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Aseptic meningitis is inflammation of the meninges with CSF lymphocytic pleocytosis and no cause apparent after routine CSF stains and cultures. Viruses are the most common cause. Other causes may be infectious or noninfectious. Symptoms include fever, headache, and meningeal signs. Viral aseptic meningitis is usually self-limited. Treatment is usually symptomatic.

Etiology

Causes may be infectious (eg, rickettsiae, spirochetes, parasites) or noninfectious (eg, intracranial tumors and cysts, drugs, systemic disorders—see Table 4: Meningitis: Causes of Aseptic Meningitis*).

Table 4
Causes of Aseptic Meningitis* Type Examples Infectious Bacterial Brucellosis, cat-scratch disease, cerebral Whipple's disease, leptospirosis, Lyme disease (neuroborreliosis), lymphogranuloma venereum, mycoplasmal infection, rickettsial infection, syphilis, TB Postinfectious Multiple viruses (eg, measles, rubella, smallpox, vaccinia, varicella) Viral Chickenpox (varicella-zoster); coxsackievirus, echovirus, and poliovirus infections; West Nile virus infection; eastern and western equine encephalitis; herpes simplex virus infection; HIV infection, cytomegalovirus infections; infectious hepatitis; infectious mononucleosis; lymphocytic choriomeningitis; mumps; St. Louis encephalitis Fungi and parasites† Ameboid infection, coccidioidomycosis, cryptococcosis, malaria, neurocysticercosis, toxoplasmosis, trichinosis Noninfectious Drugs Azathioprine Some Trade Names IMURAN Click for Drug Monograph , carbamazepine Some Trade Names TEGRETOL Click for Drug Monograph , ciprofloxacin Some Trade Names CILOXAN CIPRO Click for Drug Monograph , cytosine arabinoside (high-dose), immune globulin, muromonab CD3, isoniazid Some Trade Names INH NYDRAZID Click for Drug Monograph , NSAIDs (eg, ibuprofen Some Trade Names ADVIL MOTRIN NUPRIN Click for Drug Monograph , naproxen Some Trade Names ALEVE NAPROSYN Click for Drug Monograph , sulindac Some Trade Names CLINORIL Click for Drug Monograph , tolmetin Some Trade Names TOLECTIN Click for Drug Monograph ), OKT3 monoclonal antibody, penicillin, phenazopyridine Some Trade Names PYRIDIUM Click for Drug Monograph , ranitidine Some Trade Names ZANTAC Click for Drug Monograph , trimethoprim-sulfamethoxazole Some Trade Names Meningeal disease Behçet's syndrome with neurologic involvement, leakage of an intracranial epidermoid tumor or craniopharyngioma into the CSF, meningeal leukemia, neoplastic meningitis, sarcoidosis Parameningeal disease Brain tumor, chronic sinusitis or otitis, multiple sclerosis, stroke Reaction to intrathecal injections Air, antibiotics, chemotherapeutic drugs, spinal anesthetics, iophendylate, other dyes Vaccine reactions Many, especially pertussis, rabies, smallpox Other Lead, Mollaret's meningitis     *Aseptic refers here to conditions in which a bacterial pathogen is not readily identified with routine stains and cultures. This includes some bacteria. †Fungi and protozoa can cause a prurulent meningitis with sepsis and CSF changes similar to bacterial meningitis, except that organisms are not seen on Gram stain; thus, they are included in this category.

Enteroviruses, including echovirus and coxsackievirus, cause most cases. Mumps virus is a common cause worldwide but has been minimized in the US by vaccination. Enteroviruses and the mumps virus enter via the respiratory or GI tract and spread via the bloodstream. Mollaret's meningitis is a syndrome of self-limited, recurrent aseptic meningitis characterized by large atypical monocytes (once thought to be endothelial cells) in the CSF; it presumably is caused by herpes simplex virus type 2 or other viruses. Viruses that cause encephalitis typically also produce a low-grade aseptic meningitis.

