Category: Pediatric ME/CFS

Pediatric and Adult Patients with ME/CFS following COVID-19: A Structured Approach to Diagnosis Using the Munich Berlin Symptom Questionnaire (MBSQ)

Abstract:

Purpose A subset of patients with post-COVID-19 condition (PCC) fulfill the clinical criteria of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). To establish the diagnosis of ME/CFS for clinical and research purposes, comprehensive scores have to be evaluated.

Methods We developed the Munich Berlin Symptom Questionnaires (MBSQs) and supplementary scoring sheets (SSSs) to allow for a rapid evaluation of common ME/CFS case definitions. The MBSQs were applied to young patients with chronic fatigue and post-exertional malaise (PEM) who presented to the MRI Chronic Fatigue Center for Young People (MCFC). Trials were retrospectively registered (NCT05778006, NCT05638724).

Results Using the MBSQs and SSSs, we report on ten patients aged 11 to 25 years diagnosed with ME/CFS after asymptomatic SARS-CoV-2 infection or mild to moderate COVID-19. Results from their MBSQs and from well-established patient-reported outcome measures indicated severe impairments of daily activities and health-related quality of life.

Conclusions ME/CFS can follow SARS-CoV-2 infection in patients younger than 18 years, rendering structured diagnostic approaches most relevant for pediatric PCC clinics. The MBSQs and SSSs represent novel diagnostic tools that can facilitate the diagnosis of ME/CFS in children, adolescents, and adults with PCC and other post-viral syndromes.

What is known ME/CFS is a frequent debilitating illness. For diagnosis, an extensive differential diagnostic workup is required and the evaluation of clinical ME/CFS criteria. ME/CFS following COVID-19 has been reported in adults but not in pediatric patients younger than 19 years of age.

What is new We present novel questionnairs (MBSQs), as tools to assess common ME/CFS case definitions in pediatric and adult patients with post-COVID-19 condition and beyond. We report on ten patients aged 11 to 25 years diagnosed with ME/CFS following asymptomatic SARS-CoV-2 infection or mild to moderate COVID-19.

Source: Laura C. Peo, Katharina Wiehler, Johannes Paulick, Katrin Gerrer, Ariane Leone, Anja Viereck, Matthias Haegele, Silvia Stojanov, Cordula Warlitz, Silvia Augustin, Martin Alberer, Daniel B. R. Hattesohl, Laura Froehlich, Carmen Scheibenbogen, Lorenz Mihatsch, Rafael Pricoco, Uta Behrends. Pediatric and Adult Patients with ME/CFS following COVID-19: A Structured Approach to Diagnosis Using the Munich Berlin Symptom Questionnaire (MBSQ). medRxiv 2023.08.23.23293081; doi: https://doi.org/10.1101/2023.08.23.23293081 https://www.medrxiv.org/content/10.1101/2023.08.23.23293081v1.full-text (Full text)

One-Year Follow-up of Young People with ME/CFS Following Infectious Mononucleosis by Epstein-Barr Virus

Abstract:

Background: Infectious mononucleosis, caused by the Epstein-Barr Virus (EBV-IM), has been linked to the development of myalgic encephalomyelitis/chronic fatigue-syndrome (ME/CFS) in children, adolescents, and young adults. Our study presents the first cohort of young individuals in Germany who were diagnosed with ME/CFS following EBV-IM.

Methods: We conducted a one-year follow-up of 25 young people diagnosed with ME/CFS at our specialized tertiary outpatient service by clinical criteria requiring post-exertional malaise and with documented EBV-IM as the triggering event. Demographic information, laboratory findings, frequency and severity of symptoms, physical functioning, and health-related quality of life (HRQoL) were assessed at first visit as well as 6 and 12 months later at follow-up visits.

Results: The physical functioning and HRQoL of the cohort were significantly impaired, with young adults displaying more severe symptoms, as well as worsening of fatigue, physical and mental functioning, and HRQoL throughout the study, compared to adolescents. After one year, we found that 6/12 (54%) adolescents no longer met the diagnostic criteria for ME/CFS, indicating partial remission, while all young adults continued to fulfill the Canadian consensus criteria. Improvement in children was evident in physical functioning, symptom frequency and severity, and HRQoL, while young adults had little improvement. EBV serology and EBV DNA load did not correlate with distinct clinical features of ME/CFS, and clinical chemistry showed no evidence of inflammation. Remarkably, the median time from symptom onset to ME/CFS diagnosis was 13.8 (IQR: 9.1-34.9) months.

