Approach to the patient with chronic meningitis

16/03/15 07:34

Official reprint from UpToDate

www.uptodate.com 2015 UpToDate

Approach to the patient with chronic meningitis

Author
Daniel J Sexton, MD

Section Editor
Stephen B Calderwood, MD

Deputy Editor
Anna R Thorner, MD

Disclosures: Daniel J Sexton, MD Grant/Research/Clinical Trail Support: Cubist [C. difficile infection (Fidaxomycin)]. Consultant/Advisory
Boards: Johnson & Johnson [Pelvic mesh-related infection]; Sterilis [Medical waste disposal systems]. Other Financial Interest: National
Football League [Infection control program]. Stephen B Calderwood, MD Patent Holder: Vaccine Technologies Inc. [Vaccines (Cholera
vaccines)]. Equity Ownership/Stock Options: Pulmatrix [Inhaled antimicrobials]; PharmAthene [Anthrax (Anti-protective antigen monoclonal
antibody)]. Anna R Thorner, MD Employee of UpToDate, Inc.
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INTRODUCTION Meningitis can be classified on the basis of its underlying cause, type of inflammatory response, or
Conflict of interest policy

the time course of the illness. Based upon the time course, meningitis is defined as acute or chronic. The onset of
symptoms of acute meningitis typically is abrupt with progression over hours, but some patients become ill over several
days, especially when early symptoms are not appreciated. (See "Clinical features and diagnosis of acute bacterial
meningitis in adults".)
Acute meningitis due to infectious causes usually does not recur. However, a small number of patients with acute
meningitis may develop recurrent attacks between intervals of good health. (See "Approach to the adult with recurrent
infections", section on 'Meningitis'.)
Chronic meningitis is arbitrarily defined as meningitis lasting for four weeks or more and is a complex entity with both
infectious and noninfectious causes [1-7]. Although some authors attempting to define the syndrome of chronic
meningitis have excluded patients with meningitis occurring concurrently with mass lesions of the central nervous
system, meningitis associated with previously diagnosed systemic diseases known to cause meningitis, and meningitis
following neurosurgical procedures, this definition may be too restrictive for clinical purposes [8]. Patients with chronic
meningitis usually have a subacute onset of symptoms including fever, headache, and vomiting. The symptoms can
remain static, fluctuate, and/or slowly worsen. The symptoms and clinical course of chronic meningitis vary widely from
patient to patient.

The differential diagnosis, clinical evaluation, prognosis, and management strategies for patients with chronic meningitis,
including those in whom a diagnosis cannot be established with routine tests, will be reviewed here. Individual conditions
associated with chronic meningitis are discussed separately. (See related topics.)
LIMITATIONS OF THE LITERATURE Because of its rarity and the diversity of causes, the literature on chronic
meningitis consists largely of case reports and a small number of retrospective case series from single centers.
Selection and ascertainment basis greatly limit the utility of this literature for assessing the relative proportions of
patients with any given etiologic diagnosis and for assessing the natural history of individual patients with chronic
meningitis.
Most of these case series describe patients from referral centers or geographic areas where selection bias was likely
because of unique patient populations or because of local referral patterns. For example, one case series summarizing
the clinical features of 83 patients with chronic meningitis collected over a 16-year period in a referral hospital in New
Zealand reported that 40 percent of patients had tuberculous meningitis and that an additional 17 percent of patients
responded to empiric antituberculous therapy [9]. However, most of the patients with tuberculosis (TB) described in this
report were indigenous Maori people or Pacific island residents.

