OBJECTIVE:The aims of the study were to reflect on the methodological and conceptual evolution of the Swiss Spinal Cord Injury Cohort Study, summarize its key scientific contributions, and illustrate how such a cohort can shape future directions in spinal cord injury research, care, and policy. DESIGN:We conducted a bibliometric analysis to examine the Swiss Spinal Cord Injury Cohort Study's publication trends, leading authors, thematic areas, influential papers, and landmark findings related to morbidity, mortality, and functioning among individuals with spinal cord injury in Switzerland. RESULTS:The Swiss Spinal Cord Injury Cohort Study comprises two components: the community survey, collecting self-reported data on functioning, morbidity, and mortality in chronic spinal cord injury, and the inception cohort, which enables long-term clinical and biological monitoring of newly injured individuals. Since its inception, the Swiss Spinal Cord Injury Cohort Study has generated 174 publications, primarily from the community survey, with increasing contributions from the inception cohort. Notably, 34% of publications stem from the Swiss Spinal Cord Injury Cohort Study nested projects, highlighting the study's capacity to support additional targeted research. Key themes included secondary health conditions, mental health, healthcare use, and social participation, with growing interest in lifestyle and behavioral factors. CONCLUSIONS:The Swiss Spinal Cord Injury Cohort Study has become a key resource for advancing spinal cord injury research. Its robust, interprofessionnal design provides a foundation for translating research into improved care, policy, and quality of life for individuals with SCI.

The Integrated Neurological Change Score (INCS) combines changes in sensory and motor subscores from the International Standards for Spinal Cord Injury Classification (ISNCSCI) into a composite measure. We evaluated the INCS sensitivity to therapeutic outcomes, robustness against ceiling effects, and association to functional improvement in patients with acute cervical spinal cord injury (SCI). To this end, we conducted a retrospective analysis of data from the Nogo Inhibition in Spinal Cord Injury (NISCI) clinical trial alongside a matched cohort from the European Multicenter Study about Spinal Cord Injury (EMSCI). The NISCI trial assessed the safety and efficacy of the anti-Nogo-A antibody (NG-101) in acute cervical SCI, reporting a potential therapeutic effect in motor incomplete patients. Our findings show that the sensitivity of INCS to the effect of NG-101 is comparable to that obtained employing the changes in the Upper Extremity Motor Score (the primary outcome in the NISCI trial). Moreover, the INCS is less susceptible to ceiling effects compared to measures of upper and lower extremity or total motor scores, as observed in the NISCI trial and in the matched EMSCI cohort. This robustness may facilitate the design of more inclusive clinical trials without compromising statistical power. Finally, INCS correlates strongly with functional outcomes in self-care and walking ability, outperforming ISNCSCI motor scores. In conclusion, the INCS represents a sensitive measure of neurological change corroborating the value of ISNCSCI standards for use in SCI trials.

Background and objective Accurate segmentation of the spinal canal is important for quantitative analysis in various spinal pathologies. However, manual delineation is time-consuming and subject to inter- and intra-rater variability, especially in large multi-center studies. This work aimed to develop an automatic model to segment the spinal canal, defined as the dural sac, from T2-weighted (T2w) magnetic resonance imaging sequences. Methods This retrospective multi-site model-development study used a 3D convolutional neural network (nnUNetv2 framework) and was trained using an active learning strategy on a multi-site dataset (n > 18) with varying imaging parameters (resolution, field-of-view). The dataset included T2w images (TSE and 3D CISS) covering the cervical, thoracic, and lumbar spine from both healthy participants and patients with conditions like degenerative cervical myelopathy and traumatic spinal cord injury, including post-operative. The model was tested on unseen T2w images from two sites, including a range of acquisition protocols and clinical presentations, from mild to severe canal compression, to evaluate the performance and robustness. Comparisons were made against state-of-the-art (SOTA) models. Ethics approvals were obtained at each contributing institution; approval identifiers are reported in the main manuscript Results The proposed model achieved strong and consistent quantitative performance (e.g. mean Dice similarity coefficient of 0.95 and mean Hausdorff distance of 1.17 mm² on a healthy thoraco-lumbar test cohort), outperforming the SOTA. Notably, it showed superior robustness in challenging cases of severe spinal canal stenosis, achieving Dice scores > 0.9 where SOTA models dropped below 0.5. Conclusions The model generalized well across different MRI vendors, sequences, resolutions, and fields-of-view, for both healthy individuals and patients. The model is open-source and available in the Spinal Cord Toolbox v6.4 and higher.

