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