Dr. Ajit Surya Singh

1. Chittaranjan National Cancer Institute
(CNCI)
KOLKATA-700160

2. Central nervous system (CNS) tuberculosis (TB) is among the least
common yet most devastating forms of human mycobacterial infection.
Conceptually, clinical CNS infection is seen to comprise three categories
of illness.
1. Subacute or chronic meningitis
2. Intracranial tuberculoma
3. Spinal tuberculous arachnoiditis
Centers for Disease Control and Prevention. 2010. Data and
statistics.

3. All 3 forms occur with equal frequencies in endemic regions like India.
CNS TB occurs in 1 to 2% of all patients with active TB.
It accounts for about 8% of all extrapulmonary TB reported to occur in
immunocompetent individuals.
Case fatality rate of CNS TB is 15- 40% despite effective anti-TB
chemotherapy.
Centers for Disease Control and Prevention. 20015. Extrapulmonary tuberculosis cases and percentages by site of disease: reporting areas,20015.
Centers for Disease Control and Prevention, Atlanta, GA. http://www.cdc.gov/tb/surv20015/PDF/tabl27.pdf.

4. Tuberculosis remains a leading cause of morbidity and mortality in
the developing world.
It may account for 1/6th of the 3 million of global mortality.
Although CNS involvement by tuberculosis is seen in all age groups,
there is a predilection for younger patients, with 60-70% of cases
occurring in patients younger than 20 years of age.
In endemic regions, tuberculomas account for as many as 50% of all
intracranial masses
Male predominance

5. • Children
• HIV-infected patients
• Malnutrition
• Recent measles in children
• Alcoholism
• Malignancies
• Use of immunosuppressive agents in adults
https://doi.org/10.1128/microbiolspec.tnmi7-0044-2017

6.  CNS TB is a three step process
1. Hematogenous seeding of meninges during bacteremia of
primary TB
2. Quiescent phase: may last from few weeks to many years
3. Mycobacteria in Richs foci multiply and with immune or
traumatic stimulus rupture or grow and clinical
manifestations occur

7.  For CNS tuberculosis, the disease begins with the development of
small tuberculous foci (Rich foci) in the brain, spinal cord, or
meninges.
 The location of these foci and the capacity to control them ultimately
determine which form of CNS tuberculosis occurs.
 CNS tuberculosis manifests itself primarily as tuberculous
meningitis (TBM) and less commonly as tubercular encephalitis,
intracranial tuberculoma, or a tuberculous brain abscess

10.  Tuberculous meningitis
• - Basal and spinal
 Tuberculoma
• - Intracranial (parenchymal & extraparenchymal)
• - Spinal (parenchymal & extraparenchymal)
 Tuberculous abscess
 Tuberculous encephalopathy
 - With or without meningitis
 Spinal cord involvement secondary to skeletal tuberculosis

11.  Intracranial
 - Tuberculous meningitis
 - Tuberculoma
 - Tuberculous abscess
 - Tuberculous encephalopathy
 - Tuberculous vasculopathy
 Spinal
 - Pott’s spine and Pott’s paraplegia
 - Tuberculous arachnoiditis
 - Spinal tuberculoma
 - Spinal meningitis

12. Symptom/sign(s) Frequency reported (%)
 Fever 20–70%
 Headache 25–70%
 Meningeal irritation 35–90%
 Lethargy/drowsiness 25–30%
 Vomiting 30–70%
 Confusion/delirium 30–65%
 Focal neurologic signs 25–40%
 CN palsy 20–35%
 Hemiparesis 5–30%
https://doi.org/10.1128/microbiolspec.tnmi7-0044-2017

13.  This is the commonest manifestation of tuberculous infection of the
nervous system
 In children, it usually results from bacteraemia following the initial
phase of primary pulmonary tuberculosis
 In adults, it may occur many years after the primary infection
 Tuberculous meningitis may manifest in two forms:
1. Leptomeningitis: common
2. Pachymeningitis: rare

14.  Tuberculous meningitis, although seen in all age groups, has a peak
incidence in childhood (particularly 0-4 years of age) in high
prevalence areas.
 In low prevalence areas, it is more frequently encountered in
adolescents and adults.

