adolescents – Page 13 – American ME and CFS Society

Sleep Disturbances in Pediatric Chronic Fatigue Syndrome: A Review of Current Research

Abstract:

OBJECTIVE: Children and adolescents with chronic fatigue syndrome (CFS) frequently report sleep disturbances. However, little is known about the nature and severity of sleep disturbance and factors associated with sleep problems in pediatric CFS. The purpose of this review was to synthesize and critically appraise existing literature relating to sleep disturbances in pediatric CFS.

METHODS: Embase, CINAHL, PsychINFO, PubMed. and Medline databases were searched to retrieve all studies that included an assessment of sleep in pediatric CFS. Two reviewers independently assessed eligibility, extracted data, and systematically assessed reporting quality.

RESULTS: Six studies were included and these were mostly case-controlled designs. Findings varied across studies; however, most studies found that children and adolescents with CFS had significantly more sleep disturbances when compared to healthy controls. Significant methodological variations and limitations were apparent.

CONCLUSIONS: This review suggests that children and adolescents with CFS experience sleep disturbances. However, results need to be interpreted cautiously given the limited evidence available and its overall low quality. More research is required to elucidate the nature and extent of sleep disturbance in pediatric CFS and should focus on (1) identifying the specific types, causes, and severity of sleep disturbances; (2) the specific consequences of sleep disturbances; and (3) the most effective interventions for sleep problems in this population.

Source: Snodgrass K, Harvey A, Scheinberg A, Knight S. Sleep Disturbances in Pediatric Chronic Fatigue Syndrome: A Review of Current Research. J Clin Sleep Med. 2015 Jul 15;11(7):757-64. doi: 10.5664/jcsm.4854. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481060/ (Full article)

Plasma cytokine expression in adolescent chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescents. The pathophysiology is poorly understood, but low-grade systemic inflammation has been suggested as an important component. This study compared circulating levels of individual cytokines and parameters of cytokine networks in a large set of adolescent CFS patients and healthy controls, and explored associations between cytokines and symptoms in the CFS group.

CFS patients (12-18years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring three months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Thus, the case definition was broader than the Fukuda-criteria of CFS. Healthy controls having comparable distribution of gender and age were recruited from local schools. Twenty-seven plasma cytokines, including interleukins, chemokines and growth factors were assayed using multiplex technology. The results were subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and patients were subgrouped according to the Fukuda-criteria. A total of 120 CFS patients and 68 healthy controls were included.

CFS patients had higher scores for fatigue (p<0.001) and inflammatory symptoms (p<0.001) than healthy controls. All cytokine levels and cytokine network parameters were similar, and none of the differences were statistically different across the two groups, also when adjusting for adherence to the Fukuda criteria of CFS. Within the CFS group, there were no associations between aggregate cytokine network parameters and symptom scores. Adolescent CFS patients are burdened by symptoms that might suggest low-grade systemic inflammation, but plasma levels of individual cytokines as well as cytokine network measures were not different from healthy controls, and there were no associations between symptoms and cytokine expression in the CFS group. Low-grade systemic inflammation does not appear to be a central part of adolescent CFS pathophysiology.

Source: Wyller VB, Sørensen Ø, Sulheim D, Fagermoen E, Ueland T, Mollnes TE. Plasma cytokine expression in adolescent chronic fatigue syndrome. Brain Behav Immun. 2015 May;46:80-6. doi: 10.1016/j.bbi.2014.12.025. Epub 2014 Dec 31. https://www.ncbi.nlm.nih.gov/pubmed/25555530

Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study

Abstract:

OBJECTIVES: Although pain is a significant symptom in chronic fatigue syndrome (CFS), pain is poorly understood in adolescents with CFS. The aim of this study was to explore pain distribution and prevalence, pain intensity and its functional interference in everyday life, as well as pressure pain thresholds (PPT) in adolescents with CFS and compare this with a control group of healthy adolescents (HC).

METHODS: This is a case-control, cross-sectional study on pain including 120 adolescents with CFS and 39 HCs, aged 12-18 years. We measured pain frequency, pain severity and pain interference using self-reporting questionnaires. PPT was measured using pressure algometry. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial.

RESULTS: Adolescents with CFS had significantly lower PPTs compared with HCs (p<0.001). The Pain Severity Score and the Pain Interference Score were significantly higher in adolescents with CFS compared with HCs (p<0.001). Almost all adolescents with CFS experienced headache, abdominal pain and/or pain in muscles and joints. Moreover, in all sites, the pain intensity levels were significantly higher than in HCs (p<0.001).

CONCLUSIONS: We found a higher prevalence of severe pain among adolescents with CFS and lowered pain thresholds compared with HCs. The mechanisms, however, are still obscure. Large longitudinal population surveys are warranted measuring pain thresholds prior to the onset of CFS.

