Etiology, Epidemiology, and Pathogenesis

Meningitis is usually an acute process that is generally caused by either bacteria or viruses. Meningoencephalitis is predominantly caused by viruses, mostly enteroviruses.

Because enteroviruses are the most common cause of viral meningitis and meningoencephalitis, the incidence of these infections peaks in the summer and fall and wanes in the winter. Herpes family viruses such as herpes simplex virus (HSV) and varicella zoster (VZV) also cause meningoencephalitis, as can a number of other pathogens (Box 92-1).

Historically, the most common causes of bacterial meningitis beyond the neonatal period were Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b (Hib). Fortunately, there has been a dramatic reduction in the incidence of Hib infections after the introduction of the conjugate Hib vaccine in 1987. Additionally, there has been a reduction in the incidence of meningitis caused by S. pneumoniae since the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7); unfortunately, there are serotypes that are not contained in that vaccine that have the ability to cause disease in humans, so the effect of the PCV7has not been as dramatic as the Hib vaccine. The currently licensed vaccine for N. meningitidis covers serogroups A, C, W135, and Y. It does not elicit a protective response against serogroup B, which continues to cause both sporadic disease and outbreaks, mostly on college campuses and military bases.

All three of these bacteria colonize the upper respiratory tract (nasopharynx and oropharynx). From there, they are able to invade through the mucosal epithelium, usually when that surface is inflamed because of a viral infection, and enter the bloodstream. The bacteria circulate in the bloodstream and gain access to the CNS via the choroid plexus. The bacteria readily replicate in the subarachnoid space within the cerebrospinal fluid (CSF) because this area is normally sequestered from the immune system. In response to bacterial replication, white blood cells (WBCs) migrate to the CSF, and the ensuing inflammatory response leads to some of the signs and symptoms of meningitis.

In addition to hematogenous seeding of the CSF, bacteria can also gain access to the CNS via direct extension. Congenital malformations, such as dermoid sinuses, or traumatic injuries, including basilar skull fractures and penetrating trauma, can allow bacteria to enter the CSF. Infections of the sinuses, mastoid air cells, or middle ear can also act as portals of entry (Figure 92-1).

Figure 92-1 Bacterial meningitis.

Other causes of acute meningitis include Borrelia burgdorferi, the etiologic agent of Lyme disease; gram-negative bacilli such as Citrobacter, Salmonella, and Pseudomonas spp.; and fungal pathogens.

Clinical Presentation

Neonates and infants with meningitis often present with nonspecific signs and symptoms. The most common parental complaint is fever, and the infants frequently have a history of irritability and poor feeding. They may also develop vomiting and a bulging fontanelle. In more severe cases, infants may present with lethargy or after having a seizure and may have focal neurologic deficits on examination. Although children with meningitis can present in many ways, toddlers and school-aged children are more likely to present with the “classic” signs and symptoms. These include high fever, photophobia, headache, neck stiffness, and vomiting. Of these, fever and headache are the most common. On physical examination, these patients may have nuchal rigidity as well as Kernig’s or Brudzinski’s signs (Figure 92-2). Children with disseminated N. meningitidis infections can have a petechial or purpuric rash. Infants with enteroviral meningitis often have an erythematous, macular rash. Cranial nerve palsies, especially of cranial nerve 7, and papilledema are frequently found in patients with Lyme meningitis but are unusual in other forms of meningitis.

Figure 92-2 Kernig’s sign and Brudzinski’s neck sign.

Differential Diagnosis

The differential diagnosis of meningitis and meningoencephalitis depends on which signs and symptoms are prominent because the presentation of these infections is so varied.

The combination of fever and irritability in an infant or toddler has a very broad differential diagnosis, which includes many infectious and noninfectious etiologies. This is a situation in which a detailed medical history and thorough physical examination are critical in narrowing the differential diagnosis. There will almost always be additional information that helps to focus the differential. A history of vomiting or diarrhea points toward gastroenteritis. Tachypnea or focal findings on lung auscultation are a sign of pneumonia, either viral or bacterial. Torticollis or other unusual positioning of the head and neck or a history of drooling are concerning for a focal infection in the neck or upper thorax such as a retropharyngeal or peritonsillar abscess. Another consideration in this situation, especially for toddlers with low-grade fevers rather than high fevers, is a foreign body in the upper airway, esophagus, or trachea. Cardiac and metabolic abnormalities are also important considerations in neonates and infants who present with fever, irritability, poor feeding, and vomiting.

Neck stiffness or pain on neck flexion may also be caused by a number of processes. These include peritonsillar or retropharyngeal abscesses, cervical lymphadenitis, muscle strain or spasms, cervical epidural infections, and upper lobe pneumonia.

