Exploring the central mechanism of mind-regulation electroacupuncture in treatment of chronic fatigue syndrome with anxiety and depression comorbidity based on functional magnetic resonance imaging

Abstract:

in English, Chinese

Objectives: To observe the changes in the regional homogeneity (ReHo) and functional brain network in treatment of chronic fatigue syndrome (CFS) with anxiety and depression comorbidity with the mind-regulation electroacupuncture (EA), using resting-state functional magnetic resonance imaging (rs-fMRI).

Methods: Thirty CFS patients with anxiety and depression comorbidity were enrolled from medical staffs as the observation group. The other 30 healthy subjects were recruited from medical university students as the control group, matching gender, age and education years with the observation group. No any acupuncture intervention was delivered in the control group, and EA for regulating the mind was operated in the observation group. Main points were the emotional area of Sun‘s scalp acupuncture, the regions 1 and 8 of Sun‘s abdominal acupuncture. Supplementary acupoints included Baihui (GV 20), Guanyuan (CV 4) and bilateral.

Results: The scores of the five domains in MFI-20 (i.e. general fatigue, physical fatigue, mental fatigue, reduced motivation and reduced activity), the total score of MFI-20, and the scores of SDS, SAS and PSQI in the observation group before treatment were higher than those of the control group (P<0.05). Except the score of reduced motivation in MFI-20, the scores of the other domains and the total score of MFI-20, as well as the scores of SDS, SAS and PSQI after treatment were lower than those before treatment in the observation group (P<0.05).

Compared with the values before treatment, ReHo value was increased in the the right precuneus and decreased in the left inferior temporal gyrus and the left angular gyrus of the brain in the observation group after treatment. In the observation group, when compared with the control group, ReHo values were increased in the left inferior cerebral lobe, the interhemispheric region, the right occipital lobe and the thalamus; and it was reduced in the left middle temporal gyrus, the right posterior central gyrus, the right middle temporal gyrus, the right orbital middle frontal gyrus, the paracentral lobule and the right fusiform gyrus before treatment.

In the observation group, the functional connectivity was decreased between the right thalamus and the left posterior central gyrus, the right hippocampus and the right fusiform gyrus before treatment, respectively; it was re-constructed after treatment between the right thalamus and the left posterior central gyrus, and the right fusiform gyrus.

Compared with the control group, the functional connectivity between the right thalamus and the left posterior central gyrus, the right hippocampus, and the right fusiform gyrus was reduced before treatment; while after treatment, the functional connectivity was reduced between the right thalamus and the hippocampus in the observation group. With Spearman correlation analysis between the differential brain regions and the scores of MFI-20, SAS, SDS and PSQI, it was found that the left middle temporal gyrus, the paracentral lobule, the right precuneus, and the left inferior temporal gyrus had a partial positive correlation with the above clinical scales; and the interhemispheric region, the thalamus, the right fusiform gyrus, and the right middle temporal gyrus showed a partial negative correlation.

Conclusions: There is the decrease of ReHo in many brain regions and the numbers of the local brain functional network connectivity in CFS patients with anxiety and depression comorbidity. The mind-regulation electroacupuncture therapy may relieve the clinical symptoms of the patients through adjusting the abnormal brain regions and activating emotion-related brain regions.

Source: Zeng X, Feng C, Zhang M, Cheng W, Sun Z, Yang T. Exploring the central mechanism of mind-regulation electroacupuncture in treatment of chronic fatigue syndrome with anxiety and depression comorbidity based on functional magnetic resonance imaging. Zhongguo Zhen Jiu. 2023 Jan 12;44(1):3-11. English, Chinese. doi: 10.13703/j.0255-2930.20230603-k0003. PMID: 38191152. https://pubmed.ncbi.nlm.nih.gov/38191152/

Acupoint massage at Shenque (CV 8) for chronic fatigue syndrome: a randomized controlled trial

Abstract:

in English, Chinese

Objectives: To observe the clinical efficacy of acupoint massage at Shenque (CV 8) for chronic fatigue syndrome (CFS).

