Multiple Sclerosis-related Fatigue Research Articles

The effectiveness of a self-management occupational therapy intervention on activity performance in individuals with multiple sclerosis-related fatigue: a randomized-controlled trial.

Purpose to evaluate the effectiveness of an individual self-management occupational therapy intervention program (SMOoTh) versus relaxation on the performance of and satisfaction with relevant daily activities in individuals with multiple sclerosis (MS)-related fatigue. in a single-blind randomized-controlled trial, 31 patients with MS (SMOoTh: n=17, relaxation: n=14) were randomly allocated to three individual sessions focusing on pacing, prioritizing, ergonomics, and self-management (SMOoTh) or on stress management and relaxation (relaxation). Outcomes (blind assessor): Canadian Occupational Performance Measure (COPM) (primary), Modified Fatigue Impact Scale, Checklist Individual Strength and Short-Form Health Measure. COPM improved in the SMOoTh and relaxation group after the intervention and 3 months later (COPM performance: F=13.1, P=0.001 and COPM satisfaction: F=10.4, P=0.001); nonsignificant group differences showed a trend in favor of SMOoTh. Modified Fatigue Impact Scale, Checklist Individual Strength, and most of the Short-Form Health Measure subscales did not change. Clinically relevant changes in COPM performance scores were found in 71 and 27% of patients in the SMOoTh versus the relaxation group. Both interventions seem to be feasible approaches to improve performance of and satisfaction with relevant daily activities in people with MS, with a sustained effect after 3 months. Neither program altered change fatigue (impact) or quality of life. Future studies with larger sample sizes are needed.

Multiple sclerosis fatigue relief by bilateral somatosensory cortex neuromodulation

Multiple sclerosis-related fatigue is highly common and often refractory to medical therapy. Ten fatigued multiple sclerosis patients received two blocks of 5-day anodal bilateral primary somatosensory areas transcranial direct current stimulation in a randomized, doubleblind sham-controlled, cross-over study. The real neuromodulation by a personalized electrode, shaped on the MRderived primary somatosensory cortical strip, reduced fatigue in all patients, by 26% in average ( p = 0.002), which did not change after sham ( p = 0.901). Anodal tDCS over bilateral somatosensory areas was able to relief fatigue in mildly disabled MS patients, when the fatigue related symptoms severely hamper their quality of life. These small-scale study results support the concept that interventions modifying the sensorimotor network activity balances could be a suitable non-pharmacological treatment for multiple sclerosis fatigue.

Multiple sclerosis-related fatigue and possibilities of its correction

Multiple sclerosis (MS)-related fatigue is encountered in 75–92% of patients and it is one of the key symptoms that affect quality of life. Physicians and patients' relatives frequently underestimate MS-related fatigue; the latter may occur at any disease stage, its degree is inadequate to physical exercise and reduces after a short-term daytime rest. Fatigue due to MS is not directly related to the degree of paresis; however, it is more common in patients with pyramidal insufficiency. Overfatigue may be the first symptom of an MS exacerbation. The genesis of fatigue in MS is not known with certainty. The development of this symptom is associated with impairments in neuroimmune responses and biochemical processes and with the administration of some drugs. Special tests and scales are used to objectify the degree of fatigue. The most commonly used questionnaires are the Fatigue Severity Scores to rate physical and mental fatigue, as well as the Modified Fatigue Impact Scale in patients having MS. When a patient with MS complains about fatigue, it is necessary to rule out its other possible causes and to specify its relation to MS and the necessity of fatigue correction. Аmantadine is one of the drugs used for the symptomatic therapy of MS. This paper presents the data of randomized clinical trials evaluating the efficacy and safety of this drug for the symptomatic treatment of MS. Correction of MS-related fatigue requires a multidisciplinary approach that involves a combination of drug therapy, therapeutic exercises, active lifestyle, and relatives' understanding.

Effect of Alfacalcidol on multiple sclerosis-related fatigue: A randomized, double-blind placebo-controlled study

Context: Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS); however, there is no medication that has been approved specifically to treat MS-related fatigue. Objective: We aimed to evaluate the effect of vitamin D analogue, Alfacalcidol, on MS-related fatigue. Design, settings, participants: This was a randomized, double-blind, parallel group, placebo-controlled trial in patients with clinically definite MS by McDonald criteria conducted in a single university-affiliated medical center in Israel. Randomly selected patients from the Sheba MS Registry computerized database (N=600) were assessed using the self-report Fatigue Severity Scale (FSS). Patients with clinically meaningful fatigue (N=259) were further assessed for trial eligibility, and MS patients with significant fatigue (N=158; 61%, 118 females, mean age 41.1 ± 9.2 years and mean disease duration of 6.2 ± 5.5 years) were included in the study and randomized to receive treatment or placebo. Intervention: Alfacalcidol (1 mcg/d, N=80) or placebo (N=78) was administered for six consecutive months. Main outcome measure: The primary endpoint of the study was the change between Alfacalcidol and placebo-treated patients in the Fatigue Impact Scale (FIS) score; the cut-off point for improvement was defined as 30% decrease. All analyses followed the intention-to-treat principle and were performed for all participants based on the group they were randomly allocated regardless of whether or not they dropped out. Results: Alfacalcidol decreased the mean relative FIS score as compared with placebo (–41.6% vs. –27.4%, p=0.007, respectively). This advantage was further emphasized when the modified FIS (MFIS) relative change was calculated. Quality of Life (QoL) improved in Alfacalcidol-treated patients as compared with placebo in the RAYS psychological (p=0.033) and social (p=0.043) sub-scales. The Alfacalcidol-treated group had reduced number of relapses (p=0.006) and higher proportion of relapse-free patients (p=0.007). Reduction of relapses by Alfacalcidol became significant at 4 months of treatment, was sustained at 6 months and decayed 2 months after drug discontinuation. Alfacalcidol treatment was safe and no serious adverse events were recorded. Conclusion: Alfacalcidol is a safe and effective treatment strategy to decrease fatigue and improve QoL in patients with MS.

Aspirin is Unlikely to Have A Clinically Meaningful Effect on Multiple Sclerosis-Related Fatigue: Data From a Randomized Controlled Trial (P7.245)

Aspirin is Unlikely to Have A Clinically Meaningful Effect on Multiple Sclerosis-Related Fatigue: Data From a Randomized Controlled Trial (P7.245)

Low dose aspirin for MS-related fatigue: Results of a pilot, double-blind, randomized trial

Fatigue is one of the most common and disabling symptoms in multiple sclerosis (MS), occurring in more than 60% of patients during the course of the disease. Despite /INS;high prevalence of fatigue in MS patients, its pathophysiology was not understood completely yet and/INS; this would difficult introduction of new medication for this symptom. Wingerchuk et al. for the first time assess the effectiveness of Aspirin (ASA) on MS related fatigue and show high dose ASA (1300mg) would significantly decrease fatigue in these patients.

Treatment of sleep disorders may improve fatigue in multiple sclerosis

ObjectiveIn a previous polysomnographic cross-sectional study we found a significant relationship between sleep disorders and multiple sclerosis (MS) related fatigue. The purpose of this open follow-up observation was to compare the impact of treatment of sleep disorders on MS related fatigue measured with the Modified Fatigue Impact Scale (MFIS). MethodsNon-randomized follow-up observation: treated versus untreated patients, subgroups according to compliance with sleep medical treatment recommendations (univariate, multivariate analysis, multiple logistic regression). 66 MS patients were followed after polysomnography, 49 patients with relevant sleep disorders and 17 without. ResultsMean MFIS scores decreased from 41.2 to 26.2 (p=0.025) in patients with good compliance (GC; n=18), from 42.4 to 32.1 (p=0.12) in patients with moderate compliance (MC; n=12), and from 41.6 to 35.5 (p=0.17) in non-compliant patients (NC; n=17). Mean MFIS values increased in patients without sleep disorders from 22.9 to 25.4 (NSD; n=12, p=0.56). In multiple logistic regression, treatment of sleep disorders predicted decrease of MFIS-values (GC versus NSD odds ratio 13.4; p=0.015; 95% confidence interval (CI) 1.7–107.2, MC versus NSD odds ratio 13.8; p=0.028; 95% CI 1.3–143.3). ConclusionsSleep medical treatment may improve MS related fatigue when patients adhere to treatment recommendations.