Conclusions: ME/CFS following EBV-IM in young people is a severely debilitating disease with diagnoses protracted longer than one year in many patients and only limited responses to conventional symptom-oriented medical care. Although younger children may have a better prognosis, their condition can fluctuate and significantly impact their HRQoL. Our data emphasize that biomarkers and effective therapeutic options are also urgently needed for this very young age group to better manage their medical condition and pave the way to recovery.

Source: Rafael Pricoco, Paulina Meidel, Tim Hofberger, Hannah Zietemann, Yvonne Mueller, Katharina Wiehler, Kaja Michel, Johannes Paulick, Ariane Leone, Matthias Haegele, Sandra Mayer-Huber, Katrin Gerrer, Kirstin Mittelstrass, Carmen Scheibenbogen, Herbert Renz-Polster, Lorenz Mihatsch, Uta Behrends. One-Year Follow-up of Young People with ME/CFS Following Infectious Mononucleosis by Epstein-Barr Virus. medRxiv 2023.07.24.23293082; doi: https://doi.org/10.1101/2023.07.24.23293082 https://www.medrxiv.org/content/10.1101/2023.07.24.23293082v1 (Full text available as PDF file)

What lies beneath: White matter microstructure in pediatric myalgic encephalomyelitis/chronic fatigue syndrome using diffusion MRI

Abstract:

Recent studies in adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that changes in brain white matter microstructural organization may correlate with core ME/CFS symptoms, and represent a potential biomarker of disease. However, this has yet to be investigated in the pediatric ME/CFS population. We examined group differences in macrostructural and microstructural white matter properties, and their relationship with clinical measures, between adolescents recently diagnosed with ME/CFS and healthy controls.

Forty-eight adolescents (25 ME/CFS, 23 controls, mean age 16 years) underwent brain diffusion MRI, and a robust multi-analytic approach was used to evaluate white and gray matter volume, regional brain volume, cortical thickness, fractional anisotropy, mean/axial/radial diffusivity, neurite dispersion and density, fiber density, and fiber cross section.

From a clinical perspective, adolescents with ME/CFS showed greater fatigue and pain, poorer sleep quality, and poorer performance on cognitive measures of processing speed and sustained attention compared with controls. However, no significant group differences in white matter properties were observed, with the exception of greater white matter fiber cross section of the left inferior longitudinal fasciculus in the ME/CFS group compared with controls, which did not survive correction for intracranial volume.

Overall, our findings suggest that white matter abnormalities may not be predominant in pediatric ME/CFS in the early stages following diagnosis. The discrepancy between our null findings and white matter abnormalities identified in the adult ME/CFS literature could suggest that older age and/or longer illness duration influence changes in brain structure and brain-behavior relationships that are not yet established in adolescence.

Source: Josev EK, Chen J, Seal M, Scheinberg A, Cole RC, Rowe K, Lubitz L, Knight SJ. What lies beneath: White matter microstructure in pediatric myalgic encephalomyelitis/chronic fatigue syndrome using diffusion MRI. J Neurosci Res. 2023 Jun 18. doi: 10.1002/jnr.25223. Epub ahead of print. PMID: 37331007. https://onlinelibrary.wiley.com/doi/10.1002/jnr.25223 (Full text)

Comparison of a 20 degree and 70 degree tilt test in adolescent myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients

Abstract:

Introduction: During a standard 70-degree head-up tilt test, 90% of adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develop an abnormal reduction in cerebral blood flow (CBF). A 70-degree test might not be tolerated by young ME/CFS patients because of the high incidence of syncopal spells. This study examined whether a test at 20 degrees would be sufficient to provoke important reductions in CBF in young ME/CFS patients.

Methods: We analyzed 83 studies of adolescent ME/CFS patients. We assessed CBF using extracranial Doppler measurements of the internal carotid and vertebral arteries supine and during the tilt. We studied 42 adolescents during a 20 degree and 41 during a 70 degree test.

