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Biofabrication Sep 2022Electroceuticals provide promising opportunities for peripheral nerve regeneration, in terms of modulating the extensive endogenous tissue repair mechanisms between... (Review)
Review
Electroceuticals provide promising opportunities for peripheral nerve regeneration, in terms of modulating the extensive endogenous tissue repair mechanisms between neural cell body, axons and target muscles. However, great challenges remain to deliver effective and controllable electroceuticals via bioelectronic implantable device. In this review, the modern fabrication methods of bioelectronic conduit for bridging critical nerve gaps after nerve injury are summarized, with regard to conductive materials and core manufacturing process. In addition, to deliver versatile electrical stimulation, the integration of implantable bioelectronic device is discussed, including wireless energy harvesters, actuators and sensors. Moreover, a comprehensive insight of beneficial mechanisms is presented, including up-to-dateand clinical evidence. By integrating conductive biomaterials, 3D engineering manufacturing process and bioelectronic platform to deliver versatile electroceuticals, the modern biofabrication enables comprehensive biomimetic therapies for neural tissue engineering and regeneration in the new era.
Topics: Biocompatible Materials; Nerve Regeneration; Nerve Tissue; Peripheral Nerves; Tissue Engineering
PubMed: 35995036
DOI: 10.1088/1758-5090/ac8baa -
Neurology India 2020Chronic, focal, neuropathic pain is difficult to treat. Local nerve blocks are either ineffective or do not last. Regular neuromodulation modalities like spinal cord... (Review)
Review
BACKGROUND
Chronic, focal, neuropathic pain is difficult to treat. Local nerve blocks are either ineffective or do not last. Regular neuromodulation modalities like spinal cord stimulation (SCS) or pain pump are invasive and affect a larger area.
OBJECTIVES
To discuss the indications, technique, nuances, programming, and outcomes of peripheral neuromodulation.
METHODS
The article reviews published literature and the author's own experience of over 500 cases of peripheral neuromodulation.
RESULTS AND CONCLUSION
Peripheral neuromodulation using peripheral nerve field stimulation (PNFS) is an effective, minimally invasive, targeted method of treatment. It is a relatively new modality in the field of neuromodulation but is used more often.
Topics: Chronic Pain; Humans; Neuralgia; Peripheral Nerves; Spinal Cord Stimulation
PubMed: 33318355
DOI: 10.4103/0028-3886.302451 -
The British Journal of Radiology Jan 2023High resolution ultrasound (US) and magnetic resonance (MR) neurography are both imaging modalities that are commonly used for assessing peripheral nerves including the... (Review)
Review
High resolution ultrasound (US) and magnetic resonance (MR) neurography are both imaging modalities that are commonly used for assessing peripheral nerves including the sural nerve (SN). The SN is a cutaneous sensory nerve which innervates the lateral ankle and foot to the base of the fifth metatarsal. It is formed by contributing nerves from the tibial and common peroneal nerves with six patterns and multiple subtypes described in literature. In addition to the SN being a cutaneous sensory nerve, the superficial location enables the nerve to be easily biopsied and harvested for a nerve graft, as well as increasing the susceptibility to traumatic injury. As with any peripheral nerves, pathologies such as peripheral nerve sheath tumors and neuropathies can also affect the SN. By utilizing a high frequency probe in US and high-resolution MR neurography, the SN can be easily identified even with the multiple variations given the standard distal course. US and MRI are also useful in determining pathology of the SN given the specific image findings that are seen with peripheral nerves. In this review, we evaluate the normal imaging anatomy of the SN and discuss common pathologies identified on imaging.
