A comparative study of diffusion kurtosis imaging and diffusion tensor imaging in detecting corticospinal tract impairment in diffuse glioma patients.

PURPOSE: This study aimed to investigate the diagnostic performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in identifying aberrations in the corticospinal tract (CST), whilst elucidating the relationship between abnormalities of CST and patients' motor function. METHODS: Altogether 21 patients with WHO grade II or grade IV glioma were enrolled and divided into Group 1 and Group 2, according to the presence or absence of preoperative paralysis. DKI and DTI metrics were generated and projected onto the CST. Histograms of the CST along x, y, and z axes were developed based on DKI and DTI metrics, and compared subsequently to determine regions of aberrations on the fibers. The receiver operating characteristic curve was performed to investigate the diagnostic efficacy of DKI and DTI metrics. RESULTS: In Group 1, a significantly lower fractional anisotropy, radial kurtosis and mean kurtosis, and a higher mean diffusivity were found in the ipsilateral CST as compared to the contralateral CST. Significantly higher relative axial diffusivity, relative radial diffusivity, and relative mean diffusivity (rMD) were found in Group 1, as compared to Group 2. The relative volume of ipsilateral CST abnormalities higher than the maximum value of mean kurtosis combined with rMD exhibited the best diagnostic performance in distinguishing dysfunction of CST with an AUC of 0.93. CONCLUSION: DKI is sensitive in detecting subtle changes of CST distal from the tumor. The combination of DKI and DTI is feasible for evaluating the impairment of the CST.

Brain region changes following a spinal cord injury.

Brain-related complications are common in clinical practice after spinal cord injury (SCI); however, the molecular mechanisms of these complications are still unclear. Here, we reviewed the changes in the brain regions caused by SCI from three perspectives: imaging, molecular analysis, and electrophysiology. Imaging studies revealed abnormal functional connectivity, gray matter volume atrophy, and metabolic abnormalities in brain regions after SCI, leading to changes in the structure and function of brain regions. At the molecular level, chemokines, inflammatory factors, and damage-associated molecular patterns produced in the injured area were retrogradely transmitted through the corticospinal tract, cerebrospinal fluid, or blood circulation to the specific brain area to cause pathologic changes. Electrophysiologic recordings also suggested abnormal changes in brain electrical activity after SCI. Transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation alleviated pain and improved motor function in patients with SCI; therefore, transcranial therapy may be a new strategy for the treatment of patients with SCI.

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.

Corticospinal tract: a new hope for the treatment of post-stroke spasticity.

Stroke is the third leading cause of death and disability worldwide. Post-stroke spasticity (PSS) is the most common complication of stroke but represents only one of the many manifestations of upper motor neuron syndrome. As an upper motor neuron, the corticospinal tract (CST) is the only direct descending motor pathway that innervates the spinal motor neurons and is closely related to the recovery of limb function in patients with PSS. Therefore, promoting axonal remodeling in the CST may help identify new therapeutic strategies for PSS. In this review, we outline the pathological mechanisms of PSS, specifically their relationship with CST, and therapeutic strategies for axonal regeneration of the CST after stroke. We found it to be closely associated with astroglial scarring produced by astrocyte activation and its secretion of neurotrophic factors, mainly after the onset of cerebral ischemia. We hope that this review offers insight into the relationship between CST and PSS and provides a basis for further studies.

Hereditary Spastic Paraplegia Type 11-Clinical, Genetic and Neuroimaging Characteristics.

Hereditary spastic paraplegia (HSP) is a heterogeneous group of genetically determined diseases, characterised by progressive spastic paraparesis of the lower limbs, associated with degeneration of the corticospinal tract and the posterior column of the spinal cord. HSP occurs worldwide and the estimated prevalence is about 1-10/100,000, depending on the geographic localisation. More than 70 genes responsible for HSP have been identified to date, and reports of new potentially pathogenic variants appear regularly. All possible patterns of inheritance (autosomal dominant, autosomal recessive, X-linked and mitochondrial) have been described in families of HSP patients. Among the autosomal recessive forms of HSP (AR-HSP), hereditary spastic paraplegia type 11 is the most common one. We present a patient with diagnosed HSP 11, with a typical clinical picture and characteristic features in additional diagnostic tests.

Reconstructing the somatotopic organization of the corticospinal tract remains a challenge for modern tractography methods.

