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Science Advances Jun 2024Sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli to the central...
Sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli to the central nervous system. Single-cell RNA sequencing has provided insights into the diversity of sensory ganglia cell types in rodents, nonhuman primates, and humans, but it remains difficult to compare cell types across studies and species. We thus constructed harmonized atlases of the DRG and TG that describe and facilitate comparison of 18 neuronal and 11 non-neuronal cell types across six species and 31 datasets. We then performed single-cell/nucleus RNA sequencing of DRG from both human and the highly regenerative axolotl and found that the harmonized atlas also improves cell type annotation, particularly of sparse neuronal subtypes. We observed that the transcriptomes of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The resources presented here can guide future studies in comparative transcriptomics, simplify cell-type nomenclature differences across studies, and help prioritize targets for future analgesic development.
Topics: Animals; Humans; Ganglia, Spinal; Trigeminal Ganglion; Transcriptome; Single-Cell Analysis; Sensory Receptor Cells; Species Specificity; Mice; Atlases as Topic; Gene Expression Profiling; Rats
PubMed: 38905344
DOI: 10.1126/sciadv.adj9173 -
Journal of Hand Surgery Global Online Mar 2024Surgical reconstruction of elbow extension can help restore function in patients with tetraplegia and triceps paralysis because of spinal cord injury. Both posterior...
PURPOSE
Surgical reconstruction of elbow extension can help restore function in patients with tetraplegia and triceps paralysis because of spinal cord injury. Both posterior deltoid-to-triceps tendon transfer and transfer of the branch of the axillary nerve to the triceps motor branch of the radial nerve have been described for triceps reanimation. This systematic review aimed at reviewing current evidence in the two schools of surgery in terms of their outcome and complication profile.
METHODS
A systematic review was conducted using MEDLINE (1974-2023) and EMBASE (1946-2023) databases. The keyword terms "elbow extension," "triceps," "deltoid," "nerve transfer," "spinal cord injury," "tetraplegia," "quadriplegia," and "tetraplegic" were used in the initial search, which was supplemented with manual searches of the bibliographies of retrieved articles.
RESULTS
Twenty studies met our inclusion criteria, with 14 studies (229 limbs) on posterior deltoid-to-triceps tendon transfer, 5 studies (23 limbs) on axillary to radial nerve transfer, and 1 study (1 limb) on combined transfer. For the tendon transfer group, the majority of studies reported a median triceps power of grade 3, with a wide range of failure percentage to reach antigravity (0% to 87.5%). Common complications included gradual stretching of the musculotendinous unit, rupture of the tendon transferred, elbow contracture, and infection. For the nerve transfer group, the majority of studies also reported a median triceps power reaching grade 3. There were no reported complications or loss of power in donor action of shoulder abduction or external rotation.
CONCLUSIONS
Transfer of the axillary nerve branch to the triceps motor branch of the radial nerve in tetraplegia shows promising results, with comparable triceps muscle power compared to traditional tendon transfer and a low incidence of complication.
TYPE OF STUDY/LEVEL OF EVIDENCE
Systematic Review III.
PubMed: 38903844
DOI: 10.1016/j.jhsg.2023.11.012 -
Journal of Nanobiotechnology Jun 2024Spinal cord injury (SCI) often results in motor and sensory deficits, or even paralysis. Due to the role of the cascade reaction, the effect of excessive reactive oxygen...
