Can cystatin C in cerebrospinal fluid be a biomarker for amyotrophic lateral sclerosis? A lesson from previous studies

Background and Aim: Amyotrophic lateral sclerosis (ALS) is an idiopathic and fatal neurodegenerative disease of the motor system that results in loss of upper and lower motor neurons in the brainstem and multiple spinal cord regions. We do not have a useful biomarker for early diagnosis yet. In terms of cerebrospinal fluid (CSF), cystatin C is a candidate, but the results are controversial. In the present study, we synthesized the results of published research on cystatin C in CSF to test whether or not cystatin C level was reduced in ALS relative to other neurological disorders (OND) using a meta-analysis method. Methods: Comprehensive literature search yielded four studies that satisfied our inclusion criteria (112 ALS, 72 OND). The outcome of cystatin C concentration was expressed as the standardized mean difference (SMD) between ALS and OND. Results: The overall effect of ALS on cystatin C level in CSF was not significantly different from OND (SMD = -0.81, 95% CI -1.78 to 0.16, P - 0.10, four studies, n - 184). This result was based on heterogeneous studies (P < 0.0001, I-2 - 88%). We carried out sensitivity analysis with the exclusion of each study sequentially. There was no significant summary effect regardless of any exclusion. Conclusions: The present meta-analysis could not detect a significant difference of cystatin C in CSF between ALS and OND with heterogeneous studies. Here, we mainly discussed the possible cause of heterogeneity, which provided several suggestions for future research.