Prognostic value of tissue bridges in cervical spinal cord injury: a longitudinal, multicentre, retrospective cohort study

Abstract

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.

Figure 1:. Overview of patient flow through the study

Flow diagram highlighting the number of patients included at each stage of fractional outcome regression analysis and reasons for exclusion. Of 227 patients with acute cervical SCI, all were followed-up at 3-months post-SCI, and 136 patients also had a 12-months follow-up assessment. Inclusion and exclusion of patients are specific to distinct sensorimotor scores analysed. Reasons for dropouts included missing scores at baseline or follow-up, maxed out scores at baseline, or a normalized recovery rate of ≤–50%, attributable to the subjective nature of the neurologic assessment and its susceptibility to comorbidities. LEMS, lower extremity motor score; LT, light touch score; MS, total motor score; PP, pin prick score; SCI, spinal cord injury; UEMS, upper extremity motor score.

Figure 2:. Association between width of preserved tissue bridges and neurological recovery

This graph illustrates the association between the width of tissue bridges and (A) 3-months as well as (B) 12-months baseline-adjusted recovery in motor score (blue), pin prick score (red), and light touch score (green). Each model fit indicates the increase in neurological recovery per additional millimeter in tissue bridge width. Midsagittal tissue bridge width on the x-axis represents the sum of ventral and dorsal tissue bridges’ width. Error bars show 95% confidence intervals. For details, please refer to the methods section.