tuberculosis meningitis in childrens

1. NEUROTUBERCULOSIS
Dr.krishna

2. OBJECTIVES
 CLASSIFICATION OF NEUROTUBERCULOIS
 PATHOGENESIS OF TB MENINGITIS
 CLINICAL FEATURES AND CLINICAL STAGING
 DIAGNOSTIC CRITERIA
 COMPLICATIONS OF TB MENINGITIS
 MANAGEMENT
 DIFFERENTIAL DIAGNOSIS OF NEUROTUBERCULOSIS

3. Introduction
 CNS tuberculosis accounts for 1% of all cases of a TB
 Most Common form is TB meningitis in Indian children
 Incidence 1-4%
 Almost always associated with primary tuberculosis
 Most Common route is lymphohematogenous
 It is Highly cilical suspicious with DIAGNOSTIC DIFFICULTY
and LACK OF STANDADIZED CRITERIA.
morbidity and mortality is high for TBM

4. CLASSIFICATION OF NEURO TUBERCULOSIS
INTRACRANIAL TB
1) Tubercular meningitis and meningoencephalitis
2) Space occupying lesions
( Tuberculomas, tubercular abscess)
3) Tubercular encephalopathy
4) Tubercular vasculopathy
SPINAL TB
1) Potts spine
2) Tubercular arachnoiditis
3) spinal tuberculoma
4) Spinal meningitis and radiculomyelitis

5. PATHOGENESIS OF TB MENINGITIS
(ARNOLD RICH and HOWARD McCORDACK)
DROPLET INFECTION
PRIMARY FOCUS
BACTEREMIA
RICH
FOCUS

6. ADHESIONS
RUPTURE IN
SUBARACHNOID
SPACE
VASCULITIS ENCEPHALITIS
BASAL
CISTERNS
INTER
PEDUNCULAR
FOSSA
CRANIAL NERVE PALSIES
AND
CAROTID STENOSIS
HYDROCEPHALUS
PARALYSIS AND
ABNORMAL
MOVEMEENTS
STROKE
CEREBRAL EDEMA
RAISED ICT

7. CLINICAL FEATURES
 75 to 85% below age 5 yrs, uncommon <6M, rare < 3M
 Peak incidence is 3-5 yrs.
 Onset is subacute or chronic,taking more than 3 wks.
 Clinical manifestation grouped in to 3 stages
 STAGE 1: ( early )
prodromal stage lasts 2 to 3 wks.
symptoms nonspecific i.e lowgrade fever,anorexia
sleep disturbance,apathy,irritability,fatigue
headache,vomiting, but child is conscious.

8.  STAGE 2 ( intermediate )
1 ] Convulsions
2 ] Signs of meningeal irritation
3 ] Neurological deficits
a) cranial nerves palsy
b) motor deficits
4 ] Signs of raised intracranial pressure
5 ] Impaired consciousness

9.  STAGE 3 ( advanced )
1) Progressive neurological deficits with dilated pupils
2) Signs of brain stem compression ( opisthotonic posture,
neck retractions, decorticate, and decerebrate posture,
Hyperpyrexia, monoplegia,hemiplegia,paraplegia )
3) movement disorders
4) Deep coma and death

10. COMPLICATIONS
PARALYSIS
hemiplegia
quadriplegia
monoplegia
paraplegia
ABNORMAL MOVEMENTS
hemiballismus
tremors [ generalized ]
athetosis , dystonia , choreic movements

11. COMPLICATIONS
CRANIAL NERVE PALSIES
1 ] 3rd , 4th ,5th ,6th, 7th ,8th. Cranial nerve palsies
2 ] Horizontal gaze palsy, vertical gaze palsy.
3 ] Internuclear opthalomoplegia
MOTOR TRACTS
1 ] Decorticate spasms / rigidity
2 ] Decerebrate spasms / rigidity
HYDROCEPHALUS
1] Communicating
2] Non communicating

12. COMPLICATIONS
HYPOTHALAMIC PITUITARY SYNDROMES
Cushings disease
Obesity
Diabetes insipidus
SIADH
Precocious puberty
Persistent pyrexia
TUBERCULAR CEREBRAL VASCULAR DISEASES
OCULAR LESIONS –papillitis, papilledema optic atrophy,
vision loss ( PATHOGNOMIC –CHOROIDAL TUBERCLES)

