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Peripheral nerve damage is a common medical problem that frequently leads to significant functional limitations and long-term disabilities. Platelet-rich plasma (PRP), a growth factor-rich substance, promotes axonal regeneration in peripheral nerve injuries. This study aimed to investigate the effect of PRP on axonal regeneration in Wistar rats (Rattus norvegicus) after peripheral nerve injury via histomorphometric analysis. This study used a post-test-only control-group design. Twenty-five white rats were randomly assigned to the control or treatment groups (n=5). The control group consisted of the sham-operated and saline groups. The treatment groups consisted of local, intraperitoneal, or combined PRP. A single dose of PRP was administered after axonotmesis of the sciatic nerve. After 21 days, a surgical procedure was performed to extract sciatic nerve tissue, which was then stained with Luxol fast blue for histomorphometric analysis. The mean diameter of the fibers, diameter of the axons, number of axons, and myelin sheath thickness were analyzed using MANOVA (p<0.05). Compared with the saline group, the PRP treatment group presented a greater number of regenerating myelinated axons with larger fiber and axon diameters, and thicker myelin (p<0.05). The myelinated axons in the sham-operated group showed a typical morphology, whereas those in the saline group showed a decrease in myelinated axons, smaller fiber and axon diameters, and thinner, irregular myelin sheaths. Injection of a combination of PRP, both intraperitoneally and locally, promoted the regeneration of damaged nerves in rats. [ABSTRACT FROM AUTHOR]

A 65-year-old female patient, with no known diseases and no regular medication usage, presented with a complaint of itching that had been ongoing for the past two years. Itching initially started in approximately five cm areas on the bilateral below-knee flexor surfaces. The patient, whose complaints persisted, was referred to the internal medicine outpatient clinic by dermatology. On physical examination, erythematous excoriated papules were observed in the areas affected by itching. The patient's blood sugar, liver and kidney function tests, complete blood count, erythrocyte sedimentation rate, thyroid function tests, urinalysis, stool parasitology were all normal or negative. The patient reported a sensation of coldness in the same area, was referred to neurosurgery to investigate the etiology of possible neuropathic itching. The patient's spinal imaging, revealed a spinal mass. She underwent surgery performed by a neurosurgeon, during which the spinal mass was completely removed. She reported that her itching had completely disappeared post-operatively. The concept of itching as a variant of pain is not very new. Any damage occurring in the central nervous system or peripheral nervous system that affects the neurons responsible for transmitting and processing itch can lead to neuropathic itching. Focusing on spinal cord pathologies, any condition that damages the spinal cord may cause itching, depending on the level of damage. In cases of itching with dermatomal localization, where pain, hot or cold sensations, and paroxysmal itching are present, additional imaging methods or investigations for etiology should be performed. [ABSTRACT FROM AUTHOR]

Charcot–Marie–Tooth disease type 1E (CMT1E) is an inherited autosomal dominant peripheral neuropathy caused by mutations in the peripheral myelin protein 22 (PMP22) gene. The identical leucine‐to‐proline (L16P) amino acid substitution in PMP22 is carried by the Trembler J (TrJ) mouse and is found in CMT1E patients presenting with early‐onset disease. Peripheral nerves of patients diagnosed with CMT1E display a complex and varied histopathology, including Schwann cell hyperproliferation, abnormally thin myelin, axonal degeneration, and subaxonal morphological changes. Here, we have taken an unbiased data‐independent analysis (DIA) mass spectrometry (MS) approach to quantify proteins from nerves of 3‐week‐old, age and genetic strain‐matched wild‐type (Wt) and heterozygous TrJ mice. Nerve proteins were dissolved in lysis buffer and digested into peptide fragments, and protein groups were quantified by liquid chromatography‐mass spectrometry (LC–MS). A linear model determined statistically significant differences between the study groups, and proteins with an adjusted p‐value of less than 0.05 were deemed significant. This untargeted proteomics approach identified 3759 quality‐controlled protein groups, of which 884 demonstrated differential expression between the two genotypes. Gene ontology (GO) terms related to myelin and myelin maintenance confirm published data while revealing a previously undetected prominent decrease in peripheral myelin protein 2. The dataset corroborates the described pathophysiology of TrJ nerves, including elevated activity in the proteasome‐lysosomal pathways, alterations in protein trafficking, and an increase in three macrophage‐associated proteins. Previously unrecognized perturbations in RNA processing pathways and GO terms were also discovered. Proteomic abnormalities that overlap with other human neurological disorders besides CMT include Lafora Disease and Amyotrophic Lateral Sclerosis. Overall, this study confirms and extends current knowledge on the cellular pathophysiology in TrJ neuropathic nerves and provides novel insights for future examinations. Recognition of shared pathomechanisms across discrete neurological disorders offers opportunities for innovative disease‐modifying therapeutics that could be effective for distinct neuropathies. [ABSTRACT FROM AUTHOR]

During myelination, large quantities of proteins are synthesized and transported from the endoplasmic reticulum (ER)‐trans‐Golgi network (TGN) to their appropriate locations within the intracellular region and/or plasma membrane. It is widely believed that oligodendrocytes uptake neuronal signals from neurons to regulate the endocytosis‐ and exocytosis‐mediated intracellular trafficking of major myelin proteins such as myelin‐associated glycoprotein (MAG) and proteolipid protein 1 (PLP1). The small GTPases of the adenosine diphosphate (ADP) ribosylation factor (Arf) family constitute a large group of signal transduction molecules that act as regulators for intracellular signaling, vesicle sorting, or membrane trafficking in cells. Studies on mice deficient in Schwann cell–specific Arfs‐related genes have revealed abnormal myelination formation in peripheral nerves, indicating that Arfs‐mediated signaling transduction is required for myelination in Schwann cells. However, the complex roles in these events remain poorly understood. This review aims to provide an update on signal transduction, focusing on Arf and its activator ArfGEF (guanine nucleotide exchange factor for Arf) in oligodendrocytes and Schwann cells. Future studies are expected to provide important information regarding the cellular and physiological processes underlying the myelination of oligodendrocytes and Schwann cells and their function in modulating neural activity. [ABSTRACT FROM AUTHOR]

Altered sensory processing is a common feature in autism spectrum disorder (ASD), as recognized in the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5). Although altered responses to tactile stimuli are observed in over 60% of individuals with ASD, the neurobiological basis of this phenomenon is poorly understood. ASD has a strong genetic component and genetic mouse models can provide valuable insights into the mechanisms underlying tactile abnormalities in ASD. This review critically addresses recent findings regarding tactile processing deficits found in mouse models of ASD, with a focus on behavioral, anatomical, and functional alterations. Particular attention was given to cellular and circuit‐level functional alterations, both in the peripheral and central nervous systems, with the objective of highlighting possible convergence mechanisms across models. By elucidating the impact of mutations in ASD candidate genes on somatosensory circuits and correlating them with behavioral phenotypes, this review significantly advances our understanding of tactile deficits in ASD. Such insights not only broaden our comprehension but also pave the way for future therapeutic interventions. [ABSTRACT FROM AUTHOR]

