N-acetylaspartic acid in cerebrospinal fluid of multiple sclerosis patients determined by gas-chromatography-mass spectrometry
Open Access
- 6 April 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in Zeitschrift für Neurologie
- Vol. 254 (5), 631-637
- https://doi.org/10.1007/s00415-006-0415-5
Abstract
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-.94) in RRMS , 0.54 (IQR: 0.35-.73) in SPMS and 0.83 μmol/l (IQR: 0.56-.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-.73) and MS patients. Conclusion 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.Keywords
This publication has 31 references indexed in Scilit:
- Growth‐associated protein 43 in lesions and cerebrospinal fluid in multiple sclerosisNeuropathology and Applied Neurobiology, 2006
- MR spectroscopic evidence for glial increase but not for neuro‐axonal damage in MS normal‐appearing white matterMagnetic Resonance in Medicine, 2005
- Imaging neuronal and axonal degeneration in multiple sclerosisNeurological Sciences, 2003
- Multiple Sclerosis and Chronic Autoimmune Encephalomyelitis: A Comparative Quantitative Study of Axonal Injury in Active, Inactive, and Remyelinated LesionsThe American Journal of Pathology, 2000
- Axonal Transection in the Lesions of Multiple SclerosisNew England Journal of Medicine, 1998
- Axonal damage in acute multiple sclerosis lesionsBrain, 1997
- Defining the clinical course of multiple sclerosisNeurology, 1996
- Stable isotope dilution analysis ofN‐acetylaspartic acid in CSF, blood, urine and amniotic fluid: Accurate postnatal diagnosis and the potential for prenatal diagnosis of canavan diseaseJournal of Inherited Metabolic Disease, 1990
- Rating neurologic impairment in multiple sclerosisNeurology, 1983
- New diagnostic criteria for multiple sclerosis: Guidelines for research protocolsAnnals of Neurology, 1983