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Spinal cord injury (SCI) results in intramedullary microvasculature disruption and blood perfusion deficit at and remote from the injury site. However, the relationship between remote vascular impairment and functional recovery remains understudied. We characterized perfusion impairment in vivo , rostral to the injury, using magnetic resonance imaging (MRI), and investigated its association with lesion extent and impairment following SCI. Twenty-one patients with chronic cervical SCI and 39 healthy controls (HC) underwent a high-resolution MRI protocol, including intravoxel incoherent motion (IVIM) and T2*-weighted MRI covering C1-C3 cervical levels, as well as T2-weighted MRI to determine lesion volumes. IVIM matrices (i.e., blood volume fraction, velocity, flow indices, and diffusion) and cord structural characteristics were calculated to assess perfusion changes and cervical cord atrophy, respectively. Patients with SCI additionally underwent a standard clinical examination protocol to assess functional impairment. Correlation analysis was used to investigate associations between IVIM parameters with lesion volume and sensorimotor dysfunction. Cervical cord white and gray matter were atrophied (27.60% and 21.10%, p < 0.0001, respectively) above the cervical cord injury, accompanied by a lower blood volume fraction (-22.05%, p < 0.001) and a higher blood velocity-related index (+38.72%, p < 0.0001) in patients with SCI compared with HC. Crucially, gray matter remote perfusion deficit correlated with larger lesion volumes and clinical impairment. This study shows clinically eloquent perfusion deficit rostral to a SCI, its magnitude driven by injury severity. These findings indicate trauma-induced widespread microvascular alterations beyond the injury site. Perfusion MRI matrices in the spinal cord hold promise as biomarkers for monitoring treatment effects and dynamic changes in microvasculature integrity following SCI.

The extent of ambulatory recovery after motor incomplete spinal cord injury (miSCI) differs considerably amongst affected persons. This makes individual outcome prediction difficult and leads to increased within-group variation in clinical trials. The aims of this study on subjects with miSCI were: (1) to rank the strongest single predictors and predictor combinations of later walking capacity; (2) to develop a reliable algorithm for clinical prediction; and (3) to identify subgroups with only limited recovery of walking function. Correlation and logistic regression analyses were performed on a dataset of 90 subjects with tetra- or paraparesis, recruited in a prospective European multicenter study. Eleven measures obtained in the subacute injury period, including clinical examination, tibial somatosensory evoked potentials (tSSEP), and demographic factors, were related to ambulatory outcome (WISCI II, 6minWT) 6 months after injury. The lower extremity motor score (LEMS) alone and in combination was identified as most predictive for later walking capacity in miSCI. Ambulatory outcome of subjects with tetraparesis was correctly predicted for 92% (WISCI II) or 100% (6minWT) of the cases when LEMS was combined with either tSSEP or the ASIA Impairment Scale, respectively. For individuals with paraparesis, prediction was less distinct, mainly due to low prediction rates for individuals with poor walking outcome. A clinical algorithm was generated that allowed for the identification of a subgroup composed of individuals with tetraparesis and poor ambulatory recovery. These data provide evidence that a combination of predictors enables a reliable prediction of walking function and early patient stratification for clinical trials in miSCI.

Clinical recovery after a lesion of the central nervous system (CNS) can be attributed to mechanisms of functional compensation, neural plasticity, and/or repair. The relative impact of each of these mechanisms after a human spinal cord injury (SCI) has been explored in a prospective European multi-center study in 460 acute traumatic SCI subjects. Functional (activities of daily living and ambulatory capacity), neurological (sensory-motor deficits), and spinal conductivity (motor- and somato-sensory evoked potentials) measures were repeatedly followed over 12 months. In accordance with previous studies, complete SCI subjects (cSCI; n = 217) improved in activities of daily living unrelated to changes of the neurological condition, while incomplete SCI subjects (iSCI; n = 243) showed a greater functional and neurological recovery. The functional recovery in iSCI subjects was not related to an improvement of spinal conductivity, as reflected in unchanged latencies of the evoked potentials. This is in line with animal studies, where spinal conductivity of damaged spinal tracts has been reported to remain unchanged. These findings support the assumption that functional recovery occurs by compensation, especially in cSCI and by neural plasticity leading to a greater improvement in iSCI. Relevant repair of damaged spinal pathways does not take place.

Patients suffering from complete spinal cord injury (SCI) are the most likely candidates for the application of new interventions for neural repair and regeneration. It is assumed that some of these treatments will have their strongest impact at the segmental level. Therefore, it is important to evaluate the clinical relevance of potential changes at the segmental levels concerning both improvement and deterioration. Data of 98 motor complete SCI patients were derived from the European Multicenter Study of Human Spinal Cord Injury database. Six months after injury, the ASIA motor score and Spinal Cord Independence Measure (SCIM) were assessed as dependent variables (linear regression analysis) to disclose the difference between each segment. Separate analyses using linear regression for tetraplegic patients (n = 39) and paraplegic patients with thoracic lesions (n = 54) were performed to calculate the difference between each spinal segment. In tetraplegic patients, both the ASIA motor score and the SCIM revealed relevant differences per spinal segment (9 and 4 points, respectively) while in paraplegic patients there was no difference for the SCIM and the ASIA motor score between T2 and T8. We suggest that in complete tetraplegic patients, changes of even one spinal segment will either improve or degrade both motor function and independence. Segmental changes at the thoracic level are not assessable by the ASIA motor score and SCIM tests. Therefore, the assessment of efficacy and safety in thoracic patients by these two tests has limited value when applied to cervical SCI. These findings may be considered in clinical trials for the evaluation of beneficial effects and risk management when treating patients with spinal cord injury.