Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes ...and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.
The global pandemic of coronavirus disease 2019 (COVID-19) has revealed a surprising number of extra-pulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...infection. While myalgia is a common clinical feature of COVID-19, other musculoskeletal manifestations of COVID-19 were infrequently described early during the pandemic. There have been emerging reports, however, of an array of neuromuscular and rheumatologic complications related to COVID-19 infection and disease course including myositis, neuropathy, arthropathy, and soft tissue abnormalities. Multimodality imaging supports diagnosis and evaluation of musculoskeletal disorders in COVID-19 patients. This article aims to provide a first comprehensive summary of musculoskeletal manifestations of COVID-19 with review of imaging.
With surging numbers of patients with coronavirus disease 2019 (COVID-19) throughout the world, neuromuscular complications and rehabilitation concerns are becoming more apparent. Peripheral nerve ...injury can occur in patients with COVID-19 secondary to postinfectious inflammatory neuropathy, prone positioning-related stretch and/or compression injury, systemic neuropathy, or nerve entrapment from hematoma. Imaging of peripheral nerves in patients with COVID-19 may help to characterize nerve abnormality, to identify site and severity of nerve damage, and to potentially elucidate mechanisms of injury, thereby aiding the medical diagnosis and decision-making process. This review article aims to provide a first comprehensive summary of the current knowledge of COVID-19 and peripheral nerve imaging.
Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more ...likely than IDH-wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contributed to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures were often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, d-2-hydroxyglutarate, rapidly synchronized neuronal spike firing in a seizure-like manner, but only when non-neoplastic glial cells were present. In vitro and in vivo models recapitulated IDHmut glioma-associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibited seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.
Regeneration of peripheral nerves is remarkably restrained across transection injuries, limiting recovery of function. Strategies to reverse this common and unfortunate outcome are limited. ...Remarkably, however, new evidence suggests that a brief extracellular electrical stimulation (ES), delivered at the time of injury, improves the regrowth of motor and sensory axons.
In this work, the authors explored and tested this ES paradigm, which was applied proximal to transected sciatic nerves in mice, and identified several novel and compelling impacts of the approach. Using thy-1 yellow fluorescent protein mice with fluorescent axons that allow serial in vivo tracking of regeneration, the morphological, electrophysiological, and behavioral indices of nerve regrowth were measured.
The authors show that ES is associated with a 30%-50% improvement in several indices of regeneration: regrowth of axons and their partnered Schwann cells across transection sites, maturation of regenerated fibers in gaps spanning transection zones, and entry of axons into their muscle and cutaneous target zones. In parallel studies, the authors analyzed adult sensory neurons and their response to extracellular ES while plated on a novel microelectrode array construct designed to deliver the identical ES paradigm used in vivo. The ES accelerated neurite outgrowth, supporting the concept of a neuron-autonomous mechanism of action.
Taken together, these results support a robust role for brief ES following peripheral nerve injuries in promoting regeneration. Electrical stimulation has a wider repertoire of impact than previously recognized, and its impact in vitro supports the hypothesis that a neuron-specific reprogrammed injury response is recruited by the ES protocol.
In this review, we highlight the important role of the clinical electrodiagnostic (EDX) evaluation after cervical spinal cord injury (SCI). Our discussion focuses on the need for timely, frequent, ...and accurate EDX evaluations in the context of nerve transfer surgery to restore critical upper limb functions, including elbow extension, hand opening, and hand closing. The EDX evaluation is crucial to define the extent of lower motor neuron lesions and determine candidacy for surgery. We also discuss the important role of the postoperative EDX evaluation in determining prognosis and supporting rehabilitation. We propose a practical framework for EDX evaluation in this clinical setting.
The spinal cord facilitates communication between the brain and the body, containing intrinsic systems that work with lower motor neurons (LMNs) to manage movement. Spinal cord injuries (SCIs) can ...lead to partial paralysis and dysfunctions in muscles below the injury. While traditionally this paralysis has been attributed to disruptions in the corticospinal tract, a growing body of work demonstrates LMN damage is a factor. Motor units, comprising the LMN and the muscle fibers with which they connect, are essential for voluntary movement. Our understanding of their changes post‐SCI is still emerging, but the health of motor units is vital, especially when considering innovative SCI treatments like nerve transfer surgery. This review seeks to collate current literature on how SCI impact motor units and explore neuromuscular clinical implications and treatment avenues. SCI reduced motor unit number estimates, and surviving motor units had impaired signal transmission at the neuromuscular junction, force‐generating capacity, and excitability, which have the potential to recover chronically, yet the underlaying mechanisms are unclear. Furthermore, electrodiagnostic evaluations can aid in assessing the health lower and upper motor neurons, identify suitable targets for nerve transfer surgeries, and detect patients with time sensitive injuries. Lastly, many electrodiagnostic abnormalities occur in both chronic and acute SCI, yet factors contributing to these abnormalities are unknown. Future studies are required to determine how motor units adapt following SCI and the clinical implications of these adaptations.
•Reliance solely on surface anatomy landmarks to guide EMG electrode placement may comprise accuracy.•Here we simulated a clinical scenario where audiovisual feedback from volitional motor unit ...recordings isn’t available (e.g. muscle paralysis), which impairs accuracy in smaller and/or deeper forearm muscle targets.•We propose a greater role for neuromuscular ultrasound in EMG clinical training as well as an to assist in EMG needle guidance.
Anatomic landmarks alone may not always be sufficient to accurately guide electromyography (EMG) electrode needle placement.
Senior residents and fellows (n = 11) targeted 4 forearm muscles with anatomic landmarks alone versus with audiovisual EMG feedback. Accuracy of EMG needle placement was verified using neuromuscular ultrasound imaging.
While relatively large and superficial FCR muscle was sampled at a rate of 100% with and without audiovisual EMG feedback, accuracy of deeper and/or smaller forearm muscles (FPL, EIP, and SUP) diminished significantly without audiovisual EMG feedback.
Our study suggests that in clinical scenarios in which an electrodiagnostician relies on anatomic landmarks alone to target small and deep muscles, the risk of misplacement of needle electrode is increased. Consideration for neuromuscular ultrasound to augment training and/or real time guidance in EMG practice may be appropriate.
Introduction
Evaluation of nerve mechanical properties has the potential to improve assessment of nerve impairment. Shear wave velocity, as measured by using shear wave (SW) ultrasound elastography, ...is a promising indicator of nerve mechanical properties such as stiffness. However, elucidation of external factors that influence SW velocity, particularly nerve tension, is required for accurate interpretations.
Methods
Median and ulnar nerve SW velocities were measured at proximal and distal locations with limb positions that indirectly altered nerve tension.
Results
Shear wave velocity was greater at proximal and distal locations for limb positions that induced greater tension in the median (mean increase proximal 89.3%, distal 64%) and ulnar (mean increase proximal 91.1%, distal 37.4%) nerves.
Discussion
Due to the influence of nerve tension when SW ultrasound elastography is used, careful consideration must be given to limb positioning.
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