Progressive cervical cord atrophy parallels cognitive decline in Alzheimer's disease

Alzheimer's disease (AD) is characterized by progressive episodic memory dysfunction. A prominent hallmark of AD is gradual brain atrophy. Despite extensive research on brain pathology, the understanding of spinal cord pathology in AD and its association with cognitive decline remains understudied. We analyzed serial magnetic resonance imaging (MRI) scans from the ADNI data repository to assess whether progressive cord atrophy is associated with clinical worsening. Cervical cord morphometry was measured in 45 patients and 49 cognitively normal controls (CN) at two time points over 1.5 years. Regression analysis examined associations between cord atrophy rate and cognitive worsening. Cognitive and functional activity performance declined in patients during follow-up. Compared with controls, patients showed a greater rate of decline of the anterior-posterior width of the cross-sectional cord area per month (- 0.12%, p = 0.036). Worsening in the mini-mental state examination (MMSE), clinical dementia rating (CDR), and functional assessment questionnaire (FAQ) was associated with faster rates of cord atrophy (MMSE: r = 0.320, p = 0.037; CDR: r = - 0.361, p = 0.017; FAQ: r = - 0.398, p = 0.029). Progressive cord atrophy occurs in AD patients; its rate over time being associated with cognitive and functional activity decline

Temporal dynamics of white and gray matter plasticity during motor skill acquisition: a comparative diffusion tensor imaging and multiparametric mapping analysis

Learning new motor skills relies on neural plasticity within motor and limbic systems. This study uniquely combined diffusion tensor imaging and multiparametric mapping MRI to detail these neuroplasticity processes. We recruited 18 healthy male participants who underwent 960 min of training on a computer-based motion game, while 14 were scanned without training. Diffusion tensor imaging, which quantifies tissue microstructure by measuring the capacity for, and directionality of, water diffusion, revealed mostly linear changes in white matter across the corticospinal-cerebellar-thalamo-hippocampal circuit. These changes related to performance and reflected different responses to upper- and lower-limb training in brain areas with known somatotopic representations. Conversely, quantitative MRI metrics, sensitive to myelination and iron content, demonstrated mostly quadratic changes in gray matter related to performance and reflecting somatotopic representations within the same brain areas. Furthermore, while myelin and iron-sensitive multiparametric mapping MRI was able to describe time lags between different cortical brain systems, diffusion tensor imaging detected time lags within the white matter of the motor systems. These findings suggest that motor skill learning involves distinct phases of white and gray matter plasticity across the sensorimotor network, with the unique combination of diffusion tensor imaging and multiparametric mapping MRI providing complementary insights into the underlying neuroplastic responses

Coherent, time-shifted patterns of microstructural plasticity during motor-skill learning

Motor skill learning relies on neural plasticity in the motor and limbic systems. However, the spatial and temporal characteristics of these changes-and their microstructural underpinnings-remain unclear. Eighteen healthy males received 1 hour of training in a computer-based motion game, 4 times a week, for 4 consecutive weeks, while 14 untrained participants underwent scanning only. Performance improvements were observed in all trained participants. Serial myelin- and iron-sensitive multiparametric mapping at 3T during this period of intensive motor skill acquisition revealed temporally and spatially distributed, performance-related microstructural changes in the grey and white matter across a corticospinal-cerebellar-hippocampal circuit. Analysis of the trajectory of these transient changes suggested time-shifted cascades of plasticity from the dominant sensorimotor system to the contralateral hippocampus. In the cranial corticospinal tracts, changes in myelin-sensitive metrics during training in the posterior limb of the internal capsule were of greater magnitude in those who trained their upper limbs vs. lower limb trainees. Motor skill learning is associated with waves of grey and white matter plasticity, across a broad sensorimotor network

Coherent, time-shifted patterns of microstructural plasticity during motor-skill learning

Motor skill learning relies on neural plasticity in the motor and limbic systems. However, the spatial and temporal characteristics of these changes-and their microstructural underpinnings-remain unclear. Eighteen healthy males received 1 h of training in a computer-based motion game, 4 times a week, for 4 consecutive weeks, while 14 untrained participants underwent scanning only. Performance improvements were observed in all trained participants. Serial myelin- and iron-sensitive multiparametric mapping at 3T during this period of intensive motor skill acquisition revealed temporally and spatially distributed, performance-related microstructural changes in the grey and white matter across a corticospinal-cerebellar-hippocampal circuit. Analysis of the trajectory of these transient changes suggested time-shifted cascades of plasticity from the dominant sensorimotor system to the contralateral hippocampus. In the cranial corticospinal tracts, changes in myelin-sensitive metrics during training in the posterior limb of the internal capsule were of greater magnitude in those who trained their upper limbs vs. lower limb trainees. Motor skill learning is associated with waves of grey and white matter plasticity, across a broad sensorimotor network

