CNS tuberculosis is a severe manifestation of extrapulmonary tuberculosis, characterized by a high case fatality rate in untreated cases. The document discusses the etiology, pathogenesis, classification, diagnosis, and treatment methods for CNS tuberculosis, highlighting the critical importance of early detection and intervention. Key diagnostic techniques, clinical features, and potential complications are outlined, emphasizing the need for adjunctive steroid therapy and the role of surgery in certain cases.

1. CNS TUBERCULOSIS
By- DR.RATAN LAL MEENA
Moderator- DR. SUBHRA JAIN

2. Introduction
• One of the most devastating clinical manifestation
of EPTB.
• 5-10% of extra-pulmonary & 1% of all TB cases.
• Male predominance
• The case fatality rate is 100% on untreated case
and delayed in treatment may lead to permanent
neurological damage.

3. CONTENT
• Etiology
• Pathogenesis
• Classification
• Diagnosis
• Treatment

4. Etiology
Risk factors;
• Children> adults
• HIV co-infection
• Malnutrition
• Alcoholics
• Malignancies
• Use of
immunosuppressive
agents
Causative agent;
• Most common-
Mycobacterium tuberculosis
• In immunocomromised
patient -
Atypical mycobacteria ;
MAC, mycobacterium
intracellulare

5. Pathology
• Release of M tuberculosis results in a
T lymphocyte dependent necrotising
granulomatous inflammatory
response.
• Thick gelatinous exudate around
sylvian fissures, basal cisterns,
brainstem & cerebellum.
• 3 processes cause most of
neurological deficits:
Hydrocephalous
Adhesive arachnoiditis
Obliterative vasculitis

6. Pathogenesis
1.DROPLET INFECTION 2. Area of EXTRA CRANIAL EPTB
( subependymally located tubercle)
Primary focus bacteremia Meninges and brain
parenchyma
RICH
FOCUS

7. Rupture in
subarachnoid
space
ADHESION VASCULITIS ENCEPHALITIS
STROKE
INTER-
PENDUCULAR
FOSSA
BASAL
CISTERNS
CEREBERAL
EDEMA
HYDROCEPHALUS
CRANIAL NERVE
PALSY &
CAROTID
STENOSIS
PARALYSIS &
ABNORMAL
MOVEMENT
RAISED
ICT
MENINGITIS
OPTIC CHIASMA
LOSS OF
VISION

8. Classification
• Intracranial
- Tubercular meningitis
- Tuberculoma
- Tubercular abscess
- Tubercular encephalopathy
- Tubercular vasculopathy
• Spinal
- Pott’s spine & Pott’s paraplegia
- Tubercular arachnoiditis
- Spinal tuberculoma
- Spinal meningitis

9. TBM
• Commonest form (70-80%).
• 30% mortality & neurological sequelae > 25% survivors.
• H/o vague ill health 2-8 wks prior to meningeal irritation.
• 75% to 85% below age 5 year, uncommon <6m,rare <3 m
• Cranial nerve palsies (20-30%), 6th nerve involvement
being the most common.

10. Clinical features
Sign
• Neck rigidity
• Kerning sign
• Brudzinski sign
• Hemiplagia
• Papilloedema
• Abducens nerve palsy
• Optic atrophy
• Facial nerve palsy
• Oculomotor nerve palsy
• Chhoroidal tubercle
Symptoms
• Fever
• Altered sensorium
• Headache
• Vomiting
• Behavioural changes
• Seizure
• Weight loss

11. Staging of TBM
British Medical Research Council criteria
Stage I: Prodromal phase with no definite neurologic
symptoms.
Stage II: Signs of meningeal irritation with slight or no
clouding of sensorium & minor or no
neurological deficit.
Stage III: Severe clouding of sensorium, convulsions, focal
neurological deficit & involuntary movements.

12. Modified MRC criteria
Grade I: Alert and oriented (GCS 15) without focal
neurological deficit.
Grade II: GCS 14-10 with or without focal neurological
deficit or GCS 15 with focal neurological deficit.
Grade III: GCS less than 10 with or without focal
neurological deficit.

13. Spinal TBM
• May result from rupture of Rich foci in the spinal arachnoid
space
• The acute form presents with fever, headache, and root pains
accompanied by myelopathy
• The chronic form presents with spinal cord compression

14. Complications
• Hydrocephalus
communicating , non communicating
• Ocular lesion
papiloedema, optic atrophy, vision loss,
• Hypothalamic pituiatary syndrome
SIADH hyponatraemia (49%)
Diabetes incipidus persistent pyrexia
• Cranial nerve palsies
3rd,4th, 5th,6th,7th, horizontal & vertical gaze palsy
Internuclear ophthalmoplegia
• Paralysis & abnormal movement
• Stroke ,seizure

15. Tuberculoma
• Mass of granulation tissue made up of conglomeration of
microscopic small tubercles.
• Firm, avascular, 2-8cm, spherical granulomatous mass.
• Locations -
infratentorial- <20 year
supratentorial - >20 year
• Solitary more frequent than multiple.
• Symptoms related to size & location.
• Low grade fever, headache, vomiting, seizures,
focal neurological deficit & papilloedema

16. •CT/MRI
A central nidus of calcification with
surrounding ring like enhancement
known as target sign .
•Histology:- consist of a central core of caseating necrosis with
with a surrounding wall of florid granulomatus reaction
containing lymphocyte, giant cells,
epitheliod cells ,histiocytes.