TRIAL REGISTRATION NUMBER: Clinical Trials, NCT01040429; The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL) http://www.clinicaltrials.gov.

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: Winger A, Kvarstein G, Wyller VB, Sulheim D, Fagermoen E, Småstuen MC, Helseth S. Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study. BMJ Open. 2014 Oct 6;4(9):e005920. doi: 10.1136/bmjopen-2014-005920. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187660/ (Full article)

Cortisol output in adolescents with chronic fatigue syndrome: pilot study on the comparison with healthy adolescents and change after cognitive behavioural guided self-help treatment

Abstract:

OBJECTIVE: This study examined cortisol in adolescents with chronic fatigue syndrome (CFS) compared to healthy adolescents and changes in cortisol after cognitive behavioural guided self-help treatment. Exploratory analyses investigated the association between cortisol output and psychological variables.

METHODS: Salivary cortisol was measured upon awakening, at 15, 30, 45 and 60 min afterwards and at 12 noon, 4:00 p.m. and 8:00 p.m., in adolescents with CFS and healthy controls (HC). Groups were matched for age, gender, menarche status, menstrual cycle and awakening time. Twenty-four adolescents with CFS provided saliva samples six months after treatment. The main outcome measure was total salivary output over the day, calculated by area under the curve (AUC). The salivary awakening response was also assessed.

RESULTS: Cortisol output over the day was significantly lower in the CFS group (n=46) than in healthy controls (n=33). Within the CFS group, lower daily cortisol output was associated with higher self-reported perfectionist striving and prosocial behaviour. There were no significant group differences in the awakening response (n=47 CFS versus n=34 HC). After treatment, adolescents with CFS (n=21) showed a significant increase in daily cortisol output, up to normal levels.

CONCLUSION: The reduced daily cortisol output in adolescents with CFS is in line with adult findings. Associations between reduced cortisol output and two psychological variables-perfectionism and prosocial behaviour-are consistent with cognitive behavioural models of chronic fatigue syndrome. The mild hypocortisolism is reversible; cortisol output had returned to healthy adolescent levels by six months after cognitive behavioural guided self-help treatment.

Source: Rimes KA, Papadopoulos AS, Cleare AJ, Chalder T. Cortisol output in adolescents with chronic fatigue syndrome: pilot study on the comparison with healthy adolescents and change after cognitive behavioural guided self-help treatment. J Psychosom Res. 2014 Nov;77(5):409-14. doi: 10.1016/j.jpsychores.2014.08.018. Epub 2014 Sep 8.https://www.ncbi.nlm.nih.gov/pubmed/25260861

Orthostatic responses in adolescent chronic fatigue syndrome: contributions from expectancies as well as gravity

Abstract:

BACKGROUND: Orthostatic intolerance is common in chronic fatigue syndrome (CFS), and several studies have documented an abnormal sympathetic predominance in the autonomic cardiovascular response to gravitational stimuli. The aim of this study was to explore whether the expectancies towards standing are contributors to autonomic responses in addition to the gravitational stimulus itself.

METHODS: A total of 30 CFS patients (12-18 years of age) and 39 healthy controls underwent 20° head-up tilt test and a motor imagery protocol of standing upright. Beat-to-beat cardiovascular variables were recorded.

RESULTS: At supine rest, CFS patients had significantly higher heart rate, diastolic blood pressure, and mean arterial blood pressure, and lower stroke index and heart rate variability (HRV) indices. The response to 20° head-up tilt was identical in the two groups. The response to imaginary upright position was characterized by a stronger increase of HRV indices of sympathetic predominance (power in the low-frequency range as well as the ratio low-frequency: high-frequency power) among CFS patients.

CONCLUSIONS: These results suggest that in CFS patients expectancies towards orthostatic challenge might be additional determinants of autonomic cardiovascular modulation along with the gravitational stimulus per se.

Source: Wyller VB, Fagermoen E, Sulheim D, Winger A, Skovlund E, Saul JP. Orthostatic responses in adolescent chronic fatigue syndrome: contributions from expectancies as well as gravity. Biopsychosoc Med. 2014 Sep 15;8:22. doi: 10.1186/1751-0759-8-22. eCollection 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166398/ (Full article)

Impaired range of motion of limbs and spine in chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine whether adolescents and young adults with chronic fatigue syndrome (CFS) have a greater prevalence of impaired range of motion (ROM) of the limbs and spine than healthy control patients.

