Tag: case study

Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID share clinical features including persistent fatigue, post-exertional malaise (PEM), and gastrointestinal (GI) dysfunction. Growing evidence implicates brain-gut axis dysregulation, characterized by dysbiosis, neuroinflammation within the central nervous system (CNS), increased intestinal permeability, and microbial translocation in their pathophysiology. However, therapeutic strategies targeting these pathways remain poorly defined.

Methods: We report a case of post-COVID ME/CFS successfully treated with electroacupuncture (EA)-based deep peroneal nerve stimulation which was employed to potentiate the vagal reflex. Fatigue trajectories were assessed using the Multidimensional Fatigue Inventory over 12 weeks. Based on the case, a systematic review of randomized controlled trials (RCTs) evaluating brain-gut axis-modulating interventions in ME/CFS or Long COVID was conducted.

Results: The patient exhibited a significant reduction in total fatigue, with early improvements in motivation and mental fatigue, and delayed improvement in physical fatigue following transient systemic symptom flares. Across included RCTs (n = 8, 790 participants), four investigated gut microbiome-modulating therapies and four employed nerve stimulation. Synbiotic and herbal interventions demonstrated benefits for fatigue or PEM, accompanied by alterations in specific bacterial populations or CNS metabolisms. Regarding nerve stimulation, transcranial direct current stimulation (tDCS) combined with exercise program improved fatigue, whereas standalone tDCS, auricular or peripheral TENS showed limited efficacy.

Conclusion: Brain-gut axis-based interventions may alleviate fatigue in ME/CFS and Long COVID by potentially modulating neuroinflammation, restoring microbiome balance, and improving epithelial barrier function. EA-based vagal stimulation represents a feasible option for patients with severe or treatment-resistant symptoms. Larger mechanistic studies and rigorously designed RCTs are needed to establish therapeutic targets and optimize intervention strategies.

Source: Kim DY, Youn J, Kang N, Cho SI, Ha IH. Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review. J Transl Med. 2026 Feb 10. doi: 10.1186/s12967-026-07807-w. Epub ahead of print. PMID: 41668172. https://link.springer.com/article/10.1186/s12967-026-07807-w (Full text available as PDF file)

A Case of Psoriasis Concurrently Complicated by Sacroiliitis and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a systemic chronic disorder characterized by persistent and unexplained severe fatigue. Recent population-based studies have revealed that patients with chronic inflammatory skin dermatoses, including psoriasis, are more likely to develop ME/CFS.

Here, we report a case of psoriasis, whose exacerbation occurred concurrently with the development of sacroiliitis and the onset of ME/CFS. The pathogenesis of ME/CFS has not yet been fully elucidated, while inflammatory cytokines are involved in dysregulated interactions among the nervous, immune, and endocrine systems in the disease.

We discussed the shared immunological abnormalities of psoriasis and ME/CFS based on previous literature. Our case contributes to the understanding of the association between psoriasis and ME/CFS.

Source: Iijima M, Miyagaki T, Nakajima K, Kadono T, Watabe H. A Case of Psoriasis Concurrently Complicated by Sacroiliitis and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Cureus. 2025 Sep 16;17(9):e92435. doi: 10.7759/cureus.92435. PMID: 41111852; PMCID: PMC12529862. https://pmc.ncbi.nlm.nih.gov/articles/PMC12529862/ (Full text)

Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome in patients with bipolar affective disorder: A case report

Abstract:

Background: The COVID-19 pandemic has led to an increase in post-acute sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), potentially mediated by dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. Corticosteroids are occasionally administered to ameliorate fatigue symptoms in ME/CFS; however, their psychiatric adverse effects, particularly in individuals with preexisting mood disorders, necessitate careful consideration.

Case presentation: We report the case of a 32-year-old woman with bipolar disorder who developed ME/CFS following COVID-19 infection. Initial corticosteroid therapy with betamethasone and prednisolone, agents with potent glucocorticoid receptor (GR) activity, resulted in a manic episode with psychotic features, necessitating psychiatric hospitalization. Although mood stabilization was achieved with olanzapine and valproate, corticosteroid withdrawal subsequently led to metabolic alkalosis and hypoxemia, secondary to hypothalamic hypoadrenalism. Following a comprehensive endocrinological assessment, physiological replacement therapy with hydrocortisone, characterized by relatively higher mineralocorticoid receptor (MR) activity and lower GR potency, was initiated, resulting in the resolution of physical symptoms without destabilization of psychiatric status.

