INTRODUCTION — The term aseptic meningitis refers to patients who have clinical and laboratory evidence for meningeal inflammation with negative routine bacterial cultures. The most common causes are the enteroviruses [1]. Additional etiologies include other infections (mycobacteria, fungi, spirochetes), parameningeal infections, medications, and malignancies (table 1) [2].

Aseptic meningitis often has a similar presentation to that of bacterial meningitis (ie, fever, headache, altered mental status, stiff neck, photophobia), which can be a life-threatening illness. However, in contrast to bacterial meningitis, many patients with aseptic meningitis (particularly those who have disease caused by viruses or medications) have a self-limited course that will resolve without specific therapy.

The assessment of patients with probable aseptic meningitis is complicated by the large number of potential etiologic agents and the relatively limited diagnostic tools for identifying specific pathogens. (See "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Herpes simplex virus type 1 encephalitis".)

The symptoms, signs, and cerebrospinal fluid (CSF) findings for various etiologies of aseptic meningitis will be reviewed here. Each diagnostic entity is discussed in detail separately on the appropriate topic reviews.

MENINGITIS VERSUS ENCEPHALITIS — The presence or absence of normal brain function is the important distinguishing feature between encephalitis and meningitis. Patients with meningitis may be lethargic or distracted by headache, but their cerebral function remains normal. In contrast, patients with encephalitis commonly present with abnormalities in brain function such as altered mental status, motor or sensory deficits, altered behavior and personality changes, and speech or movement disorders. Seizures and postictal states can be seen with meningitis alone and should not be construed as definitive evidence of encephalitis. Other neurologic manifestations include hemiparesis, flaccid paralysis, and paresthesias.

However, the distinction between the two entities is frequently blurred since some patients may have both a parenchymal and meningeal process with clinical features of both. The patient is usually labeled as having meningitis or encephalitis based upon which features predominate in the illness although meningoencephalitis is also a common term that recognizes the overlap. (See "Viral encephalitis in adults".)

VIRAL MENINGITIS — A number of viruses produce aseptic meningitis including enteroviruses, herpes simplex virus (HSV), human immunodeficiency virus (HIV), West Nile virus (WNV), varicella-zoster virus (VZV), mumps, and lymphocytic choriomeningitis virus (LCM) [3]. (See "Viral encephalitis in adults".)

Enteroviruses — Aseptic meningitis occurring during the summer or fall is most likely to be caused by enteroviruses (eg, Coxsackievirus, echovirus, other non-poliovirus enteroviruses), the most common causes of viral meningitis [3]. However, seasonal variation of certain CNS viral infections is relative and not absolute. Enteroviruses continue to cause 6 to 10 percent of cases of viral meningitis in the winter and spring despite their predilection for inciting illness in the late summer and fall [4].

The presenting signs and symptoms of enteroviral meningitis are not distinctive. The onset of symptoms is characteristically abrupt and typically includes headache, fever, nausea or vomiting, malaise, photophobia, and meningismus. Rash, diarrhea, and upper respiratory symptoms may also be present.

Cerebrospinal fluid (CSF) findings are typical of other viral meningitides and include a white blood cell (WBC) count that is generally less than 250 cells/microL, a modest elevation in CSF protein concentration (generally less than 150 mg/dL), and a normal glucose concentration (table 2). (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states".)

Up to two-thirds of patients with enteroviral meningitis have a polymorphonuclear predominance in the CSF when examined early in the course of the illness. Repeat lumbar puncture after 12 to 24 hours, if performed, generally shows an evolution to a lymphocytic predominance.

Polymerase chain reaction (PCR) testing for enteroviruses can be considered if a definitive diagnosis is desired, or in the setting of an outbreak situation, but is not necessary in all patients. CSF nucleic acid amplification tests (NAATs) for enteroviruses yield sensitivities that range from 86 to 100 percent and specificities that range from 92 to 100 percent [5]. Among patients with CNS manifestations and a negative CSF NAAT, upper respiratory tract and gastrointestinal tract specimens for enterovirus may be useful to establish a diagnosis of enterovirus infection [6]. However, detection of enterovirus from the throat or stool of an individual with aseptic meningitis may represent an infection that occurred weeks previously and is unrelated to the present syndrome [5].

