Fatigue is one of the most frequent and most disabling symptoms in multiple sclerosis (MS). We investigated the possible association of the MS-related fatigue syndrome with the available disease-modifying therapies and the main disease characteristics in a cross-sectional study on 320 consecutive patients. The prevalence of severe fatigue (Fatigue Severity Scale score ≧5) was 50%. In a multivariate regression model controlling for age, disease subtype, duration and disability we did not find a significant association between the use of immunosuppressive or immunomodulatory drugs compared to no treatment (OR = 1.34, p = 0.38 for immunosuppressants; OR = 0.95, p = 0.85 for immune-modulating agents). Although all used disease-modifying agents successfully reduce disease activity and inflammation, they do not appear to exhibit a significant effect on MS-related fatigue.

Azathioprine (Aza) is a widely used immunosuppressive drug in multiple sclerosis (MS) treatment. Recently, the incidence of secondary myelodysplastic syndromes (sMDS) associated with a poor prognosis was found to be elevated in patients treated with Aza for non-malign disorders. Three hundred and seventeen MS patients were retrospectively analysed and complete blood counts were examined for those exposed to Aza. We identified one case of sMDS (cumulative dose 627 g) in a young patient and two further malignancies (cumulative doses 27 g and 54 g) in the Aza group (n = 81; 3.7%). In the non-Aza (n = 236) group, five malignancies (2.1%, P = 0.419) were identified. Including our patient, four cases of sMDS after long-term Aza therapy in MS have been reported so far. Cases suggest a time- and dose-dependent risk of sMDS in long-term therapy of MS with Aza. Long-term Aza therapy needs careful monitoring.

Background: The pathophysiology of multiple sclerosis (MS)-associated fatigue is poorly understood. Immunological mechanisms may play a role. Alterations in immunological profile indicate a chronic immune activation in MS patients with fatigue. T-regulatory (Treg) cells seem to play a key role in coordinating autoimmune mechanisms in MS. This is the first study investigating the relationship between Treg cell function and fatigue in MS patients. Methods: In this cross-sectional in vitro, ex vivo study, we isolated peripheral blood mononuclear cells (PBMCs) from 20 MS patients with fatigue, determined lymphocyte subsets by flow cytometry and suppressive function of Treg cells in PBMC cultures with antigen stimulation. Forkhead box protein 3 expression was evaluated by PCR. Results were compared with 20 MS patients without fatigue and with 19 healthy controls. Results: Leukocytes and lymphocyte subsets including Treg cell frequency did not differ in patients with and without fatigue. Co-culturing of Treg cells with CD4+CD25– cells did not lead to a significant suppression of myelin basic protein- and pokeweed mitogen-induced proliferation in MS patients in contrast to healthy controls. There were no statistical differences between MS patients with and without fatigue regarding this suppression activity. Conclusions: Fatigue seems not to be associated with impaired function of Treg cells in untreated MS patients.

Hintergrund Fatigue ist eines der häufigsten und beeinträchtigendsten Symptome bei multipler Sklerose (MS). Die Ursachen für Fatigue sind weitgehend unklar. Ziel dieser Studie ist, die Prä− valenz und Schwere von Fatigue unter den ver− schiedenen krankheitsmodifizierenden Thera− pien zu untersuchen. Methode Epidemiologische Querschnittsunter− suchung an 343 konsekutiven MS−Patienten zwi− schen November 2003 und Oktober 2004. Fa− tigue wurde mittels Fatigue Severity Scale (FSS) gemessen. Die Analyse umfasst Patienten mit schubförmiger oder sekundär progredienter MS. Die 3 Behandlungsgruppen (keine Therapie, Im− munmodulation, Immunsuppression) wurden mittels univariater Analyse mit dem FSS korre− liert. Um mögliche Effekte von Alter, Geschlecht, Verlaufsform, Schubrate, Krankheitsdauer, neu− rologischem Status in Form von der Expanded Disability Status Scale (EDSS) auszuschließen wurde eine rückwärtsgerichte logistische Re− gressionsanalyse durchgeführt. Ergebnisse 242 Patienten wurden in diese Ana− lyse eingeschlossen. Die Prävalenz von schwerer Fatigue (FSS ³ 5) war 51 %. In der multivariaten Regressionsanalyse (kontrolliert für Alter, MS− Typ, MS−Dauer und Behinderung) fand sich keine signifikante Assoziation zwischen dem Einsatz immunsuppressiver und immunmodulatorischer Therapien und Fatigue im Vergleich zu keiner Therapie (OR 1,34; p = 0,38 für Immunsuppressi− on und OR 0,95; p = 0,85 für Immunmodulation). Schlussfolgerung Obwohl die krankheitsmodifi− zierende Therapie bei MS die klinische und sub− klinische Krankheitsaktivität reduziert, scheint sie keinen Einfluss auf Prävalenz und Schwere der Fatigue−Symptomatik zu haben.Abstract ! Background Fatigue is one of the most common and disabling symptoms in multiple sclerosis (MS). The pathophysiology of fatigue is not fully understood. The aim of this study was to investi− gate a possible association between MS−related fatigue syndrome and disease modifying therapy. Methods A cross−sectional study in 343 conse− cutive patients with MS between Nov 2003 and Oct 2004 was undertaken. Fatigue was assessed with the Fatigue Severity Scale (FSS). This analy− sis compromises patients with relapsing−remit− ting and secondary progressive MS. Three treat− ment groups (¹no therapy", ¹immunomodula− tion" and ¹immunosuppression") were correlated with FSS by univariate analysis. We performed a stepwise backward logistic regression analysis to evaluate interaction with age, sex, course of disease, relapse rate, duration of disease or dis− ability assessed by the Expanded Disability Sta− tus Scale (EDSS). Results We included 242 patients in this analy− sis. The prevalence of severe fatigue (FSS ³ 5) was 51 %. In a multivariate logistic regression analysis controlled for age, course of disease, duration of disease and EDSS) there was no significant asso− ciation between ¹no treatment", ¹immunomodu− lation", ¹immunosuppression" and fatigue (OR 1.34, p = 0.38 for immunosuppression and OR 0.95, p = 0.85 for immunomodulation). Conclusions Although disease−modifying thera− pies in MS...

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