Body temperature is elevated and linked to fatigue in relapsing-remitting multiple sclerosis, even without heat exposure

Abstract

Objectives: To investigate whether (1) resting body temperature is elevated in patients with relapsing-remitting multiple sclerosis (RRMS) relative to healthy individuals and patients with secondary progressive multiple sclerosis (SPMS), and (2) warmer body temperature is linked to worse fatigue in patients with RRMS.

Design: Cross-sectional study.

Setting: Climate-controlled laboratory (∼22°C) within a nonprofit medical rehabilitation research center.

Participants: Patients with RRMS (n=50), matched healthy controls (n=40), and patients with SPMS (n=22).

Intervention: Not applicable.

Main outcome measures: Body temperature was measured with an aural infrared thermometer (normative body temperature for this thermometer, 36.75°C), and differences were compared across patients with RRMS and SPMS and healthy persons. Patients with RRMS completed measures of general fatigue (Fatigue Severity Scale [FSS]), as well as physical and cognitive fatigue (Modified Fatigue Impact Scale [MFIS]).

Results: There was a large effect of group (P<.001, ηp(2)=.132) whereby body temperature was higher in patients with RRMS (37.04°±.27°C) relative to healthy controls (36.83°±.33°C; P=.009) and patients with SPMS (36.75°±.39°C; P=.001). Warmer body temperature in patients with RRMS was associated with worse general fatigue (FSS; rp=.315, P=.028) and physical fatigue (physical fatigue subscale of the MFIS; rp=.318, P=.026), but not cognitive fatigue (cognitive fatigue subscale of the MIFS; rp=-.017, P=.909).

Conclusions: These are the first-ever demonstrations that body temperature is elevated endogenously in patients with RRMS and linked to worse fatigue. We discuss these findings in the context of failed treatments for fatigue in RRMS, including several failed randomized controlled trials (RCTs) of stimulants (modafinil). In contrast, our findings may help explain how RCTs of cooling garments and antipyretics (aspirin) have effectively reduced MS fatigue, and encourage further research on cooling/antipyretic treatments of fatigue in RRMS.

Keywords: Aspirin; Body temperature; Fatigue; Inflammation; Multiple sclerosis; Rehabilitation; Relapsing-remitting multiple sclerosis.