Category: Symptoms

Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome

We recently reported in Gut that non-coeliac wheat sensitivity (NCWS) is associated with a state of systemic immune activation in conjunction with a compromised intestinal epithelium.1 Patients with NCWS experience GI symptoms, most commonly including abdominal pain and bloating, as well as extraintestinal symptoms, among which fatigue, headache and cognitive difficulties feature prominently.1 2 A principal component analysis of the generated data from our study, including markers of antibody reactivity to wheat gluten, intestinal cell damage and systemic innate and adaptive immune responses to microbial components, found clustering of the patients and controls into discernible groups and demonstrated the potential utility of the identified biomarkers for identifying patients with NCWS.1

Extreme fatigue, in particular one that does not improve with rest, is a hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).3 Immune system abnormalities have been found to be associated with symptoms in a substantial number of patients with ME/CFS.4 5 Furthermore, many patients complain of GI symptoms of unknown aetiology.6–8 We considered whether a subset of patients with ME/CFS may exhibit serologic markers associated with NCWS, which might explain some of the corresponding symptoms. We screened serum samples from 131 patients with ME/CFS and 86 healthy controls (table 1), recruited as previously described,9 for the same markers as those in the above-mentioned study on NCWS.1 Questionnaires were used to assess GI symptoms within the past 6 months, including abdominal pain, bloating and nausea. Severity of individual symptoms was scored from 1 to 5 (1=absent; 2=mild; 3=moderate; 4=severe; 5=very severe), and a total score, based on the sum of individual symptom scores, was calculated for each subject.

Read full article HERE.

Source: Melanie Uhde, Alyssa C Indart, Xuechen B Yu, Sophie S Jang, Roberto De Giorgio, Peter H R Green, Umberto Volta, Suzanne D Vernon, Armin Alaedini. Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome. http://dx.doi.org/10.1136/gutjnl-2018-316133

Perception of induced dyspnea in fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVE: Dyspnea perception is distorted in patients with medically unexplained dyspnea. The goals of this study were 1) to replicate these results in patients with fibromyalgia and/or chronic fatigue syndrome (CFS), and 2) to investigate predictors of distorted symptom perception within the patient group, with a focus on negative affectivity (NA), psychiatric comorbidity and somatic symptom severity.

METHODS: Seventy-three patients diagnosed with fibromyalgia and/or CFS and 38 healthy controls (HC) completed a rebreathing paradigm, consisting of a baseline (60s of room air), a rebreathing phase (150s, gradually increasing ventilation, partial pressure of CO2 in the blood, and self-reported dyspnea), and a recovery phase (150s of room air). Dyspnea, respiratory flow and FetCO2 levels were measured continuously.

RESULTS: Patients reported more dyspnea than HC in the recovery phase (p=0.039), but no differences between patients and HC were found in the baseline (p=0.07) or rebreathing phase (p=0.17). No significant differences between patients and HC were found in physiological reactivity. Within the patient group, the effect in the recovery phase was predicted by somatic symptom severity (p=0.046), but not by negative affectivity or by the number of psychiatric comorbidities.

CONCLUSION: This study extended earlier findings in patients with medically unexplained dyspnea to patients with fibromyalgia and CFS. This suggests that altered symptom perception is a non-symptom-specific mechanism underlying functional somatic syndromes in general, particularly in patients with high levels of somatic symptom severity. The results are discussed in a predictive coding framework of symptom perception.

Source: Van Den Houte M, Bogaerts K, Van Diest I, De Bie J, Persoons P, Van Oudenhove L, Van den Bergh O. Perception of induced dyspnea in fibromyalgia and chronic fatigue syndrome. J Psychosom Res. 2018 Mar;106:49-55. doi: 10.1016/j.jpsychores.2018.01.007. Epub 2018 Jan 11. https://www.ncbi.nlm.nih.gov/pubmed/29455899

Energy envelope maintenance among patients with myalgic encephalomyelitis and chronic fatigue syndrome: Implications of limited energy reserves

Abstract:

Objective: The Energy Envelope Theory of myalgic encephalomyelitis and chronic fatigue syndrome postulates that individuals with myalgic encephalomyelitis and chronic fatigue syndrome may experience some increase in functioning if their level of exertion consistently remains within the limits of their available energy. Findings of several studies support this theory; however, the current study is the first to explore how an individual’s initial level of available energy may influence the relation between energy envelope maintenance and level of functioning.

