0.77–3.70)	0.182	4.85 (0.46-50)	0.185
Oral medicine (fingolimod dimethyl fumarate, teriflunomide,	1.61 (0.68–3.82)	0.275	12.17(0.98-15)	0.048
Intravenous drug (Rituximab, Tysabri, Ocrelizumab)	0.34 (0.09–1.27)	0.112	1	-
Clinical anxiety scale (abnormal to Normal range of anxiety)	2.46 (1.19–5.09)	0.015	1.38 (0.21–8.88)	0.731
Clinical depression scale (depressed to baseline depressive symptoms)	4.16 (1.86–9.25)	P < 0.001	0.36 (0.04–2.64)	0.316
Insomnia severity index (people with insomnia disorder to without clinically significant insomnia)	4.46 (2.13–9.32)	P < 0.001	5.24 (0.81-33)	0.048
Measuring the quality of life of MS patients (people with medium and high quality of life to people with low quality of life)	3.37 (1.49–7.60)	0.003	0.38 (0.02–5.27)	0.476
Sleep latency (minutes)	1.01 (1-1.02)	0.034	0.98 (0.96–1.01)	0.331
Sleep disorder (how many times you used medicine to sleep) (people who took medicine in the last week to people who did not take medicine)	5.29 (2.14-13)	P < 0.001	2.16 (0.34-13)	0.408
Morning dysfunction (problems caused by poor sleep experienced by the person during the day) (people with insomnia problems to people without problems)	8.09 (2.73–23.96)	P < 0.001	6.49 (1.05-40)	0.044

* Adjusted variables include age, gender, educational level, marital status, medication usage, disability status, type of MS, depression, anxiety, ISI, MISIS, and Pittsburgh components

Discussion

Poor sleep is often observed in patients with MS, and previous studies have shown its prevalence to be between 25 and 67% [26].In a case-control study conducted by Sahraian et al., no significant associations were found between age, gender, degree of disability, or duration of illness with sleep disorders in either the case or control groups. This finding aligns with the results of our study, suggesting that demographic and clinical characteristics may not significantly influence sleep disturbances in (MS) patients [27].

Insomnia and its associated disorders are prevalent in the general population, manifesting as prolonged sleep latency, insufficient sleep, and early awakening. Various factors contribute to insomnia, including depression, anxiety, urban lifestyle stressors, chronic illnesses, hormonal changes, sleep-disordered breathing, medication side effects, and environmental factors such as noise, inadequate lighting, and unsuitable temperatures. Our univariate analysis indicated a significant association between sleepiness and both depression and anxiety [26]. However, there are no specific guidelines for treating insomnia in patients with MS. One treatment study demonstrated improvement in insomnia as a result of treating depression in MS [28].

One of the primary contributors to insomnia and resultant sleepiness in MS patients is pain, which may stem from muscle spasms, periodic limb movements, restless legs syndrome, urinary incontinence, and depression related to the disease [29]. Pain disrupts the sleep cycle, leading to excessive daytime sleepiness(EDS) and diminished energy levels, which can further lower pain tolerance thresholds in patients [28].

Interestingly, our findings revealed that participants with a master’s degree exhibited significantly higher levels of daytime sleepiness, as measured by the ESS, compared to those with a bachelor’s degree. While this may seem counterintuitive at first glance, several potential explanations can be proposed.First, individuals with higher educational attainment may be more likely to hold demanding occupations, which are often associated with increased mental stress and irregular sleep patterns. Such lifestyle factors may contribute to the development of (EDS) in patients with MS. In fact, fatigue and EDS are among the most commonly reported symptoms in MS, affecting up to 80% of patients, and can occur even in those with mild neurological impairment [30, 31].

Moreover, higher education may correlate with increased health awareness and symptom reporting. Patients with advanced degrees might be more attuned to their bodily symptoms, leading to higher self-reported scores on sleep-related questionnaires. Psychological comorbidities such as anxiety and depression, which are common among individuals with MS, may also contribute to poor sleep quality and EDS [32, 33].