13. Criteria for diagnosing TBM
MODIFIED AHUJA CRITERIA FOR DIAGNOSIS
OF TBM IN CHILDRENS
A) MANDATORY FEATURES
1) FEVER LASTING MORE THAN 14 DAYS
2) ABNORMAL CSF FINDINGS
PLEOCYTOSIS WITH MORE THAN 20 CELLS AND
MORE THAN 60 % are LYMPHOCYTES
PROTEINS > 100 mg / dl,
sugar < 60 % of blood sugar
B) PLUS ANY TWO OF FOLLOWING CRITERIA
1) evidence of extra neural TB
2) positive family history of exposure to case

14. 3) positive mantoux reaction
4) Abnormal CT scan findings ( 2 or more )
exudate in basal cistern
hydrocephalus
infarcts
gyral enhancements

15. AIIMS PROTOCOL FOR DIAGNOSIS OF TB MENINGITIS
 Demonstration of acid fast bacilli in the CSF or fulfilment
of following criteria
ESSENTIAL
CSF showing :
Predominant lymphocyte pleocytosis > 50/mm3
protein > 60 mg/dl
sugar < 2/3 of blood sugar

16. SUPPORTIVE
Along with the essential ones, two or more of the
following clinicoinvestigational criteria:
1 ] History of fever of two weeks or more
2 ] positive family history of tuberculosis
3 ] generalized lymphadenopathy
4 ] mantoux test positive
5 ] positive radiological evidence of TB
6 ] CT SCAN evidence of basal exudates
7 ] Isolation of AFB from gastric lavage
8 ] Histologically proven tubercular
lymphadenitis

17. MANAGEMENT
DIAGNOSTIC MODALITIES
 EVIDENCE OF EXTRANEURAL TB
CHEST X RAY
USG ABDOMEN [ RETROPERITONEAL LN ,MATTED LOOPS]
TUBERCULIN SKIN TEST

18. CSF ANALYSIS
CYTOLOGY AND BIOCHEMISTRY – opaque or clear, pellicle or
Cobweb formation on long standing.
LEUCOCYTE COUNT : 100 TO 500 per microL rarely exceeds
1000 cells. lymphocytes predominate.
CSF PROTEINS 100 to 200 mg/ dl.
CSF GLUCOSE < 2/3rd of blood glucose values
MICROBIOLOGY : CSF SMEAR FOR AFB, YIELD IS LOW [ 58% ]
CSF CULTURE [ POSITIVE IN LESS THAN 50% ]

19. condition pressure leucocytes proteins glucose comments
Acute bacterial
meningitis Usually
elevated
100-10,000 or more;
PMNs predominate
Usually 100-500 Decreased,
Organisms usually seen on
Gram stain and recovered by
culture
Partially treated
bacterial
meningitis
Normal or
elevated
5-10,000; PMNs
usual but mononuclear
may be seen
Usually 100-500 Normal or
decreased
Organisms may be seen on
Gram stain
Pretreatment may render CSF
sterile.
viral meningitis Normal or
slightly
elevated
Rarely >1,000 cells. Usually 100-500 Generally
normal.
focal findings on CT or MRI
scans or EEG. HSV and
enteroviruses may be detected
by PCR of CSF
Fungal meningitis Usually elevated 5-500; PMNs early but
mononuclear cells
predominate through
most of the course.
25-500
<50;
decreases
with time if
treatment is
not provided
Budding yeast may be seen.
Organisms may be recovered in
culture
Tubercular
meningitis Usually
elevated
10-500; PMNs early, but
lymphocytes
predominate through
most of the course
100-3,000; may be
higher in presence
of block
<50 in most
cases;
decreases.
Acid-fast organisms almost
never seen on
smear.Mycobacterium
tuberculosis may be detected
by PCR of CSF

20. IMMUNOLOGICAL TESTS
DIRECT TESTS – detects Ag
culture filtrate antigen
antigen -5
immunoabsorbent affinity column purified antigen
INDIRECT TESTS – detects antibodies against BCG,PPD,AG 5
lipoarabinomannan.
Radio immune assays
ELISA
Immuno blots

21.  CSF ADENOSINE DEAMINASE [ ADA ] LEVELS
Produced by T LYMPHOCYTES,
It has good results in the diagnosis of the pleural,peritoneal
and pericardial forms of tuberculosis.
ADA activity could not distinguish between TBM and other types
of bacterial meningitis, ADA values from 1 to 4 U/L
(sensitivity>93% and specificity<80%) can help to exclude TBM
and values >8 U/L (sensitivity<59% and specificity >96%) can
improve the diagnosis of TBM. However, value between 4 and 8
U/L are insufficient to confirm or exclude the diagnosis of TBM
 TUBERCULOSTEARIC ACID
component of cell wall, high sensitivity and specificity
but costly

23. NEUROIMAGING

28. TREATMENT
 PRIMARY AIM IS
1 ] to ensure the recovery of child without neurological
deficit
2 ] it should prevent transmission and evolution of
resistant strains
3 ] start therapy with antibiotics and anti tb therapy and
reassess the patient 7 to 10 days

29. MANAGEMENT OF TB MENINGITIS
 Treatment
 Should be hospitalized –at least the first 2months
 Four anti-tb drugs are recommended for intensive phase
HRZE ( 2 months )
 Isoniazid and rifampicin are used for continuation phase
 Continuation phase is longer i.e. given for 10 months instead
of 4 months
 Corticosteroids(usually prednisolone) 2mg/kg/day daily
for 4 weeks and then gradually tapered over 1-2 weeks
before stopping.Alternately dexamethasone 0.4mg/kg/day
followed by oral prednisolone can be used.Total duration
of steroids 6 – 8 wks.

30. Pediatric dosages for intermittent therapy
DRUGS DOSAGE
(mg/kg)
6-10 kg 11-17 kg 18-25 kg 26-30 kg
ISONIAZID 10 75 150 225 300
RIFAMPICIN 10 75 150 225 300
PYRAZINAMIDE 30-35 250 500 750 1250
ETHAMBUTOL 30 200 400 600 1000
STREPTOMYCIN 15 - - - -

31. Antiepileptic drugs
 Seizures occur due to electrolyte imbalances, raised
intracranial pressures,they require the treatment of
underlying cause.
 Seizures which occurs after first week, or associated with
tuberculoma or infract require initiation of antiepileptic
drugs.
 Seizures are acute symptomatic,they do not require the
longterm treatment with AED
 PHENOBARBITONE SHOULD NOT BE USED for treatment as
it is a cerebral depressant and induces hepatic
microenzymes, induces hepatotoxicity.

32. Medical management of cerebral edema
Mannitol
 mannitol is used in emergency treatment of cerebral edema
 The dose is 5ml /kg stat followed by 2ml/kg 6th hourly for 8
doses
 Repeated use may leads to electrolyte imbalance with a
secondary increase in the intracranial pressure ( rebound
phenomenon ) hence these drugs should be used in first 48 to
72 hours.
 Glycerol, acetazolamide can be used for chronic raised
intracranial pressure.

33. Surgical management of hydrocephalus
PALUR STAGING
GRADE 1 : NORMAL SENSORIUM, NO NEUROLOGICAL DEFECIT
GRADE 2 : NORMAL SENSORIUM, WITH NEUROLOGICAL DEFECIT
GRADE 3 : ALTERED SENSORIUM, WITH OR WITHOUT DENSE NEUROLOGICAL DEFECIT
GRADE 4 : DEEP COMA WITH DECORTICATE AND DECEREBRATE POSTURE,
Indications
 non communicating hydrocephalus
 communicating hydrocephalus not responding to medical treatment.
 grade 2 and grade 3 hydrocephalus

34. Surgical management of hydrocephalus
 THERE ARE TWO OPTIONS FOR TREATMENT
VP shunt
endoscopic third ventriculostomy

35. DIFFERENTIAL DIAGNOSIS OF TB MENINGITIS
 PARTIALLY TREATED BACTERIAL MENINGITIS
 CRYPTOCOCCAL MENINGITIS
 VIRAL MENINGOENCEPHALITIS
 CARCINOMATOUS MENINGITIS
 NEUROSARCOIDITIS
 NEUROSYPHILIS

36. TUBERCULOMA
TUBERCULOMA is a cluster of micrograulomas which
coalesce in to mature noncaseating granulomas in solid
organs
Solitary lesions are most common than multiple lesions
May be infratentorial or supratentorial
Hard, nodular, comparatively avascular, and easy to shellout
Resembles meningioma

37. Clinical features
1] Intracranial tuberculomas usually present with seizures
without meningeal signs.
2] Raised ICT features due to mass effect
3] various brain stem syndromes depending on location
4] New tuberculoma developed during treatment as a result
of paradoxical response to treatment.

