Table 1.

The key clinical aspects of the major neuronal surface-targeted antibodies based on current available evidence from published patient series

	NMDAR	LGI1	CASPR2	GAD1	GlyR	GABAB
Median age of onset	21 (2–76) [5, 7, 8]	68 (28–92) [45, 50]	57 (19–80) [39]	23 (17–66) [21]	50 (1–75) [27]	62 (24–75) [25, 36]
Gender	F > M (70–90 %) [5, 7, 8]	Equal [4]	M > F ~90 % [4, 39, 107]	F > M ~80 % [21]	Equal [27]	Equal [25]
Clinical features	Frequent stereotyped progression from early cognitive dysfunction, psychiatric features and seizures, to later movement disorder, autonomic failure and reduction in consciousness [8]	FBDS LE [50] Often present in Morvan’s syndrome (coexisting with CASPR2-antibodies). Isolated epilepsy in some [59]	Morvan’s syndrome Neuropsychiatric features, insomnia, autonomic failure and neuromyotonia (often with LGI1 antibodies) [39, 107] Around 10 % have a cerebellitis [48] Around 10 % of VGKC-complex antibody-positive LE [4, 53] Isolated epilepsy noted (Irani unpublished)	Stiff person syndrome > cerebellar ataxia > LE > isolated epilepsy [19]	Stiff Person syndrome spectrum of diseases: PERM > vSPS > cSPS [27] Rarely LE [27]	LE, predominantly with seizures as presenting symptom [25, 36] Rarely cerebellar ataxia, status epilepticus or opsoclonus myoclons—usually progresses to LE [108]
Investigation findings	MRI normal in ~50–75 % [5, 7, 8] LP abnormal in 80–90 % [5, 7, 8] EEG abnormal in 80–90 % [5, 7, 8]	MRI abnormal in >60–80 % [4, 45, 50] LP Normal [45] Hyponatraemia in 60-80 % [4, 45, 50] EEG abnormal in 80 %	MRI normal in >60–90 % [4, 39] LP abnormal in 50 % [39] Hyponatraemia in 10–25 % [4, 39, 107] EEG abnormal in ~60 % if central involvement [107]	MRI abnormal in 100 % (used as selection criteria in this study) [21] LP abnormal in 22 % [21]	MRI Head abnormal in 30 %, spine in 20 % [27] LP abnormal in 60 % [27] EMG abnormal 60 % [27] EEG abnormal in 70 % [27]	MRI abnormal in ~75 % [25] LP abnormal in 60 % [25] EEG abnormal in ~90 % [25]
Tumour association	Ovarian teratoma in 30 [7] –50 % [5, 8] 6 % in <12-year olds [5]	<10 % (various tumours observed) [4, 50]	Thymoma ~40 % of Morvan’s [39] Tumour <10 % in other presentations [107]	None [21]	Thymoma <10 % [27]	50 % (lung cancer, predominantly small-cell lung cancer) [25, 108]
Immunotherapy efficacy	First-line IT leads to good outcome in 81 %, no need for ITU stay and early IT associated with better outcome [5, 8]	Steroids and PLEX reduce cognitive impairment and decrease disability [4, 45, 52]	IT reduces disability, less response if thymoma [4, 39, 107]	Poor efficacy—0 % seizure freedom [21]	90 % shows good response [27]	80 % response rate to IT ± tumour resection (if treated) [25, 108]
Prognosis (inc relapses)	6 % mortality (12 % if untreated) [5] 12–15 % relapse (median time to relapse 18 months [1–84 months]) [5, 8]	2 % mortality [4]; low rates of relapse unless treatment is withdrawn early	20–31 % mortality, (highest risk if thymoma) 7 % relapse rate [4, 39]	Low mortality, due to poor response to Rx, relapse not able to be defined [21]	10 % mortality (highest risk if thymoma) [27] 11 % relapse rate [27]	30 % mortality (predominantly tumour or chemotherapy related) [25, 26]

	AMPAR	AQP4	MOG	GABAA 2	DPPX	IgLON5
Median age of onset	60 (38–87) [16]	37 (4–78) [106]	37.5 (3–70) [106]	22 (3–63) [28]	53 (13–76) [68, 69]	59 (52–76) [70]
Gender	F > M ~90 % [16]	F > M (90 %) [106]	M > F (60 %) [106]	M > F (80 %) [28]	Equal [68, 69]	Equal [70]
Clinical features	LE	NMOSD	NMOSD—more likely to have optic neuritis, especially bilaterally [106]	Status epilepticus or epilepsia pars continua at high titres [28] LE [37]	LE with tremor, myoclonus, brainstem dysfunction and dysautonomia with 50–75 % having diarrhoea of unknown cause [68, 69]	REM and non-REM sleep disorder, sleep breathing disorder, movement disorder. Occasional rapid brainstem degeneration with dysautonomia, central hypoventilation, dysphagia and dysarthria [70]
Investigation findings	MRI abnormal in 80 % [16] LP abnormal in 90 % [16] EEG abnormal is 60 % [16]	MRI abnormal 60 % [106] LP oligoclonal bands in 20 % [106]	MRI abnormal 40 % [106] LP oligoclonal bands in 0 %, more likely to have higher cell count [106]	MRI abnormal in 100 % [28] LP abnormal in 84 % [28] EEG abnormal 100 % [28]	MRI abnormal in 66 % [68] EEG abnormal in 100 % [68] LP abnormal in 100 % [68]	Videopolysomnography—OSA, stridor and abnormal sleep architecture Neuropathology—neuronal loss and atypical brainstem tau deposition [70]
Tumour association	Lung, breast, thymoma ~70 % [16]	Rare, various infections can trigger relapse	None	16 % treated for Hodgkin’s lymphoma 10 months previously [28]	None	None
Immunotherapy efficacy	90 % response rate to IT ± oncological therapy. [16]	80 % response rate to IT, reduction in relapse rate with use of Rituximab [109–111]	Immunoresponsive [106]	50 % recovery with IT [28]	100 % gradual response to IT [68]	No response to immunotherapy [70]
Prognosis (inc relapses)	30 % mortality (higher if tumour and no treatment) 50 % relapse rate (median time to relapse 16 months) [16]	70 % have relapsing course [112]	50 % relapse (4.5 year median follow up) [106]	Mortality 33 % [28] 16 % relapse [28]	No mortality 100 % relapse rate off IT [68]	Progressive

Above data calculated by taking into account a composite figure from the largest available data series on each antibody. 1. Demographics and clinical information for anti-GAD centres on GAD LE. 2. High titre patients included only for clinical information sections

NMDAR N-methyl-d-aspartate receptor, LGI1 leucine-rich glioma-inactivated 1, CASPR2 contactin-associated protein 2, GAD glutamic acid decarboxylase, GlyR glycine receptor, GABAB γ-aminobutyric acid B, AMPAR a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, AQP4 aquaporin-4, MOG myelin oligodendrocyte glycoprotein, GABAa γ-aminobutyric acid A, DPPX dipeptidyl-peptidase-like protein-6, LE limbic encephalitis, FBDS faciobrachial dystonic seizure, SPS stiff person syndrome, vSPS variant stiff person syndrome, cSPS classical stiff person syndrome, NMOSD neuromyelitis optica spectrum disorders, REM rapid eye movement, OSA obstructive sleep apnoea, LP lumbar puncture, EEG electroencephalogram, EMG electromyelogram, PLEX plasma exchange, IT immunotherapy