The corticospinal tract (CST) is a critically important white matter fiber tract in the human brain that enables control of voluntary movements of the body. The CST exhibits a somatotopic organization, which means that the motor neurons that control specific body parts are arranged in order within the CST. Diffusion magnetic resonance imaging (MRI) tractography is increasingly used to study the anatomy of the CST. However, despite many advances in tractography algorithms over the past decade, modern, state-of-the-art methods still face challenges. In this study, we compare the performance of six widely used tractography methods for reconstructing the CST and its somatotopic organization. These methods include constrained spherical deconvolution (CSD) based probabilistic (iFOD1) and deterministic (SD-Stream) methods, unscented Kalman filter (UKF) tractography methods including multi-fiber (UKF2T) and single-fiber (UKF1T) models, the generalized q-sampling imaging (GQI) based deterministic tractography method, and the TractSeg method. We investigate CST somatotopy by dividing the CST into four subdivisions per hemisphere that originate in the leg, trunk, hand, and face areas of the primary motor cortex. A quantitative and visual comparison is performed using diffusion MRI data (N = 100 subjects) from the Human Connectome Project. Quantitative evaluations include the reconstruction rate of the eight anatomical subdivisions, the percentage of streamlines in each subdivision, and the coverage of the white matter-gray matter (WM-GM) interface. CST somatotopy is further evaluated by comparing the percentage of streamlines in each subdivision to the cortical volumes for the leg, trunk, hand, and face areas. Overall, UKF2T has the highest reconstruction rate and cortical coverage. It is the only method with a significant positive correlation between the percentage of streamlines in each subdivision and the volume of the corresponding motor cortex. However, our experimental results show that all compared tractography methods are biased toward generating many trunk streamlines (ranging from 35.10% to 71.66% of total streamlines across methods). Furthermore, the coverage of the WM-GM interface in the largest motor area (face) is generally low (under 40%) for all compared tractography methods. Different tractography methods give conflicting results regarding the percentage of streamlines in each subdivision and the volume of the corresponding motor cortex, indicating that there is generally no clear relationship, and that reconstruction of CST somatotopy is still a large challenge. Overall, we conclude that while current tractography methods have made progress toward the well-known challenge of improving the reconstruction of the lateral projections of the CST, the overall problem of performing a comprehensive CST reconstruction, including clinically important projections in the lateral (hand and face areas) and medial portions (leg area), remains an important challenge for diffusion MRI tractography.

Synergistic effect of chemogenetic activation of corticospinal motoneurons and physical exercise in promoting functional recovery after spinal cord injury.

Single therapeutic interventions have not yet been successful in restoring function after spinal cord injury. Accordingly, combinatorial interventions targeting multiple factors may hold greater promise for achieving maximal functional recovery. In this study, we applied a combinatorial approach of chronic chemogenetic neuronal activation and physical exercise including treadmill running and forelimb training tasks to promote functional recovery. In a mouse model of cervical (C5) dorsal hemisection of the spinal cord, which transects almost all descending corticospinal tract axons, combining selective activation of corticospinal motoneurons (CMNs) by intersectional chemogenetics with physical exercise significantly promoted functional recovery evaluated by the grid walking test, grid hanging test, rotarod test, and single pellet-reaching tasks. Electromyography and histological analysis showed increased activation of forelimb muscles via chemogenetic stimuli, and a greater density of vGlut1+ innervation in spinal cord grey matter rostral to the injury, suggesting enhanced neuroplasticity and connectivity. Combined therapy also enhanced activation of mTOR signaling and reduced apoptosis in spinal motoneurons, Counts revealed increased numbers of detectable choline acetyltransferase-positive motoneurons in the ventral horn. Taken together, the findings from this study validate a novel combinatorial approach to enhance motor function after spinal cord injury.

Survey Assessment of Utility in Preoperative Magnetic Resonance (MR) Tractography Surgical Planning.

