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Tuberculous Meningitis Treatment & Management

  • Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: Niranjan N Singh, MD, DM  more...
 
Updated: Dec 11, 2014
 

Approach Considerations

The duration of antimicrobial therapy for tuberculous meningitis (TBM) is unclear, and the benefits of adjuvant corticosteroids remain in doubt. Death may occur as a result of missed diagnoses and delayed treatment.

Obviously, concerns regarding transmission of other infectious diseases have led to legal constraints including quarantine, variably obligatory vaccinations, and exclusion from immigration. In the US legal system, the model indicates that if persons with potentially transmissible tuberculosis (TB) refuse to take treatment, they can and should be quarantined to protect the public. Directly observed therapy is gaining popularity, with the broadening perception that directly observed therapy should be the standard of practice.

In TBM, despite adequate treatment of hydrocephalus and various other complications, patients commonly fail to improve. This poor outcome is often associated with the extensive tuberculous exudate in the subarachnoid cisterns of the brain, which affects cerebral vessels and induces ischemia. Hence, treatment modalities should include optimizing physiologic variables to preserve cerebral perfusion.[33]

The hypercoagulable state in childhood TBM is comparable to that described in adults with pulmonary tuberculosis and may further increase the risk for infarction. Therapeutic measures that reduce the risk for thrombosis could therefore be potentially beneficial in childhood TBM.[34]

Hyaluronidase has been used in spinal arachnoiditis with good results. Gourie-Devi and Satish Chandra recommend the use of hyaluronidase administered intrathecally in cases of arachnoiditis complicating TBM.[35]

Go to Meningitis, Meningococcal Meningitis, Staphylococcal Meningitis, Haemophilus Meningitis, Viral Meningitis, and Aseptic Meningitis for more complete information on these topics.

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Antibiotic Therapy and Adjunctive Corticosteroid Therapy

The best antimicrobial agents in the treatment of TBM include isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and streptomycin (SM), all of which enter cerebrospinal fluid (CSF) readily in the presence of meningeal inflammation. Ethambutol is less effective in meningeal disease unless used in high doses. The second-line drugs include ethionamide, cycloserine, ofloxacin, and para -aminosalicylic acid (PAS).

INH, RIF, and PZA are bactericidal. RIF and SM achieve optimal CSF levels only when the meninges are inflamed. Usually, intrathecal drugs are not necessary. Treatment is best started with INH, RIF, and PZA. The addition of a fourth drug is left to the choice of the local physicians and their experience, with little evidence to support the use of one over the other.

Evidence concerning the duration of treatment is conflicting. The duration of conventional therapy is 6-9 months, although some investigators still recommend as many as 24 months of therapy. No guidelines exist as to the components and duration of treatment in the case of multidrug-resistant TBM.

Studies have shown that young children with TBM can be treated safely for 6 months with high doses of anti-TB agents without overt hepatotoxicity and with a low risk of relapse. Children must be treated for 12 months with combination antibiotic therapy and adjunctive corticosteroids. Twelve months is probably a conservative estimate of the time required for bacterial cure. The rationale behind the use of adjuvant corticosteroids lies in reducing the harmful effects of inflammation as the antibiotics kill the organisms.

The use of corticosteroids in adults is controversial; they may be indicated in the presence of increased intracranial pressure (ICP), altered consciousness, focal neurological findings, spinal block, and tuberculous encephalopathy. Treatment of tuberculoma consists of high-dose steroids and continuation of antituberculous therapy, often for a prolonged course. In tuberculous radiculomyelitis (TBRM), as in other forms of paradoxical reactions to anti-TB treatment, evidence shows that steroid treatment might have a beneficial effect.

To ascertain the immediate and underlying causes of death in adults who died in hospital with an antemortem diagnosis of tuberculosis, Martinson et al, in their autopsy studies, demonstrated disseminated, extensive tuberculosis associated with advanced HIV disease.[36] Severe bacterial infections, including salmonellosis, were the leading comorbidity, suggesting that hospitalized HIV-infected adults in whom tuberculosis is suspected may benefit from broad-spectrum antibiotic therapy.