The Influence of Radio-Frequency Transmit Field Inhomogeneities on the Accuracy of G-ratio Weighted Imaging

G-ratio weighted imaging is a non-invasive, in-vivo MRI-based technique that aims at estimating an aggregated measure of relative myelination of axons across the entire brain white matter. The MR g-ratio and its constituents (axonal and myelin volume fraction) are more specific to the tissue microstructure than conventional MRI metrics targeting either the myelin or axonal compartment. To calculate the MR g-ratio, an MRI-based myelin-mapping technique is combined with an axon-sensitive MR technique (such as diffusion MRI). Correction for radio-frequency transmit (B1+) field inhomogeneities is crucial for myelin mapping techniques such as magnetization transfer saturation. Here we assessed the effect of B1+ correction on g-ratio weighted imaging. To this end, the B1+ field was measured and the B1+ corrected MR g-ratio was used as the reference in a Bland-Altman analysis. We found a substantial bias (≈-89%) and error (≈37%) relative to the dynamic range of g-ratio values in the white matter if the B1+ correction was not applied. Moreover, we tested the efficiency of a data-driven B1+ correction approach that was applied retrospectively without additional reference measurements. We found that it reduced the bias and error in the MR g-ratio by a factor of three. The data-driven correction is readily available in the open-source hMRI toolbox (www.hmri.info) which is embedded in the statistical parameter mapping (SPM) framework

Longitudinal motor system changes from acute to chronic spinal cord injury

BACKGROUND AND PURPOSE In acute spinal cord injury (SCI), magnetic resonance imaging (MRI) reveals tissue bridges and neurodegeneration for 2 years. This 5-year study aims to track initial lesion changes, subsequent neurodegeneration, and their impact on recovery. METHODS This prospective longitudinal study enrolled acute SCI patients and healthy controls who were assessed clinically-and by MRI-regularly from 3 days postinjury up to 60 months. We employed histologically cross-validated quantitative MRI sequences sensitive to volume, myelin, and iron changes, thereby reflecting indirectly processes of neurodegeneration and neuroinflammation. General linear models tracked lesion and remote changes in volume, myelin- and iron-sensitive magnetic resonance indices over 5 years. Associations between lesion, degeneration, and recovery (using the Spinal Cord Independence Measure [SCIM] questionnaire and the International Standards for Neurological Classification of Spinal Cord Injury total motor score) were assessed. RESULTS Patients' motor scores improved by an average of 12.86 (95% confidence interval [CI] = 6.70-19.00) points, and SCIM by 26.08 (95% CI = 17.00-35.20) points. Within 3-28 days post-SCI, lesion size decreased by more than two-thirds (3 days: 302.52 ± 185.80 mm$^{2}$ , 28 days: 76.77 ± 88.62 mm$^{2}$ ), revealing tissue bridges. Cervical cord and corticospinal tract volumes transiently increased in SCI patients by 5% and 3%, respectively, accompanied by cervical myelin decreases and iron increases. Over time, progressive atrophy was observed in both regions, which was linked to early lesion dynamics. Tissue bridges, reduced swelling, and myelin content decreases were predictive of long-term motor score recovery and improved SCIM score. CONCLUSIONS Studying acute changes and their impact on longer follow-up provides insights into SCI trajectory, highlighting the importance of acute intervention while indicating the potential to influence outcomes in the later stages

