The Association of MRI-Derived Tissue Bridge Morphometrics with Baseline Impairment and Recovery in Traumatic Spinal Cord Injury: A Subanalysis of the RISCIS Randomized Controlled Trial

Early prognostic biomarkers are essential to optimize treatment and trial design in spinal cord injury (SCI). The Riluzole in SCI Study (RISCIS), a multicenter randomized controlled trial, provided evidence on secondary analyses that riluzole improved functional recovery in acute cervical SCI. The current analysis uses magnetic resonance imaging (MRI) to assess lesion and tissue bridge morphometrics against baseline impairment, functional recovery, and treatment response in RISCIS participants. In this preplanned ambispective subanalysis, 24 participants underwent T2-weighted MRI for acute cervical SCI together with neurological and functional assessments to 12 months. A subset also had diffusion tensor imaging (DTI), used to extract fractional anisotropy (FA) values. Segmentation with the Spinal Cord Toolbox (v7.2) gave ventral, dorsal, and total tissue-bridge widths and lesion volume and length. Associations with American Spinal Injury Association Impairment Scale (AIS) grade, upper extremity motor score (UEMS) and total motor score (TMS), lower extremity motor score (LEMS), light touch and pinprick sensory scores, Spinal Cord Independence Measure (SCIM), and Short Form-36 (SF-36) domains at baseline and follow-up were analyzed with regression models adjusted for age and sex. Overall recovery across TMS, SCIM, and SF-36 Physical Component Summary was analyzed with an O’Brien-style global statistical test (GST). Interactions tested whether bridge metrics modified riluzole’s effect. At baseline, greater ventral ( β = 9.65, p = 0.017) and total ( β = 6.16, p = 0.021) tissue-bridge widths were associated with higher TMS, and ventral width with higher UEMS ( β = 6.61, p = 0.010). Larger dorsal (odds ratio [OR] = 21.92, p = 0.013), ventral (OR = 4.91, p = 0.049), and total (OR = 3.70, p = 0.019) bridges corresponded to less severe baseline AIS grade. Pinprick scores increased with ventral ( β = 26.56, p = 0.020) and total ( β = 17.50, p = 0.023) bridge width, and light touch scores increased with total bridge width ( β = 16.22, p = 0.045). No imaging metric was associated with LEMS. These individual-metric associations were nominally significant but did not survive correction. In GST analyses, larger ventral ( T = 4.63, p = 0.012, p ′= 0.048) and total ( T = 4.30, p = 0.019, p ′=0.048) bridges predicted greater overall recovery; both remained significant after correction and were stable across sensitivity analyses. Ventral and total bridge width showed nominally significant interactions with riluzole treatment for upper-limb motor recovery. Exploratory DTI findings were inconclusive and sensitive to individual observations: both the FA–recovery association and the observation of poor outcome despite a preserved tissue bridge rested on a single participant. Overall, we found that midsagittal tissue-bridge width measured ∼72 h after injury from standard-of-care T2-weighted MRI was associated with baseline injury severity and multidomain functional recovery, at a timepoint substantially earlier than the 1 month at which tissue bridges have previously been quantified. Because edema may obscure lesion margins this early, acute bridge widths may underestimate spared tissue resolvable later. The treatment-interaction observation is hypothesis-generating and requires prospective confirmation. These findings support MRI-derived tissue bridges as candidate biomarkers for prognostication and enrichment of neuroprotective trials in SCI.