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Continuum (Minneapolis, Minn.) Oct 2023This article provides a framework for the initial evaluation of patients with suspected peripheral nerve disease. The key clinical elements of peripheral nerve diseases...
OBJECTIVE
This article provides a framework for the initial evaluation of patients with suspected peripheral nerve disease. The key clinical elements of peripheral nerve diseases can help the practicing neurologist differentiate among peripheral neuropathies with similar presentations.
LATEST DEVELOPMENTS
The wide range of peripheral nerve diseases with similar clinical presentations can pose a diagnostic challenge. The large array of available testing modalities (including imaging and electrodiagnostic, autonomic, laboratory, biopsy, and genetic testing) further complicates clinical decision making. Recent developments (eg, discovery of new autoantibodies, genetic variations, and histopathologic techniques) across the peripheral neuropathy spectrum have resulted in an increased need to evaluate patients logically and with a tailored diagnostic approach.
ESSENTIAL POINTS
A careful approach that focuses on key clinical elements combined with an understanding of purposeful diagnostic testing can lead to a successful diagnosis of peripheral nerve diseases.
Topics: Humans; Peripheral Nervous System Diseases; Autonomic Nervous System; Biopsy; Genetic Testing; Peripheral Nerves
PubMed: 37851032
DOI: 10.1212/CON.0000000000001333 -
World Neurosurgery Dec 2023Despite advances in the surgical management of peripheral nerve pathologies over the past several decades, it is unknown how public awareness of these procedures has...
BACKGROUND
Despite advances in the surgical management of peripheral nerve pathologies over the past several decades, it is unknown how public awareness of these procedures has changed. We hypothesize that Google searches for peripheral nerve surgery have increased over time.
METHODS
Google Trends was queried for search volumes of a list of 40 keywords related to the following topics in peripheral nerve surgery: spasticity, nerve injury, prosthetics, and nerve pain. Monthly relative search volume over the first 5 years of the study period (2010-2014) was compared with that of the last 5 years (2018-2022) of the study period.
RESULTS
Search volumes for keywords "nerve injury," "nerve laceration," "peripheral nerve injury," "nerve repair," "nerve transfer", "neuroma," "neuroma pain," "nerve pain," "nerve pain surgery," and "neuroma pain surgery" all increased more than 10% points in relative search volume over the study period (P < 0.0001 for each keyword). In contrast, searches for "rhizotomy," "spasticity surgery," "targeted muscle reinnervation," "bionic arm," and "myoelectric prosthesis" either decreased or remained stable. Technical terms such as "selective neurectomy," "hyperselective neurectomy," "regenerative peripheral nerve interface," and "regenerative peripheral nerve interface surgery" did not have adequate search volume to be reported by Google Trends.
CONCLUSIONS
The increase in Google searches related to nerve injury and pain between 2010 and 2022 may reflect increasing public recognition of these clinical entities and surgical techniques addressing them. Technical terms relating to nerve pain are infrequently searched, surgeons should use plain English terms for online discovery. Interest in spasticity and myoelectric prosthetics remains stable, indicating an opportunity for better public outreach.
Topics: Humans; Search Engine; Peripheral Nerves; Neuralgia; Neuroma; Denervation; Muscle Spasticity
PubMed: 37690579
DOI: 10.1016/j.wneu.2023.09.006 -
European Journal of Pharmacology Oct 2023Neuropathic pain (NPP) is a common syndrome associated with most forms of disease, which poses a serious threat to human health. NPP may persist even after the... (Review)
Review
Neuropathic pain (NPP) is a common syndrome associated with most forms of disease, which poses a serious threat to human health. NPP may persist even after the nociceptive stimulation is eliminated, and treatment is extremely challenging in such cases. Schwann cells (SCs) form the myelin sheaths around neuronal axons and play a crucial role in neural information transmission. SCs can secrete trophic factors to nourish and protect axons, and can further secrete pain-related factors to induce pain. SCs may be activated by peripheral nerve injury, triggering the transformation of myelinated and non-myelinated SCs into cell phenotypes that specifically promote repair. These differentiated SCs provide necessary signals and spatial clues for survival, axonal regeneration, and nerve regeneration of damaged neurons. They can further change the microenvironment around the regions of nerve injury, and relieve the pain by repairing the injured nerve. Herein, we provide a comprehensive overview of the biological characteristics of SCs, discuss the relationship between SCs and nerve injury, and explore the potential mechanism of SCs and the occurrence of NPP. Moreover, we summarize the feasible strategies of SCs in the treatment of NPP, and attempt to elucidate the deficiencies and defects of SCs in the treatment of NPP.
Topics: Humans; Schwann Cells; Myelin Sheath; Axons; Neuralgia; Nerve Regeneration; Peripheral Nerve Injuries
PubMed: 37541365
DOI: 10.1016/j.ejphar.2023.175955 -
European Review For Medical and... Dec 2023Peripheral nerve injuries present challenges in achieving full functional restoration, necessitating effective therapeutic strategies. Oxytocin, known for its...
OBJECTIVE
Peripheral nerve injuries present challenges in achieving full functional restoration, necessitating effective therapeutic strategies. Oxytocin, known for its neuroprotective and anti-inflammatory properties, has shown potential in nerve recovery. This study aims to elucidate the role of oxytocin in nerve recovery via the nuclear factor erythroid 2-related factor 2 (Nrf2) and irisin pathways.
MATERIALS AND METHODS
Adult male Wistar rats (n=30) were subjected to surgical dissection of sciatic nerves and divided into Control, Surgery and Saline Group, and Surgery and Oxytocin (OT) group. Electromyographic (EMG) recordings, inclined plane tests, and histological assessments were conducted to evaluate nerve function, and Nerve growth factor (NGF) immunoexpression and axonal parameters were measured. Plasma irisin levels, nerve NGF, and Nrf2 levels were quantified.
RESULTS
The Surgery and Saline Group exhibited impaired EMG latency, amplitude, and inclined plane score compared to Controls, while the Surgery and OT Group demonstrated improved outcomes. Histomorphometric analysis revealed increased NGF immunoexpression, axon number, diameter, and reduced fibrosis in the Surgery and OT Group. Plasma irisin levels were higher following oxytocin administration. Additionally, nerve NGF and Nrf2 levels were elevated in the Surgery and OT Group.
CONCLUSIONS
OT administration mitigated nerve injury effects, promoting functional and histological improvements. Elevated NGF and Nrf2 levels, along with increased irisin, indicated the potential interplay of these pathways in enhancing nerve recovery. The results align with OT's neuroprotective and anti-inflammatory roles, suggesting its potential as a therapeutic intervention for nerve injuries. OT's positive impact on nerve recovery is associated with its modulation of Nrf2 and irisin pathways, which collectively enhance antioxidant defense and neurotrophic support and mitigate inflammation. These findings underline OT's potential as a therapeutic agent to enhance nerve regeneration and recovery. Further research is needed to elucidate the intricate molecular mechanisms and potential clinical applications of OT in nerve injury management.
Topics: Rats; Animals; Male; Oxytocin; Peripheral Nerve Injuries; Rats, Wistar; NF-E2-Related Factor 2; Fibronectins; Nerve Growth Factor; Sciatic Nerve; Anti-Inflammatory Agents
PubMed: 38095383
DOI: 10.26355/eurrev_202312_34573 -
The Journal of Endocrinology Aug 2023Myelination allows fast and synchronized nerve influxes and is provided by Schwann cells (SCs) in the peripheral nervous system. Glucocorticoid hormones are major...
Myelination allows fast and synchronized nerve influxes and is provided by Schwann cells (SCs) in the peripheral nervous system. Glucocorticoid hormones are major regulators of stress, metabolism and immunity affecting all tissues. They act by binding to two receptors, the low-affinity glucocorticoid receptor (GR) and the high-affinity mineralocorticoid receptor (MR). Little is known about the effect of glucocorticoid hormones on the PNS, and this study focuses on deciphering the role of MR in peripheral myelination. In this work, the presence of a functional MR in SCs is demonstrated and the expression of MR protein in mouse sciatic nerve SC is evidenced. Besides, knockout of MR in SC (SCMRKO using Cre-lox system with DesertHedgeHog (Dhh) Cre promoter) was undertaken in mice. SCMRKO was not associated with alterations of performance in motor behavioral tests on 2- to 6-month-old male mice compared to their controls. No obvious modifications of myelin gene expression or MR signaling gene expression were observed in the SCMRKO sciatic nerves. Nevertheless, Gr transcript and GR protein amounts were significantly increased in SCMRKO nerves compared to controls, suggesting a possible compensatory effect. Besides, an increase in myelin sheath thickness was noted for axons with perimeters larger than 15 µm in SCMRKO illustrated by a significant 4.5% reduction in g-ratio (axon perimeter/myelin sheath perimeter). Thus, we defined MR as a new player in peripheral system myelination and in SC homeostasis.
