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Journal of Experimental & Clinical... Oct 2021Oxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN) is a severe clinical problem and potentially permanent side effect of cancer treatment. For the management of... (Review)
Review
Oxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN) is a severe clinical problem and potentially permanent side effect of cancer treatment. For the management of OIPN, accurate diagnosis and understanding of significant risk factors including genetic vulnerability are essential to improve knowledge regarding the prevalence and incidence of OIPN as well as enhance strategies for the prevention and treatment of OIPN. The molecular mechanisms underlying OIPN are complex, with multi-targets and various cells causing neuropathy. Furthermore, mechanisms of OIPN can reinforce each other, and combination therapies may be required for effective management. However, despite intense investigation in preclinical and clinical studies, no preventive therapies have shown significant clinical efficacy, and the established treatment for painful OIPN is limited. Duloxetine is the only agent currently recommended by the American Society of Clinical Oncology. The present article summarizes the most recent advances in the field of studies on OIPN, the overview of the clinical syndrome, molecular basis, therapy development, and outlook of future drug candidates. Importantly, closer links between clinical pain management teams and oncology will advance the effectiveness of OIPN treatment, and the continued close collaboration between preclinical and clinical research will facilitate the development of novel prevention and treatments for OIPN.
Topics: Antineoplastic Agents; Biomarkers; Combined Modality Therapy; Disease Management; Disease Susceptibility; Drug Development; Genetic Predisposition to Disease; Humans; Incidence; Molecular Targeted Therapy; Neoplasms; Oxaliplatin; Peripheral Nervous System Diseases; Phenotype; Polymorphism, Genetic; Prevalence; Risk Factors; Syndrome
PubMed: 34686205
DOI: 10.1186/s13046-021-02141-z -
Muscle & Nerve Mar 2017No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes... (Review)
Review
INTRODUCTION
No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures.
METHODS
This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy.
RESULTS
Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included.
CONCLUSIONS
Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. Muscle Nerve 55: 366-372, 2017.
Topics: Diabetic Neuropathies; HIV Infections; Humans; Peripheral Nervous System Diseases
PubMed: 27447116
DOI: 10.1002/mus.25264 -
Journal of Neurology, Neurosurgery, and... Nov 2020
Review
Topics: Amyloid Neuropathies, Familial; Animals; CRISPR-Cas Systems; Caenorhabditis elegans; Charcot-Marie-Tooth Disease; Disease Models, Animal; Drosophila; Genetic Therapy; High-Throughput Nucleotide Sequencing; Human Experimentation; Humans; In Vitro Techniques; Induced Pluripotent Stem Cells; Longevity; Mice; Molecular Targeted Therapy; Oligonucleotides, Antisense; Organ Size; Peripheral Nerves; Peripheral Nervous System Diseases; Primates; RNA, Small Interfering; Rats; Rodentia; Exome Sequencing; Whole Genome Sequencing; Zebrafish
PubMed: 32769113
DOI: 10.1136/jnnp-2020-323016 -
International Journal of Molecular... Oct 2020Charcot-Marie-Tooth disease (CMT) is one of the most common inherited peripheral neuropathies. CMT patients typically show slowly progressive muscle weakness and sensory... (Review)
Review
Charcot-Marie-Tooth disease (CMT) is one of the most common inherited peripheral neuropathies. CMT patients typically show slowly progressive muscle weakness and sensory loss in a distal dominant pattern in childhood. The diagnosis of CMT is based on clinical symptoms, electrophysiological examinations, and genetic testing. Advances in genetic testing technology have revealed the genetic heterogeneity of CMT; more than 100 genes containing the disease causative mutations have been identified. Because a single genetic alteration in CMT leads to progressive neurodegeneration, studies of CMT patients and their respective models revealed the genotype-phenotype relationships of targeted genes. Conventionally, rodents and cell lines have often been used to study the pathogenesis of CMT. Recently, has also attracted attention as a CMT model. In this review, we outline the clinical characteristics of CMT, describe the advantages and disadvantages of using in CMT studies, and introduce recent advances in CMT research that successfully applied the use of , in areas such as molecules associated with mitochondria, endosomes/lysosomes, transfer RNA, axonal transport, and glucose metabolism.
