Potential causal factors of CFS/ME: a concise and systematic scoping review of factors researched.

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is understood as a complex condition, likely triggered and sustained by an interplay of biological, psychological, and social factors. Little oversight exists of the field of causal research. This systematic scoping review explores potential causal factors of CFS/ME as researched by primary studies. METHODS: We searched eight databases for primary studies that examined potential causal factors of CFS/ME. Based on title/abstract review, two researchers independently sorted each study's factors into nine main categories and 71 subordinate categories, using a system developed with input given during a 2018 ME conference, specialists and representatives from a ME patient advocacy group, and using BMJ Best Practice's description of CFS/ME etiology. We also extracted data related to study design, size, diagnostic criteria and comparison groups. RESULTS: We included 1161 primary studies published between January 1979 and June 2019. Based on title/abstract analysis, no single causal factor dominated in these studies, and studies reported a mean of 2.73 factors. The four most common factors were: immunological (297 studies), psychological (243), infections (198), and neuroendocrinal (198). The most frequent study designs were case-control studies (894 studies) comparing CFS/ME patients with healthy participants. More than half of the studies (that reported study size in the title/abstract) included 100 or fewer participants. CONCLUSION: The field of causal hypotheses of CFS/ME is diverse, and we found that the studies examined all the main categories of possible factors that we had defined a priori. Most studies were not designed to adequately explore causality, rather to establish hypotheses. We need larger studies with stronger study designs to gain better knowledge of causal factors of CFS/ME.

Attention deficit and hyperactivity disorder symptoms respond to gluten-free diet in patients with coeliac disease.

Introduction: Patients with coeliac disease commonly report symptoms of 'brain fog'. The aim of this study was to assess self-reported symptoms of impaired concentration in coeliac disease before and after treatment with gluten-free diet, compared with healthy controls and patient controls. Methods: Patients with newly diagnosed coeliac disease were included consecutively from two out-patient clinics. The patients completed the questionnaires Adult ADHD Self-Report Scale v1.1 Symptoms Checklist (ASRS), Hospital Anxiety and Depression Scale (HADS) and Gastrointestinal Symptom Rating Scale (GSRS) prior to start of a gluten-free diet and after at least 12 months on the diet. Patients with an established diagnosis of inflammatory bowel disease served as patient controls (n = 36). Health care personnel at Oslo University Hospital served as healthy controls (n = 60) and filled out ASRS and HADS. Results: A total of 31 newly diagnosed coeliac patients were included in the study. Of these, 26 patients met for follow-up and repeated the questionnaires. Prior to treatment, patients with coeliac disease had significantly higher scores than healthy controls on both the ASRS (p = .0014) and HADS (p=.0004). After a gluten-free diet, their scores improved and were not significantly different from healthy controls. There were no significant differences between patients with coeliac disease prior to treatment and patient controls with inflammatory bowel disease. Conclusion: Prior to treatment, coeliac disease patients reported significantly more symptoms than healthy controls on ASRS and HADS. The differences disappeared after a minimum of 12 months on a gluten-free diet.

Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway.

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex condition. Causal factors are not established, although underlying psychological or immunological susceptibility has been proposed. We studied primary care diagnoses for children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups. METHODS: All Norwegian children born 1992-2012 constituted the study sample. Children with CFS/ME (n = 1670) or T1DM (n = 4937) were identified in the Norwegian Patient Register (NPR) (2008-2014). Children without either diagnosis constituted the general child population comparison group (n = 1337508). We obtained information on primary care diagnoses from the Norwegian Directorate of Health. For each primary care diagnosis, the proportion and 99 % confidence interval (CI) within the three groups was calculated, adjusted for sex and age by direct standardization. RESULTS: Children with CFS/ME were more often registered with a primary care diagnosis of weakness/general tiredness (89.9 % [99 % CI 88.0 to 91.8 %]) than children in either comparison group (T1DM: 14.5 % [99 % CI: 13.1 to 16.0 %], general child population: 11.1 % [99 % CI: 11.0 to 11.2 %]). Also, depressive disorder and anxiety disorder were more common in the CFS/ME group, as were migraine, muscle pain, and infections. In the 2 year period prior to the diagnoses, infectious mononucleosis was registered for 11.1 % (99 % CI 9.1 to 13.1 %) of children with CFS/ME and for 0.5 % (99 % CI (0.2 to 0.8 %) of children with T1DM. Of children with CFS/ME, 74.6 % (1292/1670) were registered with a prior primary care diagnosis of weakness / general tiredness. The time span from the first primary care diagnosis of weakness / general tiredness to the specialist health care diagnosis of CFS/ME was 1 year or longer for 47.8 %. CONCLUSIONS: This large nationwide registry linkage study confirms that the clinical picture in CFS/ME is complex. Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway. The long time span often observed from the first diagnosis of weakness / general tiredness to the diagnosis of CFS/ME might indicate that the treatment of these patients is sometimes not optimal.

Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012.

BACKGROUND: The aim of the current study was to estimate sex- and age-specific incidence rates of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) using population-based registry data. CFS/ME is a debilitating condition with large impact on patients and their families. The etiology is unknown, and the distribution of the disease in the general population has not been well described. METHODS: Cases of CFS/ME were identified in the Norwegian Patient Register (NPR) for the years 2008 to 2012. The NPR is nationwide and contains diagnoses assigned by specialist health care services (hospitals and outpatient clinics). We estimated sex- and age-specific incidence rates by dividing the number of new cases of CFS/ME in each category by the number of person years at risk. Incidence rate ratios were estimated by Poisson regression with sex, age categories, and year of diagnosis as covariates. RESULTS: A total of 5,809 patients were registered with CFS/ME during 2008 to 2012. The overall incidence rate was 25.8 per 100,000 person years (95% confidence interval (CI): 25.2 to 26.5). The female to male incidence rate ratio of CFS/ME was 3.2 (95% CI: 3.0 to 3.4). The incidence rate varied strongly with age for both sexes, with a first peak in the age group 10 to 19 years and a second peak in the age group 30 to 39 years. CONCLUSIONS: Early etiological clues can sometimes be gained from examination of disease patterns. The strong female preponderance and the two age peaks suggest that sex- and age-specific factors may modulate the risk of CFS/ME.