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International Journal of Molecular... Nov 2020Injured peripheral nerves but not central nerves have the capacity to regenerate and reinnervate their target organs. After the two most severe peripheral nerve injuries... (Review)
Review
Injured peripheral nerves but not central nerves have the capacity to regenerate and reinnervate their target organs. After the two most severe peripheral nerve injuries of six types, crush and transection injuries, nerve fibers distal to the injury site undergo Wallerian degeneration. The denervated Schwann cells (SCs) proliferate, elongate and line the endoneurial tubes to guide and support regenerating axons. The axons emerge from the stump of the viable nerve attached to the neuronal soma. The SCs downregulate myelin-associated genes and concurrently, upregulate growth-associated genes that include neurotrophic factors as do the injured neurons. However, the gene expression is transient and progressively fails to support axon regeneration within the SC-containing endoneurial tubes. Moreover, despite some preference of regenerating motor and sensory axons to "find" their appropriate pathways, the axons fail to enter their original endoneurial tubes and to reinnervate original target organs, obstacles to functional recovery that confront nerve surgeons. Several surgical manipulations in clinical use, including nerve and tendon transfers, the potential for brief low-frequency electrical stimulation proximal to nerve repair, and local FK506 application to accelerate axon outgrowth, are encouraging as is the continuing research to elucidate the molecular basis of nerve regeneration.
Topics: Animals; Axons; Humans; Muscle, Skeletal; Nerve Regeneration; Neurogenesis; Peripheral Nerve Injuries; Peripheral Nerves; Recovery of Function; Schwann Cells; Tacrolimus
PubMed: 33212795
DOI: 10.3390/ijms21228652 -
International Journal of Molecular... Jan 2022Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function... (Review)
Review
Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function impairment. These changes can cause partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, which in turn can affect the quality of life. This review aims to revisit the concepts associated with the PNI and the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to enhance the importance of new therapies, especially in severe lesions, to overcome limitations and achieve better outcomes. The urge for new approaches and the understanding of the different methods to evaluate nerve regeneration is fundamental from a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.
Topics: Animals; Biomarkers; Clinical Studies as Topic; Combined Modality Therapy; Disease Management; Disease Models, Animal; Disease Susceptibility; Humans; Peripheral Nerve Injuries; Peripheral Nerves; Treatment Outcome
PubMed: 35055104
DOI: 10.3390/ijms23020918 -
Connective Tissue Research Jan 2019Peripheral nerve injuries (PNI) resulting from trauma can be severe and permanently debilitating. Despite the armamentarium of meticulous microsurgical repair techniques... (Review)
Review
Peripheral nerve injuries (PNI) resulting from trauma can be severe and permanently debilitating. Despite the armamentarium of meticulous microsurgical repair techniques that includes direct repair, grafting of defects with autograft nerve, and grafting with cadaveric allografts, approximately one-third of all PNI demonstrate incomplete recovery with poor restoration of function. This may include total loss or incomplete recovery of motor and/or sensory function, chronic pain, muscle atrophy, and profound weakness, which can result in lifelong morbidity. Much of this impaired nerve healing can be attributed to perineural scarring and fibrosis at the site of injury and repair. To date, this challenging clinical problem has not been adequately addressed. In this review, we summarize the existing literature surrounding biological aspects of perineural fibrosis following PNI, detail current strategies to limit nerve scarring, present our own work developing reliable nerve injury models in animal studies, and discuss potential future studies which may ultimately lead to new therapeutic strategies.
Topics: Animals; Biomechanical Phenomena; Cicatrix; Humans; Peripheral Nerve Injuries; Peripheral Nerves
PubMed: 30187777
DOI: 10.1080/03008207.2018.1489381 -
The Journal of the American Academy of... Sep 2015Double crush syndrome is a distinct compression at two or more locations along the course of a peripheral nerve that can coexist and synergistically increase symptom... (Review)
Review
Double crush syndrome is a distinct compression at two or more locations along the course of a peripheral nerve that can coexist and synergistically increase symptom intensity. In addition, dissatisfaction after treatment at one site may be the result of persistent pathology at another site along a peripheral nerve. Double crush syndrome is a controversial diagnosis; some scientists and surgeons believe it is an illness construction that may do more harm than good because it emphasizes an objective pathophysiologic explanation for unexplained symptoms, disability, and dissatisfaction that may be more psychosocially mediated. However, peripheral neuropathy may coexist with compressive neuropathy and contribute to suboptimal outcomes following nerve decompression. To better manage patients' expectations, treating practitioners should be aware of the possibility of concomitant cervical radiculopathy and carpal tunnel syndrome, as well as the presence of underlying systemic neuropathy.
Topics: Carpal Tunnel Syndrome; Crush Syndrome; Decompression, Surgical; Humans; Nerve Compression Syndromes; Neurosurgical Procedures; Peripheral Nerves; Radiculopathy
PubMed: 26306807
DOI: 10.5435/JAAOS-D-14-00176 -
Neurology India 2019Peripheral nerve injuries are a heterogeneous and distinct group of disorders that are secondary to various causes commonly including motor vehicle accidents, falls,... (Review)
Review
Peripheral nerve injuries are a heterogeneous and distinct group of disorders that are secondary to various causes commonly including motor vehicle accidents, falls, industrial accidents, household accidents, and penetrating trauma. The earliest classification of nerve injuries was given by Seddon and Sunderland, which holds true till date and is commonly used. Neuropraxia, axonotmesis, and neurotmesis are the three main types of nerve injuries. The electrophysiological studies including nerve conduction studies (NCS) and electromyography (EMG) play a key role and are now considered an extension of the clinical examination in patients with peripheral nerve injuries. The electrophysiological results should be interpreted in the light of clinical examination. These studies help in localizing the site of lesion, determine the type and severity of lesion, and help in prognosticating. In neuropraxia, the compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) are elicitable on stimulating the nerve distal to the site of the lesion but demonstrate conduction block on proximal stimulation. The electrodiagnostic findings in axonotmesis and neurotmesis are similar. After few days of injury, Wallerian degeneration sets in with failure to record CMAP and SNAP. Intraoperative technique involves recording from the peripheral nerves during the intraoperative period and has proved useful in the surgical management of nerve injuries and helps in identifying the injured nerve, to determine whether the nerve is in continuity and in localizing the site of lesion. Intraoperative monitoring also helps in identifying the nerve close to an ongoing surgery so that surgical damage to the nerve can be prevented.
Topics: Action Potentials; Electrodiagnosis; Electromyography; Humans; Intraoperative Neurophysiological Monitoring; Neural Conduction; Neurosurgical Procedures; Peripheral Nerve Injuries; Peripheral Nerves; Prognosis
PubMed: 31857526
DOI: 10.4103/0028-3886.273626 -
Neurobiology of Disease Jan 2023The glial cell of the peripheral nervous system (PNS), the Schwann cell (SC), counts among the most multifaceted cells of the body. During development, SCs secure... (Review)
Review
The glial cell of the peripheral nervous system (PNS), the Schwann cell (SC), counts among the most multifaceted cells of the body. During development, SCs secure neuronal survival and participate in axonal path finding. Simultaneously, they orchestrate the architectural set up of the developing nerves, including the blood vessels and the endo-, peri- and epineurial layers. Perinatally, in rodents, SCs radially sort and subsequently myelinate individual axons larger than 1 μm in diameter, while small calibre axons become organised in non-myelinating Remak bundles. SCs have a vital role in maintaining axonal health throughout life and several specialized SC types perform essential functions at specific locations, such as terminal SC at the neuromuscular junction (NMJ) or SC within cutaneous sensory end organs. In addition, neural crest derived satellite glia maintain a tight communication with the soma of sensory, sympathetic, and parasympathetic neurons and neural crest derivatives are furthermore an indispensable part of the enteric nervous system. The remarkable plasticity of SCs becomes evident in the context of a nerve injury, where SC transdifferentiate into intriguing repair cells, which orchestrate a regenerative response that promotes nerve repair. Indeed, the multiple adaptations of SCs are captivating, but remain often ill-resolved on the molecular level. Here, we summarize and discuss the knowns and unknowns of the vast array of functions that this single cell type can cover in peripheral nervous system development, maintenance, and repair.
Topics: Humans; Schwann Cells; Peripheral Nerves; Axons; Neurons; Peripheral Nervous System; Nerve Regeneration; Peripheral Nerve Injuries
PubMed: 36493976
DOI: 10.1016/j.nbd.2022.105952 -
Journal of Neurology, Neurosurgery, and... Aug 2020Neuralgic amyotrophy (NA), also known as Parsonage-Turner syndrome, is characterised by sudden pain attacks, followed by patchy muscle paresis in the upper extremity.... (Review)
Review
Neuralgic amyotrophy (NA), also known as Parsonage-Turner syndrome, is characterised by sudden pain attacks, followed by patchy muscle paresis in the upper extremity. Recent reports have shown that incidence is much higher than previously assumed and that the majority of patients never achieve full recovery. Traditionally, the diagnosis was mainly based on clinical observations and treatment options were confined to application of corticosteroids and symptomatic management, without proven positive effects on long-term outcomes. These views, however, have been challenged in the last years. Improved imaging methods in MRI and high-resolution ultrasound have led to the identification of structural peripheral nerve pathologies in NA, most notably hourglass-like constrictions. These pathognomonic findings have paved the way for more accurate diagnosis through high-resolution imaging. Furthermore, surgery has shown to improve clinical outcomes in such cases, indicating the viability of peripheral nerve surgery as a valuable treatment option in NA. In this review, we present an update on the current knowledge on this disease, including pathophysiology and clinical presentation, moving on to diagnostic and treatment paradigms with a focus on recent radiological findings and surgical reports. Finally, we present a surgical treatment algorithm to support clinical decision making, with the aim to encourage translation into day-to-day practice.
Topics: Brachial Plexus Neuritis; Diagnosis, Differential; Humans; Peripheral Nerves
PubMed: 32487526
DOI: 10.1136/jnnp-2020-323164 -
Acta Biomaterialia Apr 2020Peripheral nerves can sustain injuries due to loss of structure and/or function of peripheral nerves because of accident, trauma and other causes, which leads to partial... (Review)
Review
Peripheral nerves can sustain injuries due to loss of structure and/or function of peripheral nerves because of accident, trauma and other causes, which leads to partial or complete loss of sensory, motor, and autonomic functions and neuropathic pain. Even with the extensive knowledge on the pathophysiology and regeneration mechanisms of peripheral nerve injuries (PNI), reliable treatment methods that ensure full functional recovery are scant. Nerve autografting is the current gold standard for treatment of PNI. Given the limitations of autografts including donor site morbidity and limited supply, alternate treatment methods are being pursued by the researchers. Neural guide conduits (NGCs) are increasingly being considered as a potential alternative to nerve autografts. The anatomy of peripheral nerves, classification of PNI, and current treatment methods are briefly yet succinctly reviewed. A detailed review on the various designs of NGCs, the different materials used for making the NGCs, and the fabrication methods adopted is presented in this work. Much progress had been made in all the aspects of making an NGC, including the design, materials and fabrication techniques. The advent of advanced technologies such as additive manufacturing and 3D bioprinting could be beneficial in easing the production of patient-specific NGCs. NGCs with supporting cells or stem cells, NGCs loaded with neurotropic factors and drugs, and 4D printed NGCs are some of the futuristic areas of interest. STATEMENT OF SIGNIFICANCE: Neural guide conduits (NGCs) are increasingly being considered as a potential alternative to nerve autografts in the treatment of peripheral nerve injuries. A detailed review on the various designs of NGCs, the different materials used for making the NGCs, and the fabrication methods (including Additive Manufacturing) adopted is presented in this work.
Topics: Animals; Biocompatible Materials; Cell Line, Tumor; Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Tissue Scaffolds
PubMed: 32044456
DOI: 10.1016/j.actbio.2020.02.003 -
Physiology (Bethesda, Md.) Nov 2022Peripheral nerve injuries often result in life-altering functional deficits even with optimal management. Unlike the central nervous system, peripheral nerves have the... (Review)
Review
Peripheral nerve injuries often result in life-altering functional deficits even with optimal management. Unlike the central nervous system, peripheral nerves have the ability to regenerate lost axons after injury; however, axonal regeneration does not equate to full restoration of function. To overcome this physiological shortcoming, advances in nerve regeneration and repair are paramount, including electrical stimulation, gene therapy, and surgical technique advancements.
Topics: Axons; Electric Stimulation; Genetic Therapy; Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves
PubMed: 35820181
DOI: 10.1152/physiol.00008.2022 -
Hand (New York, N.Y.) Jan 2023
Topics: Humans; Peripheral Nerves; Peripheral Nerve Injuries
PubMed: 36698251
DOI: 10.1177/15589447221150669