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Disruptions in the brain's connections to the hands resulting from a cervical spinal cord injury (cSCI) can lead to severe and persistent functional impairments. The integrity of these connections is an important predictor of upper extremity recovery in stroke and may similarly act as a biomarker in cSCI. In this perspective article, we review recent findings from a large cohort of individuals with cSCI, demonstrating the predictive value of corticospinal tract (CST) integrity in cSCI—CST sparing. This research underscores that, akin to stroke, the integrity of brain-to-hand connections is crucial for predicting upper extremity recovery following cSCI. We address the limitations of commonly used metrics, such as sacral sparing and the concept of central cord syndrome. Furthermore, we offer insights on emerging metrics, such as tissue bridges, emphasizing their potential in assessing the integrity of brain connections to the spinal cord. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) pathology and pathophysiology can be attributed to both primary physical injury and secondary injury cascades. Secondary injury cascades involve dysregulated metabolism and energetic deficits directly linked to compromised mitochondrial bioenergetics. Rescuing mitochondrial function and reducing oxidative stress are associated with neuroprotection. In this regard, ketosis after traumatic brain injury (TBI), or after SCI, improves secondary neuropathology by decreasing oxidative stress, increasing antioxidants, reducing inflammation, and improving mitochondrial bioenergetics. Here, we follow up on our previous study and have used an exogenous ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE), as an alternative to a ketogenic diet, focusing on mitochondrial function between 1 and 14 days after injury. Starting 3 h following a cervical level 5 (C5) hemi-contusion injury, animals were fed either a standard control diet (SD) or a ketone ester diet (KED) combined with KE administered orally (OKE). We found that mitochondrial function was reduced after SCI at all times post-SCI, accompanied by reduced expression of most of the components of the electron transport chain (ETC). The KE rescued some of the bioenergetic parameters 1 day after SCI when D-β-Hydroxybutyrate (BHB) concentrations were ~2 mM. Still, most of the beneficial effects were observed 14 days after injury, with BHB concentrations reaching values of 4–6 mM. To our knowledge, this is the first report to show the beneficial effects of KE in rescuing mitochondrial function after SCI and demonstrates the suitability of KE in ameliorating the metabolic dysregulation that occurs after traumatic SCI without requiring a restrictive dietary regime. [ABSTRACT FROM AUTHOR]

Study design: Cross-sectional Database Study. Objective: While the American Spinal Injury Association (ASIA) Impairment Scale is the standard for assessing spinal cord injuries (SCI), it has limitations due to subjectivity and impracticality. Advances in machine learning (ML) and image recognition have spurred research into their use for outcome prediction. This study aims to analyze deep learning techniques for identifying and classifying cervical SCI severity from MRI scans. Methods: The study included patients with traumatic and nontraumatic cervical SCI admitted from 2019 to 2022. MRI images were labeled by two senior resident physicians. A deep convolutional neural network was trained using axial and sagittal cervical MRI images from the dataset. Model performance was assessed using Dice Score and IoU to measure segmentation accuracy by comparing predicted and ground truth masks. Classification accuracy was evaluated with the F1 Score, balancing false positives and negatives. Result: In the axial spinal cord segmentation, we achieved a Dice score of 0.94 for and IoU score of 0.89. In the sagittal spinal cord segmentation, we obtained Dice score up to 0.9201 and IoU scores up to 0.8541. The model for axial image score classification gave a satisfactory result with an F1 score of 0.72 and AUC of 0.79. Conclusion: Our models successfully identified cervical SCI on T2-weighted MR images with satisfactory performance. Further research is needed to develop more advanced models for predicting patient outcomes in SCI cases. [ABSTRACT FROM AUTHOR]

Degenerative cervical myelopathy (DCM) is characterized by spinal cord atrophy. Accurate estimation of spinal cord atrophy is key to the understanding of neurological diseases, including DCM. However, its clinical application is hampered by difficulties in its precise and consistent estimation due to significant variability in spinal cord morphometry along the cervical spine, both within and between individuals. To characterize morphometrics of the compressed spinal cord in DCM patients. We employed our semiautomated analysis framework that incorporates the Spinal Cord Toolbox (SCT) and a normalization approach to effectively address the challenges posed by cord compression in these patients. Additionally, we examined the clinical relevance of these morphometric measures to enhance our understanding of DCM pathophysiology. Prospective study. This study investigated 36 DCM patients and 31 healthy controls (HCs). Clinical scores including 9-hole peg test for hand dexterity, hand grip strength, balance, gait speed, modified Japanese Orthopaedic Association (mJOA) score, and imaging-based spinal cord morphometrics. Using the generic spine acquisition protocol and our semiautomated analysis pipeline, spinal cord morphometrics, including cross-sectional area (CSA), anterior-posterior (AP) and transverse (RL) diameters, eccentricity, and solidity, were estimated from sagittal T2w magnetic resonance imaging (MRI) images using the Spinal Cord Toolbox (SCT). Normalized metrics were extracted from the C1 to C7 vertebral levels and compared between DCM patients and HC. Morphometric data at regions of maximum spinal cord compression (MSCC) were correlated with the clinical scores. A subset of participants underwent follow-up scans at 6 months to monitor longitudinal changes in spinal cord atrophy. Spinal cord morphometric data were normalized against the healthy population morphometry (PAM50 database) and extracted for all participants. DCM patients showed a notable reduction in CSA, AP, and RL diameter across all vertebral levels compared to HC. MSCC metrics correlated significantly with clinical scores like dexterity, grip strength, and mJOA scores. Longitudinal analysis indicated a decrease in CSA and worsening clinical scores in DCM patients. Our processing pipeline offers a reliable method for assessing spinal cord compression in DCM patients. Normalized spinal cord morphometrics, particularly the CSA could have potential for monitoring DCM disease severity and progression, guiding treatment decisions. Furthermore, to our knowledge our study is the first to apply the generic spinal cord acquisition protocol, ensuring consistent imaging across different MRI scanners and settings. Coupled with our semiautomated analysis pipeline, this protocol is key for the detailed morphometric characterization of compressed spinal cords in patients with DCM, a disease that is both complex and heterogenous. This study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) (K23:NS091430) and (R01: NS129852-01A1). [ABSTRACT FROM AUTHOR]

Cases of isolated spinal cord ischemia resulting in symptoms in neonates are rare, and there are even fewer reported cases in atraumatic births. We present a case of a presumed isolated cervical cord ischemic injury, discuss differentials to consider when evaluating a neonatal spinal cord injury, and highlight the difficulties of diagnosing a spinal cord infarction. [ABSTRACT FROM AUTHOR]

Purpose: Upper cervical fracture combined with non-contiguous lower cervical fracture are not uncommon but complicated. In order to outline a management principle for the upper cervical fracture combined with non-contiguous lower cervical fracture and assess its clinical characteristics, we retrospectively analyzed 59 cases of patients who underwent surgical treatment for upper cervical fracture combined with non-contiguous lower cervical fracture. Methods: 59 patients of upper cervical fracture combined with non-contiguous lower cervical fracture were treated by surgery in our hospital. According to the AO Spine classification for cervical fractures, there were 21 cases of type B atlas fractures, nine cases of type C atlas fractures; 15 cases of type B axis fractures, 14 cases of type C axis fractures; 19 cases of type B lower cervical fractures, 40 cases of type C lower cervical fractures. The operation time, intraoperative blood loss, complications, VAS scores, JOA scores, ASIA grades, and radiological evaluation of cervical lordosis and stability were collected and recorded. Results: Our results showed the segments of upper cervical fracture combined with non-contiguous lower cervical fracture are mainly concentrated in the atlas-axis and C6, C7 levels. There were 43 cases (72.88%) of associated injuries, mainly involving head trauma and thoracic injuries. Four patients underwent anterior approach surgery only, 43 patients underwent posterior approach surgery only, and 12 patients underwent combined anterior and posterior approach surgery in one stage. All patients had regular follow up with an average duration of 67.83 ± 11.25 months (range, 39 to 103 months). The VAS scores and JOA scores at 12 months postoperatively and at final follow-up showed significant improvement compared to preoperative scores (P < 0.05). At the final follow-up, ASIA grades had improved by 0 to 2 levels. The cervical lordosis at the final follow-up (24.71°±7.39°) showed no statistically significant difference compared to preoperative measurements (26.89°±13.32°). Surgical complications occurred in 17 patients. No cases of vertebral artery injury, screw loosening, or other internal fixation failures were found at final follow-up. Conclusions: Upper cervical fracture combined with non-contiguous lower cervical fracture can result in varying extents of cervical spinal cord injury and combined trauma in other parts. Surgical treatment of these injuries can achieve favourable clinical and radiological outcomes in the medium to long term follow-up. More research is still needed to optimize clinical decision-making regarding surgical approach. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is unsurpassed for its clinical and pathological hetherogeneity, but the biological determinants of this variability are unknown. HLA‐DRB1*15, the main genetic risk factor for MS, influences the severity and distribution of MS pathology. This study set out to unravel the molecular determinants of the heterogeneity of MS pathology in relation to HLA‐DRB1*15 status. Shotgun proteomics from a discovery cohort of MS spinal cord samples segregated by HLA‐DRB*15 status revealed overexpression of the extracellular matrix (ECM) proteins, biglycan, decorin, and prolargin in HLA‐DRB*15‐positive cases, adding to established literature on a role of ECM proteins in MS pathology that has heretofore lacked systematic pathological validation. These findings informed a neuropathological characterisation of these proteins in a large autopsy cohort of 41 MS cases (18 HLA‐DRB1*15‐positive and 23 HLA‐DRB1*15‐negative), and seven non‐neurological controls on motor cortical, cervical and lumbar spinal cord tissue. Biglycan and decorin demonstrate a striking perivascular expression pattern in controls that is reduced in MS (−36.5%, p = 0.036 and − 24.7%, p = 0.039; respectively) in lesional and non‐lesional areas. A concomitant increase in diffuse parenchymal accumulation of biglycan and decorin is seen in MS (p = 0.015 and p = 0.001, respectively), particularly in HLA‐DRB1*15‐positive cases (p = 0.007 and p = 0.046, respectively). Prolargin shows a faint parenchymal pattern in controls that is markedly increased in MS cases where a perivascular deposition pattern is observed (motor cortex +97.5%, p = 0.001; cervical cord +49.1%, p = 0.016). Our findings point to ECM proteins and the vascular interface playing a central role in MS pathology within and outside the plaque area. As ECM proteins are known potent pro‐inflammatory molecules, their parenchymal accumulation may contribute to disease severity. This study brings to light novel factors that may contribute to the heterogeneity of the topographical variation of MS pathology. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the relationship between diffusion tensor imaging (DTI) parameters, cervical spine alignments, and spinal cord morphological parameters in patients with Hirayama disease (HD). Methods: In this retrospective cohort study, 41 HD patients were recruited from the Huashan hospital from July 2017 to November 2021. Patients received X-rays, conventional magnetic resonance (MR), and DTI scans in flexion and neutral positions. The DTI parameters assessed were calculated using the region of interest (ROI) method. Paired t-tests were performed on the DTI parameters of neck flexion and neutral position. Cervical spine alignments, including flexion and neutral Cobb angles, were measured, and range of motion (ROM) was calculated. Spinal cord morphological parameters were measured, including spinal cord atrophy (SCA) and loss of attachment (LOA). Spearman's correlation analysis between DTI parameters, cervical spine alignments, and spinal cord morphological parameters was performed. Results: In comparing DTI parameters, segments of the C3/4, C4/5, C6/7, and lower cervical spine were significantly different, while segments of C5/6 were not significantly different. In Spearman's correlation analysis, the flexion Cobb angle was significantly correlated with the fractional anisotropy (FA) value (R 2 =.111, P =.033) and apparent diffusion coefficient (ADC) value (R 2 =.119, P =.027). Flexion FA values were correlated with SCA in C4/5 (R 2 =.211, P =.003), C5/6 (R 2 =.454, P <.001), and C6/7 (R 2 =.383, P <.001) while flexion ADC values were correlated with SCA in the C4/5 (R 2 =.178, P =.006), C5/6 (R 2 =.388, P <.001) and C6/7 segments (R 2 =.187, P =.005). Conclusion: The DTI parameters were correlated with the flexion Cobb angle and the SCA. These data support the dynamic cervical flexion compression hypothesis and indicate that the degree of SCA may be used to assess the condition of HD patients quantitatively. [ABSTRACT FROM AUTHOR]

