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Cerebral strokes can disrupt descending commands from motor cortical areas to the spinal cord, which can result in permanent motor deficits of the arm and hand. However, below the lesion, the spinal circuits that control movement remain intact and could be targeted by neurotechnologies to restore movement. Here we report results from two participants in a first-in-human study using electrical stimulation of cervical spinal circuits to facilitate arm and hand motor control in chronic post-stroke hemiparesis ( NCT04512690 ). Participants were implanted for 29 d with two linear leads in the dorsolateral epidural space targeting spinal roots C3 to T1 to increase excitation of arm and hand motoneurons. We found that continuous stimulation through selected contacts improved strength (for example, grip force +40% SCS01; +108% SCS02), kinematics (for example, +30% to +40% speed) and functional movements, thereby enabling participants to perform movements that they could not perform without spinal cord stimulation. Both participants retained some of these improvements even without stimulation and no serious adverse events were reported. While we cannot conclusively evaluate safety and efficacy from two participants, our data provide promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke. Electrical stimulation of cervical spinal circuits facilitates arm and hand movements in two participants with moderate and severe chronic post-stroke hemiparesis.

Purpose Operative treatment of adult spinal deformity (ASD) has been shown to improve patient health-related quality of life (HRQOL). Selection of the uppermost instrumented vertebra (UIV) in either the upper thoracic (UT) or lower thoracic (LT) spine is a pivotal decision with effects on operative and postoperative outcomes. This review overviews the multifaceted decision-making process for UIV selection in ASD correction. Methods PubMed was queried for articles using the keywords “uppermost instrumented vertebra”, “upper thoracic”, “lower thoracic”, and “adult spinal deformity”. Results Optimization of UIV selection may lead to superior deformity correction, better patient-reported outcomes, and lower risk of proximal junctional kyphosis (PJK) and failure (PJF). Patient alignment characteristics, including preoperative thoracic kyphosis, coronal deformity, and the magnitude of sagittal correction influence surgical decision-making when selecting a UIV, while comorbidities such as poor body mass index, osteoporosis, and neuromuscular pathology should also be taken in to account. Additionally, surgeon experience and resources available to the hospital may also play a role in this decision. Currently, it is incompletely understood whether postoperative HRQOLs, functional and radiographic outcomes, and complications after surgery differ between selection of the UIV in either the UT or LT spine. Conclusion The correct selection of the UIV in surgical planning is a challenging task, which requires attention to preoperative alignment, patient comorbidities, clinical characteristics, available resources, and surgeon-specific factors such as experience.

Spinal muscular atrophy (SMA) is an inherited neurodegenerative disease causing motoneuron dysfunction, muscle weakness, fatigue and early mortality. Three new therapies can slow disease progression, enabling people to survive albeit with lingering motor impairments. Indeed, weakness and fatigue are still among patients’ main concerns. Here we show that epidural spinal cord stimulation (SCS) improved motoneuron function, thereby increasing strength, endurance and gait quality, in three adults with type 3 SMA. Preclinical works demonstrated that SMA motoneurons show low firing rates because of a loss of excitatory input from primary sensory afferents. In the present study, we hypothesized that correcting this loss with electrical stimulation of the sensory afferents could improve motoneuron function. To test this hypothesis, we implanted three adults with SMA with epidural electrodes over the lumbosacral spinal cord, targeting sensory axons of the legs. We delivered SCS for 4 weeks, 2 h per day during motor tasks. Our intervention led to improvements in strength (up to +180%), gait quality (mean step length: +40%) and endurance (mean change in 6-minute walk test: +26 m), paralleled by increased motoneuron firing rates. These changes persisted even when SCS was turned OFF. Notably, no adverse events related to the stimulation were reported. ClinicalTrials.gov identifier: NCT05430113 . Improved muscle function, strength and fatigue measures were observed after electrical spinal cord stimulation in individuals with spinal muscular atrophy.

A hallmark feature of the neural system controlling breathing is its ability to exhibit plasticity. Less appreciated is the ability to exhibit metaplasticity, a change in the capacity to express plasticity (i.e., \"plastic plasticity\"). Recent advances in our understanding of cellular mechanisms giving rise to respiratory motor plasticity lay the groundwork for (ongoing) investigations of metaplasticity. This detailed understanding of respiratory metaplasticity will be essential as we harness metaplasticity to restore breathing capacity in clinical disorders that compromise breathing, such as cervical spinal injury, motor neuron disease and other neuromuscular diseases. In this brief review, we discuss key examples of metaplasticity in respiratory motor control, and our current understanding of mechanisms giving rise to spinal plasticity and metaplasticity in phrenic motor output; particularly after pre-conditioning with intermittent hypoxia. Progress in this area has led to the realization that similar mechanisms are operative in other spinal motor networks, including those governing limb movement. Further, these mechanisms can be harnessed to restore respiratory and non-respiratory motor function after spinal injury.

Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for therapies aimed at improving volitional muscle activation. Here we hypothesize that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby immediately potentiating motor output. To test this hypothesis, we identify optimal thalamic targets and stimulation parameters that enhance upper-limb motor-evoked potentials and grip forces in anesthetized monkeys. This potentiation persists after white matter lesions. We replicate these results in humans during intra-operative testing. We then design a stimulation protocol that immediately improves strength and force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions. Cerebral lesions result in loss of upper-limb motor functions. Here, the authors show that electrical stimulation of the motor thalamus can immediately and significantly improve strength and volitional force control improving arm and hand functions.

Introduction: Lateral anterior column release (ACR) is a minimally invasive option for the correction of sagittal plane deformity. To assemble a homogeneous picture of published research on ACR, an advanced bibliometric analysis was conducted to compile the top-ten most-cited articles on the topic of ACR. Methods: A keyword search using the Thomson Reuters Web of Knowledge was conducted to identify articles discussing the role of lateral ACR. The articles were then ranked based on the total number of citations to identify the ten most-cited articles published. A subjective appraisal of the findings of these articles was conducted to provide a ranked literature review and to examine trends in the study of ACR between 2012 and 2019. Results: The earliest published article on ACR was in 2012 by Deukmedjian et al. Three articles were in vitro biomechanical assessments of ACR, and seven articles were on outcome analyses, which were either case series or case controlled. The most-cited article was a biomechanical study authored by Uribe et al. The article with the highest rate of citations/year was authored by Manwaring et al. Uribe and the European Spine Journal were the most frequently cited author and journal, respectively. Conclusions: The lateral ACR approach has enjoyed significant scholarly attention since its advent. Higher-level analyses with robust control groups, larger sample sizes, and long-term follow-up are necessary to improve our understanding of this approach.

Background Cancer cachexia is an insidious process characterized by muscle atrophy with associated motor deficits, including diaphragm weakness and respiratory insufficiency. Although neuropathology contributes to muscle wasting and motor deficits in many clinical disorders, neural involvement in cachexia‐linked respiratory insufficiency has not been explored. Methods We first used whole‐body plethysmography to assess ventilatory responses to hypoxic and hypercapnic chemoreflex activation in mice inoculated with the C26 colon adenocarcinoma cell line. Mice were exposed to a sequence of inspired gas mixtures consisting of (i) air, (ii) hypoxia (11% O2) with normocapnia, (iii) hypercapnia (7% CO2) with normoxia, and (iv) combined hypercapnia with hypoxia (i.e. maximal chemoreflex response). We also tested the respiratory neural network directly by recording inspiratory burst output from ligated phrenic nerves, thereby bypassing influences from changes in diaphragm muscle strength, respiratory mechanics, or compensation through recruitment of accessory motor pools. Results Cachectic mice demonstrated a significant attenuation of the hypoxic tidal volume (0.26mL±0.01mL vs 0.30mL±0.01mL; p<0.05), breathing frequency (317±10bpm vs 344±6bpm; p<0.05) and phrenic nerve (29.5±2.6% vs 78.8±11.8%; p<0.05) responses. On the other hand, the much larger hypercapnic tidal volume (0.46±0.01mL vs 0.46±0.01mL; p>0.05), breathing frequency (392±5bpm vs 408±5bpm; p>0.05) and phrenic nerve (93.1±8.8% vs 111.1±13.2%; p>0.05) responses were not affected. Further, the concurrent hypercapnia/hypoxia tidal volume (0.45±0.01mL vs 0.45±0.01mL; p>0.05), breathing frequency (395±7bpm vs 400±3bpm; p>0.05), and phrenic nerve (106.8±7.1% vs 147.5±38.8%; p>0.05) responses were not different between C26 cachectic and control mice. Conclusions Breathing deficits associated with cancer cachexia are specific to the hypoxic ventilatory response and, thus, reflect disruptions in the hypoxic chemoafferent neural network. Diagnostic techniques that detect decompensation and therapeutic approaches that support the failing hypoxic respiratory response may benefit patients at risk for cancer cachectic‐associated respiratory failure.

INTRODUCTION Patient with TLICS 4 fall in a grey zone where treatment is at the discretion of neurosurgeon. This decision is often based on determination on whether the fracture is stable predicated on integirty of posterior ligamentous complex. MRI is often used to evaluate ligamentous injury but previous studies have shown that this MRI is too hypersensitive, leading to high rate of false positives. Load sharing classification is a repdorudicle scale that could be used to evaluate stability of a thoracolumbar fracture based on CT scan only. METHODS 111 consectutive neurologically intact patients with isolated thoracolumbar burst fracture (i.e. TLICS 4) were included in this retrospective study. Load sharing classification (LSC) score was determined based on degree of comminution (1-3), apposition (1-3), and kyphosis (1-3), total composite score of 3–9. RESULTS 44 patients underwent MRI, 15 had ligamentous injury, and 32 (28.8%) required surgery. In univariate logistic regression LSC score was associated with MRI acquisition (OR 1.7, 1.3- 2.1), presence of ligamentous injury (OR 1.5, 1.2- 2.0). In multivariate logistic regression, LSC score was assocaited with surgery (OR 3.7, 2.3-5.9), independent of MRI or PLC injury. None of the patients who did not undergo surgery required an operation with a mean follow up of 12.3 months. CONCLUSION Load sharing classification score in patients with TLICS4 is predictive of undergoing MRI, presence of ligamentous injury, and most strongly, surgical intervention. The application of load sharing classification in these patients may further guide decision making, obviating the need for MRI, and potentially save costs.

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain–computer interface (BCI) to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS‐evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other BCI studies to ensure the successful placement of stimulation electrodes. Functional imaging of the somatosensory cortex in people with spinal cord injury enabled planning for precise electrode array placement in the brain for a brain–computer interface. Stimulation through electrodes in the somatosensory cortex generated sensations of touch in digits that matched the functional imaging results used for placement.