Fatigue In Multiple Sclerosis Patients Research Articles

Exploring digital biomarkers using smartphones for fatigue assessment in patients with multiple sclerosis

AbstractObjectivesThe treatment goals for multiple sclerosis (MS) are shifting from relapse inhibition to the improvement of long‐term prognosis and quality of life (QoL). Fatigue reduces QoL in patients with MS. The methods for assessing and treating fatigue, particularly those that are easily applicable in clinical settings remain unestablished. This study aimed to explore and identify digital biomarkers related to fatigue using smartphones.MethodsThe patients with MS attending the Department of Neurology at St. Marianna University School of Medicine (Kanagawa, Japan) were surveyed via mail and responses were obtained online. The survey items included patient background such as age and sex, Fatigue Assessment Scale (FAS), which is one of the patient‐reported outcomes (PROs) and serves as a questionnaire method for assessing fatigue, as well as self‐assessments of depression, sleep, and pain. Additionally, the number of steps recorded on smartphones was collected as personal health records (PHRs) along with the time spent using smartphones.ResultsOverall, 27 (18 female) participants responded (response rate: 46.6%). The mean age was 41.0 ± 14.6 y and the majority (12 participants) had a disease duration of <5 y. According to self‐assessments, moderate or higher symptoms of depression, sleep disturbances, and pain were observed in 13 participants, 10 participants, and 6 participants, respectively. The daily number of steps ranged from 805 to 15 263 (median of 4514 steps). The number of steps was negatively correlated with FAS (r = −0.47, P = .02), and in cases with any physical disability, the number of steps was negatively correlated with FAS (r = −0.69, n = 0.01).ConclusionThe number of steps automatically measured by smartphones could be a digital biomarker reflecting fatigue in MS patients.

Virtual Reality Applications for Balance Rehabilitation and Efficacy in Addressing Other Symptoms in Multiple Sclerosis—A Review

(1) Background: Since multiple sclerosis (MS) is a neurological pathology known for its disabling effects across many domains, the introduction of virtual reality (VR) usage has been attempted, as it represents a new method of approach to rehabilitation and treatment of chronic neurological pathologies. Encouraging research has explored the use of video game consoles and VR-assisted Robot-Assisted Gait Training (RAGT) to address balance disturbances in this population. (2) Methods: The search involved two databases, Web of Science and PubMed, utilizing a selection of terms including “Virtual reality”, “Multiple sclerosis”, “Balance”, and “Rehabilitation”. Two reviewers initiated and performed the search for articles, subsequently selecting and extracting data from the studies. The PEDro scale was the tool for evaluating the quality of the articles that we introduced in our research. (3) Results: After rigorous scanning, nine articles remained eligible for our study. VR interventions, particularly compared to standard balance training, consistently improved balance in multiple sclerosis. Robotic-assisted technology with 2D VR yielded superior results in balance rehabilitation. VR interventions had varied effects on walking speed. They have shown promise in decreasing the risk of falls and improving patients’ daily lives while reducing fatigue in multiple sclerosis. (4) Conclusions: VR offers comparable or superior benefits to classical exercise and no intervention for balance but does not significantly improve functional mobility. However, it shows the potential to improve quality of life and fatigue in MS patients. Investigation of VR alongside RAGT is important to be performed with larger sample sizes and comprehensive results are needed to fully understand its efficacy in MS rehabilitation.

Comparing the effects of cerebellar and prefrontal anodal transcranial direct current stimulation concurrent with postural training on balance and fatigue in patients with multiple sclerosis: a double-blind, randomized, sham-controlled trial.

Fatigue and balance disorders are common challenges experienced by Multiple Sclerosis (MS) individuals. The purpose of this study was to compare the concurrent effects of cerebellar and prefrontal anodal trans-cranial direct current stimulation (a-tDCS) with postural training on balance and fatigue in MS patients. 51 patients were evaluated to randomly allocation to a-tDCS over cerebellum, a-tDCS over dorsolateral prefrontal cortex (DLPFC) and sham group. 46 individuals (n = 16 in experimental groups and n = 14 in control group) followed treatment. All the groups received 10 sessions of postural training. The experimental groups underwent a-tDCS with a current of 1.5mA for a period of 20min. While, in the sham group, tDCS was only activated for 30s and then turned off. The treatment included 10 sessions for four weeks. Before and after intervention, fatigue and balance were assessed using Fatigue Severity Scale (FSS), Timed Up and Go (TUG) test and Berg Balance Score (BBS), respectively. There was found a significant reduction in fatigue in the group receiving a-tDCS over the prefrontal cortex with postural training compared to the other two groups (P < 0.001). Additionally, a significant improvement was found in balance in the group receiving a-tDCS over the cerebellum concurrent with postural training in comparison to the other two groups (P < 0.001). Besides, in the sham group, the significant results were not reported in the variables. (P > 0.001). The results demonstrated that a-tDCS enhances the effects of postural training on balance and fatigue in MS patients.

