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Endre Szvetnik

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Research suggests a brain stimulation technique used for depression significantly reduces MS fatigue

In 10 seconds? Researchers have reduced fatigue in MS patients with a magnetic treatment for depression that sends electric currents deep into the brain to stimulate neuron activity.

What’s the discovery? A brain stimulation technique for depression patients has been applied to MS sufferers to reduce severe fatigue. Scientists know that depression often accompanies MS, but haven’t pinpointed any physiological causes yet.

How does this technique work? Deep transcranial magnetic brain stimulation (dTMS) uses a bucket-like device placed over the head called a H-coil. Unlike older technologies that only reach the surface of the brain, the H-coil creates a precise magnetic field to stimulate neurons up to 5.5 cm inside the brain.

Sounds painful! Around a third of patients experience some discomfort on the scalp and face during the treatment, but this can be minimised immediately by adjusting the settings and placement of the magnetic device. When tested on MS patients, dTMS was reported to reduce tiredness by around 14% on the Fatigue Severity Scale.

What else is being tried to reduce fatigue? Cognitive Behavioural Therapy (CBT) seems to be the most effective in reducing severe fatigue, but only in the short term. Relaxation therapy, aerobic exercise and energy conservation programs have also been tried, but with less success.

So is there a strong link between fatigue and depression in MS? A Spanish study found that depression coupled with physical pain makes MS patients fatigued. Other studies also suggest that the more depressed a person feels, the more likely they will be fatigued.

Is there anything that MS patients use at home? Some MS sufferers use self-management tools, like MS INFoRm, which has been shown to boost the quality of life for some. While there is still no fail-proof treatment yet, fighting fatigue is a good strategy to improve patients’ day-to-day lives.

How is Cognitive Behavioural Therapy (CBT) applied to MS? CBT is often used to treat psychological disorders, like anxiety, depression, bipolar disorder and phobias.It aims to improve people’s moods, sense of self and even physical states through recognising and replacing negative thoughts with more positive ones.

In the context of MS, patients are encouraged to focus less on fatigue, change their beliefs about the disease, and regulate sleep and social activity to help with their pain.


Safety and preliminary efficacy of deep transcranial magnetic stimulation in MS-related fatigue.

Abstract: To conduct a randomized, sham-controlled phase I/IIa study to evaluate the safety and preliminary efficacy of deep brain H-coil repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) and the primary motor cortex (MC) in patients with MS with fatigue or depression (NCT01106365).Thirty-three patients with MS were recruited to undergo 18 consecutive rTMS sessions over 6 weeks, followed by follow-up (FU) assessments over 6 weeks. Patients were randomized to receive high-frequency stimulation of the left PFC, MC, or sham stimulation. Primary end point was the safety of stimulation. Preliminary efficacy was assessed based on changes in Fatigue Severity Scale (FSS) and Beck Depression Inventory scores. Randomization allowed only analysis of preliminary efficacy for fatigue.No serious adverse events were observed. Five patients terminated participation during treatment due to mild side effects. Treatment resulted in a significant median FSS decrease of 1.0 point (95%CI [0.45,1.65]), which was sustained during FU.H-coil rTMS is safe and well tolerated in patients with MS. The observed sustained reduction in fatigue after subthreshold MC stimulation warrants further investigation.NCT01106365.This study provides Class III evidence that rTMS of the prefrontal or primary MC is not associated with serious adverse effects, although this study is underpowered to state this with any precision.

Pub.: 21 Dec '17, Pinned: 12 Feb '18

Fatigue in multiple sclerosis persists over time: a longitudinal study.

