Infectious Causes of Chronic Meningitis
| Causative Agent | CSF Formula | Helpful Diagnostic Tests | Risk Factors and Systemic Manifestations |
|---|---|---|---|
| Common Bacterial Causes | |||
| Partially treated suppurative meningitis | Mononuclear or mixed mononuclear-polymorphonuclear cells | CSF culture and Gram's stain | History consistent with acute bacterial meningitis and incomplete treatment |
| Parameningeal infection | Mononuclear or mixed polymorphonuclear-mononuclear cells | Contrast-enhanced CT or MRI to detect parenchymal, subdural, epidural, or sinus infection | Otitis media, pleuropulmonary infection, right-to-left cardiopulmonary shunt for brain abscess; focal neurologic signs; neck, back, ear, or sinus tenderness |
| Mycobacterium tuberculosis | Mononuclear cells except polymorphonuclear cells in early infection (commonly <500 WBC/µL); low CSF glucose, high protein | Tuberculin skin test may be negative; AFB culture of CSF (sputum, urine, gastric contents if indicated); tuberculostearic acid detection in CSF; identify tubercle bacillus on acid-fast stain of CSF or protein pellicle; PCR | Exposure history; previous tuberculous illness; immunosuppressed, anti-TNF therapy or AIDS; young children; fever, meningismus, night sweats, miliary TB on x-ray or liver biopsy; stroke due to arteritis |
| Lyme disease (Bannwarth's syndrome) Borrelia burgdorferi | Mononuclear cells; elevated protein | Serum Lyme antibody titer; Western blot confirmation; (pts with syphilis may have false-positive Lyme titer) | History of tick bite or appropriate exposure history; erythema chronicum migrans skin rash; arthritis, radiculopathy, Bell's palsy, meningoencephalitis-multiple sclerosis-like syndrome |
| Syphilis (secondary, tertiary) Treponema pallidum | Mononuclear cells; elevated protein | CSF VDRL; serum VDRL (or RPR); fluorescent treponemal antibody-absorbed (FTA) or MHA-TP; serum VDRL may be negative in tertiary syphilis | Appropriate exposure history; HIV-seropositive individuals at increased risk of aggressive infection; “dementia”; cerebral infarction due to endarteritis |
| Uncommon Bacterial Causes | |||
| Actinomyces | Polymorphonuclear cells | Anaerobic culture | Parameningeal abscess or sinus tract (oral or dental focus); pneumonitis |
| Nocardia | Polymorphonuclear; occasionally mononuclear cells; often low glucose | Isolation may require weeks; weakly acid fast | Associated brain abscess may be present |
| Brucella | Mononuclear cells (rarely polymorphonuclear); elevated protein; often low glucose | CSF antibody detection; serum antibody detection | Intake of unpasteurized dairy products; exposure to goats, sheep, cows; fever, arthralgia, myalgia, vertebral osteomyelitis |
| Whipple's disease Tropheryma whipplei | Mononuclear cells | Biopsy of small bowel or lymph node; CSF PCR for T. whipplei; brain and meningeal biopsy (with PAS stain and EM examination) | Diarrhea, weight loss, arthralgias, fever; dementia, ataxia, paresis, ophthalmoplegia, oculomasticatory myoclonus |
| Rare Bacterial Causes | |||
| Leptospirosis (occasionally if left untreated may last 3-4 weeks) | |||
| Fungal Causes | |||
| Cryptococcus neoformans | Mononuclear cells; count not elevated in some pts with AIDS | India ink or fungal wet mount of CSF (budding yeast); blood and urine cultures; antigen detection in CSF | AIDS and immune suppression; pigeon exposure; skin and other organ involvement due to disseminated infection |
| Coccidioides immitis | Mononuclear cells (sometimes 10-20% eosinophils); often low glucose | Antibody detection in CSF and serum | Exposure history—southwestern U.S.; increased virulence in dark-skinned races |
| Candida sp. | Polymorphonuclear or mononuclear | Fungal stain and culture of CSF | IV drug abuse; post surgery; prolonged IV therapy; disseminated candidiasis |
| Histoplasma capsulatum | Mononuclear cells; low glucose | Fungal stain and culture of large volumes of CSF; antigen detection in CSF, serum, and urine; antibody detection in serum, CSF | Exposure history—Ohio and central Mississippi River Valley; AIDS; mucosal lesions |
