Volumetric differences in hippocampal subfields and associations with clinical measures in ME/CFS Thapaliya, Staines, Marshall-Gradisnik, Su & Barnden (Australia) - ICC - 31 March 2022 - "Our study found left hippocampal subiculum, presubiculum, and fimbria volumes were significantly larger in ME/CFSICC patients compared with HC, but not for ME/CFSFukuda patients. Furthermore, this study demonstrated that multiple hippocampal subfield volumes are different in ME/CFSICC patients meeting the strict ICC case definition, and they exhibited strong associations with clinical measures. Therefore, the strict case definitions are essential in investigation of the pathophysiology of ME/CFS. Subiculum and parasubiculum volumes were larger in ME/CFS in contrast to reductions seen in other neurological disorders.""
Impaired TRPM3-dependent calcium influx and restoration using Naltrexone in natural killer cells of ME/CFS patients Eaton-Fitch, Du Preez, Cabanas, Muraki, Staines & Marshall-Gradisnik (Australia, France & Japan) - ICC - 16 February 2022 - "TRPM3-dependent Ca2+ influx was restored in ME/CFS patients following overnight treatment of isolated NK cells with NTX in vitro. Collectively, these findings validate that TRPM3 loss of function results in altered Ca2+ influx supporting the growing evidence that ME/CFS is a TRP ion channel disorder and that NTX provides a potential therapeutic intervention for ME/CFS ... ME/CFS patients were included if they met the CCC or ICC case definitions..."
Psychogenic Pseudosyncope: Real or Imaginary? Results from a Case-Control Study in ME/CFS Patients van Campen & Visser (The Netherlands) - ICC - 09 January 2022 - "The diagnosis of ME/CFS was made according to the ME/CFS criteria of the International Consensus Criteria (ICC)" "Furthermore, we speculate that the misperceptions that ME/CFS has a behavioral or psychiatric origin may have contributed to the long delay before the proper diagnosis was reached. ... The abnormal cerebral blood flow reduction while being upright makes it clear, that the origin of the attacks might not be behavioral or psychogenic, but have a clear somatic pathophysiologic background. This must be taken into consideration in patients with frequent syncopal spells and the extracranial Doppler measurements before and at end-tilt have the potential to improve the evaluation of recurrent syncope and presyncope, and might avoid misdiagnosis of a behavioral origin."
2021
Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP2 in ME/CFS Patients Murga, Aranburu, Gargiulo, Gomex-Esteban & Lafuente (Spain & Argentina) - ICC & Fukuda - 04 December 2021 - "There were no significant differences between genders in GIAP or fatigue for CFS/ME; however, sick women perceive cognitive effort higher than men. Deficits in sustained attention and the perception of fatigue, so effort after performing the proposed test are a sensitive and reliable indicator that allows us to substantiate a clinical suspicion and refer patients for further studies in order to confirm or rule out CFS/ME."
Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP2 in ME/CFS Patients Du Preez, Eaton-Fitch, Cabanas, Staines & Marshall-Gradisnik (Australia & France) - ICC - 12 November 2021 - "Importantly, these current data, along with previous studies reporting TRP dysfunction and altered expression patterns in the NK cells of ME/CFS patients provide evidence for potential channelopathy as the pathomechanism for ME/CFS. Prospective Ca2+ influx assays, isotyping, and patch-clamp electrophysiology provide additional avenues for further characterizing TRPM7 in the pathomechanism of this illness for possible targeted pharmacotherapeutic interventions for the treatment of ME/CFS."
Limbic Perfusion Is Reduced in Patients with ME/CFS Xia Li, Per Julin & Tie-Qiang Li (Sweden & China) - ICC - 01 November 2021 - "The differences in the rCBF [regional cerebral blood flow] between the ME/CSF patients and healthy controls were statistically assessed with voxel-wise and AAL ROI-based two-sample t-tests. Linear regression analysis was also performed on the rCBF data by using the symptom severity score as the main regressor. In comparison with the healthy controls, the patient group showed significant hypoperfusion (uncorrected voxel wise p ≤ 0.001, FWE p ≤ 0.01) in several brain regions of the limbic system, including the anterior cingulate cortex, putamen, pallidum, and anterior ventral insular area. For the ME/CFS patients, the overall symptom severity score at rest was significantly associated with a reduced rCBF in the anterior cingulate cortex. The results of this study show that brain blood flow abnormalities in the limbic system may contribute to ME/CFS pathogenesis."
