Neurological tuberculosis

1. NEUROLOGICAL
TUBERCULOSIS

2. CLASSIFICATION
 Tuberculous meningitis( TBM)
 Tuberculomas
 Tuberculous abscess

3. ETIOLOGY
 M.tuberculosis.
 M. bovis.

4. PATHOGENESIS
 M. tuberculosis reaches the brain , meninges and spinal cord by
hematogenous route.
 Tubercles are formed- ‘RICH FOCUS’.
 In patients with poor immunity tubercles will enlarge, undergo
caseation.
 Rupture of tubercles in to the subarachnoid space or ventricular
system will produce meningitis.
 Deeply seated tubercles – Tuberculoma, tuberculos abscess.

5. TUBERCULOUS MENINGITIS

6. PATHOPHYSIOLOGY
 Inflammatory meningeal exudate.
 Vasculitis.
 Encephalitis.
 Disturbance of CSF circulation and absorption.

7. INFLAMMATORY MENINGEAL
EXUDATE
 Thick tuberculous exudate is formed in the subarachnoid space.
 Exudate is gelatinous and granular; contains PMNL, RBCs,
macrophages, lymphocytes and monocytes.
 Tubercles may be formed, may contain Mycobacteria.
 Optic chiasma, Inter peduncular fossa,Sylvian fissure, Surface of
Pons,Cerebellum and Cerebral hemispheres, Ventricles.

8. VASCULITIS
 Inflammation of vessels traversing the exudate.
 Terminal portion of internal carotid artery and proximal portion
of middle cerebral artery within the sylvian fissure are the sites
commonly affected.
 Occlusion of vessels, leading to ischemia and infarction.

9. DISTURBANCE OF CSF FLOW AND
ABSORPTION
 Oedema of brain parenchyma or exudate will block the spinal
aqueduct or foramina of 4 th ventricles.
 Impaired absorption and circulation of CSF - Hydrocephalus.

10. ENCEPHALITIS
 ‘‘Border Zone Encephalitis’- Tissue reaction adjacent to the
zone of thick adherent exudate.
 Thrombosed vessels may produce infarction.
 C/C hydrocephalus will produce atrophy of both gray matter
and white matter.
 Diffuse cerebral oedema, demyelination and hemorrhagic leak.

11. CLINICAL FEATURES
 Presentation is more acute in children.
 Indolent course in adult.
 H/o precipitating conditions like viral or bacterial infections,
immunisation, head trauma may be present.
 Symptoms
fever
Headache
Vomiting
Siezures
Abnormal behaviour
Cranial nerve involvement- blindness, deafness.
altered sensorium.

12. SIGNS
 Features of meningeal irritation
 Fundus –papilloedema
 Cranial nerve palsy- 6th 3rd 4th 7th 2nd 8th &10th
 Focal neurological signs-Most commonly involves the anterior
circulation
 Abnormal movements-Chorea,hemiballismus,myoclonus
cerebellar ataxia.
 Altered sensorium-drowsiness ,stupor ,coma

13. Staging system
 STAGE 1 (Early)
Nonspecific symptoms.
Few or no clinical signs of meningitis
Fully conscious and alert.
 STAGE 2 (Intermediate)
Signs of meningitis
Drowsiness or lethargy
Cranial nerve palsy
 STAGE 3(Advanced)
Stupor or coma
Systemic toxicity
Gross paresis or paralysis

14. INVESTIGATIONS
 Routine laboratory studies
ESR - normal or elevated
Leucopenia or luekocytosis
Serum electrolytes- Hyponatremia,
- Hypochloremia.
 CXR-evidence of healed pulmonary tuberculosis or
miliary tuberculosis
 Mantoux test- negative in 10-15% of children and 50%
of adults.
 Extra neural cultures- Sputum, Gastric lavage, urine,
lymph node, bone marrow, liver.

15. CSF STUDIES
 Opening pressure -High (>180mm of H2O)
-Low in spinal block
 Clear or slightly opalescent
 Rarely haemorrhagic due to vasculitis.
 High CSF protein . COB WEB PHENOMENON- ‘Pellicle’
formation -due to high concentration of fibrinogen
 Hypoglycorrhachia- moderately depressed CSF sugar
 Cell count is increased with lymphocyte predominance.