The perineuronal net (PNN) is a well‐described highly specialized extracellular matrix structure found in the central nervous system. Thus far, no reports of its presence or connection to pathological processes have been described in the peripheral nervous system. Our study demonstrates the presence of a PNN in the spinal afferent innervation of the distal colon of mice and characterizes structural and morphological alterations induced in an ulcerative colitis (UC) model. C57Bl/6 mice were given 3% dextran sulfate sodium (DSS) to induce acute or chronic UC. L6/S1 dorsal root ganglia (DRG) were collected. PNNs were labeled using fluorescein‐conjugated Wisteria Floribunda (WFA) l lectin, and calcitonin gene‐related peptide (CGRP) immunofluorescence was used to detect DRG neurons. Most DRG cell bodies and their extensions toward peripheral nerves were found surrounded by the PNN‐like structure (WFA+), labeling neurons' cytoplasm and the pericellular surfaces. The amount of WFA+ neuronal cell bodies was increased in both acute and chronic UC, and the PNN‐like structure around cell bodies was thicker in UC groups. In conclusion, a PNN‐like structure around DRG neuronal cell bodies was described and found modulated by UC, as changes in quantity, morphology, and expression profile of the PNN were detected, suggesting a potential role in sensory neuron peripheral sensitization, possibly modulating the pain profile of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Schwannomas are benign and slow-growing peripheral nerve sheath neoplasms of Schwann cells. These are generally encountered in the neck, head, and flexor areas of the extremities. Even though many schwannomas are easily diagnosable, their variable morphology can occasionally create difficulty in diagnosis. In this study, we present a rare case of melanotic schwannoma of the sacrum, emphasizing the need for routine biopsy to understand the etiology. A 46-year-old man presented to the Department of Neurosurgery, Taipei Medical University Hospital, with buttock pain in the sacrum area for 1 year, which worsened in the last 1–2 months. The patient had no known history of trauma or malignancy. We evidenced an intradural extramedullary neurogenic tumor at the caudal end from S1 to S3. Histologic analysis revealed melanin deposition in the tumor cells. Round to oval tumor cells were positive for HMB-45 and S-100 proteins, suggestive of melanotic Schwannoma, which were removed by laminectomy. After 1 month, the tumor recurred and was further removed surgically. Conclusively, we observed the sacrum as an unusual anatomic site for the possible occurrence of melanotic schwannoma, especially in patients with no known history of trauma and malignancy. The possibility of melanotic schwannoma is very high. We hypothesize that melanotic schwannoma was possible because it occurred in the intradural and extramedullary regions of the spine. Hence, a routine biopsy should be performed to corroborate the exact cause and prevent incorrect presumptions. [ABSTRACT FROM AUTHOR]

Dynamic muscle fatigue during repetitive movements can lead to changes in communication between the central nervous system and peripheral muscles. This study investigated these changes by examining electromyogram (EMG) characteristics from agonist and antagonist muscles during a fatiguing task. Twenty-two healthy male university students (age: 22.92 ± 2.19 years) performed heel raises until fatigue. EMG signals from lateral gastrocnemius (GL) and tibialis anterior (TA) muscles were processed using synchrosqueezed wavelet transform (SST). Root mean square (RMS), mean frequency (MF), power across frequency ranges, wavelet coherence, and co-activation ratio were computed. During the initial 80% of the task, RMS and EMG power increased for both muscles, while MF declined. In the final 20%, GL parameters stabilized, but TA showed significant decreases. Beta and gamma intermuscular coherence increased upon reaching 60% of the task. Alpha coherence and co-activation ratio remained constant. Results suggest that the central nervous system adopts a differentiated control strategy for agonist and antagonist muscles during fatigue progression. Initially, a coordinated "common drive" mechanism enhances both muscle groups' activity. Later, despite continued increases in muscle activity, neural-muscular coupling remains stable. This asynchronous, differentiated control mechanism enhances our understanding of neuromuscular adaptations during fatigue, potentially contributing to the development of more targeted fatigue assessment and management strategies. [ABSTRACT FROM AUTHOR]

The role of Drosophila numb in regulating Notch signaling and neurogenesis has been extensively studied, with a particular focus on its effects on the peripheral nervous system (PNS). Previous studies based on a single loss-of-function allele of numb, numb1, showed an antineurogenic effect on the peripheral nervous system (PNS), which revealed that the wild-type numb suppresses Notch signaling. In the current study, we examined whether this phenotype is consistently observed in loss-of-function mutations of numb. Two more numb alleles, numbEY03840 and numbEY03852, were shown to have an antineurogenic phenotype in the PNS. We also found that introducing a wild-type numb genomic fragment into numb1 homozygotes rescued their antineurogenic phenotype. These results demonstrated that loss-of-function mutations of numb universally induce this phenotype. Many components of Notch signaling are encoded by maternal effect genes, but no maternal effect of numb was observed in this study. The antineurogenic phenotype of numb was found to be dependent on the Enhancer of split (E(spl)), a downstream gene of Notch signaling. We found that the combination of E(spl) homozygous and numb1 homozygous suppressed the neurogenic phenotype of the embryonic central nervous system (CNS) associated with the E(spl) mutation. In the E(spl) allele, genes encoding basic helix-loop-helix proteins, such as m5, m6, m7, and m8, remain. Thus, in the E(spl) allele, derepression of Notch activity by numb mutation can rescue the neurogenic phenotype by increasing the expression of the remaining genes in the E(spl) complex. We also uncovered a role for numb in regulating neuronal projections. Our results further support an important role for numb in the suppression of Notch signaling during embryonic nervous system development. [ABSTRACT FROM AUTHOR]

Serotonin (5-hydroxytryptamine, 5-HT) is a ubiquitous neurotransmitter in the human body. In the central nervous system, 5-HT affects sleep, pain, mood, appetite, and attention, while in the peripheral nervous system, 5-HT modulates peristalsis, mucus production, and blood vessel dilation. Fourteen membrane receptors mediate 5-HT activity. In agreement with the crucial roles played by 5-HT, many drugs target 5-HT receptors (5-HTRs). Therefore, it is unsurprising that many efforts have been devoted to discovering multitarget-directed ligands (MTDLs) capable of engaging one or more 5-HTRs plus another target phenotypically linked to a particular disease. In this review, we will describe medicinal chemistry efforts in designing MTDLs encompassing activity for one or more 5-HTRs, starting with atypical antipsychotics and moving to dual 5-HT1AR/serotonin transporter ligands, 5-HT6R antagonists/acetyl cholinesterases inhibitors, and 5-HT4R agonists/acetyl cholinesterases inhibitors. We will also provide an outlook on the most recent efforts made in the field. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of human placenta hydrolysate (HPH) in a mice model of CFA-induced inflammatory pain. TNF-α, IL-1β, and IL-6 are key pro-inflammatory cytokine factors for relieving inflammatory pain. Therefore, this study investigates whether HPH suppresses CFA-induced pain and attenuates the inflammatory process by regulating cytokines. In addition, the relationship between neuropathic pain and HPH was established by staining GFAP and Iba-1 in mice spinal cord tissues. This study was conducted for a total of day 28, and inflammatory pain was induced in mice by injecting CFA into the right paw at day 0 and day 14, respectively. 100 μL of 20% glucose and polydeoxyribonucleotide (PDRN) and 100, 200, and 300 μL of HPH were administered intraperitoneally twice a week. In the CFA-induced group, cold and mechanical allodynia and pro-inflammatory cytokine factors in the spinal cord and plantar tissue were significantly increased. The five groups of drugs evenly reduced pain and gene expression of inflammatory factors, and particularly excellent effects were confirmed in the HPH 200 and 300 groups. Meanwhile, the expression of GFAP and Iba-1 in the spinal cord was increased by CFA administration but decreased by HPH administration, which was confirmed to suppress damage to peripheral ganglia. The present study suggests that HPH attenuates CFA-induced inflammatory pain through inhibition of pro-inflammatory cytokine factors and protection of peripheral nerves. [ABSTRACT FROM AUTHOR]

Dengue illness, caused by the dengue viruses, continues to be a major global health concern, with increasing incidence and the emergence of severe manifestations such as neurological complications. An overview of the current understanding of dengue epidemiology, clinical manifestations, and research priorities is presented here. Dengue transmission has escalated in recent years, exacerbated by factors such as vector expansion, climate change, and socioeconomic challenges. The clinical spectrum of dengue ranges from mild febrile illness to severe manifestations, including hemorrhagic fever and neurological complications. Neurological manifestations of dengue, once considered rare, are now increasingly reported, encompassing encephalitis, myelitis, and Guillain–Barré Syndrome, among others. Diagnosis primarily relies on laboratory methods such as RT/PCR, NS1 antigen detection, and serological assays. Despite advancements in understanding the dengue pathogenesis, there remains a critical need for effective vaccines, antiviral drugs, improved surveillance methods, predictive models for disease severity, and long-term studies on post-Dengue sequelae. Integrated programs and holistic approaches to dengue control are essential for mitigating its impact. Addressing these research priorities will be pivotal in combating dengue and reducing its global burden. [ABSTRACT FROM AUTHOR]

The transcription factor nuclear factor erythroid 2‐related factor 2 (NRF2) has multifarious action with its target genes having redox‐regulating functions and being involved in inflammation control, proteostasis, autophagy, and metabolic pathways. Therefore, the genes controlled by NRF2 are involved in the pathogenesis of myriad diseases, such as cardiovascular diseases, metabolic syndrome, neurodegenerative diseases, autoimmune disorders, and cancer. Amidst this large array of diseases, diabetic neuropathy (DN) occurs in half of patients diagnosed with diabetes and appears as an injury inflicted upon peripheral and autonomic nervous systems. As a complex effector factor, NRF2 has entered the spotlight during the search of new biomarkers and/or new therapy targets in DN. Due to the growing attention for NRF2 as a modulating factor in several diseases, including DN, this paper aims to update the recently discovered regulatory pathways of NRF2 in oxidative stress, inflammation and immunity. It presents the animal models that further facilitated the human studies in regard to NRF2 modulation and the possibilities of using NRF2 as DN biomarker and/or as target therapy. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Contraceptive implant migration is a rare complication associated with contraceptive implants: migration to the ulnar nerve, emphasizing the importance of accurate diagnosis, imaging, and a multidisciplinary approach to mitigate neurovascular risks during insertion and removal procedures. The case report demonstrates the necessity for careful removal techniques and thorough patient follow‐up to ensure positive outcomes and prevent long‐term nerve damage. There are some potential risks and complications associated with contraceptive implants, including neurovascular injury. The aim of this case report is to report a rare complication associated with contraceptive implants. A 32‐year‐old female, right‐hand dominant, presented to the orthopedic clinic for the extraction of a contraceptive implant (Implanon) from her left arm. She reported intermittent numbness in the ring and little fingers. Upon examination, the Implanon was not palpable. Both Phalen's test and Tinel signs were negative. An x‐ray of the arm revealed the implant's position. Under local anesthesia through a longitudinal incision, the Implanon was found within the perineurium of the ulnar nerve. Two weeks after the operation, the patient returned to the clinic. Upon examination, there were no indications of ulnar nerve neuropathy. If a patient undergoes subdermal implant‐associated pain or is at risk of neurovascular damage during removal, it is advisable to refer the patient to a family planning specialist experienced in handling challenging implant removals, and subsequently to a peripheral nerve surgeon, to optimize outcomes. The migration of a contraceptive implant to the ulnar nerve is an exceedingly rare but possible complication. [ABSTRACT FROM AUTHOR]

Despite increasing in mass approximately 100-fold during larval life, the Drosophila CNS maintains its characteristic form. Dynamic interactions between the overlying basement membrane and underlying surface glia are known to regulate CNS structure in Drosophila , but the genes and pathways that establish and maintain CNS morphology during development remain poorly characterized. To identify genes that regulate CNS shape in Drosophila , we conducted an EMS-based, forward genetic screen of the second chromosome, uncovered 50 mutations that disrupt CNS structure, and mapped these alleles to 17 genes. Analysis of whole genome sequencing data wedded to genetic studies uncovered the affected gene for all but 1 mutation. Identified genes include well-characterized regulators of tissue shape, like LanB1 , viking , and Collagen type IV alpha1 , and previously characterized genes, such as Toll-2 and Rme-8 , with no known role in regulating CNS structure. We also uncovered that papilin and C1GalTA likely act in the same pathway to regulate CNS structure and found that the fly homolog of a glucuronosyltransferase, B4GAT1/LARGE1, that regulates Dystroglycan function in mammals is required to maintain CNS shape in Drosophila. Finally, we show that the senseless-2 transcription factor is expressed and functions specifically in surface glia found on peripheral nerves but not in the CNS to govern CNS structure, identifying a gene that functionally subdivides a glial subtype along the peripheral–central axis. Future work on these genes should clarify the genetic mechanisms that ensure the homeostasis of CNS form during development. [ABSTRACT FROM AUTHOR]

Background/Objectives: Microsurgery employs techniques requiring optical magnification and specialized instruments to operate on small anatomical structures, including small vessels. These methods are integral to plastic surgery, enabling procedures such as free tissue transfer, nerve reconstruction, replantation, and lymphatic surgery. This paper explores the historical development, advancements, and current applications of microsurgery in plastic surgery. Methods: The databases MEDLINE (via PubMed) and Web of Science were selectively searched with the term "(((microsurgery) OR (advances)) OR (robotic)) OR (AI)) AND (((lymphatic surgery) OR (peripheral nerve surgery)) OR (allotransplantation))" and manually checked for relevance. Additionally, a supplementary search among the references of all publications included was performed. Articles were included that were published in English or German up to June 2024. Results: Modern microsurgical techniques have revolutionized plastic surgery, enabling precise tissue transfers, improved nerve reconstruction, and effective lymphedema treatments. The evolution of robotic-assisted surgery, with systems like da Vinci and MUSA, has enhanced precision and reduced operative times. Innovations in imaging, such as magnetic resonance (MR) lymphography and near-infrared fluorescence, have significantly improved surgical planning and outcomes. Conclusions: The continuous advancements in microsurgery, including supermicrosurgical techniques and robotic assistance, have significantly enhanced the capabilities and outcomes of plastic surgery. Future developments in AI and robotics promise further improvements in precision and efficiency, while new imaging modalities and surgical techniques expand the scope and success of microsurgical interventions. [ABSTRACT FROM AUTHOR]

Stress and anxiety being the major contributors of morbidity, leads to many chronic diseases and is known to invariably decrease the quality of life and even life span. Autonomic Nervous System (ANS), a part of the peripheral nervous system that controls the visceral system, functioning largely under the level of consciousness, capable of being influenced by the psychological factors and influences the physiological processes happening in the body. Meditation practices mainly change functions through autonomous nervous systems, which links brain and body. Meditation is a technique of yoga practiced in India over thousands of years. Long term yogic practices have shown improvement in cardiovascular functions. Meditation is a concentrative type of meditation involving focusing of attention on breath. This was a cross sectional, comparative study. 50 subjects between 18-45 years were included for the study. 50 meditators and 50 non-meditators (control group). The meditators used to practice meditation every morning for at least 30 minutes, for 1 or more years. There was decrease in Heart rate,SBP and DBP, MAP, RR in meditation group. This difference between 2 groups is satistically highly significant(p<0.001). [ABSTRACT FROM AUTHOR]

Research on the relationship between macrophages and neuropathic pain has flourished in the past two decades. It has long been believed that macrophages are strong immune effector cells that play well-established roles in tissue homeostasis and lesions, such as promoting the initiation and progression of tissue injury and improving wound healing and tissue remodeling in a variety of pathogenesis-related diseases. They are also heterogeneous and versatile cells that can switch phenotypically/functionally in response to the micro-environment signals. Apart from microglia (resident macrophages of both the spinal cord and brain), which are required for the neuropathic pain processing of the CNS, neuropathic pain signals in PNS are influenced by the interaction of tissue-resident macrophages and BM infiltrating macrophages with primary afferent neurons. And the current review looks at new evidence that suggests sexual dimorphism in neuropathic pain are caused by variations in the immune system, notably macrophages, rather than the neurological system. PLAIN LANGUAGE SUMMARY: Neuropathic pain is defined by the International Association for the Study of Pain as pain triggered or caused by primary damage to or dysfunction of the nervous system. Following intensive research into the mechanisms of neuropathic pain, macrophages have been revealed to play an important role in pathologic pain following nerve injury. Macrophages dynamically monitor the microenvironment to maintain tissue homeostasis. Once a macrophage is exposed to a pathologic stimulus, it in turn alters its functional phenotype and interacts with nociceptors, leading to neuropathic pain. This review wants to delve into the biology of macrophages in the central and peripheral nervous system, how they are related to play a role in neuropathic pain and whether there is sexual dimorphism in macrophages. [ABSTRACT FROM AUTHOR]

Enucleation is a surgical technique to resect peripheral nerve schwannomas. The procedure has a low risk for postoperative deficit, but a small chance for recurrence, because tumor cells may remain inside the pseudocapsule that is left after resection. Magnetic resonance imaging (MRI) scans are frequently performed after surgery to investigate potential residual tumor, but currently there is little information in the literature on the value of follow-up with MRI. All patients who underwent enucleation of a peripheral nerve schwannoma between October 2013 and June 2022 were included. Postoperative MRI scans (gadolinium-enhanced) made at different time points after the surgery were re-examined for residual enhancement. Patients with residual enhancement were contacted to inform whether symptoms had recurred. A total of 75 schwannoma enucleations in 74 patients were included. The first postoperative MRI scan, performed 3 months after the surgery, showed no residual enhancement in 50 patients. In the remaining 24 patients, another MRI scan was made 1 year after the surgery, which still showed a possible remnant in 11 patients. On the third MRI scan, performed 2 years after enucleation, there were 7 suspected cases (9%). None of these patients had clinical symptoms at a mean postoperative follow-up of 5 years. Our data show that the value of postoperative MRI scans after enucleation of peripheral nerve schwannomas is limited, because residual enhancement in the beginning can be non-specific and the small percentage of patients, that persistently had a potential remnant, were all asymptomatic. [ABSTRACT FROM AUTHOR]

Background Given the high prevalence of chronic shoulder pain and encouraging early results of terminal sensory articular branch radiofrequency ablation to treat shoulder pain, research is warranted to refine the procedural technique on the basis of updated neuroanatomic knowledge with the goal of further improving patient outcomes. Objective We describe an updated radiofrequency ablation protocol that accounts for varied locations of the terminal sensory articular branches of the suprascapular, axillary, subscapular, and lateral pectoral nerves within individual patients. Design Technical note. Methods Cadaveric studies delineating the sensory innervation of the shoulder joint were reviewed, and a more comprehensive radiofrequency ablation protocol is proposed relative to historical descriptions. Conclusions The proposed radiofrequency ablation protocol, which is based on neuroanatomic dissections of the shoulder joint, will provide a safe means of more complete sensory denervation and potentially improve clinical outcomes compared with historical descriptions, the efficacy of the new protocol must be confirmed in prospective studies. [ABSTRACT FROM AUTHOR]

Biallelic SORD mutations cause one of the most frequent forms of recessive hereditary neuropathy, estimated to affect ∼10 000 patients in North America and Europe alone. Pathogenic SORD loss-of-function changes in the encoded enzyme sorbitol dehydrogenase result in abnormally high sorbitol levels in cells and serum. How sorbitol accumulation leads to peripheral neuropathy remains to be elucidated. A reproducible animal model for SORD neuropathy is essential to illuminate the pathogenesis of SORD deficiency and for preclinical studies of potential therapies. Therefore, we have generated a Sord knockout (KO), Sord −/−, Sprague Dawley rat, to model the human disease and to investigate the pathophysiology underlying SORD deficiency. We have characterized the phenotype in these rats with a battery of behavioural tests as well as biochemical, physiological and comprehensive histological examinations. Sord −/− rats had remarkably increased levels of sorbitol in serum, CSF and peripheral nerve. Moreover, serum from Sord −/− rats contained significantly increased levels of neurofilament light chain, an established biomarker for axonal degeneration. Motor performance significantly declined in Sord −/− animals starting at ∼7 months of age. Gait analysis evaluated with video motion-tracking confirmed abnormal gait patterns in the hindlimbs. Motor nerve conduction velocities of the tibial nerves were slowed. Light and electron microscopy of the peripheral nervous system revealed degenerating myelinated axons, de- and remyelinated axons, and a likely pathognomonic finding—enlarged 'ballooned' myelin sheaths. These findings mainly affected myelinated motor axons; myelinated sensory axons were largely spared. In summary, Sord −/− rats develop a motor-predominant neuropathy that closely resembles the human phenotype. Our studies revealed novel significant aspects of SORD deficiency, and this model will lead to an improved understanding of the pathophysiology and the therapeutic options for SORD neuropathy. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between human leukocyte antigen (HLA) and paraneoplastic neurological syndromes (PNS) with Hu antibodies, and potential specificities according to clinical presentation and cancer status. Methods: HLA genotypes at four-digit resolution were imputed from available genome-wide association data. Allele carrier frequencies were compared between patients (whole cohort, n = 100, and according to clinical presentation and cancer status) and matched healthy controls (n = 508) using logistic regression controlled by the three main principal components. Results: The clinical presentation of 100 anti-Hu patients involved the central nervous system (28, 28%), the peripheral nervous system (36, 36%) or both combined (36, 36%). Cancer diagnosis was certain in 75 (75%). HLA association analyses revealed that anti-Hu PNS patients were more frequently carriers of DQA1*05:01 (39% vs. 19%, OR = 2.8 [1.74–4.49]), DQB1*02:01 (39% vs. 18%, OR = 2.88 [1.79–4.64]) and DRB1*03:01 (41% vs. 19%, OR = 2.92 [1.80–4.73]) than healthy controls. Remarkably, such DR3 ~ DQ2 association was absent in patients with pure central involvement, but more specific to those manifesting with peripheral involvement: DQA1*05:01 (OR = 3.12 [1.48–6.60]), DQB1*02:01 (OR = 3.35 [1.57–7.15]) and DRB1*03:01 (OR = 3.62 [1.64–7.97]); being even stronger in cases with sensory neuropathy, DQA1*05:01 (OR = 4.41 [1.89–10.33]), DQB1*02:01 (OR = 4.85 [2.04–11.53]) and DRB1*03:01 (OR = 5.79 [2.28–14.74]). Similarly, DR3 ~ DQ2 association was only observed in patients with cancer. Discussion: Patients with anti-Hu PNS show different HLA profiles according to clinical presentation and, probably, cancer status, suggesting pathophysiological differences. [ABSTRACT FROM AUTHOR]

Hereditary transthyretin-related amyloidosis (ATTRv amyloidosis) is a rare and progressively debilitating disease characterized by the deposition of transthyretin (TTR) amyloid fibrils in various organs and tissues, most commonly in the heart and peripheral nerves. This pathological deposition can lead to significant organ dysfunction and, ultimately, organ failure. ATTRv amyloidosis exhibits a broad range of clinical presentations, from purely neurological symptoms to purely cardiac manifestations, as well as mixed phenotypes which result from both neurological and cardiac implications. This wide phenotypical spectrum realistically challenges disease diagnosis and prognosis, especially in individuals without or with an unknown family history. Multiple factors are thought to contribute to this variability, including genetic, epigenetic, and even environmental influences. Understanding these factors is crucial, as they can significantly affect disease expression and progression. This review aims to summarize each of these contributing factors, to help elucidate the current knowledge on the phenotypical variability of ATTRv amyloidosis. [ABSTRACT FROM AUTHOR]