Topics: Male; Mice; Animals; Myelin Sheath; Receptors, Mineralocorticoid; Glucocorticoids; Mice, Knockout; Schwann Cells; Sciatic Nerve
PubMed: 37195271
DOI: 10.1530/JOE-22-0334 -
The Journal of the American Academy of... Aug 2023Undertreated digital nerve injuries may result in sensory deficits and pain. Early recognition and treatment will optimize outcomes, and providers should maintain a high...
Undertreated digital nerve injuries may result in sensory deficits and pain. Early recognition and treatment will optimize outcomes, and providers should maintain a high index of suspicion when assessing patients with open wounds. Acute, sharp lacerations may be amenable to direct repair while avulsion injuries or delayed repairs require adequate resection and bridging with nerve autograft, processed nerve allograft, or conduits. Conduits are most appropriate for gaps less than 15 mm, and processed nerve allografts have demonstrated reliable outcomes across longer gaps.
Topics: Humans; Peripheral Nerves; Peripheral Nerve Injuries; Finger Injuries; Transplantation, Autologous; Plastic Surgery Procedures; Allografts
PubMed: 37205873
DOI: 10.5435/JAAOS-D-23-00255 -
Diabetes Aug 2023Diabetes peripheral neuropathy (DPN) is commonly asymptomatic in the early stage. However, once symptoms and obvious defects appear, recovery is not possible. Diagnosis... (Review)
Review
Diabetes peripheral neuropathy (DPN) is commonly asymptomatic in the early stage. However, once symptoms and obvious defects appear, recovery is not possible. Diagnosis of neuropathy is based on physical examinations, questionnaires, nerve conduction studies, skin biopsies, and so on. However, the diagnosis of DPN is still challenging, and early diagnosis and immediate intervention are very important for prevention of the development and progression of diabetic neuropathy. The advantages of MRI in the diagnosis of DPN are obvious: the peripheral nerve imaging is clear, the lesions can be found intuitively, and the quantitative evaluation of the lesions is the basis for the diagnosis, classification, and follow-up of DPN. With the development of magnetic resonance technology, more and more studies have been conducted on detection of DPN. This article reviews the research field of MRI in DPN.
Topics: Humans; Diabetic Neuropathies; Peripheral Nerves; Magnetic Resonance Imaging; Nerve Conduction Studies; Diabetes Mellitus, Type 2
PubMed: 37471598
DOI: 10.2337/db22-0912 -
Journal of Neuroinflammation Nov 2023Although peripheral nerves have an intrinsic self-repair capacity following damage, functional recovery is limited in patients. It is a well-established fact that...
BACKGROUND
Although peripheral nerves have an intrinsic self-repair capacity following damage, functional recovery is limited in patients. It is a well-established fact that macrophages accumulate at the site of injury. Numerous studies indicate that the phenotypic shift from M1 macrophage to M2 macrophage plays a crucial role in the process of axon regeneration. This polarity change is observed exclusively in peripheral macrophages but not in microglia and CNS macrophages. However, the molecular basis of axonal regeneration by M2 macrophage is not yet fully understood. Herein, we aimed to identify the M2 macrophage-derived axon regeneration factor.
METHODS
We established a peripheral nerve injury model by transection of the inferior alveolar nerve (IANX) in Sprague-Dawley rats. Transcriptome analysis was performed on the injured nerve. Recovery from sensory deficits in the mandibular region and histological reconnection of IAN after IANX were assessed in rats with macrophage depletion by clodronate. We investigated the effects of adoptive transfer of M2 macrophages or M2-derived cathepsin S (CTSS) on the sensory deficit. CTSS initiating signaling was explored by western blot analysis in IANX rats and immunohistochemistry in co-culture of primary fibroblasts and Schwann cells (SCs).
RESULTS
Transcriptome analysis revealed that CTSS, a macrophage-selective lysosomal protease, was upregulated in the IAN after its injury. Spontaneous but partial recovery from a sensory deficit in the mandibular region after IANX was abrogated by macrophage ablation at the injured site. In addition, a robust induction of c-Jun, a marker of the repair-supportive phenotype of SCs, after IANX was abolished by macrophage ablation. As in transcriptome analysis, CTSS was upregulated at the injured IAN than in the intact IAN. Endogenous recovery from hypoesthesia was facilitated by supplementation of CTSS but delayed by pharmacological inhibition or genetic silencing of CTSS at the injured site. Adoptive transfer of M2-polarized macrophages at this site facilitated sensory recovery dependent on CTSS in macrophages. Post-IANX, CTSS caused the cleavage of Ephrin-B2 in fibroblasts, which, in turn, bound EphB2 in SCs. CTSS-induced Ephrin-B2 cleavage was also observed in human sensory nerves. Inhibition of CTSS-induced Ephrin-B2 signaling suppressed c-Jun induction in SCs and sensory recovery.
CONCLUSIONS
These results suggest that M2 macrophage-derived CTSS contributes to axon regeneration by activating SCs via Ephrin-B2 shedding from fibroblasts.
Topics: Animals; Humans; Rats; Axons; Cathepsins; Ephrin-B2; Fibroblasts; Macrophages; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Rats, Sprague-Dawley; Schwann Cells
PubMed: 37946211
DOI: 10.1186/s12974-023-02943-2 -
British Journal of Anaesthesia May 2024The use of peripheral regional anaesthesia continues to increase, yet the evidence supporting its use and impact on relevant outcomes often lacks scientific rigour,... (Review)
Review
The use of peripheral regional anaesthesia continues to increase, yet the evidence supporting its use and impact on relevant outcomes often lacks scientific rigour, especially when considering the use of specific blocks for a particular surgical indication. In this narrative review, we consider the relevant literature in a 10-yr period from 2013. We performed a literature search (MEDLINE and EMBASE) for articles reporting randomised controlled trials and other comparative trials of peripheral regional anaesthetic blocks vs systemic analgesia in adult patients undergoing surgery. We evaluated measures of effective treatment and complications. A total of 128 studies met our inclusion criteria. There remains variability in the technical conduct of blocks and the outcomes used to evaluate them. There is a considerable body of evidence to support the use of interscalene blocks for shoulder surgery. Saphenous nerve (motor-sparing) blocks provide satisfactory analgesia after knee surgery and are preferred to femoral nerve blocks which are associated with falls when patients are mobilised early as part of enhanced recovery programmes. There are additional surgical indications where the efficacy of cervical plexus, intercostal nerve, and ilioinguinal/iliohypogastric nerve blocks have been demonstrated. In the past 10 yr, there has been a consolidation of the evidence indicating benefit of peripheral nerve blocks for specific indications. There remains great scope for rigorous, multicentre, randomised controlled trials of many peripheral nerve blocks. These would benefit from an agreed set of patient-centred outcomes.
Topics: Adult; Humans; Anesthesia, Conduction; Pain Management; Peripheral Nerves; Anesthetics, Local; Brachial Plexus Block; Pain, Postoperative
PubMed: 37957079
DOI: 10.1016/j.bja.2023.10.013 -
Current Opinion in Anaesthesiology Oct 2023Moderate-to-severe pain is common and remains a significant problem. Compared with opioid analgesia alone, single-shot peripheral nerve blockade has been associated with... (Review)
Review
PURPOSE OF REVIEW
Moderate-to-severe pain is common and remains a significant problem. Compared with opioid analgesia alone, single-shot peripheral nerve blockade has been associated with improved pain relief and the potential of decreased side effects. Single-shot nerve blockade, however, is limited by its relatively short duration of action. In this review, we aim to summarize the evidence related to local anaesthetic adjuncts for peripheral nerve blockade.
RECENT FINDINGS
Dexamethasone and dexmedetomidine exhibit characteristics that most closely resemble the ideal local anaesthetic adjunct. In upper limb block, dexamethasone has been demonstrated to be superior to dexmedetomidine regardless of administration route for the duration of sensory and motor blockade as well as the duration of analgesia. No clinically significant differences between intravenous and perineural dexamethasone were found. Perineural and intravenous dexamethasone have the potential to prolong sensory blockade to a greater extent than motor blockade. The evidence indicates that the mechanism of action of perineural dexamethasone in upper limb block is systemic in nature. Unlike perineural dexmedetomidine, intravenous dexmedetomidine has not been shown to result in differences in the characteristics of regional blockade compared with local anaesthetic alone.
SUMMARY
Intravenous dexamethasone is the local anaesthetic adjunct of choice, increasing the duration of sensory and motor blockade as well as the duration of analgesia by 477, 289 and 478 min, respectively. In view of this, we recommend consideration of the intravenous administration of dexamethasone at a dose of 0.1-0.2 mg/kg for all patients undergoing surgery whatever the level of postoperative pain, mild, moderate or severe. Further research should focus on the potential synergism of action between intravenous dexamethasone and perineural dexmedetomidine.
Topics: Humans; Anesthetics, Local; Dexamethasone; Dexmedetomidine; Pain, Postoperative; Peripheral Nerves
PubMed: 37314172
DOI: 10.1097/ACO.0000000000001272