Lukas Grassner

Purpose Imaging modalities, particularly magnetic resonance imaging (MRI), have become the gold standard for assessing lesion characteristics of traumatic spinal cord injuries (SCI). Diffusion tensor imaging (DTI), an advanced MRI technique, offers insights into microstructural changes in white matter tracts. While previous studies focused on either acute or chronic SCI, few have examined longitudinal changes during the transition from acute to chronic stages of injury. This study addresses this gap by analyzing the evolution of DTI metrics over the first year following cervical SCI. Methods This prospective longitudinal study involved 52 patients with traumatic cervical SCI. MRI and neurological examinations using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) were performed 1 month, 3 months, and 1 year post-injury. Linear mixed model analyses assessed DTI measures over time. Results Fractional anisotropy (FA) values gradually decreased in the reference area at the cranio-cervical junction (C0–C4; p < 0.001), indicating ongoing tissue degeneration up to one year after injury, independent of initial clinical severity. FA values at the lesion site correlated moderately with the total motor score 1 month post-SCI (R = 0.37, p = 0.033). Mean diffusivity (MD) increased significantly over time (p < 0.001), suggesting progressive microstructural changes. Axial diffusivity (AD) decreased until 3 months after injury (p < 0.001), then returned to its initial values by 1 year, reflecting dynamic pathophysiological events. Conclusion This study highlights the potential of DTI for monitoring microstructural changes after SCI. Longitudinal imaging offers insights into evolving pathology, supports prognostic modeling, and may aid treatment monitoring and outcome prediction. Graphic abstract

Magnetic resonance imaging (MRI) remains the gold standard for evaluating spinal cord tissue damage after spinal cord injury (SCI). Several MRI findings may have some prognostic potential, but their evolution over time, especially from the subacute to the chronic phase has not been studied extensively. We performed a prospective observational longitudinal study exploring the evolution of MRI parameters from the subacute to chronic phase after human traumatic cervical SCI. The study, conducted between 2016 and 2021, involved standardized neurological examinations and MRI scans 1 month, 3 months, and 1 year after SCI. The study cohort comprises 52 patients with cervical SCI. Patients were classified into AIS grades (American Spinal Injury Association Impairment Scale), and neurological recovery was assessed using the Integrated Neurological Change Score. The MRI protocol included various routine sequences, allowing the evaluation of established parameters such as intramedullary hemorrhage, lesion dimensions, maximum spinal cord compression, and various grading scales. The persistence of intramedullary hemorrhage one month after injury was associated with worse lower extremity motor scores and pinprick values after 3 months, and also in the chronic phase. In addition, dorsal column T2-weighted hyperintensities detected 3 months post-injury and in the chronic phase were related to lower pinprick sensory scores. The basic score and Sagittal Grade at 1 month were predictive for motor function 3 months after SCI and for neurological recovery between 1 and 3 months after injury. The study contributes valuable insights into the utility of routine MRI sequences for evaluating traumatic cervical SCI during the subacute to chronic phase. The identified MRI parameters and scores offer prognostic information and could support clinical decision-making.

Assessing the extent of the intramedullary lesion after spinal cord injury (SCI) might help to improve prognostication. However, because the neurological level of injury impacts the recovery potential of SCI patients, the question arises whether lesion size parameters and predictive models based on those parameters are affected as well. In this retrospective observational study, the extent of the intramedullary lesion between individuals who sustained cervical and thoracolumbar SCI was compared, and its relation to clinical recovery was assessed. In total, 154 patients with subacute SCI (89 individuals with cervical lesions and 65 individuals with thoracolumbar lesions) underwent conventional clinical magnetic resonance imaging 1 month after injury and clinical examination at 1 and 12 months. The morphology of the focal lesion within the spinal cord was manually assessed on the midsagittal slice of T ₂ -weighted magnetic resonance images and compared between cervical and thoracolumbar SCI patients, as well as between patients who improved at least one American Spinal Injury Association Impairment Scale (AIS) grade (converters) and patients without AIS grade improvement (nonconverters). The predictive value of lesion parameters including lesion length, lesion width, and preserved tissue bridges for predicting AIS grade conversion was assessed using regression models (conditional inference tree analysis). Lesion length was two times longer in thoracolumbar compared with cervical SCI patients (F = 39.48, p < 0.0001), whereas lesion width and tissue bridges width did not differ. When comparing AIS grade converters and nonconverters, converters showed a smaller lesion length (F = 5.46, p = 0.021), a smaller lesion width (F = 13.75, p = 0.0003), and greater tissue bridges (F = 12.87, p = 0.0005). Using regression models, tissue bridges allowed more refined subgrouping of patients in AIS groups B, C, and D according to individual recovery profiles between 1 month and 12 months after SCI, whereas lesion length added no additional information for further subgrouping. This study characterizes differences in the anteroposterior and craniocaudal lesion extents after SCI. The two times greater lesion length in thoracolumbar compared with cervical SCI might be related to differences in the anatomy, biomechanics, and perfusion between the cervical and thoracic spines. Preserved tissue bridges were less influenced by the lesion level while closely related to the clinical impairment. These results highlight the robustness and utility of tissue bridges as a neuroimaging biomarker for predicting the clinical outcome after SCI in heterogeneous patient populations and for patient stratification in clinical trials.

