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BioRxiv : the Preprint Server For... Jun 2024Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring...
Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP). LEAP is primarily directed to ankle extensors and hence has great clinical potential to assist postural movements. To characterize this new response, we used the decerebrate cat model to avoid the suppressive effects of anesthesia, and combined EMG and force measurement in the hindlimb with intracellular recordings in the lumbar spinal cord. Stimulation was delivered as five-second trains via bipolar electrodes placed on the cord surface, and multiple combinations of stimulation locations (L4 to S2), amplitudes (50-600 uA), and frequencies (10-40 Hz) were tested. While the optimum stimulation location and frequency differed slightly among animals, the stimulation amplitude was key for controlling LEAP duration and amplitude. To study the mechanism of LEAP, we performed in vivo intracellular recordings of motoneurons. In 70% of motoneurons, LEAP increased at hyperpolarized membrane potentials indicating a synaptic origin. Furthermore, spinal interneurons exhibited changes in firing during LEAP, confirming the circuit origin of this behavior. Finally, to identify the type of afferents involved in generating LEAP, we used shorter stimulation pulses (more selective for proprioceptive afferents), as well as peripheral stimulation of the sural nerve (cutaneous afferents). The data indicates that LEAP primarily relies on proprioceptive afferents and has major differences from pain or withdrawal reflexes mediated by cutaneous afferents. Our study has thus identified and characterized a novel postural motor response to SCS which has the potential to expand the applications of SCS for patients with motor disorders.
PubMed: 38915687
DOI: 10.1101/2024.06.13.598885 -
BioRxiv : the Preprint Server For... Jun 2024Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus that is caused by metabolic toxicity to peripheral axons. We aimed to gain deep...
Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus that is caused by metabolic toxicity to peripheral axons. We aimed to gain deep mechanistic insight into the disease process using bulk and spatial RNA sequencing on tibial and sural nerves recovered from lower leg amputations in a mostly diabetic population. First, our approach comparing mixed sensory and motor tibial and purely sensory sural nerves shows key pathway differences in affected nerves, with distinct immunological features observed in sural nerves. Second, spatial transcriptomics analysis of sural nerves reveals substantial shifts in endothelial and immune cell types associated with severe axonal loss. We also find clear evidence of neuronal gene transcript changes, like in nerves with axonal loss suggesting perturbed RNA transport into distal sensory axons. This motivated further investigation into neuronal mRNA localization in peripheral nerve axons generating clear evidence of robust localization of mRNAs such as and in human sensory axons. Our work gives new insight into the altered cellular and transcriptomic profiles in human nerves in DPN and highlights the importance of sensory axon mRNA transport as an unappreciated potential contributor to peripheral nerve degeneration.
PubMed: 38915676
DOI: 10.1101/2024.06.15.599167 -
Journal of Korean Neurosurgical Society Jun 2024The Korean Neurosurgical Society, with its 62 years of history, has witnessed substantial growth in the field of neurosurgery, producing over 3,400 neurosurgeons,...
Enhancing the Evaluation System of Training Hospitals for Neurosurgical Residency Training and Education in South Korea : Striving for Balanced Participation and Differentiation.
The Korean Neurosurgical Society, with its 62 years of history, has witnessed substantial growth in the field of neurosurgery, producing over 3,400 neurosurgeons, establishing 12 divisions and 9 regional branches, and advancing in clinical management, diagnostic methods and academic research. Despite these developments, the regulations governing neurosurgical training and evaluation methods for training hospitals have remained largely unchanged, necessitating comprehensive revisions in response to evolving medical environments. To provide balanced participation opportunities for neurosurgery residents, the Korean Neurosurgical Society formed the Training Status Investigation Standard Change Task Force (TF Team) under the Training Education Committee. This paper presents the TF Team's findings and proposals for revising training status investigation standards and evaluation criteria. Through the processes including a lot of team meetings, workshops, education programs, official communications with 12 division societies, benchmarking from other societies and analysis of encrypted data from the past 5 years for neurosurgical training hospitals, the TF Team created a revised training status investigation proposal, supplemented main surgery criteria. And we applied this revised proposal to the training status investigation data collected from training hospitals in 2022 for simulation. We reduced the score for main surgeries to 10 points, introduced core competency surgery standards, allocating 5 points each for brain core competency surgery and spine and peripheral core competency surgery, for a total of 10 points. We also adjusted the major surgery score to 13 points, expanding the total surgery index score to 33 points. We introduced additional definitions for main surgeries in the areas of spine, pediatrics, and functional surgery. The equipment score was reduced from 17 points to 9 points. We specified minimum requirements for resident allocation eligibility, and if a hospital meets all of these criteria, they become eligible to apply for resident allocation. We introduced a new bonus point system for hospitals performing mechanical thrombectomy or stenting and peripheral nerve. The proposed revisions aim to improve the training and education of neurosurgical residents and overall neurosurgical care in Korea by creating a balanced and differentiated evaluation system for training hospitals. Further monitoring, communication, and adjustments are crucial for successful implementation.
