INTRODUCTION AND EPIDEMIOLOGY
Meningitis is an inflammation of the leptomeninges, tissues that cover the brain and spinal cord. Untreated bacterial meningitis has a mortality of nearly 100%, so treat suspected bacterial meningitis promptly. Unfortunately, even with rapid antibiotic treatment, long-term neurologic sequelae occur. Viral meningitis has a range of severity. Mild cases resolve without sequelae. However, some viruses, such as herpes virus, can cause severe infections. Meningoencephalitis is an inflammation of the brain as well as the meninges. It is less common than meningitis but can be devastating.
The most common causes of bacterial meningitis vary with the child’s age. In neonates, important organisms are group B Streptococcus, Escherichia coli, and Listeria monocytogenes. Other gram-negative bacteria can be occasional causes of meningitis as well. In infants >1 month old and children, the leading organisms are Neisseria meningitides, Streptococcus pneumoniae, and Haemophilus influenzae type b. Vaccination programs have had a huge impact on the epidemiology of bacterial meningitis in developed countries. Prior to the widespread use of H. influenzae type b (Hib) conjugate vaccines, H. influenzae type b was the most common cause of bacterial meningitis in children in the United States. Since the introduction of Hib vaccines, the incidence of H. influenzae type b meningitis has decreased by 99% in the United States.1 Similar dramatic decreases have occurred in other developed countries. Immunization has also had a big impact on the incidence of meningitis from S. pneumoniae in the United States and other developed countries. At present, the primary cause of bacterial meningitis in the United States is N. meningitides.2 Other important causes of bacterial meningitis in children include Mycobacterium tuberculosis and Borrelia burgdorferi, the causative agent of Lyme disease.
Viral meningitis is fairly common. Enteroviruses are the most frequent cause. Meningoencephalitis can be caused by enteroviruses, arboviruses (including West Nile virus), and herpes viruses. Herpes simplex virus type 1 (HSV-1) infection occurs sporadically and causes a severe meningoencephalitis in children and adults. Herpes simplex virus type 2 (HSV-2) develops in neonates born to infected mothers. Varicella-zoster virus can cause CNS infections including acute cerebellar ataxia. Many other viruses can cause CNS infections, including cytomegalovirus, Ebstein-Barr virus, mumps virus, adenovirus, influenza virus, parainfluenza virus, rubeola virus, rubella virus, and rabies virus.
Fungal meningitis can occur in both normal and immunocompromised hosts. Important causes include Cryptococcus neoformans, Coccidioides immitis, and Candida albicans.
Parasite infections can cause eosinophilic meningitis, defined as meningitis with at least 10 eosinophils/mm3 of cerebrospinal fluid (CSF).3 The most frequent cause of eosinophilic meningitis throughout the world is helminth infection.
PATHOPHYSIOLOGY
Bacterial meningitis in children usually results from bacteremia, arising from organisms colonizing the nasopharynx. Less commonly, meningitis is caused by direct spread of bacteria from a contiguous site of infection, such as sinusitis, or from penetration of the CSF space from trauma, dermal sinus tracts, or open neural tube defects. Viral respiratory infections can increase the likelihood of meningitis if the nasopharynx is colonized by bacteria.
Meningitis starts with breakdown of the blood–brain barrier. Then organisms enter the subarachnoid space. Once there, they can multiply quickly because the CSF has low levels of complement, antibodies, and other host defenses. Bacterial cell wall components and toxins produce an inflammatory response that increases vascular permeability and attracts leukocytes. The inflammatory response is responsible for much of the damage that ensues. Viral pathogens also produce damage by direct tissue destruction as well inflammation.
CLINICAL FEATURES
Infants ≤30 days old are at risk for meningitis due to an immature immune response. Symptoms in this age group are variable and nonspecific and include both fever and hypothermia. Neonates can present with a history of lethargy, poor feeding, fussiness, bulging fontanelle, vomiting, diarrhea, seizures, grunting, or respiratory distress. Elements in the birth history that increase the likelihood of bacterial meningitis include prematurity, low birth weight, delivery complications, maternal infection, and maternal colonization with group B streptococci or herpes simplex. Some neonates present with few symptoms early in the course of their illness, so maintain a high degree of suspicion for early meningitis when confronted with a potentially sick newborn.
Certain signs and symptoms are especially helpful for diagnosing bacterial meningitis in infants and children. Caregiver reports of bulging fontanelle (likelihood ratio [LR] 8, 95% CI 2.4–26), or neck stiffness (LR 7.7, 95% CI 3.2–19), or seizures (outside of the febrile seizure range of 6 months to 6 years; LR 4.4, 95% CI 3.0–6.4), or reduced feeds (LR 2, 95% CI 1.2–3.4) are concerning for meningitis.4 Children with meningitis can present with the rapid onset of shock and altered mental status or with more gradual symptoms including fever, headaches, photophobia, upper respiratory symptoms, GI symptoms, irritability, and rash.
