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Peripheral Nerve Injury Treatments and Advances: One Health Perspective
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.
Journal Article
It’s never too late - balance and endurance training improves functional performance, quality of life, and alleviates neuropathic symptoms in cancer survivors suffering from chemotherapy-induced peripheral neuropathy: results of a randomized controlled trial
Background
Chemotherapy-induced peripheral neuropathy (CIPN) can affect functional performance and quality of life considerably. Since balance training has proven to enhance physical function, it might be a promising strategy to manage CIPN-induced functional impairments.
Methods
Fifty cancer survivors with persisting CIPN after finishing their treatment were randomly allocated to an intervention (IG) or active control group (CG). The IG did endurance plus balance training, the CG only endurance training (twice weekly over 12 weeks). Pre- and post-assessments included functional performance, cardiorespiratory fitness, vibration sense, and self-reported CIPN symptoms (EORTC QLQ-CIPN20).
Results
Intention-to-treat analyses (
n
= 41) did not reveal a significant group difference (CG minus IG) for sway path in semi-tandem stance after intervention (primary endpoint), adjusted for baseline. However, our per-protocol analysis of 37 patients with training compliance ≥70% revealed: the IG reduced their sway path during semi-tandem stance (− 76 mm, 95% CI -141 – -17; CG: -6 mm, 95% CI -52 – 50), improved the duration standing on one leg on instable surface (11 s, 95% CI 8–17; CG: 0 s, 95%CI 0–5) and reported decreased motor symptoms (−8points, 95% CI -18 – 0; CG: -2points 95% CI -6 – 2). Both groups reported reduced overall- (IG: -10points, 95% CI -17 – -4; CG: -6points, 95% CI -11 – -1) and sensory symptoms (IG: -7points, 95% CI -15 – 0; CG: -7points, 95% CI -15 – 0), while only the CG exhibited objectively better vibration sense (knuckle: 0.8points, 95% CI 0.3–1.3; IG: 0.0points, 95% CI -1.1 – 0.9; patella: 1.0points, 95% CI 0.4–1.6: IG: -0.8points, 95% CI -0.2 – 0.0). Furthermore, maximum power output during cardiopulmonary exercise test increased in both groups (IG and CG: 0.1 W/kg, 95% CI 0.0–0.2), but only the CG improved their jump height (2 cm, 95% CI 0.5–3.5; IG: 1 cm, 95% CI -0.4 – 3.2).
Conclusion
We suppose that endurance training induced a reduction in sensory symptoms in both groups, while balance training additionally improved patients’ functional status. This additional functional effect might reflect the IG’s superiority in the CIPN20 motor score. Both exercises provide a clear and relevant benefit for patients with CIPN.
Trial registration
German Clinical Trials Register (DRKS) number:
DRKS00005419
, prospectively registered on November 19, 2013.
Journal Article
Peripheral Nerve Regeneration and Muscle Reinnervation
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.
Journal Article
Drug-Eluting Resorbable Scaffold versus Angioplasty for Infrapopliteal Artery Disease
In a trial involving patients with infrapopliteal artery disease, the use of a drug-eluting resorbable scaffold was superior to angioplasty in reducing reintervention and maintaining patency at 1 year.
Journal Article
Evaluation of the effects of sensorimotor exercise on physical and psychological parameters in breast cancer patients undergoing neurotoxic chemotherapy
Introduction
Breast cancer is the most common cancer disease of women in industrialized countries. Neurotoxic chemotherapy drugs are known to harm peripheral nerves and cause a chemotherapy-induced peripheral neuropathy (CIPN). CIPN is one of the most common adverse events associated with Paclitaxel chemotherapy and may remain present long after the termination of chemotherapy. Thus, it reduces the patients’ quality of life (QoL) both during chemotherapy and onwards, and can impose a danger on breast cancer survivors due to an increased risk of falling and fall-related injuries.
Methods
The aim of this randomized-controlled trial (RCT) (
n
= 36) (IG: intervention group,
n
= 17) (CG: control group,
n
= 19) was to determine whether sensorimotor exercises have a positive effect on physical and psychological parameters in breast cancer patients undergoing neurotoxic chemotherapy (Paclitaxel).
Results
As a result, we were able to show significant improvements in postural stability in monopedal stance [left leg 16.17 ± 3.67 vs. 21.55 ± 5.33 (
p
< 0.001) and right leg 15.14 ± 2.30 vs. 20.85 ± 5.05 (
p
< 0.001)] and in bipedal stance [T1 vs. T0, − 0.49 (IG) vs. + 1.14 (CG)
p
= 0.039].
Discussion
These results in posturography correlate with the clinical presentation with intervention group patients scoring significantly better on the Fullerton Advanced Balance Scale [37.71 ± 2.73 vs. 34.47 ± 3.98 (
p
= 0.004)]. Moderate strength training successfully prevented a strength loss in the IG that was remarkable in the CG (− 1.60 vs. 0.60,
p
= 0.029). Concerning the psychological parameters assessed via EORTC- and MFI-questionnaires, no significant improvements were found.
Conclusion
Future studies should focus on the correlation of clinical and posturometry findings and subjective QOL such as the long-term-development of CIPN.
