RESUMEN
Peripheral neuropathies of the foot and ankle can be challenging to diagnose clinically due to concomitant traumatic and nontraumatic or degenerative orthopedic conditions. Although clinical history, physical examination, and electrodiagnostic testing comprised of nerve conduction velocities and electromyography are used primarily for the identification and classification of peripheral nerve disorders, MR neurography (MRN) can be used to visualize the peripheral nerves as well as the skeletal muscles of the foot and ankle for primary neurogenic pathology and skeletal muscle denervation effect. Proper knowledge of the anatomy and pathophysiology of peripheral nerves is important for an MRN interpretation.
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Tobillo , Pie , Imagen por Resonancia Magnética , Enfermedades del Sistema Nervioso Periférico , Humanos , Imagen por Resonancia Magnética/métodos , Enfermedades del Sistema Nervioso Periférico/diagnóstico por imagen , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Pie/diagnóstico por imagen , Pie/inervación , Tobillo/diagnóstico por imagen , Tobillo/inervación , Nervios Periféricos/diagnóstico por imagenRESUMEN
OBJECTIVE: To identify the prevalence and clinical features of leflunomide-associated peripheral neuropathy in patients with rheumatic disease over a 42-month observational period between January 1, 2016 and June 30, 2019. METHODS: A retrospective observational study was conducted using regional prescription data identifying all patients treated with leflunomide for rheumatic diseases in the Southern District Health Board of New Zealand. Medical records were used to identify patients who developed peripheral neuropathy while receiving treatment with leflunomide. Demographic characteristics, co-therapies, and additional risk factors for peripheral neuropathy were also recorded. RESULTS: A total of 482 patients were identified as receiving leflunomide for the treatment of rheumatic during the study period. In total, 23 patients developed leflunomide-induced peripheral neuropathy within the cohort giving a prevalence of 4.7%. Nerve conduction studies (NCS) performed in 18 (78.2%) of these patients confirmed a distal axonal, sensory, or sensorimotor peripheral neuropathy. The majority of patients (n = 22; 95.6%) either improved, stabilized, or resolved on cessation of the drug, with or without medication washout. Adverse symptoms were reported in association with peripheral neuropathy in 15 of the 23 patients (65.2%): these included pain, poor sleep, compromised skin integrity, poor balance, and a Charcot-like arthropathy. Additional treatment was required to manage symptoms of peripheral neuropathy including nine patients (39%) who received pain relief. CONCLUSIONS: This study supports the previously reported association between leflunomide treatment and the development of a peripheral neuropathy. However, our findings suggest that this is more common than the previous estimates. In patients with psoriatic arthritis and previous tarsitis, there appeared to be an association with a Charcot's-like arthropathy, a complication not previously noted in the literature.
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Antirreumáticos , Leflunamida , Enfermedades del Sistema Nervioso Periférico , Enfermedades Reumáticas , Humanos , Leflunamida/efectos adversos , Masculino , Femenino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Prevalencia , Nueva Zelanda/epidemiología , Anciano , Adulto , Antirreumáticos/efectos adversos , Factores de Riesgo , Factores de Tiempo , Conducción Nerviosa/efectos de los fármacosRESUMEN
BACKGROUND: Oxaliplatin, a major drug in metastatic colorectal cancer (mCRC), is responsible for cumulative, dose-limiting peripheral neuropathy (PN). Whether the hepatic arterial infusion (HAI) route can limit oxaliplatin-induced PN in comparison with the intravenous (IV) route has not been specifically explored so far. METHODS: We compared the frequency and severity of PN in oxaliplatin-naive patients with mCRC included in trials that evaluated treatment with oxaliplatin administered either by HAI (ACCORD 04, CHOICE, OSCAR, and PACHA-01 trials) or by IV route (FFCD 2000-05 trial). We retrieved anonymized, prospectively collected data from trial databases for the ACCORD 04, CHOICE, and FFCD 2000-05 trials and through a review of Gustave Roussy patients' electronic medical records for PACHA-01 and OSCAR trials. The primary endpoint was the incidence of clinically significant PN (grades 2 to 4) according to the cumulative dose of oxaliplatin received. Secondary endpoints were time to onset of neuropathy as a function of the cumulative dose of oxaliplatin, discontinuation of oxaliplatin for neurotoxicity, and safety. RESULTS: A total of 363 patients were included (IV, 300; HAI, 63). In total, 180 patients in the IV group (60%) and 30 patients in the HAI group (48%) developed clinically significant PN, with no significant difference between the two groups (p = 0.23). No difference was shown in the time to onset of PN either (p = 0.23). CONCLUSION: The administration of oxaliplatin HAI rather than IV in the treatment of mCRC does not reduce the incidence, precocity, and severity of PN.
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Antineoplásicos , Neoplasias Colorrectales , Arteria Hepática , Infusiones Intraarteriales , Compuestos Organoplatinos , Oxaliplatino , Enfermedades del Sistema Nervioso Periférico , Humanos , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Masculino , Femenino , Infusiones Intraarteriales/métodos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Persona de Mediana Edad , Infusiones Intravenosas , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Adulto , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Metástasis de la Neoplasia , Relación Dosis-Respuesta a DrogaRESUMEN
BACKGROUND: Peripheral neuropathy (PN) constitutes a dose-limiting side effect of oxaliplatin chemotherapy that often compromises the efficacy of antineoplastic treatments. Sensory neurons damage in dorsal root ganglia (DRG) are the cellular substrate of PN complex molecular origin. Dehydropeptidase-1 (DPEP1) inhibitors have shown to avoid platin-induced nephrotoxicity without compromising its anticancer efficiency. The objective of this study was to describe DPEP1 expression in rat DRG in health and in early stages of oxaliplatin toxicity. To this end, we produced and characterized anti-DPEP1 polyclonal antibodies and used them to define the expression, and cellular and subcellular localization of DPEP1 by immunohistochemical confocal microscopy studies in healthy controls and short term (six days) oxaliplatin treated rats. RESULTS: DPEP1 is expressed mostly in neurons and in glia, and to a lesser extent in endothelial cells. Rats undergoing oxaliplatin treatment developed allodynia. TNF-ð¼ expression in DRG revealed a pattern of focal and at different intensity levels of neural cell inflammatory damage, accompanied by slight variations in DPEP1 expression in endothelial cells and in nuclei of neurons. CONCLUSIONS: DPEP1 is expressed in neurons, glia and endothelial cells of DRG. Oxaliplatin caused allodynia in rats and increased TNF-α expression in DRG neurons. The expression of DPEP1 in neurons and other cells of DRG suggest this protein as a novel strategic molecular target in the prevention of oxaliplatin-induced acute neurotoxicity.
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Antineoplásicos , Ganglios Espinales , Oxaliplatino , Enfermedades del Sistema Nervioso Periférico , Animales , Oxaliplatino/toxicidad , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/metabolismo , Enfermedades del Sistema Nervioso Periférico/prevención & control , Enfermedades del Sistema Nervioso Periférico/patología , Masculino , Antineoplásicos/toxicidad , Ratas , Hiperalgesia/inducido químicamente , Hiperalgesia/metabolismo , Hiperalgesia/prevención & control , Factor de Necrosis Tumoral alfa/metabolismo , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Ratas Sprague-Dawley , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Inflamación/metabolismo , Inflamación/inducido químicamenteRESUMEN
OBJECTIVE: We assessed microvessel flow within peripheral nerves using nerve sonography in patients with peripheral neuropathy. METHODS: This study included consecutive patients with peripheral neuropathy who were admitted to our hospital. The patients were divided into two groups: inflammatory neuropathies for immune-mediated neuropathies, such as Guillain - Barré syndrome and chronic inflammatory demyelinating polyneuropathy, and the rest were defined as non-inflammatory neuropathies. We assessed nerve size and intraneural blood flow at four sites on each median and ulnar nerve. Blood flow was evaluated using color Doppler imaging, advanced dynamic flow (ADF), and superb microvascular imaging (SMI) techniques. RESULTS: Thirty-nine patients (median age, 60.0 years; 20 male) were enrolled in this study. An increase in intraneural blood flow was observed in five patients when evaluated by color Doppler, five patients by ADF, and 13 patients by SMI. An overall analysis of the three methods showed that intraneural blood flow was significantly higher in patients with inflammatory neuropathy than in those with non-inflammatory neuropathy (54.2% vs. 0%, p = 0.0005). CONCLUSIONS: Intraneural hypervascularization is more frequent in patients with inflammatory neuropathy than in those with non-inflammatory neuropathy. SIGNIFICANCE: Evaluation of microvessel flow within peripheral nerves may contribute to the diagnosis of peripheral neuropathy.
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Microvasos , Enfermedades del Sistema Nervioso Periférico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Microvasos/diagnóstico por imagen , Microvasos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico por imagen , Adulto , Ultrasonografía/métodos , Ultrasonografía Doppler en Color/métodos , Nervio Mediano/diagnóstico por imagen , Nervio Mediano/fisiopatología , Nervio Cubital/diagnóstico por imagen , Nervio Cubital/fisiopatología , Anciano de 80 o más AñosRESUMEN
Antibody-drug conjugates (ADCs) are among the fastest-growing classes of anticancer drugs, making it crucial to evaluate their potential for causing peripheral neuropathy. We analyzed data from the FAERS database (January 1, 2014, to June 30, 2023) using disproportionality and Bayesian methods. We identified 3076 cases of ADC-associated peripheral neuropathy. Our study revealed significant signals for all ADCs (ROR 1.82, 95% CI 1.76-1.89). ADCs with tubulin-binding payloads showed significant peripheral neuropathy signals (ROR 2.31, 95% CI 2.23-2.40), whereas those with DNA-targeting (ROR 0.48, 95% CI 0.39-0.59) and topoisomerase 1 inhibitor (ROR 0.56, 95% CI 0.48-0.66) payloads exhibited non-significant signals. Signals for peripheral sensory neuropathy were 4.83, 2.44, 2.74, and 2.21 (calculated based on IC025) for brentuximab vedotin, trastuzumab emtansine, enfortumab vedotin, and polatuzumab vedotin, while signals for peripheral motor neuropathy were 5.31, 0.34, 2.27, and 0.03, respectively. The median time to onset for all ADCs was 127 days (interquartile range 40-457). Tisotumab vedotin had the highest hospitalization rate at 26.67%, followed by brentuximab vedotin at 25.5%. Trastuzumab emtansine had the highest mortality rate ,with 80 deaths (11.96%) among 669 cases. Based on FAERS database, only ADCs with tubulin-binding payloads exhibited significant peripheral neuropathy signals. Brentuximab vedotin and enfortumab vedotin showed similar profiles for peripheral sensory neuropathy and motor neuropathy. Given the delayed time to onset and potentially poor outcomes, ADC-related peripheral neuropathy warrants significant attention.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Inmunoconjugados , Enfermedades del Sistema Nervioso Periférico , Farmacovigilancia , United States Food and Drug Administration , Humanos , Inmunoconjugados/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/epidemiología , Estados Unidos/epidemiología , Antineoplásicos/efectos adversos , Femenino , Masculino , Teorema de Bayes , Bases de Datos FactualesRESUMEN
Objective: Development of chemotherapy-induced peripheral neuropathy (CIPN) poses significant challenges in cancer treatment, often leading to dose reductions or treatment discontinuation. Goshajinkigan (GJG), a traditional Japanese medicine, has shown promise for alleviating CIPN symptoms. This multicenter, randomized controlled trial aimed to prospectively examine the efficacy of GJG in preventing paclitaxel-induced peripheral neuropathy. Methods: This study enrolled 55 patients with ovarian cancer undergoing first-line chemotherapy using paclitaxel and carboplatin. The participants were randomized into Groups A (GJG initiation after onset of grade 2 neuropathy) and B (prophylactic administration of GJG from 1 week before chemotherapy). The primary endpoints were the proportion with a maximum sensory neuropathy grade and visual analog scale (VAS) scores. The secondary endpoints were the rate of chemotherapy completion and paclitaxel dose reduction due to neurotoxicity. Results: Prophylactic GJG administration (Group B) resulted in significant benefits. While both groups had a similar incidence of grade 2 sensory neuropathy, all patients in Group B with grade 2 neuropathy completed treatment without requiring additional analgesics. Group B exhibited lower VAS scores by the end of the study, reduced reliance on adjuvant analgesics (27.3% vs 66.7% in Group A), and significantly less frequent persistent CIPN 6 months post-chemotherapy (18.2% vs 55.6% in Group A). No differences were observed in the chemotherapy completion rates or CIPN-related changes between the groups. Conclusion: GJG, when administered prophylactically, showed potential for mitigating CIPN symptoms during paclitaxel chemotherapy. While promising, further research with placebo controls and objective measures is essential to comprehensively validate these findings.