Objective: To analyze the influencing factors and treatment options of cervical spondylotic myelopathy (CSM) complicated with traumatic central cord syndrome (TCCS). Methods: A total of 243 patients with CSM admitted to our hospital from January 2021 to September 2022 were retrospectively analyzed, and then divided into the control group (n = 152) and the observation group (n = 91) according to the presence or absence of concurrent TCCS. The clinical data and imaging data of the two groups were compared, and multivariate logistic regression was used to analyze the influencing factors of CSM complicated with TCCS. Patients in the observation group were further divided into the zero notch anterior cervical interbody fusion device (Zero-P) group (n = 45) and the cervical spine locking plate (CSLP) group (n = 46) according to the treatment mode, and the perioperative indexes of the two groups were compared. The treatment effects were evaluated by the American Spinal Injury Association (ASIA) and the Japanese Orthopedic Association (JOA) before surgery, 1 week after surgery and 6 months after surgery. The height of intervertebral space and the cervical lordosis angle were measured. Results: Multivariate logistic regression analysis showed that the injury mechanism (hyperextension injury), hand muscle weakness, cervical instability, age, degree of cervical spinal stenosis, degree of cervical spinal cord compression, and changes in intramedullary high signal were the risk factors, while the type of compression (soft), ASIA score and JOA score were the protective factor for CSM complicated with TCCS (P < 0.05). Patients in Zero-P group had much shorter operation time and hospitalization time than these in CSLP group (P < 0.05). The cervical lordosis angle and intervertebral space height at 1 week and 6 months after operation in the two groups were both largely higher than these before operation, and the cervical lordosis angle and intervertebral space height in the Zero-P group were significantly higher than these in the CSLP group one week after surgery (P < 0.05). The ASIA score and JOA score were obviously increased in the two groups 1 week and 6 months after surgery, and the ASIA score and JOA score in the Zero-P group were significantly higher than these in the CSLP group at 1 week after surgery (P < 0.05). Conclusion: The mechanism of TCCS in CSM is still controversial, which it is generally believed to be caused by cervical hyperextension injury. The clinical symptoms are diverse, and the treatment methods are also different. This study shows that the mechanism of injury, type of compression, hand muscle weakness, cervical instability, age, cervical stenosis compression, and intramedullary high signal changes are all risk factors for CSM complicated with TCCS. Early identification of risk factors and targeted interventions can effectively reduce the complicated rate of TCCS. Zero-P and CSLP surgical fixation have good efficacy in the treatment of TCCS, and there is little difference in efficacy between the two. However, Zero-P fixation surgery has the advantages of short operation time and fast postoperative recovery. [ABSTRACT FROM AUTHOR]

Background: The co-occurrence of multiple sclerosis (MS) and cervical spondylosis (CS) may not only intensify symptoms but also complicate the management of these disorders. Magnetic resonance imaging (MRI) is the preferred modality for detecting spinal cord lesions; however, there is limited evidence assessing myelopathy in concurrent CS and MS. Objectives: This study aims to evaluate the association between CS and its effects on the spinal cord, as well as their impact on enhancing MS cervical lesions. Methods: This cross-sectional study was conducted on 104 MS patients between 2019 and 2021. Data collected included age, gender, duration and phenotype of MS, and the Extended Disability Status Scale (EDSS). Magnetic resonance imaging images were obtained and analyzed for the presence of cervical spondylosis and demyelinated cervical plaques (active/inactive). Multiple sclerosis plaques were evaluated based on their extension, enhancement, and cervical location. Cervical spondylosis was categorized into four grades using the Muhle scale. Additionally, the spinal cord cross-sectional area (SC - CSA) was measured at the C2 - C3 cervical spine level. Results: The severity of cervical spondylosis was associated with older age (P-value < 0.001), longer duration of MS (P-value = 0.04), more severe EDSS scores (P-value = 0.03), and a lower C2 - C3 CS-CSA (P-value < 0.001). However, no significant associations were found with gender (P-value = 0.90), MS plaques activity (P-value = 0.25), or extension (P-value = 0.13). Conclusions: The study findings indicate that the severity of CS is associated with age, MS duration, EDSS, and the C2 - C3 cervical spine cross-sectional area. However, the study did not find evidence supporting a relationship between CS and the extension or activity of MS plaques. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical application of zonally magnified oblique multislice (ZOOM) imaging technology in patients with degenerative cervical myelopathy (DCM) and compare it with T2WI imaging. Methods: A total of 111 patients diagnosed with DCM were recruited. According to mJOA, patients with DCM were divided into ND + group with neurological dysfunction and ND- group without neurological dysfunction. Routine MRI and ZOOM-DWI were performed on 3.0 T MRI to obtain sagittal T2WI and apparent diffusion coefficient (ADC) diagram. ADC values of the narrow segment and its adjacent upper and lower segments were measured, and compared between the ND + and ND- groups. The correlation between ADC value of cervical spinal cord and mJOA score was analyzed. Additionally, ROC curves were plotted to calculate the AUC values. Results: The comparison between ND + and ND– groups shows that there are significant differences in mJOA score, T2WI, anteroposterior diameter of spinal canal, ADC values of narrow, upper and lower segment (P < 0.05). In ND + group, there is a significant difference between ADC values of the narrow and its upper and lower segments (P < 0.001), while with no significant difference in ADC values of the upper and lower segments (P > 0.05). Results of correlation analysis indicate that in the ND + group, neurological dysfunction evaluated by mJOA scores is correlated with increased ADC values of the narrow segment (r = –0.52, P < 0.001), but not significantly correlated with ADC values of the upper and lower segments. Furthermore, T2WI, anteroposterior diameter of the spinal canal, and cervical cord ADC values all has diagnostic efficacy in evaluating neurological dysfunction in DCM (AUC > 0.5, P < 0.05), with the ADC value of the narrow segment being optimal. Conclusion: The ADC value of spinal cord obtained by small-field ZOOM-DWI can be used to evaluate neurological dysfunction in DCM, and is superior to traditional T2WI. [ABSTRACT FROM AUTHOR]