Bacteria may also cause aseptic meningitis; they include spirochetes (in syphilis, Lyme disease, or leptospirosis) and rickettsiae (in typhus, Rocky Mountain spotted fever, or ehrlichiosis). CSF abnormalities may be transient or chronic. Bacterial infections such as mastoiditis, sinusitis, brain abscess, and infective endocarditis can result in CSF with characteristics of aseptic meningitis because widespread inflammation produces vasculitis, which leads to CSF pleocytosis without bacteria in the CSF.

Noninfectious causes of meningeal inflammation include neoplastic infiltration, leakage of the contents of an intracranial cyst, intrathecal drugs, lead poisoning, and radiopaque agents. Infrequently, inflammation results from certain systemically administered drugs, presumably as a hypersensitivity reaction. The most common causative drugs are NSAIDs (especially ibuprofen Some Trade Names
ADVIL
MOTRIN
NUPRIN
Click for Drug Monograph
), antimicrobials (especially sulfa drugs), and immune modulators (eg, IV immune globulins, OKT3 monoclonal antibodies, cyclosporine Some Trade Names
NEORAL
SANDIMMUNE
Click for Drug Monograph
, vaccines).

Symptoms and Signs

Aseptic meningitis often follows a flu-like syndrome and usually produces fever and headache, but coryza is not prominent. Meningeal signs are less marked and slower to develop than in acute bacterial meningitis. Patients are usually not critically ill; systemic or nonspecific symptoms may predominate. Focal neurologic symptoms are absent. Patients with noninfectious meningeal inflammation are often afebrile.

Diagnosis and Treatment

Aseptic meningitis is suspected in any patient with fever, headache, and meningeal signs. Head CT or MRI is done before lumbar puncture if a brain mass is suspected (eg, by focal neurologic signs or papilledema). CSF findings (see Table 2: Meningitis: Antibiotic Therapy for Acute Bacterial Meningitis) include mildly or markedly elevated pressure and presence of 10 to > 1000 lymphocytes/μL. Occasionally, a few neutrophils appear during the 1st few hours of viral meningitis. CSF glucose is normal, and CSF protein is normal or moderately elevated. CSF PCR is usually done to identify viral pathogens. Diagnosis of Mollaret's meningitis is by CSF PCR for herpes simplex type 2 DNA. Drug-induced aseptic meningitis is a diagnosis of exclusion. Tests are done to diagnose causes that are suspected clinically (eg, rickettsial infection, Lyme disease, syphilis).

Differentiating bacterial meningitis, which requires specific, rapid treatment, from aseptic meningitis, which usually does not, is sometimes difficult. Even a few CSF neutrophils, which may be present in early viral meningitis, should prompt consideration of early bacterial meningitis. Bacterial meningitis that is partially treated can result in CSF with characteristics similar to those in aseptic meningitis. Listeria sp may be difficult to detect on Gram stain and may produce a meningitis with CSF monocytosis, which is more characteristic of aseptic than most bacterial meningitis. TB is notoriously difficult to identify microscopically and may produce CSF with characteristics similar to those in aseptic meningitis; clues to TB meningitis are clinical findings, elevated CSF protein, and mildly decreased CSF glucose (see Meningitis: Diagnosis and Treatment). Idiopathic intracranial hypertension sometimes mimics aseptic meningitis.

In most patients, the diagnosis is clear, and treatment requires only hydration, analgesics, and antipyretics. If listerial, partially treated, and early bacterial meningitis cannot be excluded, antibiotics effective against bacterial meningitis are given pending results of cultures or repeat CSF tests. Drug-induced aseptic meningitis resolves when the causative drug is withdrawn. Mollaret's meningitis may be treated with acyclovir Some Trade Names
ZOVIRAX
Click for Drug Monograph
(see Herpesviruses: Acyclovir).

Last full review/revision November 2005

Content last modified November 2005