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@ARTICLE{Muccioli:281826,
      author       = {Muccioli, Lorenzo and Ganceviciute, Bazile and Becker,
                      Felicitas and Minardi, Raffaella and Tappatà, Maria and
                      Bachhuber, Franziska and Alkhatib, Mahmoud and Cirak,
                      Sebahattin and Weishaupt, Jochen H and Verma, Mayank and
                      Tumani, Hayrettin and Wagner, Jan and Messahel, Souad and
                      Nitschke, Felix and Minassian, Berge A and Bisulli,
                      Francesca and Brenner, David},
      title        = {{N}eurofilament {L}ight {C}hain as a {B}iomarker of
                      {D}isease {P}rogression in {L}afora {D}isease.},
      journal      = {Neurology / Genetics},
      volume       = {11},
      number       = {6},
      issn         = {2376-7839},
      address      = {Minneapolis, Minn.},
      publisher    = {[Verlag nicht ermittelbar]},
      reportid     = {DZNE-2025-01207},
      pages        = {e200319},
      year         = {2025},
      abstract     = {Lafora disease (LD) is a severe, ultra-rare childhood-onset
                      progressive myoclonus epilepsy caused by biallelic
                      pathogenic variants in either EPM2A or NHLRC1 and currently
                      without cure. Body fluid-derived biomarkers have remained
                      largely unexplored in LD. Neurofilament light chain (NfL)
                      levels in serum (sNfL) and CSF (cNfL) reflect ongoing
                      neurodegeneration and have been established as prognostic
                      and therapeutic biomarkers in various neurologic disorders.
                      In this study, we assessed the utility of NfL as a biomarker
                      of LD in a multicenter cohort of patients with LD.We
                      conducted cross-sectional and longitudinal measurements of
                      NfL levels in serum (n = 32) and CSF (n = 25) samples from a
                      cohort of 31 patients with LD (26 independent families; mean
                      age 21 years; age range 10.2-40.3; f:m = 16:15; EPM2A:NHLRC1
                      = 16:15) at diverse disease stages (median LD stage 2) and
                      age-matched control participants with transient minor
                      neurologic conditions (mean age 21.9 years; age range
                      11.1-41.3; f:m 22:8), treated at 3 referral centers in Ulm,
                      Bologna, and Dallas. At each visit, we assessed LD stage
                      (median LD stage 2; range 0-4) and LD clinical performance
                      score (median score 10.5; range 0-18), allowing for
                      correlation with NfL measurements.When compared with control
                      participants (mean sNfL 7.72, $95\%$ CI 6.79-8.65; mean cNfL
                      306.8, $95\%$ CI 251.5-362.2), CSF and serum NfL levels were
                      increased in patients with LD (mean sNfL 13.95, $95\%$ CI
                      11.20-16.69; mean cNfL 576.9, $95\%$ CI 465.3-688.5). cNfL
                      values exhibited less variability than sNfL, resulting in
                      superior discriminatory performance between those with LD
                      and controls in receiver operating characteristic (ROC)
                      analyses (AUC sNfL = 0.80; cNfL = 0.88). NfL levels tended
                      to increase longitudinally when samples had been collected
                      ≥12 months after baseline. sNfL levels correlated with
                      both disease stage (r = 0.56) and LD Clinical Performance
                      Scale score (r = -0.49), but not with disease duration
                      (owing to genotype-dependent clinical heterogeneity).Our
                      findings support the utility of NfL, particularly sNfL, as a
                      promising biomarker of disease progression in LD. While
                      further research is needed to fully elucidate the potential
                      of NfL in this context, it holds immediate promise as an
                      exploratory outcome measure in ongoing and future clinical
                      trials.},
      cin          = {Clinical Study Center (Ulm)},
      ddc          = {610},
      cid          = {I:(DE-2719)5000077},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41143127},
      pmc          = {pmc:PMC12552056},
      doi          = {10.1212/NXG.0000000000200319},
      url          = {https://pub.dzne.de/record/281826},
}