Simple Summary: Hydrated nucleus pulposus extrusion (HNPE) is a well-known pathological condition in veterinary neurology. Any breed of middle-aged or older dogs (median 9 years old) can be affected; it has an acute spontaneous onset, is rarely exercise-associated, and commonly affects the cervical region, causing tetraparesis or tetraplegia and mild cervical hyperesthesia. This study presents the first documented case of double cervical adjacent HNPEs in a small breed dog. A 9-year-old 6 Kg intact male Yorkshire terrier was referred for an acute onset of non-ambulatory tetraparesis. MR examination of the cervical spine showed two concurrent HNPEs at sites C3-C4 and C4-C5. The dog had a remission of symptoms with conservative therapy and physiotherapy. A 9-year-old Yorkshire terrier was brought to the emergency department for inability to maintain the correct station with acute onset. Neurological examination showed a non-ambulatory tetraparesis, spontaneous proprioceptive deficit in all limbs, and decreased flexor reflex in the forelimbs. The neurological symptoms suggested a cranial cervical spinal cord with suspicion of spinal shock. The clinical differential diagnoses included degenerative (intervertebral disc extrusion), vascular, inflammatory, or neoplastic disease. No pathological findings were evident in the hematobiochemical tests or in the radiograph examination. MRI examination of the cervical spine showed the presence of two adjacent hydrated nucleus pulposus extrusions at C3-C4 and C4-C5 tracts. Treatment included analgesic and non-steroidal anti-inflammatory therapy; movement restriction was initially necessary, followed by physiotherapy. Follow-up at 4 weeks showed complete recovery. A telephone follow-up after 3 months with the owner confirmed the absence of symptoms. This article reports the first double cervical HNPE case in a dog, adding the possibility that the disease may present in this form and the success of conservative treatment as described in the literature. [ABSTRACT FROM AUTHOR]

Cervical spinal cord injury usually results in cardiorespiratory dysfunctions due to interruptions of the bulbospinal pathways innervating the cervical phrenic motoneurons and thoracic sympathetic preganglionic neurons. The present study aimed to evaluate the therapeutic effects of adrenergic agents on systemic and spinal hemodynamics during acute cervical spinal cord injury. In vivo animal study. The cardiorespiratory function and spinal cord blood flow and oxygenation level were monitored in response to cervical spinal cord contusion and intravenous infusion of three types of adrenergic agents (phenylephrine, dobutamine, and norepinephrine). Cervical spinal cord contusion resulted in immediate reduction of respiratory airflow, arterial blood pressure, and spinal cord blood flow. The arterial blood pressure and spinal cord blood flow remained lower than the preinjury value in contused animals infused with saline at 60 min postinjury. Infusion of phenylephrine (500, 1000, and 2000 μg/kg) and norepinephrine (125, 250, and 500 μg/kg) significantly increased the arterial blood pressure, while only norepinephrine augmented the spinal cord blood flow. Conversely, dobutamine (1000 and 2000 μg/kg) reduced both arterial blood pressure and spinal cord blood flow. Notably, administration of adrenergic agents tended to increase spinal cord hemorrhage in contused animals. Infusion of norepinephrine can effectively maintain the blood pressure and improve spinal cord blood flow during acute spinal cord injury. Norepinephrine may be a superior medicine for hemodynamic management; however, the potential hemorrhage should be considered when utilizing the vasopressor to regulate systemic and spinal hemodynamics at the acute injured stage. [ABSTRACT FROM AUTHOR]

Background: Cardiac pacemaker implantation may be indicated in patients with refractory bradycardia following a cervical spinal cord injury (CSCI). However, evidence about the impact of this procedure on outcomes is lacking. We planned a study to assess whether the implantation of a pacemaker would decrease mortality and hospital resource utilization in patients with CSCI. Methods: Adult patients with CSCI in the Trauma Quality Improvement Program (TQIP) database between 2016 and 2019 were retrospectively analyzed. Patients were divided into "pacemaker" and "non-pacemaker" groups, and their baseline characteristics and clinical outcomes were analyzed. Results: A total of 6774 cases were analyzed. The pacemaker group showed higher in-hospital rates of cardiac arrest, myocardial infarction, and longer duration of mechanical ventilation and ICU stay than the non-pacemaker group. Nevertheless, pacemaker placement was associated with a significant decrease in mortality (4.2% vs 26.0%, P < .01). Conclusions: Patients with CSCI requiring a pacemaker placement had better survival than those treated without a pacemaker. Pacemaker implantation should be highly considered in patients who develop refractory bradycardia after CSCI. [ABSTRACT FROM AUTHOR]

Purpose: To address the limitations of spinal cord imaging at ultra‐high field (UHF) due to time‐consuming parallel transmit (pTx) adjustments. This study introduces calibration‐free offline computed universal shim modes that can be applied seamlessly for different pTx RF coils and spinal cord target regions, substantially enhancing spinal cord imaging efficiency at UHF. Methods: A library of channel‐wise relative B1+$$ {B}_1^{+} $$ maps for the cervical spinal cord (six datasets) and thoracic and lumbar spinal cord (nine datasets) was constructed to optimize transmit homogeneity and efficiency for these regions. A tailored B0 shim was optimized for the cervical spine to enhance spatial magnetic field homogeneity further. The performance of the universal shims was validated using absolute saturation based B1+$$ {B}_1^{+} $$ mapping and high‐resolution 2D and 3D multi‐echo gradient‐recalled echo (GRE) data to assess the image quality. Results: The proposed universal shims demonstrated a 50% improvement in B1+$$ {B}_1^{+} $$ efficiency compared to the default (zero phase) shim mode. B1+$$ {B}_1^{+} $$ homogeneity was also improved by 20%. The optimized universal shims achieved performance comparable to subject‐specific pTx adjustments, while eliminating the need for lengthy pTx calibration times, saving about 10 min per experiment. Conclusion: The development of universal shims represents a significant advance by eliminating time‐consuming subject‐specific pTx adjustments. This approach is expected to make UHF spinal cord imaging more accessible and user‐friendly, particularly for non‐pTx experts. [ABSTRACT FROM AUTHOR]

Scholars usually consider the Historia anatomica corporis humani, published in 1600 by André du Laurens, as an obsolete defense of Galenic principles against the novelty of Vesalian material. Although du Laurens’s book plagiarized many illustrations from Vesalius’s De humani corporis fabrica (1543), critics such as Choulant insisted that the Historia’s iconography had “no particular anatomical or artistic value.” However, four of the Historia’s engravings appear to be original. One of these, the Tabula hæc veram spinalis medullae et nervorum ab ea prodeuntium effigiem exprimit, is now famous for depicting the intradural spinal nerves as a horsetail, leading to the addition of the term cauda equina to the anatomical lexicon. A less flamboyant figure from the same plate shows small blood vessels coursing over the surface of the cervical spinal cord. This drawing may be the first published depiction of anterior spinal arteries and veins. [ABSTRACT FROM AUTHOR]

A 23-month-old boy with poor growth, developmental delay, and hypotonia presented with acute onset of ataxia and fatigue. Magnetic resonance imaging (MRI) of the brain and spinal cord was performed as part of diagnostic work-up. MRI showed bilateral symmetrical lesions in basal ganglia, midbrain, and brainstem consistent with Leigh syndrome. Signal abnormalities were also present within the cervical cord, with enhancement of multiple cranial, spinal, and cauda equina nerve roots. Genetic testing confirmed compound heterozygosity for two pathogenic variants in SURF1 implicated in Leigh syndrome. Whilst nerve root enhancement has been described in other mitochondrial disorders, we believe this is the first published case of both cranial and spinal nerve root enhancement in Leigh syndrome. [ABSTRACT FROM AUTHOR]

(1) Background: The influence of robotic therapy on patients with sub-acute cervical spinal cord injury (SCI) for improving their activities of daily living (ADL) performance is unclear; (2) Methods: 31 subjects with cervical SCI completed the training randomly assigned to an intervention or control group during 40 sessions. All the subjects received, in each session, 30 min of upper-extremity conventional therapy. In addition, the subjects within the control group received another 30 min of conventional therapy, whereas subjects within the intervention group received 30 min of robotic therapy with Armeo Spring (Hocoma AG, Volketswil, Switzerland). Therefore, the ADL of drinking was trained by using the exoskeleton. Feasibility and efficacy measurements as clinical scales and kinematic indices, and usability questionnaires, were used as assessment at baseline and at the ending of the study (week 10); (3) Results: The intervention group significantly improved with regards to the feeding and grooming items of the Spinal Cord Independence Measure scale. The improvement in the movement smoothness related to the activity of drinking was greater in the intervention group than in the control (p = 0.034); (4) Conclusions: The findings of this study reveal that patients with cervical SCI improve their performance in ADL with robotic therapy. [ABSTRACT FROM AUTHOR]

Background: Disease progression is observed across the spectrum of people with multiple sclerosis (MS) and identification of effective treatment strategies to halt progression remains one of the greatest unmet clinical needs. Objectives: The Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) was designed to evaluate a wide range of factors associated with the onset and rate of clinical disease progression in MS and to describe the interplay between these factors. Design: A prospective cohort study. Methods: CanProCo is a national, prospective, observational cohort study that has recruited 944 individuals from 5 large academic MS centers in Canada. Participants include people with radiologically isolated syndrome (RIS), early relapsing-remitting and primary progressive MS (RRMS, PPMS), and healthy controls (HCs). Annually, participants complete self-reported questionnaires, undergo clinical evaluation and, if clinically indicated, magnetic resonance images (MRIs) of the brain and cervical spinal cord; in a subset of participants (n = 399), blood, and research MRIs of the brain and cervical spinal cord are collected. Linkages to health administrative databases are available at three sites. Results: Overall, 944 participants were recruited (53 HCs, 63 RIS, 751 RRMS, 77 PPMS). RIS and MS participants had a mean age of 39.0 years and 70.5% female. The mean time since diagnosis was 2.7 years. There were differences observed in the Expanded Disability Status Scale score and components of the MS performance test (walking speed test, manual dexterity test, processing speed test, and low-contrast visual acuity) between RIS and MS subtypes. Questionnaires revealed more symptoms of depression and anxiety and impaired physical and mental quality of life in people with RIS/MS versus HCs and differences across RIS/MS subtypes. Conclusion: Physical and mental neurological disability is prevalent even in the earliest stages of MS. Transdisciplinary approaches such as those used in CanProCo are needed to better characterize clinical progression in MS. Additional CanProCo results, including MRI, biological, and pharmaco-economic data will be forthcoming. Going forward, CanProCo's data sharing and collaborative vision will facilitate numerous global collaborations, which will inform the development and implementation of effective interventions for people with MS around the world. [ABSTRACT FROM AUTHOR]

