Pfyffer D, Smith AC, Weber KA 2nd, Grillhoesl A, Mach O, Draganich C, Berliner JC, Tefertiller C, Leister I, Maier D, Schwab JM, Thompson A, Curt A, and Freund P
Background: The accuracy of prognostication in patients with cervical spinal cord injury (SCI) needs to be improved. We aimed to explore the prognostic value of preserved spinal tissue bridges-injury-spared neural tissue adjacent to the lesion-for prediction of sensorimotor recovery in a large, multicentre cohort of people with SCI., Methods: For this longitudinal study, we included patients with acute cervical SCI (vertebrae C1-C7) admitted to one of three trauma or rehabilitation centres: Murnau, Germany (March 18, 2010-March 1, 2021); Zurich, Switzerland (May 12, 2002-March 2, 2019); and Denver, CO, USA (Jan 12, 2010-Feb 16, 2017). Patients were clinically assessed at admission (baseline), at discharge (3 months), and at 12 months post SCI. Midsagittal tissue bridges were quantified from T2-weighted images assessed at 3-4 weeks post SCI. Fractional regression and unbiased recursive partitioning models, adjusted for age, sex, centre, and neurological level of injury, were used to assess associations between tissue bridge width and baseline-adjusted total motor score, pinprick score, and light touch scores at 3 months and 12 months. Patients were stratified into subgroups according to whether they showed better or worse predicted recovery., Findings: The cohort included 227 patients: 93 patients from Murnau (22 [24%] female); 43 patients from Zurich (four [9%] female); and 91 patients from Denver (14 [15%] female). 136 of these participants (from Murnau and Zurich) were followed up for up to 12 months. At 3 months, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 9·3% (SD 0·9) of maximal total motor score (95% CI 7·5-11.2), 8·6% (0·8) of maximal pinprick score (7·0-10·1), and 10·9% (0·8) of maximal light touch score (9·4-12·5). At 12 months post SCI, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 10·9% (1·3) of maximal total motor score (8·4-13·4), 5·7% (1·3) of maximal pinprick score (3·3-8·2), and 6·9% (1·4) of maximal light touch score (4·1-9·7). Partitioning models identified a tissue bridge cutoff width of 2·0 mm to be indicative of higher or lower 3-month total motor, pinprick, and light touch scores, and a cutoff of 4·0 mm to be indicative of higher and lower 12-month scores. Compared with models that contained clinical predictors only, models additionally including tissue bridges had significantly improved prediction accuracy across all three centres., Interpretation: Tissue bridges, measured in the first few weeks after SCI, are associated with short-term and long-term clinical improvement. Thus, tissue bridges could potentially be used to guide rehabilitation decision making and to stratify patients into more homogeneous subgroups of recovery in regenerative and neuroprotective clinical trials., Funding: Wings for Life, International Foundation for Research in Paraplegia, EU project Horizon 2020 (NISCI grant), and ERA-NET NEURON., Competing Interests: Declaration of interests DP is supported by a Swiss National Science Foundation Postdoc Mobility Fellowship grant and the National Institutes of Health (NIH), and received best poster awards at the Stanford Bio-X Research Symposium and the Scientific Meeting of the International Spinal Cord Society. ACS is supported by NIH and Boettcher Foundation's Webb-Waring Biomedical Research Program. KAW is supported by grants from NIH and received honoraria for a lecture at the Massachusetts General Hospital Spinal Cord Workshop and grant review for the Norwegian Chiropractors' Research Foundation. OM declares provision of study datasets from BG Trauma Center Murnau. IL received a project grant from Wings for Life. JMS is the Scientific Director for Wings for Life Spinal Cord Research Foundation (a non-governmental organisation). AT received support for the present manuscript from the University College London (UCL)/UCL Hospitals NHS Foundation Trust National Institute for Health and Care Research Biomedical Research Centre; support from Eisai and German Aerospace Center Health Research (ERA-NET NEURON), paid to their institution; fees for work on the MSIS-29 Impact Scale to their institution; consulting fees from Sandoz Global Advisory and Novartis; honoraria from SAGE Publications for position as Editor-in-Chief and from Lancet Neurology for position as editorial board member; honoraria for lectures from Fundacio Privada Cemcat (November, 2023) and Inselspital MS Symposium (Bern; February, 2023); honorarium from the Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong (September, 2023) for academic review; fees for scientific review from the Health Research Board Ireland (January, 2024); fees for evaluation of research groups from Sant Pau Biomedical Research Institute (February, 2024); support for travel from the Clinical Trials Committee of the International Progressive MS Alliance, the National Multiple Sclerosis Society (USA) as member of the Research Programs Advisory Committee, Fundacio Privada Cemcat, European Committee for Treatment and Research in Multiple Sclerosis, European Charcot Foundation, Sobek Foundation SAB, BALCONE, MS Symposium (Bern), Annual MS Conference Poland, and Polish Neurological Society; is a guarantor of BRAIN; was a trustee of the National Brain Appeal, The National Hospital for Neurology and Neurosurgery (finished September, 2023); is Chair of Scientific Ambassadors for the Stop MS Appeal Board, MS Society UK; and is a board member of the European Charcot Foundation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)