1. TB Meningitis 9/29/2009 Morning Report Maggie Davis Hovda

2. Incidence 2005: In the US there were 186 cases of meningeal TB, which accounted for 6.3% of all extrapulmonary TB In NC, there were 5 cases, 6.9% 2007: In the US, there were 170 cases of meningeal TB, again 6.3% of cases In NC, there were 5 cases, 6.9%

3. Incidence In underdeveloped countries with higher overall incidence of TB, TB meningitis is more of a pediatric disease whereas in developed countries with lower incidence of TB, meningitis is more of an adult disease.

4. Pathogenesis TB Bacillemia (primary or late reactivation)  subependymal tubercles  rupture into the subarachnoid space  meningitis

5. Pathogenesis Dense gelatinous exudate develops at the base of the brain  surround arteries and CN at the base of the brain  hydrocephalus, vasculitis  infarction, hemiplegia, quadriplegia

6. neuropathology.neoucom.edu Tuberculous Meningitis. Donald and Shoerman, NEJM. 351:17. 10/21/2004

7. Clinical Presentation 3 Stages 1 - Pts lucid at presentation w/o focal neuro signs or hydrocephalus; prodromal, lasts 2-3 wks and characterized by insidious onset of malaise, HA, low-grade fever 2 – Meningitic phase w/ meningismus, V, lethargy, confusion, CN palsies, hemiparesis 3 – Paralytic phase – advance to stupor, coma, seizure, hemiparesis.

8. Clinical Presentation Most common clinical findings: Fever HA Vomiting Nuchal Rigidity AMS CN Palsies, esp CN III

9. Diagnosis CSF Examination Usually lymphocytic pleocytosis Paradoxic change from lymphocytic to neutrophilic predominance over 48 hr pathognomonic for TB meningitis Elevated protein with severely depressed glucose Repeated specimens for AFB culture necessary ADA level

10. Diagnosis Other Studies Brain imaging – demonstrates hydrocephalus, basilar exudates and inflammation, tuberculoma, cerebral edema, cerebral infarction CXR Abnormal, sometimes miliary pattern

11. Differential Diagnosis Fungal Meningitis Crypto, Histo, Blasto, Cocci Viral meningoencephalitis – HSV, mumps Parameningeal Infection Sphenoid sinusitis, brain abscess, spinal epidural abscess Incompletely treated Bacterial meningitis Neurosynphilis Neoplastic Meningitis – Lymphoma Neurosarcoid Neurobrucellosis

12. Treatment: Antimicrobial Therapy Start as soon as there is suspicion for TB meningitis Same Guidelines as those for pulmonary TB Intensive Phase: 4 drug regimen of Isoniazid, Rifampin, Pyrazinamide, and Ethambutol or Streptomycin for 2 months Continuation Phase: Isoniazid and Rifampin for another 7 – 10 months

13. Treatment: Adjunctive Therapy Glucocorticoids Indicated with: rapid progression from one stage to the next elevated OP on LP, CT evidence of cerebral edema worsening clinical signs after starting antiTb meds increased basilar enhancement, or moderate to advancing hydrocephalus on head CT Glucocorticoid Dosing: Dexamethasone 12 mg/d x 3 weeks followed by a slow taper Surgery: Ventriculostomy placement

14. TB Meningitis in HIV population Study in S Africa compared 20 HIV + pts vs. 17 HIV - pts Similar findings in both groups: Presentation: HA, neck stiffness, fever CSF analysis: Similar amounts of lymphocytes, neutrophils, protein, glucose, ADA levels Outcomes predicted by GCS score upon admission -Differences Both groups showed same incidence of abnormal Head CT, but HIV + more likely to have ventricular dilatation and infarct HIV + patients were more likely to suffer no neurologic deficit on discharge than HIV - pts

15. Outcomes Overall Poor Pts presenting in Stage I have 19% mortality Pts presenting in Stage III have 69% mortality Only 1/3 - 1/2 of patients demonstrate complete neurologic recovery Up to 1/3 of patients have residual severe neurologic deficits such as hemiparesis, blindness, seizure DO

16. References http://www.cdc.gov/TB/statistics/reports/surv2005/PDF/table2 7.pdf http://www.cdc.gov/TB/statistics/reports/surv2005/PDF/table2 7.pdf Donald, PR and Schoerman, JF. Tuberculous Meningitis. NEJM, 351:17. 2004. Schutte, CM. Clincial, Cerebrospinal Fluid and Pathological Findings and Outcomes in HIV-Positive and HIV-negative Patients with Tuberculous Meningitis. Infection 2001: 29: 213-217. Jacob, H et al. Acute Forms of Tuberculosis in Adults. The American Journal of Medicine (2009) 122, 12-17. Principles and Practice of Infectious Diseases. 4th Ed, c 1995. Central Nervous System Tuberculosis. www.uptodate.com