Spinal cord injury (SCI) often results in motor and sensory deficits, or even paralysis. Due to the role of the cascade reaction, the effect of excessive reactive oxygen species (ROS) in the early and middle stages of SCI severely damage neurons, and most antioxidants cannot consistently eliminate ROS at non-toxic doses, which leads to a huge compromise in antioxidant treatment of SCI. Selenium nanoparticles (SeNPs) have excellent ROS scavenging bioactivity, but the toxicity control problem limits the therapeutic window. Here, we propose a synergistic therapeutic strategy of SeNPs encapsulated by ZIF-8 (SeNPs@ZIF-8) to obtain synergistic ROS scavenging activity. Three different spatial structures of SeNPs@ZIF-8 were synthesized and coated with ferrostatin-1, a ferroptosis inhibitor (FSZ NPs), to achieve enhanced anti-oxidant and anti-ferroptosis activity without toxicity. FSZ NPs promoted the maintenance of mitochondrial homeostasis, thereby regulating the expression of inflammatory factors and promoting the polarization of macrophages into M2 phenotype. In addition, the FSZ NPs presented strong abilities to promote neuronal maturation and axon growth through activating the WNT4-dependent pathways, while prevented glial scar formation. The current study demonstrates the powerful and versatile bioactive functions of FSZ NPs for SCI treatment and offers inspiration for other neural injury diseases.
Topics: Spinal Cord Injuries; Animals; Antioxidants; Nanoparticles; Mice; Reactive Oxygen Species; Selenium; Neurons; Ferroptosis; Rats; Macrophages; RAW 264.7 Cells; Nerve Regeneration
PubMed: 38902789
DOI: 10.1186/s12951-024-02610-5 -
BMC Musculoskeletal Disorders Jun 2024Low back pain, a common problem worldwide, causes more global disability than any other condition and is associated with high costs to society. This observational... (Observational Study)
Observational Study
BACKGROUND
Low back pain, a common problem worldwide, causes more global disability than any other condition and is associated with high costs to society. This observational registry-based study describes the current trends in the medical treatment of neuropathic low back pain in the Swedish region of Västra Götaland, which has a population of 1.7 million. The study aims to; (1) identify the prevalence of neuropathic low back pain within the study population; (2) to explore the patterns of medical treatment utilization, including the prevalence and distribution of opioids (OG) and analgesics specified for neuropathic low back pain (NG) and (3) to evaluate the long-term trends and changes in medical treatment practice for neuropathic low back pain over the study period.
METHODS
This study includes a descriptive analysis of aggregated data extracted from the Swedish primary care registry VEGA and the pharmaceutical prescription registry Digitalis between the years 2017 and 2021. The data were stratified by year, age, gender, pharmaceutical code (ATC), and sub-diagnoses and presented as the prevalence of unique patients retrieving prescribed medication within six months before or after a registered diagnosis of neuropathic low back pain. The pharmaceutical codes were furthermore grouped into two groups depending on their mechanism of action; opioid group (OG) and neuropathic group (NG).
RESULTS
In all four diagnosis groups, more patients used opioid analgesics than neuropathic analgesics. The greatest difference between the opioid group and neuropathic group was in the lumbar spinal stenosis diagnosis group (67.1% vs. 40.6%), followed by the lumbar root canal stenosis diagnosis (65.9% vs. 44.2%), the nerve root and plexus compressions in intervertebral disc disorders diagnosis (57.5% vs. 40.8%), and lumbago with sciatica diagnosis (38.4% vs. 22.7%).
CONCLUSIONS
The trends suggest a general increase in the prescription rate and therefore patients' use of neuropathic analgesics for neuropathic pain associated with the studied diagnoses. However, opioid treatment remains the most common. The results indicate that the treatment for neuropathic low back pain needs to be improved.
Topics: Humans; Sweden; Registries; Low Back Pain; Male; Female; Middle Aged; Neuralgia; Adult; Aged; Analgesics, Opioid; Analgesics; Prevalence; Young Adult; Adolescent; Aged, 80 and over; Practice Patterns, Physicians'
PubMed: 38902709
DOI: 10.1186/s12891-024-07599-4 -
American Journal of Ophthalmology Jun 2024To evaluate ophthalmological, neurological, radiological, and laboratory data in patients with multiple sclerosis (MS) and to identify new ophthalmological factors that...
PURPOSE
To evaluate ophthalmological, neurological, radiological, and laboratory data in patients with multiple sclerosis (MS) and to identify new ophthalmological factors that could be helpful as biomarkers of the disease, potentially leading to an earlier prediction of disease course and disability progression.