Methods: A total of 71 patients with CFS were randomized into an observation group (36 cases, 2 cases were eliminated, 3 cases dropped out) and a control group (35 cases). Using a specially made massage instrument, acupoint massage was adopted at the the five points of Shenque (CV 8), i.e. the center and the upper, lower, left, and right parts of the inner wall. The manipulation was given 10 min a time, once every 2 days, 3 times a week for 4 weeks continuously. No intervention was delivered in the control group. Before and after treatment, the scores of fatigue scale-14 (FS-14) and Pittsburgh sleep quality index (PSQI) were observed, and the clinical efficacy was evaluated in the both groups.

Results: After treatment, the physical fatigue and mental fatigue scores, as well as the total score of FS-14 were decreased compared with those before treatment in the observation group (P<0.001); the above scores in the observation group were lower than those in the control group (P<0.001). After treatment, excepted for the sleep time and hypnotic scores, the remaining item scores and the total score of PSQI were decreased compared with those before treatment in the observation group (P<0.05); the each item score and the total score of PSQI were lower than those in the control group (P<0.05). The total effective rate in the observation group was superior to that in the control group (P<0.01).

Conclusions: Acupoint massage at Shenque (CV 8) can effectively improve the fatigue state and sleep quality in patients with chronic fatigue syndrome.

Source: Li Z, Ji R, Yan C, Chen Y, Cao Z, Wang J. Acupoint massage at Shenque (CV 8) for chronic fatigue syndrome: a randomized controlled trial. Zhongguo Zhen Jiu. 2023 Jan 12;44(1):67-70. English, Chinese. doi: 10.13703/j.0255-2930.20230307-0002. PMID: 38191162. https://pubmed.ncbi.nlm.nih.gov/38191162/

Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, and multi-faceted illness. Heterogenous onset and clinical presentation with additional comorbidities make it difficult to diagnose, characterize, and successfully treat. Current treatment guidelines focus on symptom management, but with no clear target or causative mechanism, remission rates are low, and fewer than 5% of patients return to their pre-morbid activity levels. Therefore, there is an urgent need to undertake robust clinical trials to identify effective treatments.
This review synthesizes insights from clinical trials exploring pharmacological interventions and dietary supplements targeting immunological, metabolic, gastrointestinal, neurological, and neuroendocrine dysfunction in ME/CFS patients which require further exploration. Additionally, the trialling of alternative interventions in ME/CFS based on reported efficacy in the treatment of illnesses with overlapping symptomology is also discussed. Finally, we provide important considerations and make recommendations, focusing on outcome measures, to ensure the execution of future high-quality clinical trials to establish clinical efficacy of evidence-based interventions that are needed for adoption in clinical practice.
Source: Seton KA, Espejo-Oltra JA, Giménez-Orenga K, Haagmans R, Ramadan DJ, Mehlsen J on behalf of the European ME Research Group for Early Career Researchers (Young EMERG). Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives. Journal of Clinical Medicine. 2024; 13(2):325. https://doi.org/10.3390/jcm13020325 https://www.mdpi.com/2077-0383/13/2/325 (Full text)

Nutrition and Chronobiology as Key Components of Multidisciplinary Therapeutic Interventions for Fibromyalgia and Associated Chronic Fatigue Syndrome: A Narrative and Critical Review

Abstract:

Fibromyalgia (FM) is often accompanied by chronic fatigue syndrome (CFS). It is a poorly understood disorder that mainly affects women and leads to chronic pain, fatigue, and insomnia, among other symptoms, which decrease quality of life. Due to the inefficiency of current pharmacological treatments, increasing interest is being directed towards non-pharmacological multicomponent therapies. However, nutrition and chronobiology are often overlooked when developing multicomponent therapies.

This narrative and critical review explore the relevance of nutritional and chronobiological strategies in the therapeutic management of FM and the often-associated CFS. Reviewed literature offers scientific evidence for the association of dietary habits, nutrient levels, body composition, gut microbiota imbalance, chronobiological alterations, and their interrelation with the development and severity of symptoms. This review highlights the key role of nutrition and chronobiology as relevant and indispensable components in a multidisciplinary approach to FM and CFS.