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In another report describing 114 consecutive patients with chronic meningitis admitted to a Bangkok hospital,
tuberculosis was responsible for 37 percent of cases, and Cryptococcus neoformans was the etiologic agent in 54
percent [10]. A high proportion of these patients had HIV infection and the presence or absence of HIV infection had a
major impact on the likelihood that a specific pathogen would be found. Similar problems related to selection or
ascertainment bias make it difficult to interpret reports concerning the utility of various diagnostic tests in patients with
chronic meningitis [11].
ETIOLOGIES An array of infectious agents can present as chronic meningitis, but a nearly identical syndrome can
result from a number of inflammatory, malignant, or other noninfectious diseases (table 1) [5,6]. Despite extensive
testing, an etiologic diagnosis may not be determined in up to one-third of all patients.
The initial evaluation of patients with chronic meningitis is often complex and difficult. In some cases, the diagnosis is
first suspected and later confirmed because of subtle historical or epidemiologic clues or because of associated clinical
findings that at first glance may seem to be incidental. For example, the presence of iritis or uveitis or the finding of
localized cutaneous lesions may provide a crucial clue to the presence of diseases, such as sarcoidosis, Behets
disease, granulomatosis with polyangiitis (Wegeners), uveo-meningitis syndromes, or a systemic fungal infection that
initially manifested as chronic meningitis. Similarly, the simultaneous presence of deafness and optic neuritis and uveitis
are strong clues to a diagnosis of Vogt-Koyanagi-Haradi syndrome.
CLINICAL FEATURES The clinical symptoms of patients with chronic meningitis rarely point to a specific etiologic
diagnosis. However, occasionally, a historical or epidemiologic clue can lead to the discovery of an otherwise obscure
diagnosis (table 2).
History A history of travel to the southwestern United States or southern California can be a crucial clue to the
presence of coccidioidomycosis in a patient with chronic meningitis residing in a nonendemic area. Sometimes the
history of travel may be distant, forgotten, or deemed to be inconsequential. For example, patients with
coccidioidomycosis may acquire their infection after short stays in airports in endemic areas, and such information may
be missed unless a meticulous history is obtained. Thus, all patients with chronic meningitis should be questioned about
travel or residence in geographic areas known to be endemic for coccidioidomycosis, histoplasmosis,
paracoccidioidomycosis, blastomycosis, schistosomiasis, trypanosomiasis, angiostrongylus cantonensis infection, or
cysticercosis. (See "Coccidioidal meningitis" and "Pathogenesis and clinical manifestations of disseminated
histoplasmosis".)
A past history of a positive tuberculin skin test or of a known exposure to tuberculosis (TB) may be enough justification to
institute empiric therapy for tuberculous meningitis or to pursue this diagnosis further with special cultures or testing
based upon polymerase chain reaction (PCR) technology, especially if preexisting infection with HIV is present. (See
"Central nervous system tuberculosis".)
The immune status of all patients with chronic meningitis should be assessed by both history and laboratory testing.
Patients should be questioned about risk factors for both human immunodeficiency virus (HIV) and human Tlymphotropic virus (HTLV)-I and -II (eg, a history of injection drug use, sexual promiscuity) and about possible or known
exposure to syphilis. Lyme disease is a rare cause of chronic meningitis, but patients should be asked about a past
history of skin lesions typical or suggestive of erythema migrans or travel to or contact with ticks in an endemic area for
Borrelia burgdorferi infection.
A careful review of all recent medications including the use of immunosuppressive drugs, immunoglobulin therapy, and
nonsteroidal antiinflammatory (NSAIDs) agents should be undertaken. Patients should be questioned about contact with
animals, including cats and wild game, or meat processing. The presence or absence of systemic symptoms suggesting
a vasculitic disorder, such as granulomatosis with polyangiitis (Wegeners), systemic lupus erythematosus, or Behet's
syndrome, should be sought. For example, a history of iritis, recurrent genital or oral ulcers, or of nasal inflammation may

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lead to a diagnosis of Behet's disease.

