Nerve Research Articles

Assessment of Skin Biopsy as a Diagnostic Biomarker in CSF1R-Related Disorder.

To validate a recently published study in which skin biopsy was reported as a valuable alternative to brain biopsy in diagnosing CSF1R-related disorder (CSF1R-RD). Blinded evaluation of skin samples was performed by independent reviewers using light and electron microscopy collected from a group of CSF1R variant carriers (n = 10) with various genotypes (mono and biallelic), different stages of the disease (asymptomatic and symptomatic), and exposed to different therapies (glucocorticoids, hematopoietic stem cell transplantation, and TREM2 agonist), and from a group of healthy controls (n = 5). Biopsies from patients with CSF1R-RD at various disease stages were indistinguishable from controls determined using light microscopy and electron microscopy. We found no distinctive axonal pathology in skin biopsies collected from CSF1R variant carriers at all stages of the disease. Our results are consistent with clinical and neurophysiologic features of the CSF1R-RD, in that peripheral nervous system involvement has not been reported. Studies aiming to discover new biomarkers are important, but the results must be validated with larger numbers of patients and healthy controls. Based on blinded light and electron microscopic studies of skin biopsies, there is no evidence that CSF1R-RD is associated with distinctive changes in cutaneous peripheral nerves. This suggests that skin biopsy is not useful in diagnosis of CSF1R-RD. This study provides Class III evidence that skin biopsy does not distinguish those with CSF1R-RD, or carriers, from normal controls.

Evaluation of the effect of intraoperative tropisetron on postoperative rebound pain after brachial plexus block: a randomized controlled trial.

Postoperative rebound pain after peripheral nerve block increases patient suffering and delays recovery after surgery. We tested whether the 5HT-3 receptor antagonist and α7nAChR agonist tropisetron could prevent postoperative rebound pain. A total of 115 patients were randomized to receive 5-mg/5-mL tropisetron or the same volume of normal saline. Pain intensity was measured with the numerical rating scale of pain (NRS). Rebound pain was defined as a change from mild pain (NRS ≤ 3) measured in the postanesthesia care unit to severe pain (NRS ≥ 7) within 24 hours after peripheral nerve blockade. Logistic regression was used to identify relevant factors associated with postoperative rebound pain. Tropisetron did not affect the NRS score or the incidence of rebound pain after peripheral nerve block. Logistic regression revealed that preoperative pain, bone surgery, and length of incision were risk factors for postoperative rebound pain, and patient-controlled analgesia was protective against postoperative rebound pain. Tropisetron does not affect the incidence of rebound pain after peripheral nerve block. Patients at high risk of postoperative rebound pain should be identified for appropriate management. Registration site: www.chictr.org.cn (ChiCTR2300069994).

Contemporary Approach to Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors.

Most malignant peripheral nerve sheath tumors (MPNSTs) are clinically aggressive high-grade sarcomas, arising in individuals with neurofibromatosis type 1 (NF1) at a significantly elevated estimated lifetime frequency of 8%-13%. In the setting of NF1, MPNSTs arise from malignant transformation of benign plexiform neurofibroma and borderline atypical neurofibromas. Composed of neoplastic cells from the Schwannian lineage, these cancers recur in approximately 50% of individuals, and most patients die within five years of diagnosis, despite surgical resection, radiation, and chemotherapy. Treatment for metastatic disease is limited to cytotoxic chemotherapy and investigational clinical trials. In this article, we review the pathophysiology of this aggressive cancer and current approaches to surveillance and treatment.

Diabetic Neuropathy: An Overview of Molecular Pathways and Protective Mechanisms of Phytobioactives.