Abstract: Fatigue is one of the most frequent symptoms in multiple sclerosis (MS) but there is a lack of knowledge about its behaviour over time. The aim of our study was to investigate changes in fatigue in a large cohort of MS patients and to determine the relationship between changes in disability and depression with changes in fatigue severity.We studied fatigue in 227 MS consecutive patients and again after one year. During the clinical interview, we recorded the patient's degree of disability using the Expanded Disability Status Scale and relapses; fatigue was measured by means of the Modified Fatigue Impact Scale (MFIS) and Fatigue Severity Scale (FSS) and depression was measured by the Beck Depression Inventory (BDI).After a mean follow-up of 18 months, 86.8% of patients who were fatigued at study onset remained in a fatigued status, whereas 25% of those without fatigue at onset had become fatigued at the end of follow-up. We observed that only variations on BDI scores positively correlate with variations on fatigue scales, mainly with MFIS (r = 0.49, p < 0.0001). An increase of BDI score was the factor that best predicted the increase of fatigue over time. No differences in the increase of fatigue were found between patients with and without progression of disability during the follow-up period, or between patients with or without relapses.Fatigue in MS persists over time. Changes in mood status but not in disability are related to changes in fatigue in MS patients.

Pub.: 15 Jun '06, Pinned: 14 Feb '18

A multicenter randomized controlled trial of two group education programs for fatigue in multiple sclerosis: Short- and medium-term benefits.

Abstract: Background Fatigue occurs in 75%-95% of people with multiple sclerosis (MS) and is frequently reported as the most disabling symptom. A multicomponent group program of six weekly 2-hour sessions, Fatigue: Take Control (FTC), was developed from an international MS fatigue management guideline. Objective To determine whether FTC is associated with greater improvements in fatigue than MS: Take Control (MSTC), a similarly structured general MS education program. Methods This four-site, parallel, single-blind, randomized controlled trial compared FTC and MSTC in 204 ambulatory participants with MS. The primary outcome, the Modified Fatigue Impact Scale (MFIS), and secondary outcomes of self-efficacy, physical activity, sleep, and medications were assessed at baseline, program completion, and 3 and 6 months later. Results Mean MFIS scores improved in both groups between baseline and program completion (FTC -4.4, p < 0.001; MSTC -3.8, p < 0.001), between baseline and 3 months after program completion (FTC -3.2, p = 0.01; MSTC -3.3, p = 0.01), and between baseline and 6 months after program completion (FTC -5.2, p < 0.001; MSTC -4.8, p < 0.001). These improvements were not statistically different between groups ( p = 0.64, 0.92, and 0.82, respectively). Conclusion Participation in FTC modestly improved self-reported fatigue for up to 6 months. This improvement did not differ significantly from that occurring with the control program.

Pub.: 12 Dec '17, Pinned: 14 Feb '18

Is the association between health-related quality of life and fatigue mediated by depression in patients with multiple sclerosis? A Spanish cross-sectional study.

Abstract: To determine the mediating effects of depression on health-related quality of life and fatigue in individuals with multiple sclerosis (MS).A cross-sectional study.Tertiary urban hospital.One hundred and eight patients (54% women) with MS participated in this study.Demographic and clinical data (weight, height, medication and neurological impairment), fatigue (Fatigue Impact Scale), depression (Beck Depression Inventory-II) and health-related quality of life (Short-Form Health Survey 36) were collected.Fatigue was significantly associated with bodily pain, physical function, mental health and depression. Depression was associated with bodily pain and mental health. The path analysis found direct effects from physical function, bodily pain and depression to fatigue (all, P<0.01). The path model analysis revealed that depression exerted a mediator effect from bodily pain to fatigue (B=-0.04, P<0.01), and from mental health to fatigue (B=-0.16, P<0.01). The amount of fatigue explained by all predictors in the path model was 37%.This study found that depression mediates the relationship between some health-related quality of life domains and fatigue in people with MS. Future longitudinal studies focusing on proper management of depressive symptoms in individuals with MS will help determine the clinical implications of these findings.

Pub.: 25 Jan '18, Pinned: 14 Feb '18

Fatigue in multiple sclerosis: relationship with disease duration, physical disability, disease pattern, age and sex.

