Aktuelle Neurologie 2008; 35(9): 425-429
DOI: 10.1055/s-0028-1090051
Originalarbeit

© Georg Thieme Verlag KG Stuttgart · New York

Fatigue bei therapierten und untherapierten Patienten mit schubförmiger und sekundär progredienter Multipler Sklerose

Fatigue in Treated and Untreated Patients with Relapsing-Remitting and Secondary Progressive Multiple SclerosisÖ.  Yaldizli1 , Z.  Katsarava2 , S.  Vago2 , V.  Limmroth3 , N.  Putzki1 , 2
  • 1Klinik für Neurologie, Kantonsspital St. Gallen, St. Gallen, Schweiz
  • 2Klinik für Neurologie des Universitätsklinikums Essen, Essen, Deutschland
  • 3Neurologische Klinik, Kliniken der Stadt Köln, Köln-Mehrheim
Further Information

Publication History

Publication Date:
17 November 2008 (online)

Zusammenfassung

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 Prävalenz und Schwere von Fatigue unter den verschiedenen krankheitsmodifizierenden Therapien zu untersuchen. Methode Epidemiologische Querschnittsuntersuchung an 343 konsekutiven MS-Patienten zwischen November 2003 und Oktober 2004. Fatigue wurde mittels Fatigue Severity Scale (FSS) gemessen. Die Analyse umfasst Patienten mit schubförmiger oder sekundär progredienter MS. Die 3 Behandlungsgruppen (keine Therapie, Immunmodulation, Immunsuppression) wurden mittels univariater Analyse mit dem FSS korreliert. Um mögliche Effekte von Alter, Geschlecht, Verlaufsform, Schubrate, Krankheitsdauer, neurologischem Status in Form von der Expanded Disability Status Scale (EDSS) auszuschließen wurde eine rückwärtsgerichte logistische Regressionsanalyse durchgeführt. Ergebnisse 242 Patienten wurden in diese Analyse eingeschlossen. Die Prävalenz von schwerer Fatigue (FSS ≥ 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 Immunsuppression und OR 0,95; p = 0,85 für Immunmodulation). Schlussfolgerung Obwohl die krankheitsmodifizierende Therapie bei MS die klinische und subklinische 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 investigate a possible association between MS-related fatigue syndrome and disease modifying therapy. Methods A cross-sectional study in 343 consecutive patients with MS between Nov 2003 and Oct 2004 was undertaken. Fatigue was assessed with the Fatigue Severity Scale (FSS). This analysis compromises patients with relapsing-remitting and secondary progressive MS. Three treatment groups („no therapy”, „immunomodulation” and „immunosuppression”) 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 disability assessed by the Expanded Disability Status Scale (EDSS). Results We included 242 patients in this analysis. The prevalence of severe fatigue (FSS ≥ 5) was 51 %. In a multivariate logistic regression analysis controlled for age, course of disease, duration of disease and EDSS) there was no significant association between „no treatment”, „immunomodulation”, „immunosuppression” and fatigue (OR 1.34, p = 0.38 for immunosuppression and OR 0.95, p = 0.85 for immunomodulation). Conclusions Although disease-modifying therapies in MS effectively reduce disease activity, they do not appear to have an significant effect on MS-related fatigue.