Fatigue may improve equally after balance and endurance training in multiple sclerosis: a randomised, crossover clinical trial.

Fatigue and poor balance are frequent and severe problems in multiple sclerosis (MS) that may interact. Endurance training is known to be effective on fatigue. This study aims to test if balance training is more effective against MS fatigue. A randomised crossover trial was run, recruiting 31 MS people (21 women; median age: 46 years, range: 30-64; median EDSS: 4, range: 2.5-5). Participants received balance and endurance training alternately (15 one-to-one sessions, 5 days/week) and were assessed before (T0), after (T1), and 30 days after treatment ended (T2). The Modified Fatigue Impact Scale (MFIS) with scores linearised through Rasch analysis was the primary outcome (the lower the measure, the better the condition, i.e., the lower the fatigue symptoms). The Equiscale balance scale and posturography (EquiTest) were used to assess balance. Linear mixed-effects models with ANOVA were used for significance testing. Thirteen participants had no carryover effect and were included in the primary analysis. Fatigue significantly changed across the three time points (F2,58 = 16.0; p < 0.001), but no difference across treatments was found. Altogether, both treatments significantly improved the MFIS measure at T1 (95%CI: -1.24 logits; mean: -1.67 to -0.81 logits) and T2 (95%CI: -1.04; mean: -1.49 to -0.60) compared to T0 (95%CI: -0.51; mean: -0.95 to -0.08; p ≤ 0.001). Equiscale and posturography highlighted balance improvement after balance training but not after endurance training. Balance and endurance training could similarly reduce fatigue in MS patients in the short term. However, only balance training also improved balance in MS.

Meaningful digital biomarkers derived from wearable sensors to predict daily fatigue in multiple sclerosis patients and healthy controls

Fatigue is the most common symptom among multiple sclerosis (MS) patients and severely affects the quality of life. We investigate how perceived fatigue can be predicted using biomarkers collected from an arm-worn wearable sensor for MS patients (n= 51) and a healthy control group (n= 23) at an unprecedented time resolution of more than five times per day. On average, during our two-week study, participants reported their level of fatigue 51 times totaling more than 3,700 data points. Using interpretable generalized additive models, we find that increased physical activity, heart rate, sympathetic activity, and parasympathetic activity while awake and asleep relate to perceived fatigue throughout the day-partly affected by dysfunction of the ANS. We believe our analysis opens up new research opportunities for fine-grained modeling of perceived fatigue based on passively collected physiological signals using wearables-for MS patients and healthy controls alike.

Effect of Mobile Health Self-care Training on Fatigue in Multiple Sclerosis Patients

Background: Technological advancements have facilitated disease management. These technologies can be used to educate multiple sclerosis (MS) patients at any time and place and improve the health of patients. Objectives: The present study aimed to investigate the effect of mobile health training on the fatigue levels of MS patients in Zahedan. Methods: This quasi-experimental study involved 80 MS patients who joined the Zahedan Multiple Sclerosis Association in 2023. Patients were selected through convenience sampling and then randomly assigned to either the intervention or control group. Patients in the intervention group received mobile health education on fatigue reduction strategies using a website (www.Betterlifems.ir) created by the researcher, in addition to the standard education. The control group received only the standard education. In both groups, data were collected through a demographic information questionnaire and the Fatigue Severity Scale (FSS) at the beginning and two months after the intervention, using the interview method. The SPSS software (version 26) was used to analyze the collected data via paired t-test, independent t-test, chi-square test, and analysis of covariance (ANCOVA) at a significance level set at less than 0.05 (P &lt; 0.05). Results: In the control group, the average fatigue score increased from 43.72 ± 9.04 to 44.07 ± 9.13, which did not demonstrate a significant increase (P = 0.69). Conversely, in the intervention group, the average fatigue score significantly decreased from 43.47 ± 8.15 to 30.10 ± 8.28 (P = 0.001). The ANCOVA results, which accounted for significant pretest score effects, revealed a significant difference in mean fatigue scores between the two groups after the intervention (P = 0.0001). Conclusions: This study confirms that mobile health training has a significantly positive effect on the fatigue experienced by patients with MS. Therefore, mobile health can be utilized to teach self-care strategies to manage and alleviate fatigue in MS patients.

