The documentary Left Out (De Bortgjemte) was shown on national TV in Norway in 2018 and now has its international release on YouTube with English subtitles, 29 January 2020.
Director Paul Schaathun followed some ME patients and Dr Oystein Fluge’s RituxME trial for 2 years. The resulting film is both informative and touching.
When they realised she had ME they just let go of us. “Sorry, it’s ME, we can’t do any more. We had to fend for ourselves. Anne Karen, Emile’s mother
The latest worldwide prevalence rate projects that over 65 million patients suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), an illness with known effects on the functioning of the immune and nervous systems. We performed an extensive metabolomics analysis on the plasma of 52 female subjects, equally sampled between controls and ME/CFS patients, which delivered data for about 1750 blood compounds spanning 20 super-pathways, subdivided into 113 sub-pathways.
Statistical analysis combined with pathway enrichment analysis points to a few disrupted metabolic pathways containing many unexplored compounds. The most intriguing finding concerns acyl cholines, belonging to the fatty acid metabolism sub-pathway of lipids, for which all compounds are consistently reduced in two distinct ME/CFS patient cohorts.
We compiled the extremely limited knowledge about these compounds and regard them as promising in the quest to explain many of the ME/CFS symptoms. Another class of lipids with far-reaching activity on virtually all organ systems are steroids; androgenic, progestin, and corticosteroids are broadly reduced in our patient cohort.
We also report on lower dipeptides and elevated sphingolipids abundance in patients compared to controls. Disturbances in the metabolism of many of these molecules can be linked to the profound organ system symptoms endured by ME/CFS patients.
Background:
Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date.
Methods:
RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes.
Results:
Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 76.4%), and the primary measurement tools included the Checklist Individual Strength (CIS, 36.4%) and the 36-item Short Form health survey (SF-36, 30.9%).
Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C12U) and CoQ10 + NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility.
Conclusions:
This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.
Background:
Most pediatric prevalence studies of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have been based upon data from tertiary care centers, a process known for systematic biases such as excluding youth of lower socioeconomic status and those less likely to have access to health care. In addition, most pediatric ME/CFS epidemiologic studies have not included a thorough medical and psychiatric examination. The purpose of this study was to determine the prevalence of pediatric ME/CFS from an ethnically and sociodemographically diverse community-based random sample.
Method:
A sample of 10,119 youth aged 5–17 from 5622 households in the Chicagoland area were screened. Following evaluations, a team of physicians made final diagnoses. Youth were given a diagnosis of ME/CFS if they met criteria for three selected case definitions. A probabilistic, multi-stage formula was used for final prevalence calculations.
Results: The prevalence of pediatric ME/CFS was 0.75%, with a higher percentage being African American and Latino than Caucasian. Of the youth diagnosed with ME/CFS, less than 5% had been previously diagnosed with the illness.
Conclusions:
Many youth with the illness have not been previously diagnosed with ME/CFS. These findings point to the need for better ways to identify and diagnose youth with this illness.
Background:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and debilitating disorder associated with significant disruptions in daily life including. This study aimed to examine the impact of sociodemographic and patient symptom characteristics on health-related quality of life (HRQoL) of Australians with ME/CFS.
Methods:
Self-reported data collected from 480 individuals diagnosed with ME/CFS were obtained between August 2014 and August 2018. This cross-sectional survey analysed sociodemographic, symptom characteristics and HRQoL according to the 36-Item Health Survey (SF-36). Multivariate linear regression models were used to determine ME/CFS symptoms associated with eight domains of HRQoL.
Results:
Reported HRQoL was significantly impaired in ME/CFS patients across all domains compared with the general population. Scores were the lowest for physical role (4.11 ± 15.07) and energy/fatigue (13.54 ± 13.94). Associations with females, higher body mass index (BMI), employment status, cognitive difficulties, sensory disturbances and cardiovascular symptoms were observed in the physical functioning domain. Impaired pain domain scores were associated with high BMI, annual visits to their general practitioner, flu-like symptoms and fluctuations in body temperature. Reduced well-being scores were associated with smoking status, psychiatric comorbidity, cognitive difficulties, sleep disturbances and gastrointestinal difficulties.
Conclusion:
This study provides evidence that ME/CFS has a profound and negative impact on HRQoL in an Australian cohort.