15.  Common and presents with thick tuberculous exudate within the
subarachnoid space, particularly pronounced at the base of the brain
especially in the interpeduncular fossa, anterior to the pons and around
the cerebellum and may also extend into the Sylvian fissures.
 In contrast to bacterial meningitis, extension over the surfaces of the
cerebral hemispheres is relatively uncommon.
 Eventually, mass-like regions of caseous necrosis can form within this
exudate, representing extra-axial tuberculomas.
 CSF flow is disrupted, and obstructive hydrocephalus is common.
 An additional complication is arteritis that may result in ischemic infarcts,
which are seen in approximately a third of cases, especially in children

16.  Tuberculous pachymeningitis is a rare form of CNS tuberculosis characterized by
a chronic tuberculous infection leading to a dura mater involvement.
 Common sites of involvement are cavernous sinuses, floor of middle cranial
fossa and tentorium.
 Characterized by thick plaque-like regions of pachymeningeal enhancement.
 This term should be reserved for cases where it is an isolated abnormality, and not
confused with the sometimes dramatic thickening of dura adjacent to
a tuberculoma.

18.  The clinical features of tuberculous meningitis (TBM) result from:
 Infection.
 Exudation – which may obstruct the basal cisterns and result in
hydrocephalus.
 Vasculitis – secondary to inflammation around vessels, resulting in
infarction of brain and spinal cord.
 The basal meninges are generally most severely affected.

19. Basal meningitis
 Spillage of tubercular protein in subarachnoid space causes intense
inflammation at base of brain
1) Proliferative arachnoiditis - CN & vascular injury
2) Vasculitis - thrombosis and stroke
3) Communicating hydrocephalus > Obstructive hydrocephalus

20. Clinical manifestations
Prodromal phase
Meningitic phase
Paralytic phase

21. Prodromal phase
 Two to three weeks
 Insidious onset
 Malaise
 Lassitude
 Headache
 Low-grade fever
 Personality change.

22. Meningitic phase
 Meningismus
 Protracted headache
 Vomiting
 Lethargy
 Confusion
 Varying degrees of cranial nerve and long-tract signs.

23. Paralytic phase
 Stupor and Coma
 Seizures
 Hemiparesis
 Majority of untreated patients - death within five to eight weeks of
the onset of illness.

24.  The majority of patients are adults; childhood TBM is now rare.
 Non-specific prodromal symptoms develop over 2–8 weeks.
 Staging is useful for predicting outcome.
Stage I Early Stage II intermediate Stage III advanced
Fever (in 80%) Confusion Delirium
Lethargy Cranial nerve paresis Stupor
Meningism Coma
Vasculitis -
hemi/quadriparesis, ataxia,
dysarthria
seizures, multiple cranial
nerve palsies, and/or dense
hemiplegia
Clinical features of tb meningitis

25.  Seizures may occur at the onset. Involuntary movements (chorea,
myoclonus) occur in 10%.
 Atypically the illness may develop slowly over months presenting
with dementia or rapidly like pyogenic (bacterial) meningitis.
 Occasionally cerebral features prevail rather than signs of
meningitis.
 Untreated, the illness may progress from phase 1 to death over a 3-
week period.
 Arachnoiditis inflammatory exudate may result in
hydrocephalus/dementia/blindness
Clinical features of tb meningitis

26.  General: Anaemia, leucocytosis. Hyponatraemia (if inappropriate ADH secretion occurs).
 Cerebrospinal fluid
 Cell count, differential count, cytology (50–4000/mm3 – predominantly lymphocytes)
 Glucose, with a simultaneous blood sugar (<50% blood glucose)
 Protein (>1g/l)
 Acid-fast stain, Gram stain, appropriate bacteriologic culture and sensitivity, India ink (all
causes of lymphocytic meningitis)
 Cryptococcal antigen, herpes antigen (other causes of lymphocytic meningitis)
 Culture for M. tuberculosis (50–80% positive)
 Polymerase chain reaction (PCR) to detect Mycobacterium DNA – specificity and
sensitivity 100% and 70%.

27.  Tuberculin skin test: Positive in 50% of cases. (Negative if recent steroids or
acquired primary infection.)
 Chest x-ray:
 Hilar lymphadenopathy, infiltrate, cavitations, effusion, scar.
 CT scan and MRI
 Hydrocephalus, basal meningeal thickening, infarcts, oedema, tuberculomas and
obliteration of the subarachnoid space.

