Footnotes

Acknowledgment

The authors have no potential conflicts, financial or otherwise.


References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as:
*  Of importance
** Of major importance

1.   Fukada K, Straus S, Hickie I: The chronic fatigue syndrome:
      A comprehensive approach to its definition and study. Ann
      Intern Med 1994, 121:953-959.
2.   Landay A, Jessop C, Lennette E, Levy J: Chronic fatigue
      syndrome: Clinical condition associated with immune
      activation. Lancet 1991, 338:707-712.
3.   Plioplys A: Differential diagnosis in medical assessment. In
      Handbook of Chronic Fatigue Syndrome. Edited by Jason
      L, Fennel P, Taylor R. Hoboken: John Wiley and Sons;
      2003:26-41.
4.*  Maher KJ, Klimas NG, Fletcher MA: Chronic fatigue syn-
      drome is associated with diminished intracellular perforin.
      Clin Exp Immunol 2005, 142:505-511.
      First study to see cytotoxic T-cell defects as severe as natural killer
      cell defects using intracellular perforin assay.
5.** Hickie I, Davenport T, Wakefield D, et al.: Post-infec-
      tive and chronic fatigue syndromes precipitated by viral
      pathogens: Prospective cohort study. BMJ 2006, 333:575.
      Identified the severity of the primary infection as the primary
      predictor of the course of illness for patients with CFS.
6.   Appel S, Chapman J, Shoenfeld Y: Infections and vac-
      cination in chronic fatigue syndrome: Myth or reality.
      Autoimmunity 2007, 40:48-53.
7.   Maes M, Mihaylova I, De Ruyter M: Lower serum zinc in
      chronic fatigue syndrome (CFS): Relationships to immune
      dysfunctions and relevance for the oxidative stress status in
      CFS. J Affect Disord 2006, 90:141-147.
8.   Maes M, Mihaylova I, Leunis JC: In chronic fatigue
      syndrome, the decreased levels of omega-3 poly unsaturated
      fatty acids are related to lower serum zinc and defects in T
      cell activation. Neuro Endocrinol Lett 2005, 26:745-751.
9.   Maes M, Mihaylova I, Leunis JC: Chronic fatigue syndrome
      is accompanied by an IgM-related immune response
      directed against neopitopes formed by oxidative or nitrosa-
      tive damage to lipids and proteins. Neuro Endocrinol Lett
      2006, 27:615-621.
10.   Puri BK: Long-chain polyunsaturated fatty acids and the
      pathophysiology of myalgic encephalomyelitis (chronic
      fatigue syndrome). J Clin Pathol 2007, 60:122-124.
11.*  Grans H, Nilsson M, Dahlman-Wright K, Evengard B:
      Reduced levels of oestrogen receptor B (beta) mRNA in
      Swedish patients with chronic fatigue syndrome. J Clin
      Pathol 2007, 60:195-198.
      Described genomic findings related to sex hormone pathway
      abnormalities and CFS.
12.   Cleare AJ, Bearn J, Allain T, et al.: Contrasting neuroendo-
      crine responses in depression and chronic fatigue syndrome.
      J Affect Disord 1995, 34:283-289.
13.   Demitrack MA, Dale JK, Straus SE, et al.: Evidence for
      impaired activation of the hypothalamic-pituitary-adrenal
      axis in patients with chronic fatigue syndrome. J Clin
      Endocrinol Metab 1991, 73:1224-1234.
14.   Ter Wolbeek M, van Doornen LJ, Kavelaars A, et al.: Lon-
      gitudinal analysis of pro- and anti-inflammatory cytokine
      production in severely fatigued adolescents. Brain Behav
      Immun 2007, Epub ahead of print.
15.   Berneman ZN, Ablashi DV, Li G, et al.: Human herpesvirus
      7 is a T-lymphotropic virus and is related to, but signifi-
      cantly different from, human herpesvirus 6 and human
      cytomegalovirus. Proc Natl Acad Sci 1992, 89:10552-10556.
16.   White PD, Thomas JM, Kangro HO, et al.: Predictions
      and associations of fatigue syndrome and mood disorders
      that occur after infectious mononucleosis. Lancet 2001,
      358:1946-1954.
17.   Chapenko S, Krumina A, Kozireva S, et al.: Activation of
      human herpesvirus 6 and 7 in patients with chronic fatigue
      syndrome. J Clin Virol 2006, 37(Suppl 1):S47-51.
18.*  Petersen I, Thomas JM, Hamilton WT, White PD: Risk and
      predictors of fatigue after infectious mononucleosis in a
      large primary care cohort. QJM 2006; 99:49-55.
      Described the results of a study investigating the risk factors and
      predictors of the development of fatigue syndrome following an
      infection with infectious mononucleosis, or EBV. Identified female
      sex and premorbid mood disorder as risk factors for fatigue.
19.   Gow JW, Behan WM, Simpson K, et al.: Studies on entero-
      virus in patients with chronic fatigue syndrome. Clin Infect