This retrospective study analyzed prognostic factors for neurological improvement and ambulation in 194 adult patients (≥ 15 years) with traumatic cervical spinal cord injuries treated at the neurological SCI unit (SCIU) at the Karolinska University Hospital Stockholm, Sweden, between 2010 and 2020. The primary outcome was American spinal injury association impairment scale (AIS) improvement, with secondary focus on ambulation restoration. Results showed 41% experienced AIS improvement, with 51% regaining ambulation over a median follow-up of 3.7 years. Significant AIS improvement (p < 0.001) and reduced bladder/bowel dysfunction (p < 0.001) were noted. Multivariable analysis identified initial AIS C-D (< 0.001), central cord syndrome (p = 0.016), and C0–C3 injury (p = 0.017) as positive AIS improvement predictors, while lower extremity motor score (LEMS) (p < 0.001) and longer ICU stays (p < 0.001) were negative predictors. Patients with initial AIS C-D (p < 0.001) and higher LEMS (p < 0.001) were more likely to regain ambulation. Finally, older age was a negative prognostic factor (p = 0.003). In conclusion, initial injury severity significantly predicted neurological improvement and ambulation. Recovery was observed even in severe cases, emphasizing the importance of tailored rehabilitation for improved outcomes. [ABSTRACT FROM AUTHOR]

Background: The effect of fat infiltration in the paraspinal muscles on cervical degenerative disease has been confirmed by multiple studies. However, little is known about fat infiltration in the paraspinal extensors in patients with acute cervical spinal cord injury (SCI). This study aimed to investigate the difference in paraspinal extensor fatty infiltration between patients with acute cervical SCI and healthy controls, and to further explore the protective role of the paravertebral extensor muscles in patients with cervical SCI. Methods: A total of 50 patients with acute cervical SCI admitted to the emergency department from January 2019 to November 2023 were retrospectively analyzed, including 26 males and 24 females, with an average age of 59.60 ± 10.81 years. A control group of 50 healthy middle-aged and elderly individuals was also included, comprising 28 males and 22 females, with an average age of 55.00 ± 8.21 years. Cervical spine magnetic resonance imaging (MRI) was used to measure the cross-sectional areas of the superficial and deep cervical extensor muscles, the corresponding vertebral body cross-sectional areas, and the fat area within the superficial and deep extensor muscle groups using Image J software. Differences between the two groups were compared, and the cervical SCI patients were further analyzed based on the severity of the spinal cord injury and gender differences. Results: The deep fatty infiltration ratio (DFIR) and superficial fatty infiltration ratio (SFIR) at C4-C7 in the cervical SCI group were significantly higher than those in the control group (P < 0.001). The cross-sectional area of the functional deep extensor area (FDEA) relative to the vertebral body area (VBA) and the cross-sectional area of the functional superficial extensor area (FSEA) relative to the VBA at the C5 and C6 levels in the cervical SCI group were significantly lower than those in the control group (P < 0.001, P < 0.001, P = 0.034, P = 0.004 respectively). Among the cervical SCI patients, the cross-sectional areas of the deep extensor area (DEA) and the superficial extensor area (SEA) in males were significantly higher than those in females (P < 0.001). At the C6 and C7 levels, the FDEA/VBA and FSEA/VBA ratios in the male group were higher than those in the female group (P = 0.009, P = 0.022, P = 0.019, P = 0.005, respectively). Conclusion: Patients with acute cervical SCI exhibit significantly higher fatty infiltration and a greater degree of paravertebral extensor muscle degeneration compared to healthy controls. This finding underscores the importance of the paravertebral extensor muscles in the context of cervical SCI and may guide future therapeutic strategies. [ABSTRACT FROM AUTHOR]

An 8‐year‐old female spayed German shepherd dog was presented for evaluation of a 1‐week history of right thoracic limb monoparesis. Magnetic resonance imaging (MRI) identified an intraparenchymal, T2 hypointense and T1 isointense, strongly heterogeneously contrast‐enhancing mass with moderate internal susceptibility artifact on T2* images at the level of the cranial extent of the C5 vertebral body. Euthanasia was elected after a rapid neurologic decline in the 24 hours after MRI. Necropsy and histopathology identified an intraparenchymal hemangiosarcoma arising from a hemangioma in the cervical spinal cord, with no evidence of neoplastic disease in any other examined organs. The spectrum of vasoproliferative disorders in the central nervous system in veterinary species has been codified recently, but hemangiosarcoma is considered metastatic to the central nervous system. Herein we describe the clinical, imaging, and histologic findings in a dog with a novel primary location of hemangiosarcoma in the cervical spinal cord. [ABSTRACT FROM AUTHOR]

A major portion of spinal cord injury (SCI) cases occur in the cervical region, where essential components of the respiratory neural circuitry are located. Phrenic motor neurons (PhMNs) housed at cervical spinal cord level C3–C5 directly innervate the diaphragm, and SCI-induced damage to these cells severely impairs respiratory function. In this study, we tested a biomaterial-based approach aimed at preserving this critical phrenic motor circuitry after cervical SCI by locally delivering hepatocyte growth factor (HGF). HGF is a potent mitogen that promotes survival, proliferation, migration, repair, and regeneration of a number of different cell and tissue types in response to injury. We developed a hydrogel-based HGF delivery system that can be injected into the intrathecal space for local delivery of high levels of HGF without damaging the spinal cord. Implantation of HGF hydrogel after unilateral C5 contusion-type SCI in rats preserved diaphragm function, as assessed by in vivo recordings of both compound muscle action potentials and inspiratory electromyography amplitudes. HGF hydrogel also preserved PhMN innervation of the diaphragm, as assessed by both retrograde PhMN tracing and detailed neuromuscular junction morphological analysis. Furthermore, HGF hydrogel significantly decreased lesion size and degeneration of cervical motor neuron cell bodies, as well as reduced levels surrounding the injury site of scar-associated chondroitin sulfate proteoglycan molecules that limit axon growth capacity. Our findings demonstrate that local biomaterial-based delivery of HGF hydrogel to injured cervical spinal cord is an effective strategy for preserving respiratory circuitry and diaphragm function. [ABSTRACT FROM AUTHOR]

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a promising technique for assessing spinal cord injury (SCI) that has historically been challenged by the presence of metallic stabilization hardware. This study leverages recent advances in metal-artifact resistant multi-spectral DW-MRI to enable diffusion quantification throughout the spinal cord even after fusion stabilization. Twelve participants with cervical spinal cord injuries treated with fusion stabilization and 49 asymptomatic able-bodied control participants underwent multi-spectral DW-MRI evaluation. Apparent diffusion coefficient (ADC) values were calculated in axial cord sections. Statistical modeling assessed ADC differences across cohorts and within distinct cord regions of the SCI participants (at, above, or below injured level). Computed models accounted for subject demographics and injury characteristics. ADC was found to be elevated at injured levels compared with non-injured levels (z = 3.2, p = 0.001), with ADC at injured levels decreasing over time since injury (z = -9.2, p < 0.001). Below the injury level, ADC was reduced relative to controls (z = -4.4, p < 0.001), with greater reductions after more severe injuries that correlated with lower extremity motor scores (z = 2.56, p = 0.012). No statistically significant differences in ADC above the level of injury were identified. By enabling diffusion analysis near fusion hardware, the multi-spectral DW-MRI technique allowed intuitive quantification of cord diffusion changes after SCI both at and away from injured levels. This demonstrates the approach's potential for assessing post-surgical spinal cord integrity throughout stabilized regions. [ABSTRACT FROM AUTHOR]

Cervical spinal cord injury (SCI) results in significant sensorimotor impairments below the injury level, notably in the upper extremities (UEs), impacting daily activities and quality of life. Regaining UE function remains the top priority for individuals post-cervical SCI. Recent advances in understanding adaptive plasticity within the sensorimotor system have led to the development of novel non-invasive neurostimulation strategies, such as spinal cord transcutaneous stimulation (scTS), to facilitate UE motor recovery after SCI. This comprehensive review investigates the neuromotor control of UE, the typical recovery trajectories following SCI, and the therapeutic potential of scTS to enhance UE motor function in individuals with cervical SCI. Although limited in number with smaller sample sizes, the included research articles consistently suggest that scTS, when combined with task-specific training, improves voluntary control of arm and hand function and sensation. Further, the reported improvements translate to the recovery of various UE functional tasks and positively impact the quality of life in individuals with cervical SCI. Several methodological limitations, including stimulation site selection and parameters, training strategies, and sensitive outcome measures, require further advancements to allow successful translation of scTS from research to clinical settings. This review also summarizes the current literature and proposes future directions to support establishing approaches for scTS as a viable neuro-rehabilitative tool. [ABSTRACT FROM AUTHOR]