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Medicamentos Herbarios Chinos , Paclitaxel , Enfermedades del Sistema Nervioso Periférico , Humanos , Paclitaxel/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Femenino , Persona de Mediana Edad , Medicamentos Herbarios Chinos/uso terapéutico , Anciano , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Medicina Tradicional de Asia Oriental/métodos , Carboplatino/efectos adversos , Estudios Prospectivos , Pueblos del Este de AsiaRESUMEN
OBJECTIVE: To explore the lifestyle-related characteristics of people having type 2 diabetes mellitus with peripheral neuropathy. METHODS: The phenomenological study was conducted from July 5 to September 18, 2021, at Sadabuan Health Centre, Batunadua Health Centre and Wek 3 Health Centre, Padangsidimpuan, Indonesia, and comprised diabetic neuropathy patients who had cognitive impairment, anxiety and depression. Data was collected using in-depth interviews. Data was analysed using Collaizi's method. RESULTS: There were 8 subjects with mean age 48.38±13,606 years (range: 27-65 years), and mean duration of diabetes was 6±3.207 years. The majority of participants in this study were women 6 (75%). There were 7 themes that emerged from the collected data: level of physical activity, diet, sleep pattern, habit of consuming sweet drinks, smoking habit, social interaction, and self-care. CONCLUSIONS: Diabetes mellitus patient with peripheral neuropathy had not been able to completely switch to a healthier lifestyle.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Ejercicio Físico , Estilo de Vida , Humanos , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Adulto , Masculino , Neuropatías Diabéticas/psicología , Neuropatías Diabéticas/epidemiología , Indonesia/epidemiología , Anciano , Fumar/epidemiología , Fumar/psicología , Autocuidado/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Sueño , Depresión/epidemiología , Depresión/psicología , Dieta , Relaciones Interpersonales , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/psicología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Investigación CualitativaRESUMEN
BACKGROUND AND AIMS: Prior to next-generation sequencing (NGS), the evaluation of a patient with neuropathy typically consisted of screening for acquired causes, followed by clinical genetic testing of PMP22, MFN2, GJB1, and MPZ in patients with a positive family history and symptom onset prior to age 50. In this study, we examined the clinical utility of NGS in a large cohort of patients analyzed in a commercial laboratory. METHODS: A cohort of 6849 adult patients underwent clinician-ordered peripheral neuropathy multigene panel testing ranging from 66 to 111 genes that included NGS and intragenic deletion/duplication analysis. RESULTS: A molecular diagnosis was identified for 8.4% of the cohort (n = 573/6849). Variants in PMP22, MFN2, GJB1, MPZ, and TTR accounted for 73.8% of molecular diagnoses. Results had potential clinical actionability for 398 (69.5%) patients. Our results suggest that 225/573 (39.3%) of molecular diagnoses and 113/398 (28.4%) of clinical interventions would have been missed if the testing approach had been restricted to older guidelines. INTERPRETATION: Our results highlight the need for expanded genetic testing guidelines that account for the increased number of genes associated with hereditary neuropathy, address the overlap of acquired and hereditary neuropathy, and provide broader access to genetic diagnosis for patients.
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Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedades del Sistema Nervioso Periférico , Humanos , Pruebas Genéticas/normas , Pruebas Genéticas/métodos , Enfermedades del Sistema Nervioso Periférico/genética , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Adulto , Persona de Mediana Edad , Masculino , Femenino , Estudios de Cohortes , AncianoRESUMEN
BACKGROUND AND AIMS: Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), an intracellular bacillus that systematically invades the peripheral nerves. Diagnosing leprosy neuropathy is still a defying skill, and late diagnosis and treatment are still a reality. Based on the biological characteristics of M. leprae, particularly its preference for invading the Schwann cells localized at the coldest areas of human body, we hypothesized that these areas have focal demyelination that may escape detection through standard nerve conduction studies (NCSs) protocols. METHODS: Twenty-five patients with confirmed multibacillary leprosy and 14 controls were accessed. A multisegmented NCS protocol (MP) was performed, targeting short segments through the coldest areas, to identify focal areas of slowed conduction velocity. The effectiveness of this multisegmented protocol was compared to the standard protocol (SP) to detect abnormalities. RESULTS: All leprosy patients presented an abnormal study with the MP, contrasting to 19 with the SP. The most frequent NCS pattern was an asymmetric neuropathy with focal slowing of conduction velocity, found in 23 out of 25 leprosy patients. Significant differences favoring the proposed method were observed when comparing the MP with the SP. Notably, the MP increased the sensitivity to detect abnormalities by 122%, 133%, and 257% for the median, peroneal, and tibial nerves, respectively. MP also increases sensitivity to detect focal abnormalities in the ulnar nerve. INTERPRETATION: The MP protocol significantly increases the sensitivity of NCSs to detect neurophysiological abnormalities in leprosy neuropathy.