Topics: Humans; Sural Nerve; Peroneal Nerve; Ankle; Lower Extremity; Ankle Joint; Magnetic Resonance Imaging
PubMed: 36039944
DOI: 10.1259/bjr.20220336 -
F1000Research 2019Magnetic resonance imaging (MRI) has been used extensively in revealing pathological changes in the central nervous system. However, to date, MRI is very much... (Review)
Review
Magnetic resonance imaging (MRI) has been used extensively in revealing pathological changes in the central nervous system. However, to date, MRI is very much underutilized in evaluating the peripheral nervous system (PNS). This underutilization is generally due to two perceived weaknesses in MRI: first, the need for very high resolution to image the small structures within the peripheral nerves to visualize morphological changes; second, the lack of normative data in MRI of the PNS and this makes reliable interpretation of the data difficult. This article reviews current state-of-the-art capabilities in MRI of human peripheral nerves. It aims to identify areas where progress has been made and those that still require further improvement. In particular, with many new therapies on the horizon, this review addresses how MRI can be used to provide non-invasive and objective biomarkers in the evaluation of peripheral neuropathies. Although a number of techniques are available in diagnosing and tracking pathologies in the PNS, those techniques typically target the distal peripheral nerves, and distal nerves may be completely degenerated during the patient's first clinic visit. These techniques may also not be able to access the proximal nerves deeply embedded in the tissue. Peripheral nerve MRI would be an alternative to circumvent these problems. In order to address the pressing clinical needs, this review closes with a clinical protocol at 3T that will allow high-resolution, high-contrast, quantitative MRI of the proximal peripheral nerves.
Topics: Humans; Magnetic Resonance Imaging; Peripheral Nerves; Peripheral Nervous System Diseases
PubMed: 31700612
DOI: 10.12688/f1000research.19695.1 -
The Cochrane Database of Systematic... Dec 2022Traumatic peripheral nerve injury is common and incurs significant cost to individuals and society. Healing following direct nerve repair or repair with autograft is... (Review)
Review
BACKGROUND
Traumatic peripheral nerve injury is common and incurs significant cost to individuals and society. Healing following direct nerve repair or repair with autograft is slow and can be incomplete. Several bioengineered nerve wraps or devices have become available as an alternative to direct repair or autologous nerve graft. Nerve wraps attempt to reduce axonal escape across a direct repair site and nerve devices negate the need for a donor site defect, required by an autologous nerve graft. Comparative evidence to guide clinicians in their potential use is lacking. We collated existing evidence to guide the clinical application of currently available nerve wraps and conduits.
OBJECTIVES
To assess and compare the effects and complication rates of licensed bioengineered nerve conduits or wraps for surgical repair of traumatic peripheral nerve injuries of the upper limb. To compare effects and complications against the current gold surgical standard (direct repair or nerve autograft).
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search was 26 January 2022. We searched online and, where not accessible, contacted societies' secretariats to review abstracts from the British Surgical Society of the Hand, International Federation of Surgical Societies of the Hand, Federation of European Surgical Societies of the Hand, and the American Society for Peripheral Nerve from October 2007 to October 2018.
SELECTION CRITERIA
We included parallel group randomised controlled trials (RCTs) and quasi-RCTs of nerve repair in the upper limb using a bioengineered wrap or conduit, with at least 12 months of follow-up.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane procedures. Our primary outcomes were 1. muscle strength and 2. sensory recovery at 24 months or more. Our secondary outcomes were 3. British Medical Research Council (BMRC) grading, 4. integrated functional outcome (Rosén Model Instrument (RMI)), 5. touch threshold, 6. two-point discrimination, 7. cold intolerance, 8. impact on daily living measured using the Disability of Arm Shoulder and Hand Patient-Reported Outcome Measure (DASH-PROM), 9. sensory nerve action potential, 10. cost of the device, and 11. adverse events (any and specific serious adverse events (further surgery)). We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