The presence of systemic symptoms such as weight loss, unexplained cough, or night sweats may be difficult to assess,
since such symptoms can occur as a consequence of chronic meningitis or be related to an underlying malignancy that
is the primary cause of the inflammatory reaction in the central nervous system (CNS).
A history of invasive spinal procedures, such as glucocorticoid injections for spinal pain, can be an important diagnostic
clue to the presence of fungal meningitis due to contaminated glucocorticoids. (See "Outbreak of fungal central nervous
system and osteoarticular infections in the United States: Epidemiology, clinical manifestations, and diagnosis".)
Careful questioning about the onset of symptoms is important, as it can help to determine if symptoms are intermittent
(ie, more compatible with recurrent meningitis) or continuous. This determination occasionally can be difficult if
symptoms in patients with chronic meningitis fluctuate over time.
DIAGNOSIS Patients with chronic meningitis typically undergo an array of complex diagnostic investigations including
serologic assays, multiple imaging tests, and repeated lumbar punctures (table 3). The complexity of the diagnostic
workup is illustrated by a report summarizing the diagnostic testing of 37 consecutive patients with chronic idiopathic
meningitis evaluated at the Mayo Clinic [12]. Despite a total of 2295 tests of 44 different types performed on the
cerebrospinal fluid (CSF) of these 37 patients, a diagnosis was rarely made.
The type of laboratory testing should be based upon the clinical features of an individual case and the subsequent
probability that a specific disease is present. For example, routine evaluation of patients with chronic meningitis usually
includes tuberculin skin tests, a chest radiograph and serologic testing for syphilis, and testing for the presence of HIV
infection. However, tests for unusual infectious diseases such as Lyme disease, cysticercosis, trypanosomiasis, and/or
schistosomiasis are only necessary in patients in whom there is reasonable pretest probability that the disease or
condition is present.
CSF examination Analysis of CSF reveals abnormalities in patients with chronic meningitis, but these abnormalities
are rarely diagnostic with some notable exceptions. The presence of eosinophilia can provide an important clue to the
presence of a parasitic etiology or coccidioidomycosis (see "Eosinophilic meningitis" and "Coccidioidal meningitis").
Similarly, stained smears of a centrifuged sample of the CSF may occasionally reveal infectious agents, such as fungi or
bacteria, and thus lead to a specific etiologic diagnosis.
Antigen testing of the CSF for the presence of C. neoformans and a Venereal Disease Research Laboratory (VDRL) test
for syphilis should be performed on all patients with chronic meningitis. The sensitivity and specificity of such testing for
cryptococcal meningitis is extremely high [5]; however, capsule-deficient strains of C. neoformans can rarely cause a
false-negative antigen test [13]. (See "Clinical manifestations and diagnosis of Cryptococcus neoformans
meningoencephalitis in HIV seronegative patients" and "Pathogenesis, clinical manifestations, and treatment of late
syphilis".)
Most patients with chronic meningitis have a predominance of lymphocytes, although a small percentage of patients
have a predominance of neutrophils [14]. The differential diagnosis of chronic meningitis with a neutrophil predominance
includes nocardiosis, brucellosis, and the endemic mycoses (table 4). Nontuberculous mycobacteria can also cause
chronic meningitis associated with a predominantly neutrophilic response in some cases and with a lymphocytic
response in others. Acid-fast bacilli are usually not detectable in stains of CSF in such patients. Occasionally, grampositive rods may be visualized in the CSF of patients with chronic meningitis due to nontuberculous mycobacteria [15].
Most of the case reports describing chronic meningitis due to nontuberculous mycobacteria involved patients with a prior
history of trauma or neurosurgery but occasionally central nervous system (CNS) infections have arisen secondary to
otitis media or secondary to disseminated infections such as endocarditis [15]. (See "Central nervous system
tuberculosis" and "Diagnosis of pulmonary tuberculosis in HIV-negative patients".)

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A sample of CSF should be submitted for cultures using media appropriate for aerobic bacteria, mycobacteria, and fungi.
If routine cultures are negative, it is sometimes useful to send 10 to 20 mL of CSF to the microbiology laboratory with
instructions to culture the entire sample on appropriate media. This may be particularly useful if fungal meningitis is
suspected (eg, in neurosurgical or immunocompromised patients), since the organism may be present in low numbers
and the yield of standard cultures of CSF is poor. Polymerase chain reaction (PCR) testing of a sample of CSF using
primers specific for Mycobacterium tuberculosis may be useful in some cases, but such testing is not highly sensitive
and inter- and intra-laboratory variability of test results remains a problem [16]. Whipples disease has been rarely
associated with chronic meningitis and, in such cases, PCR testing of cerebrospinal fluid has been diagnostic [17].
If a fungal pathogen is suspected, cultures of blood and urine should be submitted to the laboratory along with
notification that fungi are possible pathogens so that appropriate media and techniques can be utilized. For example,
isolator blood cultures that utilize lysis centrifugation may rarely be useful in patients with chronic meningitis due to an
underlying fungal or mycobacterial infection. If brucellosis is suspected on the basis of epidemiologic clues such as
exposure to unpasteurized milk or milk products, blood and CSF should be cultured using media incubated in a high
concentration of carbon dioxide for three weeks, and serum should be tested for the presence of anti-brucella antibodies.
If routine tests fail to disclose a likely pathogen or a likely cause for the meningitis, at least 20 to 30 mL of CSF should
also be sent for cytologic examination, flow cytometry, and immunoglobulin heavy-chain rearrangement studies by
polymerase chain reaction. (See "Clinical presentation, pathologic features, and diagnosis of primary central nervous
system lymphoma", section on 'Cerebrospinal fluid analysis'.)
Serum antibody tests studies for fungal pathogens may not accurately detect the presence of a fungal pathogen in the
CSF. Some patients with meningitis due to H. capsulatum, for example, do not have detectable antibody titers in the
serum, yet antibodies against H. capsulatum can be detected in the CSF [18]. Similarly, detection of meningitis due to
Sporothrix may not be possible unless specific serologic testing for sporotrichosis is performed on the CSF [19].
1,3-Beta-D-glucan, a cell wall component of many fungi, is detected by the beta-D-glucan assay. The beta-D-glucan
assay may be positive in patients with a variety of invasive fungal infections, including invasive candidiasis. The beta-Dglucan assay using CSF might be a useful adjunct to CSF cultures in patients with chronic Candida meningitis [20].The
beta-D-glucan assay using CSF also appeared to be useful both for diagnosing and monitoring response to treatment in
the large outbreak of fungal meningitis due to contaminated glucocorticoids; Exserohilum rostratum was the predominant
pathogen in the outbreak [21,22]. (See "Clinical manifestations and diagnosis of candidemia and invasive candidiasis in
adults", section on 'Beta-D-glucan and other antigen assays' and "Candida infections of the central nervous system",
section on 'CSF analysis' and "Outbreak of fungal central nervous system and osteoarticular infections in the United
States: Epidemiology, clinical manifestations, and diagnosis", section on 'Evaluation and diagnosis'.)
Serologic testing of serum for antibodies to Brucella, Ehrlichia, and T. gondii can rarely yield a diagnosis in a patient with
chronic meningitis, but a single positive antibody test may not be diagnostic of active infection.
Although CSF obtained from the lumbar space is usually adequate to diagnose most causes of meningitis, obtaining
spinal fluid from the ventricular space for the examination may be useful in rare cases (eg, patients with ventriculitis)
[13,23].
Imaging studies Magnetic resonance imaging (MRI) and computed tomography (CT) are useful in the evaluation of
patients with chronic meningitis, but these imaging techniques lead to specific diagnosis in a minority of patients.
However, such imaging is important since it can exclude important abnormalities such as a parameningeal focus of
infection, abscess, or a tumor. Rarely, such imaging may disclose one of these processes or the cystic changes typical
of cysticercosis. Some patients with chronic meningitis have focal or diffuse areas of meningeal enhancement, a finding
