Anti-N-methyl-D-aspartate receptor-associated encephalitis: A review of clinicopathologic hallmarks and multimodal imaging manifestations

Table 1 Magnetic resonance imaging differential diagnosis for anti-N-methyl-D-aspartate receptor-associated encephalitis

Condition	Classic imaging manifestations
NMDARE	T2/FLAIR hyperintense lesions that frequently involve the hippocampus or bilateral hippocampi
	Lesions within the infratentorial brain parenchyma and spinal cord are uncommon
	Leptomeningeal enhancement is occasionally present
Acute disseminated encephalomyelitis	Areas of high T2/FLAIR signal, predominantly within the subcortical white matter
	An “open ring” pattern of enhancement, similar to multiple sclerosis
	Lesions with peripheral diffusion restriction
Central nervous system vasculitis/PACNS	Foci of T2/FLAIR hyperintensity within the periventricular white matter or along watershed zones
	Parenchymal microhemorrhages may be present on GRE/SWI sequences
	Evidence of acute, subacute, or chronic stroke within a discrete vascular territory is present in some individuals
Creutzfeldt-Jakob disease	Symmetric T2/FLAIR hyperintensity involving the pulvinar and dorsomedial thalamic nuclei
	Diffusion restriction with concomitant T2 shine through is often present
Heroin inhalational leukoencephalopathy	Symmetric T2/FLAIR hyperintensity within the posterior limb of the internal capsules, which may extend inferiorly to the pontine corticospinal tracts
	Symmetric T2/FLAIR hyperintensity within the cerebellar white matter with sparing of the dentate nuclei
Herpes simplex encephalitis	Asymmetric T1 hypointense/T2 hyperintense edema involving the bilateral medial temporal lobes and insular cortex
	Gyral or leptomeningeal enhancement may be present
	Diffusion restriction is sometimes present
	Blooming on GRE/SWI sequences may be present in the setting of hemorrhage
Methanol poisoning	Symmetric or asymmetric T1 hyperintensity within the putamina, indicative of necrosis
	Asymmetric blooming within the putamina on GRE/SWI sequences in the setting of hemorrhage
Multiple sclerosis	Periventricular, cortical, or juxtacortical T2/FLAIR hyperintense lesions disseminated in space and time
	Infratentorial and spinal cord T2/FLAIR hyperintense lesions may develop in some individuals
	An “open ring” pattern of enhancement is present in active disease
Neuromyelitis optica	Optic nerve edema with T2/FLAIR hyperintense signal and, in some patients, optic nerve enhancement
	High T2/FLAIR signal within the spinal cord spanning at least three contiguous vertebral segments
	Brain parenchymal lesions are often absent

GRE: Gradient echo; NMDARE: Anti-N-methyl-D-aspartate receptor-associated encephalitis; PACNS: Primary angiitis of the central nervous system; SWI: Susceptibility weighted imaging.

Table 2 Cerebral metabolic patterns of autoimmune encephalopathies[18-20]

Autoantibody	Metabolic pattern
Anti-NMDA receptor	Bifrontal hypermetabolism or normal frontal lobe metabolism
	Marked bilateral parieto-occipital hypometabolism
Anti-LGI-1	Bitemporal hypermetabolism
	Bilateral fronto-occipital hypometabolism
Anti-CASPR2	Bifrontal hypermetabolism
	Basal ganglia hypermetabolism
	Bilateral temporo-parietal hypometabolism
Anti-GAD-65	Bilateral basal ganglia hypometabolism
	Bitemporal hypometabolism
Anti-Hu	Bitemporal hypermetabolism

CASPR2: Anti-contactin-associated protein 2; GAD-65: Anti-glutamic acid decarboxylase; LGI-1: Leucine-rich glioma inactivated; NMDA: Anti-N-methyl-D-aspartate receptor.

Table 3 Multimodal imaging of anti-N-methyl-D-aspartate receptor-associated encephalitis[12-24]

Ultrasound	Pelvic or scrotal ultrasound may be used to identify an underlying teratoma in the appropriate patient population
	Ultrasound-guided lymph node biopsy may be required in the setting of metastatic disease with no known primary
MRI	A normal brain MRI is present in half of patients with NMDARE
	T2/FLAIR hyperintense lesions are most commonly present within the supratentorial brain parenchyma and may correlate with prognosis:
	Type 1: Normal brain MRI; favorable prognosis
	Type 2: Hippocampal lesions only; poor prognosis
	Type 3: Lesions involving structures other than the hippocampus; intermediate prognosis
	Type 4: Lesions involving both the hippocampus and other brain structures; poor prognosis
	Infratentorial, spinal cord, and cranial nerve lesions are less common, but may occur in some individuals
	Leptomeningeal enhancement is rare, but has been described
MRS	Reduced NAA peak
	Decreased NAA/creatine ratio
	Increased choline peak
FDG PET	Brain FDG PET classically shows bifrontal hypermetabolism with parieto-occipital hypometabolism
	The frontal-to-parietooccipital metabolic gradient may correlate with prognosis, with an increased gradient portending a worse outcome
	Whole-body FDG PET may be of value to identify a primary neoplasm and/or localize a lesion for image-guided biopsy
SPECT	HMPAO and I-123-IMP SPECT may be useful for metabolic evaluation in patients with clinical features of NMDARE and a normal brain MRI and FDG PET

FDG PET: Fludeoxyglucose positron emission tomography; HMPAO: Technetium-99 hexamethyl propylenamine oxamine; I-123-IMP: N-isopropyl-p-123-I-iodoamphetamine; MRI: Magnetic resonance imaging; MRS: Magnetic resonance spectroscopy; NAA: N-acetylaspartate; NMDARE: Anti-N-methyl-D-aspartate receptor-associated encephalitis; SPECT: Single-photon emission computed tomography.