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Serum neurofilament light chain in distinct phenotypes of amyotrophic lateral sclerosis: A longitudinal, multicenter study.

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Title: Serum neurofilament light chain in distinct phenotypes of amyotrophic lateral sclerosis: A longitudinal, multicenter study.
Authors: Meyer, Thomas (AUTHOR), Dreger, Marie (AUTHOR), Grehl, Torsten (AUTHOR), Weyen, Ute (AUTHOR), Kettemann, Dagmar (AUTHOR), Weydt, Patrick (AUTHOR), Günther, René (AUTHOR), Lingor, Paul (AUTHOR), Petri, Susanne (AUTHOR), Koch, Jan Christoph (AUTHOR), Großkreutz, Julian (AUTHOR), Rödiger, Annekathrin (AUTHOR), Baum, Petra (AUTHOR), Hermann, Andreas (AUTHOR), Prudlo, Johannes (AUTHOR), Boentert, Matthias (AUTHOR), Weishaupt, Jochen H. (AUTHOR), Löscher, Wolfgang N. (AUTHOR), Dorst, Johannes (AUTHOR), Koc, Yasemin (AUTHOR)
Source: European Journal of Neurology. Sep2024, Vol. 31 Issue 9, p1-13. 13p.
Subjects: Amyotrophic lateral sclerosis, Logistic regression analysis, Motor neurons, Clinical trials, Phenotypes
Abstract: Objective: To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS). Method s : In 2949 ALS patients at 16 ALS centers in Germany and Austria, clinical characteristics and sNfL were assessed. Phenotypes were differentiated for two anatomical determinants: (1) upper and/or lower motor involvement (typical, typMN; upper/lower motor neuron predominant, UMNp/LMNp; primary lateral sclerosis, PLS) and (2) region of onset and propagation of motor neuron dysfunction (bulbar, limb, flail‐arm, flail‐leg, thoracic onset). Phenotypes were correlated to sNfL, progression, and survival. Results: Mean sNfL was ‐ compared to typMN (75.7 pg/mL, n = 1791) ‐ significantly lower in LMNp (45.1 pg/mL, n = 413), UMNp (58.7 pg/mL n = 206), and PLS (37.6 pg/mL, n = 84). Also, sNfL significantly differed in the bulbar (92.7 pg/mL, n = 669), limb (64.1 pg/mL, n = 1305), flail‐arm (46.4 pg/mL, n = 283), flail‐leg (53.6 pg/mL, n = 141), and thoracic (74.5 pg/mL, n = 96) phenotypes. Binary logistic regression analysis showed highest contribution to sNfL elevation for faster progression (odds ratio [OR] 3.24) and for the bulbar onset phenotype (OR 1.94). In contrast, PLS (OR 0.20), LMNp (OR 0.45), and thoracic onset (OR 0.43) showed reduced contributions to sNfL. Longitudinal sNfL (median 12 months, n = 2862) showed minor monthly changes (<0.2%) across all phenotypes. Correlation of sNfL with survival was confirmed (p < 0.001). Conclusions: This study underscored the correlation of ALS phenotypes – differentiated for motor neuron involvement and region of onset/propagation – with sNfL, progression, and survival. These phenotypes demonstrated a significant effect on sNfL and should be recognized as independent confounders of sNfL analyses in ALS trials and clinical practice. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Serum neurofilament light chain in distinct phenotypes of amyotrophic lateral sclerosis: A longitudinal, multicenter study.