Abstract: To evaluate the relationship between disease duration, disability, disease pattern, age and sex with fatigue in MS patients. One hundred and seventy-three clinically definite MS patients and 87 age-matched healthy controls enrolled in this cross sectional study. Demographic data (sex, age), duration of the disease and disease pattern extracted from patient's files and Kurtzke Expanded Disability Status Scale (EDSS) were recorded for each patient by an expert neurologist. Participants were asked to answer the validated and reliable Persian version of beck depression inventory (BDI) and FSS (fatigue severity score) questionnaires. Mean FSS and BDI scores were significantly different between patients and controls (p < 0.001). Patients with longer disease duration, higher EDSS and progressive type of disease had significantly higher FSS and BDI scores. Although men had higher EDSS, FSS and BDI scores were similar in both sex groups. FSS was significantly correlated with age, disease duration, BDI and EDSS. The analysis of covariance revealed that there is no difference in the covariance-adjusted means for fatigue among two disease groups (relapsing remitting and secondary progressive) except for EDSS. MS patients with longer disease duration, higher EDSS and progressive type of disease suffer from fatigue more than cases with lower EDSS, duration of disease and relapsing type of the disease.

Pub.: 26 Apr '13, Pinned: 14 Feb '18

Cognitive behavioral therapy positively affects fatigue in patients with multiple sclerosis: Results of a randomized controlled trial.

Abstract: Fatigue is a common symptom in multiple sclerosis (MS) and often restricts societal participation. Cognitive behavioral therapy (CBT) may alleviate MS-related fatigue, but evidence in literature is inconclusive.To evaluate the effectiveness of CBT to improve MS-related fatigue and participation.In a multi-center, assessor-masked, randomized controlled trial, participants with severe MS-related fatigue were assigned to CBT or control treatment. CBT consisted of 12 individual sessions with a psychologist trained in CBT, the control treatment consisted of three consultations with a MS nurse, both delivered over 16 weeks. Assessments were at baseline, 8, 16 (i.e. post-intervention), 26, and 52 weeks post-baseline. Primary outcomes were the Checklist Individual Strength-fatigue subscale (CIS20r fatigue) and the Impact on Participation and Autonomy questionnaire (IPA). Data were analyzed according to the intention-to-treat principle, using mixed-model analysis.Between 2011 and 2014, 91 patients were randomized (CBT: n = 44; control: n = 47). Between-group analysis showed a positive post-intervention effect for CBT on CIS20r fatigue (T16: -6.7 (95% confidence interval (CI) = -10.7; -2.7) points) that diminished during follow-up (T52: 0.5 (95% CI = -3.6; 4.4)). No clinically relevant effects were found on societal participation.Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect over the long term.

Pub.: 23 May '17, Pinned: 14 Feb '18

A randomized controlled trial of cognitive behavior therapy for multiple sclerosis fatigue.

Abstract: The purpose of this study was to assess the efficacy of cognitive behavior therapy (CBT) as a treatment for multiple sclerosis (MS) fatigue.A randomized controlled design was used where 72 patients with MS fatigue were randomly assigned to eight weekly sessions of CBT or relaxation training (RT). RT was designed to control for therapist time and attention. Participants were assessed before and after treatment, and at 3 and 6 months posttreatment. The primary outcome was the Fatigue Scale. Secondary outcomes included measures of stress, mood, and fatigue-related impairment.Analysis was by intention-to-treat. A group by time interaction showed that the CBT group reported significantly greater reductions in fatigue across the 8 months compared with the RT group (p < .02). Calculated effect sizes for fatigue from baseline to the end of treatment were 3.03 [95% confidence interval, 2.22-3.68] for the CBT group and 1.83 [95% confidence interval, 1.26-2.34] for the RT group. Results also indicted that both groups showed clinically significant decreases in fatigue defined as fatigue levels equivalent or less than those reported by a non-fatigued healthy comparison group. There were no significant interactions between group and any of the secondary outcome variables, with both groups showing improvements over time on all measures.Both CBT and RT appear to be clinically effective treatments for fatigue in MS patients, although the effects for CBT are greater than those for RT. Even 6 months after treatment, both treatment groups reported levels of fatigue equivalent to those of the healthy comparison group.

Pub.: 08 Feb '08, Pinned: 14 Feb '18

A pilot mixed-methods evaluation of MS INFoRm: a self-directed fatigue management resource for individuals with multiple sclerosis.

