期刊论文详细信息
BMC Medicine
Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics
Michael Maes2  Gerwyn Morris1 
[1] Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand;Department of Psychiatry, Deakin University, Geelong, Australia
关键词: Mitochondria;    Oxidative and nitrosative stress;    Autoimmunity;    Inflammation;    Chronic fatigue syndrome;    Myalgic encephalomyelitis;    Encephalomyelitis disseminata;   
Others  :  855698
DOI  :  10.1186/1741-7015-11-205
 received in 2013-06-16, accepted in 2013-08-15,  发布年份 2013
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【 摘 要 】

Background

‘Encephalomyelitis disseminata’ (multiple sclerosis) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are both classified as diseases of the central nervous system by the World Health Organization. This review aims to compare the phenomenological and neuroimmune characteristics of MS with those of ME/CFS.

Discussion

There are remarkable phenomenological and neuroimmune overlaps between both disorders. Patients with ME/CFS and MS both experience severe levels of disabling fatigue and a worsening of symptoms following exercise and resort to energy conservation strategies in an attempt to meet the energy demands of day-to-day living. Debilitating autonomic symptoms, diminished cardiac responses to exercise, orthostatic intolerance and postural hypotension are experienced by patients with both illnesses. Both disorders show a relapsing-remitting or progressive course, while infections and psychosocial stress play a large part in worsening of fatigue symptoms. Activated immunoinflammatory, oxidative and nitrosative (O+NS) pathways and autoimmunity occur in both illnesses. The consequences of O+NS damage to self-epitopes is evidenced by the almost bewildering and almost identical array of autoantibodies formed against damaged epitopes seen in both illnesses. Mitochondrial dysfunctions, including lowered levels of ATP, decreased phosphocreatine synthesis and impaired oxidative phosphorylation, are heavily involved in the pathophysiology of both MS and ME/CFS. The findings produced by neuroimaging techniques are quite similar in both illnesses and show decreased cerebral blood flow, atrophy, gray matter reduction, white matter hyperintensities, increased cerebral lactate and choline signaling and lowered acetyl-aspartate levels.

Summary

This review shows that there are neuroimmune similarities between MS and ME/CFS. This further substantiates the view that ME/CFS is a neuroimmune illness and that patients with MS are immunologically primed to develop symptoms of ME/CFS.

【 授权许可】

   
2013 Morris and Maes; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Disanto G, Berlanga AJ, Handel AE, Para AE, Burrell AM, Fries A, Handunnetthi L, De Luca GC, Morahan JM: Heterogeneity in multiple sclerosis: scratching the surface of a complex disease. Autoimm Dis 2010, 2011:932351.
  • [2]Huang YM, Liu X, Steffensen K, Sanna A, Arru G, Fois ML, Rosati G, Sotgiu S, Link H: Immunological heterogeneity of multiple sclerosis in Sardinia and Sweden. Mult Scler 2005, 11:16-23.
  • [3]Hohlfeld R, Wekerle H: Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: from pipe dreams to (therapeutic) pipelines. Proc Natl Acad Sci U S A 2004, 2004:14599-14606.
  • [4]Winkler AS, Blair D, Marsden JT, Peters TJ, Wessely S, Cleare AJ: Autonomic function and serum erythropoietin levels in chronic fatigue syndrome. J Psychosom Res 2004, 56:179-183.
  • [5]Morris G, Maes M: A neuro-immune model of myalgic encephalomyelitis/chronic fatigue syndrome. Metab Brain Dis 2012. Epub ahead of print
  • [6]Morris G, Anderson G, Galecki P, Berk M, Maes M: A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior. BMC Med 2013, 11:64.
  • [7]Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ: A report-chronic fatigue syndrome: guidelines for research. J R Soc Med 1991, 84:118-121.
  • [8]Morris G, Maes M: Case definitions and diagnostic criteria for myalgic encephalomyelitis and Chronic fatigue Syndrome: from clinical-consensus to evidence-based case definitions. Neuro Endocrinol Lett 2013, 34:185-199.
  • [9]Maes M: Nooit meer moe: CVS ontmaskerd. Brugge, Belgium: Zorro Uitgevers; 2010.
  • [10]Maes M, Twisk FN, Johnson C: Myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS), and chronic fatigue (CF) are distinguished accurately: Results of supervised learning techniques applied on clinical and inflammatory data. Psychiatr Res 2012, 200:754-760.
  • [11]Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles AC, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisbik S, Mena I, Mikovits JA, Miwa K, Murovska M, Pall ML, Stevens S: Myalgic encephalomyelitis: international consensus criteria. J Intern Med 2011, 270:327-338.
  • [12]Freeman R, Komaroff AL: Does the chronic fatigue syndrome involve the autonomic nervous system? Am J Med 1997, 102:357-364.
  • [13]Allen J, Murrary A, Di Maria C, Newton JL: Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis - a new potential diagnostic biomarker. Physiol Meas 2010, 33:231-241.
  • [14]Newton JL, Okonkwo O, Sutcliffe K, Seth A, Shin J, Jones DEJ: Symptoms of autonomic dysfunction in chronic fatigue syndrome. Q J Med 2007, 100:519-526.
  • [15]Mosqueda Garcia R, Furlan R, Snell M, Jacob G, Harris P: Primary sympathetic hyperadrenergic orthostatic tachycardia syndrome (HOT). Neurology 1997, 48:A147.
  • [16]Montague TJ, Marrie TJ, Klassen GA, Bewick DJ, Horacek BM: Cardiac function at rest and with exercise in the chronic fatigue syndrome. Chest 1989, 95:779-784.
  • [17]Pagani M, Lucini D, Mela GS, Langewitz W, Malliani A: Sympathetic overactivity in subjects complaining of unexplained fatigue. Clin Sci 1994, 87:655-661.
  • [18]De Becker P, Dendale P, De Meirleir K, Campine I, Vandenborne K, Hagers Y: Autonomic testing in patients with chronic fatigue syndrome. Am J Med 1998, 105:122S-126S.
  • [19]Soetekouw PM, Lenders JW, Bleijenberg G, Thien T, van der Meer JW: Autonomic function in patients with chronic fatigue syndrome. Clin Auton Res 1999, 9:334-340.
  • [20]Rowe PC, Boo-Holaigh I, Kan JS, Calkins H: Is neurally mediated hypotension an unrecognized cause of chronic fatigue? Lancet 1995, 345:623-624.
  • [21]Bou-Holaigh I, Rowe PC, Kan JS, Calking H: The relationship between neurally mediated hypotension and the chronic fatigue syndrome. JAMA 1995, 274:961-967.
  • [22]Streeten DH, Anderson GH Jr: The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Auton Res 1998, 8:119-124.
  • [23]Schondorf R, Freeman R: The importance of orthostatic intolerance in the chronic fatigue syndrome. Am J Med Sci 1999, 317:117-123.
  • [24]Axelrod FB, Chelimsky GG, Weese-Mayer DE: Pediatric autonomic disorders. Pediatrics 2006, 2006:309-321.
  • [25]Stewart J, Weldon A, Arlievsky N, Li K, Munoz J: Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt table testing in children with chronic fatigue syndrome. Clin Auton Res 1998, 8:221-230.
  • [26]Stewart JM, Gewitz MH, Weldon A, Munoz J: Patterns of orthostatic intolerance: the orthostatic tachycardia syndrome and adolescent chronic fatigue. J Pediatr 1999, 135:218-225.
  • [27]Stewart JM: Autonomic nervous system dysfunction in adolescents with postural orthostatic tachycardia syndrome and chronic fatigue syndrome is characterized by attenuated vagal baroreflex and potentiated sympathetic vasomotion. Pediatr Res 2000, 48:218-226.
  • [28]Shepherd C: Pacing and exercise in chronic fatigue syndrome. Physiotherapy 2001, 87:395-396.
  • [29]Iriarte J, de Castro P: Correlation between sympotom fatigue and muscular fatigue in multiple sclerosis. Eur J Neurol 1998, 5:579-585.
  • [30]Barak Y, Achiron A: Cognitive fatigue in multiple sclerosis: findings from a two-wave screening project. J Neurol Sci 2006, 245:73-76.
  • [31]Iriarte J, Subira ML, Castro P: Modalities of fatigue in multiple sclerosis: correlation with clinical and biological factors. Mult Scler 2000, 6:124-130.
  • [32]Olsson M, Lexell J, Soderberg S: The meaning of fatigue for women with multiple sclerosis. J Adv Nurs 2005, 49:7-15.
  • [33]Kos D, Kerckhofs E, Nagels G, D’hooghe B, Ilsbroukx S: Origin of fatigue in multiple sclerosis: review of the literature. Neurorehabil Neural Repair 2007, 20:1-10.
  • [34]Vucic S, Burke D, Kiernan MC: Fatigue in multiple sclerosis: mechanisms and management. Clin Neurophysiol 2010, 121:809-817.
  • [35]Boerio D, Lefaucheur JP, Hogrel JY, Creange A: Pathophysiology and treatment of fatigue in multiple sclerosis. Rev Neurol 2006, 162:311-320.
  • [36]Debouverie M, Pittion S: Fatigue and episodic exhaustion as a feature of multiple sclerosis. Rev Neurol 2006, 162:295-297.
  • [37]Bakshi R: Fatigue associated with multiple sclerosis: diagnosis, impact and management. Mult Scler 2003, 9:219-227.
  • [38]Haensch CA, Jorg J: Autonomic dysfunction in multiple sclerosis. J Neurol 2006, 253:13-19.
  • [39]Lensch E, Jost WH: Autonomic disorders in multiple sclerosis. Autoimmune Dis 2011, 2011:803841.
  • [40]Kanjwal K, Karabin B, Kanjwal Y, Grubb BP: Autonomic dysfunction presenting as postural orthostatic tachycardia syndrome in patients with multiple sclerosis. Int J Med Sci 2010, 7:62-67.
