Table 1.
Demographic and clinical characteristics of the main CNS autoantibodies targeting cell-surface antigens associated with cognitive impairment/encephalopathy according to the largest series reported.
| Cell-surface target | Female sex (%) | Typical age of onset (years) | Cognitive impairment (%) | Common clinical accompaniments | Cancer risk (cancer types) |
|---|---|---|---|---|---|
| AMPAR102,103 | 65–90 | 60–70 | 100 | LE; hyponatremia | 64% (small-cell lung) |
| CASPR2104 | 10–25 | 60–70 | 40–80 | Encephalopathy; Morvan’s/Isaac’s syndrome; ataxia | 10–20% (thymoma) |
| DPPX105 | 10–40 | 50–60 | 80–100 | GI symptoms (diarrhea, episodic severe weight loss); sleep disturbances | 10% (hematologic malignancies) |
| GABAAR51 | 50 | 40–50 | 67 | Seizures/status epilepticus; movement disorders | 40% (thymoma) |
| GABABR106,107,108 | 40–65 | 60–70 | 80–100 | LE; status epilepticus | 50% (small cell lung) |
| mGluR5109 | 45 | 20–30 | 90 | LE; viral-like prodromes; seizures | 64% (Hodgkin’s lymphoma) |
| GlyRα1110 | 45 | 40–50 | 30 | SPS; PERM | 10% (thymoma, seminoma) |
| IgLON5111 | 50 | 60–70 | 30–40 | Sleep disturbances; bulbar symptoms; ataxia | Rare |
| LGI128,79 | 35–40 | 60–70 | 90–100 | LE; FBDS; hyponatremia | 1–10% (thymoma) |
| Neurexin 3α112 | 80 | 40–50 | 60 | Encephalitis; viral-like prodrome; oro-facial dyskinesia; central hypoventilation; positive ANA | Unknown |
| NMDAR96 | 80–90 | 20–30 | 90–100 | LE; psychosis; viral-like prodrome; dyskinesias; central hypoventilation | 40–60% (teratoma, usually ovarian) |
AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; ANA, anti-nuclear antibody; CASPR2, contactin associated protein 2; CNS, central nervous system; DPPX, dipeptidyl aminopeptidase-like protein 6; FBDS, facio-brachial dystonic seizures; GABAAR, γ-aminobutyric acid type-A receptor; GABABR, γ-aminobutyric acid type-B receptor; GI, gastrointestinal; GlyRα1, glycine receptor subunit alpha-1; IgLON5, immunoglobulin-like cell adhesion molecule IgLON family member 5; LE, limbic encephalitis; LGI1, leucine-rich glioma inactivated 1; mGluR5, metabotropic glutamate receptor 5; NMDAR, N-methyl-D-aspartate receptor; ON, optic neuritis; PERM, progressive encephalopathy with rigidity and myoclonus; SPS, stiff-person syndrome. (Modified with permission from Table 1 in ref.75).