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

There are many causes (see Table 4: Meningitis: Other Causes of CSF Inflammatory Response*), which are typically classified as

• Infectious (eg, viruses, rickettsiae, spirochetes, parasites)
• Noninfectious (eg, intracranial tumors and cysts, drugs, systemic disorders)

Viruses: Enteroviruses, including echovirus, coxsackievirus, and enteroviruses 68 through 71, cause most cases of aseptic meningitis. They are transmitted through a fecal-oral, food-borne route, entering the GI tract and spreading via the bloodstream.

The next most common causes of viral meningitis are herpes simplex virus type 2 (HSV-2), HIV, and the arthropod-borne viruses. Mumps virus is a common cause worldwide but has been minimized in the US by vaccination.

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 is caused by HSV-2 and associated with prior exposure to genital herpes; most patients are unaware of their exposure.

Viruses that cause encephalitis typically also cause a low-grade aseptic meningitis.

Bacteria: Bacteria may cause lymphocytic 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 infection adjacent to the meninges can induce a sympathetic inflammatory response without bacteria being present.

Noninfectious causes: Meningeal inflammation may result from 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 ibuprofenSome Trade Names
ADVIL
MOTRIN
NUPRIN
Click for Drug Monograph
), antimicrobials (especially sulfa drugs), and immune modulators (eg, IV immune globulins, OKT3 monoclonal antibodies, cyclosporineSome Trade Names
NEORAL
SANDIMMUNE
Click for Drug Monograph
, vaccines).

Table 4
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Other Causes of CSF Inflammatory Response* Type Examples Infectious Bacterial Brucellosis, cat-scratch disease, cerebral Whipple's disease, leptospirosis, Lyme disease (neuroborreliosis), chlamydial infection, mycoplasmal infection, rickettsial infection, syphilis, TB Postinfectious Multiple viral infections (eg, measles, rubella, smallpox, vaccinia, varicella), Mycoplasma infections Viral Chickenpox (varicella-zoster); coxsackievirus, echovirus, and poliovirus infections; West Nile virus infection; St. Louis encephalitis; La Crosse (California) encephalitis; eastern and western equine encephalitis; herpes simplex virus infection; HIV infection; cytomegalovirus infections; infectious mononucleosis; lymphocytic choriomeningitis; mumps Fungi and parasites† Amebic meningitis, coccidioidomycosis, cryptococcosis, malaria, neurocysticercosis, toxoplasmosis, trichinosis Noninfectious Drugs Most commonly, NSAIDs (eg, ibuprofenSome Trade Names ADVIL MOTRIN NUPRIN Click for Drug Monograph , naproxenSome Trade Names ALEVE NAPROSYN Click for Drug Monograph , sulindacSome Trade Names CLINORIL Click for Drug Monograph , tolmetinSome Trade Names TOLECTIN Click for Drug Monograph ), especially in patients with collagen-vascular disease AzathioprineSome Trade Names IMURAN Click for Drug Monograph , carbamazepineSome Trade Names TEGRETOL Click for Drug Monograph , ciprofloxacinSome Trade Names CILOXAN CIPRO Click for Drug Monograph , cytosine arabinoside (high-dose), immune globulin, isoniazidSome Trade Names INH NYDRAZID Click for Drug Monograph , muromonab CD3, OKT3 monoclonal antibody, penicillin, phenazopyridineSome Trade Names PYRIDIUM Click for Drug Monograph , ranitidineSome Trade Names ZANTAC Click for Drug Monograph , trimethoprim/sulfamethoxazoleSome Trade Names BACTRIM SEPTRA Click for Drug Monograph 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, and smallpox Other Lead *This table includes conditions in which a bacterial pathogen is not readily identified with routine stains and cultures, as may occur in some bacterial infections. †Fungi and protozoa can cause a purulent meningitis with sepsis and CSF changes similar to bacterial meningitis, except that organisms are not seen with Gram stain; thus, they are included in this category. Other Causes of CSF Inflammatory Response* Type Examples Infectious Bacterial Brucellosis, cat-scratch disease, cerebral Whipple's disease, leptospirosis, Lyme disease (neuroborreliosis), chlamydial infection, mycoplasmal infection, rickettsial infection, syphilis, TB Postinfectious Multiple viral infections (eg, measles, rubella, smallpox, vaccinia, varicella), Mycoplasma infections Viral Chickenpox (varicella-zoster); coxsackievirus, echovirus, and poliovirus infections; West Nile virus infection; St. Louis encephalitis; La Crosse (California) encephalitis; eastern and western equine encephalitis; herpes simplex virus infection; HIV infection; cytomegalovirus infections; infectious mononucleosis; lymphocytic choriomeningitis; mumps Fungi and parasites† Amebic meningitis, coccidioidomycosis, cryptococcosis, malaria, neurocysticercosis, toxoplasmosis, trichinosis Noninfectious Drugs Most commonly, NSAIDs (eg, ibuprofenSome Trade Names ADVIL MOTRIN NUPRIN Click for Drug Monograph , naproxenSome Trade Names ALEVE NAPROSYN Click for Drug Monograph , sulindacSome Trade Names CLINORIL Click for Drug Monograph , tolmetinSome Trade Names TOLECTIN Click for Drug Monograph ), especially in patients with collagen-vascular disease AzathioprineSome Trade Names IMURAN Click for Drug Monograph , carbamazepineSome Trade Names TEGRETOL Click for Drug Monograph , ciprofloxacinSome Trade Names CILOXAN CIPRO Click for Drug Monograph , cytosine arabinoside (high-dose), immune globulin, isoniazidSome Trade Names INH NYDRAZID Click for Drug Monograph , muromonab CD3, OKT3 monoclonal antibody, penicillin, phenazopyridineSome Trade Names PYRIDIUM Click for Drug Monograph , ranitidineSome Trade Names ZANTAC Click for Drug Monograph , trimethoprim/sulfamethoxazoleSome Trade Names BACTRIM SEPTRA Click for Drug Monograph 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, and smallpox Other Lead *This table includes conditions in which a bacterial pathogen is not readily identified with routine stains and cultures, as may occur in some bacterial infections. †Fungi and protozoa can cause a purulent meningitis with sepsis and CSF changes similar to bacterial meningitis, except that organisms are not seen with Gram stain; thus, they are included in this category.