Seizures as an isolated symptom have many possible causes. These include epilepsy, brain tumors, CNS infections, or metabolic abnormalities (especially hypoglycemia). They may also occur secondarily to trauma.

As patient age increases and they are better able to verbalize their symptoms, the differential diagnosis becomes more focused. However, adolescents who present with fever and altered mental status may not be able to communicate with the medical team to describe their symptoms. The differential diagnosis of fever and altered mental status in an older child includes CNS infections, ingestions or drug use, and metabolic abnormalities including diabetic ketoacidosis.

Diagnostic Approach

The most important diagnostic procedure in the evaluation of a child with suspected bacterial meningitis is a lumbar puncture (LP; see Figure 92-1). An opening pressure should be measured at the time of the LP, and fluid should be sent for at least cell count with differential, gram stain and culture, protein, and glucose. If viral meningitis or meningoencephalitis is suspected, polymerase chain reaction tests for enteroviruses and HSV are useful. Viral culture is an additional way to make the diagnosis of viral meningitis, although many laboratories no longer perform this test. Various CNS infections have typical CSF parameters that can aid the clinician while the results of the CSF culture are pending (Table 92-1). If there is concern for elevated intracranial pressure (ICP) before performing the LP based on clinical signs such as papilledema or focal neurologic findings, it is reasonable to perform either a computed tomography (CT) scan or magnetic resonance imaging (MRI) study. These studies allow the clinician to determine whether there is a space-occupying lesion, such as a brain abscess or brain tumor, or dilatation of the ventricles. These findings indicate that there is a risk of brain herniation if a lumbar puncture were performed.

Table 92-1 Typical Cerebrospinal Fluid Parameters

Blood tests can yield additional information in children with meningitis. Although blood cultures are rarely positive, it is useful to draw a blood culture prior to the administration of antibiotics, especially if there may be a delay in performing the LP. A complete blood count (CBC) occasionally has an elevated WBC count. This is a nonspecific finding, and the remainder of the CBC is usually normal. The results of a basic metabolic panel is rarely abnormal, although some patients develop the syndrome of inappropriate antidiuretic hormone secretion and subsequently have hyponatremia. Inflammatory markers such as an erythrocyte sedimentation rate and C-reactive protein are rarely helpful and do not reliably differentiate between bacterial meningitis and other causes of meningitis. If Lyme meningitis is suspected, tests for serologic evidence of Lyme exposure are useful as long as there is a confirmatory test included in the laboratory analysis.

Management and Therapy

Patients with bacterial meningitis can be critically ill and may require admission to an intensive care unit for management of their airway and circulation. In addition to respiratory and cardiovascular support, antibiotics are the most important intervention in the treatment of patients with bacterial meningitis. In patients in whom the risk of bacterial meningitis is high, antibiotics should not be withheld pending the results of diagnostic procedures or radiographic scans. Empiric antibiotic selection should be made based on local resistance patterns, and the final treatment decision should be made based on the CSF culture and sensitivity reports. In general, the combination of an intravenous (IV) third-generation cephalosporin such as ceftriaxone or cefotaxime plus vancomycin offers excellent activity against the most common pathogens. If gram-negative bacilli are seen on the CSF Gram stain, some experts recommend broader gram-negative coverage with meropenem and consideration of adding an aminoglycoside while awaiting the results of the CSF culture. The recommended duration of therapy varies according to the causative pathogen. In general, N. meningitidis meningitis is treated for 7 days, Hib meningitis for 7 to 10 days, and pneumococcal meningitis for 14 days.

The treatment of enteroviral meningitis consists of supportive care of the patient. If HSV disease is suspected, IV acyclovir is the drug of choice and is administered in three doses of 20 mg/kg/m² per day for 3 weeks. For Lyme meningitis, the current recommendation is 14 to 28 days of ceftriaxone.

The role of dexamethasone in the treatment of children with bacterial meningitis continues to be controversial. Studies of patients with Hib meningitis found that children treated with dexamethasone had decreased morbidity and mortality. This finding has not been reproduced for other causes of bacterial meningitis. Randomized trials have found a suggestion that dexamethasone therapy 1 hour before antibiotic therapy is associated with less hearing loss in children with S. pneumoniae meningitis, but this finding did not reach statistical significance.

The most common sequela of bacterial meningitis is sensorineural hearing loss, and all children with meningitis are recommended to have a hearing test after completion of therapy. Most patients with enteroviral meningitis recover with no long-term sequelae. Neonates with HSV meningitis have high rate of morbidity and mortality, and older children with HSV meningitis often have long-term neurologic deficits.