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Cerebrospinal Fluid inCNS Infections
Osvaldo M. Takayanagui
Departamento de NeurologiaFaculdade de Medicina de Ribeirão Preto
Universidade de São Paulo
CSF in CNS Infections
1891- Heinrich Quincke
Diagnosis of CNS Infections
CSF in CNS Infections
Acute Bacterial Meningitis
CSF in CNS Infections
- Lumbar
- Cisternal
- Ventricular
- High cervical
CSF Puncture
CSF in CNS Infections
Gross appearance
Cytology
Biochemistry
Culture
Detection of antibodies
Detection of antigens
Examination of CSF
CSF in CNS Infections
Clear, colorlessXantochromia
subarachnoid bleeding↑ proteinhyperbilirubinemia
Turbidsubarachnoid bleedingmeningitis (>100 cells)
Purulentacute bacterial meningitis
Gross appearance
CSF in CNS Infections
Fuchs Rosenthal counting chamber
Cryptococcus neoformans
CSF in CNS Infections
Cytology
CSF in CNS Infections
Cytology
CSF in CNS Infections
S. pneumoniae
N. meningitidis
Haemophilus influenzae
Gram stainGram stain
CSF in CNS Infections
India ink
Cryptococcus neoformans
CSF in CNS Infections
M. tuberculosis
Ziehl-Neelsen stain
CSF in CNS Infections
Takayanagui et al – Neurology, 1995
Strongyloides stercoralis in the CSF
CSF in CNS Infections
Trypanosoma cruzi – trypomastigote in the CSF
Yoo et al. - Clin Infect Dis, 2004
CSF in CNS Infections
Acute purulent meningitis
Tuberculous meningitis
Fungal meningitisMeningeal cysticercosis
Viral meningoencephalitis
mumps (25%)
herpes simplex
herpes zoster
enterovirus
Hypoglycorrhachia
Occasionally reduced
CSF in CNS Infections
H. influenzae
Candida albicans
C. neoformans
Culture: CSF and blood
CSF in CNS Infections
M. tuberculosis
Lowenstein-Jensen culture
CSF in CNS Infections
Viral culture
CSF in CNS Infections
1- NASBA, NucliSens
2- RT-PCR, Amplicor
3- branched DNA, Quantiplex
HIV-1 RNA viral load
CSF in CNS Infections
Method
Principle
Gene
Lower limit (copies/ml)
Volume
Time
Branched DNA
Quantiplex
Hibridization
pol
500
1-2 ml
1,5 d
Amplicor
HIV-1 Monitor
RT-PCR
gag
200-400
200 µl
6 h
NASBA
NucliSens
Amplification
gag
80
10 µl-1 ml
5 h
HIV-1 - RNA viral load
CSF in CNS Infections
Carga Viral
2,14
5
6
3,67
4 ,84
1 ,9
5 ,79
4 ,925 ,27
2 ,6
3
3
4 4
3
44
4
0
1
2
3
4
5
6
7
1 2 3 4 5 6 7 8 9
Pacientes (transtorno cognitivo associado ao HIV-1)
cóp
ias/
ml e
m lo
g
PlasmaLíquor
HIV-1 - RNA viral loadPlasmaCSF
CSF in CNS Infections
Detection of Antibodies
- Indirect Imunofluorescence
- Passive Hemoagglutination
- ELISA
- Particle Agglutination
- Contraimmunoelectrophoresis
- Western blot
CSF in CNS Infections
ELISA
CSF in CNS Infections
Particle Agglutination
CSF in CNS Infections
Intern Controlrgp46-Irgp46-II
N P PPP P P PIIIIIIIcontrols
p53gp46
p32
GD21
gp21p19
p24p26p28
p36
WesternWestern BlotBlot
CSF in CNS Infections
Intrathecal IgG synthesis
IgG index =
CSF IgGSerum IgG
CSF AlbuminSerum Albumin
Reiber’s Diagram
CSF in CNS Infections
Oligoclonal IgG bands
Intrathecal IgG synthesis
CSF in CNS Infections
P1 P2 P3 P4 P5 P6 P7 P8
Polymerase Chain Reaction
C+ C - Bl P1 P2 P3 P4 P5 P6 P7 P8
CSF in CNS Infections
VírusHSV-1 HSV-2 Enterovirus CMVEpstein-BarrJC virusHIVHTLV-IHTLV-II
PCR
BacteriaM. tuberculosisT. pallidumB. burgdorferi
ProtozoaToxoplasma gondiiP. falciparum
CSF in CNS Infections
PCR
Advantages- high sensitivity and specificity- fast- requires only small CSF volumes
Disadvantages- expensive- low sensitivity for M. tuberculosis
CSF in CNS Infections
Virus
HSV-1
CMV
Varicella zoster
Epstein-Barr
JC virus
Enterovirus
Sensitivity (%)
>95
80-100
-
97
74-92
97
Specificity (%)
100
75-100
100
100
92-96
100
PCR
CSF in CNS Infections
Initial CSF
35
40
55
Test
Ziehl-Neelsen
Culture
PCR*
2 weeks later
6
6
54
Sensitivity (%)
Muniz - 1998* Specificity – 96%
Tuberculous meningitis
CSF in CNS Infections
Pressure
Leucocytes
Cytology
Glucose
Stained smear (%)
Culture (%)
Other tests
Bacteria
↑
> 1.000
PMN
60-90
85
Agglutination
CIE
Virus
nl or ↑
< 500
LM
nl
-
-
PCR
Crypto
nl or ↑
< 500
LM
70
50
Agglutination
CIE
TB
↑
< 500
LM
35
40
PCR
CSF in Meningitis
↑ ↑ ↑ ↑↑
CSF in CNS Infections
Contraindication to lumbar punction
CSF in CNS Infections
Contraindication to lumbar punction
CSF in CNS Infections
Contraindication to lumbar punction
CSF in CNS Infections
CT before CSF in suspected meningitis
Hasbun et al. N Engl J Med 345: 1727, 2001
301 patients with suspected meningitis235 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
CSF in CNS Infections
“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