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• 62 years male, Kham Bahadur Gurung
• From Syangja
• Dizziness and vomiting for 10 days
• Fever for 2 days along with headache and neck
• He was in delirious state with behavioral
• Bowel and bladder habits were normal
• He was treated outside but did not get better.
• 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,
• Other vitals: stable
• Respiratory: normal vesicular breath sounds
in both lungs
decreased air entry in right upper lobe
• Cardiovascular : S1S2M0
• Per abdomen: soft, non tender, no
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
• Causative organism: Mycobacterium
• 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
• Robert Koch demonstrated that TB was caused
by M. tuberculosis in 1882.
• HIV coinfection is the strongest risk factor for
progression to TBM.
• Unimmunized with BCG
Other contributing factors
• Substance abuse
• Diabetes mellitus
• 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
• 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
• 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
• 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
• Tuberculomas are coglomerate caseous foci
within the substance of the brain.
1. FORMATION OF RICH FOCUS
2. RUPTURE OF RICH FOCUS INTO SUBARACHNOID SPACE
• TBM is difficult to diagnose and a high index of
suspicion is needed to make an early diagnosis
• 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
Principle presentation is subacute febrile illness that
progresses through three phases:
• Choroid tubercles on opthalmoscopy -
multiple, ill-defined, raised yellow-white
nodules (granulomas) of varying size near
the optic disc
• Meningitic syndrome rapidly progressing-
suggesting acute infection
• Dementia over months or years- personality
change, social withdrawal, loss of libido, and
• Encephalitic course with stupor, coma, and
convulsions without overt signs of meningitis
• Look for BCG vaccination scar
• Visual findings: papilledema or a small grayish white
• 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.
• 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
Based on CSF findings of ↓Glucose, ↑Protein &
• 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
• Electrolyte concentrations:
- mild-to-moderate hyponatremia present in
roughly 45% of patients
- in some cases constituting a true syndrome of
inappropriate diuretic hormone secretion
• Blood urea nitrogen (BUN) and creatinine level
• Tuberculin skin testing
• CSF Analysis
-Cell counts, differential count, cytology
-Glucose level, with a simultaneous blood glucose level
-Acid-fast stain, Gram stain, India ink stain
-Cryptococcal antigen and herpes antigen testing
• 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
• Polymerase chain reaction:
- 60% sensitive in rapid detection of M. tuberculosis in
- Recommended whenever clinical suspicion is sufficiently
high for empirical therapy or AFB is negative.
- 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.
• Interferon-gamma release assay (IGRA) using
specific tuberculous antigens is a rapid,
specific and sensitive method for the
detection of tuberculous infection.
• Angiography- for narrowing of the arteries
especially the small vessels at the base of the
• Electroencephalopathy-abnormal if
meninigitis has progressed to advanced stage
• Brainstem Auditory Evoked Response Testing-
abnormal in advanced stage of meningitis
• 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
• Intensive phase
(Initial 2 months)
• A four drug regimen-
INH, RIF, PZA, and either
EMB or STM
• Continuation phase
• INH and RIF alone if the
patient makes good
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.
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
• 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.
• Dexamethasone —
-A total dose of 8 mg/day for children weighing
-12 mg/day for adults and children >25 kg,
-for 3 weeks, then tapered off gradually over the
following 3 to 4 weeks.
SECOND LINE DRUGS
• Aminoglycosides: e.g., amikacin , kanamycin
• Polypeptides: e.g., capreomycin, viomycin, enviomycin;
e.g., ciprofloxacin , levofloxacin, moxifloxacin ;
• Thioamides: e.g. ethionamide, prothionamide
• Cycloserine (the only antibiotic in its class);
• p-aminosalicylic acid (PAS or P).
• 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
• BCG vaccination offers a protective effect
(approximately 64%) against TBM.
• 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.
• Motor deficits- CN palsies, hemiparesis
• Mental impairment
• Abnormal behavior
• Brain damage
• High morbidity and mortality
• Very critical disease in terms of fatal outcome and
permanent sequelae, requiring rapid diagnosis and
• Prognosis is directly related to the clinical stage at
• 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.
TAKE HOME MESSAGE
• Start ATT empirically when suspicion of TB
• See for the BCG scar in suspected case
• Counsel the patient for medication/side
• Complete the course
• Follow up
• Harrison’s Principle of Internal Medicine
• Clinical Tuberculosis: John Crofton, Norman
Horne, Fred Miller