Association of a deficit of arousal with fatigue in multiple sclerosis: Effect of modafinil

Niepel, G; Bibani, Rashid H.; Vilisaar, Janek; Langley, R. W.; Bradshaw, C. M.; Szabadi, E.; Constantinescu, Cris S.

doi:10.1016/j.neuropharm.2012.06.036

Cited by 34 publications

(24 citation statements)

References 82 publications

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“…Correlation of fatigue and alertness, as described in earlier studies [6][7][8], was not found here. This could also be due to differences in age and disease duration of our patients.…”

Section: Discussioncontrasting

confidence: 48%

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Structural correlates for fatigue in early relapsing remitting multiple sclerosis

et al. 2015

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“…Correlation of fatigue and alertness, as described in earlier studies [6][7][8], was not found here. This could also be due to differences in age and disease duration of our patients.…”

Section: Discussioncontrasting

confidence: 48%

“…Both can have implications for all aspects of daily life, and are often not recognized promptly. Several studies have investigated the relationship between fatigue and cognition, but could not find a significant correlation [4,5]; however, deficits in reaction time and processing speed have been associated with fatigue [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Structural correlates for fatigue in early relapsing remitting multiple sclerosis

et al. 2015

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“…Finally, a UK study in 26 MS patients (17 with fatigue) and nine age-and sex-matched controls found that patients with fatigue had reduced levels of alertness and cardiovascular sympathetic activation compared with patients without fatigue and healthy controls. Modafinil showed alerting and sympathomimetic effects in all three groups, which may be how it exerts its anti-fatigue effect in MS [60].…”

Section: Association With Fatigue and Cognitive Impairmentmentioning

confidence: 80%

Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies

Findling

Hauer

Pezawas

et al. 2020

JCM

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Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used to treat MS. The analysis revealed that CAD is correlated with pathophysiological processes of MS, can trigger serious cardiovascular complications that may reduce life expectancy, and may have implications for treatment with immunotherapies, especially fingolimod. Numerous mainly small case-control or cohort studies have reported various measures of CAD (particularly heart rate variation) in MS patients, showing higher rates of abnormality versus controls. A smaller number of studies have reported on cardiac autonomic symptoms in MS, including orthostatic intolerance/dizziness in around 50% of patients. CAD also appears to be associated with disease duration and to be more common in progressive than relapsing-remitting MS. However, although a substantial evidence base suggests that assessing CAD in people with MS may be important, standardised methods to evaluate CAD in these patients have not yet been established. In addition, no studies have yet looked at whether treating CAD can reduce the burden of MS symptoms, disease activity or the rate of progression.

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“…Illustrative of this is the fact that despite several failed randomized controlled trials (RCTs), 14–16 , RRMS patients are still prescribed modafinil (a stimulant), likely based on a conceptualization of MS fatigue as stemming from dysfunctional arousal (e.g., 17 ). More promising may be exploration of an inflammatory etiology for MS fatigue, which is supported by a link between fatigue and inflammatory markers (tumor necrosis factor-alpha and interferon-gamma) 18 , and by the link between fatigue and elevated body temperature presented herein.…”

Section: Discussionmentioning

confidence: 99%

Body Temperature Is Elevated and Linked to Fatigue in Relapsing-Remitting Multiple Sclerosis, Even Without Heat Exposure

Sumowski

Leavitt²

2014

Archives of Physical Medicine and Rehabilitation

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Objective To investigate whether resting body temperature is elevated and linked to fatigue in patients with relapsing-remitting multiple sclerosis (RRMS). Design Cross-sectional study investigating (a) differences in resting body temperature across RRMS, SPMS, and healthy groups, and (b) the relationship between body temperature and fatigue in RRMS patients. Setting Climate-controlled laboratory (~22°C) within a non-profit medical rehabilitation research center. Participants Fifty patients with RRMS, 40 matched healthy controls, and 22 patients with secondary-progressive MS (SPMS). Intervention None. Main Outcome Measure(s) Body temperature was measured with an aural infrared thermometer (normal body temperature for this thermometer is 36.75°C), and differences were compared across RRMS, SPMS, and healthy persons. RRMS patients 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, ηp2=.132) whereby body temperature was higher in RRMS patients (37.04°C±0.27) relative to healthy controls (36.83 ± 0.33; p = .009) and SPMS patients (36.75°C±0.39; p=.001). Warmer body temperature in RRMS patients was associated with worse general fatigue (FSS; rp=.315, p=.028) and physical fatigue (pMFIS; rp=.318, p=.026), but not cognitive fatigue (cMIFS; rp=−.017, p=.909). Conclusions These are the first-ever demonstrations that body temperature is elevated endogenously in RRMS patients, 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.

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Association of a deficit of arousal with fatigue in multiple sclerosis: Effect of modafinil

Cited by 34 publications

References 82 publications

Structural correlates for fatigue in early relapsing remitting multiple sclerosis

Structural correlates for fatigue in early relapsing remitting multiple sclerosis

Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies

Body Temperature Is Elevated and Linked to Fatigue in Relapsing-Remitting Multiple Sclerosis, Even Without Heat Exposure

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