2013 – Page 13 – American ME and CFS Society

A qualitative natural history study of ME/CFS in the community

Abstract:

In previous qualitative research on Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS), researchers have focused on the experiences of patients with ME/CFS in tertiary care samples. This qualitative study examined the natural history of people with ME/CFS (n = 19) from a community-based sample. Findings highlighted multilayered themes involving the illness experience and the physical construction of ME/CFS.

In addition, this study further illuminated unique subthemes regarding community response and treatment, which have implications for understanding the progression of ME/CFS as well as experiences of those within patient networks. There is a need for more longitudinal qualitative research on epidemiological samples of patients with ME/CFS.

Source: Anderson VR, Jason LA, Hlavaty LE. A qualitative natural history study of ME/CFS in the community. Health Care Women Int. 2014 Jan;35(1):3-26. doi: 10.1080/07399332.2012.684816. Epub 2013 Feb 27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852694/ (Full article)

The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma

Abstract:

The aim of this article is to provide a comprehensive and updated review of the key neuropsychiatric and neuropsychological complaints associated with chronic fatigue syndrome (CFS). Neuropsychiatric and neuropsychological difficulties are common in CFS and are linked primarily to disorders of mood, affect and behaviour.

The neuropsychiatric complaint most frequently encountered amongst CFS patients is depression and in particular major depressive disorder (MDD). Despite decades of research, the precise aetiological relationship between CFS and MDD remains poorly understood. This has resulted in the development of a number of interesting and polarised hypotheses regarding the aetiological nature of CFS. Recent scientific advances have however begun to unravel a number of interesting inflammatory and immunological explanations that suggest CFS and MDD are distinct yet interrelated conditions.

The possibility that the overlap between CFS and MDD might be explained in terms of shared oxidative and nitrosative (IO&NS) pathways is an area of intense research interest and is reviewed in detail in this article. The overlap between CFS and MDD is further differentiated by variations in HPA axis activity between the two disorders. Important immunological differences between MDD and CFS are also reviewed with particular emphasis on antiviral RNase L pathways in CFS.

In addition to the presence of neuropsychiatric complaints, CFS is also associated with neuropsychological symptoms such as impaired attention, memory and reaction time. The key neuropsychological problems reported by CFS patients are also included in the review in an effort to understand the significance of cognitive impairment in CFS.

Source: Christley Y, Duffy T, Everall IP, Martin CR. The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma. Curr Psychiatry Rep. 2013 Apr;15(4):353. doi: 10.1007/s11920-013-0353-8. https://www.ncbi.nlm.nih.gov/pubmed/23440559

Fatigue heralding multiple sclerosis

Abstract:

BACKGROUND: Fatigue is a common symptom in multiple sclerosis (MS) and is an important determinant of overall well-being and disability.

OBJECTIVE: To assess the frequency with which fatigue precedes the diagnosis of MS using a retrospective database analysis.

METHODS: Between January 1, 2003 and September 30, 2008, patients diagnosed with fatigue with and without fatigue-related medications within a 3-year period prior to newly diagnosed MS were identified from the MarketScan Databases. All statistical analysis was performed using SAS.

RESULTS: Of the 16,976 patients with MS in the overall population, 5305 (31.3%) were newly diagnosed with MS and had three years of continuous healthcare coverage prior to MS diagnosis. Of these patients, 1534 (28.9%) were labeled with chronic fatigue syndrome (ICD9-780.71) or malaise or fatigue (ICD9-780.79) prior to the diagnosis of MS. One-third of these patients were labeled with fatigue one to two years before the diagnosis; 30.8% were diagnosed only with fatigue and had no other MS symptoms prior to their MS diagnosis. Among the patients diagnosed with fatigue, 10.4% were also prescribed medication for fatigue.

CONCLUSION: This study demonstrates that fatigue may herald MS, often by years. A careful history for transient neurological symptoms and a physical examination is warranted in any patient presenting with fatigue.

Source: Berger JR, Pocoski J, Preblick R, Boklage S. Fatigue heralding multiple sclerosis. Mult Scler. 2013 Oct;19(11):1526-32. doi: 10.1177/1352458513477924. Epub 2013 Feb 25. https://www.ncbi.nlm.nih.gov/pubmed/23439577

Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins

Abstract:

Myalgic encephalomyelitis (ME) is a debilitating illness of unknown etiology characterized by neurocognitive dysfunction, inflammation, immune abnormalities and gastrointestinal distress. An increasing body of evidence suggests that disruptions in the gut may contribute to the induction of neuroinflammation. Therefore, reports of human endogenous retroviral (HERV) expression in association with neuroinflammatory diseases prompted us to investigate the gut of individuals with ME for the presence of HERV proteins.

