Pediatric Aseptic Meningitis

Updated: Mar 05, 2015
  • Author: Saul N Faust, MBBS, PhD, MA, MRCPCH(UK); Chief Editor: Russell W Steele, MD  more...
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Overview

Background

Pediatric aseptic meningitis is an inflammation of the meninges caused mainly by nonbacterial organisms, specific agents, or other disease processes. Aseptic meningitis (including viral meningitis) is the most common infection of the central nervous system (CNS) in the pediatric population, occurring most frequently in children younger than 1 year. Despite advances in antimicrobial and general supportive therapies, CNS infections remain a significant cause of morbidity and mortality in children.

Because the classic signs and symptoms are often absent, especially in younger children, diagnosing pediatric CNS infections is a challenge to the emergency department (ED). Even when such infections are promptly diagnosed and treated, neurologic sequelae are not uncommon. Clinicians are faced with the daunting task of distinguishing the relatively few children who actually have CNS infections from the vastly more numerous children who come to the ED with less serious infections.

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Pathophysiology

Organisms colonize and penetrate the nasopharyngeal or oropharyngeal mucosa, survive and multiply in the blood stream, evade host immunologic mechanisms, and spread through the blood-brain barrier. Infection cannot occur until colonization of the host has taken place (usually in the upper respiratory tract). The mechanisms by which circulating viruses penetrate the blood-brain barrier and seed the cerebrospinal fluid (CSF) to cause meningitis are unclear. [1]

Viral infection causes an inflammatory response but to a lesser degree than bacterial infection does. Damage from viral meningitis may be due to an associated encephalitis and increased intracranial pressure (ICP).

The pathophysiology of aseptic meningitis caused by drugs is not well understood. This form of meningitis is infrequent in the pediatric population.

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Etiology

Although many agents and conditions are known to be associated with pediatric aseptic meningitis, often a specific cause is not identified, because a complete diagnostic investigation is not always completed. Viruses are the most common cause, and enteroviruses (EVs) are the most frequently detected viruses. The use of molecular diagnostic techniques (eg, polymerase chain reaction [PCR] assay) has significantly increased diagnostic accuracy.

Viruses

EV is a frequent cause of febrile illnesses in children. Other viral pathogens include paramyxovirus, herpesvirus, influenza virus, rubella virus, and adenovirus. Meningitis may occur in as many as 50% of children younger than 3 months with EV infection. EV infection can occur at any time during the year but is associated with epidemics in the summer and fall.

Viruses associated with aseptic meningitis include the following:

  • EV 71, EV 70, EV 75 [2, 3, 4, 5, 6, 7]
  • Polioviruses types 1, 2, and 3
  • Coxsackievirus type A (23 serotypes) and type B (6 serotypes)
  • Echoviruses (31 serotypes; see the image below) [8, 9, 10]
  • Human parechoviruses (HPeV) (6 serotypes; HPeV types 1 and 2 were previously classified as echovirus types 22 and 23 within the genus Enterovirus)
  • Arbovirus (eastern, western, and Venezuelan equine encephalitis viruses; Powassan virus; California group viruses [primarily LaCrosse virus]; St. Louis encephalitis virus; West Nile virus; and Colorado tick fever)
  • Mumps virus
  • Herpes simplex virus (HSV) types 1 and 2
  • Human herpesvirus type 6 (HHV6) and type 7 (HHV7)
  • Varicella-zoster virus (VZV)
  • Adenovirus types 3 and 7
  • Lymphocytic choriomeningitis (associated with contact with guinea pigs, hamsters, and pet mice)
  • Influenza A and B viruses, including H1N1 [11, 12]
  • Parainfluenza virus
  • Rotavirus
  • Coronavirus
  • Variola virus
  • Flavavirus [13]
    Skin lesions due to echovirus type 9 on neck and c Skin lesions due to echovirus type 9 on neck and chest of young girl. Echoviruses belong to genus Enterovirus and are associated with illnesses including aseptic meningitis, nonspecific rashes, encephalitis, and myositis.

Viral vaccines

Viral vaccines related to aseptic meningitis include the following:

Nonpyogenic bacteria

Certain bacterial infections may give rise to aseptic meningitis (eg, partially treated bacterial meningitis or brain abscess). Nonpyogenic bacteria associated with aseptic meningitis include the following:

Other organisms

Atypical organisms associated with aseptic meningitis include the following:

Parasites associated with aseptic meningitis include the following:

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 occur in children who are inpatients receiving antibiotic therapy. Fungi associated with aseptic meningitis include the following:

Additional organisms associated with aseptic meningitis include the following:

  • Blastomyces dermatitidis
  • Coccidioides immitis
  • Alternaria species
  • Aspergillus species
  • Cephalosporium species
  • Cladosporium trichoides
  • Drechslera hawaiiensis
  • Paracoccidioides brasiliensis
  • Petriellidium boydii
  • Sporotrichum schenckii
  • Ustilago species
  • Zygomycetes species