not normally diagnostic of any specific entity. However, such focal abnormalities, when present, can be useful in
selecting the site for brain biopsy if the usual diagnostic testing methods are not positive and if deterioration occurs

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during follow-up.
Brain imaging can also detect hydrocephalus that may require shunts or other neurosurgical procedures, particularly if
patients are symptomatic from increased intracranial pressure and if symptoms persist after empiric or directed medical
therapy. MRI of the spine may occasionally be useful in patients with signs or symptoms of spinal cord dysfunction or
back pain. Cerebral angiography may be diagnostic in up to two-thirds of patients with granulomatous angiitis of the
CNS; however, neither a normal angiogram nor a negative cerebral biopsy can reliably rule out this rare condition [24].
(See "Primary angiitis of the central nervous system in adults".)
Chest radiographs should be obtained in all patients with chronic meningitis. Such radiographs can lead to a diagnosis
such as tuberculosis (TB), sarcoidosis, a systemic fungal infection, or a malignancy.
Role of meningeal or brain biopsy Brain and meningeal biopsy may be useful in patients who have a progressive
deteriorating course despite empiric therapy, particularly if focal findings are detected on brain imaging. Several studies
have examined the yield of meningeal or cortical biopsy in patients with chronic meningitis who are without an etiologic
diagnosis after a careful history, clinical examination, and cultures and serologic testing of the CSF. In one case series
involving 37 patients with chronic meningitis of unknown cause who eventually underwent a biopsy, a definitive
diagnosis was made in 16 of 41 biopsies (39 percent) [11]. However, when a biopsy was performed in an area of
meningeal enhancement on either MRI or CT, a diagnosis was obtained in 12 of 15 cases (80 percent). In contrast,
surgical biopsy was diagnostic in only 2 of 22 cases (9 percent) in which the MRI showed no enhancing regions.
The findings in the preceding study are in contrast to earlier studies that failed to show a similarly high yield from
meningeal biopsy. For example, meningeal biopsy was diagnostic in only 5 of 25 patients undergoing meningeal or
cortical biopsy at a hospital in Auckland, New Zealand, during the period from 1967 to 1990 [25]. Similar disappointing
results were reported from an earlier case series from the same group involving 83 patients [9].
MANAGEMENT OF PATIENTS WITH CHRONIC MENINGITIS OF UNKNOWN CAUSE
Role of empiric therapy
Antituberculous therapy If a diagnosis is not established by the above diagnostic modalities and if symptoms
are severe or fail to improve after a period of observation, empiric therapy with antituberculous therapy may be useful
(even if the tuberculin skin test is negative). Empiric antituberculous therapy may also be warranted for patients with less
severe symptoms if epidemiologic factors or clinical findings suggest a high risk for tuberculosis (TB; eg, in patients with
a past history of direct contact with others with TB or a prior positive tuberculin skin test).
In one study including 28 patients with chronic meningitis for whom no cause could be established after a thorough
workup, almost half of the undiagnosed cases responded to empiric antituberculous medications and 11 additional
patients had a favorable or complete resolution of symptoms while on antituberculous therapy [9]. Because this study
was done in a location where TB was relatively common, this practice may not be applicable in areas with relatively low
TB prevalence.
Concurrent steroid therapy should ideally be avoided during an empiric trial of antituberculous medication because it
may obscure the evaluation of the clinical response. However, in patients with severe symptoms, concurrent steroid
therapy is reasonable and appropriate. If no improvement occurs after four to six weeks of empiric antituberculous
therapy and if all mycobacterial cultures remain negative, antituberculosis therapy can reasonably be discontinued.
Glucocorticoids Empiric glucocorticoid therapy may be useful in selected patients who fail to improve during
follow-up, despite the absence of carefully controlled studies demonstrating benefit in patients with chronic meningitis.
Some patients with chronic meningitis in whom an infectious etiology was not detected have responded dramatically to
empiric glucocorticoids as illustrated by the following findings:

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In one study of 39 patients from the Mayo Clinic with chronic meningitis of unknown cause, symptoms resolved
after the institution of glucocorticoid therapy in 19 of the 39 patients (49 percent) despite the fact that a specific
cause was not found in any of these patients [12]. The mean duration of symptoms prior to initiating glucocorticoids
in this series was 17 months; in some cases, symptoms had been present for up to nine years.
Fourteen of 39 patients (36 percent) remained symptomatic during the follow-up period; symptoms were worse at
the end of follow-up in four patients (10 percent). There were no significant differences in the clinical features at the
time of initial evaluation between patients who had a poor outcome (ie, death or worsened symptoms during followup) compared with those whose symptoms resolved, subsided, or remained stable during follow-up.
A cause for chronic meningitis was eventually established in 10 of 49 patients during follow-up. In 4 of these 10
patients, a diagnosis was obtained by repeated cerebrospinal fluid (CSF) examination (in which CSF cytology
revealed a neoplasm in four patients). A total of 21 patients underwent a meningeal or brain biopsy; a diagnosis
was obtained in 5 of these 21 patients (neoplasm was present in four of the five positive biopsies).
Seven of 17 patients with idiopathic chronic meningitis treated with glucocorticoids maintained their response to
treatment after glucocorticoids were withdrawn; treatment durations ranged from six weeks to six years [26]. A later
diagnosis of granulomatosis with polyangiitis (Wegeners) or multiple sclerosis was made in 2 of these 17 patients.
Four patients had a transient response to glucocorticoids but later died, and an additional four patients had
recurrence of symptoms upon reducing the dose of glucocorticoids.
Glucocorticoids may have to be slowly tapered and transiently reinstituted since some patients relapse rapidly when
glucocorticoid therapy is discontinued. Glucocorticoid therapy must be individualized, titrated, or reinstituted if relapse
occurs.
Antifungal therapy Empiric antifungal therapy in patients with chronic meningitis should be used with caution,
particularly if there are no compelling clinical or epidemiologic clues pointing to a specific fungal pathogen. Response to
such empiric therapy may be hard to assess because patients with fungal meningitis often respond slowly to appropriate
therapy and because such therapy can have significant side effects and/or can obscure the true diagnosis.
Prognosis Despite numerous difficulties in establishing reliable data on prognosis, most patients with chronic
meningitis in whom a diagnosis cannot be established after a thorough workup have a relatively good outcome.
Symptoms either resolve or remain stable over follow-up periods, ranging from one to three years. Repeated diagnostic
evaluations in this subgroup of patients will reveal a diagnosis in a minority of cases; the most likely diagnosis to be
uncovered during follow-up is neoplasm.
MIMICS OF CHRONIC MENINGITIS Patients with Mollaret's meningitis, a form of benign recurrent aseptic
meningitis, may be mistakenly thought of having chronic meningitis when recurrent attacks occur frequently. (See
"Aseptic meningitis in adults", section on 'Recurrent (Mollaret's) meningitis'.)
Similarly, patients with viral or postinfectious encephalitis (also known as acute disseminated encephalomyelitis, or
ADEM) and a small percentage of patients with partially treated bacterial meningitis may have symptoms lasting for
more than a month and thus may be erroneously considered to have chronic meningitis. (See "Viral encephalitis in
adults", section on 'Viral versus postinfectious encephalitis'.)
SUMMARY AND RECOMMENDATIONS
Chronic meningitis is arbitrarily defined as meningitis lasting for four weeks or more and is a complex entity with
both infectious and noninfectious causes. Patients with chronic meningitis usually have a subacute onset of
symptoms including fever, headache, and vomiting. The symptoms can remain static, fluctuate, and/or slowly
worsen. (See 'Introduction' above.)
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An array of infectious agents can present as chronic meningitis, but a nearly identical syndrome can result from a
number of inflammatory, malignant, or other noninfectious diseases (table 1). Despite extensive testing, an
etiologic diagnosis may not be determined in up to one-third of patients. (See 'Etiologies' above.)
The clinical symptoms of patients with chronic meningitis rarely point to a specific etiologic diagnosis. However,
occasionally, a historical or epidemiologic clue can lead to the discovery of an otherwise obscure diagnosis (table
2). (See 'Clinical features' above.)
Patients with chronic meningitis typically undergo an array of complex diagnostic investigations including serologic
assays, multiple imaging tests, and repeated lumbar punctures (table 3). The type of laboratory testing should be
based upon the clinical features of an individual case and the subsequent probability that a specific disease is
present. For example, routine evaluation of patients with chronic meningitis usually includes tuberculin skin tests, a
chest radiograph and serologic testing for syphilis, as well as testing for the presence of HIV infection. However,
tests for unusual infectious diseases, such as Lyme disease, cysticercosis, trypanosomiasis, and/or
schistosomiasis, are only necessary in patients in whom there is reasonable pretest probability that the disease or
condition is present. (See 'Diagnosis' above.)
Analysis of cerebrospinal fluid (CSF) reveals abnormalities in patients with chronic meningitis, but these
abnormalities are rarely diagnostic with some notable exceptions. The presence of eosinophilia can provide an
important clue to the presence of a parasitic etiology or coccidioidomycosis. Similarly, stained smears of a
centrifuged sample of the CSF may occasionally reveal infectious agents, such as fungi or bacteria, and thus lead
to a specific etiologic diagnosis. Antigen testing of the CSF for the presence of Cryptococcus neoformans and a
Venereal Disease Research Laboratory (VDRL) test for syphilis should be performed on all patients with chronic
meningitis. A sample of CSF should be submitted for cultures using media appropriate for aerobic bacteria,
mycobacteria, and fungi. Other studies that should be obtained are discussed above. (See 'CSF examination'
above.)
Magnetic resonance imaging (MRI) and computed tomography (CT) are useful in the evaluation of patients with
chronic meningitis, but these imaging techniques lead to specific diagnosis in a minority of patients. However, such
imaging is important since it can exclude important abnormalities, such as a parameningeal focus of infection,
abscess, or a tumor. Rarely, such imaging may disclose one of these processes or the cystic changes typical of
cysticercosis. (See 'Imaging studies' above.)
Brain and meningeal biopsy may be useful in patients who have a progressive deteriorating course despite empiric
therapy, particularly if focal findings are detected on brain imaging. (See 'Role of meningeal or brain biopsy'
above.)
If a diagnosis is not established despite a thorough search and if symptoms are severe or fail to improve after a
period of observation, empiric therapy with antituberculous therapy may be useful. Empiric antituberculous therapy
may also be warranted for patients with less severe symptoms if epidemiologic factors or clinical findings suggest a
high risk for TB (eg, in patients with a past history of direct contact with others with TB or a prior positive tuberculin
skin test). (See 'Antituberculous therapy' above.)
Empiric glucocorticoid therapy may be useful in selected patients who fail to improve during follow-up, despite the
absence of carefully controlled studies demonstrating benefit in patients with chronic meningitis. Some patients
with chronic meningitis in whom an infectious etiology was not detected have responded dramatically to empiric
glucocorticoids. (See 'Glucocorticoids' above.)
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