Abstract: Fatigue management interventions for individuals with multiple sclerosis (MS) often feature structured programmes requiring repeated, in-person attendance that is not possible for all individuals. We sought to determine whether MS INFoRm, a self-directed fatigue management resource for individuals with MS, was worth further, more rigorous evaluation. Our indicators of worthiness were actual use of the resource by participants over 3 months, reductions in fatigue impact and increases in self-efficacy, and participant reports of changes in fatigue management knowledge and behaviours. This was a single-group, mixed-methods, before-after pilot study in individuals with MS reporting mild to moderate fatigue. Thirty-five participants were provided with MS INFoRm by a USB flash drive to use at home for 3 months, on their own volition. Twenty-three participants completed all standardized questionnaires, semi-structured interviews and study process measures. Participants reported actively using MS INFoRm over the 3-month study period (median total time spent using MS INFoRm=315 min) as well as significantly lower overall fatigue impact (Modified Fatigue Impact Scale: t=2.6, P=0.01), increased knowledge of MS fatigue (z=-2.8, P=0.01) and greater confidence in managing MS fatigue (z=-3.3, P=0.001). Individuals with significant reductions in fatigue impact also reported behavioural changes including tracking fatigue, better communication with others, greater awareness, improved quality of life and being more proactive. This study provides evidence that further rigorous evaluation of MS INFoRm, a self-directed resource for managing fatigue, is worth pursuing.

Pub.: 13 Jan '18, Pinned: 14 Feb '18

The effectiveness of aerobic training, cognitive behavioural therapy, and energy conservation management in treating MS-related fatigue: the design of the TREFAMS-ACE programme.

Abstract: TREFAMS is an acronym for TReating FAtigue in Multiple Sclerosis, while ACE refers to the rehabilitation treatment methods under study, that is, Aerobic training, Cognitive behavioural therapy, and Energy conservation management. The TREFAMS-ACE research programme consists of four studies and has two main objectives: (1) to assess the effectiveness of three different rehabilitation treatment strategies in reducing fatigue and improving societal participation in patients with MS; and (2) to study the neurobiological mechanisms of action that underlie treatment effects and MS-related fatigue in general.Ambulatory patients (n = 270) suffering from MS-related fatigue will be recruited to three single-blinded randomised clinical trials (RCTs). In each RCT, 90 patients will be randomly allocated to the trial-specific intervention or to a low-intensity intervention that is the same for all RCTs. This low-intensity intervention consists of three individual consultations with a specialised MS-nurse. The trial-specific interventions are Aerobic Training, Cognitive Behavioural Therapy, and Energy Conservation Management. These interventions consist of 12 individual therapist-supervised sessions with additional intervention-specific home exercises. The therapy period lasts 16 weeks. All RCTs have the same design and the same primary outcome measures: fatigue - measured with the Checklist Individual Strength, and participation - measured with the Impact on Participation and Autonomy questionnaire. Outcomes will be assessed 1 week prior to, and at 0, 8, 16, 26 and 52 weeks after randomisation. The assessors will be blinded to allocation. Pro- and anti-inflammatory cytokines in serum, salivary cortisol, physical fitness, physical activity, coping, self-efficacy, illness cognitions and other determinants will be longitudinally measured in order to study the neurobiological mechanisms of action.The TREFAMS-ACE programme is unique in its aim to assess the effectiveness of three rehabilitation treatments. The programme will provide important insights regarding the most effective treatment for MS-related fatigue and the mechanisms that underlie treatment response. A major strength of the programme is that the design involves three almost identical RCTs, enabling a close comparison of the treatment strategies and a strong overall meta-analysis. The results will also support clinical practice guidelines for the treatment of MS-related fatigue.Current Controlled Trials ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628.

Pub.: 14 Aug '13, Pinned: 14 Feb '18

Does aerobic training alleviate fatigue and improve societal participation in patients with multiple sclerosis? A randomized controlled trial.

