Often polymicrobial (14–28% of cases)
Child: anaerobes (40%), aerobic and anaerobic viridans streptococci (GPC in chains), S. aureus (GPC), S. pneumoniae (GPDC), S. pyogenes (GPC in chains); less common: Enterobacteriaceae (GNR), P. aeruginosa (GNR), H. influenzae (GNCB), N. meningitidis (GNDC).
Adults: Viridans streptococci (anaerobic streptococci, S. milleri) (70%).
Enterobacteriaceae (GNR) (23–33%), S. aureus (GPC) (10–15%), N. meningitidis, Listeria sp., anaerobes (20–40%) including bacteroides (GNR), prevotella (GNR), fusobacterium (GNR), eubacterium (GPR), and propionibacterium (GPR), and more rarely S. pneumoniae, Rhodococcus sp., Group B streptococci (GPC in chains), nocardia (GPR), actinomyces (GPR), T. solium (cysticerci), Entamoeba histolytica, Schistosoma sp., and fungi (1%).
Immunocompromised: T. gondii, Cryptococcus neoformans, nocardia (GPR), Listeria sp. (GPR), mycobacteria (AFB), Aspergillus sp., C. albicans, coccidioides, Zygomycetes (mucor, rhizopus), E. histolytica.
Posttraumatic: S. aureus (GPC), viridans streptococci (GPC in chains), Enterobacteriaceae (GNR), coagulase-negative staphylococci (GPC), Propionibacterium acnes (GPR).
Blood for bacterial and fungal cultures.
Brain abscess aspirate for Gram stain (82%), bacterial (88%), AFB, fungal cultures, and cytology.
Lumbar puncture is dangerous and contraindicated.
Sources of infection in the ears, sinuses, lungs, or bloodstream should be sought for culture when brain abscess is found.
CT scan and MRI are the most valuable imaging procedures (see Chapter 6) and can guide brain biopsy if a specimen is needed.
Serum toxoplasma antibody in HIV-infected patients may not be positive at initiation of presumptive therapy. If negative or if no response to empiric therapy, biopsy may be needed to rule out lymphoma, fungal infection, or tuberculosis. Biopsy material should be sent for toxoplasma antigen (detected by direct fluorescent antibody, DFA).
Detection of toxoplasma DNA in blood or CSF samples by PCR techniques is now available from specialized or reference laboratories. PCR for toxoplasma is not useful once therapy has been started. A positive PCR result must be interpreted in the context of the clinical presentation.
(See also Toxoplasma antibody, Chapter 3.)
Occurs in patients with otitis media and sinusitis; cyanotic congenital heart disease and right-to-left shunting (eg, tetralogy of Fallot) or arteriovenous vascular abnormalities of the lung (eg, Osler-Weber-Rendu).
Most toxoplasmosis abscesses are multiple and are seen on MRI in the basal ganglia, parietal and frontal lobes (ring-enhancing lesions with contrast on CT scan).
Stereotactic CT-guided aspiration of abscess material facilitates microbiologic diagnosis.
Hicks CW et al. Identifying and managing intracranial complications of sinusitis in children: a retrospective series. Pediatr Infect Dis J 2011;30:222. [PubMed: 21416657]
Prasad KN et al. Analysis of microbial etiology and mortality in patients with brain abscess. J Infect 2006;53:221. [PubMed: 16436297]
Shachor-Meyouhas Y et al. Brain abscess in children—epidemiology, predisposing factors and management in the modern medicine era. Acta Paediatr 2010;99:1163. [PubMed: 20222876]
Arboviruses (California encephalitis group, St. Louis encephalitis, eastern and western equine encephalitis, West Nile virus, Japanese encephalitis virus in summer and fall), enteroviruses (coxsackie, echo, polio), HSV (10–20%), Bartonella henselae, lymphocytic choriomeningitis virus, tick-borne encephalitis virus, measles, rubella, VZV, rabies (Central and South America, India, Africa), Nipah virus (Malaysia), Chikungunya virus (India and Nepal), Creutzfeldt-Jakob.
Immunocompromised: CMV, VZV, EBV, West Nile virus, JC virus, HIV, Toxoplasma gondii.
CSF for pressure (elevated), cell count (WBCs elevated but variable [10–2000/mcL], mostly lymphocytes), protein (elevated, especially IgG fraction), glucose (normal), RBCs (suggestive of herpesvirus or other necrotizing virus). Repeat examination of CSF after 24 hours often useful. (See CSF [enteroviruses, HSV-2, mumps] profiles, Table 8–8).