Additional discussions of enterovirus infections are found elsewhere. (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention" and "Enterovirus and parechovirus infections: Epidemiology and pathogenesis".)

HIV infection — Primary infection with HIV frequently presents as a mononucleosis-like syndrome manifested by fever, malaise, lymphadenopathy, rash, and pharyngitis. A subset of these patients will develop meningitis or meningoencephalitis, manifested by headache, confusion, seizures or cranial nerve palsies. (See "Acute and early HIV infection: Pathogenesis and epidemiology".)

In most patients with HIV-1 meningitis, the clinical findings resolve without treatment, and patients may be erroneously assumed to have a benign cause of viral meningitis. Thus, clinicians should have a high index of suspicion for primary HIV infection in patients at increased risk for acquisition of this virus. The identification of the patient with acute HIV infection is also important from a public health viewpoint since the risk of transmission is facilitated by high levels of viremia.

The CSF profile characteristically has a lymphocytic pleocytosis, an elevated protein concentration, and normal glucose concentration (table 2). Documentation of primary HIV infection is accomplished by demonstration of seroconversion or detection of HIV-1 viremia in the absence of HIV antibody. (See "Techniques and interpretation of HIV-1 RNA quantitation" and "Screening and diagnostic testing for HIV infection".)

Herpes simplex meningitis — Primary HSV has been increasingly recognized as a cause of viral meningitis in adults. In contrast to HSV encephalitis, which is almost exclusively due to HSV-1, viral meningitis in immunocompetent adults is generally caused by HSV-2 [3]. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection".)

Between 13 and 36 percent of patients presenting with primary genital herpes have clinical findings consistent with meningeal involvement, including headache, photophobia and meningismus. On the other hand, genital lesions are present in approximately 85 percent of patients with primary HSV-2 meningitis and generally precede the onset of CNS symptoms by approximately seven days. The CSF profile includes a pleocytosis with a predominance of lymphocytes, and a normal CSF glucose concentration (table 2). HSV meningitis can also occur without evidence of genital lesions, although this is less common [3,7]. Thus, the absence of genital lesions should not deter the clinician from testing for HSV-2 infection in a patient with aseptic meningitis. (See "PCR testing for the diagnosis of herpes simplex virus in patients with encephalitis or meningitis".)

There is no standard approach to the treatment of HSV meningitis [8]. For hospitalized patients, intravenous acyclovir at 10 mg/kg administered every eight hours is reasonable. The dose should be adjusted for individuals with reduced kidney function, and recommendations are provided in the Lexicomp drug information topic within UpToDate. Patients can be switched to an oral agent on discharge for a total of 10 to 14 days of treatment.

However, the role of antiviral therapy for HSV meningitis remains unclear, especially in immunocompetent hosts. As an example, a retrospective observational study that evaluated forty-two patient episodes of HSV meningitis found that immunocompromised patients had fewer neurologic sequelae when treated with a short course of antiviral therapy [9]. By contrast, this benefit was not seen in the 27 patient episodes that occurred in immunocompetent patients. More studies are needed to help guide management decisions.

Recurrent (Mollaret's) meningitis — Mollaret's meningitis is a form of recurrent benign lymphocytic meningitis (RBLM), an uncommon illness characterized by greater than three episodes of fever and meningismus lasting two to five days, followed by spontaneous resolution [10]. There is a large patient-to-patient variation in the time course to recurrence that can vary from weeks to years. One-half of patients can also exhibit transient neurological manifestations, including seizures, hallucinations, diplopia, cranial nerve palsies, or altered consciousness.

