Meningitis and Encephalitis

Although central nervous system (CNS) infections are rare in children, they are associated with high morbidity and mortality. CNS infections are generally categorized based on the site of the inflammation or infection. An overview of neonatal infections can be found in the Neonatal Care rotation guide.

The two most common types of CNS infections include inflammation of the meninges (meningitis) or of the brain parenchyma (encephalitis). Meningitis is further characterized as bacterial, viral, or aseptic in nature. Other CNS infections include rhombencephalitis (inflammation of the brain stem), myelitis (inflammation of the spinal cord), and radiculitis (inflammation of the nerve roots).

The etiology, clinical presentation, prognosis, and treatment varies for each type of infection. In this section, we focus on the following CNS infections in children:

• Meningitis and encephalitis evaluation

• Bacterial meningitis

• Encephalitis

• Acute flaccid myelitis

Meningitis and Encephalitis Evaluation

Presentation: Patients with meningitis and encephalitis often present with symptoms of infection and increased intracranial pressure including fever, headache, vomiting, and seizures. In infants, symptoms of meningitis may be subtler and can include lethargy, poor feeding, vomiting, and bulging fontanelle. Older children may develop photophobia, confusion, or irritability. Encephalitis should be considered in patients with altered mental status, fever, seizures, and abnormal neurologic exam.

On physical exam, patients may have a Kernig sign (pain with flexion of the hip and extension of the knee) or Brudzinski sign (passive flexion of the neck triggering hip flexion).

(Source: Evidence-Based Physical Diagnosis. Elsevier 2018.)

Clinical Evaluation: All patients with suspected meningitis or encephalitis should be evaluated for risk of cerebral herniation and undergo lumbar puncture and laboratory evaluation of cerebrospinal fluid (CSF) for the following:

• cell count and differential

• protein and glucose levels

• bacterial culture

• further nonculture testing (e.g., polymerase chain-reaction or antibody testing) using retained CSF

CSF opening pressure using manometry should be obtained whenever possible to evaluate for evidence of increased intracranial pressure. The most severe complication of lumbar puncture is cerebral herniation, which can occur in patients with elevated intracranial pressure. Children with papilledema, risk of brain abscess, focal seizures, or focal neurologic findings should undergo a CT scan of the head before undergoing lumbar puncture to evaluate for ventriculomegaly, which is associated with risk of herniation with lumbar puncture.

CSF findings:

• Low glucose level, elevated protein level, and elevated leukocyte count in the CSF are consistent with bacterial meningitis.

• Elevated leukocyte count in the CSF and abnormal electroencephalogram (EEG) or imaging are typical in patients with encephalitis.

Bacterial Meningitis

Etiology and Epidemiology: The incidence of bacterial meningitis is highest in neonates. With the widespread introduction of Haemophilus influenzae type B (Hib) vaccine in the early 1990s and the Streptococcus pneumoniae conjugate vaccine in the 2000s, the incidence of bacterial meningitis has declined in the United States, especially among children younger than 5 years. Early identification and treatment of meningitis are key to reducing mortality.

The etiology and pathogenesis of bacterial meningitis vary by age:

• Newborns and infants:

  • The most common cause of bacterial meningitis in children younger than 2 months is group B streptococcus (GBS). Although maternal GBS screening during pregnancy has reduced the rate of early-onset GBS infections within the first 7 days of life, maternal screening has not led to a decrease in late-onset infection (≥7 days after birth).

  • Enteric gram-negative bacilli, including Escherichia coli, can also cause meningitis in newborns.

• Children aged 2 months to 10 years:

  • S. pneumoniae accounts for most cases of bacterial meningitis in children ages 2 months to 10 years. Rates have declined significantly with the introduction of pneumococcal vaccines.

• Children aged 11 years and older:

  • Neisseria meningitidis accounts for most cases of bacterial meningitis and is a reportable disease in the United States. Not surprisingly, rates of N. meningitidis have also declined since vaccine introduction. In 2020, about 240 total cases of meningococcal disease were reported to the Centers for Disease Control and Prevention (CDC).

The incidence rates (per 100,000 persons) of meningococcal disease in the United States by year from 1970 to 2020. The incidence rate began declining in 1995 and has remained low in 2020. (Source: Meningococcal Disease. Centers for Disease Control and Prevention 2023.)

The incidence rates (per 100,000 persons) of meningococcal disease by age group from 2011 to 2020. Infants, young adults, and adults >80 years of age have the highest rates of meningococcal disease in the United States. (Source: Meningococcal Disease. Centers for Disease Control and Prevention 2023.)

Prevention: Immunizations with Hib vaccine and pneumococcal conjugate vaccine (PCV) have had the most significant impact on incidence of bacterial meningitis. Meningococcal conjugate vaccines are recommended for young children at high risk for bacterial meningitis (e.g., patients with functional or anatomical asplenia, complement deficiencies, HIV, or those traveling to an endemic area) and for all children starting at age 11 years with a booster dose at age 16 years.

Treatment: Meningitis is a clinical emergency, and antibiotics should be given promptly. Although it is ideal to obtain CSF for culture prior to administration of antibiotics, treatment should not be delayed if there is significant concern for meningitis, with cultures following as soon as possible.

Empiric therapy for bacterial meningitis in children older than 60 days generally includes ceftriaxone and vancomycin.

• Ceftriaxone provides coverage for susceptible S. pneumoniae and N. meningitidis.

• Vancomycin is added to ceftriaxone in some locations where pneumococcal resistance to beta-lactams is high and there is concern that adequate CSF levels of ceftriaxone would not be achieved.