Background: The discovery of new prognostic biomarkers following spinal cord injury (SCI) is a rapidly growing field that could help uncover the underlying pathological mechanisms of SCI and aid in the development of new therapies. To date, this search has largely focused on the initial days after the lesion. However, during the subacute stage of SCI (weeks to months after the injury), there remains potential for sensorimotor recovery, and numerous secondary events develop in various organs. Additionally, the confounding effects of early interventions after the injury are less likely to interfere with the results. Methods: In this study, we conducted an untargeted proteomics analysis to identify biomarkers of recovery in blood serum samples during the subacute phase of SCI patients, comparing those with strong recovery to those with no recovery between 30 and 120 days. We analyzed the fraction of serum that is depleted of the most abundant proteins to unmask proteins that would otherwise go undetected. Linear models were used to identify peptides and proteins related to neurological recovery and we validated changes in some of these proteins using Enzyme-linked Immunosorbent Assay (ELISA). Results: Our findings reveal that differences in subacute recovery after SCI (from 30 to 120 days) are associated with an enrichment in proteins involved in inflammation, coagulation, and lipid metabolism. Technical validation using commercial ELISAs further confirms that high levels of SERPINE1 and ARHGAP35 are associated with strong neurological recovery, while high levels of CD300a and DEFA1 are associated with a lack of recovery. Conclusions: Our study identifies new candidates for biomarkers of neurological recovery and for novel therapeutic targets after SCI.

Background: The epidemiological international landscape of traumatic spinal cord injury (SCI) has evolved over the last decades along with given inherent differences in acute care and rehabilitation across countries and jurisdictions. However, to what extent these differences may influence neurological and functional recovery as well as the integrity of international trials is unclear. The latter also relates to historical clinical data that are exploited to inform clinical trial design and as potential comparative data.Methods: Epidemiological and clinical data of individuals with traumatic and ischemic SCI enrolled in the European Multi-Center Study about Spinal Cord Injury (EMSCI) were analyzed. Mixed-effect models were employed to account for the longitudinal nature of the data, efficiently handle missing data, and adjust for covariates. The primary outcomes comprised demographics/injury characteristics and standard scores to quantify neurological (i.e., motor and sensory scores examined according to the International Standards for the Neurological Classification of Spinal Cord Injury) and functional recovery (walking function). We externally validated our findings leveraging data from a completed North American landmark clinical trial.Results: A total of 4601 patients with acute SCI were included. Over the course of 20 years, the ratio of male to female patients remained stable at 3:1, while the distribution of age at injury significantly shifted from unimodal (2001/02) to bimodal distribution (2019). The proportional distribution of injury severities and levels remained stable with the largest percentages of motor complete injuries. Both, the rate and pattern of neurological and functional recovery, remained unchanged throughout the surveillance period despite the increasing age at injury. The findings related to recovery profiles were confirmed by an external validation cohort (n=791). Lastly, we built an open-access and online surveillance platform (“Neurosurveillance”) to interactively exploit the study results and beyond.Conclusions: Despite some epidemiological changes and considerable advances in clinical management and rehabilitation, the neurological and functional recovery following SCI has remained stable over the last two decades. Our study, including a newly created open-access and online surveillance tool, constitutes an unparalleled resource to inform clinical practice and implementation of forthcoming clinical trials targeting neural repair and plasticity in acute spinal cord injury.

