Zusammenfassung
Das chronische Erschöpfbarkeitssyndrom (CFS) ist ein
Symptomenkomplex, der, einem Katalog von Klassifikationskriterien folgend, nach
Ausschluss anderer, die chronische abnorme Erschöpfbarkeit evtl.
erklärender Erkrankungen die Zuordnung des Beschwerdebildes zu einem CFS
zulässt. Dieser „Rahmen” wurde zur Vereinheitlichung der
Durchführung wissenschaftlicher Studien konzipiert. Solche Studien
erbrachten bisher zahlreiche Hinweise auf mögliche Störungen der
komplexen Interaktionen von HPA-Achse, Neurotransmittersystemen und Mediatoren
des Immunsystems, jedoch keinen spezifischen diagnostischen Marker. Die
bisherigen Forschungsergebnisse zu Ätiologie und Pathogenese werden ebenso
referiert wie die Studien zu möglichen Therapieansätzen.
Abstract
Chronic fatigue syndrome (CFS) is an illness defined exclusively by
a group of symptoms, according to a case definition developed under the
leadership of the US Centers for Disease Control and Prevention (CDC). All of
the symptoms are nonspecific and occurring in many illnesses. There are no
biological markers or any results from other methods which provide a specific
diagnostic test for clinical use. However, there is evidence from many studies
that alterations within the complex network of HPA axis, neurotransmitter
systems and mediators of the immune system play a crucial role for the
pathogenesis of CFS. Both these findings and the therapeutic approaches are
reviewed.
-
1
Acheson E D.
The clinical syndrome variously called benign myalgic
encephalomyelitis, Iceland diseases and epidemic neuromyasthenia.
Am J Med.
1959;
26
569-595
-
2
Allain T J, Bearn J A, Coskeran P, Jones J, Checkley A, Butler J, Wessely S, Miell J P.
Changes in growth hormone, insulin, insulinlike growth
factors (IGFs), and IGF-binding protein-1 in chronic fatigue syndrome.
Biol Psychiatry.
1997;
41
567-573
-
3
Bakheit A M, Behan P O, Dinan T G, Gray C E, O’Keane V.
Possible upregulation of hypothalamic 5-hydroxytryptamine
receptors in patients with postviral fatigue syndrome.
BMJ (Clinical Research Ed.).
1992;
304
1010-1012
-
4
Bakheit A M, Behan P O, Watson W S, Morton J J.
Abnormal arginine-vasopressin secretion and water metabolism
in patients with postviral fatigue syndrome.
Acta Neurol Scand.
1993;
87
234-238
-
5
Barnes P R, Taylor D J, Kemp G J, Radda G K.
Skeletal muscle bioenergetics in the chronic fatigue
syndrome.
J Neurol Neurosurg Psychiatry.
1993;
56
679-683
-
6
Beard G M.
Neurasthenia or nervous exhaustion.
Boston Med Surg.
1869;
J III
217-221
-
7
Bearn J, Allain T, Coskeran P, Munro N, Butler J, McGregor A, Wessely S.
Neuroendocrine responses to d-fenfluramine and
insulin-induced hypoglycemia in chronic fatigue syndrome.
Biol Psychiatry.
1995;
37
245-252
-
8
Behan P O, Behan W M.
Postviral fatigue syndrome.
Crit Rev Neurobiol.
1988;
4
157-178
-
9
Behan P O, Behan W M, Gow J W, Cavanagh H, Gillespie S.
Enteroviruses and postviral fatigue syndrome (discussion
154 - 149).
Ciba Found Symp.
1993;
173
146-154
-
10
Behan P O, Behan W M, Horrobin D.
Effect of high doses of essential fatty acids on the
postviral fatigue syndrome.
Acta Neurol Scand.
1990;
82
209-216
-
11
Behan W M, More I A, Behan P O.
Mitochondrial abnormalities in the postviral fatigue
syndrome.
Acta Neuropathol (Berl).
1991;
83
61-65
-
12
Bennett A L, Fagioli L R, Schur P H, Schacterle R S, Komaroff A L.
Immunoglobulin subclass levels in chronic fatigue
syndrome.
J Clin Immunol.
1996;
16
315-320
-
13
Bennett A L, Mayes D M, Fagioli L R, Guerriero R, Komaroff A L.
Somatomedin C (insulin-like growth factor I) levels in
patients with chronic fatigue syndrome.
J Psychiatr Res.
1997;
31
91-96
-
14
Brooks J C, Roberts N, Whitehouse G, Majeed T.
