Paraneoplastic encephalomyelopathies: pathology and mechanisms

Acta Neuropathol. 2011 Oct;122(4):381-400. doi: 10.1007/s00401-011-0876-1. Epub 2011 Sep 22.


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.

Publication types

  • Review

MeSH terms

  • Humans
  • Paraneoplastic Syndromes, Nervous System / immunology
  • Paraneoplastic Syndromes, Nervous System / metabolism
  • Paraneoplastic Syndromes, Nervous System / pathology*
  • Paraneoplastic Syndromes, Nervous System / physiopathology