Cerebral blood flow remains reduced after tilt testing in ME/CFS patients van Campen, Rowe & Visser (The Netherlands & U.S.) - ICC - October 2021 - "The finding that orthostatic stress elicits a post-stress cerebral blood flow reduction and that disease severity greatly influences the cerebral blood flow reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients. ... The diagnosis of ME/CFS was established according to both the ME and CFS criteria (Carruthers et al., 2011, Fukuda et al., 1994), taking exclusion criteria for ME/CFS and any other illness that could explain symptoms into account.."
Potential Implications of Mammalian Transient Receptor Potential Melastatin 7 in the Pathophysiology of ME/CFS: A Review Du Preez, Cabanas, Staines, & Marshall-Gradisnik (Australia & France) - ICC - While this paper uses the ME/CFS label, the patient group referenced is ME-ICC. ~ MEI - 12 October 2021 - "In this review, we present TRPM7 as a potential candidate in the pathomechanism of ME/CFS, as TRPM7 is increasingly recognized as a key mediator of physiological and pathophysiological mechanisms affecting neurological, immunological, cardiovascular, and metabolic processes. A focused examination of the biochemistry of TRPM7, the role of this protein in the aforementioned systems, and the potential of TRPM7 as a molecular mechanism in the pathophysiology of ME/CFS will be discussed in this review. TRPM7 is a compelling candidate to examine in the pathobiology of ME/CFS as TRPM7 fulfils several key roles in multiple organ systems, and there is a paucity of literature reporting on its role in ME/CFS."
Diffusion Tensor Imaging Reveals Neuronal Microstructural Changes in ME/CFS Thapaliya, Marshall-Gradisnik, Staines & Barnden (Australia) - ICC - 06 August 2021 - "In this study, we evaluated [Diffusion Tensor Imaging] DTI parameters to investigate microstructural abnormalities in ME/CFS patients. We estimated DTI parameter in 25 ME/CFS patients who met Fukuda criteria (ME/CFS-Fukuda), 18 ME/CFS patients who met International Consensus Criteria (ICC) (ME/CFS-ICC) only and 26 healthy control (HC) subjects. ... Our study demonstrated that DTI parameters are sensitive to microstructural changes in ME/CFS-ICC and could potentially act as an imaging biomarker of abnormal pathophysiology in ME/CFS. The study also shows that strict case definitions are essential in investigation of the pathophysiology of ME/CFS ... The group analysis using a voxel-based method detected differences in diffusion metrics in ascending and descending tracts in the medulla, pons and midbrain of the brainstem in ME/CFS patients, but only for those meeting ICC criteria. This demonstrated the importance of strict case definitions for ME/CFS." Note: While the ME/CFS label is used, this is applicable to ME. Bold highlight was added by MEI.
Evaluating Routine Blood Tests According to Clinical Symptoms and Diagnostic Criteria in Individuals with ME/CFS Baklund, Dammen, Moum, Kristiansen, Duarte, Castro-Marrero, Helland & Strand (Norway, Spain) - ICC & CCC - 14 July 2021 - "Case criteria applied: The CCC were used as inclusion criteria when the patients initially were diagnosed by the clinicians. In the current study DSQ was applied for diagnostic classification based on different diagnostic criteria and this revealed that all the 149 patients fulfilled the Fukuda case definition, and 93.3% (n = 139) fulfilled the CCC, and 63.1% (n = 94) patients fulfilled the ICC criteria. ... Results of several routine blood tests of ME/CFS patients differed from those healthy controls. Our findings particularly highlight that decreased creatinine and CK levels may indicate greater muscle damage and metabolic disturbances in ME/CFS patients and is worthy of future studies. This is also true of results that may indicate a possible low-grade inflammation in ME/CFS patients."
Elements of Suffering in ME/CFS: The Experience of Loss, Grief, Stigma, and Trauma in the Severely and Very Severely Affected Fennell, Dorr & George (USA) - ICC - 09 May 2021 - "This review article examines the suffering of patients with ME/CFS through the lens of the Fennell Four-Phase Model of chronic illness. Using a systems approach, this phase framework illustrates the effects of suffering on the patient and can be utilized to help the clinician, patient, family, and caregivers understand and respond to the patient’s experiences. We highlight the constructs of severity, uncertainty, ambiguity, and chronicity and their role in the suffering endured by patients with ME/CFS." Even though this report uses ME/CFS, it applies to ME. ~ MEI
Deconditioning does not explain orthostatic intolerance in ME/CFS van Campen, Rowe & Visser (Netherlands, USA) - ICC & Fukuda - 04 May 2021 - This study shows that in ME/CFS patients orthostatic intolerance is not caused by deconditioning as defined on cardiopulmonary exercise testing. An abnormal high decline in cerebral blood flow during orthostatic stress was present in all ME/CFS patients regardless of their %peak VO2 results on cardiopulmonary exercise testing.
Skewing of the B cell receptor repertoire in ME/CFS Sato, Ono, Matsutani, Nakamura, Shin, Amano, Suzuki & Yamamura (Japan) - ICC, CCC & Fukuda - 27 March 2021 - Conclusion: "... we revealed a biased usage of several IGHV genes in peripheral blood B cells from ME/CFS patients. Results of receiver operating characteristic (ROC) analysis further indicated a possibility of distinguishing patients from healthy controls, based on the skewed B cell repertoire."
Open-label study with the monoamine stabilizer (-)-OSU6162 in ME/CFS Haghighi, Forsmark, Zachrisson, Carlsson, Nilsson, Carlsson, Schuit & Gottfries (Sweden, The Netherlands) - ICC & Fukuda - 02 February 2021 - Conclusion: "(‐)‐OSU6162 is well tolerated in ME/CFS patients and shows promise as a novel treatment to mitigate fatigue and improve mood and health‐related quality of life in ME/CFS. Obviously, the present results need to be confirmed in future placebo‐controlled double‐blind trials."
2020
Deep phenotyping of myalgic encephalomyelitis/chronic fatigue syndrome in Japanese population Kitami, Fukuda, Kato, Yamaguti, Nakatomi, Yamano, Kataoka, Mizuno, Tsuboi, Kogo, Suzuki, Itoh, Morioka, Kawaji, Koseki, Kikuchi, Hayashizaki, Ohno, Kuratsune & Watanabe (Japan) - ICC & Fukuda - 16 November 2020 - Conclusion: "Our study points to a cluster of sleep-related molecular changes as a prominent feature of ME/CFS in our Japanese cohort."
The Economic Impacts of ME/CFS in an Australian Cohort Close, Marshall-Gradisnik, Byrnes, Smith, Nghiem & Staines (Australia) - 21 August 2020 - Conclusion: The economic impacts of ME/CFS in Australia are significant. Improved understanding of the illness pathology, diagnosis, and management, may reduce costs, improve patient prognosis and decrease the burden of ME/CFS in Australia.
Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) Lim & Son (Republic of Korea) - 29 July 2020 - "...ME/CFS has been named differently (e.g., postviral fatigue syndrome, neurasthenia) depending on the perspectives of the researchers; likewise, diagnostic criteria or case definitions have also been changed accordingly." Conclusions: "In this review, we found three key factors that have affected ME/CFS case definitions: etiology, pathophysiology, and exclusionary disorders. These factors have impacted the specification of the main symptoms, required conditions, and range of inclusive and exclusive symptoms/disorders in the development of case definitions."
Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in CFS/ME patients Nguyen, Johnston, Chacko, Gibson, Cepon, Smith, Staines & Marshall-Gradisnik (Australia) - June 2017 - Conclusions: "This preliminary study investigates mast cell phenotypes from PBMCs in healthy controls. We report significant increase of naïve MCs in moderate and severe CFS/ME patients compared with healthy controls. Moreover, a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cells in severe CFS/ME patients. Peripheral MCs may be present in CFS/ME pathology however, further investigation to determine their role is required."
Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with CFS Loebel, Grabowski, Heidecke, Bauer, Hanitsch, Wittke, Meisel, Reinke, Volk, Fluge, Mella & Scheibenbogen (Germany, Norway) Results: "We found significantly higher autoantibody levels against M3 and M4 AChR and β2 AdR in CFS patients compared to controls. Crossreactivity between all 5 M and β1 and β2 AdR but also between M and β receptor was seen in a substantial portion of CFS patients as shown for M4 in Fig. 1C. The highest correlation was found between M3 and M4 receptor antibodies (r = 0.87), the lowest for M1 and M4 receptor antibodies (r = 0.59)." - 19 September 2015
*Note: Some studies included patients who fit additional criteria as well as ICC.
Click HERE for additional research using the CCC and/or Citing the ICC.
Note: Some studies use various labels (ME/CFS, CFS, CFS/ME) due to the inconsistent use of these labels worldwide. This list focuses on the research subjects used showing research is applicable to myalgic encephalomyelitis.