N-acetylaspartic acid in cerebrospinal fluid of multiple sclerosis patients determined by gas-chromatography-mass spectrometry.
BACKGROUND
Axonal degeneration is considered to play a major role in the development of clinical disability in multiple sclerosis (MS). N-AcetylAspartic Acid (NAA) is a neuron-specific marker constantly identified in MR-spectroscopy studies of the normal and MS brain. To our knowledge there are no studies available that evaluated NAA in cerebrospinal fluid (CSF) as a possible marker for disease severity.


OBJECTIVE
To evaluate CSF concentrations of NAA in MS in relation to disease phenotype, clinical measures of disability and MRI markers of disease burden.


METHODS
NAA concentrations were determined in CSF of 46 patients with MS (26 relapsing remitting (RRMS), 12 secondary progressive (SPMS) and 8 primary progressive (PPMS)). Prior to lumbar puncture, MS-patients underwent MRI and clinical examination, including the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC). Additionally, CSF concentrations of NAA were determined in 12 patients with other neurological diseases (OND).


RESULTS
Median CSF NAA concentration was 0.74 (IQR: 0.59-0.94) in RRMS , 0.54 (IQR: 0.35-0.73) in SPMS and 0.83 mumol/l (IQR: 0.56-1.03) in PPMS patients. SPMS patients had a significantly lower NAA concentration than RRMS patients. NAA concentrations correlated with EDSS (r = )0.37, p = 0.016), MSFC (r = 0.41, p = 0.010), normalised brain volume (r = 0.49, p = 0.001), T2 lesion load (r = )0.35, p = 0.021) and black hole lesion load (r = )0.47, p = 0.002). No differences were observed between OND (median: 0.57 IQR: 0.28-0.73) and MS patients.


CONCLUSIONS
CSF NAA concentration in MS patients is related to clinical performance and MRI measures of disease burden and may therefore be an important neuron specific marker of disease severity and possibly progression.
Jasperse
Bas
B
Dept. of Neurology, VU University Medical Center, de Boelelaan 1117, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. mms.jasperse@vumc.nl
Jakobs
Cornelis
C
Eikelenboom
M Judith
MJ
Dijkstra
Christine D
CD
Uitdehaag
Bernard M J
BM
Barkhof
Frederik
F
Polman
Chris H
CH
Teunissen
Charlotte E
CE
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000473:pathology; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D001224:Aspartic Acid; C000179:N-acetylaspartate