38. Diagnosis
Clinical assessment,
Imaging findings
Response to therapy
[SECTL] SINGLE ENHANCING CT LESIONS
1) Single enhancing CT lesions are seen in neurocysticercosis, tuberculoma,
metastatic tumours, CNS lymphomas, abscess, toxoplasmosis, fungal
granulomas and rarely with infarction.
2 ) Patients with SECTL often present with focal, focal becoming generalized
seizures And rarely status epilepticus.
3 ) Children may present with motor deficits like monoplegia, hemiplegia or
ataxia.
4 ) Large lesions may manifest with features of increased intracranial tension

39. The clinical criteria are:
 1. Seizures (partial or generalized) should be the initial symptom.
 2. There should be no features of persistently raised intracranial
pressure.
 3. There should be no history of a progressive neurological
deficit.
 4. There should be no evidence of an active systemic disease.
The radiological criteria are:
 1. CT scan should only show a solitary, contrast – enhancing
lesion.
 2. The lesion should measure less than 20 mm in maximal
diameter.
 3. Edema may or may not be present, but is not severe enough to
produce a shift of the midline structures

41. TUBERCULOMA VS NEUROCYSTICERSOSIS
TUBERCULOMA NEUROCYSTICERCOSIS
MAY PRESENT AT ANY AGE RARE BEFORE THE AGE OF 3 YEARS
PROGRESSIVE NEUROLOGICAL DEFICIT NO PROGRESSIVE NEUROLOGICAL DEFICITS
SIZE > 20 MM, IRREGULAR OUTLINE
WITH MARKED CEREBRAL EDEMA
SIZE SMALLER, REGULAR ROUNDED
OUTLINE WITH LESS CEREBRAL EDEMA
SUPRATENTORIAL OR INFRATENTORIAL USUALLY SUPRATENTORIAL
MIDLINE SHIFT SEEN MIDLINE SHIFT NOT SEEN
MRS HAS LIPID PEAK MRS HAS NO LIPID PEAK

42. TUBERCULAR ABSCESS
Tuberculous abscesses are occur in less than 10% of patients with CNS
 More common in the elderly and immunocompromised.
 may be solitary or multiple and are frequently multiloculated.
 On imaging, a TB abscess may be indistinguishable from a caseating
tuberculoma or pyogenic abscess.
 TB abscess has thinner and smoother enhancing walls, is larger (> 3
cm in diameter),and it has peripheral oedema and mass effect
 Differentiation can be done with MR spectroscopy and magnetisation
transfer imaging.
 On MR spectroscopy, TB abscess does not demonstrate aminoacids
as compared to pyogenic abscess which shows amino acids.

44. TUBERCULOSIS ENCEPHALOPATHY
 A syndrome exclusively present in infants and children, has been
described by Udani and Dasturi in Indian children with pulmonary
tuberculosis.
 The characteristic features of this entity are the development of
a diffuse cerebral disorder in the form of convulsions, stupor, and
coma, without signs of meningeal irritation or focal neurological
deficit.
 Pathologically, there is diffuse oedema of cerebral white matter
with loss of neurons in the grey matter.
 Neuroimaging shows severe unilateral or bilateral cerebral
oedema. On T2-weighted images, hyper-intensity is seen in white
matter suggesting myelin loss.

45. THANK YOU

46. ABDOMINAL TUBERCULOSIS
 TB infection of abdomen includes GI tract,peritoneum
peritoneum,omentum,mesentry,lymphnodes,liver,
spleen and pancreas
M.tuberculosis,M.bovis,M.africanum, and nontuberculosis
bacteria M.intracellulare, M.avium.
PREDISPOSING FACTORS for intestinal TB
1) Rich in lymphoid tissues
2) AFB affinity for lymphoid tissue
3) Number of bacilli ingested
4) VIRULENCE OF BACILLI

47.  Nutritional and immunological status
 Alkaline Ph in small and large intestine
 Stasis in ileocecal areas
 No digestive activity
SITE OF INVOLVEMENT IN ATB
ILEUM > ILEOCECAL > COLON > JEJUNUM >
DUODENUM > STOMACH > OESOPHAGUS

