Pediatrics, Meningitis and Encephalitis

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Pediatrics, Meningitis and Encephalitis

AUTHOR INFORMATION

Section 1 of 10

Authored by Robert Felter, MD, Chair, Professor, Department of Pediatrics and Adolescent Medicine, Tod Children's Hospital

Robert Felter, MD, is a member of the following medical societies: American Academy of Pediatrics

Edited by Garry Wilkes, MD, Director, Clinical Senior Lecturer, Department of Emergency Medicine, Bunbury Health Service; Robert Konop, PharmD, Pediatric Clinical Pharmacy Specialist Manager, Clinical Assistant Professor, Department of Clinical Pharmacy, University of Minnesota; Grace M Young, MD, Associate Professor, Department of Pediatrics, University of Maryland Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Scott H Plantz, MD, Research Director, Assistant Professor, Department of Emergency Medicine, Mount Sinai Medical Center

Author's Email:	Robert Felter, MD
Editor's Email:	Garry Wilkes, MD

eMedicine Journal, May 10 2001, Volume 2, Number 5

INTRODUCTION

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Background: Despite advances in antimicrobial and general supportive therapies, central nervous system (CNS) infections remain a significant cause of morbidity and mortality in children. As classical signs and symptoms are often not present, especially in the younger children, the diagnosis of CNS infections is a challenge to the emergency physician. Also, even for children who have had prompt diagnosis and treatment, there remains a high frequency of neurologic sequelae. This often leads to legal action against the emergency physician. The emergency physician is faced with the daunting task of separating out those few children with CNS infections from the vast majority of children who come to the ED with less serious infections.

Pathophysiology: To develop bacterial meningitis, the invading organism must gain access to the subarachnoid space. This is usually via hematogenous spread from the upper respiratory tract where the initial colonization has occurred. Less frequently, there is direct spread from a contiguous focus (e.g., sinusitis, mastoiditis, and otitis media) or through an injury, such as a skull fracture.

· The most common causative organisms in the first month of life are E. coli and group B streptococci. Listeria monocytogenes also occurs in this age range, but accounts for 5-10% of cases. There have been reports of N. meningitidis occurring in the first month of life.

· Between 30-60 days, Group B streptococcal infection occurs frequently and the gram-negative enterics decline in frequency. S. pneumoniae, H. influenzae and N. meningitidis occur rarely in this age group.

· After 2 months of age, S. pneumoniae and N. meningitidis currently cause the majority of the cases of
bacterial meningitis. H. influenzae may still occur, especially in children who have not received the HIB vaccine.

The most common causative organisms (e.g., N. meningitidis, S. pneumoniae, and H. influenzae) contain a polysaccharide capsule that allows them to colonize the nasopharynx of healthy children without any systemic or local reaction. A concurrent viral infection may facilitate the penetration of the nasopharyngeal epithelium by the bacteria. Once in the bloodstream, the polysaccharide capsule allows the bacteria to resist opsonization by the classical complement pathway and, thus, inhibit phagocytosis.

Unusual bacteria occasionally cause meningitis. Pasturella mulocida is known to cause skin infections from cat or dog bites. A recent case described a 7 week old with P. multocida meningitis after exposure to dog saliva with no wound, emphasizing the need to protect young children from this pathogen. This infection, while rare, is associated with significant morbidity and mortality.

Salmonella meningitis should be suspected in any child with this organism grown at any other site in an unwell child or one under 6 months of age. Mothers known to be infected with Salmonella during pregnancy may put their child at risk. As therapy is different for Salmonella meningitis, while rare it must be considered in the above situations.

The bacteremic phase allows penetration of the cerebral spinal fluid (CSF) through the choroid plexus. The CSF is poorly equipped to control infection because type specific antibodies do not penetrate the blood brain barrier well and complement components are absent or in low concentrations.

The cell walls of both gram-positive and gram-negative bacteria contain potent triggers of the inflammatory response. In the gram-positive bacteria, teichoic acid is considered to be the major pathogenic component. In gram-negative bacteria, lipopolysaccharide or endotoxin is the major pathogenic component. These components are released in the CSF during bacterial growth and especially with the lysis of bacterial cells. Antibiotic therapy causes a significant release of the mediators of the inflammatory response.