Conclusion: The clinical course suggests that GR-dominant corticosteroids may exacerbate psychiatric instability in patients with mood disorders. Simultaneously, MR-favoring agents, such as hydrocortisone, may offer a safer therapeutic alternative for managing HPA axis dysfunction. This case underscores the critical role of receptor selectivity in corticosteroid therapy, particularly in patients with comorbid psychiatric conditions, and highlights the necessity for individualized treatment strategies that integrate both endocrine and neuropsychiatric considerations.

Source: Nakajima K, Ayani N, Matsuoka T, Kasahara K, Nakajima Y, Ikawa H, Kitaoka R, Akimoto T, Narumoto J. Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome in patients with bipolar affective disorder: A case report. PCN Rep. 2025 Oct 12;4(4):e70222. doi: 10.1002/pcn5.70222. PMID: 41089430; PMCID: PMC12515714.

Improvement in Upper Limb and Systemic Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptoms After Surgical Treatment of Neurogenic Thoracic Outlet Syndrome

Abstract:

Thoracic outlet syndrome (TOS) is characterized by compression of nerves or blood vessels as they pass through the scalene triangle and the costoclavicular space, and under the pectoralis minor. Common symptoms include arm fatigue and heaviness, paresthesias, and neck and upper back pain, provoked by arm extension or elevation.

We have recently reported that some myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients report symptoms suggestive of TOS, specifically with respect to overhead activity, but there is uncertainty whether this overlap in symptoms is more related to ME/CFS itself or a direct contribution by TOS. This case report describes an ME/CFS patient diagnosed with TOS, who experienced major decreases in many expected and unexpected symptoms after bilateral TOS surgery.

A 19-year-old female patient with ME/CFS and the hypermobile Ehlers-Danlos syndrome (hEDS) developed progressive symptoms of numbness and tingling in the upper limbs, which did not improve after two months of physical therapy. The patient elected to undergo the rib resection with neurolysis and scalenectomy surgery on her left side. Due to the success in the reduction of symptoms, she elected to undergo the same procedure on the right side three months later.

By eight weeks after the second surgery, the patient had experienced an expected complete resolution of upper limb numbness and tingling. She also reported a complete resolution of migraines, occipital neuralgia, vertigo, and visual disturbances, along with a marked improvement in cognitive fogginess and lightheadedness.

This case report highlights the potential for marked improvements in clinical function after recognition and surgical treatment of TOS in a patient with comorbid hEDS and ME/CFS. In addition to expected improvement in upper limb symptoms and the resolution of occipital headaches, our patient noted improvement in systemic symptoms of lightheadedness, cognitive dysfunction, and visual disturbances.

This experience suggests that those with hEDS and ME/CFS should be more carefully screened for brachial plexus dysfunction. Conversely, ascertainment of systemic symptoms may enhance the diagnosis of TOS and the items assessed in surgical treatment outcome studies.

Source: Christoforou ME, Lum YW, Sroge SC, Azola AM, Rowe PC. Improvement in Upper Limb and Systemic Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptoms After Surgical Treatment of Neurogenic Thoracic Outlet Syndrome. Cureus. 2025 Aug 19;17(8):e90494. doi: 10.7759/cureus.90494. PMID: 40978926; PMCID: PMC12445393. https://pmc.ncbi.nlm.nih.gov/articles/PMC12445393/ (Full text)

HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab

Abstract:

This article summarizes the case of 30-year-old male diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and its longitudinal follow-up, which provided a secondary diagnosis of Multiple Sclerosis (MS) eight years later. The most impactful result was his response to rituximab treatment after the systematic failure of prior treatments.

Although the expression of endogenous retroviral proteins has been associated with autoimmunity, the patient did not show increased expression of the toxic protein HERV (human endogenous retrovirus)-W ENV, a target of the ongoing clinical trials with temelimab in MS and long COVID-19 cases. However, genome-wide HERV transcriptome analysis by high density microarrays clearly revealed a distinct profile in the patient’s blood supportive of an altered immune system.

Limitations of the study include sub-optimal frequency of magnetic resonance imaging to monitor lesion progression, and similarly for reassessment of HERV profiles after rituximab. Overall, the coincidence of HERV alterations and the impactful response to rituximab presents the possibility of additional, more specific, therapeutic targets encoded by other HERV elements yet to be discovered.