29.  Fungal meningitis (cryptococcosis, histoplasmosis, blastomycosis,
 coccidioidomycosis)
 Neurobrucellosis
 Neurosyphilis
 Neuroborreliosis
 Focal parameningeal infection (sphenoid sinusitis, endocarditis,
 brain abscess)
https://doi.org/10.1128/microbiolspec.tnmi7-0044-2017

30.  Viral meningoencephalitis
 Subacute/chronic meningitis
 CNS toxoplasmosis
 Partially treated bacterial meningitis
 Neoplastic meningitis (lymphoma, carcinoma
https://doi.org/10.1128/microbiolspec.tnmi7-0044-2017

31.  Normal regime:2 months
1. Isoniazid (300 mg daily)
2. Rifampicin (600 mg daily)
3. Pyrazinamide (15–30 mg/kg daily)
 Then for 6 months
1. Isoniazid and Rifampicin
 Drug resistance suspected due to previous antituberculous therapy -
Add a fourth drug – streptomycin (1 g daily) or ethambutal (25
mg/kg daily).

32.  Intrathecal therapy: Streptomycin 50 mg may be given daily or
more frequently in seriously ill patients. When obstructive
hydrocephalus occurs, combined intraventricular (through the
shunt reservoir or drainage catheter) and lumbar intrathecal
treatment injections may be administered.
 Steroid therapy: Adjunctive steroids reduce neurological
sequelae, hearing loss and mortality in patients with TBM
without HIV.

33.  Intracranial tuberculous granulomas, also known as CNS
tuberculomas, are common in endemic areas and may occur either in
isolation or along with tuberculous meningitis
 Tuberculomata may occur in cerebral hemispheres, cerebellum or
brain stem with or without tuberculous meningitis, and may
produce a space-occupying effect.
 Lesions may be single or multiple.

34.  A tuberculoma is distinct from a tuberculous abscess in that it
demonstrates evidence of granulomatous reaction and caseous
necrosis histologically.
 Tuberculomas have a solid granulomatous core made up of
epitheloid cells and macrophages containing mycobacteria and some
may undergo liquefaction.

35.  The clinical presentation of CNS tuberculoma is usually more subtle
than that of TB meningitis.
 Tuberculomas accompany TB meningitis in 10% of patients
 Lesions may occur in the brain, spinal cord, subarachnoid, subdural,
or epidural space
 Include headache, seizures, focal neurologic deficits, and
papilledema

36.  TB organisms may not necessarily be identified in tuberculomas,
whereas they are necessary to make the diagnosis of tuberculous
abscess.
 CT
 Tuberculomas may appear as a round or lobulated nodule with
moderate to marked edema.
 MRI
 Isointense to grey matter, usually appears as ring-enhancement

38.  Other infection
 Neurocysticercosis
 Cerebral toxoplasmosis
 CNS cryptococcosis
 Bacterial cerebral abscesses
 Neurosarcoidosis
 Cerebral metastases
 CNS lymphoma

39.  Most resolve over a few weeks with antituberculous therapy.

40.  This was first described by Percivall Pott. He noted this as a painful
kyphotic deformity of the spine associated with paraplegia.
 Tuberculous spondylitis, also known as Pott disease, refers to vertebral
body osteomyelitis and intervertebral diskitis from tuberculosis (TB).
 The spine is the most frequent location of musculoskeletal tuberculosis,
and commonly related symptoms are back pain and lower limb
weakness/paraplegia.
 This arises in the lower thoracic region, can extend over several segments
and may spread through the intervertebral foramen into pleura,
peritoneum or psoas muscle (psoas abscess).
 Chronic epidural infection follows tuberculous osteomyelitis of the
vertebral bodies.

41.  In developing countries, spinal TB is mostly a disease of childhood or
adolescence.
 1/5th of TB population is in India.
 3% are suffering from skeletal TB, 50% of these suffer from spinal
lesion and almost 50% are from pediatric group.
 An estimated 2 million or more patients have active spinal
tuberculosis.
 The incidence is now increasing, probably due to the development of
antibiotic resistance

43.  The spine is involved due to hematogenous spread via the venous
plexus of Batson.
 There is usually a slow collapse of one or usually more vertebral
bodies, which spreads underneath the longitudinal ligaments.
 This results in an acute kyphotic or "gibbus" deformity.
 This angulation, coupled with epidural granulation tissue and bony
fragments, can lead to cord compression.
 Unlike pyogenic infections, the discs can be preserved and it more
commonly involves the thoracic spine.
 In late-stage spinal TB, large paraspinal abscesses without severe
pain or frank pus are common, leading to the expression "cold
abscess".