The mediators of the inflammatory response include cytokines (tumor necrosis factor, interleukin 1, 6, 8, 10), platelet activating factor, nitric oxide, prostaglandins, and leukotrienes. These mediators cause disruption of the blood brain barrier, vasodilation, neuronal toxicity, meningeal inflammation, platelet aggregation, and activation of leukocytes. The capillary endothelial cell is the main site of injury in bacterial meningitis; thus, it is a vasculitis, which results in destruction of vascular integrity. The ultimate consequences are damage to the blood brain barrier, brain edema, impaired cerebral blood flow, and neuronal injury.

Because of the damage done by the body's response to the infection, various anti-inflammatory agents have been used in an attempt to decrease the morbidity and mortality of bacterial meningitis. Only dexamethasone has occasionally been proven to be effective.

Viral meningitis is the most common infection of the CNS. It most frequently occurs in children under 1 year of age. Enterovirus is the most common causative agent and is a frequent cause of febrile illnesses in children. Other viral pathogens include paramyxoviruses, herpes, influenza, rubella, and adenovirus. Meningitis may occur in up to half of children under 3 months with enteroviral infection. Enteroviral infection can occur any time during the year, but are also associated with epidemics in the summer and fall. Viral infection causes an inflammatory response but to a lesser degree than bacterial infection. Damage from viral meningitis may be due to an associated encephalitis, and increased intracranial pressure.

Although tuberculosis is the most common cause of death from a single agent in children worlwide, it is a rare infection in children in developed countries. The emergency physician must suspect this infection in children who are recent immigrants from underdeveloped countries, who are infected or are exposed to HIV infected persons, or are from poor urban centers. Tuberculous meningitis and encephalitis are two of the more serious complications of tuberculosis. In it's early stages it is difficult to diagnose and, untreated, is usually fatal. Meningitis occurs 3-6 months after the primary infection.

Fungal meningitis is rare, but may occur in immunocompromised patients; children with cancer, previous neurosurgery, or cranial trauma; or premature infants with low birth rates. Most cases are in children who are receiving antibiotic therapy and, thus, usually are inpatients.

Frequency:

In the US: In 1995 there were 5755 cases of bacterial meningitis reported. This is a dramatic decrease from the 12,920 cases reported in 1986. This is attributed to the decrease in H. influenzae meningitis since the introduction of the HIB vaccine. The occurrences by infectious agent in 1995 are:

Streptococcus pneumoniae: 1.1/100,000
Neisseria meningitidis: 0.6/100,000
Group B Streptococcus: 0.3/100,000
Listeria monocytogenes: 0.2/100,000
Haemophilus influenzae: 0.2/100,000

The incidence of neonatal meningitis has shown no significant change in the last 25 y. Viral meningitis is the most common form of aseptic meningitis and, since the introduction of mumps vaccine, is caused by enteroviruses in up to 85% of cases. Encephalitis is more difficult to estimate incidence because of difficulty in establishing the diagnosis. One report estimates an incidence of 1 in 500-1000 in the first 6 mo of life.

Internationally: The World Health Organization estimates that bacterial meningitis strikes 426,000 children under 5 y annually, with 85,000 deaths. The incidence of bacterial meningitis depends on the use of the HIB vaccine. A recent report from Japan shows an overall rate of 2.32/100,000 with the rate in children under 4 y of 7.22. The most common organisms were H. influenzae, S. pneumoniae, Group B Streptococcus, and E. coli, in that order. In Finland, where the HIB vaccine is widely used, there was a decrease from 30 cases of meningitis due to H. influenzae in children under 4 y in 1986 to no cases in 1991. The incidence of encephalitis is related to the extent of childhood vaccination. In a recent report from Japan, the overall incidence of meningoencephalitis was 3.3/100,000 with an incidence of 6.6/100,00 in children under 4 y. The most frequent causative agents were measles, herpes, and rubella.

Mortality/Morbidity: Morbidity and mortality depend on the infectious agent, age of the child, general health and prompt diagnosis and treatment. Despite improvement in antibiotic and supportive therapy, there remains a significant mortality and morbidity.

The overall mortality for bacterial meningitis is 5-10% and varies with causative organism and age. Neonatal meningitis has a mortality of 15-20%. In older children the mortality rate is 3-10%. S. pneumoniae has the highest mortality (26.3-30%). H. influenzae type B has a range of 7.7-10.3%. N. meningitidis has the lowest of the most common organisms with 3.5-10.3%.