Results: At 20 degrees, no patients developed postural orthostatic tachycardia (POTS), compared to 32% at 70 degrees (p = 0.0002). The CBF reduction during the 20 degree tilt of -27(6)% was slightly less than during the reduction during a 70 degree test [-31(7)%; p = 0.003]. Seventeen adolescents had CBF measurements at both 20 and 70 degrees. The CBF reduction in these patients with both a 20 and 70 degrees test was significantly larger at 70 degrees than at 20 degrees (p < 0.0001).

Conclusions: A 20 degree tilt in young ME/CFS patients resulted in a CBF reduction comparable to that in adult patients during a 70 degree test. The lower tilt angle provoked less POTS, emphasizing the importance of using the 70 degree angle for that diagnosis. Further study is needed to explore whether CBF measurements during tilt provide an improved standard for classifying orthostatic intolerance.

Source: van Campen CLMC, Rowe PC, Visser FC. Comparison of a 20 degree and 70 degree tilt test in adolescent myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients. Front Pediatr. 2023 May 12;11:1169447. doi: 10.3389/fped.2023.1169447. PMID: 37252045; PMCID: PMC10213432. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213432/ (Full text)

Service users’ and parents/carers’ experiences of a paediatric chronic fatigue service: A service evaluation

Abstract:

Objectives: This service evaluation explored the experiences of families receiving care in a paediatric chronic fatigue service. The evaluation aimed to improve service provision across paediatric chronic fatigue services more widely.

Methods: Children and young people aged 7-18 years (n = 25) and parents/carers (n = 25) completed a postal survey exploring experiences of a paediatric chronic fatigue service. Quantitative data were analysed descriptively, and qualitative data were analysed using thematic analysis.

Results: Most service usersand parents/carers (88%) agreed that the service met their needs, that they felt supported by staff, and most notably, a large portion (74%) reported the team increased their activity levels. A small number disagreed (7%) with statements relating to positive links with other services, ease of talking to staff and suitability of appointment type. The thematic analysis revealed three themes: help managing chronic fatigue syndrome, experience of professional support and accessibility of service. Families reported benefiting from increased understanding of chronic fatigue syndrome, learning new strategies, the team linking with schools, feeling validated and mental health support. Accessibility was a particular problem including the service location, setup of appointments and difficulty contacting the team.

Discussion: The evaluation presents recommendations for paediatric Chronic Fatigue services to improve service user experiences.

Source: Hartley G, Purrington J. Service users’ and parents/carers’ experiences of a paediatric chronic fatigue service: A service evaluation. Chronic Illn. 2023 May 25:17423953231178185. doi: 10.1177/17423953231178185. Epub ahead of print. PMID: 37231733. https://pubmed.ncbi.nlm.nih.gov/37231733/

Investigating the factors associated with meaningful improvement on the SF-36-PFS and exploring the appropriateness of this measure for young people with ME/CFS accessing an NHS specialist service: a prospective cohort study

Abstract:

Objectives: Paediatric myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is relatively common and disabling, but little is known about the factors associated with outcome. We aimed to describe the number and characteristics of young people reaching the 10-point minimal clinically important difference (MCID) of SF-36-Physical Function Subscale (SF-36-PFS), and to investigate factors associated with reaching the MCID.

Design: Prospective observational cohort.

Setting: A specialist UK National Health Service (NHS) ME/CFS service, Southwest England. Recruitment between March 2014 and August 2015.

Participants: 193 eligible patients with ME/CFS aged 8 to 17 years reported baseline data. 124 (65%) and 121 (63%) with outcome data at six- and 12-months, respectively.

Outcome measures: SF-36-PFS (primary outcome). Chalder Fatigue Questionnaire, school attendance, visual analogue pain scale, Hospital Anxiety and Depression Scale, Spence Young people Anxiety Scale, Clinical Global Impression scale, and EQ-5D-Y (secondary)

Results: At six-months 48/120 (40%) had reached the MCID for SF-36-PFS. This had increased to 63/117 (54%) at 12-months. On the CGI, 77% and 79% reported feeling either a little better, much better, or very much better. Those with worse SF-36-PFS at baseline assessment were more likely to achieve the MCID for SF-36-PFS at six-months (OR 0.97, 95% CI 0.96 to 0.99, p-value 0.003), but there was no evidence of effect at 12-months (OR 0.98, 95% CI 0.97 to 1.00, p-value 0.038). No other factors at baseline were associated with the odds of reaching the MCID at six-months. However, at 12-months there was strong evidence of an effect of pain on MCID (OR 0.97, 95% CI 0.95 to 0.99, p-value 0.001), and SF-36-PFS on MCID (OR 0.96, 95% CI 0.94 to 0.98, p-value 0.001).