OBJECTIVES:Focal spinal cord lesions occur across a variety of neurological diseases including non-traumatic cervical myelopathies which can lead to neuropathic pain. Currently, the degree to which signs and symptoms of neuropathic pain correlate with functional impairments and/or anatomical deficits remains unclear. This study aimed to identify structural and functional determinants associated with neuropathic pain in individuals with focal spinal lesions. METHODS:Individuals fulfilling the diagnostic criteria of neuropathic pain were identified among individuals with cervical myelopathy presenting with focal spinal lesions. Lesion volume and the extent of structural damage affecting the spinothalamic tract, dorsal columns, dorsal horn, and ventral horn were evaluated with tract-specific MRI of the cervical spinal cord. Quantitative sensory testing (QST) (i.e., thermal/mechanical thresholds) was performed at the most affected skin area. Additionally, contact heat-evoked potentials (CHEPs) were acquired following stimulation at the most affected skin area to objectively assess the functional integrity of the spinothalamic tract. RESULTS:MRI-derived structural damage was similar for individuals with (n=8) and without (n=8) neuropathic pain in all regions of interest (p>0.05). Mechanical hyperalgesia upon QST was observed in both groups. However, functional preservation of the spinothalamic system, measured by CHEPs, was present in 87 % of individuals with neuropathic pain, compared to 38 % of pain-free individuals (p=0.039). CONCLUSIONS:These observations suggest that segmental hyperexcitability resulting from structural spinal cord damage, in combination with residual sparing of spinothalamic afferents, may represent a key pathophysiological constellation contributing to central neuropathic pain following focal spinal lesions.

Abstract NG101 is a recombinant antibody that neutralizes the nerve growth inhibitor Nogo-A, promoting neural repair and improving upper extremity motor function in spinal cord injury (SCI). This study evaluated spinal cord MRI biomarkers to detect treatment-related structural changes and enhance patient stratification using data from 106 participants with acute cervical SCI in the phase 2b NISCI trial. We assessed lesion volume, tissue bridges, and remote changes in cross-sectional cord area (CSA), and tract-specific myelin-sensitive magnetization transfer saturation (MTsat) over six months. Compared to placebo, NG101-treated participants exhibited faster lesion volume reduction and a slower decline of CSA and MTsat in the corticospinal tracts and dorsal columns. Crucially, multimodal stratification incorporating MRI and electrophysiological measures substantially enhanced the detection of clinical treatment effects. These findings suggest NG101 slows trauma-induced progressive macro- and microstructural degeneration or promotes fiber sprouting. Combining MRI with electrophysiology enables sensitive detection of treatment effects and efficient trial designs. ClinicalTrials.gov identifier: NCT03935321.

Morphometric measures derived from spinal cord segmentations can serve as diagnostic and prognostic biomarkers in neurological diseases and injuries affecting the spinal cord. For instance, the spinal cord cross-sectional area can be used to monitor cord atrophy in multiple sclerosis and to characterize compression in degenerative cervical myelopathy. While robust, automatic segmentation methods to a wide variety of contrasts and pathologies have been developed over the past few years, whether their predictions are stable as the model is updated using new datasets has not been assessed. This is particularly important for deriving normative values from healthy participants. In this study, we present a spinal cord segmentation model trained on a multisite (n = 75 sites, 1,631 participants) dataset, including 9 different MRI contrasts and several spinal cord pathologies. We also introduce a lifelong learning framework to automatically monitor the morphometric drift as the model is updated using additional datasets. The framework is triggered by an automatic GitHub Actions workflow every time a new model is created, recording the morphometric values derived from the model’s predictions over time. As a real-world application of the proposed framework, we employed the spinal cord segmentation model to update a recently introduced normative database of healthy participants containing commonly used measures of spinal cord morphometry. Results showed that (i) our model performs well compared with its previous versions and existing pathology-specific models on the lumbar spinal cord, images with severe compression, and in the presence of intramedullary lesions and/or atrophy achieving an average Dice score of 0.95 ± 0.03; (ii) the automatic workflow for monitoring morphometric drift provides a quick feedback loop for developing future segmentation models; and (iii) the scaling factor required to update the database of morphometric measures is nearly constant among slices across the given vertebral levels, showing minimum drift between the current and previous versions of the model monitored by the framework. The code and model are open source and accessible via Spinal Cord Toolbox v7.0.

