a case of tb meningitis with presentation

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