1. A 62-year-old man presented with 10 days of dizziness, vomiting, and 2 days of fever and headache. Examination revealed neck stiffness, delirium, and signs of meningitis. 2. CSF analysis showed elevated white blood cells and protein with low glucose, consistent with tuberculous meningitis. CT head and MRI brain showed basilar enhancement. 3. Tuberculous meningitis was diagnosed and treatment initiated with a four drug antitubercular regimen along with corticosteroids. Prognosis depends on stage at diagnosis and risk factors like HIV co-infection impact outcomes.

1. CASE STUDY
Prajjwal Malla
MDGP Resident 1st yr

2. • 62 years male, Kham Bahadur Gurung
• From Syangja
• Dizziness and vomiting for 10 days
• Fever for 2 days along with headache and neck
stiffness
• He was in delirious state with behavioral
changes
• Bowel and bladder habits were normal
• He was treated outside but did not get better.

3. • Personal history: alcoholic but non smoker
• Past history : PTB 10 yrs back, treated
• Surgical history :
-Right hydrocele was operated 3 yrs ago
-Right eye was operated 1 month back
• O/E : General condition: fair, confused,
GCS:14/15, febrile
• Other vitals: stable

4. SYSTEMIC EXAMINATION
• Respiratory: normal vesicular breath sounds
in both lungs
decreased air entry in right upper lobe
• Cardiovascular : S1S2M0
• Per abdomen: soft, non tender, no
organomegaly

5. Central Nervous System:
• Higher mental function: delirious, not oriented to time,
place and person
• Neck rigidity : present
• Ophthalmoplegia : present
• Slight facial deviation on left side
• Power : intact in all the four limbs
• Tone : increased in upper limbs
• Deep tendon reflexes : exaggerated in all four limbs
• Plantar: B/L upgoing

6. LABS
• WBC: 10360/mm3
• Hb: 12.3 mg/dl
• Platelets: 458000 cu/mm
• PMN: 82%
• ESR: 14 mm
• Blood culture : no growth
after 72 hours
• Malaria parasite: not seen
• B24-negative
• S. creat: 1.4 mg/dl
• K+: 5.6 mmol/L
• Na+: 136 mmol/L
• ALP: 105 U/L
• AST: 28 U/L
• ALT: 10 U/L
• RBS: 183 mg/dl

7. CSF FLUID ANALYSIS
• WBC: 155 (↑↑)
• RBC: 15 (↑↑)
• POLYS: 42%
• LYMPHS: 58%
• GLUCOSE: 48mg/dl (↓)
• PROTEIN: 176.0mg/dl (↑↑)
• ADA: 17

8. CHEST XRAY

9. CT- HEAD

11. TUBERCULOUS MENINGITIS

12. ETIOLOGY
• Causative organism: Mycobacterium
tuberculosis
• First description of TBM credited to Robert
Whyte, on the basis of his 1768 monograph,
Observations of Dropsy in the Brain.
• Described as a distinct pathological entity in
1836
• Robert Koch demonstrated that TB was caused
by M. tuberculosis in 1882.

13. RISK FACTORS
• HIV coinfection is the strongest risk factor for
progression to TBM.
• Unimmunized with BCG
Other contributing factors
• Malnutrition
• Alcoholism
• Substance abuse
• Diabetes mellitus

14. EPIDEMIOLOGY
• In populations with a low prevalence of TB,
most cases of TBM occur in adults.
• However, TBM is more common in children
than in adults, especially in the first 5 years of
life.

15. PATHOPHYSIOLOGY
• Following primary infection or late reactivation TB
elsewhere in the body, scattered tubercles are
established in the brain, meninges, or adjacent bone.
• Subcortical or meningeal focus from which bacilli
gained access to the subarachnoid space is the critical
event for development of tuberculous meningitis .
• Due to chronic reactivation bacillemia occurs in older
adults due to immune deficiency caused by aging,
alcoholism, malnutrition, malignancy, or human
immunodeficiency virus (HIV) infection
• Head trauma may also lead to destabilization of an
established quiescent focus resulting in meningitis

16. • The spillage of tubercular protein into the subarachnoid space produces
an intense hypersensitivity reaction due to a dense gelatinous exudate,
giving rise to inflammatory changes.
• Proliferative arachnoiditis, most marked at the base of the brain,
produces a fibrous mass involving cranial nerves and penetrating vessels.
• Vasculitis with resultant thrombosis and infarction involves vessels that
traverse the basilar or spinal exudate or are located within the brain
substance itself.
• Variety of stroke syndromes may result, involving the basal ganglia,
cerebral cortex, pons, and cerebellum.
• Communicating hydrocephalus results from extension of the inflammatory
process to the basilar cisterns and impedance of CSF circulation and
resorption.

