Tuberculous meningitis: Difference between revisions
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− | * |
+ | *Meningeal infection by ''[[Mycobacterium tuberculosis]]'' |
− | * |
+ | *High mortality, often needs empiric treatment even before confirmed diagnosis |
− | == |
+ | ==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 |
||
+ | *'''Stage 1:''' normal level of consciousness, no focal neurological deficits |
||
− | === Epidemiology === |
||
+ | *'''Stage 2:''' decreased level of consciousness, significant focal neurological deficits |
||
− | * About 1% of TB cases in Canada |
||
+ | *'''Stage 3:''' seizures, comatose |
||
+ | ===Epidemiology=== |
||
− | === Differential Diagnosis === |
||
− | * Fungal meningitis |
||
− | * Sarcoidosis |
||
− | * Neoplasm |
||
+ | *About 1% of TB cases in Canada |
||
− | === Risk Factors === |
||
− | * Young |
||
− | * Female |
||
− | * Originally from endemic country |
||
− | * Previous TB |
||
+ | ===Risk Factors=== |
||
− | == Clinical Presentation == |
||
− | === History === |
||
+ | *Young |
||
− | * Prodrome (1-3 weeks) |
||
+ | *Female |
||
− | ** Personality changes |
||
+ | *Originally from endemic country |
||
− | ** Low-grade fever |
||
+ | *Previous TB |
||
− | ** Malaise |
||
− | ** Weight loss |
||
− | ** Gradual onset of worsening headache |
||
− | * Headache |
||
− | * Fevers |
||
− | * Vomiting |
||
− | * Confusion |
||
− | * Personality changes |
||
− | * Photophobia (only 5-10%) |
||
− | * Seizures |
||
+ | ==Clinical Manifestations== |
||
− | === Physical Exam === |
||
+ | ===History=== |
||
− | * Meningeal symptoms |
||
− | * Fevers |
||
− | * Vomiting |
||
− | * Meningismus |
||
− | * Focal neurological deficits |
||
− | ** Cranial nerve palsies in VI, III, and IV |
||
− | ** Hemiplegia, paraplegia |
||
− | ** Urinary retention |
||
− | * Confusion, coma |
||
+ | *Prodrome (1-3 weeks) |
||
− | == Investigations == |
||
+ | **Personality changes |
||
− | * Lumbar puncture |
||
+ | **Low-grade fever |
||
− | ** Increased lymphocytes, decreased glucose, and increased protein |
||
+ | **Malaise |
||
− | ** Need 3-5mL of CSF for culture |
||
+ | **Weight loss |
||
− | ** May need serial LPs |
||
+ | **Gradual onset of worsening headache |
||
− | * CT head |
||
+ | *Headache |
||
+ | *Fevers |
||
+ | *Vomiting |
||
+ | *Confusion |
||
+ | *Personality changes |
||
+ | *Photophobia (only 5-10%) |
||
+ | *Seizures |
||
+ | ===Physical Exam=== |
||
− | == 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 |
||
+ | *Meningeal symptoms |
||
− | == Prognosis == |
||
+ | *Fevers |
||
− | * Depends on stage at presentation |
||
+ | *Vomiting |
||
− | * Mortality is high |
||
+ | *Meningismus |
||
− | ** Stage 1: 10-20% |
||
+ | *Focal neurological deficits |
||
− | ** Stage 2: 20-40% |
||
+ | **Cranial nerve palsies in VI, III, and IV |
||
− | ** Stage 3: 60% |
||
+ | **Hemiplegia, paraplegia |
||
− | * Morbidity is high, with about 20% of patient being left with significant neurological sequelae |
||
+ | **Urinary retention |
||
− | ** Mental retardation |
||
+ | *Confusion, coma |
||
− | ** Psychiatric disorders |
||
+ | |||
− | ** Seizures |
||
+ | ===Thwaites Index=== |
||
− | ** Blindness |
||
+ | |||
− | ** Deafness |
||
+ | *Used to differentiate bacterial from tuberculous meningitis in adults before results of CSF culture are available[[CiteRef::thwaites2002di]] |
||
− | ** Ophthalmoplegia |
||
+ | *Tuberculous more likely if score ≤4; bacterial more likely if score ≥5 |
||
− | ** Hemiparesis |
||
+ | **Sensitivity 86% and specificity 79% |
||
+ | |||
+ | {| class="wikitable" |
||
+ | !Item |
||
+ | !Score |
||
+ | |- |
||
+ | |Age ≥36 years |
||
+ | | +2 |
||
+ | |- |
||
+ | |Blood WBC ≥15 |
||
+ | | +4 |
||
+ | |- |
||
+ | |≥6 days of illness |
||
+ | | -5 |
||
+ | |- |
||
+ | |CSF WBC ≥900x10<sup>3</sup> |
||
+ | | +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== |
||
+ | |||
+ | *[[Fungal meningitis]] |
||
+ | *[[Sarcoidosis]] |
||
+ | *[[Neoplasm]] |
||
+ | *Other causes of [[chronic meningitis]] |
||
+ | |||
+ | ==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 [[HIV medications|antiretrovirals]] by 8 weeks, though) |
||
+ | *Standard HREZ x2mo then HR x7-10mo |
||
+ | **Can replace [[ethambutol]] with a [[fluoroquinolone]] |
||
+ | *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 |
||
+ | |||
+ | {| 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 |
||
+ | |} |
||
+ | |||
+ | ==Further Reading== |
||
+ | |||
+ | *Treatment of Tuberculous Meningitis and Its Complications in Adults. ''Curr Treat Options Neurol''. 2018;20(3):5. doi: [https://doi.org/10.1007/s11940-018-0490-9 10.1007/s11940-018-0490-9] |
||
[[Category:Tuberculosis]] |
[[Category:Tuberculosis]] |
Latest revision as of 11:47, 13 March 2023
- Meningeal infection by Mycobacterium tuberculosis
- High mortality, often needs empiric treatment even before confirmed diagnosis
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
- Fungal meningitis
- Sarcoidosis
- Neoplasm
- Other causes of chronic meningitis
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
- Can replace ethambutol with a fluoroquinolone
- 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
- ^ 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.