Diagnostic Considerations

See the following for complete information on these topics:

Other conditions to be considered include the following:

Myoclonus
Partial seizures with secondary generalization
Seizure, partial (focal)
Benign epilepsy syndromes
Pseudomigraine with CSF pleocytosis

Differential Diagnoses

Workup

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Table 1. Examples of Physiologic Roles of Known Viral Receptors

Virus	Receptor	Abbreviation/Synonym	Function
Measles virus	Membrane cofactor protein	CD46	Regulates complement and prevents activation of complement on autologous cells
Poliovirus	CD155	hPVR/CD155	Expressed on primary human monocytes; supports poliovirus replication in vivo
HSV	Heparan sulfate	None	Cell surface proteoglycans
	Herpesvirus entry mediator A	Hve A, HVEM	TNF receptor superfamily
	Herpesvirus entry mediator B	Hve B, Human nectin-2, or Prr2alpha-Hve B	Participate in organization of epithelial and endothelial junctions
	Herpesvirus entry mediator C	Hve C, nectin1delta, or Prr1-Hve C	Immunoglobulin superfamily
	TNFSF14	hTNFSF14/HVEM-L	TNF receptor superfamily
Rabies virus	Nicotinic AChR (a-bungarotoxin binding site)	AChR	Nicotinic AChR
	NCAM	NCAM, CD56, D2CAM, Leu19, or NKH-1	Cell adhesion glycoprotein of immunoglobulin superfamily
	NGFR	NGFR	NGFR
	p75 neurotrophin receptor (p75NTR)	p75NTR
HIV-1	CD4	CD4	T lymphocyte protein with helper or inducer function in immune system
	CCR3	CCR3	Chemotactic activity
	CCR5	CCR5	Coreceptor for macrophage-tropic strain
	CCR6	CCR65	Chemotactic activity
	CXCR4	CXCR4	Coreceptor for CD4
JC virus	N-linked glycoprotein with alpha 2-6 sialic acid	N-linked glycoprotein	Unknown
Japanese B virus^[6]	Protein GRP78	---	ER-stress response protein
AChR—acetylcetylcholine receptor; CCR—chemokine receptor; HSV—herpes simplex virus; NCAM—neural cell adhesion molecule; NGFR—nerve growth factor receptor; TNF—tumor necrosis factor.

Table 2. Common Viral Encephalitides: Part 1

Virus (Family)	Viral Structure	Transmission	Mortality	Specific Clinical Patterns	Sequelae	Season
HSV (herpesvirus)	ds DNA	Unknown	70% if untreated	Rare forms: subacute, psychiatric, opercular, recurrent meningitis HSV-1: brainstem; HSV-2: myelitis	Common	All year
VZV (herpesvirus)	ds DNA	Direct contact (air), highly contagious	Variable; low in children	Rash, encephalitis in 0.1-0.2% of children with chickenpox; cerebellar ataxia (cerebellitis)	Adults worse; cerebellitis good	Late winter, spring
Influenza virus (orthomyxovirus)	ss RNA	Direct contact (air), highly contagious	Unknown	Reversible frontal syndrome in children; Guillain-Barré, myelitis	Parkinsonism (encephalitis lethargica)	Usually winter
Enteroviruses (picornavirus)	ss RNA	Fecal-oral route	Low; high for enterovirus 71	Herpangina; hand, foot, mouth disease; enterovirus 71 causes rhombencephalitis	Mild, except for enterovirus 71	Summer, fall; tropics: no season
Rabies virus (rhabdovirus)	ss RNA	Dogs, wild animals (eg, fox, wolf, skunk)	Virtually 100%	Paresthesias; confusion, spasms, hydrophobia; brainstem features	Mortality virtually 100%	All year
ds—double strand; HSV—herpes simplex virus; ss—single strand; VZV—varicella-zoster virus.

Table 3. Common Viral Encephalitides: Part 2

Virus (Family)	Viral Structure	Transmission	Mortality	Specific Clinical Patterns	Sequelae	Season
Lymphocytic choriomeningitis virus (arenavirus)	ss RNA	Rodents	Low (< 1%)	Progressive fever and myalgia; orchitis; aseptic meningitis; leukopenia, thrombocytopenia	Rare	More in winter
Lassa virus (arenavirus)	ss RNA	Rodents	15%	Multisystem disease; proteinuria	Deafness (one third)	All year
Mumps virus (paramyxovirus)	ss RNA	Direct contact (air), highly contagious	Low	Parotitis, pancreatitis, orchitis, aseptic meningitis	Frequent sequelae	Winter and spring
Measles virus (paramyxovirus)	ss RNA	Direct contact (air), highly contagious	10%	Characteristic rash; frequent EEG changes; myelitis	Frequent: mental retardation, seizures, SSPE	Winter and spring
Nipah virus (paramyxovirus)	ss RNA	Pigs; bats	40-75%	Brainstem or cerebellar signs; segmental myoclonus, dysautonomia	SSPE-like syndrome?	All year
ds—double strand; EEG—electroencephalographic; ss—single strand; SSPE—subacute sclerosing panencephalitis.