DESIGN
Retrospective, cross-sectional-study.
METHODS
Best-corrected visual acuity (BCVA), ophthalmological biomicroscopy of the anterior segment and fundus, structural optical coherence tomography (OCT) with retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC), and OCT Angiography (OCTA) with vascular density (VD) were performed. The following clinical and neuro-radiological features were assessed: MS phenotype, disease duration, clinical severity, type of treatment, and T2-weighted lesion load plus T1-weighted Gd+-enhancing lesion number on the last brain and spinal cord MRI.
RESULTS
One hundred and six patients (212 eyes) were analyzed. Sixty-six of them (62.2 %) had MS and 40 (37.8%) were matched healthy controls (HCs). patients with MS showed lower RNFL, GCC, and VD in the radial peripapillary capillary plexus than controls in both eyes (p<0.05). By Performing a logistic regression with a distinct MS outcome for both eyes, we were able to demonstrate that the value that was most predictive of MS was the average GCC thickness (p=0.009). Regression analysis demonstrated that patients with a higher T2-weighted lesions showed a lower RNFL thickness value and reduced GCC and VD values than those with a low lesion load (p<0.01 and p<0.05, respectively). Similarly, relapsing MS patients showed lower RNFL values (p<0.05).
CONCLUSIONS
Several OCT- and OCTA-optic nerve parameters could be useful prognostic biomarkers for the MS disease course in clinical practice. However, it is necessary to do additional research with larger sample sizes in order to validate these findings.
PubMed: 38901720
DOI: 10.1016/j.ajo.2024.06.011 -
Journal of Korean Neurosurgical Society Jun 2024This study aimed to evaluate the clinical effects of medial branch blocks (MBB) C2 and C3 in treating patients with medically intractable headaches.
OBJECTIVE
This study aimed to evaluate the clinical effects of medial branch blocks (MBB) C2 and C3 in treating patients with medically intractable headaches.
METHODS
The medical records of 81 patients with medically intractable headaches who underwent a C2/3 MBB between January 2019 and March 2022 were retrospectively reviewed. The degrees of pain were evaluated using a visual analogue scale (VAS) score (rating 0-10) on baseline and after procedures. To evaluate patients' satisfaction for the treatment, self-reporting measurements were examined and were categorized as excellent (>90% pain relief), good (50%-90% pain relief), fair (10%-50% pain relief), and none (<10% pain relief).
RESULTS
The total number of MBB procedure was 107. The average baseline VAS score was 7.4 ±1.5, which improved significantly to 2.6 ±2.3, 3.6 ±2.6, and 4.5 ±3.2 on 1-3 days, 3-7 days, and 3 months after the procedure, respectively (Wilks' lambda within group test, P <0.001). For the subjective feeling of pain relief, percentages of "excellent" response in the self-reporting measurements were significantly decreased over time (chi-square test; P= 0.001).
CONCLUSION
This study demonstrates clinical effectiveness of C2/3 MBB in patients with medically intractable headaches, with both early and prolonged benefits.
PubMed: 38901465
DOI: 10.3340/jkns.2024.0004 -
PloS One 2024Neurofibromatosis Type I (NF1) is a rare genetic disorder. NF1 patients frequently develop a benign tumor in peripheral nerve plexuses called plexiform neurofibroma. In...
Neurofibromatosis Type I (NF1) is a rare genetic disorder. NF1 patients frequently develop a benign tumor in peripheral nerve plexuses called plexiform neurofibroma. In the past two decades, tissue-specific Nf1 knockout mouse models were developed using commercially available tissue-specific Cre recombinase and the Nf1 flox mice to mimic neurofibroma development. However, these models develop para-spinal neurofibroma, recapitulating a rare type of neurofibroma found in NF1 patients. The NPcis mouse model developed a malignant version of neurofibroma called malignant peripheral nerve sheath tumor (MPNST) within 3 to 6 months but intriguingly without apparent benign precursor lesion. Here, we revisited the NPcis model and discovered that about 20% display clinical signs similar to Nf1 tissue-specific knockout mice models. However, a systematic histological analysis could not explain the clinical signs we observed although we noticed lesions reminiscent of a neurofibroma in a peripheral nerve, a cutaneous neurofibroma, and para-spinal neurofibroma on rare occasions in NPcis mice. We also observed that 10% of the mice developed a malignant peripheral nerve sheath tumor (MPNST) spontaneously, coinciding with their earring tag identification. Strikingly, half of the sciatic nerves from NPcis mice developed plexiform neurofibroma within 1-6 months when intentionally injured. Thus, we provided a procedure to turn the widely used NPcis sarcoma model into a model recapitulating plexiform neurofibroma.