The most common etiologic agent in Mollaret's meningitis is HSV-2, although some patients do not have evidence of genital lesions at the time of presentation [11]. Studies suggest that recurrent meningitis occurs in approximately 20 percent of patients who present with primary HSV-2 infection with meningitis [12,13]. The diagnosis can be made by PCR testing for HSV DNA in the CSF.

A randomized controlled trial evaluated whether suppressive therapy with valacyclovir (500 mg twice daily for one year) was more effective than placebo in preventing recurrent HSV-2-related recurrent meningitis [14]. Study participants had been diagnosed with meningitis related to primary HSV-2 infection or had a history of recurrent meningitis in the past. During the first year of follow-up, valacyclovir did not have an effect on the number of episodes of meningitis, although genital HSV-2 recurrences were lower in the treatment arm. However, during the second year, when patients were without study drug, the risk of recurrence of verified and probable HSV-2 meningitis was significantly higher among patients who had been exposed to valacyclovir. The trial was limited by several factors, including: inclusion of patients without a clear etiologic diagnosis at study entry, use of symptoms alone for the diagnosis of recurrent meningitis, and small sample size.

Noninfectious etiologies for Mollaret's meningitis have also been proposed. As an example, patients with an intracranial epidermoid cyst or other cystic abnormalities in the brain can develop meningeal irritation due to intermittent leakage of irritating squamous material into the CSF [15,16]. This may be detected acutely by polarizing microscopy of CSF. Imaging studies should be performed subsequently when the patient is asymptomatic, since the epidermoid cyst is often collapsed immediately after leaking its contents.

Lymphocytic choriomeningitis virus — Lymphocytic choriomeningitis virus (LCMV) is a human zoonosis caused by a rodent-borne arenavirus. LCMV is excreted in the urine and feces of rodents, including mice, rats, and hamsters, and is transmitted to humans by exposure to secretions or excretions (by direct contact or aerosol) of infected animals or contaminated environmental surfaces [17-19]. Infection is more common during winter months.

Affected patients generally present with an influenza-like systemic illness accompanied by headache and meningismus. A minority of patients develop orchitis, parotitis, myopericarditis, or arthritis.

CSF findings are typical of other causes of viral meningitis except that low glucose concentrations are observed in 20 to 30 percent of patients with LCMV meningitis and CSF WBC counts of greater than 1000/microL are not unusual [20]. The diagnosis is established by documentation of seroconversion to the virus in paired serum samples; in addition, cell culture of CSF usually detects the presence of LCMV [5]. There is no specific antiviral therapy for LCMV.

Mumps — Aseptic meningitis is the most frequent extrasalivary complication of mumps virus infection. Prior to the introduction of the mumps vaccine in 1967, this paramyxovirus was a relatively common cause of viral meningitis, accounting for between 10 and 20 percent of all cases [4,20].

The most frequent manifestations are headache, low-grade fever, and mild nuchal rigidity. The onset of meningitis is variable and can occur before, during, or after an episode of mumps parotitis, although salivary gland enlargement is only present in about 50 percent of patients with mumps CNS disease. (See "Mumps".)

The CSF profile typically reveals fewer than 500 WBC/microL with a lymphocytic predominance, but more than 1000 WBC/microL and an early neutrophil predominance can occasionally be seen. The CSF total protein is generally normal or mildly elevated and the CSF glucose levels may be mildly depressed.

Miscellaneous viruses — A number of other viruses can infrequently be associated with viral meningitis. In certain areas of the United States, arthropod-borne viruses can cause aseptic meningitis. West Nile virus, St. Louis encephalitis virus, and California encephalitis group of viruses all can cause aseptic meningitis but more frequently are associated with encephalitis. (See "Epidemiology and pathogenesis of West Nile virus infection" and "St. Louis encephalitis" and "Viral encephalitis in adults".)

