2017 – Page 13 – American ME and CFS Society

A Prospective Study of Infectious Mononucleosis in College Students

Abstract:

BACKGROUND: The present study aims to prospectively investigate possible biological and psychological factors present in college students who will go on to develop chronic fatigue syndrome (CFS) following Infectious Mononucleosis (IM). Identification of risk factors predisposing patients towards developing CFS may help to understand the underlying mechanisms and ultimately prevent its occurrence. Our study is enrolling healthy college students over the age of 18. Enrollment began in March of 2013 and is ongoing.

METHODS: Biological and psychological data are collected when students are well (Stage 1), when they develop IM (Stage 2), and approximately 6 months after IM diagnosis (Stage 3).

RESULTS: Two case studies demonstrate the progression of student symptomology across all three stages.

CONCLUSION: The Case Studies presented illustrate the usefulness of a prospective research design that tracks healthy students, following their trajectory of IM illness to either a) full recovery or b) diagnosis with CFS.

Source: Jason LA, Katz B, Gleason K, McManimen S, Sunnquist M, Thorpe T. A Prospective Study of Infectious Mononucleosis in College Students. Int J Psychiatry (Overl Park). 2017;1(2). pii: http://www.opastonline.com/wp-content/uploads/2017/01/a-prospective-study-of-infectious-mononucleosis-in-college-students-IJP-17-016.pdf. Epub 2017 Jan 20. (Full article)

Increase in the Regional Cerebral Blood Flow following Waon Therapy in Patients with Chronic Fatigue Syndrome: A Pilot Study

Abstract:

Objective Chronic fatigue syndrome (CFS) is a complex disorder, with no consensus on therapeutic options. However, Waon therapy has been reported to be an effective treatment. The purpose of this study was to evaluate changes in the cerebral blood flow (CBF) before and after Waon therapy in CFS patients and to investigate the correlation between such changes and the therapeutic efficacy of Waon therapy.

Methods Eleven patients (2 men and 9 women, mean age 27 years old) diagnosed with CFS participated in the study. The disease duration was 8-129 months, and the performance status was 5-8 (on a scale of 0-9). All patients underwent CBF scintigraphy using brain single-photon emission computed tomography (SPECT) with technetium-99m ethyl cysteinate dimer (99mTc-ECD) before and after Waon therapy. CBF changes after Waon therapy were evaluated using a statistical analysis of imaging data, which was performed with a statistical parametric mapping software program (SPM5).

Results Waon therapy reduced symptoms in all 11 patients. We also observed an increase in the CBF within the prefrontal region, orbitofrontal region, and right temporal lobe. These results indicated that an improvement in clinical symptoms was linked to an increase in the CBF.

Conclusion The results indicated abnormalities of the cerebral function in the prefrontal region, orbitofrontal region, and right temporal lobe in CFS patients and that Waon therapy improved the cerebral function and symptoms in CFS patients by increasing the regional CBF. To our knowledge, this is the first report to clarify the CBF changes in CFS patients before and after Waon therapy.

Source: Munemoto T, Soejima Y, Masuda A, Nakabeppu Y, Tei C. Increase in the Regional Cerebral Blood Flow following Waon Therapy in Patients with Chronic Fatigue Syndrome: A Pilot Study. Intern Med. 2017;56(14):1817-1824. doi: 10.2169/internalmedicine.56.8001. Epub 2017 Jul 15. https://www.jstage.jst.go.jp/article/internalmedicine/56/14/56_56.8001/_article (Full article)

Access to Medical Care for Individuals with Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: A Call for Centers of Excellence

Abstract:

The current study sought to better understand the experience of individuals with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) in accessing care for their debilitating illness. Of 898 participants, less than half had ever seen an ME or CFS specialist, though 99% of participants were interested in specialist care. Participants cited geographic and financial barriers as most frequently precluding access to specialists. Furthermore, satisfaction with specialist care greatly exceeded satisfaction with non-specialist care. These findings suggested that individuals with ME and CFS represent a medically-underserved population, due to lack of available care. The CFS Advisory Committee and NIH Pathways to Prevention Working Group recommended the creation of ME and CFS Centers of Excellence to improve the healthcare access of patients with ME and CFS. The current study documents the need for these centers, as they would ameliorate geographic and financial barriers to quality care.

Source: Sunnquist M, Nicholson L, Jason LA, Friedman KJ. Access to Medical Care for Individuals with Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: A Call for Centers of Excellence. Mod Clin Med Res. 2017 Apr;1(1):28-35. doi: 10.22606/mcmr.2017.11005. Epub 2017 Apr 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510655/ (Full article)

Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating disorder linked to diverse intracellular infections as well as physiological stress. Cytotoxic lymphocytes combat intracellular infections. Their function is attenuated by stress. Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear. Prompted by advances in the understanding of defects in lymphocyte cytotoxicity, the discovery of adaptive natural killer (NK) cell subsets associated with certain viral infections, and compelling links between stress, adrenaline, and cytotoxic lymphocyte function, we reassessed the role of cytotoxic lymphocytes in ME/CFS.

