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There is much controversy about the potential impact of spinal cord injury (SCI) on brain anatomy and function, which is mirrored in the substantial divergence of findings between animal models and human imaging studies. Given recent advances in quantitative magnetic resonance imaging (MRI) we sought to tackle the unresolved question about the link between the presumed injury associated volume differences and underlying brain tissue property changes in a cohort of chronic complete SCI patients. Using the established computational anatomy methods of voxel-based morphometry (VBM) and voxel-based quantification (VBQ), we performed statistical analyses on grey and white matter volumes as well as on parameter maps indicative for myelin, iron, and free tissue water content in the brain of complete SCI patients (n = 14) and healthy individuals (n = 14). Our regionally unbiased white matter analysis showed a significant volume reduction of the dorsal aspect at the junction between the most rostral part of the spinal cord and the medulla oblongata consistent with Wallerian degeneration of proprioceptive axons in the dorsal column tracts in SCI subjects. This observation strongly correlated with spinal cord atrophy assessed by quantification of the spinal cord cross-sectional area at the cervical level C2/3. These findings suggest that Wallerian degeneration of the dorsal column tracts represents a main contributor to the observed spinal cord atrophy, which is highly consistent with preclinical histological evidence of remote changes in the central nervous system secondary to SCI. Structural changes in other brain regions representing remote changes in the course of chronic SCI could neither be confirmed by conventional VBM nor by VBQ analysis. Whether and how MRI based brain morphometry and brain tissue property analysis will inform clinical decision making and clinical trial outcomes in spinal cord medicine remains to be determined.

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BACKGROUND: Accurate predictors of neurological recovery after cervical spinal cord injury are needed. Particularly, to tailor adequate rehabilitation plans. However, objective and quantifiable predictors are sparse. METHODS: Within the prospective European Multicenter Study about Spinal Cord Injury (EMSCI) registry, cervical spinal cord injury patients are monitored at fixed follow up visits (2, 4, 12, 24, and 48 weeks after injury) clinically and with ulnar nerve electroneurography. Associations of ulnar nerve compound muscle action potential amplitudes (CMAP) with American Spinal Cord Injury Association (ASIA) impairment scale (AIS) grades over time were analyzed using linear mixed modeling. Applying logistic regression, the prognostic value of within 4-week ulnar nerve CMAP for 1-year AIS was analyzed. To account for missing data, (1) last observation carried forward and (2) multiple imputation methods were applied. For model derivation, our centers' cohort (EMSCI-HD) was analyzed. For model validation the cohort of other centers (EMSCI-nonHD) was used. RESULTS: In the EMSCI-HD cohort, the median age (interquartile range (IQR)) was 52 (34-67) years. 58% were male. The initial AIS distribution was: A = 31%, B = 17%, C = 30%, and D = 22%). In the EMSCI-nonHD cohort, the median age was 49 (32-65) years. Compared to the EMSCI-HD cohort more patients were male (79%, p = 0.0034). The AIS distribution was: A = 33%, B = 13%, C = 21%, and D = 33%).In complete-case mixed model analyses (EMSCI-HD: n = 114; EMSCI-nonHD: n = 508) higher ulnar nerve CMAP were associated with better AIS grades over the entire follow up period. In complete-case logistic regression (EMSCI-HD: n = 90; EMSCI-nonHD: n = 444) higher ulnar nerve CMAP was an independent predictor of better AIS grades. The odds ratio for within 4-week ulnar nerve CMAP to predict 1-year AIS grade D versus A-C in the EMSCI-HD cohort was 1.24 per millivolt (confidence interval 1.07-1.44). The model was validated in an independent cervical spinal cord injury (EMSCI-nonHD) cohort (odds ratio 1.09, confidence interval 1.03-1.17). CONCLUSIONS: In cervical spinal cord injury, the consideration of early ulnar nerve CMAP improves prognostic accuracy, which is of particular importance in patients with clinical grading uncertainties.

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BACKGROUND AND PURPOSE: Direct comparison of symptomatic intracerebral hemorrhage (sICH) rates among different thrombolysis studies is complicated by the variability of definitions of sICH. The prediction of outcome still remains unclear. METHODS: Baseline data and clinical courses of patients treated with thrombolytic therapy were collected in a prospective database. The 3-month outcome was evaluated using the modified Rankin Scale. Results of 24-hour follow-up imaging were reevaluated by at least 2 independent raters. Four common definitions of sICH (National Institute of Neurological Disorders and Stroke [NINDS], European Cooperative Acute Stroke Study [ECASS] 2, Safe Implementation of Thrombolysis in Stroke [SITS], ECASS 3) were applied. Kappa interrater statistics were calculated. Our objective was to find the sICH definition with the highest predictive value for mortality, poor (modified Rankin Scale 5 or 6) and unfavorable (modified Rankin Scale ≥3) clinical outcome after 90 days. RESULTS: The data of 314 patients were analyzed. The NINDS definition revealed the highest sICH rate (7.7%); the lowest rate was found for the ECASS 3 definition (3.2%) of sICH. The highest interrater agreement was found for the ECASS 2 definition (κ 0.85) and the lowest for the NINDS definition (κ 0.57). Patients with sICH according to the SITS definition had the highest risk for death (OR, 14.4) and poor outcome (OR, 26.6). CONCLUSIONS: None of the different definitions contains an optimal combination of prediction of mortality and outcome and a high interrater agreement rate. For the clinical evaluation of mortality, we recommend using the SITS definition; for studies needing a high interrater agreement rate, we recommend using the ECASS 2 definition. Due to the lack of 1 single optimal definition, future thrombolytic trials should preferably use different definitions.

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