      Dis 1994, 18(Suppl 1):S126-129.
20.   Maes M, Mihaylova I, Leunis JC: Increased serum IgA and
      IgM against LPS of enterobacteria higher in chronic fatigue
      syndrome (CFS): Indication for the involvement of gram-
      negative bacteria in the etiology of CFS and for the presence
      of an increased gut-intestinal permeability. J Affect Disord
      2007, 99:237-240.
21.** Chia JK, Chia AY: Chronic fatigue syndrome is associated
      with chronic enterovirus infection of the stomach. J Clin
      Pathol 2007, Epub ahead of print.
      The first study to look at enterovirus in CFS. Researchers found
      enterovirus viral capsid protein 1, RNA, and noncytopathic viruses
      in the stomach biopsy specimens in the majority of CFS patients
      with chronic gastrointestinal complaints.
22.** Jerjes WK, Taylor NF, Wood PJ, Cleare AJ: Enhanced
      feedback sensitivity to prednisolone in chronic fatigue
      syndrome. Psychoneuroendocrinology 2007 32:192-198.
      Described alterations in negative feedback control of HPA axis in
      patients with CFS using dexamethasone suppression test.
23.   Rajeevan MS, Smith AK, Dimulescu I, et al.: Glucocorti-
      coid receptor polymorphisms and haplotypes associated
      with chronic fatigue syndrome. Genes Brain Behav 2007,
      6:167-176.
24.** Vernon SD, Whistler T, Cameron B, et al.: Preliminary
      evidence of mitochondrial dysfunction associated with
      post-infective fatigue after acute infection with Epstein Barr
      Virus. BMC Infect Dis 2006, 6:15.
      Described alterations in gene transcripts among patients with
      postinfective fatigue following acute infection with EBV. Found
      that the patients who developed the postinfective fatigue syndrome
      had gene expression profiles that indicated an altered host response
      during episode of acute mononucleosis when compared with those
      patients who recovered without event.
25.   Klimas NG, Salvato FR, Morgan R, Fletcher MA: Immu-
      nologic abnormalities in chronic fatigue syndrome. J Clin
      Microbiol 1990, 28:1403-1410.
26.   Landay AL, Jessop C, Lennette ET, Levy JA: Chronic
      fatigue syndrome: clinical condition associated with
      immune activation. Lancet 1991, 338:707-712.
27.   Maher K, Klimas N, Fletcher MA: Immunology. In
      Handbook of Chronic Fatigue Syndrome. Edited by Jason
      L, Fennel P, Taylor R. Hoboken: John Wiley and Sons;
      2003:124-151.
28.   Caligiuri M, Murray C, Buchwald D, et al.: Phenotypic and
      functional deficiency in natural killer cells in patients with
      chronic fatigue syndrome. J Immunol 1987, 139:3306-3313.
29.*  Siegel SD, Antoni MH, Fletcher MA, et al.: Impaired
      natural immunity, cognitive dysfunction, and physical
      symptoms in patients with chronic fatigue syndrome:
      Preliminary evidence for a subgroup? J Psychosom Res
      2006, 60:559-566.
      Identified subgroup by immune activation and cell function to
      predict symptom cluster and severity.
30.*  Kerr JR, Hodgetts A, Langford PR, et al.: Current research
      priorities in chronic fatigue syndrome/myalgic encephalitis:
      Disease mechanisms, a diagnostic test and specific treat-
      ments. J Clin Pathol 2007, 60:113-116.
      Reviews potential impact of genomics on diagnosis and treatment
      of CFS.
31.*  Kogelnik AM, Loomis K, Hoegh-Petersen M, et al.: Use
      of valganciclovir in patients with elevated antibody titers
      against Human Herpesvirus-6 (HHV-6) and Epstein-Barr
      Virus (EBV) who were experiencing central nervous system
      dysfunction including long-standing fatigue. J Clin Virol
      2006, 37 Suppl 1:S33-8.
      Phase 1 study of valganciclovir in the subgroup of CFS patients
      with high antibody titers to HHV-6 and/or EBV; phase 2 studies
      are currently underway with this group.
32.*  Lerner AM, Beqaj SH, Deeter RG, et al.: A six-month trial
      of valganciclovir in the Epstein-Barr virus subset of chronic
      fatigue syndrome: improvement in left ventricular function.
      Drugs Today (Barc). 2002, 38:549-561.
      Phase 1 study of valganciclovir suggesting that subgroup responds
      to viral suppression.
33.   Lundell K, Qazi S, Eddy L, Uckun FM: Clinical activity
      of folinic acid in patients with chronic fatigue syndrome.
      Arzneimittelforschung 2006, 56:399-404.
34.   Vermeulen RC, Scholte HR: Azithromycin in chronic
      fatigue syndrome (CFS), an analysis of clinical data. J
      Transl Med 2006, 4:34.

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