Noninvasive Electromagnetic Neuromodulation of the Central and Peripheral Nervous System for Upper-Limb Motor Strength and Functionality in Individuals with Cervical Spinal Cord Injury: A Systematic Review and Meta-Analysis.

(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.

Anatomical description of a new ligamentous supporting structure of the canine cranial cervical spinal cord.

The cranial cervical vertebral column carries a unique range of mobility with the addition of dorsal and ventral flexion and rotation. The denticulate ligaments provides support and protection of the spinal cord, but little is known of the adaption of this apparatus at the cranial cervical portion of the spinal cord. We present in this publication a new pair of ligaments in dogs that supports the spinal cord inside the vertebral canal at the level of the C1-C2 spinal segments.

Assessing Functional Recovery of Eupneic Diaphragm Activity Following Unilateral Cervical Spinal Cord Injury in Rats.

Following cSCI, activation of the DIAm can be impacted depending on the extent of the injury. The present manuscript describes a unilateral C2 hemisection (C2SH) model of cSCI that disrupts eupneic ipsilateral diaphragm (iDIAm) electromyographic (EMG) activity during breathing in rats. To evaluate recovery of DIAm motor control, the extent of deficit due to C2SH must first be clearly established. By verifying a complete initial loss of iDIAm EMG during breathing, subsequent recovery can be classified as either absent or present, and the extent of recovery can be estimated using the EMG amplitude. Additionally, by measuring the continued absence of iDIAm EMG activity during breathing after the acute spinal shock period following C2SH, the success of the initial C2SH may be validated. Measuring contralateral diaphragm (cDIAm) EMG activity can provide information about the compensatory effects of C2SH, which also reflects neuroplasticity. Moreover, DIAm EMG recordings from awake animals can provide vital physiological information about the motor control of the DIAm after C2SH. This article describes a method for a rigorous, reproducible, and reliable C2SH model of cSCI in rats, which is an excellent platform for studying respiratory neuroplasticity, compensatory cDIAm activity, and therapeutic strategies and pharmaceuticals.

A Rare Case of Cervical Spinal Arteriovenous Malformation: A Case Report.

Arteriovenous malformation (AVM) is an abnormal connection of vasculature resulting in capillary bed bypassing and leading to neurological deterioration and high risk of bleeding. Intramedullary AVMs in the cervical spinal cord are rare and require precise diagnostics and treatment. We present a clinical case of recurrent AVMs in a 28-year-old Caucasian female with sudden and severe neck pain and variable neurological symptoms along with current diagnostic and treatment modalities. Conservative treatment was partially effective. MRI and DSA confirmed AVMs at C4 level with subsequent several endovascular treatment sessions at the age of 15 and 24 with mild neurological improvement. Afterwards the patient underwent rehabilitation with minor neurological improvement. This case highlights the clinical progression and treatment of AVMs along with showcasing current pathophysiology, classification, and imaging.

Temporal dynamics of gait function in acute cervical spinal cord injury.

BACKGROUND: Following spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity. METHODS: This retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2-4 months, 4-6 months, and 6-8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau. RESULTS: In the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period. CONCLUSIONS: The plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group.

Effect of nutritional status on occurrence of pneumonia after traumatic cervical spinal cord injury.

Pneumonia after cervical spinal cord injury (CSCI) is a common and serious complication; however, its nutrition-related etiology has not yet been elucidated. This study aimed to elucidate the effects of nutritional factors on pneumonia after CSCI. Patients with acute traumatic CSCI who were admitted within 3 days after injury and followed up for at least 3 months were retrospectively examined. Occurrence of pneumonia, nutritional status, severity of dysphagia, vital capacity, use of respirators, and motor scores for paralysis were evaluated. Of 182 patients included in this study, 33 (18%) developed pneumonia. Multiple logistic regression analysis revealed that low nutritional status, severe paralysis, and low vital capacity were significant risk factors for pneumonia. The severity of paralysis, respiratory dysfunction, and poor nutritional status can affect the occurrence of pneumonia after CSCI. In addition to respiratory management, nutritional assessment and intervention may play key roles in preventing pneumonia associated with spinal cord injury-induced immune depression. Nutritional care should be provided as soon as possible when the nutritional status of a patient worsens after an injury.

