longitudinal study – Page 2 – American ME and CFS Society

Impact of Life Stressors on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Symptoms: An Australian Longitudinal Study

Abstract:

(1) Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multifaceted illness. The pathomechanism, severity and progression of this illness is still being investigated. Stressors have been implicated in symptom exacerbation for ME/CFS, however, there is limited information for an Australian ME/CFS cohort. The aim of this study was to assess the potential effect of life stressors including changes in work, income, or family scenario on symptom severity in an Australian ME/CFS cohort over five months;

(2) Methods: Australian residents with ME/CFS responded to questions relating to work, income, living arrangement, access to healthcare and support services as well as symptoms experienced;

(3) Results: thirty-six ME/CFS patients (age: 41.25 ± 12.14) completed all questionnaires (response rate 83.7%). Muscle pain and weakness, orthostatic intolerance and intolerance to extreme temperatures were experienced and fluctuated over time. Sleep disturbances were likely to present as severe. Work and household income were associated with worsened cognitive, gastrointestinal, body pain and sleep symptoms. Increased access to healthcare services was associated with improved symptom presentation;

(4) Conclusions: life stressors such as work and financial disruptions may significantly contribute to exacerbation of ME/CFS symptoms. Access to support services correlates with lower symptom scores.

Source: Balinas C, Eaton-Fitch N, Maksoud R, Staines D, Marshall-Gradisnik S. Impact of Life Stressors on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Symptoms: An Australian Longitudinal Study. Int J Environ Res Public Health. 2021 Oct 11;18(20):10614. doi: 10.3390/ijerph182010614. PMID: 34682360; PMCID: PMC8535742. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535742/ (Full text)

Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by prolonged fatigue and other physical and neurocognitive symptoms. Some studies suggest that CFS is accompanied by disruptions in the number and function of various lymphocytes. However, it is not clear which lymphocytes might influence CFS symptoms.

PURPOSE: To determine if patient reported fatigue symptoms and physical functioning scores significantly changed across time with lymphocyte counts as evidence of a relation among chronic fatigue symptoms and the immune response.

METHODS: The current longitudinal, naturalistic study assessed the cellular expression of three lymphocyte subtypes — natural killer (NK) cells (CD3-CD16+ and CD3-CD56+) and naïve T cells (CD4+CD45RA+) — to determine whether changes in lymphocytes at 4 time points across 18 months were associated with clinical outcomes, including CFS symptoms, physical functioning, and vitality, among patients with chronic fatigue.. Latent growth curve models were used to examine the longitudinal relationship between lymphocytes and clinical outcomes.

RESULTS: Ninety-three patients with Fukuda-based CFS and seven with non-CFS fatigue provided study data. Results indicated that higher proportions of naïve T cells and lower proportions of NK cells were associated with worse physical functioning, whereas higher proportions of NK cells (CD3-CD16+) and lower proportions of naïve T cells were associated with fewer CFS symptoms.

CONCLUSION: These findings suggest that lymphocytes are modestly related to clinical outcomes over time.

Source: Mehalick ML, Schmaling KB, Sabath DE, Buchwald DS. Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome. Fatigue. 2018;6(2):80-91. doi: 10.1080/21641846.2018.1426371. Epub 2018 Jan 12. https://www.ncbi.nlm.nih.gov/pubmed/30112249

Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome

Abstract:

Background: Chronic fatigue syndrome (CFS) is characterized by prolonged fatigue and other physical and neurocognitive symptoms. Some studies suggest that CFS is accompanied by disruptions in the number and function of various lymphocytes. However, it is not clear which lymphocytes might influence CFS symptoms.

Purpose: To determine if patient reported fatigue symptoms and physical functioning scores significantly changed across time with lymphocyte counts as evidence of a relation among chronic fatigue symptoms and the immune response.

Methods: The current longitudinal, naturalistic study assessed the cellular expression of three lymphocyte subtypes – natural killer (NK) cells (CD3 − CD16+ and CD3 − CD56+) and naïve T cells (CD4 + CD45RA+) – to determine whether changes in lymphocytes at 4 time points across 18 months were associated with clinical outcomes, including CFS symptoms, physical functioning, and vitality, among patients with chronic fatigue. Latent growth curve models were used to examine the longitudinal relationship between lymphocytes and clinical outcomes.