The World Health Organization’s Pocket Book of Hospital Care for Children reported the performance of signs and symptoms for bacterial meningitis in infants and children and did not find any single clinical feature distinctive enough to make a “robust diagnosis of bacterial meningitis.”5 However, the combination of fever, seizures, meningeal signs, and altered consciousness was consistently associated with bacterial meningitis.6
Infants with viral meningitis typically present with irritability and decreased activity. Headache and fever are the usual complaints in children. Other symptoms include photophobia, rashes, nausea, vomiting, and pain in the neck, back, and legs. Most children with West Nile virus will be asymptomatic or have mild illness. Severe neurologic illness from West Nile virus is more common in adults than in children.7 Arboviruses can cause viral meningitis, encephalitis or acute flaccid paralysis.
Herpes simplex virus can cause devastating infection in neonates. Infection can present in three ways: (1) as disseminated disease with involvement of the CNS in 60% to 75% of cases; (2) as primary CNS disease; or (3) as disease localized to the skin, eyes, and/or mouth. About two thirds of infants with disseminated or CNS disease will have skin lesions, but these may not be present at the time of diagnosis. Neonatal herpes infections, including herpes simplex meningitis, can occur at up to 6 weeks of age.8 Herpes infection can be transmitted through an infected maternal genital tract but may also be transmitted from a nongenital maternal infection, for example, if a mother with oral herpes kisses the baby. Herpes simplex encephalitis (HSV-1) beyond the neonatal period presents with fever, altered mental status, seizures, and focal neurologic findings. It occurs sporadically.
Neonates and infants <90 days old may have fever, normal temperature, or hypothermia. A normal temperature does exclude meningitis. Toxic appearance, lethargy, mottling, bulging fontanelle, abnormal cry, grunting, respiratory distress, and increased or decreased tone are all supportive of the diagnosis, but these signs can be absent. Jaundice or rash may occasionally be seen. Infants in the first months of life are unlikely to have a stiff neck. Fever in neonates (rectal temperature of 100.5°F or higher) should always prompt suspicion for meningitis. In the absence of fever, a clinician should be concerned about infants who are ill appearing, have the signs or symptoms listed earlier, or are just not “acting right” according to their caregivers.
Older infants (>90 days old) with meningitis may also have fever, hypothermia, toxic appearance, lethargy, mottling, bulging fontanelle, abnormal cry, grunting, and respiratory distress at presentation. Children (>36 months of age) may have fever and nuchal rigidity. The Kernig sign (with the patient lying supine and the hip flexed at 90 degrees, the patient cannot extend the knee fully without pain) and Brudzinski sign (with the patient lying supine, there is involuntary flexion of the legs with passive neck flexion) may be present. Children may have altered mental status, shock, focal neurologic signs, or signs of increased intracranial pressure. Rash or another focal sign of infection may be present. Consider bacterial meningitis in the child with seizures, outside the range of 6 months to 6 years.
DIAGNOSIS
In neonates, the most common causes of meningitis in the United States are group B Streptococcus, E. coli, and L. monocytogenes. Other organisms that cause meningitis include S. pneumoniae, other streptococci, nontypeable H. influenzae, Staphylococcus species, Klebsiella, Enterobacter, Pseudomonas, Treponema pallidum, and M. tuberculosis.9 Neonates can develop meningitis from primary viral infection with HSV or enteroviruses. The differential diagnosis of neonatal sepsis and meningitis includes infection from fungi (Candida) and protozoa (malaria crosses the placenta, and maternal malaria can infect the neonate). Noninfectious illnesses that can appear similar to sepsis and meningitis include cardiac disease, necrotizing enterocolitis, congenital adrenal hyperplasia, inborn errors of metabolism, and intracranial hemorrhage.
In older infants and children, the usual dilemma is differentiating acute viral and bacterial meningitis. The typical bacterial causes are N. meningitides, S. pneumoniae, and H. influenzae type b. Less common organisms include M. tuberculosis, Nocardia species, T. pallidum, and B. burgdorferi.2 Fungal infections and parasitic infections can produce infection of the CNS. Infections around the brain and spinal cord may appear similar to meningitis. Collagen vascular disease, malignancy, and certain drugs and toxins should also be included in the differential diagnosis.
All children suspected of having meningitis should undergo a lumbar puncture when they are clinically stable. Although establishing a diagnosis is important, patients who are unsTable but suspected of having bacterial meningitis should receive antibiotics as quickly as possible (see Table 117-1
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