Cerebrospinal fluid levels of neurofilament light chain in multiple system atrophy relative to Parkinson's disease: a meta-analysis

As a biomarker of axonal injury, neurofilament light chain (NFL) in multiple system atrophy (MSA) patients and Parkinson's disease (PD) patients has been investigated by numerous studies. However, cerebrospinal fluid (CSF) NFL changes are conflicting in MSA patients relative to PD patients to date. Therefore, the current study was carried out to find out possible heterogeneity sources. Furthermore, Neurofilament, Neurofilament light chain and Multiple system atrophy were employed to search PubMed, Springer and Medline databases until August 2016 with standard mean difference (Std.MD) being calculated. In addition, subgroup analysis and meta-regression were performed to assess possible heterogeneity sources. Nine studies were pooled, in which 212 MSA patients and 373 PD patients were involved. Moreover, CSF NFL in MSA patients was higher than that in PD patients [pooled Std.MD = 1.56, 95% CI (1.12, 2.00), p < 0.00001] with significant heterogeneity (I (2) = 76%). Besides, population variations, sample size, the difference in CSF phosphorylated tau (p-tau) levels between MSA patients and PD patients, and Hoehn-Yahr staging of PD patients were the main heterogeneity sources. As shown by meta-regression, Hedges's g of CSF NFL was correlated with CSF Std.MD of alpha-synuclein between MSA patients and healthy controls (r = -1.34824, p = 0.00025). Therefore, CSF NFL increased in MSA patients relative to PD patients. Meta-regression showed that NFL was associated with alpha-synuclein in CSF of MSA patients relative to healthy controls. Due to the influence of heterogeneity sources, more prospective large sample studies are still needed to assess CSF NFL changes in MSA patients relative to PD patients.