2020 – Page 8 – American ME and CFS Society

Association between quadrivalent human papillomavirus vaccination and selected syndromes with autonomic dysfunction in Danish females: population based, self-controlled, case series analysis

Abstract:

Objective: To evaluate the association between quadrivalent human papillomavirus vaccination and syndromes with autonomic dysfunction, such as chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome.

Design: Population-based self-controlled case series.

Setting: Information on human papillomavirus vaccinations and selected syndromes with autonomic dysfunction (chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome) identified using ICD-10 (international classification of diseases, revision 10) diagnostic codes from Danish nationwide registers.

Participants: 869 patients with autonomic dysfunction syndromes from a cohort of 1 375 737 Danish born female participants aged 10 to 44 years during 2007-16.

Main outcome measures: Self-controlled case series rate ratios (95% confidence intervals) of the composite outcome of chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome, adjusted for age and season, comparing female participants vaccinated and unvaccinated with the quadrivalent human papillomavirus vaccine. Chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome were also considered separately in secondary analyses.

Results: During 10 581 902 person years of follow-up, 869 female participants with syndromes of autonomic dysfunction (136 with chronic fatigue syndrome, 535 with complex regional pain syndrome, and 198 with postural orthostatic tachycardia syndrome) were identified. Quadrivalent human papillomavirus vaccination did not statistically significantly increase the rate of a composite outcome of all syndromes with autonomic dysfunction in a 365 day risk period following vaccination (rate ratio 0.99, 95% confidence interval 0.74 to 1.32) or the rate of any individual syndrome in the risk period (chronic fatigue syndrome (0.38, 0.13 to 1.09), complex regional pain syndrome (1.31, 0.91 to 1.90), or postural orthostatic tachycardia syndrome (0.86, 0.48 to 1.54)).

Conclusions: When vaccination is introduced, adverse events could occur in close temporal relation to the vaccine purely by chance. These results do not support a causal association between quadrivalent human papillomavirus vaccination and chronic fatigue syndrome, complex regional pain syndrome, or postural orthostatic tachycardia syndrome, either individually or as a composite outcome. An increased risk of up to 32% cannot be formally excluded, but the statistical power of the study suggests that a larger increase in the rate of any syndrome associated with vaccination is unlikely.

Source: Hviid A, Thorsen NM, Valentiner-Branth P, Frisch M, Mølbak K. Association between quadrivalent human papillomavirus vaccination and selected syndromes with autonomic dysfunction in Danish females: population based, self-controlled, case series analysis. BMJ. 2020;370:m2930. Published 2020 Sep 2. doi:10.1136/bmj.m2930 https://pubmed.ncbi.nlm.nih.gov/32878745/

Effect of ginger-separated moxibustion on fatigue, sleep quality and depression in patients with chronic fatigue syndrome: a randomized controlled trial

Abstract:

Objective: To observe the effect of ginger-separated moxibustion on fatigue, sleep quality and depression in the patients with chronic fatigue syndrome.

Methods: A total of 62 patients with chronic fatigue syndrome were randomized into an observation group (31 cases, 3 cases dropped off) and a control group (31 cases, 2 cases dropped off). In the control group, the patients had normal diet and proper physical exercise. In the observation group, on the basis of the control group, the ginger-separated moxibustion was added at Zhongwan (CV 12), Shenque (CV 8) and Guanyuan (CV 4), 30 min each time, once every two days, 3 times weekly. Separately, before treatment and after 4 weeks of treatment, the MOS item short form health survey (SF-36), the Pittsburgh sleep quality index (PSQI) scale and the self-rating depression scale (SDS) were adopted to evaluate the degrees of fatigue, sleep quality and depression in the patients of the two groups.

Results: In the observation group, the score of each item of SF-36, the score of each item of PSQI and SDS score after treatment were all improved significantly as compared with those before treatment respectively (P<0.05, P<0.01). In the control group, the scores of overall health, vitality and mental health in SF-36 and the score of sleep time of PSQI after treatment were improved as compared with those before treatment respectively (P<0.05). After treatment, the score of each item of SF-36, the scores of sleep quality, sleep time, sleep efficiency and sleep disorders of PSQI, as well as SDS score in the observation group were all better than those in the control group respectively (P<0.01, P<0.05). The score of SF-36 was relevant to the scores of PSQI and SDS in the patients of chronic fatigue syndrome (r =0.331, P<0.05; r =-0.706, P<0.01). The improvement value of SF-36 score was closely related to the improvement value of SDS score in the observation group (r =-0.657, P<0.01).