BACKGROUND: Although tractography-guided surgery is used by many surgeons, there is controversy in the published literature as it relates to its clinical utility. Here we adopted a survey-based approach with the goal of attaining a broader view of how tractography influence preoperative planning in a sampling of practicing neurosurgeons. METHODS: Three cases were prepared where the presence of a tumor distorted the optic radiation (case 1), arcuate fasciculus (case 2), and corticospinal tract (case 3). This survey was administered at the Medtronic Cranial Consortium attended by 20 practicing neurosurgeons. To avoid commercial bias, we used both the Brainlab and Medtronic platform to compute tractography. Each participant is asked to vote on a surgical trajectory before and after seeing the tractography images, as well as whether tractography added value in validating their surgical approach. RESULTS: In the 3 cases surveyed, 16%-44% of the surgeons changed the surgical corridor selected after seeing the tractography images. The most common finding associated with a change in surgical corridor involved intersection of the surgical corridor with visualized tracts. Consistently, >80% of the surgeons surveyed felt that tractography added value in their surgical planning. CONCLUSIONS: The clinical utility of tractography in preoperative planning varies as a function of surgeon and the tumor anatomy, with >80% of the participating surgeons believing that tractography added value in preoperative surgical planning.

PTEN knockout using retrogradely transported AAVs transiently restores locomotor abilities in both acute and chronic spinal cord injury.

Restoring function in chronic stages of spinal cord injury (SCI) has often been met with failure or reduced efficacy when regenerative strategies are delayed past the acute or sub-acute stages of injury. Restoring function in the chronically injured spinal cord remains a critical challenge. We found that a single injection of retrogradely transported adeno-associated viruses (AAVrg) to knockout the phosphatase and tensin homolog protein (PTEN) in chronic SCI can effectively target both damaged and spared axons and transiently restore locomotor functions in near-complete injury models. AAVrg's were injected to deliver cre recombinase and/or a red fluorescent protein (RFP) under the human Synapsin 1 promoter (hSyn1) into the spinal cords of C57BL/6 PTENFloxΔ/Δ mice to knockout PTEN (PTEN-KO) in a severe thoracic SCI crush model at both acute and chronic time points. PTEN-KO improved locomotor abilities in both acute and chronic SCI conditions over a 9-week period. Regardless of whether treatment was initiated at the time of injury (acute), or three months after SCI (chronic), mice with limited hindlimb joint movement gained hindlimb weight support after treatment. Interestingly, functional improvements were not sustained beyond 9 weeks coincident with a loss of RFP reporter-gene expression and a near-complete loss of treatment-associated functional recovery by 6 months post-treatment. Treatment effects were also specific to severely injured mice; animals with weight support at the time of treatment lost function over a 6-month period. Retrograde tracing with Fluorogold revealed viable neurons throughout the motor cortex despite a loss of RFP expression at 9 weeks post-PTEN-KO. However, few Fluorogold labeled neurons were detected within the motor cortex at 6 months post-treatment. BDA labeling from the motor cortex revealed a dense corticospinal tract (CST) bundle in all groups except chronically treated PTEN-KO mice, indicating a potential long-term toxic effect of PTEN-KO to neurons in the motor cortex which was corroborated by a loss of ß-tubulin III labeling above the lesion within spinal cords after PTEN-KO. PTEN-KO mice had significantly more ß-tubulin III labeled axons within the lesion when treatment was delivered acutely, but not chronically post-SCI. In conclusion, we have found that using AAVrg's to knockout PTEN is an effective manipulation capable of restoring motor functions in chronic SCI and can enhance axon growth of currently unidentified axon populations when delivered acutely after injury. However, the long-term consequences of PTEN-KO on neuronal health and viability should be further explored.

Quantitative Validation of the Correlation Between Optimized Pyramidal Tract Delineation After Brain Shift Compensation and Direct Electrical Subcortical Stimulation During Brain Tumor Surgery.

It remains unclear whether tractography of pyramidal tracts is correlated with the intraoperative direct electrical subcortical stimulation (DESS), and brain shift further complicates the issue. The objective of this research is to quantitatively verify the correlation between optimized tractography (OT) of pyramidal tracts after brain shift compensation and DESS during brain tumor surgery. OT was performed for 20 patients with lesions in proximity to the pyramidal tracts based on preoperative diffusion-weighted magnetic resonance imaging. During surgery, tumor resection was guided by DESS. A total of 168 positive stimulation points and their corresponding stimulation intensity thresholds were recorded. Using the brain shift compensation algorithm based on hierarchical B-spline grids combined with a Gaussian resolution pyramid, we warped the preoperative pyramidal tract models and used receiver operating characteristic (ROC) curves to investigate the reliability of our brain shift compensation method based on anatomic landmarks. Additionally, the minimum distance between the DESS points and warped OT (wOT) model was measured and correlated with DESS intensity threshold. Brain shift compensation was achieved in all cases, and the area under the ROC curve was 0.96 in the registration accuracy analysis. The minimum distance between the DESS points and the wOT model was found to have a significantly high correlation with the DESS stimulation intensity threshold (r = 0.87, P < 0.001), with a linear regression coefficient of 0.96. Our OT method can provide comprehensive and accurate visualization of the pyramidal tracts for neurosurgical navigation and was quantitatively verified by intraoperative DESS after brain shift compensation.