Topics: Amino Acyl-tRNA Synthetases; Animals; Axonal Transport; Charcot-Marie-Tooth Disease; Child; Disease Models, Animal; Drosophila melanogaster; Humans; Intracellular Membranes; L-Iditol 2-Dehydrogenase; Mitochondria; Mutation; Peripheral Nervous System Diseases
PubMed: 33049996
DOI: 10.3390/ijms21197419 -
The Bone & Joint Journal Jan 2017Nerve palsy is a well-described complication following total hip arthroplasty, but is highly distressing and disabling. A nerve palsy may cause difficulty with the... (Review)
Review
Nerve palsy is a well-described complication following total hip arthroplasty, but is highly distressing and disabling. A nerve palsy may cause difficulty with the post-operative rehabilitation, and overall mobility of the patient. Nerve palsy may result from compression and tension to the affected nerve(s) during the course of the operation via surgical manipulation and retractor placement, tension from limb lengthening or compression from post-operative hematoma. In the literature, hip dysplasia, lengthening of the leg, the use of an uncemented femoral component, and female gender are associated with a greater risk of nerve palsy. We examined our experience at a high-volume, tertiary care referral centre, and found an overall incidence of 0.3% out of 39 056 primary hip arthroplasties. Risk factors found to be associated with the incidence of nerve palsy at our institution included the presence of spinal stenosis or lumbar disc disease, age younger than 50, and smoking. If a nerve palsy is diagnosed, imaging is mandatory and surgical evacuation or compressive haematomas may be beneficial. As palsies are slow to recover, supportive care such as bracing, therapy, and reassurance are the mainstays of treatment. Cite this article: Bone Joint J 2017;99-B(1 Supple A):46-9.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Bone Lengthening; Disease Management; Female; Femoral Neuropathy; Humans; Incidence; Male; Middle Aged; Peripheral Nervous System Diseases; Prognosis; Risk Factors; Sciatic Neuropathy; Young Adult
PubMed: 28042118
DOI: 10.1302/0301-620X.99B1.BJJ-2016-0430.R1 -
World Journal of Gastroenterology Jun 2023Thalidomide is an effective treatment for refractory Crohn's disease (CD). However, thalidomide-induced peripheral neuropathy (TiPN), which has a large individual...
BACKGROUND
Thalidomide is an effective treatment for refractory Crohn's disease (CD). However, thalidomide-induced peripheral neuropathy (TiPN), which has a large individual variation, is a major cause of treatment failure. TiPN is rarely predictable and recognized, especially in CD. It is necessary to develop a risk model to predict TiPN occurrence.
AIM
To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables.
METHODS
A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model. The National Cancer Institute Common Toxicity Criteria Sensory Scale (version 4.0) was used to assess TiPN. With 18 clinical features and 150 genetic variables, five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), specificity, sensitivity (recall rate), precision, accuracy, and F1 score.
RESULTS
The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248 [ = 0.0004, odds ratio (OR): 8.983, 95% confidence interval (CI): 2.497-30.90], dose (mg/d, = 0.002), brain-derived neurotrophic factor (BDNF) rs2030324 ( = 0.001, OR: 3.164, 95%CI: 1.561-6.434), BDNF rs6265 ( = 0.001, OR: 3.150, 95%CI: 1.546-6.073) and BDNF rs11030104 ( = 0.001, OR: 3.091, 95%CI: 1.525-5.960). In the training set, gradient boosting decision tree (GBDT), extremely random trees (ET), random forest, logistic regression and extreme gradient boosting (XGBoost) obtained AUROC values > 0.90 and AUPRC > 0.87. Among these models, XGBoost and GBDT obtained the first two highest AUROC (0.90 and 1), AUPRC (0.98 and 1), accuracy (0.96 and 0.98), precision (0.90 and 0.95), F1 score (0.95 and 0.98), specificity (0.94 and 0.97), and sensitivity (1). In the validation set, XGBoost algorithm exhibited the best predictive performance with the highest specificity (0.857), accuracy (0.818), AUPRC (0.86) and AUROC (0.89). ET and GBDT obtained the highest sensitivity (1) and F1 score (0.8). Overall, compared with other state-of-the-art classifiers such as ET, GBDT and RF, XGBoost algorithm not only showed a more stable performance, but also yielded higher ROC-AUC and PRC-AUC scores, demonstrating its high accuracy in prediction of TiPN occurrence.
CONCLUSION
The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables. With the ability to identify high-risk patients using single nucleotide polymorphisms, it offers a feasible option for improving thalidomide efficacy in CD patients.
Topics: Humans; Thalidomide; Crohn Disease; Brain-Derived Neurotrophic Factor; East Asian People; Retrospective Studies; Peripheral Nervous System Diseases; Machine Learning
PubMed: 37426324
DOI: 10.3748/wjg.v29.i24.3855 -
Fukushima Journal of Medical Science Apr 2022Pancreatic cancer (PC) is a lethal disease where most tumors are too advanced at diagnosis for resection, leaving chemotherapy as the mainstay of treatment. Although the... (Review)
Review
Pancreatic cancer (PC) is a lethal disease where most tumors are too advanced at diagnosis for resection, leaving chemotherapy as the mainstay of treatment. Although the prognosis of unresectable PC is poor, it has been dramatically improved by new chemotherapy treatments, such as the combination of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel. However, as oxaliplatin and paclitaxel are common neurotoxic drugs, chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe adverse effect of both treatments. As there are no agents recommended in the ASCO guidelines, we review the methods used to treat CIPN caused by PC treatment. The efficacy of duloxetine was observed in a large randomized controlled trial (RCT). In addition, pregabalin was more effective than duloxetine for CIPN in two RCTs. Although duloxetine and pregabalin can be effective for CIPN, they have several side effects. Therefore, the choice between the two drugs should be determined according to effect and tolerability. Mirogabalin is also used in patients with PC and there is hope it will yield positive outcomes when treating CIPN in the future.
