Table 4.
Directed Differential Diagnosis of Encephalitis in US Children
| Risk Category | Established Etiology | Rare cause/mimic |
|---|---|---|
| Age | ||
| Neonates/infants | HSV, CMV, EV, HPeV | Toxoplasma gondii, Treponema pallidum, Zika virus |
| Teenagers | HIV, EBV, WNV | Treponema pallidum |
| Vaccination History | ||
| Unvaccinated | Measles, Mumps, Rubella, VZV, Poliovirus | |
| Recently Vaccinated | ADEM | |
| Season | ||
| Summer/fall | EV, WNV, LACV | Rickettsia, Ehrlichia, Anaplasma, Borrelia burgdorferi |
| Winter | Influenza, adenovirus | respiratory viruses |
| International Travel | ||
| Endemic regions | Rabies, JEV, TBEV, Measles | TB, dengue, chikungunya, Zika, Plasmodium |
| Animal Exposure | ||
| Bat/Skunk bite | Rabies | |
| Raccoon feces | Baylisascaris procyonis | |
| Rodent | LCMV | |
| Cat | Bartonella henselae | |
| Mosquito | WNV, LACV, EEEV, SLEV | |
| Tick | Powassan | Rickettsia, Ehrlichia, Anaplasma, Borrelia burgdorferi |
| Activity | ||
| Freshwater swimming | Naegleria fowleri, Acanthamoeba | |
| Eating Unpasteurized Dairy | Listeria monocytogenes | Toxoplasma, Brucella, Coxiella |
| Eating Undercooked Meat | Toxoplasma | |
| Eating Undercooked Seafood, Unwashed Vegetables | Angiostrongylus sp. | |
| Clinical Findings | ||
| Vesicular Rash | HSV, VZV, EV | |
| Lymphadenopathy | Generalized: EBV, CMV, HIV, Localized: Bartonella | |
| Psychiatric/behavioral Changes | Rabies, anti-NMDAR | |
| Respiratory symptoms | Mycoplasma, influenza, adenovirus | respiratory viruses |
| Retinitis or keratitis | WNV, CMV, Bartonella | Toxoplasma gondii, Treponema pallidum, Toxocara canis/catis |
| Parotitis | Mumps, influenza, respiratory viruses | |
| Eosinophilic CSF | Angiostrongylus sp. | Baylisascaris procyonis, Naegleria fowleri, Balamuthia mandrillaris, Acanthamoeba, TB, fungi, Toxocara canis/catis |
| Imaging/EEG Localization | ||
| Frontal lobe | Naegleria fowleri | |
| Temporal lobe | HSV | |
| Thalamus/basal ganglia | WNV, influenza | Respiratory viruses |
| Cerebellum | VZV | |
| Brainstem/basilar | Listeria monocytogenes, EV-A71, HSV | TB |
| Myelitis | Poliovirus, non-polio EVs, WNV, JEV |
Bolded organisms signify potentially treatable pathogens. Rare/cause mimics include pathogens which are rare causes of encephalitis in immunocompetent US children or which cause a clinical syndrome which mimics encephalitis. Abbreviations: HSV=herpes simplex virus, CMV=cytomegalovirus, EV=enterovirus, HPeV=human parechovirus, HIV=human immunodeficiency virus, EBV=Epstein-Barr virus, WNV=West Nile virus, LACV=La Crosse virus VZV=varicella zoster virus, ADEM=acute disseminated encephalomyelitis, JEV=Japanese encephalitis virus, TBEV=tick-borne encephalitis virus, TB=tuberculosis, LCMV=lymphocytic choriomeningitis virus, EEEV=eastern equine encephalitis virus, SLEV=St. Louis encephalitis virus, anti- NMDAR=anti-N-methyl-D-aspartate receptor encephalitis.