17. • Basal exudates

18. • Tuberculomas are coglomerate caseous foci
within the substance of the brain.

19. PATHOPHYSIOLOGY
1. FORMATION OF RICH FOCUS
2. RUPTURE OF RICH FOCUS INTO SUBARACHNOID SPACE

20. CLINICAL PRESENTATION
• TBM is difficult to diagnose and a high index of
suspicion is needed to make an early diagnosis
HISTORY:
• Recent contact with patients of TB
• Past history of TB
• History of immunosuppresion from a known
disease or from drug therapy
• Negative history of BCG vaccination-see for scar

21. Principle presentation is subacute febrile illness that
progresses through three phases:

22. • Choroid tubercles on opthalmoscopy -
multiple, ill-defined, raised yellow-white
nodules (granulomas) of varying size near
the optic disc

23. Atypical features:
• Meningitic syndrome rapidly progressing-
suggesting acute infection
• Dementia over months or years- personality
change, social withdrawal, loss of libido, and
memory deficits
• Encephalitic course with stupor, coma, and
convulsions without overt signs of meningitis

24. PHYSICAL EXAMINATION
• Look for BCG vaccination scar
• Visual findings: papilledema or a small grayish white
choroidal nodule
• cranial neuropathies:
VI most affected, then III, IV, VII and
less commonly II, VIII, X, XI, XII.
• Kernig’s sign and Brudzinki’s sign
• Tremor is the most common movement disorder seen in
the course of TBM.
• In a smaller percentage of patients, abnormal movements,
including choreoathetosis and hemiballismus, have been
observed, suggesting of deep vascular lesions.

25. • Stage I - apathy, irritability, headache, malaise, fever,
anorexia, nausea, and vomiting, without any alteration in
the level of consciousness.
• Stage II - altered consciousness without coma or delirium
but with minor focal neurological signs; symptoms and
signs of meningism and meningitis are present, in addition
to focal neurological deficits, isolated CN palsies, and
abnormal involuntary movements.
• Stage III - advanced state with stupor or coma, dense
neurological deficits, seizures, posturing, and/or abnormal
movements
CLINICAL STAGING

26. DIFFERENTIAL DIAGNOSES
Based on CSF findings of ↓Glucose, ↑Protein &
lymphocytic pleocytosis
• Subacute or chronic meningitis syndrome caused by
Cryptococcosis, Granulomatous fungal infections,
Brucellosis, and Neurosyphilis.
• Parameningeal suppurative infection, eg.brain
abscess, or spinal epidural space infection.
• Herpes encephalitis

27. WORK UP
• Electrolyte concentrations:
- mild-to-moderate hyponatremia present in
roughly 45% of patients
- in some cases constituting a true syndrome of
inappropriate diuretic hormone secretion
(SIADH).
• Blood urea nitrogen (BUN) and creatinine level
• Urinalysis
• Tuberculin skin testing

28. • CSF Analysis
-Cell counts, differential count, cytology
-Glucose level, with a simultaneous blood glucose level
-Protein level
-Acid-fast stain, Gram stain, India ink stain
-Cryptococcal antigen and herpes antigen testing

29. CSF FINDINGS IN CNS INFECTIONS

30. • Culture: (87% diagnostic)
- CSF specimens for M. tuberculosis.
- The demonstration of acid-fast bacilli (AFB) in the CSF is
the effective means for an early diagnosis.
- Minimum of 3 lumbar punctures be performed at daily
intervals.
• Polymerase chain reaction:
- 60% sensitive in rapid detection of M. tuberculosis in
CSF.
- Recommended whenever clinical suspicion is sufficiently
high for empirical therapy or AFB is negative.

