Table 1.
Clinical Associations of the Most Common Central Nervous System Cell-Surface–Directed Antibodies
| NMDAR | LGI1 | CASPR2 | AMPAR | GlyR | GABAB | AQP4 | MOG | |
|---|---|---|---|---|---|---|---|---|
| Frequent clinical associations | Diffuse encephalitis with psychiatric features, cognitive impairment, seizures, movement disorder, dysautonomia, and reduction in consciousness | LE with faciobrachial dystonic seizures and serum hyponatremia | Morvan syndrome with psychiatric features, insomnia, dysautonomia, and neuromyotonia (often with LGI1 antibodies); less frequently LE | LE | PERM but also some SPS and related syndromes | LE | NMOSD | NMOSD |
| Tumor/infectious associations | Ovarian teratoma in about 30%45,46; Relapses post-HSV encephalitis with NMDAR antibodies75–78 | <10% (various tumors described)29,30,68,69 | Thymoma (∼30%)20,157 | Lung, breast, thymoma (∼50%)41,55 | Thymoma rarely (<10%)18,89,158 | Lung (∼50%)42 | Rare159; relapses often precipitated by various infections131 | None yet known |
| Expanding phenotypic spectrum | Few cases with purely psychotic features48,53,160; predominant movement disorder161; few with predominant cryptogenic epilepsy syndrome162 | Cryptogenic epilepsies60,62 | Cryptogenic epilepsies60,62; Guillain-Barre–like syndrome163 | Atypical psychosis55 | LE, brainstem encephalitis124; cryptogenic epilepsies60,164 | Encephalopathy165 | Encephalopathy, including pediatric ADEM166 | |
| Approximate number of reported cases since first description | >700 in 6 years | ∼250 in 3 years | ∼30 in 3 years | ∼25 in 4 years | ∼60 in 5 years | ∼30 in 3 years | >2,000 in 8 years | ∼30 in 1 year |
| Prevalence in clinically defined tested cohorts | 9/48 (19%) with unknown encephalitis25 | 6/62 (10%) with unknown encephalitis25 | 24/27 (89%) with Morvan syndrome20 | 15/410 (4%) with suspected autoimmune encephalitis41 | Mainly seen in PERM21,89,91,158; 10/81 (12%) with SPS18; 1/48 (2%) pediatric encephalopathies37 | 10/70 (14%) of LE cases42 | 70–80% of patients with NMOSD100,110 | 16/215 (7%) NMOSD110 |
| Prevalence (%) in healthy/disease cohorts136 a | 0–1.2/0–1.3 | 0–0.06/0–0.0432,33 | 0–0.29/0–0.32 | 0–0.23/0–0.0441 | 0.06–1.2/0.1218 | 0/0–0.0442 | 0/0–0.04100 | 0–0.06/0.08–2112 |
| Primary cell type/antigenic target | Neuron/NR1 subunit | Neuron | Neuron | Neuron/GluR1/2 | Neuron/α1 receptor | Neuron/B1 subunit | Astrocyte/M23 arrays | Oligodendrocyte |
For neuronal- or glial-surface–directed antibodies reported in >20 cases and in >1 publication. LE produces amnesia, confusion, and seizures (additional features noted above within each antibody specificity).
Data are from Dahm et al,136 plus other papers as referenced within the table.
ADEM = acute disseminated encephalomyelitis; AMPAR = α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor; AQP4 = aquaporin-4; CASPR2 = contactin-associated protein 2; GABAB = γ-aminobutyric acidB; GlyR = glycine receptor; HSV = herpes simplex virus; LE = limbic encephalitis; LGI1 = leucine-rich glioma-inactivated 1; MOG = myelin oligodendrocyte glycoprotein; NMDAR = N-methyl-D-aspartate receptor; NMOSD = neuromyelitis optica spectrum disorder; PERM = progressive encephalomyelitis with rigidity and myoclonus; SPS = stiff-person syndrome.