CSF neurofilament and N-acetylaspartate related brain changes in clinically isolated syndrome.
BACKGROUND
Axonal damage is considered a major cause of disability in multiple sclerosis (MS) and may start early in the disease. Specific biomarkers for this process are of great interest.


OBJECTIVE
To study if cerebrospinal fluid (CSF) biomarkers for axonal damage reflect and predict disease progression already in the earliest stages of the disease, that is, in clinically isolated syndrome (CIS).


METHODS
We assessed CSF levels of neurofilament heavy (NFH), neurofilament light (NFL) and N-acetylaspartate (NAA) in 67 patients with CIS and 18 controls with neuropsychiatric diseases of non-inflammatory aetiology (NC). Patients with CIS underwent baseline magnetic resonance imaging (MRI) at 3T, and a follow-up MRI after 1 year was obtained in 28 of them.


RESULTS
Compared with NC, patients with CIS had higher NFH (p=0.05) and NFL (p<0.001) levels. No significant group differences were found for NAA. Patients' NFH levels correlated with physical disability (r=0.304, p<0.05) and with change in brain volume over 1 year of follow-up (r=-0.518, p<0.01) but not with change in T2 lesion load.


CONCLUSIONS
Our results confirm increased neurofilament levels already in CIS being related to the level of physical disability. The association of NFH levels with brain volume but not lesion volume changes supports the association of these markers with axonal damage.
Department of Neurology, Medical University of Graz, Graz, Austria. michael.khalil@medunigraz.at
M
M
Khalil
C
C
Enzinger
C
C
Langkammer
S
S
Ropele
A
A
Mader
A
A
Trentini
M L G
ML
Vane
M
M
Wallner-Blazek
G
G
Bachmaier
J-J
JJ
Archelos
M J A
MJ
Koel-Simmelink
M A
MA
Blankenstein
S
S
Fuchs
F
F
Fazekas
C E
CE
Teunissen
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000473:pathology*; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L; C051774:neurofilament protein H; D001224:Aspartic Acid; C000179:N-acetylaspartate