Abstract
Although fatigue is a common symptom in multiple sclerosis (MS), its pathomechanisms are incompletely understood. Glatiramer acetate (GA), an immunomodulatory agent approved for treatment of relapsing-remitting MS (RRMS), possesses unique mechanisms of action and has been shown to exhibit beneficial effects on MS fatigue. The objective of this study was to correlate clinical, neuropsychological, and immunological parameters in RRMS patients with fatigue before and during treatment with GA. In a prospective, open-label, multicenter trial, 30 patients with RRMS and fatigue were treated with GA for 12 months. Inclusion criterion was the presence of fatigue as one of the most frequent and disabling symptoms. Before and during treatment, fatigue was assessed using the Fatigue Severity Scale (FSS), the MS-FSS, and the Modified Fatigue Impact Scale (MFIS). In addition, fatigue and quality of life were assessed using the Visual Analog Scales (VAS). Laboratory assessments included screening of 188 parameters using real-time PCR microarrays followed by further analysis of several cytokines, chemokines, and neurotrophic factors. Fatigue self-assessments were completed in 25 patients. After 12 months of treatment with GA, 13 of these patients improved in all three scales (with the most prominent effects on the MFIS), whereas 5 patients had deteriorated. The remaining 7 patients exhibited inconsistent effects within the three scales. Fatigue and overall quality of life had improved, as assessed via VAS. Laboratory assessments revealed heterogeneous mRNA levels of cytokines, chemokines, and neurotrophic factors. In conclusion, we were not able to correlate clinical and molecular effects of GA in patients with RRMS and fatigue.
Highlights
Fatigue is a feeling of permanent tiredness at daytime and is a common symptom in all stages of multiple sclerosis (MS) [1,2]
30 patients were enrolled in our study and 25 patients were available for full analysis
Four patients were excluded because sampling was incomplete and patients were lost to follow-up
Summary
Fatigue is a feeling of permanent tiredness at daytime and is a common symptom in all stages of multiple sclerosis (MS) [1,2]. Fatigue is one of the invisible and barely measurable, and underrated symptoms, where patients describe enormous impairment of daily activities and quality of life [3]. Fatigue contributes only indirectly to the Expanded Disability Status Scale (EDSS)—a standard assessment scale of disability in MS [4]—and played a minor or no role in previous clinical trials of disease modifying treatments in MS. Functional MRI studies revealed different areas of cortical activation in fatigued MS patients as compared to non-fatigued patients, indicating different functional patterns in both groups [9,10]. Various hormones involved in the (chronic or episodic) hypercortisolemia that characterizes MS may contribute to fatigability [12,13]. Transmitters involved in attention and arousal, as well as the alteration of their synaptic activity, are discussed [14]
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