CSF analysis differentiates multiple-system atrophy from idiopathic late-onset cerebellar ataxia.
BACKGROUND
Differentiating idiopathic late-onset cerebellar ataxia (ILOCA) from ataxia due to the cerebellar subtype of multiple-system atrophy (MSA-C) can be difficult in the early stages of the disease


METHODS
The authors analyzed the levels of various CSF biomarkers in 27 patients with MSA-C and 18 patients with ILOCA and obtained cut-off points for each potential biomarker to differentiate MSA-C from ILOCA.


RESULTS
Increased levels of neurofilament light chain (NFL) and neurofilament heavy chain (NFHp35) and decreased levels of the neurotransmitter metabolites homovanillic acid (HVA), 5-hydroxyindoleaceticacid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) were observed in MSA-C compared with ILOCA patients. Receiver operating characteristic analysis showed high sensitivity and specificity levels for NFL, NFHp35, and MHPG analysis. At a cut-off of 24.4 ng/L for the NFL analysis, a sensitivity of 79% and a specificity of 94% were obtained for differentiating MSA-C from ILOCA. At a cut-off point for NFHp35 of 129.5 ng/L, sensitivity was 87% and specificity 83%. Analysis of MHPG levels (cut-off 42.5 nM) resulted in a sensitivity of 86% with a specificity of 75%. A multivariate logistic regression model selected NFL, MHPG, and tau as independent predictive biomarkers that separated the MSA-C and ILOCA groups.


CONCLUSIONS
Increased levels of neurofilament light chain and tau and decreased levels of 3-methoxy-4-hydroxyphenylethyleneglycol were associated with high accuracy levels in differentiating the cerebellar subtype of multiple-system atrophy from idiopathic late-onset cerebellar ataxia (LOCA). CSF analysis may thus serve as a useful tool in early diagnostic differentiation of LOCA.
Abdo
W F
WF
Department of Neurology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. f.abdo@neuro.umcn.nl
van de Warrenburg
B P C
BP
Munneke
M
M
van Geel
W J A
WJ
Bloem
B R
BR
Kremer
H P H
HP
Verbeek
M M
MM
D017668:Age of Onset; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002524:Cerebellar Ataxia / Q000134:cerebrospinal fluid*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000134:cerebrospinal fluid* / Q000145:classification; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L; C051774:neurofilament protein H; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid