Table 1.

Overview of presentation, diagnosis, and management of the WHO Diseases of Epidemic & Pandemic Potential.

Disease name	Vaccine available	Highest level of evidence for neurological manifestations	Affects CNS, PNS, or both	Most common systemic presentation	Most common neurological presentation	Pathogen found in CSF	Neuroimaging findings	Management
Chikungunya	No	Case series, case-control study, cross-sectional study (with systematic review covering all of these)	Majority CNS, 25% PNS	Fever, malaise, arthralgias	Encephalopathy, myelitis	IgM found in CSF	Punctate foci of T2 signal in periventricular, limbic areas	Supportive care
Cholera	Yes	Retrospective analysis, case series	CNS	Diarrhea, dehydration	Meningitis, abscess	Yes	Uncertain	Aggressive volume repletion plus antibiotic therapy
COVID-19	No	Case series, case reports	CNS, PNS	Fever, chills cough, shortness of breath, fatigue, myalgias, headache, loss of taste or smell, nausea, vomiting, diarrhea	Encephalitis, headache, Guillain-Barre syndrome, myelitis	Uncertain	Uncertain	Supportive care
Crimean-Congo hemorrhagic fever	No	Prospective cohort study, case series	CNS	Fever, myalgias, GI disturbance, hemorrhage	Headache, dizziness, encephalopathy, ICH	Uncertain, viral RNA found in brain tissue in animal models	Normal findings, or diffuse hemorrhage	Supportive care
Ebola virus disease	Yes	Large prospective cohort study	Majority CNS	High fevers, fatigue, myalgias, conjunctival injection, chest pain, arthralgias.	Headache, diffuse weakness, encephalopathy	Yes	Punctate T2 and DWI lesions in corpus callosum and cerebral white matter*	Supportive care
Hendra virus infection	No human vaccine available	Case series	CNS	Fever, respiratory symptoms	Headache, meningitis, encephalitis, seizures	Antibodies found in CSF; likely viral inclusion bodies on autopsy	Early isolated cortical signal, later deep white matter involvement	Supportive care
Influenza	Yes	Large prospective cohort study	CNS and PNS	Fever, headache, myalgia, malaise	Headache, seizure, encephalopathy	Rarely	Increased DWI signal in cortex and adjacent white matter	Supportive care
Lassa fever	No	Retrospective case series	CNS	80% asymptomatic; otherwise malaise, fever, bleeding	Sensorineural hearing loss, encephalopathy	Yes	Uncertain	Supportive care
Marburg virus disease	No	Case series, case studies	CNS	High fever, headache, malaise, myalgias, diarrhea, hemorrhage	Encephalitis, headache, hemorrhage	Antibodies in CSF	Uncertain	Supportive care
MERS-CoV	No	Retrospective case series	CNS and PNS	Respiratory disease with fever, cough, shortness of breath	Headache, encephalopathy, seizures, focal motor deficits, weakness, paresthesias, ophthalmoplegia and ataxia	No	Patchy diffusion restriction and T2 hyperintensity	Supportive care
Monkeypox	No, although some cross-reactivity from smallpox vaccine	Two case reports	CNS	Asymptomatic, or fevers and rash	Encephalitis	Uncertain	Uncertain	Supportive care
Neisseria meningitidis meningitis	Yes	Large retrospective cohorts and reviews	CNS	Fever, nausea, vomiting, myalgias, petechial rash, sepsis	Headache, neck stiffness, altered mental status	Yes	Non-specific T2 abnormalities	Antibiotic therapy plus prophylaxis for close contacts
Nipah virus infection	No	Case series	CNS	Viral pneumonia, fever	Fulminant encephalitis with headache and meningismus	Antibodies in CSF	Many asymmetric, small lesions in subcortical white matter	Supportive care
Plague	Yes, although no longer available in U.S.	Retrospective analysis, case series	CNS	Buboes, high fever, shock	Meningitis	Yes	Uncertain	Antibiotic therapy plus prophylaxis for face-to-face exposures
Rift valley fever	No, but an inactivated vaccine has been trialed in humans	Prospective study, Case-control study, cross-sectional study	CNS	Mild flu-like illness, fever, joint paint pain, muscle ache	Encephalopathy, meningoencephalitis	No, but found in animal studies	Bilateral asymmetrical cortical hyperintense areas*	Supportive care
SARS	No	Case studies, case reports	CNS	Fever, cough, shortness of breath, diarrhea	Headache, encephalitis	Yes	Uncertain	Supportive care
Smallpox	Yes, but not commonly available	Case-series, retrospective analysis (for vaccine related complications)	CNS	Fevers, malaise, vesicular/pustular rash	Encephalopathy, headaches	Uncertain	Uncertain	Supportive care; tecovirimat FDA-approved but sparsely tested
Tularemia	No	Case reports	CNS and PNS	Fever, regional tender lymphadenopathy, conjunctivitis, pharyngitis, pneumonia	Overall rare, though meningitis, ataxia, polycraniitis, and Guillain Barre syndrome have been reported	Yes	Meningeal enhancement, scattered T2-intense lesions. Can present with abscess.	Antibiotic therapy
Yellow fever	Yes	Case-series, retrospective study	CNS	Fevers, minority with hemorrhagic fever	Encephalopathy, seizures	Yes	Petechiae, perivascular hemorrhages and edema	Supportive care
Zika virus disease	No	Large retrospective cohorts	CNS and PNS	Fever, arthralgias, headache, rash	Guillain-Barre syndrome, fetal microcephaly	Yes	Typical GBS findings; infants: subcortical calcifications and microcephaly	Supportive care

^*Characterized only in individual case report.