17. TUBERCULOMA NEUROCYSTICERCOSIS
At any age Rare before 3 year
Progressive neurological deficit No progressive neurological deficit
Size >20mm,irregular outline Smaller size, regular rounded with less
cerebral edema
Supratentorial or infratentorial Usually supratentorial
Midline shift seen Midline shift not seen

18. Tubercular brain abscess
• It is characterised by an encapsulated collection of pus containg
viable bacilli without evidence of a classic tubercular
granuloma.
• 4-7.5% of pt with CNS TB.
• More common in elderly & immunocompromised.
• Usually solitary, uni/multi-loculated of variable size.
• Clinical features: partial seizures, focal neurological deficit &
↑ intracranial tension.

19. •Differentiation b/w tuberculous & pyogenic abcess is made
by MR spectroscopy.
•CT & MRI show large size lesion with marked
surrounding edema.
Tubercular
abscess
tuberculoma
Central core pus Caseating
necrosis
surrounded by
granulomatus
reaction
Peripheral rim Comparative
thicker
thin
Mycobacterium
tuberculosis
Must be
present
May or may
not present

20. Tubercular encephalopathy
• Seen in infants & children.
• Characterized by convulsions, stupor & coma with signs of
meningeal irritation or focal neurological deficit
• CSF is normal.
• MRI- diffuse brain edema & demyelination which is extensive.
• Responsive to corticosteroids.

21. Spinal TB
• Infection starts in cancellous bone usually adjacent to an inter-
vertebral disc or anteriorly under the periosteum
• Regional distributions
Thoracic (65%) most common
lumbar (20%)
cervical (10%)
thoraco-lumbar (5%), atlanto-axial region (< 1%)
• type of vertebral lesion:-
Paradiscal most common
Central
Anterior
Appendical
articular

22. Clinical features-
back pain most commen
Spine stiffness: spasm of paravertebral muscle
Deformity:-knuckle/gibbus/kyphosis
Cold abscess
Paraplagia
Other constitutinal symptoms like fever, weight
loss, cough

23. Spinal TB
• Radiological changes
Reduced disc space
Destruction of bodies
Loss of trabecular pattern
Skipped lesion
Fusiform paravertebral shadow suggest abcess formation

24. Tubercular arachnoiditis
• Features of spinal cord or nerve involvement may
predominate, but most often mixed picture.
• Subacute paraparesis, radicular pain & bladder
dysfunction.
• Hallmark of diagnosis is characteristic myelographic
picture, showing poor flow of contrast material with
multiple irregular filling defects, cyst formation &
sometimes spinal block.

25. Differential diagnosis of TBM
• Fungal meningitis (cryptococcosis, histoplasmosis,
blastomycosis, coccidioidal mycosis)
• Viral meningoencephalitis (herpes simplex, mumps)
• Partially treated bacterial meningitis
• Neurosyphills
• Focal parameningeal infection
• CNS toxoplasmosis
• Neoplastic meningitis (lymphoma, carcinoma)
• Neurosarcoidosis

26. Diagnostic methods
• CSF examination
• CSF smear examination
• CSF CULTURE examination
• Molecular& immunological test
• Adjunctive test
• Radiology

27. Diagnostic criteria for TBM
Patients with at least four of the following:
i. History of tuberculosis.
ii. Predominance of lymphocytes in the cerebrospinal fluid.
iii. A duration of illness of more than six days.
iv. A ratio of CSF glucose to plasma glucose of less than 0.5.
v. Altered consciousness
vi. Turbid cerebrospinal fluid.
vii. Focal neurologic signs.
Possible
Patients with one or more of the following:
i. Suspected active pulmonary TB on chest radiograph
ii. AFB found in any specimen other than the CSF.
iii. Clinical evidence of extrapulmonary tuberculosis.
Probable
Acid-fast bacilli seen in the cerebrospinal fluid.Definite
DefinitionClass

28. TBM
CSF examination :-
• Appearance-slightly opaque,
-cobweb formation on long standing
• leucocytosis (10-1000 x 103 cells/ml
mostly lymphocytes)
• ↑ protein 50-300mg/dl
• Glucose<50mg/dl
• CSF : plasma glucose <50%.
• In immune-suppressed CSF can be acellular or
predominant neutrophils.