• Glucocorticoids as adjunctive therapy for meningitis has been studied in randomized controlled trials. A Cochrane review demonstrated that glucocorticoids had no effect on mortality but might reduce the rate of hearing loss and neurologic sequelae in patients with bacterial meningitis in high-income countries. If glucocorticoids are administered, they should be given with or just prior to the first dose of antibiotics for maximum benefit.

Prognosis: Case fatality due to bacterial meningitis is high despite treatment with appropriate antibiotic therapy. In the United States, the case fatality rate from meningococcal meningitis varies by age group, with infants having a 9% case fatality rate and decreasing case fatality rate in older children. Survivors of bacterial meningitis may also face numerous neurologic sequelae, including hearing loss, academic delay, and behavioral issues.

Encephalitis

Etiology: Encephalitis refers to inflammation of the brain parenchyma. Etiologies of pediatric encephalitis include the following:

• Viruses are the most common cause of encephalitis. The most common viruses that cause encephalitis include herpes viruses (e.g., herpes simplex virus [HSV], varicella-zoster virus [VZV], and Epstein-Barr virus [EBV]), enteroviruses, arboviruses, and respiratory viruses (e.g., influenza). Neonatal HSV infections are most common in infants aged 0 to 28 days. However, older children and adults can also be affected by HSV encephalitis.

• Bacteria, fungi, and parasites are also associated with encephalitis (see table below). Mycoplasma pneumoniae can cause either postinfectious encephalitis or acute infection.

• Immunocompromised patients are at risk of infections with encephalitis from other opportunistic pathogens, including human herpesvirus type 6, Cryptococcus, John Cunningham virus (JC virus), Toxoplasma, and Acanthamoeba.

• Although viruses are the most common infectious cause of encephalitis, noninfectious causes of encephalitis are also important to consider, including autoinflammatory disorders and drug toxicities.

  • Acute disseminated encephalomyelitis is a common cause of postinfectious encephalitis and typically presents with MRI findings of asymmetric, multifocal lesions in white matter.

  • Anti-N-methyl-aspartate (NMDA) receptor encephalitis is another autoimmune (antibody-mediated) cause of encephalitis that is also related to infection, with a higher incidence in children with HSV. Rheumatology consultation should be considered in cases where an infectious cause of encephalitis is not identified.

(Source: A Systematic Approach to the Differential Diagnosis of Encephalitis in Children. J Pediatr Infect Dis Soc 2014.)

Diagnosis: Because the etiology of encephalitis can be broad, diagnosis often requires comprehensive testing, including imaging (head CT or MRI), drug screen, cerebrospinal studies, cultures, and molecular testing. Serology of the cerebrospinal fluid can also be tested for arbovirus. Generally, the diagnosis of encephalitis involves a tiered approach based on test results, exam findings, and patient risk factors.

A large, ring-enhancing lesion (thick arrow) is visible in the left hemisphere. (Source: Case 34-2002 — A 55-Year-Old Man with Cognitive and Sensorimotor Findings and Intracranial Lesions. N Engl J Med 2002.)

Treatment: Treatment for encephalitis involves input from infectious disease clinicians, neurologists, and general pediatricians. In some instances, distinguishing bacterial meningitis from viral encephalitis may be difficult. Therefore, empiric treatment with antibiotics is warranted when the diagnosis is unclear.

HSV is a rare cause of meningoencephalitis in pediatric patients but should be treated prior to confirmation of disease in patients with symptoms suggestive of HSV infection. In any patient with suspected HSV encephalitis, it is important to initiate treatment with acyclovir as early as possible, prior to laboratory confirmation of HSV. Definitive therapy with antibiotics, antivirals, and/or anti-inflammatory medications is based on test results and specialist input. Duration of therapy differs by organism and clinical improvement.

Acute Flaccid Myelitis

Etiology and Epidemiology: Acute flaccid myelitis (AFM), described as acute flaccid limb weakness, is a neurologic condition that has been reported increasingly in the United States. According to the CDC, 727 cases have been confirmed since 2014, mostly in children, with increases in cases in 2014, 2016 and 2018. Likely due to Covid-19 restrictions and masking, an outbreak of AFM has not been observed since 2020.

(Source: AFM Cases and Outbreaks. Centers for Disease Control and Prevention. 2023)

Research is ongoing to better understand the etiology and pathogenesis of AFM. Coxsackie A16, enterovirus A71, and enterovirus D68 (EV-D68) have been identified in some AFM cases; however, most patients have not had virus detected in their CSF. Sharp increases in cases occurring every 2 years are thought to be secondary to EV-D68 because they typically occur between August and November and EV-D68 is a common virus detected in AFM specimens. An increase in cases was noted in the summer of 2022 after many Covid-19 public health restrictions were lifted. Prior to universal vaccination in the United States, poliovirus was an important cause of AFM. Poliovirus should still be considered as a potential cause of AFM in unvaccinated or partially vaccinated individuals.

Presentation: AFM typically affects children (median age, 7.1 years) who were previously healthy and had a prodromal illness about 5 days before the onset of neurologic symptoms. Physical exam findings are generally consistent with a flaccid paralysis, typically in the upper extremities and more pronounced in proximal muscle groups. Occasionally, cranial nerves can be affected. MRI typically demonstrates spinal cord gray-matter lesions, and electrodiagnostic studies demonstrate motor neuropathy. CSF may show a mild pleocytosis with a lymphocytic predominance.

Treatment: The optimal treatment for AFM is not known; however, most cases in the United States have been treated with immunomodulatory agents. Extent of recovery from AFM has varied, with some patients experiencing full recovery of strength and others experiencing long-term deficits. Occupational and physical therapy may improve long-term outcomes.