Fatigue Impact Scale Score Research Articles

Distributed causality in resting-state network connectivity in the acute and remitting phases of RRMS

BackgroundAlthough previous studies have shown that intra-network abnormalities in brain functional networks are correlated with clinical/cognitive impairment in multiple sclerosis (MS), there is little information regarding the pattern of causal interactions among cognition-related resting-state networks (RSNs) in different disease stages of relapsing–remitting MS (RRMS) patients. We hypothesized that abnormalities of causal interactions among RSNs occurred in RRMS patients in the acute and remitting phases.MethodsSeventeen patients in the acute phases of RRMS, 24 patients in the remitting phases of RRMS, and 23 appropriately matched healthy controls participated in this study. First, we used group independent component analysis to extract the time courses of the spatially independent components from all the subjects. Then, the Granger causality analysis was used to investigate the causal relationships among RSNs in the spectral domain and to identify correlations with clinical indices.ResultsCompared with the patients in the acute phase of RRMS, patients in the remitting phase of RRMS showed a significantly lower expanded disability status scale, modified fatigue impact scale scores, and significantly higher paced auditory serial addition test (PASAT) scores. Compared with healthy subjects, during the acute phase, RRMS patients had significantly increased driving connectivity from the right executive control network (rECN) to the anterior salience network (aSN), and the causal coefficient was negatively correlated with the PASAT score. During the remitting phase, RRMS patients had significantly increased driving connectivity from the rECN to the aSN and from the rECN to the visuospatial network.ConclusionsTogether with the disease duration (mean disease duration < 5 years) and relatively better clinical scores than those in the acute phase, abnormal connections, such as the information flow from the rECN to the aSN and the rECN to the visuospatial network, might provide adaptive compensation in the remitting phase of RRMS.

Neuropsychiatric changes during the COVID-19 pandemic in multiple sclerosis patients.

This study reported on a variety of psychological reactions related to anxiety, sleep quality, depression, fatigue, and quality of life in individuals with multiple sclerosis (MS), related to the Covid-19 quarantine experience. The aim of this study was to investigate the neuropsychiatric effects of the COVID-19 pandemic in MS patients and to analyze the risk factors contributing to psychological stress. The study was designed as a prospective, cross-sectional survey study. Multiple assessment tools that are used in neurological practice, including Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Fatigue Impact Scale (FIS), Pittsburgh Sleep Quality Index (PSQI), and Multiple Sclerosis Quality of Life-54 (MSQOL-54) were administered prospectively both during the early and the peak stages of COVID-19 outbreak (ESO and PSO, respectively). The survey forms were designed using SurveyMonkey and the participants were participating in the survey via a web link and QR code. Fifty patients were included in the study. BDI scores, PSQI and FSI measurements, cognitive and social subscale scores and total FIS score, MSQOL-54 measurements, physical and mental subscale scores, and total MSQOL-54 score at PSO were significantly different than those at ESO. The body mass index values of the patients increased significantly at PSO compared to those measured at ESO. The results provide a basis for the development of psychological interventions that could minimize the prevalence of sleep disorders and depression and could improve patients' quality of life during the outbreak.

Effects of modified-release fampridine on upper limb impairment in patients with Multiple Sclerosis

BackgroundModified-release 4-aminopyridine (fampridine-MR) is used in the symptomatic treatment of walking disability in patients with multiple sclerosis (MS). Its potential for use in other MS symptoms remains unproven and its mode of action in this context is uncertain. Interest is growing in the use of upper limb outcome measures in clinical trials in patients with Multiple Sclerosis, particularly in advanced or progressive disease. This study tests the following hypotheses: (1) Fampridine-MR improves upper limb function in patients with MS and upper limb impairment. (2) Treatment with fampridine-MR is associated with measurable alterations in objective electrophysiological parameters (evoked potentials and transcranial magnetic stimulation (TMS)) which may predict response to drug treatment. MethodsStudy population: patients with MS of any disease subtype, duration and severity who have symptomatic impairment of one or both upper limbs. A healthy control group was included for validation of clinical and electrophysiological measures. Study design: randomised double blind placebo-controlled trial. Treatment details: participants allocated to either fampridine-MR 10 mg bd or placebo of identical appearance for 8 weeks. Primary outcome: performance on 9-hole peg test (9HPT) after 4 weeks. Secondary outcomes: persistence of effect on 9HPT; grip strength; visual acuity and contrast sensitivity; modified fatigue impact scale score; sensory discrimination capacity; visual, somatosensory and motor evoked potentials; resting motor threshold; paired-pulse TMS; peripheral nerve conduction studies. Results40 patients with MS (60% female, median age 52, median disease duration 13.5 years, median EDSS 6.0) were enrolled. Treatment with fampridine-MR was not associated with any change in upper limb function as measured by the clinical primary or secondary outcomes. Treatment with fampridine-MR was also not associated with any difference in electrophysiological measures of upper limb function. This held true after adjustment for hand dominance, disease duration and severity. Four patients withdrew from the trial because of lack of efficacy or side-effects; all were in the placebo arm. Three patients were admitted to hospital during the study period; one with MS exacerbation (placebo group), one with syncope (drug group) and one with UTI (drug group); otherwise there were no serious adverse events. ConclusionTreatment with fampridine-MR was well-tolerated but did not produce clinical benefit in terms of upper limb function, vision or fatigue, nor was there any measurable effect on objective electrophysiological parameters.

