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Paraneoplastic encephalomyelopathies: pathology and mechanisms

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Abstract

The last three decades have seen major advances in the understanding of paraneoplastic and idiopathic autoimmune disorders affecting the central nervous system (CNS). Neural-specific autoantibodies and their target antigens have been discovered, immunopathology and neuroimaging patterns recognized and pathogenic mechanisms elucidated. Disorders accompanied by autoantibody markers of neural peptide-specific cytotoxic effector T cells [such as anti-neuronal nuclear antibody type 1 (ANNA-1, aka anti-Hu), Purkinje cell antibody type 1 (PCA-1, aka anti-Yo) and CRMP-5 IgG] are generally poorly responsive to immunotherapy. Disorders accompanied by neural plasma membrane-reactive autoantibodies [the effectors of synaptic disorders, which include antibodies targeting voltage-gated potassium channel (VGKC) complex proteins, NMDA and GABA-B receptors] generally respond well to early immunotherapy. Here we describe in detail the neuropathological findings and pathophysiology of paraneoplastic CNS disorders with reference to antigen-specific serology and neurological and oncological contexts.

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Acknowledgments

The authors wish to acknowledge Dr Vanda A. Lennon for critical revision of the manuscript and provision of Fig. 2.

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  1. Department of Laboratory Medicine and Pathology, Mayo Clinic, College of Medicine, Rochester, MN, 55905, USA

    Andrew McKeon & Sean J. Pittock

  2. Department of Neurology, Mayo Clinic, College of Medicine, Rochester, MN, 55905, USA

    Andrew McKeon & Sean J. Pittock

  3. 200 First Street S.W., Rochester, MN, 55905, USA

    Andrew McKeon

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McKeon, A., Pittock, S.J. Paraneoplastic encephalomyelopathies: pathology and mechanisms. Acta Neuropathol 122, 381–400 (2011). https://doi.org/10.1007/s00401-011-0876-1

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