Conclusion: The ginger-separated moxibustion effectively relieves fatigue and depression condition and improves sleep quality in the patients with chronic fatigue syndrome. The fatigue condition is relevant with sleep quality and depression condition to a certain extent in the patients.

Source: Lin YF, Zhu JF, Chen YD, et al. Zhongguo Zhen Jiu. 2020;40(8):816-820. doi:10.13703/j.0255-2930.20190722-k0001 https://pubmed.ncbi.nlm.nih.gov/32869588/

Using structural and functional MRI as a neuroimaging technique to investigate chronic fatigue syndrome/myalgic encephalopathy: a systematic review

Abstract:

Objective: This systematic review aims to synthesise and evaluate structural MRI (sMRI) and functional MRI (fMRI) studies in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

Methods: We systematically searched Medline and Ovid and included articles from 1991 (date of Oxford diagnostic criteria for CFS/ME) to first April 2019. Studies were selected by predefined inclusion and exclusion criteria. Two reviewers independently reviewed the titles and abstracts to determine articles for inclusion, full text and quality assessment for risk of bias.

Results: sMRI studies report differences in CFS/ME brain anatomy in grey and white matter volume, ventricular enlargement and hyperintensities. Three studies report no neuroanatomical differences between CFS/ME and healthy controls. Task-based fMRI investigated working memory, attention, reward and motivation, sensory information processing and emotional conflict. The most consistent finding was CFS/ME exhibited increased activations and recruited additional brain regions. Tasks with increasing load or complexity produced decreased activation in task-specific brain regions.

Conclusions: There were insufficient data to define a unique neural profile or biomarker of CFS/ME. This may be due to inconsistencies in finding neuroanatomical differences in CFS/ME and the variety of different tasks employed by fMRI studies. But there are also limitations with neuroimaging. All brain region specific volumetric differences in CFS/ME were derived from voxel-based statistics that are biased towards group differences that are highly localised in space. fMRI studies demonstrated both increases and decreases in activation patterns in CFS/ME, this may be related to task demand. However, fMRI signal cannot differentiate between neural excitation and inhibition or function-specific neural processing. Many studies have small sample sizes and did not control for the heterogeneity of this clinical population. We suggest that with robust study design, subgrouping and larger sample sizes, future neuroimaging studies could potentially lead to a breakthrough in our understanding of the disease.

Source: Almutairi B, Langley C, Crawley E, Thai NJ. Using structural and functional MRI as a neuroimaging technique to investigate chronic fatigue syndrome/myalgic encephalopathy: a systematic review. BMJ Open. 2020;10(8):e031672. Published 2020 Aug 30. doi:10.1136/bmjopen-2019-031672 https://bmjopen.bmj.com/content/10/8/e031672.long (Full text)

Determination by ICP-MS and multivariate data analysis of elemental urine excretion profile during the EDTA chelation therapy: A case study

Abstract:

Background: Based on the medical history and laboratory analytical tests, a patient presenting symptoms compatible with Chronic Fatigue Syndrome was suspected of metal intoxication; therefore, a chelating therapy was attempted. In parallel, the profile of elemental excretion in urine was determined.

Methods: Chelation therapy by CaNa2EDTA was administered every two weeks and urine samples were routinely collected for 17 months. The samples were mineralized with HNO3 69 % and analyzed by Inductively-Coupled Plasma – Mass Spectrometry. Data were processed by multivariate statistical methods.

Results: Most of the toxic elements showed a peak of excretion in 12-24 h after EDTA administration, which returned to basal level by 24-36 h after the treatment. Yet, the excretion of some trace elements persisted in the urine collected 26 h after the treatment.

Conclusions: The analysis of excreted metals following the CaNa2EDTA infusion allowed to monitor dynamically the chelation therapy. The chelation therapy was effective in mobilizing and eliminating the principal heavy metals present from the body. However, since such clearance almost vanished 24 h after the treatment, a protocol with more frequent and low-dose administrations is advisable to improve the metal excretion.