Forty-eight patients from two independent cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with respect to cytotoxic lymphocyte phenotype and function. Results were compared to values from matched healthy controls. Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule content, activation status, exocytotic capacity, target cell killing, or cytokine production. One patient expressed low levels of perforin, explained by homozygosity for the PRF1 p.A91V variant. However, overall, this variant was present in a heterozygous state at the expected population frequency among ME/CFS patients.

No single patient displayed any pathological patterns of cellular responses. Increased expansions of adaptive NK cells or deviant cytotoxic lymphocyte adrenaline-mediated inhibition were not observed. In addition, supervised dimensionality reduction analyses of the full, multidimensional datasets did not reveal any reproducible patient/control discriminators.

In summary, employing sensitive assays and analyses for quantification of cytotoxic lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were not found among ME/CFS patients. These assessments of cytotoxic lymphocytes therefore do not provide useful biomarkers for the diagnosis of ME/CFS.

Source: Theorell J, Bileviciute-Ljungar I, Tesi B, Schlums H, Johnsgaard MS, Asadi-Azarbaijani B, Bolle Strand E, Bryceson YT. Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Front Immunol. 2017 Jun 26;8:723. doi: 10.3389/fimmu.2017.00723. eCollection 2017. http://journal.frontiersin.org/article/10.3389/fimmu.2017.00723/full (Full article)

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)

Impact of Rantes from jawbone on Chronic Fatigue Syndrome

Abstract:

This study elucidates the question of whether chronic inflammation in the jawbone contributes to the development of Chronic Fatigue Syndrome (CFS). Fatty degenerative osteonecrosis in jawbone (FDOJ) may contribute to CFS by induction of inflammatory mediators.

We examined seven cytokines by multiplex analysis in jawbone samples from two groups of patients. In order to clarify neurological interrelations, specimens from 21 CFS patients were analyzed from areas of previous surgery in the retromolar wisdom tooth area. Each of the retromolar jawbone samples showed clinically fatty degenerated and osteonecrotic medullary changes. As control, healthy jawbone specimens from 19 healthy patients were analyzed. All fatty necrotic and osteolytic jawbone (FDOJ) samples showed high expression of RANTES and fibroblast growth factor (FGF)-2. FDOJ cohorts showed a 30-fold mean overexpression of RANTES and a 20-fold overexpressed level of FGF-2 when compared to healthy controls. As RANTES is discussed in the literature as a possible contributor to inflammatory diseases, we hypothesize that FDOJ in areas of improper and incomplete wound healing in the jawbone may hyperactivate signaling pathways.

Constituting a hidden source of silent inflammation FDOJ may represent a hitherto unknown cause for the development of CFS.

Source: Lechner J, Huesker K, Von Baehr V. Impact of Rantes from jawbone on Chronic Fatigue Syndrome. J Biol Regul Homeost Agents. 2017 Apr-Jun;31(2):321-327. https://www.ncbi.nlm.nih.gov/pubmed/28685531

NLRP3 inflammasome activation mediates fatigue-like behaviours in mice via neuroinflammation

Abstract:

Numerous experimental and clinical studies have suggested that the interaction between the immune system and the brain plays an important role in the pathophysiology of chronic fatigue syndrome (CFS). The NLRP3 inflammasome is an important part of the innate immune system. This complex regulates proinflammatory cytokine interleukin-1β (IL-1β) maturation, which triggers different kinds of immune-inflammatory reactions.

We employed repeated forced swims to establish a model of CFS in mice. NLRP3 knockout (KO) mice were also used to explore NLRP3 inflammasome activation in the mechanisms of CFS, using the same treatment. After completing repeated swim tests, the mice displayed fatigue-like behaviours, including locomotor activity and reduced fall-off time on the rota-rod test, which was accompanied by significantly higher mature IL-1β level in the prefrontal cortex (PFC) and malondialdehyde (MDA) level in serum. We also found increased NLRP3 protein expression, NLRP3 inflammasome formation and increased mature IL-1β production in the PFC, relative to untreated mice. The NLRP3 KO mice displayed significantly moderated fatigue behaviours along with decreased PFC and serum IL-1β levels under the same treatment.

These findings demonstrated the involvement of NLRP3 inflammasome activation in the mechanism of swimming-induced fatigue. Future therapies targeting the NLRP3/IL-1β pathway may have significant potential for fatigue prevention and treatment.