Literatur

  • 1 Krupp L B, Alvarez L A, LaRocca N G. et al . Fatigue in multiple sclerosis.  Arch Neurol. 1988;  45 435-437
  • 2 Krupp L B, LaRocca N G, Muir-Nash J. et al . The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus.  Arch Neurol. 1989;  46 1121-1123
  • 3 Freal J E, Kraft G H, Coryell J K. Symptomatic fatigue in multiple sclerosis.  Arch Phys Med Rehabil. 1984;  65 135-138
  • 4 Fisk J D, Pontrefact A, Ritvo P G. et al . The impact of fatigue on patients with multiple sclerosis.  Can J Neurol Sci. 1994;  21 9-14
  • 5 Krupp L B, Pollina D A. Mechanisms and management of fatigue in progressive neurological disorders.  Curr Opin Neurol. 1996;  9 456-460
  • 6 Schwarz C E, Coulthard-Morris L, Zeng Q. Psychosocial correlates of fatigue in multiple sclerosis.  Arch Phys Med Rehabil. 1996;  9 165-170
  • 7 Bakshi R, Milettich R S, Henschel K. et al . Fatigue in multiple sclerosis: cross-sectional correlation with brain MRI findings in 71 patients.  Neurology. 1999;  53 1151-1153
  • 8 Colosimo C, Milleforini E, Grasso M G. et al . Pattern of cognitive impairment in relapsing-remitting and chronic progressive multiple sclerosis.  Neuropsychiatry Neuropsychol Behav Neurol. 1994;  7 194-210
  • 9 Giovannoni G, Thompson A J, Miller D H. et al . Fatigue is not associated with raised inflammatory markers in multiple sclerosis.  Neurology. 2001;  57 676-681
  • 10 Bakshi R, Shaikh Z A, Miletich R S. et al . Fatigue in multiple sclerosis and its relationship to depression and neurologic disability.  Mult Scler. 2000;  6 181-185
  • 11 Kroencke D C, Lynch S G, Denney D R. Fatigue in multiple sclerosis: relationship to depression, disability, and disease pattern.  Mult Scler. 2000;  6 131-136
  • 12 Branas P, Jordan R, Fry-Smith A. et al . Treatments for fatigue in multiple sclerosis: a rapid and systematic review.  Health Technol Assess. 2000;  4 41-61
  • 13 Stankoff B, Waubant E, Confavreux C. et al . Modafinil for fatigue in MS. A randomized placebo-controlled double-blind study.  Neurology. 2005;  64 1139-1143
  • 14 Rieckmann P, Toyka K V. MSTCG . Escalating immunotherapy of multiple sclerosis. New aspects and practical application.  J Neurol. 2004;  251 1329-1339
  • 15 Metz L M, Patten S B, Archibald C J. et al . The effect of immunomodulatory treatment on multiple sclerosis fatigue.  J Neurol Neurosurg Psychiatr. 2004;  75 1045-1047
  • 16 Jacobs L D, Cookfair D L, Rudick R A. et al . Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis.The Multiple Sclerosis Collaborative research group.  Ann Neurol. 1996;  39 285-294
  • 17 Bergamaschi R, Romani A, Versino M. et al . Clinical aspects of fatigue in multiple sclerosis.  Funct Neurol. 1997;  12 247-251
  • 18 Colosimo C. et al . Fatigue in MS is associated with specific clinical feature.  Acta Neurol Scand. 1995;  92 353-355
  • 19 Confavreux C, Saddier P, Grimaud J. et al . Risk of cancer from azathioprine therapy in multiple sclerosis: a case-control study.  Neurology. 1996;  46 1607-1612
  • 20 Jeffery D R, Herndon R. Review of mitoxantrone in the treatment of multiple sclerosis.  Neurology. 2004;  63 S19-S24
  • 21 Poser C M, Paty D W, Scheinberg L. et al . New diagnostic criteria for multiple sclerosis: guidelines for research protocols.  Ann Neurol. 1983;  13 227-231
  • 22 Zung W W. A self-rating depression scale.  Arch Gen Psychiat. 1965;  12 63-70
  • 23 Zung W W. The depression status inventory: an adjunct to the self-rating depression scale.  J Clin Psychol. 1972;  28 539-543
  • 24 Kiljunen M, Sulkava P, Niinistö L. et al . Depression measured by the Zung Depression Status Inventory is very rare in finnish population aged 85 and over Int.  Psychogeriatrics. 1997;  9 359-368
  • 25 Flachenecker P, Kümpfel T, Kallmann B. et al . Fatigue in Multiple Sclerosis: a comparison of different rating scales and correlation to clinical parameter.  Mult Scler. 2002;  8 523-526
  • 26 Lerdal A, Celius E G, Moum T. Fatigue and its association with sociodemographic variables among multiple sclerosis patients.  Mult Scler. 2003;  9 509-514
  • 27 Putzki N, Katsarava Z, Vago S. et al . Prevalence and severity of multiple-sclerosis-associated fatigue in treated and untreated patients.  Eur Neurol. 2008;  59 136-142
  • 28 Brod S A, Marshall G D, Henninger E M. et al . Interferon-beta 1b treatment decreases tumor necrosis factor-alpha and increases interleukin-6 production in multiple sclerosis.  Neurology. 1996;  46 1633-1638
  • 29 Martinez-Caceres E M, Rio J, Barrau M. et al . Amelioration of flu-like symptoms at the onset of interferon-beta 1b therapy in multiple sclerosis by low dose steroids is related to a decrease in interleukin-6 induction.  Ann Neurol. 1998;  44 682-685
  • 30 Salmaggi A, Corsini E, La Mantia L. et al . Immunological monitoring of azathioprine treatment in multiple sclerosis patients.  J Neurol. 1997;  244 167-174
  • 31 Heesen C, Nawrath L, Reich C. et al . Fatigue in multiple sclerosis: an example of cytokine mediated sickness behavious?.  J Neurol Neurosurg Psychiatr. 2006;  77 34-39
  • 32 Gbadamosi J, Buhmann C, Tessmer W. et al . Effects of mitoxantrone on multiple sclerosis patients' lymphocyte subpopulations and production of immunoglobulin, TNF-alpha and IL-10.  Eur Neurol. 2003;  49 137-141
  • 33 Oezency V, Kouwenhoven M, Teleshova N. et al . Multiple sclerosis: pro- and anti-inflammatory cytokines and metalloproteinases are affected differentially by treatment with IFN-beta.  J Neuroimmunol. 2000;  108 236-343
  • 34 Duddy M E, Armstrong M A, Crockard A D. et al . Changes in plasma cytokines induced by interferon-beta 1a treatment in patients with multiple sclerosis.  J Neuroimmunol. 1999;  101 98-109
  • 35 Tellez N, Rio J, Tintore M. et al . Fatigue in multiple sclerosis persists over time. A longitudinal study.  J Neurol. 2006;  253 1466-1470
  • 36 Flachenecker P, Bihler I, Weber F. et al . Cytokine mRNA expression in patients with multiple sclerosis and fatigue.  Mult Scler. 2004;  10 165-169
  • 37 Marrie R A, Fisher E, Miller D M. et al . Association of fatigue and brain atrophy in multiple sclerosis.  J Neurol Sci. 2005;  228 161-166
  • 38 Mainero C, Faroni J, Gaserini C. et al . Fatigue and magnetic resonance imaging activity in multiple sclerosis.  J Neurol. 1999;  246 454-458

Dr. Özgür Yaldizli

Neurologische Klinik, Kantonsspital St. Gallen

Rorschacherstr. 95

9007 St. Gallen

Email: Oezguer.yaldizli@kssg.ch

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