  • [41]McDougall J, McLeod JG: Autonomic nervous system function in multiple sclerosis. J Neurol Sci 2003, 215:79-85.
  • [42]Merkelbach U, Dillmann C, Kolmel J, Holz I, Muller M: Cardiovascular autonomic dysregulation and fatigue in multiple sclerosis. Mult Scler 2001, 7:320-326.
  • [43]de Seze J, Stojkovic T, Gauvrit JY, Devos D, Ayachi M, Cassim F, Saint Michel T, Pruvo JP, Guieu JD, Vermersch P: Autonomic dysfunction in multiple sclerosis: cervical spinal cord atrophy correlates. J Neurol 2001, 248:297-303.
  • [44]Nordenbo AM, Boesen F, Andersen EB: Cardiovascular autonomic function in multiple sclerosis. J Auton Nerv Syst 1989, 26:77-84.
  • [45]Mathiowetz VG, Finlayson ML, Matuska KM, Chen HY, Luo P: Randomized trial of an energy conservation course for persons with multiple sclerosis. Mult Scler 2005, 11:592-601.
  • [46]Matuska K, Mathiowetz V, Finlayson M: Use and perceived effectiveness of energy conservation strategies for managing multiple sclerosis fatigue. Am J Occup Ther 2007, 61:62-69.
  • [47]Vanage SM, Gilbertson KK, Mathiowetz V: Effects of energy conservation course on fatigue impact for persons with progressive multiple sclerosis. Am J Occup Ther 2003, 57:315-323.
  • [48]Papanicolaou DA, Amsterdamb JD, Levine S, McCann SM, Moore RC, Newbrand CH, Allen G, Nisenbaum R, Pfaff DW, Tsokos GC, Vgontzas AN, Kales A: Neuroendocrine Aspects of chronic fatigue syndrome. Neuroimmunomodulation 2003, 11:65-74.
  • [49]Reynolds NL, Brown MM, Jason LA: The relationship of Fennell phases to symptoms among patients with chronic fatigue syndrome. Eval Health Prof 2009, 32:264-280.
  • [50]Nisenbaum R, Jones JF, Unger ER, Reyes M, Reeves WC: A population-based study of the clinical course of chronic. Health Qual Life Outcomes 2003, 1:49.
  • [51]Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A: The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 1994, 121:953-959.
  • [52]Hinds GME, McCluskey DR: A retrospective study of chronic fatigue syndrome. Proc R Coll Physicians Edinburgh 1993, 23:10-14.
  • [53]Wilson A, Hickie I, Lloyd A, Hadzi-Pavlovic D, Boughton C, Dwyer J, Wakefield D: Longitudinal study of outcome of chronic fatigue syndrome. Br Med J 1994, 308:756759.
  • [54]Tiersky LA, DeLuca J, Hill N, Dhar SK, Johnson SK, Lange G, Rappolt G, Natelson BH: Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome. Appl Neuropsychol 2001, 8:41-50.
  • [55]Hill NF, Tiersky LA, Scavalla VR, Lavietes M, Natelson BH: Natural history of severe chronic fatigue syndrome. Arch Phys Med Rehabil 1999, 80:1090-1094.
  • [56]Van der Werf SP, de Vree B, Alberts M, Van der Meer JWM, Bleijenberg G: Natural course and predicting self- reported improvement in patients with chronic fatigue syndrome with a relatively short illness duration. J Psychosomat Res 2002, 53:749753.
  • [57]Peterson PK, Schenck CH, Sherman R: Chronic fatigue syndrome in Minnesota. Minn Med 1991, 74:21-26.
  • [58]Saltzstein BJ, Wyshak G, Hubbuch JT, Perry JC: A naturalistic study of the chronic fatigue syndrome among women in primary care. Gen Hosp Psychiatry 1998, 20:307316.
  • [59]Buljevac D, Flach HZ, Hop WC, Hijdra D, Laman JD, Savelkoul HF, van Der Meche FG, van Doorn PA, Hintzen RQ: Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain 2002, 125:952-960.
  • [60]Buljevac D, Hop WC, Reedeker W, Janssens AC, van der Meche FG, van Doorn PA, Hintzen RQ: Self reported stressful life events and exacerbations in multiple sclerosis: prospective study. BMJ 2003, 327:646.
  • [61]Persoons JH, Schornagel K, Breve J, Berkenbosch F, Kraal G: Acute stress affects cytokines and nitric oxide production by alveolar macrophages differently. Am J Respir Crit Care Med 1995, 152:619-624.
  • [62]Ontaneda D, Rae-Grant A: Management of acute exacerbations in multiple sclerosis. Ann Indian Acad Neurol 2009, 12:264-272.
  • [63]Nicolson GL, Nasralla M, Haier J, Erwin R, Nicolson NL, Ngwenya R: Mycoplasmal infections in chronic illnesses: fibromyalgia and chronic fatigue syndromes, Gulf War illness, HIV-AIDS and rheumatoid arthritis. Med Sentinel 1999, 4:172-176.
  • [64]Nicolson GL, Haier J, Nasralla M, Haier J, Erwin R, Nicolson NL, Ngwenya R: Mycoplasmal infections in chronic fatigue syndrome, fibromyalgia syndrome and Gulf War illness. JCFS 2000, 6:23-39.
  • [65]Nicolson GL, Nasralla M, De Meirleir K, Gan R, Haier J: Evidence for bacterial (Mycoplasma, Chlamydia) and viral (HHV-6) co-infections in chronic fatigue syndrome patients. JCFS 2003, 11:7-20.
  • [66]Nicolson GL, Gan R, Haier J: Multiple co-infections (Mycoplasma, Chlamydia, human herpesvirus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. APMIS 2003, 111:557-566.
  • [67]Nicolson GL, Nicolson NL, Haier J: Chronic fatigue syndrome patients subsequently diagnosed with Lyme Disease Borrelia burgdorferi: evidence for mycoplasma species co-infections. JCFS 2008, 14:5-17.
  • [68]Vojdani A, Choppa PC, Tagle C, Andrin R, Samimi B, Lapp CW: Detection of mycoplasma genus and mycoplasma fermentans by PCR in patients with chronic fatigue syndrome. FEMS Immunol Med Microbiol 1998, 22:355-365.
  • [69]Seishima M, Mizutani Y, Shibuya Y, Arakawa C: Chronic fatigue syndrome after human parvovirus B19 infection without persistent viremia. Dermatology 2008, 216:341-346.
  • [70]Chia JK, Chia AY: Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol 2008, 61:43-48.
  • [71]Goudsmit EM, Howes S: Pacing to manage chronic fatigue syndrome. Pacing: an additional strategy to manage fatigue in chronic fatigue syndrome. http://freespace.virgin.net/david.axford/pacing.htm webcite
  • [72]LaManca JJ, Peckerman A, Sisto SA, DeLuca J, Cook S, Natelson BH: Cardiovascular responses of women with chronic fatigue syndrome to stressful cognitive testing before and after strenuous exercise. Psychosom Med 2001, 63:756-764.
  • [73]Kerr JR, Mattey DL: Preexisting psychological stress predicts acute and chronic fatigue and arthritis following symptomatic parvovirus B19 infection. Clin Infect Dis 2008, 46:e83-e87.
  • [74]Ebers GC: Environmental factors and multiple sclerosis. Lancet Neurol 2008, 7:268-277.
  • [75]Simpson S Jr, Blizzard L, Otahal P, Van der Mei I, Taylor B: Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry 2011, 82:1132-1141.
  • [76]Buchwald D, Umali P, Umali J, Kith P, Pearlman T, Komaroff AL: Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system. Ann Intern Med 1995, 123:81-88.
  • [77]Acheson D: The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland disease and epidemic neuromyasthenia. Am J Med 1959, 26:569-595.
  • [78]Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, Tosato G, Zegans LS, Purtilo DT, Brown N, Schooley RT, Brus I: Chronic fatigue syndrome: a working case definition. Ann Intern Med 1988, 108:387-389.
  • [79]Jason LA, King CP, Frankenberry EL, Jordan KM, Tryon WW, Rademaker F, Huang CF: Chronic fatigue syndrome: assessing symptoms and activity level. J Clin Psychol 1999, 55:411-424.
  • [80]Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC: Prevalence and incidence of chronic fatigue syndrome in Wichita. Kansas. Arch Intern Med 2003, 2003:1530-1536.
  • [81]Harbo HF, Gold R, Tintore M: Sex and gender issues in multiple sclerosis. Ther Adv Neurol Disord 2013, 6:237-248.
  • [82]Haider L, Fischer MT, Frischer JM, Bauer J, Hoftberger R, Botond G, Esterbauer H, Binder CJ, Witztum JL, Lassmann H: Oxidative damage in multiple sclerosis lesions. Brain 2011, 134:1914-1924.
  • [83]Gonsette RE: Review: Oxidative stress and excitotoxicity: a therapeutic issue in multiple sclerosis? Mult Scler 2008, 14:22-34.
  • [84]Toshniwal PK, Zarling EJ: Evidence for increased lipid peroxidation in multiple sclerosis. Neurochem Res 1992, 17:205-207.
  • [85]van Horssen J, Schreibelt G, Drexhage J, Hazes T, Dijkstra CD, van der Valk P, de Vries HE: Severe oxidative damage in multiple sclerosis lesions coincides with enhanced antioxidant enzyme expression. Free Radic Biol Med 2008, 45:1729-1737.
  • [86]Smith KJ, Kapoor R, Felts A: Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol 1999, 9:69-92.
  • [87]Hill KE, Zollinger LV, Watt HE, Carlson NG, Rose JW: Inducible nitric oxide synthase in chronic active multiple sclerosis plaques: distribution, cellular expression and association with myelin damage. J Neuroimmunol 2004, 151:171-179.
