Table 22.4.

Laboratory diagnosis of selected viral diseases

Virus	CNS disease	Serology	Viral culture	Direct antigen	PCR/other
Herpes viruses
Herpes simplex	Temporal lobe encephalitis	About 2/3 seropositive on admission, not helpful in Dx	Almost always negative in CSF, throat, etc.	None for CSF	≥ 90 % sensitive on CSF—reference labs and some academic medical centers only
				FA can be done on brain biopsy
Varicella	Encephalitis in HIV patients	Not helpful diagnostically	Usually negative in CSF, throat, etc.	None for CSF	Reference labs only
				FA can be done on brain biopsy	MRI may be suggestive
Cytomegalovirus	Encephalitis in HIV patients	Almost always positive	Urine, throat, blood may be positive—consistent with but not proof of encephalitis	Antigenemia test on blood, positive test consistent with but not proof of encephalitis	If CSF positive, encephalitis likely, but asymptomatic HIV patients may also be positive
					MRI may be suggestive
Epstein-Barr Virus	Rare encephalitis in mononucleosis	Monospot test good presumptive test, may be negative in up to 20 % in 1st week	Not available	Not available	Reference labs only, not needed for diagnosis
		VCA-IgG and IgM, positive IgM virtually diagnostic
Human herpes virus 6 and 7 (HHV 6 and 7)	Seizures, encephalitis in 1–3 year olds	Reference labs only	Reference labs only	Not available	Reference labs only
Respiratory viruses
Influenza A and B	Parainfluenza occasionally, others rarely cause encephalitis	Not useful	NP swabs; throat washings	Direct antigen ELISA available for RSV (excellent sensitivity), and Influenza (moderately sensitive)	Not available
Parainfluenza 1–3			Cultures via bronchoscopy
Adenovirus			Excellent sensitivity, diagnostic if positive
Respiratory syncytial virus (RSV)
Enterovirus
Coxsackie	Summertime outbreaks of meningitis, meningoencephalitis	Not useful: too many serotypes and too much cross-reactivity	Send stool, throat, CSF	None	Available in reference labs, picks up most serotypes, may take a week to get results
Echovirus			If throat or CSF culture positive—diagnostically definitive
			If stool culture positive—presumptive (enteroviruses may be shed in stool for weeks)
Arboviruses
St. Louis encephalitis	Summertime outbreaks of encephalitis	Diagnostic, if positive	Generally not available	Not available	Not available
California encephalitis		Serum is preferred specimen; CSF not helpful
Western equine		Done in reference laboratory and public health labs
Eastern equine
La Crosse
West Nile virus
HIV	Encephalopathy	ELISA	Research labs only	P 24 antigen in serum	Reference labs, many tertiary medical centers, used for following treatment
		Confirm with Western Blot
Lymphocytic choriomeningitis virus	Meningitis	Reference laboratory	Not available	Not available	Not available
JC virus	Progressive multifocal leukoencephalopathy	Reference laboratory	Not available	Not available	Available in reference laboratories
	Mostly in HIV & other immunocompromised patients				Diagnostic if positive on CSF
					MRI highly suggestive
					Brain biopsy definitive
Rabies	Encephalitis	Reference or state public health labs	Research labs only	Direct fluorescent antibody staining of hair follicles in skin biopsy from nape of neck above the hairline—50 % positive in 1st week, higher later	RT-PCR may be available in reference labs, state public health labs. Send saliva, CSF, or tissue
		Antibody is generally undetectable before day 6, 50 % by day 8, and 100 % by day 15

Adapted with permission from Rand et al. [521]