Health related quality of life in Friedreich Ataxia in a large heterogeneous cohort

IntroductionThis study assessed the Health Related Quality of Life (HRQOL) of individuals with Friedreich Ataxia (FRDA) through responses to HRQOL questionnaires. MethodsThe SF-36, a generic HRQOL instrument, and symptom specific scales examining vision, fatigue, pain and bladder function were administered to individuals with FRDA and analyzed by comparison with disease features. Multiple linear regression models were used to study independent effects of genetic severity and age. Assessments were performed at baseline then intermittently after that. ResultsSubjects were on average young adults. For the SF36, the subscale with the lowest HRQOL score was the physical function scale, while the emotional well-being score was the highest. The physical function scale correlated with age of onset, duration, and subject age. In assessment of symptom specific scales, bladder control scores (BLCS) correlated with duration and age, while impact of visual impairment scores (IVIS) correlated with duration. In linear regression models, the BLCS, Pain Effect Score, and IVIS scores were predicted by age and GAA length; modified fatigue impact scale scores were predicted only by GAA length. Physical function and role limitation scores declined over time. No change was seen over time in other SF-36 subscores. Symptom specific scales also worsened over time, most notably the IVIS and BLCS. ConclusionThe SF-36 and symptom specific scales capture dysfunction in FRDA in a manner that reflects disease status. HRQOL dysfunction was greatest on physically related scales; such scales correlated with disease duration, indicating that they worsen with progressing disease.

The effect of fecal microbiota transplantation on IBS related quality of life and fatigue in moderate to severe non-constipated irritable bowel: Secondary endpoints of a double blind, randomized, placebo-controlled trial.

BackgroundSeverity in irritable bowel syndrome (IBS) is associated to impaired quality of life and fatigue. Fecal microbiota transplantation (FMT) induces significant relief in gastro-intestinal related complaints. The objective was to evaluate the effect of FMT on the secondary endpoints: IBS-related quality of life and fatigue in patients with non-constipated IBS.MethodIn this double-blind randomized placebo-controlled, parallel-group, single-center study, we enrolled patients with non-constipated IBS, defined by the ROME 3 criteria. We randomly assigned participants (2:1) in blocks of six to active or placebo FMT. Responder in fatigue and quality of life were defined as a decrease of 20 points in total Fatigue Impact Scale score, and improvement of 14 points in the IBS-quality of life questionnaire, respectively. In a modified-intention-to-treat population, we excluded participants who did not undergo treatment or who were diagnosed with any other disease by pinch biopsies during the treatment procedure.FindingsBetween Jan1, and Oct 30, 2015, we recruited 90 participants and randomly assigned them to active treatment (n = 60) or placebo (n = 30). Three participants did not undergo FMT and four were excluded after diagnosis of microscopic colitis, leaving 83 for final modified intention-to-treat analysis (55 in the active treatment group and 28 in the placebo group). Significant improvement in QoL (Odds ratio (OR) 3,801; confidence interval (CI) = 1,309–11,042 p = 0.011) and fatigue (OR = 4,398; CI = 1,175–16,468 and p = 0,020) was found at six months. Absence of other self reported functional disorders and presence of depression at baseline is suggested to predict a lasting effect of FMT in QoL and fatigue, respectively.InterpretationFMT induced significant relief in quality of life and fatigue. Results suggest a lasting effect of FMT in subgroups that should be further investigated in future studies. Funding Helse Nord, Norway and the Norwegian Centre of Rural Medicine, University of Tromsø, Norway.