29. Test Appearance Pressure WBC/μL Protein
mg/dL
Glucose
mg/dL
Chlori
de
Normal CSF Clear 90 – 180 mm
hg
0-5 15-45 50-80 115-
130
mEq/L
Acute
bacterial
meningitis
Turbid Increased 1000 -10000 100 – 500 < 40 Decrea
sed
Viral
meningitis
Clear Normal to
moderate
increase
5-300, rarely
>1000
Normal to
mild
increased
Normal Normal
Tuberculous
meningitis
Slightly
opaque
cobweb
formation
Increased/
decreased,
10-1000
mixed
Initially
neutrophillic
& later
lymphocytic
50-300 Decreased Decrea
sed
Fungal
meningitis
Clear Increased 40-400 mixed 50-300 Decreased Decrea
sed

30. Gram’s and India ink stain-
• a negative Gram’s & india ink stain are pre-requisites for
the diagnosis of TBM
Zeihl –Nelson’s stain-
• Rapid, inexpensive,specific for AFB
• Low sensitivity (12-69%)
• 6 ml CSF should be taken for mycobacterial study

31. Egg or agar based solid medium:-
• L-J media ; sensitivity(25-80%)
• Takes 2-8 week to isolate the organism.
Automated liquid based:-
• BACTAC ; sensitivity(55%)
• growth detect by production of
Radioactive C-14 in 2 week.

32. Molecular method
• Sensitivity (56%)
• Diagnostic yield of NAA ↑ when large volm CSF
processed
• NAA more useful than conventional bacteriology
after start of ATT
• NAA assays (CBNAAT) detect R resistance
• PCR for MTB is not affected by presence of other
bacteria

33. Immunological test-
by using RIA,ELISA, immunoblot method
• Direct test:- detect Ag like;
culture filtrate antigen
antigen-5
• Indirect test :- detect Ab against
glycolipids&Protein isolates from MTB
Ag-5 ,BCG,Lipoarabimannon

34. Tuberculin skin testing:
• sensitivity ; adult ( 40-65%)
children ( 85-90%)
• Lacks of specificity because cross react with BCG vaccination.
Interferon-gamma release assay:- ( blood test)
• IFN-gamma is cytokine,classic marker of Th-1 type cellular
immune response.
• By using tuberculous specific antigen (ESAT-6,CFP-10).
• Measured by:- ELISA technique (quantiferon test)
ELISPOT technique(T-SPOT)
• No cross react with BCG vaccination so good sensitivity &
specificity.

35. CSF tuberculostearic acid level:-
•Fatty acid component of Mycobacterial cell wall.
•Identified by gas chromatography or mass spectroscopy.
•Sensitivity -90%, specificity -90%
•Expensive equipment & complex technique has limited its
clinical use.
CSF ADA level
• raised >(5-15 iu/l)
• high ADA also in malaria, lymphoma, pyogenic abcess
• lack specificity, so not recommended as routine

36. Sensitivity & specificity of various diagnostic
tests for TBM
Menzies et al, Ann Int Med. 2007; 146: 340-354.
Diagnostic test Sensitivity Specificity
ZN staining 10-20% 100%
LJ Culture 15% (25-80) 100%
BACTEC Culture 55% 100%
ELISA 52.3% 91.6%
TB PCR 56% 98%
TST 73% 56%
QTF-GOLD 76% 98%
ELISPOT 87% 92%

37. Radiology
CHEST X RAY:
•50% TBM pt have CXR
suggesting active/previous PTB.
•10% have miliary disease.

38. CT /MRI BRAIN
•Confirm the presence and extent of basal arachnoiditis, cerebral
oedema, infarction, ventriculitis and hydrocephalus.
•Abnormalities depend upon stage of disease:
I (normal in 30%), II (Normal in 10%), III (Abnormal in all).
•Hydrocephalus (70-85%), basal meningeal enhancement (40%),
infarction (15-30%), tuberculoma (5-10%).
•Meningeal enhancement, tuberculoma or both have a sensitivity
of 89% and specificity of 100%
•Precontrast hyperdensity in basal cisterns is the most specific
radiological sign.

39. • Radiological findings also help in prognostication.
 CT brain of every TBM case either before starting
or within 48 hr of Rx (A,II).
 Pts with suspected cerebral tuberculoma/spinal
cord TB investigated by MRI (A,II), whether
surgery indicated & follow response to therapy
(A,II)

41. British Infection Society guidelines
Recommendation
• Tissue biopsy ↑ diagnostic yield than CSF for
diagnosis of tuberculoma & spinal TB (A,II).
• Careful search should be made for extra-neural
disease that may be biopsied safely(A,II).
• Stereotactic brain biopsy should be considered for
diagnosis of tuberculoma if other investigations fail
(A,II).

