Tuberculous Meningitis Differential Diagnoses

Updated: Nov 10, 2021
  • Author: Gaurav Gupta, MD, FAANS, FACS; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
  • Print

Diagnostic Considerations

Unlike many forms of bacterial meningitis, tuberculous meningitis (TBM) is often difficult to diagnose, as initial symptoms are generally subacute and often nonspecific (although occasionally may present more acutely), and neck stiffness is typically not present in the early course of the illness. [51, 57]  The duration of presenting symptoms may vary from 1 day to 9 months (on average, 2 weeks), and the prodrome is usually nonspecific, including headache, vomiting, photophobia, and fever. Meningismus may also occur. Unlike most of forms of bacterial meningitis, TBM is more likely to cause neurological deficits, including altered mental status, personality changes, and, as the lesions may result in neurovascular compression, cranial nerve deficits and infarcts. [51]  

The clinician should have a high index of clinical suspicion if a patient presents with a clinical picture of subacute meningitis or encephalitis (particularly if > 5 days) in high-risk groups or in endemic areas. There is frequently diagnostic uncertainty when differentiating TBM from other meningoencephalitides, such as partially treated meningitis. TBM must be differentiated not only from other forms of acute and subacute meningitis but also from conditions such as viral infections and cerebral abscesses. High-risk groups include patients from endemic areas (eg, from Africa or Asia), those with HIV infection or alcohol or drug abuse, homeless persons, people in correctional facilities, residents of long-term care facilities, and malnourished patients.

Diagnostic confusion often exists between TBM and other meningoencephalitides, in particular partially treated meningitis. Acid-fast bacilli are seen in only approximately 25% of cerebrospinal fluid (CSF) smears. CSF culture is time-consuming and may not yield positive results. Recent advances have sought to improve smear sensitivity, such as by nucleic acid amplification tests. [59]

In one study, 5 features independently predicted the diagnosis of TBM:

  • Prodromal stage lasting 7 days or longer

  • Optic atrophy on fundal examination

  • Focal deficit

  • Abnormal movements

  • CSF leukocytes comprising < 50% polymorphonuclear leukocytes

Validation of these criteria on another set of 128 patients revealed a sensitivity of 98.4% if at least one feature was present and a specificity of 98.3% if 3 or more were present. This simple rule is useful for physicians working in regions where TB is prevalent.

TBM must be differentiated not only from other forms of acute and subacute meningitis but also from conditions such as viral infections and cerebral abscess. The radiological differential diagnosis, which should take into account HIV status, includes cryptococcal meningitis, cytomegalovirus encephalitis, sarcoidosis, meningeal metastases, and lymphoma.

TB of any form is a notifiable disease in the United States. Mandatory notification of the appropriate health department is the responsibility of the physician who makes the diagnosis.

TBM should be considered in the differential diagnosis in any high-risk patient presenting with fever and a change in sensorium. Other problems to be considered include:

  • Infections: Fungal (cryptococcal, histoplasmosis, actinomycetic, nocardiasis, Arachnia infection, candidiasis, coccidiosis); spirochetal (Lyme disease, syphilis, leptospirosis); bacterial (partially treated bacterial meningitis, brain abscess, listeriosis, Neisseria species infection, tularemia); brucellosis; parasitic (cysticercosis, acanthamebiasis, angiostrongylosis, toxoplasmosis, trypanosomiasis); and viral (herpes, mumps, retrovirus, enterovirus [in hypogammaglobulinemics])

  • Acute hemorrhagic leukoencephalopathy

  • Behçet disease

  • Chemical meningitis

  • Chronic benign lymphocytic meningitis

  • Neoplastic: metastatic, lymphoma

  • Systemic lupus erythematosus

  • Vascular: Multiple emboli, subacute bacterial endocarditis, sinus thrombosis

  • Vasculitis: Isolated central nervous system (CNS) angiitis, systemic giant cell arteritis, Wegener granulomatosis, polyarteritis nodosa, noninfectious granulomatosis, lymphomatoid granulomatosis

  • Vogt-Koyanagi-Harada syndrome

Differential Diagnoses