Tag: adolescents

Hypothalamus Connectivity in Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling illness of unknown etiology. Increasing evidence suggests hypothalamic involvement in ME/CFS pathophysiology, which has rarely been explored using magnetic resonance imaging (MRI) in the condition. This work aimed to use MRI to examine hypothalamus connectivity in adolescents with ME/CFS and explore how this relates to fatigue severity and illness duration.

25 adolescents with ME/CFS and 23 healthy controls completed a neuroimaging protocol consisting of structural and multishell diffusion-weighted imaging sequences, in addition to the PedsQL Multidimensional Fatigue Scale to assess fatigue severity. Information about illness duration was acquired at diagnosis. Preprocessing and streamlines tractography was performed using QSIPrep combined with a custom parcellation scheme to create structural networks. The number (degree) and weight (strength) of connections between lateralized hypothalamus regions and cortical and subcortical nodes were extracted, and relationships between connectivity measures, fatigue severity, and illness duration were performed using Bayesian regression models.

We observed weak-to-moderate evidence of increased degree, but not strength, of connections from the bilateral anterior-inferior (left: pd [%] = 99.18, median [95% CI] = -22.68[-40.96 to 4.45]; right: pd [%] = 99.86, median [95% CI] = -23.35[-38.47 to 8.20]), left anterior-superior (pd [%] = 99.33, median [95% CI] = -18.83[-33.45 to 4.07]) and total left hypothalamus (pd [%] = 99.44, median [95% CI] = -47.18[-83.74 to 11.03]) in the ME/CFS group compared with controls. Conversely, bilateral posterior hypothalamus degree decreased with increasing ME/CFS illness duration (left: pd [%] = 98.13, median [95% CI]: -0.47[-0.89 to 0.03]; right: pd [%] = 98.50, median [95% CI]:-0.43[-0.82 to 0.05]).

Finally, a weak relationship between right intermediate hypothalamus connectivity strength and fatigue severity was identified in the ME/CFS group (pd [%] = 99.35, median [95% CI] = -0.28[-0.51 to 0.06]), which was absent in controls. These findings suggest changes in hypothalamus connectivity may occur in adolescents with ME/CFS, warranting further investigation.

Source: Byrne H, Knight SJ, Josev EK, Scheinberg A, Beare R, Yang JYM, Oldham S, Rowe K, Seal ML. Hypothalamus Connectivity in Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Neurosci Res. 2024 Oct;102(10):e25392. doi: 10.1002/jnr.25392. PMID: 39431934. https://onlinelibrary.wiley.com/doi/10.1002/jnr.25392 (Full text(

Characterizing Long COVID in Children and Adolescents

Key Points:

Question  What prolonged symptoms experienced by youth are most associated with SARS-CoV-2 infection?

Findings  Among 5367 participants in the RECOVER-Pediatrics cohort study, 14 symptoms in both school-age children (6-11 years) and adolescents (12-17 years) were more common in those with vs without SARS-CoV-2 infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. Empirically derived indices for PASC research and associated clustering patterns were developed.

Meaning  This study developed research indices for characterizing pediatric PASC. Symptom patterns were similar but distinguishable between school-age children and adolescents, highlighting the importance of characterizing PASC separately in different age groups.

Abstract

Importance  Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.

Objective  To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.

Design, Setting, and Participants  Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.

Exposure  SARS-CoV-2 infection.

Main Outcomes and Measures  PASC and 89 prolonged symptoms across 9 symptom domains.

Results  A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise–related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.

Conclusions and Relevance This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

Source: Rachel S. Gross, MD, MS; Tanayott Thaweethai, PhD; Lawrence C. Kleinman, MD, MPH; et al. JAMA. Published online August 21, 2024. doi:10.1001/jama.2024.12747 https://jamanetwork.com/journals/jama/article-abstract/2822770

Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls

Abstract:

Background: In patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), momentary cortisol concentrations in blood, urine, and saliva are lower compared to healthy controls. Long-term cortisol concentration can be assessed through hair, but it is unclear whether these concentrations are also lower. Additionally, it is unknown if lower cortisol extends to other patients suffering from persistent fatigue and how hair cortisol concentration (HCC) relates to fatigue levels. Therefore, this study examines HCC in fatigued patients with ME/CFS, Q fever Fatigue Syndrome (QFS), Post-COVID-19 condition (PCC), and Juvenile Idiopathic Arthritis (JIA).