Five studies involving 213 participants and 257 nerve injuries reconstructed with wraps or conduits (129 participants) or standard repair (128 participants) met the inclusion criteria. Of those in the standard repair group, 119 nerve injuries were managed with direct epineurial repair, and nine autologous nerve grafts were performed. One study excluded the outcome data for the repair using an autologous nerve graft from their analysis, as it was the only autologous nerve graft in the study, so data were available for 127 standard repairs. There was variation in the functional outcome measures reported and the time postoperatively at which they were recorded. Mean sensory recovery, assessed with BMRC sensory grading (range S0 to S4, higher score considered better) was 0.03 points higher in the device group (range 0.43 lower to 0.49 higher; 1 RCT, 28 participants; very low-certainty evidence) than in the standard repair group (mean 2.75 points), which suggested little or no difference between the groups, but the evidence is very uncertain. There may be little or no difference at 24 months in mean touch thresholds between standard repair (0.81) and repair using devices, which was 0.01 higher but this evidence is also very uncertain (95% confidence interval (CI) 0.06 lower to 0.08 higher; 1 trial, 32 participants; very low-certainty evidence). Data were not available to assess BMRC motor grading at 24 months or more. Repair using bioengineered devices may not improve integrated functional outcome scores at 24 months more than standard techniques, as assessed by the Rosén Model Instrument (RMI; range 0 to 3, higher scores better); the CIs allow for both no important difference and a better outcome with standard repair (mean RMI 1.875), compared to the device group (0.17 lower, 95% CI 0.38 lower to 0.05 higher; P = 0.13; 2 trials, 60 participants; low-certainty evidence). Data from one study suggested that the five-year postoperative outcome of RMI may be slightly improved after repair using a device (mean difference (MD) 0.23, 95% CI 0.07 to 0.38; 1 trial, 28 participants; low-certainty evidence). No studies measured impact on daily living using DASH-PROM. The proportion of people with adverse events may be greater with nerve wraps or conduits than with standard techniques, but the evidence is very uncertain (risk ratio (RR) 7.15, 95% CI 1.74 to 29.42; 5 RCTs, 213 participants; very low-certainty evidence). This corresponds to 10 adverse events per 1000 people in the standard repair group and 68 per 1000 (95% CI 17 to 280) in the device group. The use of nerve repair devices may be associated with a greater need for revision surgery but this evidence is also very uncertain (12/129 device repairs required revision surgery (removal) versus 0/127 standard repairs; RR 7.61, 95% CI 1.48 to 39.02; 5 RCTs, 256 nerve repairs; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Based on the available evidence, this review does not support use of currently available nerve repair devices over standard repair. There is significant heterogeneity in participants, injury pattern, repair timing, and outcome measures and their timing across studies of nerve repair using bioengineered devices, which make comparisons unreliable. Studies were generally small and at high or unclear risk of bias. These factors render the overall certainty of evidence for any outcome low or very low. The data reviewed here provide some evidence that more people may experience adverse events with use of currently available bioengineered devices than with standard repair techniques, and the need for revision surgery may also be greater. The evidence for sensory recovery is very uncertain and there are no data for muscle strength at 24 months (our primary outcome measures). We need further trials, adhering to a minimum standard of outcome reporting (with at least 12 months' follow-up, including integrated sensorimotor evaluation and patient-reported outcomes) to provide high-certainty evidence and facilitate more detailed analysis of effectiveness of emerging, increasingly sophisticated, bioengineered repair devices.
Topics: Humans; Upper Extremity; Peripheral Nerves
PubMed: 36477774
DOI: 10.1002/14651858.CD012574.pub2 -
PloS One 2021Clinical comparisons do not usually take laterality into account and thus may report erroneous or misleading data. The concept of laterality, well evaluated in brain and...
BACKGROUND AND PURPOSE
Clinical comparisons do not usually take laterality into account and thus may report erroneous or misleading data. The concept of laterality, well evaluated in brain and motor systems, may also apply at the level of peripheral nerves. Therefore, we sought to evaluate the extent to which we could observe an effect of laterality in MRI-collected white matter indices of the sciatic nerve and its two branches (tibial and fibular).
MATERIALS AND METHODS
We enrolled 17 healthy persons and performed peripheral nerve diffusion weighted imaging (DWI) and magnetization transfer imaging (MTI) of the sciatic, tibial and fibular nerve. Participants were scanned bilaterally, and findings were divided into ipsilateral and contralateral nerve fibers relative to self-reporting of hand dominance. Generalized estimating equation modeling was used to evaluate nerve fiber differences between ipsilateral and contralateral legs while controlling for confounding variables. All findings controlled for age, sex and number of scans performed.