PubMed: 38915210
DOI: 10.3340/jkns.2024.0067 -
Nature Communications Jun 2024Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish...
Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish sensory feedback include tactile, electrical, and peripheral nerve stimulation, however, they cannot recreate natural, intuitive sensations. Here, we establish an experimental biological sensorimotor interface and demonstrate its potential use in neuroprosthetics. We transfer a mixed nerve to a skeletal muscle combined with glabrous dermal skin transplantation, thus forming a bi-directional communication unit in a rat model. Morphological analyses indicate reinnervation of the skin, mechanoreceptors, NMJs, and muscle spindles. Furthermore, sequential retrograde labeling reveals specific sensory reinnervation at the level of the dorsal root ganglia. Electrophysiological recordings show reproducible afferent signals upon tactile stimulation and tendon manipulation. The results demonstrate the possibility of surgically creating an interface for both decoding efferent motor control, as well as encoding afferent tactile and proprioceptive feedback, and may indicate the way forward regarding clinical translation of biological communication pathways for neuroprosthetic applications.
Topics: Animals; Bionics; Rats; Muscle, Skeletal; Feedback, Sensory; Proprioception; Ganglia, Spinal; Mechanoreceptors; Muscle Spindles; Male; Female; Touch; Skin
PubMed: 38914540
DOI: 10.1038/s41467-024-49580-8 -
PloS One 2024Although a common injury there is a lack of published primary data to inform clinical management of sports related brachial plexus injuries. (Review)
Review
BACKGROUND
Although a common injury there is a lack of published primary data to inform clinical management of sports related brachial plexus injuries.
METHODS
A systematic search was completed in Medline, CINAHL, PubMed, SPORTDiscus and Web of Science databases and Google Scholar from inception to August 2023 according to the PRISMA-ScR guidelines. Methodological quality assessment of included articles was with the Joanna Briggs Institute tool. Studies providing primary data as to the rehabilitative management of diagnosed or suspected brachial plexus injuries sustained when playing contact sports were included.
RESULTS
Sixty-five studies were identified and screened, of which, 8 case reports were included, incorporating 10 participants with a mean age of 19.8 (±4.09) years. There was wide heterogeneity in injury severity, injury reporting, physical examination and imaging approaches documented. 9 of 10 participants returned to competitive sports, though follow-up periods also varied widely. Whilst return to play criteria varied between studies, the most consistent indicator was pain-free shoulder range of motion and strength.
CONCLUSIONS
There is a distinct lack of data available to inform evidence-based rehabilitation management of sports related brachial plexus injury. Only 8 individual case reports contain published data reporting on 10 athletes. Further reporting is critical to inform clinical management.
Topics: Humans; Brachial Plexus; Athletic Injuries; Young Adult; Male; Female; Range of Motion, Articular; Adult; Return to Sport; Brachial Plexus Neuropathies; Adolescent
PubMed: 38913647
DOI: 10.1371/journal.pone.0298317 -
JCI Insight May 2024Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel...
Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel subfamily N member 1 (KCNN1) mediates action potential afterhyperpolarization (AHP) and gates neuronal excitability. However, the specific contribution of DRG KCNN1 to neuropathic pain is not yet clear. We report that chronic constriction injury (CCI) of the unilateral sciatic nerve or unilateral ligation of the fourth lumbar nerve produced the downregulation of Kcnn1 mRNA and KCNN1 protein in the injured DRG. This downregulation was partially attributed to a decrease in DRG estrogen-related receptor gamma (ESRRG), a transcription factor, which led to reduced binding to the Kcnn1 promoter. Rescuing this downregulation prevented CCI-induced decreases in total potassium voltage currents and AHP currents, reduced excitability in the injured DRG neurons, and alleviated CCI-induced development and maintenance of nociceptive hypersensitivities, without affecting locomotor function and acute pain. Mimicking the CCI-induced DRG KCNN1 downregulation resulted in augmented responses to mechanical, heat, and cold stimuli in naive mice. Our findings indicate that ESRRG-controlled downregulation of DRG KCNN1 is likely essential for the development and maintenance of neuropathic pain. Thus, KCNN1 may serve as a potential target for managing this disorder.
Topics: Animals; Neuralgia; Ganglia, Spinal; Mice; Down-Regulation; Sensory Receptor Cells; Male; Peripheral Nerve Injuries; Mice, Inbred C57BL; Sciatic Nerve; Disease Models, Animal; Intermediate-Conductance Calcium-Activated Potassium Channels; Action Potentials
PubMed: 38912580
DOI: 10.1172/jci.insight.180085 -
Journal of Biomedical Optics Jul 2024Information about the spatial organization of fibers within a nerve is crucial to our understanding of nerve anatomy and its response to neuromodulation therapies. A...
NerveTracker: a Python-based software toolkit for visualizing and tracking groups of nerve fibers in serial block-face microscopy with ultraviolet surface excitation images.
SIGNIFICANCE
Information about the spatial organization of fibers within a nerve is crucial to our understanding of nerve anatomy and its response to neuromodulation therapies. A serial block-face microscopy method [three-dimensional microscopy with ultraviolet surface excitation (3D-MUSE)] has been developed to image nerves over extended depths . To routinely visualize and track nerve fibers in these datasets, a dedicated and customizable software tool is required.
AIM
Our objective was to develop custom software that includes image processing and visualization methods to perform microscopic tractography along the length of a peripheral nerve sample.
APPROACH
We modified common computer vision algorithms (optic flow and structure tensor) to track groups of peripheral nerve fibers along the length of the nerve. Interactive streamline visualization and manual editing tools are provided. Optionally, deep learning segmentation of fascicles (fiber bundles) can be applied to constrain the tracts from inadvertently crossing into the epineurium. As an example, we performed tractography on vagus and tibial nerve datasets and assessed accuracy by comparing the resulting nerve tracts with segmentations of fascicles as they split and merge with each other in the nerve sample stack.
RESULTS
We found that a normalized Dice overlap ( ) metric had a mean value above 0.75 across several millimeters along the nerve. We also found that the tractograms were robust to changes in certain image properties (e.g., downsampling in-plane and out-of-plane), which resulted in only a 2% to 9% change to the mean values. In a vagus nerve sample, tractography allowed us to readily identify that subsets of fibers from four distinct fascicles merge into a single fascicle as we move along the nerve's length.
CONCLUSIONS
Overall, we demonstrated the feasibility of performing automated microscopic tractography on 3D-MUSE datasets of peripheral nerves. The software should be applicable to other imaging approaches. The code is available at https://github.com/ckolluru/NerveTracker.
Topics: Software; Nerve Fibers; Imaging, Three-Dimensional; Algorithms; Animals; Image Processing, Computer-Assisted; Tibial Nerve; Vagus Nerve; Microscopy, Ultraviolet; Microscopy
PubMed: 38912214
DOI: 10.1117/1.JBO.29.7.076501 -
Cureus Jun 2024Background Postpartum peripheral nerve injuries can impact recovery. Elastic stockings are recommended for thromboembolism prevention, although concerns about entrapment...
Background Postpartum peripheral nerve injuries can impact recovery. Elastic stockings are recommended for thromboembolism prevention, although concerns about entrapment neuropathy exist. In this prospective observational study, we investigated the differential compressions caused by wearing elastic stockings before and after anesthesia, as well as changes in the diameters of the lower leg and ankle in parturient women undergoing spinal anesthesia for elective cesarean section (CS). Methods Eighteen pregnant women, classified by the American Society of Anesthesiologists as having physical status 2, underwent lower leg measurements taken before a CS. Elastic stockings were applied, and compression pressure was measured at pre-anesthesia, post-surgery, and six hours post-return to a hospital room. Fluid, blood loss, urine output, and neuropathy presence were recorded. For all parameters, changes at the three time points were compared for the primary analysis. For secondary analysis, participants were categorized as having intraoperative blood loss greater than (group P) or less than 1,000 g (group N), and factors were compared with pre-anesthesia and six hours post-return to a room. Data were analyzed and presented using a one-way analysis of variance with Bonferroni correction for multiple comparisons or unpaired two-tailed t-tests for pairwise comparison. Results None of the women had postoperative entrapment neuropathy. Six patients had >1,000 g of blood loss. Compression significantly increased from pre-anesthesia (left 13.6 ± 2.4, 95% CI: 12.18 to 14.52; right 13.4 ± 2.4, 95% CI: 12.41 to 14.69) to post-surgery (left, 17.4 ± 2.6, 95% CI: 15.68 to 18.12; right, 16.9 ± 2.6, 95% CI: 16.20 to 18.70) (p < 0.01). Compression pressure at post-surgery differed significantly between group P (left, 15.3 ± 1.3; right, 14.7 ± 1.8; 95% CI: -4.98 to -0.32) and group N (left, 18.1 ± 2.9; right, 17.8 ± 2.4; 95% CI: -5.38 to -0.26) (p < 0.05). The results are expressed as mean ± standard deviation, with P-values <0.05 indicating statistical significance. Conclusions In this study, no neuropathy occurred; however, over-compression risk with elastic stockings, especially when exceeding recommended pressure levels, was highlighted. Balancing thromboembolism prevention and over-compression risks is crucial for patients undergoing CSs with spinal anesthesia.
