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International Journal of Molecular... Nov 2022This study aimed to elucidate the pathomechanism of peripheral neuropathy (PN) in microscopic polyangiitis (MPA) and to identify biomarkers useful for diagnosis and...
This study aimed to elucidate the pathomechanism of peripheral neuropathy (PN) in microscopic polyangiitis (MPA) and to identify biomarkers useful for diagnosis and severity assessment. Patients with MPA ( = 37) and other non-inflammatory neurological diseases (ONDs; = 12) were enrolled, and the peripheral nerves of all patients were evaluated using nerve conduction studies. We compared the clinical characteristics and 14 serum biomarker profiles among patients with MPA and PN, MPA without PN, and ONDs. Patients with MPA had a higher prevalence of motor neuropathy than patients with ONDs. Among the patients with MPA, those with motor neuropathy had significantly higher total Birmingham Vasculitis Activity Scores and serum levels of C-reactive protein (CRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and interleukin-6 than patients without motor neuropathy. Multivariable analyses adjusted for age, serum CRP level, and diabetes mellitus showed that high serum levels of TIMP-1 were independently related to a diagnosis of motor neuropathy in MPA. Additionally, there were significant negative correlations between the serum levels of TIMP-1 and compound muscle action potential amplitudes. Serum levels of TIMP-1 may be associated with the pathomechanism of motor neuropathy in MPA and could be a useful biomarker for diagnosing and evaluating the severity of motor neuropathy in MPA.
Topics: Humans; Microscopic Polyangiitis; Tissue Inhibitor of Metalloproteinase-1; Peripheral Nervous System Diseases; Biomarkers; C-Reactive Protein
PubMed: 36362162
DOI: 10.3390/ijms232113374 -
Journal of Diabetes Investigation Sep 2020Burning and stabbing pain in the feet and lower limbs can have a significant impact on the activities of daily living, including walking, climbing stairs and sleeping.... (Review)
Review
Burning and stabbing pain in the feet and lower limbs can have a significant impact on the activities of daily living, including walking, climbing stairs and sleeping. Peripheral neuropathy in particular is often misdiagnosed or underdiagnosed because of a lack of awareness amongst both patients and physicians. Furthermore, crude screening tools, such as the 10-g monofilament, only detect advanced neuropathy and a normal test will lead to false reassurance of those with small fiber mediated painful neuropathy. The underestimation of peripheral neuropathy is highly prevalent in the South-East Asia region due to a lack of consensus guidance on routine screening and diagnostic pathways. Although neuropathy as a result of diabetes is the most common cause in the region, other causes due to infections (human immunodeficiency virus, hepatitis B or C virus), chronic inflammatory demyelinating polyneuropathy, drug-induced neuropathy (cancer chemotherapy, antiretrovirals and antituberculous drugs) and vitamin deficiencies (vitamin B , B , B , D) should be actively excluded.
Topics: Asia, Southeastern; Diabetic Neuropathies; Humans; Peripheral Nervous System Diseases; Prognosis
PubMed: 32268012
DOI: 10.1111/jdi.13269 -
Ginekologia Polska 2016Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent neurologic complications experienced by patients receiving antineoplastic drugs.... (Review)
Review
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent neurologic complications experienced by patients receiving antineoplastic drugs. Involvement of the peripheral nerves may have an important impact on daily activi-ties and lead to severe impairment of the patient's quality of life (QoL). It seems to be of crucial importance to make a correct and early diagnosis of polyneuropathy and, if possible, spare the patient unnecessary suffering or loss of function. In the preceding article we have presented epidemiology, grading and pathogenesis of the toxic CIPN. The purpose of this article is to review current knowledge of diagnostic techniques, prevention and management strategies in the context of CIPN.
Topics: Antineoplastic Agents; Disease Management; Female; Humans; Peripheral Nervous System Diseases
PubMed: 27504945
DOI: 10.5603/GP.2016.0036 -
Cancer Research Jul 2020For the constellation of neurologic disorders known as chemotherapy-induced peripheral neuropathy, mechanistic understanding and treatment remain deficient. Here, we...
