CSF cystatin C and diffusion tensor imaging parameters as biomarkers of upper motor neuron degeneration in amyotrophic lateral sclerosis.

OBJECTIVES: The establishment of biomarkers for amyotrophic lateral sclerosis (ALS) will be useful for early diagnosis and may provide evidence about pathogenesis. To elucidate whether high-field magnetic resonance (MR) findings and multimodal analysis of cerebrospinal fluid (CSF) levels of cystatin C could be indicators of upper motor neuron (UMN) involvement in ALS.

PATIENTS AND METHODS: Patients with ALS (n = 20), multiple sclerosis (n = 15), immune mediated chronic polyneuropathy (n = 17), and acute polyneuropathy (n = 12) were included in this retrospective study. Clinical indices including UMN signs were assessed, and 3.0-Tesla diffusion tensor imaging and MR spectroscopy were performed in patients with ALS. CSF levels of cystatin C were measured using enzyme-linked immunosorbent assay.

RESULTS: MR findings indicated that decreased anisotropy, increased diffusion, and increased myo-inositol/creatine ratio were also significantly correlated with UMN involvement in patients with ALS. The CSF cystatin C levels were significantly lower in patients with ALS than in the other three groups. The reduction of CSF cystatin C levels was significantly correlated with clinical UMN involvement (r = -0.505, p =  0.023).

CONCLUSIONS: Reduced cystatin C in CSF can reflect UMN involvement as shown in high-field MR of ALS, potentially providing a new biomarker for UMN degeneration in ALS.