Diagnostic and prognostic performance of urine ubiquitin carboxy-terminal hydrolase L1 across multiple acute brain injury types – A longitudinal prospective cohort study

Santtu Hellström; Antti Sajanti; Aditya Jhaveri; Abhinav Srinath; Carolyn Bennett; Ying Cao; Fredrika Koskimäki; Johannes Falter; Janek Frantzén; Seán B. Lyne; Tomi Rantamäki; Riikka Takala; Jussi P. Posti; Susanna Roine; Sulo Kolehmainen; Miro Jänkälä; Jukka Puolitaival; Romuald Girard; Melissa Rahi; Jaakko Rinne; Eero Castrén; Janne Koskimäki

Brain and Spine (Jan 2025)

Diagnostic and prognostic performance of urine ubiquitin carboxy-terminal hydrolase L1 across multiple acute brain injury types – A longitudinal prospective cohort study

Santtu Hellström,
Antti Sajanti,
Aditya Jhaveri,
Abhinav Srinath,
Carolyn Bennett,
Ying Cao,
Fredrika Koskimäki,
Johannes Falter,
Janek Frantzén,
Seán B. Lyne,
Tomi Rantamäki,
Riikka Takala,
Jussi P. Posti,
Susanna Roine,
Sulo Kolehmainen,
Miro Jänkälä,
Jukka Puolitaival,
Romuald Girard,
Melissa Rahi,
Jaakko Rinne,
Eero Castrén,
Janne Koskimäki

Affiliations

Santtu Hellström: Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, P.O. Box 52, FI-20521, Turku, Finland
Antti Sajanti: Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, P.O. Box 52, FI-20521, Turku, Finland
Aditya Jhaveri: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences, Chicago, IL, 60637, USA
Abhinav Srinath: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences, Chicago, IL, 60637, USA
Carolyn Bennett: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences, Chicago, IL, 60637, USA
Ying Cao: Department of Radiation Oncology, Kansas University Medical Center, Kansas City, KS, 66160, USA
Fredrika Koskimäki: Neurocenter, Acute Stroke Unit, Turku University Hospital, P.O. Box 52, FI-20521, Turku, Finland
Johannes Falter: Department of Neurosurgery, University Medical Center of Regensburg, Regensburg, 93042, Germany
Janek Frantzén: Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, P.O. Box 52, FI-20521, Turku, Finland
Seán B. Lyne: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Tomi Rantamäki: Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014, Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, P.O. Box 63, FI-00014, Helsinki, Finland
Riikka Takala: Perioperative Services, Intensive Care and Pain Medicine and Department of Anaesthesiology and Intensive Care, Turku University Hospital and University of Turku, P.O. Box52, FI-20521, Turku, Finland
Jussi P. Posti: Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, P.O. Box 52, FI-20521, Turku, Finland
Susanna Roine: Neurocenter, Acute Stroke Unit, Turku University Hospital, P.O. Box 52, FI-20521, Turku, Finland
Sulo Kolehmainen: Neuroscience Center, HiLIFE, University of Helsinki, P.O. Box 63, FI-00014, Helsinki, Finland
Miro Jänkälä: Department of Neurosurgery, Oulu University Hospital, Box 25, OYS, 90029, Finland
Jukka Puolitaival: Department of Neurosurgery, Oulu University Hospital, Box 25, OYS, 90029, Finland
Romuald Girard: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences, Chicago, IL, 60637, USA
Melissa Rahi: Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, P.O. Box 52, FI-20521, Turku, Finland
Jaakko Rinne: Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, P.O. Box 52, FI-20521, Turku, Finland
Eero Castrén: Neuroscience Center, HiLIFE, University of Helsinki, P.O. Box 63, FI-00014, Helsinki, Finland
Janne Koskimäki: Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, P.O. Box 52, FI-20521, Turku, Finland; Neuroscience Center, HiLIFE, University of Helsinki, P.O. Box 63, FI-00014, Helsinki, Finland; Department of Neurosurgery, Oulu University Hospital, Box 25, OYS, 90029, Finland; Corresponding author. Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, P.O. Box 52 (Hämeentie 11), FI-20521, Turku, Finland.

Journal volume & issue: Vol. 5
p. 104173

Abstract

Read online

Introduction: Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is recognized as a diagnostic and prognostic blood biomarker for traumatic brain injury (TBI). This study aimed to evaluate whether UCH-L1 concentrations measured in patients' urine post-injury could serve as a diagnostic or prognostic biomarker for outcomes in various types of acute brain injuries (ABI). Material and methods: This pilot study included 46 ABI patients: aneurysmal subarachnoid hemorrhage (n = 22), ischemic stroke (n = 16), and traumatic brain injury (n = 8), along with three healthy controls. Urine samples were collected at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) periods post-admission. UCH-L1 and creatinine levels were quantified using ELISA. UCH-L1 concentrations were compared to functional outcomes (modified Rankin Scale, mRS) and dichotomized into favorable (mRS 0–3) and unfavorable (mRS 4–6) groups. Non-parametric statistical tests and ROC analysis was performed. Results: UCH-L1 concentrations in healthy controls were significantly lower compared to both early and late samples after ABI (p ≤ 0.001). The diagnostic performance of urine UCH-L1 at early timepoint showed excellent discriminatory ability, with AUC of 97.6% (95% CI: 93.0–100, p = 0.006 (sensitivity 98%, specificity 100%). Urine UCH-L1 concentrations, both with and without creatinine normalization, did not distinguish between favorable and unfavorable outcomes in either early (p = 0.88 and p = 0.36) or late samples (p = 0.98 and p = 0.30) in any types of ABI. Discussion and conclusions: Although UCH-L1 concentrations in urine did not differentiate between favorable and unfavorable outcomes, a significant difference was observed between healthy subjects and ABI patients. This finding underscores the significant diagnostic utility of urine UCH-L1 concentrations, regardless of the type of acute brain injury.

Published in Brain and Spine

ISSN: 2772-5294 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: https://www.journals.elsevier.com/brain-and-spine

About the journal

Abstract

Keywords