Conclusions: 40% and 54% of young people reached the MCID at 6 and 12 months respectively. No factors at assessment (other than SF-36-PFS at six-months, and pain and SF-36-PFS at 12-months) are associated with MCID of SF-36-PFS at either six-, or 12- months. Further work is needed to explore the most appropriate outcome measure for capturing clinical meaningful improvement for young people with ME/CFS.

Source: Gaunt, D. M., Brigden, A. L. C., Metcalfe, C., Loades, M., & Crawley, E. M. (Accepted/In press). Investigating the factors associated with meaningful improvement on the SF-36-PFS and exploring the appropriateness of this measure for young people with ME/CFS accessing an NHS specialist service: a prospective cohort study. BMJ Open. https://research-information.bris.ac.uk/en/publications/investigating-the-factors-associated-with-meaningful-improvement- 

Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact of self-reported fatigue and illness duration

Abstract:

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex illness of unknown aetiology. Emerging theories suggest ME/CFS may reflect a progressive, aberrant state of homeostasis caused by disturbances within the hypothalamus, yet few studies have investigated this using magnetic resonance imaging in adolescents with ME/CFS.

We conducted a volumetric analysis to investigate whether whole and regional hypothalamus volumes in adolescents with ME/CFS differed compared to healthy controls, and whether these volumes were associated with fatigue severity and illness duration. 48 adolescents (25 ME/CFS, 23 controls) were recruited. Lateralised whole and regional hypothalamus volumes, including the anterior superior, superior tubular, posterior, anterior inferior and inferior tubular subregions, were calculated from T1 weighted images.

When controlling for age, sex and intracranial volume, Bayesian linear regression revealed no evidence for differences in hypothalamus volumes between groups. However, in the ME/CFS group, a negative linear relationship between right anterior superior volumes and fatigue severity was identified, which was absent in controls. In addition, Bayesian ordinal regression revealed a likely-positive association between illness duration and right superior tubular volumes in the ME/CFS group.

While these findings suggest overall comparability in regional and whole hypothalamus volumes between adolescents with ME/CFS and controls, preliminary evidence was identified to suggest greater fatigue and longer illness duration were associated with greater right anterior superior and superior tubular volumes, respectively. These regions contain the anterior and superior divisions of the paraventricular nucleus, involved in the neuroendocrine response to stress, suggesting involvement in ME/CFS pathophysiology. However, replication in a larger, longitudinal cohort is required.

Source: Hollie Byrne, Elisha K Josev, Sarah J Knight, Adam Scheinberg, Katherine Rowe, Lionel Lubitz, Marc L Seal. Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact of self-reported fatigue and illness duration. medRxiv 2023.05.16.23290031; doi: https://doi.org/10.1101/2023.05.16.23290031 (Full text available as PDF file)

Fatigue in Children and Adolescents: A Population-Based Longitudinal Study on Fatigue and Chronic Pain

Abstract:

Objective: There are limited data on the prevalence and stability of fatigue in pediatrics, particularly among youth with chronic pain. Little is known about longitudinal effects of fatigue on health outcomes such as sleep quality, psychological distress, Health-Related Quality of Life, and chronic pain.

Methods: A community-based sample of N = 1276 students (9-17 years; 52% female; 30.3% with chronic pain) from 3 schools was screened at 2 measurement points 3 months apart. Prevalence and stability of fatigue were examined. Longitudinal analyses regarding fatigue and health outcomes were run using repeated measures correlations. The impact of change in fatigue on pain progression was analyzed using multilevel linear models.