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Conducción Nerviosa , Humanos , Conducción Nerviosa/fisiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Lepra/fisiopatología , Lepra/complicaciones , Adulto Joven , Nervios Periféricos/fisiopatología , Lepra Multibacilar/fisiopatología , Lepra Multibacilar/diagnósticoRESUMEN
Immune checkpoint inhibitors have revolutionized cancer therapy and are increasingly used to treat a wide range of oncological conditions, with dramatic benefits for many patients. Unfortunately, the resulting increase in T cell effector function often results in immune-related adverse events (irAEs), which can involve any organ system, including the central nervous system (CNS) and peripheral nervous system (PNS). Neurological irAEs involve the PNS in two-thirds of affected patients. Muscle involvement (immune-related myopathy) is the most common PNS irAE and can be associated with neuromuscular junction involvement. Immune-related peripheral neuropathy most commonly takes the form of polyradiculoneuropathy or cranial neuropathies. Immune-related myopathy (with or without neuromuscular junction involvement) often occurs along with immune-related myocarditis, and this overlap syndrome is associated with substantially increased mortality. This Review focuses on PNS adverse events associated with immune checkpoint inhibition. Underlying pathophysiological mechanisms are discussed, including antigen homology between self and tumour, epitope spreading and activation of pre-existing autoreactive T cells. An overview of current approaches to clinical management is provided, including cytokine-directed therapies that aim to decouple anticancer immunity from autoimmunity and emerging treatments for patients with severe (life-threatening) presentations.
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Inhibidores de Puntos de Control Inmunológico , Enfermedades del Sistema Nervioso Periférico , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/inmunología , Enfermedades del Sistema Nervioso Periférico/terapia , Neoplasias/inmunología , Neoplasias/tratamiento farmacológicoRESUMEN
Cancer is the leading cause of disease-related death among children. Vincristine (VCR), a key component of childhood cancer treatment protocols, is associated with the risk of peripheral neuropathy (PN), a condition that may be reversible upon drug discontinuation but can also leave lasting sequelae. Single nucleotide polymorphism (SNP) in genes involved in VCR pharmacokinetics and pharmacodynamics have been investigated in relation to an increased risk of PN. However, the results of these studies have been inconsistent. A retrospective cohort study was conducted to investigate the potential association of drug transporter genes from the ATP-binding cassette (ABC) family and the centrosomal protein 72 (CEP72) gene with the development of PN in 88 Caucasian children diagnosed with cancer and treated with VCR. Genotyping was performed using real-time PCR techniques for the following SNPs: ABCB1 rs1128503, ABCC1 rs246240, ABCC2 rs717620, and CEP72 rs924607. The results indicated that age at diagnosis (OR = 1.33; 95% CI = 1.07-1.75) and the ABCC1 rs246240 G allele (OR = 12.48; 95% CI = 2.26-100.42) were associated with vincristine-induced peripheral neuropathy (VIPN). No association was found between this toxicity and CEP72 rs924607. Our study provides insights that may contribute to optimizing childhood cancer therapy in the future by predicting the risk of VIPN.
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Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Neoplasias , Enfermedades del Sistema Nervioso Periférico , Polimorfismo de Nucleótido Simple , Medicina de Precisión , Vincristina , Humanos , Vincristina/efectos adversos , Vincristina/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Niño , Femenino , Masculino , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Preescolar , Medicina de Precisión/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Adolescente , Estudios Retrospectivos , Proteínas de Ciclo Celular/genética , Lactante , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Predisposición Genética a la Enfermedad , Genotipo , Alelos , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Proteínas Asociadas a MicrotúbulosRESUMEN
The development of combination antiretroviral therapy (cART) has transformed human immunodeficiency virus (HIV) infection from a lethal diagnosis into a chronic disease, and people living with HIV on cART can experience an almost normal life expectancy. However, these individuals often develop various complications that lead to a decreased quality of life, some of the most significant of which are neuropathic pain and the development of painful peripheral sensory neuropathy (PSN). Critically, although cART is thought to induce pain pathogenesis, the relative contribution of different classes of antiretrovirals has not been systematically investigated. In this study, we measured the development of pathological pain and peripheral neuropathy in mice orally treated with distinct antiretrovirals at their translational dosages. Our results show that only nucleoside reverse transcriptase inhibitors (NRTIs), not other types of antiretrovirals such as proteinase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase strand transfer inhibitors, and CCR5 antagonists, induce pathological pain and PSN. Thus, these findings suggest that NRTIs are the major class of antiretrovirals in cART that promote the development of neuropathic pain. As NRTIs form the essential backbone of multiple different current cART regimens, it is of paramount clinical importance to better understand the underlying mechanism to facilitate the design of less toxic forms of these drugs and/or potential mitigation strategies.