Fibre density and fibre-bundle cross-section of the corticospinal tract are distinctly linked to psychosis-specific symptoms in antipsychotic-naïve patients with first-episode schizophrenia.

Multiple lines of research support the dysconnectivity hypothesis of schizophrenia. However, findings on white matter (WM) alterations in patients with schizophrenia are widespread and non-specific. Confounding factors from magnetic resonance image (MRI) processing, clinical diversity, antipsychotic exposure, and substance use may underlie some of the variability. By application of refined methodology and careful sampling, we rectified common confounders investigating WM and symptom correlates in a sample of strictly antipsychotic-naïve first-episode patients with schizophrenia. Eighty-six patients and 112 matched controls underwent diffusion MRI. Using fixel-based analysis (FBA), we extracted fibre-specific measures such as fibre density and fibre-bundle cross-section. Group differences on fixel-wise measures were examined with multivariate general linear modelling. Psychopathology was assessed with the Positive and Negative Syndrome Scale. We separately tested multivariate correlations between fixel-wise measures and predefined psychosis-specific versus anxio-depressive symptoms. Results were corrected for multiple comparisons. Patients displayed reduced fibre density in the body of corpus callosum and in the middle cerebellar peduncle. Fibre density and fibre-bundle cross-section of the corticospinal tract were positively correlated with suspiciousness/persecution, and negatively correlated with delusions. Fibre-bundle cross-section of isthmus of corpus callosum and hallucinatory behaviour were negatively correlated. Fibre density and fibre-bundle cross-section of genu and splenium of corpus callosum were negative correlated with anxio-depressive symptoms. FBA revealed fibre-specific properties of WM abnormalities in patients and differentiated associations between WM and psychosis-specific versus anxio-depressive symptoms. Our findings encourage an itemised approach to investigate the relationship between WM microstructure and clinical symptoms in patients with schizophrenia.

Tensor- and high-resolution fiber tractography for the delineation of the optic radiation and corticospinal tract in the proximity of intracerebral lesions: a reproducibility and repeatability study.

PURPOSE: Fiber tracking (FT) is used in neurosurgical planning for the resection of lesions in proximity to fiber pathways, as it contributes to a substantial amelioration of postoperative neurological impairments. Currently, diffusion-tensor imaging (DTI)-based FT is the most frequently used technique; however, sophisticated techniques such as Q-ball (QBI) for high-resolution FT (HRFT) have suggested favorable results. Little is known about the reproducibility of both techniques in the clinical setting. Therefore, this study aimed to examine the intra- and interrater agreement for the depiction of white matter pathways such as the corticospinal tract (CST) and the optic radiation (OR). METHODS: Nineteen patients with eloquent lesions in the proximity of the OR or CST were prospectively enrolled. Two different raters independently reconstructed the fiber bundles by applying probabilistic DTI- and QBI-FT. Interrater agreement was evaluated from the comparison between results obtained by the two raters on the same data set acquired in two independent iterations at different timepoints using the Dice Similarity Coefficient (DSC) and the Jaccard Coefficient (JC). Likewise, intrarater agreement was determined for each rater comparing individual results. RESULTS: DSC values showed substantial intrarater agreement based on DTI-FT (rater 1: mean 0.77 (0.68-0.85); rater 2: mean 0.75 (0.64-0.81); p = 0.673); while an excellent agreement was observed after the deployment of QBI-based FT (rater 1: mean 0.86 (0.78-0.98); rater 2: mean 0.80 (0.72-0.91); p = 0.693). In contrast, fair agreement was observed between both measures for the repeatability of the OR of each rater based on DTI-FT (rater 1: mean 0.36 (0.26-0.77); rater 2: mean 0.40 (0.27-0.79), p = 0.546). A substantial agreement between the measures was noted by applying QBI-FT (rater 1: mean 0.67 (0.44-0.78); rater 2: mean 0.62 (0.32-0.70), 0.665). The interrater agreement was moderate for the reproducibility of the CST and OR for both DSC and JC based on DTI-FT (DSC and JC ≥ 0.40); while a substantial interrater agreement was noted for DSC after applying QBI-based FT for the delineation of both fiber tracts (DSC > 0.6). CONCLUSIONS: Our findings suggest that QBI-based FT might be a more robust tool for the visualization of the OR and CST adjacent to intracerebral lesions compared with the common standard DTI-FT. For neurosurgical planning during the daily workflow, QBI appears to be feasible and less operator-dependent.