Method:The functioning, activity, and symptomatology of six groups of individuals with myalgic encephalomyelitis and chronic fatigue syndrome were compared. Groups were created based upon level of available energy (higher or lower) and energy envelope adherence (underextended, within, overextended).

Results: Results indicate that, as expected, individuals with myalgic encephalomyelitis and chronic fatigue syndrome who had higher available energy also had better functioning than individuals with lower available energy; however, this relation was less pronounced for individuals who were overexerting themselves.

Discussion: These results are consistent with the Energy Envelope Theory, and they suggest that overexertion was particularly impactful for individuals with higher levels of available energy.

Source: O’connor K, Sunnquist M, Nicholson L, Jason LA, Newton JL, Strand EB. Energy envelope maintenance among patients with myalgic encephalomyelitis and chronic fatigue syndrome: Implications of limited energy reserves. Chronic Illn. 2017 Jan 1:1742395317746470. doi: 10.1177/1742395317746470. [Epub ahead of print]

Inflammation correlates with symptoms in chronic fatigue syndrome

It is not unusual for patients who say they are sick to have normal results on standard laboratory testing. The physician often concludes that there is no “real” illness and that the patients’ symptoms likely stem from a psychological disorder. An alternative conclusion, often honored in the breach, is that the standard laboratory tests are measuring the wrong things.

Chronic fatigue syndrome (CFS)―also called myalgic encephalomyelitis/chronic fatigue syndrome―is such an illness. Often, the condition begins suddenly, following an “infectious-like” illness.

For years, patients do not return to full health. The illness waxes and wanes, and at its worst leads patients to be bedridden or unable to leave their homes. A report from the National Academies estimates that CFS affects up to 2.5 million people in the United States and generates direct and indirect expenses of $17–24 billion annually (1). The most widely used case definition (2) consists only of symptoms. This, along with typically normal results on standard laboratory tests, has raised the question of whether there are any “real” objective, biological abnormalities in CFS. In PNAS, Montoya et al. report the latest evidence that there are such abnormalities.

Indeed, research over the past 30 y has discovered pathology involving the central nervous system (CNS) and autonomic nervous system (ANS), energy metabolism (with associated oxidative and nitrosative stress), and the immune system, as described in a detailed review (4). This Commentary will briefly summarize the evidence, providing citations only to work published since this review. I will then place the report by Montoya et al. (3) in context, and speculate about the pathophysiology of the illness.

Source: Anthony Komaroff. Inflammation correlates with symptoms in chronic fatigue syndrome. PNAS  2017 ; published ahead of print August 15, 2017 doi: 10.1073/pnas.1712475114  http://www.pnas.org/content/early/2017/08/14/1712475114.extract

Chronic fatigue syndrome and idiopathic intracranial hypertension: Different manifestations of the same disorder of intracranial pressure?

Abstract:

Though not discussed in the medical literature or considered in clinical practice, there are similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) which ought to encourage exploration of a link between them. The cardinal symptoms of each – fatigue and headache – are common in the other and their multiple other symptoms are frequently seen in both.

The single discriminating factor is raised intracranial pressure, evidenced in IIH usually by the sign of papilloedema, regarded as responsible for the visual symptoms which can lead to blindness. Some patients with IIH, however, do not have papilloedema and these patients may be clinically indistinguishable from patients with chronic fatigue syndrome. Yet IIH is rare, IIH without papilloedema (IIHWOP) seems rarer still, while chronic fatigue syndrome is common. So are the clinical parallels spurious or is there a way to reconcile these conflicting observations?

