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. 2023 Jun;123(3):917-925.
doi: 10.1007/s13760-022-02091-z. Epub 2022 Sep 13.

Serum neurofilament light chain and initial severity of neurological disease predict the early neurological deterioration in Wilson's disease

Tjalf Ziemssen #  1 , Lukasz Smolinski #  2 , Anna Członkowska  2 , Katja Akgun  1 , Agnieszka Antos  2 , Jan Bembenek  2 , Iwona Kurkowska-Jastrzębska  2 , Adam Przybyłkowski  3 , Marta Skowrońska  2 , Barbara Redzia-Ogrodnik  4 , Tomasz Litwin #  5
Affiliations

Serum neurofilament light chain and initial severity of neurological disease predict the early neurological deterioration in Wilson's disease

Tjalf Ziemssen et al. Acta Neurol Belg. 2023 Jun.

Abstract

Background: In Wilson's disease (WD), early neurological deterioration after treatment initiation is associated with poor outcomes; however, data on this phenomenon are limited. Our study analysed the frequency and risk factors of early neurological deterioration in WD.

Methods: Early neurological deterioration, within 6 months from diagnosis, was defined based on the Unified Wilson's Disease Rating Scale (UWDRS): any increase in part II or an increase of ≥ 4 in part III. In total, 61 newly diagnosed WD patients were included. UWDRS scores, brain magnetic resonance imaging (MRI) scores, copper metabolism parameters, treatment type and serum neuro-filament light chain (sNfL) concentrations at diagnosis were analysed as potential risk factors of early deterioration.

Results: Early neurological deterioration was observed in 16.3% of all WD patients; all cases of worsening occurred in the neurological phenotype (27.7%). Higher scores were seen in those who deteriorated compared with those who did not for UWDRS part II (4.3 ± 5.0 vs 2.0 ± 5.9; p < 0.05), UWDRS part III (21.5 ± 14.1 vs 9.3 ± 16.4; p < 0.01) and MRI-assessed chronic damage (3.2 ± 1.6 vs 1.4 ± 2.2; p = 0.006); all these variables indicated the initial severity of neurological disease. Pre-treatment sNfL concentrations were significantly higher in patients who deteriorated compared with those who did not (33.2 ± 23.5 vs 27.6 ± 62.7 pg/mL; p < 0.01). In univariate logistic regression amongst all patients, chronic damage MRI scores, UWDRS part III scores and sNfL concentrations predicated early deterioration. In the neurological WD, only sNFL were a significant predictor. In bivariate logistic regression amongst all patients, sNfL remained the only significant predictor of deterioration when corrected for MRI scores.

Conclusion: sNfL concentrations are a promising biomarker of the risk of early neurological deterioration in WD.

Keywords: Magnetic resonance imaging; Neurological deterioration; Serum neuro-filament light chain; UWDRS; Wilson’s disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Receiver operating characteristic curves (ROC) for predictors of early neurological deterioration: UWDRS part II and III (A), MRI acute toxicity, chronic damage and total brain score (B) and sNfL (C). MRI, magnetic resonance imaging; sNfL, serum neuro-filament light chain; UWDRS, Unified Wilson’s Disease Rating Scale
See this image and copyright information in PMC

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