Background: Nearly every individual sustaining traumatic spinal cord injury receives multiple types and classes of medications to manage a litany of secondary complications. Prior clinical studies and evidence from animal models suggest that several of these medications could enhance or impede endogenous neurological recovery. However, there is a knowledge gap surrounding the spectrum of pharmacologic agents typically administered in the routine management of spinal cord injury. Objective: To systematically determine the types of medications commonly administered, alone or in combination, in the acute to subacute phase of spinal cord injury. Methods: We conducted an analysis of two largescale cohorts (the Sygen interventional trial and the SCIRehab observational cohort study) to determine what constitutes “ standards of acute pharmacological care” after spinal cord injury. Concomitant medication use, including dosage, timing and reason for administration, was tracked. Descriptive statistics were used to describe the medications administered within the first 60 days after spinal cord injury. Results: Across 2040 individuals with spinal cord injury, 775 unique medications were administered within the two months after injury. On average, patients enrolled in the Sygen trial received 9.9 ± 4.9 (range 0-34), 14.3 ± 6.3 (range 1-40), 18.6 ± 8.2 (range 0-58), and 21.5 ± 9.7 (range 0-59) medications within the first 7, 14, 30, and 60 days post-injury, respectively. Patients enrolled in the SCIRehab cohort study received on average 1.7 ± 1.7 (range 0-11), 3.7 ± 3.7 (range 0-24), 8.5 ± 6.3 (range 0-42), and 13.5 ± 8.3 (range 0-52) medications within the first 7, 14, 30, and 60 days post-injury, respectively. Polypharmacy was commonplace (up to 43 medications per day per patient). Approximately 10% of medications were administered acutely as prophylaxis (e.g., against the development of pain or infections). Conclusions: To our knowledge, this was the first time acute pharmacological practices have been comprehensively examined after spinal cord injury. Our study revealed a high degree of polypharmacy in the acute stages of spinal cord injury, with potential to both positively and negatively impact neurological recovery. This data may provide key insight to achieve better understanding of how the acute pharmacological management of spinal cord injury affects long-term recovery. All results can be interactively explored on the R _X SCI web site ( https://jutzelec.shinyapps.io/RxSCI/ ) and GitHub repository ( https://github.com/jutzca/Acute-Pharmacological-Treatment-in-SCI/ ).

The world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic. Little is known about the effects of a pandemic on non-elective neurosurgical practices, which have continued under modified conditions to reduce the spread of COVID-19. This knowledge might be critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures during the COVID-19 pandemic. A retrospective, multi-centre observational cohort study among neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of neurosurgical emergencies and related 30-day mortality rates were determined for a period reflecting the peak pandemic of the first wave in all participating countries (i.e. March 16th–April 15th, 2020), and compared to the same period in prior years (2017, 2018, and 2019). A total of 4,752 emergency neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic, there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas. Thirty-day mortality did not significantly increase overall or for any of the conditions examined during the peak of the pandemic. The neurosurgical community in these three European countries observed a decrease in the incidence of some neurosurgical emergencies with 30-day mortality rates comparable to previous years (2017–2019). Lower incidence of neurosurgical cases is likely related to restrictions placed on mobility within countries, but may also involve delayed patient presentation.

The absence of effective pharmacological interventions in acute traumatic spinal cord injury is a major problem in its management. A critical barrier in identifying such interventions lies in the vast heterogeneity of recovery profiles, which masks the potential efficacy of treatments in clinical trials. To determine the impact of temporal recovery profiles on long-term functional independence, we used EMSCI (European Multicenter Study about Spinal Cord Injury) data. Total motor scores from the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) and the Spinal Cord Independence Measure (SCIM) were used to assess neurological and functional outcomes, respectively. We developed a classification method consisting of thresholding and unsupervised machine learning clustering and applied it to the total motor score profiles. Comparing SCIM scores between classes revealed that functional independence is significantly higher among patients displaying advanced neurological recovery profile. Our study suggests that the evaluation of temporal recovery profiles can provide novel insights in spinal cord injury clinical trials.