Dr Abdullah Ansari MBBS, MD Medicine Aligarh Muslim University Spectrum of CNS TB CNS TB in India Pathophysiology TB meningitis Clinical presentation Symptoms of TBM Diagnosis of TBM Lumbar puncture for CSF CSF examination Xpert MTB/RIF HIV status / chest x ray Neuroimaging : CECT/MRI MRC staging Treatment Referral Follow up Drug resistant cases Complications of TBM Hydrocephalus Ventriculo-peritoneal shunt Stroke Optico-chiasmatic arachnoiditis Seizures CNS tuberculoma Clinical presentation Presumptive CNS tuberculoma HIV status Neuroimaging CSF examination Stereotactic or open biopsy Tuberculoma differential diagnosis CNS Tuberculoma vs Neurocysticercosis Treatment of CNS Tuberculoma Duration Paradoxical reaction Treatment failure

1. Dr Abdullah Ansari
MBBS, MD Medicine
Aligarh Muslim University

2.  TB meningitis (TBM)
 Tuberculoma : cerebral and spinal
 TB myelitis
 TB arachnoiditis
The most common form is TB meningitis
These are all severe forms of TB associated
with high incidence of death or disability

3.  Exact prevalence not known
 Accounts for 1% of all TB cases, which
equates to 17000 cases in India in 2014
(WHO 2015)
 TB meningitis case fatality rate is high
 All forms of CNS TB can leave long-term
disabilities

4.  CNS tuberculosis is secondary to some
primary focus in lungs, lymph nodes, etc
 Spread from primary is mainly hematogenous
 TNF alpha leads to altered BBB permeability
and CSF leukocytosis

5.  TB bacilli seed to the meninges or brain
parenchyma, forming metastatic caseous
lesions called Rich foci
 Rich focus increase in size until it ruptures
 Tubercles rupturing into subarachnoid space
cause meningitis
 Those deeper in the brain or spinal cord
parenchyma cause tuberculomas or
abscesses

7.  TBM is a medical emergency
 Early diagnosis and prompt treatment
with ATT saves lives

8.  TBM classically presents as subacute or
chronic meningitis with symptoms developing
over days or weeks
 Symptoms of <5 days more likely associated
with bacterial or viral meningitis
 However, TBM may present acutely with a
short duration, and this acute presentation is
not uncommon

9. Any patient with clinical features of meningitis
in the form of fever, headache, neck rigidity
and vomiting, with or without altered
sensorium and associated focal neurological
deficits for a period of 5 days or more

10. Common
symptoms
Less frequent
symptoms
Uncommon
symptoms
Headache
Fever
Vomiting
Neck stiffness
Weight loss
Confusion
Cranial nerve
palsy
Hemiparesis
Coma
Photophobia
Paraparesis
Seizures

11. 1. Rapid access to CSF examination
2. Rapid access to neuroimaging
3. Prompt treatment with ATT and supportive
care

12.  Lumbar puncture in every patient (unless
contraindicated)
 At least 6 mL of CSF collected for adults, 2–3
mL for children

13.  Cell count and differentiation
 Protein
 CSF:serum glucose ratio (simultaneous serum
samples taken)
 Gram stain for bacterial meningitis
 AFB stain for TB
 India ink and cryptococcal antigen
 Xpert MTB/RIF
 PCR-based tests

14.  Xpert MTB/RIF used as an adjunctive test
 Pooled sensitivity against culture 80.5%
 Pooled specificity against culture 97.8%
 A negative test does not rule out TBM
 Decision of ATT should be based on clinical
features and CSF profile

15.  Interferon-gamma release assays such as
ELISPOT and Quantiferon Gold are for latent
TB, hence not indicated in TBM. The use of
these tests is restricted in India
 Adenosine deaminase (ADA) is not useful in
the diagnosis of TBM

16. HIV testing
 All cases, as HIV predisposes to CNS
infections, including TBM
Chest X-ray
 All cases, for evidence of current or previous
pulmonary TB