Symptoms and Signs

Aseptic meningitis often follows a flu-like syndrome and usually causes 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

• CSF analysis
• Sometimes CT before lumbar puncture

The initial concern is whether patients presenting with headache, fever, and meningeal signs have acute bacterial meningitis requiring immediate antibiotic treatment. Viral or other aseptic meningitis should be considered when patients appear less acutely ill.

Head CT or MRI is done before lumbar puncture if a brain mass is suspected (eg, based on focal neurologic signs or papilledema). Idiopathic intracranial hypertension sometimes mimics aseptic meningitis.

Differentiating bacterial meningitis from aseptic meningitis: Because bacterial meningitis requires immediate treatment and aseptic meningitis usually does not, rapid identification of bacterial meningitis is important (and sometimes difficult).

CSF findings help make the distinction (see Table 1: Meningitis: Cerebrospinal Fluid Abnormalities in Various Infections). CSF glucose is usually decreased and protein is elevated in bacterial meningitis but not in aseptic meningitis. CSF WBCs are predominantly lymphocytes in aseptic meningitis; even a few CSF neutrophils (which may, however, be present in early viral meningitis) should prompt consideration of early bacterial meningitis. However, several types of bacterial meningitis have CSF characteristics that are similar to those of aseptic meningitis; they include partially treated bacterial meningitis, Listeria meningitis (which may be difficult to detect using Gram stain and may produce CSF monocytosis, which is more characteristic of aseptic meningitis), and TB meningitis. Clues to TB meningitis are clinical findings, elevated CSF protein, and mildly decreased CSF glucose (see Meningitis: Diagnosis). CSF pressure is somewhat variable; although it is typically normal or mildly elevated in aseptic meningitis and quite high in bacterial meningitis, it may be markedly elevated in aseptic meningitis.

Blood tests sometimes help. Serum levels of procalcitonin and C-reactive protein are much higher in bacterial infections than in viral ones.

Diagnosis of specific cause: In viral meningitis, PCR is the quickest way to identify the specific infectious agent, including enteroviruses, HSV-2, HIV, and cytomegalovirus. PCR is less reliable in West Nile virus infection, which is usually diagnosed based on IgM titers.

Tests are also done to diagnose nonviral causes of aseptic meningitis (eg, rickettsial infection, Lyme disease, syphilis). Drug-induced aseptic meningitis is a diagnosis of exclusion.

Treatment

• Supportive care

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 repeated CSF tests.

Drug-induced aseptic meningitis resolves when the causative drug is withdrawn.

Recurrent HSV-2 meningitis may be treated with acyclovirSome Trade Names
ZOVIRAX
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, famciclovirSome Trade Names
FAMVIR
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, or valacyclovirSome Trade Names
VALTREX
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(see Herpesviruses: Drugs Used to Treat Herpesvirus Infections).

Last full review/revision December 2009 by John E. Greenlee, MD

Content last modified October 2011