Traumatic Cervical Spinal Cord Injury and Income and Employment Status.

Importance: Spinal cord injury (SCI) causes drastic changes to an individual's physical health that may be associated with the ability to work. Objective: To estimate the association of SCI with individual earnings and employment status using national administrative health databases linked to income tax data. Design, Setting, and Participants: This was a retrospective, national, population-based cohort study of adults who were hospitalized with cervical SCI in Canada between January 2005 and December 2017. All acute care hospitalizations for SCI of adults ages 18 to 64 years were included. A comparison group was constructed by sampling from individuals in the injured cohort. Fiscal information from their preinjury years was used for comparison. The injured cohort was matched with the comparison group based on age, sex, marital status, province of residence, self-employment status, earnings, and employment status in the year prior to injury. Data were analyzed from August 2022 to January 2023. Main outcomes and Measures: The first outcome was the change in individual annual earnings up to 5 years after injury. The change in mean yearly earnings was assessed using a linear mixed-effects differences-in-differences regression. Income values are reported in 2022 Canadian dollars (CAD $1.00 = US $0.73). The second outcome was the change in employment status up to 5 years after injury. A multivariable probit regression model was used to compare proportions of individuals employed among those who had experienced SCI and the paired comparison group of participants. Results: A total of 1630 patients with SCI (mean [SD] age, 47 [13] years; 1304 male [80.0%]) were matched to patients in a preinjury comparison group (resampled from the same 1630 patients in the SCI group). The mean (SD) of preinjury wage earnings was CAD $46 000 ($48 252). The annual decline in individual earnings was CAD $20 275 (95% CI, -$24 455 to -$16 095) in the first year after injury and CAD $20 348 (95% CI, -$24 710 to -$15 985) in the fifth year after injury. At 5 years after injury, 52% of individuals who had an injury were working compared with 79% individuals in the preinjury comparison group. SCI survivors had a decrease in employment of 17.1 percentage points (95% CI, 14.5 to 19.7 percentage points) in the first year after injury and 17.8 percentage points (14.5 to 21.1 percentage points) in the fifth year after injury. Conclusions and Relevance: In this study, SCI was associated with a decline in earnings and employment up to 5 years after injury for adults aged 18 to 64 years in Canada.

Sex differences in spontaneous respiratory recovery following chronic C2 hemisection.

Respiratory deficits after C2 hemisection (C2Hx) have been well documented through single-sex investigations. Although ovarian sex hormones enable enhanced respiratory recovery observed in females 2 wk post-C2Hx, it remains unknown if sex impacts spontaneous respiratory recovery at chronic time points. We conducted a longitudinal study to provide a comprehensive sex-based characterization of respiratory neuromuscular recovery for 8 wk after C2Hx. We recorded ventilation and chronic diaphragm electromyography (EMG) output in awake, behaving animals, phrenic motor output in anesthetized animals, and performed diaphragm muscle histology in chronically injured male and female rodents. Our results show that females expressed a greater recovery of tidal volume and minute ventilation compared with males during subacute and chronic time points. Eupneic diaphragm EMG amplitude during wakefulness and phrenic motor amplitude are similar between sexes at all time points after injury. Our data also suggest that females have a greater reduction in ipsilateral diaphragm EMG amplitude during spontaneous deep breaths (e.g., sighs) compared with males. Finally, we show evidence for atrophy and remodeling of the fast, fatigable fibers ipsilateral to injury in females, but not in males. To our knowledge, the data presented here represent the first study to report sex-dependent differences in spontaneous respiratory recovery and diaphragm muscle morphology following chronic C2Hx. These data highlight the need to study both sexes to inform evidence-based therapeutic interventions in respiratory recovery after spinal cord injury (SCI).NEW & NOTEWORTHY In response to chronic C2 hemisection, female rodents display increased tidal volume during eupneic breathing compared with males. Females show a greater reduction in diaphragm electromyography (EMG) amplitude during spontaneous deep breaths (e.g., sighs) and atrophy and remodeling of fast, fatigable diaphragm fibers. Given that most rehabilitative interventions occur in the subacute to chronic stages of injury, these results highlight the importance of considering sex when developing and evaluating therapeutics after spinal cord injury.