CSF cultures for viruses or bacteria (low yield).
CSF PCR for CMV (33%), HSV (98%), VZV, EBV, JC virus, enterovirus, and West Nile virus.
Identification of HSV DNA in CSF by PCR techniques is now the definitive diagnostic test. HSV DNA by PCR may not be detectable early in course of illness.
Stool culture for enterovirus (2–5 days), which is frequently shed for weeks (especially in children) or in late illness.
For rabies, direct fluorescent antibody staining of skin biopsy from nape of neck (50% positive in first week) or RT-PCR on CSF or saliva.
Single serum for Bartonella (cat-scratch disease) IgM and IgG.
Test single serum for West Nile virus IgM antibody or CSF IgM antibody, or PCR of serum or CSF.
Paired sera for arboviruses and other viruses should be drawn immediately (acute specimen) and after 1–3 weeks of illness (convalescent specimen).
Urine PCR and/or serum PCR are options for diagnosis of enteroviruses.
All patients with suspected encephalitis should undergo MRI with gadolinium (most sensitive) unless contraindicated. CT scan with contrast less sensitive (50% sensitive). Temporal lobe lesions are suggestive of herpes simplex encephalitis.
Polyradiculopathy is highly suggestive of CMV in AIDS.
Consult with laboratory regarding availability of serological tests.
Baringer JR. Herpes simplex infections of the nervous system. Neurol Clin 2008;26:657. [PubMed: 18657720]
Hayes EB et al. West Nile virus: epidemiology and clinical features of an emerging epidemic in the United States. Annu Rev Med 2006;57:181. [PubMed: 16409144]
Long SS. Encephalitis diagnosis and management in the real world. Adv Exp Med Biol 2011;697:153. [PubMed: 21120725]
Acute: Enteroviruses (coxsackie, echo, polio) (90%), mumps, HSV, HIV (primary HIV seroconversion), VZV, lymphocytic choriomeningitis virus, adenovirus, parainfluenza virus 3, West Nile virus, St. Louis encephalitis virus and California group encephalitis viruses (rare).
Recurrent benign lymphocytic meningitis: HSV-2 (Mollaret meningitis).
CSF for pressure (elevated), cell count (WBCs 10–100/mcL, polomorphonuclear neutrophils (PMN searly, lymphocytes later), protein (normal or slightly elevated), and glucose (normal). On repeat CSF after 24–48 hours, an increase in lymphocytes is seen. (See CSF profiles, Table 8–8.)
CSF viral culture can be negative despite active viral infection. Enteroviruses can be isolated from the CSF in the first few days after onset (positive in 40–80%) but only rarely after the first week.
Detection of enteroviral RNA, HSV DNA, or VZV DNA in CSF by PCR from specialized or reference laboratories.
Paired sera (acute and convalescent) for antibody titers: mumps, West Nile virus, and VZV.
Consult with laboratory regarding availability of diagnostic tests for other viruses.
CT or MRI of head should be performed before lumbar puncture to evaluate for mass lesions or hydrocephalus if focal neurologic signs or papilledema are present.
Aseptic meningitis is acute meningeal inflammation in the absence of pyogenic bacteria or fungi. Diagnosis is usually made by examination of the CSF, PCR of CSF, or serologic assays and by ruling out other infectious causes of acute mental status changes or seizures (eg, toxoplasmosis, Lyme disease, neurosyphilis, tuberculosis, Rocky Mountain spotted fever, ehrlichiosis, fungal infection, and parasitic infection). Consider noninfectious causes such as nonsteroidal anti-inflammatory drugs and other medications.
Enteroviral aseptic meningitis is rare after age 40.
10–30% of patients with primary genital HSV-2 infection can have stiff neck, headache, and photophobia suggestive of recurrent meningitis.
Irani DN. Aseptic meningitis and viral myelitis. Neurol Clin 2008;26:635. [PubMed: 18657719]
Lee BE et al. Aseptic meningitis. Curr Opin Infect Dis 2007;20:272. [PubMed: 17471037]
Poulikakos PJ et al. A case of recurrent benign lymphocytic (Mollaret's) meningitis and review of the literature. J Infect Public Health 2010;3:192. [PubMed: 21126724]
Neonate: Group B streptococci (GPC) (70%), L. monocytogenes (GPR) (20%), S. pneumoniae (GPC) (10%), E. coli (GNR) and Klebsiella sp (GNR) (1%), and other streptococci.
Infant: S. pneumoniae (GPC) (47%), N. meningitidis (GNDC) (30%), group B streptococci (GPC) (18%), Listeria monocytogenes (GPR), H. influenzae (GNCB) (5%).
Child: N. meningitidis (60%), S. pneumoniae (25%), H. influenzae (8%), and other streptococci.
Adult: S. pneumoniae (60%), N. meningitidis (20%), L. monocytogenes (6%), group B streptococci (4%), other Hemophilus sp., and staphylococci (1%), Ehrlichia chaffeensis (rare).
Postneurosurgical: S. aureus (GPC), S. pneumoniae, P. acnes (GPR), coagulase-negative staphylococci (GPC), pseudomonas (GNR), E. coli (GNR), other Enterobacteriaceae, Acinetobacter (GNR).
Alcoholic patients and the elderly: In addition to the adult organisms, Enterobacteriaceae, pseudomonas, H. influenzae.
CSF for pressure (>180 mm H2O), cell count (WBCs 5000–20,000/mcL, >50% PMNs), protein (150–500 mg/dL), glucose (low <40 mg/dL). (See CSF profiles, Table 8–8.)
CSF for Gram stain of cytocentrifuged material (positive in 70–80%).
CSF culture for bacteria (positive in 70–85%).
Blood culture positive in 40–60% of patients with pneumococcal, meningococcal, and H. influenzae meningitis.
CSF antigen tests are no longer considered useful because of their low sensitivity and false-positive results.
The first priority in the care of the patient with suspected acute meningitis is therapy, then diagnosis. Start antimicrobial agents based on Gram stain, or if no bacteria are seen, start empiric antibiotics immediately based on patient age and any underlying disease process. Adjunctive dexamethasone therapy has proved beneficial, especially for pneumococcal meningitis. If lumbar puncture is performed, administer antimicrobial therapy with dexamethasone immediately after CSF collection.
The mortality rate for pneumococcal meningitis is about 20%, with 25–50% of patients having long-term neurologic complications.
With recurrent N. meningitidis meningitis, suspect a terminal complement component deficiency. With other recurrent bacterial meningitides, suspect a CSF leak; S. pneumoniae is most likely pathogen.
Therapy usually includes a 3rd generation cephalosporin plus vancomycin until culture results return. This will cover the most common pathogens as well as H. influenzae. Add ampicillin if L. monocytogenes is suspected. Therapy can be narrowed once the pathogen is identified and susceptibility results are determined.
For S. pneumoniae, there has been an increase in prevalence of penicillin- and cephalosporin-resistant strains, so susceptibility testing of pneumococcal strains is very important to guide therapy.
Bamberger DM. Diagnosis, initial management, and prevention of meningitis. Am Fam Physician 2010;82:1491. [PubMed: 21166369]
Brouwer MC et al. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010;23:467. [PubMed: 20610819]
Kim KS. Acute bacterial meningitis in infants and children. Lancet Infect Dis 2010;10:32–42. [PubMed: 20129147]
Nudelman Y et al. Bacterial meningitis: epidemiology, pathogenesis and management update. Drugs 2009;69:2577. [PubMed: 19943708]
C. neoformans (spherical, budding yeast), C. immitis (spherules), H. capsulatum.
Immunocompromised: Aspergillus sp, Pseudallescheria boydii, Candida sp., sporothrix, blastomyces.
CSF for pressure (normal or elevated), cell count (WBCs 50–1000/mcL, mostly lymphocytes), protein (elevated), and glucose (normal or decreased).
Serum cryptococcal antigen (CrAg) test (latex agglutination) for C. neoformans (>90% sensitive and specific). (This test can be performed on CSF specimens.)
For other fungi, collect at least 5 mL of CSF for fungal culture. Initial cultures are positive in 40% of coccidioides cases and 27–65% of histoplasma cases. Repeat cultures are frequently needed.
Cultures of blood, bone marrow, skin lesions, or other involved organs, if clinically indicated.
CSF India ink preparation for cryptococcus is not recommended. Cytospin Gram stain procedure concentrates CSF and can demonstrate round, budding yeast.
Serum coccidioidal serology is a serum immunodiffusion test for antibodies against the organism (75–95%). CSF serologic testing is rarely necessary. (See Coccidioides serology, Chapter 3.)
Complement fixation tests for coccidioides or histoplasma antibodies are available from reference laboratories or public health department laboratories (see Chapter 3) and can give titers that can be used to follow treatment.
