Neuroimmune Mechanisms and Emerging Intervention Strategies for Post-Stroke Fatigue: A Narrative Review

Post-stroke fatigue is a prevalent sequela of stroke that substantially impairs patients' quality of life and rehabilitation progress, yet its mechanisms and management remain heterogeneous. This narrative review synthesizes current evidence on neuroimmune pathways implicated in post-stroke fatigue and appraises emerging mechanism-targeted interventions. Studies published between 2003 and 2025 were included; all were sourced from PubMed, Web of Science, or Scopus. Search terms included "post-stroke fatigue", "neuroinflammation", "pharmacological interventions", "neuromodulation", and related terms. Only full-text, English-language articles were considered; studies were selected according to their focus on post-stroke fatigue mechanisms or interventions. Convergent data implicate low-grade, cytokine-mediated inflammation; dysregulation of the monoaminergic system - particularly dopamine and serotonin; and hyperactivity of the hypothalamic-pituitary-adrenal axis. Interventions aligned with these pathways show promise, including immunomodulation with interleukin-1 receptor antagonists; neuromodulation with transcranial direct current stimulation and repetitive transcranial magnetic stimulation; pharmacotherapy with selective serotonin reuptake inhibitors or modafinil; and non-pharmacological strategies such as aerobic exercise and cognitive behavioral therapy. A neuroimmune-informed, mechanism-targeted approach may improve outcomes in post-stroke fatigue. Priorities include standardized definitions, harmonized outcome measures, and adequately powered trials to confirm effectiveness across phenotypes.