Proton magnetic resonance spectroscopy and morphometry of the
hippocampus in chronic fatigue syndrome.
Br J Radiol.
2000;
73
1206-1208
-
15
Buchwald D, Ashley R L, Pearlman T, Kith P, Komaroff A L.
Viral serologies in patients with chronic fatigue and chronic
fatigue syndrome.
J Med Virol.
1996;
50
25-30
-
16
Buchwald D, Garrity D.
Comparison of patients with chronic fatigue syndrome,
fibromyalgia, and multiple chemical sensitivities.
Arch Intern Med.
1994;
154
2049-2053
-
17
Buchwald D, Umali P, Umali J, Kith P, Pearlman T, Komaroff A L.
Chronic fatigue and the chronic fatigue syndrome: prevalence
in a Pacific Northwest health care system.
Ann Intern Med.
1995;
123
81-88
-
18
Buchwald D, Wener M H, Pearlman T, Kith P.
Markers of inflammation and immune activation in chronic
fatigue and chronic fatigue syndrome.
J Rheumatol.
1997;
24
372-376
-
19
Butler S, Chalder T, Ron M, Wessely S.
Cognitive behaviour therapy in chronic fatigue syndrome.
Journal Of Neurology, Neurosurgery And Psychiatry.
1991;
54
153-158
-
20
Byrne E, Trounce I.
Chronic fatigue and myalgia syndrome: mitochondrial and
glycolytic studies in skeletal muscle.
J Neurol Neurosurg Psychiatry.
1987;
50
743-746
-
21
Cleare A J, Bearn J, Allain T, McGregor A, Wessely S, Murray R M, O’Keane V.
Contrasting neuroendocrine responses in depression and
chronic fatigue syndrome.
J Affect Disord.
1995;
34
283-289
-
22
Cleare A J, Heap E, Malhi G S, Wessely S, O’Keane V, Miell J.
Low-dose hydrocortisone in chronic fatigue syndrome: a
randomised crossover trial.
Lancet.
1999;
353
455-458
-
23
Coyle P K, Krupp L B, Doscher C, Amin K.
Borrelia burgdorferi reactivity in patients with severe
persistent fatigue who are from a region in which Lyme disease is endemic.
Clin Infect Dis.
1994;
18 Suppl 1
S24-27
-
24
Crofford L J.
The hypothalamic-pituitary-adrenal stress axis in
fibromyalgia and chronic fatigue syndrome.
Z Rheumatol.
1998;
57
67-71
-
25
Crofford L J, Demitrack M A.
Evidence that abnormalities of central neurohormonal systems
are key to understanding fibromyalgia and chronic fatigue syndrome.
Rheum Dis Clin North Am.
1996;
22
267-284
-
26
de Meirleir K, Bisbal C, Campine I, de Becker P, Salehzada T, Demettre E, Lebleu B.
A 37 kDa 2 - 5A binding protein as a
potential biochemical marker for chronic fatigue syndrome.
Am J Med.
2000;
108
99-105
-
27
Deale A, Chalder T, Marks I, Wessely S.
Cognitive behavior therapy for chronic fatigue syndrome: a
randomized controlled trial.
Am J Psychiatry.
1997;
154
408-414
-
28
Demitrack M A.
Chronic fatigue syndrome and fibromyalgia. Dilemmas in
diagnosis and clinical management.
Psychiatr Clin North Am.
1998;
21
671-692
-
29
Demitrack M A, Crofford L J.
Evidence for and pathophysiologic implications of
hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic
fatigue syndrome.
Ann N Y Acad Sci.
1998;
840
684-697
-
30
Dismukes W E, Wade J S, Lee J Y, Dockery B K, Hain J D.
A randomized, double-blind trial of nystatin therapy for the
candidiasis hypersensitivity syndrome.
N Engl J Med.
1990;
323
1717-1723
-
31
Dykman K D, Tone C, Ford C, Dykman R A.
The effects of nutritional supplements on the symptoms of
fibromyalgia and chronic fatigue syndrome.
Integr Physiol Behav Sci.
1998;
33
61-71
-
32
Evengard B, Briese T, Lindh G, Lee S, Lipkin W I.
Absence of evidence of Borna disease virus infection in
Swedish patients with Chronic Fatigue Syndrome.
J Neurovirol.
1999;
5
495-499
-
33
Fischler B, Le B on, Hoffmann G, Cluydts R, Kaufman L, de Meirleir K.
Sleep anomalies in the chronic fatigue syndrome. A
comorbidity study.
Neuropsychobiology.