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Neuralgia , Inhibidores de la Transcriptasa Inversa , Animales , Neuralgia/tratamiento farmacológico , Neuralgia/inducido químicamente , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/farmacología , Ratones , Masculino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/efectos adversos , Modelos Animales de Enfermedad , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Magnetic resonance neurography (MRN) is increasingly used as a diagnostic tool for peripheral neuropathies. Quantitative measures enhance MRN interpretation but require nerve segmentation which is time-consuming and error-prone and has not become clinical routine. In this study, we applied neural networks for the automated segmentation of peripheral nerves. METHODS: A neural segmentation network was trained to segment the sciatic nerve and its proximal branches on the MRN scans of the right and left upper leg of 35 healthy individuals, resulting in 70 training examples, via 5-fold cross-validation (CV). The model performance was evaluated on an independent test set of one-sided MRN scans of 60 healthy individuals. RESULTS: Mean Dice similarity coefficient (DSC) in CV was 0.892 (95% confidence interval [CI]: 0.888-0.897) with a mean Jaccard index (JI) of 0.806 (95% CI: 0.799-0.814) and mean Hausdorff distance (HD) of 2.146 (95% CI: 2.184-2.208). For the independent test set, DSC and JI were lower while HD was higher, with a mean DSC of 0.789 (95% CI: 0.760-0.815), mean JI of 0.672 (95% CI: 0.642-0.699), and mean HD of 2.118 (95% CI: 2.047-2.190). CONCLUSION: The deep learning-based segmentation model showed a good performance for the task of nerve segmentation. Future work will focus on extending training data and including individuals with peripheral neuropathies in training to enable advanced peripheral nerve disease characterization. RELEVANCE STATEMENT: The results will serve as a baseline to build upon while developing an automated quantitative MRN feature analysis framework for application in routine reading of MRN examinations. KEY POINTS: Quantitative measures enhance MRN interpretation, requiring complex and challenging nerve segmentation. We present a deep learning-based segmentation model with good performance. Our results may serve as a baseline for clinical automated quantitative MRN segmentation.
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Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Adulto , Femenino , Redes Neurales de la Computación , Enfermedades del Sistema Nervioso Periférico/diagnóstico por imagen , Nervio Ciático/diagnóstico por imagen , Nervios Periféricos/diagnóstico por imagen , Nervios Periféricos/anatomía & histología , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome side effect in patients exposed to taxanes in the treatment of cancer and may affect quality of life dramatically. Here we assessed whether serum levels of neurofilament light (NfL) and tau (two neuroaxonal injury biomarkers) and glial fibrillary acidic protein (GFAP, a biomarker for astrocytic activation) correlate with the development of CIPN in the adjuvant setting of early breast cancer. MATERIALS AND METHODS: Using ultrasensitive single molecule array technology, serum levels of NfL, GFAP, and tau were measured before and every 3 weeks in 10 women receiving adjuvant EC (epirubicin 90 mg/m² and cyclophosphamide 600 mg/m²) every 3 weeks × 3, followed by weekly paclitaxel 80 mg/m² × 9-12 weeks after surgery due to early breast cancer. CIPN was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) and the questionnaire EORTC QLQ CIPN-20. RESULTS: Serum levels of GFAP increased successively during cycles of EC. NfL increased instead in response to the treatment of paclitaxel. NfL and GFAP continued to rise throughout exposure of cumulatively higher doses of paclitaxel and were reduced 3 months after the end of chemotherapy. Serums levels of tau were marginally affected by exposure to chemotherapy. Women with worse symptoms of CIPN had higher concentrations of NfL than women with mild symptoms of CIPN. INTERPRETATION: NfL and GFAP are promising biomarkers to identify women at risk of developing CIPN. Larger prospective studies are now needed.
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Biomarcadores , Neoplasias de la Mama , Epirrubicina , Proteína Ácida Fibrilar de la Glía , Proteínas de Neurofilamentos , Paclitaxel , Enfermedades del Sistema Nervioso Periférico , Proteínas tau , Humanos , Femenino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/sangre , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/sangre , Proteínas de Neurofilamentos/sangre , Persona de Mediana Edad , Proteína Ácida Fibrilar de la Glía/sangre , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Proteínas tau/sangre , Adulto , Biomarcadores/sangre , Epirrubicina/efectos adversos , Epirrubicina/administración & dosificación , Astrocitos/efectos de los fármacos , Astrocitos/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/efectos adversos , Ciclofosfamida/administración & dosificación , Anciano , Quimioterapia Adyuvante/efectos adversosRESUMEN
OBJECTIVES: Childhood cancer survivors are at risk for chemotherapy-induced peripheral neuropathy (CIPN). Physical therapy (PT) improves CIPN symptoms, but little is known about survivors' PT utilization. We described characteristics of survivors with ≥ grade 2 CIPN, investigated PT referral and attendance, and described characteristics of survivors who attended and did not attend PT. METHODS: Childhood cancer survivors <21 years old at cancer diagnosis and ≥2 years posttherapy, living in the United States, evaluated at a regional survivorship clinic were included in this retrospective analysis if they had motor CIPN. Symptomatic CIPN (≥grade 2 by Common Terminology Criteria for Adverse Events) and PT referral/attendance were tabulated. Patient characteristics from the medical record, and neighborhood characteristics (retrieved using survivors' zip code from the National Neighborhood Data Archive) were described by group. RESULTS: Among 91 survivors with CIPN (median 17.5 years old, 8.1 years postcancer diagnosis, 45.1% female), 35 (38.5%) had ≥ grade 2 CIPN. Survivors with ≥ grade 2 CIPN were 28.6% female, and 45.7% were <13 years old. Twenty-four (68.6%) survivors with ≥ grade 2 CIPN agreed to PT referral, and 15 (42.9%) attended PT. Among survivors who attended PT, 73.3% were <13 years old. Neighborhood characteristics of survivors included median percentage of adults without a high school diploma (6.7% PT attendees, 12.5% nonattendees), median percentage of adults who are foreign-born (11.5% PT attendees, 16.4% nonattendees), and median percentage of households with an annual income of <$15,000 (3.2% PT attendees, 6.5% nonattendees). CONCLUSIONS: While 68.6% of survivors with ≥ grade 2 CIPN were referred to PT, only 42.9% attended. Studies to better understand barriers to PT attendance and interventions to improve attendance are needed, especially in older survivors. IMPLICATIONS FOR NURSING PRACTICE: Nurses can play a key role in survivor education and care coordination to help optimize PT attendance.
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Antineoplásicos , Supervivientes de Cáncer , Neoplasias , Enfermedades del Sistema Nervioso Periférico , Modalidades de Fisioterapia , Derivación y Consulta , Humanos , Femenino , Masculino , Supervivientes de Cáncer/estadística & datos numéricos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Derivación y Consulta/estadística & datos numéricos , Adolescente , Estudios Retrospectivos , Niño , Neoplasias/tratamiento farmacológico , Modalidades de Fisioterapia/estadística & datos numéricos , Adulto Joven , Antineoplásicos/efectos adversos , Adulto , Estados Unidos/epidemiología , PreescolarRESUMEN
OBJECTIVES: Provide an overview of scientific reports and literature related to the role(s) of phytocompounds and nutrients in neuroprotection. Discuss how these properties may inform nutrition- and dietary interventions to mitigate chemotherapy-induced peripheral neuropathy (CIPN), for which there are no effective treatments. METHODS: A literature search (2010-2023) was conducted in PubMed and Google Scholar where search terms-diet, nutrition, neuroprotection, neurodegenerative diseases, and social determinants of health-were used to narrow articles. From this search, manuscripts were reviewed to provide an overview of the neuroprotective properties of various phytocompounds and nutrients and their observed effects in neurodegenerative conditions and CIPN. Social determinant of health factors (SDOH) related to economic stability and access to nutritious foods were also reviewed as potential barriers to dietary interventions. RESULTS: Twenty-eight publications were included in this literature review. Phytocompounds found in green tea (EGCG), turmeric (curcumin), cruciferous vegetables (sulforaphane), as well as certain vitamins, are promising, targeted interventions to mitigate CIPN. SDOH factors such as economic instability and limited access to nutritious foods may act as barriers to dietary interventions and limit their generalizability. CONCLUSION: Dietary interventions focused on the use of phytocompounds and vitamins with known antioxidant, anti-inflammatory, and neuroprotective properties, hold promise and may provide patients with natural, non-pharmacological therapeutics for the management and/or prevention of CIPN. However, rigorous clinical trial research is needed to explore these effects in humans. IMPLICATIONS FOR NURSING PRACTICE: Nurses support cancer survivors at the point-of-care, particularly during and after neurotoxic chemotherapy treatments. If future research supports dietary interventions to mitigate CIPN, nurses will ultimately be positioned to help translate this knowledge into clinical practice through educating patients on how to infuse nutrient-rich foods into their diets. Further, nurses will need to be conscious of SDOH factors that may impede access to these foods.