Study objectives: Physiological dearousal characterized by an increase in parasympathetic nervous system activity is important for good-quality sleep. Previous research shows that nocturnal parasympathetic activity (reflected by heart rate variability [HRV]) is diminished in individuals with chronic fatigue syndrome (CFS), suggesting hypervigilant sleep. This study investigated differences in nocturnal autonomic activity across sleep stages and explored the association of parasympathetic activity with sleep quality and self-reported physical and psychological wellbeing in individuals with CFS.
Methods:
Twenty-four patients with medically diagnosed CFS, and 24 matched healthy control individuals participated. Electroencephalography and HRV were recorded during sleep in participants’ homes using a minimally invasive ambulatory device. Questionnaires were used to measure self-reported wellbeing and sleep quality.
Results:
Sleep architecture in patients with CFS differed from that of control participants in slower sleep onset, more awakenings, and a larger proportion of time spent in slow-wave sleep (SWS). Linear mixed-model analyses controlling for age revealed that HRV reflecting parasympathetic activity (normalized high frequency power) was reduced in patients with CFS compared to control participants, particularly during deeper stages of sleep.
Poorer self-reported wellbeing and sleep quality was associated with reduced during deeper sleep, but not during wake before sleep, rapid eye movement sleep, or with the proportion of time spent in SWS.
Conclusions:
Autonomic hypervigilance during the deeper, recuperative stages of sleep is associated with poor quality sleep and self-reported wellbeing. Causal links need to be confirmed but provide potential intervention opportunities for the core symptom of unrefreshing sleep in CFS.
Purpose:
Chronic fatigue syndrome (CFS)/myalgic encephalopathy (ME) is relatively common in children and is disabling at an important time in their development. This study aimed to develop a conceptual framework of paediatric CFS/ME using the patient-perspective to ensure that the content of a new outcome measure includes the outcomes most important to young people.
Methods: We developed a child-centred interactive card ranking exercise that included health-related quality of life (HRQoL) outcomes identified from a previous review of the literature as well as qualitative work. Adolescents and their parents selected and ranked the outcomes most important to them and discussed each outcome in further detail. Adolescents were purposively sampled from a single specialist paediatric CFS/ME service in England. Interviews were audio recorded and transcribed verbatim, and thematic framework analysis was used to develop the final conceptual framework.
Results:
We interviewed 43 participants in which there are 21 adolescents, 12–17 years of age with mild–moderate CFS/ME and their parents (20 mothers and 2 fathers). ‘Symptoms’, ‘tiredness’, ‘payback and crashing’ and ‘activities and hobbies’ were ranked most important to improve by both children and parents. Children ranked ‘school’ higher than parents and parents ranked ‘mood’ higher than children.
A youth- specific CFS/ME conceptual framework of HRQoL was produced that included 4 outcome domains and 11 subdomains: sleep, tiredness, problems concentrating, individual symptoms, fluctuation and payback, daily and general activities, participation in school, leisure and social life, mood, anxiety and self-esteem.
Conclusions:
An interactive card ranking exercise worked well for adolescents aged 12–17 to elicit the most important outcomes to them and explore each domain in further detail. We developed a final conceptual framework of HRQoL that forms the basis of a new paediatric patient-reported outcome measure (PROM) in CFS/ME.
Background:
Yoga is a representative mind-body therapy. Our previous studies have demonstrated that isometric yoga (i.e. yoga programs that we developed so individuals can practice yoga poses with a self-adjustable isometric load) reduces the fatigue of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, the underlying mechanisms remain unclear. Several studies have suggested that the micro-ribonucleic acid (miRNA) expression of ME/CFS patients is different from that of healthy subjects. However, it has not to date been determined if the practice of isometric yoga can affect miRNA expression. Therefore, we sought to investigate if isometric yoga is associated with changes in the expression levels of serum miRNA of patients with ME/CFS.
Methods:
The study included nine patients with ME/CFS who failed to show satisfactory improvement after at least 6 months of treatment administered at our hospital. Patients practiced recumbent isometric yoga for 3 months; they met with a yoga instructor every 2 to 4 weeks and participated in daily in-home sessions. The effect of recumbent isometric yoga on fatigue was assessed by comparing pre- and post-intervention scores on the Japanese version of the 11-item Chalder fatigue scale (CFQ 11). Patient blood samples were drawn pre- and post-intervention, just prior to practicing recumbent isometric yoga with an instructor. The serum was used for miRNA array analysis with known human miRNAs.
