Neonatal Meningitis Workup

Updated: Feb 12, 2018
  • Author: Gaurav Gupta, MD, FAANS, FACS; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA  more...
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Approach Considerations

Delayed diagnosis of neonatal meningitis is a potentially critical pitfall. Failure to perform a lumbar puncture and detect infection in a neonate with mild fever and minimal, nonspecific clinical findings is problematic; all neonates in whom meningitis might be the cause of symptoms should undergo CSF examination. Delay in treatment because of equivocal laboratory screening tests or because findings are altered by prior partial treatment may cause significant harm.

In a 2001 survey of pediatricians, “meningitis or other infectious disease” and “newborn conditions other than congenital vision/hearing loss” were the 2 most frequent bases reported for malpractice suits. [28] In this survey, “the most prevalent condition for which claims were filed against pediatricians was neurological impairment of an infant. Thirty percent of claims paid were for this condition alone. However, the second most prevalent condition, meningitis, resulted in a higher percentage of paid claims (46%) and a higher total and average indemnity.”


Laboratory Studies

Suspected bacterial infection is often, but not uniformly, confirmed by positive results from cultures of cerebrospinal fluid (CSF) or blood. CSF cultures should be obtained in all symptomatic infants; despite the close relationship between bacterial sepsis and meningitis, it has been estimated that 15-30% of infants with CSF-proven meningitis will have negative blood cultures. [29]

A study from Duke emphasized that with the exception of CSF culture, no single CSF value can be relied upon to exclude neonatal meningitis. [30] The onus is on the clinician to justify initiation of antimicrobial and antiviral therapy, regardless of the CSF values.

Polymerase chain reaction (PCR) assay is a powerful diagnostic tool with excellent sensitivity and specificity. It permits identification of group B streptococcal (GBS) antigen in urine or CSF, and it is the standard for identification of herpes simplex virus (HSV) and enterovirus in CSF. In neonates, PCR is 71-100% sensitive for HSV but 98-99% specific. [16] If initial HSV PCR is negative and HSV meningitis is suspected, a repeat lumbar puncture 5-7 days later may be useful. Blood in the CSF can also lead to false-negative results.

As PCR becomes more widely available, recognition of enteroviral infections has increased. [12] Additionally, PCR for human parechovirus-3 is becoming more widely available.

Rapid screening is available with latex particle agglutination (LGA) testing of urine, which can be performed for GBS, E coli, and Streptococcus pneumoniae. Unfortunately, the presence of GBS antigen does not prove invasive disease.

If vesicles are present on the skin, evaluation for HSV infection should include cultures of fluid from these vesicles. Swabs of the nasopharynx, conjunctiva, and rectum have also been used to identify viral agents. DNA from HSV or enteroviruses can be identified from either vesicles or CSF by using PCR.

It should be kept in mind that interpretation of CSF findings is more difficult in neonates than in older children, especially in premature infants whose more permeable blood-brain barrier causes higher levels of glucose and protein.

The classic finding of decreased CSF glucose, elevated CSF protein, and pleocytosis is seen more with gram-negative meningitis and with late gram-positive meningitis; this combination also is suggestive of viral meningitis, especially HSV. Only if all 3 parameters are normal does the lumbar puncture provide evidence against infection; no single CSF parameter exists that can reliably exclude the presence of meningitis in a neonate. [30]

The number of white blood cells (WBCs) found in the CSF in healthy neonates varies according to gestational age. Many authors use a cutoff value of 20-30/µL. Bacterial meningitis commonly causes CSF pleocytosis greater than 100/µL, with predominantly polymorphonuclear leukocytes (PMNs) gradually evolving to lymphocytes. In neonates with viral meningitis, the picture may be similar but with a less dramatic pleocytosis. HSV meningitis may be particularly associated with a large number of red blood cells (RBCs) in the CSF.

If the mother is symptomatic, maternal investigation may be warranted; bacterial or viral cultures can provide valuable adjunctive information.


Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is the neuroimaging modality of choice for identifying focal areas of infection, infarction, secondary hemorrhage, cerebral edema, hydrocephalus, or, rarely, abscess formation. It should be considered in the context of focal neurological abnormalities, persistent infection, or clinical deterioration. Sinovenous occlusions, ventriculitis, and subdural collections are best diagnosed with MRI.

Follow-up MRI scans are useful for following the resolution of the infection, as well as for contributing to prognostication. If available, magnetic resonance spectroscopy can add important information on the metabolic function of the neonatal brain.

Several studies have documented periventricular white matter abnormalities on MRI in infants with neonatal meningitis. [31] Newer MRI technologies, including diffusion-weighted and diffusion tensor imaging, have allowed this association to be evaluated in more detail, and such evaluation may prove to have prognostic implications. [32]


Other Imaging Modalities

Although computed tomography (CT) carries the risk of exposing the neonatal brain to radiation, the rapidity and ease with which it can be obtained (in comparison with MRI) makes it useful in decision-making for potential neurosurgical interventions, such as ventriculostomy for hydrocephalus or surgical drainage of empyema or abscess. It may be particularly appropriate for a critically ill neonate being considered for neurosurgery.

Cranial ultrasonography provides an alternative imaging modality for critically ill neonates, but it does not provide optimal detail in all circumstances. However, it is a low-risk and thus is useful in monitoring ventricular size for hydrocephalus during the acute phase of meningitis.

Chest radiography provides important information about the lung parenchyma and the cardiac silhouette. Meningitis or sepsis may occur with pneumonia but may be indistinguishable from surfactant deficiency, pulmonary hypertension, and obstructive cardiac disease.



Electroencephalography (EEG) is not an essential part of the initial diagnostic process. However, in neonates who are unresponsive or have seizures presenting as episodes of apnea, bradycardia, or rhythmic focal movements, EEG monitoring provides useful information to guide treatment with anticonvulsant drugs.

EEG also has some prognostic utility. In a study by Klinger et al, infants with normal or mildly abnormal EEGs had better outcomes, whereas those with moderately-to-markedly abnormal EEGs were more likely to die or to suffer adverse outcomes. [33] In a study by Poblano et al, EEG was predictive of microcephaly and spasticity at 9-month follow-up. [34]


Lumbar Puncture

Lumbar puncture is indicated for evaluation of the CSF in all neonates suspected of having sepsis or meningitis, even in the absence of neurological signs.

Many clinicians are reluctant to perform this procedure on a critically ill infant. Although the theoretical complications of lumbar puncture include trauma, brain-stem herniation, introduction of infection, and hypoxic stress, none of these complications were reported in a meta-analysis of more than 10,000 infants who underwent lumbar puncture. [29]

Meningitis, however, increases the risk of death in neonates. Stoll et al reported a mortality of 23% in babies with CSF-proven meningitis, compared with a mortality of 9% in neonates whose lumbar puncture results were not consistent with meningitis. [35] Additionally, many infants who had negative blood cultures had positive CSF cultures, suggesting that cases of meningitis may be missed.

In cases of bacterial meningitis, repeat lumbar puncture should be performed 24-48 hours after initiation of therapy to ensure sterilization of the CSF. After a full course of therapy for PCR-proven HSV, repeat lumbar puncture should be undertaken to rule out incompletely treated infections.