Diabetic neuropathy (DN) is a common and debilitating complication of diabetes mellitus that affects the peripheral nerves and causes pain, numbness, and impaired function. The pathogenesis of DN involves multiple molecular mechanisms, such as oxidative stress, inflammation, and pathways of advanced glycation end products, polyol, hexosamine, and protein kinase C. Phytochemicals are natural compounds derived from plants that have various biological activities and therapeutic potential. Flavonoids, terpenes, alkaloids, stilbenes, and tannins are some of the phytochemicals that have been identified as having protective potential for diabetic neuropathy. These compounds can modulate various cellular pathways involved in the development and progression of neuropathy, including reducing oxidative stress and inflammation and promoting nerve growth and repair. In this review, the current evidence on the effects of phytochemicals on DN by focusing on five major classes, flavonoids, terpenes, alkaloids, stilbenes, and tannins, are summarized. This compilation also discusses the possible molecular targets of numerous pathways of DN that these phytochemicals modulate. These phytochemicals may offer a promising alternative or complementary approach to conventional drugs for DN management by modulating multiple pathological pathways and restoring nerve function.

Local Anesthetics, Local Anesthetic Systemic Toxicity (LAST), and Liposomal Bupivacaine.

Local anesthetics have played a vital role in the multimodal analgesia approach to patient care by decreasing the use of perioperative opioids, enhancing patient satisfaction, decreasing the incidence of postoperative nausea and vomiting, decreasing the length of hospital stay, and reducing the risk of chronic postsurgical pain. The opioid-reduced anesthetic management for perioperative analgesia has been largely successful with the use of local anesthetics during procedures such as peripheral nerve blocks and neuraxial analgesia. It is important that practitioners who use local anesthetics are aware of the risk factors, presentation, and management of local anesthetic systemic toxicity (LAST).

Nerve Injury Following Regional Nerve Block: A Literature Review of Its Etiologies, Risk Factors, and Prevention.

Postoperative nerve injury after nerve block is complex and multifactorial. The mechanisms, etiologies, and risk factors are explored. This review article conducts a literature search and summarizes current evidence and best practices in prevention of nerve injury. Emerging technology such as ultrasound, injection pressure monitors, and nerve stimulators for peripheral nerve block have been incorporated into regular practice to reduce the rate of nerve injury. Studies show avoidance of intrafascicular injection, limiting concentrations/volumes of local anesthetic, and appropriate patient selection are the most significant controllable factors in limiting the negative consequences of nerve block. Peripheral nerve injury is an uncommon occurrence after nerve block and is obscured by surgical manipulation, positioning, and underlying neural integrity. Underlying neural integrity is not always evident despite an adequate history and physical exam. Surgical stress, independently of nerve block, may exacerbate these neurologic disease processes and make diagnosing a postoperative nerve injury more challenging. Prevention of nerve injury by surgical teams, care with positioning, and avoidance of intrafascicular injection with nerve block are the most evidence-based practices.

Advances in Exosome-Based Therapies for the Repair of Peripheral Nerve Injuries.

Peripheral nerve injuries (PNIs) are the term used to describe injuries that occur to the nerve fibers of the peripheral nervous system (PNS). Such injuries may be caused by trauma, infection, or aberrant immunological response. Although the peripheral nervous system has a limited capacity for self-repair, in cases of severe damage, this process is either interrupted entirely or is only partially completed. The evaluation of variables that promote the repair of peripheral nerves has consistently been a focal point. Exosomes are a subtype of extracellular vesicles that originate from cellular sources and possess abundant proteins, lipids, and nucleic acids, play a critical role in facilitating intercellular communication. Due to their modifiable composition, they possess exceptional capabilities as carriers for therapeutic compounds, including but not limited to mRNAs or microRNAs. Exosome-based therapies have gained significant attention in the treatment of several nervous system diseases due to their advantageous properties, such as low toxicity, high stability, and limited immune system activation. The objective of this review article is to provide an overview of exosome-based treatments that have been developed in recent years for a range of PNIs, including nerve trauma, diabetic neuropathy, amyotrophic lateral sclerosis (ALS), glaucoma, and Guillain-Barre syndrome (GBS). It was concluded that exosomes could provide favorable results in the improvement of peripheral PNIs by facilitating the transfer of regenerative factors. The development of bioengineered exosome therapy for PNIs should be given more attention to enhance the efficacy of exosome treatment for PNIs.

4D-Printed MXene-Based Artificial Nerve Guidance Conduit for Enhanced Regeneration of Peripheral Nerve Injuries.