Greater Lower Limb Fatigability in People with Prediabetes than Controls.

The study purpose was to compare perceived fatigability and performance fatigability after high-velocity contractions with knee extensor muscles between people with prediabetes, people with type 2 diabetes (T2D), and controls without diabetes matched for age, body mass index, and physical activity. Twenty people with prediabetes (11 men, 9 women: 63.1 ± 6.0 yr, 26.9 ± 4.2 kg·m, 8030 ± 3110 steps per day), 39 with T2D (23 men, 16 women: 61.2 ± 8.5 yr, 29.4 ± 6.4 kg·m, 8440 ± 4220 steps per day), and 27 controls (13 men, 14 women: 58.1 ± 9.4 yr, 27.3 ± 4.3 kg·m, 8400 ± 3000 steps per day) completed the Fatigue Impact Scale as a measure of perceived fatigability and a fatigue protocol including 120 maximal-effort, high-velocity concentric contractions (MVCC; 1 contraction/3 s) with the knee extensors using a submaximal load (30% maximum) to quantify performance fatigability. Electrical stimulation was used to assess voluntary activation and contractile function of the knee extensor muscles before and after the fatigue protocol. Fatigue Impact Scale scores were not different between people with prediabetes, people with T2D, and controls (12.5 ± 15.1, 18.3 ± 22.7, and 12.6 ± 18.6, respectively; P = 0.517). However, people with prediabetes had greater reductions in MVCC power during the fatigue protocol than did controls (31.8% ± 22.6% vs 22.1% ± 21.1%, P < 0.001), and both groups had lesser reductions than the T2D group (44.8% ± 21.9%, P < 0.001). Similarly, the prediabetes group had larger reductions in electrically evoked twitch amplitude than the control group (32.5% ± 24.9% vs 21.3% ± 33.0%, P < 0.001), but lesser reductions than those with T2D (44.0% ± 23.4%, P < 0.001). For all three groups, a greater decline in MVCC power was associated with larger reductions of twitch amplitude (r = 0.350, P < 0.001). People with prediabetes have greater performance fatigability of the knee extensors due to contractile mechanisms compared with controls, although less performance fatigability than that of people with T2D.

Fatigue scores correlate with other self-assessment data, but not with clinical and biomarker parameters, in CIS and RRMS

BackgroundFatigue is common in multiple sclerosis and is associated with reduced quality of life. This study aimed to assess the correlation between fatigue scores and data from other self-assessment questionnaires, neuropsychological tests and neuroimaging, as well as data on neuroimmunological markers in cerebrospinal fluid (CSF) and serum/plasma, in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). MethodsModified fatigue impact scale (MFIS) scores were determined in 38 patients with newly diagnosed CIS or RRMS at baseline and after one year in a prospective longitudinal cohort study. Non-parametric correlation analyses were used to assess associations between MFIS scores and other self-assessment questionnaire data (Hospital Anxiety and Depression scale (HAD), Multiple Sclerosis Impact Scale 29 (MSIS-29) and Short Form 36 (SF-36)), as well as with neuropsychological test performances (e.g. Auditory Consonant Trigram Test (ACTT)), clinical parameters (e.g. disease duration and expanded disability status scale (EDSS)), magnetic resonance imaging (MRI) data (number of T2 lesions in brain MRI and total brain volume) and several neurodegenerative/neuroinflammatory markers in CSF and serum/plasma (IL-1β, IL-6, CXCL1, CXCL10, CXCL13, CCL-22 in plasma; neurofilament light chain (NFL) in serum; IL-6, CXCL1, CXCL10, CXCL13, CCL22, NFL and chitinase-3-like-1 (CHI3L1) in CSF. CSF and serum/plasma from 21 age- and sex-matched healthy controls were available for comparison. ResultsAt both baseline and one-year follow-up, fatigue scores correlated significantly with HAD, MSIS-29 and SF-36 scores and ACTT performance (Spearman´s rho 0.45–0.78, all p ≤ 0.01) but not with the other neuropsychological test results, disease duration, EDSS ratings, number of T2 lesions, total brain volume or neurodegenerative/neuroinflammatory markers, including neurofilament light chain levels in CSF and serum. In group comparisons, MFIS scores were similar in patients fulfilling no evidence of disease activity-3 (NEDA-3) (n = 18) and patients not fulfilling NEDA-3 (n = 20) during one year of follow-up (p > 0.01). ConclusionsIn this cohort of patients with newly diagnosed CIS and RRMS, fatigue scores were associated with mood, disease impact on daily life and quality of life as well as with alterations of attentive functions. Study results indicate that subjective fatigue scores are not well reflected by some commonly used and objectively measurable disease parameters like EDSS, T2 lesions and NFL levels.