Source: Robotti E, Quasso F, Manfredi M, et al. Determination by ICP-MS and multivariate data analysis of elemental urine excretion profile during the EDTA chelation therapy: A case study [published online ahead of print, 2020 Aug 14]. J Trace Elem Med Biol. 2020;62:126608. doi:10.1016/j.jtemb.2020.126608

Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls

Abstract:

For the past 30 years, there has been a lack of objective tools for diagnosing Gulf War Illness (GWI), which is largely characterized by central nervous system (CNS) symptoms emerging from 1991 Gulf War (GW) veterans. In a recent preliminary study, we reported the presence of autoantibodies against CNS proteins in the blood of veterans with GWI, suggesting a potential objective biomarker for the disorder.

Now, we report the results of a larger, confirmatory study of these objective biomarkers in 171 veterans with GWI compared to 60 healthy GW veteran controls and 85 symptomatic civilian controls (n = 50 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and n = 35 irritable bowel syndrome (IBS)). Specifically, we compared plasma markers of CNS autoantibodies for diagnostic characteristics of the four groups (GWI, GW controls, ME/CFS, IBS).

For veterans with GWI, the results showed statistically increased levels of nine of the ten autoantibodies against neuronal “tubulin, neurofilament protein (NFP), Microtubule Associated Protein-2 (MAP-2), Microtubule Associated Protein-Tau (Tau), alpha synuclein (α-syn), calcium calmodulin kinase II (CaMKII)” and glial proteins “Glial Fibrillary Acidic Protein (GFAP), Myelin Associated Glycoprotein (MAG), Myelin Basic Protein (MBP), S100B” compared to healthy GW controls as well as civilians with ME/CFS and IBS.

Next, we summed all of the means of the CNS autoantibodies for each group into a new index score called the Neurodegeneration Index (NDI). The NDI was calculated for each tested group and showed veterans with GWI had statistically significantly higher NDI values than all three control groups. The present study confirmed the utility of the use of plasma autoantibodies for CNS proteins to distinguish among veterans with GWI and other healthy and symptomatic control groups.

Source: Mohamed B. Abou-Donia, Elizabeth S. Lapadula, Maxine H. Krengel, Emily Quinn, Jessica LeClair, Joseph Massaro, Lisa A. Conboy, Efi Kokkotou, Maria Abreu, Nancy G. Klimas, Daniel D. Nguyen and Kimberly Sullivan. Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls. Brain Sci. 2020, 10(9), 610; https://doi.org/10.3390/brainsci10090610 https://www.mdpi.com/2076-3425/10/9/610/htm (Full text)

How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS

Abstract:

We propose a framework for understanding and interpreting the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to singular or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states.

Thus, the predominantly neuro-immune manifestations, underlined by a hyper-metabolic state, that characterize early disease, may be followed by various processes leading to multi-systemic abnormalities and related symptoms. This abnormal state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production.

These processes do not seem to happen uniformly; although a spiraling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. With time variation in disease presentation, no single ME/CFS case description, set of diagnostic criteria, or molecular feature is currently representative of all patients at different disease stages. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may support future research design and health care interventions for people with ME/CFS.

Source: Nacul L, O’Boyle S, Palla L, et al. How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS. Front Neurol. 2020;11:826. Published 2020 Aug 11. doi:10.3389/fneur.2020.00826 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431524/ (Full text)

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review

Abstract:

Background: Since the 1990s, neuroimaging has been utilised to study Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a debilitating illness with unknown aetiology. While brain abnormalities in ME/CFS have been identified, relatively little is known regarding which specific abnormalities are consistently observed across research groups and to what extent the observed abnormalities are reproducible.

Method: To identify consistent and inconsistent neuroimaging observations in ME/CFS, this retrospective and systematic review searched for studies in which neuroimaging was used to investigate brain abnormalities in ME/CFS in Ovid MEDLINE, PubMed (NCBI), and Scopus from January 1988 to July 2018. A qualitative synthesis of observations was performed to identify brain abnormalities that were consistently and inconsistently reported.

Results: 63 full-text articles were included in the synthesis of results from 291 identified papers. Additional brain area recruitment for cognitive tasks and abnormalities in the brain stem are frequent observations in 11 and 9 studies using different modalities from different research teams respectively. Also, sluggish blood oxygenation level-dependent (BOLD) signal responses to tasks, reduced serotonin transporters, and regional hypometabolism are consistent observations by more than two research teams. Single observations include abnormal brain tissue properties, regional metabolic abnormalities, and association of brain measures with ME/CFS symptoms. Reduced resting cerebral blood flow and volumetric brain changes are inconsistent observations across different studies.