Repairing larger defects (> 5mm) in peripheral nerve injuries (PNIs) remains a significant challenge when using traditional artificial nerve guidance conduits (NGCs). We propose a novel approach that combines 4D printing technology with poly(L-lactide-co-trimethylene carbonate) (PLATMC) and Ti3C2Tx MXene nanosheets, thereby imparting shape memory properties to the NGCs. Upon body temperature activation, the printed sheet-like structure can quickly self-roll into a conduit-like structure, enabling optimal wrapping around nerve stumps. This design enhances nerve fixation and simplifies surgical procedures. Moreover, the integration of microchannel expertly crafted through 4D printing, along with the incorporation of MXene nanosheets, introduces electrical conductivity. This feature facilitates the guided and directional migration of nerve cells, rapidly accelerating the healing of the PNI. By leveraging these advanced technologies, the developed NGCs demonstrate remarkable potential in promoting peripheral nerve regeneration, leading to substantial improvements in muscle morphology and restored sciatic nerve function, comparable to outcomes achieved through autogenous nerve transplantation. This article is protected by copyright. All rights reserved.

Influence of peripheral axon geometry and local anatomy on magnetostimulation chronaxie.

Rapid switching of Magnetic Resonance Imaging (MRI) gradient fields induces electric fields that can cause peripheral nerve stimulation (PNS) and so accurate characterization of PNS is required to maintain patient safety and comfort while maximizing MRI performance. The minimum magnetic gradient amplitude that causes stimulation, the PNS threshold, depends on intrinsic axon properties and the spatial and temporal properties of the induced electric field. The PNS strength-duration curve is widely used to characterize simulation thresholds for periodic waveforms and is parameterized by the chronaxie and rheobase. Safety limits to avoid unwanted PNS in MRI rely on a single chronaxie value to characterize the response of all nerves. However, experimental magnetostimulation peripheral nerve chronaxie values vary by an order of magnitude. Given the diverse range of chronaxies observed and the importance of this number in MRI safety models, we seek a deeper understanding of the mechanisms contributing to chronaxie variability. We use a coupled electromagnetic-neurodynamic peripheral nerve stimulation model to assess geometric sources of chronaxie variability. We study the impact of the position of the stimulating magnetic field coil relative to the body, along with the effect of local anatomical features and nerve trajectories on the driving function and the resulting chronaxie. We find realistic variation of local axon and tissue geometry can modulate a given axon's chronaxie by up to 2-fold. Our results identify the temporal rate of charge redistribution as the underlying determinant of the chronaxie. This charge distribution is a function of both intrinsic axon properties and the spatial stimulus along the nerve; thus, examination of the local tissue topology, which shapes the electric fields, as well as the nerve trajectory, are critical for better understanding chronaxie variations and defining more biologically informed MRI safety guidelines.

Construction of bupivacaine-loaded gelatin-based hydrogel delivery system for sciatic nerve block in mice.

Peripheral nerve blockade (PNB) is a common treatment to relieve postoperative pain. However, local anesthetics alone have a short duration of action and severe side effects during postoperative analgesia. In order to overcome these limitations, the present study reported an injectable hydrogel with a drug slow-release profile for regional nerve blockade. The injectable hydrogel was prepared by crosslinking with gelatin and NHS-PEG-NHS, which was degradable in the physiological environment and displayed sustainable release of anesthetics locally, thus improving the disadvantage of the high toxicity of local anesthetics. In this regard, we conducted a series of in vitro characterizations and proved that the hydrogel has a porous three-dimensional mesh structure with high drug loading capability, and sustainable drug release profile. And cytotoxicity experiments confirmed the good biocompatibility of the hydrogel. It was shown that using the animal sciatic nerve block model, the analgesic effect was greatly improved in vivo, and there was no obvious evidence of permanent inflammation or nerve damage in the block site's sections. This locally slow-release platform, combined with local anesthetics, is therefore a promising contender for long-acting analgesia.

Surgical outcome of isolated benign peripheral nerve sheath tumors without neurofibromatosis

BackgroundBenign peripheral nerve sheath tumors (BPNSTs) include schwannomas and neurofibromas. About 10% of soft tissue sarcomas are malignant peripheral nerve sheath tumors (MPNSTs), which are invasive and aggressive tumors. These can happen occasionally or after radiation exposure. Up to 90% of schwannomas are made up of differentiated neoplastic Schwann cells. Malignant transformation of schwannomas is rare.MethodsWe collected the medical records of all patients (including their family histories), performed comprehensive physical and neurological assessments, and checked for the presence of a Tinel-like sign, as well as screening for neurofibromatosis (NF) signs. Magnetic resonance imaging (MRI), nerve conduction studies, and ultrasound were done for all cases.ResultsWe have operated on 21 patients with age range 29–52 years. The mean age was 39.4 years. 14 of these patients were females and 7 were males. The presenting symptoms were just swelling at nerve site in 14 patients, spontaneous pain at the nerve sites in 7 patients, and sensory deficit at the nerve distribution sites in 9 patients. The other 12 patients were sensory intact and only 7 patients had motor deficit. Postoperatively all patients had improved motor and sensory deficit and none of intact patients were worsened. Preoperatively we did MRI to show important nearby vascular structure anatomical abnormalities and we ordered nerve studies to all patients that showed abnormalities, which was only in 9 patients. Gross total resection was done in 18 patients and other 3 cases had partial resection to avoid sensory and motor deficits. The pathological analysis revealed 11 schwannomas and 10 neurofibromas. With 1 year follow up there was no recurrence in any patients.ConclusionBenign pheripheral nerve sheath tumours are safely resected without increased sensory and motor deficits after surgery and with improve clinical outcome with no recurrence on follow up.

Neither injury induced macrophages within the nerve, nor the environment created by Wallerian degeneration is necessary for enhanced in vivo axon regeneration after peripheral nerve injury.

Since the 1990s, evidence has accumulated that macrophages promote peripheral nerve regeneration and are required for enhancing regeneration in the conditioning lesion (CL) response. After a sciatic nerve injury, macrophages accumulate in the injury site, the nerve distal to that site, and the axotomized dorsal root ganglia (DRGs). In the peripheral nervous system, as in other tissues, the macrophage response is derived from both resident macrophages and recruited monocyte-derived macrophages (MDMs). Unresolved questions are: at which sites do macrophages enhance nerve regeneration, and is a particular population needed. Ccr2 knock-out (KO) and Ccr2gfp/gfp knock-in/KO mice were used to prevent MDM recruitment. Using these strains in a sciatic CL paradigm, we examined the necessity of MDMs and residents for CL-enhanced regeneration in vivo and characterized injury-induced nerve inflammation. CL paradigm variants, including the addition of pharmacological macrophage depletion methods, tested the role of various macrophage populations in initiating or sustaining the CL response. In vivo regeneration, measured from bilateral proximal test lesions (TLs) after 2 d, and macrophages were quantified by immunofluorescent staining. Peripheral CL-enhanced regeneration was equivalent between crush and transection CLs and was sustained for 28 days in both Ccr2 KO and WT mice despite MDM depletion. Similarly, the central CL response measured in dorsal roots was unchanged in Ccr2 KO mice. Macrophages at both the TL and CL, but not between them, stained for the pro-regenerative marker, arginase 1. TL macrophages were primarily CCR2-dependent MDMs and nearly absent in Ccr2 KO and Ccr2gfp/gfp KO mice. However, there were only slightly fewer Arg1+ macrophages in CCR2 null CLs than controls due to resident macrophage compensation. Zymosan injection into an intact WT sciatic nerve recruited Arg1+ macrophages but did not enhance regeneration. Finally, clodronate injection into Ccr2gfp KO CLs dramatically reduced CL macrophages. Combined with the Ccr2gfp KO background, depleting MDMs and TL macrophages, and a transection CL, physically removing the distal nerve environment, nearly all macrophages in the nerve were removed, yet CL-enhanced regeneration was not impaired. Macrophages in the sciatic nerve are neither necessary nor sufficient to produce a CL response.

Mesenchymal stem cells’ “garbage bags” at work: Treating radial nerve injury with mesenchymal stem cell-derived exosomes

Unlike central nervous system injuries, peripheral nerve injuries (PNIs) are often characterized by more or less successful axonal regeneration. However, structural and functional recovery is a senile process involving multifaceted cellular and molecular processes. The contemporary treatment options are limited, with surgical intervention as the gold-standard method; however, each treatment option has its associated limitations, especially when the injury is severe with a large gap. Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI. The recent pilot study is a leap forward in the field, which is expected to pave the way for more enormous, systematic, and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach, in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.

Long-Term Follow-Up of a Case of Probable Aspergillus Skull Base Osteomyelitis With Galactomannan Test and Literature Review.

We report a probable case of Aspergillus basicranial infection diagnosed by pathogenic serological examination presenting atypical initial manifestations, and highlight the importance of serological examination to avoid treatment delay and disease management. An 84-year-old diabetic patient presented with right peripheral nerve palsy, intolerable otalgia, hearing loss, dysphagia, hoarseness, and bucking. The patient was diagnosed a probable Aspergillus skull base osteomyelitis with cranial neuritis and meningitis of central nervous system. Galactomannan test was used in combination with 1-3-β-D-glucan and magnetic resonance imaging to follow-up during the continuous treatment of voriconazole. To date, the patient has remained in clinical remission for over 39 months but the drug cannot be stopped safely.

Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis

BackgroundEndothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI). However, the interplay between them remains unclear. We aimed to elucidate the effects and underlying mechanisms of SCs-Exos on INRV following PNI.ResultsWe found that GW4869 inhibited INRV, as well as that normoxic SCs-Exos (N-SCs-Exos) exhibited significant pro-INRV effects in vivo and in vitro that were potentiated by hypoxic SCs-Exos (H-SCs-Exos). Upregulation of glycolysis emerged as a pivotal factor for INRV after PNI, as evidenced by the observation that 3PO administration, a glycolytic inhibitor, inhibited the INRV process in vivo and in vitro. H-SCs-Exos more significantly enhanced extracellular acidification rate/oxygen consumption rate ratio, lactate production, and glycolytic gene expression while simultaneously suppressing acetyl-CoA production and pyruvate dehydrogenase E1 subunit alpha (PDH-E1α) expression than N-SCs-Exos both in vivo and in vitro. Furthermore, we determined that H-SCs-Exos were more enriched with miR-21-5p than N-SCs-Exos. Knockdown of miR-21-5p significantly attenuated the pro-glycolysis and pro-INRV effects of H-SCs-Exos. Mechanistically, miR-21-5p orchestrated EC metabolism in favor of glycolysis by targeting von Hippel-Lindau/hypoxia-inducible factor-1α and PDH-E1α, thereby enhancing hypoxia-inducible factor-1α-mediated glycolysis and inhibiting PDH-E1α-mediated oxidative phosphorylation.ConclusionThis study unveiled a novel intrinsic mechanism of pro-INRV after PNI, providing a promising therapeutic target for post-injury peripheral nerve regeneration and repair.Graphical

Assessment for Diabetic Neuropathy: Treatment and Neurobiological Perspective.

Diabetic neuropathy, also known as diabetic peripheral sensorimotor neuropathy (DPN), is a consequential complexity of diabetes, alongside diabetic nephropathy, diabetic cardiomyopathy, and diabetic retinopathy. It is characterized by signs and symptoms of peripheral nerve damage in diabetes patients after ruling out other causes. Approximately 20% of people with diabetes are affected by this painful and severe condition. The development of diabetic neuropathy is influenced by factors such as impaired blood flow to the peripheral nerves and metabolic issues, including increased polyol pathway activation, myo-inositol loss, and nonenzymatic glycation. The present review article provides a brief overview of the pathological changes in diabetic neuropathy and the mechanisms and types of DPN. Various diagnostic tests and biomarkers are available to assess nerve damage and its severity. Pharmacotherapy for neuropathic pain in diabetic neuropathy is complex. This review will explore current treatment options and potential future developments to improve the quality of life for patients suffering from diabetic neuropathy.

Advanced nerve regeneration enabled by neural conformal electronic stimulators enhancing mitochondrial transport

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

Shape-Persistent Conductive Nerve Guidance Conduits for Peripheral Nerve Regeneration.