Frequency and characteristics of chronic fatigue syndrome in multiple sclerosis patients at a university hospital in Eastern Saudi Arabia.

Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease that affects various parts of the central nervous system. Fatigue, a common symptom, transient, prolonged, or chronic experienced by individuals with MS, can significantly impact daily functioning. It can be associated with underlying pathological processes or can have an idiopathic cause, such as chronic fatigue syndrome (CFS). The study aimed to assess the presence and etiology of fatigue in MS patients and its relationship with CFS. This cross-sectional study was conducted in the Eastern Province of Saudi Arabia. Data were collected using a questionnaire from a sample of 225 MS patients receiving care at our university hospital. The questionnaire included the Centers for Disease Control and Prevention (CDC) criteria for diagnosing CFS and the Expanded Disability Status Scale to evaluate fatigue in MS patients. Of the total of 225 MS patients who participated in this study, 87.1% were diagnosed with relapsing-remitting MS, 6.7% with primary progressive MS, 3.6% with clinically isolated syndrome, and 2.7% with secondary progressive MS. About 53% had experienced fatigue that persisted for over 6 months. Analysis of CFS diagnosis revealed that 7.3% of patients met both CDC criteria and self-reported answers while 17.5% reported having CFS despite not meeting the CDC criteria. These findings highlight a significant lack of agreement between patient-reported diagnoses and established criteria, indicating poor agreement (P = 0.028). The study found an association between CFS and MS, and a significant impact on daily functioning. The study revealed lack of agreement between patient-reported diagnoses and established criteria for CFS. This emphasizes the need for a standardized approach to diagnosis and evaluation of fatigue in MS patients.

Overview of the Current Pathophysiology of Fatigue in Multiple Sclerosis, Its Diagnosis and Treatment Options - Review Article.

Fatigue is a common, debilitating and often underestimated symptom in patients with multiple sclerosis (MS). The exact pathophysiological mechanism of fatigue in MS is still unknown. However, there are many theories involving different immunological, metabolic and inflammatory mechanisms of fatigue. Owing to the subjective nature of this symptom, its diagnosis is still very limited and is still based only on diagnostic questionnaires. Although several therapeutic agents have been used in the past to try to influence fatigue in MS patients, no single effective approach for the treatment of fatigue has yet been found. This review article aims to provide the reader with information on the current theories on the origin and mechanism of fatigue in MS, as well as diagnostic procedures and, finally, current therapeutic strategies for the management of fatigue in MS patients.

Investigating the link between regional oxygen metabolism and cognitive speed in multiple sclerosis: Implications for fatigue

BackgroundMost multiple sclerosis (MS) patients experience fatigue and cognitive decline but the underlying mechanisms remain unknown. Previous work has shown whole brain resting cerebral metabolic rate of oxygen (CMRO2) is associated with the extent of these symptoms. However, it is not known if the association between global CMRO2 and MS-related cognitive speed and fatigue can be localized to specific brain regions. Based upon previous research suggesting prefrontal involvement in MS-related changes in cognitive speed and fatigue, we hypothesized that oxygen metabolic changes within prefrontal cortex (PFC) might form the pathophysiologic basis of cognitive performance and fatigue in MS patients. ObjectiveInvestigate whether PFC ΔCMRO2 is associated with cognitive speed and fatigue in MS. MethodsMS and healthy control (HC) participants were scanned using a dual-­echo fMRI sequence and underwent a hypercapnia calibration experiment that permitted estimation of ΔCMRO2 while performing a scanner version of symbol-digit modalities task, a measure of information processing speed and utilized in the clinic as a reliable sentinel biomarker for global cognitive impairment in MS. Participants then completed the Modified Fatigue Impact Scale (MFIS) to measure fatigue. ResultsMS patients exhibited significant reductions in cognitive performance relative to HCs (p < 0.04). Prefrontal ΔCMRO2 explained significant variability (ΔR2 = 0.11) in cognitive speed, over and above disease and demographic variables, for the MS group only. Prefrontal ΔCMRO2 was not associated with fatigue across groups. ΔCMRO2 in visual and motor areas were not associated with cognitive performance or fatigue for either group. ConclusionPrefrontal oxygen metabolism may be a sensitive measure of MS-related cognitive decline.