We suggest that it is a quirk of clinical measurement that has created this discrepancy. Specifically, that the criteria put in place to define IIH have led to a failure to appreciate the existence, clinical significance or numerical importance of patients with lower level disturbances of intracranial pressure. We argue that this has led to a grossly implausible distortion of the epidemiology of IIH such that the milder form of the illness (IIHWOP) is seen as less common than the more severe and that this would be resolved by recognising a connection with chronic fatigue syndrome.

We hypothesise, therefore, that IIH, IIHWOP, lesser forms of IIH and an undetermined proportion of chronic fatigue cases are all manifestations of the same disorder of intracranial pressure across a spectrum of disease severity, in which this subset of chronic fatigue syndrome would represent the most common and least severe and IIH the least common and most extreme.

Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Source: Higgins JNP, Pickard JD, Lever AML. Chronic fatigue syndrome and idiopathic intracranial hypertension: Different manifestations of the same disorder of intracranial pressure? Med Hypotheses. 2017 Aug;105:6-9. doi: 10.1016/j.mehy.2017.06.014. Epub 2017 Jun 24. https://www.ncbi.nlm.nih.gov/pubmed/28735654 

Subtyping Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) By Course of Illness

Abstract:
Past research has subtyped patients with Myalgic Encephalolyelitis (ME) and Chronic Fatigue Syndrome (CFS) according to factors related to illness onset, illness duration, and age. However, no classification system fully accounts for the wide range of symptom severity, functional disability, progression, and prognosis seen among patients. This study examined whether illness trajectories among individuals with CFS were predictive of different levels of symptomology, functional disability, and energy expenditure.
Of the participants (N=541), the majority described their illness as Fluctuating (59.7%), with 15.9% Constantly Getting Worse, 14.1% Persisting, 8.5% Relapsing and Remitting, and 1.9% Constantly Getting Better. The illness courses were associated with significant differences in symptomology on select domains of the DSQ, functioning on select subscales of the SF-36, and on overall levels of energy expenditure.
The significant symptomatic and functional differences between groups suggest that subtyping patients with CFS according to illness course is a promising method for creating more homogeneous groups of patients.
Source:  Jamie Stoothoff, Kristen Gleason, Stephanie McManimen, Taylor Thorpe and Leonard A. Jason.  Subtyping Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) By Course of Illness. Symbiosis, June 26, 2017. https://symbiosisonlinepublishing.com/biosensors-biomarkers-diagnostics/biosensors-biomarkers-diagnostics13.pdf (Full article)

Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome

Abstract:

Unrefreshing sleep is a hallmark of chronic fatigue syndrome/myalgic encephalomyelitis (CFS). This study examined brain structure variations associated with sleep quality in patients with CFS. 38 patients with CFS (34.8 ± 10.1 years old) and 14 normal controls (NCs) (34.7 ± 8.4 years old) were recruited. All subjects completed the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index (PSQI), and Chalder Fatigue Scale (CFQ) questionnaires. Brain MRI measures included global and regional grey and white matter volumes, magnetization transfer T1 weighted (MT-T1w) intensities, and T1 weighted (T1w) and T2 weighted spin echo signal intensities.

We performed voxel based group comparisons of these regional brain MRI measures and regressions of these measures with the PSQI and CFQ scales adjusted for age, anxiety and depression, and the appropriate global measure. In CFS patients, negative correlations were observed in the medial prefrontal cortex (mPFC) between PSQI and MT-T1w intensities (family-wise error corrected cluster, PFWE < 0.05) and between PSQI and T1w intensities (PFWE < 0.05). In the same mPFC location, both MT and T1w intensities were lower in CFS patients compared with NCs (uncorrected voxel P < 0.001).

This study is the first to report that brain structural differences are associated with unrefreshing sleep in CFS. This result refutes the suggestion that unrefreshing sleep is a misperception in CFS patients and further investigation of this symptom is warranted.