Abstract Understanding how the injured nervous system adapts to training is key to advancing rehabilitation across neurological disorders. Using spinal cord injury (SCI) as a model of severe motor-sensory disruption, we investigate whether training-induced structural plasticity in the brain is preserved despite ongoing neurodegeneration. Thirty-two healthy controls and 17 chronic SCI patients (SCI > 6 months) undergo training in a bimanual-bipedal computer-controlled motion game for one hour, four times a week, over one month, with longitudinal microstructural MRI at 3 T, including multiparameter mapping and diffusion MRI. All SCI patients exhibit performance improvements over the training period. These improvements are accompanied by spatially and temporally distributed changes in both gray and white matter, encompassing alterations in volumetric and myelin-sensitive MRI markers. SCI patients demonstrate trajectories of training-induced neuroplasticity that are comparable to, and in some cases greater than, those of healthy controls. Our findings highlight a fundamental capacity of the injured nervous system to adapt through rehabilitation, with evidence from SCI patients showing that—despite severe motor and sensory deficits—the brain can undergo learning-related structural changes. These results suggest that the mechanisms of training-induced plasticity observed in SCI may generalize to rehabilitation across a broad spectrum of neurological disorders.

Abstract The early somatosensory brainstem and thalamic nuclei are classically viewed as relays of peripheral input, yet research in animal models indicates they also receive top-down cortical signals. Whether such processing exists in humans remains unknown. Using cervical spinal cord injury (SCI), in which peripheral somatosensory input is reduced or absent while cortical processing is preserved, we tested whether top-down processing can elicit activation across the somatosensory nuclei. We combined 3 Tesla functional and quantitative MRI data to assess activity and structural properties along the somatosensory hand pathway in a cross-sectional study of 16 individuals with chronic cervical SCI (mean age ± s.e.m.=52.4 ± 3.5 years) and 20 age-, sex-, and handedness-matched able-bodied control subjects (mean age=50.8 ± 3.5 years). Participants were visually cued to make overt or, in cases of hand paralysis, attempted right- and left-hand movements. Activation was quantified across the cuneate nucleus, ventroposterior lateral thalamus, and primary somatosensory hand cortex, while structural properties were assessed using quantitative MRI measures sensitive to myelin and tissue integrity, including magnetisation transfer saturation (MTsat) and effective transverse relaxation rate (R2*), alongside morphometric measures. Despite reduced or absent peripheral input, SCI participants exhibited robust and lateralised activation across all levels of the somatosensory pathway. This pattern persisted even in a participant with complete hand paralysis who lacked bottom-up afferent input during the fMRI task, indicating that top-down processing alone is sufficient to drive activity in early somatosensory relays. We simultaneously observed structural degeneration in the cuneate nucleus of SCI participants, marked by reduced volume and myelin-sensitive metrics (MTsat and R2*), consistent with secondary degeneration. The extent of atrophy was related to time since injury and reduced sensorimotor hand function, but showed no significant relationship with functional activation, suggesting that preserved corticocuneate signalling is not dependent on the degree of structural degeneration. This provides the first evidence that the cuneate nuclei in humans are subject to both bottom- up and top-down somatosensory processing. Although these nuclei are vulnerable to structural atrophy following dorsal column injury, our results suggest that top-down processing remains intact decades after SCI. This may have implications for the development of rehabilitation treatments targeting preserved somatosensory processing after injury.