| Blastomyces dermatitidis | Mononuclear cells | Fungal stain and culture of CSF; biopsy and culture of skin, lung lesions; antibody detection in serum | Midwestern and southeastern U.S.; usually systemic infection; abscesses, draining sinus, ulcers |
| Aspergillus sp. | Mononuclear or polymorphonuclear | CSF culture | Sinusitis; granulocytopenia or immunosuppression |
| Sporothrix schenckii | Mononuclear cells | Antibody detection in CSF and serum; CSF culture | Traumatic inoculation; IV drug use; ulcerated skin lesion |
| Rare Fungal Causes | |||
| Xylohypha (formerly Cladosporium) trichoides and other dark-walled (dematiaceous) fungi such as Curvularia, Drechslera; Mucor, and, after water aspiration, Pseudallescheria boydii, iatrogenic Exserohilum rostratum infection following spinal blocks | |||
| Protozoal Causes | |||
| Toxoplasma gondii | Mononuclear cells | Biopsy or response to empirical therapy in clinically appropriate context (including presence of antibody in serum) | Usually with intracerebral abscesses; common in HIV-seropositive pts |
| Trypanosomiasis Trypanosoma gambiense, T. rhodesiense | Mononuclear cells, elevated protein | Elevated CSF IgM; identification of trypanosomes in CSF and blood smear | Endemic in Africa; chancre, lymphadenopathy; prominent sleep disorder |
| Rare Protozoal Causes | |||
| Acanthamoeba sp. causing granulomatous amebic encephalitis and meningoencephalitis in immunocompromised and debilitated individuals. Balamuthia mandrillaris causing chronic meningoencephalitis in immunocompetent hosts. | |||
| Helminthic Causes | |||
| Cysticercosis (infection with cysts of Taenia solium) | Mononuclear cells; may have eosinophils; glucose level may be low | Indirect hemagglutination assay in CSF; ELISA immunoblotting in serum | Usually with multiple cysts in basal meninges and hydrocephalus; cerebral cysts, muscle calcification |
| Gnathostoma spinigerum | Eosinophils, mononuclear cells | Peripheral eosinophilia | History of eating raw fish; common in Thailand and Japan; subarachnoid hemorrhage; painful radiculopathy |
| Angiostrongylus cantonensis | Eosinophils, mononuclear cells | Recovery of worms from CSF | History of eating raw shellfish; common in tropical Pacific regions; often benign |
| Baylisascaris procyonis (raccoon ascarid) | Eosinophils, mononuclear cells | Infection follows accidental ingestion of B. procyonis eggs from raccoon feces; fatal meningoencephalitis | |
| Rare Helminthic Causes | |||
| Trichinella spiralis (trichinosis); Fasciola hepatica (liver fluke), Echinococcus cysts; Schistosoma sp. The former may produce a lymphocytic pleocytosis whereas the latter two may produce an eosinophilic response in CSF associated with cerebral cysts (Echinococcus) or granulomatous lesions of brain or spinal cord | |||
| Viral Causes | |||
| Mumps | Mononuclear cells | Antibody in serum | No prior mumps or immunization; may produce meningoencephalitis; may persist for 3-4 weeks |
| Lymphocytic choriomeningitis | Mononuclear cells | Antibody in serum | Contact with rodents or their excreta; may persist for 3-4 weeks |
| Echovirus | Mononuclear cells; may have low glucose | Virus isolation from CSF | Congenital hypogammaglobulinemia; history of recurrent meningitis |
| HIV (acute retroviral syndrome) | Mononuclear cells | p24 antigen in serum and CSF; high level of HIV viremia. | HIV risk factors; rash, fever, lymphadenopathy; lymphopenia in peripheral blood; syndrome may persist long enough to be considered as “chronic meningitis”; or chronic meningitis may develop in later stages (AIDS) due to HIV |
| Herpes simplex (HSV) | Mononuclear cells | PCR for HSV, CMV DNA; CSF antibody for HSV, EBV | Recurrent meningitis due to HSV-2 (rarely HSV-1) often associated with genital recurrences; EBV associated with myeloradiculopathy, CMV with polyradiculopathy |
Abbreviations: AFB, acid-fast bacillus; EM, electron microscopy; FTA, fluorescent treponemal antibody absorption test; HSV, herpes simplex virus; MHA-TP, microhemagglutination assay-T. pallidum; PAS, periodic acid-Schiff; RPR, rapid plasma reagin test; TB, tuberculosis; VDRL, Venereal Disease Research Laboratories test.