  • [88]Koch M, Mostert J, Arutjunyan A, Stepanov M, Teelken A, Heersema D, De Keyser J: Peripheral blood leukocyte NO production and oxidative stress in multiple sclerosis. Mult Scler 2008, 14:159-165.
  • [89]Basu S: Isoprostanes: novel bioactive products of lipid peroxidation. Free Radic Res 2004, 38:105-122.
  • [90]Greco A, Minghetti L, Levi G: Isoprostanes, novel markers of oxidative injury, help understanding the pathogenesis of neurodegenerative diseases. Neurochem Res 2000, 25:1357-1364.
  • [91]Morrow JD: The isoprostanes - unique products of arachidonate peroxidation: their role as mediators of oxidant stress. Curr Pharm 2006, 12:895-902.
  • [92]Mattsson N, Haghighi S, Andersen O, Yao Y, Rosengren L, Blennow K, Pratico D, Zetterberg H: Elevated cerebrospinal fluid F2- isoprostane levels indicating oxidative stress in healthy siblings of multiple sclerosis patients. Neurosci Lett 2007, 414:233-236.
  • [93]Maes M, Mihaylova I, Leunis JC: Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins. Neuro Endocrinol Lett 2006, 27:615-621.
  • [94]Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis/chronic fatigue syndrome. Neuro Endocrinol Lett 2009, 30:715-722.
  • [95]Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett 2009, 30:470-476.
  • [96]Maes M, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Sci Monit 2011, 17:SC11-SC15.
  • [97]Manuel y Keenoy B, Moorkens G, Vertommen J, Noe M, Neve J, De Leeuw I: Magnesium status and parameters of the oxidant-antioxidant balance in patients with chronic fatigue: effects of supplementation with magnesium. J Am Coll Nutr 2000, 19:374-382.
  • [98]Manuel-y-Keenoy B, Moorkens G, Vertommen J, De Leeuw I: Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome. Life Sci 2001, 68:2037-2049.
  • [99]Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA: Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Letters 2003, 335:151-154.
  • [100]Miwa K, Fujita M: Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. Heart Vessels 2010, 25:319-323.
  • [101]Kennedy G, Spence VA, McLaren M, Hill A, Underwood C, Belch JJ: Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Free Radic Biol Med 2005, 39:584-589.
  • [102]Maes M, Mihaylova I, Kubera M, Bosmans E: Not in the mind but in the cell: increased production of cyclo-oxygenase-2 and inducible NO synthase in chronic fatigue syndrome. Neuro Endocrinol Lett 2007, 28:463-469.
  • [103]Jammes Y, Steinberg JG, Delliaux S: Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med 2011, 272:74-84.
  • [104]Jammes Y, Steinberg JG, Mambrini O, Bregeon F, Delliaux S: Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med 2005, 257:299-310.
  • [105]Fulle S, Pietrangelo T, Mancinelli R, Saggini R, Fano G: Specific correlations between muscle oxidative stress and chronic fatigue syndrome: a working hypothesis. J Muscle Res Cell Motil 2007, 28:355-362.
  • [106]Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL: Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep 2000, 5:35-41.
  • [107]Shungu DC, Weiduschat N, Murrough JW, Mao X, Pillemer S, Dyke JP, Medow MS, Natelson BH, Stewart JM, Mathew SJ: Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology. NMR Biomed 2012, 25:1073-1087.
  • [108]Syburra C, Passi S: Oxidative stress in patients with multiple sclerosis. Ukr Biokhim Zh 1999, 71:112-115.
  • [109]de Bustos F, Jiménez-Jiménez FJ, Molina JA, Gómez-Escalonilla C, de Andrés C, del Hoyo P, Zurdo M, Tallón-Barranco A, Berbel A, Porta-Etessam J, Parrilla G, Arenas J: Serum levels of coenzyme Q10 in patients with multiple sclerosis. Acta Neurol Scand 2000, 101:209-211.
  • [110]Choi IY, Lee SP, Denney DR, Lynch SG: Lower levels of glutathione in the brains of secondary progressive multiple sclerosis patients measured by 1H magnetic resonance chemical shift imaging at 3 T. Mult Scler 2011, 17:289-296.
  • [111]Ghazavi A, Kianbakht S, Ghasami K, Mosayebi G: High copper and low zinc serum levels in Iranian patients with multiple sclerosis: a case control study. Clin Lab 2012, 58:161-164.
  • [112]Maes M, Mihaylova I, Leunis JC: In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation. Neuro Endocrinol Lett 2005, 26:745-751.
  • [113]Dujmovic I, Mangano K, Pekmezovic T, Quattrocchi C, Mesaros S, Stojsavljevic N, Nicoletti F, Drulovic J: The analysis of IL-1 beta and its naturally occurring inhibitors in multiple sclerosis: the elevation of IL-1 receptor antagonist and IL-1 receptor type II after steroid therapy. J Neuroimmunol 2009, 207:101-106.
  • [114]Argaw AT, Zhang Y, Snyder BJ, Zhao ML, Kopp N, Lee SC, Raine CS, Brosnan CF, John GR: IL-1beta regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program. J Immunol 2006, 177:5574-5584.
  • [115]Hauser SL, Doolittle TH, Lincoln R, Brown RH, Dinarello CA: Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6. Neurology 1990, 40:1735-1739.
  • [116]Sharief MK, Hentges R: Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis. N Engl J Med 1991, 325:467-472.
  • [117]Al-Omaishi J, Bashir R, Gendelman HE: The cellular immunology of multiple sclerosis. J Leukoc Biol 1999, 65:444-452.
  • [118]Frei K, Fredrikson S, Fontana A, Link H: Interleukin-6 is elevated in plasmain multiple sclerosis. J Neuroimmunol 1991, 31:147-153.
  • [119]Carrieri PB, Provitera V, De Rosa T, Tartaglia G, Gorga F, Perrella O: Profile of cerebrospinal fluid and serum cytokines in patients with relapsing-remitting multiple sclerosis. A correlation with clinical activity. Immunopharmacol Immunotoxicol 1998, 20:373-382.
  • [120]Gajewski TF, Schell SR, Nau G, Fitch FW: Regulation of T-cell activation: differences among T-cell subsets. Immunol Rev 1989, 111:79-110.
  • [121]Murphy KM, Reiner SL: The lineage decisions of helper T cells. Nat Rev Immunol 2002, 2002:933-944.
  • [122]Imam SA, Guyton MK, Haque A, Vandenbark A, Tyor WR, Ray SK, Banik NL: Increased calpain correlates with Th1 cytokine profile in PBMCs from MS patients. J Neuroimmunol 2007, 190:139-145.
  • [123]Koguchi K, Anderson DE, Yang L, O’Connor KC, Kuchroo VK, Hafler DA: Dysregulated T cell expression of TIM3 in multiple sclerosis. J Exp Med 2006, 203:1413-1418.
  • [124]Cannella B, Raine CS: The adhesion molecule and cytokine profile of MS lesions. Ann Neurol 1995, 37:424-435.
  • [125]Navikas V, Link H: Cytokines and the pathogenesis of multiple sclerosis. J Neurosci Res 1996, 45:322-333.
  • [126]Rodriguez-Sainz Mdel C, Sanchez-Ramon S, de Andres C, Rodriguez-Mahou M, Munoz-Fernandez MA: Th1/Th2 cytokine balance and nitric oxide in cerebrospinal fluid and serum from patients with multiple sclerosis. Eur Cytokine Netw 2002, 13:110-114.
  • [127]Maes M, Twisk FNM, Kubera M, Ringel K: Evidence for inflammation and activation of cell-mediated immunity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopteri. J Affect Disord 2012, 136:933-939.
  • [128]Morris G, Maes M: Increased nuclear factor-κB and loss of p53 are key mechanisms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Hypotheses 2012, 79:607-613.
  • [129]Maher KJ, Klimas NG, Fletcher MA: Chronic fatigue syndrome is associated with diminished intracellular perforin. Clin Exp Immunol 2005, 142:505-511.
  • [130]Broderick G, Fuite J, Kreitz A, Vernon SD, Klimas N, Fletcher MA: A formal analysis of cytokine networks in chronic fatigue syndrome. Brain Behav Immun 2010, 24:1209-1217.
  • [131]Rose JW, Hill KE, Watt HE, Carlson NG: Inflammatory cell expression of cyclooxygenase-2 in the multiple sclerosis lesion. J Neuroimmunol 2004, 149:40-49.
  • [132]Carlson NG, Rojas MA, Redd JW, Tang P, Wood B, Hill KE, Rose JW: Cyclooxygenase-2 expression in oligodendrocytes increases sensitivity to excitotoxic death. J Neuroinflammation 2010, 7:25.
  • [133]Gveric D, Kaltschmidt C, Cuzner ML, Newcombe J: Transcription factor NF-κB and inhibitor IκBα are localized in macrophages in active multiplesclerosis lesions. J Neuropathol Exp Neurol 1998, 57:168-178.
  • [134]Bonetti B, Stegagno C, Cannella B, Rizzuto N, Moretto G, Raine CS: Activation of NF-kappaB and c-jun transcription factors in multiple sclerosis lesions. Implications for oligodendrocyte pathology. Am J Pathol 1999, 155:1433-1438.
  • [135]Mattson MP, Camandola S: NF-kappaB in neuronal plasticity and neurodegenerative disorders. J Clin Invest 2001, 107:247-254.
  • [136]Link H, Fredrikson S: HLA-DR expression and neopterin levels as activity markers in multiple sclerosis. Riv Neurol 1987, 57:154-158.
  • [137]Khorami H, Neyestani TR, Kadkhodaee M, Lotfi J: Increased urinary neopterin: creatinine ratio as a marker of activation of cell- mediated immunity and oxidative stress in the Iranian patients with multiple sclerosis. Iran J Allergy Asthma Immunol 2003, 2:155-158.
