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Unveiling the relationship between autonomic involvement, fatigue, and cognitive dysfunction in early relapsing–remitting multiple sclerosis

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Abstract

Background

Fatigue is a common, yet disabling, symptom in patients with multiple sclerosis (PwMS). Fatigue has shown to be associated with self-reported autonomic nervous system (ANS) symptoms, particularly for cognitive fatigue; however, the question whether ANS involvement is related to cognitive impairment has never been addressed. We performed a study to unveil the complex relationship between fatigue, ANS symptoms, and cognitive impairment.

Methods

We prospectively recruited early PwMS that were tested with Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale (MFIS) and Composite Autonomic Symptoms Scale-31 (COMPASS-31) scale. We performed a comparison between fatigued and non-fatigued patients and between cognitive unimpaired and impaired patients. We evaluated the association of COMPASS-31, MFIS, BDI, STAI, and BICAMS scores, and the analysis was repeated for each scale’s sub-scores. A multivariable analysis was performed to elucidate predictors of fatigue.

Results

Forty-four patients were recruited. Fatigued patients had higher COMPASS-31 total, orthostatic intolerance, secretomotor, and pupillomotor scores. No differences in fatigue and ANS symptoms were found between cognitive impaired and unimpaired patients. MFIS total score correlated with STAI state (p = 0.002) and trait (p < 0.001), BDI (p < 0.001), COMPASS-31 total (p < 0.001), orthostatic intolerance (p < 0.001), pupillomotor scores (p = 0.006). Multivariable analysis showed that BDI (p < 0.001) and COMPASS-31 (p = 0.021) predicted MFIS score. Sub-scores analysis showed that orthostatic intolerance has a relevant role in fatigue.

Conclusion

ANS symptoms are closely related with fatigue. Orthostatic intolerance may have a predominant role. Cognitive impairment seems not to be associated with ANS symptoms.

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Data availability

Data are available upon reasonable request.

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Authors and Affiliations

  1. Neurology Unit, Department of Medical, Surgical and Health Sciences, Cattinara University Hospital, ASUGI, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy

    Alessandro Dinoto, Sara Baldini, Maria Elisa Morelli, Fulvio Pasquin, Alessio Bratina, Antonio Bosco, Arianna Sartori & Paolo Manganotti

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  1. Alessandro Dinoto
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  2. Sara Baldini
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  3. Maria Elisa Morelli
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  4. Fulvio Pasquin
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  8. Paolo Manganotti
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Corresponding author

Correspondence to Alessandro Dinoto.

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The study was approved by the local ethical committee.

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Patients gave their informed consent to participate.

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Patients gave their informed consent for publication.

Competing interests

A Dinoto has received funding for travel from Novartis, Genzyme, Biogen, and Laborest. S Baldini has received funding from Merk. ME Morelli has received funding for travel from Genzyme, Biogen, Roche. F Pasquin has received funding for travel from Genzyme. A Bratina has received funding for travel and/or speaker honoraria from Almirall. A Bosco has received funding for travel and/or speaker honoraria from Teva, Biogen, and Genzyme. A Sartori has received funding for travel honoraria from Novartis, Teva, Merk, Genzyme, Roche, and Biogen. P Manganotti declares no competing interests.

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Dinoto, A., Baldini, S., Morelli, M.E. et al. Unveiling the relationship between autonomic involvement, fatigue, and cognitive dysfunction in early relapsing–remitting multiple sclerosis. Neurol Sci 42, 4281–4287 (2021). https://doi.org/10.1007/s10072-021-05487-6

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