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Neurofilament light chain and C reactive protein explored as predictors of survival in amyotrophic lateral sclerosis
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  • Published on: 28 July 2020
    Answer to response of professor Kawada

    Our findings demonstrate that serum C-reactive protein (CRP) does not predict survival in amyotrophic lateral sclerosis (ALS), neither in a univariate model nor in a multivariate model including other established prognostic factors for survival in ALS. In contrast, in a similar multivariate model, serum neurofilament light chain (NfL) is an independent predictor of survival in ALS. Further, we investigated the combination of serum CRP and NfL within the same multivariate survival model. The results indicated that elevated levels of serum NfL (Hazard ratio: 1.83 [95% CI: 1.23-2.74] p = 0.003), but not of serum CRP (Hazard ratio: 0.93 [95% CI = 0.63-1.37], p = 0.7), are associated with a shorter survival in ALS. From these data, we can conclude that there is no evidence that combining both markers would improve the prediction of survival in ALS.

    Moreover, we determined the disease progression rate (DPR) at time of sampling for 368 patients with ALS. The DPR was calculated as (48 – ALS-FRS-R)/(disease duration). We found a significant correlation between the DPR and serum NfL levels (rs = 0.519 [95% CI = 0.437-0.592], p < 0.0001) as well as serum CRP levels (rs = 0.294 [95% CI = 0.194-0.387], p < 0.0001). Accordingly, patients with a DPR in the upper quartile had significantly elevated levels of serum NfL (median [range]: 183 [11.1-738] pg/mL vs. 67.9 [0.300-262] pg/mL, p < 0.0001) and serum CRP (median [range]: 0.336 [0.0150-30.0] mg/dL vs. 0.0775 [0.0150-2.7...

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    Conflict of Interest:
    None declared.
  • Published on: 27 April 2020
    RE: Neurofilament light chain and C reactive protein explored as predictors of survival in amyotrophic lateral sclerosis

    De Schaepdryver et al. assessed the prognostic ability of serum neurofilament light chain (NfL) and C-reactive protein (CRP) in patients with amyotrophic lateral sclerosis (ALS) (1). Although two indicators can significantly predict the prognosis, the superiority by the combination of NfL and CRP should be checked for the analysis. I want to discuss NfL and ALS prognosis from recent publications.

    Verde et al. conducted a prospective study to determine the diagnostic and prognostic performance of serum NfL in patients with ALS (2). Serum NfL positively correlated with disease progression rate in patients with ALS, and higher levels were significantly associated with shorter survival. In addition, serum NfL did not differ among patients in different ALS pathological stages, and NfL levels were stable over time within each patient.

    Regarding the first query, Thouvenot et al. reported that serum NfL could be used as a prognostic marker for ALS at the time of diagnosis (3). Gille et al. recognized the relationship of serum NfL with motor neuron degeneration in patients with ALS (4). They described that serum NfL was significantly associated with disease progression rate and survival, and it could be recommended as a surrogate biomarker of ALS. These two papers presented no information whether NfL can be used for monitoring of ALS progression in each patient.

    De Schaepdryver et al. used two indicators, and I suspect that the authors can present information r...

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    Conflict of Interest:
    None declared.