31. • Neuroimaging:
- CT & MRI are helpful in detection.
- CT can present the extent of basilar arachnoiditis,
cerebral edema and infarction, and the presence and
course of hydrocephalus.
• Hydrocephalus combined with marked basilar
enhancement is indicative of advanced meningitic disease
and carries a poor prognosis.
• Marked basilar enhancement correlates well with vasculitis
and, therefore, with a risk for basal ganglia infarction.

32. MRI showing basilar enhancement

33. • Interferon-gamma release assay (IGRA) using
specific tuberculous antigens is a rapid,
specific and sensitive method for the
detection of tuberculous infection.

34. OTHERS
• Angiography- for narrowing of the arteries
especially the small vessels at the base of the
brain
• Electroencephalopathy-abnormal if
meninigitis has progressed to advanced stage
• Brainstem Auditory Evoked Response Testing-
abnormal in advanced stage of meningitis

35. TREATMENT
• The mainstay of treatment for TB is clinical
suspicion & starting of empirical therapy.
• First line drugs — Isoniazid (INH), rifampin
(RIF), and pyrazinamide (PZA) are bactericidal,
can be administered orally all having good
meningeal penetration.

37. RECOMMENDED REGIMEN
• Intensive phase
(Initial 2 months)
• A four drug regimen-
INH, RIF, PZA, and either
EMB or STM
• Continuation phase
(9-12 months)
• INH and RIF alone if the
patient makes good
progress.

38. DURATION OF THERAPY
• 9 to 12 months in drug-sensitive infections.
• If PZA is omitted or cannot be tolerated,
treatment should be extended to 18 months
with isoniazid and thiacetazone.

39. VALUE OF CORTICOSTEROIDS
• has now been established by a controlled trial.
• Particularly for young children and severely ill.
• Begin with Prednisolone 30 mg twice daily
(1mg/kg twice daily for chidren) for 4-6 weeks
then decrease over several weeks as the patient
improves.
• For the patients on rifampicin the dose should be
increased by half, i.e. 45 mg for adults and 1.5
mg/kg for children. The reason being Rifampicin
antagonises the action of Prednisolone.

40. • Dexamethasone —
-A total dose of 8 mg/day for children weighing
<25 kg;
-12 mg/day for adults and children >25 kg,
-for 3 weeks, then tapered off gradually over the
following 3 to 4 weeks.

41. SECOND LINE DRUGS
• Aminoglycosides: e.g., amikacin , kanamycin
• Polypeptides: e.g., capreomycin, viomycin, enviomycin;
• Fluoroquinolones:
e.g., ciprofloxacin , levofloxacin, moxifloxacin ;
• Thioamides: e.g. ethionamide, prothionamide
• Cycloserine (the only antibiotic in its class);
• p-aminosalicylic acid (PAS or P).

42. OTHERS
• Macrolides: e.g., clarithromycin
• Linezolid (LZD)
• Thioacetazone (T)
• Immunomodulators- cytokine-based therapy which
enhance both the mycobacterial killing activity of
effector cells and the restriction of bacterial
intracellular multiplication
• BCG vaccination offers a protective effect
(approximately 64%) against TBM.

43. SURGICAL INTERVENTION
• In patients with evidence of obstructive
hydrocephalus and neurological deterioration
who are undergoing treatment for TBM,
placement of a ventricular drain or
ventriculoperitoneal or ventriculoatrial shunt
should not be delayed.

44. COMPLICATIONS
• Hydrocephalus
• Infarctions
• Coma/stupor
• Motor deficits- CN palsies, hemiparesis
• Seizures
• Mental impairment
• Abnormal behavior
• Brain damage
• High morbidity and mortality

45. PROGNOSIS
• Very critical disease in terms of fatal outcome and
permanent sequelae, requiring rapid diagnosis and
treatment.
• Prognosis is directly related to the clinical stage at
diagnosis.
• Kumar et al reported that children with TBM who have
been vaccinated with BCG appear to maintain better
mentation and have superior outcomes.
• Coexisting HIV encephalopathy and diminished
immune competence contribute to the more severe
clinical and neuroradiological features.

46. TAKE HOME MESSAGE
• Start ATT empirically when suspicion of TB
• See for the BCG scar in suspected case
• Counsel the patient for medication/side
effects
• Complete the course
• Follow up

47. REFERENCES
• Harrison’s Principle of Internal Medicine
• Clinical Tuberculosis: John Crofton, Norman
Horne, Fred Miller
• Medscape
• Uptodate