Aseptic meningitis can also be associated with varicella zoster virus infection [21], Epstein-Barr virus, cytomegalovirus, human herpes virus-6, and adenoviruses. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Aseptic meningitis' and "Human herpesvirus 6 infection in children: Clinical manifestations, diagnosis, and treatment", section on 'Less common manifestations' and "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults", section on 'Neurologic manifestations' and "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection", section on 'Nervous system'.)

OTHER INFECTIONS

Spirochetes — The two major spirochetes that need to be considered in the differential diagnosis of aseptic meningitis are Treponema pallidum, the causative agent of syphilis, and Borrelia burgdorferi, the spirochete that causes Lyme disease. Leptospirosis can also cause an aseptic meningitis syndrome. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

Syphilis — Treponema pallidum, the causative agent of syphilis, disseminates to the central nervous system during early infection. Syphilitic meningitis can present in the setting of secondary syphilis with headache, malaise, and disseminated rash. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Neurologic/ocular findings'.)

Cerebrospinal fluid (CSF) findings include a lymphocytic pleocytosis with an elevated protein concentration; occasionally a depressed glucose concentration may also be seen. Specific serum treponemal tests are almost always positive. The CSF venereal disease research laboratory test (VDRL) has a generally accepted sensitivity of 30 to 70 percent, but is highly specific in the absence of visible blood contamination. A more detailed discussion of how to diagnose neurosyphilis is found elsewhere. (See "Neurosyphilis", section on 'Diagnosis'.)

Lyme disease — Lyme meningitis typically occurs in the late summer and early fall, the same time as the peak incidence of enteroviral meningitis. During the acute primary infection, some patients develop headache, neck stiffness, and photophobia. Fever is usually mild; Kernig and Brudzinski signs are usually absent on physical examination, and neurologic features can include cranial nerve palsies, especially involving the facial nerve which may be bilateral.

The diagnosis of aseptic meningitis due to Lyme disease is facilitated when other characteristic findings are present, such as erythema migrans. When Lyme meningitis occurs alone, the diagnosis can be missed unless the clinician considers other risk factors, such as potential exposure to ticks or travel history. (See "Epidemiology of Lyme disease" and "Diagnosis of Lyme disease".)

Fungal infections — The two major fungal infections that should be considered in the differential diagnosis of aseptic meningitis include cryptococcus and coccidioidomycosis.

Cryptococcal infection — Cryptococcus neoformans produces infection following inhalation through the respiratory tract. The organism disseminates hematogenously and has a propensity to localize to the CNS, particularly in patients with severe deficiencies in cell-mediated immunity. (See "Clinical manifestations and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-seronegative patients" and "Epidemiology, clinical manifestations, and diagnosis of Cryptococcus neoformans meningoencephalitis in patients with HIV".)

Symptoms typically begin in an indolent fashion, usually over a period of one to two weeks. The three most common symptoms are fever, malaise, and headache. Stiff neck, photophobia, and vomiting are seen in one-fourth to one-third of patients.

The CSF WBC count is typically low (<50/microL) with a mononuclear predominance and the protein and glucose concentrations are usually only slightly abnormal.

Coccidioidal infection — Coccidioides immitis is endemic in desert regions of the southwestern United States and Central and South America. This infection has protean manifestations, and primary infection is frequently unrecognized. Meningitis is the most lethal complication of coccidioidomycosis and is therefore crucial to recognize.

Symptoms of meningitis, including persistent and severe headache, usually develop within several months of the initial infection. Abnormal neurologic findings on physical examination are frequently absent early in the course of coccidioidal meningitis.

The CSF WBC counts ranges from one to several hundred cells. A significant numbers of eosinophils may be present, but this finding is not specific for coccidioidal meningitis. The CSF glucose concentration may be depressed and is occasionally profoundly low in association with an elevation of the CSF protein concentration. (See "Coccidioidal meningitis".)

Tuberculous meningitis — Patients with tuberculous meningitis frequently have protracted headache, vomiting, confusion, and varying degrees of cranial nerve signs. Mental status changes can occur, leading to coma, seizures, and at times hemiparesis. Signs of disseminated TB are of diagnostic importance, but are often absent.