Up to 30% of children will have neurological sequelae. This varies by organism, with S. pneumoniae having the highest rate of complications. Several studies indicate that the complication rate from S. pneumoniae meningitis did not vary if the infection was from a penicillin sensitive or resistant strain. These studies showed that dexamethasone did not improve outcomes. Another study showed a low (less than 5%)hearing loss in children diagnosed with meningococcal meningitis. Sensorineural hearing loss is one of the most frequent problems. As many of the children affected are very young and cognitive and motor skills are immature, some of the sequelae may not be recognized for years. A recent study followed children who recovered from meningitis for 5-10 y. They found 1-4 school-age meningitis survivors had either serious and disabling sequelae or a functionally important behavior disorder, neuropsychiatric or auditory dysfunction that impaired their performance in school. Children at greatest risk for hearing loss include evidence of increased intracranial pressure, abnormal CT scan, male sex, low glucose levels in the patients cerebrospinal fluid, infection by S. pneumoniae, and presence of nuchal rigidity.

Viral Meningoencephalitis:

Enteroviral infection usually has few complications. Herpes simplex and arbovirus infections, in addition to viral infections in AIDS patients, can result in severe neurological disease.

Tuberculous Meningitis:

Morbidity and mortality are related to the stage of the disease. Stage I has a 30% significant morbidity, Stage II 56% and Stage III 94%.

Race: Bacterial meningitis more frequently occurs in black and Hispanic children. This is thought to be more related to socioeconomic, rather than racial factors.

Sex: There is a male predominance in bacterial meningitis. A recent report from Finland showed males more often had mumps and varicella encephalitis, whereas, females had adenoviral and Mycoplasma encephalitis.

Age: For both meningitis and encephalitis, the greatest occurrence is in children under 4 y with a peak from 3-8 mo.

CLINICAL

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History:

Bacterial Meningitis:

The younger the child, the less likely he or she is to exhibit the classical symptoms of fever, headache and meningeal signs.

Meningitis in the neonatal period is associated with maternal infection or pyrexia at delivery. The child under 3 months may have very non-specific symptoms, including hyper- or hypothermia, change in sleeping or eating habits, irritability or lethargy, vomiting, high pitched cry, or seizures.

Meningismus and a bulging fontanel may be seen but are not needed to suspect the diagnosis.

A child who is quiet at rest, but who cries when moved or comforted may have meningeal irritation (paradoxical irritability).

After 3 months of age, the child may display symptoms more often associated with bacterial meningitis, with fever, vomiting, irritability or lethargy or any change in behavior.

After 2-3 years of age, children may complain of headache, stiff neck and photophobia.

The clinical course may be brief and fulminant, with rapid progression of symptoms or may follow a more gradual course, with several days of upper respiratory infection progressing to more severe symptoms.

The fulminant course is more often associated with N. meningitidis infection.

Viral Meningitis:

In areas with wide spread vaccination of children, enteroviruses are the most common causes of viral meningitis.

The onset is variable and may have several days of fever, anorexia and general malaise.
It may also present as a rather abrupt onset of fever, nausea, vomiting and headache.

Additional symptoms are shared with enteroviral infections, such as pharyngitis, conjunctivitis, and myositis.

Other causes of viral meningitis may also have signs of encephalitis.

Arboviral infections frequently have associated encephalitis and seizures.

Adenoviral, mumps and varicella-zoster infections tend to be more severe than enteroviral infections and often have evidence of encephalitis.

In areas with low vaccination rates, mumps virus is often the most frequent cause of meningitis.

Tuberculous Meningitis:

Occurring 3-6 months after primary infection, this may present suddenly or insidiously and usually has 3 clinical stages.

The first stage consists of 1-2 weeks of fever, headache, malaise and irritability.

The second stage may occur suddenly and consists of more typical meningeal signs.

The final stage consists of worsening neurological condition, coma and death.

Fungal meningitis occurs in immunocompromised patients and has a variable presentation.

Physical: The physical examination shows a wide variation based on age and infecting organism. It is important to remember that the younger the child, the less specific the symptoms.

In the young infant there rarely are findings which definitely point to meningitis.

The infant may be febrile or hypothermic.

Bulging of the fontanel, diastasis of the sutures as well as nuchal rigidity point to meningitis but are usually late findings.

As the child grows older the physical becomes more reliable.

Meningeal signs (e.g., headache, nuchal rigidity, positive Kernig's and Brudzinski's sign) should be sought and their presence or absence recorded.

Focal neurological signs may be present in up to 15% of patients and are associated with a worse prognosis.

Seizures occur in up to 30% of children with bacterial meningitis.

Obtundation and coma occur in 15-20% of patients and are more frequent with pneumococcal meningitis.

Encephalitis may present like meningitis or the symptoms of the systemic viral infection may predominate.

Causes:

Risk Factors for Bacterial Meningitis: