Aseptic Meningitis in Adults

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Official reprint from UpToDate®

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Aseptic meningitis in adults

Author: Rodrigo Hasbun, MD, MPH, FIDSA
Section Editor: Allan R Tunkel, MD, PhD, MACP
Deputy Editor: Jennifer Mitty, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2023. | This topic last updated: Nov 16, 2022.
INTRODUCTION
The term aseptic meningitis syndrome was initially described in 1925 by Wallgren as an acute
community-acquired meningitis with a negative cerebrospinal fluid (CSF) Gram stain and
culture, absence of a systemic illness or parameningeal focus, and a benign clinical outcome.
The most common etiologies are viruses (enteroviruses, arboviruses, herpes simplex virus type
2) [1]. However, this term also includes more than 100 causes, such as other infections
(mycobacteria, fungi, spirochetes), parameningeal infections, medications, and malignancies
( table 1) [2]. In many patients with aseptic meningitis, this diagnostic uncertainty has
fostered hospital admissions and unnecessary cranial imaging and empirical antibiotic therapy.
This topic will provide an overview of the diagnostic approach to patients who present with
presumed aseptic meningitis, as well as a review of the most common etiologies. The approach
to diagnosis and management of patients with suspected bacterial meningitis is presented
elsewhere. (See "Clinical features and diagnosis of acute bacterial meningitis in adults".)
INITIAL EVALUATION
Clinical evaluation
History — In patients who present with suspected meningitis, the initial history provides
important information that impacts diagnostic testing and empiric treatment. (See 'Diagnostic
testing' below and 'Antimicrobial therapy' below.)
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It is important to assess for underlying conditions, especially those that may result in some
degree of immune compromise. In addition, clinicians should evaluate for:
● Features consistent with bacterial meningitis – Patients with bacterial meningitis are
usually quite ill and often present soon after symptom onset. The classic triad of acute
bacterial meningitis consists of fever, nuchal rigidity, and a change in mental status but is
only present in 41 percent of patients [3]. Patients with aseptic meningitis often present
with a few-day history of fever, headache, stiff neck, nausea, and photophobia. In contrast
to bacterial meningitis, patients do not present with altered mental status and the onset
may be less acute. A detailed discussion of the clinical features of bacterial meningitis are
presented elsewhere. (See "Clinical features and diagnosis of acute bacterial meningitis in
adults", section on 'Clinical features'.)
● Features consistent with encephalitis – The presence or absence of normal brain

function is the important distinguishing feature between encephalitis and aseptic
meningitis.
• Patients with aseptic meningitis may be transiently lethargic but their cerebral function
remains normal.
• By contrast, patients with encephalitis commonly have altered mental status. A

consensus statement of the international encephalitis consortium developed the
following case definition for encephalitis: altered mental status for more than 24 hours
without an alternative diagnosis (major criteria) with at least two (possible) or three or
more (probable or confirmed) of the following six criteria: 1) fever >38°C (100.4°F); 2)
generalized or partial seizures not attributed to a pre-existing seizure disorder; 3) new
onset focal neurologic findings; 4) cerebrospinal fluid (CSF) white blood cell (WBC)
count >5/microL; 5) new or acute neuroimaging abnormalities; and 6) abnormal
electroencephalogram consistent with encephalitis [4].
However, the distinction between the two entities can sometimes be 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".)
● Clues to help identify etiology — Clinicians should bear in mind the following points:
• Travel and exposure history – A travel and exposure history can provide important
clues. Clinicians should assess for exposures to mosquitoes (arboviruses), rodents
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(lymphocytic choriomeningitis virus [LCMV]), and ticks (Borrelia burgdorferi), as well as

travel to certain areas (tuberculosis, coccidioidal infection), sexual activity (herpes
simplex virus [HSV]-2, human immunodeficiency virus [HIV], Treponema pallidum), and
contact with other individuals with similar symptoms or viral exanthems
(enteroviruses). (See "Evaluation of fever in the returning traveler" and "Skin lesions in
the returning traveler" and "Approach to illness associated with travel to Latin America
and the Caribbean" and "Approach to illness associated with travel to South Asia".)
• Season – Certain infections have a seasonal distribution. As an example, aseptic

meningitis occurring during the summer or fall is most likely to be caused by
enteroviruses (eg, Coxsackievirus, echovirus, other nonpoliovirus enteroviruses) or by
human parechovirus [5]. Other infections that occur during this time frame include
arboviral and Lyme meningitis. However, infections due to other pathogens (eg, herpes
viruses) can occur at any time. (See "Enterovirus and parechovirus infections: Clinical
features, laboratory diagnosis, treatment, and prevention" and "Nervous system Lyme
disease" and "Clinical manifestations and diagnosis of West Nile virus infection".)
• New medications – Patients should be specifically questioned about use of drugs

associated with meningitis (eg, nonsteroidal anti-inflammatory drugs [NSAIDs],
intravenous immune globulin, trimethoprim-sulfamethoxazole). (See 'Drug-induced
meningitis' below.)
Physical examination
● General findings – Patients with meningitis typically present with fever and signs of
meningeal irritation (eg, nuchal rigidity and photophobia). Tests to illustrate meningismus,
such as Kernig and Brudzinski signs ( table 2), may be positive but were originally
developed and tested in patients with severe, late-stage untreated bacterial and
tuberculous (TB) meningitis in the preantibiotic era.
● Findings concerning for bacterial meningitis – It can be difficult to distinguish aseptic

and bacterial meningitis on clinical exam alone. However, one distinguishing feature may
be the presence of altered mental status and focal neurologic signs in patients with
bacterial meningitis. In addition, although rash can be associated with many types of
meningitis, the presence of petechiae and palpable purpura would be suggestive of
meningococcal disease. (See "Clinical features and diagnosis of acute bacterial meningitis
in adults", section on 'Clinical features'.)
● Findings suggestive of a specific agent – Certain exam findings may be suggestive of a

specific etiology:
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• A diffuse maculopapular exanthem in a mildly ill patient may be consistent with

enteroviral infection, West Nile virus, HIV seroconversion, or syphilis.
• Parotitis suggests mumps meningitis, particularly in an unvaccinated patient. (See

'Mumps' below.)
• Dermatomal vesicular lesions suggest varicella-zoster virus (VZV) infection, but the
absence should not preclude testing (zoster sine herpete). (See 'Herpes virus
meningitis' below.)
• Painful ulcerative genital lesions suggest a primary episode of HSV-2 infection. (See
'Herpes virus meningitis' below.)
• Oropharyngeal thrush and cervical lymphadenopathy are consistent with primary HIV
infection. (See 'HIV' below.)
• Asymmetric flaccid paralysis strongly suggests the possibility of West Nile virus
meningitis or Enterovirus D68 or 71 [6]. (See 'Arboviruses' below.)
Laboratory testing — Patients with aseptic meningitis can have a wide range of laboratory
findings (WBC count, platelet count, liver function). The specific pattern depends upon the
etiologic agent. (See 'Infections due to specific pathogens' below.)
The typical CSF profile of patients with aseptic meningitis is described in the table ( table 3).
However, patients with viral meningitis can present with a neutrophilic pleocytosis in up to 25
percent of cases that can switch to a lymphocytic predominance if a repeat lumbar puncture
(LP) is done and with mild hypoglycorrhachia (CSF glucose between 30 and 45 mg/dL) [7,8]. (See
"Cerebrospinal fluid: Physiology and utility of an examination in disease states".)
Diagnostic testing — For patients with suspected meningitis, blood cultures and CSF testing
should be performed. Serologies (eg, Lyme, arboviruses) and polymerase chain reaction (PCR)
testing may also be helpful in identifying the etiology.
Blood cultures — All patients with suspected meningitis should have blood cultures obtained.
This is particularly helpful to identify an organism in the setting of bacterial meningitis or a
parameningeal focus. (See "Clinical features and diagnosis of acute bacterial meningitis in
adults", section on 'Blood tests' and "Pathogenesis, clinical manifestations, and diagnosis of
brain abscess", section on 'Laboratory studies'.)
Cerebrospinal fluid — An LP should be promptly performed in all patients with suspected

meningitis. The decision to perform imaging (eg, computed tomography [CT] scan) prior to LP is
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discussed elsewhere. (See "Clinical features and diagnosis of acute bacterial meningitis in
adults", section on 'Indications for CT scan before LP'.)
● The opening CSF pressure should be noted and CSF should be sent for cell count, glucose,
protein, and bacterial culture.
● Molecular tests for the most common etiologies (eg, enteroviruses, herpes viruses) should
routinely be done to decrease the use of antimicrobial therapy, avoid or decrease length
of stay for viral pathogens, and reduce the use of cranial imaging [9,10]. A rapid multiplex
PCR that detects 14 etiologies in one hour is available and can identify the most common
viral, bacterial, and fungal causes of meningitis [11]. However, this test should not be
routinely performed because of concerns of false-positive results (eg, cytomegalovirus
[CMV] and human herpesvirus 6 [HHV6]) in patients without a compatible disease and is
best utilized with infectious diseases consultation. More detailed information on molecular
testing is presented in a separate topic review. (See "Molecular diagnosis of central
nervous system infections", section on 'Types of tests'.)
● A West Nile virus immunoglobulin (Ig)M in the CSF or serum should be sent in all patients
that present between June and October in the United States [12]. (See "Clinical
manifestations and diagnosis of West Nile virus infection", section on 'Serologic tests'.)
● Additional CSF testing depends upon the concern for a specific pathogen, as discussed
below. (See 'Infections due to specific pathogens' below.)
Other types of testing — Other types of testing can be performed to help determine the
etiology in patients with aseptic meningitis. As examples:
● Disease-specific serology testing should be performed if certain conditions are suspected

(eg, syphilis, Lyme disease). (See "Syphilis: Screening and diagnostic testing", section on
'Approach to testing' and "Diagnosis of Lyme disease", section on 'Early disseminated and
late Lyme disease'.)
● HIV antibody testing should be done in all patients with meningitis [13]. If acute HIV is
being considered, blood testing for HIV RNA should be performed. (See "Acute and early
HIV infection: Clinical manifestations and diagnosis".)
● If aseptic meningitis due to HSV is suspected, the patient should be evaluated for
concomitant genital lesions, and any active lesions should be swabbed. (See
"Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus
infection".)
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ANTIMICROBIAL THERAPY
Role of empiric therapy — The decision to administer empiric antimicrobial therapy in a

patient with possible aseptic meningitis depends upon the concern for bacterial meningitis
based on the history, physical examination, and cerebrospinal fluid (CSF) findings ( table 3).
(See "Cerebrospinal fluid: Physiology and utility of an examination in disease states".)
● Antimicrobial therapy for bacterial meningitis – Antibiotics should be initiated

promptly in those with suspected bacterial meningitis. In patients with a CSF leukocytosis
and a negative Gram stain, factors predictive of bacterial meningitis include serum
leukocytes >10.0 x109/L, CSF leukocytes >2000 per mm3, CSF granulocytes >1180 per mm3,
CSF protein >2.2 g/L, CSF glucose <1.9 mmol/L, and/or fever on admission. In one study,
these factors were included in a risk score, which was dichotomized in "low-risk" (zero
variables present) and "high-risk" (>0 variables present) [14]. This risk score had a 99.6 to
100 percent sensitivity in identifying a low-risk subgroup [14,15]. Regimen selection is
summarized in the table ( table 4) and discussed in detail in a separate topic review. (See
"Initial therapy and prognosis of bacterial meningitis in adults".)
When it is not clear whether the patient has a viral or bacterial process, the treating
physician can choose empiric antibiotics for 48 hours while awaiting culture results. The
lumbar puncture (LP) should be done in the emergency department before the initiation
of antibiotic therapy to avoid impacting the sensitivity of the CSF culture [9]. A delay in
performing the LP is associated with an increase in the cost of hospitalization [16].
If the patient is symptomatically improved and culture results are negative, clinicians
should assess if the patient may have had bacterial meningitis that has been partially
treated with previous antibiotics. If there is no concern for partially treated meningitis, or
if it is confirmed to have a viral etiology, then antibiotics can generally be stopped. A
repeat LP off of antibiotics may be indicated in patients with persistent symptoms who do
not have a clear diagnosis. (See "Approach to the patient with chronic meningitis".)
● Antiviral therapy – Empiric therapy with intravenous acyclovir should be initiated if there
is a concern for herpes simplex virus (HSV) or varicella-zoster virus (VZV) encephalitis. (See
"Herpes simplex virus type 1 encephalitis" and "Treatment of herpes zoster in the
immunocompetent host", section on 'Neurologic complications'.)
Empiric therapy with intravenous acyclovir is also reasonable if clinical findings (eg,
vesicular skin lesions) are suggestive of HSV or VZV. (See 'Herpes virus meningitis' below
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and "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus
infection" and "Epidemiology, clinical manifestations, and diagnosis of herpes zoster".)
Tailored therapy — If an infectious agent is identified and is amenable to therapy (eg,

spirochetal infection such as Lyme disease or syphilis), therapy should be tailored to the best
possible treatment option. (See 'Infections due to specific pathogens' below.)
INFECTIONS DUE TO SPECIFIC PATHOGENS
Viral meningitis — A number of viruses produce aseptic meningitis, with some typically
presenting during the summer and fall (eg, enteroviruses, parechoviruses, arboviruses, Toscana
in the Mediterranean), and others presenting year round (eg, herpes simplex virus [HSV], HIV,
varicella-zoster virus [VZV]) [5,9].
Enteroviruses and parechoviruses — Aseptic meningitis occurring during the summer or fall
is most likely to be caused by enteroviruses (eg, Coxsackievirus, echovirus, other nonpoliovirus
enteroviruses) or by human parechovirus, the most common causes of viral meningitis [5].
However, seasonal variation of certain central nervous system (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
[17,18].
Enteroviral meningitis has a subacute presentation with a median duration of symptoms of

three days before presentation. Signs and symptoms typically include headache, fever, nausea
or vomiting, malaise, photophobia, and meningismus [19,20]. Rash, diarrhea, and upper
respiratory symptoms may also be present [9].
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 with a lymphocytic
pleocytosis, a modest elevation in CSF protein concentration (generally less than 100 mg/dL)
[21], and a normal glucose concentration ( table 3).
Polymerase chain reaction (PCR) testing for enteroviruses should be done in patients
presenting with aseptic meningitis to confirm the diagnosis, as this can decrease the economic
burden on health systems by decreasing the use of unnecessary antimicrobial therapy, cranial
imaging, and frequency/duration of hospital admissions [9,22,23]. 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. NAAT testing is included in multiplex PCR tests
that can be performed in one hour [11].
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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".)
Herpes virus meningitis — The two most common herpes viruses causing aseptic meningitis
are HSV and VZV [23].
● Meningitis due to HSV – HSV is a leading cause of aseptic meningitis [22]. In contrast to
HSV encephalitis, which is almost exclusively due to HSV-1, viral meningitis in
immunocompetent adults is generally caused by HSV-2 [9]. The typical CSF profile includes
a pleocytosis with a predominance of lymphocytes and a normal CSF glucose
concentration ( table 3).
HSV-2 meningitis is more commonly seen in young females with 50 percent of them
having a history of genital herpes and 30 percent having a history of previous viral
meningitis [5,24]. However, in a large prospective study of 205 patients with HSV
meningitis, only 8 percent had genital mucocutaneous lesions [24]. 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".)
For patients who present with HSV meningitis, we administer antiviral therapy. There is no
standard approach to treatment of HSV meningitis [25]. For hospitalized patients, we
administer intravenous acyclovir (10 mg/kg every eight hours). The dose should be
adjusted for individuals with reduced kidney function; recommendations are provided in
the Lexicomp drug information topic on acyclovir within UpToDate. Patients can be
switched to oral valacyclovir (1 g every eight hours) on discharge for a total of 10 days of
treatment. Oral acyclovir should not be used as it has poor oral bioavailability (15 to 35
percent). Considerations for management of recurrent HSV meningitis are discussed
below. (See 'Recurrent (Mollaret) meningitis' below.)
Most patients with HSV meningitis have a good prognosis; however, in a prospective study
of 205 adults, one-third had unfavorable outcomes (neuropsychological and
neurocognitive) at the time of discharge with 11 percent having sequelae at six-month
follow-up [24]. Although antiviral therapy is typically administered given the low risk of
treatment, the benefit of antiviral therapy for HSV meningitis remains unclear, especially in
immunocompetent hosts. As an example, in a retrospective observational study that
evaluated forty-two patient episodes of HSV meningitis, immunocompromised patients
had fewer neurologic sequelae when treated with a short course of antiviral therapy [25].
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By contrast, this benefit was not seen in a study of 60 immunocompetent patients with
HSV meningitis [26].
● Meningitis due to varicella-zoster virus – VZV can cause aseptic meningitis in patients
with or without typical skin lesions [23,26]; the latter are known as zoster sine herpete.
VZV is likely an underdiagnosed etiology, as only 1.2 percent of patients with aseptic
meningitis undergo a CSF VZV PCR [22]. In a study of 1126 patients in the United Kingdom
with suspected meningitis, in which a VZV PCR was routinely done, VZV was the third most
common cause of viral meningitis [23]. The treatment of VZV meningitis is presented
elsewhere. (See "Treatment of herpes zoster in the immunocompetent host", section on
'Neurologic complications'.)
● Meningitis due to other herpes viruses – Aseptic meningitis may be due to herpes
viruses other than HSV and VZV. Cytomegalovirus (CMV), Epstein-Barr virus, and human
herpesvirus 6 (HHV6) have all been reported to cause aseptic meningitis [9]. These are
discussed in detail separately. (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'.)
Arboviruses — Arboviruses (arthropod-borne viruses) are an important cause of aseptic