CSF analysis typically shows elevated protein and lowered glucose concentrations with a mononuclear pleocytosis. (See "Central nervous system tuberculosis: An overview".)

Bacterial infections — There are a variety of ways in which bacterial infections can lead to a clinical picture of aseptic meningitis with a CSF pleocytosis:

●Parameningeal sources, such as an epidural abscess or subdural empyema, sinus, or ear infection, can occasionally lead to meningitis. A thorough history and physical examination can lead to appropriate imaging and the correct diagnosis. (See "Spinal epidural abscess" and "Intracranial epidural abscess" and "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis" and "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Complications and sequelae'.)

●Bacterial endocarditis can lead to brain abscesses and seeding of the cerebrospinal fluid via hematogenous seeding. (See "Complications and outcome of infective endocarditis", section on 'Neurologic complications'.)

●A lymphocytic CSF profile and sterile cultures may be seen in partially treated bacterial meningitis. (See "Clinical features and diagnosis of acute bacterial meningitis in adults".)

Angiostrongylus infection — Angiostrongylus cantonensis, the rat lungworm, is a parasite that is endemic in Southeast Asia and Pacific that can also cause an aseptic meningitis. Symptoms include severe headache, stiff neck, paresthesias, and uncommonly facial nerve palsy [22,23].

The diagnosis of cerebral angiostrongyliasis is generally based upon the clinical presentation, CSF eosinophilia, and an epidemiologic history of known or possible exposure to infective A. cantonensis larvae. The CSF protein concentration is usually elevated, but the glucose concentration is normal or only minimally reduced. Peripheral blood and CSF eosinophilia frequently occur. (See "Eosinophilic meningitis".)

NEOPLASMS OF THE LEPTOMENINGES — Hematologic malignancies, have a particular propensity to seed the CNS, especially large cell lymphomas and acute leukemias. Solid tumors frequently causing carcinomatous meningitis include breast cancer, lung cancer, melanoma, gastrointestinal malignancies, and cancers of unknown primary origin. (See "Treatment of leptomeningeal disease from solid tumors".)

Meningeal signs caused by tumor invasion of the leptomeninges and secondary inflammation are common. Headache, nausea, and vomiting may be presenting symptoms of increased intracranial pressure.

The diagnosis of neoplastic meningitis is the cytologic identification of malignant cells within the cerebrospinal fluid (CSF). The CSF profile may include an elevated protein concentration and a lymphocytic pleocytosis; a very high protein concentration suggests a CSF block. There may be a low glucose concentration, sometimes close to zero. CSF eosinophilia can be seen in Hodgkin lymphoma.

DRUG-INDUCED MENINGITIS — Drug-induced meningitis is an unusual adverse reaction that is usually a diagnosis of exclusion [24-26]. A number of drugs can induce symptoms and signs of aseptic meningitis including nonsteroidal anti-inflammatory drugs (NSAIDs) [24-28], certain antibiotics (eg, trimethoprim-sulfamethoxazole) [29], intravenous immune globulin [24,25,30], rofecoxib, cetuximab [31], antiepileptic drugs [32,33], infliximab [34], and OKT3 antibodies.

Two mechanisms have been proposed for drug-induced meningitis: a delayed hypersensitivity type reaction and direct meningeal irritation [26].

The cerebrospinal fluid (CSF) profile typically has a neutrophilic pleocytosis. Symptoms often resolve a few days after drug discontinuation [24,30,31].

There are also multiple reports of drug-induced meningitis in patients with autoimmune disease [27,29,35]. Many of these reports implicate use of NSAIDs. It is unclear whether these patients are inherently at increased risk or whether the incidence is greater as a result of the prevalent usage of nonsteroidal anti-inflammatory drugs [36]. (See "Manifestations of systemic lupus erythematosus affecting the peripheral nervous system".)

