Classical paraneoplastic CNS syndromes associated with onconeural antibodies | CNS syndromes associated with neuronal surface antibodies | |
Main syndromes |
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Age range (years) and sex | Mainly adults (40–70); both genders (PCD more frequent in women). | NMDAR-Ab encephalitis common in children and young women |
Antibodies commonly detected or recently reported | Antibodies 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* |
Tumours | SCLC, breast, ovary, testicular |
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Relationship between antibody and tumour | Antibody usually indicates the presence of a particular tumour type | Antibody presence does not indicate if a case is paraneoplastic |
Immunotherapy | Not usually effective | Generally effective |
Outcome | Poor; improvement or stabilisation related mainly to tumour treatment | Variable but generally good; possible spontaneous remission |
Neuropathology | Loss of neurons, gliosis, T cell infiltrates in close apposition to neurons, some with immunophenotype of cytotoxic T cells | Limited data Variable T cells, B cells and plasma cell infiltrates but less intense than in patients with paraneoplastic disease.9a |
Prevalent pathogenic mechanism | Antibodies are markers for the tumour and are not likely to be pathogenic. T cell cytotoxicity is the proposed pathogenic mechanism | Autoantibody 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.