Table 1.
Clinical features of neural specific autoantibody–associated syndromes
| Antibody | Neurological presentations | Epilepsy association (3+, 2+, 1+) | Epilepsy presentations | Brain MRI | Specific cancer type (proportion of patients with cancer) |
|---|---|---|---|---|---|
| LGI1 | FBDS, piloerection seizures, PDS, limbic encephalitis, hyponatremia | 3+ | FBDS, unilateral piloerection, paroxysmal dizzy spells | Medial temporal FLAIR hyperintensity, T1 basal ganglia hyperintensity (FBDS cases) | Thymoma (10–15%) |
| GABA-B | SE, limbic encephalitis | 3+ | Crescendo seizures, SE is frequent. | Medial temporal FLAIR hyperintensity | Small cell lung cancer (50–60%) |
| GABA-A | SE, autoimmune encephalitis | 3+ | Crescendo seizures and status epilepticus | Multifocal cortical and subcortical hyperintensity | Thymoma (10–30%) |
| NMDA-R | Oral dyskinesia, catatonia, neuropsychiatric dysfunction, autonomic dysfunction, refractory epilepsy | 3+ | Crescendo seizures, status epilepticus, and encephalopathy (EEG: extreme delta-brush) | Normal or nonspecific cortical and/or subcortical changes | Ovarian teratoma (20–30%) |
| GAD65 | SPS, hyperekplexia, brainstem encephalitis (especially African–Americans) | 2+ | Multifocal epilepsy, drug-resistant epilepsy, rarely SE | Multifocal cortical and subcortical hyperintensity or brainstem hyperintensity | Lung carcinoma (small cell or nonsmall cell), Thymoma (< 10%) |
| AMPA-R | Limbic encephalitis | 2+ | SE has been reported | Cortical atrophy, deep gray nuclei FLAIR hyperintensity | Thymoma, small cell lung cancer, breast adenocarcinoma (50–70%) |
| mGluR5 | Encephalopathy, mood changes, movement disorder and seizures | 2+ | Seizures are common, SE in children | Normal in 50%, limbic/cortical FLAIR changes | Hodgkin lymphoma (50–70%) |
| ANNA-1/Hu | Limbic encephalitis, sensory neuronopathy, autonomic dysfunction | 2+ | Temporal and/or extratemporal seizures, rarely SE | Normal or medial temporal FLAIR hyperintensity | Small cell lung cancer, neuroendocrine tumors (> 70%) |
| Ma-1/Ma-2 | Limbic encephalitis, brainstem encephalitis | 2+ | Focal unaware seizure or bilateral tonic–clonic | Brainstem FLAIR hyperintensity or medial temporal FLAIR hyperintensity | Testicular germ cell tumor†, small cell lung cancer‡ (50–70%) |
| Amphiphysin | SPS, PERM, transverse myelitis | 2+ | Limbic encephalitis and seizures can occur in up to 30% of patients. | Normal or nonspecific cortical and/or subcortical changes | Small cell lung cancer, breast cancer (50–70%) |
| ANNA-2/Ri | Stridor, laryngospasm, jaw dystonia, opsoclonus myoclonus | 1+ | Seizures are rare | brainstem FLAIR hyperintensity and/or atrophy | Small cell lung cancer, breast cancer (> 70%) |
| CASPR-2 | Neuromyotonia, Morvan’s syndrome, limbic encephalitis, refractory epilepsy, sleep disorder | 1+ | Nonspecific | Normal or medial temporal FLAIR hyperintensity | Thymoma (10–20%) |
| Glycine | SPS, PERM | 1+ | Rarely associated with seizures | Normal or nonspecific cortical and/or subcortical changes | Thymoma (< 5%) |
| DPPX | Diarrhea, hyperekplexia, ambiguous sleep, parasomnias, PERM, | 1+ | Rarely associated with seizures | Normal or nonspecific cortical and/or subcortical changes | Lymphoma (< 10%) |
| GFAPα | Meningo-encephalomyelitis, tremor, ataxia, autonomic dysfunction | 1+ | Rarely associated with seizures | Peri-radial/patchy enhancement or diffuse subcortical hyperintensity | Ovarian teratoma (20%) |
| CRMP-5 | Choreoathetosis, optic neuritis, retinitis, limbic encephalitis, ataxia, transverse myelitis, polyradiculoneuropathy | 1+ | Rarely associated with seizures (focal aware and focal unaware) | Normal or medial temporal FLAIR hyperintensity | Small cell lung cancer, thymoma (50–70%) |
| Neurexin-3α | Prodrome of fever, headache and gastrointestinal symptoms followed by development of encephalopathy and seizures | 1+ | Limited data available | Normal | None |
| MOG | ADEM, ON, TM | 1+ | Focal seizures with secondary generalization and status epilepticus | Multifocal demyelination, involvement of corpus callosum, deep gray nuclei | None |
| AK5 | Limbic encephalitis | Rare | Limited data available. 1 patient reported to have seizure 6 months after disease onset | Bilateral medial temporal FLAIR hyperintensity | None |
| IgLON5 | Parasomnias, REM, and NREM dysfunction, brainstem dysfunction, hyperexcitability disorder | Rare | Rarely associated with nocturnal frontal lobe epilepsy | Normal or nonspecific cortical and/or subcortical changes | None |
ADEM = acute disseminated encephalomyelitis; AMPA-R = amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ANNA-1 = antineuronal nuclear antibody type 1; ANNA-2 = antineuronal nuclear antibody type 2; AK5 = adenylate kinase 5; CBA = cell-based assay; CASPR-2 = contactin-associated protein-like 2; CRMP-5 = collapsin response mediator protein-5; DPPX = dipeptidyl-peptidase-like protein 6; EMG = electromyography; FLAIR = fluid-attenuated inversion recovery; GABA-A = γ-aminobutyric acid type A; GABA-B = γ-aminobutyric acid type B; GAD65 = glutamic acid decarboxylase 65; GFAP = glial fibrillary acidic protein; LGI1 = leucine-rich glioma-inactivated protein 1; MOG = myelin oligodendrocyte glycoprotein; NMDA-R = N-methyl-d-aspartate receptor; ON = optic neuritis; PERM = progressive encephalomyelitis with rigidity and myoclonus; PDS = Paroxysmal dizzy spells, REM = rapid eye movement; SPS = stiff person syndrome; TM = transverse myelitis; WB = Western blot
*Coexisting LGI1 and CASPR-2 antibodies
†Ma-2 antibodies
‡Ma-1 antibodies with or without Ma-2 antibodies