To solve the problems of slow regeneration and mismatch of axon regeneration after peripheral nerve injury, nerve guidance conduits (NGCs) have been widely used to promote nerve regeneration. Multichannel NGCs have been widely studied to mimic the structure of natural nerve bundles. However, multichannel conduits are prone to structural instability. Thermo-responsive shape memory polymers (SMPs) can maintain a persistent initial structure over the body temperature range. Electrical stimulation (ES), utilized within nerve NGCs, serves as a biological signal to expedite damaged nerve regeneration. Here, an electrospun shape-persistent conductive NGC is designed to maintain the persistent tubular structure in the physiological temperature range and improve the conductivity. The physicochemical and biocompatibility of these P, P/G, P/G-GO, and P/G-RGO NGCs are conducted in vitro. Meanwhile, to evaluate biocompatibility and peripheral nerve regeneration, NGCs are implanted in subcutaneous parts of the back of rats and sciatic nerves assessed by histology and immunofluorescence analyses. The conductive NGC displays a stable structure, good biocompatibility, and promoted nerve regeneration. Collectively, the shape-persistent conductive NGC (P/G-RGO) is expected to promote peripheral nerve recovery, especially for long-gap and large-diameter nerves.

Biodistribution and preclinical safety profile of legubicin: A novel conjugate of doxorubicin and a legumain-cleavable peptide linker.

Legubicin is a novel conjugate of doxorubicin and a legumain-cleavable peptide linker. It has been developed to ameliorate the side effects of doxorubicin. Biodistribution in tumor-bearing mice, acute tolerance, and potential systemic toxic effects in Sprague-Dawley rats and beagle dogs of legubicin were assessed. Legubicin exists mainly as a protein complex in plasma after entering the circulation. Compared with conventional doxorubicin at an equal molar dose in mice, we found higher exposure to doxorubicin in tumor (approximately 1.7-fold increase) while lower exposure in normal tissues (an ~3.26-, 3.46-, and 1.29-fold reduction in heart, kidney, and plasma, respectively) in tumor-bearing mice after intravenous injection of legubicin. The acute maximum tolerance dose (MTD) of legubicin was >16 mg/kg doxorubicin equivalent in female rats, 11 mg/kg doxorubicin equivalent in male rats (LD50 of conventional doxorubicin is 10.51 mg/kg), and >8mg/kg doxorubicin equivalent in dogs (MTD of conventional doxorubicin is 1.5mg/kg). Four-week repeat-dose toxicity studies of intravenous legubicin were conducted in rats (5, 10, and 25 mg/kg/dose once weekly) and dogs (3/1.5, 10/5, and 20/10mg/kg/dose once weekly); the dose levels were reduced from the second dose due to intolerable legubicin-associated toxicity at 20 mg/kg. Major organs of toxicity included the gastrointestinal tract, lymphoid and hematopoietic organs, kidney, skin, liver, reproductive organs, and peripheral nerves, which are all associated with doxorubicin. However, cardiotoxicity was only noted at MTD dose levels. Altogether, our results confirm an improved safety profile of legubicin over conventional doxorubicin and support its clinical benefit for treating cancer.

The Use of Mirror Therapy in Peripheral Seventh Nerve Palsy: A Systematic Review

Background: Conservative therapy is currently the elective treatment for peripheric facial palsy according to scientific literature. The success of conservative therapy is due to physiotherapy and the application of its methods. The aim of this systematic review was to assess mirror therapy, a physiotherapeutic method. Objectives: The aim of the following systematic review is to evaluate the effectiveness of using mirror therapy in patients with peripheral paralysis of the seventh cranial nerve. Methods: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The screening of literature was carried out on Cochrane, PEDro, PubMed/Medline, Scopus and Web of Science databases up until August 2022. All studies were randomized controlled trials (RCTs) and 5 articles met the inclusion criteria and were included in this study. The risk of bias was evaluated with PEDro and Jadad scales. Discussion: In the present study, we reviewed 5 RCTs that compared mirror therapy with other physiotherapy treatments or placebo to reduce pain, depression and improve range of motion in patients with peripheric facial nerve palsy. Conclusions: Further studies are needed to determine the effectiveness of this type of treatment, but nevertheless the data obtained are very encouraging.