Table 2.
Clinical features of main forms of autoimmune encephalitis (AE) associated with known specific antibodies against neuronal surface antigens.
| Antigen | Median age (range) | Sex ratio (M:F) | Main clinical syndrome | Other syndromes | Imaging | CSF features | Other features | Associations | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| Antigens with well-known neuronal roles – excitatory or inhibitory | |||||||||
| N-methyl-D-aspartate receptor (NMDAR) (1-3) | 21 (2 months-85 years) | 1:4 | Psychiatric syndrome, sleep disorders, seizures, amnesia followed by movement disorders, catatonia, autonomic instability, hypoventilation | Few cases with purely psychotic features; few with cryptogenic epilepsy | MRI: often normal or transient FLAIR or contrast enhanicng cortical or subcortical lesions. PET: relative frontal and temporal glucose hypermetabolism with occipital hypometabolism | Lymphocytosis in early stages (70%) and OCBs after (>50%); Abs usually present | EEG: frequent slow, disorganized activity (90%). Infrequent epileptic activity (20%). Rarely extreme delta brush pattern. | Ovarian teratoma in about 60%; post-HSV encephalitis (mainly children). Recently a few cases related to SARS-Cov2 infections have been reported. | ~50% improve in 4 weeks with first line IT. 80% reach mRS 0–2. 12% relapsed within 2 years ~5% mortality. |
| α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) (4) | 55 (14-92) | 2:1 | LE with prominent seizures | Psychosis | Brain MRI: abnormal in 85% (usually bilateral temporal involvement) | Usually abnormal (75): lymphocytosis, OCBs; abs usually present | EEG: abnormali in 45% | Tumor in 70% cases (lung, thymoma, breast, ovary) | Most patients improve with IT; mortality related to underlying malignancy (15%) |
| Gamma-aminobutyric acid A receptor (GABAAR) (5) | 40 (2 months-88 years) | 1:1 | LE with prominent seizures/status epilepticus | Psychiatric syndromes and catatonia; various presentation including SPS, opsoclonus, ataxia | Brain MRI: diffuse cortical and subcortical FLAIR signal abnormalities | Abnormal in up to 50% (lymphocytosis +/- OCBs); abs can be absent in the CSF | EEG: usually abnormal (80%) with epileptic activity and encephalopathy | Tumor in 15% cases (mostly thymoma) | Most patients improve with IT; mortality related to status epilepticus (20%) |
| Gamma-aminobutyric acid B receptor (GABABR) (6) | 61 (16-67) | 1.5:1 | LE with prominent seizures | Ataxia, opsoclonus, status epilepticus | Brain MRI: abnormal in 70% | Common pleyocitosis (80%); rare OCBs. Abs usually present | EEG: usually abnormal (75%) with epileptic activity | Tumor in 50% (mainly lung) | Most patients improve with IT; mortality related to malignancy |
| Metabotropic glutamate receptor 5 (mGluR5) (7) | 29 (6-75) | 1.5:1 | Encephalitis with psychiatric, cognitive, movement disorders, sleep dysfunction, and seizures | Ophelia syndrome | Brain MRI: abnormal in 50% | Lynphocitosis; abs presence unknown | Tumor (60%)(Hodgkin lymphoma, SCLC) | Response to IT | |
| Glycine receptor (GlyR) (8) | 50 (1-75) | 1:1 | Progressive encephalitis with rigidity and myoclonus or stiff person syndrome | LE, brainstem encephalitis; cryptogenic epilepsy | Brain MRI: mostly normal or non-specific; 5% temporal lobe inflammation. Spinal cord: lesions in 20%. |
Pleocytosis in half of the cases, OCBs (20%); Abs can be absent in the CSF | EEG: 70% abnormal (mostly diffuse/focal slowing, 15% focal epileptic). EMG: continuous motor unit activity, spontaneous or stimulus-induced activity in 60% | Thymoma (15%) | Usually improve with IT. |
