Tuberculous meningitis

1. BY Dr. Sabahat PGR Paeds Medicine TUBERCULOUS MENINGITIS

2. TUBERCULOUS MENINGITIS Definition: It is inflammation of the leptomenings (pia-arachnoid) by Mycobacterium tuberculosis

3. TUBERCULOUS MENINGITIS

4. Pathogenesis Tuberculous meningitis is always a secondary lesion with primary usually in the lungs Meningitis results from formation of a metastatic caseous lesion in the cerebral cortex, meninges and choroid plexus during the process of initial occult lympho-hematogenous spread of primary infection . TUBERCULOUS MENINGITIS

5. Then Caseous foci form on the surface of brain ( Rich’s foci). They increase in the size and discharge bacilli in CSF. A thick , gelatinous exudate may infiltrate the cortical or meningeal blood vessel , producing inflammation, obstruction , or infarction . Most commonly involved site is the brain stem causing frequent involvement of 3rd , 6 th and 7 th cranial nerves. Basal cisterns are obstructed causing communicating hydrocephalus . Accompanying inflammation may cause cerebral edema. TUBERCULOUS MENINGITIS

6. Clinical Features: In a classical case, onset is insidious but may be fulminant in certain cases. A more rapid progression of the disease may occur in young infants in whom symptoms develop for only several days before the onset of acute hydrocephalus brain infarction , or seizures. Classically , the onset is gradual (over several weeks). The clinical manifestations may be divided into 3 stages and each stage last approximately 1 week . TUBERCULOUS MENINGITIS

7. Stage 1(Prodromal stage ) : L asts for 1-2 weeks The child becomes listless or irritable ,loss interest in the play ,has fever, anorexia,vomiting , constipation and weight loss. M ay complain of headaches and drowsiness. N o focal neurologic signs. M ay be loss of or stagnation of the developmental milestones. TUBERCULOUS MENINGITIS

8. Stage 2: Onset is more abrupt. Signs of meningeal irritation with increased CSF pressure . Positive K erning and Brudziniski signs with increased tendon jerks and extensor plantar responses. There may be generalized hypertonia. Headache is cardinal symptom in older children with constant Fever. Vomiting and constipation may become severe. Abducent nerve paralysis is common . Oculomotor lesion causes internal squint . Facial palsy is also common. May have disorientation , and speech and movement disorders. TUBERCULOUS MENINGITIS

9. In the infants anterior fontanelle may be bulging and sutures become separated with “crackpot” sign. In older children papilledema develops. Head circumference starts enlarging rapidly. Choroid tubercles may be seen on fundoscopy. Child is semiconscious and develops convulsions. TUBERCULOUS MENINGITIS

10. Stage 3: Rapidly become comatose . High grade irregular fever and convulsions. There may be hemiplegia or paraplegia. E xtreme neck stiffness opisthotonus develops with the decerebrate rigidity and pupil become dilated and fixed. D eterioration of vital signs especially hypertension. Death may occur if treatment is started late during this stage. TUBERCULOUS MENINGITIS

11. DIAGONSIS Suspicion: A high index of clinical suspicion is important where tuberculosis contact is positive . Tuberculin skin test is negative is 50% of the patients. Blood: ESR is high Total and differential leukocyte count reveals normal count with predominant lymphocytosis . X-Rays Chest: Chest X-rays may be normal in 20-50% of the cases . Usually there is some evidence of tuberculosis in the lungs , hilar adenopathy , and patch of pneumonia or miliary tuberculosis TUBERCULOUS MENINGITIS

12. 4. LUMBER PUNCTURE (CSF examination): CSF pressure increased. Color is clear, hazy or straw colored. Cobweb is formed when left for over 12 hours. Protein is markedly raised ( 400-5,000mg/dl) because of hydrocephalus and spinal block. Glucose is decreased (below 40 mg/dl). Pleocytosis with predominant lymphocytes (10-500/mm3). Smear and culture: Ziehl- Nelson stain may reveal acid-fast bacilli . CSF culture confirms the diagnosis. Mycodot : Antigen detection by polymerase chain reaction . TUBERCULOUS MENINGITIS