Prognostic value of tissue bridges in cervical spinal cord injury: a longitudinal, multicentre, retrospective cohort study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Wings for Life, International Foundation for Research in Paraplegia, EU project Horizon 2020 (NISCI grant), and ERA-NET NEURON.

The relationship between the structural changes in the cervical spinal cord and sensorimotor function of children with thoracolumbar spinal cord injury (TLSCI).

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To study the relationship between the structural changes in the cervical spinal cord (C2/3 level) and the sensorimotor function of children with traumatic thoracolumbar spinal cord injury (TLSCI) and to discover objective imaging biomarkers to evaluate its functional status. SETTING: Xuanwu Hospital, Capital Medical University, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, China. METHODS: 30 children (age range 5-13 years) with TLSCI and 11 typically developing (TD) children (age range 6-12 years) were recruited in this study. Based on whether there is preserved motor function below the neurological level of injury (NLI), the children with TLSCI are divided into the AIS A/B group (motor complete) and the AIS C/D group (motor incomplete). A Siemens Verio 3.0 T MR scanner was used to acquire 3D high-resolution anatomic scans covering the head and upper cervical spinal cord. Morphologic parameters of the spinal cord at the C2/3 level, including cross-sectional area (CSA), anterior-posterior width (APW), and left-right width (LRW) were obtained using the spinal cord toolbox (SCT; https://www.nitrc.org/projects/sct ). Correlation analyses were performed to compare the morphologic spinal cord parameters and clinical scores determined by the International Standard for Neurological Classification of Spinal Cord Injuries (ISNCSCI) examination. RESULTS: CSA and LRW in the AIS A/B group were significantly lower than those in the TD group and the AIS C/D group. LRW was the most sensitive imaging biomarker to differentiate the AIS A/B group from the AIS C/D group. Both CSA and APW were positively correlated with ISNCSCI sensory scores. CONCLUSIONS: Quantitative measurement of the morphologic spinal cord parameters of the cervical spinal cord can be used as an objective imaging biomarker to evaluate the neurological function of children with TLSCI. Cervical spinal cord atrophy in children after TLSCI was correlated with clinical grading; CSA and APW can reflect sensory function. Meanwhile, LRW has the potential to be an objective imaging biomarker for evaluating motor function preservation.

Biological variation in cervical spinal cord MRI morphometry in healthy individuals and people with multiple sclerosis.

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.

Acute Hyperoxia Improves Spinal Cord Oxygenation and Circulatory Function Following Cervical Spinal Cord Injury in Rats.

Spinal cord injury is associated with spinal vascular disruptions that result in spinal ischemia and tissue hypoxia. This study evaluated the therapeutic efficacy of normobaric hyperoxia on spinal cord oxygenation and circulatory function at the acute stage of cervical spinal cord injury. Adult male Sprague Dawley rats underwent dorsal cervical laminectomy or cervical spinal cord contusion. At 1-2 days after spinal surgery, spinal cord oxygenation was monitored in anesthetized and spontaneously breathing rats through optical recording of oxygen sensor foils placed on the cervical spinal cord and pulse oximetry. The arterial blood pressure, heart rate, blood gases, and peripheral oxyhemoglobin saturation were also measured under hyperoxic (50% O2) and normoxic (21% O2) conditions. The results showed that contused animals had significantly lower spinal cord oxygenation levels than uninjured animals during normoxia. Peripheral oxyhemoglobin saturation, arterial oxygen partial pressure, and mean arterial blood pressure are significantly reduced following cervical spinal cord contusion. Notably, spinal oxygenation of contused rats could be improved to a level comparable to uninjured animals under hyperoxia. Furthermore, acute hyperoxia elevated blood pressure, arterial oxygen partial pressure, and peripheral oxyhemoglobin saturation. These results suggest that normobaric hyperoxia can significantly improve spinal cord oxygenation and circulatory function in the acute phase after cervical spinal cord injury. We propose that adjuvant normobaric hyperoxia combined with other hemodynamic optimization strategies may prevent secondary damage after spinal cord injury and improve functional recovery.