1997;
35
115-122
-
34
Fukuda K, Straus S E, Hickie I, Sharpe M C, Dobbins J G, Komaroff A.
The chronic fatigue syndrome: a comprehensive approach to its
definition and study. International Chronic Fatigue Syndrome Study Group.
Annals Intern Med.
1994;
121
953-959
-
35
Goodnick P J, Sandoval R.
Psychotropic treatment of chronic fatigue syndrome and
related disorders.
J Clin Psychiatry.
1993;
54
13-20
-
36
Gow J W, Behan W M, Simpson K, McGarry F, Keir S, Behan P O.
Studies on enterovirus in patients with chronic fatigue
syndrome.
Clin Infect Dis.
1994;
18 Suppl 1
126-129
-
37
Gray J B, Martinovic A M.
Eicosanoids and essential fatty acid modulation in chronic
disease and the chronic fatigue syndrome published erratum appears in Med
Hypotheses 1995 Aug;45(2): 219.
Medical Hypotheses.
1994;
43
31-42
-
38
Holmes G P, Kaplan J E, Gantz N M, Komaroff A L, Schonberger L B, Straus S E, Jones J F, Dubois R E, Cunningham-Rundles C, Pahwa S. et al .
Chronic fatigue syndrome: a working case definition.
Ann Intern Med.
1988;
108
387-389
-
39
Ichise M, Salit I E, Abbey S E, Chung D G, Gray B, Kirsh J C, Freedman M.
Assessment of regional cerebral perfusion by 99Tcm-HMPAO
SPECT in chronic fatigue syndrome.
Nucl Med Commun.
1992;
13
767-772
-
40
Jones J F, Ray C G, Minnich L L, Hicks M J, Kibler R, Lucas D O.
Evidence for active Epstein-Barr virus infection in patients
with persistent, unexplained illnesses: elevated anti-early antigen
antibodies.
Ann Intern Med.
1985;
102
1-7
-
41
Kent-Braun J A.
Central and peripheral contributions to muscle fatigue in
humans during sustained maximal effort.
Eur J Appl Physiol Occup Physiol.
1999;
80
57-63
-
42
Kent-Braun J A, Sharma K R, Weiner M W, Massie B, Miller R G.
Central basis of muscle fatigue in chronic fatigue
syndrome.
Neurology.
1993;
43
125-131
-
43
Komaroff A L.
The biology of chronic fatigue syndrome.
Am J Med.
2000;
108
169-171
-
44
Landay A L, Jessop C, Lennette E T, Levy J A.
Chronic fatigue syndrome: clinical condition associated with
immune activation.
Lancet.
1991;
338
707-712
-
45
Lawrie S M, Manders D N, Geddes J R, Pelosi A J.
A population-based incidence study of chronic fatigue.
Psychol Med.
1997;
27
343-353
-
46
Lawrie S M, Pelosi A J.
Chronic fatigue syndrome in the community. Prevalence and
associations.
Br J Psychiatry.
1995;
166
793-797
-
47
Le B on, Hoffmann G, Murphy J, de Meirleir K, Cluydts R, Pelc I.
How significant are primary sleep disorders and sleepiness in
the chronic fatigue syndrome?.
Sleep Res Online.
2000;
3
43-48
-
48
Lindh G, Samuelson A, Hedlund K O, Evengard B, Lindquist L, Ehrnst A.
No findings of enteroviruses in Swedish patients with chronic
fatigue syndrome.
Scand J Infect Dis.
1996;
28
305-307
-
49
Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J.
A double-blind, placebo-controlled trial of intravenous
immunoglobulin therapy in patients with chronic fatigue syndrome.
Am J Med.
1990;
89
561-568
-
50
Lloyd A R, Hickie I, Boughton C R, Spencer O, Wakefield D.
Prevalence of chronic fatigue syndrome in an Australian
population.
Med J Aust.
1990;
153
522-528
-
51
Manian F A.
Simultaneous measurement of antibodies to Epstein-Barr virus,
human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses
in chronic fatigue syndrome: is there evidence of activation of a nonspecific
polyclonal immune response?.
Clin Infect Dis.
1994;
19
448-453
-
52
Manu P, Lane T J, Matthews D A, Castriotta R J, Watson R K, Abeles M.
Alpha-delta sleep in patients with a chief complaint of
chronic fatigue.
South Med J.
1994;
87
465-470
-
53
Mawle A C, Nisenbaum R, Dobbins J G, Gary H E, Jr. , Stewart J A, Reyes M, Steele L, Schmid D S, Reeves W C.
