The Child With Aseptic

Meningitis
Jason G. Newland, MD,* Samir S. Shah, MD, and Theoklis E. Zaoutis, MD

EDUCATIONAL OBJECTIVES

To realize that partially treated bacterial

meningitis may present with similar
cerebrospinal fluid findings as viral
meningitis.
To realize that the course of enteroviral
meningitis usually is self-limited and benign.
To realize that enteroviruses are the most
common cause of aseptic meningitis and may
be detected within 24 hours using RT-PCR.

Key Questions
1 What is meant by the term aseptic meningitis?
2 What are the most common causes of aseptic
meningitis?

3 What clinical and laboratory features suggest

enteroviruses as the most likely cause of this
toddlers illness?
4 What laboratory test(s) can be performed to
confirm diagnosis?
5 What is the prognosis for aseptic meningitis?
The child with fever, headache, stiff neck, and photophobia requires prompt evaluation for meningitis.
Bacterial meningitis mandates rapid initiation of antimicrobial therapy whereas aseptic meningitis is often selflimited and needs no specific therapy. Because discrimination between these two entities at the time of
presentation may be difficult, children with these symptoms and cerebrospinal fluid (CSF) pleocytosis are frequently admitted to the hospital to receive broad-spectrum antibiotics pending bacterial culture results. CSF
From the *Department of Pediatrics, University of Nebraska Medical Center/
Creighton University Medical Center, Omaha, NE and the Divisions of
General Pediatrics and Infectious Diseases, The Childrens Hospital of
Philadelphia, Philadelphia, PA.
Address correspondence and reprint requests to Dr. Samir S. Shah, 2nd
floor, Division of General Pediatrics, The Childrens Hospital of
Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA
19104. E-mail: shahs@email.chop.edu

218

cell counts have wide areas of overlap between aseptic

and bacterial meningitis, and the administration of antibiotics before lumbar puncture may hinder accurate diagnosis. Advances in the use of polymerase chain reaction techniques may alter our management of the child
with meningitis. In this issue, we discuss the diagnostic
and therapeutic approaches to the child with aseptic
meningitis, with a focus on enteroviral infection, which
is the most common identifiable cause in children.

Case Presentation

In August, a previously healthy 3-year old boy presented to the general pediatric clinic with a 2-day
history of fever as high as 38.9C. He has experienced nonbilious emesis, decreased activity, and anorexia. He has not traveled recently and does not
have any pets. He has not received antibiotics before
the evaluation. Ill contacts include his mother and
brother, who both have fever, cough, and rhinorrhea. On examination, the child was alert and responded appropriately. There was marked photophobia and nuchal rigidity. The tympanic
membranes were normal in appearance and mobility. There was no lymphadenopathy, abdominal tenderness, or petechiae. The remainder of the examination was normal.
A complete blood count revealed 10,000 white
blood cells/mm3 with 55% neutrophils, 3% bands,
37% lymphocytes, 3% monocytes, and 2% eosinophils. CSF analysis showed 3 red blood cells/mm3
and 110 white blood cells/mm3 with 23% neutrophils, 58% lymphocytes, and 19% monocytes. The
CSF protein and glucose were 55 mg/dl and 50
mg/dl, respectively. The serum glucose was 90 mg/
dl. No organisms were identified on CSF Gram stain.

What is meant by the term aseptic

meningitis?
Aseptic meningitis syndrome refers to meningeal
inflammation in the absence of a readily identifiable
bacterial cause.1 Although viruses are most commonly implicated, no cause can be identified in up to
40% of cases. If the patient has received antibiotics
Pediatric Case Reviews Volume 3 Number 4 October 2003

before lumbar puncture, a negative CSF culture does

not exclude a bacterial etiology.
Clinical Pearl: Partially treated bacterial meningitis may present with similar CSF findings as viral
meningitis. This possibility should be considered in
every patient presenting with aseptic meningitis.

