Journal ArticleDOI
Diagnostic-prognostic value and electrophysiological correlates of CSF biomarkers of neurodegeneration and neuroinflammation in amyotrophic lateral sclerosis.
Samir Abu-Rumeileh,Veria Vacchiano,Corrado Zenesini,Barbara Polischi,Silvia de Pasqua,E. Fileccia,Angela Mammana,Vitantonio Di Stasi,Sabina Capellari,Fabrizio Salvi,Rocco Liguori,Piero Parchi,BoReALS +12 more
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TLDR
Among all biomarkers, NfL yielded the highest diagnostic performance and was the best predictor of disease progression rate and survival in ALS and contribute to the understanding of the pathophysiological and electrophysiological correlates of biomarker changes.Abstract:
Neurofilament light chain protein (NfL) is currently the most accurate cerebrospinal fluid (CSF) biomarker in amyotrophic lateral sclerosis (ALS) in terms of both diagnostic and prognostic value, but the mechanism underlying its increase is still a matter of debate. Similarly, emerging CSF biomarkers of neurodegeneration and neuroinflammation showed promising results, although further studies are needed to clarify their clinical and pathophysiological roles. In the present study we compared the diagnostic accuracy of CSF NfL, phosphorylated (p)-tau/total (t)-tau ratio, chitinase-3-like protein 1 (YKL-40) and chitotriosidase 1 (CHIT1), in healthy controls (n = 43) and subjects with ALS (n = 80) or ALS mimics (n = 46). In ALS cases, we also investigated the association between biomarker levels and clinical variables, the extent of upper motor neuron (UMN) and lower motor neuron (LMN) degeneration, and denervation activity through electromyography (EMG). ALS patients showed higher levels of CSF NfL, YKL-40, CHIT1, and lower values of p-tau/t-tau ratio compared to both controls and ALS mimics. Among all biomarkers, NfL yielded the highest diagnostic performance (> 90% sensitivity and specificity) and was the best predictor of disease progression rate and survival in ALS. NfL levels showed a significant correlation with the extent of LMN involvement, whereas YKL-40 levels increased together with the number of areas showing both UMN and LMN damage. EMG denervation activity did not correlate with any CSF biomarker change. These findings confirm the highest value of NfL among currently available CSF biomarkers for the diagnostic and prognostic assessment of ALS and contribute to the understanding of the pathophysiological and electrophysiological correlates of biomarker changes.read more
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Journal ArticleDOI
Trial of Antisense Oligonucleotide Tofersen for <i>SOD1</i> ALS
TL;DR: Tofersen was shown to reduce superoxide dismutase 1 (SOD1) protein synthesis in patients with ALS associated with mutations in SOD1 as discussed by the authors , but did not improve clinical end points and was associated with adverse events.
Journal ArticleDOI
Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS.
Timothy M. Miller,Merit Cudkowicz,Angela Genge,Pamela J. Shaw,Gen Sobue,Robert C. Bucelli,Adriano Chiò,Philip Van Damme,Albert C. Ludolph,Jonathan D. Glass,Jinsy A. Andrews,Suma Babu,Michael Benatar,Christopher J McDermott,Thos Cochrane,Sowmya Chary,Sheena Chew,Han Zhu,Fan Wu,Ivan Nestorov,D. Graham,Peng Sun,Manjit McNeill,Laura Fanning,Toby A. Ferguson,Stephanie Fradette +25 more
TL;DR: Tofersen was shown to reduce the superoxide dismutase 1 (SOD1) protein synthesis in patients with ALS associated with mutations in SOD1 as mentioned in this paper , but did not improve clinical end points and was associated with adverse events.
Journal ArticleDOI
Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers.
Elisabetta Zucchi,Valentina Bonetto,Gianni Sorarù,Ilaria Martinelli,Piero Parchi,Rocco Liguori,Jessica Mandrioli +6 more
TL;DR: How NFs are impacting research and clinical management in ALS and other MNDs is discussed and how NFs may provide a useful tool for the early enrolment of patients in clinical trials is discussed.
Journal ArticleDOI
Non-neuronal cells in amyotrophic lateral sclerosis - from pathogenesis to biomarkers.