Malignant melanotic schwannoma of the cervical spinal cord: a case report.

Spinal cord malignant melanotic schwannoma (MMNST) is a rare central nervous system tumor that originates from the spinal cord or spinal myelin sheath cells and can produce melanin. This type of tumor is usually highly aggressive and malignant, with a poor prognosis. The clinical manifestations of spinal cord MMNST are mainly pain, paresthesia, muscle weakness, muscle atrophy, etc., and symptoms of spinal cord compression, such as intestinal and bladder dysfunction, paraplegia, etc. Early detection of tumor lesions can facilitate tumor removal, improve patients' quality of life, and prolong patients' survival. In this case report, a 27-year-old young woman was diagnosed with MMNST of the cervical spinal cord due to weakness of her limbs in our hospital, and underwent surgical resection. The patient's limbs returned to normal after surgery. It is worth mentioning that the patient visited our hospital 7 months ago for "right upper limb pain for 3 days" and was diagnosed with a cervical spine space-occupying lesion at the same position this time, but the pathology report was "hemosiderosis". The patient's limbs returned to normal after surgery. It is worth mentioning that the patient visited our hospital 7 months ago for "right upper limb pain for 3 days" and was diagnosed with a cervical spine space-occupying lesion at the same position this time, but the pathology report was "hemosiderosis". This case report aims to raise awareness of the problem of spinal cord MMNST and contribute to greater knowledge of this rare tumor. This case report aims to raise awareness of the problem of spinal cord MMNST and contribute to greater knowledge of this rare tumor.

Focal compression of the cervical spinal cord alone does not indicate high risk of neurological deterioration in patients with a diagnosis of mild degenerative cervical myelopathy.

Degenerative Cervical Myelopathy (DCM) is the functional derangement of the spinal cord resulting from vertebral column spondylotic degeneration. Typical neurological symptoms of DCM include gait imbalance, hand/arm numbness, and upper extremity dexterity loss. Greater spinal cord compression is believed to lead to a higher rate of neurological deterioration, although clinical experience suggests a more complex mechanism involving spinal canal diameter (SCD). In this study, we utilized machine learning clustering to understand the relationship between SCD and different patterns of cord compression (i.e. compression at one disc level, two disc levels, etc.) to identify patient groups at risk of neurological deterioration. 124 MRI scans from 51 non-operative DCM patients were assessed through manual scoring of cord compression and SCD measurements. Dimensionality reduction techniques and k-means clustering established patient groups that were then defined with their unique risk criteria. We found that the compression pattern is unimportant at SCD extremes (≤14.5 mm or > 15.75 mm). Otherwise, severe spinal cord compression at two disc levels increases deterioration likelihood. Notably, if SCD is normal and cord compression is not severe at multiple levels, deterioration likelihood is relatively reduced, even if the spinal cord is experiencing compression. We elucidated five patient groups with their associated risks of deterioration, according to both SCD range and cord compression pattern. Overall, SCD and focal cord compression alone do not reliably predict an increased risk of neurological deterioration. Instead, the specific combination of narrow SCD with multi-level focal cord compression increases the likelihood of neurological deterioration in mild DCM patients.

Prolonged intermittent hypoxia differentially regulates phrenic motor neuron serotonin receptor expression in rats following chronic cervical spinal cord injury.

Low-dose (< 2 h/day), acute intermittent hypoxia (AIH) elicits multiple forms of serotonin-dependent phrenic motor plasticity and is emerging as a promising therapeutic strategy to restore respiratory and non-respiratory motor function after spinal cord injury (SCI). In contrast, high-dose (> 8 h/day), chronic intermittent hypoxia (CIH) undermines some forms of serotonin-dependent phrenic motor plasticity and elicits pathology. CIH is a hallmark of sleep disordered breathing, which is highly prevalent in individuals with cervical SCI. Interestingly, AIH and CIH preconditioning differentially impact phrenic motor plasticity. Although mechanisms of AIH-induced plasticity in the phrenic motor system are well-described in naïve rats, we know little concerning how these mechanisms are affected by chronic SCI or intermittent hypoxia preconditioning. Thus, in a rat model of chronic, incomplete cervical SCI (lateral spinal hemisection at C2 (C2Hx), we assessed serotonin type 2A, 2B and 7 receptor expression in and near phrenic motor neurons and compared: 1) intact vs. chronically injured rats; and 2) the impact of preconditioning with varied "doses" of intermittent hypoxia (IH). While there were no effects of chronic injury or intermittent hypoxia alone, CIH affected multiple receptors in rats with chronic C2Hx. Specifically, CIH preconditioning (8 h/day; 28 days) increased serotonin 2A and 7 receptor expression exclusively in rats with chronic C2Hx. Understanding the complex, context-specific interactions between chronic SCI and CIH and how this ultimately impacts phrenic motor plasticity is important as we leverage AIH-induced motor plasticity to restore breathing and other non-respiratory motor functions in people with chronic SCI.

Strategies and safety simulations for ultrasonic cervical spinal cord neuromodulation.

Objective. Focused ultrasound spinal cord neuromodulation has been demonstrated in small animals. However, most of the tested neuromodulatory exposures are similar in intensity and exposure duration to the reported small animal threshold for possible spinal cord damage. All efforts must be made to minimize the risk and assure the safety of potential human studies, while maximizing potential treatment efficacy. This requires an understanding of ultrasound propagation and heat deposition within the human spine.Approach. Combined acoustic and thermal modelling was used to assess the pressure and heat distributions produced by a 500 kHz source focused to the C5/C6 level via two approaches (a) the posterior acoustic window between vertebral posterior arches, and (b) the lateral intervertebral foramen from which the C6 spinal nerve exits. Pulse trains of fifty 0.1 s pulses (pulse repetition frequency: 0.33 Hz, free-field spatial peak pulse-averaged intensity: 10 W cm-2) were simulated for four subjects and for ±10 mm translational and ±10∘rotational source positioning errors.Main results.Target pressures ranged between 20%-70% of free-field spatial peak pressures with the posterior approach, and 20%-100% with the lateral approach. When the posterior source was optimally positioned, peak spine heating values were below 1 ∘C, but source mispositioning resulted in bone heating up to 4 ∘C. Heating with the lateral approach did not exceed 2 ∘C within the mispositioning range. There were substantial inter-subject differences in target pressures and peak heating values. Target pressure varied three to four-fold between subjects, depending on approach, while peak heating varied approximately two-fold between subjects. This results in a nearly ten-fold range between subjects in the target pressure achieved per degree of maximum heating.Significance. This study highlights the utility of trans-spine ultrasound simulation software and need for precise source-anatomy positioning to assure the subject-specific safety and efficacy of focused ultrasound spinal cord therapies.

PTEN inhibition promotes robust growth of bulbospinal respiratory axons and partial recovery of diaphragm function in a chronic model of cervical contusion spinal cord injury.

High spinal cord injury (SCI) leads to persistent and debilitating compromise in respiratory function. Cervical SCI not only causes the death of phrenic motor neurons (PhMNs) that innervate the diaphragm, but also damages descending respiratory pathways originating in the rostral ventral respiratory group (rVRG) located in the brainstem, resulting in denervation and consequent silencing of spared PhMNs located caudal to injury. It is imperative to determine whether interventions targeting rVRG axon growth and respiratory neural circuit reconnection are efficacious in chronic cervical contusion SCI, given that the vast majority of individuals are chronically-injured and most cases of SCI involve contusion-type damage to the cervical region. We therefore employed a rat model of chronic cervical hemicontusion to test therapeutic manipulations aimed at reconstructing damaged rVRG-PhMN-diaphragm circuitry to achieve recovery of respiratory function. At a chronic time point post-injury, we systemically administered: an antagonist peptide directed against phosphatase and tensin homolog (PTEN), a central inhibitor of neuron-intrinsic axon growth potential; an antagonist peptide directed against receptor-type protein tyrosine phosphatase sigma (PTPσ), another important negative regulator of axon growth capacity; or a combination of these two peptides. PTEN antagonist peptide (PAP4) promoted partial recovery of diaphragm motor activity out to nine months post-injury (though this effect depended on the anesthetic regimen used during recording), while PTPσ peptide did not impact diaphragm function after cervical SCI. Furthermore, PAP4 promoted robust growth of descending bulbospinal rVRG axons caudal to the injury within the denervated portion of the PhMN pool, while PTPσ peptide did not affect rVRG axon growth at this location that is critical to control of diaphragmatic respiratory function. In conclusion, we find that, when PTEN inhibition is targeted at a chronic time point following cervical contusion, our non-invasive PAP4 strategy can successfully promote significant regrowth of damaged respiratory neural circuitry and also partial recovery of diaphragm motor function.