In eight out of 12 individuals with ME, immunoreactivity to HERV proteins was observed in duodenal biopsies. In contrast, no immunoreactivity was detected in any of the eight controls. Immunoreactivity to HERV Gag and Env proteins was uniquely co-localized in hematopoietic cells expressing the C-type lectin receptor CLEC4C (CD303/BDCA2), the co-stimulatory marker CD86 and the class II major histocompatibility complex HLA-DR, consistent with plasmacytoid dendritic cells (pDCs). Although the significance of HERVs present in the pDCs of individuals with ME has yet to be determined, these data raise the possibility of an involvment of pDCs and HERVs in ME pathology. To our knowledge, this report describes the first direct association between pDCs and HERVs in human disease.

Source: De Meirleir KL, Khaiboullina SF, Frémont M, Hulstaert J, Rizvanov AA, Palotás A, Lombardi VC. Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins. In Vivo. 2013 Mar-Apr;27(2):177-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776582/ (Full article)

Views on the nature of chronic fatigue syndrome: content analysis

Abstract:

OBJECTIVES: Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), has provoked much controversy and led to arguments between the medical profession and patient organizations. A particular focus for debate is the categorization of the condition as physical or psychological in its nature. The aim of this study was to compare how the written media, patient organizations and medical authorities regard the illness.

DESIGN: Content analysis of newspaper articles, ME patient organization websites, and medical websites and textbooks were assessed by two independent assessors.

SETTING:Three national UK newspapers, UK ME websites, and UK medical websites and textbooks, were accessed during 2010.

PARTICIPANTS: 146 source files were scored from 36 patients’ organizations, 72 media articles and 38 medical authorities.

MAIN OUTCOME MEASURED: The overall opinion of an article or website was rated using a five point Likert scale, from ‘extremely psychological’ (scored as 1), ‘moderately psychological’ (2), ‘both psychological and physical’ (3), ‘moderately physical’ (4) or ‘extremely physical’ (5).

RESULTS: Eighty-nine percent (32 of 36) of ME patient organizations considered the illness to be physical, compared with 58% (42/72) of newspaper articles, and 24% (9/38) of medical authorities. Sixty-three percent (24/38) of medical authorities regarded the illness as both physical and psychological. The inter-group differences of the Likert scores were statistically significant (χ(2) = 27.37, 2 df, P < 0.001).

CONCLUSION: The considerable disagreement, particularly between ME patient organizations and medical authorities, may help to explain the gulf in understanding between doctors and patients and the consequent reluctance of some patients to engage in behavioural treatments.

Source: Hossenbaccus Z, White PD. Views on the nature of chronic fatigue syndrome: content analysis. JRSM Short Rep. 2013 Jan;4(1):4. doi: 10.1258/shorts.2012.012051. Epub 2013 Jan 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572659/ (Full articles)

Human endogenous retrovirus-K18 superantigen expression and human herpesvirus-6 and human herpesvirus-7 viral loads in chronic fatigue patients

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a complex, heterogeneous disease characterized by debilitating fatigue that is not improved with bed rest and worsens after physical activity or mental exertion. Despite extensive research into a cause of CFS, no definitive etiology has been determined; however, a large percentage of CFS patients note an acute infectious event that triggers their fatigue.

METHODS: Blood and saliva were collected from 39 CFS cases and 9 healthy control subjects. Peripheral blood mononuclear cells (PBMCs) were tested for human endogenous retrovirus-K18 (HERV-K18) env transcripts using a TaqMan quantitative polymerase chain reaction (qPCR). In addition, viral copy number of human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) were measured in both saliva and PBMCs using TaqMan qPCRs. Transcript levels and viral copy number were compared to patient CFS symptom severity.

RESULTS: HERV-K18 env transcripts were not significantly different between healthy control subjects and CFS patients. Also, HERV-K18 env transcripts did not correlate with HHV-6 viral copy number or HHV-7 viral copy number in either PBMCs or saliva. HHV-6 viral copy number and HHV-7 viral copy number in both PBMCs and saliva were not significantly different between healthy control subjects and CFS patients. HERV-K18 env transcripts, HHV-6 viral copy number, and HHV-7 viral copy number did not correlate with CFS symptom severity.