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Antineoplásicos , Enfermedades del Sistema Nervioso Periférico , Humanos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Antineoplásicos/efectos adversos , Fitoquímicos/uso terapéutico , Fitoquímicos/farmacología , Nutrientes , Neoplasias/tratamiento farmacológico , Suplementos Dietéticos , Femenino , MasculinoAsunto(s)
Antineoplásicos , Supervivientes de Cáncer , Neoplasias , Enfermedades del Sistema Nervioso Periférico , Humanos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Supervivientes de Cáncer/psicología , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Síndromes de Neurotoxicidad/etiología , Disfunción Cognitiva/inducido químicamente , Femenino , Deterioro Cognitivo Relacionado con la Quimioterapia , MasculinoRESUMEN
Paclitaxel (PTX) is a microtubule stabilizer that disrupts the normal cycle of microtubule depolymerization and repolymerization, leading to cell cycle arrest and cancer cell death. It is commonly used as a first-line chemotherapeutics for various malignancies, such as breast cancer, non-small cell lung cancer, and ovarian cancer. However, PTX chemotherapy is associated with common and serious side effects, including chemotherapy-induced peripheral neuropathy (CIPN). As cancer treatment advances and survival rates increase, the impact of CIPN on patients' quality of life has become more significant. To date, there is no effective treatment strategy for CIPN. Surtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+) dependent protein deacetylase located on mitochondria. It transfers the acetyl group of the lysine side chain of acetylated substrate proteins to NAD+, producing deacetylated proteins to regulate mitochondrial energy metabolic processes. SIRT3 has been found to play an important role in various diseases, including aging, neurodegenerative diseases, cancer, heart disease, metabolic diseases, etc. However, the role of SIRT3 in CIPN is still unknown. This study found for the first time that activating SIRT3 helps to improve paclitaxel-induced CIPN. Nicotinamide riboside (NR) can protect dorsal root ganglion (DRG) mitochondria against oxidative damage caused by paclitaxel through activating SIRT3-MnSOD2 and SIRT3-Nrf2 pathway. Moreover, NR can enhance the anticancer activity of paclitaxel. Together, our research provides new strategy and candidate drug for the treatment of CIPN.
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Niacinamida , Paclitaxel , Enfermedades del Sistema Nervioso Periférico , Compuestos de Piridinio , Sirtuina 3 , Paclitaxel/toxicidad , Sirtuina 3/metabolismo , Animales , Compuestos de Piridinio/farmacología , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Enfermedades del Sistema Nervioso Periférico/metabolismo , Niacinamida/análogos & derivados , Niacinamida/farmacología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/toxicidad , Ratones , Humanos , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , MasculinoRESUMEN
The analysis of nerve regeneration in the chemotherapy-induced peripheral neuropathy (CIPN) model can be achieved using the compartmentalized culture system. This system enables us to isolate the cell body from the axon physically and fluidically, therefore allowing for the independent manipulation of the cell body and axons. Compartmentalized chambers mimic the human body conditions, and can be used to study axonal degeneration, disease modeling, and drug screening. This culture system is applied to the CIPN model to study and analyze axonal behavior in response to paclitaxel (PTX) with and without fluocinolone acetonide (FA) and to better understand the site-specific target of PTX. Therefore, this compartmentalized system allows for the independent treatment of chemotherapy drugs to the cell body or axonal side which enables monitoring their reaction as a result of the treatment.