17. CT brain with contrast
 All cases, with high priority for comatose or
deteriorating patients
 Hydrocephalus, if detected requires
neurosurgical intervention
MRI brain with contrast
 Selected cases, may assist where diagnosis is
uncertain, in complex cases, and in HIV-
positive patients

18.  Involvement of the leptomeninges common
 Thick tuberculous exudate in subarachnoid
space, particularly at the base of brain
 Caseous necrosis may form within exudate
representing tuberculomas
 Hydrocephalus is common
 An arteritis and associated ischemic infarcts

19. Stage I :
 Mild cases, without altered consciousness or focal
neurological signs
Stage II :
 Moderate cases, with altered consciousness but not
comatose and with moderate neurological signs, e.g.
single cranial nerve palsies, paraparesis, and
hemiparesis
Stage III :
 Severe cases, for comatose patients and with multiple
cranial nerve palsies, hemiplegia or paraplegia, or
both

20. Treatment of TBM

21. 1. Microbiological cure
2. Prevention of complications, morbidity and
mortality
3. Management of treatment complications

22.  Intensive phase: 2 months RHZE
 Continuation phase: at least 7 months RHE
 Duration: Standard first-line ATT for at least
9 months

23.  These recommendations were made by the INDEX-TB
Guidelines Panel at the INDEX-TB meeting in 2015
 The Technical Advisory Sub-committee for CNS TB, who
drafted these clinical practice points, expressed a
preference for an alternative approach to the continuation
phase
◦ recommend the use of pyrazinamide instead of ethambutol
◦ treatment to be continued in all patients for a total of at least 12
months
 The current RNTCP guidance is to use ethambutol in
continuation phase because of the risk of isoniazid mono-
resistance
 If vision is impaired or cannot be assessed, use
streptomycin instead of ethambutol in the intensive phase.
Use of streptomycin in pregnant women, and patients with
kidney impairment or hearing loss should be avoided

24.  ATT should be started as early as possible in
all cases of TBM
 Presumptive TBM patients should be referred
to a secondary/tertiary care centre
immediately

25.  Patients assessed for clinical response at the
end of treatment and at intervals for 2 years
 Sustained resolution of clinical features
including headache and fever should guide
stopping of ATT
 Residual neurological deficits may be
permanent

26.  Drug-resistant TBM should be suspected in
patients with poor response to standard ATT
and history of exposure to MDR-TB

27. HIV-negative patients
 Steroids are recommended for at least 4
weeks, with appropriate tapering
Suggested regimen
 Intravenous dexamethasone 0.4 mg/kg/24 hr
in 3–4 divided doses preferred with a slow
switch to oral therapy and taper

28. HIV-positive patients
 Steroids may be used in absence of other
life-threatening opportunistic infections
 Important are cryptococcal meningitis and
cerebral toxoplasmosis
 Steroids associated with increased adverse
events and disability in HIV-associated
cryptococcal meningitis

29.  Patients who develop hydrocephalus with
raised intracranial pressure may require CSF
diversion by ventriculo-peritoneal shunt
insertion

30. Complications of TBM

31.  Symptoms and signs of raised intracranial
pressure are worsening headache, vomiting,
ocular palsies, decreasing conscious level,
papilloedema
 Urgent neuroimaging if patient deteriorating

32.  VP shunt indicated for patients at all stages of
severity with hydrocephalus or raised ICP not
responding to ATT and steroids
 Early shunt insertion may be beneficial
 Treatment with diuretics such as mannitol
until shunt insertion

33.  External ventricular drainage is not usually
recommended, unless surgery is
contraindicated or urgent CSF diversion is
indicated to buy time before a shunt can be
inserted

34.  Focal neurological deficit consistent with a
stroke syndrome
 Stroke in TBM may not be clinically apparent
and diagnosed on neuroimaging
 Stroke is a significant contributor to disability
following TBM