Dynamics of progressive degeneration of major spinal pathways following spinal cord injury: A longitudinal study.

BACKGROUND: Following spinal cord injury (SCI), disease processes spread gradually along the spinal cord forming a spatial gradient with most pronounced changes located at the lesion site. However, the dynamics of this gradient in SCI patients is not established. OBJECTIVE: This study tracks the spatiotemporal dynamics of remote anterograde and retrograde spinal tract degeneration in the upper cervical cord following SCI over two years utilizing quantitative MRI. METHODS: Twenty-three acute SCI patients (11 paraplegics, 12 tetraplegics) and 21 healthy controls were scanned with a T1-weighted sequence for volumetry and a FLASH sequence for myelin-sensitive magnetization transfer saturation (MTsat) of the upper cervical cord. We estimated myelin content from MTsat maps within the corticospinal tracts (CST) and dorsal columns (DC) and measured spinal cord atrophy by means of left-right width (LRW) and anterior-posterior width (APW) on the T1-weighted images across cervical levels C1-C3. MTsat in the CST and LRW were considered proxies for retrograde degeneration, while MTsat in the DC and APW provided evidence for anterograde degeneration, respectively. Using regression models, we compared the temporal and spatial trajectories of these MRI readouts between tetraplegics, paraplegics, and controls over a 2-year period and assessed their associations with clinical improvement. RESULTS: Linear rates and absolute differences in myelin-sensitive MTsat indicated retrograde and anterograde neurodegeneration in the CST and DC, respectively. Changes in MTsat within the CST and in LRW progressively developed over time forming a gradient towards lower cervical levels by 2 years after injury, especially in tetraplegics (change per cervical level in MTsat: -0.247 p.u./level, p = 0.034; in LRW: -0.323 mm/level, p = 0.024). MTsat within the DC was already decreased at cervical levels C1-C3 at baseline (1.5 months after injury) in both tetra- and paraplegics, while linear decreases in APW over time were similar across C1-C3, preserving the spatial gradient. The relative improvement in light touch score was associated with MTsat within the DC at baseline (rs = 0.575, p = 0.014). CONCLUSION: Rostral and remote to the injury, the CST and DC show ongoing structural changes, indicative of myelin reductions and atrophy within 2 years after SCI. While anterograde degeneration in the DC was already detectable uniformly at C1-C3 early following SCI, retrograde degeneration in the CST developed over time revealing specific spatial and temporal neurodegenerative gradients. Disentangling and quantifying such dynamic pathological processes may provide biomarkers for regenerative and remyelinating therapies along entire spinal pathways.

Reconstruction of the Corticospinal Tract in Patients with Motor-Eloquent High-Grade Gliomas Using Multilevel Fiber Tractography Combined with Functional Motor Cortex Mapping.

BACKGROUND AND PURPOSE: Tractography of the corticospinal tract is paramount to presurgical planning and guidance of intraoperative resection in patients with motor-eloquent gliomas. It is well-known that DTI-based tractography as the most frequently used technique has relevant shortcomings, particularly for resolving complex fiber architecture. The purpose of this study was to evaluate multilevel fiber tractography combined with functional motor cortex mapping in comparison with conventional deterministic tractography algorithms. MATERIALS AND METHODS: Thirty-one patients (mean age, 61.5 [SD, 12.2] years) with motor-eloquent high-grade gliomas underwent MR imaging with DWI (TR/TE = 5000/78 ms, voxel size = 2 × 2 × 2 mm3, 1 volume at b = 0 s/mm2, 32 volumes at b = 1000 s/mm2). DTI, constrained spherical deconvolution, and multilevel fiber tractography-based reconstruction of the corticospinal tract within the tumor-affected hemispheres were performed. The functional motor cortex was enclosed by navigated transcranial magnetic stimulation motor mapping before tumor resection and used for seeding. A range of angular deviation and fractional anisotropy thresholds (for DTI) was tested. RESULTS: For all investigated thresholds, multilevel fiber tractography achieved the highest mean coverage of the motor maps (eg, angular threshold = 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold = 71.8%, 22.6%, and 11.7%) and the most extensive corticospinal tract reconstructions (eg, angular threshold = 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold = 26,485 mm3, 6308 mm3, and 4270 mm3). CONCLUSIONS: Multilevel fiber tractography may improve the coverage of the motor cortex by corticospinal tract fibers compared with conventional deterministic algorithms. Thus, it could provide a more detailed and complete visualization of corticospinal tract architecture, particularly by visualizing fiber trajectories with acute angles that might be of high relevance in patients with gliomas and distorted anatomy.