Influence of Transcranial Direct Current Stimulation and Exercise on Physical Capacity and Gait in Multiple Sclerosis: A Cross-Over Pilot Study.

Physical capacity provides a link between disease or impairment and limitations in activity; in multiple sclerosis (MS), it is limited and decreased. The aim of this study was to study the effects of exercise and transcranial direct current stimulation (tDCS) on the left dorsolateral prefrontal cortex area in MS patients with fatigue and an impaired gait ability. A cross-over design was carried out on fifteen patients with two disability associations, but three were excluded. Before and after each intervention, the 6 min walk test (6MWT) and the 2 min walk test (2MWT) were used to assess walking ability and the Modified Fatigue Impact Scale (MFIS) was used to assess fatigue. A total of twelve patients were enrolled (48.0 median age, Kurtzke Disability Scale (EDSS) 3.66 ± 1.3): five females and seven males. After the application of the exercise program, significant improvements were observed in the 6MWT (p < 0.001, g = 0.159) and 2MWT (p < 0.001, g = 0.182). Furthermore, fatigue was significantly reduced after the application of the exercise program (p < 0.05, g = 0.742) and after tDCS (p < 0.05, g = 0.525). We could consider therapeutic exercise in the future to improve the walking ability and fatigue in MS patients. Furthermore, tDCS did not exert a significant improvement in walking ability, but it appeared to influence fatigue. Clinical trial registration code: ACTRN12622000264785.

Perception of Quality of Life and Fatigue in Multiple Sclerosis Patients Treated with High-Dose Vitamin D

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with symptoms that greatly affect quality of life (QoL). One of the most prevalent symptoms of MS is fatigue, also one of the main factors reducing QoL. Low levels of vitamin D (VD) are associated with worse QoL and with increased risk of developing more severe forms of the disease. Methods: In this cross-sectional study, we compared perceptions of quality of life and fatigue in 324 patients, subdivided into four groups, according to their treatment: high-dose VD therapy only, disease-modifying therapy (DMT) only, both treatments, and no treatments. All subjects completed the MSQOL-54 and the FSS questionnaires via an online survey. Results: High-dose VD treatment was associated with an increased perception of physical QoL (83.60 vs. 66.92, p &lt; 0.001), mental QoL (75.52 vs. 59.80, p &lt; 0.001), and fatigue (1.89 vs. 2.98, p &lt; 0.001), compared to the DMT-only group. Treatment with DMT was associated with a worse perception of physical QoL compared to no treatment (70.58 vs. 76.53, p = 0.024). Conclusions: high-dose VD treatment is well-tolerated and associated with an increased perception of QoL in people with MS.

Assessment of muscle fatigue in multiple sclerosis patients in electromyographic examinations.

Although surface electromyography (sEMG) is the method used to assess muscle fatigue in patients with multiple sclerosis (PwMS), no pattern of signal change has been established. The differences shown in the parameters of other neurophysiological tests between PwMS and control groups (CG) suggest the differentiation of the sEMG signal. The purpose of the study was to verify potential differences in the fatigue sEMG signal in PwMS compared to CG. Cross-sectional study. Chair and Department of Functional Diagnostics and Physical Medicine. A randomised group of patients diagnosed with MS (30, 20-41 years). A random sample of young, healthy adults (median 28, 20-39 years). Measurement of sEMG was performed from extensor carpi radialis (ECR) and FCR (flexor carpi radialis) during 60-80% of maximum voluntary contraction (MVC) of extension and then flexion for 60sec, accordance with the fatigue protocol in Research XP Master Edition software (v. 1.08.27). Root mean square amplitude (A<inf>RMS</inf>) were lower for muscle in the PwMS compared to the CG (ECR P=0.0001, FCU P<0.0001). In the CG, the A<inf>RMS</inf> value increases during fatigue contraction (ECR P=0.0003, FCU P<0.0001), while in the PwMS) the A<inf>RMS</inf> value decreases (ECR: P<0.0001, FCU P<0.0001. The PwMS show an opposite pattern of preservation of the absolute value of A<inf>RMS</inf> during prolonged contraction to fatigue, compared with healthy subjects. The results are important for clinical trials using sEMG to assess fatigue in PwMS. Knowledge of the differences in the time domain changes in sEMG signal between healthy subjects and PwMS is crucial for correctly interpreting the results.