Topics: Animals; Neurofibroma, Plexiform; Disease Models, Animal; Mice; Sciatic Nerve; Mice, Knockout; Neurofibromatosis 1; Neurofibromin 1
PubMed: 38900740
DOI: 10.1371/journal.pone.0301040 -
Journal of Otolaryngology - Head & Neck... 2024Neck dissections (ND) are a routine procedure in head and neck oncology. Given the postoperative functional impact that some patients experience, it is imperative to...
BACKGROUND
Neck dissections (ND) are a routine procedure in head and neck oncology. Given the postoperative functional impact that some patients experience, it is imperative to identify and track quality of life (QoL) symptomatology to tailor each patient's therapeutic needs. To date, there is no validated French-Canadian questionnaire for this patient-population. We therefore sought to translate and validate the Neck Dissection Impairment Index (NDII) in Canadian French.
METHODS
A 3-phased approach was used. Phase 1: The NDII was translated from English to Canadian French using a "forward and backward" translational technique following international guidelines. Phase 2: A cognitive debriefing session was held with 10 Canadian French-speaking otolaryngology patients to evaluate understandability and acceptability. Phase 3: The final version was administered prospectively to 30 patients with prior history of ND and 30 control patients. These patients were asked to complete the questionnaire 2 weeks after their first response. Test-retest reliability was calculated with Spearman's correlation. Internal consistency was elicited using Cronbach's alpha.
RESULTS
NDII was successfully translated and validated to Canadian French. Cronbach's alpha revealed high internal consistency (0.92, lower 95% confidence limit 0.89). The correlation for test-retest validity were strong or very strong (0.61-0.91).
CONCLUSION
NDII is an internationally recognized QoL tool for the identification of ND-related impairments. This validated Canadian French version will allow clinicians to adequately assess the surgery-related QoL effect of neck surgery in the French-speaking population, while allowing French institutions to conduct and/or participate in multisite clinical trials requiring the NDII as an outcome measure.
Topics: Humans; Quality of Life; Neck Dissection; Female; Male; Middle Aged; Canada; Surveys and Questionnaires; Translations; Head and Neck Neoplasms; Reproducibility of Results; Aged; Adult; Prospective Studies; Surgical Oncology
PubMed: 38899627
DOI: 10.1177/19160216241263852 -
BMC Musculoskeletal Disorders Jun 2024Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often...
BACKGROUND
Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS.
METHODS
A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle.
RESULTS
The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge.
CONCLUSION
Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.
Topics: Humans; Spinal Fractures; Male; Middle Aged; Thoracic Vertebrae; Female; Retrospective Studies; Spondylitis, Ankylosing; Lumbar Vertebrae; Robotic Surgical Procedures; Fracture Fixation, Internal; Treatment Outcome; Aged; Operative Time; Length of Stay; Pedicle Screws; Adult; Blood Loss, Surgical; Follow-Up Studies
PubMed: 38898448
DOI: 10.1186/s12891-024-07597-6 -
ELife Jun 2024Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying...
Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation, and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.
Topics: Animals; Mice; Osteoclasts; Cellular Senescence; Sensory Receptor Cells; Disease Models, Animal; Male; Nerve Growth Factor; Netrin-1; Mice, Inbred C57BL
PubMed: 38896465
DOI: 10.7554/eLife.92889