cns tb
DESCRIPTION
CNS tuberculosis breif.TRANSCRIPT
![Page 1: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/1.jpg)
7We
Care
CNS TUBERCULOSIS
MAJ MANOJ
![Page 2: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/2.jpg)
7We
Care
Incidence
• 10% cases of TB have CNS involvement
• 60-80 % between age of 06 mnths to 05 yrs.
• Male pedominence
• Case fatality 100% in untreated cases.
![Page 3: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/3.jpg)
7We
Care• While pulmonary disease is the most common manifestation of TB
• the involvement of the CNS and tuberculous meningitis represents its most severe form
• The case fatality rate of untreated TBM is almost 100% and a delay in treatment may lead to permanent neurological damage
![Page 4: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/4.jpg)
7We
Care• The causative agents of TBM is M. tuberculosis and less commonly NTM.
• The incidence of CNS infection due to the latter has increased since the onset of the HIV epidemic mainly mycobacterium avium complex (MAC)
![Page 5: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/5.jpg)
7We
Care
CLASSIFICATIONIntracranialTuberculosis
Spinal tuberculosis
Tuberculous meningitisTBM with miliary spreadTuberculous encephalopathyTuberculous vasculopathy CNS tuberculoma brain abscess
Pott’s spine and paraplegia
![Page 6: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/6.jpg)
7We
Care
Pathogenesis
1) Entrance of the bacilli into the host with subsequent lung invasion and regional lymph node dissemination leading to the primary complex formation.
2) In case of CNS involvement the characteristic lesions known as Rich’s foci tuberculous subpial or subependymal foci about 1 mm in diameter are formed
![Page 7: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/7.jpg)
7We
Care
Pathogenesis
CNS TB is a three step process 1)Hematogenous seeding of meninges during
bacteremia of primary TB• In case of miliary TB dissemination to the CNS
is more probable and particularly involved in the pathogenesis of TBM in childhood
• spread from a site of tuberculous otitis or calvarial osteitis also exists
![Page 8: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/8.jpg)
7We
Care 2) Quiescent phase: may last from few weeks to many years.
3)mycobacteria in Richs foci multiply and with immune or traumatic stimulus rupture or grow and clinical manifestations occur.
![Page 9: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/9.jpg)
7We
Care• In adults and older children there may not be any immune response and cause latent disease or
• immune recognition or reactivation causes formation of the CNS lesions
• the rupture of a Rich’s focus and release of bacilli into subarachnoid space giving rise to a T cell granulomatous response leading to TBM
![Page 10: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/10.jpg)
7We
Care• Triad of a) macrophages b) T helper lymphocytes and c) host plays a central role
• interferon interleukin1 TNF • granuloma formation
![Page 11: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/11.jpg)
7We
Care
![Page 12: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/12.jpg)
7We
Care
PATHOGENESIS OF COMPLICATIONS
Inflammatory reaction can lead to• Adhesion formation due to the cell and fibrin
rich basal meningeal exudates• Obliterative vasculitis: mainly affecting the
internal carotid artery, proximal middle cerebral artery and perforating vessels of the basal ganglia
• Encephalitis: due to extention into the parenchyma
![Page 13: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/13.jpg)
7We
Care• Cranial n palsies: adhesions in the interpendicular fossa cranial nerves II IV and VI are affected.
• Hydrocephalus: obstruction of the basal cisterns the outflow of the forth ventricle or the cerebral aqueduct and have poor prognosis .
• Spinal meningitis: direct extension from vertebrea or intracranial spread.
![Page 14: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/14.jpg)
7We
Care
Clinical staging
Stage I ( alert no focal neurological signs)IrritabilityExcessive cry Apathy Low grade fever
![Page 15: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/15.jpg)
7We
Care• Stage II(non comatose) • Signs of meningeal irritation• Signs of increased ICT• Altered sensorium• Convulsions• Focal neurodeficits
![Page 16: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/16.jpg)
7We
Care Stage III(comatose)• Deep coma• Multiple cranial N palsies• Decerebrate or decorticate rigidity
![Page 17: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/17.jpg)
7We
Care
Clinical features
• Prodromal: A)Infants: 1.poor feeding 2. irritability 3.
drowsiness 4. bulging fontanelles B)Elder : headache and mental state changes• Cranial N : 20-30% . A) II III IV VI VII blindness squint diplopia VI MC B) IX X XI XI less commonly.
![Page 18: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/18.jpg)
7We
Care• Vascular : MCA ACA involvement or vascular endarteritis
N deficits monoparesis hemiparesis• Cerebral edema: raised ICT hydrocephalus tentorial
herniation seizures• Tuberculoma: seizures localizing sign raised ICT
![Page 19: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/19.jpg)
7We
Care• Meningoencephalitis: altered sensorium to terminal illness.
![Page 20: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/20.jpg)
7We
Care
DIAGNOSIS
• CSF:increase in pressure with the appearance clear to slightly turbid with a delicate web-like clot formation, due to the high protein level
• Pleocytosis of 10–1000 leucocytes/ mm3 with a lymphocytic predominance.
• CSF biochemistry reduced glucose levels increased lactate levels while protein levels increased
![Page 21: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/21.jpg)
7We
Care
DIAGNOSISCONDITION WHITE BLOOD
CELLS(CELLS/MCL)PROTEIN (MG/DL)
G LUCOSE (MG/DL)
NORMAL VALUE 0-5 UPTO 30 (NEWBORN) 15-45 40-85
TBM ELEVATED 10-1000(<500)
INCREASED (50-500)
DECREASED(<40)
BACTERIAL M ELEVATED (>1000) INCREASED(>250)
DECREASED(<40)
VIRAL ELEVATED (<100) INCRESEAD(<100)
NORMAL OR DECREASED(>40)
CRYPTOCOCAL M ELEVATED L>PMN INCREASED DECREASED
![Page 22: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/22.jpg)
7We
CareMicroscopy :• Rapid inexpensive, technically simple and
specific for AFB• Lacks senstivity: unable to discriminate
between M. tuberculosis and other mycobacteria and unable to discriminate between viable and non viable bacilli
![Page 23: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/23.jpg)
7We
Care• Culture:Gold Standard method and for definite diagnosis of the disease
• in clinical suspicion the isolation of the agent from other specimens such as gastric aspirate bronchial aspirate sputum or lymph node also guides the diagnosis
![Page 24: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/24.jpg)
7We
Care• Egg-based Lovenstein-Jensen-LJ Petragnani and Ogawa
• Agar-based Middlebrook 7H10 and 7H11• Liquid media Middlebrook 7H9 Kirchner BioFM
and Dubos • With liquid culture medium incubation time is
12-15 days and 40-60 days with solid media• Meximum yeild with combination of liquid and
agar based.
![Page 25: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/25.jpg)
7We
Care• liquid cultures a mix of growth supplements (OADC- Oleic acid, Albumin, Dextrose,
• Catalase) and antibiotics (PANTA- Polymyxin B, Amphotericin B, Nalidixic acid Trimethoprim, Azlocillin) are used, which collectively prevent the growth of environmental bacteria.
• A positive result must be confirmed by performing a ZN smear of the colonies with AFB being demonstrated.
![Page 26: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/26.jpg)
7We
Care• Adenosine deaminase levels and TBM• enzyme involved in the purine catabolism
related to the activated T lymphocytes and macrophages in response to TB antigens
![Page 27: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/27.jpg)
7We
Care
Molecular diagnosis
• Nucleic acid-based amplification (NAA) tests allow the direct detection of mycobacterial DNA or RNA Post-amplification analysis includes electrophoresis hybridization restriction or sequencing of the products
• hybridization being the most commonly used one
![Page 28: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/28.jpg)
7We
Care• Newer techniques based on real-time PCR amplify simultaneously different DNA targets followed by fluorimetric detection
• The low sensitivity may be due to paucibacillary nature of CSF
• minimum suggested volume of the fluid is 2ml
![Page 29: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/29.jpg)
7We
Care
Neuroimaging
CT finding in case of non-complicated TBM • can be entirely normal • diffuse brain edema and lepto-meningeal
inflammation with increased uptake of contrast material in CECT
• The meningeal enhancement is more pronounced in the basal cisterns.
![Page 30: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/30.jpg)
7We
Care CT finding of complicated cases• communicating hydrocephalus• ventriculitis• parenchymal spread (infarction, cerebritis and
abscess)• Empyema (epidural, subdural)• tuberculomas in the brain.
![Page 31: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/31.jpg)
7We
Care
![Page 32: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/32.jpg)
7We
Care
![Page 33: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/33.jpg)
7We
Care• MRI is the most sensitive test• superior to CT in detecting parenchymal
abnormalities, such as tuberculomas, abscesses, and infarctions.
• MRI also readily depicts hydrocephalus
![Page 34: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/34.jpg)
7We
Care
![Page 35: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/35.jpg)
7We
Care
Treatment
• 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
![Page 36: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/36.jpg)
7We
Care
Role of steroids
• 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
![Page 37: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/37.jpg)
7We
Care
TREATMENTDRUG DAILY DOSE IN MG/KG THRICE WEEKLY
INH 10(10-15) 10 (8-12)
RIFAMPICIN 15(10-15) 10 (8-12)
PYRIZINAMIDE 35(30-40) 35 (30-40)
ETHAMBUTOL 20(15-25) 30 (20-35)
![Page 38: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/38.jpg)
7We
Care• Steroids are associated with lesser mortality in Stage 3 TBM.
• Steroids are useful to decrease intracranial tension and also for decreasing perilesional edema
• Enhanced resolution of the basal exudate may also occur.
![Page 39: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/39.jpg)
7We
Care
neuropathology.neoucom.edu
Tuberculous Meningitis. Donald and Shoerman, NEJM. 351:17. 10/21/2004
![Page 40: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/40.jpg)
7We
Care
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
![Page 41: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/41.jpg)
7We
Care
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
![Page 42: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/42.jpg)
7We
Care
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
![Page 43: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/43.jpg)
7We
Care
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
![Page 44: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/44.jpg)
7We
Care
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
![Page 45: CNS TB](https://reader035.vdocuments.net/reader035/viewer/2022062418/556c8dc8d8b42a7a738b4aa8/html5/thumbnails/45.jpg)
7We
Care
References• http://www.cdc.gov/TB/statistics/reports/surv2005/PDF/table27.p
df• 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