Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls.
BACKGROUND
Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls).


METHODS
The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA).


RESULTS
The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R2of 0.97 and Q2of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R2of 0.80 and Q2of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations.


CONCLUSIONS
On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples.
Department of Microbiology, Dr. Ram Manohar Lohia Institute of Medical Sciences (RMLIMS), Vibhuti Khand, Gomti Nagar, Lucknow 226010, India; Amity Institute of Biotechnology, Amity University Uttar Pradesh, Malhaur. Lucknow 226028, India.
Tanushri
T
Chatterji
Centre of Biomedical Research, formerly Centre of Biomedical Magnetic Resonance (CBMR), Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus, Rae Bareli Road, Lucknow 226014, India.
Suruchi
S
Singh
Department of Microbiology, Dr. Ram Manohar Lohia Institute of Medical Sciences (RMLIMS), Vibhuti Khand, Gomti Nagar, Lucknow 226010, India. Electronic address: sen_manodeep6@yahoo.com.
Manodeep
M
Sen
Department of Neurology, Dr. Ram Manohar Lohia Institute of Medical Sciences (RMLIMS), Vibhuti Khand, Gomti Nagar, Lucknow 226010, India.
Ajai Kumar
AK
Singh
Department of Radiodiagnosis, Dr. Ram Manohar Lohia Institute of Medical Sciences (RMLIMS), Vibhuti Khand, Gomti Nagar, Lucknow 226010, India.
Gaurav Raj
GR
Agarwal
Department of Neurosurgery, Dr. Ram Manohar Lohia Institute of Medical Sciences (RMLIMS), Vibhuti Khand, Gomti Nagar, Lucknow 226010, India.
Deepak Kumar
DK
Singh
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Malhaur. Lucknow 226028, India.
Janmejai Kumar
JK
Srivastava
Department of Orthopaedics, King George's Medical University, Shahmina Road, Chowk, Lucknow 226003, India.
Alka
A
Singh
Department of Orthopaedics, King George's Medical University, Shahmina Road, Chowk, Lucknow 226003, India.
Rajeshwar Nath
RN
Srivastava
Centre of Biomedical Research, formerly Centre of Biomedical Magnetic Resonance (CBMR), Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus, Rae Bareli Road, Lucknow 226014, India. Electronic address: roy@cbmr.res.in.
Raja
R
Roy
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008581:Meningitis / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000378:metabolism; D055432:Metabolomics; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy; D055815:Young Adult
D015415:Biomarkers
Cerebrospinal fluid; Meningitis; Metabolic profiling; NMR spectroscopy; Negative controls; Positive controls