AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Aseptic meningitis is an inflammation of the meninges caused mainly by nonbacterial organisms, specific agents, or other disease processes.

Pathophysiology

Organisms colonize and penetrate the nasopharyngeal or oropharyngeal mucosa, survive and multiply in the blood stream, evade host immunological 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.

Frequency

United States

The incidence is estimated at 75,000 cases per year in the United States. Prior to the introduction of the measles, mumps, and rubella (MMR) vaccine program, the mumps virus was the most common cause of meningitis (accounting for 5-11 of 100,000 cases of meningitis). It now accounts for approximately 0.3 of 100,000 cases of meningitis. In a North American study from 1998-1999, most cases occurred between July and October (Lee, 2006).

International

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 herpes simplex virus (HSV) (Hensel, 1992). Ninety-one (77.8%) cases were due to other causes. Sixty-four percent of cases occurred in the spring and summer.

Mortality/Morbidity

The overall mortality and morbidity rates for aseptic meningitis are unclear. In one Taiwanese study of enterovirus 71 infections, 78 of 408 hospitalized children died (Huang, 1999). Of children with rhombencephalitis due to enteroviral infection, 14% died.

More recent studies have suggested better outcome. In both a Canadian study of 802 patients (1998-99) and a Korean study of 2201 children (1987-2003), no deaths were reported (Lee, 2006; Lee, 2005).

Race

In one South African study, the median age of white children with aseptic meningitis (age 64 mo) was significantly greater than that of nonwhite children (age 45 mo; P >.0001) and that of black children (26 mo; P >.014) (Donald, 1986).

Sex

Until recently, no sex predilection had been reported for enteroviral infection, although reactivation of herpes simplex virus type 2 (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 (Hensel, 1992).

A recent Korean study of 2201 children showed a male-to-female ratio of 2:1 (Lee, 2005).

Age

Aseptic meningitis is more common in children than in adults. In the Mainz study, 69% of the patients were aged 5 years or older (Hensel, 1992). However, in the 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%).

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

Headache, neck stiffness, and photophobia are classic symptoms of aseptic meningitis in older children. These symptoms may be absent in younger children, who more commonly present with rash, diarrhea, and cough. Fever may be present. Seizures are more common in aseptic meningitis caused by specific viruses (eg, arboviruses). Other nonspecific symptoms may include arthralgia, myalgia, sore throat, weakness, and lethargy. Recent travel history and/or exposure to ticks or other biting insects are important aspects of the patient's history. The history varies according to the etiologic agent.

• Enteroviruses
• • Onset is usually acute, but it can be insidious over a week prior to presentation or can follow an acute febrile illness.
  • Rash, when present, is erythematous, maculopapular, and vesicular, appearing on the soles of the feet, palms, or mucous membranes.
  • Fever may last up to 5 days.
  • Anorexia, nausea, and vomiting are common.
  • Sore throat may occur.
  • Rare symptoms include flaccid paralysis, pericarditis, myocarditis, and conjunctivitis.
• Herpes viruses
• In older teenagers and adults, aseptic meningitis may be associated with reactivation of HSV-2 infections.
• Reactivation of varicella zoster infections is rare in immunocompetent children.
• Aseptic meningitis caused by the mumps virus occurs 7-10 days following parotitis.
• Aseptic meningitis associated with Mycoplasma pneumoniae infection usually occurs 3-21 days following the respiratory infection.

Physical

• Examination should specifically exclude a nonblanching petechial rash, other signs of bacterial meningitis, and features suggestive of a noninfectious etiology.
• Fever and lymphadenopathy may be present.
• Neurological examination includes evaluating for signs of meningismus (eg, photophobia, neck stiffness, positive Kernig sign) and focal or generalized neurological signs.

Causes

Many etiologic agents cause aseptic meningitis, although an agent is identified in only about 10% of cases because a complete diagnostic investigation is often not completed. In one study, an etiologic agent was found in an estimated 50-70% of cases. Viruses are the most frequent cause. The use of molecular diagnostic techniques such as polymerase chain reaction has significantly increased diagnostic accuracy.

• Viruses associated with aseptic meningitis
• • Enterovirus 71, enterovirus 70
  • Polioviruses types 1, 2, and 3
  • Coxsackievirus type A (23 serotypes), coxsackievirus type B (6 serotypes)
  • Echoviruses (31 serotypes)
  • Arbovirus (eastern, western, and Venezuelan equine encephalitis viruses; Powassan virus; California group viruses [primarily LaCrosse virus]; St. Louis encephalitis virus; West Nile virus; Colorado tick fever)
  • Mumps
  • HSV types 1 and 2
  • Cytomegalovirus (CMV)
  • Epstein-Barr virus (EBV)
  • Human herpesvirus type 6 (HHV6), human herpesvirus type 7 (HHV7)
  • Varicella-zoster virus (VZV)
  • Adenoviruses (types 3 and 7)
  • Human immunodeficiency virus (HIV)
  • Lymphocytic choriomeningitis (associated with contact with guinea pigs, hamsters, and pet mice)
  • Rhinovirus
  • Measles
  • Rubella
  • Influenza A and B
  • Parainfluenza
  • Parvovirus B19
  • Rotavirus
  • Coronavirus
  • Variola virus
• Vaccines related to aseptic meningitis
  • MMR
  • Polio
  • Rabies
• Bacterial infection associated with aseptic meningitis - Partially treated bacterial meningitis or brain abscess
• Nonpyogenic bacteria associated with aseptic meningitis
  • Mycobacterium tuberculosis
  • Leptospira
  • Treponema pallidum
  • Borrelia (relapsing fever, Lyme disease)
  • Nocardia
  • Bartonella
  • Atypical mycobacteria
  • Brucella
• Atypical organisms associated with aseptic meningitis
  • Chlamydia
  • Rickettsia
  • Mycoplasma
• Parasites associated with aseptic meningitis
  • Roundworms
  • Tapeworms
  • Flukes
  • Amoebae
  • Toxoplasma
• Fungi associated with aseptic meningitis
  • Candida
  • Histoplasma
  • Cryptococcus
• Other organisms associated with aseptic meningitis
  • 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 associated with aseptic meningitis
  • Leukemia
  • Behçet disease
  • System lupus erythematosus (SLE)
  • Sarcoidosis
  • CNS tumor
  • Kawasaki disease
• Other associations with aseptic meningitis
  • Immunoglobulin replacement therapy
  • Heavy metal poisoning
  • Intrathecal agents
  • Foreign bodies (eg, shunt or reservoir)
  • Drugs

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

Viral encephalitis
Meningoencephalitis
Acute disseminated encephalomyelitis (ADEM)
Atypical migraine
Hydrocephalus
Partially treated bacterial meningitis

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

• WBC count
• C-reactive protein (CRP)
• Blood and cerebrospinal fluid culture to exclude bacterial meningitis
• Viral culture of throat swabs and stool sample
• Serology: Save serum for paired convalescent sample comparison of serology at 2-3 weeks following acute illness.
• CSF evaluation including cell count and differential and glucose and protein levels
• Polymerase chain reaction
• • Polymerase chain reaction for many of the common etiologic agents of aseptic meningitis is increasingly available through state health departments, the Centers for Disease Control and Prevention, and research laboratories.
  • Polymerase chain reaction of CSF can detect as few as 10 copies of viral nucleic acid. The ability to amplify the DNA from HSV-1 and HSV-2, VZV, CMV, HHV6A and HHV6B, and EBV in a single reaction and similar progress has revolutionized the diagnosis of enteroviral and other viral infections (eg, human herpesvirus type 7 [HHV7], West Nile virus).

Imaging Studies

• If focal neurologic signs or any unusual features are present, early CT scan or MRI should be performed.

Other Tests

• Consider EEG if atypical febrile seizures have occurred. A neuroimaging study is required for complicated cases, including children with meningoencephalitis.
• Obtain viral throat swab and nasopharyngeal aspirate.
• Obtain stool sample for viral studies.

Procedures

• Lumbar puncture should be considered in the absence of contraindications. Typical findings include the following:
• • CSF pressure that is within the reference range or increased
  • Lymphocytic predominance in the CSF (Although this is typical, neutrophils can predominate in early stages.)
  • CSF protein concentration of 0.5-2 g/L
  • CSF glucose within the reference range (>66% blood glucose level)
• Avoid lumbar puncture in patients with depressed levels of consciousness, shock, or any of the features listed below. Immediately begin treatment in these patients. Contraindications to lumbar puncture include the following:
• Prolonged or focal seizures
• Focal neurologic signs
• Widespread purpuric or petechial rash
• Glasgow Coma Scale score of less than 13
• Pupillary dilatation or asymmetry
• Impaired oculocephalic reflexes (doll's eye reflex)
• Abnormal posture or movement - Decerebrate or decorticate movement or cycling
• Signs of impending brain herniation (eg, inappropriate low pulse, raised blood pressure, irregular respiration)
• Coagulation disorder
• Papilledema
• Hypertension

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medical Care

Management is supportive. Administer adequate analgesia.

• If meningoencephalitis is suspected, administer high-dose intravenous acyclovir until HSV infection can be excluded.
• If bacterial meningitis cannot be excluded based on the initial history, examination and investigation are required. Use an intravenous third-generation cephalosporin in combination with intravenous vancomycin until a pyogenic (ie, primarily pneumococcal and meningococcal) bacterial cause is ruled out.
• If tuberculous meningitis is suspected or proven, administer specific antimicrobial therapy and intravenous corticosteroids.
• Pleconaril, an investigational agent with activity against most strains of enteroviruses, appears promising for the treatment of aseptic meningitis caused by this group of viruses.
• Seizures should be treated with appropriate emergency therapies.