Results: Ninety-three patients with Fukuda-based CFS and seven with non-CFS fatigue provided study data. Results indicated that higher proportions of naïve T cells and lower proportions of NK cells were associated with worse physical functioning, whereas higher proportions of NK cells (CD3 − CD16+) and lower proportions of naïve T cells were associated with fewer CFS symptoms.

Conclusion: These findings suggest that lymphocytes are modestly related to clinical outcomes over time.

Source: Melissa L. Mehalick, Karen B. Schmaling, Daniel E. Sabath & Dedra S.Buchwald. Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome. Fatigue: Biomedicine, Health & Behavior, Published online: 12 Jan 2018. http://www.tandfonline.com/action/showCitFormats?doi=10.1080%2F21641846.2018.1426371

Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway

Abstract:

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex condition. Causal factors are not established, although underlying psychological or immunological susceptibility has been proposed. We studied primary care diagnoses for children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups.

METHODS: All Norwegian children born 1992-2012 constituted the study sample. Children with CFS/ME (n = 1670) or T1DM (n = 4937) were identified in the Norwegian Patient Register (NPR) (2008-2014). Children without either diagnosis constituted the general child population comparison group (n = 1337508). We obtained information on primary care diagnoses from the Norwegian Directorate of Health. For each primary care diagnosis, the proportion and 99 % confidence interval (CI) within the three groups was calculated, adjusted for sex and age by direct standardization.

RESULTS: Children with CFS/ME were more often registered with a primary care diagnosis of weakness/general tiredness (89.9 % [99 % CI 88.0 to 91.8 %]) than children in either comparison group (T1DM: 14.5 % [99 % CI: 13.1 to 16.0 %], general child population: 11.1 % [99 % CI: 11.0 to 11.2 %]). Also, depressive disorder and anxiety disorder were more common in the CFS/ME group, as were migraine, muscle pain, and infections. In the 2 year period prior to the diagnoses, infectious mononucleosis was registered for 11.1 % (99 % CI 9.1 to 13.1 %) of children with CFS/ME and for 0.5 % (99 % CI (0.2 to 0.8 %) of children with T1DM. Of children with CFS/ME, 74.6 % (1292/1670) were registered with a prior primary care diagnosis of weakness / general tiredness. The time span from the first primary care diagnosis of weakness / general tiredness to the specialist health care diagnosis of CFS/ME was 1 year or longer for 47.8 %.

CONCLUSIONS: This large nationwide registry linkage study confirms that the clinical picture in CFS/ME is complex. Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway. The long time span often observed from the first diagnosis of weakness / general tiredness to the diagnosis of CFS/ME might indicate that the treatment of these patients is sometimes not optimal.

Source: Bakken IJ, Tveito K, Aaberg KM, Ghaderi S, Gunnes N, Trogstad L, Magnus P, Stoltenberg C, Håberg SE. Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway. BMC Fam Pract. 2016 Sep 2;17(1):128. doi: 10.1186/s12875-016-0527-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010760/ (Full article)

Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study

Abstract:

PURPOSE: To examine progressive brain changes associated with chronic fatigue syndrome (CFS).

MATERIALS AND METHODS: We investigated progressive brain changes with longitudinal MRI in 15 CFS and 10 normal controls (NCs) scanned twice 6 years apart on the same 1.5 Tesla (T) scanner. MR images yielded gray matter (GM) volumes, white matter (WM) volumes, and T1- and T2-weighted signal intensities (T1w and T2w). Each participant was characterized with Bell disability scores, and somatic and neurological symptom scores. We tested for differences in longitudinal changes between CFS and NC groups, inter group differences between pooled CFS and pooled NC populations, and correlations between MRI and symptom scores using voxel based morphometry. The analysis methodologies were first optimized using simulated atrophy.

RESULTS: We found a significant decrease in WM volumes in the left inferior fronto-occipital fasciculus (IFOF) in CFS while in NCs it was unchanged (family wise error adjusted cluster level P value, PFWE < 0.05). This longitudinal finding was consolidated by the group comparisons which detected significantly decreased regional WM volumes in adjacent regions (PFWE< 0.05) and decreased GM and blood volumes in contralateral regions (PFWE < 0.05). Moreover, the regional GM and WM volumes and T2w in those areas showed significant correlations with CFS symptom scores (PFWE < 0.05).