Systematic review and meta-analysis of reflexology for people with multiple sclerosis: Systematic Review and Meta-Analysis.

Research on reflexology therapy for multiple sclerosis (MS) is limited, and the evaluation is mixed. Our aim is to confirm the efficacy of reflexology therapy for MS. The preferred reporting items for systematic reviews and meta-analyses guidelines were followed. The search strategy was conducted in PubMed, Embase, the Cochrane Library, and the Science Citation Index. The quality of the included trials was assessed by the Cochrane Handbook. The main results were summarized and analyzed in RevMan 5.4. A total of 11 studies were included in the final analysis. There were significant differences [mean difference (MD) -0.90, 95% confidence interval (CI) -1.37 to -0.43, heterogeneity I2 = 0%] between the Precision Reflexology and Sham Reflexology groups in visual analogue scale pain. There was a significant difference (MD -1.00, 95% CI -1.42 to -0.58, heterogeneity I2 = 93%) between the Precision Reflexology and Sham Reflexology groups on the fatigue severity scale. There was no difference between the Precision Reflexology and Sham Reflexology groups in physical function (MD 6.88, 95% CI -3.36 to 17.13, heterogeneity I2 = 31%), role disorder due to physical problems (MD 10.20, 95% CI -4.91 to 25.30, heterogeneity I2 = 0%), physical pain (MD 7.68, 95% CI -0.09 to 15.45, heterogeneity I2 = 0%), role disorder due to emotional problems (MD 3.41, 95% CI -11.55 to 18.37, heterogeneity I2 = 0%), energy (MD 3.27, 95% CI -4.32 to 10.87, heterogeneity I2 = 0%), emotional well-being (MD 1.79, 95% CI -4.76 to 8.34, heterogeneity I2 = 0%), social function (MD 5.72, 95% CI -3.48 to 14.91, heterogeneity I2 = 0%), or general health (MD 2.63, 95% CI -4.36 to 9.62, heterogeneity I2 = 0%). Reflexology therapy can be used as an effective intervention for the pain and fatigue of MS patients while improving the quality of life.

Assessing the impacts of L-carnitine and modafinil on fatigue in Iraqi multiple sclerosis patients.

Fatigue is a prevalent symptom experienced by individuals diagnosed with multiple sclerosis (MS), which greatly affects their daily activities and causes frustration and depression, thus affecting their lives and society. This can be prevented through the use of medicines such as L-carnitine and modafinil. The study aimed to examine the effect of L-carnitine and modafinil on fatigue and which one is better for MS patients. This was a clinical trial. This clinical trial was conducted in cooperation between Al-Kut University College and an MS consultant at Al-Zahraa Teaching Hospital in addition to the private neurological clinic from October 1, 2022, to March 15, 2023. Forty participants were split into two groups; both of which were almost identical characteristics regarding age, disease duration, and degree of fatigue. Group I (n = 20): relapsing-remitting MS patients with fatigue received modafinil. Group II (n = 20): relapsing-remitting MS patients with fatigue received L-carnitine. Fatigue was evaluated according to the Modified Fatigue Impact Scale (MFIS). The statistical work was done in SPSS (IBM Corp., Chicago, IL, USA, version 24). P values were calculated by the t-test. Significant data have P = 0.05. After 2 months of treatment, the results show a significant decrease in MFIS in both groups with a higher reduction in patients who use L-carnitine. Both modafinil and L-carnitine show a significant influence on fatigue in MS patients, and these effects are more in L-carnitine.

Validity and reliability characteristics of the Silhouettes Fatigue Scale in measuring multiple sclerosis-related fatigue in Turkish-speaking adults.