Although we found no prior studies specifically linking education level to EDS in MS patients, similar associations have been suggested in the general population, where higher educational and occupational demands can negatively impact sleep [34]. Therefore, it is plausible that these factors may exacerbate sleep disturbances and fatigue in individuals with MS, leading to greater reported sleepiness among those with higher education.

Our findings suggest that, daily dysfunction was more common in the group receiving injectable medications(including interferon beta-1a, interferon beta-1b and glatiramer acetate).

In our study, we observed that oral medications were significantly associated with increased sleepiness. Conversely, research by Gammo et al. indicated that Fingolimod had a protective effect against depression, anxiety, and insomnia, though this was statistically significant only for depression, highlighting discrepancies in findings [35]. Factors such as the timing of diagnosis, degree of disability, comorbidities, and the dosage and duration of medication use may influence these outcomes. S. Dogan et al. found that anxiety and depression symptoms are higher in multiple sclerosis patients compared to the healthy group, and the quality of sleep and life are worse [36].It is known that sleep disorders, including insomnia, restless legs syndrome, sleep-related movement disorders, and sleep-related breathing disorders, frequently coexist in MS patients [37].Sleep disturbances, possibly due to anxiety and depression, may affect the immune system, potentially worsening MS symptoms and exacerbating sleep problems [38].The limited evidence available suggests that subjective sleep quality is affected by MS and should be considered by clinicians to prevent sleep-related symptoms such as depression and anxiety. To reach a comprehensive conclusion in this area, it is essential to conduct well-designed prospective studies [39].

Additionally, a study by Emily K et al. found that sleepiness was not significantly related to the quality of life in MS patients; however, those with sleep disorders reported a lower quality of life, which aligns with our results [40]. Another study conducted in Australia demonstrated that medication use could lead to sleep disturbances, compromising sleep quality and hindering daily functioning, further supporting our findings [28].

In the study by Kotterba et al. a high prevalence of sleep disorders and a low quality of life were observed in patients with MS. Furthermore, the study identified a relationship between anxiety and fatigue with poor sleep quality, which aligns with the findings of our study [41].

Limitations of the study

The mental and emotional state of patients when responding to questions can influence the accuracy of their answers, presenting an uncontrollable limitation. Including other patients with central nervous system disorders in the study and comparing the results with those of the current patients could have led to more appropriate conclusions.

Additionally, had the study been designed as observational, with the possibility of following up with individuals and incorporating a control group for comparison, we might have reached more satisfactory conclusions.

Conclusions

We recommend further research on which habits in these patients could predict problematic sleep. Public health efforts on prevention programs could provide further causal evidence regarding MS patients or factors that can be modified to improve sleep habits in these patients. The variables of education level (postgraduate to bachelor’s degree), oral medications, (ISI), and morning dysfunction in the presence of other variables exhibited a significant correlation with (ESS). Supportive treatment measures and therapeutic and diagnostic interventions can be beneficial in treating patients with MS.

Electronic supplementary material

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Abbreviations

ESS

Epworth Sleepiness Scale

PSQI

Pittsburg Sleep Quality Index

MS

Multiple sclerosis

ISI

Insomnia Severity Index

HADS

Hospital Anxiety and Depression Scale

REM

Rapid eye movement

MSIS

Multiple Sclerosis Impact Scale

SPMS

Secondary progressive multiple sclerosis

RRMS

Relapsing-remitting multiple sclerosis

EDSS

Expanded Disability Status Scale

EDS

Excessive Daytime Sleepiness

Author contributions

F.A. and E.K. conceived of the presented idea. F.A. developed the theory and performed the computations. S.B. and E.K. verified the analytical methods. FA. And E.K. to investigate and supervised the findings of this work. All authors discussed the results and contributed to the final manuscript.

Funding

None.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Informed consent was obtained from all participants regarding the research conditions and their involvement in the study.This study was approved by the Ethics Committee of Kashan University of Medical Sciences(IR.KAUMS.MEDNT.REC.1397.058).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.