48.  TYPES OF ABDOMINAL TUBERCULOSIS IN CHILDREN
TB OF INTESTINE
ULCERATIVE
HYPERTROPHIC
ULCEROHYPERTROPHIC
STRICTURE FORMATION
FISTULA
PERITONEAL TB
PERITONITIS
ASCITES
a ) generalized
b ) localized

49. DRY PLASTIC TYPE
ADHESION INTERLOOPS
FIBROPLASTIC
MILIARY TB PERITONEUM
granular peritoneal surface
OMENTAL TB
rolled up
miliary
TB OF LYMPH NODES
retroperitoneal
peri pancreatic
portahepatis

50.  CLINICAL FEATURES
PERITONEAL TB
1) most common in HIV, CIRRHOSIS,DM
MALIGNANCY,PERITONEALDIALYSIS
2) abdominal distention,Ascitis, soft cystic lump
secondary to loculated ascites
3) tenderness, doughy abdomen, hepatomegaly, Ascites.
OESOPHAGEOUS –rare, involves upper and midoesophagus
dysphagia, odynophagia,ulcer, Tracheo-oesophageal
fistula, hematemesis

51. Gastric – rare due to less LN, low PH
ulcerative form commonest ( lesser curvature )
presents with features of Gastric outlet obstruction
INTESTINE –two types
ulcerative- diarrhea and malabsorption
stricture –intestinal obstruction,
constipation,obstipation vomiting,diarrhea,abdominal
distention and coliky pain,enterocutaneous fistulas
COLORECTAL – weightloss, anemia, GI bleed

52.  HEPATOBILIARY TB
Tuberculomas, tubercular abscess, granulomatous hepatitis
pain, fever jaundice, hepatomegaly, tenderness, splenomegaly ascites
PANCREATIC TUBERCULOSIS
CBD obstruction, chronic pancreatitis,pancreatic mass
SPLENIC TUBERCULOSIS
splenic abscess and splenic granulomas

53. CRITERIA FOR DIAGNOSING ABDOMINAL TB
 DEFINITIVE
1) Histological evidence with caseation necrosis
2 ) A good typical gross description of operative findings with
biopsy of mesenteric nodes showing histological evidence of
tuberculosis
3) Animal inoculation or culture of suspected tissue resulting in
Growth of M.Tuberculosis
4) Histological demonstration of acid fast bacilli in lesion.

54.  MODIFIED
1 ) Histological evidence of caseating granulomas.
2) Presence of M.Tuberculosis in sputum or tissue or ascitic fluid
Clinical/radiological/operative evidence of proven
tuberculosis elsewhere with good therapeutic response
3 ) Good therapeutic response to antitubercular chemotheraphy

55. COMPLICATINS
 INTESTINAL OBSTRUCTION
 FISTULA FORMATION, PERFORATION
 ENTEROLITHIASIS,
 COCOON FORMATION,
 TRACTION DIVERTICULA
 MALOBSORPTION

56. INVESTIGATIONS
 HAEMATOLOGY AND SERUM BIOCHEMISTRY
ANEMIA, HYPOALBUMENIA, RAISED ESR , TOTAL
LEUCOCYTE COUNT INCREASES PREDOMINANTLY LYMPHOCYTOSIS
 ASCITIC FLUID ANALYSIS
EXUDATIVE ,
FLUID PROTEIN > 3gm/dl ,SAAG < 1.1 ,
ASCITIC / BLOOD GLUCOSE RATIO 0.96
WBC COUNTS > 1000 /mm3 AFB CULTURE,
ADA IN ASCITIC FLUIDS > 33U/L
 MANTOUX TEST POSITIVE IN 50 TO 60 %

57.  MALABSORPTION STUDIES
 PLAIN X RAY ABDOMEN
 BARIUM ENEMA
 BARIUM MEAL FOLLOW THROUGH
 PERCUTANEOUS FISTULOGRAM
 ABDOMINAL ULTRASOUND
 CT ABDOMEN

64. TREATMENT
MEDICAL TREATMENT
6 MONTHS SHORT COURSE TREATMENT WITH 4 MONTHS HRZE AND 2
MONTHS HR
SURGICAL TREATMENT
TO MANAGE COMPLICATIONS SUCH AS OBSTRUCTION ,PERFORATION, AND
MASSIVE HAEMORRAGE
STRICTURES BY STRICTUROPLASTY OR RESECTION
PERFORATION BY RESECTION AND ANASTOMOSIS
SURGERY FOLLOWED BY FULL COURSE OF ATT

65. THANK YOU