Table 1

CNS syndromes associated with antineuronal antibodies

Classical paraneoplastic CNS syndromes associated with onconeural antibodiesCNS syndromes associated with neuronal surface antibodies
Main syndromes
  • PCD

  • Encephalomyelitis

  • LE

  • Brainstem encephalitis

  • LE

  • Morvan's syndrome

  • NMDAR-Ab encephalitis

  • PERM

  • Cerebellar ataxia

Age range (years) and sexMainly adults (40–70); both genders (PCD more frequent in women).NMDAR-Ab encephalitis common in children and young women
Antibodies commonly detected or recently reportedAntibodies against intracellular antigens or PNS related onconeural antibodies (Hu, Yo, Ri, Ma2, Cv2/CRMP5, amphiphysin, Sox1/2)Antibodies to VGKC complex antigens (LGI1 or CASPR2), NMDAR, AMPAR, GABABR, GlyR, VGCC-Ab, mGluR1, mGluR5*
TumoursSCLC, breast, ovary, testicular
  • Teratoma, thymoma, SCLC, breast

  • No tumour found in many cases, particularly LE associated with LGI1-Ab

Relationship between antibody and tumourAntibody usually indicates the presence of a particular tumour typeAntibody presence does not indicate if a case is paraneoplastic
ImmunotherapyNot usually effectiveGenerally effective
OutcomePoor; improvement or stabilisation related mainly to tumour treatmentVariable but generally good; possible spontaneous remission
NeuropathologyLoss of neurons, gliosis, T cell infiltrates in close apposition to neurons, some with immunophenotype of cytotoxic T cellsLimited data Variable T cells, B cells and plasma cell infiltrates but less intense than in patients with paraneoplastic disease.9a
Prevalent pathogenic mechanismAntibodies are markers for the tumour and are not likely to be pathogenic. T cell cytotoxicity is the proposed pathogenic mechanismAutoantibody mediated, probably downregulation of target antigen but may be complement mediated damage in some conditions
  • * Glutamic acid decarboxylase (GAD) antibodies are not neuronal surface antibodies as they target an intracellular antigen but they do not generally associate with tumours, and are considered to be markers of immune mediated syndromes.

  • AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; CASPR2, contactin associated protein 2; GABABR, gamma-aminobutyric acid B receptor; GlyR, glycine receptor; LE, limbic encephalitis; LGI1-Ab, leucine rich glioma inactivated 1 protein antibody; mGluR, metabotropic glutamate receptor; NMDAR-Ab, N-methyl-D-aspartate receptor antibody; PCD, paraneoplastic cerebellar degeneration; PERM, progressive encephalomyelitis with rigidity and myoclonus; PNS, paraneoplastic neurological syndromes; SCLC, small cell lung cancer; VGCC-Ab, voltage gated calcium channel antibody; VGKC, voltage gated potassium channel.