Motor skills training-induced activation of descending pathways mediating cortical command to hindlimb motoneurons in experimental diabetic rats.

Diabetes disrupts the corticospinal tract (CST) system components that control hindlimb and trunk movement, resulting in weakness of the lower extremities. However, there is no information about a method to improve these disorders. This study aimed to investigate the rehabilitative effects of 2 weeks of aerobic training (AT) and complex motor skills training (ST) on motor disorders in streptozotocin-induced type 1 diabetic rats. In this study, electrophysiological mapping of the motor cortex showed that the diabetes mellitus (DM)-ST group had a larger motor cortical area compared to the DM-AT group and sedentary diabetic animals. Moreover, hand grip strength and rotarod latency increased in the DM-ST group; however, these two parameters did not change in the DM-AT group, as well as in control and sedentary diabetic rats. Furthermore, in the DM-ST group, cortical stimulation-induced and motor-evoked potentials were preserved after the interception of the CST; however, this potential disappeared after additional lesions were made on lateral funiculus, suggesting that their function extends to activating motor descending pathways other than the CST locating lateral funiculus. According to immunohistochemical analysis, the larger fibers present on the dorsal part of the lateral funiculus, which corresponds to the rubrospinal tract of the DM-ST group, expressed the phosphorylated growth-associated protein, 43 kD, which is a specific marker of axons with plastic changes. Additionally, electrical stimulation of the red nucleus revealed expansion of the hindlimb-responsible area and increased motor-evoked potentials of the hindlimb in the DM-ST group, suggesting a strengthening of synaptic connections between the red nucleus and spinal interneurons driving motoneurons. These results reveal that ST induces plastic changes in the rubrospinal tract in a diabetic model, which can compensate for diabetes by disrupting the CST system components that control the hindlimb. This finding suggests that ST can be a novel rehabilitation strategy to improve motor dysfunctions in diabetic patients.

Severity of in vivo corticospinal tract degeneration is associated with survival in amyotrophic lateral sclerosis: a longitudinal, multicohort study.

BACKGROUND AND PURPOSE: This study sought to evaluate the relationship of progressive corticospinal tract (CST) degeneration with survival in patients with amyotrophic lateral sclerosis (ALS). METHODS: Forty-one ALS patients and 42 healthy controls were prospectively recruited from the Canadian ALS Neuroimaging Consortium. Magnetic resonance imaging scanning and clinical evaluations were performed on participants at three serial visits with 4-month intervals. Texture analysis was performed on T1-weighted magnetic resonance imaging scans and the texture feature 'autocorrelation' was quantified. Whole-brain group-level comparisons were performed between patient subgroups. Linear mixed models were used to evaluate longitudinal progression. Region-of-interest and 3D voxel-wise Cox proportional-hazards regression models were constructed for survival prediction. For all survival analyses, a second independent cohort was used for model validation. RESULTS: Autocorrelation of the bilateral CST was increased at baseline and progressively increased over time at a faster rate in ALS short survivors. Cox proportional-hazards regression analyses revealed autocorrelation of the CST as a significant predictor of survival at 5 years follow-up (hazard ratio 1.28, p = 0.005). Similarly, voxel-wise whole-brain survival analyses revealed that increased autocorrelation of the CST was associated with shorter survival. ALS patients stratified by median autocorrelation in the CST had significantly different survival times using the Kaplan-Meier curve and log-rank tests (χ2  = 7.402, p = 0.007). CONCLUSIONS: Severity of cerebral degeneration is associated with survival in ALS. CST degeneration progresses faster in subgroups of patients with shorter survival. Neuroimaging holds promise as a tool to improve patient management and facilitation of clinical trials.

A Diffusion Tensor Imaging-Based Prognostic Classification for Surgery of Intrinsic Lesions Involving the Motor Pathways.