16. CSF STUDIES …
MICROBIOLOGICAL INVESTIGATIONS
 Demonstration of mycobacteria in CSF.
 Smear will be positive only in <25% of cases.
 Bacterial yield can be increased by
Using pellicle
Centrifuged sediment
Repeated CSF sampling
Using fluorochrome staining.
Ventricular and cisternal fluid.
 Culture of CSF for mycobacteria.

17. OTHER DIAGNOSTIC TESTS
 Immunological tests
Antigens - ELISA or RIA for soluble tuberculous antigens.
Antibodies –ELISA test to detect IgG and IgM antibodies

18. BIOCHEMICAL ASSAYS
 Adenosine deaminase (ADA)
Sensitivity-73%-100%.
 Radiolabelled Bromide Partition Test
Based on the disruption of BBB in TBM.
Oral or IV (82 Br) Ammonium bromide.
Concentration of radio isotope in serum and CSF is
determined simultaneously after 1-2 days of equilibrium.
Normal serumBr : CSF Br > 3.
TBM < or = 1.6.
 Tuberculostearic acid in CSF.
Sensitivity - 95%, specificity-99%.

19. Diagnostic Test …
 Molecular techeniques.
Polymerase Chain Reaction (PCR)
 Radiological investigations
Plain radiograph of the skull -
Calcification of basal meninges or brain parenchyma,
Destruction of skull due to extension of infection.
Separation of sutures due to hydrocephalus in children.

20. Diagnostic Test …
 Angiographic evaluation
‘Angiographic Triad of TBM’
 Hydrocephalic pattern of vessels.
 Narrowing of vessels at the base of brain.
 Narrowed or occluded small and medium sized vessels with
scanty collaterals.

21.  Plain CT Head
Findings are nonspecific
Ventricular enlargement due to hydrocephalus.
Periventricular lucency due to ependymal exudate.
Areas of low attenuation –Infarction.
 Contrast enhanced CT
Increased meningeal enhancement
 MRI with gadolinium enhancement
More sensitive
Thickened cranial nerves can be identified.
 MR Angiography-
Vascular narrowing.

22. DIFFERENTIAL DIAGNOSES
 Partially treated bacterial meningitis
 Fungal meningitis
 Syphilitic meningitis
 Carcinomatous meningitis
 Collagen vascular diseases

23. SEROUS (STERILE) TBM
.
 Results when tubercles rupture into the meninges without
releasing any viable mycobacterium
 Tuberculoprotein is responsible for the immunological reaction
 Distinctive CSF profile and good clinical prognosis.
 CSF- Increased pressure, Protein and cell count with normal
sugar.
 Complete recovery can occur without treatment in days to weeks

24. Treatment of TBM

25. Anti tuberculous chemo therapy
 PRINCIPLES
 Drugs should cross the BBB to achieve a level above MIC
 Chemotherapy should be directed against both intra cellular
and extracellular organisms
 Multiple drugs should be used to prevent emergence of drug
resistance

26. DRUGS
 1st line drugs
INH
• Small non protein bound molecule
• Excellent penetration of both inflammed and noninflammed
meninges.
• CSF concentration much higher than MIC .
• In TBM CSF concentration is about 90% of plasma
concentration
RIFAMPICIN
• Poor CSF penetration
• In TBM concentration just above MIC will be obtained

27. Drugs …….
 PYRAZINAMIDE
Effective against intracellular organisms in acidic pH
Excellent CSF penetration
CSF concentration is equal to serum concentration in presence of
inflammation.
 ETHAMBUTOL
CSF penetration is poor in the absence of inflammation.In
inflammed meninges CSF level is 10-50% of plasma level
 STREPTOMYCIN
Good penetration of inflammed meninges

28. Drugs …..
 2nd line drugs
Good CSF penetration for -
ETHIONAMIDE
CYCLOSERINE
OFLOXACIN
AMINO-GLYCOSIDES
Poor CSF penetration for -
PAS