Immune responses associated with chronic fatigue syndrome: a
case-control study.
J Infect Dis.
1997;
175
136-141
-
54
Moldofsky H.
Fibromyalgia, sleep disorder and chronic fatigue
syndrome.
Ciba Found Symp.
1993;
173
262-271
-
55
Nakaya T, Takahashi H, Nakamur Y, Kuratsune H, Kitani T, Machii T, Yamanishi K, Ikuta K.
Borna disease virus infection in two family clusters of
patients with chronic fatigue syndrome.
Microbiol Immunol.
1999;
43
679-689
-
56
Neeck G, Crofford L J.
Neuroendocrine perturbations in fibromyalgia and chronic
fatigue syndrome.
Rheum Dis Clin North Am.
2000;
26
989-1002
-
57
Nix W A, Egle U T.
Das chronische Erschöpfbarkeitssyndrom.
Akt Neurologie.
1998;
25
6-12
-
58
Norregaard J, Bulow P M, Prescott E, Jacobsen S, Danneskiold-Samsoe B.
A four-year follow-up study in fibromyalgia. Relationship to
chronic fatigue syndrome.
Scand J Rheumatol.
1993;
22
35-38
-
59
Parker A J, Wessely S, Cleare A J.
The neuroendocrinology of chronic fatigue syndrome and
fibromyalgia.
Psychol Med.
2001;
31
1331-1345
-
60
Peakman M, Deale A, Field R, Mahalingam M, Wessely S.
Clinical improvement in chronic fatigue syndrome is not
associated with lymphocyte subsets of function or activation.
Clin Immunol Immunopathol.
1997;
82
83-91
-
61
Peterson P K, Pheley A, Schroeppel J, Schenck C, Marshall P, Kind A, Haugland J M, Lambrecht L J, Swan S, Goldsmith S.
A preliminary placebo-controlled crossover trial of
fludrocortisone for chronic fatigue syndrome.
Arch Intern Med.
1998;
158
908-914
-
62
Peterson P K, Shepard J, Macres M, Schenck C, Crosson J, Rechtman D, Lurie N.
A controlled trial of intravenous immunoglobulin G in chronic
fatigue syndrome.
Am J Med.
1990;
89
554-560
-
63
Plioplys A V, Plioplys S.
Amantadine and L-carnitine treatment of Chronic Fatigue
Syndrome.
Neuropsychobiology.
1997;
35
16-23
-
64
Preedy V R, Smith D G, Salisbury J R, Peters T J.
Biochemical and muscle studies in patients with acute onset
post-viral fatigue syndrome.
J Clin Pathol.
1993;
46
722-726
-
65
Price J R, Couper J.
Cognitive behaviour therapy for adults with chronic fatigue
syndrome.
Cochrane Database Syst Rev.
2000;
CD
001 027
-
66
Prins J B, Bleijenberg G, Bazelmans E, Elving L D, de Boo T M, Severens J L, van der Wilt G J, Spinhoven P, van der Meer J W.
Cognitive behaviour therapy for chronic fatigue syndrome: a
multicentre randomised controlled trial.
Lancet.
2001;
357
841-847
-
67
Reeves W C, Stamey F R, Black J B, Mawle A C, Stewart J A, Pellett P E.
Human herpesviruses 6 and 7 in chronic fatigue syndrome: a
case-control study.
Clin Infect Dis.
2000;
31
48-52
-
68
Rowe P C, Calkins H, DeBusk K, McKenzie R, Anand R, Sharma G, Cuccherini B A, Soto N, Hohman P, Snader S, Lucas K E, Wolff M, Straus S E.
Fludrocortisone acetate to treat neurally mediated
hypotension in chronic fatigue syndrome: a randomized controlled trial.
Jama.
2001;
285
52-59
-
69
Schutzer S E, Natelson B H.
Absence of Borrelia burgdorferi-specific immune complexes in
chronic fatigue syndrome.
Neurology.
1999;
53
1340-1341
-
70
Schwartz R B, Komaroff A L, Garada B M, Gleit M, Doolittle T H, Bates D W, Vasile R G, Holman B L.
SPECT imaging of the brain: comparison of findings in
patients with chronic fatigue syndrome, AIDS dementia complex, and major
unipolar depression.
AJR.
1994;
162
943-951
-
71
Sharpe M, Clements A, Hawton K, Young A H, Sargent P, Cowen P J.
Increased prolactin response to buspirone in chronic fatigue
syndrome.
Journal Of Affective Disorders.