What are the most common causes of

aseptic meningitis?
The diverse common causes of aseptic meningitis
include infectious agents (Table 1) and noninfectious
conditions (Table 2).2 Non-polio enteroviruses (EV),
including coxsackieviruses A and B, echoviruses, and
numbered enteroviruses, account for approximately
95% of all cases of aseptic meningitis in which a causative agent is identified.1 In the United States, enteroviral disease occurs during the summer and early autumn. In humans, the only known reservoir,
transmission of the virus occurs via the fecal oral
route.
Other infectious disease considerations during the
summer and autumn include tick-borne illnesses (e.g.,
Rocky Mountain spotted fever, ehrlichiosis, and
Lyme disease) and arbovirus infections. Arboviruses
(arthropod-borne viruses) primarily cause encephalitis but are also associated with aseptic meningitis, particularly during epidemic periods. The most common
arthropod vector-transmitted causes of aseptic meningitis in the United States are St. Louis encephalitis
virus (SLE), California encephalitis virus (LaCrosse
strain), Eastern equine encephalitis, Western equine
encephalitis, and West Nile virus (WNV). SLE virus
caused 60% of childhood cases of aseptic meningitis
during one epidemic period.3 During 2002, West Nile
virus, another flavivirus, was responsible for the largest arboviral meningoencephalitis epidemic documented in the Western hemisphere. However, only 31
(1%) of the 2,354 reported cases occurred in children
younger than 9.4
Unlike EV, tick-borne illness, and arboviruses,
lymphocytic choriomeningitis (LCM) virus is primarily seen during the winter months. The reservoirs for
this virus include house mice, guinea pigs, and hamsters. Cases of LCM virus disease are more common
in the winter as a result of the migration of mice indoors.5 Influenza A and B may also cause aseptic meningitis during the winter months.1 Other causes of
aseptic meningitis such as herpes simplex virus do not
have such a clear seasonal distribution.
Mycobacterium tuberculosis should also be considered in the child with aseptic meningitis, especially
if the patient has a subacute onset, modest lymphocytic pleocytosis, and protein and glucose abnormalities similar to those seen in bacterial meningitis (low
CSF glucose and elevated CSF protein). Fungi and
parasites are rare causes.

What clinical and laboratory features

suggest enteroviruses as the most likely
cause of this toddlers illness?
Pediatric Case Reviews Volume 3 Number 4 October 2003

TABLE 1 Differential Diagnosis for

Aseptic Meningitis
Syndrome

Enteroviruses
Echoviruses
Group A and B coxsackieviruses
Poliovirus
Numbered enteroviruses
Herpes viruses
Herpes simplex virus 1 and 2
Varicella-zoster virus
Cytomegalovirus
EpsteinBarr virus
Human herpes virus 6
Respiratory viruses
Influenza A and B
Parainfluenza viruses
Adenoviruses
Arboviruses
St. Louis encephalitis virus
Eastern equine encephalitis virus
Western equine encephalitis virus
LaCrosse virus
West Nile virus
Other Viruses
Human immunodeficiency virus (HIV)
Mumps virus
Lymphocytic choriomeningitis virus
Rabies virus
Spirochetes
Leptospira species (leptospirosis)
Borrelia burgdorferi (Lyme)
Treponema pallidum (syphilis)
Rickettsiae
Rickettsia rickettsii (Rocky Mountain spotted fever)
Rickettsia typhi (typhus)
Bacteria
Partially treated meningitis
Mycobacteria tuberculosis
Mycoplasma pneumoniae
Brucella species
Bartonella species (cat-scratch disease)
Parameningeal infection (e.g., mastoiditis, brain abscess)
Fungi
Cryptococcus neoformans
Coccidioides immitis
Histoplasma capsulatum
Parasites
Taenia solium (cysticercosis)
Toxoplasma gondii
Baylisascaris procyonis
Plasmodium falciparum (malaria)

Enteroviral meningitis is primarily seen in children, with those younger than 1 year affected most
frequently.6 The illness begins with fever (38 40C),
anorexia, and vomiting.7 Headache, a common symptom in children old enough to comprehend and communicate this as a symptom, develops 2 to 3 days
later. In children older than 1 year, nuchal rigidity and
photophobia are common.7 The presence of other
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TABLE 2 Noninfectious Causes of

Aseptic Meningitis

Vascular Disease
Subarachnoid hemorrhage
Cerebral venous thrombosis
Primary vasculitis (e.g., systemic lupus erythematosus)
Malignancy
Primary central nervous system tumor
Metastatic spread
Systemic Disease
Behcet disease
Kawasaki disease
Sarcoid
Status epilepticus
Others
Iatrogenic Conditions
Intrathecal medications
Ventricular shunts
Spinal anesthesia

identifiable enteroviral syndromes in the community,

such as herpangina and hand-foot-mouth disease,
supports the diagnosis, because outbreaks tend to be
epidemic and seasonal.8 CSF analysis in children with
enteroviral meningitis reveals a white blood cell count
(WBC) typically between 100 and 500 cells/mm3, but
CSF WBC counts as high as 2,000 cells/mm3 occasionally occur. In the first 1 or 2 days of illness neutrophils predominate, but transition to a lymphocytic
pleocytosis may occur within several days.9 Normally, the CSF protein concentration is mildly increased whereas the CSF glucose is normal.