Bright light therapy with a head-mounted device for anxiety, depression, sleepiness and fatigue in patients with Parkinson's disease.

The beneficial effects of bright light therapy (BLT) on the disabling non-motor symptoms of Parkinson's disease (PD) remain uncertain. The objective of this study was to investigate if daily BLT, with a head-mounted device (Luminette®), has a beneficial effect on depression, anxiety, daytime sleepiness and fatigue in patients with PD. In this double-blind, placebo-controlled study, 16 patients with PD were randomized to receive either 1month of BLT or 1month of placebo therapy, separated by a 2-week washout period, in a crossover fashion. Patients completed questionnaires for the Hospital Anxiety and Depression Scale (HADS), the Epworth Sleepiness Scale (ESS) and the Fatigue Impact Scale (FIS) before and after each treatment period. The primary outcome measures were changed from baseline in scores between treatment groups. No significant changes were observed in the HADS anxiety scores and FIS scores after BLT and after placebo. The ESS scores decreased non-significantly only after BLT. A post hoc analysis of patients who had baseline ESS scores > 11 revealed a significantly greater decrease in ESS scores after BLT than after placebo. Future studies investigating the effect of BLT on sleepiness could focus specifically on patients with high ESS scores.

Muscle performance and fatigue in compensated chronic liver disease

Background: A common and debilitating symptom in patients with chronic liver disease is fatigue (CLD). Muscle dysfunction has been suggested to be a key mechanism of fatigue in CLD.Objective: We aimed to evaluate fatigue and the potential association with muscle performance and physical activity in outpatients with CLD.Methods: Two-hundred seventy outpatients with CLD were included, (52 ± 15 years, mean ± SD; 151 females) with autoimmune hepatitis (n = 49), primary biliary cholangitis (n = 45), primary sclerosing cholangitis (n = 46), chronic hepatitis B (n = 57) or C (n = 73). Patients with a Child-Pugh >6 were excluded. The questionnaire Fatigue Impact Scale (FIS) was used to evaluate fatigue, and physical activity was evaluated through a self-reported level of physical activity. Muscle function was assessed with four muscle tests, walking speed, handgrip strength, standing heel-rise test (SHT) and ‘Timed Up and Go’ test (TUG).Results: The median total FIS score was 30 (40% had FIS > 40, considered high-fatigue). Diminished muscle performance was observed in the SHT (% of predicted value: 53 ± 26%) and with maximum grip strength (85 ± 20%). The FIS score was significantly different between groups of CLDs (p = .004). In multivariate analysis the TUG (p = .001), SHT (p = .005), antidepressants (p < .001), and level of physical activity (p = .001) were associated with fatigue (R2 = 29%). Subjects with higher levels of physical activity had lower FIS (p < .001).Conclusions: In patients with CLD, fatigue was associated with low muscle performance and reduced level of physical activity, which could be a potential therapeutic target.

Impact of autoimmune comorbidity on fatigue, sleepiness and mood in myasthenia gravis.

Disease burden in myasthenia gravis (MG) and in other autoimmune disorders is often determined by common accompanying symptoms such as fatigue, sleepiness and mood disturbances. Many MG patients have a second autoimmune disease, but it is unclear whether autoimmune comorbidities add to the severity of fatigue, sleepiness and mood disturbances. We ascertained the presence of autoimmune comorbidities in 69 well-characterized MG patients. To assess fatigue, sleepiness and mood disturbances, we applied the Fatigue Severity Scale (FSS), the Fatigue Impact Scale (FIS), the Epworth Sleepiness Scale (ESS), as well as the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) to all patients. Thirteen MG patients had concomitant autoimmune thyroid disease (AITD), including 1 patient with rheumatoid arthritis as third autoimmune disease. Fatigue (68.1%), excessive daytime sleepiness (14.5%), moderate-severe depression (20.3%) and anxiety (26.1%) were common, but MG patients with and without autoimmune comorbidities had similar FSS, FIS, ESS, BDI and STAI scores. The presence of autoimmune comorbidities was not associated with altered clinical and immunological MG characteristics, but MG patients with autoimmune comorbidities have more often been treated with corticosteroids than patients without autoimmune comorbidities (92.3% vs. 60.7%; p = 0.03). While many MG patients were affected by fatigue, sleepiness, depression and anxiety, the present study does not suggest that coexisting autoimmune diseases substantially contribute to the magnitude of these cumbersome comorbid symptoms. However, the higher frequency of steroid treatment may have counterbalanced the effects of the autoimmune comorbidity.