Source: Martín-Martínez E, Gil-Perotin S, Giménez-Orenga K, Barea-Moya L, Oltra E. HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab. Int J Mol Sci. 2025 May 20;26(10):4885. doi: 10.3390/ijms26104885. PMID: 40430026; PMCID: PMC12111851. https://pmc.ncbi.nlm.nih.gov/articles/PMC12111851/ (Full text)

Case Report: The intersection of psychiatry and medicine: diagnostic and ethical insights from case studies

Abstract:

The intersection of psychiatry and medicine presents unique diagnostic and ethical challenges, particularly for conditions involving significant brain-body interactions, such as psychosomatic, somatopsychic, and complex systemic disorders. This article explores the historical and contemporary issues in diagnosing such conditions, emphasizing the fragmentation of medical and psychiatric knowledge, biases in clinical guidelines, and the mismanagement of complex illnesses.

Diagnostic errors often arise from insufficient integration between general medicine and psychiatry, compounded by the reliance on population-based guidelines that neglect individual patient needs. Misclassification of conditions like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme disease, and fibromyalgia as psychosomatic or psychogenic has led to stigmatization and delayed care. While these conditions are referenced as emblematic examples of misclassified and poorly understood disorders, the five clinical cases discussed in this article do not directly illustrate these diseases. Instead, they exemplify shared diagnostic and ethical dilemmas at the medicine–psychiatry interface, including uncertainty, fragmentation, and the risk of epistemic injustice.

The article critically examines terms like medically unexplained symptoms and functional disorders, highlighting their limitations and potential for misuse. Case examples underscore the consequences of diagnostic inaccuracies and the urgent need for improved approaches. Ethical considerations are also explored, emphasizing respecting patient experiences, promoting individualized care, and acknowledging the inherent uncertainties in medical diagnosis.

Advances in technologies such as brain imaging and molecular diagnostics offer hope for bridging the gap between psychiatry and medicine, enabling more accurate assessments and better patient outcomes. The article concludes by advocating comprehensive training at the medicine-psychiatry interface and a patient-centered approach that integrates clinical observation, research insights, and a nuanced understanding of mind-body dynamics.

Source: Monaco F, Vignapiano A, D’Angelo M, Raffone F, Di Stefano V, Boccia A, Longobardi A, Gruttola BD, Fornaro M, Corrivetti G, Martino I, Steardo L, Steardo L Jr. Case Report: The intersection of psychiatry and medicine: diagnostic and ethical insights from case studies. Front Psychiatry. 2025 Apr 22;16:1576179. doi: 10.3389/fpsyt.2025.1576179. PMID: 40330647; PMCID: PMC12053010. https://pmc.ncbi.nlm.nih.gov/articles/PMC12053010/ (Full text)

Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological adverse effect after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations. However, clinicians do not recognize the condition well, and no case report has shown a full recovery.

Case presentation: We present a 65-year-old Japanese female who experienced severe fatigue, postexertional malaise, orthostatic intolerance, and various symptoms after her third SARS-CoV-2 vaccination. Following thorough examinations and excluding other potential diagnoses, she met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The symptoms persisted for 30 months and improved ultimately with comprehensive treatment and a self-management strategy, including pacing management, pharmacological treatments, and psychiatric interventions to support those struggling with the despair over the devastating symptoms.

Conclusion: This case report describes ME/CFS following the SARS-CoV-2 vaccination and its full recovery. It illustrates the importance of considering the differential diagnosis of psychiatric disorders and addressing the condition through psychiatric interventions. Our findings provide new insights into treating ME/CFS and the vaccination-related adverse effects.

Source: Kurotori I, Sasao W, Abe M. Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report. PCN Rep. 2025 Apr 27;4(2):e70111. doi: 10.1002/pcn5.70111. PMID: 40291166; PMCID: PMC12034265. https://pmc.ncbi.nlm.nih.gov/articles/PMC12034265/ (Full text)

Clinical Remission After Therapeutic Apheresis in a Patient Suffering from Long Term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case Report

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multifactorial illness characterized by profound fatigue persisting for more than six months, post-exertional malaise, cognitive impairments, and a range of systemic symptoms. Until now, no accepted causal treatment regimens have been available; therapeutic options include different approaches, such as alleviation of symptoms and promotion of energy conservation.

In this study, we report the case of a 49-year-old female presented to our center suffering from ME/CFS for more than 15 years, characterised by a strong energy loss and neurological and systemic symptoms; previous therapies remained unsuccessful. Therefore, we decided to perform double-filtration apheresis.

After comprehensive laboratory evaluation, including investigation of persistent viral infections, the patient was treated eight times with double-filtration apheresis within a period of 2 years, which resulted in a remarkable sustained clinical remission and significant improvement in her quality of life. Therefore, we conclude that double-filtration apheresis could be an effective therapeutic tool for the treatment of ME/CFS.

