Tuberculous meningitis: Difference between revisions

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* Dexamethasone 3mg po qid x2wk then taper over 6-8wks
  
* Dexamethasone 3mg po qid x2wk then taper over 6-8wks
 
** High risk of IRIS
  
** High risk of IRIS
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  +
{| class="wikitable"
  +
! 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%
  +
|-
  +
! colspan=4 | 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%
  +
|-
  +
! colspan=4 | 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
  +
|}
   
 
== Prognosis ==
  
== Prognosis ==

Revision as of 18:08, 5 June 2020

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

Differential Diagnosis

  • Fungal meningitis
  • Sarcoidosis
  • Neoplasm

Risk Factors

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

Clinical Presentation

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

Investigations

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

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
    • Can replace ethambutol with a fluoroquinolone
  • Dexamethasone 3mg po qid x2wk then taper over 6-8wks
    • High risk of IRIS
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

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
    • Seizures
    • Blindness
    • Deafness
    • Ophthalmoplegia
    • Hemiparesis

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.

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