1996;
41
71-76
-
72
Sharpe M, Hawton K, Clements A, Cowen P J.
Increased brain serotonin function in men with chronic
fatigue syndrome.
BMJ (Clinical Research Ed.).
1997;
315
164-165
-
73
Sharpe M C, Archard L C, Banatvala J E, Borysiewicz L K, Clare A W, David A, Edwards R H, Hawton K E, Lambert H P, Lane R J. et al .
A report-chronic fatigue syndrome: guidelines for
research.
J R Soc Med.
1991;
84
118-121
-
74
Spaeth M, Stratz T, Schmalisch P, Mueller W, Pongratz D.
Carnitine deficiency and fibromyalgia.
Arthritis Rheum.
1999;
42
150
-
75
Späth M, Welzel D, Farber L.
Treatment of chronic fatigue syndrome with 5-HT3 receptor
antagonists-preliminary results.
Scand J Rheumatol Suppl.
2000;
113
72-77
-
76
Straus S E, Dale J K, Peter J B, Dinarello C A.
Circulating lymphokine levels in the chronic fatigue
syndrome.
J Infect Dis.
1989;
160
1085-1086
-
77
Straus S E, Dale J K, Tobi M, Lawley T, Preble O, Blaese R M, Hallahan C, Henle W.
Acyclovir treatment of the chronic fatigue syndrome. Lack of
efficacy in a placebo-controlled trial.
N Engl J Med.
1988;
319
1692-1698
-
78
Suhadolnik R J, Peterson D L, O’Brien K, Cheney P R, Herst C V, Reichenbach N L, Kon N, Horvath S E, Iacono K T, Adelson M E, de Meirleir K, de Becker P, Charubala R, Pfleiderer W.
Biochemical evidence for a novel low molecular weight
2 - 5A-dependent RNase L in chronic fatigue syndrome.
J Interferon Cytokine Res.
1997;
17
377-385
-
79
Swanink C M, van der Meer J W, Vercoulen J H, Bleijenberg G, Fennis J F, Galama J M.
Epstein-Barr virus (EBV) and the chronic fatigue syndrome:
normal virus load in blood and normal immunologic reactivity in the EBV
regression assay.
Clin Infect Dis.
1995;
20
1390-1392
-
80
Swanink C M, Vercoulen J H, Bleijenberg G, Fennis J F, Galama J M, van der Meer J W.
Chronic fatigue syndrome: a clinical and laboratory study
with a well matched control group.
J Intern Med.
1995;
237
499-506
-
81
Tobi M, Morag A, Ravid Z, Chowers I, Feldman-Weiss V, Michaeli Y, Ben-Chetrit E, Shalit M, Knobler H.
Prolonged atypical illness associated with serological
evidence of persistent Epstein-Barr virus infection.
Lancet.
1982;
1
61-64
-
82
Vercoulen J H, Swanink C M, Zitman F G, Vreden S G, Hoofs M P, Fennis J F, Galama J M, van der Meer J W, Bleijenberg G.
Randomised, double-blind, placebo-controlled study of
fluoxetine in chronic fatigue syndrome.
Lancet.
1996;
347
858-861
-
83
Vollmer-Conna U, Hickie I, Hadzi-Pavlovic D, Tymms K, Wakefield D, Dwyer J, Lloyd A.
Intravenous immunoglobulin is ineffective in the treatment of
patients with chronic fatigue syndrome.
Am J Med.
1997;
103
38-43
-
84
Wessely S, Chalder T, Hirsch S, Wallace P, Wright D.
The prevalence and morbidity of chronic fatigue and chronic
fatigue syndrome: a prospective primary care study.
Am J Public Health.
1997;
87
1449-1455
-
85
Wessely S, Nimnuan C, Sharpe M.
Functional somatic syndromes: one or many ?.
Lancet.
1999;
354
936-939
-
86
Wessely S, Powell R.
Fatigue syndromes: a comparison of chronic
“postviral” fatigue with neuromuscular and affective
disorders.
J Neurol Neurosurg Psychiatry.
1989;
52
940-948
-
87
Whiting P, Bagnall A M, Sowden A J, Cornell J E, Mulrow C D, Ramirez G.
Interventions for the treatment and management of chronic
fatigue syndrome: a systematic review.
Jama.
2001;
286
1360-1368
Dr. med. M. Späth
Friedrich-Baur-Institut · Universität
München
Ziemssenstraße 1a · 80336 München ·
Phone: 089/5160-7420
Fax: 089/5160-7422
Email: Michael.Spaeth@lrz.uni-muenchen.de