Exploration of Neuroprotective Therapy

Table 1. Eligibility criteria for study inclusion and exclusion

Criterion	Inclusion criteria	Exclusion criteria
Population	Adults (≥ 18 years) diagnosed with ME/CFS according to Fukuda (1994), Canadian Consensus Criteria (2003), or IOM/SEID (2015)	Subjects < 18 years; animal studies; cases without a clear ME/CFS diagnosis
Study design	Original quantitative (experimental or observational), qualitative, mixed-methods, and theoretical studies proposing mechanistic hypotheses	Case series with < 5 participants; narrative or systematic reviews; editorials; letters; conference abstracts
Language	English-language full-text publications	Publications in other languages without at least an English abstract
Outcome measures	Direct assessments of orexin-A, orexin-B, or prepro-orexin; HPA axis markers (cortisol, ACTH); inflammatory cytokines; hypothalamic neuroimaging	Studies lacking direct measurements of these parameters (e.g., unrelated biomarkers)
Comorbidities	Participants with ME/CFS without a primary diagnosis of fibromyalgia or major psychiatric disorders (e.g., major depression, anxiety)	Studies in which comorbid conditions (fibromyalgia, depression, etc.) are not clearly segregated
Publication type	Original research articles with detailed methodology	Editorials; commentaries; protocols; abstracts without full text

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ACTH: adrenocorticotropic hormone; HPA: hypothalamic-pituitary-adrenal; IOM: Institute of Medicine; ME/CFS: myalgic encephalomyelitis/chronic fatigue syndrome; SEID: systemic exertion intolerance disease

Declarations

Acknowledgments

AI-Assisted Work Statement: During the preparation of this work, the author utilized DALL·E 3 (OpenAI) to generate illustrative icons featured in Figure 2. Additionally, the author employed ChatGPT-4.5 (OpenAI) to assist with grammar, stylistic refinement, and proofreading of the manuscript. All outputs generated by these tools were critically reviewed and edited by the author to ensure accuracy, coherence, and scholarly integrity. The author takes full responsibility for the content of this publication.

Author contributions

NLA: Conceptualization, Methodology, Investigation, Data curation, Formal analysis, Writing—original draft, Writing—review & editing, Validation.

Conflicts of interest

The author declares that he has no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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