35.  Acute stroke or evidence of on-going
vasculopathy may warrant continuation of
steroids, usually intravenously
 There is some evidence that aspirin may
prevent stroke in TBM

36.  Visual loss, which may arise during treatment
with ATT, or on withdrawal of corticosteroids
 Characteristic CT and MRI findings

37.  Intravenous dexamethasone is the first-line
treatment
 Methylprednisolone pulse or oral thalidomide
in patients not responding to steroids
 Microsurgical intervention and intrathecal
hyaluronidase not recommended

38.  Generalized seizures secondary to
encephalopathy
 Tuberculoma or infarction may cause
secondary generalized seizure

39.  Acute management with anti-epileptic drugs
 Anti-epileptics and ATT have potential drug
interactions & increased risk of hepatotoxicity
 Prophylactic anti-epileptics not required
 Continued treatment with anti-epileptic
drugs in patients with recurrent seizure

41.  CNS Tuberculoma is an important cause of
intracranial space-occupying lesions
 Less common than TBM and has lower
morbidity and mortality
 Tuberculoma can arise anywhere in the brain
or spinal cord

42.  A mass lesion causing focal neurological
deficits
 Seizures
 In-concurrence with TBM

43.  Any patient presenting with seizures,
headache, fever or focal neurological deficits
with neuroimaging features consistent with a
mass lesion of inflammatory nature

44.  A previous history of TB and contact with
pulmonary TB case make tuberculoma more
likely

45.  Active TB elsewhere in the body makes
tuberculoma more likely
 Chest X-ray
 CT chest for TB, other lesions amenable to
biopsy, and look for features suggestive of
other pathology such as malignancy

46.  HIV testing is important
 HIV-positives are at increased risk of
tuberculoma, and other diagnoses such as
coccidiomycosis and toxoplasmosis
 Other causes of immunosuppression are also
important

47.  MRI / CT scan findings consistent with
tuberculoma
 Ring-enhancing lesions with surrounding
vasogenic edema
 Associated leptomeningeal and/or
pachymeningeal enhancement

48.  CSF can be normal, or similar to TBM
 The sensitivity of culture for Mtb is low
 PCR-based tests require further investigation
in tuberculoma

49.  Biopsy rarely performed as this is a highly
invasive procedure
 It may be indicated in patients where the
diagnosis remains very uncertain after non-
invasive tests, or there is no response to ATT

50.  Neurocysticercosis
 Pyogenic abscess
 Metastatic lesions from a primary malignancy
elsewhere in the body, e.g. lung cancer
 Glioma
 Demyelinating lesion

51. CNS Tuberculoma Neurocysticercosis
Lesion
Size >20 mm because
of conglomeration and
often multiple
Size <20 mm and may
be single or multiple
Edema More Less
Midline shift More common Less common
Outline Irregular Smooth
Target appearance Present Present
Scolex Absent Present
Meningitis features May be present Absent

52. Treatment of CNS Tuberculoma

53. 1. Resolution of neurological and
constitutional symptoms
2. Resolution of the lesion on neuroimaging

54.  There is a lack of evidence for optimum
duration of treatment
 ATT given for 9 to 12 months initially, with
repeat neuroimaging at 3 months and 9–12
months to monitor treatment response
 Treatment tailored to clinical and radiological
response

55.  Paradoxical reaction may occur with increase
in size and number of lesions
 Usual in first 3 months of treatment
 Treated with steroids as well as continued
ATT

56.  Treatment failure suspected when lesions
either increase in size or fail to reduce in size
after 3 to 6 months ATT despite appropriate
dosing and good adherence
 The clinician considers the benefits and risks
of biopsy against empirical second-line
treatment for suspected MDR-TB, or
persisting with first-line treatment for
suspected paradoxical reaction

57. If performed due to strong consideration of an
alternative diagnosis, the specimens should
be sent for
1. Histopathology with staining for AFB
2. Mtb culture and drug susceptibility testing
3. Other microbiological tests as indicated by
the case history