Autoantibody-mediated encephalitis: Not just paraneoplastic, not just limbic, and not untreatable

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FIGURE 1
Left, axial fluid-attenuated inversion recovery magnetic resonance imaging shows increased signal in the hippocampus bilaterally (yellow arrows). Right, fluorodeoxyglucose positron-emission tomography shows hypermetabolism in the hippocampi (black arrows).
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FIGURE 2

TABLE 1

Neuronal antibodies associated with limbic encephalitis

Antigen location	Antibody	Frequency of tumor occurrence	Tumor association	Responsiveness to treatment
Intracellular	ANNA1 (anti-Hu)	> 75%	Small cell lung cancer	Poor
	Anti-CV2 (CRMP)	> 75%	Small cell lung cancer, thymoma	Poor, but longer survival than with ANNA1
	Anti-Ma2	~ 90%	Testicular germ cell tumor	Better than with ANNA1; prognosis is worse with co-occurrence of anti-Ma1
	Anti-GAD65	< 33%	None	Seizure outcome inferior to that in anti-VGKC limbic encephalitis
Cell surface (common)^6,7	Anti-NMDA receptor	38%	Ovarian teratoma	Very good, but slow recovery
Cell surface (common)^6,7	Anti-LGI1	0	None	Very good, quicker recovery than with NMDA receptor encephalitis
Cell surface (rare)^8,9	Anti-AMPA receptor	70%	Thymoma, breast, lung	Good
Cell surface (rare)^8,9	Anti-GABA_B receptor	47%	Small cell lung cancer	Good

AMPA = alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ANNA1 = antineuronal nuclear antibody 1; CRMP = collapsin-responsive mediated protein; GABA_B = gamma-aminobutyric acid; GAD = glutamic acid decarboxylase; LGI1 = leucine-rich glioma-inactivated protein 1; NMDA = N-methyl-d-aspartate; VGKC = voltage-gated potassium channel

TABLE 2

Neuronal antibodies associated with brainstem and cerebellar encephalitis

Syndrome	Antigen location	Antibody	Tumor association	Prognosis
Brainstem	Intracellular	Anti-Hu (ANNA1)	Small-cell lung cancer	Poor
		Anti-Ri (ANNA2)	Breast, lung	Poor
		Anti-Ma2	Testicular germ cell tumor	Good
	Cell surface	Anti-NMDA (second stage disease)	Ovarian teratoma	Very good
		Anti-GQ1b	None	Very good
		Anti-NMO (antiaquaporin 4)	None	Good
Cerebellar	Intracellular	Anti-Yo	Ovarian, breast	Poor
		Anti-Ri	Breast, lung	Good
		Anti-Tr	Hodgkin lymphoma	Fair
		Anti-GAD	None	Good
	Cell surface	Anti-VGCC	Small-cell lung cancer	Fair
	Cell surface	Anti-mGluR1	Hodgkin lymphoma in remission	Good (three cases re- ported, two improved)

ANNA = antineuronal nuclear antibody; GAD = glutamic acid decarboxylase; GQ1b = ganglioside GQ1b; mGLuR1 = metabotropic glutamate receptor type 1; NMDA = N-methyl-d-aspartate; NMO = neuromyelitis optica; VGCC = voltage-gated calcium channel

TABLE 3

Antibodies associated with neurologic syndromes

Antigen location	Antibody	Characteristic neurologic syndrome
Intracellular	Anti-Yo (Purkinje cell cytoplasmic antibody type 1)	Paraneoplastic cerebellar degeneration
	Anti-glutamic acid decarboxylase	Stiff person syndrome (progressive encephalomyelitis with rigidity, myoclonus)
	Anti-Hu (ANNA1)	Multiple, including paraneoplastic sensory neuropathy, paraneoplastic encephalomyelitis
	Anti-Ma2	Encephalitis, limbic or upper brainstem
	Antiamphiphysin	Stiff person syndrome, paraneoplastic encephalomyelitis, limbic encephalitis
	Anti-CV2 (CRMP)	Multiple, including uveitis, optic neuritis, retinitis, paraneoplastic cerebellar degeneration
Cell surface	Anti-NMDA receptor	Multistage syndrome, starting with limbic encephalitis and psychiatric changes followed by brainstem dysfunction
	Anti-CASPR2	Encephalitis or peripheral nerve hyperexcitability (if both, Morvan syndrome)
	Anti-LGI1	Limbic encephalitis with faciobrachial dystonic seizures
	Anti-AMPA receptor	Limbic encephalitis, isolated psychiatric disturbances
	Anti-GABA_B receptor	Limbic encephalitis, early prominent seizures
	Anti-glycine receptor	Stiff person syndrome

AMPA = alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ANNA = antineuronal nuclear antibody; CASPR2 = contactin-associated protein 2; CRMP = collapsin-responsive mediated protein; GABA_B = gamma-aminobutyric acid B; LGI1 = leucine-rich glioma-inactivated protein 1; NMDA = N-methyl-d-aspartate