There are no approved interventional therapies, aside from neurorehabilitation, that enhance neurological recovery after acute traumatic spinal cord injury. A key challenge is the lack of biomarkers surpassing clinical standards for optimal stratification. We evaluated electrophysiological markers of preserved neuronal function to improve enrichment strategies over clinical measures. We hypothesized that participants with preserved electrophysiological markers would achieve greater neurological and functional recovery in response to a plasticity-inducing intervention. We conducted a retrospective stratification analysis of data from the recently completed randomized, placebo-controlled, phase 2b Nogo Inhibition in spinal cord injury (NISCI) trial (NCT03935321) investigating the efficacy of NG101, a recombinant human antibody that neutralizes the neurite outgrowth-inhibiting protein Nogo-A. Participants aged 18-70 years with acute (4-28 days) cervical spinal cord injury were eligible. At screening, all participants underwent clinical neurological examination and electrophysiological recordings (i.e. somatosensory evoked potentials). Treatment effect sizes for the recovery of upper extremity motor scores and spinal cord independence measure of self-care (6-month change) between NG101 and placebo groups were compared for stratification based on clinical versus electrophysiological criteria. Power analyses were conducted to estimate the required sample sizes needed for each method. The cohort included 116 participants (45.5 ± 16.8 years old, 74 NG101 and 41 placebo). Clinical stratification showed greater functional recovery in motor-incomplete participants treated with NG101 versus placebo [estimate 0.02 (95% confidence interval: 0.006-0.038), P = 0.007]. Electrophysiological stratification revealed greater functional recovery in participants with preserved somatosensory evoked potentials treated with NG101 versus placebo [0.04 (0.015-0.054), P < 0.001]. Effect sizes were large for electrophysiological stratification (Cohen's d = 0.94) but small for clinical stratification (Cohen's d = 0.46). Power analyses demonstrated smaller required sample sizes for electrophysiological stratification (required n = 32) versus clinical stratification (required n = 120). This study shows the value of electrophysiology in comparison to clinical measures for biomarker-driven enrichment and improved power in acute spinal cord injury trials. We emphasize the importance of functionally spared neuronal pathways in promoting recovery in response to plasticity-inducing interventions, such as anti-Nogo-A antibodies.

Spinal cord injury (SCI) leads to profound disruptions in sensorimotor processing. Seminal research in nonhuman primates suggests this sensory deprivation causes functional remapping in the primary somatosensory cortex (S1), where somatotopic representations of deprived body parts, such as the hand in cervical SCI, become responsive to touch on intact body parts, such as the face. However, evidence for such remapping in humans remains inconclusive. We investigated face-to-hand remapping in 16 chronic cervical SCI patients (15 male, 1 female) and 21 able-bodied controls (19 male, 2 female) using two fMRI experiments. Experiment 1 employed a lip movement task, while Experiment 2 investigated the full architecture of S1 face reorganization through vibrotactile stimulation of the forehead, lips, and chin. We assessed (1) the level of face activity in the anatomical S1 hand area, (2) cortical shifts in peak face activity, (3) face-part separability in the S1 hand area, and (4) correlations with clinical characteristics that may drive face-to-hand area remapping. Our results revealed no significant evidence in favor of face-to-hand area remapping in tetraplegic patients across markers of face-to-hand remapping during either lip movement or vibrotactile stimulation of face parts. Furthermore, our markers of remapping did not correlate with clinical characteristics. Together, these findings indicate that cortical face-to-hand remapping could not be demonstrated in our cohort of chronic cervical SCI patients, highlighting the need to revisit assumptions of large-scale face-to-hand reorganization after SCI.

Introduction In patients with acute spinal cord injury (SCI) and degenerative cervical myelopathy (DCM), spinal cord compression is considered a main contributor to spinal cord damage, associated with cerebrospinal fluid (CSF) space obstruction. CSF pressure (CSFP) dynamics are studied as a potential indirect biomechanical marker for spinal cord compression, and as a proxy to estimate spinal cord perfusion pressure (SCPP). Research question Evidence for safety and feasibility of CSFP dynamics in clinical trials as well as interrelations with neuroimaging and intraspinal pressure, and relation to preclinical CSFP models. Material and methods Systematic review. This review followed PRISMA guidelines, risk of bias assessment with ROBINS-I tool, PROSPERO registration (CRD42024545629). Results 11 relevant papers were identified (n = 212 patients, n = 194 intraoperative, n = 18 bedside). Risk of bias for safety reporting was low-moderate. Intraoperative CSFP assessments were commonly performed in acute SCI. CSFP was assessed to calculate SCPP (7/11), to evaluate effects from surgical decompression (5/11) and for therapeutic CSF drainage (3/11). The adverse event rate associated with the intrathecal catheter was 8% (n = 15/194). Discussion and conclusion The preliminary safety and feasibility profile of CSFP assessments in spinal cord compression encourages clinical application. However, a deeper risk-benefit analysis is limited as the clinical value is not yet determined, given challenges of defining disease specific critical CSFP and SCPP thresholds. The interrelation between measures of CSFP and neuroimaging is yet to be proven. Targeted preclinical studies are essential to improve our understanding of complex CSFP-cord compression interrelations.