Results: In the total community sample, 4.4% reported severe fatigue symptoms. The prevalence of severe fatigue was significantly higher in students with chronic pain (11.4%) compared to those without (1.3%). Fatigue symptoms persisted for several months, worsening of symptoms was more common and improvement less common in children with chronic pain. Sleep, psychological distress, and Health-Related Quality of Life were significantly associated with fatigue across both measurement points (rs = |0.16-0.44|), with no significant differences in the strength of correlations between children with and without chronic pain (ps > .05). There was a significant interaction between change in fatigue and courses of pain intensity and functional impairment.

Conclusions: Fatigue is highly prevalent, particularly in youth with chronic pain. The negative association of fatigue with health outcomes, and its impact on the course of pain, require early identification and treatment of those affected to prevent negative long-term consequences.

Source: Sommer A, Grothus S, Claus BB, Stahlschmidt L, Wager J. Fatigue in Children and Adolescents: A Population-Based Longitudinal Study on Fatigue and Chronic Pain. J Pediatr Psychol. 2023 May 10:jsad026. doi: 10.1093/jpepsy/jsad026. Epub ahead of print. PMID: 37164626. https://pubmed.ncbi.nlm.nih.gov/37164626/

Objective sleep measures in chronic fatigue syndrome patients: A systematic review and meta-analysis

Abstract:

Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report disrupted and unrefreshing sleep in association with worsened fatigue symptoms. However, the nature and magnitude of sleep architecture alteration in ME/CFS is not known, with studies using objective sleep measures in ME/CFS generating contradictory results.

The current manuscript aimed to review and meta-analyse of case-control studies with objective sleep measures in ME/CSF. A search was conducted in PubMed, Scopus, Medline, Google Scholar, and Psychoinfo databases.

After review, 24 studies were included in the meta-analysis, including 20 studies with 801 adults (ME/CFS = 426; controls = 375), and 4 studies with 477 adolescents (ME/CFS = 242; controls = 235), who underwent objective measurement of sleep.

Adult ME/CFS patients spend longer time in bed, longer sleep onset latency, longer awake time after sleep onset, decreased sleep efficiency, decreased stage 2 sleep, increased Stage 3, and longer rapid eye movement sleep latency.

However, adolescent ME/CFS patients had longer time in bed, longer total sleep time, longer sleep onset latency, and reduced sleep efficiency.

The meta-analysis results demonstrate that sleep is altered in ME/CFS, with changes seeming to differ between adolescent and adults, and suggesting sympathetic and parasympathetic nervous system alterations in ME/CFS.

Source: Abdalla Z. Mohamed, Thu Andersen, Sanja Radovic, Peter Del Fante, Richard Kwiatek, Vince Calhoun, Sandeep Bhuta, Daniel F. Hermens, Jim Lagopoulos, Zack Shan. Objective sleep measures in chronic fatigue syndrome patients: A systematic review and meta-analysis. Sleep Medicine Reviews, 2023, 101771.  https://www.sciencedirect.com/science/article/abs/pii/S1087079223000278

Adults with ME/CFS report surprisingly high rates of youth symptoms: A qualitative analysis of patient blog commentary

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness that impacts pediatric populations.

Objective: The current study aimed to better understand adult perceptions of their experiences leading up to their diagnosis of ME/CFS.

Method: Patients provided data regarding symptoms of ME/CFS they may have experienced during childhood through a popular community blog forum, with participants interacting via blog comments in real-time and across various geographical locations.

Results: Descriptive analyses indicated that roughly 43% of adult survey participants reported having developed ME/CFS prior to age 18. A standard content analysis of patient blog commentary revealed several themes, such as poor mental health, family pattern/history, healthy childhood preceding sick adulthood, feeling misunderstood, lack of clarity until adulthood, sharing of resources, poor school functioning, isolation/poor social supports, and coping mechanisms.

Conclusion: There are unique benefits and insights that can be used by investigators who collaborate with patient organizations as a means of better understanding ME/CFS illness severity, presentation, and lived experiences.

Source: Johnson M, Torres C, Watts-Rich H, Jason L. Adults with ME/CFS report surprisingly high rates of youth symptoms: A qualitative analysis of patient blog commentary. Work. 2023 Mar 9. doi: 10.3233/WOR-220484. Epub ahead of print. PMID: 36911960. https://content.iospress.com/articles/work/wor220484 (Full text)