29. Treatment regimens
 WHO
Short course chemo therapy
2 months intensive phase with HREZ
+
4 months continuation phase with HR
 ATS
2 months intensive phase with HREZ
+
6-8 months continuation phase with HR

30. RNTCP Guide lines
 In patients with TB meningitis on CAT-I treatment 4 drugs used during
intensive phase – HRZE should be replaced by HRZS as
ETHAMBUTOL does not penetrate CSF
 Continuation phase for the treatment of TBM and spinal TB with
neurological complication should be given for 6-7 months ,extending the total
duration of treatment to 8-9 months

31. STEROIDS
 Inflammatory process in TBM is a hypersensitivity response to
tuberculous antigens
 Most beneficial in patients with complications
Clinical stage 2 and above
Raised ICT
Cerebral edema
Stupor
FND
Spinal block
Hydrocephalus
Basal optico chiasmatic pachymeningitis

32. Steroids ……
 Prednisolone 60 mg daily or 1 mg/kg /day
 Dexamethasone 8-16 mg daily or 0.3-0.6 mg/kg/day
DURATION
3-6 weeks; slowly tapered over 2-4 weeks
CSF PARAMETERS affected
Opening pressure
Protein content
Leucocyte count

33. Surgery
 Relief of hydrocephalus
 Ventriculo peritoneal shunt
 Temporary external ventricular drains

34. CNS TUBERCULOMA
 Unruptured tubercles will be walled of from the adjacent
parenchyma by fibrous capsule.
 Single or multiple.
 Sites-Cerebral hemispheres, basal ganglia, brain
stem,cerebellum,Substance of spinal cord.
 Clinical features -Siezures ,Increased ICT,FND.
 CSF study -Not contributory.
 Contrast enhanced CT
Uniform contrast enhancement
Ring enhancing lesion.

35. CNS Tuberculoma…
 Biopsy- ‘Gold standard’ investigation.
Caseating granuloma.
AFB smear and culture.
 Treatment
Medical treatment with ATT,Steroids,Anticonvulsants.
Surgery

36. TUBERCULOUS BRAIN ABSCESS
 Results from liquefaction of caseous core of the granuloma.
 Acute clinical presentation - Fever,headache,FND
 Diagnosis by CT head or MRI
 Treatment
-ATT - poor response
-Surgery

37. SPINAL CORD TUBERCULOSIS
 Inflammatory lesions - arachnoiditis,vasculitis
 Space occupying lesions - Tuberculomas (intramedullary or
epidural)
 Subarachnoid space is filled with thick tuberculous exudate.
 Nerve roots traversing the space are compressed
 Vessels are inflammed and narrowed.
 Adjacent parenchyma –edematous,demyelinated,atrophic.

38. SPINAL CORD TB …
 Presents with acute onset of spinal block,
transverse myelitis like syndrome, slow ascending paralysis
 CSF - Not obtained in spinal block.
- High protein, low sugar ,lymphocytic pleocytosis.
 Myelography
 CT scan and MRI-enhance subarachnoid exudate.
 Treatment- ATT,steriods, surgery.

39. PROGNOSIS
 Mortality has declined with the introduction of effective ATT.
 Prognosis depends on
Stage at diagnosis and start of treatment.
Extremes of age.
Co-existance of miliary disease.

40. SEQUELAE
Children
 Intellectual & emotonal impairment
 Neurologic sequelae
Spastic hemi paresis
Seizure disorder
Ataxia& Inco -ordination
Persistent cranial nerve palsy

41. Sequelae….
Adults
 Chronic organic brain syndrome
 Cranial nerve palsy- 6th , 8th, Optic atrophy
 Paraplegia & hemiparesis
 Syringo-myelia
 Endocrinological-Hypo pituitarism , DI
 Chronic hypothermia

42. AIDS & CNS TB
 Common form of extra-pulmonary TB in AIDS patients
 Commonest CNS infection in AIDS in some parts of the world
 Atypical features
 Coincident infection with other CNS opportunistic pathogens
 Standard anti tuberculous therapy is effective