Related Conditions to Nodo-paranodopathies: A Narrative Review of Central and Extraneural Associations

In recent years, nodo-paranodopathies have been recognized as a distinct group of immune-mediated neuropathies. As knowledge has expanded and clinical observation has increased, it has become evident that their involvement is not limited to the peripheral nervous system but may also extend to other organs and systems. A Medline search until December 2025 was performed focusing on studies that explored both neurological and extra-neurological manifestations associated with antibodies against neurofascins (NFs) and contactins. The literature highlights an association with central nervous system disorders – such as combined central and peripheral demyelination, multiple sclerosis, neuromyelitis optica, and developmental disorders – as well as with conditions affecting other systems, including renal disease, diabetes mellitus, malignancies, and systemic autoimmune disorders. Although the role of NFs and contactins has been clearly demonstrated in certain peripheral neuropathies, the available literature indicates that they may participate in a wide range of pathological processes that extend beyond the nervous system. Accumulating evidence supports the view that nodo-paranodopathies represent a spectrum of systemic immune-mediated disorders, exhibiting heterogeneous clinical manifestations and varying degrees of organ involvement.