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. 2024 Feb;271(2):794-803.
doi: 10.1007/s00415-023-12015-3. Epub 2023 Oct 6.

The value of routine blood work-up in clinical stratification and prognosis of patients with amyotrophic lateral sclerosis

Francesco Gentile  1 , Alessio Maranzano  2 , Federico Verde  2   3 , Veronica Bettoni  4 , Eleonora Colombo  2 , Alberto Doretti  2 , Marco Olivero  1 , Francesco Scheveger  1 , Claudia Colombrita  5 , Ilaria Bulgarelli  5 , Edoardo Gioele Spinelli  6   7   8 , Erminio Torresani  5 , Stefano Messina  2 , Luca Maderna  2 , Federica Agosta  6   7   8 , Claudia Morelli  2 , Massimo Filippi  6   7   8   9   10 , Vincenzo Silani  2   3 , Nicola Ticozzi  11   12
Affiliations

The value of routine blood work-up in clinical stratification and prognosis of patients with amyotrophic lateral sclerosis

Francesco Gentile et al. J Neurol. 2024 Feb.

Abstract

Background: There is an unmet need in amyotrophic lateral sclerosis (ALS) to provide specific biomarkers for the disease. Due to their easy availability, we aimed to investigate whether routine blood parameters provide useful clues for phenotypic classification and disease prognosis.

Methods: We analyzed a large inpatient cohort of 836 ALS patients who underwent deep phenotyping with evaluation of the clinical and neurophysiological burden of upper (UMN) and lower (LMN) motor neuron signs. Disability and progression rate were measured through the revised ALS Functional Rating Scale (ALSFRS-R) and its changes during time. Cox regression analysis was performed to assess survival associations.

Results: Creatinine significantly correlated with LMN damage (r = 0.38), active (r = 0.18) and chronic (r = 0.24) denervation and baseline ALSFRS-R (r = 0.33). Creatine kinase (CK), alanine (ALT) and aspartate (AST) transaminases correlated with active (r = 0.35, r = 0.27, r = 0.24) and chronic (r = 0.37, r = 0.20, r = 0.19) denervation, while albumin and C-reactive protein significantly correlated with LMN score (r = 0.20 and r = 0.17). Disease progression rate showed correlations with chloride (r = -0.19) and potassium levels (r = -0.16). After adjustment for known prognostic factors, total protein [HR 0.70 (95% CI 0.57-0.86)], creatinine [HR 0.86 (95% CI 0.81-0.92)], chloride [HR 0.95 (95% CI 0.92-0.99)], lactate dehydrogenase [HR 0.99 (95% CI 0.99-0.99)], and AST [HR 1.02 (95% CI 1.01-1.02)] were independently associated with survival.

Conclusions: Creatinine is a reliable biomarker for ALS, associated with clinical features, disability and survival. Markers of nutrition/inflammation may offer additional prognostic information and partially correlate with clinical features. AST and chloride could further assist in predicting progression rate and survival.

Keywords: Amyotrophic lateral sclerosis; Biomarkers; Blood; Survival.

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Conflict of interest statement

F. Gentile, A. Maranzano, F. Verde, V. Bettoni, E. Colombo, A. Doretti, M. Olivero, F. Scheveger, C. Colombrita, I. Bulgarelli, E.G. Spinelli, E. Torresani, S. Messina, L. Maderna and C. Morelli report no disclosure. F. Agosta is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Biogen Idec, Roche, Zambon and Italfarmaco; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), the European Research Council and the Foundation Research on Alzheimer Disease. M. Filippi is Editor in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Associate Editor of Radiology, and Associate Editor of Neurological Sciences; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). V. Silani received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, LiquidWeb, Srl and Novartis Pharma AG. He receives or he has received research support from the Italian Ministry of Health, AriSla, and E-Rare Joint Translational Call. He is on. the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemproal Degeneration, European Neurology, American Journal of Neurodegenerative Disease and Frontiers in Neurology. N. Ticozzi received compensation for consulting services from Amylyx Pharmaceutical, Biogen, Italfarmaco and Zambon Biotech SA. He received research funding from the Italian Ministry of Health and AriSLA. He is associate editor of Frontiers in Aging Neuroscience.

Figures

Fig. 1
Fig. 1
Summary chart of the correlation network of blood parameters associated with amyotrophic lateral sclerosis. The correlations with three clinical domains of ALS, namely clinical features (UMN/LMN signs), disability, and survival, were labelled with different colours (green, blue, and red, respectively). ± positive/negative correlations
See this image and copyright information in PMC

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