Diseases and other conditions or events

Diseases associated with aseptic meningitis include the following:

  • Leukemia
  • Behçet disease
  • Sj ö gren syndrome [16]
  • Dermoid and epidermoid cysts [17]
  • CNS tumor
  • Recurrent benign endothelioleukocytic aseptic meningitis (Mollaret meningitis) [19]
  • Neonatal-onset multisystem inflammatory disorder (one of the cryopyrin-associated periodic syndromes [CAPS]) [20]

Other conditions or events associated with aseptic meningitis include the following:

  • Immunoglobulin replacement therapy
  • Heavy metal poisoning
  • Intrathecal agents
  • Foreign bodies (eg, shunt or reservoir)
  • Drugs
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Epidemiology

United States Statistics

The incidence of aseptic meningitis in the United States has been estimated to be approximately 75,000 cases per year. Before the introduction of the MMR vaccine program, the mumps virus was the most common cause, accounting for 5-11 of 100,000 cases of meningitis; it now accounts for approximately 0.3 of 100,000 cases, and EV has become the most common cause. In a North American study from 1998-1999, most cases occurred between July and October. [21]

International Statistics

In a university clinic in Mainz, Germany, from 1986-1989, 12 (10.3%) of 117 cases of acute aseptic meningitis were due to the mumps virus, 3 (7.7%) were due to Borrelia burgdorferi, 3 (2.6%) were due to tick-borne encephalitis, and 2 (1.7%) were due to (HSV). [22] Ninety-one (77.8%) cases were due to other causes. Sixty-four percent of cases occurred in the spring and summer.

In a tertiary care children’s hospital in Athens, Greece, 506 cases of aseptic or viral meningitis were reviewed from 1994 through 2002; the estimated annual incidence was 17 cases per 100,000 children younger than 14 years. [23] Most cases occurred during summer (38%) and autumn (24%), and 47 of 96 patients (48.9%) had positive results for enteroviral RNA on CSF polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF).

The Austrian reference laboratory for poliomyelitis received 1,388 stool specimens for EV typing from patients with acute flaccid paralysis or aseptic meningitis between 1999 and 2007; 201 samples from 181 cases were positive for nonpoliomyelitis EV. [24] The mean patient age was 5-6 years, with 90% of cases in children younger than 14 years. Aseptic meningitis was identified in 65.6% of the cases. Echovirus 30 was the most frequent viral cause of aseptic meningitis, due to an epidemic in 2000, followed by coxsackievirus B types 1-6 and EV 71.

A new outbreak of E-30 occurred between April and September 2013 in Marseille, South-East France. A study concluded that almost all E-30 emerged from local circulation of one parental virus. The findings also showed that human enterovirus outbreaks cause an excess of emergency ward consultations but probably also an excess of consultations to general practitioners who receive majority of the non-specific viral illness. [25]

Age-related demographics

Aseptic meningitis is more common in children than in adults. In the Mainz study, 69% of the patients were aged 5 years or older, [22] and in the Athens study, the median age was 5 years (range, 1 month to 14 years). [23] However, in a Korean study, a higher incidence was reported in individuals younger than 1 year (10% of total affected) and in individuals aged 4-7 years (44.1%). [26]

Sex-related demographics

Until comparatively recently, no sex predilection had been reported for EV infection, although reactivation of HSV-2 infection occurs mostly in adults (with a female-to-male ratio of 6:1). In the Mainz study, 66% of the patients were male. [22]

A Korean study of 2201 children reported a male-to-female ratio of 2:1. [26] In Japan, an outbreak of aseptic meningitis caused by echovirus type 30 in 54 patients showed a male-to-female ratio of 2.2:1. [27] The Athens study also showed a higher prevalence in males, with a male-to-female ratio of 1.8:1. [23]

Race-related demographics

In a South African study, the median age of white children with aseptic meningitis (64 months) was significantly greater than that of nonwhite children (45 months) and that of black children (26 months). [28]

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Prognosis

Full recovery is usual after uncomplicated viral aseptic meningitis. Most cases resolve within 7-10 days.

Recurrence is possible (known as Mollaret, or benign recurrent meningitis). Associated viruses include Epstein-Barr virus (EBV), coxsackieviruses B5 and B2, echoviruses 9 and 7, herpes simplex virus (HSV)-1 and HSV-2, and human immunodeficiency virus (HIV).

Overall mortality and morbidity for aseptic meningitis are unclear. In a Taiwanese study of EV 71 infections, 78 of 408 hospitalized children died. [7] Of children with rhombencephalitis due to EV infection, 14% died.

Subsequent studies suggested better outcomes. In both a Canadian study of 802 patients (1998-99) [21] and a Korean study of 2201 children (1987-2003), [26] no deaths were reported. In the Athens study of 506 children, no serious complications or deaths were reported. [23]

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Patient Education

For more information, visit the Meningitis Foundation of America Web site. The Meningitis Research Foundation offers useful material for nonexperts, parents, and health care professionals.

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