Modulation of input from primary afferent fibres has long been examined at the level of the first relays of these fibres. However, recent studies reveal that input to the spinal cord may also be modulated at the level of the very entry of afferent fibres to the spinal grey matter before action potentials in intraspinal collaterals of afferent fibres reach their target neurons. Such modulation greatly depends on the actions of GABA via extrasynaptic membrane receptors. In the reported study we hypothesized that the increase in excitability of afferent fibres following epidural polarization close to the site where collaterals of afferent fibres leave the dorsal columns is due to the release of GABA from two sources: not only GABAergic interneurons but also glial cells. We present evidence, primo, that GABA released from both these sources contributes to a long‐lasting increase in the excitability and a shortening of the refractory period of epidurally stimulated afferent fibres and, secondo, that effects of epidural polarization on the release of GABA are more critical for these changes than direct effects of DC on the stimulated fibres. The experiments were carried out in deeply anaesthetized rats in which changes in compound action potentials evoked in hindlimb peripheral nerves by dorsal column stimulation were used as a measure of the excitability of afferent fibres. The study throws new light on the modulation of input to spinal networks but also on mechanisms underlying the restoration of spinal functions. [ABSTRACT FROM AUTHOR]

Background and Aims: The goal of this study was to define basic constituents of the adult peripheral nervous system (PNS) using intact human nerve tissues. Methods: We combined fluorescent and chromogenic immunostaining methods, myelin‐selective fluorophores, and routine histological stains to identify common cellular and noncellular elements in aldehyde‐fixed nerve tissue sections. We employed Schwann cell (SC)‐specific markers, such as S100β, NGFR, Sox10, and myelin protein zero (MPZ), together with axonal, extracellular matrix (collagen IV, laminin, fibronectin), and fibroblast markers to assess the SC's relationship to myelin sheaths, axons, other cell types, and the acellular environment. Results: Whereas S100β and Sox10 revealed mature SCs in the absence of other stains, discrimination between myelinating and non‐myelinating (Remak) SCs required immunodetection of NGFR along with axonal and/or myelin markers. Surprisingly, our analysis of NGFR+ profiles uncovered the existence of at least 3 different novel populations of NGFR+/S100β− cells, herein referred to as nonglial cells, residing in the stroma and perivascular areas of all nerve compartments. An important proportion of the nerve's cellular content, including circa 30% of endoneurial cells, consisted of heterogenous S100β negative cells that were not associated with axons. Useful markers to identify the localization and diversity of nonglial cell types across different compartments were Thy1, CD34, SMA, and Glut1, a perineurial cell marker. Interpretation: Our optimized methods revealed additional detailed information to update our understanding of the complexity and spatial orientation of PNS‐resident cell types in humans. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors have revolutionized cancer therapy and are increasingly used to treat a wide range of oncological conditions, with dramatic benefits for many patients. Unfortunately, the resulting increase in T cell effector function often results in immune-related adverse events (irAEs), which can involve any organ system, including the central nervous system (CNS) and peripheral nervous system (PNS). Neurological irAEs involve the PNS in two-thirds of affected patients. Muscle involvement (immune-related myopathy) is the most common PNS irAE and can be associated with neuromuscular junction involvement. Immune-related peripheral neuropathy most commonly takes the form of polyradiculoneuropathy or cranial neuropathies. Immune-related myopathy (with or without neuromuscular junction involvement) often occurs along with immune-related myocarditis, and this overlap syndrome is associated with substantially increased mortality. This Review focuses on PNS adverse events associated with immune checkpoint inhibition. Underlying pathophysiological mechanisms are discussed, including antigen homology between self and tumour, epitope spreading and activation of pre-existing autoreactive T cells. An overview of current approaches to clinical management is provided, including cytokine-directed therapies that aim to decouple anticancer immunity from autoimmunity and emerging treatments for patients with severe (life-threatening) presentations. Some patients who are treated with checkpoint inhibitors experience peripheral nervous system (PNS) immune-related adverse events (irAEs). O'Hare and Guidon describe the spectrum of PNS irAE phenotypes, discuss their underlying mechanisms and outline a consensus-based, pathophysiology-driven approach to their clinical management. Key points: Checkpoint inhibitors have improved cancer outcomes but the resultant increase in T cell effector function can result in immune-related adverse events (irAEs). Neurological irAEs occur in 1–2% of all patients treated with checkpoint inhibitors and most frequently (in about two-thirds of individuals) involve the peripheral nervous system (PNS). The most common presentation of PNS irAEs is immune-related myopathy, which can be associated with immune-related neuromuscular junction involvement; immune-related neuropathy most commonly presents as polyradiculoneuropathy or cranial neuropathies. irAEs are largely driven by excessive T cell activity and autoimmunity resulting from factors including antigen homology between self and tumour, epitope spreading and activation of pre-existing autoreactive T cells. Clinical management of PNS irAEs is guided by syndrome subtype, severity and comorbidities, most notably myocarditis; research focuses on prevention, identification of new targeted treatments and strategies for severe, life-threatening PNS irAEs. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is vital for synaptic plasticity, cell persistence, and neuronal development in peripheral and central nervous systems (CNS). Numerous intracellular signalling pathways involving BDNF are well recognized to affect neurogenesis, synaptic function, cell viability, and cognitive function, which in turn affects pathological and physiological aspects of neurons. Stroke has a significant psycho-socioeconomic impact globally. Central post-stroke pain (CPSP), also known as a type of chronic neuropathic pain, is caused by injury to the CNS following a stroke, specifically damage to the somatosensory system. BDNF regulates a broad range of functions directly or via its biologically active isoforms, regulating multiple signalling pathways through interactions with different types of receptors. BDNF has been shown to play a major role in facilitating neuroplasticity during post-stroke recovery and a pro-nociceptive role in pain development in the nervous system. BDNF-tyrosine kinase receptors B (TrkB) pathway promotes neurite outgrowth, neurogenesis, and the prevention of apoptosis, which helps in stroke recovery. Meanwhile, BDNF overexpression plays a role in CPSP via the activation of purinergic receptors P2X4R and P2X7R. The neuronal hyperexcitability that causes CPSP is linked with BDNF-TrkB interactions, changes in ion channels and inflammatory reactions. This review provides an overview of BDNF synthesis, interactions with certain receptors, and potential functions in regulating signalling pathways associated with stroke and CPSP. The pathophysiological mechanisms underlying CPSP, the role of BDNF in CPSP, and the challenges and current treatment strategies targeting BDNF are also discussed. [ABSTRACT FROM AUTHOR]

Here, a novel kind of composite scaffold was fabricated by loading vascular endothelial growth factor (VEGF) and gastrodin liposome (GAS-LP) into electrospun silk fibroin/graphene oxide(SF/GO)nanofibrous and silk fibroin sponge-filled, respectively. Our results demonstrated that VEGF and GAS exhibited different release patterns in vitro which VEGF showed rapid release rate in the first few days while GAS was released slowly and continuously as encapsulated in liposomes. The scaffolds realized the combination of intraneural vascularization drugs and electrical stimulation effectively, leading to enhanced growth of RSC96 cells. Furthermore, the scaffolds could protect RSC96 cells in an inflammatory environment. [ABSTRACT FROM AUTHOR]

The human hand, with its intricate sensory capabilities, plays a pivotal role in our daily interactions with the world. This remarkable organ possesses a wide range of natural sensors that enrich our experiences, enabling us to perceive touch, position, and temperature. These natural sensors work in concert to provide us with a rich sensory experience, enabling us to distinguish between various textures, gauge the force of our grip, determine the position of our fingers without needing to see them, perceive the temperature of objects we come into contact with or detect if a cloth is wet or dry. This complex sensory system is fundamental to our ability to manipulate objects, explore our surroundings, and interact with the world and people around us. In this article, we summarize the research performed in our laboratories over the years and our findings to restore both touch, position, and temperature modalities. The combination of intraneural stimulation, sensory substitution, and wearable technology opens new possibilities for enhancing sensory feedback in prosthetic hands, promising improved functionality and a closer approximation to natural sensory experiences for individuals with limb differences. [ABSTRACT FROM AUTHOR]

During the past four decades, ultrasound has become popular as an imaging modality applied to the musculoskeletal (MSK) system, particularly outside the USA, due to its low cost, accessibility, and lack of ionizing radiation. A basic requirement in performing these examinations is to have a core group of radiologists and ultrasound technologists with expertise in MSK ultrasound. The extent to which ultrasound will be part of the imaging offered by a particular radiology practice or in an academic institution will vary according to expertise, availability, and reimbursements. A brief discussion of the technical capabilities of the current generation of ultrasound scanners will be followed by a description of some of the more prevalent MSK ultrasound imaging applications. The extent to which training to perform these exams within and outside of Radiology plays a role is discussed. Applications that are unique to ultrasound, such as dynamic evaluation of musculoskeletal anatomy and some, US-guided interventions are an important part of MSK imaging. Ultrasound is increasingly important in the assessment of superficial structures, such as tendons, small joints, and peripheral nerves. These applications help to establish the place of ultrasound as an important part of the Radiologists approach to MSK imaging. Outside of radiology, for a variety of clinical subspecialties, ultrasound already plays an integral role in MSK imaging. [ABSTRACT FROM AUTHOR]

Intra-articular tumours are uncommonly encountered in routine practice and may present diagnostic challenges to pathologists. Challenges unique to this site include distinction from more common reactive synovial conditions, which are far more common; histologic variability; superimposed reactive changes; and often, lack of provided clinicoradiological context. This article reviews the pathology of the synovial tumours and tumour-like lesions, including diagnostic pearls, pitfalls and rare entities. [ABSTRACT FROM AUTHOR]

Amyloid neuropathy is caused by deposition of insoluble β‐pleated amyloid sheets in the peripheral nervous system. It is most common in: (1) light‐chain amyloidosis, a clonal non‐proliferative plasma cell disorder in which fragments of immunoglobulin, light or heavy chain, deposit in tissues, and (2) hereditary transthyretin (ATTRv) amyloidosis, a disorder caused by autosomal dominant mutations in the TTR gene resulting in mutated protein that has a higher tendency to misfold. Amyloid fibrils deposit in the endoneurium of peripheral nerves, often extensive in the dorsal root ganglia and sympathetic ganglia, leading to atrophy of Schwann cells in proximity to amyloid fibrils and blood–nerve barrier disruption. Clinically, amyloid neuropathy is manifested as a length‐dependent sensory predominant neuropathy associated with generalized autonomic failure. Small unmyelinated nerves are involved early and prominently in early‐onset Val30Met ATTRv, whereas other ATTRv and light‐chain amyloidosis often present with large‐ and small‐fiber involvement. Nerve conduction studies, quantitative sudomotor axon testing, and intraepidermal nerve fiber density are useful tools to evaluate denervation. Amyloid deposition can be demonstrated by tissue biopsy of the affected organ or surrogate site, as well as bone‐avid radiotracer cardiac imaging. Treatment of light‐chain amyloidosis has been revolutionized by monoclonal antibodies and stem cell transplantation with improved 5‐year survival up to 77%. Novel gene therapy and transthyretin stabilizers have revolutionized treatment of ATTRv, improving the course of neuropathy (less change in the modified Neuropathy Impairment Score + 7 from baseline) and quality of life. With great progress in amyloidosis therapies, early diagnosis and presymptomatic testing for ATTRv family members has become paramount. ANN NEUROL 2024;96:423–440 [ABSTRACT FROM AUTHOR]

Summary: Perineural anaesthesia is a useful technique in equine surgery, providing pre‐emptive targeted anaesthesia of the surgical site, reducing volatile anaesthetic requirements, improving recovery quality and providing postoperative pain relief. Surgery under standing sedation in horses has increased in popularity, mandating the need for effective locoregional anaesthesia and analgesic techniques. Nerve location techniques offer greater accuracy than blind techniques when placing injectate. These methods can help to avoid structures such as blood vessels and minimise direct nerve damage during needle placement, reducing the risk of procedure‐related complications. This review will discuss the most pertinent research in the veterinary literature where objective methods of nerve location have been used to perform peripheral nerve blocks in horses. The efficacy of using objective methods to perform nerve blocks in equine anaesthesia is discussed by the authors, providing useful information to equine anaesthetists, and potentially improve the quality of anaesthesia and analgesia in horses. [ABSTRACT FROM AUTHOR]

The 2021 World Health Organization Classification of Central Nervous System Tumours introduced significant revisions to the categorization of paraspinal and nerve sheath tumours. This updated system encompasses seven tumour types: schwannoma, neurofibroma, perineurioma, hybrid nerve sheath tumours, malignant melanotic nerve sheath tumour, malignant peripheral nerve sheath tumour and cauda equina neuroendocrine tumour. This review provides an image‐rich cytologic reference of these tumours, with particular emphasis on intraoperative smear preparations. Knowledge of the key cytological features of these tumours and their differential diagnoses will help guide classification of these challenging entities. [ABSTRACT FROM AUTHOR]

Dopamine (DA) D2-like receptors in both the central nervous system (CNS) and the periphery are key modulators of metabolism. Moreover, disruption of D2-like receptor signaling is implicated in dysglycemia. Yet, the respective metabolic contributions of CNS versus peripheral D2-like receptors, including D2 (D2R) and D3 (D3R) receptors, remain poorly understood. To address this, we developed new pharmacological tools, D2-like receptor agonists with diminished and delayed blood-brain barrier capability, to selectively manipulate D2R/D3R signaling in the periphery. We designated bromocriptine methiodide (BrMeI), a quaternary methiodide analog of D2R/D3R agonist and diabetes drug bromocriptine, as our lead compound based on preservation of D2R/D3R binding and functional efficacy. We then used BrMeI and unmodified bromocriptine to dissect relative contributions of CNS versus peripheral D2R/D3R signaling in treating dysglycemia. Systemic administration of bromocriptine, with unrestricted access to CNS and peripheral targets, significantly improved both insulin sensitivity and glucose tolerance in obese, dysglycemic mice in vivo. In contrast, metabolic improvements were attenuated when access to bromocriptine was restricted either to the CNS through intracerebroventricular administration or delayed access to the CNS via BrMeI. Our findings demonstrate that the coordinated actions of both CNS and peripheral D2-like receptors are required for correcting dysglycemia. Ultimately, the development of a first-generation of drugs designed to selectively target the periphery provides a blueprint for dissecting mechanisms of central versus peripheral DA signaling and paves the way for novel strategies to treat dysglycemia. Article Highlights: We developed new pharmacological tools with diminished blood-brain barrier capability to selectively manipulate peripheral dopamine D2-like receptor signaling. Our lead compound, bromocriptine methiodide (BrMeI), shows preserved dopamine D2-like receptor binding and functional efficacy. We used BrMeI and unmodified bromocriptine to dissect relative contributions of central nervous system versus peripheral dopamine signaling in treating dysglycemia. Systemic administration of the dopaminergic agonist bromocriptine significantly improves dysglycemia, while metabolic improvements are attenuated after restricting access to the brain or periphery via BrMeI. Tandem, coordinated actions of both brain and peripheral dopamine D2-like receptors are required for correcting dysglycemia. [ABSTRACT FROM AUTHOR]

Mode of birth has been linked to offspring health. Changes in DNA methylation (DNAm) may represent a potential mechanism; however, findings are heterogeneous and limited to early infancy. This preregistered study examined whether mode of birth (vaginal birth compared with elective or emergency cesarean section) affects DNAm at birth, in childhood, and adolescence and whether these effects are modified by the postnatal care environment, specifically by breastfeeding and mother–infant bonding. Using data from 876 mother–infant dyads from the U.K. Avon Longitudinal Study of Parents and Children, we examined differentially methylated cytosine-phosphate-guanine dinucleotides and regions associated with mode of birth. DNAm was quantified using Illumina Infinium Human Methylation 450 K BeadChip in cord blood (at birth) and in peripheral blood (at 7 and 15–17 years). Analyses controlled for maternal age, education, smoking during pregnancy, child sex, gestational week at birth, and batch effects. We also examined interactions of mode of birth with breastfeeding practices and mother–infant bonding. In cord blood, two cytosine-phosphate-guanine dinucleotides (cg05230316; cg13230077) were linked to mode of birth (pFDR <.050). DNAm in childhood or adolescence was not statistically associated with mode of birth (pFDR >.050), and breastfeeding and mother–infant bonding were not moderators (p >.050). Overall, findings suggest mode of birth may have a small effect on cord blood DNAm, but these effects may not persist into later developmental stages. Other postnatal influences should be considered, and further investigation is needed to address study limitations. Public Significance Statement: This study suggests that the mode of birth, whether a child is born vaginally or by emergency or elective cesarean section, has a small effect on how the child's genes are methylated in cord blood cells at birth. DNA methylation in peripheral blood cells during childhood and adolescence was not predicted by mode of birth. Breastfeeding and mother–infant bonding did not buffer the effects of mode of birth, highlighting the necessity to further investigate other postnatal factors as potential determinants of the offspring methylome across development. [ABSTRACT FROM AUTHOR]

Background At least 128,000 patients in the United States each year suffer from foot drop. This is a debilitating condition, marked by the inability to dorsiflex and/or evert the affected ankle. Such patients are rendered to a lifetime of relying on an ankle-foot orthosis (AFO) for walking and nighttime to prevent an equinovarus contracture. Methods This narrative review explores the differential diagnosis of foot drop, with a particular focus on clinical presentation and recovery, whether spontaneously or through surgery. Results Contrary to popular belief, foot drop can be caused by more than just insult to the common peroneal nerve at the fibular head (fibular tunnel). It is a common endpoint for a diverse spectrum of nerve injuries, which may explain its relatively high prevalence. From proximal to distal, these conditions include lumbar spine nerve root damage, sciatic nerve palsy at the sciatic notch, and common peroneal nerve injury at the fibular head. Each nerve condition is marked by a unique clinical presentation, frequency, likelihood for spontaneous recovery, and cadre of peripheral nerve techniques. Conclusion The ideal surgical technique for treating foot drop, other than neurolysis for compression, remains elusive as traditional peripheral nerve procedures have been marred by a wide spectrum of functional results. Based on a careful understanding of why past techniques have achieved limited success, we can formulate a working set of principles to help guide surgical innovation moving forward, such as fascicular nerve transfer. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the performance of gradient array coils in minimizing switched‐gradient‐induced electric fields (E‐fields) and improving peripheral nerve stimulation (PNS) thresholds while generating gradient fields with adjustable linearity across customizable regions of linearity (ROLs). Methods: A body gradient array coil is used to reduce the induced E‐fields on the surface of a body model by modulating applied currents. This is achieved by performing an optimization problem with the peak E‐field as the objective function and current amplitudes as unknown variables. Coil dimensions and winding patterns are fixed throughout the optimization, whereas other engineering metrics remain adjustable. Various scenarios are explored by manipulating adjustable parameters. Results: The array design consistently yields lower E‐fields and higher PNS thresholds across all scenarios compared with a conventional coil. When the gradient array coil generates target gradient fields within a 44‐cm‐diameter spherical ROL, the maximum E‐field is reduced by 10%, 18%, and 61% for the X, Y, and Z gradients, respectively. Transitioning to a smaller ROL (24 cm) and relaxing the gradient linearity error results in further E‐field reductions. In oblique gradients, the array coil demonstrates the most substantial reduction of 40% in the Z–Y direction. Among the investigated scenarios, the most significant increase of 4.3‐fold is observed in the PNS thresholds. Conclusion: Our study demonstrated that gradient array coils offer a promising pathway toward achieving high‐performance gradient coils regarding gradient strength, slew rate, and PNS thresholds, especially in scenarios in which linear magnetic fields are required within specific target regions. [ABSTRACT FROM AUTHOR]

The development of views on cerebral activation in the sleep–waking cycle, starting with the work of Constantin von Economo, is examined. We focus on the cyclic activation of high-amplitude discharges during sleep, which, with certain reservations, can include K-complexes and patterns of δ-like waves. Given the involvement of the peripheral nervous system in this process, the integrative role of cyclic activation of high-amplitude discharges in the organization of the sleep–waking cycle is discussed. [ABSTRACT FROM AUTHOR]

Background: Sterile α and Toll/IL-1 receptor motif-containing 1 (SARM1) is a central regulator of programmed axon death and a crucial nicotinamide adenine dinucleotide (NAD+) hydrolase (NADase) in mammalian tissues, hydrolyzing NAD+ and playing an important role in cellular NAD+ recycling. Abnormal SARM1 expression is linked to axon degeneration, which causes disability and disease progression in many neurodegenerative disorders of the peripheral and central nervous systems. Methods: In this study, we use PC6 assay of hydrolase activity, DRG axon regeneration and CIPN model to screen for potent SARM1 Inhibitors. Results: Two novel SARM1 inhibitors (compound 174 and 331P1) are charcterized for its high potency for SARM1 NADase. In a chemotherapy-induced peripheral neuropathy (CIPN) myopathy model, compound 331P1 treatment prevented the decline in neurofilament light chain (NfL) levels caused by axonal injury in a dose-dependent manner, associated with elevated intraepidermal nerve fiber (IENF) intensity in mouse foot paw tissue, suggesting its functionality in reversing axon degeneration. Conclusions: The newly designed SARM1 inhibitor 331P1 is a promising candidate due to its excellent in vivo efficacy, favorable CYP inhibition properties, and attractive safety profiles. The 331P1 compound possesses the potential to be developed as a novel neuroprotective therapy that can prevent or halt the neurodegenerative process in CIPN. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective review evaluates pain and patient-defined functional goal improvement utilizing bipolar peripheral nerve stimulation (PNS) in chronic neuropathic and nociceptive pain states. Patients and Methods: Our dataset includes 24 patients who underwent implantation of a permanent peripheral nerve stimulator from January 2018 through December 2022. A total of 29 leads were implanted amongst 24 patients, with 5 patients having leads at 2 different dermatomes. Fifteen leads were placed for primarily neuropathic pain, and 14 leads were placed for nociceptive pain. Inclusion criteria were the following: pain duration greater than 6 months, documented peri-procedural Numerical Pain Rating Scale (NPRS) and greater than 60 days follow-up post implant. Results: Data was collected and analyzed showing that 89.6% of implants at 6 months follow-up and 70% at 12 months follow-up achieved 50% or greater pain relief. A significant reduction in NPRS scores when comparing pre-procedure pain scores (Median = 7, n = 29) to 6-month follow-up data (Median = 2, n = 29), p< 0.001 with a large effect size, r =  0.61. Ninety-three percent of patients reported achieving their personal functional goal. Twelve of the fourteen (86%) leads implanted for primary nociceptive pain and fourteen of the fifteen (93%) leads implanted for neuropathic pain achieved ≥ 50% relief at 6 months. At twelve months, seven leads in each group provided ≥ 50% sustained pain relief. Of the 14 patients that were on opioids, 6 discontinued, while another 2 had a reduction in oral morphine milligram equivalents (MME) at the 12-month follow-up. Conclusion: This retrospective review demonstrates the potential clinical application of PNS in both nociceptive and neuropathic pain states. Further prospective studies are warranted to validate the effectiveness of PNS in the treatment of refractory nociceptive and neuropathic pain states. [ABSTRACT FROM AUTHOR]