In acute human spinal cord injury (SCI), magnetic resonance imaging (MRI) reveals progressive neuroanatomical changes at the lesion site and in remote regions. Here, we aimed to elucidate the structural underpinnings of these neuroanatomical changes and to characterize their spatiotemporal distribution in a rat contusion SCI model, using both histology and MRI. First, rats subjected to a thoracic contusion SCI (T8) and sham-operated rats were sacrificed at 56 days post-injury (dpi), and SMI-32 immunohistochemistry was used to assess remote axonal degeneration at cervical segments C2-C5. Second, to evaluate the effect of severity and time since injury on axonal degeneration, rats of varying injury severity were sacrificed at 2, 30, and 90 dpi, respectively, followed by SMI-32 immunohistochemistry. Third, ex vivo structural MRI and diffusion tensor imaging were performed rostral to the injury site (C3-T6) at 90 dpi. Histological evidence of axonal degeneration emerged as early as 2 dpi rostral to the injury site, persisting at 90 dpi. Severity-dependent degeneration occurred within the fasciculus gracilis and the periphery of the medio- and ventrolateral columns. Corresponding MRI changes, including lower fractional anisotropy in these regions and smaller gray matter area, were detected. In contrast, the dorsal corticospinal tract exhibited lower fractional anisotropy without clear histological abnormalities, potentially due to atrophy-related mislocalization. This highlights the value of correlative, multimodal approaches and the need for further methodological refinement. The number of SMI-32+ axonal profiles correlated negatively, while gray matter area and fractional anisotropy correlated positively with locomotion assessed by Basso, Beattie, and Bresnahan scores. This study demonstrates in independent experiments that neuroanatomical MRI changes observed after SCI, occurring remote from the injury site, are linked to axonal degeneration. Experimental SCI offers translational insights into underlying mechanisms and potential avenues for neuroprotective or rehabilitative approaches.

Spinal cord injury (SCI) is a devastating incidence leading to permanent paralysis and loss of sensory-motor functions potentially resulting in the formation of lesions within the spinal cord. Imaging biomarkers obtained from magnetic resonance imaging (MRI) scans can predict the functional recovery of individuals with SCI and help choose the optimal treatment strategy. Currently, most studies employ manual quantification of these MRI-derived biomarkers, which is a subjective and tedious task. In this work, we propose (i) a universal tool for the automatic segmentation of intramedullary SCI lesions, dubbed SCIsegV2, and (ii) a method to automatically compute the width of the tissue bridges from the segmented lesion. Tissue bridges represent the spared spinal tissue adjacent to the lesion, which is associated with functional recovery in SCI patients. The tool was trained and validated on a heterogeneous dataset from 7 sites comprising patients from different SCI phases (acute, sub-acute, and chronic) and etiologies (traumatic SCI, ischemic SCI, and degenerative cervical myelopathy). Tissue bridges quantified automatically did not significantly differ from those computed manually, suggesting that the proposed automatic tool can be used to derive relevant MRI biomarkers. SCIsegV2 and the automatic tissue bridges computation are open-source and available in Spinal Cord Toolbox (v6.4 and above) via the sct_deepseg-task seg_sc_lesion_t2w_sci and sct_analyze_lesion functions, respectively.