A Shorthair castrated 8-year-old tomcat was brought to a veterinary hospital for slowly progressive onset of tetraplegia developing within last 14 days. The clinical and blood examinations at admission showed no abnormalities, the neurological examination showed severe cervical pain and tetraplegia with lower motor neuron deficits on thoracic limbs and normal withdrawal with increased patellar reflexes on pelvic limbs. Deep pain perception was present on all four limbs. The neuroanatomic localisation was C6-T2 lesion. Magnetic resonance imaging of the cervical spine demonstrated severe spondylosis deformans, degeneration of multiple IVD, and ventral extradural right sided spinal cord compression at the level C7-T1. Mildly hyperintense on T2-weighted and STIR, mildly hypointense on T1-weighted pre-contrast, and homogeneously contrast-enhancing mass on T1-weighted post-contrast images was observed at this area. This article describes an interesting case of a tumor in a cat localised in the cervicothoracic spinal segment extradurally compressing the spinal cord and causing severe neurological dysfunction. These clinical symptoms were successfully treated through a ventral slot surgery, the tumor was well circumscribed and comfortably removable through this approach. This rare tumor is considered benign and prognosis is favourable after surgical removal due to its non-invasive growth pattern. After surgery, the cat was observed continuously for a few months and the recovery was sufficient with no recurrence of neurological symptoms by now. This case is worth attention mainly because, despite the serious clinical presentation, it has a good long term prognosis and does not require a complex surgical approach. [ABSTRACT FROM AUTHOR]

Background and Purpose: The first randomized placebo-controlled therapeutic trial in radiologically isolated syndrome (RIS), ARISE, demonstrated that treatment with dimethyl fumarate (DMF) delayed the onset of a first clinical event related to CNS demyelination and was associated with a significant reduction in new and/or newly enlarging T2-weighted hyperintense lesions. The purpose of this study was to explore the effect of DMF on volumetric measures, including whole brain, thalamic, and subcortical gray matter volumes, brainstem and upper cervical spine three-dimensional (3D) volumes, and brainstem and upper cervical spine surface characteristics. Methods: Standardized 3T MRIs including 3D isotropic T1-weighted gradient echo images were acquired at baseline and end-of-study according to the ARISE study protocol. The acquired data were analyzed using Structural Image Evaluation Using Normalization of Atrophy (SIENA), FreeSurfer v7.3, and an in-house pipeline for 3D conformational metrics. Multivariate mixed models for repeated measures were used to analyze rates of change in whole brain, thalamic, subcortical gray matter, as well as change in the 3D surface curvature of the dorsal pons and dorsal medulla and 3D volume change at the medulla-upper cervical spinal cord. Results: The study population consisted of 64 RIS subjects (DMF:30, placebo:34). No significant difference was seen in whole brain, thalamic, or subcortical gray matter volumes in treated vs. untreated RIS patients. A significant difference was observed in dorsal pons curvature with the DMF group having a lower least squares mean change of − 4.46 (standard estimate (SE): 3.77) when compared to placebo [6.94 (3.71)] (p = 0.036). In individuals that experienced a first clinical event, a greater reduction in medulla–upper cervical spinal cord volume (p = 0.044) and a decrease in surface curvature was observed at the dorsal medulla (p = 0.009) but not at the dorsal pons (p = 0.443). Conclusions: The benefit of disease-modifying therapy in RIS may extend to CNS structures impacted by neurodegeneration that is below the resolution of conventional volumetric measures. [ABSTRACT FROM AUTHOR]

The article discusses the development and benefits of total body positron emission tomography (PET) scanners, which have an extended axial field of view and improved sensitivity compared to traditional scanners. These scanners allow for simultaneous imaging of the entire body, resulting in higher sensitivity, improved signal-to-noise ratio, shorter scan times, and the ability to conduct pediatric scans without anesthesia. The article highlights the clinical and research applications of total body PET scanners, including the quantification of mu-opioid receptors in the monkey brain, spinal cord, and peripheral organs. The study demonstrates the feasibility and advantages of using total body PET scanners for preclinical research. [Extracted from the article]

Purpose: Mu-opioid receptors (MORs) are widely expressed in the central nervous system (CNS), peripheral organs, and immune system. This study measured the whole body distribution of MORs in rhesus macaques using the MOR selective radioligand [11C]carfentanil ([11C]CFN) on the PennPET Explorer. Both baseline and blocking studies were conducted using either naloxone or GSK1521498 to measure the effect of the antagonists on MOR binding in both CNS and peripheral organs. Methods: The PennPET Explorer was used for MOR total-body PET imaging in four rhesus macaques using [11C]CFN under baseline, naloxone pretreatment, and naloxone or GSK1521498 displacement conditions. Logan distribution volume ratio (DVR) was calculated by using a reference model to quantitate brain regions, and the standard uptake value ratios (SUVRs) were calculated for peripheral organs. The percent receptor occupancy (%RO) was calculated to establish the blocking effect of 0.14 mg/kg naloxone or GSK1521498. Results: The %RO in MOR-abundant brain regions was 75–90% for naloxone and 72–84% for GSK1521498 in blocking studies. A higher than 90% of %RO were observed in cervical spinal cord for both naloxone and GSK1521498. It took approximately 4–6 min for naloxone or GSK1521498 to distribute to CNS and displace [11C]CFN from the MOR. A smaller effect was observed in heart wall in the naloxone and GSK1521498 blocking studies. Conclusion: [11C]CFN total-body PET scans could be a useful approach for studying mechanism of action of MOR drugs used in the treatment of acute and chronic opioid use disorder and their effect on the biodistribution of synthetic opioids such as CFN. GSK1521498 could be a potential naloxone alternative to reverse opioid overdose. [ABSTRACT FROM AUTHOR]

Background and Objectives: We studied the clinical significance of an amplitude decrement and disappearance alarm criteria in transcranial motor-evoked potential (MEP) monitoring during surgeries on extramedullary tumors at the cervical spine with reference to postoperative morbidity. Material and Methods: We diagnosed and surgically treated fourteen patients with intradural extramedullary ventral or ventrolateral lesions to the cervical spinal cord in the Clinic of Neurosurgery at the University Hospital St Ivan Rilski from January 2018 to July 2022. Eight cases were diagnosed with schwannoma, and the remaining six had meningiomas. The follow-up period for neurological assessment was six months. Results: A decrease in the intraoperative transcranial MEPs of 50% or more compared to baseline in two cases (14.3%) resulted in an immediate postoperative motor deficit. One patient demonstrated full neurological recovery within six months, while the other exhibited only partial improvement. In six cases (42.9%) with preoperative motor deficits, tumor resection and decompression of the cervical spinal cord led directly to an increment of the transcranial MEPs by more than 20%. Postoperatively and at the 6-month follow-up, these patients showed recovery from the preoperative deficits. In the remaining cases, MEPs were stable during surgery with no clinical deterioration of the motor function. Conclusions: The decremented MEP criteria corresponded to postoperative motor deficit, whereas the improvement of the same parameters after decompression implied future recovery of preoperative motor deficits. The combination of different MEP criteria is likely to be helpful when tailored to a specific case of ventral or ventrolateral extramedullary lesions in the cervical spine. [ABSTRACT FROM AUTHOR]

Objective: Cervical spinal immobilisation procedures often include rigid cervical collars which, despite associated complications, may provide less immobilisation than previously thought. The present study reports the incidence of worsening neurological outcomes following soft collar application, and additionally reports patient comfort, compliance with spinal immobilisation, and paramedic perspectives on usage. Methods: This was an observational cohort study conducted in selected metropolitan and regional areas of NSW Ambulance between 1 May 2022 and 31 March 2023. Soft collars were used exclusively in place of rigid collars. The SPEED (SPinal Emergency Evaluation of Deficits) tool was used to evaluate new or worsening neurological deficits following pre‐hospital soft collar application. Secondary outcomes included patient‐reported comfort of the device, and paramedic assessment of efficacy. Results: Overall, 2098 soft collars were applied, of which 74 patients (3.5%) were subsequently found to have a cervical spine injury. Eight patients had a spinal cord injury, of which two experienced a worsening neurological deficit after soft collar application. In both instances, comprehensive case reviews determined that this was unlikely to have been attributable to the soft collar. The majority of patients found the soft collar comfortable, and they were well‐tolerated by patients who generally complied with immobility directions. Paramedics found the collar easy to apply, and felt it assisted in minimising patient movement. Conclusions: Pre‐hospital use of soft collars does not appear to increase the risk of significant injury. Patients found these devices relatively comfortable, and clinicians reported overall ease of use with good patient compliance with immobility directives. [ABSTRACT FROM AUTHOR]

Purpose: Advancing the development of 7 T MRI for spinal cord imaging is crucial for the enhanced diagnosis and monitoring of various neurodegenerative diseases and traumas. However, a significant challenge at this field strength is the transmit field inhomogeneity. Such inhomogeneity is particularly problematic for imaging the small, deep anatomical structures of the cervical spinal cord, as it can cause uneven signal intensity and elevate the local specific absorption ratio, compromising image quality. This multisite study explores several RF shimming techniques in the cervical spinal cord. Methods: Data were collected from 5 participants between two 7 T sites with a custom 8Tx/20Rx parallel transmission coil. We explored two radiofrequency (RF) shimming approaches from an MRI vendor and four from an open‐source toolbox, showcasing their ability to enhance transmit field and signal homogeneity along the cervical spinal cord. Results: The circularly polarized (CP), coefficient of variation (CoV), and specific absorption rate (SAR) efficiency shim modes showed the highest B1+ efficiency, and the vendor‐based "patient" and "volume" modes showed the lowest B1+ efficiency. The coefficient of variation method produced the highest CSF/spinal cord contrast on T2*‐weighted scans (ratio of 1.27 ± 0.03), and the lowest variation of that contrast along the superior–inferior axis. Conclusion: The study's findings highlight the potential of RF shimming to advance 7 T MRI's clinical utility for central nervous system imaging by enabling more homogenous and efficient spinal cord imaging. Additionally, the research incorporates a reproducible Jupyter Notebook, enhancing the study's transparency and facilitating peer verification. [ABSTRACT FROM AUTHOR]