Younger age, female sex, and high number of awakenings and arousals predict fatigue in patients with sleep disorders: a retrospective polysomnographic observational study

BackgroundThe Fatigue Severity Scale (FSS) is widely used to assess fatigue, not only in the context of multiple sclerosis-related fatigue, but also in many other medical conditions. Some polysomnographic studies have shown high FSS values in sleep-disordered patients without multiple sclerosis. The Modified Fatigue Impact Scale (MFIS) has increasingly been used in order to assess fatigue, but polysomnographic data investigating sleep-disordered patients are thus far unavailable. Moreover, the pathophysiological link between sleep architecture and fatigue measured with the MFIS and the FSS has not been previously investigated.MethodsThis was a retrospective observational study (n = 410) with subgroups classified according to sleep diagnosis. The statistical analysis included nonparametric correlation between questionnaire results and polysomnographic data, age and sex, and univariate and multiple logistic regression.ResultsThe multiple logistic regression showed a significant relationship between FSS/MFIS values and younger age and female sex. Moreover, there was a significant relationship between FSS values and number of arousals and between MFIS values and number of awakenings.ConclusionYounger age, female sex, and high number of awakenings and arousals are predictive of fatigue in sleep-disordered patients. Further investigations are needed to find the pathophysiological explanation for these relationships.

The association between multiple sclerosis-related fatigue and balance as a function of central sensory integration

BackgroundFatigue and impaired upright postural control (balance) are the two most common complaints in persons with multiple sclerosis (MS), with limited evidence on how they are related. ObjectiveTo examine the relationship between symptomatic fatigue and balance as a function of central sensory integration in persons with multiple sclerosis. Materials and methodsSeventeen persons with relapsing-remitting MS were enrolled in this cross-sectional study. Primary measurements included fatigue (modified fatigue impact scale – MFIS); balance (dynamic posturography, sensory organization testing – SOT); and walking capacity (six-minute walk test – 6MWT). ResultsFatigue scores were significantly associated with balance: MFIS total (r=−0.78; p<0.001), physical subscale (r=−0.77; p<0.001), cognitive subscale (r=−0.75; p=0.001) and psychosocial subscale (r=−0.53; p=0.030) scores. MFIS total score was a significant predictor of balance (p≤0.001), accounting for 62% of the variability in SOT composite scores. Significant differences in fatigue (d=1.75; p=0.005) and balance (d=1.74; p=0.005) were found for participants who had cerebellar and brainstem involvement compared to those without. ConclusionsSymptomatic fatigue is significantly related to balance and is a significant predictor of balance as a function of central sensory integration in persons with MS. Fatigue and balance are associated with cerebellar and brainstem involvement. This study provides early evidence supporting the theory that for those persons with MS who struggle to maintain steady balance during tasks that stimulate the central sensory integration process, complaints of significant levels of fatigue are probable.

Detection of Clinically Important Change in Multiple Sclerosis-Related Fatigue and Relationship to Cognitive Performance (P04.109)

Objective: Evaluate 1) the responsiveness of the Modified Fatigue Impact Scale (MFIS) for multiple sclerosis (MS)-related fatigue and 2) relationships between subjective fatigue assessment and measures of cognitive function. Background MS-related fatigue, including cognitive fatigue, is common. The MFIS is routinely used to measure MS-related fatigue but its responsiveness and ability to detect clinically important change after therapy is not known. Previous research found that cognitive performance and fatigue were not related. However, potentially more sensitive instruments such as the MFIS might detect an underlying relationship. Design/Methods: Ambulatory patients with MS-related fatigue persisting at least 6 weeks completed the MFIS, Fatigue Severity Scale (FSS), SF-36, and questionnaires. Cognitive performance measures included the Paced Auditory Serial Addition Test (PASAT) and others. All testing was administered on days 0, 7, and 21. Amantadine was initiated on day 7. Global assessment of change (GAC) comparing pre-to post-treatment status was rated as poor, fair, good, or excellent. Paired t-tests and Fisher9s exact test were used to evaluate outcomes and correlations were calculated for mean change scores. Effect size and correlations between changes in MFIS, GAC, and PASAT were calculated. Results: 22 patients were enrolled. Improvement in post-treatment scores was detected for the MFIS (p=0.004) and the PASAT (p=0.02), among others. The MFIS effect size was moderate (0.61) but there was a weak association between MFIS change and GAC (r=0.26; NS). Changes in PASAT scores correlated with changes in the SF-36 physical subscale (r=0.42; p=0.05), MFIS-Cognitive subscale (r=0.39; p=0.07), and MFIS-Social subscale (r=0.37; p=0.09). Conclusions: Fatigue, as measured by the MFIS, may be associated with cognitive performance. However, despite moderate effect size, change in MFIS is not associated with qualitative self-assessment of therapeutic response. Further work is needed to find instruments that detect clinically important change in subjective fatigue and objective cognitive performance. Disclosure: Dr. Thaera has nothing to disclose. Dr. Wingerchuk has received research support from Genentech, Inc,, Genzyme Corporation, Alexion and the Guthy-Jackson Charitable Foundation.