  • [138]Giovannoni G, Lai M, Kidd D, Thorpe JW, Miller DH, Thompson AJ, Keir G, Feldmann M, Thompson EJ: Daily urinary neopterin excretion as an immunological marker of disease activity in multiple sclerosis. Brain 1997, 120:1-13.
  • [139]Rejdak K, Leary SM, Petzold A, Thompson AJ, Miller DH, Giovannoni G: Urinary neopterin and nitric oxide metabolites as markers of interferon beta-1a activity in primary progressive multiple sclerosis. Mult Scler 2010, 16:1066-1072.
  • [140]Fredrikson S, Link H, Eneroth P: CSF neopterin as marker of disease activity in multiple sclerosis. Acta Neurol Scand 1987, 75:352-355.
  • [141]Buchwald D, Wener MH, Pearlman T, Kith P: Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome. J Rheumatol 1997, 24:372-376.
  • [142]Matsuda J, Gohchi K, Gotch N: Serum concentrations of 2′,5′-oligoadenylate synthetase, neopterin, and beta-glucan in patients with chronic fatigue syndrome and in patients with major depression. J Neurol Neurosurg Psychiatry 1994, 57:1015-1016.
  • [143]Chao CC, Gallagher M, Phair J, Peterson PK: Serum neopterin and interleukin-6 levels in chronic fatigue syndrome. J Infect Dis 1990, 162:1412-1413.
  • [144]Chao CC, Janoff EN, Hu SX, Thomas K, Gallagher M, Tsang M, Peterson PK: Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. Cytokine 1991, 3:292-298.
  • [145]Fransson ME, Liljenfeldt LS, Fagius J, Totterman TH, Loskog AS: The T-cell pool is anergized in patients with multiple sclerosis in remission. Immunology 2009, 126:92-101.
  • [146]Saresella M, Marventano I, Longhi R, Lissoni F, Trabattoni D, Mendozzi L, Caputo D, Clerici M: CD4 + CD25 + FoxP3 + PD1- regulatory T cells in acute and stable relapsing-remitting multiple sclerosis and their modulation by therapy. FASEB J 2008, 22:3500-3508.
  • [147]Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA: Loss of functional suppression by CD4 + CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 2004, 199:971-979.
  • [148]Ni L, Ma CJ, Zhang Y, Nandakumar S, Zhang CL, Wu XY, Borthwick T, Hamati A, Chen XY, Kumaraguru U, Moorman JP, Yao ZQ: PD-1 modulates regulatory T cells and suppresses T-cell responses in HCV-associated lymphoma. Immunol Cell Biol 2011, 89:535-539.
  • [149]Costantino CM, Baecher-Allan C, Hafler DA: Multiple sclerosis and regulatory T cells. J Clin Immunol 2008, 28:697-706.
  • [150]Zozulya AL, Wiendl H: The role of regulatory T cells in multiple sclerosis. Nat Clin Pract Neurol 2008, 4:384-398.
  • [151]Libera DD, Mitri DD, Bergami A, Centonze D, Gasperini C, Grasso MG, Galgani S, Martinelli V, Comi G, Avolio C, Martino G, Borsellino G, Sallusto F, Battistini L, Furlan R: T regulatory cells are markers of disease activity in multiple sclerosis patients. PLoS ONE 2011, 6:e21386.
  • [152]D’Souza M, Fontenot AP, Mack DG, Lozupone C, Dillon S, Meditz A, Wilson CC, Connick E, Palmer BE: Programmed death 1 expression on HIV-specific CD4+ T cells is driven by viral replication and associated with T cell dysfunction. J Immunol 2007, 179:1979-1987.
  • [153]Song SJ, Feng X, Guo JJ, Iu YN, Lun WH, Wei HS, Liu SA: Relationship of CD4+ CD25hi regulatory T (Treg) cells to disease progression in HIV-infected patients. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2009, 23:361-363.
  • [154]Hofstetter HH, Gold R, Hartung HP: Th17 cells in MS and experimental autoimmune encephalomyelitis. Int MS J 2009, 16:12-18.
  • [155]Peelen E, Damoiseaux J, Smolders J, Knippenberg S, Menheere P, Tervaert JW, Hupperts R, Thewissen M: Th17 expansion in MS patients is counterbalanced by an expanded CD39+ regulatory T cell population during remission but not during relapse. J Neuroimmunol 2011, 240–241:97-103.
  • [156]Weissert R: Differential response to treatment of relapsing-remitting multiple sclerosis with IFN-β: is there a dichotomy into T-helper-1 and −17 driven disease? Future Neurol 2010, 5:481-484.
  • [157]Edwards LJ, Robins RA, Constantinescu CS: Th17/Th1 phenotype in demyelinating disease. Cytokine 2010, 50:19-23.
  • [158]Kostic M: Role of Th1 and Th17 immune responces in pathogenesis of multiple sclerosis. Acta Medica Medianae 2010, 49:61-69.
  • [159]Ziegler SF, Buckner JH: FOXP3 and the regulation of Treg/Th17 differentiation. Microbes Infect 2009, 11:594-598.
  • [160]Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, Victora GD, Shen Y, Du J, Rubtsov YP, Rudensky AY, Ziegler SF, Littman DR: TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008, 453:236-240.
  • [161]Liu DH, Liu ZD, Li YZ, Zhang HY, Hu CJ, Zhang YB, Whang DX: Expression of lymphocyte subsets and CD25 ~ + regulative T Cells in peripheral blood of patients with chronic fatigue syndrome. Labeled Immunoassays and Clinical Medicine. Abstract 2011, 2011–02. http://en.cnki.com.cn/Article_en/CJFDTOTAL-BJMY201102012.htm webcite
  • [162]Gallo P, Piccinno MG, Pagni S, Argentiero V, Giometto B, Bozza F, Tavolato B: Immune activation in multiple sclerosis: study of IL-2, sIL-2R, and gamma-IFN levels in serum and cerebrospinal fluid. J Neurol Sci 1989, 92:9-15.
  • [163]Gallo P, Piccinno MG, Tavolato B, Siden A: A longitudinal study on IL-2, sIL-2R, IL-4 and IFN-gamma in multiple sclerosis CSF and serum. J Neurol Sci 1991, 101:227-232.
  • [164]Gallo P, Pagni S, Piccinno MG, Giometto B, Argentiero V, Chiusole M, Bozza F, Tavolato B: On the role of interleukin-2 (IL-2) in multiple sclerosis (MS). IL-2-mediated endothelial cell activation. Ital J Neurol Sci 1992, 13:65-68.
  • [165]Sharief MK, Hentges R, Ciardi M, Thompson EJ: In vivo relationship of interleukin-2 and soluble IL-2 receptor to blood-brain barrier impairment in patients with active multiple sclerosis. J Neurol 1993, 240:46-50.
  • [166]Cheney PR, Dorman SE, Bell DS: Interleukin-2 and the chronic fatigue syndrome. Ann Intern Med 1989, 110:321.
  • [167]Lombardi V, Hagen KS, Hunter KW, Diamond JW, Smith-Gagen J, Yang W, Mikovits JA: Xenotropic murine leukemia virus-related virus-associated chronic fatigue syndrome reveals a distinct inflammatory signature. In Vivo 2011, 25:307-314.
  • [168]Popmihajlov Z, Smith KA: Negative feedback regulation of T cells via interleukin-2 and FOXP3 reciprocity. PLoS ONE 2008, 3:e1581.
  • [169]Klimas N, Koneru AO: Chronic fatigue syndrome: inflammation, immune function, and neuroendocrine interactions. Curr Rheumatol Rep 2007, 9:482-487.
  • [170]Capelli E, Zola R, Lorusso L, Venturini L, Sardi F, Ricevuti G: Chronic fatigue syndrome/myalgic encephalomyelitis: an update. Int J Immunopathol Pharmacol 2010, 23:981-989.
  • [171]Jones JF, Straus SE: Chronic Epstein-Barr virus infection. Annu Rev Med 1987, 38:195-209.
  • [172]Borysiewicz LK, Haworth SJ, Cohen J, Mundin J, Rickinson A, Sissons JG: Epstein-Barr virus - specific immune defects in patients with persistent symptoms following infectious mononucleosis. Q J Med 1986, 58:111-121.
  • [173]Klimas N, Salvato F, Morgan R, Fletcher MA: Immunologic abnormalities in chronic fatigue syndrome. J Clin Microbiol 1990, 28:1403-1410.
  • [174]Behan PO, Behan WHM, Bell EJ: The postviral fatigue syndrome - an analysis of the findings in 50 cases. J Infect 1985, 10:211-222.
  • [175]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 infection. Lancet 1982, 1:61-64.
  • [176]Morimoto C, Torimoto Y, Levinson G, Rudd CE, Schrieber M, Dang NH, Letvin NL, Schlossman SF: 1 F7, a novel cell surface molecule involved in helper function of CD4 cells. J Immunol 1989, 143:3430-3439.
  • [177]Nakao H, Eguchi K, Kawakami A, Migita K, Otsubo T, Ueki Y, Shimomura C, Tezuka H, Matsunaga M, Maeda K, et al.: Increment of Tal positive cells in peripheral blood of patients with rheumatoid arthritis. J Rheumatol 1989, 16:904-910.
  • [178]Eguchi K, Ueki Y, Shimomura C, Otsubo T, Nakao H, Migita K, Kawakami A, Matsunaga M, Tezuka H, Ishikawa N: Increment in the Tal + in the peripheral blood and thyroid tissue of patients with Graves’ disease. J Immunol 1989, 142:4233-4240.
  • [179]Preller V, Gerber A, Togni M, Wrenger S, Schraven B, Rocken C, Marguet D, Ansorge S, Brocke S, Reinhold D: CD26/DP IV in T cell activation and autoimmunity. Adv Exp Med Biol 2006, 575:187-193.