The purpose of this study is to investigate the reliability and validity as well as the clinical utility of the Silhouettes Fatigue Scale (SFS), a single-item visual scale to assess fatigue, in adult patients with multiple sclerosis (MS). The study included 61 MS patients and 73 matched healthy controls. Demographic data and disease-related variables of all participants were recorded. Then, the SFS, Visual Analogue Scale (VAS)-fatigue, Fatigue Impact Scale (FIS), Fatigue Severity Scale (FSS), and Beck Depression Inventory (BDI) were applied. SFS, VAS-fatigue, and FSS were repeated after one week. Reliability was evaluated with the intra-class correlation coefficient (ICC) and Bland-Altman analysis. Validity was tested by comparison of healthy controls and patients with MS and correlations with other scales. Accuracy and clinical utility were also evaluated. SFS scores were 4.49 ± 3.11 (mean ± SD) in MS patients and 1.40 ± 1.44 in healthy controls (p < .001). The ICC for SFS was 0.946. The mean difference between test-retest measurements of SFS was -0.04651 (-95% CI, -0.4815-0.38848), and there was no systemic bias. SFS scores were not correlated with the expanded disability status scale, whereas they were poorly correlated with BDI. Correlations ranging from poor to good were calculated between the SFS and other fatigue-related scales. The optimum cut-off score of the SFS scale was four, with a sensitivity of 0.72 and a specificity of 0.84. This study demonstrated that the SFS is a reliable, responsive, and valid scale with acceptable sensitivity and specificity to assess and quantify clinically significant fatigue in MS patients. These findings as well as the brief and understandable nature of the SFS were encouraging that this scale has good clinical utility.

The Correlation Between Daytime Sleepiness and Physical Fatigue in Multiple Sclerosis Patients

The Correlation Between Daytime Sleepiness and Physical Fatigue in Multiple Sclerosis Patients

Intensive Circuit Class Therapy in Patients with Relapsing-Remitting Multiple Sclerosis.

ObjectiveLong-term physiotherapy is of considerable benefit to patients with multiple sclerosis (MS) who have motor dysfunction or gait impairment. The aim of this study was to determine the effectiveness of a 12-week intensive circuit class therapy for patients with MS, with a wider focus on fatigue and gait ability.MethodsA total of 46 patients with relapsing-remitting MS were divided randomly into 2 groups: 23 patients (mean Expanded Disability Status Scale (EDSS) 2.33 ± 0.74) participated in an intensive 12-week course of intensive circuit class therapy, and 23 patients (mean EDSS 2.04 ± 0.63) served as a control group. The EDSS, Timed Up and Go (TUG) test and Four-Stage Balance Test (FSBT) made up the physical testing part, supplemented by questionnaires such as the Modified Fatigue Impact Scale (MFIS), 12-Item Multiple Sclerosis Walking Scale (MSWS-12), Beck Depression Inventory (BDI) and 36-Item Short Form Survey (SF-36).ResultsSignificant improvements were found among intensive circuit class therapy-exercising patients in FSBT (p < 0.05), TUG test (p < 0.01), MFIS (p < 0.01), BDI (p < 0.05), MSWS-12 (p < 0.05) and the 3 subscales of SF-36 after 12 weeks of intensive circuit class therapy, while there were no significant changes in the control group.ConclusionIntensive circuit class therapy is an effective therapeutic approach for improving gait and balance problems in patients with MS. It has also proved to alleviate fatigue and symptoms of depression.LAY ABSTRACTGait impairment and fatigue are among the most common manifestations of multiple sclerosis (MS). In this study we aimed to test the effect of 12-week intensive circuit class therapy (ICT) on motor skills and fatigue in MS patients. Forty-six MS patients with mild to moderate disability were randomly assigned to those who underwent the ICT, or to the control group. The ICT patients exercised intensively one day per week on nine different stations with two experienced physiotherapists, the control group patients continued their routine daily exercise. Intensively exercising MS patients then improved significantly in the overall balance, gait and fatigue parameters, while there was no significant improvement in the control group. These findings indicate that ICT is an effective therapy for MS patients with gait, balance or fatigue problems.

ADAPTED MEDITERRANEAN DIET IMPACT ON THE SYMPTOMS OF CHRONIC FATIGUE, SERUM LEVELS OF OMEGA-3 POLYUNSATURATED FATTY ACIDS (PUFAS) AND INTERLEUKIN 17 (IL-17) IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS UNDERGOING DISEASE-MODIFYING THERAPY: A PILOT STUDY