What laboratory test(s) can be performed

to confirm diagnosis?
In the past, isolation of EV in cell culture was the
mainstay of laboratory diagnosis. Although cell culture allows for accurate diagnosis, the time to virus
isolation by cell culture ranges from 4 to 8 days.10
This makes it unlikely that culture results will affect
clinical decision-making, especially if the patients
bacterial cultures remain negative and the symptoms
have resolved. Additionally, some EVs are difficult to
grow in cell culture. For example, group A coxsackieviruses require inoculation into suckling mice for
detection. This test is rarely used today.
Reverse transcription-polymerase chain reaction
(RT-PCR), a new diagnostic modality, has improved
the ability to detect EV. The EV RT-PCR assay amplifies the highly conserved 5' nontranslated region of
the EV genome, allowing for the detection of all EV
serotypes. More importantly, the sensitivity and specificity of this test are high, ranging 86% to 100% and
92% to 100%, respectively.11 In some tertiary care
medical centers, RT-PCR provides the clinician a result within 24 hours of specimen collection, offering
the potential for affecting patient management. Ram220

ers et al. showed that routine use of an enteroviral

RT-PCR assay on CSF samples decreased the length of
stay, duration of antibiotic use, and the use of ancillary tests in children with viral meningitis.12
Clinical Pearl: RT-PCR, the diagnostic test of
choice for EV meningitis, provides a rapid diagnosis,
allowing a clinician to discontinue antibiotics and
discharge the patient from the hospital sooner than
if cell culture methods were used.

What is the appropriate management for

this patient?
The management of EV meningitis is primarily
supportive. Children may require antipyretics, analgesia, and intravenous fluid hydration. The risk associated with bacterial meningitis makes it appropriate
to consider empirical therapy with an antibiotic active
against Streptococcus pneumoniae and Neisseria
meningitidis, the most likely bacterial pathogens. In
this case, the child received ceftriaxone and vancomycin. However, with the aid of RT-PCR it was possible
to discontinue these antibiotics once the EV genome
was amplified from the CSF.

What is the prognosis for aseptic

meningitis?
Overall prognosis in young children with EV meningitis is good,1 but serious complications occur in
approximately 10% of cases. Febrile seizures are the
most common complication.1 Rare complications include increased intracranial pressure, encephalitis,
and the syndrome of inappropriate antidiuretic hormone secretion.13 Most children with EV meningitis
will have a self-limited illness that lasts approximately
1 week. Therefore, no special follow-up is needed in
patients with uncomplicated EV meningitis.
Some patient populations are at increased risk for
prolonged and potentially severe EV disease. Because
humoral immunity is important in fighting EV infection, patients with antibody-deficient states such as
X-linked agammaglobulinemia, severe combined immune deficiency, and bone marrow transplant, are at
increased risk for having chronic EV disease.14 These
patients may receive the investigational antiviral
agent, pleconaril, for treatment. Pleconaril prevents
viral replication by inhibiting viral uncoating and
blocking viral attachment to host-cell receptors.15 Patients with certain antibody-deficient conditions
should also receive monthly immune globulin for prophylaxis against chronic EV meningoencephalitis.16

Conclusion
On the second day of hospitalization, the EV
genome was amplified from the CSF. The patients
symptoms improved and he was discharged with the
diagnosis of EV meningitis. Isolation by cell culture
did not occur until 5 days after the CSF was
collected.
Pediatric Case Reviews Volume 3 Number 4 October 2003

Summary of Key Points

are the most common cause of

Enteroviruses
aseptic meningitis and may be detected within
24 hours using RT-PCR.

treated bacterial meningitis may

Partially
present with CSF findings similar to those
seen with enterovirus infection. This possibility
should be considered in every patient
presenting with aseptic meningitis.

course of enteroviral meningitis usually is

The
self-limited and benign.
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