  • [180]Ishii T, Ohnuma K, Murakami A, Takasawa N, Kobayashi S, Dang NH, Schlossman SF, Morimoto C: CD26-mediated signaling for T cell activation occurs in lipid rafts through its association with CD45RO. Proc Natl Acad Sci U S A 2001, 98:12138-12143.
  • [181]Pacheco R, Lluis C, Franco R: Role of CD26-adenosine deaminase interaction in T cell-mediated immunity. Inmunologia 2005, 24:235-245.
  • [182]Bengsch B, Seigel B, Flecken T, Wolanksi J, Blum HE, Thimme R: Human Th17 cells express high levels of enzymatically active dipeptidylpeptidase IV (CD26). J Immunol 2012, 188:5438-5447.
  • [183]Krakauer M, Sorenson PS, Sellebjerg F: CD4(+) memory T cells with high CD26 surface expression are enriched for Th1 markers and correlate with clinical severity of multiple sclerosis. J Neuroimmunol 2006, 181:157-164.
  • [184]Constantinescu CS, Kamoun M, Dotti M, Farber RE, Galetta SL, Rostami A: A longitudinal study of the T cell activation marker CD26 in chronic progressive multiple sclerosis. J Neurol Sci 1995, 130:178-182.
  • [185]Sellebjerg F, Ross C, Koch-Henriksen N, Sorensen PS, Frederiksen JL, Bendtzen K, Sorensen TL: CD26 + CD4 + T cell counts and attack risk in interferon-treated multiple sclerosis. Mult Scler 2005, 11:641-645.
  • [186]Fletcher MA, Zeng XR, Maher K, Levis S, Hurwitz B, Antoni M, Broderick G, Klimas NG: Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26. PLoS ONE 2010, 5:e10817.
  • [187]Martin P, Sanchez-Madrid F: CD69: an unexpected regulator of TH17 cell-driven inflammatory responses. Sci Signal 2011, 4:pe14.
  • [188]Perrella O, Carrieri PB, De Mercato R, Buscaino GA: Markers of activated T Lymphocytes and T cell receptor Gamma/Delta + in patients with multiple sclerosis. Eur Neurol 1993, 33:152-155.
  • [189]Huang YM, Hussien Y, Jin YP, Soderstrom M, Link H: Multiple sclerosis: deficient in vitro responses of blood mononuclear cells to IFN-beta. Acta Neurol Scand 2001, 104:249-256.
  • [190]Mihaylova I, DeRuyter M, Rummens JL, Bosmans E, Maes M: Decreased expression of CD69 in chronic fatigue syndrome in relation to inflammatory markers: evidence for a severe disorder in the early activation of T lymphocytes and natural killer cells. Neuro Endocrinol Lett 2008, 28:477-483.
  • [191]Zhang C, Zhang J, Tian Z: The regulatory effect of natural killer Cells: do “NK-reg cells” exist? Cell Mol Immunol 2006, 3:241-254.
  • [192]Benczur M, Petrynyl GG, Palffy G, Varga M, Talas M, Kotsy B, Foldes I, Hollan SR: Dysfunction of natural killer cells in multiple sclerosis: a possible pathogenetic factor. Clin Exp Immunol 1980, 39:657-662.
  • [193]Jiang W, Chai NR, Maric D, Bielekova B: Unexpected role for granzyme K in CD56 bright NK cell-mediated immunoregulation of multiple sclerosis. J Immunol 2011, 187:781-790.
  • [194]Kastrukoff LF, Lau A, Wee R, Zecchini D, White R, Paty DW: Clinical relapses of multiple sclerosis are associated with ‘novel’ valleys in natural killer cell functional activity. J Neuroimmunol 2003, 145:103-114.
  • [195]Takahashi K, Aranami T, Endoh M, Miyake S, Yamamura T: The regulatory role of natural killer cells in multiple sclerosis. Brain 2004, 127:1917-1927.
  • [196]Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, McFarland H, Henkart PA, Martin R: Regulatory CD56 bright natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A 2006, 103:5941-5946.
  • [197]Caligiuri M, Murray C, Buchwald D, Levine H, Cheney P, Peterson D, Komaroff AL, Ritz J: Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J Immunol 1987, 139:3306-3313.
  • [198]Whiteside TL, Friberg D: Natural killer cells and natural killer cell activity in chronic fatigue syndrome. Am J Med 1998, 105:27S-34S.
  • [199]Genc K, Dona DL, Reder AT: Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy. J Clin Invest 1997, 99:2664-2671.
  • [200]Nijs J, McGregor NR, De Becker P, Verhas M, Englebienne P, De Meirleir K: Monitoring a hypothetical channelopathy in chronic fatigue syndrome: preliminary observations. JCFS 2003, 11:117-133.
  • [201]Nijs J, Coomans D, Nicolson GL, De Becker P, Christian D, De Meirleir K: Immunophenotyping predictive of mycoplasma infection in patients with chronic fatigue syndrome. JCFS 2003, 11:51-69.
  • [202]Tirelli U, Marotta G, Improta S, Pinto A: Immunological abnormalities in patients with chronic fatigue syndrome. Scand J Immunol 1994, 40:601-608.
  • [203]Anderton SM, Fillatreau S: Activated B cells in autoimmune diseases: the case for a regulatory role. Nat Clin Pract Rheumatol 2008, 4:657-666.
  • [204]Barned S, Goodman AD, Mattson DH: Frequency of anti-nuclear antibodies in multiple sclerosis. Neurology 1995, 45:384-385.
  • [205]Fukazawa T, Moriwaka F, Mukai M, Hamada T, Koike T, Tashiro K: Anticardiolipin antibodies in Japanese patients with multiple sclerosis. Acta Neurol Scand 1993, 88:184-189.
  • [206]IJdo JW, Conti-Kelly AM, Greco P, Abedi M, Amos M, Provenzale JM, Greco TP: Anti-phospholipid antibodies in patients with multiple sclerosis and MS-like illnesses: MS or APS? Lupus 1999, 8:109-115.
  • [207]Vyshkina T, Kalman B: Autoantibodies and neurodegeneration in multiple sclerosis. Lab Invest 2008, 88:796-807.
  • [208]Nordal GJ, Vandvik B: Evidence of local synthesis of smooth-muscle antibodies in the central nervous system in isolated cases of multiple sclerosis and chronic lymphocytic meningoencephalitis. Scand J Immunol 1977, 6:327-334.
  • [209]Arnon R, Crisp E, Kelley R, Ellison GW, Myers LW, Tourtellotte WW: Anti-ganglioside antibodies in multiple sclerosis. J Neurol Sci 1980, 46:179-186.
  • [210]Schott K, Schaefer JE, Richartz E, Batra A, Eusterschulte B, Klein R, Berg PA, Bartels M, Mann K, Buchkremer G: Autoantibodies to serotonin in serum of patients with psychiatric disorders. Psychiatr Res 2003, 121:51-57.
  • [211]Hokama Y, Camproa CE, Hara C, Higa N, Siu N, Lau R, Kuribayashi T, Yabusaki K: Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins. J Clin Lab Anal 2008, 22:99-105.
  • [212]Hokama Y, Camproa CE, Hara C, Kuribayashi T, Le Huynh D, Yabusaki K: Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome. J Clin Lab Anal 2009, 23:210-212.
  • [213]Konstantinov K, von Mikecz A, Buckwalk D, Jones J, Gerace L, Tan EM: Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome. J Clin Invest 1996, 98:1888-1896.
  • [214]Buchwald MD, Wener MH, Komaroff AL: Antineuronal antibody levels in chronic fatigue syndrome patients with neurologic abnormalities. Arthritis Rheum 1991, 34:1485-1486.
  • [215]Nishikai M: Antinuclear antibodies in patients with chronic fatigue syndrome. Nippon Rinsho 2007, 65:1067-1070.
  • [216]Bassi N, Amital D, Amital H, Doria A, Shoenfeld Y: Chronic fatigue syndrome: characteristics̃and possible causes for its pathogenesis. Isr Med Assoc J 2008, 10:79-82.
  • [217]Klein R, Berg PA: High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders. Eur J Med Res 1995, 1:21-26.
  • [218]Tanaka S, Kuratsune H, Hidaka Y, Hakariya Y, Tatsumi KI, Takano T, Kanakura Y, Amino N: Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome. Int J Mol Med 2003, 12:225-230.
  • [219]Geffard M, Bodet D, Martinet Y, Dabadie MP: Detection of the specific IgM and IgA circulating in sera of multiple sclerosis patients: interest and perspectives. Immunoanalyse Biologie Specialisee 2002, 17:302-310.
  • [220]Daverat P, Geffard M, Orgogozo JM: Identification and characterization of anti-conjugated azelaic acid antibodies in multiple sclerosis. J Neuroimmunol 1989, 22:129-314.
  • [221]Maneta-Peyret L, Daverat P, Geffard M, Cassagne C, Orgogozo JM: Natural seric anti-fatty acid antibodies in multiple sclerosis. Neurosci Lett 1987, 80:235-239.
  • [222]Boullerne A, Petry KG, Geffard M: Circulating antibodies directed against conjugated fatty acids in sera of patients with multiple sclerosis. J Neuroimmunol 1996, 65:75-81.
  • [223]Naidoo R, Knapp ML: Studies of lipid peroxidation products in cerebrospinal fluid and serum in multiple sclerosis and other conditions. Clin Chem 1992, 38:2449-2454.
  • [224]Maes M, Mihaylova I, Leunis JC: Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression. Neuro Endocrinol Lett 2007, 28:861-867.
  • [225]McFarland HF: The B cell-old player, new position on the team. N Engl J Med 2008, 2008:664-665.
  • [226]Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH, HERMES Trial Group: B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. New Engl J Med 2008, 358:676-688.
  • [227]Monson NL, Cravens PD, Frohman EM, Hawker K, Racke MK: Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis. Arch Neurol 2005, 62:258-264.
  • [228]Maurer MA, Rakocevic G, Leung CS, Quast I, Lukacisin M, Goebels N, Munz C, Wardemann H, Dalakas M, Lnemann JD: Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity. J Clin Invest 2012, 122:1393-1402.
  • [229]Cross AH, Stark JL, Lauber J, Ramsbottom MJ, Lyons JA: Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 2006, 180:63-70.
  • [230]Bar-Or A, Fawaz L, Fan B, Darlington PJ, Rieger A, Ghorayeb C, Calabresi PA, Waubant E, Hauser SL, Zhang J, Smith CH: Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol 2010, 67:452-461.
  • [231]Reichardt P, Dornbach B, Rong S, Beissert S, Gueler F, Loser K, Gunzer M: Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse. Blood 2007, 110:1519-1529.
  • [232]Petereit HF, Moeller-Hartmann W, Reske D, Rubbert A: Rituximab in a patient with multiple sclerosis-effect on B cells, plasma cells and intrathecal IgG synthesis. Acta Neurol Scand 2008, 117:399-403.
  • [233]Fluge O, Bruland O, Risa K, Storstein A, Kristoffersen EK, Sapkota D, Næss H, Dahl O, Nyland H, Mella O: Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome: a double-blind and placebo-controlled study. PLoS ONE 2011, 6:e26358.
  • [234]Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A, Racewicz AJ, van Vollenhoven RF, Li NF, Agarwal S, Hessey EW, Shaw TM, DANCER Study Group: The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 2006, 54:1390-1400.
  • [235]Eisenberg R: Update on rituximab. Ann Rheum Dis 2005, 64:iv55-iv57.
  • [236]Gurcan HM, Keskin DB, Stern JN, Nitzberg MA, Shekhani H, Ahmed AR: A review of the current use of rituximab in autoimmune diseases. Int Immunopharmacol 2009, 9:10-25.
  • [237]Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T: Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004, 350:2572-2581.
  • [238]Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC, REFLEX Trial Group: Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006, 54:2793-2806.
  • [239]Tokunaga M, Saito K, Kawabata D, Imura Y, Fujii T, Nakayamada S, Tsujimura S, Nawata M, Iwata S, Azuma T, Mimori T, Tanaka Y: Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis 2007, 66:470-475.
  • [240]Devauchelle-Pensec V, Pennec Y, Morvan J, Pers JO, Daridon C, Jousse-Joulin S, Roudaut A, Jamin C, Renaudineau Y, Roue IQ, Cochener B, Youinou P, Saraux A: Improvement of Sjogren’s syndrome after two infusions of rituximab (anti-CD20). Arthritis Rheum 2007, 57:310317.
  • [241]Ireland S, Monson N: Potential impact of B cells on T cell function in multiple sclerosis. Mult Scler Int 2011, 2011:423971.
  • [242]van de Veerdonk FL, Lauwerys B, Marijnissen RJ, Timmermans K, Di Padova F, Koenders MI, Gutierrez-Roelens I, Durez P, Netea MG, van der Meer JW, van den Berg WB, Joosten LA: The anti-CD20 antibody rituximab reduces the Th17 cell response. Arthritis Rheum 2011, 63:1507-1516.
  • [243]Lederer JA, Liou JS, Kim S, Rice N, Lichtman AH: Regulation of NF-kappa B activation in T helper 1 and T helper 2 cells. J Immunol 1996, 156:56-63.
  • [244]Jazirehi AR, Huerta-Yepez S, Cheng G, Bonavida B: Rituximab (chimericanti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin’s lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis. Cancer Res 2005, 65:264-276.
  • [245]Bonavida B: Rituximab-induced inhibition of antiapoptotic cell survival pathways: implications in chemo/immunoresistance, rituximab unresponsiveness, prognostic and novel therapeutic interventions. Oncogene 2007, 26:3629-3636.
  • [246]Vigna-Perez M, Hernandez-Castro B, Paredes-Saharopulos O, Portales-Perez D, Baranda L, Abud-Mendoza C, Gonzalez-Amaro R: Clinical and immunological effects of rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res Ther 2006, 8:R83.
  • [247]Vigna-Perez M, Abud-Mendoza C, Cuevas-Orta E, Baranda L, Paredes-Saharopulos O, Moreno R, Gonzalez-Amaro R: In vivo effect of rituximab on regulatory T cells and apoptosis in patients with rheumatoid arthritis. Immunologia 2006, 25:167-172.
  • [248]Tavazzi B, Batocchi AP, Amorini AM, Nociti V, D’Urso S, Longo S, Gullotta S, Picardi M, Lazzarino G: Serum metabolic profile in multiple sclerosis patients. Mult Scler Int 2011, 2011:167156.
  • [249]Amorini AM, Petzold A, Tavazzi B, Eikelenboom J, Keir G, Belli A, Giovannoni G, Di Pietro V, Polman C, D’Urso S, Vagnozzi R, Uitdehaag B, Lazzarino G: Increase of uric acid and purine compounds in biological fluids of multiple sclerosis patients. Clin Biochem 2009, 42:1001-1006.
  • [250]Amorini M, Lazzarino G, Galvano F, Fazzina G, Tavazzi B, Galvano G: Cyanidin-3-O-beta-glucopyranoside protects myocardium and erythrocytes from oxygen radical-mediated damages. Free Radic Res 2003, 37:453-460.
  • [251]Signoretti S, Di Pietro V, Vagnozzi R, Lazzarino G, Amorini AM, Belli A, D’Urso S, Tavazzi B: Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat. Mol Cell Biochem 2010, 333:269-277.
  • [252]Lazzarino G, Amorini AM, Eikelenboom MJ, Killestein J, Belli A, Di Pietro V, Tavazzi B, Barkhof F, Polman CH, Uitdehaag BM, Petzold A: Cerebrospinal fluid ATP metabolites in multiple sclerosis. Mult Scler 2010, 16:549-554.
  • [253]Lassman H, van Horssen J: The molecular basis of neurodegeneration in multiple sclerosis. FEBS Lett 2011, 585:3715-3723.
  • [254]Lu F, Selak M, O’Connor J, Croul S, Lorenzana C, Butunoi C, Kalman B: Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis. J Neurol Sci 2000, 177:95-103.
  • [255]Mahad D, Ziabreva I, Lassmann H, Turnbull D: Mitochondrial defects in acute multiple sclerosis lesions. Brain 2008, 131:1722-1735.
  • [256]Mahad D, Ziabreva I, Campbell G, Lax N, White K, Hanson PS, Lassmann H, Turnbull DM: Mitochondrial changes within axons in multiple sclerosis. Brain 2009, 132:1161-1174.
  • [257]Campbell GR, Ziabreva I, Reeve AK, Krishnan KJ, Reynolds R, Howell O, Lassmann H, Turnbull DM, Mahad DJ: Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis. Ann Neurol 2011, 69:481-492.
  • [258]Higgins GC, Beart PM, Shin YS, Chen MJ, Cheung NS, Nagley P: Oxidative stress: emerging mitochondrial and cellular themes and variations in neuronal injury. J Alzheimers Dis 2010, 20:S453-S473.
  • [259]Mao P, Reddy H: Is multiple sclerosis a mitochondrial disease? Biochim Biophys Acta 2010, 1802:66-79.
  • [260]van Horssen J, Witte ME, Schreibelt G, de Vries HE: Radical changes in multiple sclerosis pathogenesis. Biochem Biophys Acta 2011, 1812:141-150.
  • [261]Behan WM, More IA, Behan PO: Mitochondrial abnormalities in the postviral fatigue syndrome. Acta Neuropathol 1991, 83:61-65.
  • [262]Plioplys AV, Plioplys S: Electron-microscopic investigation of muscle mitochondria in chronic fatigue syndrome. Neuropsychobiology 1995, 32:175-181.
  • [263]Lane RJ, Barrett MC, Taylor DJ, Kemp GJ, Lodi R: Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle. Neuromuscul Disord 1998, 8:204-209.
  • [264]Myhill S, Booth NE, McLaren-Howard J: Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med 2009, 2:1-16.
  • [265]Vermeulen RCW, Kurt RM, Visser FC, Sluiter W, Scholte HR: Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. J Transl Med 2010, 8:93.
  • [266]Arnold DL, Bore PJ, Radda GK, Styles P, Taylor DJ: Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. Lancet 1984, 1:1367-1369.
  • [267]Lane RJM, Barrett MC, Woodrow D, Moss J, Fletcher R, Archard LC: Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 1998, 64:362-367.
  • [268]Allen DG, Lamb GD, Westerbland H: Skeletal muscle fatigue: cellular mechanisms. Physiol Rev 2008, 88:287-332.
  • [269]Wong R, Lopaschuk G, Zhu G, Walker D, Catellier D, Burton D, Teo K, Collins-Nakai R, Montague T: Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy. Chest 1992, 102:1716-1722.
  • [270]Mathew SJ, Mao X, Keegan KA, Levine SM, Smith EL, Heier LA, Otcheretko V, Coplan JD, Shungu DC: Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study. NMR Biomed 2009, 22:251-258.
  • [271]Murrough JW, Mao X, Collins KA, Kelly C, Andrade G, Nestadt P, Levine SM, Mathew SJ, Shungu DC: Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder. NMR Biomed 2010, 23:643-650.
  • [272]Pozzilli C, Passafiume D, Bernardi S, Incoccia C, Bastianello S, Bozzao L, Lenzi GL, Fleschi C: SPECT, MRI and cognitive functions in multiple sclerosis. J Neurol Neurosurg Psychiatry 1991, 54:110-115.
  • [273]Adhya S, Johnson G, Herbert J, Jaggi H, Babb JS, Grossman RI, Inglese M: Pattern of hemodynamic impairment in multiple sclerosis: dynamic susceptibility contrast perfusion MR imaging at 3.0 T. Neuroimage 2006, 33:1029-1035.