CONCLUSION: The results suggested that CFS is associated with IFOF WM deficits which continue to deteriorate at an abnormal rate. J. Magn. Reson. Imaging 2016;44:1301-1311.

Source: Shan ZY, Kwiatek R, Burnet R, Del Fante P, Staines DR, Marshall-Gradisnik SM, Barnden LR. Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study. J Magn Reson Imaging. 2016 Nov;44(5):1301-1311. doi: 10.1002/jmri.25283. Epub 2016 Apr 28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111735/ (Full article)

Chronic Fatigue Syndrome at Age 16 Years

Abstract:

BACKGROUND: In the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, chronic disabling fatigue lasting ≥6 months affected 1.3% of 13-year-olds, was equally common in boys and girls, and became more prevalent with increasing family adversity.

METHODS: ALSPAC data were used to estimate the prevalence of chronic fatigue syndrome (CFS) at age 16 years, defined by parental report of unexplained disabling fatigue lasting ≥6 months. We investigated gender and a composite 14-item family adversity index as risk factors. School absence data were obtained from the National Pupil Database. Multiple imputation was used to address bias caused by missing data.

RESULTS: The prevalence of CFS was 1.86% (95% confidence interval [CI]: 1.47 to 2.24). After excluding children with high levels of depressive symptoms, the prevalence was 0.60% (95% CI: 0.37 to 0.84). Authorized school absences were much higher (mean difference: 35.6 [95% CI: 26.4 to 44.9] half-day sessions per academic year) and reported depressive symptoms were much more likely (odds ratio [OR]: 11.0 [95% CI: 5.92 to 20.4]) in children with CFS than in those without CFS. Female gender (OR: 1.95 [95% CI: 1.33 to 2.86]) and family adversity (OR: 1.20 [95% CI: 1.01 to 1.42] per unit family adversity index) were also associated with CFS.

CONCLUSIONS: CFS affected 1.9% of 16-year-olds in a UK birth cohort and was positively associated with higher family adversity. Gender was a risk factor at age 16 years but not at age 13 years or in 16-year-olds without high levels of depressive symptoms.

Source: Collin SM, Norris T, Nuevo R, Tilling K, Joinson C, Sterne JA, Crawley E. Chronic Fatigue Syndrome at Age 16 Years. Pediatrics. 2016 Feb;137(2):e20153434. doi: 10.1542/peds.2015-3434. Epub 2016 Jan 25. http://pediatrics.aappublications.org/content/137/2/e20153434.long (Full article)

Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients

Abstract:

BACKGROUND: Research has identified immunological abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), a heterogeneous illness with an unknown cause and absence of diagnostic test. There have been no CFS/ME studies examining innate and adaptive immune cells longitudinally in patients with varying severities. This is the first study to investigate immune cells over 6 months while also examining CFS/ME patients of varying symptom severity.

METHODS: Participants were grouped into 18 healthy controls, 12 moderate and 12 severe CFS/ME patients and flow cytometry was used to examine cell parameters at 0 and 6 months.

RESULTS: Over time, iNKT CD62L expression significantly increased in moderate CFS/ME patients and CD56(bright) NK receptors differed in severe CFS/ME. Naïve CD8(+)T cells, CD8(-)CD4(-) and CD56(-)CD16(-) iNKT phenotypes, γδ2T cells and effector memory subsets were significantly increased in severe CFS/ME patients at 6 months. Severe CFS/ME patients were significantly reduced in CD56(bright)CD16(dim) NKG2D, CD56(dim)CD16(-) KIR2DL2/DL3, CD94(-)CD11a(-) γδ1T cells and CD62L(+)CD11a(-) γδ1T cells at 6 months.

CONCLUSIONS: Severe CFS/ME patients differed from controls and moderate CFS/ME patients over time and expressed significant alterations in iNKT cell phenotypes, CD8(+)T cell markers, NK cell receptors and γδT cells at 6 months. This highlights the importance of further assessing these potential immune biomarkers longitudinally in both moderate and severe CFS/ME patients.