| Antigens that modulate localization or function of potassium channels | |||||||||
| Leucine-rich glioma inactivated 1 (LGI1) (9-10) | 60 (30-80) but observed also in children | 2:1 | LE with or without FBDS and or generalized seizures | Cryptogenic epilepsy; neuromyotonia | MRI: medial temporal lobe hyperintensity (75%) | Usually normal, rare OCBs; abs can be absent | EEG: epileptiform activity in 30% of cases; focal slowing in 20%. Frequent hyponatremia (70%). | Tumor in 10% cases (mainly thymoma) | Despite recovery, cognitive deficits persist in many patients. One-third of patients relapse. |
| Contactin-associated protein like 2 (CASPR2) (11) | 65 (25-77) but observed also in children | 9:1 | LE, MoS, NMT | Cerebellar ataxia, movement disorders, cryptogenic epilepsies, Guillain-Barre–like syndrome | MRI: medial temporal lobe hyperintensity (30%) | Usually normal (70%); rare OCB, pleocytosis and increased protein; abs can be absent | EEG: epileptiform activity in 40% of cases; focal slowing in 20%. Frequent hyponatremia (70%). | Tumor in 30% cases (mainly thymoma) | Response to immunotherapy. Relapse in 25% of cases. |
| Dipeptidyl-peptidase-like protein-6 (DPPX) (12) | 53 (13-76) | 1.5:1 | Cognitive impairment, brainstem symptoms and diarrhea | Cerebellar ataxia, PERM | MRI: usually normal or non-specific | Pleocytosis, elevated proteins (30%); Abs usually present | EEG: 70% abnormal (mostly diffuse/focal slowing) | B cells tumor (10% cases) | Response to immunotherapy (70%) |
| Antigen with likely cell-cell interaction functions but unclear overall role | |||||||||
| Ig-Like Domain-Containing Protein family member 5 (IgLON5) (13) | 64 (46-83) | 1:1 | NREM sleep disorder, abnormal movement and behaviours with obstructive sleep apnoea and stridor, gait instability and brainstem symptoms | Dementia, movement disorders (chorea); isolated dysphagia | MRI: usually normal or non-specific (80%) | Pleocytosis (30%), increased proteins (50%); Abs usually present | Tauopathy at neuropathology | Up to 50% respond to initial IT but a sustained response is rare. | |
| Neurexin3α (14) | 44 (23-57) | 1:2 | Prodromal fever, headache, or gastrointestinal symptoms, followed by confusion, seizures, and decreased level of consciousness | MRI: abnormal in 20% (mesial temporal involvement) | Pleocytosis in all cases | Elevated mortality (40%) | |||
| Antigens normally considered to be associated with demyelinating disease and sometimes associated with encephalitic features | |||||||||
| AQP4 (15-16) | 32-41 | 5-10:1 | NMOSD, LETM, ON | Area postrema syndrome, narcolepsy | Brain: frequent over time (85%); mainly medulla, hypothalamus and diencephalon. Spinal cord: usually LE lesions. Optic nerve: extensive, often involving chiasm and tracts. | Abnormal in up to 80% (pleocytosis, elevated protein); rare OCBs (10-15%). | Rare cancer association | Respond to IT but sequelae as well as relapses are frequent. | |
| MOG (17-18) | 37 (1-74) | 1:1 | NMOSD, LETM, ON, ADEM, TM | Encephalitis, brainstem encephalitis, seizures | Brain: abnormal in 75% (WM subcortical lesions +/- brainstem involvement) Spinal cord: abnormal in 50%; frequent conus medullaris involvement. Optic nerve: extensive, often bilateral lesions; frequent chiasmal involvement. |
Abnormal in 60% (pleocytosis; rare OCBs). | Can be triggered by infections and vaccinations | Usually respond to corticosteroids (75%) Common relapses. | |
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