Cerebrospinal Fluid in CNS Infections
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1 Cerebrospinal Fluid in CNS Infections Osvaldo M. Takayanagui Departamento de Neurologia Faculdade de Medicina de Ribeirão Preto Universidade de São Paulo
2 Diagnosis of CNS Infections Heinrich Quincke
3 Acute Bacterial Meningitis
4 CSF Puncture - Lumbar - Cisternal - Ventricular - High cervical
5 Examination of CSF Gross appearance Cytology Biochemistry Culture Detection of antibodies Detection of antigens
6 Gross appearance Clear, colorless Xantochromia subarachnoid bleeding protein hyperbilirubinemia Turbid subarachnoid bleeding meningitis (>100 cells) Purulent acute bacterial meningitis
7 Fuchs Rosenthal counting chamber Cryptococcus neoformans
8 Cytology CSF in CNS Infections
9 Cytology CSF in CNS Infections
10 S. pneumoniae CSF in CNS Infections Haemophilus influenzae N. meningitidis Gram stain
11 India ink Cryptococcus neoformans
12 Ziehl-Neelsen stain M. tuberculosis
13 Strongyloides stercoralis in the CSF Takayanagui et al Neurology, 1995
14 Trypanosoma cruzi trypomastigote in the CSF Yoo et al. - Clin Infect Dis, 2004
15 Hypoglycorrhachia Acute purulent meningitis Tuberculous meningitis Fungal meningitis Meningeal cysticercosis Viral meningoencephalitis mumps (25%) herpes simplex herpes zoster Occasionally reduced enterovirus
16 Culture: CSF and blood C. neoformans H. influenzae Candida albicans
17 Lowenstein-Jensen culture M. tuberculosis
18 Viral culture CSF in CNS Infections
19 HIV-1 RNA viral load 1- NASBA, NucliSens 2- RT-PCR, Amplicor 3- branched DNA, Quantiplex
20 HIV-1 - RNA viral load Method Principle Gene Branched DNA Quantiplex Hibridization pol Amplicor HIV-1 Monitor RT-PCR gag Lower limit (copies/ml) Volume Time ml 1,5 d µl 6 h NASBA NucliSens Amplification gag µl-1 ml 5 h
21 HIV-1 - RNA viral load Plasma CSF Carga Viral 7 Plas ma cópias/ml em log ,14 2, ,67 4, ,9 3 5,79 4 4,92 4 5,27 4 Líquor Pacientes (transtorno cognitivo associado ao HIV-1)
22 Detection of Antibodies - Indirect Imunofluorescence - Passive Hemoagglutination - ELISA - Particle Agglutination - Contraimmunoelectrophoresis - Western blot
23 ELISA CSF in CNS Infections
24 Particle Agglutination CSF in CNS Infections
25 Western Blot controls I I I I P P N P I I P P P I P Intern Control rgp46-i rgp46-ii p53 gp46 p36 p32 p28 p26 p24 gp21 p19 GD21
26 Intrathecal IgG synthesis IgG index = CSF IgG Serum IgG CSF Albumin Serum Albumin Reiber s Diagram
27 Intrathecal IgG synthesis Oligoclonal IgG bands
28 Polymerase Chain Reaction P1 P2 P3 P4 P5 P6 P7 P8 C+ C - Bl P1 P2 P3 P4 P5 P6 P7 P8
29 Vírus HSV-1 HSV-2 Enterovirus CMV Epstein-Barr JC virus HIV HTLV-I HTLV-II PCR Bacteria M. tuberculosis T. pallidum B. burgdorferi Protozoa Toxoplasma gondii P. falciparum
30 PCR Advantages - high sensitivity and specificity - fast - requires only small CSF volumes Disadvantages - expensive - low sensitivity for M. tuberculosis
31 PCR Virus HSV-1 CMV Varicella zoster Epstein-Barr JC virus Enterovirus Sensitivity (%) > Specificity (%)
32 Tuberculous meningitis Test Initial CSF Sensitivity (%) 2 weeks later Ziehl-Neelsen Culture PCR* * Specificity 96% Muniz
33 CSF in Meningitis Bacteria Virus Crypto TB Pressure nl or nl or Leucocytes > < 500 < 500 < 500 Cytology PMN LM LM LM Glucose nl Stained smear (%) Culture (%) Other tests Agglutination PCR Agglutination PCR CIE CIE
34 Contraindication to lumbar punction
35 Contraindication to lumbar punction
36 Contraindication to lumbar punction
37 CT before CSF in suspected meningitis 301 patients with suspected meningitis 235 who had brain CT - 11 (5%) mass effect Clinical features associated with abnormal CT - Dilated pupils - Hemiparesis - Focal seizures - Rapid decrease in the level of consciousness - Decerebrate or decorticate posture Hasbun et al. N Engl J Med 345: 1727, 2001
38 I have seen diagnostic errors and serious harm come to patients more frequently because of failure to carry out an LP than from the LP itself Fishman, 1992
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