APPROACH TO THE PATIENT — The clinical presentation of aseptic meningitis is generally nonspecific, with fever, headache, nausea and vomiting, occasionally accompanied by photophobia and a stiff neck. Physical examination typically reveals signs of nuchal rigidity.

As noted above, the approach to patients with aseptic meningitis is complicated by the diverse range of etiologic agents and relatively limited available diagnostic tools.

Historical clues — Clinicians should bear in mind the following points:

●Obtain a comprehensive travel and exposure history, including exposure to rodents (LCMV), ticks (Lyme), and tuberculosis, sexual activity (HSV-2, HIV, syphilis), and contact with other individuals with similar symptoms or viral exanthems (enteroviruses).

●Consider potential nonviral etiologies. Patients should be specifically questioned about preceding use of drugs associated with meningitis (eg, NSAIDs, intravenous immune globulin, trimethoprim-sulfamethoxazole).

Clues on physical examination — Physical examination may reveal findings suggestive of a specific agent:

●A diffuse maculopapular exanthem in a mildly ill patient may be consistent with enteroviral infection, primary HIV, or syphilis.

●Parotitis suggests mumps meningitis in an unvaccinated patient.

●Severe vesicular and ulcerative genital lesions suggests a primary episode of HSV-2 infection.

●Oropharyngeal thrush and cervical lymphadenopathy is consistent with primary HIV infection.

●Asymmetric flaccid paralysis strongly suggests the possibility of West Nile virus meningitis [26]. (See "Clinical manifestations and diagnosis of West Nile virus infection".)

Management — Based upon the history, physical examination, and cerebrospinal fluid (CSF) findings, patients can be classified as having probable bacterial meningitis, probable viral meningitis, or indeterminant (table 2). (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states".)

●For patients with suspected bacterial meningitis (eg, WBC count >1000/microL, glucose concentration <40 mg/dL [2.2 mmol/L], protein concentration >100 mg/dL), antibiotics should be initiated promptly. (See "Initial therapy and prognosis of bacterial meningitis in adults".)

●Patients with probable viral meningitis include those with CSF findings of cell count <500/microL, >50 percent CSF lymphocytes, protein concentration less than 80 to 100 mg/dL, normal glucose concentration, and negative Gram stain. Patients who are elderly, immunocompromised, or have received antibiotics prior to presentation should be given antibiotics even if viral meningitis is the suspected diagnosis. Otherwise, the clinician can consider observing the patient without antibiotic therapy.

●When it is not clear whether the patient has a viral or bacterial process, the treating physician can choose empiric antibiotics after obtaining blood and CSF cultures or observation with repeat lumbar puncture (LP) in 6 to 24 hours. The majority of clinicians opt for empiric antibiotics until culture results are available in 24 to 48 hours. If the patient is symptomatically improved and culture results are negative, then antibiotics can generally be stopped without a repeat LP if the suspicion for bacterial meningitis is unlikely. However, repeat LP may be indicated in patients with persistent symptoms who do not have a clear diagnosis.

Many patients fall into the indeterminate category because of the lack of specificity of presenting symptoms and signs and because each CSF finding taken in isolation often displays significant overlap among patients with viral and bacterial meningitis. (See "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'Cerebrospinal fluid analysis'.)

Examination of multiple parameters with the use of a nomogram may be helpful in deciding which patients should be treated empirically [37]. However, the 2004 Infectious Diseases Society of America guidelines on bacterial meningitis suggested that these prediction rules should not be used to make clinical decisions in individual patients [38]. These guidelines can be accessed through the Infectious Diseases Society of America's website [39].

Thus, in view of the serious consequences if treatment of bacterial meningitis is delayed, the threshold to initiate empiric antibiotic therapy pending the results of cultures should be relatively low. (See "Initial therapy and prognosis of bacterial meningitis in adults".)