Methods: Adolescent and young adult patients with ME/CFS (n=12), QFS (n=20), PCC (n=8), JIA (n=19), and controls (n=57) were included. Patients participated in a randomized cross-over trial (RCT) targeting fatigue through lifestyle and dietary self-management strategies. HCC was measured pre-post RCT in patients and once in controls, quantified using a LC-MS/MS-based method. Fatigue severity was measured with the Checklist Individual Strength-8. HCC was compared between groups with ANOVAs. Relations between HCC, fatigue severity, and other variables were investigated using linear regression analyses.

Results: The ME/CFS (p=.009) and QFS (p=.047) groups had lower HCC compared to controls. Overall, HCC was negatively associated with the presence of symptoms related to chronic fatigue syndromes (e.g., sleeping issues, often feeling tired, trouble thinking clearly; β=-0.018, p=.035), except in the QFS group (β=.063, p<.001). Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (Mdif=.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658).

Conclusion: Lower cortisol concentration can also be observed in the long-term. Lower HCC is not limited to ME/CFS, as it was also observed in QFS. The role of cortisol may differ between these diagnoses and appears to be unrelated to fatigue levels.

Source: Vroegindeweij A, Eijkelkamp N, van den Berg SAA, van de Putte EM, Wulffraat NM, Swart JF, Nijhof SL. Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls. Psychoneuroendocrinology. 2024 Jun 28;168:107117. doi: 10.1016/j.psyneuen.2024.107117. Epub ahead of print. PMID: 38986244. https://pubmed.ncbi.nlm.nih.gov/38986244/

Bulk RNA sequencing for analysis of post COVID-19 condition in adolescents and young adults

Abstract:

Background: Post COVID-19 condition (PCC) is a complication of SARS-COV-2 infection and can lead to long-term disability.

Methods: The present study was designed to analyse the gene expression patterns of PCC through bulk RNA sequencing of whole blood and to explore the potential molecular mechanisms of PCC. Whole blood was collected from 80 participants enrolled in a prospective cohort study following SARS-CoV-2 infected and non-infected individuals for 6 months after recruitment and was used for bulk RNA sequencing. Identification of differentially expressed genes (DEG), pathway enrichment and immune cell deconvolution was performed to explore potential biological pathways involved in PCC.

Results: We have found 13 differentially expressed genes associated with PCC. Enriched pathways were related to interferon-signalling and anti-viral immune processes.

Conclusion: The PCC transcriptome is characterized by a modest overexpression of interferon-stimulated genes, pointing to a subtle ongoing inflammatory response.

Source: Sommen SL, Zhao Z, Segtnan S, Stiansen-Sonerud T, Selvakumar J, Beier Havdal L, Gjerstad J, Wyller VBB, Lund Berven L. Bulk RNA sequencing for analysis of post COVID-19 condition in adolescents and young adults. J Transl Med. 2024 Mar 26;22(1):312. doi: 10.1186/s12967-024-05117-7. PMID: 38532465. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05117-7 (Full text)

Management of severe ME/CFS in children and young people in the UK: a British Paediatric Surveillance Unit study

Abstract:

Objective: Severe myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) in children and young people (CYP) is a little-understood condition which significantly impacts education, development and quality of life. We used data from a population-wide surveillance study to explore the screening investigation, referral and management of suspected cases of paediatric severe ME/CFS.

Methods: A British Paediatric Surveillance Unit (BPSU) study reported cases of CYP with suspected severe ME/CFS between February 2018 and February 2019. Paediatricians reporting cases to BPSU and allied healthcare professionals in two large specialist paediatric ME/CFS centres were invited to complete questionnaires for CYP meeting the surveillance case definition. The study focused primarily on CYP with confirmed severe ME/CFS and the extent to which their care met NICE (The National Institute for Health and Care Excellence) recommendations but also considered separately those with probable or possible severe ME/CFS.

Results: This study includes a total of 92 CYP with suspected severe ME/CFS; 33 meeting criteria for severe ME/CFS and an additional 59 classified as probable or possible severe ME/CFS. For 16 possible cases, incomplete investigation to exclude alternative diagnoses prevented confirmation of a severe ME/CFS diagnosis. Only 21 of 33 (64%) confirmed severe ME/CFS cases had been referred to specialist services. The management provided varied considerably between patients and four received nothing at all. Of the management provided, the most frequent approaches were medication (67%), activity management (61%) and physiotherapy (61%). Domiciliary assessments and support, and social services referrals were received by 12% and 6% of confirmed severe cases. Similar proportions of management approaches were seen in probable/possible severe ME/CFS.