BACKGROUND:Spastic muscle tone, often observed after spinal cord injury (SCI), is thought to contribute to body support during walking at a lower level of neural organisation. Understanding the link between damage to specific spinal tracts and the development of spastic muscle tone and mobility could enhance our knowledge of the neural structures crucial for recovery of function after SCI. METHODS:In this retrospective observational study, MRI-based assessments of descending spinal tract damage were related to the development of spastic muscle tone and mobility. Focal damage to the corticospinal (CST) and reticulospinal tracts (RST) was assessed on transversal T2-weighted scans of 49 patients with SCI one month post-injury. The extent of tract damage was then associated with the degree of spastic muscle tone measured by the Modified Ashworth Scale (MAS), and changes in mobility subscore of the Spinal Cord Independence Measure (SCIM). FINDINGS:The extent of CST damage was predictive for the level of MAS score with a positive relationship (β = 0.043, SE = 0.016, OR: 1.044, 95% CI: 1.014-1.080, P = 0.006). This association was negatively modulated by the interaction between CST and RST damage (β = -0.002, SE = 0.001, OR: 0.998, 95% CI: 0.997-0.999, P = 0.004)-i.e. extensive RST damage weakened the relationship between CST damage and MAS score. The extent of RST damage was related to the change in SCIM mobility subscore, independent of MAS score (β: -0.683, SE = 0.231, 95% CI: -1.135 to -0.230, P = 0.007). INTERPRETATION:The extent of CST damage, along with the preservation of the RST, reliably predicts spastic muscle tone, while preserved RST structure alone serves as an independent predictor of mobility outcomes. These observations highlight the role of the reticulospinal system in the functional recovery of mobility and may have broader relevance for other neurological conditions with spinal cord involvement. FUNDING:Swiss National Science Foundation.

AbstractObjectiveTo characterize structural integrity of the lumbosacral enlargement and conus medullaris within one month after spinal cord injury (SCI).MethodsLumbosacral cord MRI data were acquired in patients with sudden onset (<7 days) SCI at the cervical or thoracic level approximately one month after injury and in healthy controls. Tissue integrity and loss were evaluated through diffusion tensor (DTI) and T2*‐weighted imaging (cross‐sectional area [CSA] measurements). Associations with the degree of neurological impairment were assessed using linear mixed‐effects models.ResultsTwenty‐one patients with SCI showed lower white matter (WM) fractional anisotropy (FA) (≤−13.3%) and higher WM radial diffusivity (≤14.6%) compared to 27 healthy controls. Differences were most pronounced in the lateral columns of WM. CSA measurements revealed no group differences. For the lateral columns, lower FA values were associated with lower motor scores and lower amplitudes of motor evoked potentials. For the dorsal columns, lower FA values were associated with lower amplitudes of somatosensory evoked potentials from the lower extremities.InterpretationOne month after SCI, first signs of WM degeneration were apparent, without indication of tissue loss. The more pronounced differences observed in the lateral column could be attributed to anterograde degeneration of the motor tracts. The variability among DTI measurements remote from the lesion site can be partially explained by the degree of the SCI‐induced neurological impairment. Together with previous studies, our findings indicate that impaired tissue integrity precedes tissue loss. The presented techniques have potential applications in monitoring the progression of various neurological diseases.

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e., height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1 ± 6.6 years old, 125 females). We show that body height correlates with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44 ≤ r ≤ 0.62). Intracranial volume (ICV) correlates with body height (r = 0.46) and the brain volumes and CSA-WM (0.37 ≤ r ≤ 0.77). In comparison, age correlates with cortical GM volume, precentral GM volume, and cortical thickness (-0.21 ≥ r ≥ -0.27). Body weight correlates with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20 ≥ r ≥ -0.23). Body weight further correlates with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r = -0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlates with brain volumes (0.39 ≤ r ≤ 0.64), and with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22 ≥ r ≥ -0.25). Linear mixture of age, sex, or sex and age, explained 2 ± 2%, 24 ± 10%, or 26 ± 10%, of data variance in brain volumetry and SC CSA. The amount of explained variance increased to 33 ± 11%, 41 ± 17%, or 46 ± 17%, when body height, ICV, or body height and ICV were added into the mixture model. In females, the explained variances halved suggesting another unidentified biological factor(s) determining females' central nervous system (CNS) morphology. In conclusion, body size and ICV are significant biological variables. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure; and body size and ICV should be considered as covariates in statistical analyses. Normalization of different brain regions with ICV diminishes their correlations with body size, but simultaneously amplifies ICV-related variance (r = 0.72 ± 0.07) and suppresses volume variance of the different brain regions (r = 0.12 ± 0.19) in the normalized measurements.

