Table 1.

Clinical features of anti-synaptic and anti-glutamic acid decarboxylase autoimmune encephalitides

Clinical features	NMDAR, (NR1 subunit)	VGKC-complex (Kv1 subunit, LGI1, CASPR2)	AMPAR (GluR1, GluR2 subunits)	GABABR (B1 subunit)	GAD (65 kDa)
Age (years)	18 to 50	Less than 50	Less than 50	60 to 70	Less than 50
Sex (% female)	75%	66%	Greater than 50%	50%	Less than 50%
Etiology
Paraneoplastic (%, and commonly occurring cancers)	9% to 56% have ovarian teratoma, predominately females less than 18 years of age	10% to 30%; low titers; SCLC; thymoma; CASPR2>>LGI-1	50% to 70%; SCLC, breast carcinoma; thymoma	50%; SCLC thymoma	Rarely associated with cancer
Nonparaneoplastic	Approximately 50%	70%; high titers	30% to 50%	50%	Frequent
Anatomical subtype
Limbic encephalitis	Less common	Typical	Typical	Typical	Typical
Panencephalitis	Typical	Rare (involving basal ganglia)	Unclear	Unclear	Less common
CSF abnormal (%)	90%	40%	90%	80%	20%
Psychiatric Features	Common and pronounced: Anxiety, agitation, paranoid delusions, perceptual changes, erratic behavior, speech changes, severe psychosis	Agitation, anxiety, panic-attacks, depression, psychosis, hallucinations, delusions, delirium, confabulation	Atypical psychosis, which can be isolated	Paranoia, behavioral changes	Depression, atypical psychosis (case reports)
Neurological Features	Early features: seizures, cognitive/memory impairment; Late features: catatonia, orofacial and limb dyskinesia, dystonia, autonomic dysfunction, reduced level of consciousness, aphasia, central hypoventilation	LGI1: limbic encephalitis (more common): amnesia temporal lobe seizures, tonic seizures, and hypernatremia. Extrapyramidal symptoms (choreoathetosis) and extra-temporal (faciobrachial dystonic) seizures (less common). CASPR2: limbic encephalitis, Morvan's syndrome (neuromyotonia, REM disorder, insomnia, and autonomic dysfunction).	Memory impairment, temporal lobe seizures	Prominent temporal lobe seizures, memory impairment, concomitant glutamic acid decarboxylase autoantibodies	Stiff-person syndrome, cerebellar ataxia, cognitive/memory impairment, epilepsy (often mesial temporal)
Response to treatment	Highly responsive to immune therapy and removal of ovarian teratoma	Highly responsive to immune therapy	Moderately responsive to immune therapy	Moderately responsive to immune therapy	Often refractory to immune therapy
Relapse risk	20% often with psychiatric signs; may indicate tumor reoccurrence	Rarely relapses	Tendency to relapse (based on small case series)	Tendency to relapse (based on small case series)	Tendency to be chronic and relapse

AMPAR, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)-propanoic acid receptor; CASPR-2, contactin associated protein 2; CNS, central nervous system; CSF, cerebrospinal fluid; GABA_BR, gamma aminobutyric acid B receptor; GAD, glutamic acid decarboxylase; LGI-1, leucine-rich glioma inactivated-1; NMDAR, N-methyl-D-aspartate receptor; REM, rapid eye movements; SCLC small cell lung cancer; VGKC; voltage-gated potassium channel.