meningitis that can be transmitted by mosquitos, ticks, or sandflies [22]. Many of these also
present as encephalitis. (See "Arthropod-borne encephalitides".)
The most common arbovirus in the United States is West Nile virus, a flavivirus. Neuroinvasive
disease, which develops in about one percent of patients with West Nile virus infection, typically
occurs during the summer and fall and presents as aseptic meningitis, encephalitis,
retinopathy, or acute flaccid paralysis/myelitis. Patients with meningitis typically present with
fever, headache, nausea, vomiting, stiff neck, photophobia, and occasionally with a
maculopapular rash [22]. The CSF profile resembles enteroviral meningitis, sometimes
presenting with a neutrophilic pleocytosis [7]. Patients may have persistent headaches, memory
impairment, and chronic fatigue years after infection [6]. (See "Epidemiology and pathogenesis
of West Nile virus infection" and "St. Louis encephalitis" and "Viral encephalitis in adults".)
HIV — Primary infection with HIV frequently presents as a mononucleosis-like syndrome,

manifested by fever, malaise, lymphadenopathy, rash, and pharyngitis. A subset of these
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patients will develop meningitis or meningoencephalitis, with headache, confusion, seizures, or

cranial nerve palsies. (See "Acute and early HIV infection: Pathogenesis and epidemiology".)
In patients with acute HIV, the CSF profile characteristically has a lymphocytic pleocytosis, an
elevated protein concentration, and a normal glucose concentration ( table 3).
Documentation of primary HIV infection is accomplished by demonstrating HIV-1 viremia with
or without HIV antibody. (See "Acute and early HIV infection: Clinical manifestations and
diagnosis", section on 'Diagnosis'.)
Clinicians should have a high index of suspicion for primary HIV infection in patients with risk
factors for HIV transmission ( table 5). 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 (eg, enterovirus). Identifying patients with acute HIV infection is
important so that antiretroviral therapy can be instituted. (See "Acute and early HIV infection:
Treatment".)
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 [9]. Infection is more common during winter months.
Affected patients generally present with an influenza-like systemic illness accompanied by

headache and meningismus. Although LCMV is rarely documented as a cause of aseptic
meningitis, a seroprevalence of 5 percent was documented in a study of 400 patients with
neurologic infections in Finland [27]. A minority of patients with LCMV 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 [27]. The diagnosis is established by
serologic testing, documenting seroconversion in paired serum samples two to four weeks
apart. There is no specific antiviral therapy for LCMV.
Mumps — Aseptic meningitis is the most frequent extra-salivary 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 [27]. With the introduction of the measles, mumps, and rubella (MMR) vaccine, the
incidence of meningitis caused by mumps is <1 percent of all cases of meningitis and
encephalitis in the United Kingdom and United States [10,23].
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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; however, 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.
Spirochetes — The two major spirochetes that should be considered in the differential
diagnosis of aseptic meningitis are T. pallidum, the causative agent of syphilis, and B.
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 — T. pallidum, the causative agent of syphilis, disseminates to the CNS during early
infection. Syphilitic meningitis can present in the setting of early syphilis with headache,
malaise, and disseminated rash. (See "Syphilis: Epidemiology, pathophysiology, and clinical
manifestations in patients without HIV", section on 'Neurologic findings'.)
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 (VDRL) test is
often negative (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 presented
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. Meningitis usually occurs several weeks to
a few months after the tick bite and may be the first manifestation of Lyme disease. Clinically,
Lyme disease is largely indistinguishable from viral meningitis, with headache, fever (which is
usually mild), photosensitivity, and neck stiffness. In one study, children were unlikely to have
Lyme meningitis if all of the following were absent: ≥7 days of headache, any cranial neuritis, or
≥70 percent CSF mononuclear cells [28]; this rule of 7's classifies children as low-risk for Lyme
meningitis with a 98 percent sensitivity and a 100 percent negative predictive value. (See
"Nervous system Lyme disease", section on 'Meningitis'.)
The diagnosis of Lyme disease meningitis is facilitated when other characteristic findings are
present, such as erythema migrans. When Lyme meningitis occurs alone, the diagnosis can be
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missed unless the clinician considers other risk factors, such as potential exposure to ticks or
travel history. The diagnosis of Lyme meningitis is generally made through serologic testing.
(See "Epidemiology of Lyme disease" and "Diagnosis of Lyme disease".)
Antibiotic regimens for the treatment of Lyme meningitis are summarized in the table
( table 6) and discussed in detail separately. (See "Treatment of Lyme disease", section on
'Acute neurologic manifestations'.)
Fungal infections — Cryptococcus and coccidioidomycosis are the two major fungal infections
that should be considered in the differential diagnosis of aseptic meningitis.
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 patients without HIV" and "Epidemiology, clinical manifestations, and
diagnosis of Cryptococcus neoformans meningoencephalitis in patients with HIV".)
Symptoms typically begin in a subacute presentation, 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.
A definitive diagnosis of cryptococcal meningoencephalitis is made by culturing the organism

from the CSF. In immunocompromised persons at risk for cryptococcal meningitis, a positive
cryptococcal polysaccharide antigen in the CSF or serum strongly suggests the presence of
infection before the cultures become positive. (See "Clinical manifestations and diagnosis of
Cryptococcus neoformans meningoencephalitis in patients without HIV" and "Epidemiology,
clinical manifestations, and diagnosis of Cryptococcus neoformans meningoencephalitis in
patients with HIV".)
Treatment typically includes induction therapy with amphotericin plus flucytosine, followed by
consolidation and maintenance therapy with fluconazole. (See "Cryptococcus neoformans:
Treatment of meningoencephalitis and disseminated infection in patients without HIV" and
"Cryptococcus neoformans meningoencephalitis in persons with HIV: Treatment and
prevention".)
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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 range from one to several hundred cells. A significant number 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.
A definitive diagnosis of coccidioidal meningitis is supported by isolating Coccidioides species

from CSF or other CNS specimens; however, most cases are presumptively diagnosed by
identifying anticoccidioidal antibodies in the CSF and/or a CSF coccidioidal antigen. For most
patients with coccidioidal meningitis, fluconazole is the treatment of choice and has to be
continued for life.
Coccidioidal meningitis is discussed in detail in a separate topic review. (See "Coccidioidal

meningitis".)
Tuberculous meningitis — Patients with tuberculous (TB) meningitis typically present with a
subacute to chronic presentation, with protracted headache, vomiting, confusion, and varying
degrees of cranial nerve signs with basilar involvement on magnetic resonance imaging (MRI)
of the brain. Mental status changes can occur, leading to coma, seizures, and, at times,
hemiparesis. Although signs of disseminated TB are of diagnostic importance, they are often
absent. The Lancet consensus criteria can be useful to differentiate TB meningitis from bacterial
meningitis but is not able to differentiate it from other types of chronic meningitis, such as
neurobrucellosis or fungal meningitis [29]. (See "Clinical features and diagnosis of acute
bacterial meningitis in adults" and "Approach to the patient with chronic meningitis".)
CSF analysis typically shows elevated protein and lowered glucose concentrations with a
mononuclear pleocytosis ( table 3). The diagnosis may be definitively established in the
setting of CSF with positive smear for acid-fast bacilli, CSF culture positive for Mycobacterium
tuberculosis, or CSF with positive NAAT. However, definitive diagnosis can be challenging, and a
presumptive diagnosis of TB meningitis may be made in the setting of relevant clinical and
epidemiologic factors and typical CSF findings. (See "Tuberculous meningitis: Clinical
manifestations and diagnosis".)
3/29/23, 1:28 PM 1296
Patients with tuberculosis meningitis are typically treated for 9 to 12 months ( table 7). (See
"Central nervous system tuberculosis: Treatment and prognosis".)
Angiostrongylus infection — Angiostrongylus cantonensis, the rat lungworm, is a parasite that

is endemic in Southeast Asia and the Pacific and can cause aseptic meningitis. Symptoms
include severe headache, stiff neck, paresthesias, and uncommon facial nerve palsy [30].
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", section on 'Angiostrongylus cantonensis'.)
ADDITIONAL CONSIDERATIONS
Bacterial central nervous system infections — When evaluating a patient with aseptic
meningitis it is important to assess for prior antibiotic use. A lymphocytic cerebrospinal fluid
(CSF) profile and sterile cultures may be seen in partially treated bacterial meningitis. (See
"Clinical features and diagnosis of acute bacterial meningitis in adults".)
There are other ways in which bacterial infections can lead to a clinical picture of aseptic
meningitis with a CSF pleocytosis. As an example, parameningeal sources, such as an epidural
abscess or subdural empyema, sinus, or ear infection can occasionally lead to meningitis with
negative CSF cultures [31]. (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 also lead to brain abscesses and seeding of the CSF via
hematogenous seeding. (See "Complications and outcome of infective endocarditis", section on
'Neurologic complications'.)
Neoplasms of the leptomeninges — Several neoplasms involve the leptomeninges.

Hematologic malignancies have a particular propensity to seed the central nervous system
(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".)
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Meningeal signs caused by tumor invasion of the leptomeninges and secondary inflammation
are common. In such patients, headache, nausea, and vomiting may be the presenting
symptoms of increased intracranial pressure.
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.
The diagnosis of neoplastic meningitis is the cytologic identification of malignant cells within
the CSF.
Drug-induced meningitis — Drug-induced meningitis is an unusual adverse reaction that is

usually a diagnosis of exclusion [32]. Two mechanisms have been proposed for drug-induced
meningitis, a delayed hypersensitivity type reaction and direct meningeal irritation [32].
In a study of 329 patients with drug-induced meningitis [33], the CSF profile was either purulent
(45 percent) or lymphocytic (33 percent). The majority of patients (96 percent) had complete
resolution of symptoms after drug discontinuation.
The most commonly implicated medications are nonsteroidal anti-inflammatory drugs

(NSAIDs), certain antibiotics (eg, trimethoprim-sulfamethoxazole), intravenous immune
globulin, vaccines, intrathecal antimetabolites, corticosteroids, and anaesthetics.
Recurrent/chronic meningitis
Recurrent (Mollaret) meningitis — Mollaret 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 [22,34]. There is large patient-to-patient variation in the time course to recurrence,
which 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 of Mollaret meningitis is herpes simplex virus (HSV)-2; some
patients may have evidence of genital lesions at the time of presentation [22]. HSV-1 and
Epstein Barr virus can rarely be the cause of RBLM [22]. The management of HSV meningitis is
discussed above. (See 'Herpes virus meningitis' above.)
In patients with recurrent meningitis due to HSV-2, the use of suppressive therapy should be
determined on a case-by-case basis. Although suppressive therapy can lead to a decrease in
3/29/23, 1:28 PM 1296
genital outbreaks and possibly recurrent meningitis outbreaks, available data does not support
the use of suppressive antiviral therapy for preventing recurrent meningitis [35].
Only one small, randomized trial has 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 [35]. Study participants had been diagnosed with acute
meningitis related to primary HSV-2 infection or had a history of recurrent meningitis in the
past. During the first year of follow-up, suppressive 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 higher among patients who
had been exposed to valacyclovir (hazard ratio, 3.29: 95% CI, 10.06-10.21). This 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 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 [36]. This may be detected 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. (See "Uncommon brain tumors", section on
'Epidermoid cyst'.)
Other forms of chronic meningitis — Chronic meningitis is defined as meningitis lasting for
four weeks or more and is a complex entity with both infectious and noninfectious causes
( table 8). The symptoms can remain static, fluctuate, and/or slowly worsen. Despite extensive
testing, an etiologic diagnosis may not be determined in up to one-third of patients. The
approach to patients with chronic meningitis is presented in a separate topic review. (See
"Approach to the patient with chronic meningitis".)
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 5th to 6th 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 10th to 12th grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.
3/29/23, 1:28 PM 1296
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
● Definition and etiologies – The term aseptic meningitis typically describes an acute
community-acquired meningitis with a negative cerebrospinal fluid (CSF) Gram stain and
culture. (See 'Introduction' above.)
The most common etiologies are viruses. However, this term also includes more than 100
causes, such as other infections (mycobacteria, fungi, spirochetes), parameningeal
infections, medications, and malignancies ( table 1). (See 'Infections due to specific
pathogens' above.)
● Initial evaluation – The initial evaluation of a patient with presumed meningitis includes a
careful clinical evaluation as well as specific diagnostic testing. This evaluation informs the
use of empiric antimicrobial therapy.
• Clinical evaluation – Clinicians should evaluate patients for features consistent with
bacterial meningitis or encephalitis, as well as historical clues or physical exam findings
that may support a specific etiology. This includes the presence of underlying
conditions, especially those that may result in some degree of immune compromise.
(See 'Clinical evaluation' above.)
• Diagnostic testing – For patients with suspected meningitis, blood cultures should be
obtained, and a lumbar puncture (LP) should be promptly performed. The decision to
perform imaging (eg, CT scan) prior to LP is discussed elsewhere. (See "Clinical features
and diagnosis of acute bacterial meningitis in adults", section on 'Indications for CT
scan before LP'.)
CSF should be sent for cell count, glucose, protein, and bacterial culture. In addition,
when aseptic meningitis is being considered, molecular tests for the most common
etiologies (eg, enterovirus, herpes viruses) should be performed. (See 'Cerebrospinal
fluid' above.)
Additional types of serum and CSF testing depend upon the concern for a specific
pathogen. (See 'Infections due to specific pathogens' above.)
3/29/23, 1:28 PM 1296
● Antimicrobial therapy
• Role of empiric therapy – The decision to administer empiric antimicrobial therapy in

a patient with possible aseptic meningitis depends primarily upon the concern for
bacterial meningitis, which is based on the history, physical examination, and CSF
findings ( table 3). (See 'Role of empiric therapy' above.)
When it is not clear whether the patient has a viral or bacterial process, the treating
physician can choose empiric antibiotics for 48 hours while awaiting culture results
( table 4).
Empiric therapy with intravenous acyclovir should be initiated if there is a concern for
herpes simplex virus (HSV) or varicella-zoster virus (VZV) encephalitis or if clinical
findings (eg, vesicular skin lesions) are suggestive of herpes virus infection.
• Tailored therapy – If an infectious agent is identified and is amenable to therapy (eg,

spirochetal infection such as Lyme disease or syphilis), therapy should tailored to the
best possible treatment option. (See 'Infections due to specific pathogens' above.)
• If no source identified – A repeat LP off of antibiotics may be indicated in patients

with persistent symptoms who do not have a clear diagnosis. (See 'Additional
considerations' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate acknowledges R Paul Johnson, MD, who contributed to an earlier
version of this topic review.
Use of UpToDate is subject to the Terms of Use.
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considerations for the economic evaluation of potential therapies. Pharmacoeconomics
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2. Connolly KJ, Hammer SM. The acute aseptic meningitis syndrome. Infect Dis Clin North Am
1990; 4:599.
3. Bijlsma MW, Brouwer MC, Kasanmoentalib ES, et al. Community-acquired bacterial
meningitis in adults in the Netherlands, 2006-14: a prospective cohort study. Lancet Infect
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Dis 2016; 16:339.

4. Venkatesan A, Tunkel AR, Bloch KC, et al. Case definitions, diagnostic algorithms, and
priorities in encephalitis: consensus statement of the international encephalitis
consortium. Clin Infect Dis 2013; 57:1114.
5. Kupila L, Vuorinen T, Vainionpää R, et al. Etiology of aseptic meningitis and encephalitis in
an adult population. Neurology 2006; 66:75.
6. Murray KO, Nolan MS, Ronca SE, et al. The Neurocognitive and MRI Outcomes of West Nile
Virus Infection: Preliminary Analysis Using an External Control Group. Front Neurol 2018;
9:111.
7. Jaijakul S, Salazar L, Wootton SH, et al. The clinical significance of neutrophilic pleocytosis in
cerebrospinal fluid in patients with viral central nervous system infections. Int J Infect Dis
2017; 59:77.
8. Shrikanth V, Salazar L, Khoury N, et al. Hypoglycorrhachia in adults with community-
acquired meningitis: etiologies and prognostic significance. Int J Infect Dis 2015; 39:39.
9. Hasbun R. Acute Aseptic Meningitis Syndrome. In: Meningitis and Encephalitis: Manageme
nt and Prevention Challenges, Hasbun R (Ed), Springer, 2018. p.43.
10. Hasbun R, Rosenthal N, Balada-Llasat JM, et al. Epidemiology of Meningitis and Encephalitis
in the United States, 2011-2014. Clin Infect Dis 2017; 65:359.
11. Leber AL, Everhart K, Balada-Llasat JM, et al. Multicenter Evaluation of BioFire FilmArray
Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal
Fluid Specimens. J Clin Microbiol 2016; 54:2251.
12. Vanichanan J, Salazar L, Wootton SH, et al. Use of Testing for West Nile Virus and Other
Arboviruses. Emerg Infect Dis 2016; 22.
13. Ma B, Vigil KJ, Hasbun R. HIV Testing in Adults Presenting With Central Nervous System
Infections. Open Forum Infect Dis 2020; 7:ofaa217.
14. van Soest TM, Horst LT, Chekrouni N, et al. A risk score for identifying patients at a low risk
of bacterial meningitis amongst adults with cerebrospinal fluid leucocytosis and a negative
gram stain result: a derivation and validation study. Clin Microbiol Infect 2023; 29:360.
15. Spanos A, Harrell FE Jr, Durack DT. Differential diagnosis of acute meningitis. An analysis of
the predictive value of initial observations. JAMA 1989; 262:2700.
16. Balada-Llasat JM, Rosenthal N, Hasbun R, et al. Cost of managing meningitis and
encephalitis among adult patients in the United States of America. Int J Infect Dis 2018;
71:117.
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17. MEYER HM Jr, JOHNSON RT, CRAWFORD IP, et al. Central nervous system syndromes of
"vital" etiology. A study of 713 cases. Am J Med 1960; 29:334.
18. Abedi GR, Watson JT, Nix WA, et al. Enterovirus and Parechovirus Surveillance - United
States, 2014-2016. MMWR Morb Mortal Wkly Rep 2018; 67:515.
19. Sulaiman T, Salazar L, Hasbun R. Acute versus subacute community-acquired meningitis:
Analysis of 611 patients. Medicine (Baltimore) 2017; 96:e7984.
20. Jaijakul S, Arias CA, Hossain M, et al. Toscana meningoencephalitis: a comparison to other
viral central nervous system infections. J Clin Virol 2012; 55:204.
21. Zakhour R, Aguilera E, Hasbun R, Wootton SH. Risk Classification for Enteroviral Infection in
Children With Meningitis and Negative Gram Stain. Pediatr Emerg Care 2018; 34:791.
22. Shukla B, Aguilera EA, Salazar L, et al. Aseptic meningitis in adults and children: Diagnostic
and management challenges. J Clin Virol 2017; 94:110.
23. McGill F, Griffiths MJ, Bonnett LJ, et al. Incidence, aetiology, and sequelae of viral meningitis
in UK adults: a multicentre prospective observational cohort study. Lancet Infect Dis 2018;
18:992.
24. Jakobsen A, Skov MT, Larsen L, et al. Herpes Simplex Virus 2 Meningitis in Adults: A
Prospective, Nationwide, Population-Based Cohort Study. Clin Infect Dis 2022; 75:753.
25. Noska A, Kyrillos R, Hansen G, et al. The role of antiviral therapy in immunocompromised
patients with herpes simplex virus meningitis. Clin Infect Dis 2015; 60:237.
26. Kaewpoowat Q, Salazar L, Aguilera E, et al. Herpes simplex and varicella zoster CNS
infections: clinical presentations, treatments and outcomes. Infection 2016; 44:337.
27. Fevola C, Kuivanen S, Smura T, et al. Seroprevalence of lymphocytic choriomeningitis virus
and Ljungan virus in Finnish patients with suspected neurological infections. J Med Virol
2018; 90:429.
28. Garro A, Avery RA, Cohn KA, et al. Validation of the Rule of 7's for Identifying Children at
Low-risk for Lyme Meningitis. Pediatr Infect Dis J 2021; 40:306.
29. Sulaiman T, Medi S, Erdem H, et al. The diagnostic utility of the "Thwaites' system" and
"lancet consensus scoring system" in tuberculous vs. non-tuberculous subacute and
chronic meningitis: multicenter analysis of 395 adult patients. BMC Infect Dis 2020; 20:788.
30. Tsai HC, Lee SS, Huang CK, et al. Outbreak of eosinophilic meningitis associated with
drinking raw vegetable juice in southern Taiwan. Am J Trop Med Hyg 2004; 71:222.
31. Tattevin P, Tchamgoué S, Belem A, et al. Aseptic meningitis. Rev Neurol (Paris) 2019;
175:475.
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32. Morassutti AL, Thiengo SC, Fernandez M, et al. Eosinophilic meningitis caused by
Angiostrongylus cantonensis: an emergent disease in Brazil. Mem Inst Oswaldo Cruz 2014;
109:399.
33. Bihan K, Weiss N, Théophile H, et al. Drug-induced aseptic meningitis: 329 cases from the
French pharmacovigilance database analysis. Br J Clin Pharmacol 2019; 85:2540.
34. Shalabi M, Whitley RJ. Recurrent benign lymphocytic meningitis. Clin Infect Dis 2006;
43:1194.
35. Aurelius E, Franzen-Röhl E, Glimåker M, et al. Long-term valacyclovir suppressive treatment

after herpes simplex virus type 2 meningitis: a double-blind, randomized controlled trial.
Clin Infect Dis 2012; 54:1304.
36. Achard JM, Lallement PY, Veyssier P. Recurrent aseptic meningitis secondary to intracranial
epidermoid cyst and Mollaret's meningitis: two distinct entities or a single disease? A case
report and a nosologic discussion. Am J Med 1990; 89:807.
Topic 1296 Version 23.0
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GRAPHICS
Differential diagnosis of selected causes of aseptic meningitis
Viral
Adenovirus Influenza A and B

Arboviruses Lymphocytic choriomeningitis virus
Coxsackieviruses types A and B Measles
Cytomegalovirus Mumps
Echoviruses Parainfluenza
Encephalomyocarditis virus Poliovirus
Epstein-Barr virus Rotavirus
Herpes simplex virus types 1 and 2 Rubella
Human herpes virus 6 (in children) Toscana virus
Human Parechovirus Varicella-zoster virus
Human immunodeficiency virus
Bacterial
Actinomyces spp Mycoplasma pneumoniae

Bacterial endocarditis Nocardia spp
Borrelia burgdorferi (Lyme disease) Parameningeal bacterial infection (epidural,
Borrelia recurrentis (relapsing fever) subdural abscess)
Brucella spp Partially treated bacterial meningitis
Chlamydia spp Rickettsia spp
Leptospira spp Spirillum minor (rat bite fever)
Mycobacterium tuberculosis Treponema pallidum (syphilis)
Mycoplasma hominis Ureoplasma ureolyticum
Fungal
Aspergillus spp
Blastomyces dermatitidis
Candida spp
Coccidioides immitis
Cryptococcus neoformans
Histoplasma capsulatum
Sporothrix schenckii
Parasitic
Angiostrongylus cantonensis
Taenia solium (cysticercosis)
3/29/23, 1:28 PM 1296
Toxoplasma gondii
Trichinella spiralis
Drug
Anti-CD3 monoclonal antibody

Azathioprine
lbuprofen
Other NSAIDs
Pyridium (phenazopyridine)
Trimethoprim-sulfamethoxazole
Malignancy
Leukemia
Lymphoma
Metatstatic carcinomas and adenocarcinomas
Autoimmune
Behçet disease
Sarcoidosis
Systemic lupus erythematosus
Vogt-Koyanagi-Harada syndrome
Other
Epidermoid cyst
Postvaccination
NSAIDs: nonsteroidal anti-inflammatory drugs.
Modified from Connolly KJ, Hammer SM. The acute aseptic meningitis syndrome. Infect Dis Clin North Am 1990; 4:599.
Graphic 79745 Version 5.0
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Signs of meningeal irritation
Signs of meningeal
Maneuver Positive test
irritation
Kernig sign Place patient supine with hip The test is positive when there
flexed at 90 degrees. Attempt to is resistance to extension at the
extend the leg at the knee. knee to >135 degrees or pain in
the lower back or posterior
thigh.
Brudzinski sign Place patient in the supine The test is positive when there
position and passively flex the is flexion of the knees and hips
head toward the chest. of the patient.
Jolt accentuation of headache Patient rotates his/her head The test is positive if the patient
horizontally two to three times reports exacerbation of his/her
per second. headache with this maneuver.
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Typical cerebrospinal fluid findings in central nervous system infections*
Total white blood cell

Glucose (mg/dL) Protein (mg/dL)
(cells/microL)
100 to 100 to
<10 ¶ 10 to 40 Δ ◊ 50 to 300 § >1000
500 1000
More Bacterial Bacterial Bacterial Viral meningitis Bacterial Bacterial or Ea

common meningitis meningitis meningitis meningitis viral ba
Nervous system
meningitis me
Lyme disease
(neuroborreliosis) TB Vir
meningitis me
Encephalitis
Ne
Neurosyphilis
TB
TB meningitis ¥
me
Less TB Neurosyphilis Early bacterial Some Encephalitis En

common meningitis meningitis cases of
Some viral
mumps
Fungal infections
and LCMV
meningitis (such as
mumps and
LCMV)
TB: tuberculosis; LCMV: lymphocytic choriomeningitis virus.
* It is important to note that the spectrum of cerebrospinal fluid values in bacterial meningitis is so
wide that the absence of one or more of these findings is of little value. Refer to the UpToDate topic
reviews on bacterial meningitis for additional details.
¶ <0.6 mmol/L.
Δ 0.6 to 2.2 mmol/L.
◊ 1 to 5 g/L.
§ 0.5 to 3 g/L.
¥ Cerebrospinal fluid protein concentrations may be higher in some patients with tuberculous
meningitis; concentrations >500 mg/dL are an indication of blood-brain barrier disruption or
increased intracerebral production of immunoglobulins, and extremely high concentrations, in the
range of 2 to 6 g/dL, may be found in association with subarachnoid block.
3/29/23, 1:28 PM 1296
Recommendations for empiric antimicrobial therapy for purulent

meningitis based on patient age and specific predisposing condition*
Predisposing Common bacterial

Antimicrobial therapy
factor pathogens
Age
<1 month Streptococcus agalactiae, Escherichia Ampicillin plus cefotaxime; OR

coli, Listeria monocytogenes ampicillin plus an aminoglycoside
1 to 23 months Streptococcus pneumoniae, Neisseria Vancomycin plus a third-generation

meningitidis, S. agalactiae, cephalosporin ¶ Δ ◊
Haemophilus influenzae, E. coli
2 to 50 years N. meningitidis, S. pneumoniae Vancomycin plus a third-generation

cephalosporin ¶ Δ ◊
>50 years S. pneumoniae, N. meningitidis, L. Vancomycin plus ampicillin plus a

monocytogenes, aerobic gram- third-generation cephalosporin ¶ Δ
negative bacilli
Head trauma
Basilar skull fracture S. pneumoniae, H. influenzae, group Vancomycin plus a third-generation

A beta-hemolytic streptococci cephalosporin ¶ Δ
Penetrating trauma Staphylococcus aureus, coagulase- Vancomycin plus cefepime; OR

negative staphylococci (especially vancomycin plus ceftazidime; OR
Staphylococcus epidermidis), aerobic vancomycin plus meropenem
gram-negative bacilli (including
Pseudomonas aeruginosa)
Postneurosurgery Aerobic gram-negative bacilli Vancomycin plus cefepime; OR

(including P. aeruginosa), S. aureus, vancomycin plus ceftazidime; OR
coagulase-negative staphylococci vancomycin plus meropenem
(especially S. epidermidis)
Immunocompromised S. pneumoniae, N. meningitidis, L. Vancomycin plus ampicillin plus

state monocytogenes, aerobic gram- cefepime; OR vancomycin plus
negative bacilli (including P. meropenem §
aeruginosa)
* For recommended doses, refer to the UpToDate content on treatment of bacterial meningitis in
children and adults.
¶ Ceftriaxone or cefotaxime.
Δ Some experts would add rifampin if dexamethasone is also given.
◊ Add ampicillin if meningitis caused by Listeria monocytogenes is suspected.
3/29/23, 1:28 PM 1296
§ Meropenem provides sufficient coverage for Listeria when used as part of an initial regimen.
However, if Listeria is identified, the patient should generally be switched to a regimen that includes
ampicillin. Refer to the UpToDate topic that discusses treatment of Listeria for a discussion of
regimen selection.
Modified with permission from: Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial
meningitis. Clin Infect Dis 2004; 39:1267. Copyright © 2004 University of Chicago Press.
3/29/23, 1:28 PM 1296
Estimated per-act risk for acquisition of HIV, by exposure route
Risk per 10,000 exposures to an

Exposure route
infected source (risk)
Blood- Blood transfusion 9000 (9/10)

borne
Needle-sharing injection drug use 67 (1/150)
exposure
Percutaneous needle stick 23 (1/435)
Mucous membrane exposure to blood 10 (1/1000)

(eg, splash to eye)
Sexual Receptive anal intercourse 138 (1/72)

exposure
Insertive anal intercourse 11 (1/900)
Receptive penile-vaginal intercourse 8 (1/1250)
Insertive penile-vaginal intercourse 4 (1/2500)
Receptive or insertive penile-oral 0-4

intercourse
Other Biting, spitting, throwing body fluids Negligible

(including semen and saliva), sharing sex
toys
There are scant empiric data on per contact risk of exposure. This table lists the estimated risk by
exposure type in the absence of antiretroviral treatment of the HIV-infected source and in the
absence of amplifying factors. Most of these estimates are derived through modeling studies of
different cohorts. Clinicians need to be aware that estimates of sexual risk are often based on
studies of monogamous couples among whom amplifying factors have been treated and repeated
exposure may offer as yet unexplained protection from infection. Using a single value for assessing
risk of HIV transmission based on route of sexual exposure fails to reflect the variation associated
with important cofactors. A variety of amplifying factors and conditions have been identified, and
these factors can be expected to increase transmission probability.
Data from:
1. Donegan E, Stuart M, Niland JC, et al. Infection with human immunodeficiency virus type 1 (HIV-1) among recipients
of antibody-positive blood donations. Ann Intern Med 1990; 113:733-9.
2. Baggaley RF, Boily MC, White RG, Alary M. Risk of HIV-1 transmission for parenteral exposure and blood transfusion: A
systematic review and meta-analysis. AIDS 2006; 20:805.
3. Kaplan EH, Heimer R. HIV incidence among New Haven needle exchange participants: updated estimates from
syringe tracking and testing data. J Acquir Immune Defic Syndr 1995; 10:175-6.
4. Patel P, Borkowf CB, Brooks JT, et al. Estimating per-act HIV transmission risk: A systematic review. AIDS 2014;
28:1509-19.
5. Cohen MS. Amplified transmission of HIV-1: Missing link in the HIV pandemic. Trans Am Clin Climatol Assoc 2006; 117:
213–225.
6. Centers for Disease Control and Prevention, US Department of Health and Human Services. Updated Guidelines for
Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV—
3/29/23, 1:28 PM 1296
United States, 2016.
3/29/23, 1:28 PM 1296
Treatment of Lyme disease*
Adult Pediatric
Drug Comment
dose dose
Erythema migrans (early disease)
Doxycycline ¶ Δ ◊ 100 mg 4.4 Patients with early

orally mg/kg/day disseminated disease
twice orally who present with
daily for divided multiple erythema
10 days twice daily migrans lesions are
(maximum treated the same
100 mg per way as those with a
dose) for 10 single erythema
days migrans lesion.
For patients unable
to tolerate the
or Amoxicillin 500 mg 50 preferred regimens,
orally 3 mg/kg/day alternative
times orally treatments include:
daily for divided 3 Azithromycin (in
14 days times daily adults: 500 mg
(maximum orally once daily;
500 mg per in children: 10
dose) for 14 mg/kg/day
days [maximum 500
mg per dose]) for
7 days (range 5 to
10 days); or
or Cefuroxime 500 mg 30
axetil orally mg/kg/day Clarithromycin (in
twice orally adults: 500 mg
daily for divided orally twice daily;
14 days twice daily in children: 15
(maximum mg/kg/day
500 mg per divided twice
dose) for 14 daily [maximum
days 500 mg per
dose]) for 14 to
21 days.
Neurologic disease §
Acute neurologic Doxycycline ¶ Δ ◊ 100 mg 4.4 For patients with

disease, such as: orally mg/kg/day isolated facial nerve
twice orally palsy (eg, no
3/29/23, 1:28 PM 1296
Cranial nerve palsy daily for divided evidence of

(eg, facial nerve 14 to 21 twice daily meningitis or
palsy) days (maximum radiculoneuropathy),
Meningitis 100 mg per amoxicillin or
dose) for 14 cefuroxime is an
Radiculoneuropathy
to 21 days alternative in
(early disseminated
patients with
disease)
contraindications to
doxycycline. For
patients with other
forms of acute
neurologic disease,
most experts would
Severe neurologic Ceftriaxone ¥ ‡ 2 g IV 50 to 75 initiate IV therapy
disease, including once mg/kg IV (eg, ceftriaxone) if
encephalitis daily for once daily doxycycline cannot
14 to 28 (maximum be used.
days 2 g per In the United States,
dose) for 14 most practitioners
to 28 days favor using longer
courses of antibiotics
(eg, 28 days) for
those with evidence
of severe neurologic
disease.
Carditis
Mild (eg, asymptomatic Doxycycline ¶ Δ ◊ 100 mg 4.4

patients with first-degree orally mg/kg/day
atrioventricular block twice orally
and PR interval <300 daily for divided
milliseconds) 14 to 21 twice daily
days (maximum
100 mg per
dose) for 14
to 21 days
or Amoxicillin 500 mg 50
orally 3 mg/kg/day
times orally
daily for divided 3
14 to 21 times daily
days (maximum
500 mg per
dose) for 14
to 21 days
3/29/23, 1:28 PM 1296
axetil orally mg/kg/day
twice orally
daily for divided
14 to 21 twice daily
days (maximum
500 mg per
dose) for 14
to 21 days
More serious disease (eg, Ceftriaxone ¥ ‡ 2 g IV 50 to 75 A parenteral

symptomatic, second- or once mg/kg IV antibiotic regimen is
third-degree daily for once daily recommended for
atrioventricular block, 14 to 21 (maximum initial treatment for
first-degree days 2 g per hospitalized patients.
atrioventricular block dose) for 14 IV antibiotics should
with PR interval ≥300 to 21 days be continued until
milliseconds) high-grade
atrioventricular block
has resolved and the
PR interval has
become less than
300 milliseconds. The
patient may then be
switched to oral
therapy to complete
a 14- to 21-day
course.
A temporary
pacemaker may be
necessary for some
patients with carditis.
Arthritis
Initial treatment † Doxycycline ¶ ◊ 100 mg ≥8 years: Cefuroxime is a

orally 4.4 suitable alternative
twice mg/kg/day in patients with
daily for orally contraindications to
28 days divided doxycycline and
twice daily amoxicillin, although
(maximum it has not been
100 mg per assessed in clinical
dose) for studies for this
28 days ◊ indication.
3/29/23, 1:28 PM 1296
orally 3 mg/kg/day
times orally
daily for divided 3
28 days times daily
(maximum
500 mg per
dose) for 28
days
Persistent arthritis with Ceftriaxone ¥ 2 g IV 50 to 75 IV therapy should be

little or no response to once mg/kg IV administered to
oral antibiotics (despite daily for once daily patients who
adequate prior oral 14 to 28 (maximum presented with
therapy) days 2 g per moderate-to-severe
dose) for 14 arthritis and had
to 28 days minimal or no
response to oral
therapy.
Retreatment with a
second course of oral
or 100 mg ≥8 years: therapy can be used
Doxycycline ¶ ◊ orally 4.4 for those with
twice mg/kg/day persistent arthritis
daily for orally who initially
28 days divided presented with mild
twice daily arthritis (even if
(maximum there is a minimal
100 mg per response to therapy)
dose) for as well as those with
28 days ◊ moderate-to-severe
disease who had a
partial response to
oral therapy. If there
is an incomplete
response after the
or Amoxicillin 500 mg 50 second course of oral
orally 3 mg/kg/day treatment, then IV
times orally therapy should be
daily for divided 3 administered.
28 days times daily For patients who fail
(maximum to respond to oral
500 mg per and IV therapy, the
dose) for 28 use of disease-
days modifying
antirheumatic drugs
3/29/23, 1:28 PM 1296
or arthroscopic
synovectomy may be
indicated.
Acrodermatitis chronica atrophicans
Doxycycline ¶ ◊ 100 mg 4.4

orally mg/kg/day
twice orally
daily for divided
days (maximum
100 mg per
dose) for 21
to 28 days ◊
orally 3 mg/kg/day
times orally
daily for divided 3
21 to 28 times daily
days (maximum
500 mg per
dose) for 21
to 28 days
orally mg/kg/day
twice orally
daily for divided
days (maximum
500 mg per
dose) for 21
to 28 days
This table is meant for use with UpToDate content on Lyme disease. Refer to UpToDate content for
additional details on management of special populations (eg, pediatric and pregnant patients) and
management of those with persistent symptoms after treatment.
IV: intravenous.
* A complete response to treatment may be delayed beyond the treatment duration, regardless of
the clinical manifestation of Lyme disease. However, in most patients with persistent symptoms the
duration of treatment should not be extended.
¶ For pregnant and lactating patients, tetracyclines are generally avoided in favor of a beta-lactam
(eg, amoxicillin, cefuroxime). In the setting of neurologic disease or contraindication to a beta-
lactam, the decision to use doxycycline must be decided on a case-by-case basis. Although most
3/29/23, 1:28 PM 1296
tetracyclines are contraindicated in pregnancy because of the risk of hepatotoxicity in the mother
and potential adverse effects on fetal bone and teeth, limited data suggest these events are
extremely rare with doxycycline when short courses are used.
Δ Doxycycline also has activity against coinfections such as Anaplasma phagocytophilum and Borrelia
miyamotoi but not against Babesia microti.
◊ The American Academy of Pediatrics supports the use of doxycycline for children <8 years of age if
it is administered for ≤21 days. However, the data on safety of doxycycline in this population are
limited, and some providers still prefer a beta-lactam rather than doxycycline unless there is
evidence of neurologic disease or infection with Anaplasma. Studies have not evaluated the safety of
doxycycline in children <8 years of age when the duration of treatment is >21 days (eg, Lyme
arthritis).
§ For patients with neurologic disease, there are no studies to help guide length of therapy within
the range suggested by the guidelines, and there are no diagnostic tests to determine clearance of
infection or predict the success of therapy.
¥ Alternative IV agents include cefotaxime 2 g IV every 8 hours for 14 to 28 days for adults and 150
to 200 mg/kg/day in 3 divided doses (maximum 6 g per day) for children, or penicillin G 18 to 24
million units per day divided into doses given every 4 hours in adults and 200,000 to 400,000
units/kg/day divided every 4 hours (maximum 18 to 24 million units per day) in children.
‡ Doxycycline can be used in patients intolerant of beta-lactam antibiotics.
† On rare occasion, patients may present with late-stage neurologic disease and arthritis. In this
setting, IV therapy is usually preferred for initial treatment.
Adapted from:
1. Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical Practice Guidelines by the Infectious Diseases Society of
America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020
Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease. Arthritis Rheumatol 2021; 73:12.
2. Sanchez E, Vannier E, Wormser GP, Hu LT, et al. Diagnosis, treatment, and prevention of Lyme disease, human
granulocytic anaplasmosis, and babesiosis: a review. JAMA 2016; 315:1767.
3. American Academy of Pediatrics. Lyme disease. In: Red Book: 2018 Report of the Committee on Infectious Diseases,
31st ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, 2018. p.515.
3/29/23, 1:28 PM 1296
First-line antituberculosis drugs for treatment of CNS tuberculosis: Adult

dosing*
Drug Preparations Daily dose
Isoniazid ¶ Tablets (50 mg, 100 mg, 300 5 mg/kg (usual maximum dose
mg); elixir (50 mg/5 mL); 300 mg)
aqueous solution (100 mg/mL)
for intravenous or
intramuscular injection
Rifampin (rifampicin) Δ Capsules (150 mg, 300 mg); 10 mg/kg (usual maximum
capsule contents may be dose 600 mg)
suspended for oral
administration; aqueous
solution for intravenous
injection
Rifabutin Δ Capsule (150 mg) 5 mg/kg (usual maximum dose

300 mg)
Pyrazinamide ◊ Tablet (500 mg, scored) Patient weight 40 to 55 kg § :

1000 mg (18.2 to 25 mg/kg)
Patient weight 56 to 75 kg § :
1500 mg (20 to 26.8 mg/kg)
Patient weight 76 to 90 kg § ¥ :
2000 mg ‡ (22.2 to 26.3
mg/kg)
Ethambutol † Tablets (100 mg, 400 mg) Patient weight 40 to 55 kg § :

800 mg (14.5 to 20 mg/kg)
1200 mg (16 to 21.4 mg/kg)
1600 mg ‡ (17.8 to 21.1
mg/kg)
Adult dosing listed in this table is used in patients ≥15 years old or weighing >40 kg.
Antituberculous agents are used in multidrug combination regimens of varying duration, which
are described in detail in a separate table (refer to the UpToDate table on regimens for treatment
of drug-susceptible tuberculosis) and in the accompanying text.
CNS: central nervous system.

3/29/23, 1:28 PM 1296
* Dosing based on actual weight is acceptable in patients who are not obese. For obese patients
(>20% above ideal body weight [IBW]), dosing based on IBW may be preferred for initial doses.
Some clinicians prefer a modified IBW (IBW + [0.40 × (actual weight − IBW)]) as is done for initial
aminoglycoside doses. Because tuberculosis drug dosing for obese patients has not been
established, therapeutic drug monitoring may be considered for such patients.
¶ Pyridoxine (vitamin B6; 25 to 50 mg/day) is given with isoniazid to individuals at risk for
neuropathy (eg, pregnant women, breastfeeding infants, and individuals with HIV infection,
diabetes, alcoholism, malnutrition, chronic renal failure, or advanced age). For patients with
peripheral neuropathy, experts recommend increasing pyridoxine dose to 100 mg/day.
Δ Rifabutin dose may need to be adjusted when there is concomitant use of protease inhibitors or
nonnucleoside reverse transcriptase inhibitors. Refer to the UpToDate topic on treatment of
pulmonary tuberculosis in HIV-infected adults for specific dose adjustments.
◊ For patients with creatinine clearance <30 mL/min (by Cockroft-Gault equation) or for patients
receiving intermittent hemodialysis, pyrazinamide dosing consists of 25 to 35 mg/kg (ideal body
weight) per dose orally 3 times per week (NOT daily); max 2.5 g per dose. On the day of
hemodialysis, medications should be administered after hemodialysis. Monitoring of serum drug
concentrations should be considered to ensure adequate drug absorption without excessive
accumulation and to assist in avoiding toxicity.
§ Based on estimated lean body weight.
¥ Patients >90 kg should have serum concentration monitoring. In obese patients, weight-based
dosing is likely best based on measurements of ideal (versus total) body weight.
‡ Maximum dose regardless of weight.
† For patients with creatinine clearance <30 mL/min (by Cockroft-Gault equation) or for patients
receiving intermittent hemodialysis, ethambutol dosing consists of 20 to 25 mg/kg (ideal body
weight) per dose orally 3 times per week (NOT daily); max 1.6 g per dose. On the day of
hemodialysis, medications should be administered after hemodialysis. Monitoring of serum drug
concentrations should be considered to ensure adequate drug absorption without excessive
accumulation and to assist in avoiding toxicity.
Data adapted from:

1. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and
Prevention/Infectious Diseases Society of American clinical practice guidelines: Treatment of drug-susceptible
tuberculosis. Clin Infect Dis 2016; 63:e147.
2. Curry International Tuberculosis Center and California Department of Public Health, 2016: Drug-Resistant
Tuberculosis: A Survival Guide for Clinicians, Third Edition.
3/29/23, 1:28 PM 1296
Potential causes of chronic meningitis
Infections Noninfectious conditions Drugs

Mycobacterial Neoplastic Nonsteroidal anti-
Mycobacterium tuberculosis Sarcoidosis inflammatory drugs
Spirochetal Systemic lupus Intravenous

erythematosus immunoglobulin
Borrelia burgdorferi
Granulomatosis with Intrathecal agents
Treponema pallidum
polyangiitis (Wegener's)
Leptospira species
Behçet syndrome
Bacterial
Fabry disease
Brucella species
Central nervous system
Francisella tularensis
vasculitis
Actinomyces species
Vogt-Koyanagi-Harada
Listeria monocytogenes disease
Ehrlichia chaffeensis Chemical or drug-induced
Nocardia species meningitis
Tropheryma whipplei Idiopathic (up to one-third of
(Whipple disease) cases)
Viral Rheumatoid arthritis
Human immunodeficiency
virus
Cytomegalovirus
Epstein-Barr virus
Human T cell lymphotrophic
virus I and II
Enterovirus
Herpes simplex virus
Varicella-zoster virus
Cache Valley virus
Fungal
Cryptococcus
neoformans/gattii
Sporothrix
Histoplasma
Blastomyces
Coccidioides
Other (eg, Scedosporium
apiospermum,
Paracoccidioides,
dematiaceous molds)
3/29/23, 1:28 PM 1296
Parasitic
Taenia solium (cysticercosis)
Angiostrongylus
Schistosoma
Toxoplasma
Acanthamoeba
Balamuthia mandrillaris
3/29/23, 1:28 PM 1296
Contributor Disclosures
Rodrigo Hasbun, MD, MPH, FIDSA Grant/Research/Clinical Trial Support: Biofire
[Meningitis/encephalitis]. Speaker's Bureau: Biofire [Meningitis/encephalitis]. All of the relevant financial
relationships listed have been mitigated. Allan R Tunkel, MD, PhD, MACP Other Financial Interest:
American College of Physicians [Deputy Editor – Medical Knowledge Self-Assessment Program]. All of the
relevant financial relationships listed have been mitigated. Jennifer Mitty, MD, MPH No relevant financial
relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
Conflict of interest policy

Aseptic Meningitis in Adults

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Official reprint from UpToDate®

Aseptic meningitis in adults

● Features consistent with encephalitis – The presence or absence of normal brain

• By contrast, patients with encephalitis commonly have altered mental status. A

(lymphocytic choriomeningitis virus [LCMV]), and ticks (Borrelia burgdorferi), as well as

• Season – Certain infections have a seasonal distribution. As an example, aseptic

• New medications – Patients should be specifically questioned about use of drugs

● Findings concerning for bacterial meningitis – It can be difficult to distinguish aseptic

● Findings suggestive of a specific agent – Certain exam findings may be suggestive of a

• A diffuse maculopapular exanthem in a mildly ill patient may be consistent with

• Parotitis suggests mumps meningitis, particularly in an unvaccinated patient. (See

Cerebrospinal fluid — An LP should be promptly performed in all patients with suspected

● Disease-specific serology testing should be performed if certain conditions are suspected

Role of empiric therapy — The decision to administer empiric antimicrobial therapy in a

● Antimicrobial therapy for bacterial meningitis – Antibiotics should be initiated

Tailored therapy — If an infectious agent is identified and is amenable to therapy (eg,

INFECTIONS DUE TO SPECIFIC PATHOGENS

Enteroviral meningitis has a subacute presentation with a median duration of symptoms of

Arboviruses — Arboviruses (arthropod-borne viruses) are an important cause of aseptic

HIV — Primary infection with HIV frequently presents as a mononucleosis-like syndrome,

patients will develop meningitis or meningoencephalitis, with headache, confusion, seizures, or

Lymphocytic choriomeningitis virus — Lymphocytic choriomeningitis virus (LCMV) is a

Affected patients generally present with an influenza-like systemic illness accompanied by

CSF findings include a lymphocytic pleocytosis with an elevated protein concentration;

Cryptococcal infection — Cryptococcus neoformans produces infection following inhalation

A definitive diagnosis of cryptococcal meningoencephalitis is made by culturing the organism

Coccidioidal infection — Coccidioides immitis is endemic in desert regions of the southwestern

A definitive diagnosis of coccidioidal meningitis is supported by isolating Coccidioides species

Coccidioidal meningitis is discussed in detail in a separate topic review. (See "Coccidioidal

Angiostrongylus infection — Angiostrongylus cantonensis, the rat lungworm, is a parasite that

Neoplasms of the leptomeninges — Several neoplasms involve the leptomeninges.

Drug-induced meningitis — Drug-induced meningitis is an unusual adverse reaction that is

The most commonly implicated medications are nonsteroidal anti-inflammatory drugs

Recurrent (Mollaret) meningitis — Mollaret meningitis is a form of recurrent benign

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

SUMMARY AND RECOMMENDATIONS

• Role of empiric therapy – The decision to administer empiric antimicrobial therapy in

• Tailored therapy – If an infectious agent is identified and is amenable to therapy (eg,

• If no source identified – A repeat LP off of antibiotics may be indicated in patients

Use of UpToDate is subject to the Terms of Use.

1. Parasuraman TV, Frenia K, Romero J. Enteroviral meningitis. Cost of illness and

Dis 2016; 16:339.

35. Aurelius E, Franzen-Röhl E, Glimåker M, et al. Long-term valacyclovir suppressive treatment

Differential diagnosis of selected causes of aseptic meningitis

Adenovirus Influenza A and B

Actinomyces spp Mycoplasma pneumoniae

Anti-CD3 monoclonal antibody

NSAIDs: nonsteroidal anti-inflammatory drugs.

Graphic 79745 Version 5.0

Signs of meningeal irritation

Graphic 82677 Version 4.0

Typical cerebrospinal fluid findings in central nervous system infections*

Total white blood cell

More Bacterial Bacterial Bacterial Viral meningitis Bacterial Bacterial or Ea

Less TB Neurosyphilis Early bacterial Some Encephalitis En

TB: tuberculosis; LCMV: lymphocytic choriomeningitis virus.

Δ 0.6 to 2.2 mmol/L.

Graphic 76324 Version 11.0