Topics: Antineoplastic Agents; Duloxetine Hydrochloride; Humans; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Peripheral Nervous System Diseases; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 35197393
DOI: 10.5387/fms.2021-32 -
Neurotoxicology May 2017The mechanism of toxicity of hydrogen sulfide (HS) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether...
The mechanism of toxicity of hydrogen sulfide (HS) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether chronic exposure causes effects, including peripheral neuropathy, is yet unclear. The city of Rotorua, New Zealand, sits on an active geothermal field and the population has some of the highest measured ambient HS exposures. A previous study in Rotorua provided evidence that HS is associated with peripheral neuropathy. Using clinical methods, the present study sought to investigate and possibly confirm this association in the Rotorua population. The study population comprised 1635 adult residents of Rotorua, aged 18-65. Collected data relevant to the peripheral neuropathy investigation included symptoms, ankle stretch reflex, vibration sensitivity, as measured by the timed-tuning fork test and a Bio-Thesiometer (Bio-Medical Instrument Co., Ohio), and light touch sensitivity measured by monofilaments. An exposure metric, estimating time-weighted HS exposure across the last 30 years was used. Principal components analysis was used to combine data across the various indicators of possible peripheral neuropathy. The main data analysis used linear regression to examine associations between the peripheral nerve function indicators and HS exposure. None of the peripheral nerve function indicators were associated with HS exposure, providing no evidence that HS exposure at levels found in Rotorua is a cause of peripheral neuropathy. The earlier association between HS exposure and peripheral neuropathy diagnoses may be attributable to the ecological study design used. The possibility that HS exposure misclassification could account for the lack of association found cannot be entirely excluded.
Topics: Adolescent; Adult; Aged; Environmental Exposure; Humans; Hydrogen Sulfide; Middle Aged; New Zealand; Peripheral Nervous System Diseases; Young Adult
PubMed: 28223159
DOI: 10.1016/j.neuro.2017.02.006 -
Scientific Reports Jun 2022This work aimed to determine the incidence density of taxane-induced peripheral neuropathy (TIPN) and its risk factors among women with breast cancer. One hundred and...
This work aimed to determine the incidence density of taxane-induced peripheral neuropathy (TIPN) and its risk factors among women with breast cancer. One hundred and forty-one women with breast cancer participated in this cohort study. TIPN symptoms were evaluated with the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20) at five-time points throughout chemotherapy treatment. Over three months, 125 (89%) and 59 (44.03%) women with breast cancer were identified with sensory and motor neuropathy, respectively. The sensory neuropathy incidence density was 21 per 1000 person-days. The motor neuropathy incidence density was 6 per 1000 person-days. This study discovered a significant link between age and the incidence density of sensory neuropathy (HR = 1.02; 95% CI: 1.01-1.05) as well as motor neuropathy (HR = 1.05; 95% CI: 1.01-1.08). These findings imply that screening may be necessary to detect early TIPN symptoms and provide appropriate rehabilitation programs, particularly for elderly persons.
Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Cohort Studies; Female; Humans; Incidence; Peripheral Nervous System Diseases; Quality of Life; Taxoids
PubMed: 35739233
DOI: 10.1038/s41598-022-14870-y -
The Review of Diabetic Studies : RDS 2015Diabetic peripheral neuropathies (DPN) are a heterogeneous group of disorders caused by neuronal dysfunction in patients with diabetes. They have differing clinical... (Review)
Review
Diabetic peripheral neuropathies (DPN) are a heterogeneous group of disorders caused by neuronal dysfunction in patients with diabetes. They have differing clinical courses, distributions, fiber involvement (large or small), and pathophysiology. These complications are associated with increased morbidity, distress, and healthcare costs. Approximately 50% of patients with diabetes develop peripheral neuropathy, and the projected rise in the global burden of diabetes is spurring an increase in neuropathy. Distal symmetrical polyneuropathy (DSPN) with painful diabetic neuropathy, occurring in around 20% of diabetes patients, and diabetic autonomic neuropathy (DAN) are the most common manifestations of DPN. Optimal glucose control represents the only broadly accepted therapeutic option though evidence of its benefit in type 2 diabetes is unclear. A number of symptomatic treatments are recommended in clinical guidelines for the management of painful DPN, including antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids, and topical agents such as capsaicin. However, monotherapy is frequently not effective in achieving complete resolution of pain in DPN. There is a growing need for head-to-head studies of different single-drug and combination pharmacotherapies. Due to the ubiquity of autonomic innervation in the body, DAN causes a plethora of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. The current treatment of DAN is largely symptomatic, and does not correct the underlying autonomic nerve deficit. A number of novel potential candidates, including erythropoietin analogues, angiotensin II receptor type 2 antagonists, and sodium channel blockers are currently being evaluated in phase II clinical trials.
Topics: Autonomic Nervous System Diseases; Diabetic Neuropathies; Humans; Peripheral Nervous System Diseases
PubMed: 26676662
DOI: 10.1900/RDS.2015.12.63