Autologous hematopoietic stem cell transplantation improves fatigue in multiple sclerosis

Background: Fatigue is a common problem in multiple sclerosis (MS) affecting as many as 90% of patients. The Fatigue Impact Scale (FIS) is a validated measure of fatigue in MS patients. The cause of fatigue in MS is likely multifactorial, with some evidence that ongoing central nervous system (CNS) inflammation is a contributing factor. Immunoablation and autologous hematopoietic stem cell transplantation (aHSCT) have been shown to halt ongoing CNS inflammation. Objective: To investigate whether halting all ongoing inflammation with aHSCT impacts FIS scores in patients with severe MS. Methods: In the Canadian aHSCT study (ClinicalTrials.gov, NCT01099930), 23 patients underwent aHSCT and had FIS prospectively collected every 6 months for 36 months of follow-up. Change in FIS was analysed by repeated-measures analysis of variance (RMANOVA) with multiple linear regression to determine independent predictors. Results: The median FIS score decreased 36%, from 36 to 23 (p = 0.001), and four patients had 100% reduction. Improvement in FIS correlated with lower age and Expanded Disability Status Scale at baseline, as well as increased independence as evidenced by a return to gainful employment and even driving. Conclusion: Patients had significantly less fatigue on average after aHSCT. This may serve to better understand the contribution of ongoing CNS inflammation to fatigue peculiar to MS.

Altered levels of cytokines in patients with irritable bowel syndrome are not correlated with fatigue

IntroductionA considerable number of patients with gastrointestinal complaints attributable to irritable bowel syndrome (IBS) have shown evidence of immune activation. Fatigue is also frequently reported by IBS patients and the condition is considered as a common comorbidity of IBS. Therefore, it is interesting to see whether these two conditions share the same pathophysiological mechanism.AimsTo investigate the potential role of cytokine profiles in patients with IBS and the relationship between cytokine profiles and fatigue.Materials and methodsThirty-eight patients with IBS (32 females, 6 males, age range 18–70 years) and 22 healthy individuals (control group) (17 females, 5 males, age range 24–42 years) were included. IBS was diagnosed according to Rome III criteria, and severity of IBS symptoms and fatigue were evaluated using the Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS) and Fatigue Impact Scale (FIS), respectively. FIS scores of 25 or higher were defined as fatigue. Blood samples were also taken, and the Luminex® platform (Cytokine Human Ultrasensitive Magnetic 10-Plex Panel) was used for quantifying human cytokines’ profile (granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α) in serum.ResultsThe serum levels of IL-5, IL-6, IL-10, and TNF-α were significantly higher in patients with IBS compared to healthy controls (p=0.003, p=0.011, p=0.007, and p=0.02, respectively). Conversely, serum levels of cytokine IL-1β were significantly higher in the control group (p=0.03). The findings were consistent when comparing nonatopic patients with controls. Fatigue was demonstrated in 84.2% of the IBS patients. Scores of IBS-SSS were not significantly correlated with FIS scores (r=0.2, p=0.19), and they were not significantly different in patients with FIS scores >25 compared to patients with FIS scores <25 (p=0.11). None of the cytokine levels were significantly different in IBS patients with FIS scores >25 compared to IBS patients with FIS scores <25. Moreover, the cytokine levels in participants did not vary significantly between patients with diarrhea, constipation, or mixed bowel habits in multiple comparisons of patients.ConclusionsThe cytokines IL-5, IL-6, IL-10, and TNF-α may contribute to the development of IBS. However, serum levels of cytokines were not significantly different in IBS patients with fatigue compared with IBS patients without fatigue. Thus, the significance of cytokine levels may be less important than anticipated in search of common underlying mechanisms, and other factors should be explored in future studies.

