9.29.09 Davis-Hovda TB Meningitis (1)

TB Meningitis9/29/2009 Morning ReportMaggie Davis Hovda

Incidence2005: 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%

IncidenceIn 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.

PathogenesisTB Bacillemia (primary or late reactivation) subependymal tubercles rupture into the subarachnoid space meningitis

PathogenesisDense gelatinous exudate develops at the base of the brain surround arteries and CN at the base of the brain hydrocephalus, vasculitis infarction, hemiplegia, quadriplegia

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

Clinical Presentation3 Stages1 - 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 fever2 Meningitic phase w/ meningismus, V, lethargy, confusion, CN palsies, hemiparesis3 Paralytic phase advance to stupor, coma, seizure, hemiparesis.

Clinical PresentationMost common clinical findings:FeverHAVomitingNuchal RigidityAMSCN Palsies, esp CN III

DiagnosisCSF ExaminationUsually lymphocytic pleocytosisParadoxic change from lymphocytic to neutrophilic predominance over 48 hr pathognomonic for TB meningitisElevated protein with severely depressed glucoseRepeated specimens for AFB culture necessary ADA level

DiagnosisOther StudiesBrain imaging demonstrates hydrocephalus, basilar exudates and inflammation, tuberculoma, cerebral edema, cerebral infarctionCXRAbnormal, sometimes miliary pattern

Differential DiagnosisFungal MeningitisCrypto, Histo, Blasto, CocciViral meningoencephalitis HSV, mumpsParameningeal InfectionSphenoid sinusitis, brain abscess, spinal epidural abscessIncompletely treated Bacterial meningitisNeurosynphilisNeoplastic Meningitis LymphomaNeurosarcoidNeurobrucellosis

Treatment: Antimicrobial TherapyStart as soon as there is suspicion for TB meningitisSame Guidelines as those for pulmonary TBIntensive Phase: 4 drug regimen of Isoniazid, Rifampin, Pyrazinamide, and Ethambutol or Streptomycin for 2 monthsContinuation Phase: Isoniazid and Rifampin for another 7 10 months

Treatment: Adjunctive TherapyGlucocorticoids Indicated with:rapid progression from one stage to the nextelevated OP on LP, CT evidence of cerebral edemaworsening clinical signs after starting antiTb medsincreased basilar enhancement, or moderate to advancing hydrocephalus on head CTGlucocorticoid Dosing: Dexamethasone 12 mg/d x 3 weeks followed by a slow taperSurgery: Ventriculostomy placement

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

OutcomesOverall PoorPts presenting in Stage I have 19% mortalityPts presenting in Stage III have 69% mortalityOnly 1/3 - 1/2 of patients demonstrate complete neurologic recoveryUp to 1/3 of patients have residual severe neurologic deficits such as hemiparesis, blindness, seizure DO

Referenceshttp://www.cdc.gov/TB/statistics/reports/surv2005/PDF/table27.pdfDonald, 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

*Illustrates that although the rates of pulmonary TB are decreasing in US, the rates of Meningeal TB are not and as have seen and will discuss more, morbidity and mortality from TB meningitis high*-rupture of tubercle associated head trauma or depressed host immunity*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 (white arrows). Courtesy of Richard H. Hewlett, Department of Anatomical Pathology, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa*Clinical presentation varies from insidious onset to picture of full-blown acute meningitis-Our patient presented in stage II-most pts have change in mental status, ~50% present with Stage III sx*-50% Pts have an abnl CXR, but