Abstract: Evidence supporting the effectiveness of aerobic training, specific for fatigue, in severely fatigued patients with multiple sclerosis (MS) is lacking.To estimate the effectiveness of aerobic training on MS-related fatigue and societal participation in ambulant patients with severe MS-related fatigue.Patients ( N = 90) with severe MS-related fatigue were allocated to 16-week aerobic training or control intervention. Primary outcomes were perceived fatigue (Checklist Individual Strength (CIS20r) fatigue subscale) and societal participation. An improvement of ⩾8 points on the CIS20r fatigue subscale was considered clinically relevant. Outcomes were assessed by a blinded observer at baseline, 2, 4, 6 and 12 months.Of the 89 patients that started treatment (median Expanded Disability Status Scale (interquartile range), 3.0 (2.0-3.6); mean CIS20r fatigue subscale (standard deviation (SD)), 42.6 (8.0)), 43 received aerobic training and 46 received the control intervention. A significant post-intervention between-group mean difference (MD) on the CIS20r fatigue subscale of 4.708 (95% confidence interval (CI) = 1.003-8.412; p  = 0.014) points was found in favour of aerobic training that, however, was not sustained during follow-up. No effect was found on societal participation.Aerobic training in MS patients with severe fatigue does not lead to a clinically meaningful reduction in fatigue or societal participation when compared to a low-intensity control intervention.

Pub.: 23 May '17, Pinned: 14 Feb '18

Predictors for employment status in people with multiple sclerosis: a 10-year longitudinal observational study.

Abstract: To identify predictors for employment status after 10 years in a cohort of people with multiple sclerosis (MS), with the aim to increase knowledge concerning factors present at an early stage important for working life and work-life balance.A 10-year longitudinal observational cohort study.People with a definite MS diagnosis, who at inclusion were outpatients at an MS Centre at a university hospital in Stockholm, Sweden.A consecutive sample of 154 people with MS of working age were included at baseline of which a total of 116 people participated in the 10-year follow-up - 27 people declined participation and 11 were deceased.Baseline data on personal factors and functioning were used as independent variables. Employment status 10 years after baseline, categorized as full-time work, part-time work and no work, was used as the dependent variable. A generalized ordinal logistic regression was used to analyse the predictive value of the independent variables.Not applicable.Employment status.Predictors for full- or part-time work after 10 years were young age (p=0.002), low perceived physical impact of MS (p=0.02), fatigue (p=0.03), full-time work (p=0.001) and high frequency of social/lifestyle activities (p=0.001) at baseline. Low perceived physical impact of MS (p=0.02) at baseline also predicted full-time work after 10 years.This study underlines the complexity of working life for people with MS, and indicates that it may be valuable to give more attention to the balance between working and private life, both in clinical practice and future research, in order to achieve a sustainable working life over time.

Pub.: 07 Feb '18, Pinned: 14 Feb '18

The impact of visible and invisible symptoms on employment status, work and social functioning in Multiple Sclerosis.

Abstract: Frequently diagnosed in young adulthood, multiple sclerosis (MS) and several MS-related factors can influence patients' unemployment status and negatively affect work productivity and daily functioning.We examined MS patients' employment status and evaluated clinical features influencing it. Furthermore, we investigated patients' burdens due to visible and invisible MS symptoms through their worsening daily functioning.The study included outpatients affected by MS according to the 2010 McDonald criteria. The co-occurrence of invisible symptoms (fatigue, depression and apathy) was stated using validated, self-administered tools: Fatigue Severity Scale (FSS); Beck Depression Inventory-Second Edition (BDI-II); Apathy Evaluation Scale (AES). Impairment in daily functioning due to MS was assessed using the Work and Social Adjustment Scale (WSAS). Descriptive statistics, hierarchical regression analyses, Pearson's correlation, and the t-test were conducted.Of the 123 participants, 52 (42.3%) were unemployed. Results showed employment to be positively associated with higher education levels (p 0.01); female gender (p 0.03) and higher disability (p 0.02) showed negative associations with employment. No associations were found between employment and fatigue or clinically relevant depressive and apathetic symptoms. High correlations were found between WSAS score and Expanded Disability Status Scale score (r = 565, p < 0.001), BDI-II score (r = 588, p < 0.001), and FSS score (r = 545, p < 0.001).Our study revealed physical disability's significance in determining MS patients' unemployment. Alternatively, invisible MS symptoms negatively affected principally patients' social lives. Therefore, programs should be designed to improve MS patients' work integration and daily activities.

Pub.: 06 Feb '18, Pinned: 14 Feb '18