Table 1. Differential diagnosis of autoimmune encephalitis anatomical syndromes and suggested additional testing.

ADEM, acute disseminated encephalomyelitis; AHL, acute hemorrhagic leukoencephalitis; ANA, antinuclear antibody; AQP4, aquaporin-4; CJD, Creutzfeldt-Jacob disease; CLIPPERS, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids; CPM, central pontine myelinolysis; CSF, cerebrospinal fluid; DaT scan, dopamine transporter scan; ENA, extractable nuclear antigens; GFAP, glial fibrillar acidic protein; GPA, gliomatosis with polyangitis; GQ1b, anti-ganglioside Q1B antibody; HHV6, human herpes virus-6; HSV, herpes simplex virus; JCV, John Cunningham virus; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; MSA-C, cerebellar multiple system atrophy; NMOSD, neuromyelitis optica spectrum disorder; PML, progressive multifocal leukoencephalopathy; SCA, spinocerebellar ataxia; VEP, visual evoked potentials; VZV, varicella zoster virus; WNV, West Nile virus Adapted with permission from Abboud et al. [12]

Anatomical classification of autoimmune encephalitis	Differential diagnosis	Possible additional testing as appropriate
Limbic encephalitis	HSV, VZV, HHV6	CSF viral PCR, CSF VZV IgG/IgM
Cortical/subcortical encephalitis	ADEM, AHL, tumefactive MS, Marburg, PML, CJD, lupus cerebritis, Behcet, neurosarcoidosis, neurosyphilis, lymphoma, anoxic injury, seizure-related changes	MOG-IgG, CSF JCV PCR, CSF prion panel (RTQuIC), ANA/ENA, HLA-B51, ACE, CT chest (to rule out sarcoidosis), treponemal antibodies, CSF cytology and flow cytometry
Striatal encephalitis	CJD, WNV, toxic encephalopathy, anoxic injury, hyperglycaemic injury, uraemia	Prion panel, WNV IgM, CSF viral PCR, toxicology screen, metabolic panel
Diencephalic encephalitis	Neurosarcoidosis, Behcet, Wernicke, Whipple	ACE, CT chest (to rule out sarcoidosis), HLA-B51, thiamine level
Brainstem encephalitis	Rhombencephalitis (listeria), viral, CLIPPERS, neurosarcoidosis, Behcet, lymphoma, PML, CPM, Erdheim-Chester, Whipple	CSF bacterial culture, CSF viral PCR, HLA-B51, CSF cytology and flow cytometry, CSF JCV PCR, bone scan
Cerebellitis or cerebellar degeneration	Viral or post-viral cerebellitis, coeliac disease, Miller Fisher syndrome, vitamin E deficiency, MSA-C, SCA	Viral PCR, coeliac antibodies, anti-GQ1b, vitamin E level, DaT scan
Meningoencephalitis	Tuberculosis, neurosarcoidosis, Behcet, bacterial or viral infection, leptomeningeal carcinomatosis, GPA, IgG4-related disease	Bacterial PCR, ACE, CT chest, HLA-B51, CSF bacterial culture, CSF viral PCR, CSF cytology and flow cytometry
Encephalomyelitis and/or opticospinal syndrome	ADEM, WNV	MOG-IgG, WNV IgM, CSF viral PCR