Source: Hardcastle SL, Brenu EW, Johnston S, Nguyen T, Huth T, Ramos S, Staines D, Marshall-Gradisnik S. Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients. J Transl Med. 2015 Sep 14;13:299. doi: 10.1186/s12967-015-0653-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568602/ (Full article)

Longitudinal follow-up of employment status in patients with chronic fatigue syndrome after mononucleosis

Abstract:

OBJECTIVE: To examine the effect of early clinical and demographic factors on occupational outcome, return to work or awarded permanent disability pension in young patients with chronic fatigue syndrome (CFS).

DESIGN: Longitudinal cohort study.

INTERVENTION: A written self-management programme including a description of active coping strategies for daily life was provided.

SETTING, PARTICIPANTS: Patients with CFS after mononucleosis were evaluated at Department of Neurology, Haukeland University Hospital during 1996-2006 (contact 1). In 2009 self-report questionnaires were sent to all patients (contact 2).

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary measure was employment status at contact 2. Secondary measures included clinical symptoms, and Fatigue Severity Scale (FSS) scores on both contacts, and Work and Social Adjustment Scale (WSAS) at contact 2.

RESULTS: Of 111 patients at contact 1, 92 (83%) patients returned the questionnaire at contact 2. Mean disease duration at contact 1 was 4.7 years and at contact 2 11.4 years. At contact 1, 9 (10%) were part-time or full-time employed. At contact 2, 49 (55%) were part-time or full-time employed. Logical regression analysis showed that FSS≥5 at contact 2 was associated with depression, arthralgia and long disease duration (all at contact 1).

CONCLUSIONS: About half of younger patients with CFS with long-term incapacity for work experienced marked improvement including full-time or part-time employment showing better outcomes than expected. Risk factors for transition to permanent disability were depression, arthralgia and disease duration.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Source: Nyland M, Naess H, Birkeland JS, Nyland H. Longitudinal follow-up of employment status in patients with chronic fatigue syndrome after mononucleosis. BMJ Open. 2014 Nov 26;4(11):e005798. doi: 10.1136/bmjopen-2014-005798. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248085/ (Full article)

CFS in Children and Adolescent: Ten Years of Retrospective Clinical Evaluation

Abstract:

Aim. To estimate number of children being diagnosed with chronic fatigue syndrome (CFS). Methods. For a period of 10 years (2002-2011) data from children being referred for fatigue symptoms were collected retrospectively.

Results. Thirty-seven children were referred. Four were excluded due to incorrect coding. Six (18%) patients received other diagnoses at the end of evaluation time. Of the 27 who received the diagnosis G93.3, four had a previous chronic illness, while 23 patients were previously healthy. All patients reported onset of fatigue symptom in relation to an infection, and all tested positive for IgG to either Epstein-Barr virus, cytomegalovirus or borrelia, indicating previous infection. There were 16 (59%) boys among the 27 patients. The mean age at the debut of fatigue symptoms was 141 months (SD 30) for boys and 136 months (SD 31) for girls, respectively. Being underweight, defined as BMI < 17.5, was found in 12 (44%) patients.

Conclusion. An increasing number of children and adolescents are evaluated for CFS. The clinical assessment of children and adolescents with possible CFS need systematically evaluation. Nutritional status, possible eating disorder, and psychosocial issues need to be addressed and evaluated carefully. A multidisciplinary approach is essential when assessing CFS in children and adolescents. There is a need for European guidelines.

Source: Elgen I, Hikmat O, Aspevik TN, Hagen EM. CFS in Children and Adolescent: Ten Years of Retrospective Clinical Evaluation. Int J Pediatr. 2013;2013:270373. doi: 10.1155/2013/270373. Epub 2013 Jun 16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697308/ (Full article)

Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.

METHODS: Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.

RESULTS: Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.

CONCLUSIONS: Our results support the role of cytokines in the pathophysiology of CFS.

Source: Stringer EA, Baker KS, Carroll IR, Montoya JG, Chu L, Maecker HT, Younger JW. Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology. J Transl Med. 2013 Apr 9;11:93. doi: 10.1186/1479-5876-11-93. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637529/ (Full article)