Consultations

Referral to a specialized pediatric intensive care unit is appropriate if the level of consciousness is reduced and the airway cannot be maintained.

Activity

Recovery can be prolonged, and rest is occasionally advised.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Drug therapy is currently not a component of the standard of care for this condition. Follow standard local analgesic regimens.

Acyclovir, ceftriaxone/cefotaxime, vancomycin, or antituberculous medication should be considered if diagnosis of Viral Encephalitis; Meningitis, Bacterial; or Tuberculous Meningitis cannot be excluded.

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Further Outpatient Care

• Follow-up consultations should include a full neuromuscular and developmental assessment plus bilateral audiometry.

Complications

• Serious complications are uncommon but can include unilateral deafness following mumps meningitis, chronic enteroviral meningitis (especially in patients with agammaglobulinemia), and hydrocephalus following lymphocytic choriomeningitis virus infection. Rhombencephalitis has been reported as a complication of enterovirus 71 infection.
• Other reported sequelae include seizure disorders, behavioral problems, and speech delay (unrelated to hearing loss). In a Korean study, 0.7% of children had neurological problems such as seizures, amnesia, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and hydrocephalus, although none were permanent (Lee, 2005).

Prognosis

• Full recovery is usual after uncomplicated viral aseptic meningitis. Most cases resolve within 7-10 days.
• Psychological sequelae may be more common than in bacterial meningitis.
• Recurrence is possible (known as Mollaret, or benign recurrent meningitis). Associated viruses include EBV, coxsackieviruses B5 and B2, echoviruses 9 and 7, HSV-1 and HSV-2, and HIV.

Patient Education

• For excellent patient education resources, visit eMedicine's Brain and Nervous System Center and Children's Health Center. Also, see eMedicine's patient education articles Meningitis in Adults and Meningitis in Children.
• For more information, visit the Meningitis Foundation of America Web site.
• The Meningitis Research Foundation has excellent sections for nonexperts, parents, and health care professionals.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

• Cherry JD, Nielsen KA. Aseptic meningitis and viral meningitis. Textbook of Pediatric Infectious Diseases, Feigin RD, Cherry JD, Demmler GJ. 2004;1:497-505.
• Donald PR, Burger PJ, Becker WB. Paediatric meningitis in the western Cape. A 3-year hospital-based prospective survey. S Afr Med J. Sep 27 1986;70(7):391-5. [Medline].
• Dourado I, Cunha S, Teixeira MG, et al. Outbreak of aseptic meningitis associated with mass vaccination with a urabe-containing measles-mumps-rubella vaccine: implications for immunization programs. Am J Epidemiol. Mar 1 2000;151(5):524-30. [Medline].
• Hensel M, Gutjahr P, Kamin W, Schmitt HJ. [Meningitis in 154 children of a pediatric clinic in Germany: clinical and epidemiologic aspects]. Klin Padiatr. May-Jun 1992;204(3):163-70. [Medline].
• Huang CC, Liu CC, Chang YC, et al. Neurologic complications in children with enterovirus 71 infection. N Engl J Med. Sep 23 1999;341(13):936-42. [Medline].
• Jeffery KJ, Read SJ, Peto TE, et al. Diagnosis of viral infections of the central nervous system: clinical interpretation of PCR results. Lancet. Feb 1 1997;349(9048):313-7. [Medline].
• Jolles S, Sewell WA, Leighton C. Drug-induced aseptic meningitis: diagnosis and management. Drug Saf. Mar 2000;22(3):215-26. [Medline].
• Lee BE, Chawla R, Langley JM, et al. Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of aseptic meningitis. BMC Infect Dis. 2006;6:68. [Medline]. [Full Text].
• Lee KY, Burgner D, Lee HS, et al. The changing epidemiology of pediatric aseptic meningitis in Daejeon, Korea from 1987 to 2003. BMC Infect Dis. 2005;5:97. [Medline]. [Full Text].
• Negrini B, Kelleher KJ, Wald ER. Cerebrospinal fluid findings in aseptic versus bacterial meningitis. Pediatrics. Feb 2000;105(2):316-9. [Medline]. [Full Text].
• Rice P. Viral meningitis and encephalitis. Medicine. 2005;33(4):60-63.
• Rotbart HA. Viral meningitis. Semin Neurol. 2000;20(3):277-92. [Medline].
• Wong KT, Lum LC, Lam SK. Enterovirus 71 infection and neurologic complications. N Engl J Med. Feb 3 2000;342(5):356-8. [Medline].
• Yamamoto T, Nakamura Y. A single tube PCR assay for simultaneous amplification of HSV-1/-2, VZV, CMV, HHV-6A/-6B, and EBV DNAs in cerebrospinal fluid from patients with virus-related neurological diseases. J Neurovirol. Oct 2000;6(5):410-7. [Medline].

Article Last Updated: Jan 22, 2007