A.Terminology. Aseptic meningitis refers to subarachnoid inflammation from any cause other than pyogenic bacteria or fungi. The differential includes viruses, other microorganisms, and non-infectious causes. Since most cases are caused by viruses, the terms "aseptic" and "viral" meningitis are often used synonymously.

herpes simplex
varicella-zoster
adenoviruses
Epstein-Barr virus
parvovirus (erythema infectiosum)
lymphocytic choriomeningitis virus

Non-Viral Infections
partially treated bacterial meningitis
parameningeal infection

spirochetal infections
syphilis
leptospirosis

fungal
cryptococcal meningitis
coccidioidomycosis
histoplasmosis

Rocky Mountain Spotted Fever
Mycoplasma pneumoniae
Bartonella henselae (cat scratch disease)
amebic meningoencephalitis

Non-Infectious Etiology
brain tumor
carcinomatous meningitis
chemical meningitis
intrathecal drugs and radiographic dyes
lead poisoning
benign intracranial hypertension

b. Large studies conducted from 1955 to 1962 among patients of all ages (1-3), found multiple agents
caused aseptic meningitis. Mumps virus and poliovirus infections are now controlled by
immunization in the U.S.

C. A prospective study conducted at three Baltimore hospitals from 1986 to 1990 showed > 90% of viruses
isolated from children under 2 y/o are coxsackie B viruses and echoviruses; coxsackie A viruses appear to
cause < 3% of cases (4).

A.Seasonality. Aseptic meningitis disease activity corresponds to the seasonal pattern observed with all
enterovirus infections, i.e., a marked summer-fall predominance. Disease occurs at a lower incidence at other
times of the year.

1. Based on continuous surveillance in Olmsted County, MN the overall population-based rate of physician-
diagnosed aseptic meningitis was 17.8 per 100,000 person-years from 1976 through 1981 (5). This rate
compares closely with the 17.8 cases per 100,000 persons under 20 years of age discharged from Maryland
hospitals from 1979 through 1983 (Unpublished Data, Hospital Services Cost Review Commission, State of
Maryland, 1984) and is similar to a two-year survey in Israel which found a rate of 21.6 per 100,000 person-
years (6).

2. The age-specific incidence has varied somewhat among different reported outbreaks (7-14), but most data
indicate that aseptic meningitis is predominantly a disease of infants less than a year of age. A declining
number of cases are recognized among persons within increasingly older age groups (7,10). These data are
likely to contain some case-ascertainment bias; i.e., febrile infants are more likely to have lumbar punctures
than older children and adults.

1. In the older child and adult aseptic meningitis presents with fever to 400 C, headache, meningismus, nausea
and vomiting (10). Other signs of enterovirus infection, i.e., rash, are present in a minority of cases. Altered
mentation, seizures, and focal neurological signs are unusual and suggest a diagnosis of
meningoencephalitis.

2. In infants less than a year of age the characteristic symptoms and signs of meningitis are difficult to elicit by history and exam. The most common symptoms are fever and irritability (15). In practice, aseptic meningitis is often diagnosed during the clinical evaluation of febrile infants without an apparent source of fever.

B. Laboratory Diagnosis
1. The peripheral WBC and differential are usually non-specific.
2. CSF examination (Table 3).

a. The CSF white cell count usually ranges from 10 to 500 cells, but WBC > 2000 have been reported in as
many as 18E/'0 of cases in one series (16). Virus may occasionally be isolated from the CSF of
symptomatic infants with CSF WBC counts (15,17).

a. Cell culture virus isolation rates from the CSF have varied from 20% to 90% in various reports. Viruses
are less often isolated from CSF than from the GI tract (Table 4). Enteroviruses are often isolated from the
oropharynx for 1-2 weeks after onset of symptoms, and from the feces for 3-8 weeks.

b. The use of the polymerase chain reaction (PCR) to detect enterovirus RNA in CSF is likely to be more
rapid and more sensitive than cell culture (20). Sawyer, et al, found that PCR detected enteroviral RNA in
97% of culture positive CSF specimens, and in 66% of of culture negative CSF specimens from aseptic
meningitis patients (21 ).

a. The most important task of the physician managing a suspected case of aseptic meningitis is to rule out
more serious, treatable causes of meningitis. This may be the most difficult when the patient has
previously received antibiotics that could potentially mask the diagnostic CSF findings of bacterial
meningitis.

( 1 ) Studies of large numbers of children withH. influenza bacterial meningitis suggest that prior antibiotic
treatment slightly but significantly reduces the rate of positive gram stain and culture results, the
percentage of CSF PMN, and the CSF protein concentration (23). However, virtually all patients with
partially treated bacterial meningitis will have one or more CSF values that suggest bacterial disease.

3. Tuberculous meningitis and cryptococcal meningitis may initially be confused with viral meningitis.
Persistence of CNS symptoms for more that 3-5 days, or progressive neurological dysfunction should
provoke a workup for these pathogens.

4. Spirochetal meningitis is most likely to occur in older children and adults
a. syphilis
b. leptospirosis
c. Lyme disease

12% of patients with aseptic meningitis developed signs of encephalitis during the acute illness (26). Specific signs included seizures (3.4%), weakness (1.0%), and coma (3.7%). Most patients were teenagers and young adults. Virtually all the complications were associated with