STUDY DESIGN:Systematic literature review. OBJECTIVE:Update on diagnostic utility of electrophysiology in lumbar spinal canal stenosis (LSCS). SUMMARY OF BACKGROUND:LSCS is a highly prevalent degenerative spine condition characterized by neurogenic claudication, radicular pain, and muscle weakness. While lumbar spine MRI is the imaging modality for detecting spinal canal narrowing, it correlates poorly with clinical symptoms. Electrophysiological methods, including electromyography (EMG), nerve conduction studies (NCS), and evoked potentials (MEP and SEP), may provide complementary information on neural dysfunction. Current guidelines support paraspinal electromyography (EMG) mapping for symptomatic patients with imaging confirmed stenosis (grade B). In contrast, the diagnostic value of other electrophysiologic tests in LSCS remains uncertain. METHODS:A systematic literature search was conducted in Medline and Embase for original studies on LSCS between 2020 and 2024. Two independent reviewers screened studies for inclusion. The extracted data was synthesized qualitatively. Study quality was assessed using the Robins-V2 tool. PROSPERO registration (CRD42024622427). RESULTS:Thirteen studies met the inclusion criteria; study quality was moderate. Needle EMG of the limbs was evaluated in 23% of studies to detect denervation as a sign of radiculopathy. Twenty-three percent of the studies examined tibial nerve SEP or cauda equina MEP conduction time for lesion localization, with varying findings and utility for diagnosing LSCS. Surface EMG was investigated in 31% of studies and revealed significantly altered muscle activation patterns and compensatory gait adaptations in LSCS. CONCLUSION:There is an increasing number of studies combining surface EMG with gait assessments and tasks. This approach is interesting for being noninvasive, with clinical utility to be further determined. On the basis of previous guidelines, paraspinal mapping is considered the gold-standard electrophysiological diagnostic tool. Interestingly, there were no recent studies on paraspinal mapping, indicating a shift to alternative methods.

Intravoxel incoherent motion (IVIM) measurements allow to probe tissue microcirculation non-invasively. Spinal cord perfusion has been shown to be altered following different neurological pathologies. A non-invasive imaging protocol to assess perfusion in the cervical cord is, therefore, clinically relevant. This work aimed at assessing the reliability of IVIM parameters sensitive to perfusion changes in the cervical cord by determining the test-retest variability across subjects and different post-processing fitting algorithms. IVIM test-retest scans were acquired in the cervical cord (C1-C3) of 10 healthy subjects on a 3T MRI scanner, with a 15-minute break in-between. IVIM parameters, including microvascular volume fraction ( F ), pseudo-diffusion coefficient ( D * ), blood flow-related coefficient ( F · D * ), and diffusion coefficient ( D ), were derived using voxel-wise and region of interest (ROI)-wise fits. The reliability of each IVIM parameter was determined with coefficients of variation (CV), intraclass correlation coefficients (ICC), Bland-Altman analysis, and linear regression. To assess the effects of the different fitting approaches, a two-way repeated-measures analysis of variance (ANOVA) was conducted on the CVs calculated across fitting algorithms. Mean CVs of IVIM parameters calculated across subjects using the voxel-wise fit were lower in the white matter (WM) and grey matter (GM): (WM: 2.6% to 15.6%; GM: 2.2% to 16.4%) compared with those calculated using the ROI-wise fit approach (WM: 4.5% to 32.2%; GM: 3.4% to 53.4%). The voxel-wise fit in the WM yielded higher ICC values (good-to-excellent, 0.71-0.97) compared to the ROI-wise fit approach (poor-to-excellent, 0.49-0.90). IVIM parameters, derived using the voxel-wise fitting approach, demonstrated a high reliability in the cervical cord. Results highlight the high variability of IVIM parameter values depending on the fitting approach, underlining the importance of characterizing the reliability of IVIM acquisition and fitting configuration in the relevant organ of interest. Robust IVIM metrics using a voxel-wise one-step approach, observed across scans and subjects, can facilitate studies targeting perfusion impairment and pave the way to future clinical trials assessing perfusion impairment as a potential quantitative biomarker.