Source: Shan ZY, Kwiatek R, Burnet R, Del Fante P, Staines DR, Marshall-Gradisnik SM, Barnden LR. Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome. NMR Biomed. 2017 Jun 29. doi: 10.1002/nbm.3757. [Epub ahead of print] http://onlinelibrary.wiley.com/doi/10.1002/nbm.3757/full

Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS

Abstract:

BACKGROUND: There are considerable phenotypic and neuroimmune overlaps between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). While the precise aetiologies of both MS and ME/CFS are unclear, evidence suggests that deterioration in cognitive function is widely prevalent in patients with either condition. Little is known about differing risk factors or exposures, which may lead to severe cognitive or sleep symptoms. This study aims to gauge the extent of cognitive and sleep symptoms in ME/CFS and MS patients participating in the UK ME/CFS Biobank and identify the characteristics of those experiencing severe symptoms.

METHODS: This was a cross-sectional study of 395 UK ME/CFS Biobank participants, recruited from primary care and the community, using similar standardised protocols, and matched by age, sex and geographical area. Data were collected from participants using a standardized written questionnaire at clinical visits. Cognitive symptoms included problems with short-term memory, attention, and executive function. Sleep symptoms included unrefreshing sleep and poor quality or inadequate duration of sleep. All participants reported symptoms based on an ordinal severity scale. Multivariable logistic regression was carried out in the ME/CFS group to investigate socio-demographic factors associated with severe symptoms.

RESULTS: All cognitive and sleep symptoms were more prevalent in the ME/CFS group, with 'trouble concentrating' (98.3%) the most commonly reported symptom. Severe symptoms were also more commonly reported in the ME/CFS group, with 55% reporting 'severe, unrefreshing sleep'. Similarly, in the MS group, the most commonly reported severe symptoms were sleep-related. Logistic regression analysis revealed that ME/CFS patients aged over 50 years were more than three times as likely to experience severe symptoms than those younger than 30 (OR 3.23, p = 0.031). Current smoking was associated with severe symptoms, increasing the risk by approximately three times (OR 2.93, p = 0.003) and those with household incomes of more than £15,000 per year were less likely to experience severe symptoms compared to those earning less than this (OR 0.31, p = 0.017).

CONCLUSIONS:Cognitive and sleep symptoms are more common in ME/CFS patients than in MS patients and healthy controls, providing further support for existing evidence of central nervous system abnormalities in ME/CFS. Our findings suggest that people with ME/CFS who are smokers, or have a low income, are more likely to report severe cognitive and sleep symptoms. Future research should aim to develop strategies to prevent the progression of severe cognitive and sleep symptoms through early interventions that prioritise patients identified as being at highest risk.

Source: Jain V, Arunkumar A, Kingdon C, Lacerda E, Nacul L. Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS. BMC Neurol. 2017 Jun 20;17(1):117. doi: 10.1186/s12883-017-0896-0. https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-017-0896-0 (Full article)

Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia

Abstract:

BACKGROUND: Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) share some similar symptoms with fibromyalgia (FM). Prior research has found increased illness severity when patients have FM that is comorbid with ME and CFS. For example, post-exertional malaise (PEM) has been shown to be more severe in those with comorbid FM. However, PEM can be separated into two factors, Muscle and General PEM. It is unknown if the more severe PEM findings in comorbid FM are due to the Muscle or General PEM factor.

PURPOSE:The purpose of this study was to determine if the PEM differences seen between patients with and without comorbid FM exist for the Muscle or General PEM factors.

METHOD: An international convenience sample was collected via an online questionnaire. The questionnaire assessed the frequency and severity of several PEM-related symptoms. Additionally, participants provided information regarding the course and characteristics of their illness.

RESULTS: Participants that indicated a comorbid diagnosis of FM displayed significantly more frequent and severe PEM symptoms in the Muscle and General PEM factors. The FM group also indicated significantly worse physical functioning compared to the group without comorbid FM.

DISCUSSION: The secondary diagnosis of FM in addition to ME and CFS appears to amplify the PEM symptomatology and worsen patients' physical functioning. The findings of this study have notable implications on the inclusion of patients with comorbid FM in ME and CFS research studies.

Source: McManimen SL, Jason LA. Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia. SRL Neurol Neurosurg. 2017;3(1):22-27. Epub 2017 Mar 10. https://www.ncbi.nlm.nih.gov/pubmed/28603794