Demographic, clinical and paraclinical features of neuronal autoantibody syndromes
| Neuronal auto-antibody (Ref.) and predominant IgG subclass | Median age, years (range) | Sex ratio (M:F) | Clinical features | MR brain scan findings | CSF findings | EEG findings | Other investigations | Immunotherapy response and outcomes |
| NMDAR10 25 43 56
IgG1 | 21 (2 months–85 years) | 1:4 | Encephalitis with prominent polysymptomatic neuropsychiatric presentation, polymorphic movement disorder, language disorder, autonomic dysfunction, coma and central apnoea. | 70%–80% normal or non-specific, with a typical limbic encephalitis in a minority. | 80% abnormal (lymphocytic pleocytosis, unpaired oligoclonal bands common). | 90% abnormal (slowing most common, 20% epileptiform abnormalities, rarely extreme delta brush pattern). | Ovarian teratoma in 60% of adult, female patients. After HSV encephalitis, particularly children can develop NMDAR (and other neuronal surface) autoantibodies. | ~50% improve in 4 weeks with first line immunotherapy (IT). ~70% of non-responders improve soon after 2nd line IT. Improvement up to 24 months, with 80% reaching mRS 0–2. 10%–15% relapse risk—reduced by IT and tumour removal ~5% mortality. |
| LGI1*33 49 57
IgG4 | 64 (31–84) | 2:1 | Limbic encephalitis with frequent focal seizures, including characteristic facio-brachial dystonic seizures. | ~75% abnormal. ~40% increased signal/swelling in medial temporal lobes (unilateral >bilateral). | ~25% abnormal (mild pleocytosis with elevated protein). | ~50% abnormal (~30% epileptiform abnormal, ~20% focal slowing). | >90% with HLA-DRB1*07:01. Hyponatraemia common (~70%). | At 2 years, 1/3 fully recovered, 1/3 functionally independent but unable to work, 1/3 severely disabled or dead. Relapses in 20%–30%; associated with poor outcomes. |
| CASPR2*30 49 55
IgG4 | 66 (25–77) | 9:1 |
Main syndromes: peripheral nerve hyperexcitability, limbic encephalitis and Morvan’s syndrome. | ~30% increased signal in medial temporal lobes. | ~30% abnormal (pleocytosis, elevated protein±oligoclonal bands). | ~70% abnormal (40% epileptiform abnormal). | HLA-DRB1*11:01. Thymoma in ~20% (often with LGI1 antibodies in addition) Electromyography may demonstrate hyperexcitability (fasciculations, myokymia). | ~50% with good or full response to tumour therapy/IT. ~45% with partial IT response. ~25% relapse. |
| GABAAR20 21
IgG1 | 40 (2 months–88 years) | 1:1 | Encephalitis with frequent status epilepticus. | >80% cortical and subcortical FLAIR signal abnormalities involving 2+ brain regions. | 25–50% lymphocytic pleocytosis±oligoclonal bands and elevated protein. | >80% abnormal (encephalopathy with ictal abnormalities). | Thymoma ~30%. | IT-responsive, however, mortality due to status epilepticus or related complications ~10–20%. |
| GABABR22
IgG1 | 61 (16–77) | 1.5:1 | Limbic encephalitis with prominent seizures. | ~70% abnormal (45% increased signal in medial temporal lobes. | ~80% lymphocytic pleocytosis. | ~75% with ictal abnormalities. | Tumours in ~50% (mostly SCLC). | ~90% show response to IT, those with tumour have poorer prognosis with recurrent neurological symptoms and higher mortality. |
| AMPAR58 | Mean 53.1 (14–92) | 2:1 | Limbic encephalitis with prominent confusion, amnesia, seizures and psychiatric/behavioural symptoms. | ~85% abnormal (67% with bilateral mesial temporal involvement). | ~70% abnormal. | 45% abnormal. | Tumour identified in ~70% (thymus, SCLC, breast, ovary). | Most patients showed improvement from peak of disease, median mRS=1 in survivors. ~15% of reported patients died (commonly due to complications from malignancy). |
| DPPX27 | 53 (13–76) | 1.5:1 | Multifocal encephalitis with myoclonus, tremors and hyperekplexia, prominent diarrhoea/weight loss. | 100% normal or non-specific. | ~30% abnormal (mild pleocytosis and elevated protein). | ~70% abnormal (focal or diffuse slowing). | ~10% with B-cell neoplasm (gastrointestinal follicular lymphoma, ; leukaemia). | 60%–70% improve with IT. |
| GlyR28
IgG1/3 | 50 (1–75) | 1:1 |
3 main syndromes: stiff-person spectrum disorder PERM (progressive encephalopathy with rigidity and myoclonus limbic encephalitis). |
Brain: temporal lobe inflammation in 5%, abnormal ~30%, mostly non-specific. Cord: ~20% (mostly short/patchy lesions, 5% longitudinally extensive lesion). | ~40% pleocytosis, 20% oligoclonal bands. | ~70% abnormal (55% diffuse slowing, 15% focal epileptic abnormal, 5% focal slowing). | EMG abnormal 60% (continuous motor unit activity, spontaneous or stimulus-induced activity, neuromyotonia) Thymoma in 15%. | ~10% mortality in initial case series. Good outcomes in survivors with median mRS=1 at latest follow-up. Duration of follow-up 18 months–7 years, 82% treated with IT. |
| MOG17–19 59 | 37 (1–74) | 1:1 | Optic neuritis, transverse myelitis, brainstem encephalitis, encephalitis. |
Brain: ~75% abnormal (bilateral poorly demarcated subcortical lesions), ~30% brainstem involvement. Cord: ~50% abnormal, mixed STM/LTM with frequent conus medullaris involvement. Orbit: extensive, often bilateral, optic nerve lesions with frequent chiasmal involvement. | ~60% lymphocytic pleocytosis oligoclonal bands uncommon. | Not reported. | Visual evoked potentials may show evidence of previous optic neuritis. | ~75% have good response to corticosteroids. ~60% make a full or good recovery. Relapses are common. |
| IgLON532 60
IgG1/4 | 64 (46–83) | 1:1 |
4 main syndromes: sleep disorder (REM and NREM parasomnias, sleep apnoea) Bulbar syndrome Progressive supranuclear palsy-like syndrome Cognitive syndrome±chorea. | ~80% normal/ non-specific. ~15% brainstem atrophy. 5% bilateral hippocampal atrophy. | 30% CSF pleocytosis. 50% elevated protein (mean 64 mg/dL, 52–192). ~10% unpaired oligoclonal bands. | Not reported. | HLA-DRB1*10:01/HLA-DQB*05:01 alleles in 87%. No history of autoimmunity or cancer in 91%. | Up to 50% respond to initial IT but far fewer have a sustained response. Response better with combination therapy vs monotherapy (67% vs 32%) and better for second-line vs first-line therapy (59% vs 32%). |
| Neurexin-3α61 | 44 (23–57) | 1:2 | Encephalitis. | 20% mesial temporal T2/FLAIR signal abnormal. | 100% abnormal (pleocytosis, elevated Ig index). | Not reported | 40% mortality despite IT, remaining 60% partial recovery in initial series. |
*LGI1-antibodies and CASPR2-antibodies were historically classified as antibodies against the Voltage-Gated Potassium Channel.
AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; CASPR2, contact-associated protein 2; CSF, cerebrospinal fluid; DPPX, dipeptidyl peptidase-like protein 6; EEG, electroencephalogram; GABAA/BR, gamma aminobutyric acid; GlyR, glycine receptor; HSV, herpes simplex virus; IgLON5, immunoglobulin-like cell-adhesion molecule 5; IT, immunotherapy; L, long-segment; LGI1, leucine-rich glioma inactivated protein 1; MOG, myelin-oligodendrocyte glycoprotein; mRS, modified Rankin score; NMDAR, N-methyl-D-aspartate receptor; (N)REM, (non)-rapid eye-movement sleep; S, short-segment; SCLC, Small Cell Lung Cancer; TM, transverse myelitis.