CNS Tuberculosis

05 November 2004

1. Meningitis / Hydrocephalus

2. Tuberculoma

3. Vasculitis / Spinal artery syndromes

4. Potts # / paraplegia

5. Myeloradiculitis

6. Ocular: choroiditis, papillitis, retinitis, vitritis, vasculitis, dacroadentis, scleritis.

Organisms

Mycobacterium tuberculosis (aerosol)

Mycobacterium bovis (unpasteurised milk)

Epidemiology 

1950-85: 6% annual decline

1985-99: 16% annual increase (increasing proportion of extrapulmonary TB)

                   result of:      1. HIV especially in countries where TB is

common eg. sub-Saharan Africa

                                      2. homelessness / crowding

                                      3. IV drug use

                                      4. immunosuppression from increasing age,

transplants, CRF.

Tuberculous Meningitis

Pathology

Initially bacterial seeding of meninges & subpial regions with tubercle formation, then subsequent rupture with discharge into subarachnoid space.

Gelatinous basal (optochiasmatic) meningitis

Exudate can also surround spinal cord.

Tubercles present in ependyma & choroid plexus

Arteries become inflamed & occluded with consequent brain infarction.

CSF resorption is impaired & occasional blocking of aqueduct or fourth ventricle with subsequent hydrocephalus.

Clinical Features

66 % will have active disease elsewhere commonly pulmonary

Risk groups: HIV, alcoholics, pediatrics, immigrants

75% neck stiffness with Kernig’s or Brudzinski signs

50% headaches

20% Papilledema

Subacute onset with low grade fever, lethargy, confusion, meningismus, cranial nerve palsies (ocular/ facial/ deafness), occasionally seizures.

Kennedy et al. Tuberculous meningitis JAMA 241: 264, 1979. 

Investigations

CSF: increased pressure, initial PMN predominance before lymphocyte predominance, elevated protein, reduced glucose

 ZN stain positive in 80% after 4 LP

Culture positive in 70%

PCR positive in 80%

CT/MRI: search for presence of hydrocephalus, meningeal enhancement & thickening, tuberculomas, prognostic indicator.

DSA: vasculitis involving Circle of Willis & primary branches.

UCE for SiADH

Treatment

General recommendation is for 18 mths of treatment initially 2  mths of quadruple therapy.

NB Clinical outcome depends on which stage therapy is initiated

1. Isoniazid is most effective drug. 5 mg/kg adults ; 10 mg/kg kids

Crosses BBB regardless of  inflammation.

SE:  rash, neuropathy (esp malnourished, diabetics, anemic), hepatitis (especially alcoholics, elderly)

2. Rifampicin: 600 mg; 15 mg/kg for children

Crosses BBB dependent upon  inflammation.

SE: urine discoloration, hepatotoxicity

3. Ethambutol: 750 mg

Crosses BBB dependent upon  inflammation.

SE: optic neuropathy

4. Pyrazinamide: 30-50 mg/kg.

Crosses BBB regardless of  inflammation.

SE: rash, GI upset, hepatitis

5. Pyridoxine 25 –50 mg.

Streptomycin if resistance to other drugs but crosses BBB poorly; can be intrathecal but significant ototoxicity. More toxic in elderly, CRF, contraindicated in pregnancy.

Steroids only in vasculitis, subarachnoid block, grade 2-3 meningitis for 3 mths.

? Intrathecal hyaluronidase for adhesions.

VP shunt for hydrocephalus (beware tuberculous peritonitis)

Serial CT scanning for following course of hydrocephalus.

Mortality

100% if untreated

10% overall esp infants & elderly.

21% in HIV patients due to delay in dx & drug resistance.

Stage I         96% complete recovery (conscious, rational, +/- meningismus, no focal neurology, no hydrocephalus).

Stage II        78% complete recovery (confused, focal neuro signs)

Stage III      21% complete recovery (comatose / delirious, dense hemiplegia or paraplegia).

25% suffer neurologic sequelae (intellectual impairment, deafness, seizures, hemiparesis, psychiatric disturbances, visual & oculomotor disorders).

Tuberculomas

Tumor like mass of granulation tissue in parenchyma

30% of intracranial masses in developing countries such as India

CSF: may have mild elevation of protein, glucose normal, TB culture & PCR usually negative.

Biopsy often performed as DDx is neoplasm.

Treatment is usually medical with prolonged course of therapy of 18 mths (recently shown 9 mths as effective as 18 mths) with reduction in size, disappearance or calcification.

Maybe initial swelling at commencement of tuberculous therapy (which can lead to the first clinical manifestation of tuberculoma) can be alleviated with steroids.

If mass effect surgery indicated.

Serial CT scanning for following course of tuberculoma.

Myeloradiculitis

Meningeal exudate can invade / encase cord  and spinal roots.

Pott’s paraplegia : compression by an epidural mass of granulation tissue.

Mechanical angulation (gibbus deformity / Pott’s #) can result in compression.

Thrombosis of spinal artery

Treatment always involves antituberculous chemotherapy as prolonged course.

Steroids for exudate complications.

Surgery for Pott’s paraplegia & #.

General workup for CNS TB

CXR

Sputum MCS, ZN stain +/- PCR  with sensitivity testing

HIV serology

Mantoux test (unreliable)

Search for disease elsewhere if clinically suspected.

Contact tracing

Notifiable disease

All treatment is observed to ensure compliance.

Chemoprophylaxis for contacts

BCG does reduce incidence of tuberculous meningitis and active  tuberculosis with 75% efficacy esp in children (contraindicated in advanced HIV).