Cerebellar pial arteriovenous fistula (PAVF) in adults presenting with congestive edema of the brainstem and cervical cord has rarely been reported. Here, we report such a case. A 59-year-old man presented with progressive weakness and numbness of the limbs and hiccups for 6 months. On physical examination, his limbs had grade III muscle strength, and he was unable to stand or walk. He also had occasional incontinence and retention. There was a positive Babinski sign in both lower limbs. Below the neck, he had hypoesthesia of the skin. Magnetic resonance imaging (MRI) showed edema of the brainstem and upper cervical cord. Digital subtraction angiography (DSA) confirmed there was a cerebellar nongalenic-type PAVF lesion; the feeding arteries were the branches of the posterior inferior cerebellar artery (PICA); and the draining vein was a single cortical vein that ultimately entered the venous systems of the brainstem and upper cervical cord. Casting Onyx-18 via the PICA obliterated the PAVF. Postoperatively, the patient recovered gradually. Two and a half months later, he could walk using a crutch and had no incontinence. Six-month follow-up MRI and DSA revealed recession of the edema of the brainstem and cervical cord and no recurrence of this PAVF. One year later, he was nearly normal. In conclusion and extremely rarely, cerebellar nongalenic-type PAVF can present with congestive edema of the brainstem and high cervical cord. This treatment by Onyx-18 embolization can resolve PAVF. [ABSTRACT FROM AUTHOR]

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

The primary aim of this study is to assess the viability of employing multimodal radiomics techniques for distinguishing between cervical spinal cord injury and spinal cord concussion in cervical magnetic resonance imaging. This is a multicenter study involving 288 patients from a major medical center as the training group, and 75 patients from two other medical centers as the testing group. Data regarding the presence of spinal cord injury symptoms and their recovery status within 72 h were documented. These patients underwent sagittal T1-weighted and T2-weighted imaging using cervical magnetic resonance imaging. Radiomics techniques are used to help diagnose whether these patients have cervical spinal cord injury or spinal cord concussion. 1197 radiomics features were extracted for each modality of each patient. The accuracy of T1 modal in testing group is 0.773, AUC is 0.799. The accuracy of T2 modal in testing group is 0.707, AUC is 0.813. The accuracy of T1 + T2 modal in testing group is 0.800, AUC is 0.840. Our research indicates that multimodal radiomics techniques utilizing cervical magnetic resonance imaging can effectively diagnose the presence of cervical spinal cord injury or spinal cord concussion. [ABSTRACT FROM AUTHOR]

Little is known about the electrophysiologic activity of the intact human spinal cord during volitional movement. We analyzed epidural spinal recordings from a total of five human subjects of both sexes during a variety of upper extremity movements and found that these spinal epidural electrograms contain spectral information distinguishing periods of movement, rest, and sensation. Cervical epidural electrograms also contained spectral changes time-locked with movement. We found that these changes were primarily associated with increased power in the theta (4–8 Hz) band and feature increased theta phase to gamma amplitude coupling, and this increase in theta power can be used to topographically map distinct upper extremity movements onto the cervical spinal cord in accordance with established myotome maps of the upper extremity. Our findings have implications for the development of neurostimulation protocols and devices focused on motor rehabilitation for the upper extremity, and the approach presented here may facilitate spatiotemporal mapping of naturalistic movements. [ABSTRACT FROM AUTHOR]

The accuracy of prognostication in patients with cervical spinal cord injury (SCI) needs to be improved. We aimed to explore the prognostic value of preserved spinal tissue bridges—injury-spared neural tissue adjacent to the lesion—for prediction of sensorimotor recovery in a large, multicentre cohort of people with SCI. For this longitudinal study, we included patients with acute cervical SCI (vertebrae C1–C7) admitted to one of three trauma or rehabilitation centres: Murnau, Germany (March 18, 2010–March 1, 2021); Zurich, Switzerland (May 12, 2002–March 2, 2019); and Denver, CO, USA (Jan 12, 2010–Feb 16, 2017). Patients were clinically assessed at admission (baseline), at discharge (3 months), and at 12 months post SCI. Midsagittal tissue bridges were quantified from T2-weighted images assessed at 3–4 weeks post SCI. Fractional regression and unbiased recursive partitioning models, adjusted for age, sex, centre, and neurological level of injury, were used to assess associations between tissue bridge width and baseline-adjusted total motor score, pinprick score, and light touch scores at 3 months and 12 months. Patients were stratified into subgroups according to whether they showed better or worse predicted recovery. The cohort included 227 patients: 93 patients from Murnau (22 [24%] female); 43 patients from Zurich (four [9%] female); and 91 patients from Denver (14 [15%] female). 136 of these participants (from Murnau and Zurich) were followed up for up to 12 months. At 3 months, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 9·3% (SD 0·9) of maximal total motor score (95% CI 7·5–11.2), 8·6% (0·8) of maximal pinprick score (7·0–10·1), and 10·9% (0·8) of maximal light touch score (9·4–12·5). At 12 months post SCI, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 10·9% (1·3) of maximal total motor score (8·4–13·4), 5·7% (1·3) of maximal pinprick score (3·3–8·2), and 6·9% (1·4) of maximal light touch score (4·1–9·7). Partitioning models identified a tissue bridge cutoff width of 2·0 mm to be indicative of higher or lower 3-month total motor, pinprick, and light touch scores, and a cutoff of 4·0 mm to be indicative of higher and lower 12-month scores. Compared with models that contained clinical predictors only, models additionally including tissue bridges had significantly improved prediction accuracy across all three centres. Tissue bridges, measured in the first few weeks after SCI, are associated with short-term and long-term clinical improvement. Thus, tissue bridges could potentially be used to guide rehabilitation decision making and to stratify patients into more homogeneous subgroups of recovery in regenerative and neuroprotective clinical trials. Wings for Life, International Foundation for Research in Paraplegia, EU project Horizon 2020 (NISCI grant), and ERA-NET NEURON. [ABSTRACT FROM AUTHOR]

Individuals diagnosed with ankylosing spondylitis (AS) face an increased risk of spine fractures, specifically cervical spine fractures (CS-Fxs). In the past two decades, biological disease-modifying antirheumatic drugs (bDMARDs) have provided considerable relief from pain and an enhanced sense of wellbeing for a large segment of AS patients. Despite these improvements, it remains unclear whether extended use of bDMARDs can indeed reduce the risk of spine fractures. In this study, we aimed to investigate the evolving patterns and epidemiology of traumatic CS-Fxs in both AS and non-AS populations. We hypothesized that the risk of CS-Fxs among AS patients would show a decreasing trend over time, while the risk among non-AS patients would remain constant. Retrospective cohort study based on a prospective database. A total of 3,598 consecutive patients with CS-Fxs were treated at Oslo University Hospital over an 8-year period. CS-Fxs in AS patients were contrasted with non-AS-related CS-Fxs in terms of temporal trends, age, sex, injury mechanism, associated cervical spinal cord injury (cSCI), need for surgical fixation, and 30-day mortality. Data regarding all CS-Fxs diagnosed between 2015 and 2022 were extracted from the Southeast Norway population-based quality control database for traumatic CS-Fxs. Categorical data were summarized using frequencies, and continuous data were summarized using medians. The Wilcoxon rank-sum test was used to compare continuous variables, and the chi-squared test and Fischer exact test were used to compare categorical variables. To investigate the trend in the incidence of fractures, two different Poisson models were fitted with the number of non-AS and AS fractures as dependent variables and the year as the explanatory variable. Over an 8-year period, we registered 3,622 CS-Fxs in 3598 patients, with AS patients accounting for 125 of these fractures. Relative to their non-AS counterparts, AS patients presented a 9-fold and 8-fold higher risk of initial and subsequent CS-Fxs, respectively. We observed a declining trend in AS-related CS-Fxs with an annual linear decrease of 8.4% (p=.026), whereas non-AS-related CS-Fxs showed an annual linear increase of 3.7% (p<.001). AS patients sustaining CS-Fxs were typically older (median age 70 vs 63 years), predominantly male (89% vs 67%), and more frequently experienced injuries due to falls (82% vs 57%). They also exhibited a higher prevalence of subaxial CS-Fxs (91% vs 62%), fewer C0-C2 CS-Fxs (14% vs 44%), a higher rate of associated cSCI (21% vs 11%), and a greater tendency for surgical fixation (66% vs 21%). We observed a 30-day mortality rate of 11% in AS patients and 5.4% in non-AS patients (p=.005). The results of this study confirm the elevated risk of CS-Fxs among AS patients, although this risk appears to show a decreasing trend. The most plausible explanation for this risk reduction is the widespread application of bDMARDs [ABSTRACT FROM AUTHOR]