Within-participants reliability and measurement error of magnetization transfer imaging determinations within the healthy cervical spinal cord.

PURPOSE: To assess the within-participant reliability and measurement error in the determination of MTR in the healthy human cervical spinal cord. METHODS AND MATERIALS: A total of twenty healthy controls (10 male, mean ± sd age: 33.9 ± 3.5 years, 10 females, mean ± sd age: 47.5 ± 14.4 years), with no family history of any neurological disorders or a contraindication to MRI scanning were recruited over a period of two months. Each participant was scanned twice with a 3T MRI scanner using standard MTI sequences. Spinal Cord Toolbox (v5.4) was used for image post-processing. Data were first segmented and then registered to a template and then MTR was computed. The within-participant coefficients of variation (CV%), single and average within-participants intraclass correlation coefficients (ICC) and Bland-Altman plots were determined for MT values over the volume between the 2nd and 5th cervical vertebrae for the total WM and for specific WM regions: dorsal column (DC), ventral column (VC) and lateral column (LC). RESULTS: MTR showed poor to excellent within-participant reliability for the total WM, DC, VC and LC with single/average ICC values of 0.03/0.06, 0.10/0.18, 0.39/0.75, and 0.001/0.002, respectively, and the CV% reported an acceptable variation with values less than 10%. The Bland-Altman plots showed good within-participant agreement between the scan-rescan values. CONCLUSION: This study demonstrates that clinical trials using MTI technique are feasible and shows that quantitative MTI can monitor tissue changes in degenerative WM patients. IMPLICATIONS FOR PRACTICE: MTI with its MTR index provide broad assessment of the integrity of white matter tissue and are being studied widely in brain as a diagnostic tool for the assessment of different neurological diseases.

Effects of Photon versus Carbon-Ion Irradiation in the Rat Cervical Spinal Cord - a Serial T2 and Diffusion-weighted Magnetic Resonance Imaging Study.

Carbon-ion irradiation is increasingly used at the skull base and spine near the radiation-sensitive spinal cord. To better characterize the in vivo radiation response of the cervical spinal cord, radiogenic changes in the high-dose area were measured in rats using magnetic resonance imaging (MRI) diffusion measurements in comparison to conventional photon irradiations. In this longitudinal MRI study, we examined the gray matter (GM) of the cervical spinal cord in 16 female Sprague-Dawley rats after high-dose photon (n = 8) or carbon-ion (12C) irradiation (n = 8) and in 6 sham-exposed rats until myelopathy occurred. The differences in the diffusion pattern of the GM of the cervical spinal cord were examined until the endpoint of the study, occurrence of paresis grade II of both forelimbs was reached. In both radiation techniques, the same order of the occurrence of MR-morphological pathologies was observed - from edema formation to a blood spinal cord barrier (BSCB) disruption to paresis grade II of both forelimbs. However, carbon-ion irradiation showed a significant increase of the mean apparent diffusion coefficient (ADC; P = 0.031) with development of a BSCB disruption in the GM. Animals with paresis grade II as a late radiation response had a highly significant increase in mean ADC (P = 0.0001) after carbon-ion irradiation. At this time, a tendency was observed for higher mean ADC values in the GM after 12C irradiation as compared to photon irradiation (P = 0.059). These findings demonstrated that carbon-ion irradiation leads to greater structural damage to the GM of the rat cervical spinal cord than photon irradiation due to its higher linear energy transfer (LET) value.

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

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