RESULTS
A main effect of laterality was found in radial, axial, and mean diffusivity for the tibial nerve. Axial diffusivity was found to be lateralized in the sciatic nerve. When evaluating mean MTR, a main effect of laterality was found for each nerve division. A main effect of sex was found in the tibial and fibular nerve fiber bundles.
CONCLUSION
For the evaluation of nerve measures using DWI and MTI, in either healthy or disease states, consideration of underlying biological metrics of laterality in peripheral nerve fiber characteristics need to considered for data analysis. Integrating knowledge regarding biological laterality of peripheral nerve microstructure may be applied to improve how we diagnosis pain disorders, how we track patients' recovery and how we forecast pain chronification.
Topics: Adolescent; Diffusion Tensor Imaging; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Nerve Fibers; Peripheral Nerves; Young Adult
PubMed: 34914714
DOI: 10.1371/journal.pone.0260256 -
Medicina (Kaunas, Lithuania) Jun 2023Ultrasound (US) is a non-invasive tool for the in vivo detection of peripheral nerve alterations. In this study, we applied nerve US to assist the discrimination...
Ultrasound (US) is a non-invasive tool for the in vivo detection of peripheral nerve alterations. In this study, we applied nerve US to assist the discrimination between the spectrum of amyotrophic lateral sclerosis (ALS, = 11), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, = 5), and genetically confirmed Charcot-Marie-Tooth disease (CMT, = 5). All participants and = 15 controls without neurological diseases underwent high-resolution US of the bilateral tibial nerve. The nerve cross-sectional area (CSA) and nerve microvascular blood flow were compared between the groups and related to cerebrospinal fluid (CSF) measures, clinical symptoms, and nerve conduction studies. The analyses are part of a larger multimodal study on the comparison between US and 7 Tesla (7T) magnetic resonance neurography (MRN). The patients and controls were matched with respect to their demographical data. CMT had the longest disease duration, followed by CIDP and ALS. CSA was related to age, weight, and disease duration. CSA was larger in CMT and CIDP compared to ALS and controls. The blood flow was greatest in CIDP, and higher than in CMT, ALS, and controls. In ALS, greater CSA was correlated with greater CSF total protein and higher albumin quotient. The US measures did not correlate with clinical scores or nerve conduction studies in any of the subgroups. Our results point towards the feasibility of CSA and blood flow to discriminate between ALS, CIDP, and CMT, even in groups of small sample size. In ALS, larger CSA could indicate an inflammatory disease subtype characterized by reduced blood-nerve barrier integrity. Our upcoming analysis will focus on the additive value of 7T MRN in combination with US to disentangle the spectrum between more inflammatory or more degenerative disease variants among the disease groups.
Topics: Humans; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Amyotrophic Lateral Sclerosis; Peripheral Nerves; Polyneuropathies; Ultrasonography
PubMed: 37512004
DOI: 10.3390/medicina59071192 -
Muscle & Nerve Jan 2023Neuralgic amyotrophy (NA), also referred to as idiopathic brachial plexitis and Parsonage-Turner syndrome, is a peripheral nerve disorder characterized by acute severe... (Review)
Review
Neuralgic amyotrophy (NA), also referred to as idiopathic brachial plexitis and Parsonage-Turner syndrome, is a peripheral nerve disorder characterized by acute severe shoulder pain followed by progressive upper limb weakness and muscle atrophy. While NA is incompletely understood and often difficult to diagnose, early recognition may prevent unnecessary tests and interventions and, in some situations, allow for prompt treatment, which can potentially minimize adverse long-term sequalae. High-resolution ultrasound (HRUS) has become a valuable tool in the diagnosis and evaluation of NA. Pathologic HRUS findings can be grouped into four categories: nerve swelling, swelling with incomplete constriction, swelling with complete constriction, and fascicular entwinement, which may represent a continuum of pathologic processes. Certain ultrasound findings may help predict the likelihood of spontaneous recovery with conservative management versus the need for surgical intervention. We recommend relying heavily on history and physical examination to determine which nerves are clinically affected and should therefore be assessed by HRUS. The nerves most frequently affected by NA are the suprascapular, long thoracic, median and anterior interosseous nerve (AIN) branch, radial and posterior interosseous nerve (PIN) branch, axillary, spinal accessory, and musculocutaneous. When distal upper limb nerves are affected (AIN, PIN, superficial radial nerve), the lesion is almost always located in their respective fascicles within the parent nerve, proximal to its branching point. The purpose of this review is to describe a reproducible, standardized, ultrasonographic approach for evaluating suspected NA, and to share reliable techniques and clinical considerations when imaging commonly affected nerves.
Topics: Humans; Brachial Plexus Neuritis; Peripheral Nerves; Peripheral Nervous System Diseases; Radial Nerve; Constriction, Pathologic; Shoulder Pain
PubMed: 36040106
DOI: 10.1002/mus.27705 -
International Journal of Molecular... Oct 2023Appropriate animal models, mimicking conditions of both health and disease, are needed to understand not only the biology and the physiology of neurons and other cells... (Review)
Review
Appropriate animal models, mimicking conditions of both health and disease, are needed to understand not only the biology and the physiology of neurons and other cells under normal conditions but also under stress conditions, like nerve injuries and neuropathy. In such conditions, understanding how genes and different factors are activated through the well-orchestrated programs in neurons and other related cells is crucial. Knowledge about key players associated with nerve regeneration intended for axonal outgrowth, migration of Schwann cells with respect to suitable substrates, invasion of macrophages, appropriate conditioning of extracellular matrix, activation of fibroblasts, formation of endothelial cells and blood vessels, and activation of other players in healthy and diabetic conditions is relevant. Appropriate physical and chemical attractions and repulsions are needed for an optimal and directed regeneration and are investigated in various nerve injury and repair/reconstruction models using healthy and diabetic rat models with relevant blood glucose levels. Understanding dynamic processes constantly occurring in neuropathies, like diabetic neuropathy, with concomitant degeneration and regeneration, requires advanced technology and bioinformatics for an integrated view of the behavior of different cell types based on genomics, transcriptomics, proteomics, and imaging at different visualization levels. Single-cell-transcriptional profile analysis of different cells may reveal any heterogeneity among key players in peripheral nerves in health and disease.
Topics: Rats; Animals; Endothelial Cells; Rats, Wistar; Peripheral Nerves; Diabetic Neuropathies; Schwann Cells; Nerve Degeneration; Nerve Regeneration; Axons; Peripheral Nerve Injuries; Diabetes Mellitus
PubMed: 37894921
DOI: 10.3390/ijms242015241 -
Journal of Anatomy Nov 2022Schwann cells (SCs) are fundamental components of the peripheral nervous system (PNS) of all vertebrates and play essential roles in development, maintenance, function,... (Review)
Review
Schwann cells (SCs) are fundamental components of the peripheral nervous system (PNS) of all vertebrates and play essential roles in development, maintenance, function, and regeneration of peripheral nerves. There are distinct populations of SCs including: (1) myelinating SCs that ensheath axons by a specialized plasma membrane, called myelin, which enhances the conduction of electric impulses; (2) non-myelinating SCs, including Remak SCs, which wrap bundles of multiple axons of small caliber, and perysinaptic SCs (PSCs), associated with motor axon terminals at the neuromuscular junction (NMJ). All types of SCs contribute to PNS regeneration through striking morphological and functional changes in response to nerve injury, are affected in peripheral neuropathies and show abnormalities and a diminished plasticity during aging. Therefore, methodological approaches to study and manipulate SCs in physiological and pathophysiological conditions are crucial to expand the present knowledge on SC biology and to devise new therapeutic strategies to counteract neurodegenerative conditions and age-derived denervation. We present here an updated overview of traditional and emerging methodologies for the study of SCs for scientists approaching this research field.
Topics: Animals; Axons; Myelin Sheath; Nerve Regeneration; Peripheral Nerve Injuries; Schwann Cells
PubMed: 34988978
DOI: 10.1111/joa.13606