Conclusion: Neuroimaging studies of ME/CFS have frequently observed additional brain area recruitment during cognitive tasks and abnormalities in the brain stem. The frequent observation of additional brain area recruitment and consistent observation of sluggish fMRI signal response suggest abnormal neurovascular coupling in ME/CFS.

Source: Shan ZY, Barnden LR, Kwiatek RA, Bhuta S, Hermens DF, Lagopoulos J. Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review. J Transl Med. 2020;18(1):335. Published 2020 Sep 1. doi:10.1186/s12967-020-02506-6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466519/ (Full text)

Chronic Fatigue Syndrome: An Evaluation of a Community Based Management Programme for Adolescents and their Families

Abstract:

Background: Young people with chronic fatigue syndrome (CFS), families and clinicians may differ in their attributions about CFS and consequently in their approach to treatment. Research that clarifies the best treatment approaches is clearly needed. We have sought to develop a model that engages young people and their families in a collaborative way. The approach adopts an optimistic and holistic stance using an active rehabilitation model paying attention to the integrated nature of the physiological and psychological aspects of the illness.

Method: This small study set out to evaluate this approach from a service user perspective. Semi-structured interviews were carried out with young people and their parents separately in order to elicit their views on key treatment elements and their perceived degree of recovery.

Results: Improvements are indicated in all key areas addressed and qualitative information suggests that families value this approach.

Conclusion: Further research is needed to address treatment issues for families who choose not to opt into the service model.

Source: Ashby B, Wright B, Jordan J. Chronic Fatigue Syndrome: An Evaluation of a Community Based Management Programme for Adolescents and their Families. Child Adolesc Ment Health. 2006;11(1):13-18. doi:10.1111/j.1475-3588.2005.00383.x https://pubmed.ncbi.nlm.nih.gov/32811062/

Illness Beliefs in Chronic Fatigue Syndrome: A Study Involving Affected Adolescents and their Parents

Abstract:

Background: The aim of the study was too investigate the beliefs of young people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and their parents, about illness causes and management.

Method: Twenty-one young people with CFS/ME and their parents participated in an open-ended interview.

Results: Infective causes were identified by the majority of respondents, and psychological ones by a minority. Many highlighted reducing activity and resting in symptom management. Positive and negative experiences of psychiatric and psychological treatments were recorded.

Conclusion: Professionals should carefully explore the illness related beliefs of young people with CFS/ME and parental beliefs in order to agree treatment plans.

Source: Richards J, Chaplin R, Starkey C, Turk J. Illness Beliefs in Chronic Fatigue Syndrome: A Study Involving Affected Adolescents and their Parents. Child Adolesc Ment Health. 2006;11(4):198-203. doi:10.1111/j.1475-3588.2006.00409.x https://pubmed.ncbi.nlm.nih.gov/32810979/

Activity measurement in pediatric chronic fatigue syndrome

Abstract:

Objectives: Individuals with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) experience debilitating symptoms, including post-exertional malaise, an intensification of symptoms after physical or cognitive exertion. Previous studies found differences in the activity levels and patterns of activity among individuals with ME and CFS, compared to healthy controls; however, limited research exists on the activity levels of pediatric patients. The objective of this study was to examine differences in activity between healthy children and youth with ME and CFS.

Methods: The present study examines the objective (i.e., ActiGraphy) and self-reported levels of activity among children (ages 5 to 17) enrolled in a community-based study of pediatric CFS.

Results: Children with ME and CFS evidenced lower activity levels than healthy control children. Moreover, participants with ME and CFS evidenced increased nighttime activity and delayed initiation of daytime activity. Participants’ self-reported activity data significantly correlated with their ActiGraph data, suggesting that children with ME and CFS are able to accurately describe their activity level.

Discussion: This study highlights differences in activity level and diurnal/nocturnal activity patterns between healthy children and those with ME and CFS. These differences should be considered in identifying appropriate supports and accommodations for children with ME and CFS.

Source: Loiacono B, Sunnquist M, Nicholson L, Jason LA. Activity measurement in pediatric chronic fatigue syndrome [published online ahead of print, 2020 Aug 17]. Chronic Illn. 2020;1742395320949613. doi:10.1177/1742395320949613 https://pubmed.ncbi.nlm.nih.gov/32806955/