Walczak et al. (2024)
- Authors: Piotr Walczak, Shen Li, Xunming Ji, Johannes Boltze.
- Institutes: Center for Advanced Imaging Research, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, USA; Department of Neurology and Psychiatry, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China; School of Life Sciences, University of Warwick, Coventry, UK.
- Publisher: Neuroprotection
- Link: DOI
Summary
This editorial is significant for the ME/CFS community because it officially categorizes the illness alongside other major neurological and inflammatory disorders in a high-level medical journal. By framing ME/CFS and Long COVID as essential models for understanding oxidative stress, the authors help move the condition into the scientific mainstream, which can lead to increased research funding and awareness. The focus on shared “vicious circles” of inflammation provides a biological explanation for why symptoms can be so persistent and debilitating. While many of the discussed therapies are still in the experimental stage, the recognition of these specific biological drivers is a critical step toward moving away from symptom management and toward addressing the actual cause of the illness.
What was researched?
This editorial explores the complex biological pathways—or pathomechanisms—that drive various central nervous system (CNS) disorders, with a specific focus on neuroinflammation and oxidative stress. It synthesizes recent research to highlight shared biological characteristics between conditions like Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Long COVID, and Major Depressive Disorder (MDD).
Why was it researched?
CNS disorders are notoriously difficult to diagnose and treat because they involve multiple organ systems and intricate cellular interactions that are not yet fully understood. The authors argue that identifying common drivers, such as immune system dysfunction and metabolic stress, is a mandatory prerequisite for developing the next generation of targeted and personalized medical treatments.
How was it researched?
This paper is a high-level scientific editorial and literature review that introduces a specialized issue of the journal Neuroprotection. The authors analyzed and integrated findings from multiple studies, including a conceptual framework comparing ME/CFS and Long COVID, systematic reviews on the role of astrocytes in brain inflammation, and research into blood-brain barrier permeability. They specifically looked at how emerging concepts, such as mitochondrial transfer and exosome therapy, might offer new ways to treat these complex illnesses.
What has been found?
The researchers highlighted that ME/CFS and Long COVID share strikingly similar clinical profiles, with excessive oxidative stress acting as a central driver of the disease in both conditions. They found that neuroinflammation is not just a side effect but a major contributor to these illnesses, often involving a “vicious circle” where brain cells called astrocytes remain in a permanent inflammatory state. Additionally, the editorial notes that immunomodulatory approaches, such as low-dose IL-2 💊 and certain antidepressant medications 💊, are showing potential in clinical research for their ability to regulate the immune-inflammatory balance in patients with related neurological symptoms.
Discussion
The authors emphasize that while the link between oxidative stress and neuroinflammation is a strong lead, research into the specific pathomechanisms of ME/CFS is still in its infancy. They note that many current hypotheses require further confirmation and that the diversity of symptoms among patients makes it challenging to create a “one-size-fits-all” diagnostic test. They also highlight the potential of using ME/CFS and Long COVID as models to understand more traditional neurodegenerative diseases.
Conclusion & Future Work
The editorial concludes that a deeper understanding of cellular communication and metabolic stress will be the foundation for future diagnostic breakthroughs. The authors suggest that subsequent research should focus on the role of exosomes and the integrity of the blood-brain barrier to identify more precise therapeutic targets. They advocate for a shift toward “precision medicine,” where treatments are tailored to the specific inflammatory markers found in an individual patient.