Table 4. Common Arboviral Encephalitides

Virus (Family)	Vector	Reservoir	Mortality	Specific Clinical Patterns	Sequelae	Season
Eastern equine virus (alphavirus)	Aedes sollicitans	Birds	35%	Severe, rapid progression	Common, especially in children	June to October
Western equine virus (alphavirus)	Culex tarsalis	Birds	10%	Classic encephalitis	Moderate in infants; low in others	July to October
Venezuelan equine encephalitis virus (alphavirus)	Mosquito species	Horses, small mammals	~ 0.4 %	Low rate (4%) of CNS involvement	Mild	Rainy season
St Louis encephalitis virus (flavivirus)	Culex pipiens,C tarsalis	Birds	2% in young people; 20% in elderly people	SIADH	More in elderly people	August to October
Japanese encephalitis virus (flavivirus)	Culex taeniorhynchus	Birds	33% (50% in elderly people)	Extrapyramidal features	50% neuro psychiatric; parkinsonism	Summer
West Nile virus (flavivirus)	Culex,Aedes spp	Birds	In US: 12% (elderly people only)	Motor or brainstem involvement	Usually not prominent	Summer
Far East encephalitis virus (flavivirus)	Ixodes persulcatus (tick)	Small mammals, birds	20%	Epilepsia partialis continua	Frequent; residual weakness	Spring to early summer
Central European encephalitis virus (flavivirus)	Ixodes ricinus (tick)	Small mammals, birds	Less common than in Far East	Limb-girdle paralysis (spine/medulla)	Less common than in Far East	April to October
Powassan virus (flavivirus)	Ixodes cookei (tick)	Small mammals, birds	High	Severe encephalitis	Common (50%)	May to December
Dengue virus (flavivirus)	Aedes spp	Mosquitoes	Low, except hemorrhagic	Flulike syndrome; possible CNS involvement	Mild, except for hemorrhagic	Rainy season
La Crosse virus (bunyavirus)	Aedes triseriatus	Small mammals	Low (< 1%)	Mild, primarily in children	Mild; seizures	Summer
Colorado tick fever virus (orbivirus)	Dermacentor andersoni (tick)	Small mammals	Low		Mild
CNS—central nervous system; SIADH—syndrome of inappropriate antidiuretic hormone secretion.

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Author

Francisco de Assis Aquino Gondim, MD, PhD, MSc, FAAN Professor Adjunto of Neurology and Clinical Skills, Department of Internal Medicine, Universidade Federal do Ceará, Brazil

Francisco de Assis Aquino Gondim, MD, PhD, MSc, FAAN is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, International Parkinson and Movement Disorder Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Consultant for Pfizer, PTC Therapeutics and Alnylam<br/>Serve(d) as a speaker or a member of a speakers bureau for: Speaker for Shire, PTC Therapeutics and BSL Beringer<br/>Received travel grants from for: Aché, Biogen, Genzyme, Ipsen, Novartis, Baxter, Teva, Pfizer.

Coauthor(s)

Florian P Thomas, MD, PhD, MA, MS Chair, Neuroscience Institute and Department of Neurology, Director, Hereditary Neuropathy Center, Co-Director, Center for Memory Loss and Brain Health, Co-Director, ALS Center, Hackensack University Medical Center; Associate Dean of Faculty, Founding Chair and Professor, Department of Neurology, Hackensack Meridian School of Medicine

Florian P Thomas, MD, PhD, MA, MS is a member of the following medical societies: Academy of Spinal Cord Injury Professionals, American Academy of Neurology, American Neurological Association, Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Gisele Oliveira, MD Resident Physician, Department of Neurology, St Louis University School of Medicine

Gisele Oliveira, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

J Stephen Huff, MD, FACEP Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

J Stephen Huff, MD, FACEP is a member of the following medical societies: American Academy of Neurology, American College of Emergency Physicians, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Viral Encephalitis Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

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