Virological Diagnosis of Central Nervous System Infections by Use of PCR Coupled with Mass Spectrometry Analysis of Cerebrospinal Fluid Samples

Abstract Background: A biomarker for the diagnosis of childhood-onset ataxia and central nervous system hypomyelination (CACH)/vanishing white matter disease (VWM) would have clinical utility and pathophysiologic significance. Methods: We used 2-dimensional gel electrophoresis/mass spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/VWM with that of unaffected controls. We characterized selected spots by in-gel digestion, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry, and nanospray Fourier transform mass spectrometry. Results: A specific transferrin spot pattern was detected in the CSF samples of the CACH/VWM group (n = 7), distinguishing them from the control group (n = 23) and revealing that patients with CACH/VWM have a deficiency of the asialo form of transferrin usually present in healthy cerebrospinal fluid. The glycopeptide structure, determined from isolated transferrin spots by use of in-gel digestion and extraction, was found to be consistent with earlier reports. Conclusions: The transferrin isoform abnormality in the cerebrospinal fluid of patients with CACH/VWM appears unique and is a potential clinical diagnostic biomarker. The rapid, efficient diagnosis of this disorder would have a significant impact on clinical studies exploring new strategies for the management and treatment of this disease.

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Interleukin 6 in Cerebrospinal Fluid of Patients with Meningitis is not a Useful Diagnostic Marker in the Differential Diagnosis of Meningitis

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329703400206 ◽

1997 ◽

Vol 34 (2) ◽

pp. 165-169 ◽

Cited By ~ 14

Author(s):

L F López-Cortés ◽

M Cruz-Ruiz ◽

J Gómez-Mateos ◽

D Jiménez-Hernández ◽

P Viciana-Fernández ◽

...

Keyword(s):

Central Nervous System ◽

Monoclonal Antibody ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Differential Diagnosis ◽

Interleukin 6 ◽

Diagnostic Marker ◽

Neurological Diseases ◽

Central Nervous System Infections ◽

Pyogenic Meningitis

We assayed interleukin 6 (IL-6) concentrations in cerebrospinal fluid (CSF) from patients affected by meningitis of different aetiologies, and verified whether IL-6 can be used as a diagnostic marker in the differential diagnosis of meningitis. We used a monoclonal antibody enzyme immunoassay to test 98 CSF samples classified as pyogenic (15), viral (15), self-resolving aseptic meningitis (20), other infectious meningitis (9), neoplastic (4) and normal CSF from patients with (20) and without (15) non-infectious neurological diseases. CSF IL-6 concentrations were increased in pyogenic meningitis (100%) and in more than 50% of viral and other subarachnoid space infections, and rarely in patients without central nervous system infections. Though patients affected by pyogenic meningitis showed the highest levels of CSF IL-6, only a cut-off point ≥10000 pg/mL was able to discriminate pyogenic meningitis from those of other aetiologies with a specificity ≥94% and a positive predictive value of ≥0·75 but the sensitivity was ≤60%. Therefore, CSF IL-6 concentration is not a good diagnostic marker in the differential diagnosis of meningitis.

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