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Neuroscience Letters Jan 2021Neurons are polarized cells whose fundamental functions are to receive, conduct and transmit signals. In bilateral animals, the nervous system is divided into the... (Review)
Review
Neurons are polarized cells whose fundamental functions are to receive, conduct and transmit signals. In bilateral animals, the nervous system is divided into the central (CNS) and peripheral (PNS) nervous system. The main function of the PNS is to connect the CNS to the limbs and organs, essentially serving as a relay between the brain and spinal cord and the rest of the body. Sensory axons can be up to 3 feet in length. Because of its long-reaching and complex structure, the peripheral nervous system (PNS) is exposed and vulnerable to many genetic, metabolic and environmental predispositions. Lipids and lipid intermediates are essential components of nerves. About 50 % of the brain dry weight consist of lipids, which makes it the second highest lipid rich tissue after adipose tissue. However, the role of lipids in neurological disorders in particular of the peripheral nerves is not well understood. This review aims to provide an overview about the role of lipids in the disorders of the PNS.
Topics: Animals; Humans; Lipid Metabolism; Lipids; Neurons; Peripheral Nervous System; Peripheral Nervous System Diseases
PubMed: 33166639
DOI: 10.1016/j.neulet.2020.135455 -
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 -
Magyar Onkologia Jun 2016Longer remissions and better overall survival rates can be achieved with the introduction of new, effective treatments and targeted therapies in the past 1-2 decades,... (Review)
Review
Longer remissions and better overall survival rates can be achieved with the introduction of new, effective treatments and targeted therapies in the past 1-2 decades, however, the incidence of side effects is also increasing parallelly. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially debilitating side effect due to peripheral somatic or autonomic nerve dysfunction. CIPN becomes increasingly important, as it affects patients' quality of life, and it is very often a dose limiting factor with the potential for reduced treatment efficacy. The pathomechanism, diagnosis, prevention and treatment possibilities are described in this review with special attention to the different groups of drugs.
Topics: Antineoplastic Agents; Humans; Incidence; Neoplasms; Peripheral Nervous System Diseases; Quality of Life
PubMed: 27275643
DOI: No ID Found -
BMJ Open Sep 2023Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects of chemotherapeutic drugs. Numerous clinical trials of various...
Efficacy and safety of drug therapy for the prevention and treatment of chemotherapy-induced peripheral neuropathy: a protocol for a systematic review and network meta-analysis.
INTRODUCTION
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects of chemotherapeutic drugs. Numerous clinical trials of various targeted drugs for the prevention or treatment of CIPN have been conducted; however, previous systematic reviews with direct comparisons have failed to demonstrate the efficacy of these drugs in the prevention or treatment of CIPN. In addition, no systematic reviews have indirectly compared CIPN prevention and treatment. This article describes a protocol for evaluating the efficacy and safety of drug therapy for the prevention and treatment of CIPN. The results of the proposed systematic review with network meta-analysis (NMA) will provide new insights into the prevention and treatment of CIPN.
METHODS AND ANALYSIS
We will conduct a literature search in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov to find relevant articles published through January 2023. We will include studies that investigated the efficacy and safety of vitamin B, goshajinkigan, non-steroidal anti-inflammatory analgesics, opioids, calcium and magnesium, antidepressants and anticonvulsants on CIPN. Two authors will individually screen the retrieved reports and review the full text based on the selection criteria. The primary outcome is the incidence and severity of CIPN. The risk of bias will be assessed using V.2.0 of the Cochrane risk-of-bias tool. We will apply a frequentist random-effects NMA model to pool effect sizes across trials using risk ratios and mean differences with their 95% CIs. Competing interventions will be ranked using the surface under cumulative ranking probabilities. Heterogeneity will be assessed using the heterogeneity variance τ, Cochran's Q test and I² statistic.
ETHICS AND DISSEMINATION
This review does not require ethical approval. The research will be published in a peer-reviewed journal.
PROSPERO REGISTRATION NUMBER
CRD42022371829.
Topics: Humans; Network Meta-Analysis; Systematic Reviews as Topic; Drug-Related Side Effects and Adverse Reactions; Peripheral Nervous System Diseases; Antineoplastic Agents; Meta-Analysis as Topic; Review Literature as Topic
PubMed: 37699621
DOI: 10.1136/bmjopen-2022-070645 -
Patient Education and Counseling Sep 2019To describe the frequency and characteristics of chemotherapy-induced peripheral neuropathy (CIPN) assessment and management communication approaches between patients... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To describe the frequency and characteristics of chemotherapy-induced peripheral neuropathy (CIPN) assessment and management communication approaches between patients receiving neurotoxic chemotherapy and clinicians.
METHODS
The data used in this analysis originated from a randomized controlled trial in which adults with cancer self-reported treatment-related symptoms using web-based symptom assessment technology. Three-to-six weeks after study initiation, each participant's outpatient visit was audio-recorded. Audio recordings and associated clinician notes for 159 participants who received platinum and/or taxane-based chemotherapy were coded for the presence of several CIPN assessment and management communication characteristics.
RESULTS
Participants received low cumulative neurotoxic chemotherapy doses (75%) at the time of audio recording. CIPN was discussed and documented in 44% and 46% of participant-clinician encounters. In symptomatic participants, clinicians asked an average of 0.7 open-ended questions, appropriately managed 70% of cases, and asked upper and lower extremity CIPN questions in 25% of cases.
CONCLUSIONS
Clinicians infrequently discussed and documented CIPN in participants with low CIPN severity, however appropriately managed mild CIPN. Development of interventions to translate existing recommended CIPN communication approaches into practice are required.
PRACTICE IMPLICATIONS
Effective participant-clinician communication is required at each clinic visit during chemotherapy treatment to identify initial signs of CIPN and offer appropriate treatment.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Communication; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Physician-Patient Relations; Quality of Life
PubMed: 31003878
DOI: 10.1016/j.pec.2019.04.012 -
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 -
Experimental Neurology Apr 2020Neuronal cell cultures have been used as an essential tool for studying pathomechanisms of toxicity of chemotherapeutic drugs and to develop neuroprotective approaches.... (Review)
Review
Neuronal cell cultures have been used as an essential tool for studying pathomechanisms of toxicity of chemotherapeutic drugs and to develop neuroprotective approaches. They offer the opportunity to dissect disease mechanisms and molecular pathways while allowing precise control of a variety of confounding factors of the physio-chemical environment. As such, a growing number of in vitro studies are published each year to decipher mechanisms of neurotoxicity of taxanes, vinca alcaloids, proteasome inhibitors and platin derivatives and/or to test neuroprotective strategies. Here, we provide a review of cell culture techniques and outcome measures that have been used in the past or are currently employed to model chemotherapy induced neuropathy in vitro. Furthermore, we discuss their advantages as well as their limitations and ways to enhance efficiency and reproducibility of cell culture studies in the field of toxic neuropathy.
Topics: Animals; Antineoplastic Agents; Cell Line; Cells, Cultured; Humans; In Vitro Techniques; Neurotoxicity Syndromes; Peripheral Nervous System Diseases
PubMed: 31812556
DOI: 10.1016/j.expneurol.2019.113140 -
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 -
BioMed Research International 2014The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy in patients with systemic lupus erythematosus (SLE) and nephritis (SLE-LN) remain...
BACKGROUND AND AIM
The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy in patients with systemic lupus erythematosus (SLE) and nephritis (SLE-LN) remain unsatisfactory. This study aimed to determine the autoantibodies levels in SLE-LN patients with peripheral neuropathy.
METHODS
Data of 559 SLE-LN patients were collected retrospectively, including titers of autoantibodies, electrodiagnostic studies, and clinical manifestations.
RESULTS
The neurologic manifestations of the SLE-LN patients were diverse and nonspecific. The prevalence rate of peripheral polyneuropathy was 2.68%, of which about 73.33% was mixed sensory-motor polyneuropathy. Numbness and functional gastrointestinal problems were the most prevalent symptoms and these were noted in every subtype of peripheral neuropathy. Among all the serology markers, anti-Ro was significantly associated with neuropathy related to SLE (P = 0.009).
CONCLUSION
Peripheral neuropathy among LN patients is rare and may be easily overlooked. This study demonstrated that positive anti-Ro antibody may imply neuropathy in LN patients. Thus, anti-Ro can be considered a biomarker that should be added to the panel of conventional autoantibodies in LN patients.
Topics: Adult; Autoantibodies; Demography; Diabetes Complications; Female; Humans; Lupus Nephritis; Male; Middle Aged; Peripheral Nervous System Diseases
PubMed: 24864250
DOI: 10.1155/2014/524940 -
Journal of Cancer Survivorship :... Apr 2021To gain more insight into the course of chemotherapy-induced peripheral neuropathy (CIPN) and its impact on health-related quality of life (HRQoL) in a population-based...
PURPOSE
To gain more insight into the course of chemotherapy-induced peripheral neuropathy (CIPN) and its impact on health-related quality of life (HRQoL) in a population-based sample of colorectal cancer (CRC) patients up to 2 years after diagnosis.
METHODS
All newly diagnosed CRC patients from four hospitals in the Netherlands were eligible for participation in an ongoing prospective cohort study. Patients (n = 340) completed questions on CIPN (EORTC QLQ-CIPN20) and HRQoL (EORTC QLQ-C30) before initial treatment (baseline) and 1 and 2 years after diagnosis.
RESULTS
Among chemotherapy-treated patients (n = 105), a high sensory peripheral neuropathy (SPN) level was reported by 57% of patients at 1 year, and 47% at 2-year follow-up, whereas a high motor peripheral neuropathy (MPN) level was reported by 47% and 28%, at years 1 and 2, respectively. Linear mixed model analyses showed that SPN and MPN symptoms significantly increased from baseline to 1-year follow-up and did not return to baseline level after 2 years. Patients with a high SPN or MPN level reported a worse global quality of life and a worse physical, role, emotional, cognitive, and social functioning compared with those with a low SPN or MPN level.
CONCLUSIONS
Future studies should focus on understanding the mechanisms underlying CIPN so targeted interventions can be developed to reduce the impact of CIPN on patient's lives.
IMPLICATIONS FOR CANCER SURVIVORS
Patients need to be informed of both CIPN and the impact on HRQoL.
Topics: Antineoplastic Agents; Colorectal Neoplasms; Humans; Peripheral Nervous System Diseases; Prospective Studies; Quality of Life; Surveys and Questionnaires
PubMed: 33185839
DOI: 10.1007/s11764-020-00923-6