Longitudinal motor system changes from acute to chronic spinal cord injury

Background and purpose: In acute spinal cord injury (SCI), magnetic resonance imaging (MRI) reveals tissue bridges and neurodegeneration for 2 years. This 5-year study aims to track initial lesion changes, subsequent neurodegeneration, and their impact on recovery. // Methods: This prospective longitudinal study enrolled acute SCI patients and healthy controls who were assessed clinically—and by MRI—regularly from 3 days postinjury up to 60 months. We employed histologically cross-validated quantitative MRI sequences sensitive to volume, myelin, and iron changes, thereby reflecting indirectly processes of neurodegeneration and neuroinflammation. General linear models tracked lesion and remote changes in volume, myelin- and iron-sensitive magnetic resonance indices over 5 years. Associations between lesion, degeneration, and recovery (using the Spinal Cord Independence Measure [SCIM] questionnaire and the International Standards for Neurological Classification of Spinal Cord Injury total motor score) were assessed. // Results: Patients' motor scores improved by an average of 12.86 (95% confidence interval [CI] = 6.70–19.00) points, and SCIM by 26.08 (95% CI = 17.00–35.20) points. Within 3–28 days post-SCI, lesion size decreased by more than two-thirds (3 days: 302.52 ± 185.80 mm2, 28 days: 76.77 ± 88.62 mm2), revealing tissue bridges. Cervical cord and corticospinal tract volumes transiently increased in SCI patients by 5% and 3%, respectively, accompanied by cervical myelin decreases and iron increases. Over time, progressive atrophy was observed in both regions, which was linked to early lesion dynamics. Tissue bridges, reduced swelling, and myelin content decreases were predictive of long-term motor score recovery and improved SCIM score. // Conclusions: Studying acute changes and their impact on longer follow-up provides insights into SCI trajectory, highlighting the importance of acute intervention while indicating the potential to influence outcomes in the later stages

Quantifying neurodegeneration of the cervical cord and brain in degenerative cervical myelopathy : A multicentre study using quantitative magnetic resonance imaging

BACKGROUND AND PURPOSE Simultaneous assessment of neurodegeneration in both the cervical cord and brain across multiple centres can enhance the effectiveness of clinical trials. Thus, this study aims to simultaneously assess microstructural changes in the cervical cord and brain above the stenosis in degenerative cervical myelopathy (DCM) using quantitative magnetic resonance imaging (MRI) in a multicentre study. METHODS We applied voxelwise analysis with a probabilistic brain/spinal cord template embedded in statistical parametric mappin (SPM-BSC) to process multi parametric mapping (MPM) including effective transverse relaxation rate (R2*), longitudinal relaxation rate (R1), and magnetization transfer (MT), which are indirectly sensitive to iron and myelin content. Regression analysis was conducted to establish associations between neurodegeneration and clinical impairment. Thirty-eight DCM patients (mean age ± SD = 58.45 ± 11.47 years) and 38 healthy controls (mean age ± SD = 41.18 ± 12.75 years) were recruited at University Hospital Balgrist, Switzerland and Toronto Western Hospital, Canada. RESULTS Remote atrophy was observed in the cervical cord (p = 0.002) and in the left thalamus (0.026) of the DCM group. R1 was decreased in the periaqueductal grey matter (p = 0.014), thalamus (p = 0.001), corpus callosum (p = 0.0001), and cranial corticospinal tract (p = 0.03). R2* was increased in the primary somatosensory cortices (p = 0.008). Sensory impairments were associated with increased iron-sensitive R2* in the thalamus and periaqueductal grey matter in DCM. CONCLUSIONS Simultaneous assessment of the spinal cord and brain revealed DCM-induced demyelination, iron deposition, and atrophy. The extent of remote neurodegeneration was associated with sensory impairment, highlighting the intricate and expansive nature of microstructural neurodegeneration in DCM, reaching beyond the stenosis level

Improving Diagnostic Workup Following Traumatic Spinal Cord Injury: Advances in Biomarkers

PURPOSE OF REVIEW Traumatic spinal cord injury (SCI) is a life-changing event with drastic implications for patients due to sensorimotor impairment and autonomous dysfunction. Current clinical evaluations focus on the assessment of injury level and severity using standardized neurological examinations. However, they fail to predict individual trajectories of recovery, which highlights the need for the development of advanced diagnostics. This narrative review identifies recent advances in the search of clinically relevant biomarkers in the field of SCI. RECENT FINDINGS Advanced neuroimaging and molecular biomarkers sensitive to the disease processes initiated by the SCI have been identified. These biomarkers range from advanced neuroimaging techniques, neurophysiological readouts, and molecular biomarkers identifying the concentrations of several proteins in blood and CSF samples. Some of these biomarkers improve current prediction models based on clinical readouts. Validation with larger patient cohorts is warranted. Several biomarkers have been identified-ranging from imaging to molecular markers-that could serve as advanced diagnostic and hence supplement current clinical assessments