CONCLUSIONS: We fail to demonstrate a difference in HERV-K18 env transcripts, HHV-6 viral copy number, and HHV-7 viral copy number between CFS patients and healthy controls. Our data do not support the hypothesis of reactivation of HHV-6 or HHV-7 in CFS.

Source: Oakes B, Hoagland-Henefield M, Komaroff AL, Erickson JL, Huber BT. Human endogenous retrovirus-K18 superantigen expression and human herpesvirus-6 and human herpesvirus-7 viral loads in chronic fatigue patients. Clin Infect Dis. 2013 May;56(10):1394-400. doi: 10.1093/cid/cit086. Epub 2013 Feb 13. http://cid.oxfordjournals.org/content/56/10/1394.long (Full article)

Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course

Abstract:

BACKGROUND: A high prevalence of chronic fatigue has previously been reported following giardiasis after a large waterborne outbreak in Bergen, Norway in 2004. The aim of this study was to describe and evaluate differential diagnoses and natural course of fatigue five years after giardiasis among patients who reported chronic fatigue three years after the infection.

METHODS: Patients who three years after Giardia infection met Chalder’s criteria for chronic fatigue (n=347) in a questionnaire study among all patients who had laboratory confirmed giardiasis during the Bergen outbreak (n=1252) were invited to participate in this study five years after the infection (n=253). Structured interviews and clinical examination were performed by specialists in psychiatry, neurology and internal medicine/infectious diseases. Fukuda et al’s 1994 criteria were used to diagnose chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF). Self-reported fatigue recorded with Chalder Fatigue Questionnaire three and five years after infection were compared.

RESULTS: 53 patients were included. CFS was diagnosed in 41.5% (22/53) and ICF in 13.2% (7/53). Chronic fatigue caused by other aetiology was diagnosed in 24.5% (13/53); five of these patients had sleep apnoea/hypopnoea syndrome, six had depression and five anxiety disorder, and among these two had more than one diagnosis. Fatigue had resolved in 20.8% (11/53). Self-reported fatigue score in the cohort was significantly reduced at five years compared to three years (p<0.001).

CONCLUSION: The study shows that Giardia duodenalis may induce CFS persisting as long as five years after the infection. Obstructive sleep apnoea/hypopnoea syndrome, depression and anxiety were important differential diagnoses, or possibly comorbidities, to post-infectious fatigue in this study. Improvement of chronic fatigue in the period from three to five years after giardiasis was found.

Source: Mørch K, Hanevik K, Rivenes AC, Bødtker JE, Næss H, Stubhaug B, Wensaas KA, Rortveit G, Eide GE, Hausken T, Langeland N. Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course. BMC Gastroenterol. 2013 Feb 12;13:28. doi: 10.1186/1471-230X-13-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598369/ (Full article)

Is chronic fatigue syndrome in older patients a different disease? — a clinical cohort study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling disorder characterised by persistent fatigue with a typical age of diagnosis of 35-50 years. CFS does present in those aged over 50 but whether this is a different disease in older age groups has not been considered. Therefore, we performed a clinical cohort study to examine and differentiate the clinical and autonomic features in CFS patients aged over 50.

DESIGN: A total of 179 Fukuda diagnosed CFS patients were recruited, and 25 older CFS patients (50 + years) were matched case by case for gender and length of history to 25 younger CFS patients (16-29 years). A range of symptomatic-based questionnaires were used in addition to heart rate variability and baroreceptor sensitivity to assess autonomic function.

RESULTS: Chronic fatigue syndrome can present for the first time in an older population. Older CFS patients demonstrate increased fatigue (Fatigue impact scale; 85 ± 33 vs. 107 ± 27, P = 0·02) (Chalder fatigue scale; 9 ± 3 vs. 11 ± 1, P = 0·002) and caseness for depression (Hospital Anxiety and Depression scale; 7 ± 3 vs. 10 ± 4; P = 0·005). There is a greater autonomic dysfunction in older CFS patients, with reduced parasympathetic function (HFnu; 49·1 ± 18 vs. 36·2 ± 18, P = 0·01, RR30 : 15; ± , P = 0·02) and increased sympathetic function (LFnu; 51·5 ± 17 vs. 63·8 ± 18, P = 0·01). Baroreflex sensitivity was substantially reduced (BRS; 19·7 ± 12 vs. 9·9 ± 5, P = 0·0004), and left ventricular ejection time prolonged (LVET; 274·6 ± 16 vs. 285·8 ± 9, P = 0·004).