42. Principles of treatment of TBM
Treatment should be started early in suspected TBM.
Drugs must adequately cross blood-CSF barrier to
achieve therapeutic concentrations.
H & Z penetrates CSF freely & potent early
bactericidal activity.
R penetrates CSF less (max concn 30% of plasma)

43. Treatment
• RNTCP- CAT1/CAT2.
• BTS & ATS recommend 9-12 mth ATT, extend to 18,
who do not tolerate Z.

44. Adjunctive steroid therapy
INDICATIONS
CLINICAL:-
• Clinical stages 2 and above
• Evidence of raised intracranial pressure
• Focal neurological deficit suggesting arteritis.
RADIOLOGICAL:-
• Cerebral oedema
• Hydrocephalus
• Infarcts
• Opticochiasmatic pachymeningitis.

45. Adjunctive steroid therapy
Rationale behind use:
• ↓ inflammation within
subarachnoid space,
• ↓ mortality & long term
neurological complications &
permanent sequelae reduced.
 Largest RCT recommends
steroids in pt with TBM for 6-
8 wk.
Main argument:
they ↓ meningeal
inflammation & can affect
CSF penetration of ATT.
Thwaites GE et al. N Engl J Med 2004; 351: 1741-51;
Lancet Neurol 2007; 6: 280-6.

46. British Infection Society guidelines
Recommendation
• Pts with TBM receive adjunctive corticosteroids
regardless of disease severity at presentation (A,I).
• >14 yr dexamethasone 0.4 mg/kg/d, ≤14 yr: 0.6
mg/kg/d for 4 wks, ↓ course over 4 wks (A,I).
• In tuberculoma without meningitis or with spinal cord
TB, may be helpful in those with uncontrolled
symptoms, worsening on ATT or who have acute
spinal cord compression secondary to vertebral TB
(B,II).

47. Monitoring therapy
• CSF cell count ↓ by 50% during 1st mth but may not
become normal for a yr.
• CSF glucose normalize in 1-2 mth & protein becomes
normal by 12 mth or longer.
• CSF cultures should be sterile by 1st mth.

48. Role of surgery in CNS TB
 Aim: ↓ size of space-occupying lesion, thereby diminish
intracranial pressure & eradicate pathogen.
 Indication: hydrocephalus, TB cerebral abscess & vertebral TB
with paraparesis.
Early V-P shunting should be considered in those with non-
communicating hydrocephalus & in those with communicating
hydrocephalus failing medical management.
Urgent surgical decompression should be considered in extra-
dural lesions causing paraparesis.

49. Prognosis
Pts with no focal deficits & only minor lethargy
recover without sequelae.
Comatose pts- 50% mortality & ↑ incidence of
residual disability.
Late sequelae:
• Cranial nerve deficits,
• Gait disturbance, hemiplegia,
• Blindness, deafness,
• Dementia & pychiatric disturbance
• Various syndromes of hypothalamic or pituitary
dysfunction.

50. Poor prognostic factors
• Stage of disease.
• Presence of miliary disease
• Severe disease on admission
• Delay in initiation of treatment
• Extremes of age, preexisting debilitating condition
• Very abnormal CSF (very ↓ glucose or ↑ protein)

51. Empirical treatment: when to
start, when to stop?

52. British Infection Society guidelines
Recommendation
o Low sensitivity of all currently available rapid
diagnostic tests means empirical therapy need to be
started in many with suspected CNS TB.
o Therapeutic response should not be used to determine
when to stop treatment (B,III).
o Safest approach: complete course of treatment in all
unless alternative diagnosis is made (B,III).

53. Conclusion
• CNS TB is serious disease with 100% mortality in
untreated cases
• Early diagnosis & treatment prevent further
deterioration.
• CSF studies, CT & MRI & brain biopsy, if
necessary, aid in diagnosis.

54. Thank you

55. Cerebral tuberculoma without meningitis
• Clinical features depend on anatomical location, but
often asymptomatic.
• CSF examination- not specific.
Spinal TB
• Can affect any part of spinal cord: nerve roots,
therefore can present with upper or lower motor
neuron involvement or mixed clinical picture.

56. 1.Prodromal phase (early)
Last for 2-3 week, symptoms nonspecific i.e. Low grade fever,
anorexia, irritability vomiting, headache, but conscious.
2.Meningitic phase ( intermediate)
neurologic feature: cranial nerve palsy , motor deficits
sign of raised ICT ,sign of meningeal irritation , impaired
conciousness .
3.Paralytic phase (advanced)
sign of brain stem compression (opisthotonic posture, neck
retraction,decorticate and decerebrate posture,hemiplagia
,paraplagia,
deep coma and death.