Document Detail


Association of a deficit of arousal with fatigue in multiple sclerosis: Effect of modafinil.
MedLine Citation:
PMID:  22766394     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system, leading to chronic disability. Fatigue is a common and distressing symptom of MS which is unrelated to its clinical form, stage of development, the degree of disability, or the lesion load on magnetic resonance imaging. Fatigue in MS is associated with excessive daytime sleepiness and autonomic dysfunction. Recently it has been reported that the wakefulness-promoting drug modafinil may relieve fatigue in MS patients and ameliorate the associated cognitive difficulties. However, it is not clear to what extent the anti-fatigue effect of modafinil may be related to its alerting and sympathetic activating effects. We addressed this question by comparing three groups of subjects, MS patients with fatigue, MS patients without fatigue and healthy controls, matched for age and sex, on measures of alertness (self-ratings on the Epworth and Stanford Sleepiness Scales and on a battery of visual analogue scales; critical flicker fusion frequency; Pupillographic Sleepiness Test; choice reaction time) and autonomic function (systolic and diastolic blood pressure, heart rate, pupil diameter), and by examining the effect of a single dose (200 mg) of modafinil on these measures. MS patients with fatigue, compared with healthy controls, had reduced level of alertness on all the tests used; MS patients without fatigue did not differ from healthy controls. MS patients with fatigue had a reduced level of cardiovascular sympathetic activation compared to the other two groups. Modafinil displayed alerting and sympathomimetic effects in all three groups of subjects. As fatigue in MS is associated with reduced levels of alertness and sympathetic activity, modafinil may exert its anti-fatigue effect in MS by correcting these deficiencies. The anti-fatigue effect of modafinil may reflect the activation of the noradrenergic locus coeruleus (LC), since there is evidence that this wakefulness-promoting nucleus is damaged in MS, and that modafinil, probably via the dopaminergic system, can stimulate the LC.
Authors:
Graham Niepel; Rashid H Bibani; Janek Vilisaar; Robert Langley; Christopher M Bradshaw; Elemer Szabadi; Cris S Constantinescu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-2
Journal Detail:
Title:  Neuropharmacology     Volume:  -     ISSN:  1873-7064     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
Division of Academic Clinical Neurology, School of Clinical Sciences, University of Nottingham and Nottingham University Hospital Trust, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
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