Short-Time Strategy for Fibromyalgia Treatment Based on Olive Nutraceutical and Inflammatory Gut-Brain Axis Control Diet (IGUBAC) Diet®

Fibromyalgia syndrome is defined as chronic widespread pain and tenderness. It is associated with fatigue, sleep disorder, functional somatic syndromes, mental and physical disorders, as well as disability and diminished quality of life. We aimed to analyse the effects of an olive tree-based supplement and a gluten-free, FODMAP and low histamine diet (IGUBAC-Diet®), with antioxidant and anti-inflammatory characteristics, in women with fibromyalgia. A randomized, controlled, clinical trial, with 31 women (55.87±11.86 years) diagnosed with fibromyalgia was conducted in 2016. Chronic Pain Grade Scale, Pain Catastrophizing Scale, Fatigue Severity and Impact Scale were used. Anthropometric parameters and symptoms progression were measured before and after two months of treatment with olive tree-based supplement and IGUBAC-Diet®. Other secondary outcome measures include blood biochemical analysis. Patients improved Chronic Pain Grade Scale scores after intervention and all groups experienced a reduction in the perception of pain catastrophizing. Positive changes were found all groups for Fatigue Severity Scale, but not for Fatigue Impact Scale scores. Significant variations (p &lt; 0.05) were observed in symptoms frequency. The olive tree-based food supplement and the gluten-free, FODMAP and low histamine diet had beneficial effects on the intensity of fibromyalgia symptoms. This short-time strategy may be used to improve fibromyalgia patient’s well-being.

Reduction of body iron in HFE-related haemochromatosis and moderate iron overload (Mi-Iron): a multicentre, participant-blinded, randomised controlled trial

The iron overload disorder hereditary haemochromatosis is most commonly caused by HFE p.Cys282Tyr homozygosity. In the absence of results from any randomised trials, current evidence is insufficient to determine whether individuals with hereditary haemochromatosis and moderately elevated serum ferritin, should undergo iron reduction treatment. This trial aimed to establish whether serum ferritin normalisation in this population improved symptoms and surrogate biomarkers. This study was a multicentre, participant-blinded, randomised controlled trial done at three centres in Australia. We enrolled people who were homozygous for HFE p.Cys282Tyr, aged between 18 and 70 years, with moderately elevated serum ferritin, defined as 300-1000 μg/L, and raised transferrin saturation. Participants were randomly assigned, via a computer-generated random number, to undergo either iron reduction by erythrocytapheresis (treatment group) or sham treatment by plasmapheresis (control group). Randomisation was stratified by baseline serum ferritin (<600 μg/L or ≥600 μg/L), sex, and study site. Erythrocytapheresis and plasmapheresis were done every 3 weeks, the number of procedures and volume of red cells or plasma removed determined on the basis of each patient's haemoglobin, haematocrit, and serum ferritin concentration, as well their height and weight. In the erythrocytapheresis group, the target was to reduce serum ferritin to less than 300 μg/L. The number of procedures for the control group was based on the initial serum ferritin and prediction of decrease in serum ferritin of approximately 120 μg/L per treatment. The primary outcome was patient-reported Modified Fatigue Impact Scale (MFIS) score, measured at baseline and before unblinding. Analyses were by intention to treat, including the safety analysis. The trial is registered with ClinicalTrials.gov, number NCT01631708, and has been completed. Between Aug 15, 2012, and June 9, 2016, 104 participants were randomly assigned to the treatment (n=54) and control (n=50) groups, of whom 94 completed the study (50 in the treatment group and 44 in the control group). Improvement in MFIS score was greater in the treatment group than in the control group (mean difference -6·3, 95% CI -11·1 to -1·4, p=0·013). There was a significant difference in the cognitive subcomponent (-3·6, -5·9 to -1·3, p=0·0030), but not in the physical (-1·90 -4·5 to 0·63, p=0·14) and psychosocial (-0·54, -1·2 to 0·11, p=0·10) subcomponents. No serious adverse events occurred in either group. One participant in the control group had a vasovagal event and 17 participants (14 in the treatment group and three in the control group) had transient symptoms assessed as related to hypovolaemia. Mild citrate reactions were more common in the treatment group (32 events [25%] in 129 procedures) compared with the control group (one event [1%] in 93 procedures). To our knowledge, this study is the first to objectively assess the consequences of iron removal in individuals with hereditary haemochromatosis and moderately elevated serum ferritin. Our results suggest that serum ferritin normalisation by iron depletion could be of benefit for all individuals with hereditary haemochromatosis and elevated serum ferritin levels. National Health and Medical Research Council (Australia).

Fatigue in familial Mediterranean fever and its relations with other clinical parameters.