STUDY DESIGN: Case-control study comparing rates of abnormal ROM in 48 consecutive adolescents and young adults with CFS and 48 healthy control patients matched by sex and joint hypermobility. We examined range of ankle dorsiflexion, passive straight-leg raise, seated slump, upper-limb neurodynamic test, prone knee bend, and prone press-up. Abnormal ROM was defined before the study began. The number of abnormal responses ranged from 0 (normal ROM throughout) to 11 (impaired ROM in all areas tested).

RESULTS: The median number of areas with impaired ROM was greater in patients with CFS at the onset of stretch in the involved limb (5 vs 2, P<.001) and at end-range (2 vs 0, P<.001). Patients with CFS were more likely to have greater than 3 areas of impaired ROM (OR 6.0, 95% CI 2.1-17.3; P<.001) and were more likely to develop abnormal symptomatic responses to the individual tests and to the overall assessment (40% vs 4%; P<.001).

CONCLUSIONS: Impaired ROM is more common in subjects with CFS than in healthy adolescents and young adults matched by sex and joint hypermobility. Adding a longitudinal strain to the nerves and soft tissues provoked symptoms in some subjects with CFS. The causes, functional impact, and optimal treatment of these abnormalities warrant further study.

Source: Rowe PC, Marden CL, Flaherty MA, Jasion SE, Cranston EM, Johns AS, Fan J, Fontaine KR, Violand RL. Impaired range of motion of limbs and spine in chronic fatigue syndrome. J Pediatr. 2014 Aug;165(2):360-6. doi: 10.1016/j.jpeds.2014.04.051. Epub 2014 Jun 11. https://www.ncbi.nlm.nih.gov/pubmed/24929332

Predictors of Post-Infectious Chronic Fatigue Syndrome in Adolescents

Abstract:

This study focused on identifying risk factors for adolescent post-infectious chronic fatigue syndrome (CFS), utilizing a prospective, nested case-control longitudinal design in which over 300 teenagers with Infectious Mononucleosis (IM) were identified through primary care sites and followed.

Baseline variables that were gathered several months following IM, included autonomic symptoms, days in bed since IM, perceived stress, stressful life events, family stress, difficulty functioning and attending school, family stress and psychiatric disorders. A number of variables were predictors of post-infectious CFS at 6 months; however, when autonomic symptoms were used as a control variable, only days spent in bed since mono was a significant predictor. Step-wise logistic regression findings indicated that baseline autonomic symptoms as well as days spent in bed since mono, which reflect the severity of illness, were the only significant predictors of those who met CFS criteria at 6 months.

Source: Jason LA, Katz BZ, Shiraishi Y, Mears CJ, Im Y, Taylor R. Predictors of Post-Infectious Chronic Fatigue Syndrome in Adolescents. Health Psychol Behav Med. 2014 Jan 1;2(1):41-51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956649/ (Full article)

The role of hypocortisolism in chronic fatigue syndrome

Abstract:

BACKGROUND: There is accumulating evidence of hypothalamic-pituitary-adrenal (HPA) axis hypofunction in chronic fatigue syndrome (CFS). However, knowledge of this hypofunction has so far come exclusively from research in adulthood, and its clinical significance remains unclear. The objective of the current study was to assess the role of the HPA-axis in adolescent CFS and recovery from adolescent CFS.

METHOD: Before treatment, we compared the salivary cortisol awakening response of 108 diagnosed adolescent CFS patients with that of a reference group of 38 healthy peers. Salivary cortisol awakening response was measured again after 6 months of treatment in CFS patients.

RESULTS: Pre-treatment salivary cortisol levels were significantly lower in CFS-patients than in healthy controls. After treatment recovered patients had a significant rise in salivary cortisol output attaining normalization, whereas non-recovered patients improved slightly, but not significantly. The hypocortisolism found in CFS-patients was significantly correlated to the amount of sleep. Logistic regression analysis showed that an increase of one standard deviation in the difference between pre- and post-treatment salivary cortisol awakening response was associated with a 93% higher odds of recovery (adjusted OR 1.93 (1.18 to 3.17), p=0.009). Pre-treatment salivary cortisol did not predict recovery.

CONCLUSIONS: Hypocortisolism is associated with adolescent CFS. It is not pre-treatment cortisol but its change to normalization that is associated with treatment success. We suggest that this finding may have clinical implications regarding the adaptation of future treatment strategies.

Source: Nijhof SL, Rutten JM, Uiterwaal CS, Bleijenberg G, Kimpen JL, Putte EM. The role of hypocortisolism in chronic fatigue syndrome. Psychoneuroendocrinology. 2014 Apr;42:199-206. doi: 10.1016/j.psyneuen.2014.01.017. Epub 2014 Jan 30. https://www.ncbi.nlm.nih.gov/pubmed/24636516

Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial

Abstract:

IMPORTANCE: Chronic fatigue syndrome (CFS) is a disabling condition with unknown disease mechanisms and few treatment options.