Background and Aims: Degenerative cervical myelopathy (DCM) is a debilitating condition characterized by compression of the cervical spinal cord, leading to neurological deficits. This study aimed to investigate the association between comorbidities like diabetes mellitus (DM) and obesity and quality of life (QOL) in preoperative patients with DCM, and to examine the distribution of pain and numbness. Methods: A cross‐sectional study with 86 preoperative patients with DCM was conducted. Patient‐reported outcome measures (PROMs) including Core Outcome Measure Index for the neck (COMI‐Neck), Neck Disability Index (NDI), EQ‐5D‐3L, SF‐12v2 assessed QOL, and baseline characteristics were collected. Patients were categorized by diabetic and obesity status, resulting in 17 with and 69 without DM, and 27 obese, 59 nonobese patients. In the statistical analysis, we compared PROMs and baseline characteristics, and conducted MANCOVA to investigate the association of DM and obesity with PROMs. Results: The study found no significant differences in preoperative QOL between patients with and without DM or obesity. Additionally, the results of MANCOVA indicated that neither DM nor obesity alone, nor their combination, had an association with the total scores of PROMs. In each group, the Symptom‐specific well‐being score on the COMI‐Neck was notably high, implying distressing current symptoms (median: 10). On the NDI, the median score for pain intensity, lifting, work, and recreation subitems was 3. Pain was predominantly reported in the neck and lower back, while numbness was more prevalent in the peripheral regions of the upper and lower limbs. Conclusion: Preoperative QOL was not significantly affected by the presence of DM and/or obesity. DCM‐related symptoms may mask the associations with these comorbidities. Regardless of the preoperative condition, it is important to address the PROMs items that posed challenges before surgery. Key points: Degenerative cervical myelopathy (DCM) significantly affects patients' quality of life.This study examines the association between diabetes mellitus and obesity with quality of life in preoperative patients with DCM, an underexplored area.Limited associations of diabetes mellitus and obesity with preoperative quality of life suggest prioritizing interventions targeting DCM‐related symptoms in preoperative counseling and postoperative care. [ABSTRACT FROM AUTHOR]

Traumatic cervical spinal cord injury (TCSCI) often causes varying degrees of motor dysfunction, common assessed by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), in association with the American Spinal Injury Association (ASIA) Impairment Scale. Accurate prediction of motor function recovery is extremely important for formulating effective diagnosis, therapeutic and rehabilitation programs. The aim of this study is to investigate the validity of a novel nested ensemble algorithm that uses the very early ASIA motor score (AMS) of ISNCSCI examination to predict motor function recovery 6 months after injury in TCSCI patients. This retrospective study included complete data of 315 TCSCI patients. The dataset consisting of the first AMS at ≤ 24 h post-injury and follow-up AMS at 6 months post-injury was divided into a training set (80%) and a test set (20%). The nested ensemble algorithm was established in a two-stage manner. Support Vector Classification (SVC), Adaboost, Weak-learner and Dummy were used in the first stage, and Adaboost was selected as second-stage model. The prediction results of the first stage models were uploaded into second-stage model to obtain the final prediction results. The model performance was evaluated using precision, recall, accuracy, F1 score, and confusion matrix. The nested ensemble algorithm was applied to predict motor function recovery of TCSCI, achieving an accuracy of 80.6%, a F1 score of 80.6%, and balancing sensitivity and specificity. The confusion matrix showed few false-negative rate, which has crucial practical implications for prognostic prediction of TCSCI. This novel nested ensemble algorithm, simply based on very early AMS, provides a useful tool for predicting motor function recovery 6 months after TCSCI, which is graded in gradients that progressively improve the accuracy and reliability of the prediction, demonstrating a strong potential of ensemble learning to personalize and optimize the rehabilitation and care of TCSCI patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nowadays, there are increasing reports on the digitization and visualization system of acupuncture points for adults in traditional Chinese medicine, and the digitization and visualization system of acupuncture points for children in traditional Chinese medicine and the simulation system of acupuncture manipulation for Mongolian medicine training have been reported. However, there are no reports on relevant systems for children in Mongolian medicine. OBJECTIVE: To develop a simulation system of acupuncture points for children in Mongolian medicine, in the hope that it can be used for clinical teaching, manipulation practice and research on acupuncture safety. METHODS: Based on the tomographic anatomical dataset of preschool boys, a three-dimensional (3D) digital virtual anatomical model of children with multiple internal organs and tissues was constructed by using PhotoShop.2021 and Digihuman Reconstruction System software. The relevant annotation information database of 27 acupoints such as Dinghui acupoint of Mongolian medicine was compiled by the Unity database language. The Mongolian gold needle and silver needle were selected to record the acupuncture point teaching video on the 3D printed head and neck resin model of children. In Unity3D software, children’s anatomical model, acupoint annotation information database and acupuncture operation video were integrated and coded, and a 3D digital children’s Mongolian acupuncture acupoint visualization system integrating simulation acupuncture training, clinical teaching and acupuncture safety research was successfully created. RESULTS AND CONCLUSION: This study was based on real children’s specimens. In order to reduce the error of two-dimensional segmentation, the manual layer-by-layer segmentation section image method was used to ensure the accuracy of the 3D model to the greatest extent. The Digihuman Reconstruction System was used to extract and save the individual segmentation data while maximizing the accuracy of the 3D model. PhotoShop.2021 software was used to complete the 3D reconstruction of the outer skin of the head and neck of children and the internal bony structure, cervical spinal cord, blood vessels and nerves, muscles and ligaments. After 3D reconstruction, the basic morphology of each independent structure and the integrity of the overall contour were verified in MeshLab software and the final fine adjustment and anatomical position confirmation were conducted using 3-matic research 13.0 software. The real anatomical morphology of the head and neck of preschool children was successfully simulated and restored. Unity3D software was used to integrate the 3D model of children, acupuncture operation video and acupoint annotation database, and the 3D digital Mongolian acupuncture acupoint visualization system for children was successfully constructed. Based on the real continuous fault ultra-thin dataset of preschool boys in China, China’s first 3D digitization and visualization system of acupuncture points in the head and neck of children in Mongolian medicine was developed. Compared with the previous acupuncture soft works, this system is more suitable for the anatomical morphological development characteristics of Asian children, and has a high value of application in the fields of research on the safety of acupuncture in Mongolian medicine, clinical teaching and acupuncture simulation training. [ABSTRACT FROM AUTHOR]

(1) Background: Restoring arm and hand function is one of the priorities of people with cervical spinal cord injury (cSCI). Noninvasive electromagnetic neuromodulation is a current approach that aims to improve upper-limb function in individuals with SCI. The aim of this study is to review updated information on the different applications of noninvasive electromagnetic neuromodulation techniques that focus on restoring upper-limb functionality and motor function in people with cSCI. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to structure the search protocol. A systematic review of the literature was performed in three databases: the Cochrane Library, PubMed, and Physiotherapy Evidence Database (PEDro). (3) Results: Twenty-five studies were included: four were on transcranial magnetic stimulation (TMS), four on transcranial direct current stimulation (tDCS), two on transcutaneous spinal cord stimulation (tSCS), ten on functional electrical stimulation (FES), four on transcutaneous electrical nerve stimulation (TENS), and one on neuromuscular stimulation (NMS). The meta-analysis could not be completed due to a lack of common motor or functional evaluations. Finally, we realized a narrative review of the results, which reported that noninvasive electromagnetic neuromodulation combined with rehabilitation at the cerebral or spinal cord level significantly improved upper-limb functionality and motor function in cSCI subjects. Results were significant compared with the control group when tSCS, FES, TENS, and NMS was applied. (4) Conclusions: To perform a meta-analysis and contribute to more evidence, randomized controlled trials with standardized outcome measures for the upper extremities in cSCI are needed, even though significant improvement was reported in each non-invasive electromagnetic neuromodulation study. [ABSTRACT FROM AUTHOR]

Background and purpose: There are distinct challenges in the preprocessing of spinal cord fMRI data, particularly concerning the mitigation of voluntary or involuntary movement artifacts during image acquisition. Despite the notable progress in data processing techniques for movement detection and correction, applying motion correction algorithms developed for the brain cortex to the brainstem and spinal cord remains a challenging endeavor. Methods: In this study, we employed a deep learning-based convolutional neural network (CNN) named DeepRetroMoCo, trained using an unsupervised learning algorithm. Our goal was to detect and rectify motion artifacts in axial T2*- weighted spinal cord data. The training dataset consisted of spinal cord fMRI data from 27 participants, comprising 135 runs for training and 81 runs for testing. Results: To evaluate the efficacy of DeepRetroMoCo, we compared its performance against the sct_fmri_moco method implemented in the spinal cord toolbox. We assessed the motion-corrected images using two metrics: the average temporal signal-to-noise ratio (tSNR) and Delta Variation Signal (DVARS) for both raw and motion-corrected data. Notably, the average tSNR in the cervical cord was significantly higher when DeepRetroMoCo was utilized for motion correction, compared to the sct_fmri_moco method. Additionally, the average DVARS values were lower in images corrected by DeepRetroMoCo, indicating a superior reduction in motion artifacts. Moreover, DeepRetroMoCo exhibited a significantly shorter processing time compared to sct_fmri_moco. Conclusion: Our findings strongly support the notion that DeepRetroMoCo represents a substantial improvement in motion correction procedures for fMRI data acquired from the cervical spinal cord. This novel deep learning-based approach showcases enhanced performance, offering a promising solution to address the challenges posed by motion artifacts in spinal cord fMRI data. [ABSTRACT FROM AUTHOR]