For the constellation of neurologic disorders known as chemotherapy-induced peripheral neuropathy, mechanistic understanding and treatment remain deficient. Here, we present the first evidence that chronic sensory neuropathy depends on nonlinear interactions between cancer and chemotherapy. Global transcriptional profiling of dorsal root ganglia revealed differential expression, notably in regulators of neuronal excitability, metabolism, and inflammatory responses, all of which were unpredictable from effects observed with either chemotherapy or cancer alone. Systemic interactions between cancer and chemotherapy also determined the extent of deficits in sensory encoding and ion channel protein expression by single mechanosensory neurons, with the potassium ion channel Kv3.3 emerging as one potential contributor to sensory neuron dysfunction. Validated measures of sensorimotor behavior in awake, behaving animals revealed dysfunction after chronic chemotherapy treatment was exacerbated by cancer. Notably, errors in precise forelimb placement emerged as a novel behavioral deficit unpredicted by our previous study of chemotherapy alone. These original findings identify novel contributors to peripheral neuropathy and emphasize the fundamental dependence of neuropathy on the systemic interaction between chemotherapy and cancer. SIGNIFICANCE: These findings highlight the need to account for pathobiological interactions between cancer and chemotherapy as a major contributor to neuropathy and will have significant and immediate impact on future investigations in this field.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Colorectal Neoplasms; Disease Models, Animal; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Male; Oxaliplatin; Peripheral Nervous System Diseases; Rats; Rats, Inbred F344; Sensory Receptor Cells
PubMed: 32345673
DOI: 10.1158/0008-5472.CAN-19-2331 -
Muscle & Nerve Feb 2023Repair of genomic DNA is a fundamental housekeeping process that quietly maintains the health of our genomes. The consequences of a genetic defect affecting a component... (Review)
Review
Repair of genomic DNA is a fundamental housekeeping process that quietly maintains the health of our genomes. The consequences of a genetic defect affecting a component of this delicate mechanism are quite harmful, characterized by a cascade of premature aging that injures a variety of organs, including the nervous system. One part of the nervous system that is impaired in certain DNA repair disorders is the peripheral nerve. Chronic motor, sensory, and sensorimotor polyneuropathies have all been observed in affected individuals, with specific physiologies associated with different categories of DNA repair disorders. Cockayne syndrome has classically been linked to demyelinating polyneuropathies, whereas xeroderma pigmentosum has long been associated with axonal polyneuropathies. Three additional recessive DNA repair disorders are associated with neuropathies, including trichothiodystrophy, Werner syndrome, and ataxia-telangiectasia. Although plausible biological explanations exist for why the peripheral nerves are specifically vulnerable to impairments of DNA repair, specific mechanisms such as oxidative stress remain largely unexplored in this context, and bear further study. It is also unclear why different DNA repair disorders manifest with different types of neuropathy, and why neuropathy is not universally present in those diseases. Longitudinal physiological monitoring of these neuropathies with serial electrodiagnostic studies may provide valuable noninvasive outcome data in the context of future natural history studies, and thus the responses of these neuropathies may become sentinel outcome measures for future clinical trials of treatments currently in development such as adeno-associated virus gene replacement therapies.
Topics: Humans; Peripheral Nervous System Diseases; DNA Repair; Xeroderma Pigmentosum; Cockayne Syndrome; Polyneuropathies
PubMed: 36190439
DOI: 10.1002/mus.27721 -
International Journal of Molecular... Dec 2020Chemotherapy-induced peripheral neuropathy (CIPN), one of major dose-limiting side effects of first-line chemotherapeutic agents such as paclitaxel, oxaliplatin,... (Review)
Review
Chemotherapy-induced peripheral neuropathy (CIPN), one of major dose-limiting side effects of first-line chemotherapeutic agents such as paclitaxel, oxaliplatin, vincristine, and bortezomib is resistant to most of existing medicines. The molecular mechanisms of CIPN have not been fully understood. High mobility group box 1 (HMGB1), a nuclear protein, is a damage-associated molecular pattern protein now considered to function as a pro-nociceptive mediator once released to the extracellular space. Most interestingly, HMGB1 plays a key role in the development of CIPN. Soluble thrombomodulin (TMα), known to degrade HMGB1 in a thrombin-dependent manner, prevents CIPN in rodents treated with paclitaxel, oxaliplatin, or vincristine and in patients with colorectal cancer undergoing oxaliplatin-based chemotherapy. In this review, we describe the role of HMGB1 and its upstream/downstream mechanisms in the development of CIPN and show drug candidates that inhibit the HMGB1 pathway, possibly useful for prevention of CIPN.
Topics: Animals; Antineoplastic Agents; HMGB1 Protein; Humans; Neoplasms; Pain; Peripheral Nervous System Diseases
PubMed: 33396481
DOI: 10.3390/ijms22010367 -
Brain : a Journal of Neurology Jan 2023Peripheral neuropathy is a common problem in patients with Parkinson's disease. Peripheral neuropathy's prevalence in Parkinson's disease varies between 4.8-55%,...
