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Abstract Details

Neurofilaments in Amyotrophic Lateral Sclerosis: A Systemic Review and Meta-analysis
Neuromuscular and Clinical Neurophysiology (EMG)
P6 - Poster Session 6 (8:00 AM-9:00 AM)
11-009
The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in amyotrophic lateral sclerosis (ALS).
Neurofilament proteins have been implicated to be altered in ALS.

Studies in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to August 17, 2023 which investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS and were assessed by two reviewers. Study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in CSF and blood, and clinical outcome were recorded.
Sixty studies with 8801 participants were included. CSF NfL exhibited AUC of 0.92 and sensitivity of 0.87 (95% CI, 083 to 0.89) and specificity of 0.84 (95% CI, 0.77 to 0.89) in distinguishing ALS from disease mimics. Similarly, CSF pNfH exhibited AUC of 0.91 and sensitivity of 0.84 (95% CI, 0.78 to 0.88) and specificity of 0.86 (95% CI, 0.76 to 0.92) in distinguishing ALS from disease mimics. CSF NfL correlated with corresponding levels in blood (r=0.78 [95% CI, 0.72 to 0.83]), while the correlation between CSF and serum levels of pNfH was lower (r=0.65 [95% CI, 0.54 to 0.74]). Blood NfL exhibited sensitivity of 0.91 (95% CI, 0.88 to 0.93) and specificity of 0.89 (95% CI, 0.81 to 0.94) in distinguishing ALS from controls. Higher blood NfL levels were associated with more severe symptoms assessed by the ALS Functional Rating Scale Revised score (r=-0.31 [95% CI, -0.40 to -0.22]), faster disease progression rate (r=0.46 [95% CI, 0.42 to 0.51]), and shorter survival (HR=3.89 [95% CI, 2.91 to 5.19]).

Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores, while NfL is also associated and measures of disease progression, supporting its use in clinical diagnostics and management.
Authors/Disclosures
Pashtun-Poh Shahim, MD, PhD
PRESENTER 		Pashtun-Poh Shahim has nothing to disclose.
Gina Norato Gina Norato has nothing to disclose.
Henrik Zetterberg (Sahlgrenska University Hospital/Molndal) Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley and Elsevier. Henrik Zetterberg has stock in Brain Biomarker Solutions.
Kaj Blennow Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ALZPath. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AriBio. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Beckman-Coulter. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BioArctic. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moleac Pte. Ltd. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurimmune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Pharma. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prothena. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quanterix. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Diagnostics. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens Healthineers. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AC Immune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ALZPath. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AriBio. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Beckman-Coulter. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BioArctic. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Moleac Pte. Ltd. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurimmune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ono Pharma. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prothena. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Quanterix. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Diagnostics. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Siemens Healthineers. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Julius Clinical. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AC Immune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Celdara Medical. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Diagnostics. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Co-founder with Brain Biomarker Solutions.
Leighton Chan (NIH) No disclosure on file
Christopher Grunseich, MD (National Institutes of Health) The institution of Dr. Grunseich has received research support from AnnJi Pharmaceuticals.