Therapeutic effects of whole‐body devices applying pulsed electromagnetic fields (PEMF): A systematic literature review

Pulsed electromagnetic fields (PEMF) delivered by whole-body mats are promoted in many countries for a wide range of therapeutic applications and for enhanced well-being. However, neither the therapeutic efficacy nor the potential health hazards caused by these mats have been systematically evaluated. We conducted a systematic review of trials investigating the therapeutic effects of low-frequency PEMF devices. We were interested in all health outcomes addressed so far in randomized, sham-controlled, double-blind trials. In total, 11 trials were identified. They were focused on osteoarthritis of the knee (3 trials) or the cervical spine (1), fibromyalgia (1), pain perception (2), skin ulcer healing (1), multiple sclerosis-related fatigue (2), or heart rate variability and well-being (1). The sample sizes of the trials ranged from 12 to 71 individuals. The observation period lasted 12 weeks at maximum, and the applied magnetic flux densities ranged from 3.4 to 200 µT. In some trials sporadic positive effects on health were observed. However, independent confirmation of such singular findings was lacking. We conclude that the scientific evidence for therapeutic effects of whole-body PEMF devices is insufficient. Acute adverse effects have not been reported. However, adverse effects occurring after long-term application have not been studied so far. In summary, the therapeutic use of low-frequency whole-body PEMF devices cannot be recommended without more scientific evidence from high-quality, double-blind trials.

P300 and treatment effect of modafinil on fatigue in multiple sclerosis

To evaluate the value of visual and auditory P300 for predicting the response of multiple sclerosis-related fatigue to modafinil treatment, 33 patients were treated with 100 mg modafinil once daily for 4 weeks, following a 4-week baseline phase and an optional 8-week extension phase. The main clinical outcome parameter was a decrease in the fatigue visual analogue score (VAS) before and after 4 weeks of treatment. Patients with shorter auditory P300 latency at baseline were more likely to benefit from modafinil treatment. Auditory P300 latency predicted treatment response with a specificity of 76% and a sensitivity of 75% at a cut-off latency of 350 ms. Visual P300 latency could not be used to predict treatment response. Baseline auditory P300 latency predicted treatment response, whereas visual P300 latency did not. Clinical improvement did not correlate with changes in either visual or auditory P300.

Treatment of multiple sclerosis-related fatigue: pharmacological and non-pharmacological approaches

Fatigue is a common symptom in multiple sclerosis (MS). As fatigue includes a variety of aspects, its treatment is best approached in a multidisciplinary fashion that includes nonpharmacological interventions and medications. In individuals with mild fatigue non-pharmacological treatment including yoga, aerobic exercises, cooling therapy and energy conservation techniques might be considered. Several pharmacological treatments for patients with significant fatigue have proved to be effective. Among these agents, amantadine and aminopyridines are the most frequently used. More recently also aspirin and carnitine have been used to treat MS fatigue but they need to be confirmed in larger studies.

Establishing a physiological basis to multiple sclerosis—related fatigue: A case report

Objective: Although fatigue is a common debilitating complaint in multiple sclerosis (MS), its relationship to the cardiopulmonary exercise response has yet to be defined. Design: A patient with MS manifested primarily by profound fatigue undergoes complete pulmonary function testing and a maximal incremental cycle ergometry study with gas exchange measurements and determination of ejection fractions. Setting: Outpatient, community hospital pulmonary function laboratory. Results: The patient is found to have respiratory muscle weakness and a severely depressed exercise performance. The latter was associated with an early anaerobic threshold but a normal central cardiovascular response (radionuclide ventriculography), implying problems in peripheral O 2 distribution/utilization. The respiratory muscle involvement, although substantial, was nonlimiting to the exercise performance. Conclusions: Despite its central neuropathophysiology, MS as it relates to fatigue may be associated with an abnormal peripheral exercise response, namely, problems in peripheral O 2 utilization. Such a concept could prove invaluable as it would provide a physiological basis for defining the severity and therapy of “MS fatigue.”