• Tuberculous meningitis
• CNS tuberculoma

Tuberculous (TB) meningitis is correctly characterized as a meningoencephalitis, as it affects not only meninges but also brain parenchyma and vasculature. The primary pathologic event is formation of thick TB exudate within subarachnoid space, most prominently at the base of the brain.70 Accompanying this exudate is inflammation affecting adjacent blood vessels. Ischemic cerebral infarction, resulting from vascular occlusion, is a common sequela most often found in the distribution of the middle cerebral artery (reflecting presence of TB exudate within sylvian fissure) and striate arteries as they penetrate the base of the brain.70 Another characteristic feature of TB meningitis is hydrocephalus secondary to CSF dynamic disturbance.

TB meningitis is divided into three clinical stages:

Stage	Neurologic syndrome
I (early)	Nonspecific (e.g., generalized malaise)
II (intermediate)	Lethargy Meningismus Moderate focal neurologic deficits (e.g., cranial nerve palsies)
III (advanced)	Seizures Severe neurologic deficits (e.g., paresis) Stupor or coma

Seizures are a presenting complaint in 10–20% of children, and more than 50% can develop seizures during their initial hospitalization.71 Seizures are generally more frequent in younger children.70 For adults, seizures are the initial presenting manifestation in 10–15% of cases.70

Diagnosis

Diagnosis of CNS tuberculosis begins with the usual investigations required for diagnosing TB:

• purified protein derivative (PPD) delayed-hypersensitivity test
• chest x-ray
• sputum acid-fast bacillus

The usefulness of the tuberculin test in diagnosing acute TB is controversial, and its use in diagnosing TB meningitis is of similarly questionable value. Up to 60% of patients with TB meningitis do not react to PPD testing.72,73

Characteristic lumbar puncture results include:

• Opening pressure: elevated in about 50% of patients
• Glucose: moderate reduction
• Protein: elevated
• Pleocytosis: moderate (Differentials may vary: initially both neutrophils and lymphocytes can be seen, but this usually converts to predominantly lymphocytes over several weeks.)
• Culture (acid-fast bacillus stain): insensitive (Culture is the diagnostic gold standard for TB meningitis but the concentration of mycobacteria causing meningitis can be small, so they are difficult to isolate.)

No radiologic changes are pathognomonic, but some are sufficiently characteristic to raise clinical suspicion:

• Noncontrast CT: hydrocephalus and hypodensities (consistent with TB exudate, infarcts, or both)
• Contrast CT: meningeal enhancement, frequently surrounding basal cisterns, sylvian fissure, and brain stem
• MRI: involved cranial nerves appear as thickened structures entrapped in enhancing basilar TB exudate

Treatment

Principles guiding treatment of TB meningitis are similar to those for other forms of TB, with the added requirement that antimycobacterial agents must penetrate the blood-brain barrier. Therapeutic options depend upon the probability of drug resistance:70

Low probability of drug resistance:

1. Isoniazid 300 mg q.d. x 6 mos Rifampin 600 mg q.d. x 6 mos Pyrazinamide 15–30 mg/kg q.d. x 2 mos
2. Isoniazid 300 mg q.d. x 9–18 mos Rifampin 600 mg q.d. x 9–18 mos Pyrazinamide 15–30 mg/kg q.d. x 9–18 mos
3. Isoniazid 300 mg q.d. x 1 mo, then 900 mg b.i.w. x 8 mos Rifampin 600 mg q.d. x 1 mo, then 600 mg b.i.w. x 8 mos

High probability of drug resistance:

1. Isoniazid 300 mg q.d. x 9–18 mos
   Rifampin 600 mg q.d. x 9–18 mos
   Pyrazinamide 15–30 mg/kg q.d. x 9–18 mos
   Streptomycin 1 g q.d. x 2 mos
2. Individual case sensitivity–determined regimen

The use of steroids in TB meningitis is controversial. Amelioration of symptoms (including seizure control, spinal block prophylaxis, and reported mortality reduction in children) is the prime benefit, but this must be balanced against the risks of systemic steroid complication, steroid withdrawal, and reports of worsening of long-term neurologic outcome. Most authorities now advocate steroid use in TB meningitis only in the context of extreme neurologic compromise, elevated intracranial pressure, impending herniation, or impending spinal block.

Table adapted from MB Bader. Role of ciprofloxacin in fatal seizures. Chest 1992;101:883–884.
Adapted from: Goldstein MA and Harden CL. Infectious states. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;83-133.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised March 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

The initial pathogenesis of CNS tuberculoma is identical to that of tuberculous (TB) meningitis. Instead of rupturing into subarachnoid space, however, tubercles continue to grow, walled off from brain parenchyma and meninges by a dense fibrous capsule. Grossly, the lesions are well-circumscribed masses varying in size from less than a centimeter up to several centimeters. A patient can have one or several, localized to any brain region. Tuberculomas occasionally develop during or after treatment for TB meningitis.

Clinical sequelae of CNS tuberculomas are those of single or multiple intracranial mass lesions, primarily seizures and correlates of increased intracranial pressure. The features of the seizures can strongly suggest lesion location. Neuroimaging, especially MRI, is diagnostically indispensable, although biopsy remains the gold standard.

One study examining the clinical course of cerebral tuberculoma in patients with and without HIV infection found that cerebral tuberculoma in HIV-negative patients was more likely to be characterized by seizures.78

Intracranial tuberculoma without evidence of systemic TB is relatively rare and difficult to diagnose. It is often clinically quiescent for a long time, and a seizure can be an important sentinel event in such cases. Tseng et al. reported a patient without any history of TB who presented with focal left-hand seizures. Neuroimaging revealed a leptomeningeal lesion in the left frontoparietal region. Subsequent histopathologic analysis of a biopsy sample was consistent with tuberculoma.74 Tosomeen et al. reported a similarly seizure-presenting case of multiple intracranial tuberculomas.75

If the caseous core of a tuberculoma liquefies, a TB abscess results. These patients tend to be clinically worse overall than those with correspondingly sized tuberculoma. Again, focal seizures can be an important initial clinical manifestation.76

Adapted from: Goldstein MA and Harden CL. Infectious states. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;83-133.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised March 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.