Histoplasma antigen can be detected in urine (90%), blood (70%), or CSF (61%) in cases of histoplasma meningitis.
The clinical presentation of fungal meningitis in non-immunocompromised and immunocompromised patients is that of an indolent chronic meningitis.
Before AIDS, cryptococcal meningitis was seen both in patients with cellular immunologic deficiencies and in patients who lacked obvious defects (about 50%).
In AIDs patients, cryptococcus is the most common cause of meningitis and may present with normal CSF findings.
Titer of CSF CrAg can be used to monitor therapeutic success (falling titer) or failure (unchanged or rising titer) or to predict relapse during suppressive therapy (rising titer) in immunocompetent patients, though not in patients with AIDS.
Ginsberg L et al. Chronic and recurrent meningitis. Pract Neurol 2008;8:348. [PubMed: 19015295]
Honda H et al. Central nervous system infections: meningitis and brain abscess. Infect Dis Clin North Am 2009;23:609. [PubMed: 19665086]
Li SS et al. Cryptococcus. Proc Am Thorac Soc 2010;7:186.[PubMed: 20463247]
Wheat LJ et al. Diagnosis and management of central nervous system histoplasmosis. Clin Infect Dis 2005;40:844. [PubMed: 15736018]
Williams PL. Coccidioidal meningitis. Ann N Y Acad Sci 2007;1111:377. [PubMed: 17363442]
Spirochetal meningitis/neurologic diseases
B. burgdorferi (neuroborreliosis), T. pallidum (neurosyphilis), leptospira, other borreliae
Neuroborreliosis: CSF for pressure (normal or elevated), cell count (WBCs elevated, mostly lymphocytes), protein (may be elevated), and glucose (normal).
Serum and CSF for serologic testing for antibody by ELISA or IFA. False-positive serologic tests may occur. Western blots should be used to confirm borderline or positive results. CSF serology for anti-B. burgdorferi IgM (90%). PCR is very specific for detecting Borrelia DNA, but sensitivity is variable owing to stage of disease and type of body fluid tested. (See Lyme disease serologies, Chapter 3.)
Acute syphilitic meningitis: CSF for pressure (elevated), cell count (WBCs 25–2000/mcL, mostly lymphocytes), protein (elevated), and glucose (normal or low). (See CSF profiles, Table 8–8.)
Serum VDRL. (See VDRL, serum, Chapter 3.)
CSF VDRL is the preferred test (see Chapter 3), but is only 66% sensitive for acute syphilitic meningitis.
Neurosyphilis: CSF for pressure (normal), cell count (WBCs normal or slightly increased, mostly lymphocytes), protein (normal or elevated), glucose (normal), and positive CSF VDRL.
Serum RPR or VDRL with confirmatory FTA-ABS, or TP PA testing should be done with a positive serum result before CSF VDRL is performed.
Traditionally, nontreponemal serologic tests (RPR or VDRL) are used as screening tests for detection of syphilis. Because of the lack of specificity for these tests, positive screening tests must be confirmed with FTA-ABS or TP PA treponemal-specific assays. A new syphilis testing algorithm using treponemal tests for screening followed by a nontreponemal serology test has been proposed.
Leptospirosis: CSF cell count (WBCs <500/mcL, mostly monocytes), protein (slightly elevated), and glucose (normal).
Urine for dark-field examination of sediment to detect leptospira organisms.
Blood and CSF dark-field examination positive only in acute phase prior to meningitis.
Serum for serology for IgM by EIA (93% specificity) and ELISA.
Neurosyphilis is a late stage of infection and can present with meningovascular (hemiparesis, seizures, aphasia), parenchymal (general paresis, tabes dorsalis), or asymptomatic (latent) disease. In HIV-infected patients, neurosyphilis can present in secondary syphilis.
Because there is no single highly sensitive or specific test for neurosyphilis, the diagnosis must depend on a combination of clinical and laboratory data. Therapy of suspected neurosyphilis should not be withheld on the basis of a negative CSF VDRL if clinical suspicion is high.
In HIV neurosyphilis, treatment failures may be common.
Lyme disease can present as a lymphocytic meningitis, facial palsy, or painful radiculitis.
Leptospirosis follows exposure to urine of infected rodents, small animals, or livestock.
