BackgroundFatigue is a disabling syndrome in multiple sclerosis (MS), which may be associated with inflammation and faster disease progression.ObjectiveTo analyze the significance of cognitive fatigue for subsequent disease progression.MethodWe followed 46 MS patients and 14 healthy controls in a study over 17 months. At the beginning (t1) and at the end (t2) of the study participants scored their fatigue, performed the Multiple Sclerosis Functional Composite and received MRI scanning, encompassing MPR T1, FLAIR, and DTI sequences. At t1, MS patients were divided into those with and those without cognitive fatigue (cut-off score for moderate cognitive fatigue of the Fatigue Scale for Motor and Cognition). We calculated ANCOVAs for repeated measurement to analyze the relevance of cognitive fatigue status for the number of relapses and for MRI parameters.ResultsAt t1, but not at t2, patients with cognitive fatigue showed increased axial and radial diffusivity of corpus callosum fibers. At t2, these patients showed significantly more loss of brain parenchyma and greater enlargement of lateral ventricles. Moreover, they developed more relapses, but there was no difference in lesion load or in performance deterioration. Additional analyses showed that only cognitive fatigue but not a more general score for fatigue (Fatigue Severity Scale) had an impact on the worsening of the disease status.ConclusionPatients with cognitive fatigue may develop more brain atrophy and relapses during the next 17 months than patients without cognitive fatigue. Hence, experiencing cognitive fatigue might indicate more aggressive inflammatory processes and subsequent neurodegeneration.

BackgroundCognitive fatigue and autonomic abnormalities are frequent symptoms in MS. Our model of MS-related fatigue assumes a shared neural network for cognitive fatigue and autonomic failures, i.e., aberrant vagus nerve activity induced by inflammatory processes. Therefore, they should occur in common.ObjectiveTo explore the relationship between cognitive fatigue and autonomic symptoms in MS patients, using self-reported questionnaires.MethodsIn 95 MS patients, cognitive fatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions and autonomic abnormalities with the Composite Autonomic Symptom Scale-31 (COMPASS-31). We used exploratory correlational analyses and hierarchical regression analysis, controlling for age, depressive mood, disease status, and disease duration, to analyze the relation between autonomic abnormalities and cognitive fatigue.ResultsThe cognitive fatigue score strongly correlated with the COMPASS-31 score (r = 0.47, p < 0.001). Regression analysis revealed that a model, including the COMPASS-31 domains: pupillomotor, orthostatic intolerance, and bladder, best predict the level of cognitive fatigue (R2 = 0.47, p < 0.001) after forcing the covariates into the model.ConclusionIn MS patients, cognitive fatigue and autonomic dysfunction share a proportion of variance. This supports our model assuming that fatigue might be explained at least partially by inflammation-induced vagus nerve activity.

One of the most frequent symptoms in multiple sclerosis (MS) is fatigue. It has a major impact on quality of life as well as on professional activity. Even nowadays it is still unclear what constitutes an adequate assessment of the perceived fatigue.The following overview will discuss different possibilities to assess fatigue with the help of questionnaires, clinical interviews or the objective measurement of cognitive performance. Furthermore, a structured guideline for the assessment of fatigue will be proposed. Clinical criteria for MS related fatigue include the main symptoms, their everyday relevance, the possible causal relation with the cause of disease (the underlying MS), as well as an exclusion of other possible somatic or psychological reasons. It is recommended to use the “Würzburger Erschöpfungs-Inventar bei Multipler Sklerose (WEIMUS)” (English: Würzburg Fatigue Inventory for Multiple Sclerosis) and especially the “Fatigue Scale for Motor and Cognitive Functions” (FSMC), as these questionnaires distinguish between motor and cognitive fatigue and due to the larger number of research studies using the FSMC. Moreover, the presence of depression, quality of sleep and daytime sleepiness should be assessed. In addition, general cognitive performance as well as performance during monotonous stimulation (vigilance) should be assessed. This may be relevant for the evaluation of a patient’s capacity to work, and for determining prognosis, as there are indications for a relation to relapse frequency, a change from a clinically isolated syndrome (CIS) to an MS diagnosis with an increase of brain atrophy.All in all, it can be said, that despite the growing convergence of diagnostic criteria, the available studies of the objective as well as the subjective assessment of fatigue are still not sufficient and further research is needed.

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Background: The causes of fatigue in multiple sclerosis (MS) and other inflammatory disorders are not well understood. One possible cause that might explain fatigue in inflammatory disorders appears to be the immunological process itself, triggering neural activity that is experienced as fatigue.Objectives: To investigate whether salivary IL-1ß concentration, associated with systemic inflammation, is related to subjective fatigue in MS.Methods: 116 MS patients (62 relapsing remitting MS, 54 secondary progressive MS) and 51 healthy controls participated in this study. Salivary concentration of IL-1ß was determined using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Fatigue was assessed using various fatigue scales. We compared IL-1ß concentration between groups and performed regression analyses to investigate which variables best predict fatigue scores.Results: We found that the IL-1ß concentration best predicts fatigue scores in relapsing remitting MS patients, even though the IL-1ß concentration did not differ significantly between relapsing remitting MS patients and healthy controls. Secondary progressive MS patients showed a somewhat elevated IL-1ß concentration compared to relapsing remitting MS patients and healthy controls. Furthermore, disease modifying treatment had a significant effect on the IL-1ß concentration, with treated patients showing a lower IL-1ß concentration than non-treated patients.Conclusions: The present study points to a significant relation between the proinflammatory cytokine IL-1ß and fatigue in relapsing remitting MS patients. It also suggests a potential effect of disease modifying treatment on the peripheral IL-1ß concentration.

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