Source: Burgard H. Clinical Remission After Therapeutic Apheresis in a Patient Suffering from Long Term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case Report. Int Med Case Rep J. 2024 Dec 6;17:997-1002. doi: 10.2147/IMCRJ.S476044. PMID: 39660109; PMCID: PMC11629661. https://pmc.ncbi.nlm.nih.gov/articles/PMC11629661/ (Full text)

Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein–Barr Virus

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem disabling disease with unclear etiology and pathophysiology, whose typical symptoms include prolonged debilitating recovery from fatigue or postexertional malaise (PEM). Disrupted production of adenosine triphosphate (ATP), the intracellular energy that fuels cellular activity, is a cause for fatigue.

Here, we present a long-term case of ME/CFS: a 75-year-old Caucasian female patient, whose symptoms of ME/CFS were clearly triggered by an acute infection of the Epstein–Barr virus 24 years ago (mononucleosis). Before then, the patient was a healthy professional woman.

A recent DNA sequence analysis identified missense variants of mitochondrial respiratory chain enzymes, including ATP6 (ChrMT: 8981A > G; Q152R) and Cox1 (ChrMT: 6268C > T; A122V). Protein subunits ATP6 and Cox1 are encoded by mitochondrial DNA outside of the nucleus: the Cox1 gene encodes subunit 1 of complex IV (CIV: cytochrome c oxidase) and the ATP6 gene encodes subunit A of complex V (CV: ATP synthase). CIV and CV are the last two of five essential enzymes that perform the mitochondrial electron transport respiratory chain reaction to generate ATP.

Further analysis of the blood sample using transmission electron microscopy demonstrated abnormal, circulating, extracellular mitochondria. These results indicate that the patient had dysfunctional mitochondria, which may contribute directly to her major symptoms, including PEM and neurological and cognitive changes. Furthermore, the identified variants of ATP6 (ChrMT: 8981A > G; Q152R) and Cox1 (ChrMT: 6268C > T; A122V), functioning at a later stage of mitochondrial ATP production, may play a role in the abnormality of the patient’s mitochondria and the development of her ME/CFS symptoms.

Source: Gaoyan G. Tang-Siegel, David W. Maughan, Milah B. Frownfelter, Alan R. Light, “Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein–Barr Virus”, Case Reports in Genetics, vol. 2024, Article ID 6475425, 10 pages, 2024. https://doi.org/10.1155/2024/6475425 https://www.hindawi.com/journals/crig/2024/6475425/ (Full text)

Longitudinal Cytokine and Multi-Modal Health Data of an Extremely Severe ME/CFS Patient with HSD Reveals Insights into Immunopathology, and Disease Severity

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) presents significant challenges in patient care due to its intricate multisystem nature, comorbidities, and global prevalence. To address these complexities, we employed a comprehensive approach, integrating longitudinal cytokine profiling with extensive clinical, health, textual, pharmaceutical, and nutraceutical data, and performed personalized analyses using AI.

Focusing on an exceptionally severe ME/CFS patient with hypermobility spectrum disorder (HSD) and marginal symptom improvements, our study highlights the dynamic nature of symptoms, severity, triggers, and modifying factors. As part of this study, we introduced an updated platform and two applications, ME-CFSTrackerApp, and LexiTime, facilitating real-time symptom tracking and enhancing physician-patient communication.

Our longitudinal cytokine profiling underscores the significance of Th2-type cytokines and synergistic activities between mast cells and eosinophils, leading to skewing of Th1 toward Th2 immune responses in ME/CFS pathogenesis, especially in cognitive impairment and sensorial intolerance. This suggests a potentially shared underlying mechanism with major comorbidities.

Additionally, our data reveal potential roles of BCL6 and TP53 pathways in ME/CFS etiology and emphasize the importance of investigating low-dose drugs with partial agonist activity in ME/CFS treatment. Our analyses underscore the patient-centered care approach for better healthcare management.

Source: Fereshteh Jahanbani1, Justin C. Sing, Rajan D. Maynard, Shaghayegh Jahanbani, Janet Dafoe, Whitney Dafoe, Nathan Jones, Kelvin J. Wallace, Azuravesta Rastan, Hannes Rost, Holden Maecker, Michael P. Snyder, Ronald W. Davis. Longitudinal Cytokine and Multi-Modal Health Data of an Extremely Severe ME/CFS Patient with HSD Reveals Insights into Immunopathology, and Disease Severity. Front. Immunol. Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders. Volume 15 – 2024 | doi: 10.3389/fimmu.2024.1369295 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1369295/abstract