Kent ME et al. Reexamining syphilis: an update on epidemiology, clinical manifestations, and management. Ann Pharmacother 2008;42:226. [PubMed: 18212261]
O'Connell S. Lyme borreliosis: current issues in diagnosis and management. Curr Opin Infect Dis 2010;23:231. [PubMed: 20407371]
Sena AC et al. Novel Treponema pallidum serologic tests: a paradigm shift in syphilis screening for the 21st century. Clin Infect Dis 2010;51:700. [PubMed: 20687840]
Stoner BP. Current controversies in the management of adult syphilis. Clin Infect Dis 2007;44 (Suppl 3):S130. [PubMed: 17342666]
Toyokawa T et al. Diagnosis of acute leptospirosis. Expert Rev Anti Infect Ther 2011;9:111. [PubMed: 21171882]
Victoriano AF et al. Leptospirosis in the Asia Pacific region. BMC Infect Dis 2009;9:147. [PubMed: 19732423]
T. gondii, Naegleria fowleri, T. solium (cysticerci), Acanthamoeba (granulomatous amebic encephalitis GAE), Balamuthia sp. (GAE), Angiostrongylus (eosinophilic meningoencephalitis), Trypanosoma sp.
CSF for pressure (normal or elevated), cell count (WBCs 100–1000/mcL, chiefly monocytes, lymphocytes), protein (elevated), glucose (normal to low). Serum serology to detect antibodies for T. gondii, E. chaffeensis, A. phagocytophilum.
Toxoplasmosis: CT or MRI of brain, serology, Giemsa-stained touch prep of brain tissue, CSF PCR.
Naegleria: CSF wet mount for amebic trophozoites, or hematoxylin and eosin stain of brain tissue. Serologic tests not helpful.
Cysticercosis: Characteristic findings on CT and MRI are diagnostic. Serology is less sensitive.
Balamuthia: Culture not helpful. Indirect immunofluorescence or PCR of brain tissue to detect organism.
Angiostrongyliasis: CSF pressure (normal or elevated), cell count (WBC eosinophilic pleocytosis), protein (elevated), glucose (normal). CSF wet mount, ELISA serology.
Trypanosomiasis: Blood-Giemsa stain on thick and thin smears. CSF wet mount. Serologic tests by ELISA, IFA have 93–98% sensitivity and 99% specificity in acute stages. Serologic tests may be negative in chronic stages.
Naegleria follows exposure to warm, fresh, and polluted water (eg, swimming pools, sewers, fresh-water lakes).
Pereira-Chioccola VL et al. Toxoplasma gondii infection and cerebral toxoplasmosis in HIV-infected patients. Future Microbiol 2009;4:1363. [PubMed: 19995194]
Ramirez-Avila L et al. Eosinophilic meningitis due to Angiostrongylus and Gnathostoma species. Clin Infect Dis 2009;48:322. [PubMed: 19123863]
Visvesvara GS. Amebic meningoencephalitides and keratitis: challenges in diagnosis and treatment. Curr Opin Infect Dis 2010;23:590. [PubMed: 20802332]
M. tuberculosis (MTb),
CSF for pressure (elevated), cell count (WBCs 100–500/mcL, PMNs early, lymphocytes later), protein (elevated), glucose (decreased). (See CSF profiles, Table 8–8.)
CSF for AFB stain. Stain is positive in only 30%; culture may be negative in 15–25% of cases. Cytocentrifugation and repeat smears increase yield.
CSF for AFB culture (positive in <70%). Repeated sampling of the CSF during the first week of therapy is recommended; ideally, 3 or 4 specimens of 5–10 mL each should be obtained (87% yield with 4 specimens). CSF PCR available but sensitivity of most assays is low (50%). Positive CSF PCR is helpful with appropriate clinical picture, but negative PCR does not rule out tuberculous meningitis.
DNA hybridization probes are available for rapid identification of mycobacteria from culture.
Tuberculous meningitis is usually secondary to rupture of a subependymal tubercle from pulmonary focus or may be a consequence of miliary tuberculosis rather than blood-borne invasion.
Because CSF stain and culture are not sensitive for tuberculous meningitis, diagnosis and treatment should be based on a combination of clinical and microbiologic data.
Evidence of inactive or active extrameningeal tuberculosis, especially pulmonary, is seen in 75% of patients.
Garg RK. Tuberculous meningitis. Acta Neurol Scand 2010;122:75. [PubMed: 20055767]
Garg RK et al. Tuberculous meningitis in patients infected with human immunodeficiency virus. J Neurol 2011;258:3. [PubMed: 20848123]
Thwaites GE et al. Update on tuberculosis of the central nervous system: pathogenesis, diagnosis, and treatment. Clin Chest Med 2009;30:745. [PubMed: 19925964]