Table 1.
Autoantibodies associated with limbic encephalitis.
| Symptoms | Tumor Association | Image | Prognosis | |
|---|---|---|---|---|
| Cell-surface | ||||
| LGI1 | LE, seizure including FBDS, hyponatremia, paroxysmal dizziness spells, pain, dysautonomia | <10% SCLC, thymoma |
Normal or nonspecific changes; T2-mesiotemporal hyperintensity; T1-bright basal ganglia in FBDS | Almost fair response to immunotherapy but high relapse rate (15–35%) |
| CASPR2 | LE, Morvan syndrome, neuromyotonia, seizure, neuropathic pain, dysautonomia | 10–40% (44% for LGI1 and CASPR2 dual seropositivity) thymoma |
Normal or nonspecific changes; T2 mesiotemporal hyperintensity | Favorable response to immunotherapy but high relapse rate (35%) |
| AMPAR | LE, confusion, psychiatric symptoms, seizure | 50–70% lung, breast, thymoma |
T2 mesiotemporal hyperintensity | Favorable response to immunotherapy but common relapse |
| GABA-BR | LE, seizure, dysautonomia, movement disorder, rapidly progressive dementia | 50–60% SCLC |
T2 mesiotemporal hyperintensity | Frequent co-expression with other Abs; poor prognosis with concurrent tumor or convulsive SE; relapse rate (20%) |
| mGluR5 | LE, Ophelia syndrome seizures, movement disorders | 50% Hodgkin lymphoma |
Limbic and extra-limbic (thalamus, pons, frontal or parieto-occipital cortex, cerebellum) | Complete or partial recovery to immunotherapy |
| DPPX | LE, BE, diarrhea, CNS hyperexcitability, PERM, dysautonomia | <10–30% B cell tumor |
Normal or nonspecific T2/FLAIR white matter abnormalities | Chronic and second-line immunotherapy frequently required, relapse rate (23%) |
| Synaptic | ||||
| GAD | LE, SPS, PERM, seizure, CA, oculomotor dysfunction, diabetes | <15% (higher with coexisting Abs, esp. GABA-BR Ab) lung, thymoma |
T2 mesiotemporal hyperintensity | 70% had partial improvement with immunotherapy |
| Intracellular | ||||
| Ma | LE, BE, diencephalic encephalitis, seizure, CS | 90% testicular, lung and pleural |
Nonspecific | Favorable in anti-Ma2 but poorer in anti-Ma |
| Hu | LE, CS, BE, dysautonomia, sensory neuropathy |
>90% SCLC |
Nonspecific | Poor |
| Ri | LE, CS, BE, OMS, movement disorders | >90% woman-breast, man-lung and bladder |
Nonspecific | Common co-expression with other Abs |
| CRMP5 | LE, encephalomyelitis, CS, SPS | >90% SCLC, thymoma |
Normal or T2 mesiotemporal hyperintensity | Poor |
| SOX1 | LE, LEMS, CS, neuropathy, LEMS | 30–60% SCLC |
Normal or T2 mesiotemporal hyperintensity | Common co-expression with other Abs; poor response to treatment |
| AK5 | LE | No data | Hippocampal atrophy | Poor response to treatment |
Abs: antibodies; AK5: adenylate kinase 5; AMPAR: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor; BE: brainstem encephalitis; CASPR2: contactin-associated protein-like 2; CRMP5: collapsin response-mediator protein-5; CNS: central nervous system; CS: cerebellar syndrome including paraneoplastic cerebellar degeneration; DPPX: dipeptidyl peptidase-like protein 6; FBDS: faciobrachial dystonic seizures; GABA-BR: γ-aminobutyric acid B receptor; GAD: glutamic acid decarboxylase; LE: limbic encephalitis; LEMS: Lambert-Eaton myasthenic syndrome; LGI1: leucine-rich, glioma inactivated 1; mGluR5: metabotropic glutamate receptor subtype 5; OMS: opsoclonus-myoclonus syndrome; PERM: progressive encephalomyelitis with rigidity and myoclonus; SCLC: small-cell lung cancer; SE: status epilepticus; SOX1: sex-determining region Y (SRY)-box 1; SPS: stiff-person syndrome.