For patients with suspected viral meningitis or indeterminate CSF results, the CSF should be sent for virus detection assay (eg, polymerase chain reaction [PCR] for HSV and enteroviruses), as well as for bacterial culture and routine CSF studies. In patients with cutaneous clues as to the etiology (eg, genital herpes or herpes zoster), PCR testing is preferred. Other tests to consider in selected patients include: serum treponemal and nontreponemal tests and CSF Venereal Disease Research Laboratory (VDRL) and fluorescent treponemal antibody absorption (FTA-ABS) tests, HIV antigen/antibody or RNA tests, Lyme serology, and acute/convalescent serologic testing for specific viruses (LCMV, mumps, measles). (See "Syphilis: Screening and diagnostic testing" and "Diagnosis of Lyme disease".)

The differential diagnosis should be broadened for the patient with lymphocytic predominance in the CSF and negative bacterial cultures if symptoms worsen or persist. Evaluation should include a repeat CSF analysis with removal of large volume of fluid (3 to 5 mL, if possible) for fungal and mycobacterial cultures, and imaging of the CNS and sinuses with magnetic resonance imaging (MRI) or computed tomography (CT). Potential noninfectious etiologies should also be considered (table 1).

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see "Patient education: Viral meningitis (The Basics)")

SUMMARY AND RECOMMENDATIONS — The diagnosis of a patient with aseptic meningitis may be difficult because of the large variety of potential etiologic agents and the overlap between self-limited viral illnesses and potentially fatal bacterial infections.

Management — A careful history should include travel and exposure history, including exposure to rodents (LCMV), ticks (Lyme disease), mosquitoes (West Nile virus, St. Louis encephalitis virus) and patients with tuberculosis, sexual activity (HSV-2, HIV, syphilis), travel (C. immitis, A. cantonensis) and contact with other individuals with similar symptoms or viral exanthems (enteroviruses). The patient should also be questioned about medications and other comorbidities.

The opening cerebrospinal fluid (CSF) pressure should be noted and CSF should be sent for cell count, glucose, protein and culture or specific antigen or nucleic acid tests for viruses, as well as culture for bacteria. Whether additional studies (eg, culture for fungi and mycobacteria) should be performed will depend on the clinical presentation (see discussion above and individual topic cards).

Based upon the history, physical examination and CSF findings, patients can often be classified as having probable bacterial or viral meningitis, although overlap can be frequent, particularly if bacterial meningitis has been partially treated with previous antibiotics.

Suspected bacterial meningitis — For patients with suspected bacterial meningitis, antibiotics should be initiated promptly. (See "Initial therapy and prognosis of bacterial meningitis in adults".)

Suspected viral meningitis — The approach to empiric antibiotic therapy in the patient with suspected viral meningitis will depend upon the clinical appearance of the patient and underlying host factors. Patients who are elderly, immunocompromised, or have received antibiotics prior to presentation may be considered for empiric therapy for 48 hours, even if viral meningitis is the suspected diagnosis. Otherwise, the clinician can consider observing the patient without antibiotic therapy.

If HIV is a diagnostic consideration, then blood testing for HIV RNA and HIV antibody should be performed. (See "Techniques and interpretation of HIV-1 RNA quantitation" and "Screening and diagnostic testing for HIV infection".)

If aseptic meningitis due to HSV is suspected (eg, concomitant genital lesions), empiric therapy with acyclovir (10 mg/kg intravenously every eight hours) can be considered for hospitalized patients. (See "Acyclovir: An overview".)

Unclear etiology — When it is not clear whether the patient has a viral or bacterial process, we recommend empiric antibiotics after obtaining blood and CSF cultures or observation with repeat lumbar puncture in 6 to 24 hours. If the patient is symptomatically improved and culture results are negative, then antibiotics can generally be stopped without a repeat LP. However, repeat LPs may be indicated in patients with persistent symptoms who do not have a clear diagnosis.

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge R Paul Johnson, MD, who contributed to an earlier version of this topic review.