Source: Carrasco-Querol N, Cabricano-Canga L, Bueno Hernández N, Gonçalves AQ, Caballol Angelats R, Pozo Ariza M, Martín-Borràs C, Montesó-Curto P, Castro Blanco E, Dalmau Llorca MR, et al. Nutrition and Chronobiology as Key Components of Multidisciplinary Therapeutic Interventions for Fibromyalgia and Associated Chronic Fatigue Syndrome: A Narrative and Critical Review. Nutrients. 2024; 16(2):182. https://doi.org/10.3390/nu16020182 https://www.mdpi.com/2072-6643/16/2/182 (Full text)

Post-COVID cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction: national prospective study

Abstract:

The spectrum, pathophysiology, and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national longitudinal study of cognition in 351 COVID-19 patients who had required hospitalisation, compared to 2,927 normative matched controls.

Cognitive deficits were global and associated with elevated brain injury markers and reduced anterior cingulate cortex volume one year after admission. The severity of the initial infective insult, post-acute psychiatric symptoms, and a history of encephalopathy were associated with greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Treatment with corticosteroids during the acute phase appeared protective against cognitive deficits. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 is immune-mediated, and should guide the development of therapeutic strategies.

Source: Benedict Michael, Greta Wood, Brendan Sargent et al. Post-COVID cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction: national prospective study, 05 January 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3818580/v1] https://www.researchsquare.com/article/rs-3818580/v1 (Full text)

Central 5-HTergic hyperactivity induces myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like pathophysiology

Abstract:

Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a significant medical challenge, with no indisputable pathophysiological mechanism identified to date.

Methods: Based on clinical clues, we hypothesized that 5-hydroxytryptamine (5-HT) hyperactivation is implicated in the pathogenic causes of ME/CFS and the associated symptoms. We experimentally evaluated this hypothesis in a series of mouse models.

Results: High-dose selective serotonin reuptake inhibitor (SSRI) treatment induced intra- and extracellular serotonin spillover in the dorsal raphe nuclei of mice. This condition resulted in severe fatigue (rota-rod, fatigue rotating wheel and home-cage activity tests) and ME/CFS-associated symptoms (nest building, plantar and open field test), along with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis response to exercise challenge. These ME/CFS-like features induced by excess serotonin were additionally verified using both a 5-HT synthesis inhibitor and viral vector for Htr1a (5-HT1A receptor) gene knockdown.

Conclusions: Our findings support the involvement of 5-HTergic hyperactivity in the pathophysiology of ME/CFS. This ME/CFS-mimicking animal model would be useful for understanding ME/CFS biology and its therapeutic approaches.

Source: Lee JS, Kang JY, Park SY, Hwang SJ, Bae SJ, Son CG. Central 5-HTergic hyperactivity induces myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like pathophysiology. J Transl Med. 2024 Jan 8;22(1):34. doi: 10.1186/s12967-023-04808-x. PMID: 38191373. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04808-x (Full text)

Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study

Abstract:

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities.

During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.

Source: Ozonoff, A., Jayavelu, N.D., Liu, S. et al. Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study. Nat Commun 15, 216 (2024). https://doi.org/10.1038/s41467-023-44090-5 https://www.nature.com/articles/s41467-023-44090-5 (Full text)

Gut Microbiome Composition and Dynamics in Hospitalized COVID-19 Patients and Patients with Post-Acute COVID-19 Syndrome

Abstract:

The gut microbiome plays a pivotal role in the modulation of host responses during viral infections, and recent studies have underscored its significance in the context of coronavirus disease 2019 (COVID-19). We aimed to investigate the dynamics and compositional changes in the gut microbiome of COVID-19 patients, addressing both the acute phase and the recovery process, with a particular focus on the emergence of post-COVID-19 conditions.
Involving 146 COVID-19 patients and 110 healthy controls, this study employed a shotgun metagenomics approach for cross-sectional and longitudinal analyses with one- and three-month follow-ups. We observed a decline in taxonomic diversity among hospitalized COVID-19 patients compared to healthy controls, while a subsequent increase in alpha diversity was shown during the recovery process.
A notable contribution of Enterococcus faecium was identified in the acute phase of the infection, accompanied by an increasing abundance of butyrate-producing bacteria (e.g., Roseburia, Lachnospiraceae_unclassified) during the recovery period. We highlighted a protective role of the Prevotella genus in the long-term recovery process and suggested a potential significance of population-specificity in the early gut microbiome markers of post-acute COVID-19 syndrome.
Our study represents distinctive gut microbiome signatures in COVID-19, with potential diagnostic and prognostic implications, pinpointing potential modulators of the disease progression.
Source: Brīvība M, Silamiķele L, Birzniece L, Ansone L, Megnis K, Silamiķelis I, Pelcmane L, Borisova D, Rozenberga M, Jagare L, et al. Gut Microbiome Composition and Dynamics in Hospitalized COVID-19 Patients and Patients with Post-Acute COVID-19 Syndrome. International Journal of Molecular Sciences. 2024; 25(1):567. https://doi.org/10.3390/ijms25010567 https://www.mdpi.com/1422-0067/25/1/567 (Full text)

Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden

Abstract:

Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction.

Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever.

In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.

Key points:

  • Cardiovascular autonomic dysfunction (CVAD), in particular postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia, are among the most frequent and distinct phenotypes of post-COVID-19 syndrome; one-third of highly symptomatic patients can be affected.
  • CVAD arises from a malfunction of the autonomic control of the circulation, and can involve failure or inadequate or excessive activation of the sympathetic and parasympathetic components of the autonomic nervous system.
  • As well as global circulatory disturbances, CVAD in post-COVID-19 syndrome can manifest as microvascular and endothelial dysfunction, with local symptoms such as headache, brain fog, chest pain, dyspnoea and peripheral circulatory symptoms, including skin discolouration, oedema, Raynaud-like phenomena, and heat and cold intolerance.
  • A structured diagnostic work-up based on a detailed patient history, cardiovascular autonomic testing, long-term electrocardiogram and blood-pressure monitoring, and ancillary cardiac and peripheral vascular tests will lead to an appropriate diagnosis.
  • Management of CVAD in post-COVID-19 syndrome should involve a correct diagnosis, patient education, and both non-pharmacological and pharmacological methods; a tailored exercise training programme, blood volume expansion and compression garments are especially effective.
  • Pharmacological approaches target heart rate control, blood volume expansion, promotion of vasoconstriction and venoconstriction, and reduction of hyperadrenergic drive.

Source: Fedorowski, A., Fanciulli, A., Raj, S.R. et al. Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden. Nat Rev Cardiol (2024). https://doi.org/10.1038/s41569-023-00962-3 https://www.nature.com/articles/s41569-023-00962-3

New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series

Abstract:

Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, is characterized by persistent symptoms after acute SARS-CoV-2 infection that can vary from patient to patient. Here, we present a case series of four patients with a history of SARS-CoV-2 infection referred to the Post-Acute COVID-19 Syndrome (PACS) Clinic at Stanford University for evaluation of persistent symptoms, who also experienced new-onset alcohol sensitivity.

Alcohol reactions and sensitivity are not well characterized in the literature as it relates to post-viral illness. While there have been some anecdotal reports of new alcohol sensitivity in PASC patients in the media, there is a paucity of published data in the medical literature about this topic. During their medical consultation, the patients self-reported new changes in their symptoms or behaviors following the use of alcohol. A new onset of alcohol sensitivities should be assessed along with other post-COVID-19 symptoms and may provide novel avenues to explore the pathobiology of illness and potential interventions.

Source: Eastin E F, Tiwari A, Quach T C, et al. (December 29, 2023) New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series. Cureus 15(12): e51286. doi:10.7759/cureus.51286 https://www.cureus.com/articles/152512-new-alcohol-sensitivity-in-patients-with-post-acute-sequelae-of-sars-cov-2-pasc-a-case-series#!/ (Full text)