OBJECTIVE: To explore the pathophysiology of CFS and assess clonidine hydrochloride pharmacotherapy in adolescents with CFS by using a hypothesis that patients with CFS have enhanced sympathetic activity and that sympatho-inhibition by clonidine would improve symptoms and function.

DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled from a single referral center recruiting nationwide in Norway. A referred sample of 176 adolescents with CFS was assessed for eligibility; 120 were included (34 males and 86 females; mean age, 15.4 years). A volunteer sample of 68 healthy adolescents serving as controls was included (22 males and 46 females; mean age, 15.1 years). The CSF patients and healthy controls were assessed cross-sectionally at baseline. Thereafter, patients with CFS were randomized 1:1 to treatment with low-dose clonidine or placebo for 9 weeks and monitored for 30 weeks; double-blinding was provided. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial.

INTERVENTIONS: Clonidine hydrochloride capsules (25 µg or 50 µg twice daily for body weight <35 kg or >35 kg, respectively) vs placebo capsules for 9 weeks.

MAIN OUTCOMES AND MEASURES: Number of steps per day.

RESULTS: At baseline, patients with CFS had a lower number of steps per day (P < .001), digit span backward score (P = .002), and urinary cortisol to creatinine ratio (P = .001), and a higher fatigue score (P < .001), heart rate responsiveness (P = .02), plasma norepinephrine level (P < .001), and serum C-reactive protein concentration (P = .04) compared with healthy controls. There were no significant differences regarding blood microbiology evaluation. During intervention, the clonidine group had a lower number of steps per day (mean difference, -637 steps; P = .07), lower plasma norepinephrine level (mean difference, -42 pg/mL; P = .01), and lower serum C-reactive protein concentration (mean ratio, 0.69; P = .02) compared with the CFS placebo group.

CONCLUSIONS AND RELEVANCE: Adolescent CFS is associated with enhanced sympathetic nervous activity, low-grade systemic inflammation, attenuated hypothalamus-pituitary-adrenal axis function, cognitive impairment, and large activity reduction, but not with common microorganisms. Low-dose clonidine attenuates sympathetic outflow and systemic inflammation in CFS but has a concomitant negative effect on physical activity; thus, sympathetic and inflammatory enhancement may be compensatory mechanisms. Low-dose clonidine is not clinically useful in CFS.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01040429.

Source: Sulheim D, Fagermoen E, Winger A, Andersen AM, Godang K, Müller F, Rowe PC, Saul JP, Skovlund E, Øie MG, Wyller VB. Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial. JAMA Pediatr. 2014 Apr;168(4):351-60. doi: 10.1001/jamapediatrics.2013.4647. https://www.ncbi.nlm.nih.gov/pubmed/24493300

Valacyclovir treatment of chronic fatigue in adolescents

Abstract:

Chronic fatigue syndrome (CFS) presents with fatigue, low motivation, diminished mood, and reduced activity, all symptoms having extensive diagnostic overlaps with depression. Studies have linked chronic viral infections with CFS, and antiviral therapy has effectively treated CFS in adult patients.

In a retrospective case series, 15 adolescents and preteens referred to the author for treatment-resistant depression or mood disorder were evaluated and found to have met the Fukuda diagnostic criteria for CFS. While a subset (4/15) had been diagnosed in the past with CFS, the majority had a current diagnosis of depression or a mood disorder. The Diagnostic and Statistical Manual-IV Text Revision (DSM-IV TR) criteria for depression were not met in all patients, although 3 cases of mood disorder not otherwise specified (MD-NOS) and 1 case of Tourette syndrome (TS) plus MD-NOS were diagnosed. Baseline scores on the Children’s Depression Inventory (CDI) were below the cutoff for depression in all but 1 patient. Baseline self-assessment scales for CFS or fatigue were obtained and sleep was evaluated with sleep logs.

All patients were treated subsequently with valacyclovir, with 93% having a positive response. At the end of treatment, scores on fatigue self-assessment scales improved significantly (P < .001). Vigor subscale scores also improved significantly (P < .001). Some patients experienced complete resolution of symptoms. Although not every patient was tested, available laboratory testing revealed increased counts of natural killer (NK) cells and decreased human herpesvirus 6 (HHV-6) antibody titers in all patients who responded to valacyclovir.

This article discusses the significance of infectious agents in the pathogenesis of psychiatric symptoms. The study’s data support an intriguing hypothesis that a portion of treatment-resistant depression in fact may be undiagnosed CFS or other chronic viral infection.

Source: Henderson TA. Valacyclovir treatment of chronic fatigue in adolescents. Adv Mind Body Med. 2014 Winter;28(1):4-14. https://www.ncbi.nlm.nih.gov/pubmed/24445302