Table 1.

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; GABA_A/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.