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  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Meyer%2C+Thomas%22&quot;&gt;Meyer, Thomas&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Dreger%2C+Marie%22&quot;&gt;Dreger, Marie&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Grehl%2C+Torsten%22&quot;&gt;Grehl, Torsten&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Weyen%2C+Ute%22&quot;&gt;Weyen, Ute&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Kettemann%2C+Dagmar%22&quot;&gt;Kettemann, Dagmar&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Weydt%2C+Patrick%22&quot;&gt;Weydt, Patrick&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22G&#252;nther%2C+Ren&#233;%22&quot;&gt;G&#252;nther, Ren&#233;&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Lingor%2C+Paul%22&quot;&gt;Lingor, Paul&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Petri%2C+Susanne%22&quot;&gt;Petri, Susanne&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Koch%2C+Jan+Christoph%22&quot;&gt;Koch, Jan Christoph&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Gro&#223;kreutz%2C+Julian%22&quot;&gt;Gro&#223;kreutz, Julian&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22R&#246;diger%2C+Annekathrin%22&quot;&gt;R&#246;diger, Annekathrin&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Baum%2C+Petra%22&quot;&gt;Baum, Petra&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Hermann%2C+Andreas%22&quot;&gt;Hermann, Andreas&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Prudlo%2C+Johannes%22&quot;&gt;Prudlo, Johannes&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Boentert%2C+Matthias%22&quot;&gt;Boentert, Matthias&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Weishaupt%2C+Jochen+H%2E%22&quot;&gt;Weishaupt, Jochen H.&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22L&#246;scher%2C+Wolfgang+N%2E%22&quot;&gt;L&#246;scher, Wolfgang N.&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Dorst%2C+Johannes%22&quot;&gt;Dorst, Johannes&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Koc%2C+Yasemin%22&quot;&gt;Koc, Yasemin&lt;/searchLink&gt; (AUTHOR)
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22European+Journal+of+Neurology%22&quot;&gt;European Journal of Neurology&lt;/searchLink&gt;. Sep2024, Vol. 31 Issue 9, p1-13. 13p.
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  Data: &lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Amyotrophic+lateral+sclerosis%22&quot;&gt;Amyotrophic lateral sclerosis&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Logistic+regression+analysis%22&quot;&gt;Logistic regression analysis&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Motor+neurons%22&quot;&gt;Motor neurons&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Clinical+trials%22&quot;&gt;Clinical trials&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Phenotypes%22&quot;&gt;Phenotypes&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Objective: To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS). Method s : In 2949 ALS patients at 16 ALS centers in Germany and Austria, clinical characteristics and sNfL were assessed. Phenotypes were differentiated for two anatomical determinants: (1) upper and/or lower motor involvement (typical, typMN; upper/lower motor neuron predominant, UMNp/LMNp; primary lateral sclerosis, PLS) and (2) region of onset and propagation of motor neuron dysfunction (bulbar, limb, flail‐arm, flail‐leg, thoracic onset). Phenotypes were correlated to sNfL, progression, and survival. Results: Mean sNfL was ‐ compared to typMN (75.7 pg/mL, n = 1791) ‐ significantly lower in LMNp (45.1 pg/mL, n = 413), UMNp (58.7 pg/mL n = 206), and PLS (37.6 pg/mL, n = 84). Also, sNfL significantly differed in the bulbar (92.7 pg/mL, n = 669), limb (64.1 pg/mL, n = 1305), flail‐arm (46.4 pg/mL, n = 283), flail‐leg (53.6 pg/mL, n = 141), and thoracic (74.5 pg/mL, n = 96) phenotypes. Binary logistic regression analysis showed highest contribution to sNfL elevation for faster progression (odds ratio [OR] 3.24) and for the bulbar onset phenotype (OR 1.94). In contrast, PLS (OR 0.20), LMNp (OR 0.45), and thoracic onset (OR 0.43) showed reduced contributions to sNfL. Longitudinal sNfL (median 12 months, n = 2862) showed minor monthly changes (&lt;0.2%) across all phenotypes. Correlation of sNfL with survival was confirmed (p &lt; 0.001). Conclusions: This study underscored the correlation of ALS phenotypes – differentiated for motor neuron involvement and region of onset/propagation – with sNfL, progression, and survival. These phenotypes demonstrated a significant effect on sNfL and should be recognized as independent confounders of sNfL analyses in ALS trials and clinical practice. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of European Journal of Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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