Since uveitis is often treated with immunosuppressive and corticosteroid therapy, such treatment may have catastrophic consequences if patients with tuberculous granulomatous uveitis were not properly diagnosed and managed.

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Drain or Shunt Placement

In patients with evidence of obstructive hydrocephalus and neurological deterioration who are undergoing treatment for TBM, placement of a ventricular drain or ventriculoperitoneal or ventriculoatrial shunt should not be delayed. Studies suggest that prompt ventriculoatrial or ventriculoperitoneal shunting improves outcome, particularly in patients presenting with minimal neurological deficit.

Unless a mass effect is compromising vital structures, surgical intervention is rarely required in the treatment of tuberculomas.

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Prevention of Tuberculous Meningitis

BCG vaccination offers a protective effect (approximately 64%) against TBM. Improvement in weight for age was associated with a decreased risk of the disease; however, further studies are needed to evaluate the association, if any, between nutritional status and vaccine efficacy.

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Long-Term Monitoring

The effectiveness of the treatment guidelines is determined by 2 major factors: (1) the cure rate and (2) the level of acquired drug resistance.

The cure rate is defined, for all registered patients whose sputum smear or culture result is positive, as the proportion of patients who completed treatment and had negative sputum cultures at 4 months and at the end of the treatment period. It is evaluated from the result of the cohort analysis performed yearly by the National Tuberculosis Control Program. The cure rate is the most important factor in determining final outcomes and is related inversely to the rate of acquired drug resistance and directly to the rate of noncompliance with treatment.

As drug resistance becomes more prevalent, the requirement of rapid sensitivity testing becomes more urgent. This is particularly so in TBM because inappropriate treatment can be fatal.

Treatment and review defaulters must be identified, and every effort must be made to locate them and promptly reinstitute therapy or observation.

Treatment defaulters are those who fail to attend supervised daily or biweekly chemotherapy or fail to collect their supply of drugs for self-administered oral chemotherapy. Review defaulters are those who fail to attend a follow-up appointment for review of sputum or other examinations, for progress review, and for further management after the examinations have been completed. Patients also tend to default review while undergoing investigations to rule out active TB.

Defaulter contacts could be made by phone, mail, and, if the yield is negative, a home visit. Home visits are made for defaulter retrieval, health education of newly diagnosed patients and their families, and contact investigation. The nurse, physician assistant, nurse practitioner, medical social worker, or public health inspector of the health facility generally makes home visits. When facilities are not available for home visiting, the treating physician has the responsibility to notify the health department.

Patients should be asked for information about their contacts so that these individuals may be traced and investigated. All family contacts must be investigated. Household contacts who admit to having cough lasting for more than 2 weeks and children without a noticeable bacillus Calmette-Guérin (BCG) scar during home visits should be advised to attend the nearest health facility for further investigations.

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Contributor Information and Disclosures
Author

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American College of International Physicians, American Heart Association, American Stroke Association, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, National Association of Managed Care Physicians, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Niranjan N Singh, MD, DM Associate Professor of Neurology, University of Missouri-Columbia School of Medicine

Niranjan N Singh, MD, DM is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Headache Society

Disclosure: Nothing to disclose.

Acknowledgements

Pieter R Kark, MD, MA, FAAN, FACP Instructor in Palliative Care, The Lifetime Healthcare Companies

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.

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.

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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. Courtesy of Robert Schelper, MD, Associate Professor of Pathology, State University of New York Upstate Medical University.
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. Courtesy of Robert Schelper, MD, Associate Professor of Pathology, State University of New York Upstate Medical University.
Hematoxylin and eosin stain showing caseation in tuberculosis. Courtesy of Robert Schelper, MD, Associate Professor of Pathology, State University of New York Upstate Medical University.
 
 
 
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