13. 5. GASTRIC LAVAGE OR SPUTUM EXAMINATION for tubercle bacilli. 6. LYMPH NODE BIOPSY in certain cases to confirm the diagnosis. 7. FUNDOSCOPY (choroid tubercles , papilledema or optic atrophy) 8. CT SCAN with contrast may help establish a diagnosis of tuberculous meningitis. It also aids in evaluating the success of therapy. There may be: Brain stem meningitis (Brain Enhancement ). Hydrocephalus, Focal infarcts Tuberculomas (CT scan may be normal during the early stages of the TBM). TUBERCULOUS MENINGITIS

14. MANAGEMENT: Specific Treatment : Start treatment with 4 anti- tuberculous drugs and treatment should be continued for 12 months. Isoniazid (INH): It is the drug of first choice . It is rapidly absorbed and penetrates into the CSF. Isoniazid and rifampicin and highly bactericidal for M.tuberculosis . Dose is 10-15 mg/kg/day. Main side effect are hepatotoxicity , peripheral neuropathy ,optic neuritis, hypersensitivity and fever. Neuritis is due to competitive inhibition of pyridoxine. Transient elevation of amino- transferases may be seen at 6-12 weeks, but therapy should continue . TUBERCULOUS MENINGITIS

15. Rifampicin: It is also a first line drug , well absorbed and penetrates CSF well. Dose is 10-20mg/kg/day one half an hour before breakfast It causes orange discoloration of the urine and tears , GIT disturbance and hepato -toxicity . Combined use of INH and rifampicin increases the risk of hepatotoxicity , which can be decreases by lowering the dose of INH (10 mg/kg/day) TUBERCULOUS MENINGITIS

16. Pyrazinamide It is bactericidal in acid medium and enters CSF readily. It is used as a third drugs for 2-3 months initially Dose is 30 mg/kg/day. Main side effect are arthralgia ,arthritis ,hyper- uricemia (gout) 4 . Streptomycin: It is bactericidal for extracellular tubercle bacilli, but its penetration into macrophages is poor. Its penetrance into CFS through inflamed meninges is excellent but do not cross the un-inflamed meninges. Dose 20-40 mg/kg/day given 1/M for 2 months . Side effect are ototoxicity (vestibular or hearing loss) nephrotoxicity and may cause hypersensitivity reactions . TUBERCULOUS MENINGITIS

17. 5. Ethambutol : It is not recommended below 6 years of age. Dose 15-25 mg/kg once daily. Side effects are Optic neuritis ,hypersensitivity and GIT upsets. TUBERCULOUS MENINGITIS

18. GENERAL MEASURES: Corticosteroids: D ecrease mortality rate and long term neurologic sequelae . R educe vasculitis ,inflammation , and intracranial pressure. Dose of prednisolone is 1-2mg/kg/day for 6-8 weeks . H elp to reduce cerebral edema and prevents formation of adhesions . Careful record of vital signs TUBERCULOUS MENINGITIS

19. 3. Daily monitoring of complications: Main complications are to be monitored Raised intracranial pressure Drugs toxicity, etc. 4. Phenobarbitone : Dose 5 mg/kg/day to control convulsions. 5. Antipyretics: Paracetamol ( 10—15mg/kg/dose 4-6 hourly) and fresh water sponging to control temperature. 6. Pyridoxine: 1 mg/kg/day daily to prevent polyneuritis. TUBERCULOUS MENINGITIS

20. 7. Feeding : NG tubes feeding according to requirement . Ideally 100 calories /kg/day are given . Iron and multivitamins can be added too. 8. Bed Sores : Change posture every two hours. 9. Care of comatose Patient. 10. Care of bowel and bladder . 11. Screening: I mportant to screen the family members for tuberculosis and treat infected persons. TUBERCULOUS MENINGITIS

21. COMPLICATIONS: Mental retardation Cranial nerve palsies (3 rd , 6 th and 7 th ) Blindness (optic atrophy) Deafness Hydrocephalus Hemiplegia, paraplegia Epilepsy Endocrine disturbances (diabetes insipidus). Tuberculoma. TUBERCULOUS MENINGITIS

22. PROGNOSIS: It depends upon two factors: Age of patient Stage of disease at which treatment started. Without treatment it is fatal . In stage1, 100% cure rate is expected. Even with optimal therapy mortality ranges from 30-50% and incidence of neurologic sequelae is 75-80% especially in stage 3. There may be blindness, deafness , paraplegia, mental retardation and diabetes insipidus. Infants and young children have poor prognosis as compared to older children TUBERCULOUS MENINGITIS