Peripheral neuropathy is a common problem in patients with Parkinson's disease. Peripheral neuropathy's prevalence in Parkinson's disease varies between 4.8-55%, compared with 9% in the general population. It remains unclear whether peripheral neuropathy leads to decreased motor performance in Parkinson's disease, resulting in impaired mobility and increased balance deficits. We aimed to determine the prevalence and type of peripheral neuropathy in Parkinson's disease patients and evaluate its functional impact on gait and balance. A cohort of consecutive Parkinson's disease patients assessed by movement disorders specialists based on the UK Brain Bank criteria underwent clinical, neurophysiological (nerve conduction studies and quantitative sensory testing) and neuropathological (intraepidermal nerve fibre density in skin biopsy punches) evaluation to characterize the peripheral neuropathy type and aetiology using a cross-sectional design. Gait and balance were characterized using wearable health-technology in OFF and ON medication states, and the main parameters were extracted using validated algorithms. A total of 99 Parkinson's disease participants with a mean age of 67.2 (±10) years and mean disease duration of 6.5 (±5) years were assessed. Based on a comprehensive clinical, neurophysiological and neuropathological evaluation, we found that 40.4% of Parkinson's disease patients presented peripheral neuropathy, with a predominance of small fibre neuropathy (70% of the group). In the OFF state, the presence of peripheral neuropathy was significantly associated with shorter stride length (P = 0.029), slower gait speed (P = 0.005) and smaller toe-off angles (P = 0.002) during straight walking; significantly slower speed (P = 0.019) and smaller toe-off angles (P = 0.007) were also observed during circular walking. In the ON state, the above effects remained, albeit moderately reduced. With regard to balance, significant differences between Parkinson's disease patients with and without peripheral neuropathy were observed in the OFF medication state during stance with closed eyes on a foam surface. In the ON states, these differences were no longer observable. We showed that peripheral neuropathy is common in Parkinson's disease and influences gait and balance parameters, as measured with mobile health-technology. Our study supports that peripheral neuropathy recognition and directed treatment should be pursued in order to improve gait in Parkinson's disease patients and minimize balance-related disability, targeting individualized medical care.
Topics: Humans; Aged; Parkinson Disease; Cross-Sectional Studies; Prevalence; Gait; Peripheral Nervous System Diseases; Gait Disorders, Neurologic; Postural Balance
PubMed: 35088837
DOI: 10.1093/brain/awac026 -
BMC Cancer Nov 2023Current chemotherapy-induced peripheral neuropathy (CIPN) assessment tools mostly have poor sensitivity and weak anti-interference, so that it is sometimes difficult to...
BACKGROUND
Current chemotherapy-induced peripheral neuropathy (CIPN) assessment tools mostly have poor sensitivity and weak anti-interference, so that it is sometimes difficult to provide substantive guidance for clinical intervention. This study aimed to develop an assessment tool dedicated for oxaliplatin to address these limitations.
METHODS
This study screened 445 OIPN-related literatures for producing a symptom list, and developed the questionnaire module through expert supplement, item generation, content correlation analysis, pre-testing, and item improvement. The validation phase used a Chinese population-based prospective cohort study from June 2021 to July 2022. Patients were requested to complete the tested questionnaire, QLQ-CIPN20 and the CTCAE grading one day before cycles 2-6 of chemotherapy. Cronbach's α coefficient and intraclass correlation coefficient (ICC) were calculated for the internal consistency and stability analysis, respectively. Exploratory factor analysis was conducted to investigate the construct validity. The correlations among the tested questionnaire, QLQ-CIPN20 and CTCAE were compared for the criterion validity analysis. Wilcoxon signed-rank sum test was utilized to compare the sensitivity between the tested questionnaire and QLQ-CIPN20.
RESULT
A 20-item CIPN assessment tool named chemotherapy-induced peripheral neuropathy integrated assessment - oxaliplatin subscale (CIPNIA-OS) was developed. The validation phase included 186 patients. Cronbach's α coefficient of CIPNIA-OS was 0.764 (> 0.7), and ICC was 0.997 (between 0.9 and 1). The structure of CIPNIA-OS containing seven factors was examined. The correlation coefficient between CIPNIA-OS and CTCAE was 0.661 (95%CI 0.623 to 0.695), which was significantly higher than that between QLQ-CIPN20 and CTCAE (0.417, 95%CI 0.363 to 0.469, p < 0.01). Besides, the total score of CIPNIA-OS was mostly higher than QLQ-CIPN20, with an average difference of 2.189 (CI 95% 2.056 to 2.322), and the difference gradually expanded with the progress of chemotherapy (p < 0.05).