Objective of this randomized, controlled, multi-site clinical trial was to compare long-term safety and efficacy of mPNS in patients with chronic, intractable, post-traumatic or post-surgical neuropathic pain to comprehensive Conventional Medical Management (CMM). Methods: A total of 65 patients with post-traumatic, post-surgical neuropathy were treated within a multicenter, randomized, clinical trial comparing the safety and effectiveness of mPNS + CMM to CMM alone. Patients were randomized 1:1 and followed through 90 days. The primary endpoint is a proportion of responders, 50% or greater reduction in pain at Day 90. The secondary endpoints included the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) and Patient Global Impression of Change (PGIC). Results: At 3 months, 71% of subjects were considered responders (> 50% pain relief) in the mPNS + CMM group vs 13% of subjects in the CMM group. The mPNS + CMM group had a mean reduction in VAS scores at Day 90 of 3.8 points (> 50% reduction), while CMM showed less than a 1-point (0.7 point) mean reduction or ~10% reduction (p < 0.0001). The EQ-5D-3L score increased in the mPNS + CMM study group, whereas the CMM group showed no improvement in EQ-5D-3L at Day 90. PGIC responder rates were 80.6% and 4.3% at Day 90 for mPNS + CMM and CMM groups, respectively. Conclusion: mPNS + CMM was superior to CMM in a randomized prospective study when used for treatment of post-traumatic, post-surgical neuropathy. Due to the lack of other effective non-invasive treatments for neuropathic pain, mPNS should be considered much earlier in the treatment algorithm. [ABSTRACT FROM AUTHOR]

Central and peripheral nervous system lesions may disrupt the intricate balance of the prime movers of the wrist. In spasticity, hyperactive wrist flexors create a flexion moment and, if untreated, can lead to flexion contractures. In patients with C6 spinal cord injury and tetraplegia, the posterior interosseus nerve is typically affected by a complex pattern of upper and/or lower motoneuron lesions causing radial deviation of the wrist due to loss of ulnar deviation actuators. In this report, we illustrate severe pathomechanics that may occur even with relatively modest changes in wrist balance. These results illustrate how thorough understanding of muscle-tendon-joint interaction aids in designing tendon and nerve reconstructive surgeries to normalize wrist positions and balance in neuromuscular conditions. [ABSTRACT FROM AUTHOR]

Nerve transfer for motor nerve paralysis is an established technique for treating complex nerve injuries. However, nerve transfer for sensory reconstruction has not been widely used, and published research on this topic is limited compared to motor nerve transfer. The indications and outcomes of nerve transfer for the restoration of sensory function remain unproven. This scoping review examines the indications, outcomes and complications of sensory nerve transfer. In total, 22 studies were included; the major finding is that distal sensory nerve transfers are more successful than proximal ones in succeeding protective sensation. Although the risk of extension of the sensory deficit with donor site loss and morbidity from neuromas remain a barrier to wider adoption, these complications were not reported in the review. Further, the scarcity of studies and small patient series limit the ability to determine sensory nerve transfer success. However, sensory restoration remains an opportunity for surgeons to pursue. Level of evidence: II [ABSTRACT FROM AUTHOR]

This study aimed to investigate the therapeutic potential of human adipose‐derived mesenchymal stem cells (hADSCs) modified with recombinant adeno‐associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate‐buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control‐hADSCs group), or rAAV VEGF165 vector (VEGF165‐hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium‐binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165‐hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain‐derived neurotrophic factor (BDNF) and glial cell‐derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV‐VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies. [ABSTRACT FROM AUTHOR]

Objectives: Vitamin B complexes are frequently used in clinical practice for peripheral nerve trauma. However, there is a lack of scientific data on their effectiveness. This study aims to investigate the impact of the vitamin B complex on nerve recovery in a rat model of peripheral nerve paralysis. Materials and Methods: Sixty male Wistar Albino rats were divided into six groups. Models of nerve injury, including blunt trauma, nerve incision, and autograft, were performed on all rats approximately 1 cm distal to the sciatic notch. B-complex vitamins were injected intraperitoneally at 0.2 mL/day to the treatment groups. The control groups were given 0.2 mL/day saline. After 1 month, the study was terminated, electromyography (EMG) was performed to measure the conduction velocity, and nerve tissue was taken from the repair line. The sciatic function indexes (SFIs) were calculated and analyzed. The histopathological samples were stained with hematoxylin and eosin and Toluidine blue and examined with a light microscope. Pathologically, myelination, fibrosis, edema, and mast cell densities in the nervous tissue were evaluated. Results: The vitamin B treatment groups demonstrated significant improvements in SFI compared to the control groups, indicating functional improvement in nerve damage (p < 0.05). In the nerve graft group, the vitamin B group showed a shorter latency, higher velocity, and larger peak-to-peak compared to the controls (p < 0.05). In the nerve transection group, the vitamin B group had better latency, velocity, and peak-to-peak values than the controls (p < 0.05). In the crush injury group, the vitamin B group exhibited an improved latency, velocity, and peak-to-peak compared to the controls (p < 0.05). Better myelination, less fibrosis, edema, and mast cells were also in the vitamin B group (p < 0.05). Conclusions: Vitamin B treatment significantly improves nerve healing and function in peripheral nerve injuries. It enhances nerve conduction, reduces fibrosis, and promotes myelination, indicating its therapeutic potential in nerve regeneration. [ABSTRACT FROM AUTHOR]

Abstract The neural and immune systems sense and respond to external stimuli to maintain tissue homeostasis. These systems do not function independently but rather interact with each other to effectively exert biological actions and prevent disease pathogenesis, such as metabolic, inflammatory, and infectious disorders. Mutual communication between these systems is also affected by tissue niche-specific signals that reflect the tissue environment. However, the regulatory mechanisms underlying these interactions are not completely understood. In addition to the peripheral regulation of neuro–immune crosstalk, recent studies have reported that the central nervous system plays essential roles in the regulation of systemic neuro–immune interactions. In this review, we provide an overview of the molecular basis of peripheral and systemic neuro–immune crosstalk and explore how these multilayered interactions are maintained.

The blood vessel lumen is an extremely rare location for a benign peripheral nerve sheath tumor like schwannoma. Less than 10 cases have been previously reported. In this report, we present a case of a 68-year-old woman who had a soft tissue nodule at the posterior calf of her left leg during a physical examination. Pathological examination was performed after complete surgical excision. The patient underwent follow-up for 12 months after surgery without evidence of recurrence or any other complication. This is the first case of intravascular schwannoma reported as a cause of vein obstruction. Microscopically, the tumor was composed of Schwann spindle cells that were immunoreactive for S100 protein and SOX10. This tumor was surrounded by a well-defined vascular smooth muscle wall. Prospective series are required to improve the knowledge on the underlying mechanisms of intravascular schwannoma development.

Diabetes is a multifunctional chronic disease that affects both the central and/or peripheral nervous systems. This study assessed whether nicotinamide (NAm) or conjugate of nicotinic acid with gamma-aminobutyric acid (N-GABA) could be potential neuroprotective agents against type 1 diabetes (T1D)-induced nervous system impairments in rats. After six weeks of T1D, induced by streptozotocin, nonlinear male Wistar rats were treated for two weeks with NAm (100 mg/kg, i. p.) or N-GABA (55 mg/kg, i. p.). Expression levels of myelin basic protein (MBP) were analyzed by immunoblotting. Polyol pathway parameters of the sciatic nerves were assessed spectrophotometrically, and their structure was examined histologically. NAm had no effect on blood glucose or body weight in T1D, while N-GABA reduced glucose by 1.5-fold. N-GABA also increased MBP expression by 1.48-fold, enhancing neuronal myelination, while NAm showed no such effect. Activation of the polyol pathway was observed in the T1D sciatic nerves. Both compounds decreased sorbitol content and aldose reductase activity, thereby alleviating changes similar to primary degeneration in the sciatic nerves and preventing peripheral neuropathy development. These results demonstrate that NAm and, more notably, N-GABA may exert neuroprotective effects against T1D-induced nervous system impairments by increasing MBP expression levels, improving myelination processes in the brain, inhibiting the polyol pathway, and partially restoring morphometric parameters in the sciatic nerves. This suggests their potential therapeutic efficacy as promising agents for the prevention of T1D-induced nervous system alterations. [ABSTRACT FROM AUTHOR]