Rationale and Methods of a Surveillance System for Hematopoietic Stem Cell Transplantation in Patients With Hematological Malignancies: A Qualitative Participatory Action Research Approach in Middle-I

Neuroimmunological overlap syndromes represent a group of conditions in which autoimmune-mediated central nervous system (CNS) inflammation co-occurs with systemic connective tissue disorders (CTDs). The nervous and immune systems exhibit bidirectional interactions through the peripheral nervous system (PNS), forming neuroimmune cell units that regulate inflammation and maintain tissue homeostasis (, ). Various cytokines, inflammatory mediators, and neurotransmitters produced by nerve and immune cells create feedback loops between immune cells and central, peripheral, sympathetic, and parasympathetic nerves (). The blood–brain barrier (BBB) normally protects the CNS from circulatory inflammatory signals, but injury to the CNS disrupts this balance through interference with the sympathetic nervous system, PNS, and hypothalamic–pituitary–adrenal axis (, ). The focus on optic neuritis, myelitis, and CTDs is driven by their clinical mimicry, high morbidity when misdiagnosed, and shared immunopathology. Psychiatric comorbidities including depression, anxiety, and mood disturbances are common in RA patients, adversely affecting quality of life, treatment adherence, and biological therapy response (). Neuromyelitis optica spectrum disorder (NMOSD) exemplifies this overlap; traditionally considered a monophasic disorder with bilateral optic neuritis and transverse myelitis, it now includes relapsing cases with aquaporin-4 antibodies (AQP4-IgG) and coexisting autoimmune disorders such as SLE or Sjögren syndrome (, ). Chronic peripheral inflammation in RA is closely linked to CNS involvement including meningitis, rheumatoid nodules, and cerebral vasculitis (, ). Some MS immunotherapies may aggravate NMO, underscoring the need for early and accurate diagnosis (, ). Several existing reviews address NMOSD, MOGAD, or CTD-associated neurological disease individually, but few examine their shared pathophysiology, overlapping biomarker landscape, and divergent treatment pathways within a unified framework. The novel contribution of this review is threefold: (i) it integrates molecular and cellular pathways linking systemic autoimmunity (SLE, SS, RA) to CNS injury with disease-specific biology of NMOSD, MOGAD, and MS within a neuroimmune-continuum framework; (ii) it contrasts treatment pathways for AQP4-IgG-seropositive NMOSD supported by four approved biologics with distinct mechanisms against the under-validated treatment landscape for MOGAD and CTD-associated neuroinflammation; and (iii) it critically appraises emerging biomarkers (GFAP, NfL, single-cell transcriptomics) and precision-medicine tools, distinguishing validated utility from promising but unproven research directions.