Tuberculous meningitis

From IDWiki

Background

Classification

  • Stage 1: normal level of consciousness, no focal neurological deficits
  • Stage 2: decreased level of consciousness, significant focal neurological deficits
  • Stage 3: seizures, comatose

Epidemiology

  • About 1% of TB cases in Canada

Risk Factors

  • Young
  • Female
  • Originally from endemic country
  • Previous TB

Clinical Manifestations

History

  • Prodrome (1-3 weeks)
    • Personality changes
    • Low-grade fever
    • Malaise
    • Weight loss
    • Gradual onset of worsening headache
  • Headache
  • Fevers
  • Vomiting
  • Confusion
  • Personality changes
  • Photophobia (only 5-10%)
  • Seizures

Physical Exam

  • Meningeal symptoms
  • Fevers
  • Vomiting
  • Meningismus
  • Focal neurological deficits
    • Cranial nerve palsies in VI, III, and IV
    • Hemiplegia, paraplegia
    • Urinary retention
  • Confusion, coma

Thwaites Index

  • Used to differentiate bacterial from tuberculous meningitis in adults before results of CSF culture are available1
  • Tuberculous more likely if score ≤4; bacterial more likely if score ≥5
    • Sensitivity 86% and specificity 79%
Item Score
Age ≥36 years +2
Blood WBC ≥15 +4
≥6 days of illness -5
CSF WBC ≥900x103 +3
CSF % PMN ≥75 +4

Complications and Prognosis

  • Depends on stage at presentation
  • Mortality is high
    • Stage 1: 10-20%
    • Stage 2: 20-40%
    • Stage 3: 60%
  • Morbidity is high, with about 20% of patient being left with significant neurological sequelae
    • Mental retardation, psychiatric disorders, seizure, blindness, deafness, ophthalmoplegia, hemiparesis

Differential Diagnosis

Investigations

  • Lumbar puncture
    • Increased lymphocytes, decreased glucose, and increased protein
    • Need 3-5mL of CSF for culture
    • May need serial LPs
  • CT head

Diagnosis

  • Gold standard is mycobacterial culture (71% sensitive, 100% specific)
    • Sensitivity increases with volume and number of samples
  • Microscopy for acid-fast bacilli is 20-80% sensitive and 100% specific
  • PCR is 85-95% sensitive and 98% specific
    • Used to confirm but not exclude the diagnosis

Management

  • Rule out neoplasm and fungus, then start empiric treatment
  • HIV test (delay antiretrovirals by 8 weeks, though)
  • Standard HREZ x2mo then HR x7-10mo
  • Adjunctive steroids for high risk of IRIS
    • Dexamethasone 3mg po qid x2wk then taper over 6-8wks
    • Prednisolone 120 mg PO daily x1wk, 90 mg x1wk, 60 mg x1wk, 30 mg x1wk, 15 mg x1wk, 5 mg x1wk
Drug Dose Duration CSF penetration
Rifampin 10 mg/kg (max 600 mg) 12 months 10-20%
Isoniazid 5 mg/kg (max 300 mg) 12 months 80-90%
Pyrazinamide 25 mg/kg 2 months 90-100%
Ethambutol 15 mg/kg 2 months 20-30%
Second-line treatments
Levofloxacin 10-15 mg/kg Throughout treatment 70-80%
Moxifloxacin 400 mg Throughout treatment 70-80%
Amikacin 15 mg/kg (max 1 g) Intensive phase only 10-20%
Kanamycin 15 mg/kg (max 1 g) Intensive phase only 10-20%
Capreomycin 15 mg/kg (max 1 g) Intensive phase only Probably very low
Ethionamide or prothionamide 15-20 mg/kg (max 1 g) Throughout treatment 80-90%
Cycloserine 10-15 mg/kg (max 1 g) Throughout treatment 80-90%
Linezolid 600 mg Throughout treatment 30-70%
Other drugs with uncertain benefit
Clofazimine 100 mg daily Probably low
p-aminosalicylic acid 200-300 mg/kg Probably very low
Bedaquiline Probably very low
Delamanid No data

Further Reading

  • Treatment of Tuberculous Meningitis and Its Complications in Adults. Curr Treat Options Neurol. 2018;20(3):5. doi: 10.1007/s11940-018-0490-9

References

  1. ^  GE Thwaites, TTH Chau, K Stepniewska, NH Phu, LV Chuong, DX Sinh, NJ White, CM Parry, JJ Farrar. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features. The Lancet. 2002;360(9342):1287-1292. doi:10.1016/s0140-6736(02)11318-3.