Fatigue is a common problem in patients with rheumatic disease. It may cause disability and poor quality of life. The aim of this study is to investigate fatigue in FMF patients as a disabling symptom and its associations with clinical and demographic variables. FMF patients were recruited into the study according to FMF Tel Hashomer criteria. Control group is composed of healthy individuals. Demographic and clinical features of the patients including PRAS scores were noted. Visual analogue score of pain (VAS-pain) and VAS-fatigue were used as clinical parameters. Pittsburgh Sleep Quality Index (PSQI), Multidimensional Assessment of Fatigue (MAF), Nottingham Health Profile (NHP), Fatigue Severity Scale (FSS), Fatigue Impact Scale (FIS) and Hospital Anxiety and Depression Scale (HADS) were filled out by both control and study group. Sixty-one FMF patients and 61 age and gender (44 female, 17 male in each group)-matched controls were enrolled into the study. Mean age of FMF and control group were 35.5 ± 11.8 and 35.8 ± 11.7years, respectively. The mean disease duration was 82.5 ± 81.7months. Difference between mean of VAS-pain, VAS-fatigue, PSQI total score, MAF, all subsets of NHP, FSS, FIS, and HADS scores of FMF patients was significantly higher than of control group (p = 0.0001). This study has shown that fatigue in FMF is associated with a number of psychological, sleep, quality of life and disease-related factors. FMF group had increased pain, fatigue, sleep disturbance and decreased quality of life compared to control group. FMF patients with fatigue may benefit from pharmacological and psychological interventions which target these factors.

Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial

BackgroundFatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. ObjectiveTo describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. Design/methodsThe study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of <7.0 are eligible to participate. Participants will be randomized to one of four predefined sequences of medication administration. Each sequence comprises four 6-week periods of treatment with one of the 3 study drugs or placebo, and three 2-week washout periods between medication periods. Results136 participants will be randomized over two years in two academic centers in the United States starting in the Summer 2017. Complete enrollment is expected by early 2019. The primary outcome of the study is the modified fatigue impact scale (MFIS) score while participants receive the maximally tolerated dose of each study medication (or placebo). Safety and tolerability of the medications and heterogeneity of treatment effect will also be assessed. ConclusionsResults of the proposed study will provide evidence-based and personalized treatment options for patients affected by MS-related fatigue.Clinicaltrials.gov registration number: NCT03185065

Meta-analysis of the efficacy of modafinil versus placebo in the treatment of multiple sclerosis fatigue

BackgroundClinical trials examining the therapeutic benefit of modafinil in MS fatigue provide conflicting data. The goal of this study was to systematically evaluate the efficacy of modafinil using a meta-analytic method. MethodsA systematic literature search was performed on published peer reviewed articles from 2000 to 2017 using the Cochrane Library, PubMed, and EMBASE. This review included double blind, randomized controlled trials, which evaluated modafinil in MS fatigue. The primary outcome measure was the estimated treatment difference in the Modified Fatigue Impact Scale score (MFIS) and Fatigue Severity Scale score (FSS). A secondary outcome measure was the estimated treatment difference in the Symbol Digit Modalities Test (SDMT). ResultsA total of 303 patients from five randomized controlled trials were included in the analyses. Modafinil was superior to placebo with an estimated treatment difference according to the MFIS (MD = −5.27, 95% CI: −8.51 to −2.03, P = 0.001). For the FSS, there was no significant difference between the two groups (MD = 2.50, 95%CI: −0.70 to 5.70, P = 0.13). For the secondary outcome, there was no significant difference between groups studied using the SDMT (MD = 0.23, 95% CI: −0.25 to 0.71, P = 0.35). ConclusionsOur meta-analysis showed that modafinil was an effective pharmacologic therapy for MS fatigue. Additional research is required to determine optimal dosing and treatment schedules.

Integrated Imaginative Distention Therapy to Cope with Fatigue. DIMMI SI Study: The First Randomized Controlled Trial in Multiple Sclerosis.

