Table 1

Demographic, clinical and paraclinical features of neuronal autoantibody syndromes

Neuronal auto-antibody (Ref.) and predominant IgG subclassMedian age, years (range)Sex ratio (M:F)Clinical featuresMR brain scan findingsCSF findingsEEG findingsOther investigationsImmunotherapy response and outcomes
NMDAR10 25 43 56
IgG1
21
(2 months–85 years)
1:4Encephalitis 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)
2:1Limbic 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)
9:1Main 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)
1:1Encephalitis 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)
1.5:1Limbic 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.
AMPAR58Mean 53.1
(14–92)
2:1Limbic 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).
DPPX2753
(13–76)
1.5:1Multifocal 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)
1:13 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 5937
(1–74)
1:1Optic 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)
1:14 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-3α6144
(23–57)
1:2Encephalitis.20% mesial temporal T2/FLAIR signal abnormal.100% abnormal (pleocytosis, elevated Ig index).Not reported40% 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.