Conclusion: Full investigation is frequently incomplete in CYP with suspected severe ME/CFS and recommendations for referral and management are poorly implemented, in particular the needs of CYP who are unable to leave their home might be poorly met.

Source: Royston AP, Burge S, Idini I, Brigden A, Pike KC. Management of severe ME/CFS in children and young people in the UK: a British Paediatric Surveillance Unit study. BMJ Paediatr Open. 2024 Mar 7;8(1):e002436. doi: 10.1136/bmjpo-2023-002436. PMID: 38453418. https://bmjpaedsopen.bmj.com/content/8/1/e002436 (Full text)

How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review

Abstract:

Background: Post Coronavirus disease (COVID) and other post-viral infection syndromes present an overlap of pathogenesis, onset, progression, and symptom profile. We aimed to systematically describe studies on post-viral conditions and determine the entity of post COVID compared to other post-viral conditions in children.

Methods: We conducted a systematic search of the Embase, MEDLINE, Cochrane Library, and GoogleScholar databases (January 1946-3 November 2023), according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The main outcomes were differences in condition duration, symptom type, and development of chronic symptoms. This systematic review was registered on PROSPERO (CRD42023401789).

Findings: 35/5051 studies were included, with 42,934 children, adolescents and young adults (0-20 years old) overall. Twenty-eight studies focused on post COVID symptoms, followed by five papers on Respiratory Syncytial Virus (RSV) and Rhinovirus, one study on Epstein-Barr Virus (EBV), and one on gastrointestinal viruses. Studies on post COVID mainly reported data on older children/adolescents, describing long-lasting symptoms, including fatigue, neurologic, cardiorespiratory, musculoskeletal, mental health, and gastrointestinal symptoms. The maximum described symptoms duration was eighteen months, with an average follow-up of seven months. The development of chronic symptoms was reported by 30 studies (93.8%) for 10,473/28,474 patients (36.8%). Recovery was achieved in 18,001/28,474 cases (63.2%). The study on EBV reported persistent fatigue in adolescents for a similar duration (6 months, 46% chronic). Studies on RSV and Rhinovirus were mainly done in children under three years, with development of recurrent wheezing (up to 3 years).

Interpretation: Post-viral fatigue was a shared feature between post COVID and post EBV conditions. A better understanding of post COVID as a unique condition, sharing features with other post-viral syndromes, is needed. The healthcare burden and socio-economic consequences for children and their families warrant further investigation and development of appropriate healthcare management plans. The foremost requirement is the establishment of consistent and shareable definitions, as well as a consensus on outcomes, to effectively evaluate follow-up and quantify the burden of different viral infections.

Source: Minotti C, McKenzie C, Dewandel I, Bekker C, Sturniolo G, Doni D, Giaquinto C, Van Der Zalm MM, Donà D. How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review. EClinicalMedicine. 2024 Feb 2;68:102436. doi: 10.1016/j.eclinm.2024.102436. PMID: 38333536; PMCID: PMC10850405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10850405/ (Full text)

A suffering body, hidden away from others: The experience of being long-term bedridden with severe myalgic encephalomyelitis/chronic fatigue syndrome in childhood and adolescence

Abstract:

In this article, we present findings from a qualitative study examining how young women experience being long-term bedridden with myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), during childhood and adolescence. The aim is to explore how young women who fell ill with ME/CFS during childhood and adolescence look back on their lived experience of being long-term bedridden from the vantage point of being fully or partially recovered.

Informed by a phenomenological theoretical perspective, the researchers applied a narrative methodological approach involving the analysis of interviews with 13 women, aged 16–29 years at the time of the interview. Attention was particularly paid to how participants structured their narratives and to the events (telling moments) they identified as important.

Four major storylines were developed: Ambivalent responses to the presence of others; A body on the edge of life; An eternity in the dark; and Recasting painful memories of being bedridden and alone.

Based on our findings, we argue that the experience of being long-term bedridden with ME/CFS during childhood and adolescence can be understood and communicated as a plot in which individuals find themselves pushed to the extreme limit of suffering and loneliness.