Background: The recommended treatment for cervical spinal cord injury (cSCI) is surgical decompression and stabilization within 24 h after injury. The aims of the study were to estimate our institutional compliance with this recommendation and identify potential factors associated with surgical delay. Methods: Population-based retrospective database study of patients operated for cSCI in 2015-2022 within the South-East Norway Health Region (3.1 million inhabitants). Data extracted were demographics, injury description, management timeline, place of primary triage [local hospital (LH) or neurotrauma center (NTC)]. Main outcome variables were: (1) time from injury to surgery at NTC, (2) time from injury to admission NTC, and (3) time from admission NTC to surgery. Results: We found 243 cSCI patients having acute neck surgery. Their median age was 63 years (IQR 47-74 years), 77% were male, 48% were =65 years old. Primary triage at an LH occurred in 150/243 (62%). The median time from injury to acute surgery was 27.8 h (IQR 15.4-61.9 h), and 47% had surgery within 24 h. The median time from injury to NTC admission was 5.6 h (IQR 1.9-19.4 h), and 67% of the patients were admitted to the NTC within 12 h. Significant factors associated with increased time from injury to NTC admission were transfer via LH, severe preinjury comorbidities, less severe cSCI, time of injury other than night, absence of multiple injuries. The median time from NTC admission to surgery was 16.7 h (IQR 9.5-31.0 h), and 70% had surgery within 24 h. Significant factors associated with increased time from NTC admission to surgery were increasing age and non-translational injury morphology. Conclusion: Less than half of the patients with cSCI were operated on within the recommended 24 h time frame after injury. To increase the fraction of early surgery, we suggest the following: (1) patients with clinical suspicion of cSCI should be transported directly to the NTC from the scene of the accident, (2) MRI should be performed only at the NTC, (3) at the NTC, surgery should commence on the same calendar day as arrival or as the first operation the following day. [ABSTRACT FROM AUTHOR]

Introduction: New diagnostic techniques are a substantial research focus in degenerative cervical myelopathy (DCM). This cross-sectional study determined the significance of cardiac-related spinal cord motion and the extent of spinal stenosis as indicators of mechanical strain on the cord. Methods: Eighty-four DCM patients underwent MRI/clinical assessments and were classified as MRI+ [T2-weighted (T2w) hyperintense lesion in MRI] or MRI-(no T2w-hyperintense lesion). Cord motion (displacement assessed by phasecontrast MRI) and spinal stenosis [adapted spinal canal occupation ratio (aSCOR)] were related to neurological (sensory/motor) and neurophysiological readouts [contact heat evoked potentials (CHEPs)] by receiver operating characteristic (ROC) analysis. Results: MRI+ patients (N = 31; 36.9%) were more impaired compared to MRI-patients (N = 53; 63.1%) based on the modified Japanese Orthopedic Association (mJOA) subscores for upper {MRI+ [median (Interquartile range)]: 4 (4-5); MRI-: 5 (5-5); p < 0.01} and lower extremity [MRI+: 6 (6-7); MRI-: 7 (6-7); p = 0.03] motor dysfunction and the monofilament score [MRI+: 21 (18-23); MRI-: 24 (22-24); p < 0.01]. Both patient groups showed similar extent of cord motion and stenosis. Only in the MRI-group displacement identified patients with pathologic assessments [trunk/lower extremity pin prick score (T/LEPP): AUC = 0.67, p = 0.03; CHEPs: AUC = 0.73, p = 0.01]. Cord motion thresholds: T/LEPP: 1.67 mm (sensitivity 84.6%, specificity 52.5%); CHEPs: 1.96 mm (sensitivity 83.3%, specificity 65.6%). The aSCOR failed to show any relation to the clinical assessments. Discussion: These findings affirm cord motion measurements as a promising additional biomarker to improve the clinical workup and to enable timely surgical treatment particularly in MRI-DCM patients. [ABSTRACT FROM AUTHOR]

A neurological dogma is that the contralateral effects of brain injury are set through crossed descending neural tracts. We have recently identified a novel topographic neuroendocrine system (T-NES) that operates via a humoral pathway and mediates the left-right side-specific effects of unilateral brain lesions. In rats with completely transected thoracic spinal cords, unilateral injury to the sensorimotor cortex produced contralateral hindlimb flexion, a proxy for neurological deficit. Here, we investigated in acute experiments whether T-NES consists of left and right counterparts and whether they differ in neural and molecular mechanisms. We demonstrated that left- and right-sided hormonal signaling is differentially blocked by the δ-, κ- and µ-opioid antagonists. Left and right neurohormonal signaling differed in targeting the afferent spinal mechanisms. Bilateral deafferentation of the lumbar spinal cord abolished the hormone-mediated effects of the left-brain injury but not the right-sided lesion. The sympathetic nervous system was ruled out as a brain-to-spinal cord-signaling pathway since hindlimb responses were induced in rats with cervical spinal cord transections that were rostral to the preganglionic sympathetic neurons. Analysis of gene–gene co-expression patterns identified the left- and right-side-specific gene co-expression networks that were coordinated via the humoral pathway across the hypothalamus and lumbar spinal cord. The coordination was ipsilateral and disrupted by brain injury. These findings suggest that T-NES is bipartite and that its left and right counterparts contribute to contralateral neurological deficits through distinct neural mechanisms, and may enable ipsilateral regulation of molecular and neural processes across distant neural areas along the neuraxis. Graphical Abstract [ABSTRACT FROM AUTHOR]

Background and Purpose: Conclusions from prior literature regarding the impact of sex, age, and height on spinal cord (SC) MRI morphometrics are conflicting, while the effect of body weight on SC morphometrics has been found to be nonsignificant. The purpose of this case‐control study is to assess the associations between cervical SC MRI morphometric parameters and age, sex, height, and weight to establish their potential role as confounding variables in a clinical study of people with multiple sclerosis (MS) compared to a cohort of healthy volunteers. Methods: Sixty‐nine healthy volunteers and 31 people with MS underwent cervical SC MRI at 3 Tesla field strength. Images were centered at the C3/C4 intervertebral disc and processed using Spinal Cord Toolbox v.4.0.2. Mixed‐effects linear regression models were used to evaluate the effects of biological variables and disease status on morphometric parameters. Results: Sex, age, and height had significant effects on cord and gray matter (GM) cross‐sectional area (CSA) as well as the GM:cord CSA ratio. There were no significant effects of body weight on morphometric parameters. The effect of MS disease duration on cord CSA in the C4 level was significant when controlling for all other variables. Conclusions: Studies of disease‐related changes in SC morphometry should control for sex, age, and height to account for physiological variation. [ABSTRACT FROM AUTHOR]

Background: Cervical spinal cord (cSC) lesions and atrophy contribute to disability in multiple sclerosis (MS), but associations with specific sensorimotor dysfunction require further exploration. Objective: To investigate the associations of brain and cSC magnetic resonance imaging (MRI) measures with sensorimotor impairment in MS. Methods: One hundred fifty-one MS patients and 69 healthy controls underwent 3T MRI and clinical assessments including Expanded Disability Status Scale (EDSS), 9-hole peg test (9-HPT), finger tapping test (FTT), timed 25-foot walk test (T25FWT), and vibration detection threshold (VDT). Random forest ranked brain (T2-hyperintense lesion volume (T2-LV) and normalized deep gray matter (GM), cortical and white matter (WM) volumes) and cSC (T2-LV and total, GM, and WM cross-sectional areas (CSAs) at C2/C3 level) MRI measures relevance in explaining EDSS milestones (EDSS ⩾3.0, ⩾4.0, and ⩾6.0), VDT, pyramidal and sensory functional systems (P-FS and S-FS ⩾2), and motor tests impairment. Results: Various combinations of brain and cSC MRI measures explained EDSS milestones (area under the curve (AUC) =0.879–0.900), VDT (R 2 = 0.194), and impaired P-FS (AUC = 0.820), S-FS (AUC = 0.795), 9-HPT (AUC = 0.793), FTT (AUC = 0.740), and T25FWT (AUC = 0.825). cSC GM CSA was the most informative feature for all outcomes, except 9-HPT. Conclusion: cSC MRI measures, especially GM CSA, explain EDSS and sensorimotor dysfunction better than brain measures in MS. [ABSTRACT FROM AUTHOR]

Proton relative biological effectiveness (RBE) is a dynamic variable influenced by factors like linear energy transfer (LET), dose, tissue type, and biological endpoint. The standard fixed proton RBE of 1.1, currently used in clinical planning, may not accurately represent the true biological effects of proton therapy (PT) in all cases. This uncertainty can contribute to radiation-induced normal tissue toxicity in patients. In late-responding tissues such as the spinal cord, toxicity can cause devastating complications. This study investigated spinal cord tolerance in mice subjected to proton irradiation and characterized the influence of fractionation on proton- induced myelopathy at entrance (ENT) and Bragg peak (BP) positions. Cervical spinal cords of 8-week-old C57BL/6J female mice were irradiated with single- or multi-fractions (18x) using lateral opposed radiation fields at 1 of 2 positions along the Bragg curve: ENT (dose-mean LET = 1.2 keV/μm) and BP (LET = 6.9 keV/μm). Mice were monitored over 1 year for changes in weight, mobility, and general health, with radiation-induced myelopathy as the primary biological endpoint. Calculations of the RBE of the ENT and BP curve (RBE ENT/BP) were performed. Single-fraction RBE ENT/BP for 50% effect probability (tolerance dose (TD 50), grade II paresis, determined using log-logistic model fitting) was 1.10 ± 0.06 (95% CI) and for multifraction treatments it was 1.19 ± 0.05 (95% CI). Higher incidence and faster onset of paralysis were seen in mice treated at the BP compared with ENT. The findings challenge the universally fixed RBE value in PT, indicating up to a 25% mouse spinal cord RBE ENT/BP variation for multifraction treatments. These results highlight the importance of considering fractionation in determining RBE for PT. Robust characterization of proton-induced toxicity, aided by in vivo models, is paramount for refining clinical decision-making and mitigating potential patient side effects. [ABSTRACT FROM AUTHOR]