Journal Article
Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial
PurposeOver half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms.MethodsCancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0–10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness.ResultsExercise reduced CIPN symptoms of hot/coldness in hands/feet (−0.46 units, p = 0.045) and numbness and tingling (− 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076).ConclusionsExercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients.Trial registrationClinical Trials.gov, # NCT00924651, http://www.clinicaltrials.gov.
Journal Article
Current Status of Therapeutic Approaches against Peripheral Nerve Injuries: A Detailed Story from Injury to Recovery
Peripheral nerve injury is a complex condition with a variety of signs and symptoms such as numbness, tingling, jabbing, throbbing, burning or sharp pain. Peripheral nerves are fragile in nature and can easily get damaged due to acute compression or trauma which may lead to the sensory and motor functions deficits and even lifelong disability. After lesion, the neuronal cell body becomes disconnected from the axon's distal portion to the injury site leading to the axonal degeneration and dismantlement of neuromuscular junctions of targeted muscles. In spite of extensive research on this aspect, complete functional recovery still remains a challenge to be resolved. This review highlights detailed pathophysiological events after an injury to a peripheral nerve and the associated factors that can either hinder or promote the regenerative machinery. In addition, it throws light on the available therapeutic strategies including supporting therapies, surgical and non-surgical interventions to ameliorate the axonal regeneration, neuronal survival, and reinnervation of peripheral targets. Despite the availability of various treatment options, we are still lacking the optimal treatments for a perfect and complete functional regain. The need for the present age is to discover or design such potent compounds that would be able to execute the complete functional retrieval. In this regard, plant-derived compounds are getting more attention and several recent reports validate their remedial effects. A plethora of plants and plant-derived phytochemicals have been suggested with curative effects against a number of diseases in general and neuronal injury in particular. They can be a ray of hope for the suffering individuals.
Journal Article
Evaluation of the effect of N-acetylcysteine on the prevention and amelioration of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled study
Purpose
The aim of the current study was to evaluate the effect of N-acetylcysteine (NAC) on the incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients.
Method
A prospective randomized controlled open label study was conducted on 75 breast cancer patients receiving adjuvant paclitaxel 80 mg/m
2
weekly for 12 weeks. Eligible patients were randomized to either the low dose group; 1200 mg daily NAC, the high dose group; 1200 mg NAC twice daily or the control group; received paclitaxel only. The primary endpoint was the incidence of different grades of PIPN using National Cancer Institute’s common toxicity criteria for adverse event (NCI-CTCAE) while secondary endpoints were the severity of PIPN using modified total neuropathy score (mTNS), quality of life (QOL) using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTX) subscale, serum nerve growth factor (NGF), and serum malondialdehyde (MDA).
Results
At the end of the 12-week period, the incidence of grade (2, 3) peripheral neuropathy was significantly lower in the high dose group (28.6%) compared to the low dose group (61.9%) and the control group (100%),
p
value < 0.001. A significant improvement in the mTNS and QOL scores was observed after 6 and 12 weeks in the high dose group and the low dose group compared to the control,
p
value < 0.001. Significantly higher levels of serum NGF in the high dose group and lower level of serum MDA in the high dose and the low dose group were observed.
Conclusion
Oral NAC (1200 mg once and twice daily) might reduce the incidence and severity of PIPN and improve the patients’ QOL.
Trial registry
Clinical Trial.gov registration number: NCT03492047.
Journal Article
Routine versus clinically indicated replacement of peripheral intravenous catheters: a randomised controlled equivalence trial
Summary Background The millions of peripheral intravenous catheters used each year are recommended for 72–96 h replacement in adults. This routine replacement increases health-care costs and staff workload and requires patients to undergo repeated invasive procedures. The effectiveness of the practice is not well established. Our hypothesis was that clinically indicated catheter replacement is of equal benefit to routine replacement. Methods This multicentre, randomised, non-blinded equivalence trial recruited adults (≥18 years) with an intravenous catheter of expected use longer than 4 days from three hospitals in Queensland, Australia, between May 20, 2008, and Sept 9, 2009. Computer-generated random assignment (1:1 ratio, no blocking, stratified by hospital, concealed before allocation) was to clinically indicated replacement, or third daily routine replacement. Patients, clinical staff, and research nurses could not be masked after treatment allocation because of the nature of the intervention. The primary outcome was phlebitis during catheterisation or within 48 h after removal. The equivalence margin was set at 3%. Primary analysis was by intention to treat. Secondary endpoints were catheter-related bloodstream and local infections, all bloodstream infections, catheter tip colonisation, infusion failure, catheter numbers used, therapy duration, mortality, and costs. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12608000445370. Findings All 3283 patients randomised (5907 catheters) were included in our analysis (1593 clinically indicated; 1690 routine replacement). Mean dwell time for catheters in situ on day 3 was 99 h (SD 54) when replaced as clinically indicated and 70 h (13) when routinely replaced. Phlebitis occurred in 114 of 1593 (7%) patients in the clinically indicated group and in 114 of 1690 (7%) patients in the routine replacement group, an absolute risk difference of 0·41% (95% CI −1·33 to 2·15%), which was within the prespecified 3% equivalence margin. No serious adverse events related to study interventions occurred. Interpretation Peripheral intravenous catheters can be removed as clinically indicated; this policy will avoid millions of catheter insertions, associated discomfort, and substantial costs in both equipment and staff workload. Ongoing close monitoring should continue with timely treatment cessation and prompt removal for complications. Funding Australian National Health and Medical Research Council.
Journal Article