  • [274]Brooks DJ, Leenders KL, Head G, Marshall J, Legg NJ, Jones T: Studies on regional cerebral oxygen utilisation and cognitive function in multiple sclerosis. J Neurol Neurosurg Psychiatry 1984, 47:1182-1191.
  • [275]Raschid W, Parkes LM, Ingle GT, Chard DT, Toosy AT, Altmann DR, Symms MR, Tofts PS, Thompson AJ, Miller DH: Abnormalities of cerebral perfusion in multiple sclerosis. J Neurol Neurosurg Psychiatry 2004, 75:1288-1293.
  • [276]Costa DC, Tannock C, Brostoff J: Brainstem perfusion is impaired in chronic fatigue syndrome. QJM 1995, 88:767-773.
  • [277]Fischler B, D’Haenen H, Cluydts R, Michiels V, Demets K, Bossuyt A, Kaufman L, De Meirleir K: Comparison of 99m Tc HMPAO SPECT scan between chronic fatigue syndrome, major depression and healthy controls: an exploratory study of clinical correlates of regional cerebral blood flow. Neuropsychobiol 1996, 34:175-183.
  • [278]Schwartz RB, Garada BM, Komaroff AL, Tice HM, Gleit M, Jolesz FA, Holman BL: Detection of intracranial abnormalities in patients with chronic fatigue syndrome: comparison of MR imaging and SPECT. AJR Am J Roentgenol 1994, 162:935-941.
  • [279]Ichise M, Salit IE, Abbey SE, Chung DG, Gray B, Kirsh JC, Freedman M: Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome. Nucl Med Commun 1992, 13:767-772.
  • [280]Tirelli U, Chierichetti F, Tavio M, Simonelli C, Bianchin G, Zanco P, Ferlin G: Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data. Am J Med 1998, 105:54S-58S.
  • [281]Il’ves AG, Prakhova LN, Kataeva GV, Rudas MS, Tomolian NA, Skoromets AA, Stoliarov ID: Changes of cerebral glucose metabolism in patients with multiple sclerosis and their role in formation of the clinical picture and progression of the disease. Zh Nevrol Psikhiatr Im SS Korsakova 2003, 2:53-60.
  • [282]Roelcke U, Kappos L, Lechner-Scott J, Brunnschweiler H, Huber S, Ammann W, Plohmann A, Dellas S, Maguire RP, Missimer J, Radu EW, Steck A, Leenders KL: Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue A 18F fluorodeoxyglucose positron emission tomography study. Neurology 1997, 48:1566-1571.
  • [283]Paulasu E, Perani D, Fazio F, Comi G, Pozzilli C, Martinelli V, Filippi M, Bettinardi V, Sirabian G, Passafiume D, Anzini A, Lenzi GL, Canal N, Fieschi C: Functional basis of memory impairment in multiple sclerosis: a [18F]FDG PET study. Neuroimage 1996, 4:87-96.
  • [284]Siessmeier T, Nix W, Hardt J, Schreckenberger M, Egle U, Bartenstein P: Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 2003, 74:922-928.
  • [285]Neema M, Stankiewicz J, Arora A, Guss ZD, Bakshi R: MRI in multiple sclerosis: what’s inside the toolbox? Neurotherapeutics 2007, 4:602-617.
  • [286]Kohler SJ, Yen Y, Wolber J, Chen AP, Albers MJ, Bok R, Zhang V, Tropp J, Nelson S, Vigneron DB, Kurhanewicz J, Hurd RE: In vivo 13 carbon metabolic imaging at 3T with hyperpolarized 13C-1-pyruvate. Magn Reson Med 2007, 58:65-69.
  • [287]Dousset V, Brochet B, Deloire MS, Lagoarde L, Barroso B, Caille JM, Petry KG: MR imaging of relapsing multiple sclerosis patients using ultra-small-particle iron oxide and compared with gadolinium. Am J Neuroradiol 2006, 27:1000-1005.
  • [288]Chen JW, Querol Sans M, Bogdanov A Jr, Weissleder R: Imaging of myeloperoxidase in mice by using novel amplifiable paramagnetic substrates. Radiology 2006, 240:473-481.
  • [289]Bakshi R, Dmochowski J, Shaikh ZA, Jacobs L: Gray matter T2 hypointensity is related to plaques and atrophy in the brains of multiple sclerosis patients. J Neurol Sci 2001, 185:19-26.
  • [290]Laule C, Vavasour IM, Kolind SH, Traboulsee AL, Moore GR, Li DK, Mackay AL: Long T2 water in multiple sclerosis: what else can we learn from multi-echo T2 relaxation? J Neurol 2007, 254:1579-1587.
  • [291]Bo L, Geurts JJ, Mork SJ, van der Valk P: Grey matter pathology in multiplesclerosis. Acta Neurol Scand Suppl 2006, 183:48-50.
  • [292]Miller DH, Soon D, Fernando KT, MacManus DG, Barker GJ, Yousry TA, Fisher E, O’Connor PW, Phillips JT, Polman CH, Kappos L, Hutchinson M, Havrdova E, Lublin FD, Giovannoni G, Wajgt A, Rudick R, Lynn F, Panzara MA, Sandrock AW, AFFIRM Investigators: MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology 2007, 68:1390-1401.
  • [293]Horakova D, Kalincik T, Dusankova JB, Dolezal O: Clinical correlates of grey matter pathology in multiple sclerosis. BMC Neurol 2012, 12:10.
  • [294]Prinster A, Quarantelli M, Orefice G, Lanzillo R, Brunetti A, Mollica C, Salvatore E, Morra VB, Coppola G, Vacca G, Alfano B, Salvatore M: Grey matter loss in relapsing-remitting multiple sclerosis: a voxel-based morphometry study. Neuroimage 2006, 29:859-867.
  • [295]Morgen K, Sammer G, Courtney SM, Wolters T, Melchior H, Blecker CR, Oschmann P, Kaps M, Vaitl D: Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing-remitting MS. Neuroimage 2005, 30:891-898.
  • [296]Okada T, Tanak M, Kuratsune H, Watanabe Y, Sadato N: Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol 2004, 4:14.
  • [297]Barnden LR, Crouch B, Kwiatek R, Burnet R, Mernone A, Chryssidis S, Scroop G, Del Fante P: A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis. NMR Biomed 2011, 24:1302-1312.
  • [298]Puri BK, Jakeman PM, Agour M, Gunatilake KD, Fernando KA, Gurusinghe AI, Treasaden IH, Waldman AD, Gishen P: Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3-T MRI study. Br J Radiol 2011, 85:e270-e273.
  • [299]Natelson BH, Cohen JM, Brassloff I, Lee HJ: A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome. J Neurol Sci 1993, 120:213-217.
  • [300]Lange G, DeLuca J, Maldjian JA, Lee H, Tiersky LA, Natelson BH: Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome. J Neurol Sci 2005, 171:3-7.
  • [301]Matthews PM, Francis G, Antel J, Arnold DL: Proton magnetic resonance spectroscopy for metabolic characterization of plaques in multiple sclerosis. Neurology 1991, 41:1251-1256.
  • [302]Butteriss DJA, Ismail A, Ellison DW, Birchall D: Use of serial proton magnetic resonance spectroscopy to differentiate low grade glioma from tumefactive plaque in a patient with multiple sclerosis. BJR 2003, 76:662-665.
  • [303]Hattingen E, Magerkurth J, Pilatus U, Hubers A, Wahl M, Ziemann U: Combined (1)H and (31)P spectroscopy provides new insights into the pathobiochemistry of brain damage in multiple sclerosis. NMR Biomed 2011, 24:536-546.
  • [304]Inglese M, Liu S, Babb JS, Mannon LJ, Grossman RI, Gonen O: Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing-remitting MS. Neurology 2004, 63:170-172.
  • [305]Gustafsson MC, Dahlqvist O, Jaworski J, Lundberg P, Landtblom AM: Low choline concentrations in normal-appearing white matter of patients with multiple sclerosis and normal MR imaging brain scans. AJNR Am J Neuroradiol 2007, 28:1306-1312.
  • [306]Richards TL: Proton MR spectroscopy in multiple sclerosis: value in establishing diagnosis, monitoring progression, and evaluating therapy. Am J Roentgenol 1991, 157:1073-1078.
  • [307]Davie CA, Hawkins CP, Barker GJ, Brennan A, Tofts PS, Miller DH, McDonald WI: Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain 1994, 117:49-58.
  • [308]Simone IL, Federico F, Trojano M, Tortorella C, Liguori M, Giannini P, Picciola E, Natile G, Livrea P: High resolution proton MR spectroscopy of cerebrospinal fluid in MS patients. Comparison with biochemical changes in demyelinating plaques. J Neurol Sci 1996, 144:182-190.
  • [309]Brooks JC, 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.
  • [310]Chaudhuri A, Condon B, Gow J, Brennan D, Hadley D: Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome. Brain Imaging 2003, 14:225-228.
  • [311]Puri BK, Counsell SJ, Zaman R, Main J, Collins AG, Hajnal JV, Davey NJ: Relative increase in choline in the occipital cortex in chronic fatigue syndrome. Acta Psychiatr Scand 2002, 106:224-226.
  • [312]Tomoda A, Miike T, Yamada E, Honda H, Moroi T, Ogawa M, Ohtani Y, Morishita S: Chronic fatigue syndrome in childhood. Brain Dev 2001, 22:60-64.
  • [313]Sharma KR, Kent-Braun J, Mynhier MA, Weiner MW, Miller RG: Evidence of an abnormal intramuscular component of fatigue in multiple sclerosis. Muscle Nerve 1995, 18:1403-1411.
  • [314]Steens A, de Vries A, Hemmen J, Heersema T, Heerings M, Maurits N, Zijdewind I: Fatigue perceived by multiple sclerosis patients is associated with muscle fatigue. Neurorehabil Neural Repair 2012, 26:48-57.