Source: Krabbe, S. H., Bjorbækmo, W. S., Mengshoel, A. M., Sveen, U., & Groven, K. S. (2024). A suffering body, hidden away from others: The experience of being long-term bedridden with severe myalgic encephalomyelitis/chronic fatigue syndrome in childhood and adolescence. Nursing Inquiry, e12625. https://doi.org/10.1111/nin.12625 https://onlinelibrary.wiley.com/doi/10.1111/nin.12625 (Full text)

Case Report: Rapid and partially persistent, improvements of anorexia nervosa and probable myalgic encephalo-myelitis/chronic fatigue syndrome upon metreleptin treatment during two dosing episodes

Abstract

A comorbidity of anorexia nervosa (AN) and myalgic encephalomyelitis (ME/CSF) is uncommon. A 17-year-old male adolescent with possible onset of ME/CFS after an Epstein Barr Virus infection (EBV) and later onset of AN during a second period of weight loss was twice treated off-label with metreleptin for 15 and 11 days, respectively.

As in previous cases, eating disorder specific cognitions and mood improved. Interestingly, fatigue and post-exertional muscle pain (P-EMP) improved, too. We discuss potential mechanisms. Treatment with metreleptin may prove beneficial in AN and in ME/CSF associated with substantial weight loss.

Source: Jochen Antel, Johannes Hebebrand, Linda Von Piechowski, Cordula Kiewert, Burkhard Stüve, Gertraud Gradl-Dietsch. Rapid and partially persistent, improvements of anorexia nervosa and probable myalgic encephalo-myelitis/chronic fatigue syndrome upon metreleptin treatment during two dosing episodes. Front. Psychiatry, Sec. Adolescent and Young Adult Psychiatry, Volume 14 – 2023. https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1267495/abstract

Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents

Abstract:

SARS-CoV-2 infection causes transient cardiorespiratory and neurological disorders, and severe acute illness is rare among children. Post COVID-19 condition (PCC) may cause profound, persistent phenotypes with increasing prevalence. Its manifestation and risk factors remain elusive. In this monocentric study, we hypothesized that atopy, the tendency to produce an exaggerated immunoglobulin E (IgE) immune response, is a risk factor for the manifestation of pediatric PCC.
We present a patient cohort (n = 28) from an early pandemic period (2021–2022) with comprehensive evaluations of phenotypes, pulmonary function, and molecular investigations. PCC predominantly affected adolescents and presented with fatigue, dyspnea, and post-exertional malaise. Sensitizations to aeroallergens were found in 93% of cases.
We observed elevated IgE levels (mean 174.2 kU/L, reference < 100 kU/L) regardless of disease severity. Concurrent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) was found in 29% of patients that also faced challenges in school attendance. ME/CFS manifestation was significantly associated with elevated immunoglobulin G subclasses IgG3 (p < 0.05) and IgG4 (p < 0.05). A total of 57% of patients showed self-limiting disease courses with mean recovery at 12.7 months (range 5–25 months), 29% at 19.2 months (range 12–30 months), and the rest demonstrated overall improvement. These findings offer additional insights into immune dysregulation as a risk factor for pediatric PCC.
Source: Körner RW, Bansemir OY, Franke R, Sturm J, Dafsari HS. Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents. Children. 2023; 10(10):1598. https://doi.org/10.3390/children10101598 https://www.mdpi.com/2227-9067/10/10/1598 (Full text)

The Impact of Post-COVID-19 Syndrome in Adolescents: A Pilot Study

Abstract:

Background: Post-COVID-19 syndrome has emerged as a long-term complication in adults and children; its effect on adolescents’ performance in school is not well studied.

Objectives: To study the physical/psychological impact of prolonged post-COVID-19 symptoms on school performance.

Methods: This is a cross-sectional study using Google Forms, a web-based fully anonymized survey of children in grades 10-12.

Results: The study included 54 students with a mean age of 16 years of whom 32 had COVID-19. Two were hospitalized and 10 had symptoms lasting more than four weeks. Commonly reported chronic symptoms were fatigue and cough. Seven students quit sports; eight had a decrease in their academic performance. Adolescents being infected more than once or not being fully vaccinated were more likely to develop prolonged symptoms and quit sports while academic performance in school was not affected. Three out of 10 (30%) students who had COVID-19 and responded to the questionnaire reported not seeking help.

Conclusion: Post-COVID-19 syndrome is associated with a decline in physical but not mental performance in school. Being infected more than once with SARS-CoV-2 seems to play an important role in the persistence of post-COVID-19 symptoms despite the fact that some adolescents are hesitant to seek medical or psychological care.

Source: El Khoury J, Skoury M, El Khoury MY. The Impact of Post-COVID-19 Syndrome in Adolescents: A Pilot Study. Cureus. 2023 Jun 19;15(6):e40655. doi: 10.7759/cureus.40655. PMID: 37476124; PMCID: PMC10356177. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10356177/ (Full text)