Purpose: This pilot study was designed to investigate the impact of a moderate-calorie Mediterranean diet compared to a regular diet with omega-3 PUFAs (eicosapentaenoic and docosahexaenoic acids) supplementation on fatigue symptoms in patients with relapsing-remitting multiple sclerosis (RRMS) and to assess the optional benefit of the diet on their quality of life. Material/Methods: This 12-month pilot study was conducted in 2021 at the Department of Neurology, Medical University – Pleven, Bulgaria. A total of 60 patients with RRMS aged 18-64 were selected from the database of the Neurology Clinic at the University Hospital "Dr Georgi Stranski" – Pleven. From the selected patients, only 30 were included in the pilot phase and respectively assigned to the nutritional arms. Blood samples were collected twice – at the first and second visit in 3 months, for metabolic and dietary parameters analysis. Symptoms of fatigue were assessed with Fatigue Scale for Motor and Cognitive Functions (FSMC) and Modified Fatigue Impact Scale (MFIS). Results: From the 30 participants included in the study, 17 patients attended the clinic centre for complete follow-up; the remaining 13 were only partially observed. The dynamics of the followed-up parameters showed a statistically significant change in the body mass index (BMI), the fatigue symptoms in the FSMC and MFIS scales, total cholesterol and triglycerides levels, and the serum concentrations of IL17A, EPA and DHA. The metabolic caloric values were also found to be significantly changed. Conclusions: Despite the small study size limitation, this pilot study might be of benefit for further extensive research on the potential favorable impact of diet and lifestyle modifications on the symptoms of fatigue in multiple sclerosis patients.

DEPRESSION AND FATIGUE ARE DUE TO OBSTRUCTIVE SLEEP APNEA IN MULTIPLE SCLEROSIS.

To our knowledge, there is no study investigating whether fatigue and depression as the most commonly reported symptoms in multiple sclerosis (MS) and obstructive sleep apnea (OSA) patients have arisen from primary mechanisms of MS or from secondary associated conditions such as OSA in MS patients. The aim of our survey study was to determine whether depression and fatigue in MS patients were associated with clinical features of OSA or with MS. We conducted a self-administered survey using four validated questionnaires (STOP-BANG, Epworth Sleepiness Scale, Fatigue Severity Scale and The Center for Epidemiologic Studies Depression Scale-Revised) in 28 consecutive outpatients with proven MS. The prevalence of MS patients at an increased risk of OSA was 29% and age was positively correlated with this risk (p=0.019). None of the clinical features of MS patients (subtype, disability status, disease duration, modifying therapy, other medication) was correlated with depression and fatigue. On the contrary, excessive daytime sleepiness as a hallmark of OSA was significantly and positively associated with the level of depressive symptoms (p=0.004) and level of fatigue (p=0.015). Also, depression was significantly and positively correlated with the increased risk of OSA (p=0.015) and age of MS patients (p=0.016). Finally, a significant positive correlation was found between fatigue severity and level of depressive symptoms (p=0.003). OSA is a common disorder in MS patients. The clinical features and risk factors for OSA in MS patients are associated with the two most commonly reported symptoms of depression and fatigue, thus supporting the hypothesis that both symptoms are due to a secondary condition in MS.

Effects of non-invasive brain stimulation in multiple sclerosis: systematic review and meta-analysis.

Objective:The objective of this meta-analysis was to summarize evidence on the therapeutic effects of non-invasive brain stimulation (NIBS) on core symptoms of multiple sclerosis (MS). Specifically, findings from studies deploying transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) protocols were summarized in this review.Methods:We systematically searched articles published in four databases, until 31 May 2021, which compared the effects of active tDCS or rTMS with sham intervention in MS patients. We used a random-effects model for this meta-analysis. Meta-regression and subgroup meta-analysis were used to examine the effects of stimulation dose and different stimulation protocols, respectively.Results:Twenty-five randomized controlled trials (RCTs) were included in this review, consisting of 19 tDCS and 6 rTMS studies. tDCS led to a significant and immediate reduction of fatigue with a large effect size (Hedges’s g = −0.870, 95% confidence intervals (CI) = [−1.225 to −0.458], number needed to treat (NNT) = 2). Particularly, a subgroup analysis showed that applying tDCS over the left DLPFC and bilateral S1 led to fatigue reductions compared to sham stimulation. Furthermore, tDCS had favorable effects on fatigue in MS patients with low physical disability but not those with high physical disability, and additionally improved cognitive function. Finally, whereas rTMS was observed to reduce muscle spasticity, these NIBS protocols showed no further effect on MS-associated pain and mood symptoms.Conclusion:tDCS in MS alleviates fatigue and improves cognitive function whereas rTMS reduces muscle spasticity. More high-quality studies are needed to substantiate the therapeutic effects of different NIBS protocols in MS.