Results:
The average CFQ 11 score decreased significantly (from 25.3 ± 5.5 to 17.0 ± 5.8, p < 0.0001) after practicing recumbent isometric yoga for 3 months. The miRNA microarray analysis revealed that four miRNAs were significantly upregulated, and 42 were downregulated after the intervention period.
Conclusions:
This explorative pilot study is the first to demonstrate changes in the serum levels of several miRNAs after regular practice of recumbent isometric yoga. These miRNAs might represent biomarkers for the fatigue-relieving effects of isometric yoga of patients with ME/CFS.
Background: Cognitive function disturbance is a frequently described symptom of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). In this study, the effects of a structured exercise programme (SEP) upon cognitive function in ME/CFS patients was examined.
Methods:
Out of the 53 ME/CFS patients initiating SEP 34 (64%) completed the 16 week programme. Cognitive function was assessed using a computerized battery test consisting of a Simple Reaction Time (SRT) (repeated three times) and Choice Reaction Time (CRT) measurements, a Visual Attention Test (VAT) and a Delayed Matching to Sample (DMS) assessment.
Results:
Statistically significant improvement was noted in the third attempt to SRT in reaction time for correct answers, p=0.045, r=0.24. Moreover, significant improvement was noted in VAT reaction time, number of correct answers and errors committed, p=0.02, omega=0.03, p=0.007, r=0.34 and p=0.004, r=0.35, respectively. Non-significant changes were noted in other cognitive tests.
Conclusions:
A substantial number of participants were unwilling or unable to complete the exercise programme. ME/CFS patients able to complete the SEP showed improved visual attention both in terms of reaction time and correctness of responses and processing speed of simple visual stimuli.
Comment on Science4ME blog:
69 patients identified with Fukuda diagnosis, only 34 were able to complete C-PET and exercise program. No control group. A range of cognitive tests on the 34 showed some improvement in average performance after the activity program on a few of the tests relating to reaction time and accuracy, but the results were not significant when corrected for multiple comparisons. Despite this, the authors claim exercise is effective in improving cognitive function for some CFS patients.
Naltrexone is used as an off-label treatment in low doses for several chronic immune-modulated disorders in many countries. Although only small-scale clinical trials have been performed, these suggest efficacy in several diseases including Crohn’s disease, fibromyalgia and Gulf War Illness. Despite numerous internet reports of response to low-dose naltrexone (LDN), no clinical trials exist in people with chronic fatigue syndrome.
This condition is characterised by chronic profound fatigue, postexertional malaise, pain and autonomic and neurocognitive disturbances.
This series of three case reports compiled by people with long-term ill-health due to chronic fatigue syndrome shows the range of responses they observed when taking LDN, from life changing to a reduction in some symptoms only. Treatment doses ranged from 4 to 12 mg.
Clinical trials may be warranted to explore the potential use of naltrexone in people with these debilitating illnesses which currently have no licensed treatments available.
From discussion:
The mechanism of action for naltrexone at low dose in this disease group is unknown. It is possibly due to rebound of endorphins following short-term suppression or to direct action suppressing inflammation induced by microglia.39–41 There have been no formal dosing studies of naltrexone at low dose in any disorder. Therefore, although the dose of 3–4.5 mg is established in clinical practice, some practitioners use 9 mg (Klimas, personal communication, 2017) or higher(42) in chronic fatigue syndrome. Causality and dosing need further study.
…Internet reports suggest side effects can be troublesome initially, particularly increased fatigue and headaches.44 Two double-blind, placebo-controlled studies in people with fibromyalgia found no difference in tolerability between LDN and placebo but an increased frequency of vivid dreams and headaches.27 28 Recent work in Norway has found that individuals may experience fewer side effects if starting naltrexone at 6 mg, even if the final dose taken is lower than this (personal communication Brian Haviland 2018).
Patients’ perspective
Case 2
After 25 years of living with the devastating effects of myalgic encephalomyelitis, I was struggling to cope with the limited options for symptom and pain management. Having had many bad reactions to medications, I was hesitant to try a medication that would affect my immune system so I started out at an extremely low dose and slowly increased dosage. While the dreaming was at times disturbing, the positive changes gave me a hope for improvement I had not had in many years. The subsequent improvements have led to a much higher quality of life and I would like to see this medication as an approved option for others in my situation.
