Tb Meningitis

Case study

Case

• A 70year old male NKCM came with the complain of

• Low grade fever -5yrs –on & off• Severe Headache-15-20dys• Behavioural changes- 2wks

According to the attendant (son) he has been ill on & off since the past 5-6yrs when he used to develop a low grade intermittent self resolving fever. It was sudden & non specific happening bout 1-3dys & the fever free period varied from weeks to months.

Now since the past few weeks he had a headache which wasn’t relieved by anything. He also was restless & disoriented. His talk & behaviour was odd to the family so they brought him for treatment. He was labelled as having dementia since the past year.

He was a smoker *quit since some years* & had a persistent dry cough. No history of vomiting, Night sweats, loss of consciousness or loss of function but

on/off nausea present.

Past hx- Pulmunary TB diagnosed on CXR/Sputum test 2yrs ago took ATT for only 2 weeks Hernia repair & Hemorrhoidectomy -6-7yrs ago.

Social History- Contact Hx of TB from work collegue.

Family History- not significant.

Investigations• CBCHb-12.1, Pcv-37, TLC-5.9, Plt-267• UCENa-142, K-3.4, Co3-21, Cl-103,Urea-44, Crt-0.84 SGPT- 10, RBS-91• Urine D/RPH-5.5, Protein- 10mg/dl, Sp.grav-1.025, Rbs-

numerous, Blood-3+, pus-2, Epi-2, Bacteria-few

• CSF-D/RVolume-10mlColorless, clearGlucose-43 ( Serum Rbs-83)Protein-87Rbc-64, 000cu/mmWbc- 200cu/mm ------Neu- 6, Lymp-92, Mono-2

ESR-32AFB –ve

CXR- Fibrosis.

CT scan showing basilar & Vascular enhancement

CT showing ventricular dilatation

TB Meningitis

Clinical features Principle presentaion is subacute febrile illness that progresses

through three discernible phases:

The prodromal phase

2-3weeks

malaise, lassitude, headache, low-grade fever, and personality change.

The meningitic phase neurologic features, such as meningismus, protracted headache, vomiting, lethargy, confusion, and varying degrees of cranial nerve and long-tract signs.

The paralytic phase, confusion ,stupor and coma, seizures, and often hemiparesis. death

• Choroid tubercles on opthalmoscopy -multiple, ill-defined, raised yellow-white nodules (granulomas)

of varying size near the optic disk

• CXR abnormalities- single or multiple lesions

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

Clinical stages

It is useful for prognosis and therapy

• Stage I patients are lucid with no focal neurologic signs or evidence of hydrocephalus.

• Stage II patients exhibit lethargy, confusion; may have mild focal signs, such as cranial nerve palsy or hemiparesis.

• Stage III represents advanced illness with delirium, stupor, coma, seizures, multiple cranial nerve palsies, and/or dense hemiplegia.

Pathogenesis & suseptibility• 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 .More common in miliary TB because of higher chance of forming Juxta ependymal meningitis.

• Meningitis can develop as a complicatin of primary infection in infants/children

• Due to chronic reactivation bacillemia in older adults 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 substance itself. Multiple lesions are common and a 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. Obstruction of the aqueduct develops less frequently, from contraction of exudate surrounding the brain stem or from a strategically placed brain stem tuberculoma.

Ventricular dilatation is present (asterisks), as well as inflammatory exudate in the ambient cistern (black arrows) and multiple foci of vasculitis-associated subacute, ischemic necrosis

Diagnosis

Cerebrospinal fluid examination:• Protein 100-500mg/dl • Glucose <45 mg/dL (80%)• Initial stages PMN predominance later

changed to lymphocytic dominance.

• 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: nucleic acid-based amplification test (NAAT) relies upon the polymerase chain reaction (PCR) is 60% sensitive in rapid detection of M. tuberculosis in CSF. Recommended whenever clinical suspicion is sufficiently high for empirical therapy or AFB is negative.

• Neuroradiology: 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. The high interferon-gamma concentration in the CSF increases further after the antigen stimulation, suggesting theoretically the presence of tuberculous antigen-specific T cells.

DIFFERENTIAL DIAGNOSIS

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, sphenoid sinusitis, brain abscess, or spinal epidural space infection.

• Herpes encephalitis

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.

Drug Dose Side-effects

INH (Isoniazid) 5-10 mg/kg per day Hepatitis, hypersensitivity

Rifampin (RIF) 10 mg/kg per day (600 mg in adults)

Hepatic toxicity, red-orange staining, Drug interactions.

Pyrazinamide (PZA) 15 to 30 mg/kg per day(max 2g)

Peripheral neuropathy, abdominal pain

Streptomycin 15 mg/kg per day IM-1g in adults20 to 40 mg/kg per day in children)

Deafness, dizziness

Ethambutol 25 mg/kg/day single dose

optic neuritis

Pyridoxine (VitB6) 50mg daily

First line drugs

Recommended regimen

• Intensive phase (Initial 2months) — A four drug regimen that includes INH, RIF, PZA, and either EMB or STM

• Continuation phase (7-10m) — INH and RIF alone if the isolate is fully susceptible.

• 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.

Glucocorticoid regimen

• 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.

• Prednisone — A dose of 2 to 4 mg/kg per day for children; 60 mg/day for adults, for 3 weeks, then tapered off gradually over the following 3 weeks.

Second line drugs

• Aminoglycosides: e.g., amikacin (AMK), kanamycin (KM);

• Polypeptides: e.g., capreomycin, viomycin, enviomycin;

• Fluoroquinolones: e.g., ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF);

• Thioamides: e.g. ethionamide, prothionamide

• Cycloserine (the only antibiotic in its class);

• p-aminosalicylic acid (PAS or P).

Others

• Macrolides: e.g., clarithromycin (CLR);• Linezolid (LZD);• Thioacetazone (T);

• Immunomodulators- cytokine-based therapy but more research needed for other cytokines and chemokines that may enhance both the mycobacterial killing activity of effector cells and the restriction of bacterial intracellular multiplication

Surgical Intervention

• Patients with hydrocephalus may require surgical decompression of the ventricular system by shunt.

Complications

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

Take home message

• Start ATT empirically when suspicion of TB• Counsel the patient for medication/side

effects• Complete the course• Follow up

The End