Björn Friedhelm Vahsen,Elizabeth Gray,Alexander G. Thompson,Olaf Ansorge,Daniel C. Anthony,Sally A. Cowley,Kevin Talbot,Martin R Turner +7 more
TL;DR: In this article, the authors provide an overview of the diverse roles of non-neuronal cells in relation to the pathogenesis of amyotrophic lateral sclerosis (ALS) and the emerging potential of nonneuron cell biomarkers to advance therapeutic development.
Journal ArticleDOI
Neurofilament Light Chain as Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.
TL;DR: In this article, the authors illustrate the significance of neurofilament light chain (NFL) as a biomarker for ALS and FTD and discuss unsolved issues and potential for future developments.
References
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Journal ArticleDOI
El Escorial revisited : revised criteria for the diagnosis of amyotrophic lateral sclerosis
TL;DR: The criteria described below represent the result of a three-day workshop, convened at Airlie Conference Center, Warrenton, Virginia on 2–4 April, 1998 by the World Federation of Neurology Research Committee on Motor Neuron Diseases, and are placed on the WFN ALS website.
Journal ArticleDOI
Electrodiagnostic criteria for diagnosis of ALS.
Mamede de Carvalho,Reinhard Dengler,Andrew Eisen,John D. England,Ryuji Kaji,Jun Kimura,Kerry R. Mills,Hiroshi Mitsumoto,Hiroyuki Nodera,Jeremy M. Shefner,Michael Swash +10 more
TL;DR: The utility of needle EMG and nerve conduction studies was affirmed and electrophysiological evidence for chronic neurogenic change should be taken as equivalent to clinical information in the recognition of involvement of individual muscles in a limb.
Journal ArticleDOI
The phenotypic variability of amyotrophic lateral sclerosis
Bart Swinnen,Wim Robberecht +1 more
TL;DR: The phenotypic variability of ALS is reviewed and how it is reflected in familial and sporadic ALS, in the degree of upper and lower motor neuron involvement, in motor and extramotor involvement, and in the spectrum of ALS and frontotemporal dementia.
Journal ArticleDOI
Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model
Henk Jan Westeneng,Thomas P. A. Debray,Anne E. Visser,Ruben P A van Eijk,James Rooney,Andrea Calvo,Sarah Martin,Christopher J McDermott,Alexander G. Thompson,Susana Pinto,Xenia Kobeleva,Angela Rosenbohm,Beatrice Stubendorff,Helma Sommer,Bas M. Middelkoop,Annelot M. Dekker,Joke van Vugt,Wouter van Rheenen,Alice Vajda,Mark Heverin,Mbombe Kazoka,Hannah Hollinger,Marta Gromicho,Sonja Körner,Thomas M. Ringer,A. Rödiger,A. Gunkel,Christopher Shaw,Annelien L. Bredenoord,Michael A van Es,Philippe Corcia,Philippe Couratier,Markus Weber,Julian Grosskreutz,Albert C. Ludolph,Susanne Petri,Mamede de Carvalho,Philip Van Damme,Kevin Talbot,Martin R Turner,Pamela J. Shaw,Ammar Al-Chalabi,Adriano Chiò,Orla Hardiman,Orla Hardiman,Karel G.M. Moons,Jan H. Veldink,Leonard H. van den Berg +47 more
TL;DR: An externally validated model is developed to predict survival without tracheostomy and non-invasive ventilation for more than 23 h per day in European patients with ALS and could be applied to individualised patient management, counselling, and future trial design.
Journal ArticleDOI
Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients
Petra Steinacker,Emily Feneberg,Jochen H. Weishaupt,Johannes Brettschneider,Hayrettin Tumani,Peter M. Andersen,Christine A. F. von Arnim,Sarah Böhm,Jan Kassubek,Christian Kubisch,Christian Kubisch,Dorothée Lulé,Hans-Peter Müller,Rainer Muche,Elmar H. Pinkhardt,Patrick Oeckl,Angela Rosenbohm,Sarah Anderl-Straub,Alexander E Volk,Alexander E Volk,Patrick Weydt,Albert C. Ludolph,Markus Otto +22 more
TL;DR: Neurofilaments in CSF have a high relevance for the differential diagnosis of MNDs and should be included in the diagnostic work-up of patients and their value as prognostic markers should be investigated further.
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