CONCLUSION
This study developed an original CIPN questionnaire which was dedicated for OIPN assessment. It was a comprehensive tool that covered acute OIPN symptoms and integrated features from several proven CIPN assessment tools. The validation results supported that CIPNIA-OS had satisfactory reliability, stability, construct, criterion validity, and was more accuracy and sensitive than QLQ-CIPN20 in the evaluation of OIPN.
Topics: Humans; Oxaliplatin; Antineoplastic Agents; Neoplasms; Reproducibility of Results; Prospective Studies; Quality of Life; Peripheral Nervous System Diseases
PubMed: 37964212
DOI: 10.1186/s12885-023-11541-7 -
Revista Da Associacao Medica Brasileira... Feb 2019Peripheral neuropathy is a disorder that affects the cell body, axon or myelin of motor or peripheral sensory neurons and occurs in 60-100% of patients who are submitted... (Review)
Review
INTRODUCTION
Peripheral neuropathy is a disorder that affects the cell body, axon or myelin of motor or peripheral sensory neurons and occurs in 60-100% of patients who are submitted to dialysis due to chronic kidney disease. Uremic neuropathy is attributed to the accumulation of organic waste, evident in patients with reduced glomerular filtration rate.
OBJECTIVES
This review aims to make clinical characteristics of uremic neuropathy evident enabling early diagnosis and treatment.
METHODS
This is a literature review of articles published on PubMed over the last 10 years using "Uremic Neuropathy" as "Title/Abstract".
RESULTS
A total of nine articles that met the inclusion criteria were included. UN is a distal symmetric sensorimotor polyneuropathy that occurs due to the accumulation of uremic toxins associated with an oxidative stress-related free radical activity. Hyperkalemia is thought to play an important role in its pathophysiology. Diagnosis depends on nerve conduction studies, and treatment includes dialysis or renal transplant.
CONCLUSION
Clinical presentations of UN are broad and non-specific; nonetheless, it is important to detect early changes in order to avoid its progression. The earlier UN is diagnosed and treated, the more successful are the clinical outcomes.
Topics: Humans; Kidney Transplantation; Peripheral Nervous System Diseases; Renal Dialysis; Uremia
PubMed: 30892456
DOI: 10.1590/1806-9282.65.2.281 -
Journal of Palliative Medicine Jun 2022Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment with no effective preventative strategy or definitive... (Review)
Review
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment with no effective preventative strategy or definitive treatment. To synthesize empiric literature from randomized controlled trials (RCTs) of pharmacological and nonpharmacological management of CIPN. Articles published between January 1, 2010, and February 28, 2021, were identified using keywords searching Medline, PubMed, CINAHL, Web of Science, Cochrane Library, and Embase. RCTs that recruited individuals who were post-chemotherapy and experienced persistent CIPN symptoms. Three independent reviewers screened a total of 2023 abstracts. After screening, full-text review, and quality appraisal, 22 articles were included in this review. Data related to study design, participant characteristics, interventions, controls, outcome measures, and relevant findings were extracted from full texts. Descriptive quantitative summaries were calculated and narrative analysis was performed. Of the 22 studies, 4 investigated pharmacologic treatments, 2 compared acupuncture to pharmacologic treatments, and 16 studies examined nonpharmacologic treatments. Pharmacologic studies reported mixed results with evidence of participant response varying by history of chemotherapeutic agent. Acupuncture, exercise/physical therapy, and neurofeedback appear to be effective treatments for CIPN. Evidence regarding biophysical agents and cognitive-behavioral therapy is equivocal. Scrambler therapy is not supported. Studies included in this review share several limitations, including widely variable outcome measures, small and demographically homogenous samples, and nonstandardized treatment protocols. This scoping review summarized the current body of high-quality RCTs investigating treatment for CIPN. The majority of studies in this review reports benefits of pharmacologic and nonpharmacologic interventions, although management may require a multipronged approach and should be tailored to the individual. Clinical implications are proposed and suggestions made for future research include implementation of standardized intervention protocols, use of outcome measures representative of the spectrum of CIPN symptoms, and stratification by the chemotherapeutic agent.
Topics: Acupuncture Therapy; Antineoplastic Agents; Drug-Related Side Effects and Adverse Reactions; Humans; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic
PubMed: 35128938
DOI: 10.1089/jpm.2021.0512