Tuberculous Meningitis Differential Diagnoses

  • Author: Tarakad S Ramachandran, MBBS, FRCP(C), FACP; Chief Editor: Karen L Roos, MD   more...
 
Updated: Mar 29, 2011
 
 

Diagnostic Considerations

Tuberculous meningitis (TBM) continues to pose a diagnostic problem. A high index of clinical suspicion is absolutely essential. TBM should be a strong consideration when a patient presents with a clinical picture of meningoencephalitides, especially in high-risk groups, including persons with malnutrition, those who abuse alcohol or drugs, homeless persons, people in correctional facilities, residents of long-term care facilities, and patients with known HIV infection.

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 seldom yields positive results. The sensitivities of many of the new tests are still under study, and these tests may not become generally available for some time; when they do, they are likely to prove costly.

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 less than 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 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.

Other problems to be considered

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

  • 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

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Tarakad S Ramachandran, MBBS, FRCP(C), FACP  Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, FRCP(C), FACP is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners, American College of International Physicians, American College of Managed Care Medicine, American College of Physicians, American Heart Association, American Stroke Association, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, and Royal Society of Medicine

Disclosure: Abbott Labs None None; Teva Marion None None; Boeringer-Ingelheim Honoraria Speaking and teaching

Specialty Editor Board

Frederick M Vincent Sr, MD  Clinical Professor, Department of Neurology and Ophthalmology, Michigan State University Colleges of Human and Osteopathic Medicine

Frederick M Vincent Sr, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Forensic Examiners, American College of Legal Medicine, American College of Physicians, and Michigan State Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Florian P Thomas, MD, MA, PhD, Drmed  Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Director, Neuropathy Association Center of Excellence, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University School of Medicine

Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Paraplegia Society, Consortium of Multiple Sclerosis Centers, and National Multiple Sclerosis Society

Disclosure: Nothing to disclose.

Chief Editor

Karen L Roos, MD  John and Nancy Nelson Professor of Neurology, Professor of Neurological Surgery, Department of Neurology, Indiana University School of Medicine

Karen L Roos, MD is a member of the following medical societies: American Academy of Neurology and American Neurological Association

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Pieter R Kark, MD, to the development and writing of this article.

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Tuberculoma is the round gray mass in the left corpus callosum. The red meninges on the right are consistent with irritation and probable meningeal reaction to tuberculosis.
MRI of the brain in a patient with 8 CD4 cells/mL. The patient's history includes previous interstitial pneumonia, pericarditis, adnexitis, and a positive result on the Mantoux test. His recent history includes fever, headache, strabismus, diplopia, and cough. Laboratory studies revealed hyponatremia. Liquoral findings strongly suggested a diagnosis of tuberculous meningitis, and culture results were positive for Mycobacterium tuberculosis. The MRI shows the presence, in and over the sellar seat, with parasellar left extension, of tissue with irregular margins, marked inhomogeneous enhancement, and compression of optic chiasm and of the third ventricle. Presence of nodular areas with marked enhancement of basal cisterns is an expression of leptomeningeal involvement. This patient died after 2 months of inadequate antituberculosis therapy (ie, poor compliance). Courtesy of Salvatore Marra, AIDS Imaging (http://members.xoom.it/Aidsimaging).
Fluorochrome for tuberculosis. Fluorescent staining procedures are used with auramine O or auramine-rhodamine as the primary fluorochrome dye. After decolorization with an acid-alcohol preparation, the smear is counterstained with acridine orange or thiazine red and scanned at a lower magnification with a 25X dry objective fluorescent microscope. Acid-fast bacilli appear as yellow-green fluorescent thin rods against a dark background.
Hematoxylin and eosin stain showing caseation in tuberculosis.
 
 
 
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