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The recent discovery of pathogenic antibodies targeting cell adhesion molecules of the node of Ranvier has prompted efforts to develop a new classification for a subset of antibody-mediated peripheral neuropathies. These autoimmune nodo- and paranodopathies encompass epitopes such as neurofascin 155, neurofascin 186, contactin-1, and contactin-associated protein 1, with a high likelihood of involving additional yet unidentified proteins. So far, the investigation of this subset of patients was primarily focused on adults, with only rare reports of pediatric cases. Low awareness among pediatricians and insufficient availability of appropriate diagnostic methods in many laboratories may mask a higher pediatric incidence than currently observed. Diagnosis is made by transfected cell-based assays and ELISA to characterize the specific target antigen and antibody subclass that provides insight into the pathophysiology. Clinical features often resemble those of CIDP or GBS in adults, whilst in pediatric patients, although rare, an atypical CIDP phenotype has predominantly been reported. Yet, in contrast to classical immune-mediated neuropathies, the clinical course is usually rapidly progressive, and response to classical first-line therapy often poor. Although electrophysiological signs of demyelination are observed, segmental demyelination and inflammation are not present on pathological examination. Rather, few neuropathological reports demonstrate features of axonal neuropathy without signs of true de- or remyelination. This review aims to summarize recent findings on such nodo- and paranodoneuropathies, shining light on features of these disorders in pediatric patients, a still little-explored field with only a few reports currently present. [ABSTRACT FROM AUTHOR]

Paraneoplastic neurologic syndromes (PNS) represent a rare group of immune-mediated complications associated with an underlying tumor. Ectopic protein expression in neoplastic cells or an aberrant immune regulation in the course of hematooncologic diseases or thymomas trigger an autoimmune response that may affect any part of the central and/or peripheral nervous system. Recent advances in drug therapies as well as novel animal models and neuropathologic studies have led to further insights on the immune pathomechanisms of PNS. Although the syndromes share common paths in pathogenesis, they may differ in the disease course, prognosis, and therapy targets, depending on the localization and type of antibody epitope. Neuropathologic hallmarks of PNS associated with antibodies directed against intracellular epitopes are characterized by T cell-dominated inflammation, reactive gliosis including microglial nodules, and neuronal degeneration. By contrast, the neuropathology of cell surface antibody-mediated PNS strongly depends on the targeted antigen and varies from B cell/plasma cell-dominated inflammation and well-preserved neurons together with a reduced expression of the target antigen in anti-NMDAR encephalitis to irreversible Purkinje cell loss in anti-P/Q-type VGCC antibody-associated paraneoplastic cerebellar degeneration. The understanding of different pathomechanisms in PNS is important because they strongly correspond with therapy response and prognosis, and should guide treatment decisions., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)