BACKGROUND: The critical role of different adjuncts in improving the neurological outcome in intrinsic brain lesions affecting eloquent areas is demonstrated by their more diffuse utilization. Neurosurgeons often rely on preoperative and intraoperative diffusion tensor imaging tractography to improve the operative strategy and prognosis. We aimed to identify and validate a diffusion tensor imaging-based classification considering the relationship between the brain lesion and the corticospinal tract to predict a >50% reduction of motor evoked potentials (MEPs) during surgical excision of lesions involving the motor pathways. METHODS: We included patients consecutively enrolled at our institution between April 2020 and September 2022 with 3 patterns of increasing complexity according to the relationship between the lesion and the corticospinal tract as identified on preoperative diffusion tensor imaging. Outcome measures were >50% reduction in intraoperative MEPs and neurological outcome defined as unchanged, improved, or worsened. RESULTS: The study included 83 patients. A statistically significant linear trend between higher rates of reduction of MEPs and higher classification grades was observed (P = 0.001), with sensitivity 0.60, specificity 0.88, accuracy 0.83, and area under the curve 0.75. Higher grades were associated with worse neurological outcomes (P = 0.02). CONCLUSIONS: The classification proved reliable in anticipating reduction in intraoperative MEPs and in predicting neurological outcome. Using this classification in patients undergoing surgery for lesions involving the motor pathways could help in counseling the patient, surgical planning, enhancing teamwork of operating room personnel, and improving the patient's prognosis.

Associations between myelin water imaging and measures of fall risk and functional mobility in multiple sclerosis.

BACKGROUND AND PURPOSE: Myelin water fraction (MWF) deficits as measured by myelin water imaging (MWI) have been related to worse motor function in persons with multiple sclerosis (PwMS). However, it is unknown if measures from MWI metrics in motor areas relate to fall risk measures in PwMS. The objective of this study was to examine the relationship between MWI measures in motor areas to performance on clinical measures of fall risk and disability in PwMS. METHODS: Sixteen individuals with relapsing-remitting MS participated (1 male, 15 female; age 47.1 years [12.3]; Expanded Disability Status Scale 4.0 [range 0-6.5]) and completed measures of walking and fall risk (Timed 25 Foot Walk [T25FW] and Timed Up and Go). MWF and the geometric mean of the intra-/extracellular water T2 (geomT2IEW ) values reflecting myelin content and contribution of large-diameter axons/density, respectively, were assessed in three motor-related regions. RESULTS: The geomT2IEW of the corticospinal tract (r = -.599; p = .018) and superior cerebellar peduncles (r = -.613; p = .015) demonstrated significant inverse relationships with T25FW, suggesting that decreased geomT2IEW was related to slower walking. Though not significant, MWF in the corticospinal tract and superior cerebellar peduncles also demonstrated fair relationships with the T25FW, suggesting that worse performance on the T25FW was associated with lower MWF values. CONCLUSIONS: MWI of key motor regions was associated with walking performance in PwMS. Further MWI studies are needed to identify relationships between pathology and clinical function in PwMS to guide targeted rehabilitation therapies aimed at preventing falls.

Circuit reconstruction of newborn neurons after spinal cord injury in adult rats via an NT3-chitosan scaffold.

An implanted neurotrophin-3 (NT3)-chitosan scaffold can recruit endogenous neural stem cells to migrate to a lesion region and differentiate into mature neurons after adult spinal cord injury (SCI). However, the identities of these newborn neurons and whether they can form functional synapses and circuits to promote recovery after paraplegia remain unknown. By using combined advanced technologies, we revealed here that the newborn neurons of several subtypes received synaptic input from the corticospinal tract (CST), rubrospinal tract (RST), and supraspinal tracts. They formed a functional neural circuit at the injured spinal region, further driving the local circuits beneath the lesion. Our results showed that the NT3-chitosan scaffold facilitated the maturation of spinal neurons and the reestablishment of the spinal neural circuit in the lesion region 12 weeks after SCI. Transsynaptic virus experiments revealed that these newborn spinal neurons received synaptic connections from the CST and RST and drove the neural circuit beneath the lesion via newly formed synapses. These re-established circuits successfully recovered the formation and function of the neuromuscular junction (NMJ) beneath the lesion spinal segments. These findings suggest that the NT3-chitosan scaffold promotes the formation of relay neural circuits to accommodate various types of brain descending inputs and facilitate functional recovery after paraplegia.