  • [315]Flachenecker P, Bihler I, Weber F, Gottschalk M, Toyka KV, Rieckmann P: Cytokine mRNA expression in patients with multiple sclerosis and fatigue. Mult Scler 2004, 10:165-169.
  • [316]Goebel MU, Baase J, Pithan V, Exton M, Saller B, Schedlowski M, Limmroth V: Acute interferon beta-1b administration alters hypothalamic-pituitary-adrenal axis activity, plasma cytokines and leukocyte distribution in healthy subjects. Psychoneuroendocrinol 2002, 27:881-892.
  • [317]Hautecoeur P, Forzy G, Gallois P, Demirbilek V, Feugas O: Variations of IL2, IL6, TNF alpha plasmatic levels in relapsing remitting multiple sclerosis. Acta Neurol Belg 1997, 97:240-243.
  • [318]Pokryszko-Dragan A, Frydecka I, Kosmaczewska A, Ciszak L, Bilinska M, Gruszka E, Podemski R, Frydecka D: Stimulated peripheral production of interferon-gamma is related to fatigue and depression in multiple sclerosis. Clin Neurol Neurosurg 2012, 114:1153-1158.
  • [319]Heesen C, Nawrath L, Reich C, Bauer N, Schulz KH, Gold SM: Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour? J Neurol Neurosurg Psychiatry 2006, 77:34-39.
  • [320]Sharma KR, Kent-Braun J, Mynhier MA, Weiner MW, Miller RG: Evidence of an abnormal intramuscular coponet of fatigue in multiple sclerosis. Muscle Nerve 2009, 18:1403-1411.
  • [321]Konecny L, Pospisil P, Dufek M, Drlikova L, Anbais FH, Erajhi AA, Dobsak P, Vank P, Siegelova J: Functional impairment in multiple sclerosis. Scripta Medica (BRNO) 2007, 80:225-232.
  • [322]Lenman AJ, Tulley FM, Vrbova G, Dimitrijevic MR, Towle JA: Muscle fatigue in some neurological disorders. Muscle Nerve 1989, 12:938-942.
  • [323]Kent-Braun JA, Sharma KR, Miller RG, Weiner MW: Postexercise phosphocreatine resynthesis is slowed in multiple sclerosis. Muscle Nerve 1994, 17:835-841.
  • [324]Kent-Braun JA, Ng AV, Castro M, Weiner MW, Gelinas D, Dudley GA, Miller RG: Strength, skeletal muscle composition, and enzyme activity in multiple sclerosis. J Appl Physiol 1997, 83:1998-2004.
  • [325]Petajan JH, White AT: Motor-evoked potentials in response to fatiguing grip exercise in multiple sclerosis. Clin Neurophysiol 2000, 111:2188-2195.
  • [326]Leocani L, Rovaris M, Boneschi FM, Medaglini S, Rossi P, Martinelli V, Amadio S, Comi G: Multimodal evoked potentials to assess the evolution of multiple sclerosis: a longitudinal study. J Neurol Neurosurg Psychiatry 2006, 77:1030-1035.
  • [327]Di Lazzaro V, Oliviero A, Profice P, Ferrara L, Saturno E, Pilato F, Tonali P: The diagnostic value of motor evoked potentials. Clin Neurophysiol 1999, 110:1297-1307.
  • [328]Colombo B, Martinelli Boneschi F, Rossi P, Rovaris M, Maderna L, Filippi M, Comi G: MRI And motor evoked potential findings in nondisabled multiple sclerosis with and without fatigue. J Neurol 2000, 247:506-509.
  • [329]Zeller D, Aufm Kampe K, Biller A, Stefan K, Gentner R, Schutz A, Bartsch A, Bendszus M, Toyka KV, Rieckmann P, Classen J: Rapid-onset central motor plasticity in multiple sclerosis. Neurology 2010, 74:728-735.
  • [330]Ng AV, Miller RG, Gelinas D, Kent-Braun JA: Functional relationships of central and peripheral muscle alterations in multiple sclerosis. Muscle Nerve 2004, 29:843-852.
  • [331]Kuspinar A, Andersen RE, Teng SY, Asano M, Mayo NE: Predicting exercise capacity through submaximal fitness tests in persons with multiple sclerosis. Arch Phys Med Rehabil 2010, 91:1410-1417.
  • [332]Savci S, Inal-Ince D, Arikan H, Guclu-Gunduz A, Cetisli-Korkmaz N, Armutlu K, Karabudak R: Six-minute walk distance as a measure of functional exercise capacity in multiple sclerosis. Disabil Rehabil 2005, 27:1365-1371.
  • [333]Bakshi R, Miletich RS, Kinkel PR, Emmet ML, Kinkel WR: High-resolution fluorodeoxyglucose positron emission tomography shows both global and regional cerebral hypometabolism in multiple sclerosis. J Neuroimaging 1998, 8:228-234.
  • [334]Bakshi R, Shaikh ZA, Miletich RS, Czarnecki D, Dmochowski J, Henschel K, Janardhan V, Dubey N, Kinkel PR: Fatigue in multiple sclerosis and its relationship to depression and neurologic disability. Mult Scler 2000, 6:181-185.
  • [335]Blinkenberg M, Rune K, Jensen CV, Ravnborg M, Kyllingsbaek S, Holm S, Paulson OB, Sorensen PS: Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS. Neurology 2000, 54:558-564.
  • [336]Murai H, Kiyosawa M, Suzuki Y, Mizoguchi S, Ishii K, Ishikawa K, Akashi T: A case of multiple sclerosis with homonymous hemianopia examined by positron emission tomography. Jpn J Ophthalmol 2004, 48:591-593.
  • [337]De Keyser J, Steen C, Mosert JP, Koch MW: Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance. J Cereb Blood Flow Metabol 2008, 28:1645-1651.
  • [338]Zamboni P, Menegatti E, Weinstock-Guttman B, Dwyer MG, Schirda CV, Malagoni AM, Hojnacki D, Kennedy C, Carl E, Bergsland N, Magnano C, Bartolomei I, Salvi F, Zivadinov R: Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report. BMC Med 2011, 9:22.
  • [339]Tang PPZ, White AT, Topaz S, Petajan JH: Abstract. Muscle energy metabolism in multiple sclerosis measured by in vivo 31P Mrs 476. Med Sci Sports Exerc 1997, 29:83.
  • [340]Hu J, Xu Y, Jiang Q, Sehgal V, Shen Y, Xuan Y, Xia Y: Spectral pattern of total creatine and trimethyl ammonium in multiple sclerosis. Magn Reson Imaging 2004, 22:427-429.
  • [341]Inglese M, Park SJ, Johnson G, Babb JS, Miles L, Jaggi H, Herbert J, Grossman RI: Deep gray matter perfusion in multiple sclerosis: dynamic susceptibility contrast perfusion magnetic resonance imaging at 3 T. Arch Neurol 2007, 64:196-202.
  • [342]Sacco P, Hope PA, Thickbroom GW, Byrnes ML, Mastaglia FL: Corticomotor excitability and perception of effort during sustained exercise in chronic fatigue syndrome. Clin Neurophysiol 1999, 110:1883-1891.
  • [343]Samii A, Wassermann E, Ikoma K, Mercuri B, George MS, O’Fallon A, Dale JK, Straus SE, Hallett M: Decreased postexercise facilitation of motor evoked potentials with chronic fatigue or depression. Neurology 1996, 47:1410-1414.
  • [344]Samii A, Wassermann EM, Ikoma K, Mercuri B, Hallett M: Characterization of postexercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation. Neurology 1996, 46:1376-1382.
  • [345]Starr A, Scalise A, Gordon R, Michalewski H, Caramia M: Motor excitability in chronic fatigue syndrome. Clin Neurophysiol 2000, 111:2025-2031.
  • [346]Chaudhuri A, Behan P: Fatigue and basal ganglia. J Neurol Sci 2000, 179:34-42.
  • [347]Chaudhuri A, Behan P: Neurological dysfunction in chronic fatigue syndrome. JCFS 2000, 6:51-68.
  • [348]Schillings ML, Kalkman JS, van der Werf SP, van Engelen BG, Bleijenberg G, Zwartz MJ: Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome. Clin Neurophysiol 2004, 115:2518-2524.
  • [349]Kent-Braun JA, Sharma KR, Weiner MW, Massie B, Miller RG: Central basis of muscle fatigue in chronic fatigue syndrome. Neurology 1993, 43:125-131.
  • [350]Newham DJ, Davies JM, Mayston MJ: Voluntary force generation and activation in the knee muscles of stroke patients with mild spastic hemiparesis. J Physiol 1995, 483:128.
  • [351]Kent-Braun JA, Miller RG: Central fatigue during isometric exercise in amyotrophic lateral sclerosis. Muscle Nerve 2000, 2000:909-914.
  • [352]Davey NJ, Puri BK, Nowicky AV, Main J, Zaman R: Voluntary motor function in patients with chronic fatigue syndrome. J Psychosom Res 2001, 50:17-20.
  • [353]Davey NJ, Puri BK, Catley M, Main J, Nowicky AV, Zaman R: Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome. Int J Clin Pract 2003, 57:262-264.
  • [354]Araque A: Astrocyte-neuron signaling in the brain-implications for disease. Curr Opin Investig Drugs 2006, 7:619-624.
  • [355]Chvatal A, Anderov M, Neprasova H, Prajerova I, Benesova J, Butenko O, Verkhratsky A: Pathological potential of astroglia. Physiol Res 2008, 57:S101-S110.
  • [356]Yoshiuchi K, Farkas J, Natelson BH: Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Clin Physiol Funct Imaging 2006, 26:83-86.
  • [357]Unger ER, Miller AH, Jones JF, Drake DF, Tian H, Pagnoni G: Decreased basal ganglia activation in chronic fatigue syndrome subjects is associated with increased fatigue. FASEB J 2012, 26:1035.20.
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