Table 3

Differential diagnosis of autoimmune encephalitis anatomical syndromes and suggested additional testing

Anatomical Classification of autoimmune encephalitisDifferential diagnosisPossible Additional testing as appropriate
Limbic encephalitisHSV, VZV, HHV6CSF viral PCR, CSF VZV IgG/IgM
Cortical/subcortical encephalitisADEM, AHL, tumefactive MS, Marburg, PML, CJD, lupus cerebritis, Behcet, neurosarcoidosis, neurosyphilis, lymphoma, anoxic injury, seizure-related changesMOG-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 encephalitisCJD, WNV, toxic encephalopathy, anoxic injury, hyperglycaemic injury, uraemiaPrion panel, WNV IgM, CSF viral PCR, toxicology screen, metabolic panel
Diencephalic encephalitisNeurosarcoidosis, Behcet, Wernicke, WhippleACE, CT chest (to rule out sarcoidosis), HLA-B51, thiamine level
Brainstem encephalitisRhombencephalitis (listeria), viral, CLIPPERS, neurosarcoidosis, Behcet, lymphoma, PML, CPM, Erdheim-Chester, WhippleCSF bacterial culture, CSF viral PCR, HLA-B51, CSF cytology and flow cytometry, CSF JCV PCR, bone scan
Cerebellitis or cerebellar degenerationViral or post-viral cerebellitis, coeliac disease, Miller Fisher syndrome, vitamin E deficiency, MSA-C, SCAViral PCR, coeliac antibodies, anti-GQ1b, vitamin E level, DaT scan
MeningoencephalitisTuberculosis, neurosarcoidosis, Behcet, bacterial or viral infection, leptomeningeal carcinomatosis, GPA, IgG4-related diseaseBacterial PCR, ACE, CT chest, HLA-B51, CSF bacterial culture, CSF viral PCR, CSF cytology and flow cytometry
Encephalomyelitis and/or opticospinal syndromeADEM, WNVMOG-IgG, WNV IgM, CSF viral PCR
  • ADEM, acute disseminated encephalomyelitis; AHL, acute haemorrhagic 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.