PubMed: 38912079
DOI: 10.7759/cureus.62809 -
Frontiers in Neurology 2024Treatment for post-traumatic greater occipital neuralgia (GON) includes serial injections of steroid/anesthetic. While these injections can alleviate pain, effects can...
BACKGROUND
Treatment for post-traumatic greater occipital neuralgia (GON) includes serial injections of steroid/anesthetic. While these injections can alleviate pain, effects can be transient, frequently lasting only 1 month. As a potential alternative, platelet-rich plasma (PRP) injections are an emerging biological treatment with beneficial effects in peripheral nerve disorders. We investigated the feasibility, safety, and effectiveness of a single PRP injection for post-traumatic GON in comparison to saline or steroid/anesthetic injection.
METHODS
In this pilot randomized, double-blinded, placebo-controlled trial, 32 adults with post-traumatic GON were allocated 1:1:1 to receive a single ultrasound-guided injection of (1) autologous PRP (2) steroid/anesthetic or (3) normal saline. Our primary outcome was feasibility (recruitment, attendance, retention) and safety (adverse events). Exploratory measures included headache intensity and frequency (daily headache diaries) and additional questionnaires (headache impact, and quality of life) assessed at pre-injection, 1 week, 1 month, and 3 months post-injection.
RESULTS
We screened 67 individuals, 55% were eligible and 95% of those participated. Over 80% of daily headache diaries were completed with 91% of participants completing the 3-month outcome questionnaires. No serious adverse events were reported. There were no significant differences between groups for headache intensity or frequency. Headache impact on function test-6 scores improved at 3 month in the PRP ( = -9.7, 95% CI [-15.6, -3.74], = 0.002) and saline ( = -6.7 [-12.7, -0.57], = 0.033) groups but not steroid/anesthetic group ( = 0.135).
CONCLUSION
PRP is a feasible and safe method for treating post-traumatic GON with comparable results to saline and steroid/anaesthetic. Further trials with larger sample sizes are required.https://clinicaltrials.gov/, identifier NCT04051203.
PubMed: 38911584
DOI: 10.3389/fneur.2024.1400057 -
BMC Oral Health Jun 2024Isaacs' syndrome, also known as neuromyotonia or peripheral nerve hyperexcitability, is a rare disorder that affects the peripheral nervous system. Clinical findings...
BACKGROUND
Isaacs' syndrome, also known as neuromyotonia or peripheral nerve hyperexcitability, is a rare disorder that affects the peripheral nervous system. Clinical findings include cramps, fasciculations, and myokymia; however, there are few reports of dental treatment for trismus.
CASE PRESENTATION
A patient with trismus due to Isaacs' syndrome experienced swelling and pain in the gingiva surrounding his right lower first molar. He was diagnosed with chronic apical periodontitis by a dentist near his home. However, the patient was informed that dental treatment and medication could not be administered because of the presence of Isaacs' syndrome, and he visited the Geriatric Dentistry and Perioperative Oral Care Center at Kyushu University Hospital 2 weeks later. The patient's painless mouth-opening distance (between incisors) was 20 mm at that time, and medication, including amoxicillin capsules and acetaminophen, was administered because the dental extraction forceps or endodontic instruments were difficult to insert into the oral cavity for treatment. Two months after his initial visit, the patient visited us complaining of pain in the same area. However, he had recently undergone plasmapheresis treatment in neurology to alleviate limited mouth opening and systemic myalgia, resulting in a pain-free mouth-opening distance of approximately 35 mm. During this temporary period in which he had no restriction in mouth opening, we performed tooth extraction and bridge restoration on the mandibular right first molar and created an oral appliance for sleep bruxism.
CONCLUSIONS
Plasmapheresis therapy transiently reduced trismus, rendering dental interventions feasible, albeit temporarily. This case report underscores the importance of close collaboration between neurologists and dentists who encounter similar cases while furnishing valuable insights to inform dental treatment planning.
Topics: Humans; Male; Trismus
PubMed: 38909199
DOI: 10.1186/s12903-024-04485-2