Source: Zhang Z, Ma X, Xia Z, Chen J, Liu Y, Chen Y, Zhu J, Li J, Yu H, Zong Y, Lu G. NLRP3 inflammasome activation mediates fatigue-like behaviours in mice via neuroinflammation. Neuroscience. 2017 Jul 3. pii: S0306-4522(17)30453-0. doi: 10.1016/j.neuroscience.2017.06.048. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28684277

A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls

Abstract:

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic pain syndrome. A plausible pathogenesis of the disease is uncertain and the pursuit of measurable biomarkers for objective identification of affected individuals is a continuing endeavour in FMS research. Our objective was to perform an explorative metabolomics study (1) to elucidate the global urinary metabolite profile of patients suffering from FMS, and (2) to explore the potential of this metabolite information to augment existing medical practice in diagnosing the disease.

METHODS: We selected patients with a medical history of persistent FMS (n = 18), who described their recent state of the disease through the Fibromyalgia Impact Questionnaire (FIQR) and an in-house clinical questionnaire (IHCQ). Three control groups were used: first-generation family members of the patients (n = 11), age-related individuals without any indications of FMS or related conditions (n = 10), and healthy young (18-22 years) individuals (n = 20). All subjects were female and the biofluid under investigation was urine. Correlation analysis of the FIQR showed the FMS patients represented a well-defined disease group for this metabolomics study. Spectral analyses of urine were conducted using a 500 MHz 1H nuclear magnetic resonance (NMR) spectrometer; data processing and analyses were performed using Matlab, R, SPSS and SAS software.

RESULTS AND DISCUSSION: Unsupervised and supervised multivariate analyses distinguished all three control groups and the FMS patients, and significant increases in metabolites related to the gut microbiome (hippuric, succinic and lactic acids) were observed. We have developed an algorithm for the diagnosis of FMS consisting of three metabolites – succinic acid, taurine and creatine – that have a good level of diagnostic accuracy (Receiver Operating Characteristic (ROC) analysis – area under the curve 90%) and on the pain and fatigue symptoms for the selected FMS patient group.

CONCLUSION: Our data and comparative analyses indicated an altered metabolic profile of patients with FMS, analytically detectable within their urine. Validation studies may substantiate urinary metabolites to supplement information from medical assessment, tender-point measurements and FIQR questionnaires for an improved objective diagnosis of FMS.

Source: Malatji BG, Meyer H, Mason S, Engelke UFH, Wevers RA, van Reenen M, Reinecke CJ. A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls. BMC Neurol. 2017 May 11;17(1):88. doi: 10.1186/s12883-017-0863-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426044/ (Full article)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that affects children and adolescents as well as adults. The etiology has not been established. While many pediatricians and other health-care providers are aware of ME/CFS, they often lack essential knowledge that is necessary for diagnosis and treatment. Many young patients experience symptoms for years before receiving a diagnosis.

This primer, written by the International Writing Group for Pediatric ME/CFS, provides information necessary to understand, diagnose, and manage the symptoms of ME/CFS in children and adolescents. ME/CFS is characterized by overwhelming fatigue with a substantial loss of physical and mental stamina. Cardinal features are malaise and a worsening of symptoms following minimal physical or mental exertion. These post-exertional symptoms can persist for hours, days, or weeks and are not relieved by rest or sleep.

Other symptoms include cognitive problems, unrefreshing or disturbed sleep, generalized or localized pain, lightheadedness, and additional symptoms in multiple organ systems. While some young patients can attend school, on a full or part-time basis, many others are wheelchair dependent, housebound, or bedbound.

Prevalence estimates for pediatric ME/CFS vary from 0.1 to 0.5%. Because there is no diagnostic test for ME/CFS, diagnosis is purely clinical, based on the history and the exclusion of other fatiguing illnesses by physical examination and medical testing. Co-existing medical conditions including orthostatic intolerance (OI) are common.

Successful management is based on determining the optimum balance of rest and activity to help prevent post-exertional symptom worsening. Medications are helpful to treat pain, insomnia, OI and other symptoms. The published literature on ME/CFS and specifically that describing the diagnosis and management of pediatric ME/CFS is very limited. Where published studies are lacking, recommendations are based on the clinical observations and practices of the authors.

Source: Rowe PC, Underhill RA, Friedman KJ, Gurwitt A, Medow MS, Schwartz MS, Speight N, Stewart JM, Vallings R, Rowe KS. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer. Front Pediatr. 2017 Jun 19;5:121. doi: 10.3389/fped.2017.00121. eCollection 2017. http://journal.frontiersin.org/article/10.3389/fped.2017.00121/full

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