44.  Paradiscal: This is the commonest type. In this, the contagious areas
two adjacent vertebrae along with the intervening disc are affected.
 Central: Body of single vertebrae affected leading to early collapse of
the weakened vertebrae. The nearby disc maybe normal. The
collapse may be a ‘wedging’ or ‘concertina’ collapse.
 Anterior: Infection is localised to anterior part of vertebral body.
Infection spreads up and down under the anterior longitudinal
ligament.
 Posterior: Posterior complex vertebrae i.e., the pedicle, lamina,
spinous process and transverse process is affected.

45. Types of pott’s disease

46.  The classic systemic features of weight loss, night fever and cachexia
are often absent.
 Pain occurs over the affected area and is made worse by weight
bearing.
 Symptoms and signs of cord compression occur in approximately
20% of cases.
 The onset may be gradual as pus, caseous material or granulation
tissue accumulate, or sudden as vertebral bodies collapse and a
kyphosis develops.

47.  ACTIVE STAGE:
 Back pain
1. Diffuse “radicular pain”, commonest presenting complaint.
2. Presents in the arm (cervical root), girdle (dorsal root), abdomen
(dorso-lumbar root), groin (lumbar root), sciatic (lumbo-sacral root)
 Stiffness
1. Very early symptom.
2. Protective mechanism of the body.

48.  Cold abscess
 Patient may present with a swelling ‘cold abscess’ or problems
secondary to its compression effects on nearby vicera.
 Paraplegia (if neglected in early stages)
 Deformity
 Constituional symptoms
 Fever, Weight loss, Night sweats

49.  Healed stage:
 No systemic features but deformity persists.
 Radiological evidence of bone healing
 Patient may present with cold abscess or due to its
compression effects
1. Retropharyngeal abscess — Dysphagia ,dyspnea, hoarseness
of voice
2. Mediastinal abscess—Dysphagia
3. Psoas abscess— Flexion deformity of hip

51.  Straight x – ray
1. Reduced disc space, Blurred paradiscal margins, Destruction of bodies, Loss of
trabecular pattern, Increased prevertebral soft tissue shadow, Subluxation
/dislocation, Decreased lordosis or Kyphosis
 CT / MRI
1. T1: hypointense marrow in adjacent vertebrae
2. T2: hyperintense marrow, disc, soft tissue infection
3. T1 C+ (Gd): marrow, subligamentous, discal, dural enhancement
4. The paraspinal collections are typically well circumscribed, with fluid centers
and well-defined enhancing margins.

53.  Brucellosis
 Fungal infection
 Sarcoidosis
 Pyogenic infection/spondylitis
 Metastasis

54.  A needle biopsy is often sufficient
 Long-term anti-tuberculous therapy is commenced.
 If signs of cord compression develop, decompression is necessary.
 Anterior Transthoracic Decompression with strut graft fusion is
sometimes performed. This permits clearance of pus and caseous
debris without retracting the spinal cord.
 Posterolateral approach (costotransversectomy): One or more ribs
are resected medially, along with the transverse processes.

55.  Tuberculous meningomyelitis is a relatively rare but serious
type of nervous system tuberculosis.
 This disorder is now more frequent in AIDS patients.
 This disease is caused by invasion of the spinal cord or
the spinal meninges which may result from downward spread of
intracranial infection or direct spread from epidural infection.
 Occasionally arises from rupture of local metastatic focus;
resultant infection is confined to the spinal level.
 Tuberculosis Infection of the leptomeninges results in an
exudate that encases the spinal cord and nerve roots.

56.  It can be Ascending myelitis, Root involvement, Descending myelitis
 Results in
Back pain
Root pain, paraesthesia
Weakness mainly lower limb
Pyramidal and segmental.
Sensory loss.
Sphincter disturbance

57.  Imaging may be normal while CSF shows high protein, lymphocytes and rarely
acid fast bacilli.

58.  Cytomegalovirus
 Cryptococcus
 Syphilis
 Lymphoma.
.

59.  Laminectomy and meningeal biopsy may be required to establish
diagnosis.
 Antituberculous drugs - Rifampicin 0.45 g/d + ethambutol 0.75 g/d +
pyrazi- namide 1.5 g/d + isoniazid 0.6 g/d.
 Surgically treated with abscess debridement and spinal stabilization