CONCLUSIONS: Older CFS patients demonstrate a disease phenotype very different from younger patients. The combination of differing underlying pathogenic mechanisms and the physiological aspects of ageing result in a greater disease impact in older CFS patients.

Source: Lewis I, Pairman J, Spickett G, Newton JL. Is chronic fatigue syndrome in older patients a different disease? — a clinical cohort study. Eur J Clin Invest. 2013 Mar;43(3):302-8. doi: 10.1111/eci.12046. Epub 2013 Feb 9. https://www.ncbi.nlm.nih.gov/pubmed/23397955

Chronic fatigue syndrome: 3 cases and a discussion of the natural history of attention-deficit/hyperactivity disorder

Abstract:

Fatigue is commonly reported in the primary care setting; however, its cause is often unclear. This article presents 3 cases involving patients with chronic fatigue syndrome who responded poorly to treatment. After clinical evaluation, all patients were found to meet criteria for attention-deficit/hyperactivity disorder (ADHD) and underwent a standard regimen of a psychostimulant medication.

After treatment with psychostimulants, the 3 patients reported improved symptoms of fatigue and pain, and cognitive and core ADHD symptoms. These cases suggest that ADHD and chronic fatigue syndrome (and possibly fibromyalgia) share a common underlying mechanism. This article presents a model suggesting that over time, ADHD (predominantly inattentive type) develops into a syndrome of chronic fatigue and pain. These cases indicate that fatigue may be an important presenting symptom of adult ADHD. These cases also suggest the need for additional research to determine the prevalence of ADHD in patients who present with fatigue, and, in those meeting criteria for ADHD, the responsiveness of fatigue to psychostimulant treatment.

Source: Young JL. Chronic fatigue syndrome: 3 cases and a discussion of the natural history of attention-deficit/hyperactivity disorder. Postgrad Med. 2013 Jan;125(1):162-8. doi: 10.3810/pgm.2013.01.2631. https://www.ncbi.nlm.nih.gov/pubmed/23391682

A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria

Abstract:

BACKGROUND: Chronic Fatigue Syndrome case designation criteria are scored as physicians’ subjective, nominal interpretations of patient fatigue, pain (headaches, myalgia, arthralgia, sore throat and lymph nodes), cognitive dysfunction, sleep and exertional exhaustion.

METHODS: Subjects self-reported symptoms using an anchored ordinal scale of 0 (no symptom), 1 (trivial complaints), 2 (mild), 3 (moderate), and 4 (severe). Fatigue of 3 or 4 distinguished “Fatigued” from “Not Fatigued” subjects. The sum of the 8(Sum8) ancillary criteria was tested as a proxy for fatigue. All subjects had history and physical examinations to exclude medical fatigue, and ensure categorization as healthy or CFS subjects.

RESULTS: Fatigued subjects were divided into CFS with ≥4 symptoms or Chronic Idiopathic Fatigue (CIF) with ≤3 symptoms. ROC of Sum8 for CFS and Not Fatigued subjects generated a threshold of 14 (specificity=0.934; sensitivity=0.928). CFS (n=256) and CIF (n=55) criteria were refined to include Sum8≥14 and ≤13, respectively. Not Fatigued subjects had highly skewed Sum8 responses. Healthy Controls (HC; n=269) were defined by fatigue≤2 and Sum8≤13. Those with Sum8≥14 were defined as CFS-Like With Insufficient Fatigue Syndrome (CFSLWIFS; n=20). Sum8 and Fatigue were highly correlated (R(2)=0.977; Cronbach’s alpha=0.924) indicating an intimate relationship between symptom constructs. Cluster analysis suggested 4 clades each in CFS and HC. Translational utility was inferred from the clustering of proteomics from cerebrospinal fluid.

CONCLUSIONS: Plotting Fatigue severity versus Sum8 produced an internally consistent classifying system. This is a necessary step for translating symptom profiles into fatigue phenotypes and their pathophysiological mechanisms.

Source: Baraniuk JN, Adewuyi O, Merck SJ, Ali M, Ravindran MK, Timbol CR, Rayhan R, Zheng Y, Le U, Esteitie R, Petrie KN. A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria. Am J Transl Res. 2013;5(1):53-68. Epub 2013 Jan 21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560481/ (Full article)