IntroductionFatigue is a frequent, disabling, and difficult to treat symptom in neurological disease and in other stress-related conditions; Integrated Imaginative Distention (IID) is a therapy combining muscular and imaginative relaxation, feasible also in disabled subjects; the DIMMI SI trial was planned to evaluate IID efficacy on fatigue.MethodsThe design was a parallel, randomised 1:1 (intervention:waiting list), controlled, open-label trial. Participants were persons with multiple sclerosis (pwMS), persons with insomnia (pwINS), and health professionals (HP) as conditions related to fatigue and stress. The primary outcome was the post-intervention change of fatigue; secondary outcomes were changes in insomnia, stress, and quality of life (QoL). Eight IID weekly training group sessions were delivered by a skilled psychotherapist. The study lasted 12 months.ResultsOne hundred and forty-four subjects were enrolled, 48 for each condition. The mean change in Modified Fatigue Impact Scale (MFIS) score among exposed was 7.7 [95% CI 1.1, 14.4] (P = 0.023) in pwMS; 7.1 [1.9, 12.3] (P = 0.007) among pwINS, and 11.3 [4.3, 18.2] among HP (P = 0.002). At the last follow-up, the benefit was confirmed on physical fatigue for pwMS, on total fatigue for pwINS and HP.ConclusionsDIMMI SI is the first randomized controlled trial evaluating the efficacy of IID on fatigue. IID resulted a complementary intervention to reduce fatigue in stress-related conditions, in both health and disease status. NCT02290990ClinicalTrials.gov.Electronic supplementary materialThe online version of this article (doi:10.1007/s40120-017-0081-9) contains supplementary material, which is available to authorized users.

Personalized, bilateral whole-body somatosensory cortex stimulation to relieve fatigue in multiple sclerosis

Background: The patients suffering from multiple sclerosis (MS) often consider fatigue the most debilitating symptom they experience, but conventional medicine currently offers poorly efficacious therapies. Objective: We executed a replication study of an innovative approach for relieving MS fatigue. Methods: According to the sample size estimate, we recruited 10 fatigued MS patients who received 5-day transcranial direct current stimulation (tDCS) in a randomized, double-blind, Sham-controlled, crossover study, with modified Fatigue Impact Scale (mFIS) score reduction at the end of the treatment as primary outcome. A personalized anodal electrode, shaped on the magnetic resonance imaging (MRI)-derived individual cortical folding, targeted the bilateral whole-body primary somatosensory cortex (S1) with an occipital cathode. Results: The amelioration of fatigue symptoms after Real stimulation (40% of baseline) was significantly larger than after Sham stimulation (14%, p = 0.012). Anodal whole body S1 induced a significant fatigue reduction in mildly disabled MS patients when the fatigue-related symptoms severely hampered their quality of life. Conclusion: This second result in an independent group of patients supports the idea that neuromodulation interventions that properly select a personalized target might be a suitable non-pharmacological treatment for MS fatigue.

Sulbutiamine shows promising results in reducing fatigue in patients with multiple sclerosis

BackgroundFatigue is the most frequent and often debilitating symptom for patients with multiple sclerosis (MS). There are no available effective therapies for fatigue associated with MS, and it is unclear whether a successful therapy of MS leads to clinical improvement. Sulbutiamine is a lipophilic compound that crosses the blood–brain barrier more readily than thiamine and increases the levels of thiamine and thiamine phosphate esters in the brain. Whereas several clinical trials have demonstrated the beneficial effects of sulbutiamine in patients with asthenia, there have been no reports on the effects of sulbutiamine on fatigue in patients with MS. ObjectivesOur study was designed to evaluate the short-term effects of sulbutiamine on fatigue in patients with MS. MethodsPatients were included if fatigue was one of their three predominant symptoms. They were required to have a total score on the Fatigue Impact Scale (FIS) of >20, and on the Beck Depression Inventory of <17, and no relapse in the last 3 months prior to onset of the study. Patients were advised to receive 400mg orally of sulbutiamine once daily for two months. The outcome of the study was in the changes of FIS. ResultsTwenty-six patients with MS (18 females and 8 males) were selected. The patients were 18–57 years of age (mean:37,2). The average score of Expanded Disability Status Scale (EDSS) of the patients was 2,71. A significant number of the subjects who were on some kind of disease modifying treatment (DMT) demonstrated obvious improvement in their total FIS scores, whereas none of the subjects who were not on any DMT improved (13/23 vs. 0/5). The average fatigue score was 77 (SD:30,5) at the baseline and 60,5 (SD:29,7) on Day 60, respectively. Sulbutiamine intake resulted in a significant reduction on the total score of FIS and on all three subscales assessing physical, cognitive, and psychosocial functioning (all p-values < 0,01). There were no serious adverse events. ConclusionsSulbutiamin appears to be effective in treating fatigue in MS; particularly in patients who were on some DMT, but not on those who were not. It is well-tolerated by all. This observation may encourage further evaluations of the efficacy of sulbutiamine on fatigue in MS.